TY - JOUR AN - 18014673 AU - Frost, W. H. DA - Aug ET - 08/01 J2 - American journal of public health and the nation's health LA - eng N1 - Frost, W H Am J Public Health Nations Health. 1937 Aug;27(8):759-66. PY - 1937 RN - fulltext fulltext_1208 SN - 0002-9572 (Print) 0002-9572 (Linking) SP - 759-66 ST - How Much Control of Tuberculosis? T2 - Am J Public Health Nations Health TI - How Much Control of Tuberculosis? UR - http://www.ncbi.nlm.nih.gov/pubmed/18014673http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1563282/pdf/amjphnation01049-0029.pdf VL - 27 ID - 2262 ER - TY - JOUR AN - 13458543 AU - Feldmann, F. M. DA - Oct ET - 10/01 J2 - American journal of public health and the nation's health LA - eng N1 - FELDMANN, F M Not Available Am J Public Health Nations Health. 1957 Oct;47(10):1235-41. PY - 1957 RN - fulltext fulltext_1208 SN - 0002-9572 (Print) 0002-9572 (Linking) SP - 1235-41 ST - How much control of tuberculosis: 1937-1957-1977 T2 - Am J Public Health Nations Health TI - How much control of tuberculosis: 1937-1957-1977 UR - http://www.ncbi.nlm.nih.gov/pubmed/13458543http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1551316/pdf/amjphnation01093-0004.pdf VL - 47 ID - 2263 ER - TY - JOUR AB - The second report of the Medical Research Council trial of tuberculosis vaccines in adolescents (Medical Research Council, 1959) contained an estimate of the benefit to be expected from BCG vaccination. If all those tuberculin-negative on entry to the trial in 1950–52, at the age of 14 years, had been vaccinated with BCG, the reduction in the incidence of tuberculosis in the ensuing five years would have been 59 per cent.The present study, by taking into account the recent decrease in risk of exposure to tuberculous infection in England and Wales, provides similar estimates of the scope for BCG vaccination, which are more up to date and also applicable to the whole country.Of the tuberculosis notifications among those aged 15–19 years in England and Wales in 1958, it is estimated that 52 per cent could have been prevented by BCG vaccination at the age of 14 years of all who were then tuberculin-negative. This estimate for 1958 is compared with that for 1953, which was 60 per cent. There has thus been a moderate decline in the scope for BCG vaccination during these five years. If the trend in exposure to tuberculous infection continues, BCG vaccination of all tuberculin-negative children who are aged 14 years now (1959) would apparently reduce the incidence when they become 15–19 years of age by rather less than half.In terms of the numbers of cases preventable by BCG vaccination of children aged 14 years, the scope has declined very considerably, from about 2,950 notifications among those aged 15–19 years in 1953, to 1,400 in the same age group in 1958. We may in a few years reach a situation in this country in which mass vaccination of older school children prevents only small numbers of cases of tuberculosis in adolescents. If, however, the protection from vaccination is maintained, cases will also be prevented in those aged 20 years and over.It is estimated that the official scheme for BCG vaccination at the age of 13 years, which started at the end of 1953, reduced the numbers of notifications at ages 15–19 years in England and Wales by 50 in 1956, 156 in 1957 and 241 in 1958. These small numbers are due to incomplete coverage of the 15–19 year age group in these years and the slow development of the scheme.It is suggested that a central bureau should be established to collect and interpret the information in connexion with the official vaccination scheme. This could make a valuable contribution to the eradication of tuberculosis from this country. AU - Sutherland, I. PY - 1959 RN - fulltext fulltext_1208 SP - 413-24 ST - An estimation of the scope for BCG vaccination in preventing tuberculosis among those aged 15–19 years in England and Wales at the present time T2 - Tubercle TI - An estimation of the scope for BCG vaccination in preventing tuberculosis among those aged 15–19 years in England and Wales at the present time UR - http://www.sciencedirect.com/science/article/pii/S0041387959800969 VL - 40 ID - 2264 ER - TY - JOUR AN - 14004185 AU - Waaler, H. AU - Geser, A. AU - Andersen, S. DA - Jun ET - 06/01 J2 - American journal of public health and the nation's health LA - eng N1 - WAALER, H GESER, A ANDERSEN, S Not Available Am J Public Health Nations Health. 1962 Jun;52:1002-13. PY - 1962 RN - fulltext fulltext_1208 SN - 0002-9572 (Print) 0002-9572 (Linking) SP - 1002-13 ST - The use of mathematical models in the study of the epidemiology of tuberculosis T2 - Am J Public Health Nations Health TI - The use of mathematical models in the study of the epidemiology of tuberculosis UR - http://www.ncbi.nlm.nih.gov/pubmed/14004185http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1523050/pdf/amjphnation00492-0106.pdf VL - 52 ID - 2265 ER - TY - JOUR AU - Subramaniam, M. DA - 1965 J2 - Ind.J.Tub. KW - Asia epidemiology India infection interpretation models prevalence risk of infection tuberculin tuberculin testing tuberculosis Tumkur LB - 7006 N1 - TY - JOUR TB Transmission, pathogenesis, and epidemiology Infection with tubercle bacilli Descript epi: infection TBN testing - interpretation PY - 1965 RN - fulltext fulltext_1208 SP - 101-110 ST - Mathematical approach to the study of tuberculin sensitivity T2 - Indian J Tuberc TI - Mathematical approach to the study of tuberculin sensitivity VL - 12 ID - 2266 ER - TY - JOUR AN - 6018702 AU - Brogger, S. DA - Mar ET - 03/01 J2 - The American review of respiratory disease KW - Adolescent Adult Aged BCG Vaccine Child Child, Preschool Evaluation Studies as Topic Female Humans Infant Infant, Newborn Male Middle Aged Models, Theoretical *Systems Analysis Thailand Tuberculosis/*prevention & control LA - eng N1 - Brogger, S Am Rev Respir Dis. 1967 Mar;95(3):419-34. PY - 1967 RN - fulltext fulltext_1208 SN - 0003-0805 (Print) 0003-0805 (Linking) SP - 419-34 ST - Systems analysis in tuberculosis control: a model T2 - Am Rev Respir Dis TI - Systems analysis in tuberculosis control: a model UR - http://www.ncbi.nlm.nih.gov/pubmed/6018702 VL - 95 ID - 2267 ER - TY - JOUR AN - 14754 AU - Ferebee, S. H. KW - Americas epidemiology infection models morbidity mortality tuberculosis USA N1 - IN FILE TB Transmission, pathogenesis, and epidemiology Infection with tubercle bacilli Predict epi of morbidity: prospects for the epidemic PY - 1967 RN - fulltext fulltext_1208 SP - 4-7 ST - An epidemiological model of tuberculosis in the United States T2 - Nat.Tuberc.Assoc.Bull. TI - An epidemiological model of tuberculosis in the United States UR - file://C:\literature_pdf\rm14754.pdf VL - 53 ID - 2268 ER - TY - JOUR AN - 5582655 AU - Juchniewicz, M. AU - Olakowski, T. AU - Mardon, K. ET - 01/01 KW - *Epidemiologic Methods Humans Models, Theoretical Poland Prognosis Retrospective Studies Tuberculosis/*prevention & control LA - pol N1 - Juchniewicz, M Olakowski, T Mardon, K Poland Gruzlica i choroby pluc; tuberculosis et pneumonologia Gruzlica. 1967;35(10):961-7. OP - Prognozowanie sytuacji epidemiologicznej gruzlicy na podstawie modelu epidemiometrycznego. (Doniesienie wstepne) PY - 1967 RN - fulltext fulltext_1208 SN - 0017-4955 (Print) 0017-4955 (Linking) SP - 961-967 ST - [Prognostication of the epidemiological situation of tuberculosis, based on an epidemiological model (Preliminary report)] T2 - Gruzlica i Choroby Pluc TI - [Prognostication of the epidemiological situation of tuberculosis, based on an epidemiological model (Preliminary report)] UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=5582655 VL - 35 ID - 2269 ER - TY - JOUR AB - The regional management of tuberculosis in developing nations is studied utilizing the tools of systems analysis. A tuberculosis system is visualized, the system being made up of components which are the epidemiological categories that characterize the disease. The interaction of these components determines the future state of the disease. Controls in the form of therapy, vaccinations, or prophylaxis may be superimposed on the natural processes, thus altering the future course of the disease. A descriptive mathematical model describing the flows between the various categories can be used to predict the trends both with and without intervention. An optimization model is derived from the descriptive model under the assumption that a program of reproduction of active cases has been specified. The optimization model would be used to select the forms of control which achieve the specified reduction program at least cost. Optimization is accomplished via linear programming. AN - 6059199 AU - ReVelle, C. S. AU - Lynn, W. R. AU - Feldmann, F. DA - Nov DP - Nlm ET - 11/01 KW - International Cooperation Models, Theoretical Systems Analysis Tuberculosis, Pulmonary/ prevention & control LA - eng N1 - ReVelle, C S Lynn, W R Feldmann, F United states The American review of respiratory disease Am Rev Respir Dis. 1967 Nov;96(5):893-909. PY - 1967 RN - fulltext fulltext_1208 SN - 0003-0805 (Print) 0003-0805 (Linking) SP - 893-909 ST - Mathematical models for the economic allocation of tuberculosis control activities in developing nations T2 - Am Rev Respir Dis TI - Mathematical models for the economic allocation of tuberculosis control activities in developing nations VL - 96 ID - 2270 ER - TY - JOUR AN - 5710260 AU - Waaler, H. T. DA - Dec ET - 12/01 J2 - Bulletin of the International Union against Tuberculosis KW - Adolescent Adult Aged *BCG Vaccine Child Child, Preschool *Costs and Cost Analysis Female Humans Infant Infant, Newborn Male Middle Aged Models, Theoretical Norway Operations Research Tuberculosis/prevention & control United States LA - eng N1 - Waaler, H T FRANCE Bull Int Union Tuberc. 1968 Dec;41:42-52. PY - 1968 RN - fulltext fulltext_1208 SN - 0074-9249 (Print) 0074-9249 (Linking) SP - 42-52 ST - Cost-benefit analysis of BCG-vaccination under various epidemiological situations T2 - Bull Int Union Tuberc TI - Cost-benefit analysis of BCG-vaccination under various epidemiological situations UR - http://www.ncbi.nlm.nih.gov/pubmed/5710260 VL - 41 ID - 2271 ER - TY - JOUR AU - Waaler, H. T. DO - WHO/TB/Techn.Information/67.54 KW - epidemiology fatality infection models morbidity tuberculosis LB - 4826 N1 - TY - JOUR TB Transmission, pathogenesis, and epidemiology Tuberculosis Predict epi of morbidity: prospects for the epidemic PY - 1968 RN - fulltext fulltext_1208 SP - 591-600 ST - A dynamic model for the epidemiology of tuberculosis T2 - American Review of Respiratory Disease TI - A dynamic model for the epidemiology of tuberculosis UR - Printout in Models Box 1 (In EndNote no PDF) VL - 98 ID - 2272 ER - TY - BILL AN - 4904991 DA - Jan 1 KW - Diagnosis: Computer-Assisted Tuberculosis: Pulmonary Methods Humans Models: Theoretical Statistics as Topic LB - p31852 M1 - 11 PY - 1969 RN - fulltext fulltext_1208 SP - 59-64 ST - [A statistical model for evaluating the activity of minor forms of pulmonary tuberculosis] T2 - Probl Tuberk TI - [A statistical model for evaluating the activity of minor forms of pulmonary tuberculosis] UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=4904991 VL - 47 ID - 2273 ER - TY - JOUR AB - The problems of management of tuberculosis in developing nations are studied utilizing the tools of systems analysis. The tuberculosis system consists of interacting components which are the “states of nature” of the disease. The interaction of these components determine the future state of the disease. Controls in the form of therapy, vaccinations or prophylaxis may be superimposed on the natural processes, thus altering the future course of the disease. A descriptive mathematical model describing the flows between the various categories is used to predict the trends both with and without intervention. An optimization model is derived from the descriptive model under the assumption that a program of reduction of active cases has been specified. The optimization model selects the forms of control which achieve the specified reduction program at least cost. Optimization is accomplished via linear programming. The model is general in that the parameters, costs and initial conditions may be varied for different situations. The descriptive mathematical model and the optimization model which determines the most efficient controls are intended to improve decision-making in public health management of tuberculosis. AU - Reveller, Charles AU - Lynn, Walter AU - Feldmann, Floyd DO - 10.1287/mnsc.16.4.B190 IS - 4 PY - 1969 SP - B-190-B-211 ST - An Optimization Model of Tuberculosis Epidemiology T2 - Management Science TI - An Optimization Model of Tuberculosis Epidemiology UR - http://pubsonline.informs.org/doi/abs/10.1287/mnsc.16.4.B190 VL - 16 ID - 4829 ER - TY - JOUR AU - Styblo, K. AU - Meijer, J. AU - Sutherland, I. DA - 1969 J2 - Bull.Int.Union Tuberc. KW - epidemiology models Netherlands population research risk of infection surveillance transmission tubercle tuberculosis LB - 302 N1 - TY - JOUR TB Transmission, pathogenesis, and epidemiology Infection with tubercle bacilli Etiol epi: risk of infection Risk of infection - models L1 - file://C:\literature_pdf\rm00302.pdf PY - 1969 RN - fulltext fulltext_1208 RP - IN FILE SP - 1-104 ST - The transmission of tubercle bacilli - its trend in a human population. Tuberculosis Surveillance Research Unit Report No. 1 TI - The transmission of tubercle bacilli - its trend in a human population. Tuberculosis Surveillance Research Unit Report No. 1 VL - 42 ID - 2274 ER - TY - JOUR AB - Given an adequate definition of the disease problem in epidemiological terms, it is possible to measure the epidemiological effectiveness of control measures in terms of problem reduction. This is to be distinguished from the clinical efficacy of the same measures. The practical difficulty in assessing the epidemiological effectiveness of control measures experimentally can be overcome by the construction of simulation models and the use of computers, whereby the problem reduction associated with various control strategies can be estimated numerically.By varying the levels of certain parameters of the model systematically, the sensitivity of the effectiveness of control measures to the epidemiological, operational, clinical and social parameters of a situation can be assessed. A series of articles analysing this relationship is under preparation. This first article analyses the sensitivity of the effectiveness of BCG vaccination and of the chemotherapy of tuberculosis to changes in the coverage of the eligible population groups. A previously formulated postulate stating that the marginal effectiveness of these measures decreases as their coverage increases is validated by this first series of simulations. The significance of this finding for planning national tuberculosis control strategies is discussed, as well as possible bias in the method applied. AN - 5309169 AU - Waaler, H. T. AU - Piot, M. A. ET - 01/01 J2 - Bulletin of the World Health Organization KW - Adolescent Adult Aged Antitubercular Agents/therapeutic use BCG Vaccine Child Child, Preschool Computers Epidemiologic Methods Humans Infant Infant, Newborn Middle Aged *Models, Theoretical Population Tuberculosis/*prevention & control LA - eng N1 - Waaler, H T Piot, M A SWITZERLAND Bull World Health Organ. 1969;41(1):75-93. PY - 1969 RN - fulltext fulltext_1208 SN - 0042-9686 (Print) 0042-9686 (Linking) SP - 75-93 ST - The use of an epidemiological model for estimating the effectiveness of tuberculosis control measures. Sensitivity of the effectiveness of tuberculosis control measures to the coverage of the population T2 - Bull World Health Organ TI - The use of an epidemiological model for estimating the effectiveness of tuberculosis control measures. Sensitivity of the effectiveness of tuberculosis control measures to the coverage of the population UR - http://www.ncbi.nlm.nih.gov/pubmed/5309169http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2427408/pdf/bullwho00218-0087.pdf VL - 41 ID - 2275 ER - TY - JOUR AN - 4915929 AU - Revelle, C. AU - Male, J. DA - Sep DP - Nlm ET - 09/01 KW - Costs and Cost Analysis Histological Techniques Humans Models, Theoretical Sputum/microbiology Tuberculin Test Tuberculosis/diagnosis/ prevention & control/radiography LA - eng N1 - Revelle, C Male, J United states The American review of respiratory disease Am Rev Respir Dis. 1970 Sep;102(3):403-11. PY - 1970 RN - fulltext fulltext_1208 SN - 0003-0805 (Print) 0003-0805 (Linking) SP - 403-11 ST - A mathematical model for determining case finding and treatment activities in tuberculosis control programs T2 - Am Rev Respir Dis TI - A mathematical model for determining case finding and treatment activities in tuberculosis control programs VL - 102 ID - 2276 ER - TY - JOUR AN - 5425564 AU - Waaler, H. T. DA - Jun DP - Nlm ET - 06/01 KW - Health Planning Humans Mathematics Models, Theoretical Tuberculosis, Pulmonary/epidemiology/ prevention & control LA - eng N1 - Waaler, H T France Bulletin of the International Union against Tuberculosis Bull Int Union Tuberc. 1970 Jun;43:337-44. PY - 1970 RN - fulltext fulltext_1208 SN - 0074-9249 (Print) 0074-9249 (Linking) SP - 337-44 ST - Model simulation and decision-making in tuberculosis programmes T2 - Bull Int Union Tuberc TI - Model simulation and decision-making in tuberculosis programmes VL - 43 ID - 2277 ER - TY - JOUR AB - Different combinations of coverage levels of BCG vaccination and of case-finding and treatment may achieve the same problem reduction in epidemiological terms. But the same problem reduction, in man-years of tuberculosis, may be valued differently in social terms.A social-time-preference parameter, of the form 1/(1+r)(t), is relevant to this evaluation and the level of r is critical for policy decision. The present paper studies the sensitivity of the effectiveness of BCG vaccination and of case-finding and treatment to the level of r, and the epidemiological mechanism underlying such sensitivity. A high value of r can be visualized as corresponding to a close planning horizon, a lower value of r to a more distant one. At any level of epidemiological effectiveness, a planner with a high value of r would favour case-finding and treatment, and a planner with a low value of r would tend to emphasize BCG vaccination. This influence of the social-time-preference parameter on the planner's decision is found to depend on the discounting effect of the parameter on the one hand, and on the different age- and time-patterns of the preventive effect of the major control measures, on the other. AN - 5312319 AU - Waaler, H. T. AU - Piot, M. A. DP - Nlm ET - 01/01 KW - Adolescent Adult Age Factors Aged BCG Vaccine Child Child, Preschool Humans Mathematics Middle Aged Models, Theoretical Time Factors Tuberculosis/ prevention & control LA - eng N1 - Waaler, H T Piot, M A Switzerland Bulletin of the World Health Organization Bull World Health Organ. 1970;43(1):1-16. PY - 1970 RN - fulltext fulltext_1208 SN - 0042-9686 (Print) 0042-9686 (Linking) SP - 1-16 ST - Use of an epidemiological model for estimating the effectiveness of tuberculosis control measures. Sensitivity of the effectiveness of tuberculosis control measures to the social time preference T2 - Bull World Health Organ TI - Use of an epidemiological model for estimating the effectiveness of tuberculosis control measures. Sensitivity of the effectiveness of tuberculosis control measures to the social time preference VL - 43 ID - 2278 ER - TY - JOUR AU - Chorba, R. W. AU - Sanders, J. L. PY - 1971 RN - fulltext fulltext_1208 SP - 144 ST - Planning models for tuberculosis control programs T2 - Health Services Research TI - Planning models for tuberculosis control programs UR - http://pubmedcentralcanada.ca/picrender.cgi?accid=PMC1067333&blobtype=pdf VL - 6 ID - 2279 ER - TY - JOUR AN - 5572852 AU - Endo, S. AU - Aoki, K. DA - Apr KW - Adolescent Adult Age Factors Aged BCG Vaccine Child Child, Preschool Epidemiologic Methods Humans Infant Infant, Newborn Japan Middle Aged Models, Theoretical *Systems Analysis Tuberculosis/*epidemiology/*prevention & control LA - jpn N1 - Journal Article Japan [Tuberculosis] PY - 1971 RN - fulltext fulltext_1208 SN - 0022-9776 (Print) SP - 99-111 ST - [Estimation of future epidemiological trends of tuberculosis in Japan and the evaluation of tuberculosis control programmes by simulation analysis] T2 - Kekkaku TI - [Estimation of future epidemiological trends of tuberculosis in Japan and the evaluation of tuberculosis control programmes by simulation analysis] UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=5572852 VL - 46 ID - 2280 ER - TY - JOUR AU - Sutherland, I. DA - 1971 J2 - Bull.Int.Union Tuberc. KW - epidemiology infection models research reversion risk of infection surveillance tuberculin tuberculosis LB - 4516 N1 - TY - JOUR TB Transmission, pathogenesis, and epidemiology Infection with tubercle bacilli Predict epi: risk of infection Risk of infection - models L1 - file://C:\literature_pdf\rm04516.pdf PY - 1971 RN - fulltext fulltext_1208 RP - IN FILE SP - 115-118 ST - The effect of tuberculin reversion upon the estimate of the annual risk of tuberculous infection. Tuberculosis Surveillance Research Unit Report No. 2 TI - The effect of tuberculin reversion upon the estimate of the annual risk of tuberculous infection. Tuberculosis Surveillance Research Unit Report No. 2 VL - 45 ID - 2281 ER - TY - BILL AN - 5086128 DA - Aug 11 KW - Partial Pressure Tuberculosis: Pulmonary Pulmonary Circulation Pulmonary Alveoli Humans Mathematics Models: Biological Oxygen Inhalation Therapy LB - p31846 M1 - 5 PY - 1972 RN - fulltext fulltext_1208 SP - 1237-9 ST - [Mathematical model of pulmonary tuberculosis and its treatment by lowering the partial pressure of oxygen] T2 - Dokl Akad Nauk SSSR TI - [Mathematical model of pulmonary tuberculosis and its treatment by lowering the partial pressure of oxygen] UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=5086128 VL - 205 ID - 2283 ER - TY - JOUR AN - 5077111 AU - Canetti, G. AU - Sutherland, I. AU - Svandova, E. DA - Feb 1 KW - Remission: Spontaneous Immunity France Adult Adolescent Drug Resistance: Microbial Middle Aged Epidemiologic Methods Tuberculosis: Pulmonary Netherlands Tuberculin Test Humans Great Britain Male Health Surveys Czechoslovakia Disease Outbreaks Female Mycobacterium Infections Age Factors Aged LB - p14661 PY - 1972 RN - fulltext fulltext_1208 SP - 116-34 ST - Endogenous reactivation and exogenous reinfection: their relative importance with regard to the development of non-primary tuberculosis T2 - Bull Int Union Tuberc TI - Endogenous reactivation and exogenous reinfection: their relative importance with regard to the development of non-primary tuberculosis UR - http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Retrieve&list_uids=5077111&dopt=abstractplus VL - 47 ID - 2282 ER - TY - BILL AN - 4775093 DA - Jan 1 KW - Costs and Cost Analysis Age Factors BCG Vaccine Humans Mathematics Tuberculosis Probability Models: Theoretical Statistics as Topic Epidemiologic Methods Socioeconomic Factors LB - p31839 M1 - 6 PY - 1973 RN - fulltext fulltext_1208 SP - 561-84 ST - [Mathematical model in tuberculosis] T2 - Ftiziologia TI - [Mathematical model in tuberculosis] UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=4775093 VL - 22 ID - 2284 ER - TY - JOUR AU - Horwitz, O. DA - 1973 J2 - Am.J.Epidemiol. KW - clinical epidemiology infection models morbidity mortality tuberculosis LB - 1172 N1 - TY - JOUR TB Transmission, pathogenesis, and epidemiology Tuberculosis Predict epi of morbidity:prospects for the epidemic PY - 1973 RN - fulltext fulltext_1208 RP - IN FILE SP - 148-159 ST - Disease, cure, and death: epidemiologic and clinical parameters for chronic diseases illustrated by a model - tuberculosis TI - Disease, cure, and death: epidemiologic and clinical parameters for chronic diseases illustrated by a model - tuberculosis VL - 97 ID - 2285 ER - TY - JOUR AU - Lotte, A. AU - Uzan, J. DA - 1973 J2 - Int.J.Epidemiol. KW - epidemiology France infection models risk of infection tuberculosis LB - 293 N1 - TY - JOUR TB Transmission, pathogenesis, and epidemiology Infection with tubercle bacilli Predict epi: risk of infection Risk of infection - models PY - 1973 RN - fulltext fulltext_1208 SP - 265-282 ST - Evolution of the rates of tuberculous infection in France and calculation of the annual risk by means of a mathematical model T2 - Int J Epidemiol TI - Evolution of the rates of tuberculous infection in France and calculation of the annual risk by means of a mathematical model VL - 2 ID - 2286 ER - TY - JOUR AB - Owing to the wide range of tuberculo statics, the treatment of tuberculosis is characerized by the possibility of applying a series of therapeutical schemes or variants"with adifferent clinical and epidemiologic efficiency in terms of ?he association of the drugs, their administration, dose, duration, etc. Epidemiologic Simplies thf preventive effect of chemotherapy in a community, overa^WenPeriod ^ ^ ^ optimization nodel 0f chemotherapy applied as acontrol.measure withinalimited area to chronic and hyperchronic patien^^^^^^ ^^^ health benefit of the population within the respective area. AN - 4775094 AU - Rusu, G. DA - Jan 1 KW - Mathematics Age Factors Humans Tuberculosis Probability Models: Theoretical Epidemiologic Methods Socioeconomic Factors LB - p31840 PY - 1973 RN - fulltext fulltext_1208 SP - 585-92 ST - [A Markovian model in tuberculosis epidemiology] T2 - Ftiziologia TI - [A Markovian model in tuberculosis epidemiology] UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=4775094 VL - 22 ID - 2287 ER - TY - JOUR AN - 9595 AU - de Ville de Goyet, C. KW - Africa AFRO epidemiology infection models risk of infection South Africa Transkei tuberculin tuberculosis N1 - IN FILE TB Transmission, pathogenesis, and epidemiology Tuberculosis Descript epi: morbidity Africa - South Africa PY - 1974 RN - fulltext fulltext_1208 SP - 957-960 ST - Annual risk of tuberculosis infection in the Transkei. Problems connected with its estimation from the data of a tuberculin survey T2 - S.Afr.Med.J. TI - Annual risk of tuberculosis infection in the Transkei. Problems connected with its estimation from the data of a tuberculin survey UR - file://C:\literature_pdf\rm09596.pdf VL - 48 ID - 2288 ER - TY - JOUR AN - 4467941 AU - Waaler, H. AU - Rouillon, A. ET - 01/01 J2 - Bulletin of the International Union against Tuberculosis KW - Adolescent *BCG Vaccine Costs and Cost Analysis Health Planning Humans Infant Models, Theoretical Psychology Time Factors Tuberculosis/*epidemiology LA - fre N1 - Waaler, H Rouillon, A FRANCE Bull Int Union Tuberc. 1974;49(1):181-206. OP - Politiques de vaccination BCG en fonction de la situation epidemiologique PY - 1974 RN - fulltext fulltext_1208 SN - 0074-9249 (Print) 0074-9249 (Linking) SP - 181-206 ST - [BCG vaccination policies as a function of the epidemiological situation] T2 - Bull Int Union Tuberc TI - [BCG vaccination policies as a function of the epidemiological situation] UR - http://www.ncbi.nlm.nih.gov/pubmed/4467941 VL - 49 ID - 2289 ER - TY - JOUR AB - Data on the dynamics of the tuberculosis situation in rural South India, obtained by the National Tuberculosis Institute, Bangalore, were fed into a mathematical model. By this means predictions about the future tuberculosis situation have been made under a wide range of hypothetical assumptions. AN - 4549350 AU - Waaler, H. T. AU - Gothi, G. D. AU - Baily, G. V. AU - Nair, S. S. ET - 01/01 J2 - Bulletin of the World Health Organization KW - Adolescent Adult Aged Antitubercular Agents/*administration & dosage/standards BCG Vaccine Child Child, Preschool Computers Demography Female Fertility Forecasting Humans India Infant Longitudinal Studies Male Middle Aged Models, Theoretical Rural Health Rural Population Tuberculosis/*epidemiology/prevention & control LA - eng M3 - Research Support, U.S. Gov't, Non-P.H.S. N1 - Waaler, H T Gothi, G D Baily, G V Nair, S S SWITZERLAND Bull World Health Organ. 1974;51(3):263-71. PY - 1974 RN - fulltext fulltext_1208 SN - 0042-9686 (Print) 0042-9686 (Linking) SP - 263-71 ST - Tuberculosis in rural South India. A study of possible trends and the potential impact of antituberculosis programmes T2 - Bull World Health Organ TI - Tuberculosis in rural South India. A study of possible trends and the potential impact of antituberculosis programmes UR - http://www.ncbi.nlm.nih.gov/pubmed/4549350http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2366280/pdf/bullwho00469-0048.pdf VL - 51 ID - 2290 ER - TY - JOUR AB - A large-scale computer service is not always available in many countries with tuberculosis problems needing epidemiological analysis. To facilitate work in such countries, a simple epidemiological model was made to calculate annual trends in the prevalence and incidence of tuberculosis and its infection, in tuberculosis mortality, and in BCG coverage, using average parameter values not specific for age groups or birth year cohorts. To test its approximation capabilities and limits, the model was applied to epidemiological data from Japan, where sufficient information was available from repeated nation-wide sample surveys and national statistics. The approximation was found to be satisfactory within certain limits. The model is best used with a desk-top computer, but the calculations can be performed with a small calculator or even by hand. AN - 1084802 AU - Azuma, Y. ET - 01/01 J2 - Bulletin of the World Health Organization KW - BCG Vaccine Epidemiologic Methods Humans Japan *Models, Theoretical Tuberculosis/*epidemiology/mortality/prevention & control LA - eng N1 - Azuma, Y SWITZERLAND Bull World Health Organ. 1975;52(3):313-22. PY - 1975 RN - fulltext fulltext_1208 SN - 0042-9686 (Print) 0042-9686 (Linking) SP - 313-22 ST - A simple simulation model of tuberculosis epidemiology for use without large-scale computers T2 - Bull World Health Organ TI - A simple simulation model of tuberculosis epidemiology for use without large-scale computers UR - http://www.ncbi.nlm.nih.gov/pubmed/1084802http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2366382/pdf/bullwho00465-0076.pdf VL - 52 ID - 2291 ER - TY - JOUR AN - 1185919 AU - Azuma, Y. DA - Jul ET - 07/01 J2 - Kekkaku : [Tuberculosis] KW - Adolescent Adult Child Child, Preschool Humans Infant Infant, Newborn Japan Middle Aged *Models, Theoretical Tuberculosis, Pulmonary/*epidemiology LA - jpn N1 - Azuma, Y JAPAN Kekkaku. 1975 Jul;50(7):199-207. PY - 1975 RN - fulltext fulltext_1208 SN - 0022-9776 (Print) 0022-9776 (Linking) SP - 199-207 ST - [Estimation of the epidemiological time trend of tuberculosis in Japan, a trial with a simple epidemiological simulation model (author's transl)] T2 - Kekkaku TI - [Estimation of the epidemiological time trend of tuberculosis in Japan, a trial with a simple epidemiological simulation model (author's transl)] UR - http://www.ncbi.nlm.nih.gov/pubmed/1185919 VL - 50 ID - 2292 ER - TY - JOUR AB - The prevalence of tuberculous infection in a population is generally estimated from calculating the proportion of tested individuals who react with at least 10 mm of induration to 5 TU of PPD-S tuberculin. Reactions due to infection with atypical mycobacteria, however, may cause the prevalence to be overestimated. This paper is concerned with an alternative method of estimating the prevalence of infection with Mycobacterium tuberculosis. The method utilizes population distributions of reaction size by dividing study populations into two groups--individuals with and without known exposure to tuberculosis. The mathematical model developed here removes the effect of atypical infections and provides a truer picture of tuberculous infection. Data from a Navy recruit population demonstrate the use of the model with the result that among recruits with no known exposure to tuberculosis, the estimated prevalence is reduced by about one-half. Among recuits with known exposure to tuberculosis, there is essentially no difference between the two methods. Important advantages in using this method are that probabilities of true infection by induration size are generated, and that itis less sensitive to variations caused by differences in reading techniques and in tuberculin potencies. Furthermore, it is applicable to other diseases if the underlying assumptions are met. AN - 1124761 AU - Rust, P. AU - Thomas, J. DA - Apr DP - Nlm ET - 04/01 KW - Epidemiologic Methods Humans Male Mathematics Models, Theoretical Naval Medicine Probability Tuberculin Test Tuberculosis, Pulmonary/ epidemiology United States LA - eng N1 - Rust, P Thomas, J United states American journal of epidemiology Am J Epidemiol. 1975 Apr;101(4):311-22. PY - 1975 RN - fulltext fulltext_1208 SN - 0002-9262 (Print) 0002-9262 (Linking) SP - 311-22 ST - A method for estimating the prevalence of tuberculosis infection T2 - Am J Epidemiol TI - A method for estimating the prevalence of tuberculosis infection UR - http://aje.oxfordjournals.org.ez.lshtm.ac.uk/content/101/4/311.full.pdf VL - 101 ID - 2293 ER - TY - JOUR AU - Sutherland, I. AU - Fayers, P. M. DA - 1975 J2 - Bull.Int.Union Tuberc. KW - age infection models risk of infection tuberculosis LB - 4519 N1 - TY - JOUR TB Transmission, pathogenesis, and epidemiology Infection with tubercle bacilli Predict epi: risk of infection Risk of infection - models L1 - file://C:\literature_pdf\rm04519.pdf PY - 1975 RN - fulltext fulltext_1208 RP - IN FILE SP - 70-81 ST - The association of the risk of tuberculous infection with age T2 - Bull.Int.Union Tuberc. TI - The association of the risk of tuberculous infection with age VL - 50 ID - 2294 ER - TY - JOUR AU - Waaler, H. AU - Galtung, O. AU - Mordal, K. DA - 1975 J2 - Bull.Int.Union Tuberc. KW - epidemiology Europe infection models Norway research risk of infection surveillance tuberculin tuberculin testing tuberculosis LB - 4517 N1 - TY - JOUR TB Transmission, pathogenesis, and epidemiology Infection with tubercle bacilli Predict epi: risk of infection Risk of infection - models L1 - file://C:\literature_pdf\rm04517.pdf PY - 1975 RN - fulltext fulltext_1208 RP - IN FILE SP - 5-61 ST - The risk of tuberculous infection in Norway. Tuberculosis Surveillance Research Unitn Report No. 3 TI - The risk of tuberculous infection in Norway. Tuberculosis Surveillance Research Unitn Report No. 3 VL - 50 ID - 2295 ER - TY - JOUR AB - Decisions about delivery programs to improve health status are characterized by indivisibilities or "lumpiness," interdependencies between case types with varying health output, high fixed costs, administrative constraints, and qualitative quity and political considerations. The nature of the constraints and the goal of health services strongly suggest a mathematical programming model to maximize a comprehensive measure of health status. In a previously unreported development, binary integer programming can be extended to consider shared fixed costs, a widespread problem in optimizing effectiveness measures such as health status. The model proposed here applies conceptually across all target populations and health programs and could be used to optimize the output of a total health system. The effects of such optimization would be appropriately reflected in the weighted life expectancy computed as a social indicator. AN - 135728 AU - Chen, M. M. AU - Bush, J. W. DA - Sep DP - Nlm ET - 09/01 KW - Cost-Benefit Analysis Health Services Humans Mass Screening Models, Theoretical Phenylketonurias/prevention & control Systems Analysis Tuberculin Test Tuberculosis/prevention & control LA - eng N1 - Chen, M M Bush, J W United states Inquiry : a journal of medical care organization, provision and financing Inquiry. 1976 Sep;13(3):215-27. PY - 1976 RN - fulltext fulltext_1208 SN - 0046-9580 (Print) 0046-9580 (Linking) SP - 215-27 ST - Maximizing health system output with political and administrative constraints using mathematical programming T2 - Inquiry TI - Maximizing health system output with political and administrative constraints using mathematical programming VL - 13 ID - 2296 ER - TY - JOUR AN - 13026 AU - Rajalalkshmi, R. AU - Nair, S. S. KW - culture diagnosis incremental yield laboratory microscopy models specimen collection sputum tuberculosis yield N1 - TB Diagnosis of tuberculosis Laboratory diagnosis Specimen collection, transport and decontamination Specimen - collection PY - 1976 RN - fulltext fulltext_1208 SP - 118-121 ST - Estimation of number of repeat examinations required to detect all tuberculosis cases in the community T2 - Indian J.Pub.Hlth. TI - Estimation of number of repeat examinations required to detect all tuberculosis cases in the community UR - file://C:\literature_pdf\rm13026.pdf VL - 20 ID - 2297 ER - TY - JOUR AU - Sutherland, I. J2 - Advances in Tuberculosis Research KW - epidemiology models risk of infection tubercle tuberculosis LB - 296 N1 - TY - JOUR TB Transmission, pathogenesis, and epidemiology Infection with tubercle bacilli Etiol epi: risk of infection Risk of infection - models L1 - file://C:\literature_pdf\rm00296.pdf PY - 1976 RN - fulltext fulltext_1208 RP - IN FILE SP - 1-63 ST - Recent studies in the epidemiology of tuberculosis, based on the risk of being infected with tubercle bacilli T2 - Advances in Tuberculosis Research TI - Recent studies in the epidemiology of tuberculosis, based on the risk of being infected with tubercle bacilli VL - 19 ID - 2298 ER - TY - JOUR AN - 1030279 AU - Sutherland, I. AU - Svandova, E. AU - Radhakrishna, S. ET - 01/01 J2 - Bulletin of the International Union against Tuberculosis KW - Adolescent Adult Female Humans Male Middle Aged *Models, Biological Recurrence Risk *Tuberculosis, Pulmonary LA - eng N1 - Sutherland, I Svandova, E Radhakrishna, S FRANCE Bull Int Union Tuberc. 1976;51(1):171-9. PY - 1976 RN - fulltext fulltext_1208 SN - 0074-9249 (Print) 0074-9249 (Linking) SP - 171-9 ST - Alternative models for the development of tuberculosis disease following infection with tubercle bacilli T2 - Bull Int Union Tuberc TI - Alternative models for the development of tuberculosis disease following infection with tubercle bacilli UR - http://www.ncbi.nlm.nih.gov/pubmed/1030279 VL - 51 ID - 2299 ER - TY - JOUR AN - 615153 AU - Nair, S. S. DA - Jul-Sep ET - 07/01 KW - *BCG Vaccine Humans *Models, Theoretical Time Factors Tuberculosis/*prevention & control LA - eng N1 - Nair, S S Comparative Study India Indian journal of public health Indian J Public Health. 1977 Jul-Sep;21(3):111-31. PY - 1977 RN - fulltext fulltext_1208 SN - 0019-557X (Print) 0019-557X (Linking) SP - 111-131 ST - A simple model for planning and assessment of programmes for tuberculosis control T2 - Indian Journal of Public Health TI - A simple model for planning and assessment of programmes for tuberculosis control UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=615153file://C:\literature_pdf\rm00731.pdf VL - 21 ID - 2300 ER - TY - BILL AN - 752918 DA - Dec 1 KW - Costs and Cost Analysis Tuberculosis: Pulmonary Brazil Humans Mathematics Models: Theoretical Socioeconomic Factors LB - p31842 M1 - 4 PY - 1978 RN - fulltext fulltext_1208 SP - 455-70 ST - [Application of a mathematical model for choosing the best combination of instruments for the detection and treatment of pulmonary tuberculosis] T2 - Rev Saude Publica TI - [Application of a mathematical model for choosing the best combination of instruments for the detection and treatment of pulmonary tuberculosis] UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=752918 VL - 12 ID - 6484 ER - TY - JOUR AU - Stevens, R. G. AU - Lee, J. A. H. DA - 1978 J2 - Am.J.Epidemiol. KW - Americas chemotherapy cohort epidemiology models mortality tuberculosis USA LB - 1249 N1 - TY - JOUR TB Transmission, pathogenesis, and epidemiology Tuberculosis deaths Descript epi: mortality Mortality - cohort studies PY - 1978 RN - fulltext fulltext_1208 SP - 120-126 ST - Tuberculosis: generation effects and chemotherapy TI - Tuberculosis: generation effects and chemotherapy VL - 107 ID - 2302 ER - TY - JOUR AU - Sivaraman, V. AU - Umasankar, V. PY - 1979 RN - fulltext fulltext_1208 SP - 4-10 ST - A simulation model of tuberculosis epidemiology adaptability to Indian conditions T2 - Ind. J. Tub. TI - A simulation model of tuberculosis epidemiology adaptability to Indian conditions UR - Print out in Chris's box VL - 26 ID - 2303 ER - TY - JOUR AB - This study illustrates how cost-effectiveness calculations provide help in decisions involving a choice between introduction of a new diagnostic procedure or a new therapy for a particular clinical problem. This type of problem is critical for areas where financial resources are limiting. Our analysis is centered on the value of diagnosis and treatment in tuberculous meningitis (Tbm) and, because of its importance to developing countries, our epidemiologic data were derived from India. When financial costs are ignored, the introduction of second line therapy (e.g., Rifampin) leads to more cures than does the introduction of even a perfect diagnostic test. However, diagnostic tests (e.g., the Bromide partition test or possibly radioassays) markedly improve case finding and to some extent increase cure rates. All affects vary markedly with the prevalence of tuberculous meningitis in the population under study. For example, net financial savings would occur were a perfect nuclear test available and conventional therapy used at a prevalence of Tbm of 30% whereas there would be a net loss if the prevalence rose to 80%. This study underscores the need for detailed studies on the radiobromide partition test and for the development of new diagnostic tests, perhaps a radioimmunoassay of either the acid fast bacillus or of an antibody to it. AN - 6771138 AU - McNeil, B. J. AU - Thompson, M. AU - Adelstein, S. J. DA - Jun DP - Nlm ET - 06/01 J2 - European journal of nuclear medicine KW - Antitubercular Agents/administration & dosage/therapeutic use Bromine/diagnostic use Cost-Benefit Analysis Decision Theory Developing Countries Humans India Length of Stay Radioisotopes/diagnostic use Tuberculosis, Meningeal/diagnosis/drug therapy/ economics LA - eng N1 - McNeil, B J Thompson, M Adelstein, S J Research Support, U.S. Gov't, P.H.S. Germany, west Eur J Nucl Med. 1980 Jun;5(3):271-6. PY - 1980 RN - fulltext fulltext_1208 SN - 0340-6997 (Print) 0340-6997 (Linking) SP - 271-6 ST - Cost effectiveness calculations for the diagnosis and treatment of tuberculous meningitis T2 - Eur J Nucl Med TI - Cost effectiveness calculations for the diagnosis and treatment of tuberculous meningitis VL - 5 ID - 2304 ER - TY - JOUR AB - An epidemiological model was used to estimate the size of the tuberculosis problem in Singapore from 1975 to 2025. It was shown that even without any control activities after 1979 there would be a reduction of the tuberculosis indices in the country. If the present control programme was pursued unchanged, a reduction of the tuberculosis problem by 10.0% and 14.5% would be expected in 2000 and 2025 respectively. Tuberculosis would be expected to remain a major public health problem over the next fifty years. In Singapore's context increased case finding and treatment of bacteriologically positive cases of tuberculosis would be the most effective ways of further reducing the tuberculosis problem over the next fifty years. Practical methods of implementing this were suggested. Reduced BCG coverage of infants was not expected to increase the tuberculosis problem to any significant extent over this period. Treatment relapse rates were shown not to be a sensitive variable that would affect the tuberculosis problem in Singapore. AN - 7283384 AU - Goh, E. H. AU - Fam, K. L. DA - Jan IS - 1 KW - Adolescent Adult *BCG Vaccine Child Child, Preschool *Forecasting Humans Immunization Schedule Infant Infant, Newborn Models, Biological Singapore Tuberculosis/*epidemiology/prevention & control N1 - Goh, E H Fam, K L eng Singapore 1981/01/01 Ann Acad Med Singapore. 1981 Jan;10(1):40-9. PY - 1981 SN - 0304-4602 (Print) 0304-4602 (Linking) SP - 40-9 ST - A dynamic model of tuberculosis epidemiology for Singapore T2 - Ann Acad Med Singapore TI - A dynamic model of tuberculosis epidemiology for Singapore UR - https://www.ncbi.nlm.nih.gov/pubmed/7283384 VL - 10 ID - 2704 ER - TY - BILL AN - 6803059 DA - Feb 15 KW - Adult Mass Screening Middle Aged Humans Mathematics Tuberculosis Adolescent Cost-Benefit Analysis Models: Theoretical Male Female Japan LB - p31832 M1 - 2 PY - 1982 RN - fulltext fulltext_1208 SP - 47-57 ST - [Use of a mathematical model for evaluation of tuberculosis case-finding with mass miniature radiography (author's transl)] T2 - Kekkaku TI - [Use of a mathematical model for evaluation of tuberculosis case-finding with mass miniature radiography (author's transl)] UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=6803059 VL - 57 ID - 2306 ER - TY - JOUR AU - Collins, J. J. DA - 1982 KW - cohort epidemiology Europe Great Britain medical models mortality tuberculosis LB - 1253 N1 - TY - JOUR TB Transmission, pathogenesis, and epidemiology Tuberculosis deaths Descript epi: mortality Mortality - cohort studies PY - 1982 RN - fulltext fulltext_1208 SP - 409-427 ST - The contribution of medical measures to the decline of mortality from respiratory tuberculosis: an age-period-cohort model T2 - Demography TI - The contribution of medical measures to the decline of mortality from respiratory tuberculosis: an age-period-cohort model VL - 19 ID - 2305 ER - TY - JOUR AB - Information on the risk of tuberculous infection in the Netherlands has been linked with information on the incidence of tuberculosis, in an attempt to estimate the risks of developing the disease following infection or reinfection. It was postulated that: (a) those with a recent primary infection had a characteristic risk of developing progressive primary tuberculosis; (b) those with a distant (i.e. not recent) primary infection and a recent reinfection had a characteristic risk of developing exogenous tuberculosis; and (c) those with a distant primary infection but no recent reinfection had a characteristic risk of developing endogenous tuberculosis. The information on the risk of tuberculous infection was used to estimate the size of the population in each of these infection classes for different age-groups and calendar years in the Netherlands. Using multiple regression to link these population figures with the information on tuberculosis incidence in the same age group and calendar year, it was possible to estimate the above risks of developing tuberculosis. For Netherlands males aged 15-69 years during the period 1951-70 the three risks of developing pulmonary tuberculosis were estimated to be: (a) 5.06 per cent annually (for 5 years) following primary infection; (b) 1.91 per cent annually (for 5 years) following reinfection; (c) 0.0253 per cent annually, after the first 5 years following primary infection, in the absence of reinfection. The corresponding (and significantly different) estimated annual risks of development of pulmonary tuberculosis for females were 5.85, 1.10 and 0.0020 per cent respectively. From these risks, it may be estimated that the degree of protection conferred by a distant primary infection, against pulmonary tuberculosis arising from a recent reinfection, was 63 per cent for males and 81 per cent for females. The estimated relative proportions of cases of progressive primary, exogenous and endogenous tuberculosis varied considerably with age and calendar year. Progressive primary tuberculosis was dominant at the younger ages, exogenous and endogenous tuberculosis at older ages. At these older ages, the great majority of cases in the Netherlands in the early 1950s appeared to be exogenous in origin, but by 1970, with the decrease in the risk of infection, the exogenous contribution had dwindled substantially, especially among males. AN - 6763793 AU - Sutherland, I. AU - Svandova, E. AU - Radhakrishna, S. DA - Dec ET - 12/01 J2 - Tubercle KW - Adolescent Adult Age Factors Aged Epidemiologic Methods Female History, 18th Century History, 20th Century Humans Male Middle Aged *Models, Biological Netherlands Recurrence Risk Sex Factors Tuberculosis, Pulmonary/*epidemiology/etiology/history LA - eng M3 - Historical Article N1 - Sutherland, I Svandova, E Radhakrishna, S SCOTLAND Tubercle. 1982 Dec;63(4):255-68. PY - 1982 RN - fulltext fulltext_1208 SN - 0041-3879 (Print) 0041-3879 (Linking) SP - 255-68 ST - The development of clinical tuberculosis following infection with tubercle bacilli. 1. A theoretical model for the development of clinical tuberculosis following infection, linking from data on the risk of tuberculous infection and the incidence of clinical tuberculosis in the Netherlands T2 - Tubercle TI - The development of clinical tuberculosis following infection with tubercle bacilli. 1. A theoretical model for the development of clinical tuberculosis following infection, linking from data on the risk of tuberculous infection and the incidence of clinical tuberculosis in the Netherlands UR - http://www.ncbi.nlm.nih.gov/pubmed/6763793http://ac.els-cdn.com/S0041387982800135/1-s2.0-S0041387982800135-main.pdf?_tid=5a366d31da488d96f9d9423663709bf6&acdnat=1345013641_fafdd63c26ae10575d849ec75af0d748 VL - 63 ID - 2307 ER - TY - BILL AB - Simulation and predictive models of tb epidemiological trends in the Czech Socialist Republic (CSR) for the 1949-2000 period were devised taking into account several variants of tb control measures. AZUMA'S simulation model from Japan was used as the basis for the mathematical processing and adapted in different parts to satisfy the conditions prevailing in the CSR. The initial conditions and parameters to go into the equations of the model were determined or estimated from statistical data for the whole of CSR or from the results of some of the more detailed partial studies. An Olivetti P 6060 minicomputer was used for calculations. Statistical data were found in satisfactory agreement with trends estimated from model simulations. The simulation models revealed that the epidemiological trends were most influenced by the treatment, less by the BCG vaccination and the least by the active case finding. As suggested by the predictive simulations, discontinuation of the programme of tb control would result in a major deterioration of the epidemiological situation. AN - 6858243 DA - Jan 1 KW - Humans Tuberculosis: Pulmonary BCG Vaccine Mathematics Models: Theoretical Male Czechoslovakia Female LB - p31837 M1 - 2 PY - 1983 RN - fulltext fulltext_1208 SP - 148-56 ST - [Measuring the effectiveness of different variants of tuberculosis control using simulation models] T2 - Z Erkr Atmungsorgane TI - [Measuring the effectiveness of different variants of tuberculosis control using simulation models] UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=6858243 VL - 160 ID - 2308 ER - TY - JOUR AN - 2504 AU - Snider, D. E., Jr. AU - Caras, G. J. AU - Koplan, J. P. KW - cost effectiveness isoniazid preventive therapy tuberculosis N1 - IN FILE TB Intervention strategies Preventive chemotherapy No sub-heading PY - 1986 RN - fulltext fulltext_1208 SP - 1579-1583 ST - Preventive therapy with isoniazid. Cost-effectiveness of different durations of therapy T2 - JAMA TI - Preventive therapy with isoniazid. Cost-effectiveness of different durations of therapy UR - file://C:\literature_pdf\rm02504.pdf VL - 255 ID - 2309 ER - TY - JOUR AB - An analysis is carried out on pulmonary tuberculosis survey data from Taiwan and Korea. A mathematical model based on a Markov process is developed and used to estimate transition rates between various disease states, as well as certain 'infection parameters', which measure the strength of the relative contributions of different disease states and of endogenous reactivation to the incidence of tuberculosis in the population. It is found that endogenous reactivation plays a primary role in generating cases, followed by chronic sources of infection, particularly those with drug-sensitive organisms. Some recommendations are made with regard to optimizing treatment regimens. The methodology can easily be applied to other countries. AD - Department of Medicine, University of British Columbia, Vancouver, Canada. AN - 3440669 AU - Schulzer, M. AU - Enarson, D. A. AU - Grzybowski, S. AU - Hong, Y. P. AU - Kim, S. J. AU - Lin, T. P. DA - Dec DP - Nlm ET - 12/01 KW - Adult Aged Epidemiologic Methods Humans Korea Middle Aged Models, Theoretical Probability Random Allocation Recurrence Taiwan Tuberculosis, Pulmonary/classification/ epidemiology LA - eng N1 - Schulzer, M Enarson, D A Grzybowski, S Hong, Y P Kim, S J Lin, T P Research Support, Non-U.S. Gov't England International journal of epidemiology Int J Epidemiol. 1987 Dec;16(4):584-9. PY - 1987 RN - fulltext fulltext_1208 SN - 0300-5771 (Print) 0300-5771 (Linking) SP - 584-9 ST - An analysis of pulmonary tuberculosis data in Taiwan and Korea T2 - Int J Epidemiol TI - An analysis of pulmonary tuberculosis data in Taiwan and Korea UR - http://ije.oxfordjournals.org.ez.lshtm.ac.uk/content/16/4/584.full.pdf VL - 16 ID - 2310 ER - TY - JOUR AB - In this paper, a simplified model describing the stochastic process underlying the etiology of contagious and noncontagious diseases with mass screening is developed. Typical examples might include screening of tuberculosis in urban ghetto areas, venereal diseases in the sexually active, or AIDS in high risk population groups. The model is addressed to diseases which have zero or negligible latent periods. In the model, it is assumed that the reliabilities of the screening tests are constant, and independent of how long the population unit has the disease. Both tests with perfect and imperfect reliabilities are considered. It is shown that most of the results of a 1978 study by W.P. Pierskalla and J.A. Voelker for noncontagious diseases can be generalized for contagious diseases. A mathematical program for computing the optimal test choice and screening periods is presented. It is shown that the optimal screening schedule is equally spaced for tests with perfect reliability. Other properties relating to the managerial problems of screening frequencies, test selection, and resource allocation are also presented. AN - 10303164 AU - Lee, H. L. AU - Pierskalla, W. P. DA - Nov-Dec DP - Nlm ET - 10/06 KW - Communicable Diseases/ etiology/transmission Health Resources Health Services Research Mass Screening/ organization & administration Models, Statistical LA - eng N1 - Lee, H L Pierskalla, W P Research Support, U.S. Gov't, Non-P.H.S. Review United states Operations research Oper Res. 1988 Nov-Dec;36(6):917-28. PY - 1988 RN - fulltext fulltext_1208 SN - 0030-364X (Print) 0030-364X (Linking) SP - 917-28 ST - Mass screening models for contagious diseases with no latent period T2 - Oper Res TI - Mass screening models for contagious diseases with no latent period VL - 36 ID - 2311 ER - TY - JOUR AB - This study illustrates the use of disease modeling and simulation techniques to the study of the spread of disease within and between social networks. A Reed-Frost type model of disease spread is used to construct a simulation of the spread of tuberculosis within three prehistoric populations of the Lower Illinois River Valley during Middle Woodland, Late Woodland, and Mississippian times. A high and low population size was modeled for each time period. Late Woodland model 2 (low population estimate) is the only model that experienced pathogen extinction with host survival. The rest of the models experienced rapid and severe host population decline. The results of the simulation suggest that a social network size of between 180 and 440 persons is required under the conditions of this model for host-pathogen coexistence (i.e., endemicity) to occur. The severe population decline experienced by these populations suggests that tuberculosis as modeled here could not have existed in these populations. Future refinements of modeling and simulation techniques can provide additional insights into how disease spreads among social contacts. AD - Department of Anthropology, Case Western Reserve University, Cleveland, Ohio 44106. AN - 3066224 AU - McGrath, J. W. DA - Dec DO - 10.1002/ajpa.1330770409 [doi] DP - Nlm ET - 12/01 KW - History, Ancient History, Medieval Humans Illinois Models, Biological Social Environment Tuberculosis/history/ transmission LA - eng N1 - McGrath, J W Historical Article United states American journal of physical anthropology Am J Phys Anthropol. 1988 Dec;77(4):483-96. PY - 1988 RN - fulltext fulltext_1208 SN - 0002-9483 (Print) 0002-9483 (Linking) SP - 483-96 ST - Social networks of disease spread in the lower Illinois valley: a simulation approach T2 - Am J Phys Anthropol TI - Social networks of disease spread in the lower Illinois valley: a simulation approach UR - http://onlinelibrary.wiley.com/doi/10.1002/ajpa.1330770409/abstract VL - 77 ID - 2312 ER - TY - JOUR AB - Isoniazid chemoprophylaxis is not recommended for all persons infected with tubercle bacilli. Because of the small but significant risk of isoniazid hepatotoxicity, chemoprophylaxis is reserved for only those at the highest risk of tuberculosis activation. To evaluate this policy, we performed a cost-effectiveness analysis of isoniazid chemoprophylaxis for two populations with positive tuberculin skin tests: recent tuberculin converters, who are at high risk for activation, and older tuberculin reactors, who have a low risk for activation and for whom chemoprophylaxis is not now recommended. The cost-effectiveness ratios found were stable, despite wide variations in model assumptions and probability estimates. For high-risk tuberculin reactors, chemoprophylaxis resulted in net medical care monetary savings, extended life expectancy, and fewer fatal illnesses. For low-risk tuberculin reactors, chemoprophylaxis resulted in positive, but small, health effects. Because the cost to gain these positive effects were also small, the resulting cost-effectiveness ratios were reasonable and in the realm of accepted prevention strategies: $12,625 to gain one year of life and $35,011 to avert one death. These findings suggest that the current policy is too restrictive and that many in the large population of low-risk tuberculin reactors should be considered for isoniazid chemoprophylaxis. AD - Department of Community Medicine, Mount Sinai School of Medicine, New York, NY 10029. AN - 3134928 AU - Rose, D. N. AU - Schechter, C. B. AU - Fahs, M. C. AU - Silver, A. L. DA - Mar-Apr ET - 03/01 KW - Adult Age Factors Cost-Benefit Analysis Drug-Induced Liver Injury/etiology/mortality Humans Isoniazid/adverse effects/*therapeutic use Life Expectancy Male Middle Aged Risk Factors Tuberculin Test Tuberculosis/diagnosis/mortality/*prevention & control LA - eng N1 - Rose, D N Schechter, C B Fahs, M C Silver, A L United states American journal of preventive medicine Am J Prev Med. 1988 Mar-Apr;4(2):102-9. PY - 1988 RN - fulltext fulltext_1208 SN - 0749-3797 (Print) 0749-3797 (Linking) SP - 102-9 ST - Tuberculosis prevention: cost-effectiveness analysis of isoniazid chemoprophylaxis T2 - Am J Prev Med TI - Tuberculosis prevention: cost-effectiveness analysis of isoniazid chemoprophylaxis UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3134928 VL - 4 ID - 2313 ER - TY - JOUR AB - The epidemiological model Eskimo has been utilized to simulate some epidemiological parameters relative to tuberculosis in a restricted geographical area of northern Italy. After having identified a series of features relative to the regimens applied in the area in the period 1982-86 and which were found to be compatible with the observed data, this hypothesis has been utilized to project data on tuberculosis for the period 1986-1996. The results have indicated that the incidence in the area should stabilize around values of 20 new cases per year (per 100,000 population). A decrease in the incidence can be expected to occur only if the regimens so far employed are brought to a greater part of the patients' population (increasing coverage). The effects of importing the disease from developing countries through immigration and of the AIDS epidemic are likely to negatively affect the trend of tuberculosis incidence in the future. AN - 2488908 AU - Acocella, G. AU - Comaschi, E. AU - Nonis, A. AU - Rossanigo, C. AU - Migliori, G. B. DA - Jan-Dec DP - Nlm ET - 01/01 KW - Cohort Studies Computer Simulation Emigration and Immigration Forecasting Humans Italy/epidemiology Models, Theoretical Retrospective Studies Tuberculosis/ epidemiology LA - eng N1 - Acocella, G Comaschi, E Nonis, A Rossanigo, C Migliori, G B Italy Giornale italiano di chemioterapia G Ital Chemioter. 1989 Jan-Dec;36(1-3):11-6. PY - 1989 RN - fulltext fulltext_1208 SN - 0017-0445 (Print) 0017-0445 (Linking) SP - 11-6 ST - Past, present and future trends in tuberculosis epidemiology in a region of northern Italy. An analysis carried out through the application of a simulation model (Eskimo) T2 - G Ital Chemioter TI - Past, present and future trends in tuberculosis epidemiology in a region of northern Italy. An analysis carried out through the application of a simulation model (Eskimo) VL - 36 ID - 2314 ER - TY - JOUR AB - An epidemiological model of tuberculosis, based on the natural history of tuberculosis and the control programmes in Indonesia, was constructed. This model was used for estimating future tuberculosis-prevented cases and costs for three treatment strategies--the 100% standard course, the 100% short course, and the existing strategy (a combination of 65% standard course and 35% short course)--in accordance with the master plan of the Indonesian Government's tuberculosis control programme. A cost-effectiveness analysis of the three strategies confirmed that the short-course strategy was the most cost-effective. Sensitivity analysis, which applied a broad range of parameters, continued to confirm the short-course strategy as the most cost-effective. If the short-course strategy had been applied in 1980 instead of the existing strategy (using the most likely parameters), the short-course strategy would prevent 1.8 million sputum-positive cases and would save 61.0 million dollars by the year 2000. AD - Division of Chronic Disease Control, Centers for Disease Control, Atlanta, Georgia 30333. AN - 2498217 AU - Joesoef, M. R. AU - Remington, P. L. AU - Jiptoherijanto, P. T. DA - Mar ET - 03/01 J2 - International journal of epidemiology KW - Antitubercular Agents/*administration & dosage Cost-Benefit Analysis Drug Therapy, Combination Humans Indonesia Models, Theoretical National Health Programs/*economics Sensitivity and Specificity Tuberculosis, Pulmonary/*drug therapy/economics/epidemiology LA - eng M3 - Research Support, Non-U.S. Gov't N1 - Joesoef, M R Remington, P L Jiptoherijanto, P T ENGLAND Int J Epidemiol. 1989 Mar;18(1):174-9. PY - 1989 RN - fulltext fulltext_1208 SN - 0300-5771 (Print) 0300-5771 (Linking) SP - 174-9 ST - Epidemiological model and cost-effectiveness analysis of tuberculosis treatment programmes in Indonesia T2 - Int J Epidemiol TI - Epidemiological model and cost-effectiveness analysis of tuberculosis treatment programmes in Indonesia UR - http://www.ncbi.nlm.nih.gov/pubmed/2498217http://ije.oxfordjournals.org.ez.lshtm.ac.uk/content/18/1/174.full.pdf VL - 18 ID - 2315 ER - TY - JOUR AB - The role of isoniazid prophylaxis in low-risk patients with positive Mantoux skin tests has recently been questioned. In general, recent research has focused on the risk/benefit ratio. We, therefore, decided to extend these data and apply a cost-effectiveness analysis of the routine use of isoniazid prophylaxis from a societal perspective. Costs per case prevented were calculated for a 20-, 50-, and 70-yr-old low-risk patient who had a positive Mantoux test with base, high, and low costings. Rates were also calculated based on the use of direct costs alone and direct and indirect costs combined. Costs varied from Canadian $8,586.00 in a 20-yr-old patient to $40,102.00 in a 70-yr-old patient per case prevented based on direct costs with costs ranging from $3,236.00 to $11,320.00 with both direct and indirect costs included. These costs could be considered reasonable from a societal perspective but do not address the issue of any increased life expectancy resulting from chemoprophylaxis. AD - Department of Medicine, McMaster University, Hamilton, Ontario, Canada. AN - 2121080 AU - Fitzgerald, J. M. AU - Gafni, A. DA - Oct DP - Nlm ET - 10/01 J2 - The American review of respiratory disease KW - Adolescent Adult Aged Canada Child Cost-Benefit Analysis Humans Isoniazid/adverse effects/ therapeutic use Middle Aged Tuberculin Test Tuberculosis, Pulmonary/diagnosis/ economics/prevention & control LA - eng N1 - Fitzgerald, J M Gafni, A United states Am Rev Respir Dis. 1990 Oct;142(4):848-53. PY - 1990 RN - fulltext fulltext_1208 SN - 0003-0805 (Print) 0003-0805 (Linking) SP - 848-53 ST - A cost-effectiveness analysis of the routine use of isoniazid prophylaxis in patients with a positive Mantoux skin test T2 - Am Rev Respir Dis TI - A cost-effectiveness analysis of the routine use of isoniazid prophylaxis in patients with a positive Mantoux skin test VL - 142 ID - 2316 ER - TY - JOUR AB - The progression of HIV-related disease from infection to death is represented as a staged Markov model. Transitions between stages are considered reversible. The model is fitted to data from a cohort of African prostitutes by means of maximum likelihood. It appears that the progression to symptomatic disease (Centers for Disease Control stage IV) in this population is considerably more rapid than that reported from studies in Western countries. AD - Kenya Medical Research Institute, Nairobi. AN - 2175619 AU - Nagelkerke, N. J. AU - Plummer, F. A. AU - Holton, D. AU - Anzala, A. O. AU - Manji, F. AU - Ngugi, E. N. AU - Moses, S. DA - Aug DP - Nlm ET - 08/01 KW - Acquired Immunodeficiency Syndrome/classification/ epidemiology/transmission Centers for Disease Control and Prevention (U.S.) Cohort Studies Female Humans Kenya/epidemiology Markov Chains Models, Biological Prostitution Socioeconomic Factors Tanzania/ethnology United States/epidemiology individual prognoses, for developing and testing intervention strategies, for determining the reproductive rate of the disease, and for prevalence of the disease. Mathematical modeling of HIV infection in Africa is necessitated because the disease is more widespread and the immune system is constantly active due to the exposure to diseases such as malaria and tuberculosis. The Markov model for this analysis was selected because parametric estimation is not based on the time a stage is entered, but on the duration between observations and the stages at the time of observation. The HIV infected female prostitutes in the Pumwani area of Nairobi, Kenya (a population primarily of Tanzanian origin) have been identified as a study population since 1985, and seen every 6 months in clinic, or as needed. Data are constricted by the movement out of the area in the end stage of disease, which is only partially solved by tracking with community health workers. The stages identified in incubation estimation are stage 1: seropositive but symptom free (CDC stage II) stage 2: generalized lymphadenopathy (CDC stage III) stage 3: symptomatic disease (CDC stage IV) and stage 4: death. Data reflect the movement back and forth between stage 1 and 2, between 2 and 3, so the model is not a pure Longini model but rather a timed homogeneous staged model with reversible stages called transition parameters computed in a numerical differentiation. The Fortran computer program for the analyses is available from the authors. The results suggest a quick transition between seroconversion and lymphadenopathy (2.4 months) and unlikely reversal, with the mean waiting time until passage to stage 3 is approximately 2.6 years and conversions are common. Since opportunistic infections are treatable, this makes sense. Assuming a correct model, the estimation of the transition time of 20 months of h34 value of .01 and .05, the mean passage time from stage 1, 2, 3 to 4 (death) is 9.1, 8.9, and 6.2 years 12.9, 12.7, and 10.1 years respectively. The implications are that 1) when infectiousness is hypothesized to be not uniform, peak infectivity occurs earlier in Africa than in the West at least among prostitutes, or 2) if infectivity is constant throughout the incubation period, then HIV transmission must be higher in Africa to explain the high rate of infection. LA - eng N1 - Nagelkerke, N J Plummer, F A Holton, D Anzala, A O Manji, F Ngugi, E N Moses, S Research Support, Non-U.S. Gov't United states AIDS (London, England) AIDS. 1990 Aug;4(8):743-7. PY - 1990 RN - fulltext fulltext_1208 excl_noTB SN - 0269-9370 (Print) 0269-9370 (Linking) SP - 743-7 ST - Transition dynamics of HIV disease in a cohort of African prostitutes: a Markov model approach T2 - AIDS TI - Transition dynamics of HIV disease in a cohort of African prostitutes: a Markov model approach VL - 4 ID - 2317 ER - TY - JOUR AD - CASE WESTERN RESERVE UNIV,METROHLTH MED CTR,CLEVELAND,OH 44106. AN - WOS:A1991GJ22700072 AU - Suen, J. S. AU - Cebul, R. D. AU - Speroff, T. AU - Daniel, T. M. DA - Oct-Dec IS - 4 J2 - Med. Decis. Mak. KW - Health Care Sciences & Services Medical Informatics LA - English M3 - Meeting Abstract N1 - ISI Document Delivery No.: GJ227 Times Cited: 0 Cited Reference Count: 0 Suen, js cebul, rd speroff, t daniel, tm 0 Hanley & belfus inc Philadelphia PY - 1991 SN - 0272-989X SP - 331-331 ST - MODELING TUBERCULOSIS AND THE EFFECTIVENESS OF ALTERNATIVE CONTROL STRATEGIES IN AN HIV-PREVALENT POPULATION T2 - Medical Decision Making TI - MODELING TUBERCULOSIS AND THE EFFECTIVENESS OF ALTERNATIVE CONTROL STRATEGIES IN AN HIV-PREVALENT POPULATION UR - ://WOS:A1991GJ22700072 VL - 11 ID - 6399 ER - TY - JOUR AN - 12954 AU - Balasangameshwara, V. H. AU - Chakraborty, A. K. AU - Chaudhuri, K. KW - Asia case-finding epidemiology India infection interventions models morbidity mortality tuberculosis N1 - IN FILE TB Transmission, pathogenesis, and epidemiology Tuberculosis Predict epi of morbidity: prospects for the epidemic PY - 1992 RN - fulltext fulltext_1208 SP - 87-98 ST - A mathematical construct of epidemiological time trend in tuberculosis - a fifty year study T2 - Indian J.Tuberc. TI - A mathematical construct of epidemiological time trend in tuberculosis - a fifty year study UR - file://C:\literature_pdf\rm12954.pdf VL - 39 ID - 2318 ER - TY - JOUR AB - OBJECTIVE: To study the impact of the HIV epidemic on tuberculosis (TB) incidence in developing countries. DESIGN: A simple mathematical model is constructed using figures from published reports to estimate the rise of TB incidence as the HIV epidemic expands. METHOD: Two groups with different risk of developing TB are identified: individuals with dual infection of HIV and Mycobacterium tuberculosis and the rest of the population. The model is based on a combination of the incidence and the percentage of TB in these two groups. The expected rise in TB incidence and the percentage of TB cases that will be HIV-positive are plotted against the prevalence of HIV. CONCLUSIONS: Unless appropriate action is taken, TB incidence in developing countries will double as the prevalence of HIV infection reaches 13 per hundred adults. AD - Spanish Red Cross, La Paz, Bolivia. AN - 1466853 AU - Bermejo, A. AU - Veeken, H. AU - Berra, A. DA - Oct DP - Nlm ET - 10/01 KW - Cohort Studies Developing Countries Forecasting HIV Infections/complications/ epidemiology Humans Models, Theoretical Tuberculosis/complications/ epidemiology HIV infection greatly increases the risk of developing active TB among those with latent Mycobacterium tuberculosis infection. Thus researchers have used data from existing research to develop a mathematical model to gauge the increase in TB incidence in developing countries while considering rising HIV prevalence among adults. They look at 2 groups with sizable differences in risk of acquiring TB: adults with both HIV and M. tuberculosis infections and all other adults. The researchers plot the expected increase in TB incidence and percentage of TB cases that also have HIV infection against HIV prevalence. According to the model, when the prevalence of HIV infection hits 13% of adults in developing countries, the number of new TB cases doubles. Most of this increase will occur in areas that already lack diagnostic services, drugs, hospital beds, and other needed supplies. TB chemoprophylaxis treatment of HIV-positive people could result in a lower increase in TB incidence, however. WHO has set a goal of 50% reduction in LA - eng N1 - Bermejo, A Veeken, H Berra, A Comparative Study United states AIDS (London, England) AIDS. 1992 Oct;6(10):1203-6. PY - 1992 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0269-9370 (Print) 0269-9370 (Linking) SP - 1203-6 ST - Tuberculosis incidence in developing countries with high prevalence of HIV infection T2 - AIDS TI - Tuberculosis incidence in developing countries with high prevalence of HIV infection VL - 6 ID - 2319 ER - TY - JOUR AB - Tuberculosis remains the leading cause of death in the world from a single infectious disease, although there is little knowledge of the mechanisms of its pathogenesis and protection from it. After a century of decline in the United States, tuberculosis is increasing, and strains resistant to multiple antibiotics have emerged. This excess of cases is attributable to changes in the social structure in cities, the human immunodeficiency virus epidemic, and a failure in certain major cities to improve public treatment programs. The economic costs of not adequately addressing the problem of tuberculosis in this country are estimated from an epidemiological model. AD - Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461. AN - 1509256 AU - Bloom, B. R. AU - Murray, C. J. DA - Aug 21 ET - 08/21 J2 - Science KW - Acquired Immunodeficiency Syndrome/complications Animals Antibiotics, Antitubercular/pharmacology/therapeutic use Drug Resistance, Microbial History, 17th Century History, 19th Century History, 20th Century History, Ancient Humans Mycobacterium tuberculosis/drug effects Tuberculosis/complications/drug therapy/*epidemiology/transmission United States/epidemiology L1 - internal-pdf://2568331268/Bloom-1992-Tuberculosis_ commentary on a reeme.pdf LA - eng M3 - Historical Article Research Support, Non-U.S. Gov't Review N1 - Bloom, B R Murray, C J New York, N.Y. Science. 1992 Aug 21;257(5073):1055-64. PY - 1992 RN - fulltext fulltext_1208 SN - 0036-8075 (Print) 0036-8075 (Linking) SP - 1055-64 ST - Tuberculosis: commentary on a reemergent killer T2 - Science TI - Tuberculosis: commentary on a reemergent killer UR - http://www.ncbi.nlm.nih.gov/pubmed/1509256 http://science.sciencemag.org/content/sci/257/5073/1055.full.pdf VL - 257 ID - 2320 ER - TY - JOUR AB - The impact of the human immunodeficiency virus (HIV) on tuberculosis is well documented. Its effect in populations with a high proportion of dually infected individuals is likely to be significant. Sub-Saharan Africa is one such region and to better document the effect of HIV infection on tuberculosis there we developed a mathematical model to predict the likely extra numbers of tuberculosis cases due to it. A mathematical model was developed using a variety of scenarios giving a range of risks for the period 1980-2000. The four scenarios included (1) a low rate of 1% risk of tuberculosis infection in year 0 (1980) with 45% tuberculosis infection prevalence, and an HIV prevalence of 2% in 1989; (2) a 2% risk of tuberculosis infection in year 0 with 60% tuberculosis infection prevalence, and a 2% HIV prevalence in 1989; (3) a 2% risk of tuberculosis infection in year 0 with 60% tuberculosis infection prevalence, and a 10% HIV prevalence in 1989; and (4) a 2% risk of tuberculosis infection in year 0 with 60% tuberculosis infection prevalence and a 20% HIV prevalence in 1989. Under scenarios 1 and 2, a 50-60% increase in smear-positive rates in the subpopulation (15-45 years old) is predicted for the year 2000, under scenario 3, smear-positive rates in the subpopulation in the year 2000 are expected to increase four-fold from the 1980 baseline. Under scenario 4, a 10-fold increase in smear-positive rates in 2000 is expected in the subpopulation. Under this scenario, total disease will have increased 12-fold in the subpopulation.(ABSTRACT TRUNCATED AT 250 WORDS) AD - Department of Medicine, Vancouver General Hospital, British Columbia, Canada. AN - 1525378 AU - Schulzer, M. AU - Fitzgerald, J. M. AU - Enarson, D. A. AU - Grzybowski, S. DA - Feb DO - 0962-8479(92)90080-4 [pii] 10.1016/0962-8479(92)90080-4 [doi] DP - Nlm ET - 02/01 KW - Adolescent Adult Africa/epidemiology Child HIV Infections/ complications Humans Incidence Middle Aged Models, Biological Opportunistic Infections/complications/ epidemiology Prevalence Risk Factors Tuberculosis, Pulmonary/complications/ epidemiology well-documented. Its effect on populations with a high proportion of dually infected individuals is likely to be significant. Sub-Saharan Africa is one such region and in order to better document the effect of HIV infection on tuberculosis in that region, the authors developed a mathematical model to predict the likely extra numbers of tuberculosis due to it. A mathematical model was developed using a variety of scenarios which provided a range of risks for the 1980-2000 period. The 4 scenarios included: a low rate of 1% risk of tuberculosis infection in the year 0 (1980) with 45% tuberculosis infection prevalence and a HIV prevalence of 2% in 1989 a 2% risk of tuberculosis infection in year 0 with 60% tuberculosis infection prevalence and a 2% HIV prevalence in 1989 a 2% risk of tuberculosis infection in year 0 with 60% tuberculosis infection prevalence and a 10% HIV prevalence in 1989 and a 2% risk of tuberculosis infection in year 0 with 60% tuberculosis infection prevalence and a 20% HIV prevalence in 1989. In scenarios 1 and 2, a 50-60% increase in smear-positive rates in the subpopulation (ages 15-45 years old) is predicted for the year 2000 in scenario 3, smear-positive rates in the subpopulation in the year 2000 are expected to increase 4-fold from the 1980 baseline and in scenario 4, a 10-fold increase in smear-positive rates in the year 200 is expected in the subpopulation. Total disease will have increased 12-fold in the subpopulation in this scenario. These data suggest that there will be a dramatic increase in the number of tuberculosis cases due to HIV infection in sub-Saharan Africa which will likely strain the already fragile health care system in this region. (author's modified) LA - eng N1 - Schulzer, M Fitzgerald, J M Enarson, D A Grzybowski, S Scotland Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Tuber Lung Dis. 1992 Feb;73(1):52-8. PY - 1992 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0962-8479 (Print) 0962-8479 (Linking) SP - 52-8 ST - An estimate of the future size of the tuberculosis problem in sub-Saharan Africa resulting from HIV infection T2 - Tuber Lung Dis TI - An estimate of the future size of the tuberculosis problem in sub-Saharan Africa resulting from HIV infection UR - http://ac.els-cdn.com/0962847992900804/1-s2.0-0962847992900804-main.pdf?_tid=cffaa2ae794e91d787e584ec38b9d418&acdnat=1345013225_6e9459f9bf03fac6da11deacd622154e VL - 73 ID - 2321 ER - TY - JOUR AB - Concerns have been raised about whether the interaction between tuberculosis and human immunodeficiency virus (HIV) may lead worldwide to a recrudescent tuberculosis pandemic. These concerns are particularly grave in Africa which has a high prevalence of both tuberculosis and HIV. This study used a computer simulation model to examine the effect of tuberculosis-HIV interactions on tuberculosis prevalence and mortality in Africa. The model then assessed the impact of expanding treatment and chemoprophylaxis programmes on tuberculosis prevalence and mortality over the next decade. In communities where 20% of the population is infected with HIV and 25% receive treatment for tuberculosis, deaths from tuberculosis would be 100% higher than in communities where none of the population is HIV-infected. In a population the size of Uganda's, during one decade there would be approximately an additional 530,000 deaths from tuberculosis. When 50% of patients with active tuberculosis receive treatment, one death will be averted for every 2.5 people who receive treatment. The prevalence of active tuberculosis could be cut by over 90% in a decade by providing effective chemoprophylaxis to 30% of individuals with inactive TB. In conclusion, TB is only one example of a preventable and treatable infectious disease which can be spread through casual contact and which, because of its higher prevalence among the HIV positive population, may lead to a preventable increase in incidence of infection among the general population. AD - Department of Health Care Policy, Harvard Medical School, Boston, MA 02115. AN - 8249065 AU - Heymann, S. J. DA - Jul-Aug DP - Nlm ET - 07/01 KW - AIDS-Related Opportunistic Infections/drug therapy/epidemiology/ prevention & control Africa/epidemiology Computer Simulation Humans Models, Biological Prevalence Tuberculosis/drug therapy/epidemiology/ prevention & control LA - eng N1 - Heymann, S J Research Support, Non-U.S. Gov't England Transactions of the Royal Society of Tropical Medicine and Hygiene Trans R Soc Trop Med Hyg. 1993 Jul-Aug;87(4):406-11. PY - 1993 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0035-9203 (Print) 0035-9203 (Linking) SP - 406-11 ST - Modelling the efficacy of prophylactic and curative therapies for preventing the spread of tuberculosis in Africa T2 - Trans R Soc Trop Med Hyg TI - Modelling the efficacy of prophylactic and curative therapies for preventing the spread of tuberculosis in Africa UR - http://ac.els-cdn.com/003592039390014H/1-s2.0-003592039390014H-main.pdf?_tid=8ad90a4371d1c405a8a164c4f5f14d1d&acdnat=1345012470_496d33934a357930490bdffc26f770dd VL - 87 ID - 2322 ER - TY - JOUR AB - A deterministic model is proposed for the study of the dynamics of acquired immunodeficiency syndrome (AIDS) and tuberculosis (TB) co-infection. The model is comprised by a set of sixteen ordinary differential equations representing different states of both diseases, and it is intended to provide a theretical framework for the study of the interaction between both infections. Numerical simulations of the model resulted in three striking outcomes: first, the pathogenicity of Human Immunodeficiency Virus (HIV) is enhanced by the presence of TB, and vice-versa; second, the prevalence of AIDS is higher in the presence of TB; and third, relative risk analysis demonstrated a much stronger influence of AIDS on TB than the other way around. AU - Massad, Eduardo AU - Burattini, Marcelo Nascimento AU - Coutinho, Francisco Antonio Bezerra AU - Yang, Hyung Mo AU - Raimundo, Silvia Martorano DO - 10.1016/0895-7177(93)90013-O PY - 1993 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0895-7177 SP - 7-21 ST - Modeling the interaction between aids and tuberculosis T2 - Mathematical and Computer Modelling TI - Modeling the interaction between aids and tuberculosis UR - http://www.sciencedirect.com/science/article/pii/089571779390013O VL - 17 ID - 2323 ER - TY - JOUR AB - As a result of many interacting variables, including crowded shelters and limited access to health care, homeless persons are at high risk for tuberculosis. Using traditional approaches, control of tuberculosis in this population has been difficult. Decision analysis was used to investigate the cost-effectiveness of BCG (bacillus Calmette-Guerin) vaccination in persons attending homeless shelters. This vaccination was cost-effective over a wide range of assumptions. Using conservative assumptions, a vaccine that was at least 40 percent effective would result in a net cost savings. If the efficacy of the vaccine were 50 percent, $4,000 would be saved, 12 life-years gained, and 23 cases of active tuberculosis prevented for every 1,000 persons vaccinated. Further study of the BCG vaccine in homeless persons and other populations at risk is warranted. AD - Division of General Medicine, University of Iowa College of Medicine, Iowa City. AN - 8131444 AU - Nettleman, M. D. DA - Apr DP - Nlm ET - 04/01 J2 - Chest KW - Adult BCG Vaccine/economics Cost-Benefit Analysis Decision Support Techniques Homeless Persons Humans Middle Aged Tuberculosis, Pulmonary/economics/ prevention & control United States Vaccination/economics LA - eng N1 - Nettleman, M D Research Support, Non-U.S. Gov't United states Chest. 1993 Apr;103(4):1087-90. PY - 1993 RN - fulltext fulltext_1208 SN - 0012-3692 (Print) 0012-3692 (Linking) SP - 1087-90 ST - Use of BCG vaccine in shelters for the homeless. A decision analysis T2 - Chest TI - Use of BCG vaccine in shelters for the homeless. A decision analysis VL - 103 ID - 2324 ER - TY - JOUR AB - The cost-effectiveness of chemotherapy for pulmonary sputum smear-positive tuberculosis was examined in the national tuberculosis control programmes of Malawi, Mozambique and Tanzania. In these three programmes, routine cure rates have exceeded 80 per cent. Average, average incremental and marginal unit costs for standard, short-course and retreatment regimens with and without hospitalization have been measured. The average incremental cost per year of life saved through chemotherapy ranged from US $0.90-3.10. In all conditions, short-course chemotherapy is preferable to standard 12-month chemotherapy. When hospitalization during the intensive phase of chemotherapy increases the cure rate by 10-15 percentage points, it can be relatively cost-effective. Analysing the cost-effectiveness of short-course and standard chemotherapy, where the depth of the margin of benefit is different, illustrates some of the dangers of simplistic use of cost-effectiveness ratios. AN - 10172113 AU - de Jonghe, E. AU - Murray, C. J. AU - Chum, H. J. AU - Nyangulu, D. S. AU - Salomao, A. AU - Styblo, K. DA - Apr-Jun KW - Ambulatory Care/economics Comparative Study Cost-Benefit Analysis/statistics & numerical data Data Collection Developing Countries Health Care Costs/*statistics & numerical data Hospitalization/economics Human Laboratory Techniques and Procedures/economics Malawi Mozambique National Health Programs/*economics Program Evaluation/*economics Tanzania Tuberculosis, Pulmonary/diagnosis/*drug therapy/*economics/transmission N1 - 95015805 0749-6753 Journal Article Review Review, Tutorial PY - 1994 RN - fulltext fulltext_1208 SP - 151-181 ST - Cost-effectiveness of chemotherapy for sputum smear-positive pulmonary tuberculosis in Malawi, Mozambique and Tanzania T2 - International Journal of Health Planning and Management TI - Cost-effectiveness of chemotherapy for sputum smear-positive pulmonary tuberculosis in Malawi, Mozambique and Tanzania UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10172113 VL - 9 ID - 2325 ER - TY - JOUR AB - Forecasts of tuberculosis morbidity and mortality are presented for the decade 1990-99. An estimated 88 million new cases of tuberculosis, of which 8 million will be attributable to HIV infection, will occur in the world during the decade; 30 million people are predicted to die of tuberculosis in the same period, including 2.9 million attributable to HIV infection. The number of new tuberculosis cases occurring each year is predicted to increase from 7.5 million (143 cases per 100,000) in 1990 to 8.8 million (152 per 100,000) in 1995 and 10.2 million (163 per 100,000) in the year 2000. In 1990, 2.5 million persons were estimated to have died of tuberculosis; at the same level of availability of treatment, it is predicted that 3.0 million tuberculosis deaths will occur in 1995 and 3.5 million in 2000. Demographic factors, such as population growth and changes in the age structure of populations, will account for 79.5% of the predicted increases in new cases. Age-specific incidence rates in sub-Saharan Africa are increasing due to the HIV epidemic and will account for the remaining 20.5% of the forecast increase in new cases. In WHO's South-East Asian Region and in Central and South America the age-specific incidence rates are expected to fall during 1990-2000, but at a slower rate than in previous years because of the expected increase in HIV seroprevalence.(ABSTRACT TRUNCATED AT 250 WORDS) AD - Imperial Cancer Research Fund, Radcliffe Infirmary, University of Oxford, England. AN - 8205640 AU - Dolin, P. J. AU - Raviglione, M. C. AU - Kochi, A. DP - Nlm ET - 01/01 KW - AIDS-Related Opportunistic Infections/epidemiology Adolescent Adult Age Factors Aged Child Demography Developing Countries Forecasting Humans Incidence Middle Aged Population Growth Tuberculosis/ epidemiology/mortality LA - eng N1 - Dolin, P J Raviglione, M C Kochi, A Switzerland Bulletin of the World Health Organization Bull World Health Organ. 1994;72(2):213-20. PY - 1994 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0042-9686 (Print) 0042-9686 (Linking) SP - 213-20 ST - Global tuberculosis incidence and mortality during 1990-2000 T2 - Bull World Health Organ TI - Global tuberculosis incidence and mortality during 1990-2000 UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2486541/pdf/bullwho00413-0034.pdf VL - 72 ID - 2326 ER - TY - JOUR AB - The lognormal distribution typically is used to model variability in respiratory penetration values. The lognormal model is a good descriptor where the average penetration value is low, but may be a poor descriptor where the average penetration value is high because a significant fraction of penetration values could be predicted to exceed unity. In this regard, the beta distribution offers greater flexibility than the lognormal in modeling penetration values over the physically plausible interval [0,1]. The beta distribution also is shown to be mathematically convenient for describing the risk of airborne transmission of tuberculosis among a respirator-wearing population. Infection can occur following inhalation of respirable particles, termed droplet nuclei, carrying viable Mycobacterium tuberculosis bacilli. Based on the expected number of infectious doses inhaled, the Poisson probability model traditionally is used to predict an individual's risk of infection. This article synthesizes the beta distribution, as applied to average penetration values among a respirator-wearing population, and the Poisson distribution, as applied to an individual's infection risk, to describe the population risk of M. tuberculosis infection. AD - Center for Occupational and Environmental Health, School of Public Health, University of California, Berkeley 94720. AN - 8017292 AU - Nicas, M. DA - Jun DO - 10.1080/15428119491018781 [doi] DP - Nlm ET - 06/01 KW - Humans Models, Statistical Occupational Diseases/ epidemiology/ etiology Poisson Distribution Respiratory Protective Devices Risk Tuberculosis/ epidemiology/ transmission LA - eng N1 - Nicas, M United states American Industrial Hygiene Association journal Am Ind Hyg Assoc J. 1994 Jun;55(6):515-24. PY - 1994 RN - fulltext fulltext_1208 SN - 0002-8894 (Print) 0002-8894 (Linking) SP - 515-24 ST - Modeling respirator penetration values with the beta distribution: an application to occupational tuberculosis transmission T2 - Am Ind Hyg Assoc J TI - Modeling respirator penetration values with the beta distribution: an application to occupational tuberculosis transmission UR - http://www.tandfonline.com/doi/abs/10.1080/15428119491018781 VL - 55 ID - 2327 ER - TY - JOUR AB - A mathematical model is introduced to study the accelerating impact of HIV infection on the incidence rates of tuberculosis (TB) disease. A sexually active population (15-49 years) is followed cross-sectionally over a period of time. Beginning with the year in which HIV infection was probably first present in the population, the model calculates the growing yearly incidence rates of new TB disease in HIV-positive and in HIV-negative individuals. Model equations, derived by an actuarial method, are developed recursively. Input information required for the calculations includes the age distribution of the study population, pre-HIV annual TB infection rates, annual HIV infection and mortality rates, and estimates of annual TB disease breakdown rates in the absence and in the presence of HIV infection. With correct input data, the model provides a useful blueprint for health agencies in designing effective programmes for curbing the future course of these dual epidemics in the population. AD - Respiratory Division, Vancouver General Hospital, BC, Canada. AN - 8082969 AU - Schulzer, M. AU - Radhamani, M. P. AU - Grzybowski, S. AU - Mak, E. AU - Fitzgerald, J. M. DA - Apr DP - Nlm ET - 04/01 KW - AIDS-Related Opportunistic Infections/ mortality Adolescent Adult Canada/epidemiology Cross-Sectional Studies Female HIV Infections/ mortality Humans Incidence Male Middle Aged Models, Theoretical Risk Factors Survival Analysis Tuberculosis, Pulmonary/ mortality LA - eng N1 - Schulzer, M Radhamani, M P Grzybowski, S Mak, E Fitzgerald, J M Research Support, Non-U.S. Gov't England International journal of epidemiology Int J Epidemiol. 1994 Apr;23(2):400-7. PY - 1994 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0300-5771 (Print) 0300-5771 (Linking) SP - 400-7 ST - A mathematical model for the prediction of the impact of HIV infection on tuberculosis T2 - Int J Epidemiol TI - A mathematical model for the prediction of the impact of HIV infection on tuberculosis UR - http://ije.oxfordjournals.org.ez.lshtm.ac.uk/content/23/2/400.full.pdf VL - 23 ID - 2328 ER - TY - JOUR AB - In developed countries the major tuberculosis epidemics declined long before the disease became curable in the 1940s. We present a theoretical framework for assessing the intrinsic transmission dynamics of tuberculosis. We demonstrate that it takes one to several hundred years for a tuberculosis epidemic to rise, fall and reach a stable endemic level. Our results suggest that some of the decline of tuberculosis is simply due to the natural behaviour of an epidemic. Although other factors must also have contributed to the decline, these causal factors were constrained to operate within the slow response time dictated by the intrinsic dynamics. AD - Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco General Hospital 94143-1347, USA. AN - 7585186 AU - Blower, S. M. AU - McLean, A. R. AU - Porco, T. C. AU - Small, P. M. AU - Hopewell, P. C. AU - Sanchez, M. A. AU - Moss, A. R. DA - Aug ET - 08/01 J2 - Nature medicine KW - *Disease Outbreaks Europe/epidemiology Humans *Models, Statistical Nonlinear Dynamics North America/epidemiology Sampling Studies Time Factors Tuberculosis, Pulmonary/*epidemiology/transmission LA - eng M3 - Comparative Study Research Support, U.S. Gov't, P.H.S. N1 - Blower, S M McLean, A R Porco, T C Small, P M Hopewell, P C Sanchez, M A Moss, A R 1R29DA08153/DA/NIDA NIH HHS/ AI33831/AI/NIAID NIH HHS/ K08AI01137-01/AI/NIAID NIH HHS/ Nat Med. 1995 Aug;1(8):815-21. PY - 1995 RN - fulltext fulltext_1208 SN - 1078-8956 (Print) 1078-8956 (Linking) SP - 815-21 ST - The intrinsic transmission dynamics of tuberculosis epidemics T2 - Nat Med TI - The intrinsic transmission dynamics of tuberculosis epidemics UR - http://www.ncbi.nlm.nih.gov/pubmed/7585186 VL - 1 ID - 2329 ER - TY - JOUR AB - The expected upsurge in the number of new cases of tuberculosis resulting from the HIV/AIDS epidemic prompted an examination of the feasibility of prevention strategies to limit the increase in clinical tuberculosis. A computer spreadsheet model was developed to estimate the costs and benefits that would result from isoniazid chemoprophylaxis for tuberculosis in a hypothetical cohort of 100,000 HIV-seropositive people in South Africa over a period of 8 years. At a 50% prevalence of tuberculosis infection among those at high background risk, and 5-10% among those at low risk, there would have been 34,000 cases of active tuberculosis in the cohort and their contacts if no prophylactic therapy had been used. On the other hand, a chemoprophylaxis policy would have meant only 12,200 cases of tuberculosis, if a patient compliance rate of 68.5% had been assumed. Such a policy would have prevented 21,800 cases of active tuberculosis. The estimated total discounted cost of a chemoprophylaxis programme would have been R51.3 million. In the absence of preventive therapy the discounted cost of treating patients with active tuberculosis would have been R91.9 million over the 8-year period. Therefore, if the benefits of chemoprophylaxis were defined in terms of averted health care costs, such a policy would have resulted in net savings of R40.6 million. This study did not estimate losses in production associated with tuberculosis treatment or the value of preventing tuberculosis per se, though such indirect costs would have increased the benefit of the prevention programme.(ABSTRACT TRUNCATED AT 250 WORDS) AD - Department of Community Health, University of the Witwatersrand, Johannesburg. AN - 7597538 AU - Masobe, P. AU - Lee, T. AU - Price, M. DA - Feb DP - Nlm ET - 02/01 KW - Ambulatory Care/ economics Computer Simulation Cost of Illness Costs and Cost Analysis Feasibility Studies HIV Seropositivity/ complications Hospitalization/ economics Humans Isoniazid/economics/ therapeutic use Patient Compliance South Africa Tuberculosis/economics/ prevention & control LA - eng N1 - Masobe, P Lee, T Price, M South africa South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde S Afr Med J. 1995 Feb;85(2):75-81. PY - 1995 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0256-9574 (Print) 0256-9574 (Linking) SP - 75-81 ST - Isoniazid prophylactic therapy for tuberculosis in HIV-seropositive patients--a least-cost analysis T2 - S Afr Med J TI - Isoniazid prophylactic therapy for tuberculosis in HIV-seropositive patients--a least-cost analysis VL - 85 ID - 2330 ER - TY - JOUR AB - OBJECTIVE: To compare tuberculin screening of all kindergartners and high school entrants (screen-all strategy) vs screening limited to high-risk children (targeted screening). DESIGN: Decision, cost-effectiveness, and cost-benefit analyses. SETTING AND SUBJECTS: Students in a large urban and rural county. DEFINITIONS: High risk of tuberculosis infection was defined as birth in a county with a high prevalence of tuberculosis. Low risk was defined as birth in the United States. OUTCOME MEASURES: Tuberculosis cases prevented for 10, 000 children screened. Net costs, net cost per case prevented, benefit-cost ratio, and incremental cost-effectiveness. RESULTS: The screen-all strategy would prevent 14.9 cases per 10,000 children screened; targeted screening would prevent 84.9 cases per 10,000 children screened. The screen-all strategy is more costly than no screening; the benefit-cost ratio is 0.58. Targeted screening would result in a net savings; the benefit-cost ratio is 1.2. Screening all children is cost saving only if the reactor rate is 20% or greater. The cost per additional case prevented for screening all children compared with targeted screening (+34 666) is more than twice as high as treatment and contact tracing for a case of tuberculosis (+16 392). CONCLUSIONS: Targeted screening of schoolchildren is much less costly than mass screening and is more efficient in prevention of tuberculosis. AD - Disease Control and Prevention Division, County of Santa Clara Public Health Department, San Jose, CA, USA. AN - 7637141 AU - Mohle-Boetani, J. C. AU - Miller, B. AU - Halpern, M. AU - Trivedi, A. AU - Lessler, J. AU - Solomon, S. L. AU - Fenstersheib, M. DA - Aug 23-30 DP - Nlm ET - 08/23 J2 - JAMA : the journal of the American Medical Association KW - Adolescent California/epidemiology Child Child, Preschool Cost-Benefit Analysis/methods Decision Trees Health Care Costs/ statistics & numerical data Humans Mass Screening/ economics/standards Risk Factors School Health Services/ economics Tuberculin Test Tuberculosis/economics/epidemiology/ prevention & control LA - eng N1 - Mohle-Boetani, J C Miller, B Halpern, M Trivedi, A Lessler, J Solomon, S L Fenstersheib, M United states JAMA. 1995 Aug 23-30;274(8):613-9. PY - 1995 RN - fulltext fulltext_1208 SN - 0098-7484 (Print) 0098-7484 (Linking) SP - 613-9 ST - School-based screening for tuberculous infection. A cost-benefit analysis T2 - JAMA TI - School-based screening for tuberculous infection. A cost-benefit analysis UR - http://jama.jamanetwork.com/data/Journals/JAMA/9401/jama_274_8_037.pdf VL - 274 ID - 2331 ER - TY - JOUR AB - SETTING: National tuberculin skin test surveys. OBJECTIVES: To review the operating characteristics of the tuberculin skin test, to ascertain the validity of estimating prevalence and risk of infection from tuberculin skin test surveys under various conditions, and to review constraints in the estimation of the magnitude of the tuberculosis problem in the community from such surveys. METHODS: This report utilizes hypothetical and selected real data obtained in regional and national surveys at various points in time to exemplify methodological issues. RESULTS: Risk of infection, the essence to be abstracted from tuberculin skin test surveys, theoretically allows for a comparison of the extent of transmission of tubercle bacilli in various populations. However, the conduct of tuberculin skin test surveys and the analysis and interpretation of their results are not free from important technical problems. Accurate estimation of infection prevalence is particularly vulnerable to the great variability of the test's specificity under various circumstances. Furthermore, the annual risk of infection has averaging characteristics that preclude a rapid assessment of changes in transmission patterns. Finally, estimates of infection risk do not necessarily provide a standardized parameter to derive incidence of infectious cases, because of variations in the quality of intervention and varying risks of progression from latent infection to overt tuberculosis. CONCLUSIONS: While tuberculin skin test surveys provide the currently most widely used means of assessing tuberculosis transmission patterns over prolonged periods of time in a community, results from such surveys must be interpreted with caution when accurate estimates of the tuberculosis problem are sought. AD - Tuberculosis Section, International Union Against Tuberculosis and Lung Disease, Paris, France. AN - 7780092 AU - Rieder, H. L. DA - Apr KW - Child Child, Preschool Humans Incidence Infant Models, Statistical Predictive Value of Tests Prevalence Tanzania/epidemiology *Tuberculin Test Tuberculosis/*epidemiology/pathology LA - eng N1 - Journal Article Scotland the official journal of the International Union against Tuberculosis and Lung Disease PY - 1995 RN - fulltext fulltext_1208 SN - 0962-8479 (Print) SP - 114-121 ST - Methodological issues in the estimation of the tuberculosis problem from tuberculin surveys T2 - Tubercle and Lung Disease TI - Methodological issues in the estimation of the tuberculosis problem from tuberculin surveys UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7780092http://ac.els-cdn.com/0962847995905529/1-s2.0-0962847995905529-main.pdf?_tid=c07e572e-6b37-11e2-a32a-00000aacb360&acdnat=1359589977_76de43cdb6962b4403e18004d77ee7f5 VL - 76 ID - 2332 ER - TY - JOUR AB - We use mathematical models to investigate the within-host dynamics of mycobacterial infections. In particular, we investigate the mechanisms by which bacteria such as Mycobacterium tuberculosis and Mycobacterium leprae persist at low densities for extended periods, and attain high densities much later. We suggest that the persistence of bacteria in face of immune pressure may result from the bacteria having a very slow growth rate, or having a dormant stage. We show that whereas these mechanisms may lead to long-term persistence, this will be obtained at relatively low densities. We then suggest that the long-term persistence of bacteria may result in the loss of immunity because of the deletion of specific T-cells arriving from the thymus, and the exhaustion of the specific T-cells as these cells reach the Hayflick limit and die. This loss of immunity will allow the bacteria to attain a high density. We propose experiments capable of testing our models and discuss the implications of the models for the treatment of infected hosts. AD - Department of Biology, Emory University, Atlanta, Georgia 30322, USA. AN - 8920248 AU - Antia, R. AU - Koella, J. C. AU - Perrot, V. DA - Mar 22 DO - 10.1098/rspb.1996.0040 [doi] DP - Nlm ET - 03/22 KW - Humans Leprosy/drug therapy/etiology/microbiology Mathematics Models, Biological Mycobacterium Infections/ etiology/microbiology Mycobacterium leprae/growth & development/immunology Mycobacterium tuberculosis/growth & development/immunology Time Factors Tuberculosis/drug therapy/etiology/microbiology LA - eng N1 - Antia, R Koella, J C Perrot, V Research Support, Non-U.S. Gov't England Proceedings. Biological sciences / The Royal Society Proc Biol Sci. 1996 Mar 22;263(1368):257-63. PY - 1996 RN - fulltext fulltext_1208 SN - 0962-8452 (Print) 0962-8452 (Linking) SP - 257-63 ST - Models of the within-host dynamics of persistent mycobacterial infections T2 - Proc Biol Sci TI - Models of the within-host dynamics of persistent mycobacterial infections UR - http://rspb.royalsocietypublishing.org/content/263/1368/257.full.pdf VL - 263 ID - 2333 ER - TY - JOUR AB - Tuberculosis, although preventable and curable, causes more adult deaths than any other infectious disease. A theoretical framework for designing effective control strategies is developed and used to determine treatment levels for eradication, to assess the effects of noneradicating control, and to examine the global goals of the World Health Organization. The theory is extended to assess how suboptimal control programs contribute to the evolution of drug resistance. A new evaluation criterion is defined and used to suggest how control strategies can be improved. In order to control tuberculosis, treatment failure rates must be lower in developing countries than in developed countries. AD - Department of Epidemiology and Biostatistics, University of California San Francisco, CA 94143-1347, USA. AN - 8662538 AU - Blower, S. M. AU - Small, P. M. AU - Hopewell, P. C. DA - Jul 26 ET - 07/26 J2 - Science KW - Adult Antitubercular Agents/*therapeutic use Developed Countries Developing Countries Disease Outbreaks/*prevention & control Drug Resistance, Microbial Humans *Models, Biological Models, Statistical Mycobacterium tuberculosis/drug effects Treatment Failure Tuberculosis, Multidrug-Resistant/drug therapy/*epidemiology/transmission Tuberculosis, Pulmonary/microbiology/*prevention & control/transmission World Health Organization L1 - internal-pdf://0696966960/Blower-1996-Control strategies for tuberculosi.pdf LA - eng M3 - Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. N1 - Blower, S M Small, P M Hopewell, P C 1R29DA08153/DA/NIDA NIH HHS/ AI33831/AI/NIAID NIH HHS/ AI35969/AI/NIAID NIH HHS/ New York, N.Y. Science. 1996 Jul 26;273(5274):497-500. PY - 1996 RN - fulltext fulltext_1208 SN - 0036-8075 (Print) 0036-8075 (Linking) SP - 497-500 ST - Control strategies for tuberculosis epidemics: new models for old problems T2 - Science TI - Control strategies for tuberculosis epidemics: new models for old problems UR - http://www.ncbi.nlm.nih.gov/pubmed/8662538 http://science.sciencemag.org/content/sci/273/5274/497.full.pdf VL - 273 ID - 2334 ER - TY - JOUR AB - OBJECTIVE: To develop more effective methods to assess tuberculosis (TB) control strategies so we can meet national goals for the elimination of TB in the United States. DESIGN: Using a semi-Markov model that divided the US population into 3 age groups and 18 clinical states based on disease status and risk for TB and human immunodeficiency virus (HIV) infection, we measured the effects of 5 changes in TB policy, introduced singly and in combination: (1) increased coverage and (2) improved efficacy of preventive therapy, (3) increased coverage and (4) improved efficacy of treatment, and (5) introduction of BCG vaccination. RESULTS: A BCG vaccination program that reached 10% of eligible children and 1% of eligible adults each year would produce a 17% reduction in cases and an 11% decline in deaths over 10 years. Preventive therapy programs among the general population would have little effect on the number of TB cases, but a program targeting HIV-infected patients would reduce HIV-associated TB cases and deaths 14% to 20%. A 10% improvement in the coverage and efficacy of both preventive therapy and treatment, coupled with the BCG vaccination program, would lead to a 47% decline in TB cases and a 50% decline in TB deaths relative to baseline over 10 years. CONCLUSIONS: Improvements in treatment coverage or effectiveness alone are unlikely to reach established national goals for the elimination of TB. These goals can be achieved through a combination of improvements in current programs with targeted preventive therapy and BCG vaccination programs. AD - Channing Laboratory, Brigham and Women's Hospital, Boston, Mass 02115, USA. AN - 8968016 AU - Brewer, T. F. AU - Heymann, S. J. AU - Colditz, G. A. AU - Wilson, M. E. AU - Auerbach, K. AU - Kane, D. AU - Fineberg, H. V. DA - Dec 18 DP - Nlm ET - 12/18 KW - Adolescent Adult Age Distribution Antitubercular Agents/therapeutic use BCG Vaccine Child Communicable Disease Control HIV Infections Humans Middle Aged Models, Theoretical Policy Making Probability Tuberculosis/epidemiology/ prevention & control Tuberculosis, Multidrug-Resistant United States/epidemiology L1 - internal-pdf://0346664946/Brewer-1996-Evaluation of tuberculosis control.pdf LA - eng N1 - Brewer, T F Heymann, S J Colditz, G A Wilson, M E Auerbach, K Kane, D Fineberg, H V 1 F32 HS00079/HS/AHRQ HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states JAMA : the journal of the American Medical Association JAMA. 1996 Dec 18;276(23):1898-903. PY - 1996 RN - fulltext fulltext_1208 SN - 0098-7484 (Print) 0098-7484 (Linking) SP - 1898-903 ST - Evaluation of tuberculosis control policies using computer simulation T2 - JAMA TI - Evaluation of tuberculosis control policies using computer simulation UR - http://jama.jamanetwork.com/article.aspx?articleid=411957 https://jamanetwork.com/journals/jama/articlepdf/411957/jama_276_23_034.pdf VL - 276 ID - 2335 ER - TY - JOUR AU - Moore, R. D. AU - Chaulk, C. P. AU - Griffiths, R. AU - Cavalcante, S. AU - Chaisson, R. E. DA - 1996 J2 - Am.J.Respir.Crit.Care Med. KW - control cost effectiveness DOT interventions tuberculosis LB - 4779 N1 - TY - JOUR TB Tuberculosis control Treatment No sub-heading Directly observed therapy PY - 1996 RN - fulltext fulltext_1208 SP - 1013-1019 ST - Cost-effectiveness of directly observed versus self-administered therapy for tuberculosis T2 - Am.J.Respir.Crit.Care Med. TI - Cost-effectiveness of directly observed versus self-administered therapy for tuberculosis VL - 154 ID - 2336 ER - TY - JOUR AB - An adverse health impact is often treated as a binary variable (response vs. no response), in which case the risk of response is defined as a monotonically increasing function R of the dose received D. For a population of size N, specifying the forms of R(D) and of the probability density function (pdf) for D allows determination of the pdf for risk, and computation of the mean and variance of the distribution of incidence, where the latter parameters are denoted E[SN] and Var[SN], respectively. The distribution of SN describes uncertainty in the future incidence value. Given variability in dose (and risk) among population members, the distribution of incidence is Poisson-binomial. However, depending on the value of E[SN], the distribution of incidence is adequately approximated by a Poisson distribution with parameter mu = E[SN], or by a normal distribution with mean and variance equal to E[SN] and Var[SN]. The general analytical framework is applied to occupational infection by Mycobacterium tuberculosis (M. tb). Tuberculosis is transmitted by inhalation of 1-5 microns particles carrying viable M. tb bacilli. Infection risk has traditionally been modeled by the expression: R(D) = 1 - exp(-D), where D is the expected number of bacilli that deposit in the pulmonary region. This model assumes that the infectious dose is one bacillus. The beta pdf and the gamma pdf are shown to be reasonable and especially convenient forms for modeling the distribution of the expected cumulative dose across a large healthcare worker cohort. Use of the the analytical framework is illustrated by estimating the efficacy of different respiratory protective devices in reducing healthcare worker infection risk. AD - Center for Occupational and Environmental Health, School of Public Health, University of California, Berkeley 94720, USA. AN - 8819343 AU - Nicas, M. DA - Aug DP - Nlm ET - 08/01 KW - Cohort Studies Health Personnel Humans Models, Biological Occupational Diseases/epidemiology/ etiology/prevention & control Poisson Distribution Respiratory Protective Devices Risk Assessment Risk Factors Tuberculosis, Pulmonary/epidemiology/ etiology/prevention & control LA - eng N1 - Nicas, M United states Risk analysis : an official publication of the Society for Risk Analysis Risk Anal. 1996 Aug;16(4):527-38. PY - 1996 RN - fulltext fulltext_1208 SN - 0272-4332 (Print) 0272-4332 (Linking) SP - 527-38 ST - An analytical framework for relating dose, risk, and incidence: an application to occupational tuberculosis infection T2 - Risk Anal TI - An analytical framework for relating dose, risk, and incidence: an application to occupational tuberculosis infection VL - 16 ID - 2337 ER - TY - JOUR AB - STUDY OBJECTIVES: To compare the costs and effectiveness of directly observed therapy (DOT) vs self-administered therapy (SAT) for the treatment of active tuberculosis. DESIGN: Decision analysis. SETTING: We used published rates for failure of therapy, relapse, and acquired multidrug resistance during the initial treatment of drug-susceptible tuberculosis cases using DOT or SAT. We estimated costs of tuberculosis treatment at an urban tuberculosis control program, a municipal hospital, and a hospital specializing in treating drug-resistant tuberculosis. OUTCOME MEASURES: The average cost per patient to cure drug-susceptible tuberculosis, including the cost of treating failures of initial treatment. RESULTS: The direct costs of initial therapy with DOT and SAT were similar ($1,206 vs $1,221 per patient, respectively), although DOT was more expensive when patient time costs were included. When the costs of relapse and failure were included in the model, DOT was less expensive than SAT, whether considering outpatient costs only ($1,405 vs $2,314 per patient treated), outpatient plus inpatient costs ($2,785 vs $10,529 per patient treated), or outpatient, inpatient, and patients' time costs ($3,999 vs $12,167 per patient treated). Threshold analysis demonstrated that DOT was less expensive than SAT through a wide range of cost estimates and clinical event rates. CONCLUSION: Despite its greater initial cost, DOT is a more cost-effective strategy than SAT because it achieves a higher cure rate after initial therapy, and thereby decreases treatment costs associated with failure of therapy and acquired drug resistance. This cost-effectiveness analysis supports the widespread implementation of DOT. AD - Denver Disease Control Service, Denver Health and Hospitals, and the Department of Medicine, University of Colorado Health Sciences Center, 80204, USA. AN - 9228359 AU - Burman, W. J. AU - Dalton, C. B. AU - Cohn, D. L. AU - Butler, J. R. AU - Reves, R. R. DA - Jul ET - 07/01 KW - Antitubercular Agents/*administration & dosage/economics/therapeutic use Communicable Disease Control/economics Cost-Benefit Analysis Costs and Cost Analysis *Decision Support Techniques Drug Therapy, Combination Hospital Costs Humans Patient Compliance Self Administration Treatment Failure Tuberculosis/*drug therapy/*economics/epidemiology Tuberculosis, Multidrug-Resistant/*drug therapy/*economics/epidemiology United States/epidemiology LA - eng N1 - Burman, W J Dalton, C B Cohn, D L Butler, J R Reves, R R Comparative Study United states Chest Chest. 1997 Jul;112(1):63-70. PY - 1997 RN - fulltext fulltext_1208 SN - 0012-3692 (Print) 0012-3692 (Linking) SP - 63-70 ST - A cost-effectiveness analysis of directly observed therapy vs self-administered therapy for treatment of tuberculosis T2 - Chest TI - A cost-effectiveness analysis of directly observed therapy vs self-administered therapy for treatment of tuberculosis UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9228359 VL - 112 ID - 2338 ER - TY - JOUR AB - Incomplete treatment of patients with infectious tuberculosis (TB) may not only lead to relapse but also to the development of antibiotic resistant TB-one of the most serious health problems facing society today. In this article, we formulate one-strain and two-strain TB models to determine possible mechanisms that may allow for the survival and spread of naturally resistant strains of TB as well as antibiotic-generated resistant strains of TB. Analysis of our models shows that non-antibiotic co-existence is possible but rare for naturally resistant strains while co-existence is almost the rule for strains that result from the lack of compliance with antibiotic treatment by TB infected individuals. AD - Biometrics Unit, Cornell University, Ithaca, NY 14853, USA. AN - 9225454 AU - Castillo-Chavez, C. AU - Feng, Z. DA - Jun ET - 06/01 KW - Antitubercular Agents/*pharmacology *Drug Resistance, Microbial Humans *Models, Theoretical Tuberculosis/*drug therapy/epidemiology L1 - internal-pdf://1263453073/10.1.1.1015.3529.pdf LA - eng N1 - Castillo-Chavez, C Feng, Z Research Support, U.S. Gov't, Non-P.H.S. Germany Journal of mathematical biology J Math Biol. 1997 Jun;35(6):629-56. PY - 1997 RN - fulltext fulltext_1208 SN - 0303-6812 (Print) 0303-6812 (Linking) SP - 629-656 ST - To treat or not to treat: the case of tuberculosis T2 - Journal of Mathematical Biology TI - To treat or not to treat: the case of tuberculosis UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9225454 VL - 35 ID - 2339 ER - TY - JOUR AB - OBJECTIVE: To assess the economic benefits and costs of providing isoniazid preventive therapy for tuberculosis (TB) in HIV-infected persons in Zambia. DESIGN: A spreadsheet model incorporating variables drawn from published studies and unpublished data. SUBJECTS: Data drawn from a number of different studies and published literature involving a range of subjects. SETTING: Zambia. RESULTS: Using data primarily from Zambia we have modelled the costs and benefits of a TB preventive therapy programme using daily isoniazid for 6 months. The basecase scenario assumes recruitment at a voluntary testing and counselling site where HIV seroprevalence is 30%; persons with HIV have a 25% probability of developing active TB during their lifetime; two additional cases of TB would be prevented per person completing a course of preventive therapy; compliance would be 63%, and the efficacy of the isoniazid in preventing active TB of 60%. The costs under this scenario would exceed the benefits by a factor of 1.16 [benefit: cost ratio (BCR) of 0.86]. However, if preventing one case of TB prevented an additional five cases, the benefits would exceed the costs by a significant margin (BCR of 1.71). Other scenarios indicate that the targeted preventive therapy of persons with HIV whose occupation or living situation places them in contact with a large number of others (teachers and students, health personnel, military and police, miners, prisoners, etc.) would yield significant net benefit. The operational challenge for TB preventive therapy is thus to identify and target large numbers of such persons. AD - Department of Public Health and Policy, London School of Hygiene and Tropical Medicine, UK. AN - 9189218 AU - Foster, S. AU - Godfrey-Faussett, P. AU - Porter, J. DA - Jun DP - Nlm ET - 06/01 KW - AIDS-Related Opportunistic Infections/economics/ prevention & control Antitubercular Agents/economics/ therapeutic use Cost-Benefit Analysis Humans Isoniazid/economics/ therapeutic use Models, Economic Tuberculosis/economics/ prevention & control Zambia the economic costs and benefits of providing daily isoniazid preventive therapy for tuberculosis (TB) for 6 months in HIV-infected persons in Zambia. The base case scenario assumes recruitment at a voluntary testing and counseling site where HIV seroprevalence is 30%, HIV-infected individuals have a 25% probability of developing active TB during their lifetime, two additional cases of TB would be prevented per person completing a course of preventive therapy, compliance would be 63%, and an efficacy of isoniazid in preventing active TB of 60%. The costs under that scenario would exceed benefits by a factor of 1.16, or a benefit/cost ratio (BCR) of 0.86. However, if preventing one case of TB prevented an additional five cases, the benefits would exceed the costs by a BCR of 1.71. Other scenarios indicate likely significant net benefits from the targeted preventive therapy of HIV-infected persons whose occupation or living situation brings them into contact with a large number of other people. LA - eng N1 - Foster, S Godfrey-Faussett, P Porter, J Research Support, Non-U.S. Gov't United states AIDS (London, England) AIDS. 1997 Jun;11(7):919-25. PY - 1997 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0269-9370 (Print) 0269-9370 (Linking) SP - 919-25 ST - Modelling the economic benefits of tuberculosis preventive therapy for people with HIV: the example of Zambia T2 - AIDS TI - Modelling the economic benefits of tuberculosis preventive therapy for people with HIV: the example of Zambia UR - http://graphics.tx.ovid.com/ovftpdfs/FPDDNCDCLFEDDD00/fs047/ovft/live/gv031/00002030/00002030-199707000-00012.pdf VL - 11 ID - 2340 ER - TY - JOUR AB - We evaluated the efficacy of recommended tuberculosis (TB) infection control measures by using a deterministic mathematical model for airborne contagion. We examined the percentage of purified protein derivative conversions under various exposure conditions, environmental controlstrategies, and respiratory protective devices. We conclude that environmental control cannot eliminate the risk for TB transmission during high-risk procedures; respiratory protective devices, and particularly high-efficiency particulate air masks, may provide nearly complete protection if used with air filtration or ultraviolet irradiation. Nevertheless, the efficiency of these control measures decreases as the infectivity of the source case increases. Therefore, administrative control measures (e.g., indentifying and isolating patients with infectious TB) are the most effective because they substantially reduce the rate of infection. AD - Dipartimento di Matematica, Universita di Perugia, Perugia, Italy. AN - 9284378 AU - Gammaitoni, L. AU - Nucci, M. C. DA - Jul-Sep DP - Nlm ET - 07/01 KW - Cross Infection/prevention & control/transmission Disease Outbreaks Europe/epidemiology Health Personnel Humans Mathematics Models, Biological Occupational Diseases/prevention & control Respiratory Protective Devices Risk Factors Tuberculosis, Pulmonary/epidemiology/ prevention & control/transmission United States/epidemiology LA - eng N1 - Gammaitoni, L Nucci, M C Research Support, Non-U.S. Gov't Review United states Emerging infectious diseases Emerg Infect Dis. 1997 Jul-Sep;3(3):335-42. PY - 1997 RN - fulltext fulltext_1208 SN - 1080-6040 (Print) 1080-6040 (Linking) SP - 335-42 ST - Using a mathematical model to evaluate the efficacy of TB control measures T2 - Emerg Infect Dis TI - Using a mathematical model to evaluate the efficacy of TB control measures VL - 3 ID - 2341 ER - TY - JOUR AB - BACKGROUND: Tuberculosis has been declining in developed countries for a long time, as a result of the intrinsic epidemiological characteristics of this disease, combined with improvement in the standard of living and more recently the use of antibiotics. In these low prevalence countries, decisions concerning the objectives of tuberculosis programmes have to be taken and the consequences of short term changes in the sanitary situation have to be assessed. METHODS: A deterministic model, without age structure, of the dynamics of pulmonary tuberculosis is proposed. The model extends that of Waaler and is intended to be more suitable for application to developed countries. The flows between seven subgroups of population, based on the natural history of the disease, are modelled and vaccination is taken into account. Values of model parameters and initial prevalences were deduced from published data. RESULTS: As a first step, qualitative comparisons are performed between the model-predicted decline in the annual risk of infection (ARI) and data from the Netherlands tuberculosis survey. Using parameter values suited to France, our model shows that the predicted decline is slower in France than in the Netherlands; a result which tallies with epidemiological observations. Uses of the model as a decision tool are illustrated in two cases, that of ending systematic BCG vaccination and that of a sudden increase in the number of infectious cases. AD - Institut Francais de Recherche Scientifique, Developpement en Cooperation, (ORSTOM), Paris, France. AN - 9126520 AU - Garcia, A. AU - Maccario, J. AU - Richardson, S. DA - Feb DP - Nlm ET - 02/01 KW - Epidemiologic Methods France/epidemiology Humans Incidence Models, Theoretical Netherlands/epidemiology Risk Assessment Time Factors Tuberculosis/ epidemiology LA - eng N1 - Garcia, A Maccario, J Richardson, S Comparative Study Research Support, Non-U.S. Gov't England International journal of epidemiology Int J Epidemiol. 1997 Feb;26(1):190-203. PY - 1997 RN - fulltext fulltext_1208 SN - 0300-5771 (Print) 0300-5771 (Linking) SP - 190-203 ST - Modelling the annual risk of tuberculosis infection T2 - Int J Epidemiol TI - Modelling the annual risk of tuberculosis infection UR - http://ije.oxfordjournals.org/content/26/1/190.full.pdf VL - 26 ID - 2342 ER - TY - JOUR AB - For tuberculosis and number of other bacterial infections, treatment with a single antimicrobial drug frequently fails due to the ascent of mutants resistant to that drug. To minimize the likelihood of this occurrence, multiple drugs with independent resistance mechanisms are used simultaneously. None the less, multiply resistant bacteria sometimes emerge even when patients are simultaneously treated with two or more drugs, and the ascent of these multiply-resistant mutants may result in treatment failure in the patient and spread of these resistant bacteria to other hosts. We consider two mathematical models of antibacterial chemotherapy which can account for the ascent of multiple antibiotic resistance within hosts treated with multiple antibiotics. In both, multiple resistance evolves because of selection favouring mutants resistant to fewer than all of the chemotherapeutic agents employed, intermediates. In one model, this occurs because of temporal fluctuations in the concentrations of the antibiotics in the course of normal treatment and/or because of non-adherence to the treatment regime. In the other, intermediates are favoured and multiple resistance evolves because of tissue and somatic cell heterogeneity. In the effective concentrations of the antibiotics and physiological variation in the sensitivity of subpopulations of bacteria to different antibiotics. We discuss the limitations (and assets) of this model and approach and the implications for the design of antibiotic treatment regimes. Finally, we consider how the assumptions behind this model and the predictions made from its analysis could be tested experimentally. AD - Department of Biology, Emory University, Atlanta, GA 30322, USA. AN - 9189638 AU - Lipsitch, M. AU - Levin, B. R. DP - NLM ET - 1997/01/01 J2 - Ciba Foundation symposium KW - Animals Anti-Bacterial Agents/*therapeutic use Bacteria/*drug effects Bacterial Infections/*drug therapy Biological Evolution *Drug Resistance, Multiple/genetics Humans *Models, Biological *Models, Theoretical LA - eng N1 - Lipsitch, M Levin, B R GM33782/GM/NIGMS NIH HHS/United States Journal Article Research Support, U.S. Gov't, P.H.S. Review Netherlands Ciba Found Symp. 1997;207:112-27; discussion 127-30. PY - 1997 SN - 0300-5208 (Print) 0300-5208 SP - 112-27; discussion 127-30 ST - The within-host population dynamics of antibacterial chemotherapy: conditions for the evolution of resistance T2 - Ciba Found Symp TI - The within-host population dynamics of antibacterial chemotherapy: conditions for the evolution of resistance VL - 207 ID - 3175 ER - TY - JOUR AU - Marcus, Alexander M. AU - Rose, David N. AU - Sacks, Henry S. AU - Schechter, Clyde B. DO - 10.1006/pmed.1996.0123 KW - Bacille Calmette-Guérin BCG health care worker isoniazid occupational health prevention tuberculin tuberculosis vaccination PY - 1997 RN - fulltext fulltext_1208 SN - 0091-7435 SP - 201-207 ST - BCG Vaccination to Prevent Tuberculosis in Health Care Workers: A Decision Analysis T2 - Preventive Medicine TI - BCG Vaccination to Prevent Tuberculosis in Health Care Workers: A Decision Analysis UR - http://www.sciencedirect.com/science/article/pii/S0091743596901231 VL - 26 ID - 2345 ER - TY - JOUR AB - BACKGROUND: Tuberculin skin testing using the purified protein derivative is recommended as part of a tuberculosis control program for health care workers. However, compliance with skin testing programs has been poor and their cost-effectiveness is unknown. METHODS: A Markov-based decision analysis was performed to determine the cost-effectiveness of tuberculin skin testing over the entire lifetimes of physicians who are now in medical school. Assumptions were deliberately chosen to present a conservative estimate of cost-effectiveness. Indirect costs were not included. RESULTS: Annual testing cost $29,000 per life-year saved and $39,000 per case of pulmonary tuberculosis prevented. In contrast, particulate respirators have been shown to cost millions of dollars per case prevented. Skin testing every 6 months was cost-effective in a subpopulation at high risk of infection (> or = 1.8-fold). During their entire lifetimes, physicians now in medical school can expect to avert 137 cases of pulmonary tuberculosis, prevent 7 tuberculosis deaths, and save 182 life-years because of skin testing programs. Improved compliance with annual skin testing and prophylactic isoniazid could more than triple this benefit. If available, a moderately effective vaccine would be even more cost-effective than tuberculin skin testing programs. CONCLUSIONS: Tuberculin skin testing is cost-effective and should be an integral part of any tuberculosis control program. Vaccination may one day be a feasible and cost-effective alternative to skin testing programs. AD - Department of Internal Medicine, Virginia Commonwealth University, Richmond, USA. AN - 9164378 AU - Nettleman, M. D. AU - Geerdes, H. AU - Roy, M. C. DA - May 26 DP - Nlm ET - 05/26 J2 - Archives of internal medicine KW - Adult Aged Antitubercular Agents/therapeutic use BCG Vaccine/ economics Cause of Death Chemoprevention Cooperative Behavior Cost-Benefit Analysis Decision Support Techniques Feasibility Studies Humans Isoniazid/therapeutic use Markov Chains Middle Aged Occupational Diseases/ prevention & control Physicians Respiratory Protective Devices/economics Risk Factors Sensitivity and Specificity Time Factors Tuberculin Test/ economics Tuberculosis, Pulmonary/ prevention & control Value of Life LA - eng N1 - Nettleman, M D Geerdes, H Roy, M C United states Arch Intern Med. 1997 May 26;157(10):1121-7. PY - 1997 RN - fulltext fulltext_1208 SN - 0003-9926 (Print) 0003-9926 (Linking) SP - 1121-7 ST - The cost-effectiveness of preventing tuberculosis in physicians using tuberculin skin testing or a hypothetical vaccine T2 - Arch Intern Med TI - The cost-effectiveness of preventing tuberculosis in physicians using tuberculin skin testing or a hypothetical vaccine UR - http://archinte.jamanetwork.com/data/Journals/INTEMED/17545/archinte_157_10_009.pdf VL - 157 ID - 2346 ER - TY - JOUR AB - A simulation model of tuberculosis (TB) transmission among hospital employees is described. A hypothetical cohort of 1000 workers was divided into low-, medium-, and high-risk groups. The number of TB patients admitted daily was treated as a Poisson random variable. A patient imparted a daily infection risk that was identical for all workers within a risk group but that varied between risk groups. In some scenarios, infected employees were assigned a daily risk of developing TB disease. If disease developed, the individual remained on the job for 3 calendar weeks and imparted a substantial infection risk to 25 close contacts. Simulations were run over 5-year intervals. Cumulative infection incidence increased over time and with more TB patients admitted. Given a scenario in which there were 600, 300, and 100 susceptibles in the low-, medium-, and high risk groups, respectively, 50 TB patients admitted annually and accounting for disease among infected employees, at 5 years there were approximately 100 primary infections (due to infection by patients), 40 secondary infections (due to infection by diseased coworkers), five primary disease cases, and two secondary disease cases. The input parameter values and simulation outcomes were reasonably consistent with the sparse information reported in the literature. AD - Nicas, M (reprint author), UNIV CALIF BERKELEY,SCH PUBL HLTH,CTR ENVIRONM & OCCUPAT HLTH,BERKELEY,CA 94720, USA. AN - WOS:A1997YK07100009 AU - Nicas, M. AU - Seto, E. DA - Oct DO - 10.1111/j.1539-6924.1997.tb00901.x IS - 5 J2 - Risk Anal. KW - tuberculosis risk modeling occupational tuberculosis infection-control programs cdc tb survey member hospitals risk Public, Environmental & Occupational Health Mathematics Mathematical Methods In Social Sciences LA - English M3 - Article N1 - ISI Document Delivery No.: YK071 Times Cited: 2 Cited Reference Count: 16 Nicas, M Seto, E Niosh cdc hhs [k01-oh00155-01] 3 0 Plenum publ corp New york PY - 1997 SN - 0272-4332 SP - 609-616 ST - A simulation model for occupational tuberculosis transmission T2 - Risk Analysis TI - A simulation model for occupational tuberculosis transmission UR - ://WOS:A1997YK07100009 VL - 17 ID - 6347 ER - TY - JOUR AB - BACKGROUND: Isoniazid chemoprophylaxis effectively prevents the development of active infectious tuberculosis. Current guidelines recommend withholding this prophylaxis for low-risk tuberculin reactors older than 35 years of age because of the risk for fatal isoniazid-induced hepatitis. However, recent studies have shown that monitoring for hepatotoxicity can significantly reduce the risk for isoniazid-related death. OBJECTIVE: To evaluate the effectiveness and cost-effectiveness of monitored isoniazid prophylaxis for low-risk tuberculin reactors older than 35 years of age. DESIGN: A Markov model was used to compare the health and economic outcomes of prescribing or withholding a course of prophylaxis for low-risk reactors 35, 50, or 70 years of age. Subsequent analyses evaluated costs and benefits when the effect of transmission of Mycobacterium tuberculosis to contacts was included. MEASUREMENTS: Probability of survival at 1 year, number needed to treat, life expectancy, and cost per year of life gained for individual persons and total population. RESULTS: Isoniazid prophylaxis increased the probability of survival at 1 year and for all subsequent years. For 35-year old, 50-year-old, and 70-year-old tuberculin reactors, life expectancy increased by 4.9 days, 4.7 days, and 3.1 days, respectively, and costs per person decreased by $101, $69, and $11, respectively. When the effect of secondary transmission to contacts was included, the gains in life expectancy per person receiving prophylaxis were 10.0 days for 35-year-old reactors, 9.0 days for 50-year-old reactors, and 6.0 days for 70-year-old reactors. Costs per person for these cohorts decreased by $259, $203, and $100, respectively. The magnitude of the benefit of isoniazid prophylaxis is moderately sensitive to the effect of isoniazid on quality of life. The hypothetical provision of isoniazid prophylaxis for all low-risk reactors older than 35 years of age in the U.S. population could prevent 35,176 deaths and save $2.11 billion. CONCLUSIONS: Monitored isoniazid prophylaxis reduces mortality rates and health care costs for low-risk tuberculin reactors older than 35 years of age, although reductions for individual patients are small. For the U.S. population, however, the potential health benefits and economic savings resulting from wider use of monitored isoniazid prophylaxis are substantial. We should consider expanding current recommendations to include prophylaxis for tuberculin reactors of all ages with no contraindications. AD - Santa Clara Valley Medical Center, San Jose, California USA. AN - 9412307 AU - Salpeter, S. R. AU - Sanders, G. D. AU - Salpeter, E. E. AU - Owens, D. K. DA - Dec 15 DP - Nlm ET - 12/31 J2 - Annals of internal medicine KW - Adult Aged Antitubercular Agents/adverse effects/economics/ therapeutic use Cost-Benefit Analysis Decision Trees Drug-Induced Liver Injury/etiology/mortality Health Care Costs Humans Isoniazid/adverse effects/economics/ therapeutic use Life Expectancy Markov Chains Middle Aged Quality of Life Sensitivity and Specificity Tuberculin Test Tuberculosis/ prevention & control/transmission LA - eng N1 - Salpeter, S R Sanders, G D Salpeter, E E Owens, D K Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United states Ann Intern Med. 1997 Dec 15;127(12):1051-61. PY - 1997 RN - fulltext fulltext_1208 SN - 0003-4819 (Print) 0003-4819 (Linking) SP - 1051-61 ST - Monitored isoniazid prophylaxis for low-risk tuberculin reactors older than 35 years of age: a risk-benefit and cost-effectiveness analysis T2 - Ann Intern Med TI - Monitored isoniazid prophylaxis for low-risk tuberculin reactors older than 35 years of age: a risk-benefit and cost-effectiveness analysis UR - http://annals.org/data/Journals/AIM/19897/0000605-199712150-00001.pdf VL - 127 ID - 2347 ER - TY - JOUR AB - The basic reproductive rate (R0) is a measure of the severity of an epidemic. On the basis of replicated Latin hypercube sampling, the authors performed an uncertainty and sensitivity analysis of the basic reproductive rate of tuberculosis (TB). The uncertainty analysis allowed for the derivation of a frequency distribution for R0 and the assessment of the relative contribution each of the three components of R0 made when TB epidemics first arose centuries ago. (The three components of R0 are associated with fast, slow, and relapse TB.) R0 estimates indicated the existence of fairly severe epidemics when TB epidemics first arose. The R0 for the susceptible persons who developed TB slowly (R0(slow)) contributed the most to the R0 estimates; however, the relative R0(slow) contribution decreased as the severity of TB epidemics increased. The sensitivity of the magnitude of R0 to the uncertainty in estimating values of each of the input parameters was assessed. These results indicated that five of the nine input parameters, because of their estimation uncertainty, were influential in determining the magnitude of R0. This uncertainty and sensitivity methodology provides results that can aid investigators in understanding the historical epidemiology of TB by quantifying the effect of the transmission processes involved. Additionally, this method can be applied to the R0 of any other infectious disease to estimate the probability of an epidemic outbreak. AD - Epidemiology Program School of Public Health, University of California, Berkeley, USA. AN - 9199543 AU - Sanchez, M. A. AU - Blower, S. M. DA - Jun 15 DP - Nlm ET - 06/15 KW - Adult Aged Disease Outbreaks/ statistics & numerical data Disease Transmission, Infectious Humans Incidence Life Expectancy Middle Aged Models, Statistical Population Dynamics Reproduction Sample Size Survival Rate Tuberculosis/ epidemiology/transmission LA - eng N1 - Sanchez, M A Blower, S M 1R29DA08153/DA/NIDA NIH HHS/United States AI33831/AI/NIAID NIH HHS/United States D43-TW00003/TW/FIC NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states American journal of epidemiology Am J Epidemiol. 1997 Jun 15;145(12):1127-37. PY - 1997 RN - fulltext fulltext_1208 SN - 0002-9262 (Print) 0002-9262 (Linking) SP - 1127-37 ST - Uncertainty and sensitivity analysis of the basic reproductive rate. Tuberculosis as an example T2 - Am J Epidemiol TI - Uncertainty and sensitivity analysis of the basic reproductive rate. Tuberculosis as an example UR - http://aje.oxfordjournals.org/content/145/12/1127.full.pdf VL - 145 ID - 2348 ER - TY - JOUR AB - The study evaluates the economic costs and benefits of improving tuberculosis control interventions in Thailand. Provider costs are determined on the basis of marginal treatment costs for varying case numbers and estimates of the cost of required infrastructure changes. Indirect costs are calculated as income lost due to morbidity and premature mortality. An epidemiological model is used to calculate case numbers and mortality under current control conditions and a scenario of improved control. An improved control strategy initially leads to a higher number of detected cases. For longer projection periods, the epidemiological impact of curing a higher proportion of infectious sources results in lower case numbers than those expected without programme improvement. Model simulations show a reduction of total annual case numbers through improved control measures by an average 45% after a simulation period of 20 years. The corresponding societal savings in form of reduced indirect costs from the disease are U.S.$2.4 billion. Reductions in direct provider costs can be expected as a result of decreased numbers of detected cases for longer evaluation periods, as well as a lower proportion of multi-drug-resistant cases. The mean value of predicted savings is U.S.$8.3 million. Since this value is likely to be higher than the required investment in improved infrastructure, net savings can be expected. The result of an uncertainty analysis shows a wide range of potential additional costs or net savings with respect to direct provider costs. Indirect cost calculations show net savings for all parameter values. AD - Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland. AN - 9194242 AU - Sawert, H. AU - Kongsin, S. AU - Payanandana, V. AU - Akarasewi, P. AU - Nunn, P. P. AU - Raviglione, M. C. DA - Jun IS - 12 KW - Communicable Disease Control/*economics Cost Savings *Cost of Illness Cost-Benefit Analysis Forecasting *Health Care Costs Humans Models, Statistical Morbidity Risk Factors Thailand/epidemiology Tuberculosis/*economics/epidemiology/*prevention & control Value of Life L1 - internal-pdf://3098386177/1-s2.0-S0277953696002894-main.pdf N1 - Sawert, H Kongsin, S Payanandana, V Akarasewi, P Nunn, P P Raviglione, M C eng England 1997/06/01 Soc Sci Med. 1997 Jun;44(12):1805-16. PY - 1997 SN - 0277-9536 (Print) 0277-9536 (Linking) SP - 1805-16 ST - Costs and benefits of improving tuberculosis control: the case of Thailand T2 - Soc Sci Med TI - Costs and benefits of improving tuberculosis control: the case of Thailand UR - https://www.ncbi.nlm.nih.gov/pubmed/9194242 VL - 44 ID - 2702 ER - TY - JOUR AU - Smith, P. J. AU - Thompson, T. J. AU - Jereb, J. A. DA - 1997 KW - epidemiology models morbidity outbreaks tuberculosis LB - 5102 N1 - TY - JOUR TB Transmission, pathogenesis, and epidemiology Tuberculosis Predict epi: prospects for the epidemic PY - 1997 RN - fulltext fulltext_1208 SP - 485-496 ST - A model for interval-censored tuberculosis outbreak data T2 - Stat.Med. TI - A model for interval-censored tuberculosis outbreak data VL - 16 ID - 2349 ER - TY - JOUR AB - Many aspects of the natural history of tuberculosis are poorly understood. Though it is recognized that clinical tuberculosis may follow shortly after initial infection ('primary' disease), or many years thereafter through either endogenous reactivation or after reinfection, the relative importance of these mechanisms is often disputed. The issue is complicated by the fact that the risks of developing disease are age-dependent, and reflect infection risks which may change over time. This paper estimates the age-dependent risks of developing tuberculosis using an age-structured deterministic model of the dynamics of tuberculous infection and disease in England and Wales since 1900. The work extends the classical studies of Sutherland and colleagues. The best estimates of the risks of developing 'primary' disease (within 5 years of initial infection) were approximately 4%, 9% and 14% for individuals infected at ages 0-10, 15 years and over 20 years respectively, and a previous infection appeared to impart little protection against (further) reinfection, but 16-41% protection against disease subsequent to reinfection for adolescents and adults. We also provide evidence that reinfection made an important contribution to tuberculous morbidity in the past, as (i) exclusion of exogenous disease from the model considerably worsened the fit to observed notification rates, and (ii) the dramatic decline in the risk of tuberculous infection from 1950 in England and Wales accelerated the decline in morbidity among all individuals, even among the older age groups with a high prevalence of tuberculous infection. We conclude that the risk of infection is the single most important factor affecting the magnitude of the tuberculous morbidity in a population, as it determines both the age pattern of initial infection (and hence the risk of developing disease) and the risk of reinfection. AD - Department of Epidemiology and Population Sciences, London School of Hygiene & Tropical Medicine, UK. AN - 9363017 AU - Vynnycky, E. AU - Fine, P. E. KW - Adolescent Adult Age Distribution Age of Onset Aged Child Child, Preschool Disease Progression England/epidemiology Human Incidence Infant Male Middle Age *Models, Statistical Morbidity Population Surveillance Recurrence Risk Factors Sensitivity and Specificity Support, Non-U.S. Gov't Time Factors Tuberculosis, Pulmonary/*epidemiology/*transmission Wales/epidemiology PY - 1997 RN - fulltext fulltext_1208 SP - 183-201. ST - The natural history of tuberculosis: the implications of age-dependent risks of disease and the role of reinfection T2 - Epidemiol Infect TI - The natural history of tuberculosis: the implications of age-dependent risks of disease and the role of reinfection UR - C:\users\rw\Papers\Vynnycky, Epi and Inf, 1997.pdfhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808840/pdf/9363017.pdf VL - 119 ID - 2351 ER - TY - JOUR AB - Tuberculosis (TB) was thought to be safely in decline in the United States in the mid-1980s because the number of cases had dropped by 74% between 1953 and 1985. An increase in TB cases was reported, however, in 1986, and an upward trend in TB incidence has continued. The turnaround in TB is well correlated with the rise of the HIV (human immunodeficiency virus) epidemic. The purpose of this work is to investigate, through the use of mathematical models, the magnitude and duration of the effect that the HIV epidemic may have on TB. Models are developed which reflect the transmission dynamics of both TB and HIV, and the relative merits of these models are discussed. The models are then linked together to form a model for the combined spread of both diseases. A numerical study is performed to investigate the influence of certain key parameters. The effect that HIV will have on the general population is found to be dependent on the contact structure between the general population and the HIV risk groups, as well as a possible shift in the dynamics associated with TB transmission. AD - Department of Statistics, University of South Carolina, Columbia 29208, USA. AN - 9198358 AU - West, R. W. AU - Thompson, J. R. DA - Jul 1 DO - S0025556497000011 [pii] DP - Nlm ET - 07/01 KW - AIDS-Related Opportunistic Infections/ epidemiology/transmission Forecasting Humans Models, Statistical Numerical Analysis, Computer-Assisted Population Surveillance Reproducibility of Results Risk Factors Tuberculosis/ epidemiology/transmission United States/epidemiology LA - eng N1 - West, R W Thompson, J R United states Mathematical biosciences Math Biosci. 1997 Jul 1;143(1):35-60. PY - 1997 RN - fulltext fulltext_1208 SN - 0025-5564 (Print) 0025-5564 (Linking) SP - 35-60 ST - Modeling the impact of HIV on the spread of tuberculosis in the United States T2 - Math Biosci TI - Modeling the impact of HIV on the spread of tuberculosis in the United States VL - 143 ID - 2352 ER - TY - JOUR AB - Epidemic control strategies alter the competitive dynamics between drug-sensitive and drug-resistant pathogens. In this paper, we describe and discuss a mathematical model that can be used to understand, and to predict, the effects of epidemic control strategies on both drug-sensitive and drug-resistant Mycobacterium tuberculosis. We begin by briefly reviewing the structure of the model. We then present new analytical results, and show how these results can be used: (i) to predict the epidemiological outcomes of epidemic control strategies an (ii) to design epidemic control strategies. We also include two new factors in our epidemic control models (reinfection and treatment delay); we discuss the epidemiological consequences of these two factors in the design of control strategies. Finally, we conclude with a brief discussion of the implications of our theoretical results for tuberculosis control in light of recently reported results from the WHO's Global Project on Anti-tuberculosis Drug Resistance Surveillance. AD - Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA AN - WOS:000080857400005 AU - Blower, S. AU - Porco, T. AU - Lietman, T. J2 - Innov Appl Math LA - English N1 - Bn14a Times Cited:4 Cited References Count:28 Innovations in Applied Mathematics PY - 1998 SP - 51-72 ST - Tuberculosis: The evolution of antibiotic resistance and the design of epidemic control strategies T2 - Mathematical Models in Medical and Health Science TI - Tuberculosis: The evolution of antibiotic resistance and the design of epidemic control strategies UR - ://WOS:000080857400005 ID - 4830 ER - TY - JOUR AB - The high prevalence of tuberculosis in developing countries and the recent resurgence of tuberculosis in many developed countries suggests that current control strategies are suboptimal. The increase in drug-resistant cases exacerbates the control problems. Currently employed epidemic control strategies are not devised on the basis of a theoretical understanding of the transmission dynamics of Mycobacterium tuberculosis. We describe and discuss a theoretical framework based upon mathematical transmission models that can be used for understanding, predicting, and controlling tuberculosis epidemics. We illustrate how the theoretical framework can be used to predict the temporal dynamics of the emergence of drug resistance, to predict the epidemiological consequences of epidemic control strategies in developing and developed countries, and to design epidemic control strategies. AD - Department of Microbiology and Immunology, University of California San Francisco, 94143, USA. AN - 9725765 AU - Blower, S. M. AU - Gerberding, J. L. DA - Aug DP - Nlm ET - 09/02 KW - Disease Outbreaks Drug Resistance, Microbial Health Policy Humans Models, Biological Mycobacterium tuberculosis Tuberculosis/epidemiology/microbiology/ prevention & control LA - eng N1 - Blower, S M Gerberding, J L Research Support, U.S. Gov't, P.H.S. Review Germany Journal of molecular medicine (Berlin, Germany) J Mol Med (Berl). 1998 Aug;76(9):624-36. PY - 1998 RN - fulltext fulltext_1208 SN - 0946-2716 (Print) 0946-2716 (Linking) SP - 624-36 ST - Understanding, predicting and controlling the emergence of drug-resistant tuberculosis: a theoretical framework T2 - J Mol Med (Berl) TI - Understanding, predicting and controlling the emergence of drug-resistant tuberculosis: a theoretical framework VL - 76 ID - 2353 ER - TY - JOUR AB - This article focuses on the study of an age-structure model for the disease transmission dynamics of tuberculosis in populations that are subjected to a vaccination program. We first show that the infection-free steady state is globally stable if the basic reproductive number R0 is below one, and that an endemic steady state exists when the reproductive number in the presence of vaccine is above one. We then apply the theoretical results to vaccination policies to determine the optimal age or ages at which an individual should be vaccinated. It is shown that the optimal strategies can be either one- or two-age strategies. AD - Biometrics Unit, Cornell University, Ithaca, NY 14853, USA. AN - 9711046 AU - Castillo-Chavez, C. AU - Feng, Z. DA - Aug 1 ET - 08/26 J2 - Mathematical biosciences KW - Age Distribution *BCG Vaccine Health Policy Humans *Models, Biological Prevalence Public Health Tuberculosis/epidemiology/*prevention & control/transmission *Vaccination World Health LA - eng M3 - Research Support, U.S. Gov't, Non-P.H.S. N1 - Castillo-Chavez, C Feng, Z Math Biosci. 1998 Aug 1;151(2):135-54. PY - 1998 RN - fulltext fulltext_1208 SN - 0025-5564 (Print) 0025-5564 (Linking) SP - 135-54 ST - Global stability of an age-structure model for TB and its applications to optimal vaccination strategies T2 - Math Biosci TI - Global stability of an age-structure model for TB and its applications to optimal vaccination strategies UR - http://www.ncbi.nlm.nih.gov/pubmed/9711046http://www.sciencedirect.com/science/article/pii/S0025556498100160 VL - 151 ID - 2354 ER - TY - JOUR AB - BACKGROUND: WHO advocates the use of directly observed treatment with a short-course drug regimen as part of the DOTS strategy, but the potential effect of this strategy worldwide has not been investigated. METHODS: We developed an age-structured mathematical model to explore the characteristics of tuberculosis control under DOTS, and to forecast the effect of improved case finding and cure on tuberculosis epidemics for each of the six WHO regions. FINDINGS: In countries where the incidence of tuberculosis is stable and HIV-1 absent, a control programme that reaches the WHO targets of 70% case detection and 85% cure would reduce the incidence rate by 11% (range 8-12) per year and the death rate by 12% (9-13) per year. If tuberculosis has been in decline for some years, the same case detection and cure rates would have a smaller effect on incidence. DOTS saves a greater proportion of deaths than cases, and this difference is bigger in the presence of HIV-1. HIV-1 epidemics cause an increase in tuberculosis incidence, but do not substantially reduce the preventable proportion of cases and deaths. Without greater effort to control tuberculosis, the annual incidence of the disease is expected to increase by 41% (21-61) between 1998 and 2020 (from 7.4 million to 10.6 million cases per year). Achievement of WHO targets by 2010 would prevent 23% (15-30) or 48 million cases by 2020. INTERPRETATION: The potential effect of chemotherapy (delivered as DOTS) on tuberculosis is greater in many developing countries now than it was in developed countries 50 years ago. To exploit this potential, case detection and cure rates urgently need to be improved in the main endemic areas. AD - Global Tuberculosis Programme, WHO, Geneva, Switzerland. dyec@who.ch AN - 9863786 AU - Dye, C. AU - Garnett, G. P. AU - Sleeman, K. AU - Williams, B. G. DA - Dec 12 DO - S0140673698031997 [pii] DP - Nlm ET - 12/24 KW - Communicable Disease Control Developing Countries Europe/epidemiology HIV Infections/epidemiology Health Priorities Humans Incidence Models, Theoretical Netherlands/epidemiology Sensitivity and Specificity Tuberculosis/epidemiology/ prevention & control World Health Organization L1 - internal-pdf://0321645842/1-s2.0-S0140673698031997-main.pdf LA - eng N1 - Dye, C Garnett, G P Sleeman, K Williams, B G England Lancet Lancet. 1998 Dec 12;352(9144):1886-91. PY - 1998 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0140-6736 (Print) 0140-6736 (Linking) SP - 1886-91 ST - Prospects for worldwide tuberculosis control under the WHO DOTS strategy. Directly observed short-course therapy T2 - Lancet TI - Prospects for worldwide tuberculosis control under the WHO DOTS strategy. Directly observed short-course therapy UR - http://ac.els-cdn.com/S0140673698031997/1-s2.0-S0140673698031997-main.pdf?_tid=28243448b090057ef68206195322d939&acdnat=1345104104_a8557f9be98cd1c666ed199d7693b80f VL - 352 ID - 2355 ER - TY - JOUR AB - OBJECTIVES: To evaluate the relative efficacy of personal respiratory protection as the concentrations of infectious aerosols increase or as room ventilation rates decrease. METHODS: We modified the Wells-Riley mathematical model of airborne transmission of disease by adding a variable for respirator leakage. We modeled three categories of infectiousness using various room ventilation rates and classes of respirators over a 10-hour exposure period. RESULTS: The risk of infection decreases exponentially with increasing room ventilation or with increasing personal respiratory protection. The relative efficacy of personal respiratory protection decreases as room ventilation rates increase or as the concentrations of infectious aerosols decrease. CONCLUSIONS: These modeling data suggest that the risk of occupational tuberculosis probably can be lowered considerably by using relatively simple respirators combined with modest room ventilation rates for the infectious aerosols likely to be present in isolation rooms of newly diagnosed patients. However, more sophisticated respirators may be needed to achieve a comparable risk reduction for exposures to more highly concentrated aerosols, such as may be generated during cough-inducing procedures or autopsies involving infectious patients. There is probably minimal benefit to the use of respirators in well-ventilated isolation rooms with patients receiving appropriate therapy. AD - National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver 80206, USA. fennelly.kevin@njrc.org AN - 9801283 AU - Fennelly, K. P. AU - Nardell, E. A. DA - Oct DP - Nlm ET - 11/04 KW - Air Microbiology Hospitals Humans Infection Control/ standards Occupational Diseases/etiology/ prevention & control Occupational Exposure/ adverse effects Patient Isolation Respiratory Protective Devices/utilization Tuberculosis, Pulmonary/etiology/ prevention & control United States Ventilation LA - eng N1 - Fennelly, K P Nardell, E A U50/CCU810073/PHS HHS/United States Research Support, U.S. Gov't, P.H.S. United states Infection control and hospital epidemiology : the official journal of the Society of Hospital Epidemiologists of America Infect Control Hosp Epidemiol. 1998 Oct;19(10):754-9. PY - 1998 RN - fulltext fulltext_1208 SN - 0899-823X (Print) 0899-823X (Linking) SP - 754-9 ST - The relative efficacy of respirators and room ventilation in preventing occupational tuberculosis T2 - Infect Control Hosp Epidemiol TI - The relative efficacy of respirators and room ventilation in preventing occupational tuberculosis VL - 19 ID - 2356 ER - TY - JOUR AB - Exposure of populations to microbes which share antigens with pathogens can influence the apparent efficacy of vaccines. This may explain the great variation (from below 0 to 80%) observed in protection by Bacillus Calmette Guerin (BCG) against tuberculosis. This paper explores three models for the effect of such heterologous immunity, and demonstrates that: (a) if the immune responses to the microbial antigens in nature and in the vaccines differ qualitatively, there will be no effect on observed efficacy; (b) if the immune responses differ only quantitatively, the observed vaccine efficacy will be reduced, and it will be minimal when vaccine-induced and heterologous protection are of similar magnitude; and (c) if the heterologous exposure can block the vaccine action, then observed efficacy will be reduced and may even appear negative. These results provide important guidance for the interpretation of BCG's utility and for the development and evaluation of new vaccines, in particular against tuberculosis. AD - Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK. pfine@lshtm.ac.uk AN - 9796044 AU - Fine, P. E. AU - Vynnycky, E. KW - Antibodies, Bacterial/biosynthesis Antibodies, Heterophile/biosynthesis Antigens, Heterophile/*immunology BCG Vaccine/*immunology Environmental Exposure Human Models, Biological Mycobacterium/*immunology Support, Non-U.S. Gov't Treatment Outcome Tuberculosis/prevention & control PY - 1998 RN - fulltext fulltext_1208 SP - 1923-8. ST - The effect of heterologous immunity upon the apparent efficacy of (e.g. BCG) vaccines T2 - Vaccine TI - The effect of heterologous immunity upon the apparent efficacy of (e.g. BCG) vaccines UR - http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9796044 VL - 16 ID - 2357 ER - TY - JOUR AB - OBJECTIVES: This study tested the hypothesis, first proposed by Chaussinand, that individual-level immunity acquired from exposure to tuberculosis may have contributed to the disappearance of leprosy from western Europe. METHODS: The epidemiological consequences of cross-immunity were assessed by the formulation of a mathematical model of the transmission dynamics of tuberculosis and leprosy. RESULTS: The conditions under which Mycobacterium tuberculosis could have eradicated Mycobacterium leprae were derived in terms of the basic reproductive rates of the two infections and the degree of cross-immunity. CONCLUSIONS: If the degree of cross-immunity between two diseases within an individual is known, then the epidemiological consequences of this cross-immunity can be assessed with transmission modeling. The results of this analysis, in combination with previous estimates of the basic reproductive rate of tuberculosis and degree of cross-immunity, imply that tuberculosis could have contributed to the decline of leprosy if the basic reproductive rate of leprosy was low. AD - University of California, San Francisco, USA. AN - 9431277 AU - Lietman, T. AU - Porco, T. AU - Blower, S. DA - Dec DP - Nlm ET - 02/07 KW - Cause of Death Comorbidity Cross Reactions Disease Progression Europe Humans Immunity, Active Incidence Leprosy/epidemiology/immunology/transmission Models, Statistical Reproducibility of Results Time Factors Tuberculosis/epidemiology/immunology/transmission LA - eng N1 - Lietman, T Porco, T Blower, S United states American journal of public health Am J Public Health. 1997 Dec;87(12):1923-7. PY - 1998 RN - fulltext fulltext_1208 SN - 0090-0036 (Print) 0090-0036 (Linking) SP - 1923-7 ST - Leprosy and tuberculosis: the epidemiological consequences of cross-immunity T2 - Am J Public Health TI - Leprosy and tuberculosis: the epidemiological consequences of cross-immunity VL - 87 ID - 2344 ER - TY - JOUR AB - SETTING: Patient non-compliance and/or spatial heterogeneity in drug concentration or effectiveness may contribute to the emergence of drug resistance during multiple-drug chemotherapy of tuberculosis. OBJECTIVE: Using mathematical models of mycobacterial population dynamics under antimicrobial treatment, to assess the effects of non-compliance, heterogeneity and other factors on the success of treatment. DESIGN: A mathematical model is used to generate predictions about the ascent of drug resistance in treated hosts with non-compliance and/or a 'protected compartment' of bacteria where only one drug is active; simulations of a more realistic version of this model take into account random mutation, and different assumptions about the size of, and growth rate of bacteria in, the protected compartment. RESULTS: The existence of a protected compartment can increase the likelihood of resistance to the single drug active in that compartment, but only if bacteria resistant to that drug can grow in the protected compartment or if the host is non-adherent to the treatment regimen. However, the protected compartment may also slow the ascent of bacteria resistant to drugs not active in it (e.g. isoniazid) by providing a reservoir of non-selected mycobacteria. The model predicts that relative rates of killing are more important than mutation rates in determining the order in which resistant mutants ascend. Model predictions, in combination with data about drug resistance patterns, suggest that non-compliance, but not heterogeneity, is an important cause of treatment failure. CONCLUSION: Patterns of acquired drug resistance may be used to infer processes of selection during treatment; mathematical models can aid in generating predictions about the relative impacts of treatment parameters in the evolution of resistance, and eventually in suggesting improved treatment protocols. AD - Department of Biology, Emory University, Atlanta, Georgia, USA. lipsitch@biology.emory.edu AN - 9526190 AU - Lipsitch, M. AU - Levin, B. R. DA - Mar DP - Nlm ET - 04/04 KW - Antitubercular Agents/ pharmacology Drug Resistance, Microbial Drug Resistance, Multiple Humans Mathematics Models, Theoretical Mutation Mycobacterium tuberculosis/ drug effects/genetics Population Dynamics Treatment Refusal Tuberculosis/drug therapy L1 - internal-pdf://3214225008/s4.pdf.crdownload LA - eng N1 - Lipsitch, M Levin, B R PY - 1998 RN - fulltext fulltext_1208 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 187-99 ST - Population dynamics of tuberculosis treatment: mathematical models of the roles of non-compliance and bacterial heterogeneity in the evolution of drug resistance T2 - Int J Tuberc Lung Dis TI - Population dynamics of tuberculosis treatment: mathematical models of the roles of non-compliance and bacterial heterogeneity in the evolution of drug resistance VL - 2 ID - 2358 ER - TY - JOUR AB - An epidemiological model of tuberculosis has been developed and applied to five regions of the world. Globally, 6.7 million new cases of tuberculosis and 2.4 million deaths from tuberculosis are estimated for 1998. Based on current trends in uptake of the World Health Organization's strategy of directly observed treatment, short-course, we expect a total of 225 million new cases and 79 million deaths from tuberculosis between 1998 and 2030. Active case-finding by using mass miniature radiography could save 23 million lives over this period. A single contact treatment for tuberculosis could avert 24 million cases and 11 million deaths; combined with active screening, it could reduce mortality by nearly 40%. A new vaccine with 50% efficacy could lower incidence by 36 million cases and mortality by 9 million deaths. Support for major extensions to global tuberculosis control strategies will occur only if the size of the problem and the potential for action are recognized more widely. AD - Center for Population and Development Studies, Harvard School of Public Health, 9 Bow Street, Cambridge, MA 02138, USA. AN - 9811895 AU - Murray, C. J. AU - Salomon, J. A. DA - Nov 10 DP - Nlm ET - 11/13 KW - Communicable Disease Control Humans Models, Biological Models, Theoretical Tuberculosis/ epidemiology/ prevention & control World Health Organization LA - eng N1 - Murray, C J Salomon, J A United states Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13881-6. PY - 1998 RN - fulltext fulltext_1208 SN - 0027-8424 (Print) 0027-8424 (Linking) SP - 13881-6 ST - Modeling the impact of global tuberculosis control strategies T2 - Proc Natl Acad Sci U S A TI - Modeling the impact of global tuberculosis control strategies UR - http://www.pnas.org/content/95/23/13881.full.pdf VL - 95 ID - 2359 ER - TY - JOUR AD - Harvard Center for Population and Development Studies, Cambridge, Massachusetts 02138, USA. AN - 9755959 AU - Murray, C. J. AU - Salomon, J. A. DA - Sep ET - 10/02 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Cost-Benefit Analysis Humans Models, Theoretical Tuberculosis, Pulmonary/epidemiology/*prevention & control World Health *World Health Organization LA - eng N1 - Murray, C J Salomon, J A FRANCE Int J Tuberc Lung Dis. 1998 Sep;2(9 Suppl 1):S9-15. PY - 1998 RN - fulltext fulltext_1208 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - S9-15 ST - Expanding the WHO tuberculosis control strategy: rethinking the role of active case-finding T2 - Int J Tuberc Lung Dis TI - Expanding the WHO tuberculosis control strategy: rethinking the role of active case-finding UR - http://www.ncbi.nlm.nih.gov/pubmed/9755959 VL - 2 ID - 2360 ER - TY - JOUR AB - A hypothetical cohort of 25,000 TB patients and their contacts were followed for a 10-year period; rates of treatment default, infectiousness following partial treatment, relapse, hospitalization, and development of drug-resistant TB were included. The average cost per case cured was $16,846 with 15% of patients starting DOT, $17,323 with 100% starting DOT, and $20,106 with none starting DOT. The incremental cost per additional case cured was $24,064 when all patients, started treatment on DOT, indicating that outpatient DOT provides a cost-effective method of improving health outcomes for TB patients and their contacts while controlling direct costs. AD - MEDTAP International, Bethesda, MD, USA. AN - 10186738 AU - Palmer, C. S. AU - Miller, B. AU - Halpern, M. T. AU - Geiter, L. J. DA - May ET - 04/07 KW - Adult Ambulatory Care/*economics Bias (Epidemiology) Cost-Benefit Analysis *Decision Support Techniques Health Care Costs/*statistics & numerical data Health Services Research Humans Observation/*methods Outcome Assessment (Health Care) *Patient Compliance/psychology *Professional-Patient Relations Sensitivity and Specificity Treatment Failure Tuberculosis/*drug therapy/*economics/psychology United States L1 - internal-pdf://1171538998/Palmer-1998-A model of the cost-effectiveness.pdf LA - eng N1 - Palmer, C S Miller, B Halpern, M T Geiter, L J Comparative Study Research Support, U.S. Gov't, P.H.S. United states Journal of public health management and practice : JPHMP J Public Health Manag Pract. 1998 May;4(3):1-13. PY - 1998 RN - fulltext fulltext_1208 SN - 1078-4659 (Print) 1078-4659 (Linking) SP - 1-13 ST - A model of the cost-effectiveness of directly observed therapy for treatment of tuberculosis T2 - J Public Health Manag Pract TI - A model of the cost-effectiveness of directly observed therapy for treatment of tuberculosis UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10186738 VL - 4 ID - 2361 ER - TY - JOUR AB - Previously we have formulated transmission models of untreated tuberculosis epidemics (Blower et al., Nature, Medicine 1 (1995), 815-821); in this paper, we present time-dependent uncertainty and sensitivity analyses in order to quantitatively understand the transmission dynamics of tuberculosis epidemics in the absence of treatment. The time-dependent uncertainty analysis enabled us to evaluate the variability in the epidemiological outcome variables of the model during the progression of a tuberculosis epidemic. Calculated values (from the uncertainty analysis) for the disease incidence, disease prevalence, and mortality rates were approximately consistent with historical data. The time-dependent sensitivity analysis revealed that only a few of the model's input parameters significantly affected the severity of a tuberculosis epidemic; these parameters were the disease reactivation rate, the fraction of infected individuals who develop tuberculosis soon after infection, the number of individuals that an infectious individual infects per year, the disease death rate, and the population recruitment rate. Our analysis demonstrates that it is possible to improve our understanding of the behavior of tuberculosis epidemics by applying time-dependent uncertainty and sensitivity analysis to a transmission model. AD - San Francisco Department of Public Health, 25 Van Ness Avenue, Suite 710, San Francisco, California, 94102, USA. travis_porco@dph.sf.ca.us AU - Porco, T. C. AU - Blower, S. M. DO - 10.1006/tpbi.1998.1366 KW - Disease Outbreaks/statistics & numerical data Humans Incidence Models, Biological Prevalence Sensitivity and Specificity Tuberculosis/epidemiology/mortality/transmission N1 - LR: 20071114; CI: Copyright 1998; GR: 1R29DA08153/DA/NIDA NIH HHS/United States; GR: AI33831/AI/NIAID NIH HHS/United States; JID: 0256422; ppublish PY - 1998 RN - fulltext fulltext_1208 SN - 0040-5809; 0040-5809 SP - 117-132 ST - Quantifying the intrinsic transmission dynamics of tuberculosis T2 - Theoretical population biology TI - Quantifying the intrinsic transmission dynamics of tuberculosis VL - 54 Y2 - Oct ID - 2362 ER - TY - JOUR AB - SETTING: A major out-patient tuberculosis clinic in Nairobi, Kenya. OBJECTIVE: To ascertain the cost-effectiveness of the polymerase chain reaction (PCR) for the diagnosis of tuberculosis in an urban setting in a developing country. DESIGN: A cost-effectiveness analysis of PCR and direct smear microscopy examination based on theoretical modelling. The cost-effectiveness was expressed in costs per correctly diagnosed tuberculosis patient for each of the two diagnostic techniques. Data were obtained from the literature, from the staff and the register at the health facility and from structured interviews with patients. Assumptions were made when no data were available. RESULTS: The PCR is expected to be more specific and sensitive than the routine procedure for diagnosis, but it is also more costly. The routine procedure based on direct smear microscopy turned out to be 1.8 times as cost-effective as PCR. CONCLUSION: It is concluded that the PCR method can potentially be a cost-effective screening procedure for tuberculosis, provided that the largest contributing cost component, the costs of the PCR-kit, can be reduced substantially. AD - Royal Tropical Institute, The Netherlands. AN - 9526197 AU - Roos, B. R. AU - van Cleeff, M. R. AU - Githui, W. A. AU - Kivihya-Ndugga, L. AU - Odhiambo, J. A. AU - Kibuga, D. K. AU - Klatser, P. R. DA - Mar DP - Nlm ET - 04/04 KW - Bacteriological Techniques/economics Cost-Benefit Analysis Humans Kenya Models, Theoretical Polymerase Chain Reaction/ economics Sensitivity and Specificity Sputum/ microbiology Tuberculosis, Pulmonary/ diagnosis LA - eng N1 - Roos, B R van Cleeff, M R Githui, W A Kivihya-Ndugga, L Odhiambo, J A Kibuga, D K Klatser, P R Comparative Study Research Support, Non-U.S. Gov't France The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Int J Tuberc Lung Dis. 1998 Mar;2(3):235-41. PY - 1998 RN - fulltext fulltext_1208 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 235-41 ST - Cost-effectiveness of the polymerase chain reaction versus smear examination for the diagnosis of tuberculosis in Kenya: a theoretical model T2 - Int J Tuberc Lung Dis TI - Cost-effectiveness of the polymerase chain reaction versus smear examination for the diagnosis of tuberculosis in Kenya: a theoretical model VL - 2 ID - 2363 ER - TY - JOUR AB - BACKGROUND: Isoniazid prophylaxis for 12 months effectively prevents tuberculosis in HIV-infected persons and may decrease the incidence of other HIV-related disease and mortality. Recent clinical trials have found that some short-course regimens also effectively prevent tuberculosis. OBJECTIVE: To compare the benefits, risks, and cost-effectiveness of isoniazid prophylaxis and short-course prophylaxis regimens. DESIGN: Decision and cost-effectiveness analysis. SETTING: United States. PATIENTS: Hypothetical patients who are HIV-infected and have CD4 counts of 200 cells/mm3 or less and positive results on tuberculin skin tests. INTERVENTIONS: Isoniazid prophylaxis lasting 12 months and six short-course prophylaxis regimens of isoniazid, rifampin, and pyrazinamide alone or in combination. MEASUREMENTS: 5-year survival rate, life expectancy, lifetime incidence of tuberculosis, and cost per quality-adjusted life-year saved. RESULTS: Compared with no prophylaxis, the 12-month isoniazid regimen increased 5-year survival rates by 9% and life expectancy by 8.7 months, decreased incidence of tuberculosis by 27%, and saved 4 medical care dollars for every 1 spent on prophylaxis. Regimens of isoniazid for 6 months, isoniazid and rifampin for 3 months, and rifampin and pyrazinamide for 2 months had similar results: 6.2- to 8.6-month increases in life expectancy, 19% to 26% reductions in incidence of tuberculosis, and 1 to 7 medical care dollars saved for every 1 spent on prophylaxis. A 3-month regimen of isoniazid, rifampin, and pyrazinamide resulted in fewer clinical benefits and was the only regimen tested that did not save medical care dollars. CONCLUSIONS: Prophylaxis decreases the incidence of tuberculosis and increases life expectancy for HIV-infected patients. Some regimens save medical care dollars, and some short-course regimens have clinical and economic benefits similar to those of the 12-month isoniazid regimen. Short-course prophylaxis is a reasonable alternative to the 12-month isoniazid regimen. AD - Long Island Jewish Medical Center, New Hyde Park, New York 11042, USA. AN - 9841583 AU - Rose, D. N. DA - Nov 15 ET - 12/05 KW - AIDS-Related Opportunistic Infections/*prevention & control Antibiotics, Antitubercular/administration & dosage Antitubercular Agents/*administration & dosage/adverse effects/economics Cost-Benefit Analysis Decision Trees Drug Administration Schedule Drug Therapy, Combination Drug-Induced Liver Injury/etiology Humans Isoniazid/*administration & dosage/adverse effects/economics Pyrazinamide/administration & dosage Quality-Adjusted Life Years Rifampin/administration & dosage Survival Rate Tuberculosis/*prevention & control LA - eng N1 - Rose, D N United states Annals of internal medicine Ann Intern Med. 1998 Nov 15;129(10):779-86. PY - 1998 RN - fulltext fulltext_1208 SN - 0003-4819 (Print) 0003-4819 (Linking) SP - 779-86 ST - Short-course prophylaxis against tuberculosis in HIV-infected persons. A decision and cost-effectiveness analysis T2 - Ann Intern Med TI - Short-course prophylaxis against tuberculosis in HIV-infected persons. A decision and cost-effectiveness analysis UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9841583http://annals.org/data/Journals/AIM/19920/0000605-199811150-00005.pdf VL - 129 ID - 2364 ER - TY - JOUR AB - The authors used epidemiologic data on tuberculosis to construct a model for the time delay from initial latent infection to active disease, when infection transmission occurs. They used case rate tables in the United States to calculate the fractional rate of change per annum (A) in the incidence of active tuberculosis. They then derived estimates for the effective reproductive number (R) and the cumulative transmission, defined as the number of people whom one infected person will infect in his or her lifetime and over many multiple successive transmissions, respectively. For A of -4 percent per year, the average US condition from 1930 to 1995, they estimate the reproductive number to be about 0.55 and the cumulative transmission to be about 1.2. The estimated rate of the new latent infections in the United States is 80,000 per year, the estimated prevalence of latent infections is 5 percent, and the number of transmissions of infection per active case is 3.5. From the model, the authors predicted active case rates in various age groups and compared them with published tables. The comparison suggests that the risk of activation decreases rapidly, then gradually, for the first 10 years after initial infection; the risk is relatively constant from 10 to 40 years and may decrease again after 40 years. The authors also discuss how this model can be used to help make decisions about tuberculosis control measures in the population. AD - Center for Radiophysics and Space Research, Cornell University, Ithaca, NY 14853, USA. AN - 9508108 AU - Salpeter, E. E. AU - Salpeter, S. R. DA - Feb 15 DP - Nlm ET - 03/21 KW - Age Distribution Humans Incidence Models, Theoretical Prevalence Prospective Studies Retrospective Studies Tuberculosis/ epidemiology/transmission United States/epidemiology LA - eng N1 - Salpeter, E E Salpeter, S R Research Support, Non-U.S. Gov't United states American journal of epidemiology Am J Epidemiol. 1998 Feb 15;147(4):398-406. PY - 1998 RN - fulltext fulltext_1208 SN - 0002-9262 (Print) 0002-9262 (Linking) SP - 398-406 ST - Mathematical model for the epidemiology of tuberculosis, with estimates of the reproductive number and infection-delay function T2 - Am J Epidemiol TI - Mathematical model for the epidemiology of tuberculosis, with estimates of the reproductive number and infection-delay function UR - http://aje.oxfordjournals.org/content/147/4/398.full.pdf VL - 147 ID - 2365 ER - TY - JOUR AU - Sawert, H. AU - Girardi, E. AU - Antonucci, G. AU - Raviglione, M. C. AU - Viale, P. AU - Ippolito, G. DA - 1998 KW - Antitubercular Agents/*economics/therapeutic use AIDS-Related Opportunistic Infections/*economics/microbiology/*prevention & control Cost-Benefit Analysis Human Isoniazid/*economics/therapeutic use Italy Life Expectancy Patient Compliance Prospective Studies Quality-Adjusted Life Years Support,Non-U.S.Gov't Survival Analysis Tuberculosis/*economics/etiology/*prevention & control LB - 451 N1 - RefMgr field[1]: Journal RefMgr field[8]: Not in File PY - 1998 RN - fulltext fulltext_1208 SP - 2112-2121 ST - Preventive therapy for tuberculosis in HIV-infected persons: analysis of policy options based on tuberculin status and CD4+ cell count. Gruppo Italiano di Studio Tubercolosi e AIDS (GISTA) T2 - Archives of Internal Medicine TI - Preventive therapy for tuberculosis in HIV-infected persons: analysis of policy options based on tuberculin status and CD4+ cell count. Gruppo Italiano di Studio Tubercolosi e AIDS (GISTA) UR - http://archinte.jamanetwork.com/article.aspx?articleid=210066 VL - 158 ID - 2366 ER - TY - JOUR AB - SETTING: England and Wales. OBJECTIVE: To estimate the magnitude and trend in the annual risk of infection with Mycobacterium tuberculosis in England and Wales since 1901. DESIGN: Estimates for the prechemotherapy era are derived assuming that 1% of new infections among 0-4 year olds led to fatal tuberculosis meningitis, as found in the Netherlands. The estimates are validated against data from the 1949-1950 national tuberculin survey. We explore the trend thereafter using tuberculous meningitis notifications and data from the 1971-1973 national tuberculin survey, and discuss the utility of data collected under the national bacille Calmette-Guerin (BCG) vaccination scheme for estimating the annual risk of infection. RESULTS: Tuberculosis meningitis mortality rates among 0-4 year olds declined at 4% per annum until 1950, and suggest that the annual risk of infection declined from 12% in 1901 to 1.9% in 1949. The decline in the annual risk of infection probably accelerated in 1950, although its magnitude cannot be determined accurately. CONCLUSION: An accelerated decline in the annual risk of infection in England and Wales from 1950 probably resulted from the introduction of chemotherapy, which dramatically reduced the prevalence of sources of infection in the population. Data collected during the national BCG vaccination scheme were found to be unsuitable for estimating infection risks. AD - Department of Epidemiology and Population Sciences, London School of Hygiene and Tropical Medicine, UK. AN - 9441091 AU - Vynnycky, E. AU - Fine, P. E. DA - Oct ET - 01/24 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Adolescent Age Distribution BCG Vaccine/*administration & dosage Child Child, Preschool Data Collection England/epidemiology Female Humans Incidence Infant Male Mycobacterium tuberculosis/*immunology Risk Factors Sex Distribution Survival Rate Tuberculin/diagnostic use Tuberculosis, Meningeal/diagnosis/*epidemiology/*prevention & control Wales/epidemiology LA - eng M3 - Research Support, Non-U.S. Gov't N1 - Vynnycky, E Fine, P E FRANCE Int J Tuberc Lung Dis. 1997 Oct;1(5):389-96. PY - 1998 RN - fulltext fulltext_1208 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 389-96 ST - The annual risk of infection with Mycobacterium tuberculosis in England and Wales since 1901 T2 - Int J Tuberc Lung Dis TI - The annual risk of infection with Mycobacterium tuberculosis in England and Wales since 1901 UR - http://www.ncbi.nlm.nih.gov/pubmed/9441091 VL - 1 ID - 2350 ER - TY - JOUR AB - The net and basic reproduction numbers are among the most widely-applied concepts in infectious disease epidemiology. A net reproduction number (the average number of secondary infectious cases resulting from each case in a given population) of above 1 is conventionally associated with an increase in incidence; the basic reproduction number (defined analogously for a 'totally susceptible' population) provides a standard measure of the 'transmission potential' of an infection. Using a model of the epidemiology of tuberculosis in England and Wales since 1900, we demonstrate that these measures are difficult to apply if disease can follow reinfection, and that they lose their conventional interpretations if important epidemiological parameters, such as the rate of contact between individuals, change over the time interval between successive cases in a chain of transmission (the serial interval). The net reproduction number for tuberculosis in England and Wales appears to have been approximately 1 from 1900 until 1950, despite concurrent declines in morbidity and mortality rates, and it declined rapidly in the second half of this century. The basic reproduction number declined from about 3 in 1900, reached 2 by 1950, and first fell below 1 in about 1960. Reductions in effective contact between individuals over this period, measured in terms of the average number of individuals to whom each case could transmit the infection, meant that the conventional basic reproduction number measure (which does not consider subsequent changes in epidemiological parameters) for a given year failed to reflect the 'actual transmission potential' of the infection. This latter property is better described by a variant of the conventional measure which takes secular trends in contact into account. These results are relevant for the interpretation of trends in any infectious disease for which epidemiological parameters change over time periods comparable to the infectious period, incubation period or serial interval. AD - Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, England. AN - 9825782 AU - Vynnycky, E. AU - Fine, P. E. DA - Oct ET - 11/24 J2 - Epidemiology and infection KW - Adolescent Adult Aged Child Child, Preschool Disease Susceptibility/*epidemiology Disease Transmission, Infectious/statistics & numerical data England/epidemiology Epidemiologic Methods Female Humans Infant Infant, Newborn Male Middle Aged Risk Factors Time Factors Tuberculosis/*epidemiology Wales/epidemiology LA - eng M3 - Research Support, Non-U.S. Gov't N1 - Vynnycky, E Fine, P E ENGLAND Epidemiol Infect. 1998 Oct;121(2):309-24. PY - 1998 RN - fulltext fulltext_1208 SN - 0950-2688 (Print) 0950-2688 (Linking) SP - 309-24 ST - The long-term dynamics of tuberculosis and other diseases with long serial intervals: implications of and for changing reproduction numbers T2 - Epidemiol Infect TI - The long-term dynamics of tuberculosis and other diseases with long serial intervals: implications of and for changing reproduction numbers UR - http://www.ncbi.nlm.nih.gov/pubmed/9825782 VL - 121 ID - 2367 ER - TY - JOUR AU - Bell, J. C. AU - Rose, D. N. AU - Sacks, H. S. DA - 1999 KW - Africa control cost effectiveness HIV interventions NTP preventive therapy tuberculosis Preventive Therapy TB and HIV LB - 6488 N1 - TY - JOUR TB Intervention strategies Preventive chemotherapy No sub-heading PY - 1999 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SP - 1549-1556 ST - Tuberculosis preventive therapy for HIV-infected people in sub-Saharan Africa is cost-effective T2 - AIDS TI - Tuberculosis preventive therapy for HIV-infected people in sub-Saharan Africa is cost-effective UR - http://graphics.tx.ovid.com/ovftpdfs/FPDDNCDCLFEDDD00/fs046/ovft/live/gv023/00002030/00002030-199908200-00016.pdf VL - 13 ID - 2368 ER - TY - JOUR AB - The availability of DNA fingerprinting techniques for Mycobacterium tuberculosis has led to attempts to estimate the extent of recent transmission in populations, using the assumption that groups of tuberculosis patients with identical isolates ("clusters") are likely to reflect recently acquired infections. It is never possible to include all cases of tuberculosis in a given population in a study, and the proportion of isolates found to be clustered will depend on the completeness of the sampling. Using stochastic simulation models based on real and hypothetical populations, the authors demonstrate the influence of incomplete sampling on the estimates of clustering obtained. The results show that as the sampling fraction increases, the proportion of isolates identified as clustered also increases and the variance of the estimated proportion clustered decreases. Cluster size is also important: the underestimation of clustering for any given sampling fraction is greater, and the variability in the results obtained is larger, for populations with small clusters than for those with the same number of individuals arranged in large clusters. A considerable amount of caution should be used in interpreting the results of studies on clustering of M. tuberculosis isolates, particularly when sampling fractions are small. AD - Infectious Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, England, United Kingdom. AN - 10025480 AU - Glynn, J. R. AU - Vynnycky, E. AU - Fine, P. E. DA - Feb 15 ET - 02/20 J2 - American journal of epidemiology KW - Bias (Epidemiology) Cluster Analysis *DNA Fingerprinting Epidemiologic Methods Humans Models, Statistical Mycobacterium tuberculosis/*genetics Sampling Studies San Francisco South Africa Stochastic Processes Tuberculosis, Pulmonary/*transmission LA - eng M3 - Research Support, Non-U.S. Gov't N1 - Glynn, J R Vynnycky, E Fine, P E Am J Epidemiol. 1999 Feb 15;149(4):366-71. PY - 1999 RN - fulltext fulltext_1208 SN - 0002-9262 (Print) 0002-9262 (Linking) SP - 366-71 ST - Influence of sampling on estimates of clustering and recent transmission of Mycobacterium tuberculosis derived from DNA fingerprinting techniques T2 - Am J Epidemiol TI - Influence of sampling on estimates of clustering and recent transmission of Mycobacterium tuberculosis derived from DNA fingerprinting techniques UR - http://www.ncbi.nlm.nih.gov/pubmed/10025480http://aje.oxfordjournals.org/content/149/4/366.full.pdf VL - 149 ID - 2369 ER - TY - JOUR AB - Since 1985, there has been a renewed epidemic of tuberculosis (TB) that was previously thought to be in check. There is evidence to believe the main factor for this resurgence has been the human immunodeficiency virus (HIV). Co-infection with HIV and M. Tuberculosis has profound implications for the course of both diseases. This study represents a first attempt to understand how the introduction of an opportunistic infection, namely Mycobacterium tuberculosis, the bacteria that causes TB, affects the dynamic interaction of HIV-1 and the immune system. We create a mathematical model using ordinary differential equations to describe the interaction of HIV and TB with the immune system. It is known that infection with TB can decrease the CD4(+) T cell counts-a key marker of AIDS progression; thus, it shortens survival in HIV infected individuals. Another main marker for HIV progression is the viral load. If this load is increased due to the presence of opportunistic infections, the disease progression is much more rapid. We also explore the effects of drug treatment on the TB infection in the doubly-infected patient. AD - Department of Microbiology and Immunology, The University of Michigan Medical School, 6730 Medical Science Building II, Ann Arbor, Michigan, 48109-0620, USA. AN - 9925811 AU - Kirschner, D. DA - Feb DO - S0040-5809(98)91382-X [pii] 10.1006/tpbi.1998.1382 [doi] DP - Nlm ET - 02/02 KW - AIDS-Related Opportunistic Infections/ immunology/mortality CD4 Lymphocyte Count Disease Progression HIV-1/ immunology Humans Macrophages/immunology Models, Immunological Models, Theoretical Mycobacterium tuberculosis/ immunology Survival Rate Tuberculosis, Pulmonary/ immunology/mortality Viral Load LA - eng N1 - Kirschner, D United states Theoretical population biology Theor Popul Biol. 1999 Feb;55(1):94-109. PY - 1999 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0040-5809 (Print) 0040-5809 (Linking) SP - 94-109 ST - Dynamics of co-infection with M. Tuberculosis and HIV-1 T2 - Theor Popul Biol TI - Dynamics of co-infection with M. Tuberculosis and HIV-1 UR - http://ac.els-cdn.com/S004058099891382X/1-s2.0-S004058099891382X-main.pdf?_tid=189b89f5729a64420cd0d53151ea421c&acdnat=1345012541_8bb51f37ee63fbdd230b9d23f406634c VL - 55 ID - 2370 ER - TY - JOUR AU - Marchand, R. AU - Tousignant, P. AU - Chang, H. DA - 1999 J2 - Int.J.Epidemiol. KW - case-finding cost effectiveness elderly infection institutions screening tuberculin testing tuberculosis LB - 9035 N1 - TY - JOUR TB Tuberculosis control Case-finding No sub-heading PY - 1999 RN - fulltext fulltext_1208 SP - 563-570 ST - Cost-effectiveness of screening compared to case-finding approaches to tuberculosis in long-term care facilities for the elderly T2 - International Journal of Epidemiology TI - Cost-effectiveness of screening compared to case-finding approaches to tuberculosis in long-term care facilities for the elderly VL - 28 ID - 2371 ER - TY - JOUR AB - We assessed the direct and indirect economic costs and benefits of the current policy of revaccinating tuberculin-negative schoolchildren in the Czech Republic. The analysis is conducted from the perspective of the payer for health care. In considering whether revaccination should be discontinued, we consistently made assumptions which tend to favor revaccination. The direct costs of revaccination are estimated at Czech Koruna (KCR) 15.0 million (US$0.46 million) annually. The direct benefits are the treatment costs saved for future cases averted by revaccination. These range from KCR 0.5 million (US$0.015 million, ambulatory care, excluding transmission benefits) to KCR 13.7 million (US$0.4 million, hospitalization, including transmission benefits). Costs exceed benefits even if children are revaccinated without prior tuberculin testing. The major indirect cost is the loss of work output attributable to tuberculosis morbidity. Counting the averted loss in output as a benefit does not change the results qualitatively, although there is a 50% chance that the benefits will be greater than costs if treatment continues to be hospital-based. Thus, the costs of revaccination in the Czech Republic are found to exceed benefits over most, plausible variations in parameter values. The cost-benefit ratio is especially large if patients are given ambulatory treatment, as recommended by the World Health Organization. AD - Department of Health Systems, World Health Organization, Geneva, Switzerland. AN - 10217591 AU - Pathania, V. S. AU - Trnka, L. AU - Krejbich, F. AU - Dye, C. DA - Apr 9 KW - Ambulatory Care/economics BCG Vaccine/*economics/immunology Child Cohort Studies Cost of Illness Cost-Benefit Analysis Czech Republic/epidemiology Health Care Costs Hospitalization/economics Human Immunization Schedule Incidence Insurance, Health/economics Life Expectancy Multivariate Analysis Time Factors Treatment Outcome Tuberculin Test/economics Tuberculosis/economics/epidemiology/immunology/*prevention & control Vaccination/*economics World Health Organization N1 - 99231943 0264-410x Journal Article PY - 1999 RN - fulltext fulltext_1208 SP - 1926-1935 ST - A cost-benefit analysis of BCG revaccination in the Czech Republic T2 - Vaccine TI - A cost-benefit analysis of BCG revaccination in the Czech Republic UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10217591 VL - 17 ID - 2372 ER - TY - JOUR AB - To determine the incremental cost of directly observed therapy (DOT) for patients with tuberculosis at low risk for treatment default, we applied a model of DOT effectiveness to 1,377 low-risk patients in California during 1995. The default rate for this cohort, which consisted of those with no recent history of substance abuse, homelessness, or incarceration, was 1.7%. The model predicted that DOT and self-administered therapy (SAT) cured 93.1 and 90.8% of these patients, respectively. DOT would initially cost $1.83 million more than SAT, but avert $569,191 in treatment cost for relapse cases and their contacts, for a net incremental cost of $1.27 million ($919 per patient treated), or $40,620 per additional case cured. The cost-effectiveness of DOT was sensitive to the default rate and relapse rate after completing SAT. DOT would generate cost savings only when the default and relapse rates were more than 32.2 and 9.2%, respectively. Given the low default rate and resulting high incremental cost of DOT, provision of DOT to low-risk patients in California should be evaluated in the context of resource availability, competing program priorities, and program success in completing self-administered therapy with a low relapse rate. AD - California Department of Health Services, Tuberculosis Control Branch, Berkeley, CA, USA. AN - 10430732 AU - Snyder, D. C. AU - Chin, D. P. DA - Aug ET - 08/03 KW - Adult Antitubercular Agents/*economics/therapeutic use California Cost-Benefit Analysis Female Health Resources/economics Humans Male Outcome and Process Assessment (Health Care) *Patient Compliance Patient Dropouts Recurrence Risk Self Administration/economics Tuberculosis, Pulmonary/drug therapy/*economics LA - eng N1 - Snyder, D C Chin, D P Comparative Study United states American journal of respiratory and critical care medicine Am J Respir Crit Care Med. 1999 Aug;160(2):582-6. PY - 1999 RN - fulltext fulltext_1208 SN - 1073-449X (Print) 1073-449X (Linking) SP - 582-6 ST - Cost-effectiveness analysis of directly observed therapy for patients with tuberculosis at low risk for treatment default T2 - Am J Respir Crit Care Med TI - Cost-effectiveness analysis of directly observed therapy for patients with tuberculosis at low risk for treatment default UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10430732 VL - 160 ID - 2373 ER - TY - JOUR AU - Snyder, D. C. AU - Paz, E. A. AU - Mohle-Boetani, J. C. AU - Fallstad, R. AU - Black, R. L. AU - Chin, D. P. DA - 1999 J2 - Am.J.Respir.Crit.Care Med. KW - cost effectiveness effectiveness interventions methadone prevention preventive therapy screening substance abuse tuberculosis LB - 6572 N1 - TY - JOUR TB Intervention strategies Preventive chemotherapy No sub-heading PY - 1999 RN - fulltext fulltext_1208 SP - 178-185 ST - Tuberculosis prevention in methadone maintenance clinics. Effectiveness and cost-effectiveness TI - Tuberculosis prevention in methadone maintenance clinics. Effectiveness and cost-effectiveness VL - 160 ID - 2374 ER - TY - JOUR AB - BACKGROUND: The dramatic decline in tuberculosis (TB) in developed countries during the past century has been attributed to many factors, including improvements in living and social conditions and, more recently, effective treatment. Each of these changes should have reduced the average number of individuals 'effectively contacted' (i.e. sufficiently to transmit infection) by each infectious TB case. METHOD: Estimates of the average number of individuals effectively contacted by each infectious TB case, for each year since 1900 in England and Wales, are derived as the ratio between published estimates of the annual risk of infection and estimates of the prevalence of infectious cases, as derived using a published model of the epidemiology of TB. RESULTS: The results suggest that each infectious case contacted, on average, about 22 individuals in 1900 sufficiently to transmit Mycobacterium tuberculosis infection, and that this number declined to about 10 by 1950 and to approximately one by 1990. CONCLUSIONS: Although several factors contributed to the decline in TB in developed countries during this century, a major contributor has been the decline in the number of effective contacts by each case over time. Similar declines have doubtless occurred over the past century for many infections in developed countries. AD - Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, UK. AN - 10342699 AU - Vynnycky, E. AU - Fine, P. E. DA - Apr ET - 05/26 J2 - International journal of epidemiology KW - Adolescent Adult Age Distribution Aged Child Child, Preschool Contact Tracing/*trends Disease Transmission, Infectious/*prevention & control Female Great Britain/epidemiology Humans Male Middle Aged Models, Statistical Population Surveillance Prevalence Reproducibility of Results Risk Factors Sex Distribution Survival Rate Tuberculosis, Pulmonary/*epidemiology/*transmission LA - eng M3 - Research Support, Non-U.S. Gov't N1 - Vynnycky, E Fine, P E ENGLAND Int J Epidemiol. 1999 Apr;28(2):327-34. PY - 1999 RN - fulltext fulltext_1208 SN - 0300-5771 (Print) 0300-5771 (Linking) SP - 327-34 ST - Interpreting the decline in tuberculosis: the role of secular trends in effective contact T2 - Int J Epidemiol TI - Interpreting the decline in tuberculosis: the role of secular trends in effective contact UR - http://www.ncbi.nlm.nih.gov/pubmed/10342699http://ije.oxfordjournals.org/content/28/2/327.full.pdf VL - 28 ID - 2375 ER - TY - JOUR AB - Adherence to therapy in patients with tuberculosis (TB) is a major determinant of their outcomes. Unfortunately, there are no currently known predictors of adherence, given that this phenomenon represents a complex, task-specific behavior. Notwithstanding criticisms from civil liberty advocates, directly observed therapy (DOT), facilitated by education, holistic care, enablers and incentives, is still the best strategy to ensure patient adherence to treatment. To enhance delivery of DOT, short-course chemotherapy (SCC) must be strongly advocated. Monitoring of patient progress, dependable drug supply, and adequate programme funding are other important elements of the entire strategy. Indeed, since the global resurgence of TB and associated rampant drug resistance in the 1990s, directly observed therapy, short-course (DOTS) has now become the WHO strategy for effective TB control. Data obtained so far in different continents worldwide have underscored the unrivalled efficacy of DOTS in ensuring treatment success and preventing development of acquired drug resistance. The recent WHO/International Union against Tuberculosis and Lung Disease (IUATLD) global project on anti-TB drug resistance surveillance has also revealed that countries in which >33-90% of the population has access to the WHO DOTS strategy have, as a group, lower levels of drug resistance: primary multidrug-resistant (MDR) (1.4%; median) and acquired MDR index (0. 6; median). The use of SCC was also inversely associated with the prevalence of combined resistance to any drug. Countries with MDR rates >2% reported using SCC in a median of 70% of their patients, compared with 100% in countries with MDR rates <2% (WHO/TB/97.229). Despite greater initial cost, DOTS is a more cost-effective strategy than self-administered therapy because it decreases the re-treatment costs associated with therapy failure and acquired drug resistance. Finally, in addition to harnessing the complementary roles of a national tuberculosis programme and community participation, DOTS might be further enhanced by the use of newly developed drugs with a long duration of action or more potent bactericidal and sterilizing activities. AD - Tuberculosis and Chest Unit, Grantham Hospital, Hong Kong, China. AN - 10449895 AU - Yew, W. W. DO - 48479 DP - Nlm ET - 08/18 J2 - Chemotherapy KW - Antitubercular Agents/ administration & dosage Drug Administration Schedule Humans International Cooperation Monitoring, Physiologic Patient Advocacy Patient Compliance Physician-Patient Relations Tuberculosis, Multidrug-Resistant/ drug therapy/prevention & control Tuberculosis, Pulmonary/ drug therapy/prevention & control World Health LA - eng N1 - Yew, W W Switzerland Chemotherapy. 1999;45 Suppl 2:26-33. PY - 1999 RN - fulltext fulltext_1208 SN - 0009-3157 (Print) 0009-3157 (Linking) SP - 26-33 ST - Directly observed therapy, short-course: the best way to prevent multidrug-resistant tuberculosis T2 - Chemotherapy TI - Directly observed therapy, short-course: the best way to prevent multidrug-resistant tuberculosis VL - 45 Suppl 2 ID - 2376 ER - TY - JOUR AU - Aparicio, J. P. AU - Capurro, A. F. AU - Castillo-Chavez, C. DA - 2000 KW - airborne contacts infection models transmission tuberculosis LB - 8135 N1 - TY - JOUR TB Transmission, pathogenesis, and epidemiology Infection with tubercle bacilli Etiol epi: RF for infection Transmission - airborne PY - 2000 RN - fulltext fulltext_1208 SP - 327-341 ST - Transmission and dynamics of tuberculosis on generalized households T2 - J.Theor.Biol. TI - Transmission and dynamics of tuberculosis on generalized households VL - 206 ID - 2377 ER - TY - JOUR AB - SETTING: From 1958 to 1978, Baltimore maintained one of the highest pulmonary tuberculosis (TB) rates in the US. But, from 1978 to 1992 its TB rate declined by 64.3% and its ranking for TB fell from second highest among large US cites to twenty-eighth. This TB trend coincided with the implementation of an aggressive directly observed therapy (DOT) program by Baltimore's Health Department. OBJECTIVES: We used modeling to estimate the range of TB cases prevented in Baltimore under DOT. Case estimates equal the difference between the observed number of TB cases in Baltimore versus the expected number if Baltimore's TB trend was replaced by the TB trend for the US (low estimate) or the TB trend for all US cities with over 250,000 residents (high estimate). Economic savings are estimated. RESULTS: Without DOT we estimate there would have been between 1,577 (53.6%) and 2,233 (75.9%) more TB cases in Baltimore, costing $18.8 million to $27.1 million. Cases prevented and expenditures saved increased with increased DOT participation. CONCLUSION: Our model predicts that Baltimore's TB decline accompanying DOT resulted in health care savings equal to twice the city's total TB control budget for this period. These results are most plausibly due to DOT, since it was the only major change in Baltimore's TB control program, and rising TB risk factors-AIDS, injection drug use, poverty-in a city where TB had been epidemic should have triggered a TB increase as in comparable US cities, rather than the observed decline. As national TB rates continue to decline it will be important to identify ways to capture and reinvest these savings to support effective TB control programs. AD - Annie E. Casey Foundation, Baltimore, Maryland 21202, USA. patc@aecf.org AN - 10751064 AU - Chaulk, C. P. AU - Friedman, M. AU - Dunning, R. DA - Mar DP - Nlm ET - 04/06 KW - Antitubercular Agents/ administration & dosage/economics Cost Savings Cost of Illness Humans Maryland/epidemiology Models, Economic Prevalence Risk Factors Tuberculosis, Pulmonary/ drug therapy/economics/ epidemiology LA - eng N1 - Chaulk, C P Friedman, M Dunning, R France The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Int J Tuberc Lung Dis. 2000 Mar;4(3):201-7. PY - 2000 RN - fulltext fulltext_1208 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 201-7 ST - Modeling the epidemiology and economics of directly observed therapy in Baltimore T2 - Int J Tuberc Lung Dis TI - Modeling the epidemiology and economics of directly observed therapy in Baltimore VL - 4 ID - 2378 ER - TY - JOUR AB - Although tuberculosis (TB) screening of immigrants has been conducted for over 50 yr in many industrialized countries, its cost- effectiveness has never been evaluated. We prospectively compared the yield and cost-effectiveness of two immigrant TB screening programs, using close-contact investigation and passive case detection. Study subjects included all immigration applicants undergoing radiographic screening, already arrived immigrants requiring surveillance for inactive TB, and close contacts of active cases resident in Montreal, Quebec, Canada, who were referred from June 1996 to June 1997 to the Montreal Chest Institute (MCI), a referral center specializing in respiratory diseases. For all subjects seen, demographic data, investigations, diagnoses, and therapy were abstracted from administrative data bases and medical charts. Estimated costs of detecting and treating each prevalent active case and preventing future active cases, based on federal and provincial health reimbursement schedules, were compared with the costs for passively diagnosed cases of active TB. Over a period of 1 yr, the three programs detected 27 cases of prevalent active TB and prevented 14 future cases. As compared with passive case detection, close-contact investigation resulted in net savings of $815 for each prevalent active case detected and treated and of $2,186 for each future active case prevented. The incremental cost to treat each case of prevalent active TB was $39,409 for applicant screening and $24,225 for surveillance, and the cost of preventing each case was $33,275 for applicants and $65,126 for surveillance. Close-contact investigation was highly cost effective and resulted in net savings. Immigrant applicant screening and surveillance programs had a significant impact but were much less cost effective, in large part because of substantial operational problems. AD - Respiratory Epidemiology Unit, McGill University, Montreal, QC, Canada. AN - 11112118 AU - Dasgupta, K. AU - Schwartzman, K. AU - Marchand, R. AU - Tennenbaum, T. N. AU - Brassard, P. AU - Menzies, D. DA - Dec DP - Nlm ET - 12/09 KW - Cohort Studies Contact Tracing/ economics/methods/statistics & numerical data Cost-Benefit Analysis/economics/statistics & numerical data Emigration and Immigration/statistics & numerical data Humans Markov Chains Mass Screening/ economics/methods/statistics & numerical data Population Surveillance/methods Prospective Studies Quebec Sensitivity and Specificity Treatment Outcome Tuberculosis, Pulmonary/diagnosis/drug therapy/ economics/transmission LA - eng N1 - Dasgupta, K Schwartzman, K Marchand, R Tennenbaum, T N Brassard, P Menzies, D Comparative Study Research Support, Non-U.S. Gov't United states American journal of respiratory and critical care medicine Am J Respir Crit Care Med. 2000 Dec;162(6):2079-86. PY - 2000 RN - fulltext fulltext_1208 SN - 1073-449X (Print) 1073-449X (Linking) SP - 2079-86 ST - Comparison of cost-effectiveness of tuberculosis screening of close contacts and foreign-born populations T2 - Am J Respir Crit Care Med TI - Comparison of cost-effectiveness of tuberculosis screening of close contacts and foreign-born populations UR - http://ajrccm.atsjournals.org/content/162/6/2079.full.pdf VL - 162 ID - 2379 ER - TY - JOUR AB - Current theory in the molecular epidemiology of tuberculosis holds that tuberculosis cases harboring Mycobacterium tuberculosis strains with a common deoxyribonucleic acid (DNA) fingerprint are the result of recent M. tuberculosis transmission. Here we propose a mathematical approach independent of DNA fingerprinting to estimating the percentage of recent transmissions responsible for current tuberculosis incidence. The "short-term reproductive number" of tuberculosis is defined as the average number of tuberculosis cases developing within 1 year of infection. Multiplying the short-term reproductive number by the number of tuberculosis cases in each year and dividing by the subsequent year's tuberculosis case burden equals the proportion of tuberculosis cases in the subsequent year that are due to recent transmission. We carried out separate calculations for human immunodeficiency virus (HIV)-negative and HIV-positive tuberculosis cases. We applied the model to pulmonary (infectious) tuberculosis cases diagnosed in New York City during 1989-1993, using tuberculosis and AIDS surveillance data. Model-based estimates of the proportion of tuberculosis due to recent transmission were lower than estimates based on DNA fingerprints. Reconciliation of these divergent estimates may require the re-estimation of model parameters from data collected de novo, additional model development, and further advances in DNA fingerprinting methods. AD - Department of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School, Newark 07103-2714, USA. AN - 10874545 AU - Davidow, A. L. AU - Alcabes, P. AU - Marmor, M. DA - Jul DP - Nlm ET - 06/30 KW - Acquired Immunodeficiency Syndrome/complications Adult Aged DNA Fingerprinting DNA, Viral/analysis Disease Outbreaks Disease Progression Disease Transmission, Infectious Female Humans Male Middle Aged Models, Theoretical Mycobacterium tuberculosis New York City/epidemiology Tuberculosis, Pulmonary/ epidemiology/virology LA - eng N1 - Davidow, A L Alcabes, P Marmor, M 1P30AI27742/AI/NIAID NIH HHS/United States HL51517/HL/NHLBI NIH HHS/United States R21 AI42521/AI/NIAID NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Epidemiology (Cambridge, Mass.) Epidemiology. 2000 Jul;11(4):394-401. PY - 2000 RN - fulltext fulltext_1208 SN - 1044-3983 (Print) 1044-3983 (Linking) SP - 394-401 ST - The contribution of recently acquired Mycobacterium tuberculosis infection to the New York City tuberculosis epidemic, 1989-1993 T2 - Epidemiology TI - The contribution of recently acquired Mycobacterium tuberculosis infection to the New York City tuberculosis epidemic, 1989-1993 VL - 11 ID - 2380 ER - TY - JOUR AB - We have developed a computer-implemented, multivariate Markov chain model to project tuberculosis (TB) incidence in the United States from 1980 to 2010 in disaggregated demographic groups. Uncertainty in model parameters and in the projections is represented by fuzzy numbers. Projections are made under the assumption that current TB control measures will remain unchanged for the projection period. The projections of the model demonstrate an intermediate increase in national TB incidence (similar to that which actually occurred) followed by continuing decline. The rate of decline depends strongly on geographic, racial, and ethnic characteristics. The model predicts that the rate of decline in the number of cases among Hispanics will be slower than among white non-Hispanics and black non-Hispanics a prediction supported by the most recent data. AD - Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4945, USA. smd@hal.cwru.edu AN - 10756148 AU - Debanne, S. M. AU - Bielefeld, R. A. AU - Cauthen, G. M. AU - Daniel, T. M. AU - Rowland, D. Y. DA - Mar-Apr DP - Nlm ET - 04/11 KW - Adolescent Adult Aged Child Child, Preschool Computer Simulation Emigration and Immigration Ethnic Groups Female Humans Male Markov Chains Middle Aged Models, Biological Multivariate Analysis Tuberculosis, Pulmonary/ epidemiology United States/epidemiology LA - eng N1 - Debanne, S M Bielefeld, R A Cauthen, G M Daniel, T M Rowland, D Y Research Support, Non-U.S. Gov't United states Emerging infectious diseases Emerg Infect Dis. 2000 Mar-Apr;6(2):148-57. PY - 2000 RN - fulltext fulltext_1208 SN - 1080-6040 (Print) 1080-6040 (Linking) SP - 148-57 ST - Multivariate Markovian modeling of tuberculosis: forecast for the United States T2 - Emerg Infect Dis TI - Multivariate Markovian modeling of tuberculosis: forecast for the United States VL - 6 ID - 2381 ER - TY - JOUR AB - BACKGROUND: Tuberculosis (TB) is still amongst the most important causes of human morbidity and mortality, killing approximately two million people each year. Standard short-course chemotherapy (SSCC) can rapidly control illness and dramatically reduce the chance of death, but the impact of treatment has rarely been evaluated in these terms. METHOD: We developed a mathematical model that makes use of routinely-collected data to calculate the number of deaths directly prevented by TB treatment (i.e. excluding those due to reduced transmission). The method was applied to the world's largest TB control programme covering over 500 million people in 12 provinces of China. RESULTS: Counties which had been enrolled in the programme since 1991 were, by 1997, preventing at least 46% (37-56%) of the TB deaths that would otherwise have occurred. If replicated across the entire TB control programme area, this would amount to 30 000 (range 26 000-59 000) deaths directly prevented each year. CONCLUSIONS: Short-course chemotherapy has substantially reduced TB mortality in half of China. The analytical method described here could be applied to TB control operations in many other countries, and should help to quantify the true burden of tuberculosis alleviated by SSCC. AD - Communicable Disease Control, Prevention and Eradication, World Health Organization, Geneva, Switzerland. AN - 10869331 AU - Dye, C. AU - Fengzeng, Z. AU - Scheele, S. AU - Williams, B. DA - Jun DP - Nlm ET - 06/28 KW - Anti-Bacterial Agents/ therapeutic use China/epidemiology Cost of Illness Forecasting Humans Models, Theoretical Mortality/trends Preventive Medicine Tuberculosis, Pulmonary/drug therapy/ mortality/prevention & control LA - eng N1 - Dye, C Fengzeng, Z Scheele, S Williams, B England International journal of epidemiology Int J Epidemiol. 2000 Jun;29(3):558-64. PY - 2000 RN - fulltext fulltext_1208 SN - 0300-5771 (Print) 0300-5771 (Linking) SP - 558-64 ST - Evaluating the impact of tuberculosis control: number of deaths prevented by short-course chemotherapy in China T2 - Int J Epidemiol TI - Evaluating the impact of tuberculosis control: number of deaths prevented by short-course chemotherapy in China UR - http://ije.oxfordjournals.org/content/29/3/558.full.pdf VL - 29 ID - 2382 ER - TY - JOUR AB - Antibiotic resistance is a growing impediment to the control of infectious diseases worldwide, tuberculosis (TB) being among them. TB kills two million people each year and foci of multidrug-resistant TB (MDR-TB) have been identified in Eastern Europe, Africa, Asia, and Latin America. A critical question for health policy is whether standardized short-course chemotherapy for TB, based on cheap first-line drugs, can prevent and reverse the spread of drug resistance. Here we use mathematical modeling, in conjunction with treatment results from six countries, to show that best-practice short-course chemotherapy is highly likely to bring strains resistant to either of the two key drugs isoniazid and rifampicin under control and to prevent the emergence of MDR-TB. However, it is not certain to contain MDR-TB once it has emerged, partly because cure rates are too low. We estimate that approximately 70% of prevalent, infectious MDR-TB cases should be detected and treated each year, and at least 80% of these cases should be cured, in order to prevent outbreaks of MDR-TB. Poor control programs should aim to increase case detection and cure rates together for three reasons: (i) these variables act synergistically; (ii) when either is low, the other cannot succeed alone; and (iii) the second-line drugs needed to raise MDR-TB cure rates are few and extremely costly. We discuss the implications of these results for World Health Organization policy on the management of antibiotic resistance. AD - Communicable Disease Control, Prevention and Eradication, World Health Organization, CH-1211 Geneva 27, Switzerland. dyec@who.ch AN - 10859359 AU - Dye, C. AU - Williams, B. G. DA - Jul 5 DO - 10.1073/pnas.140102797 [doi] 140102797 [pii] DP - Nlm ET - 06/22 KW - Antitubercular Agents/ therapeutic use Drug Resistance, Multiple Humans Isoniazid/therapeutic use Models, Theoretical Practice Guidelines as Topic Rifampin/therapeutic use Tuberculosis, Pulmonary/ drug therapy/prevention & control World Health Organization L1 - internal-pdf://3473116560/Dye-2000-Criteria for the control of drug-resi.pdf LA - eng N1 - Dye, C Williams, B G United states Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):8180-5. PY - 2000 RN - fulltext fulltext_1208 SN - 0027-8424 (Print) 0027-8424 (Linking) SP - 8180-5 ST - Criteria for the control of drug-resistant tuberculosis T2 - Proc Natl Acad Sci U S A TI - Criteria for the control of drug-resistant tuberculosis UR - http://www.pnas.org/content/97/14/8180.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC16690/pdf/pq008180.pdf VL - 97 ID - 2383 ER - TY - CHAP A2 - Portaels, F. A2 - Bastian, I. AB - Threshold theory in infectious disease epidemiology states that there is some combination of case detection and cure rates above which tuberculosis, including multidrug-resistant tuberculosis (MDR; resistance to at least isoniazid and rifampicin) cannot spread through a population. The analytical challenge in MDR control is to identify which combinations of case detection and cure rates ensure that the number of MDR cases will decline, and to calculate the rate of decline. AU - Dye, C. AU - Williams, B. G. AU - Bastian, I. C3 - www CY - Dortrecht LB - 25 N1 - RefMgr field[1]: Book Chapter RefMgr field[8]: Not in File PB - Kluwer Academic Publishers PY - 2000 RN - fulltext fulltext_1208 ST - Population dynamics and control of multidrug-resistant tuberculosis T2 - MDR Mycobacterium Tuberculosis TI - Population dynamics and control of multidrug-resistant tuberculosis ID - 2384 ER - TY - JOUR AB - Following primary tuberculosis (TB) infection, only approximately 10% of individuals develop active T.B. Most people are assumed to mount an effective immune response to the initial infection that limits proliferation of the bacilli and leads to long-lasting partial immunity both to further infection and to reactivation of latent bacilli remaining from the original infection. Infected individuals may develop active TB as a consequence of exogenous reinfection, i.e., acquiring a new infection from another infectious individual. Our results in this paper suggest that exogenous reinfection has a drastic effect on the qualitative dynamics of TB. The incorporation of exogenous reinfection into our TB model allows the possibility of a subcritical bifurcation at the critical value of the basic reproductive number R(0)=1, and hence the existence of multiple endemic equilibria for R(0)<1 and the exogenous reinfection rate larger than a threshold. Our results suggest that reducing R(0) to be smaller than one may not be sufficient to eradicate the disease. An additional reduction in reinfection rate may be required. These results may also partially explain the recently observed resurgence of TB. AD - Department of Mathematics, Purdue University, West Lafayette, Indiana, 47907-1395, USA. AN - 10828216 AU - Feng, Z. AU - Castillo-Chavez, C. AU - Capurro, A. F. DA - May DO - 10.1006/tpbi.2000.1451 [doi] S0040-5809(00)91451-5 [pii] DP - Nlm ET - 06/01 KW - Disease Susceptibility Emigration and Immigration Endemic Diseases/statistics & numerical data Humans Models, Biological Tuberculosis/ epidemiology/prevention & control/ transmission LA - eng N1 - Feng, Z Castillo-Chavez, C Capurro, A F Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United states Theoretical population biology Theor Popul Biol. 2000 May;57(3):235-47. PY - 2000 RN - fulltext fulltext_1208 SN - 0040-5809 (Print) 0040-5809 (Linking) SP - 235-47 ST - A model for tuberculosis with exogenous reinfection T2 - Theor Popul Biol TI - A model for tuberculosis with exogenous reinfection UR - http://ac.els-cdn.com/S0040580900914515/1-s2.0-S0040580900914515-main.pdf?_tid=3bb76eba266c190e215b1de750b07574&acdnat=1345012329_4b250005c2ef4164ec2df2d398ddaf54 VL - 57 ID - 2385 ER - TY - JOUR AB - OBJECTIVE: Because delay in the diagnosis of tuberculosis (TB) contributes to the spread of disease and the associated mortality risk, the authors examined the effectiveness and cost of recent advances in methods of diagnosing TB and testing for drug susceptibility, comparing these rapid methods to traditional approaches. METHODS: Decision analysis was used to compare newer rapid and older nonrapid methods for diagnosing TB and testing for drug susceptibility. The average time to diagnosis, average time to treatment, average mortality, and cost of caring for patients evaluated for TB were compared. RESULTS: Using a combination of solid medium and broth cultures, nucleic acid probes for identification, and radiometric broth drug susceptibility testing would lead to diagnosis on average 15 days faster and to appropriate therapy on average five days sooner than methods currently employed by many U.S. laboratories. The average mortality would drop by five patients per 1000 patients evaluated (31%) and the average cost per patient would drop by $272 (18%). CONCLUSIONS: In this era of cost containment, it is important to incorporate test sensitivity and specificity when evaluating technologies. Tests with higher unit costs may lead to lower medical expenditures when diagnostic accuracy and speed are improved. U.S. laboratories should employ available rapid techniques for the diagnosis of TB. AD - Department of Health and Social Behavior, Harvard School of Public Health, Boston, MA 02115, USA. AN - 10822480 AU - Heymann, S. J. AU - Brewer, T. F. AU - Ettling, M. DA - Nov-Dec ET - 05/24 KW - Bacteriological Techniques/economics/*standards Cost Control Cost-Benefit Analysis Decision Trees Drug Resistance, Microbial Health Expenditures/statistics & numerical data Humans Mass Screening/economics/*methods Microbial Sensitivity Tests Mycobacterium tuberculosis/*isolation & purification Prevalence Reproducibility of Results Sensitivity and Specificity Time Factors Tuberculosis/*diagnosis/economics/*microbiology/mortality/prevention & control United States/epidemiology L1 - internal-pdf://0325095967/Heymann-2000-Effectiveness and cost of rapid a.pdf LA - eng N1 - Heymann, S J Brewer, T F Ettling, M 1 F32 HS00079/HS/AHRQ HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Public health reports (Washington, D.C. : 1974) Public Health Rep. 1997 Nov-Dec;112(6):513-23. PY - 2000 RN - fulltext fulltext_1208 SN - 0033-3549 (Print) 0033-3549 (Linking) SP - 513-23 ST - Effectiveness and cost of rapid and conventional laboratory methods for Mycobacterium tuberculosis screening T2 - Public Health Rep TI - Effectiveness and cost of rapid and conventional laboratory methods for Mycobacterium tuberculosis screening UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10822480 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1381931/pdf/pubhealthrep00037-0071.pdf VL - 112 ID - 2343 ER - TY - JOUR AB - OBJECTIVE: Tuberculosis (TB) control programs have been less successful among children than among adults in the United States. Between 1992 and 1997, the rate of decline of TB cases among 0- to 14-year-old children was less than the rate of decline among any other age group of US-born persons. Because of the higher prevalence of active TB among adults and their higher infectivity, most programs for TB in the United States have targeted adults. The inherent assumption has been that by targeting adults, from whom children may become infected, TB morbidity and mortality among children also will be reduced effectively. METHODS: Using a semi-Markov model that divided the US population into age groups <15 years old and >/=15 years old and into 18 clinical states based on the risk for or presence of TB and human immunodeficiency virus infection, we developed a computer-based simulation model to examine the effect of a range of potential TB control strategies on projected TB cases and deaths in children. We compare the impact of interventions targeted at children with the impact of interventions targeted at adults on pediatric morbidity and mortality. RESULTS: After 10 years, a 5% increase in the number of adults with TB who enter treatment would only lead to a.05% decline in TB cases among children, compared with predicted cases without this intervention. Improving treatment efficacy among those adults who are already receiving treatment for their TB leads to a smaller decline in cases among children of only.003%. In contrast, a 5% increase in the number of children who enter treatment leads to a 25% decline, after 10 years, in the number of TB cases among children and a 16% decline in the number of TB deaths. In the presence of immigration of tuberculin-positive children, the benefit of targeting programs directly at children is magnified. CONCLUSIONS: Marginal changes in programs targeted directly at children are significantly more effective at further reducing pediatric TB morbidity and mortality than the same changes in programs targeted at adults with the indirect goal of reducing spread to children. Marginal increases in the number of children who enter treatment are far more effective at decreasing morbidity and mortality than equivalent marginal increases in treatment effectiveness. Unfortunately, declining insurance coverage and increasing restrictions on services to immigrants have made it harder for those who are at greatest risk of TB to get medical care. Marginal increases in preventive therapy rates substantially reduce future pediatric TB cases and deaths among children with TB infection and human immunodeficiency virus. AD - Harvard School of Public Health, Brigham and Women's Hospital, Boston, MA 02115, USA. jheymann@hsph.harvard.edu AN - 10878170 AU - Heymann, S. J. AU - Brewer, T. F. AU - Wilson, M. E. AU - Colditz, G. A. AU - Fineberg, H. V. DA - Jul DP - Nlm ET - 07/06 KW - Adolescent Adult Child Child, Preschool Computer Simulation Humans Infant Infant, Newborn Prevalence Survival Rate Tuberculosis/epidemiology/mortality/ prevention & control United States/epidemiology LA - eng N1 - Heymann, S J Brewer, T F Wilson, M E Colditz, G A Fineberg, H V 1K08 AI01444-01A1/AI/NIAID NIH HHS/United States Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. United states Pediatrics Pediatrics. 2000 Jul;106(1):E1. PY - 2000 RN - fulltext fulltext_1208 SN - 1098-4275 (Electronic) 0031-4005 (Linking) SP - E1 ST - Pediatric tuberculosis: what needs to be done to decrease morbidity and mortality T2 - Pediatrics TI - Pediatric tuberculosis: what needs to be done to decrease morbidity and mortality UR - http://pediatrics.aappublications.org/content/106/1/e1.full.pdf VL - 106 ID - 2386 ER - TY - JOUR AB - Isoniazid taken daily for 12 mo and isoniazid and rifampin taken daily for 4 mo are both recommended options for patients with radiographic evidence of previous tuberculosis and positive tuberculin skin tests who have not had prior treatment. We compared the completion rates, number of adverse effects, and cost effectiveness of these two regimens. Patients were treated at the San Francisco Tuberculosis Clinic from 1993 through 1996. A Markov model was developed to assess impact on life expectancy and costs. One thousand twenty-two patients, with a mean age of 52 yr, and > 90% foreign born, were treated; 545 received isoniazid and 477 received isoniazid and rifampin. For isoniazid, 79.8% completed 12 mo of therapy and 4.9% had adverse effects versus 83.6% completion, 6.1% adverse effects for isoniazid and rifampin (p > 0.05 for all between-group comparisons). Both regimens increased life expectancy by 1.4-1.5 yr. Compared with isoniazid, isoniazid and rifampin produced net incremental savings of $135 per patient treated. In patients with radiographic evidence of prior tuberculosis who have not been previously treated, isoniazid for 12 mo and isoniazid and rifampin for 4 mo have similar rates of completion and adverse effects, and both increase life expectancy compared with no treatment. Isoniazid and rifampin for 4 mo is cost saving compared with isoniazid alone. This advantage was maintained even when compared with 9 mo of isoniazid, the new American Thoracic Society/Centers for Disease Control (ATS/CDC) recommendation for treatment with isoniazid alone. AD - Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital Medical Center, and the Department of Medicine, University of California, San Francisco, CA, USA. rjasmer@itsa.ucsf.edu AN - 11069790 AU - Jasmer, R. M. AU - Snyder, D. C. AU - Chin, D. P. AU - Hopewell, P. C. AU - Cuthbert, S. S. AU - Antonio Paz, E. AU - Daley, C. L. DA - Nov DP - Nlm ET - 11/09 J2 - American journal of respiratory and critical care medicine KW - Antitubercular Agents/ administration & dosage/economics Cost-Benefit Analysis Drug Administration Schedule Drug Costs Drug Therapy, Combination Female Health Care Costs Humans Isoniazid/ administration & dosage/adverse effects/economics Life Expectancy Male Middle Aged Outcome Assessment (Health Care) Patient Compliance Recurrence Rifampin/ administration & dosage/adverse effects/economics San Francisco Tuberculosis, Pulmonary/ drug therapy/ economics/radiography LA - eng N1 - Jasmer, R M Snyder, D C Chin, D P Hopewell, P C Cuthbert, S S Antonio Paz, E Daley, C L AI01549/AI/NIAID NIH HHS/United States AI34238/AI/NIAID NIH HHS/United States Comparative Study Research Support, U.S. Gov't, P.H.S. United states Am J Respir Crit Care Med. 2000 Nov;162(5):1648-52. PY - 2000 RN - fulltext fulltext_1208 SN - 1073-449X (Print) 1073-449X (Linking) SP - 1648-52 ST - Twelve months of isoniazid compared with four months of isoniazid and rifampin for persons with radiographic evidence of previous tuberculosis: an outcome and cost-effectiveness analysis T2 - Am J Respir Crit Care Med TI - Twelve months of isoniazid compared with four months of isoniazid and rifampin for persons with radiographic evidence of previous tuberculosis: an outcome and cost-effectiveness analysis UR - http://ajrccm.atsjournals.org/content/162/5/1648.full.pdf VL - 162 ID - 2387 ER - TY - JOUR AB - We use 2 simple mathematical models (one a preexposure vaccine model and the other a postexposure vaccine model) to provide general insight into the effects of vaccination on tuberculosis epidemics. We discuss how these models can be used as health policy tools: to identify which vaccines are "equivalent," to design control strategies, and to predict the epidemiological impact of different vaccination strategies. Our results show that even moderately effective vaccines could have a significant effect on reducing tuberculosis epidemics if they can be coupled with moderate to high treatment rates. We suggest that both preexposure and postexposure tuberculosis vaccines can be used to help eliminate tuberculosis in developing countries. In developed countries, only a preexposure vaccine (used in combination with a high level of treatment) would be necessary to eliminate tuberculosis. AD - Francis I. Proctor Foundation and Department of Ophthalmology, University of California San Francisco, San Francisco, CA 94143, USA. AN - 10875909 AU - Lietman, T. AU - Blower, S. M. DA - Jun DO - CID990621 [pii] 10.1086/313881 [doi] DP - Nlm ET - 07/06 KW - BCG Vaccine Disease Outbreaks/ prevention & control Humans Models, Biological Tuberculosis, Pulmonary/epidemiology/ prevention & control Vaccination LA - eng N1 - Lietman, T Blower, S M K08AI01441/AI/NIAID NIH HHS/United States R01AI41935/AI/NIAID NIH HHS/United States Research Support, U.S. Gov't, P.H.S. Review United states Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Clin Infect Dis. 2000 Jun;30 Suppl 3:S316-22. PY - 2000 RN - fulltext fulltext_1208 SN - 1058-4838 (Print) 1058-4838 (Linking) SP - S316-22 ST - Potential impact of tuberculosis vaccines as epidemic control agents T2 - Clin Infect Dis TI - Potential impact of tuberculosis vaccines as epidemic control agents UR - http://cid.oxfordjournals.org/content/30/Supplement_3/S316.full.pdf VL - 30 Suppl 3 ID - 2388 ER - TY - JOUR AB - OBJECTIVE: To assess the cost-effectiveness of adding school based Mantoux screening programs to the New South Wales current TB prevention strategy. METHOD: A decision analysis model compared the costs and consequences of screening strategies against the current no-screen strategy. Costs associated with screening and with treating future cases of TB were considered. Consequences considered were deaths and adult cases of TB prevented. The study was based on data from prevalence surveys conducted in 1992 and 1994 in Central and South Western Sydney, New South Wales. Screening strategies considered were screening all or only overseas born (OSB) 6 year olds and all or only OSB 14 year olds in school settings. RESULTS: Screening 14 year olds prevented more deaths and adult cases of TB than screening 6 year olds for a similar cost. For both age groups targeted screening of OSB children was more cost-effective than screening all children. Targeted screening of 14 year olds--the most cost effective option--cost $17,956 (costs and benefits discounted at 5%) per adult case prevented, equivalent to approximately $130,000 per life year saved. The cost-effectiveness ratios decline substantially if lower discount rates and less conservative assumptions are applied. CONCLUSION: Targeted screening was more cost effective than screening all children, however, there are ethical implications of targeting a group based on their origin of birth. IMPLICATIONS: As prevention and control of TB continues to be a high priority for NSW, the implications of a school based screening program should be seriously considered. AD - Centre for Health Economics, Research and Evaluation, University of Sydney, New South Wales. AN - 10937400 AU - Lowin, A. AU - Slater, J. AU - Hall, J. AU - Alperstein, G. DA - Jun DP - Nlm ET - 08/11 J2 - Australian and New Zealand journal of public health KW - Adolescent Adult Child Cost-Benefit Analysis Decision Theory Health Services Research Humans Mass Screening/ economics/methods New South Wales/epidemiology School Health Services/ economics Tuberculin Test/economics/ methods Tuberculosis/ diagnosis/prevention & control LA - eng N1 - Lowin, A Slater, J Hall, J Alperstein, G Research Support, Non-U.S. Gov't Australia Aust N Z J Public Health. 2000 Jun;24(3):247-53. PY - 2000 RN - fulltext fulltext_1208 SN - 1326-0200 (Print) 1326-0200 (Linking) SP - 247-53 ST - Cost effectiveness analysis of school based Mantoux screening for TB infection T2 - Aust N Z J Public Health TI - Cost effectiveness analysis of school based Mantoux screening for TB infection UR - http://onlinelibrary.wiley.com/store/10.1111/j.1467-842X.2000.tb01564.x/asset/j.1467-842X.2000.tb01564.x.pdf?v=1&t=h6geefvr&s=99a4a3e086ebe7c619f8cc41eb3b0e94c9846b8f VL - 24 ID - 2390 ER - TY - JOUR AB - INTRODUCTION: The potential cost-effectiveness of screening depends on the risk of tuberculosis (TB) in the population being screened and the rate at which the screening outcome (prevention) is achieved. AIMS: To compare the cost-effectiveness of contact screening for TB for: (1) contact screening as it actually occurred in Victoria in 1991 (Model 1); (2) the process which should have occurred had the 1991 contact screening guidelines been followed (Model 2); (3) a hypothetical evidence-based model (Model 3). METHODS: Three models were constructed according to the aims. The cost-effectiveness of contact screening is presented as costs to government per unit outcome (in the form of cases prevented, cases found and contacts traced) for each model. Assumptions about disease behaviour were consistent between models. A sensitivity analysis was performed to examine the effect of the assumptions made in Model 3 about rates of referral and treatment of infected contacts, and about the efficacy of isoniazid (INH) in preventing TB. RESULTS: The total cost of Model 1 was greater than that of the other Models. Model 1 is the least cost-effective, costing $309 065 per case prevented, and Model 3 is the most cost-effective, costing $32 210 per case prevented. The cost of Model 2 was $58 742 per case prevented. The incremental cost-effectiveness of Model 3 compared to Model 2 is $107 per additional contact screened, and $3881 per additional case prevented. Case finding is not as cost-effective as best-practice case prevention, ranging from $231 799 per case found in Model 1 to $205 596 per case found in Model 2. The sensitivity analysis shows that the cost-effectiveness of Model 3 decreases with lower referral rates, lower rates of preventive therapy, and lower efficacy of INH. However, even allowing for reduced programme parameters, Model 3 is most cost-effective. DISCUSSION: Costing policy options is an important component of programme delivery, but needs to be considered in the context of the product being purchased, e.g. the prevention of disease, or case finding. Case finding as a product of contact screening is expensive in all three models. Prevention of TB, on the other hand, can be cost-effective, as shown in Model 3. It was least cost-effective in Model 1, largely because prevention was not considered a priority, and few infected contacts actually received preventive therapy. Clear programme aims, adherence to guidelines and high rates of preventive therapy are essential in order to achieve cost-effectiveness. AD - Department of Public Health and Community Medicine, Westmead Hospital, Westmead, Australia. RainaM@nch.edu.au AN - 10903541 AU - Macintyre, C. R. AU - Plant, A. J. AU - Hendrie, D. DA - Jul DO - 10.1002/1099-1050(200007)9:5<411::AID-HEC524>3.0.CO;2-9 [pii] ET - 07/21 KW - Antitubercular Agents/economics/therapeutic use Contact Tracing Cost of Illness Cost-Benefit Analysis Drug Costs *Evidence-Based Medicine Humans Isoniazid/economics/therapeutic use Mass Screening/*economics/standards Models, Econometric New South Wales *Practice Guidelines as Topic Tuberculosis/*diagnosis/drug therapy/economics/*prevention & control LA - eng N1 - Macintyre, C R Plant, A J Hendrie, D Research Support, Non-U.S. Gov't England Health economics Health Econ. 2000 Jul;9(5):411-21. PY - 2000 RN - fulltext fulltext_1208 SN - 1057-9230 (Print) 1057-9230 (Linking) SP - 411-21 ST - The cost-effectiveness of evidence-based guidelines and practice for screening and prevention of tuberculosis T2 - Health Econ TI - The cost-effectiveness of evidence-based guidelines and practice for screening and prevention of tuberculosis UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10903541 VL - 9 ID - 2391 ER - TY - JOUR AB - We consider a simple unstructured individual based stochastic epidemic model with contact tracing. Even in the onset of the epidemic, contact tracing implies that infected individuals do not act independent of each other. Nevertheless, it is possible to analyze the embedded non-stationary Galton-Watson process. Based upon this analysis, threshold theorems and also the probability for major outbreaks can be derived. Furthermore, it is possible to obtain a deterministic model that approximates the stochastic process, and in this way, to determine the prevalence of disease in the quasi-stationary state and to investigate the dynamics of the epidemic. AD - Biomathematik, Universitat Tubingen, Auf der Morgenstelle 10, D-72076, Tubingen, Germany. johannes.mueller@uni-tuebingen.de AN - 10704637 AU - Muller, J. AU - Kretzschmar, M. AU - Dietz, K. DA - Mar DO - S0025-5564(99)00061-9 [pii] DP - Nlm ET - 03/08 KW - Communicable Diseases/epidemiology/ transmission Computer Simulation Contact Tracing/economics/ statistics & numerical data Disease Outbreaks/ statistics & numerical data Female Humans Male Models, Biological Prevalence Sexually Transmitted Diseases/epidemiology Stochastic Processes Tuberculosis/epidemiology LA - eng N1 - Muller, J Kretzschmar, M Dietz, K Comparative Study United states Mathematical biosciences Math Biosci. 2000 Mar;164(1):39-64. PY - 2000 RN - fulltext fulltext_1208 SN - 0025-5564 (Print) 0025-5564 (Linking) SP - 39-64 ST - Contact tracing in stochastic and deterministic epidemic models T2 - Math Biosci TI - Contact tracing in stochastic and deterministic epidemic models UR - http://ac.els-cdn.com/S0025556499000619/1-s2.0-S0025556499000619-main.pdf?_tid=70d9bb8a42a340b1a448eb257fe83e11&acdnat=1345012817_4f26fbbdf286867526670b1b80de9081 VL - 164 ID - 2392 ER - TY - JOUR AB - Most models for contaminant dispersion in indoor air are deterministic and do not account for the probabilistic nature of the pollutant concentration at a given room position and time. Such variability can be important when estimating concentrations involving small numbers of contaminant particles. This article describes the use of probabilistic models termed Markov chains to account for a portion of this variability. The deterministic and Markov models are related in that the former provide the expected concentration values. To explain this relationship, a single-zone (well-mixed room) scenario is described as a Markov chain. Subsequently, a two-zone room is cast as a Markov model, and the latter is applied to assessing a health care worker's risk of tuberculosis infection. Airborne particles carrying Mycobacterium tuberculosis bacilli are usually present in small numbers in a room occupied by an infectious tuberculosis patient. For a given scenario, the Markov model permits estimates of variability in exposure intensity and the resulting variability in infection risk. AD - Center for Occupational and Environmental Health, School of Public Health, University of California, Berkeley 94720, USA. AN - 10976677 AU - Nicas, M. DA - Jul-Aug DP - Nlm ET - 09/08 KW - Air Microbiology Air Pollution, Indoor/ analysis Humans Markov Chains Models, Statistical Occupational Exposure/analysis/prevention & control Tuberculosis/prevention & control/transmission Ventilation LA - eng N1 - Nicas, M K01-OH00155-01/OH/NIOSH CDC HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states AIHAJ : a journal for the science of occupational and environmental health and safety AIHAJ. 2000 Jul-Aug;61(4):484-91. PY - 2000 RN - fulltext fulltext_1208 SN - 1529-8663 (Print) 1529-8663 (Linking) SP - 484-91 ST - Markov modeling of contaminant concentrations in indoor air T2 - AIHAJ TI - Markov modeling of contaminant concentrations in indoor air VL - 61 ID - 2393 ER - TY - JOUR AB - The present study examines whether pulmonary tuberculosis (PTB) has an annual seasonal pattern. A mathematical model is also obtained to forecast the pattern of incidence. The data for the study are the cases of PTB reported throughout Spain, published in the Epidemiology Bulletin by the Carlos III Health Center of the Spanish Ministry of Health in a 26-year period, 1971-1996. The analytical results show that the low rates in tuberculosis notifications over the period 1971-1981 have changed, halting in 1982 and reversing with high incidence from 1983 onwards. An annual seasonal pattern was also shown with higher incidence during summer and autumn. With the mathematical model we predicted the disease behaviour in 1997 and the results were compared to the reported cases. In Spain, as in several industrialised countries, the reason for this recent increase in the number of reported cases is, mainly, the human immunodeficiency virus (HIV) infection. The seasonal trend, with higher incidence in winter, can be attributed to the increase in indoor activities, much more common than in a warm climate. The tubercle bacilli expelled from infected persons in a room with closed windows may remain infectious for a long time, increasing the risk of exposure of healthy persons to the bacilli. As the preclinical period, from exposure to clinical onset, may be of several weeks, the high incidence in spring would be explained. Moreover, in winter and spring the infections of viral aetiology, like flu, are more frequent and cause immunological deficiency which is another reason for the seasonal trend observed. An incidence greater than that foreseen by the mathematical model would express a failure in epidemiologic surveillance, and thus the results of this study may be used to assess a quality of the preventive measures. AD - Statistical Department, University of Barcelona, Spain. rios@porthos.bio.ub.es AN - 10997837 AU - Rios, M. AU - Garcia, J. M. AU - Sanchez, J. A. AU - Perez, D. DA - May DP - Nlm ET - 09/21 KW - Cohort Studies Humans Likelihood Functions Models, Statistical Seasons Spain/epidemiology Time Factors Tuberculosis, Pulmonary/ epidemiology LA - eng N1 - Rios, M Garcia, J M Sanchez, J A Perez, D Comparative Study Netherlands European journal of epidemiology Eur J Epidemiol. 2000 May;16(5):483-8. PY - 2000 RN - fulltext fulltext_1208 SN - 0393-2990 (Print) 0393-2990 (Linking) SP - 483-8 ST - A statistical analysis of the seasonality in pulmonary tuberculosis T2 - Eur J Epidemiol TI - A statistical analysis of the seasonality in pulmonary tuberculosis VL - 16 ID - 2394 ER - TY - JOUR AB - All adult immigrant applicants to Canada undergo chest radiographic screening for tuberculosis (TB). Tuberculin skin testing could reduce the number of chest X-rays, and identify more candidates for prophylaxis. We modeled the cost-effectiveness of chest radiography and tuberculin skin testing for TB prevention over a 20-yr time frame, among three simulated cohorts of 20-yr-old immigrants. Compared with no screening, radiographic screening prevented 4.3% of expected active TB cases in the highest risk cohort (50% TB-infected, 10% human immunodeficiency virus [HIV] seroprevalence), and 8.0% in the lowest risk cohort (5% TB-infected, 1% HIV seroprevalence). Tuberculin skin testing further reduced the expected incidence 8.0% and 4.0%, respectively. Compared with no screening, radiographic screening cost $3,943 Canadian per active TB case prevented in the highest risk cohort, and $236,496 per case prevented in the lowest risk group. Compared with radiographic screening, mass tuberculin skin testing cost $32,601 per additional case prevented in the highest risk group, and $68,799 per additional case prevented in the lowest risk group. Chest radiographic screening of young immigrants from countries with a high prevalence of TB is a relatively inexpensive means of TB prevention. Tuberculin skin testing is considerably less cost-effective. For immigrants from low-prevalence countries, both interventions are extremely costly with negligible impact. The cost-effectiveness of either strategy would be greatly enhanced by increased adherence to chemoprophylaxis recommendations. Radiographic screening of groups with a high prevalence of tuberculous infection will then likely save money. AD - Respiratory Division, McGill University Health Centre, and Respiratory Epidemiology Unit, McGill University, Montreal, Quebec, Canada. kevins@meakins.lan.mcgill.ca AN - 10712322 AU - Schwartzman, K. AU - Menzies, D. DA - Mar DP - Nlm ET - 03/11 KW - AIDS-Related Opportunistic Infections/economics/epidemiology/prevention & control Adult Canada Cost-Benefit Analysis Cross-Sectional Studies Emigration and Immigration/ statistics & numerical data Female Humans Male Mass Chest X-Ray/economics Mass Screening/economics Tuberculin Test/economics Tuberculosis, Pulmonary/economics/ epidemiology/prevention & control LA - eng N1 - Schwartzman, K Menzies, D Comparative Study Research Support, Non-U.S. Gov't United states American journal of respiratory and critical care medicine Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):780-9. PY - 2000 RN - fulltext fulltext_1208 SN - 1073-449X (Print) 1073-449X (Linking) SP - 780-9 ST - Tuberculosis screening of immigrants to low-prevalence countries. A cost-effectiveness analysis T2 - Am J Respir Crit Care Med TI - Tuberculosis screening of immigrants to low-prevalence countries. A cost-effectiveness analysis VL - 161 ID - 2395 ER - TY - JOUR AB - We propose a stepwise mutation model to describe the dynamics of DNA fingerprint variation in Mycobacterium tuberculosis. The genome of M. tuberculosis carries insertion sequences (IS6110) that are relatively stable over time periods of months but have an observable transposition rate over longer time scales. Variability in copy number and genomic location of (IS6110) can be harnessed to generate a DNA fingerprint for each strain, by digesting the genome with a restriction enzyme and using a portion of the element as a probe for Southern blots. The number of bands found for a given genome approximates the number of copies of IS6110 it carries. A large data set of such fingerprints from tuberculosis (TB) cases in San Francisco provides an observed distribution of IS6110 copy number. Implementation of the model through deterministic and stochastic simulation indicates some general features of IS/TB dynamics. By comparing observations with outcomes of the model, we conclude that the IS/TB system is very heterogeneous and far from equilibrium. We find that the transposition parameters have a much stronger effect than the epidemic parameters on copy number distribution. AD - Department of Biological Sciences, and Division of Infectious Diseases and Geographic Medicine, Stanford University, CA 94305, USA. markt@charles.stanford.edu AN - 10716736 AU - Tanaka, M. M. AU - Small, P. M. AU - Salamon, H. AU - Feldman, M. W. DA - Mar 28 KW - DNA Fingerprinting *Epidemiology, Molecular Human Models, Genetic Monte Carlo Method Mycobacterium tuberculosis/*genetics *Repetitive Sequences, Nucleic Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Tuberculosis/*epidemiology N1 - 20202670 0027-8424 Journal Article PY - 2000 RN - fulltext fulltext_1208 SP - 3532-3537 ST - The dynamics of repeated elements: applications to the epidemiology of tuberculosis T2 - Proceedings of the National Academy of Sciences of the USA TI - The dynamics of repeated elements: applications to the epidemiology of tuberculosis UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10716736http://www.ncbi.nlm.nih.gov/pmc/articles/PMC16274/pdf/pq003532.pdf VL - 97 ID - 2396 ER - TY - JOUR AU - Taylor, Z. DA - 2000 KW - Americas control strategies cost effectiveness elimination infection interventions preventive therapy screening tuberculosis USA LB - 8025 N1 - TY - JOUR TB Periodical PY - 2000 RN - fulltext fulltext_1208 SP - S127-S133 ST - The cost-effectiveness of screening for latent tuberculosis infection T2 - Int.J.Tuberc.Lung Dis. TI - The cost-effectiveness of screening for latent tuberculosis infection VL - 4(suppl 2) ID - 2397 ER - TY - JOUR AB - The lifetime risk of developing disease, the incubation period, and the time period between infection and transmission (the serial interval) are three important measures for interpreting trends in tuberculous infection and disease but are complicated by strong age dependencies regarding disease risk and by the potential for reinfection to occur. By using a model of the epidemiology of tuberculosis in England and Wales, the authors demonstrated that all three measures changed dramatically during the 20th century largely as a result of declines in the risk of infection. The estimated lifetime risk was highest following infection in early adulthood and declined with year of infection; the age-weighted average was approximately 12% during the last 50 years. Incubation period distributions depend on whether they are viewed prospectively (from infection to disease onset) or retrospectively (since infection for cases with disease onset at a particular time). As children rarely develop infectious forms of tuberculosis, infections acquired in childhood are associated with considerably longer serial intervals than those acquired in adulthood. These unusual properties are probably shared by other infections with long intervals between infection and disease. The results are important for interpreting data on transmission patterns, as are now being derived from molecular epidemiologic studies. AD - Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom. emilia.vynnycky@lshtm.ac.uk AN - 10933272 AU - Vynnycky, E. AU - Fine, P. E. DA - Aug 1 ET - 08/10 J2 - American journal of epidemiology KW - Adult Aged Child Child, Preschool England/epidemiology Humans Incidence Male *Models, Statistical Molecular Epidemiology Recurrence Risk Time Factors Tuberculosis, Pulmonary/*epidemiology/mortality/transmission Wales/epidemiology LA - eng M3 - Research Support, Non-U.S. Gov't N1 - Vynnycky, E Fine, P E Am J Epidemiol. 2000 Aug 1;152(3):247-63. PY - 2000 RN - fulltext fulltext_1208 SN - 0002-9262 (Print) 0002-9262 (Linking) SP - 247-63 ST - Lifetime risks, incubation period, and serial interval of tuberculosis T2 - Am J Epidemiol TI - Lifetime risks, incubation period, and serial interval of tuberculosis UR - http://www.ncbi.nlm.nih.gov/pubmed/10933272http://aje.oxfordjournals.org/content/152/3/247.full.pdf VL - 152 ID - 2398 ER - TY - JOUR AB - OBJECTIVE: To describe the economic benefits of a better tuberculosis (TB) vaccine by modeling prevented TB medical spending and lost productivity throughout the world. DESIGN: One model is based on benefits obtained from reducing the impact of TB on health spending. An alternative model is based on minimizing the impact of TB on health spending and lost productivity due to death and disability. Both models are applied to various world populations based on secondary data. RESULTS: In terms of avoided medical spending, preventing 100% of the TB risk in a single individual is estimated to be worth from $38 for males in formerly socialist countries to S0.23 for children in Asia. More than 1 billion people would reckon their expected medical savings to exceed $25.00 if they received a 75% effective vaccine of 10 years' duration. Preventing lost productivity is worth substantially more throughout the world. CONCLUSIONS: Improved TB vaccines would be of substantial immediate financial value to most of the populations of the world, including the poorest. The scientific uncertainties surrounding the development of a better vaccine could be a larger obstacle than investor uncertainty over whether a vaccine would be profitable. AD - Department of Population and Family Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA. dbishai@jhsph.edu AN - 11716349 AU - Bishai, D. M. AU - Mercer, D. DA - Nov DP - Nlm ET - 11/22 KW - Adolescent Adult Aged Bacterial Vaccines/ economics Child Cost Savings Cost of Illness Efficiency Female Health Care Costs Humans Male Middle Aged Models, Economic Mycobacterium tuberculosis/ immunology Risk Factors Tuberculosis/ economics/epidemiology/ prevention & control Vaccination/ economics LA - eng N1 - Bishai, D M Mercer, D Research Support, Non-U.S. Gov't France The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Int J Tuberc Lung Dis. 2001 Nov;5(11):984-93. PY - 2001 RN - fulltext fulltext_1208 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 984-93 ST - Modeling the economic benefits of better TB vaccines T2 - Int J Tuberc Lung Dis TI - Modeling the economic benefits of better TB vaccines VL - 5 ID - 2399 ER - TY - JOUR AB - This study estimated to what extent tuberculosis transmission in the Netherlands depends on the age and sex of source cases. DNA fingerprints of Mycobacterium tuberculosis isolates were matched to patient information in the Netherlands Tuberculosis Register for 1993-1998. Clusters were defined as groups of patients with pulmonary tuberculosis whose isolates had identical DNA fingerprints. Source cases were assigned by using two models. The first-case model assumed that the first diagnosed case was the source case. The incidence rate model estimated source case probabilities from the incidence rates of potential source cases and the time of diagnosis. DNA fingerprints of 6,102 isolates were matched to patient information on 5,080 (83%) cases, 3,479 of whom had pulmonary disease. According to both models, the number of infectious cases generated per source case was lower for female than for male source cases and decreased with increasing age of the source case. The authors concluded that transmission of tuberculosis is associated with the age and sex of source cases as well as the age of secondary cases. Increased transmission among immigrant groups in the Netherlands is largely attributable to the relatively young age of immigrant source cases. AD - Royal Netherlands Tuberculosis Association, The Hague, The Netherlands. borgdorffm@kncvtbc.nl AN - 11700248 AU - Borgdorff, M. W. AU - Nagelkerke, N. J. AU - de Haas, P. E. AU - van Soolingen, D. DA - Nov 15 ET - 11/09 J2 - American journal of epidemiology KW - Adult Age Factors Aged Cluster Analysis DNA Fingerprinting Female Humans Incidence Male Middle Aged *Models, Statistical Mycobacterium tuberculosis/genetics/*isolation & purification Netherlands/epidemiology Sex Factors Sputum/microbiology Time Factors Tuberculosis, Pulmonary/*epidemiology/genetics/*transmission LA - eng N1 - Borgdorff, M W Nagelkerke, N J de Haas, P E van Soolingen, D Am J Epidemiol. 2001 Nov 15;154(10):934-43. PY - 2001 RN - fulltext fulltext_1208 SN - 0002-9262 (Print) 0002-9262 (Linking) SP - 934-43 ST - Transmission of Mycobacterium tuberculosis depending on the age and sex of source cases T2 - Am J Epidemiol TI - Transmission of Mycobacterium tuberculosis depending on the age and sex of source cases UR - http://www.ncbi.nlm.nih.gov/pubmed/11700248http://aje.oxfordjournals.org/content/154/10/934.full.pdf VL - 154 ID - 2400 ER - TY - JOUR AB - CONTEXT: The rate of tuberculosis (TB) among US homeless persons may be 20 times that of the general adult population. Studies suggest that the majority of urban homeless TB cases are attributable to ongoing transmission of TB. Optimal TB-control strategies in both chronically and transiently homeless populations are not known. OBJECTIVE: To examine the effects of TB-control strategies on projected TB cases and deaths in US homeless populations using a computer-based simulation model. DESIGN, SETTING, AND POPULATION: The US general population and a theoretical population of 2 million homeless individuals in 1995 were divided into 18 clinical states based on the risk for or presence of TB and human immunodeficiency virus (HIV) infection in a semi-Markov model. MAIN OUTCOME MEASURES: Prevalence of transiently and chronically homeless individuals with active TB and deaths from TB as a function of public health measures taken to control and eliminate TB, including improvement of treatment effectiveness, improvement in access to treatment, and vaccination with BCG. RESULTS: A 10% increase in access to treatment among homeless persons with active TB produced larger declines in predicted TB cases and deaths after 10 years (cases and deaths among chronically homeless persons decreased 12.5% and 19.8% and among transiently homeless persons dropped 35.9% and 32.4%, respectively) than improvements in the effectiveness of treatment programs (cases and deaths among chronically homeless persons declined 7.2% and 3.1% and among transiently homeless persons dropped 10.9% and 4.1%, respectively). A 10% increase in access to treatment among homeless persons with latent TB infection led to a 6.7% decline in TB among chronically homeless persons and a 5.7% decline among transiently homeless persons, while a 10% improvement in effectiveness of treatment for latent TB infection was associated with declines of 3.0% and 3.3%, respectively. When treatment for latent TB infection was modeled to be the same in vaccinated and nonvaccinated populations, BCG vaccination led to TB case declines of 15.4% and 21.5% in chronically and transiently homeless populations, respectively. CONCLUSIONS: Overcoming barriers faced by homeless individuals in accessing TB treatment programs will be crucial to reducing the burden of TB in this high-risk group. Increased treatment access, improvement in the effectiveness of treatment programs, and BCG vaccination of HIV-negative homeless individuals have the best chance to markedly decrease TB morbidity and mortality. AD - Channing Laboratory, 181 Longwood Ave, Boston, MA 02115, USA. timothy.brewer@channing.harvard.edu AN - 11497538 AU - Brewer, T. F. AU - Heymann, S. J. AU - Krumplitsch, S. M. AU - Wilson, M. E. AU - Colditz, G. A. AU - Fineberg, H. V. DA - Aug 15 DO - jcu10000 [pii] DP - Nlm ET - 08/22 KW - Antitubercular Agents/therapeutic use BCG Vaccine Health Services Accessibility Homeless Persons/statistics & numerical data Humans Medically Uninsured Models, Theoretical Risk Tuberculosis/epidemiology/ prevention & control United States/epidemiology Vaccination LA - eng N1 - Brewer, T F Heymann, S J Krumplitsch, S M Wilson, M E Colditz, G A Fineberg, H V 1K08 AI01444-01A1/AI/NIAID NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States JAMA : the journal of the American Medical Association JAMA. 2001 Aug 15;286(7):834-42. PY - 2001 RN - fulltext fulltext_1208 SN - 0098-7484 (Print) 0098-7484 (Linking) SP - 834-42 ST - Strategies to decrease tuberculosis in us homeless populations: a computer simulation model T2 - JAMA TI - Strategies to decrease tuberculosis in us homeless populations: a computer simulation model UR - http://jama.jamanetwork.com/article.aspx?articleid=194096 VL - 286 ID - 2401 ER - TY - JOUR AU - Feng, Z. AU - Huang, W. AU - Castillo-Chavez, C. PY - 2001 RN - fulltext fulltext_1208 SP - 425-452 ST - On the role of variable latent periods in mathematical models for tuberculosis T2 - Journal of Dynamics and Differential equations TI - On the role of variable latent periods in mathematical models for tuberculosis VL - 13 ID - 2403 ER - TY - JOUR AU - Jones, T. F. AU - Schaffner, W. DA - 2001 J2 - Am.J.Respir.Crit.Care Med. KW - case-finding cost effectiveness institutions prisons screening tuberculosis LB - 8818 N1 - TY - JOUR TB Tuberculosis control Case-finding No sub-heading PY - 2001 RN - fulltext fulltext_1208 SP - 77-81 ST - Miniature chest radiograph screening for tuberculosis in jails. A cost-effectiveness analysis TI - Miniature chest radiograph screening for tuberculosis in jails. A cost-effectiveness analysis VL - 164 ID - 2404 ER - TY - JOUR AB - Environmental control measures (ventilation, high-efficiency particulate air filtration, and upper room ultraviolet germicidal irradiation [UVGI]) are recommended to effectively control tuberculosis (TB) transmission from unsuspected TB patients in high-risk settings, but the effectiveness of their use is not often clear. This study presents a simulation model for a hypothetical hospital waiting room, in which the number of susceptible immunocompetent people in the waiting room follows a Poisson distribution (M = 5) in either low (annual number of TB patients = 5) or high TB risk settings (annual number of TB patients = 50), and used the model to evaluate the reduction of TB transmission risk by upper room UVGI. An exponential dose-response model was used for TB transmission and a two-zone model was used for evaluating the effect of upper room UVGI. Upper room UVGI reduced TB risk by 1.6-fold at 3 microW/cm2 UV irradiance in the upper room in the low TB risk setting and by 4.1-fold at 15 microW/cm2 UV irradiance in the upper room in the high TB risk setting. Use of upper room UVGI also reduced the mean annual new infection rate from 2.2 to 1.3 infections per year at 3 microW/cm2 and to 0.6 infections per year at 15 microW/cm2 in our hypothetical high-risk settings. The effect of upper room UVGI was sensitive to both vertical air velocity (air mixing) and UV irradiance level. Results from partitioning variability indicate that most variability of TB transmission risk came from waiting time in our hypothetical hospital. AD - Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA. gko@email.unc.edu AN - 11726019 AU - Ko, G. AU - Burge, H. A. AU - Nardell, E. A. AU - Thompson, K. M. DA - Aug DP - Nlm ET - 12/01 KW - Computer Simulation Cost-Benefit Analysis Disease Transmission, Infectious/ prevention & control Environment, Controlled Health Facility Environment Humans Incidence Models, Theoretical Risk Tuberculosis/ epidemiology Ultraviolet Rays LA - eng N1 - Ko, G Burge, H A Nardell, E A Thompson, K M United States Risk analysis : an official publication of the Society for Risk Analysis Risk Anal. 2001 Aug;21(4):657-73. PY - 2001 RN - fulltext fulltext_1208 SN - 0272-4332 (Print) 0272-4332 (Linking) SP - 657-73 ST - Estimation of tuberculosis risk and incidence under upper room ultraviolet germicidal irradiation in a waiting room in a hypothetical scenario T2 - Risk Anal TI - Estimation of tuberculosis risk and incidence under upper room ultraviolet germicidal irradiation in a waiting room in a hypothetical scenario VL - 21 ID - 2405 ER - TY - JOUR AB - OBJECTIVE: The prompt diagnosis of smear-negative pulmonary tuberculosis (PTB) is a clinical challenge. It may be achieved by a number of tests which have varying accuracies, costs and degrees of invasiveness. The objective of this study was to compare the cost-effectiveness of clinical judgement (empirical), the Roche Cobas amplicor assay for Mycobacterium tuberculosis (amplicor), acid-fast staining of bronchoalveolar lavage specimens (BAL), nucleic acid amplification tests of bronchoalveloar lavage specimens for M. tuberculosis (BAL + NAA), computed tomography (CT) and amplicor assay followed by BAL. METHODOLOGY: The range of predictive values of the various strategies were derived from published data and a new study of 441 consecutive adult patients with suspected smear-negative PTB prospectively stratified into three pretest risk groups: low, intermediate and high. The cost-effectiveness was evaluated with a decision tree model (DATA software). RESULTS: The incidence of PTB was 5.7% (4% culture positive) for the whole group, 95% in the high-risk group, 0.9% in the low-risk group and 3.4% in the intermediate-risk group. The sensitivity of the empirical approach was 49% and of the amplicor assay was 44%. Patient outcomes were expressed as life expectancy for the base case of a 58-year-old man with a pretest probability of 5.7%. At this low pretest risk the differences in life expectancies between tests was < 0.1 years and the empirical approach incurred the lowest cost. Sensitivity analysis at increasing pretest risks showed better life expectancies (approximately 1 years) for CT scan and test combinations than empirical and amplicor for additional costs of US$243-US$309. Bronchoalveolar lavage had the worst overall cost-effectiveness. CONCLUSIONS: We conclude that the pretest risk of active PTB was a key determinant of test utility; that the AMPLICOR assay was comparable to clinical judgement; that BAL was the least useful test; and that with increasing risks, CT scan and test combinations performed better. Further studies are needed to better define patients with intermediate risk for PTB and to directly compare the cost-effectiveness of more sensitive nucleic acid amplification tests such as the enhanced Gen Probe, CT scan and test combinations/sequences in these patients. AD - Department of Medicine, National University of Singapore, Singapore. mdclimtk@nus.edu.sg AN - 11192555 AU - Lim, T. K. AU - Cherian, J. AU - Poh, K. L. AU - Leong, T. Y. DA - Dec ET - 02/24 KW - Bacteriological Techniques/economics/*standards *Bronchoalveolar Lavage Fluid Bronchoscopy/economics/*standards Cost-Benefit Analysis Decision Trees Humans Life Expectancy Male Middle Aged Nucleic Acid Amplification Techniques/economics/*standards Patient Selection Risk Factors Sensitivity and Specificity Sputum/*microbiology Tomography, X-Ray Computed/economics/*standards Tuberculosis, Pulmonary/*diagnosis/microbiology LA - eng N1 - Lim, T K Cherian, J Poh, K L Leong, T Y Case Reports Comparative Study Validation Studies Australia Respirology (Carlton, Vic.) Respirology. 2000 Dec;5(4):403-9. PY - 2001 RN - fulltext fulltext_1208 SN - 1323-7799 (Print) 1323-7799 (Linking) SP - 403-9 ST - The rapid diagnosis of smear-negative pulmonary tuberculosis: a cost-effectiveness analysis T2 - Respirology TI - The rapid diagnosis of smear-negative pulmonary tuberculosis: a cost-effectiveness analysis UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11192555 VL - 5 ID - 2389 ER - TY - JOUR AB - This study examined whether costs associated with tuberculosis (TB) screening and directly observed preventive therapy (DOPT) among drug injectors attending a syringe exchange are justified by cases and costs of active TB cases prevented and examined the impact of monetary incentives to promote adherence on cost-effectiveness. We examined program costs and projected savings using observed adherence and prevalence rates and literature estimates of isoniazid (INH) preventive therapy efficacy, expected INH hepatoxicity rates, and TB treatment costs; we conducted sensitivity analyses for a range of INH effectiveness, chest X-ray (CXR) referral adherence, and different strategies regarding anergy among persons affected with human immunodeficiency virus (HIV). For 1,000 patients offered screening, incorporating real observed program adherence rates, the program would avert $179,934 in TB treatment costs, for a net savings of $123,081. Assuming a modest risk of TB among HIV-infected anergic persons, all strategies with regard to anergy were cost saving, and the strategy of not screening for anergy and not providing DOPT to HIV-infected anergic persons resulted in the greatest cost savings. If an incentive of $25 per person increased CXR adherence from the observed 31% to 50% or 100%, over a 5-year follow-up the net cost savings would increase to $170,054 and $414,856, respectively. In this model, TB screening and DOPT at a syringe exchange is a cost-effective intervention and is cost-saving compared to costs of treating active TB cases that would have occurred in the absence of the intervention. This model is useful in evaluating the cost impact of planned program refinements, which can then be tested. Monetary incentives for those referred for screening CXRs would be justified on a cost basis if they had even a modest beneficial impact on adherence. AD - Beth Israel Medical Center, First Avenue at 16th Street, New York City, NY 10003, USA. dperlman@bethisraelny.org AN - 11564856 AU - Perlman, D. C. AU - Gourevitch, M. N. AU - Trinh, C. AU - Salomon, N. AU - Horn, L. AU - Des Jarlais, D. C. DA - Sep DO - 10.1093/jurban/78.3.550 ET - 09/21 KW - AIDS-Related Opportunistic Infections/complications/diagnosis/prevention & control Adolescent Adult Antitubercular Agents/economics/therapeutic use/toxicity Cost-Benefit Analysis Female HIV Seropositivity Humans Incidence Isoniazid/economics/therapeutic use/toxicity Male Mass Screening/*economics Middle Aged *Needle-Exchange Programs New York City Substance Abuse, Intravenous/epidemiology Tuberculosis/*diagnosis/epidemiology/*prevention & control LA - eng N1 - Perlman, D C Gourevitch, M N Trinh, C Salomon, N Horn, L Des Jarlais, D C R01 DA9005/DA/NIDA NIH HHS/United States Research Support, U.S. Gov't, P.H.S. United States Journal of urban health : bulletin of the New York Academy of Medicine J Urban Health. 2001 Sep;78(3):550-67. PY - 2001 RN - fulltext fulltext_1208 SN - 1099-3460 (Print) 1099-3460 (Linking) SP - 550-67 ST - Cost-effectiveness of tuberculosis screening and observed preventive therapy for active drug injectors at a syringe-exchange program T2 - J Urban Health TI - Cost-effectiveness of tuberculosis screening and observed preventive therapy for active drug injectors at a syringe-exchange program UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11564856http://www.springerlink.com/content/c7n6868776414512/fulltext.pdf VL - 78 ID - 2406 ER - TY - JOUR AB - HIV affects the pathogenesis and the transmission of Mycobacterium tuberculosis. We used a discrete event simulation model to predict the potential impact of HIV on increasing the probability and the expected severity of tuberculosis outbreaks. Our predictions reveal that an HIV epidemic can significantly increase the frequency and severity of tuberculosis outbreaks, but that this amplification effect of HIV on tuberculosis outbreaks is very sensitive to the tuberculosis treatment rate. At moderate or low treatment rates, even a moderate HIV epidemic can cause the average size of tuberculosis outbreaks to almost double in comparison with the expected outbreak size when HIV is absent. However, we determined that the amplification effect of HIV can be substantially reduced if the treatment rate of tuberculosis is very high. We discuss the significant implications of these results for the global control of tuberculosis. Our results also reveal that occasionally a "normal-virulence" strain of M. tuberculosis can be expected to generate a large outbreak. We discuss the implications of these results in understanding the virulence of M. tuberculosis and in the planned elimination of tuberculosis in the United States. AD - San Francisco Department of Public Health, San Francisco, California, USA. AN - 11744831 AU - Porco, T. C. AU - Small, P. M. AU - Blower, S. M. DA - Dec 15 DP - Nlm ET - 12/18 KW - Antitubercular Agents/therapeutic use Computer Simulation Disease Outbreaks HIV Infections/ epidemiology Humans Models, Biological Tuberculosis/drug therapy/ epidemiology/prevention & control United States LA - eng N1 - Porco, T C Small, P M Blower, S M AI35969/AI/NIAID NIH HHS/United States AI41935/AI/NIAID NIH HHS/United States DA10135/DA/NIDA NIH HHS/United States Research Support, U.S. Gov't, P.H.S. United States Journal of acquired immune deficiency syndromes (1999) J Acquir Immune Defic Syndr. 2001 Dec 15;28(5):437-44. PY - 2001 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1525-4135 (Print) 1525-4135 (Linking) SP - 437-44 ST - Amplification dynamics: predicting the effect of HIV on tuberculosis outbreaks T2 - J Acquir Immune Defic Syndr TI - Amplification dynamics: predicting the effect of HIV on tuberculosis outbreaks VL - 28 ID - 2407 ER - TY - JOUR AB - BACKGROUND: The international controversy surrounding the use and effectiveness of the Bacillus Calmette-Guerin (BCG) vaccine and the low incidence of tuberculosis (TB) among Japanese children prompted this study. METHODS: We compared 'universal BCG vaccination' with 'no vaccination at all' using a cost-effectiveness analysis. The study population was a hypothetical cohort comprising a total of 1.2 million infants born in 1996 at locations all over Japan. A model was developed to calculate the number of TB cases prevented by the vaccination programme. Assuming 40-80% overall vaccine efficacy (64-86% for TB-meningitis) and 10 years of protection, we calculated the cost and number of immunizations required to prevent one child from developing TB, the total number of TB cases averted by vaccination and total costs required for the programme. RESULTS: Based on an assumption of flexible vaccine efficacy (40-80%), we estimated that 111-542 TB cases including 10-27 of TB-meningitis would be prevented during the 10 years after BCG vaccination among the cohort of infants born in 1996. About US$35 950-175 862 or 2125-10 399 immunizations would be required to prevent one child from developing TB. Sensitivity analyses covering a wide duration of protection, incidence of TB, vaccine coverage and discount rate, revealed that other than vaccine efficacy, the cost of preventing a single case of TB is highly sensitive to the duration of BCG protection and TB incidence. CONCLUSION: The cost per case of TB prevented is heavily dependent on vaccine efficacy and the duration of protection, and is high compared with the cost of treating one child who has developed TB. AD - Department of General Medicine and Clinical Epidemiology, Kyoto University Graduate School of Medicine, Kyoto, Japan. AN - 11369746 AU - Rahman, M. AU - Sekimoto, M. AU - Takamatsu, I. AU - Hira, K. AU - Shimbo, T. AU - Toyoshima, K. AU - Fukui, T. DA - Apr J2 - International journal of epidemiology KW - BCG Vaccine/adverse effects/*economics Child Child, Preschool Cost-Benefit Analysis *Health Planning Humans Immunization Programs/*economics Infant Japan/epidemiology Models, Econometric Tuberculosis/epidemiology/mortality/*prevention & control LA - eng N1 - Comparative Study Journal Article Research Support, Non-U.S. Gov't England PY - 2001 RN - fulltext fulltext_1208 SN - 0300-5771 (Print) SP - 380-385 ST - Economic evaluation of universal BCG vaccination of Japanese infants T2 - Int J Epidemiol TI - Economic evaluation of universal BCG vaccination of Japanese infants UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11369746 VL - 30 ID - 2408 ER - TY - JOUR AB - This paper documents and attempts to explain the epidemic spread of tuberculosis (TB) in Russia during the 1990s. After several decades of decline, the notification rate of all new TB cases among permanent residents increased by 7.5% per year from 1991-1999 and the death rate by 11% per year. Growth was quickest from 1993-1995 but increased again after the economic crisis of August 1998. Approximately 120 000 new cases and 30 000 deaths were reported in 1999. Case detection and cure rates have fallen in Russia since the mid-1980s; the fall has been accompanied by a higher frequency of severe disease among cases, and higher death and case fatality rates. With a mathematical model describing the deterioration in case finding and cure rates we could replicate the average rate of increase in incidence 1991-1999 but not the precise timing of the observed changes. Other factors that probably helped to shape the observed rise in caseload include enhanced transmission due to the mixing of prison and civilian populations, an increase in susceptibility to disease, and changes in the proportion of cases detected by surveillance. Although our explanation for the resurgence of TB is incomplete, we have identified a set of measures that can be implemented now to cut transmission, incidence and deaths. AD - Department of Epidemiology and Antituberculosis Care Organization, Research Institute of Phthisiopulmonology, I. M. Setchenov Medical Academy, 4 Dostoevsky Street, 101478 Moscow, Russian Federation. AN - 11516384 AU - Shilova, M. V. AU - Dye, C. DA - Jul 29 DO - 10.1098/rstb.2001.0895 [doi] DP - Nlm ET - 08/23 KW - Humans Prevalence Prisons Quality of Health Care Russia/epidemiology Survival Rate Treatment Outcome Tuberculosis/drug therapy/ epidemiology LA - eng N1 - Shilova, M V Dye, C Research Support, Non-U.S. Gov't England Philosophical transactions of the Royal Society of London. Series B, Biological sciences Philos Trans R Soc Lond B Biol Sci. 2001 Jul 29;356(1411):1069-75. PY - 2001 RN - fulltext fulltext_1208 SN - 0962-8436 (Print) 0962-8436 (Linking) SP - 1069-75 ST - The resurgence of tuberculosis in Russia T2 - Philos Trans R Soc Lond B Biol Sci TI - The resurgence of tuberculosis in Russia UR - http://rstb.royalsocietypublishing.org.ez.lshtm.ac.uk/content/356/1411/1069.full.pdf VL - 356 ID - 2409 ER - TY - JOUR AB - Though it is recognized that the extent of 'clustering' of isolates from tuberculosis cases in a given population is related to the amount of disease attributable to recent transmission, the relationship between the two statistics is poorly understood. Given age-dependent risks of disease and the fact that a long study (e.g. spanning several years) is more likely to identify transmission-linked cases than a shorter study, both measures, and thus the relationship between them, probably depend strongly on the ages of the cases ascertained and study duration. The contribution of these factors is explored in this paper using an age-structured model which describes the introduction and transmission of M. tuberculosis strains with different DNA fingerprint patterns in The Netherlands during this century, assuming that the number of individuals contacted by each case varies between cases and that DNA fingerprint patterns change over time through random mutations, as observed in several studies. Model predictions of clustering in different age groups and over different time periods between 1993 and 1997 compare well against those observed. According to the model, the proportion of young cases with onset in a given time period who were 'clustered' underestimated the proportion of disease attributable to recent transmission in this age group (by up to 25% in males); for older individuals, clustering overestimated this proportion. These under- and overestimates decreased and increased respectively as the time period over which the cases were ascertained increased. These results have important implications for the interpretation of estimates of the proportion of disease attributable to recent transmission, based on 'clustering' statistics, as are being derived from studies of the molecular epidemiology of tuberculosis in many populations. AD - Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine. AN - 11293682 AU - Vynnycky, E. AU - Nagelkerke, N. AU - Borgdorff, M. W. AU - van Soolingen, D. AU - van Embden, J. D. AU - Fine, P. E. KW - Adolescent Adult Age Factors Aged Child Child, Preschool Cluster Analysis *DNA Fingerprinting Epidemiology, Molecular Female Human Infant Infant, Newborn Life Style Longitudinal Studies Male Middle Age Models, Biological Mutation Mycobacterium tuberculosis/*classification/genetics/isolation & purification Netherlands Support, Non-U.S. Gov't Time Factors Tuberculosis/epidemiology/prevention & control/*transmission PY - 2001 RN - fulltext fulltext_1208 SP - 43-62. ST - The effect of age and study duration on the relationship between 'clustering' of DNA fingerprint patterns and the proportion of tuberculosis disease attributable to recent transmission T2 - Epidemiol Infect TI - The effect of age and study duration on the relationship between 'clustering' of DNA fingerprint patterns and the proportion of tuberculosis disease attributable to recent transmission UR - http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11293682http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869673/pdf/11293682.pdf VL - 126 ID - 2410 ER - TY - JOUR AB - A key issue for the study of tuberculosis infection (TB) is to understand why individuals infected with Mycobacterium tuberculosis experience different clinical outcomes. Elaborating the immune mechanisms that determine whether an infected individual will suffer active TB or latent infection can aid in developing treatment and prevention strategies. To better understand the dynamics of M. tuberculosis infection and immunity, we have developed a virtual human model that qualitatively and quantitatively characterizes the cellular and cytokine control network operational during TB infection. Using this model, we identify key regulatory elements in the host response. In particular, factors affecting cell functions, such as macrophage activation and bactericidal capabilities, and effector T cell functions such as cytotoxicity and cytokine production can each be determinative. The model indicates, however, that even if latency is achieved, it may come at the expense of tissue damage if the response is not properly regulated. A balance in Th1 and Th2 immune responses governed by IFN-gamma, IL-10, and IL-4 facilitate this down-regulation. These results are further explored through virtual deletion and depletion experiments. AD - Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. AN - 11160244 AU - Wigginton, J. E. AU - Kirschner, D. KW - Acute Disease Animals Disease Progression Humans Immunity, Cellular Interleukin-10/biosynthesis/deficiency/genetics Macrophage Activation/genetics/immunology Macrophages/*immunology/metabolism/microbiology Mice Mice, Knockout *Models, Immunological Mycobacterium tuberculosis/growth & development/*immunology Sequence Deletion Tuberculosis/etiology/*immunology/microbiology/prevention & control LA - eng N1 - Wigginton, J E Kirschner, D HL62119-01/HL/NHLBI NIH HHS/United States Comparative Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Journal of immunology (Baltimore, Md. : 1950) J Immunol. 2001 Feb 1;166(3):1951-67. PY - 2001 RN - fulltext fulltext_1208 SN - 0022-1767 (Print) 0022-1767 (Linking) SP - 1951-1967 ST - A model to predict cell-mediated immune regulatory mechanisms during human infection with Mycobacterium tuberculosis T2 - Journal of Immunology TI - A model to predict cell-mediated immune regulatory mechanisms during human infection with Mycobacterium tuberculosis UR - http://www.ncbi.nlm.nih.gov/pubmed/11160244http://www.jimmunol.org/content/166/3/1951.full.pdf VL - 166 ID - 2411 ER - TY - JOUR AB - The risk of developing active tuberculosis is highest within the first 2 years of infection. Therefore, an intervention that targets persons with recent infection, such as identifying contacts of active cases, could be particularly effective as an epidemic control measure. A mathematical model of a tuberculosis epidemic is formulated and used to evaluate the strategy of targeting therapy to persons with recently acquired latent tuberculosis infection. The model is used to quantify the effectiveness of therapy for early latent tuberculosis infection in reducing the prevalence of active tuberculosis. The model is also used to demonstrate how effective therapy for early latent tuberculosis infection has to be to eliminate tuberculosis, when used in conjunction with therapy for active tuberculosis. Analysis of the model suggests that programs such as contact investigations, which identify and treat persons recently infected with Mycobacterium tuberculosis, may have a substantial effect on controlling tuberculosis epidemics. AD - Department of Medicine, Veterans' Affairs Medical Center, San Francisco 94121, USA. eziv@itsa.ucsf.edu AN - 11207156 AU - Ziv, E. AU - Daley, C. L. AU - Blower, S. M. DA - Feb 15 ET - 02/24 J2 - American journal of epidemiology KW - Antitubercular Agents/therapeutic use Humans *Models, Theoretical Mycobacterium tuberculosis/isolation & purification Risk Factors Time Factors Treatment Outcome Tuberculosis/*drug therapy/epidemiology/prevention & control LA - eng M3 - Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. N1 - Ziv, E Daley, C L Blower, S M R01-AI41935/AI/NIAID NIH HHS/ Am J Epidemiol. 2001 Feb 15;153(4):381-5. PY - 2001 RN - fulltext fulltext_1208 SN - 0002-9262 (Print) 0002-9262 (Linking) SP - 381-5 ST - Early therapy for latent tuberculosis infection T2 - Am J Epidemiol TI - Early therapy for latent tuberculosis infection UR - http://www.ncbi.nlm.nih.gov/pubmed/11207156http://aje.oxfordjournals.org/content/153/4/381.full.pdf VL - 153 ID - 2413 ER - TY - JOUR AB - Abrupt changes in environmental conditions--broadly understood to include demographic and social dynamics--can seriously impact the local or global disease dynamics of a population. These changes in the evolutionary landscape, which may occur over relatively short time-scales, are very likely to play a critical role in disease evolution. The potential impact of demographic, social and epidemiological shifts on the evolution of tuberculosis epidemics in the United States over the past century and a half is the main subject of this article. Evidence is provided to support the hypothesis that the observed substantial decreases in the incidence of active tuberculosis are the result of abrupt reductions in the rates of disease progression. AD - Department of Biometrics & Mathematical and Theoretical Biology Institute, Cornell University, 431 Warren Hall, Ithaca, NY 14853-7801, USA. jpa9@cornell.edu AN - 12051976 AU - Aparicio, J. P. AU - Capurro, A. F. AU - Castillo-Chavez, C. DA - Mar 21 DO - 10.1006/jtbi.2001.2489 [doi] S0022519301924890 [pii] DP - Nlm ET - 06/08 KW - Disease Outbreaks Disease Progression Humans Life Style Models, Statistical Nutritional Physiological Phenomena Prevalence Social Environment Tuberculosis/ epidemiology/microbiology/transmission United States/epidemiology Urbanization LA - eng N1 - Aparicio, Juan P Capurro, AngelL F Castillo-Chavez, Carlos Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England Journal of theoretical biology J Theor Biol. 2002 Mar 21;215(2):227-37. PY - 2002 RN - fulltext fulltext_1208 SN - 0022-5193 (Print) 0022-5193 (Linking) SP - 227-37 ST - Markers of disease evolution: the case of tuberculosis T2 - J Theor Biol TI - Markers of disease evolution: the case of tuberculosis UR - http://ac.els-cdn.com/S0022519301924890/1-s2.0-S0022519301924890-main.pdf?_tid=248e607c3524c38ff4ea031877b0a45e&acdnat=1345011913_2c141ed2452b2d827ae048d90a11fd90 VL - 215 ID - 2414 ER - TY - JOUR AB - OBJECTIVE: The annual risk of infection (ARI) for tuberculosis is the probability that an individual without previous contact with the tubercle bacillus has of being infected during the course of a year. The ARI is the most appropriate indicator for estimating the degree of tuberculosis infection in a population. The objective of this paper was to estimate the ARI and its trends in the city of Cali, Colombia, using data provided by the Municipal Secretariat of Health. METHODS: We used a deterministic model of the dynamics of pulmonary tuberculosis. The flows among the population subgroups were based on the natural history of the disease, taking vaccination into account. Using the data from the Municipal Secretariat of Health, we estimated the initial conditions and the values of the parameters. RESULTS: The mean ARI values were 1.24% in the 1970s, 0.93% in the 1980s, and 0.85% in the 1990s. In order to assess trends, we attempted to predict the annual risk, utilizing a nonlinear least-squares adjustment of the data on the overall percentage for each year. With that approach, we projected that the ARI in 2003 would be 1.3%, indicating a return to the patterns found in the 1970s. CONCLUSIONS: The estimated risk of tuberculosis infection in Cali during the decades of the 1970s, the 1980s, and the 1990s was very high in comparison with the risk in countries such as the Netherlands, which in 1985 had an ARI of 0.012%. However, the ARI in Cali is not so high in comparison to indices for other countries of South America, which range from 0.5% to 1.5%. This model and the simulation it produced showed a rising trend in the ARI for Cali, as well as demonstrated that the ARI will tend to continue to rise if control measures are not improved. AD - Universidad Autonoma de Occidente, Departamento de Ciencias Basicas, Calle 25 No. 115-85, Cali, Colombia. AN - 11998182 AU - de la Pava, E. AU - Salguero, B. AU - Alzate, A. DA - Mar J2 - Revista panamericana de salud publica = Pan American journal of public health KW - Colombia Humans *Models, Statistical Risk Assessment Time Factors Tuberculosis/*epidemiology LA - spa N1 - English Abstract Journal Article United States OP - Modelo matematico del riesgo anual de infeccion tuberculosa en Cali. PY - 2002 RN - fulltext fulltext_1208 SN - 1020-4989 (Print) SP - 166-171 ST - [A mathematical model of the annual risk of tuberculosis infection in Cali, Colombia] T2 - Rev Panam Salud Publica TI - [A mathematical model of the annual risk of tuberculosis infection in Cali, Colombia] UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11998182 VL - 11 ID - 2415 ER - TY - JOUR AB - The discovery of high prevalences of antibiotic resistance in some pathogens, in some parts of the world, has provoked fears of a widespread loss of drug efficacy. Here, we use a mathematical model to investigate the evolution of resistance to four major anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol and streptomycin) in 47 sites around the world. The model provides a new method of estimating the relative risk of treatment failure for patients carrying drug-resistant strains and the proportion of patients who develop resistance after failing treatment. Using estimates of these two quantities together with other published data, we reconstructed the epidemic spread of isoniazid resistance over the past 50 years. The predicted median prevalence of resistance among new cases today was 7.0% (range 0.9-64.3%), close to the 6.3% (range 0-28.1%) observed. Predicted and observed prevalences of resistance to isoniazid plus rifampicin (multidrug-resistant or MDR-TB) after 30 years of combined drug use were also similar, 0.9% (0.1-5.9%) and 1.0% (range 0-14.1%), respectively. With current data, and under prevailing treatment practices, it appears that MDR-TB will remain a localized problem, rather than becoming a global obstacle to tuberculosis control. To substantiate this result, further measurements are needed of the relative fitness of drug-resistant strains. AD - Communicable Diseases, World Health Organization, Geneva, Switzerland. dyec@who.int AN - 12123297 AU - Dye, C. AU - Espinal, M. A. DA - Jan 7 DO - 10.1098/rspb.2000.1328 [doi] DP - Nlm ET - 07/19 KW - Antitubercular Agents/ pharmacology Drug Resistance, Multiple, Bacterial Humans Isoniazid/pharmacology Microbial Sensitivity Tests Models, Biological Mycobacterium tuberculosis/ drug effects Prevalence Rifampin/pharmacology Treatment Failure Tuberculosis, Multidrug-Resistant/drug therapy/ epidemiology/microbiology Tuberculosis, Pulmonary/drug therapy/ epidemiology/microbiology L1 - internal-pdf://0211382621/Dye-2002-Will tuberculosis become resistant to.pdf LA - eng N1 - Dye, C Espinal, M A England Proceedings. Biological sciences / The Royal Society Proc Biol Sci. 2001 Jan 7;268(1462):45-52. PY - 2002 RN - fulltext fulltext_1208 SN - 0962-8452 (Print) 0962-8452 (Linking) SP - 45-52 ST - Will tuberculosis become resistant to all antibiotics? T2 - Proc Biol Sci TI - Will tuberculosis become resistant to all antibiotics? UR - http://rspb.royalsocietypublishing.org.ez.lshtm.ac.uk/content/268/1462/45.full.pdf http://rspb.royalsocietypublishing.org/content/royprsb/268/1462/45.full.pdf VL - 268 ID - 2402 ER - TY - JOUR AU - Feng, Z. AU - Iannelli, M. AU - Milner, F. A. PY - 2002 SP - 1634-1656 ST - A two-strain tuberculosis model with age of infection T2 - SIAM J Appl Math TI - A two-strain tuberculosis model with age of infection VL - 62 ID - 3946 ER - TY - JOUR AB - Studies of early bactericidal activity (EBA) are important in the rapid evaluation of new antituberculosis drugs. Historically, these have concentrated on the log fall in the viable count in sputum during the first 48 hours of therapy. In this paper, we provide a mathematical model that suggests that the viable count in sputum follows an exponential decay curve with the equation V = S + Me(-kt) (where V is the viable count, M the population of bacteria susceptible to the test drug, S the population susceptible only to sterilizing agents, t the day of sputum collection as related to start of therapy, k the rate constant for the bacteria killed each day, and e the Napierian constant). We demonstrate that data from clinical trials fits the exponential decay model. We propose that future EBA studies should be performed by measuring daily quantitative counts for at least 5 days. We also propose that the comparison of the early bactericidal activity of antituberculosis drugs should be evaluated using the time taken to reduce the viable count by 50% (vt(50)). A further reiterative refinement following a rule set based on statistically the best fit to the exponential decay model is described that will allow investigators to identify anomalous results and thus enhance the accuracy in measuring early bactericidal activity. AD - Academic Department of Medical Microbiology, Royal Free and University College Medical School, London, United Kingdom. stepheng@rfc.ucl.ac.uk AN - 12091167 AU - Gillespie, S. H. AU - Gosling, R. D. AU - Charalambous, B. M. DA - Jul 1 DP - Nlm ET - 07/02 KW - Anti-Infective Agents/pharmacology Antitubercular Agents/ pharmacology Ciprofloxacin/pharmacology Clinical Trials as Topic/statistics & numerical data Colony Count, Microbial Drug Evaluation/ statistics & numerical data Humans Isoniazid/pharmacology Models, Biological Mycobacterium tuberculosis/ drug effects Regression Analysis Sputum/microbiology Tuberculosis, Pulmonary/ drug therapy LA - eng N1 - Gillespie, Stephen H Gosling, Roland D Charalambous, Bambos M Research Support, Non-U.S. Gov't United States American journal of respiratory and critical care medicine Am J Respir Crit Care Med. 2002 Jul 1;166(1):31-5. PY - 2002 RN - fulltext fulltext_1208 SN - 1073-449X (Print) 1073-449X (Linking) SP - 31-5 ST - A reiterative method for calculating the early bactericidal activity of antituberculosis drugs T2 - Am J Respir Crit Care Med TI - A reiterative method for calculating the early bactericidal activity of antituberculosis drugs UR - http://ajrccm.atsjournals.org/content/166/1/31.full.pdf VL - 166 ID - 2417 ER - TY - JOUR AD - Fac Ciencias Lisboa, DBV, P-1749016 Lisbon, Portugal. Ctr Matemat & Aplicacoes Fundamentais, P-1649003 Lisbon, Portugal. Gomes, MC (reprint author), Fac Ciencias Lisboa, DBV, Bloco C2,Piso 4,Campo Grande, P-1749016 Lisbon, Portugal. AN - WOS:000172946800008 AU - Gomes, M. C. AU - Margheri, A. AU - Rebelo, C. DA - Feb DO - 10.1016/s0362-546x(00)00211-x IS - 4 J2 - Nonlinear Anal.-Theory Methods Appl. KW - tuberculosis bifurcation stability persistence epidemiology mortality Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: 506AB Times Cited: 2 Cited Reference Count: 27 Gomes, MC Margheri, A Rebelo, C Rebelo, Carlota/M-2582-2015; Margheri, Alessandro/M-8717-2015; Gomes, Manuel/F-9633-2011 Rebelo, Carlota/0000-0001-5818-8892; Margheri, Alessandro/0000-0001-6475-3405; Gomes, Manuel/0000-0002-2679-0974 2 0 3 Pergamon-elsevier science ltd Oxford PY - 2002 SN - 0362-546X SP - 617-636 ST - Stability and persistence in a compartment model of pulmonary tuberculosis T2 - Nonlinear Analysis-Theory Methods & Applications TI - Stability and persistence in a compartment model of pulmonary tuberculosis UR - ://WOS:000172946800008 VL - 48 ID - 6263 ER - TY - JOUR AB - Optimal control theory is applied to a system of ordinary differential equations modeling a two-strain tuberculosis model. Seeking to reduce the latent and infectious groups with the resistant-strain tuberculosis, we use controls representing two types of treatments. The optimal controls are characterized in terms of the optimality system, which is solved numerically for several scenarios. AD - Oak Ridge Natl Lab, Div Math & Comp Sci, Oak Ridge, TN 37831 USA Univ Tennessee, Dept Math, Knoxville, TN 37996 USA Purdue Univ, Dept Math, W Lafayette, IN 47907 USA AN - WOS:000178082300001 AU - Jung, E. AU - Lenhart, S. AU - Feng, Z. DA - Nov IS - 4 J2 - Discrete Cont Dyn-B KW - mathematical model tuberculosis optimal control antibiotic resistance strategies LA - English N1 - 594zl Times Cited:111 Cited References Count:15 PY - 2002 SN - 1531-3492 SP - 473-482 ST - Optimal control of treatments in a two-strain tuberculosis model T2 - Discrete and Continuous Dynamical Systems-Series B TI - Optimal control of treatments in a two-strain tuberculosis model UR - ://WOS:000178082300001 VL - 2 ID - 4831 ER - TY - JOUR AB - The effects of standard patterns of population growth in blended SI-SEI models (of which models for 'fast and slow' tuberculosis are an instance) are considered. When the incidence has the 'true mass action' form, the system is globally stable under both exponential and logistic population dynamics, whereas sustained oscillations occur in the case of bilinear incidence. This shows in the final analysis, the minimal dynamical ingredients needed to generate oscillations in basic epidemiological models: provided the population is exponentially growing and the incidence is bilinear, at least a fraction of the newly exposed individuals must enter the infective state with a delay. AD - Dipartimento Stat & Mat Applicata Econ, I-56124 Pisa, Italy Dipartimento Sci Econ & Metodi Quantitat, I-28100 Novara, Italy AN - WOS:000181449600002 AU - Manfredi, P. AU - Salinelli, E. DA - Jun IS - 2 J2 - Ima J Math Appl Med KW - basic epidemiological models exponential and logistic population dynamics sustained oscillations dependent death rate epidemic models tuberculosis LA - English N1 - 653qy Times Cited:6 Cited References Count:20 PY - 2002 SN - 0265-0746 SP - 95-111 ST - Population-induced oscillations in blended SI-SEI epidemiological models T2 - Ima Journal of Mathematics Applied in Medicine and Biology TI - Population-induced oscillations in blended SI-SEI epidemiological models UR - ://WOS:000181449600002 VL - 19 ID - 4832 ER - TY - JOUR AB - A population model for the transmission dynamics of tuberculosis (TB) which incorporates a preventive vaccine and an effective therapeutic treatment is analysed qualitatively. The existence and uniqueness of the associated endemic equilibrium are discussed. By constructing a Lyapunov function, the global stability of the disease-free equilibrium of the model is established. The stability analysis of the diseasefree equilibrium reveals that the disease dynamics depends on a threshold quantity called the basic reproduction number (R0) such that the disease will be eradicated from the community if R0 < 1 and it persists if R0 > 1. The model is adapted and used to study the case where no preventive vaccine is administered. In addition to establishing the global stability of the vaccination-free model, the optimal treatment rate needed for disease eradication is determined. The vaccination-free model is then extended to monitor the effect of exogenous re-infection in the transmission dynamics of TB. Our analysis shows that the vaccination-free model with exogenous re-infection may undergo the phenomenon of bistability where a stable endemic equilibrium can co-exist with the stable disease-free equilibrium when R0 < 1. This shows that, unlike in the case without exogenous re-infection, reducing R0 to values less than unity may fail to eradicate the disease. AU - Moghadas, S. M. AU - Gumbo, A. B. IS - 3 PY - 2002 SP - 411-428 ST - ANALYSIS OF A MODEL FOR TRANSMISSION DYNAMICS OF TB T2 - Canadian Applied Mathematics Quarterly TI - ANALYSIS OF A MODEL FOR TRANSMISSION DYNAMICS OF TB UR - http://ami.math.ualberta.ca/CAMQ/pdf_files/vol_10/10_3/10_3e.pdf VL - 10 ID - 4937 ER - TY - JOUR AB - There is wide variation in endemic tuberculosis (TB) levels between countries and we seek to identify possible causes of these differences. In this study we present an epidemiological model of Mycobacterium tuberculosis infection to investigate the effects of host genetics and demographic factors on epidemic TB. We discuss the general framework for this approach and present analytical results to identify important parameters affecting steady-state prevalence and incidence rates of TB disease. We then use numerical simulations of our model to observe the effects of a genetically susceptible subpopulation on TB disease dynamics at the population level. Finally, we simulate infection within a genetically heterogeneous population in two demographic settings: India (a typical population with high TB prevalence) and the USA (a typical population with low TB prevalence). Results show that changes in transmission parameters, the fraction of the population genetically susceptible to infection, and demographic factors strongly affect TB prevalence and incidence rates. AD - Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA. AN - 12387922 AU - Murphy, B. M. AU - Singer, B. H. AU - Anderson, S. AU - Kirschner, D. DA - Nov-Dec DO - S0025556402001335 [pii] DP - Nlm ET - 10/22 KW - Computer Simulation Demography Disease Outbreaks Genetic Predisposition to Disease Humans India/epidemiology Models, Theoretical Tuberculosis/ epidemiology/genetics/immunology/transmission United States/epidemiology LA - eng N1 - Murphy, Brian M Singer, Benjamin H Anderson, Shoana Kirschner, Denise 5 T32 AI07528/AI/NIAID NIH HHS/United States R01 HL62119/HL/NHLBI NIH HHS/United States Comparative Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Mathematical biosciences Math Biosci. 2002 Nov-Dec;180:161-85. PY - 2002 RN - fulltext fulltext_1208 SN - 0025-5564 (Print) 0025-5564 (Linking) SP - 161-85 ST - Comparing epidemic tuberculosis in demographically distinct heterogeneous populations T2 - Math Biosci TI - Comparing epidemic tuberculosis in demographically distinct heterogeneous populations UR - http://ac.els-cdn.com/S0025556402001335/1-s2.0-S0025556402001335-main.pdf?_tid=c442474c03637019ddb7f06fa7db5546&acdnat=1345012736_fe7a70aea1d9e14e5fc4f705b497ddf7 VL - 180 ID - 2418 ER - TY - JOUR AB - Recently developed molecular techniques have revolutionized the epidemiology of tuberculosis. Multiple studies have used these tools to examine the population structure of Mycobacterium tuberculosis isolates in different communities. The distributions of clusters of M. tuberculosis isolates in these settings may variously reflect social mixing patterns or the differential fitness of specific clones of the organism. We developed an individual-based microsimulation of tuberculosis transmission to explore social and demographic determinants of cluster distribution and to observe the effect of transmission dynamics on the empiric data from molecular epidemiologic studies. Our results demonstrate that multiple host-related factors contribute to wide variation in cluster distributions even when all strains of the organism are assumed to be equally transmissible. These host characteristics include interventions such as chemotherapy, vaccination and chemoprophylaxis, HIV prevalence, the age structure of the population, and the prevalence of latent tuberculosis infection. We consider the implications of these results for the interpretation of cluster studies of M. tuberculosis as well as the more general application of microsimulation models to infectious disease epidemiology. AD - Department of Epidemiology, Harvard School of Public Health and Infectious Disease Unit, Massachusetts General Hospital, 677 Huntington Avenue, Boston, MA, 02115, USA. mmurray@hsph.harvard.edu AN - 11818527 AU - Murray, M. DA - Feb 5 DO - 10.1073/pnas.022618299 ET - 01/31 J2 - Proceedings of the National Academy of Sciences of the United States of America KW - Cluster Analysis HIV Infections/epidemiology Humans Incidence Molecular Epidemiology Mycobacterium tuberculosis/*genetics Netherlands/epidemiology Prevalence Prisoners/statistics & numerical data Tuberculosis/*epidemiology/transmission United States/epidemiology LA - eng M3 - Comparative Study Research Support, U.S. Gov't, P.H.S. N1 - Murray, Megan PY - 2002 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0027-8424 (Print) 0027-8424 (Linking) SP - 1538-43 ST - Determinants of cluster distribution in the molecular epidemiology of tuberculosis T2 - Proc Natl Acad Sci U S A TI - Determinants of cluster distribution in the molecular epidemiology of tuberculosis UR - http://www.ncbi.nlm.nih.gov/pubmed/11818527http://www.ncbi.nlm.nih.gov/pmc/articles/PMC122226/pdf/pq0302001538.pdf VL - 99 ID - 2419 ER - TY - JOUR AB - Among the goals of the molecular epidemiology of infectious disease are to quantify the extent of ongoing transmission of infectious agents and to identify host- and strain-specific risk factors for disease spread. I demonstrate the potential bias in estimates of recent transmission and the impact of risk factors for clustering by using computer simulations to reconstruct populations of tuberculosis patients and sample from them. The bias consistently results in underestimating recent transmission and the impact of risk factors for recent transmission. AD - Department of Epidemiology, Harvard School of Public Health, Boston, Massachussetts 02115, USA. mmurray@hsph.harvard.edu AN - 11971768 AU - Murray, M. DA - Apr DO - 10.3201/eid0804.000444 [doi] DP - Nlm ET - 04/25 KW - Algeria/epidemiology Computer Simulation Humans Molecular Epidemiology/ methods Monte Carlo Method Mycobacterium tuberculosis/isolation & purification Netherlands/epidemiology Odds Ratio Risk Factors Selection Bias Sudan/epidemiology Tuberculosis/ epidemiology/ transmission United States/epidemiology LA - eng N1 - Murray, Megan K08 A1-01430-01/PHS HHS/United States Research Support, U.S. Gov't, P.H.S. United States Emerging infectious diseases Emerg Infect Dis. 2002 Apr;8(4):363-9. PY - 2002 RN - fulltext fulltext_1208 SN - 1080-6040 (Print) 1080-6040 (Linking) SP - 363-9 ST - Sampling bias in the molecular epidemiology of tuberculosis T2 - Emerg Infect Dis TI - Sampling bias in the molecular epidemiology of tuberculosis VL - 8 ID - 2420 ER - TY - JOUR AB - SETTING: England and Wales. OBJECTIVE: To quantify the relative contribution of vaccination, chemotherapy and preventive therapy to the reduction in tuberculosis incidence in England and Wales between 1953 and 1990. DESIGN: A compartmental model of tuberculosis transmission was fitted to notification data between 1913 and 1939 to estimate pre-vaccination parameters. Best-fit estimates of the rates of chemotherapy and preventive therapy were derived by fitting the model to notification data between 1953 and 1990. Published vaccination rates were used. MAIN OUTCOME MEASURE: Number of cases of pulmonary tuberculosis averted. RESULTS: The numbers of respiratory tuberculosis cases averted between 1953 and 1990 by the use of preventive therapy, vaccination and chemotherapy were 288318, 57085 and 206996, respectively. CONCLUSIONS: Of those interventions considered, preventive therapy has the greatest impact on transmission. The duration of infectiousness is long, with an onset that is likely to pre-date sputum positivity. AD - Division of Primary Care and Population Health Sciences, Imperial College School of Medicine at St. Mary's, London, United Kingdom. RPitman@phls.org.uk AN - 12068980 AU - Pitman, R. AU - Jarman, B. AU - Coker, R. DA - Jun KW - *Antibiotic Prophylaxis Antitubercular Agents/*therapeutic use England/epidemiology Humans Incidence Intervention Studies *Models, Theoretical *Preventive Medicine Program Evaluation Research Support, Non-U.S. Gov't Tuberculosis Vaccines/*therapeutic use Tuberculosis, Pulmonary/*prevention & control/*transmission Wales/epidemiology N1 - 1027-3719 (Print) Journal Article PY - 2002 RN - fulltext fulltext_1208 SP - 485-491 ST - Tuberculosis transmission and the impact of intervention on the incidence of infection T2 - International Journal of Tuberculosis and Lung Disease TI - Tuberculosis transmission and the impact of intervention on the incidence of infection UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12068980 VL - 6 ID - 2421 ER - TY - JOUR AU - Raimundo, Silvia Martorano AU - Yang, Hyun Mo AU - Bassanezi, Rodney Carlos AU - Ferreira, Marizete A. C. DO - doi:10.1142/S0218339002000457 PY - 2002 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SP - 61-83 ST - THE ATTRACTING BASINS AND THE ASSESSMENT OF THE TRANSMISSION COEFFICIENTS FOR HIV AND M. TUBERCULOSIS INFECTIONS AMONG WOMEN INMATES T2 - Journal of Biological Systems TI - THE ATTRACTING BASINS AND THE ASSESSMENT OF THE TRANSMISSION COEFFICIENTS FOR HIV AND M. TUBERCULOSIS INFECTIONS AMONG WOMEN INMATES UR - http://www.worldscientific.com/doi/abs/10.1142/S0218339002000457 VL - 10 ID - 2422 ER - TY - JOUR AB - We introduce a spatial stochastic model for the spread of tuberculosis and HIV. We have three parameters: the size of the social cluster for each individual and the infection rates within and outside the social cluster. We show that when the infection rate from outside the cluster is low (this is presumably the case for tuberculosis and HIV) then an epidemic is possible only if the typical social cluster and the within infection rate are large enough. These results may be important in formulating new hypotheses for the transmission of TB and HIV. AD - Department of Mathematics, University of Colorado, Colorado Springs, Colorado 80933-7150, USA. schinazi@math.uccs.edu AN - 11969388 AU - Schinazi, R. B. DA - Mar DO - 10.1006/tpbi.2001.1567 [doi] S0040580901915679 [pii] DP - Nlm ET - 04/24 KW - Cluster Analysis Disease Outbreaks HIV Infections/epidemiology/transmission Humans Models, Statistical Population Density Risk Factors Social Support Stochastic Processes Tuberculosis/ epidemiology/ transmission LA - eng N1 - Schinazi, Rinaldo B United States Theoretical population biology Theor Popul Biol. 2002 Mar;61(2):163-9. PY - 2002 RN - fulltext fulltext_1208 SN - 0040-5809 (Print) 0040-5809 (Linking) SP - 163-9 ST - On the role of social clusters in the transmission of infectious diseases T2 - Theor Popul Biol TI - On the role of social clusters in the transmission of infectious diseases UR - http://ac.els-cdn.com/S0040580901915679/1-s2.0-S0040580901915679-main.pdf?_tid=e2b0ecad40d9f15e4534b3e5d0a67fcd&acdnat=1345013207_d1cc27591f1ef54a2bede8b9d0d62360 VL - 61 ID - 2423 ER - TY - JOUR AB - Models that incorporate local and individual interactions are introduced in the context of the transmission dynamics of tuberculosis (TB). The multi-level contact structure implicitly assumes that individuals are at risk of infection from close contacts in generalized household (clusters) as well as from casual (random) contacts in the general population. Epidemiological time scales are used to reduce the dimensionality of the model and singular perturbation methods are used to corroborate the results of time-scale approximations. The concept and impact of optimal average cluster or generalized household size on TB dynamics is discussed. We also discuss the potential impact of our results on the spread of TB. AD - Department of Biometrics, Mathematical and Theoretical Biology Institute, Cornell University, 432 Warren Hall, Ithaca, NY 14853-7801, USA. AN - 12387923 AU - Song, B. AU - Castillo-Chavez, C. AU - Aparicio, J. P. DA - Nov-Dec DO - S0025556402001128 [pii] DP - Nlm ET - 10/22 KW - Cluster Analysis Contact Tracing Humans Models, Biological Numerical Analysis, Computer-Assisted Time Factors Tuberculosis/epidemiology/ transmission LA - eng N1 - Song, Baojun Castillo-Chavez, Carlos Aparicio, Juan Pablo Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United States Mathematical biosciences Math Biosci. 2002 Nov-Dec;180:187-205. PY - 2002 RN - fulltext fulltext_1208 SN - 0025-5564 (Print) 0025-5564 (Linking) SP - 187-205 ST - Tuberculosis models with fast and slow dynamics: the role of close and casual contacts T2 - Math Biosci TI - Tuberculosis models with fast and slow dynamics: the role of close and casual contacts UR - http://ac.els-cdn.com/S0025556402001128/1-s2.0-S0025556402001128-main.pdf?_tid=ff43b778ac75d49e2ef08bce209549ec&acdnat=1345013627_f0917b7a8507859196d4207b8f56129c VL - 180 ID - 2424 ER - TY - JOUR AB - Mathematical models for Tuberculosis with linear and logistic growth rates are considered. The global dynamic structure for the logistic recruitment model is analyzed with the help of a strong version of the Poincare-Bendixson Theorem. The nature of the global dynamics of the same model with a linear recruitment rate is established with the use of explicit threshold quantities controlling the absolute and relative spread of the disease and the likelihood of extinction or persistence of the total population. The classification of planar quadratic systems helps rule out the existence of closed orbits (limit cycles). AD - Cornell Univ, Dept Biometr, Ithaca, NY 14853 USA AN - WOS:000176237600016 AU - Song, B. J. AU - Castillo-Chavez, C. AU - Aparicio, J. P. J2 - Ima V Math KW - tuberculosis global stability monotone systems density-dependent recruitment rates autonomous differential-equations growing-populations hiv aids transmission reinfection infections diseases epidemic LA - English N1 - Bu52j Times Cited:7 Cited References Count:33 Ima Volumes in Mathematics and Its Applications PY - 2002 SP - 275-294 ST - Global dynamics of Tuberculosis models with density dependent demography T2 - Mathematical Approaches for Emerging and Reemerging Infectious Diseases: Models, Methods, and Theory TI - Global dynamics of Tuberculosis models with density dependent demography UR - ://WOS:000176237600016 VL - 126 ID - 4833 ER - TY - JOUR AB - OBJECTIVE: To estimate the cost-effectiveness of directly observed treatment compared to conventional therapy in reducing the spread of multidrug-resistant tuberculosis, for an industrialised country (represented by the United States of America) and a developing country (South Africa). METHODS: Monte Carlo analysis using published data on probability, cost and health impact. RESULTS: In both countries, directly observed treatment is the dominant strategy, yielding cost savings and improved health outcomes. Cost savings for directly observed treatment relative to conventional therapy become more significant as more expensive second-line drugs are used in treatments. CONCLUSIONS: The cost-effectiveness of directly observed treatment relative to conventional therapy is demonstrated for both the USA and South Africa. Cost savings are more pronounced (especially for South Africa) as the likelihood of multidrug-resistant tuberculosis increases and more expensive second-line therapies are used. Given that health care resources are more severely constrained in developing countries, the data contained in this study are useful in guiding the design of policies for the effective management of multidrug-resistant tuberculosis in settings with limited resources. AD - Health Economics Group, School of Health Policy and Practice, University of East Anglia, Norwich, United Kingdom. AN - 11769772 AU - Wilton, P. AU - Smith, R. D. AU - Coast, J. AU - Millar, M. AU - Karcher, A. DA - Dec DP - Nlm ET - 01/05 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Antitubercular Agents/economics/ therapeutic use Cost-Benefit Analysis Decision Trees Directly Observed Therapy/ economics Evaluation Studies as Topic Humans Monte Carlo Method South Africa Treatment Outcome Tuberculosis, Multidrug-Resistant/ drug therapy/ economics United States L1 - internal-pdf://1566446810/s10.pdf LA - eng N1 - Wilton, P Smith, R D Coast, J Millar, M Karcher, A Comparative Study France Int J Tuberc Lung Dis. 2001 Dec;5(12):1137-42. PY - 2002 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 1137-42 ST - Directly observed treatment for multidrug-resistant tuberculosis: an economic evaluation in the United States of America and South Africa T2 - Int J Tuberc Lung Dis TI - Directly observed treatment for multidrug-resistant tuberculosis: an economic evaluation in the United States of America and South Africa VL - 5 ID - 2412 ER - TY - JOUR AB - OBJECTIVE: To determine whether elimination of tuberculosis in the Dutch population can be achieved by the year 2030, taking into account the impact of immigration. METHODS: The incidence of tuberculosis (all forms) in the period 1970 to 2030 was estimated using a life-table model for the Dutch population without the impact of immigration. The influence of immigration on tuberculosis incidence among the Dutch was modelled using four immigrant scenarios, distinguished by the assumed contact rate between immigrants and the Dutch population, and by different projections (middle, upper) of the future size of the immigrant population in The Netherlands. RESULTS: The incidence of smear-positive tuberculosis among the Dutch is projected to be 1.4 per million in the scenario without the influence of immigrant cases, and ranging from 3.8 to 11.8 per million in the four immigrant scenarios. In all immigrant scenarios, the prevalence of tuberculosis infection will continue to decline and be less than 1% by the year 2030. At least 60% of Dutch tuberculosis cases in the year 2030 are expected to be the result of transmission from a foreign source case. CONCLUSION: Using a prevalence of tuberculosis infection of less than 1% as the elimination criterion, tuberculosis will probably be eliminated from the indigenous Dutch population by 2030. However, the incidence of smear-positive tuberculosis is expected to remain higher than 1 per million, and the majority of new tuberculosis cases among the Dutch may be attributable to recent infection from a foreign source case. AD - Pallas, Health Research and Consultancy, Rotterdam, The Netherlands. AN - 11931411 AU - Wolleswinkel-van, B. J. AU - Nagelkerke, N. J. AU - Broekmans, J. F. AU - Borgdorff, M. W. DA - Feb DP - Nlm ET - 04/05 KW - Adolescent Adult Age Distribution Aged Child Emigration and Immigration/ statistics & numerical data Female Humans Male Middle Aged Models, Statistical Netherlands/epidemiology Prevalence Risk Factors Sex Distribution Tuberculosis, Pulmonary/ epidemiology/prevention & control LA - eng N1 - Wolleswinkel-van, den Bosch J H Nagelkerke, N J D Broekmans, J F Borgdorff, M W France The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Int J Tuberc Lung Dis. 2002 Feb;6(2):130-6. PY - 2002 RN - fulltext fulltext_1208 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 130-6 ST - The impact of immigration on the elimination of tuberculosis in The Netherlands: a model based approach T2 - Int J Tuberc Lung Dis TI - The impact of immigration on the elimination of tuberculosis in The Netherlands: a model based approach VL - 6 ID - 2425 ER - TY - JOUR AB - The comparative-genomic sequencing of two Mycobacterium tuberculosis strains enabled us to identify single nucleotide polymorphism (SNP) markers for studies of evolution, pathogenesis, and epidemiology in clinical M. tuberculosis. Phylogenetic analysis using these "comparative-genome markers" (CGMs) produced a highly unusual phylogeny with a complete absence of secondary branches. To investigate CGM-based phylogenies, we devised computer models to simulate sequence evolution and calculate new phylogenies based on an SNP format. We found that CGMs represent a distinct class of phylogenetic markers that depend critically on the genetic distances between compared "reference strains." Properly distanced reference strains generate CGMs that accurately depict evolutionary relationships, distorted only by branch collapse. Improperly distanced reference strains generate CGMs that distort and reroot outgroups. Applying this understanding to the CGM-based phylogeny of M. tuberculosis, we found evidence to suggest that this species is highly clonal without detectable lateral gene exchange. We noted indications of evolutionary bottlenecks, including one at the level of the PHRI "C" strain previously associated with particular virulence characteristics. Our evidence also suggests that loss of IS6110 to fewer than seven elements per genome is uncommon. Finally, we present population-based evidence that KasA, an important component of mycolic acid biosynthesis, develops G312S polymorphisms under selective pressure. AD - Department of Medicine, Center for Emerging Pathogens, New Jersey Medical School, Newark, New Jersey 07103, USA. allandda@umdnj.edu AN - 12754238 AU - Alland, D. AU - Whittam, T. S. AU - Murray, M. B. AU - Cave, M. D. AU - Hazbon, M. H. AU - Dix, K. AU - Kokoris, M. AU - Duesterhoeft, A. AU - Eisen, J. A. AU - Fraser, C. M. AU - Fleischmann, R. D. DA - Jun DP - Nlm ET - 05/20 KW - Bacterial Proteins/genetics/metabolism Computational Biology Computer Simulation DNA Transposable Elements Evolution, Molecular Genome, Bacterial Humans Mycobacterium tuberculosis/ genetics/ pathogenicity Phylogeny Polymorphism, Genetic Polymorphism, Single Nucleotide LA - eng N1 - Alland, David Whittam, Thomas S Murray, Megan B Cave, M Donald Hazbon, Manzour H Dix, Kim Kokoris, Mark Duesterhoeft, Andreas Eisen, Jonathan A Fraser, Claire M Fleischmann, Robert D AI40125/AI/NIAID NIH HHS/United States AI46669/AI/NIAID NIH HHS/United States AI49352/AI/NIAID NIH HHS/United States Comparative Study Research Support, U.S. Gov't, P.H.S. United States Journal of bacteriology J Bacteriol. 2003 Jun;185(11):3392-9. PY - 2003 RN - fulltext fulltext_1208 SN - 0021-9193 (Print) 0021-9193 (Linking) SP - 3392-9 ST - Modeling bacterial evolution with comparative-genome-based marker systems: application to Mycobacterium tuberculosis evolution and pathogenesis T2 - J Bacteriol TI - Modeling bacterial evolution with comparative-genome-based marker systems: application to Mycobacterium tuberculosis evolution and pathogenesis UR - http://jb.asm.org/content/185/11/3392.full.pdf VL - 185 ID - 2426 ER - TY - JOUR AB - Tuberculosis (TB) is a disease that is closely associated with poverty, with transmission occurring in situations where infected persons are in close contact with others in confined spaces. While it is well recognised that overcrowding increases the risk of transmission, this increased risk has not been quantified and the relationship between overcrowding and duration of exposure is not well understood. This paper analyses three epidemiological models that have been used to predict the transmission of airborne disease in confined spaces: the Mass Action model, Riley, Murphy and Riley's model and Gammaitoni and Nucci's model. A study is presented to demonstrate the range of applicability of each model and show how they can be applied to the transmission of both TB and diseases with short incubation periods such as measles. Gammiatoni and Nucci's generalised formulation is shown to be the most suitable for modelling airborne transmission in ventilated spaces, and it is subsequently used in a parametric study to evaluate the effect of physical and environmental factors on the rate of disease transmission. The paper also presents reported quanta production data for several TB outbreaks and demonstrates that the greatest risk of TB infection is during clinical procedures that produce large quantities of aerosol, such as bronchoscopy or intubation. AD - Aerobiological Research Group, School of Civil Engineering, University of Leeds, Leeds, United Kingdom. c.b.beggs@leeds.ac.uk AN - 14598959 AU - Beggs, C. B. AU - Noakes, C. J. AU - Sleigh, P. A. AU - Fletcher, L. A. AU - Siddiqi, K. DA - Nov DP - Nlm ET - 11/06 KW - Disease Transmission, Infectious/ statistics & numerical data Environmental Exposure Humans Models, Statistical Population Density Risk Assessment Risk Factors Time Factors Tuberculosis, Pulmonary/ epidemiology/ transmission LA - eng N1 - Beggs, C B Noakes, C J Sleigh, P A Fletcher, L A Siddiqi, K Review France The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Int J Tuberc Lung Dis. 2003 Nov;7(11):1015-26. PY - 2003 RN - fulltext fulltext_1208 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 1015-26 ST - The transmission of tuberculosis in confined spaces: an analytical review of alternative epidemiological models T2 - Int J Tuberc Lung Dis TI - The transmission of tuberculosis in confined spaces: an analytical review of alternative epidemiological models VL - 7 ID - 2427 ER - TY - JOUR AB - Tuberculosis (TB) is a major public health problem in complex emergencies. Humanitarian agencies usually postpone the decision to offer TB treatment and opportunities to treat TB patients are often missed. This paper looks at the problem of tuberculosis treatment in these emergencies and questions whether treatment guidelines could be more flexible than international recommendations. A mathematical model is used to calculate the risks and benefits of different treatment scenarios with increasing default rates. Model outcomes are compared to a situation without treatment. An economic analysis further discusses the findings in a trade-off between the extra costs of treating relapses and failures and the savings in future treatment costs. In complex emergencies, if a TB programme could offer 4-month treatment for 75% of its patients, it could still be considered beneficial in terms of public health. In addition, the proportion of patients following at least 4 months of treatment can be used as an indicator to help evaluate the public health harm and benefit of the TB programme. AN - 15173 AU - Biot, M. AU - Chandramohan, D. AU - Porter, J. D. H. KW - adherence displaced persons drug resistance emergency relief epidemiology immigrants migration models treatment tuberculosis L1 - internal-pdf://0471661017/Biot%2520Math%2520Model.pdf N1 - IN FILE TB Transmission, pathogenesis, and epidemiology Tuberculosis Descript epi: morbidity Displaced persons PY - 2003 RN - fulltext fulltext_1208 SP - 211-218 ST - Tuberculosis treatment in complex emergencies: are risks outweighing benefits? T2 - Trop.Med.Intern.Health TI - Tuberculosis treatment in complex emergencies: are risks outweighing benefits? UR - file://C:\literature_pdf\rm15173.pdf VL - 8 ID - 2428 ER - TY - JOUR AB - Traditional cost-effectiveness analysis (CEA) assumes that program costs and benefits scale linearly with investment-an unrealistic assumption for epidemic control programs. This paper combines epidemic modeling with optimization techniques to determine the optimal allocation of a limited resource for epidemic control among multiple noninteracting populations. We show that the optimal resource allocation depends on many factors including the size of each population, the state of the epidemic in each population before resources are allocated (e.g. infection prevalence and incidence), the length of the time horizon, and prevention program characteristics. We establish conditions that characterize the optimal solution in certain cases. AD - Department of Management Science and Engineering, Stanford University, Terman Building, Stanford, CA 94305, USA. brandeau@stanford.edu AN - 12842316 AU - Brandeau, M. L. AU - Zaric, G. S. AU - Richter, A. DA - Jul KW - Communicable Disease Control/*economics Cost-Benefit Analysis Disease Outbreaks/economics/*prevention & control Health Services Needs and Demand/economics/statistics & numerical data Human Models, Econometric Prevalence Quality-Adjusted Life Years Resource Allocation/economics/*methods/statistics & numerical data Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. World Health N1 - 0167-6296 Journal Article PY - 2003 RN - fulltext fulltext_1208 SP - 575-98 ST - Resource allocation for control of infectious diseases in multiple independent populations: beyond cost-effectiveness analysis T2 - Journal of Health Economics TI - Resource allocation for control of infectious diseases in multiple independent populations: beyond cost-effectiveness analysis UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12842316 VL - 22 ID - 2429 ER - TY - JOUR AB - Mycobacterium tuberculosis remains a leading infectious cause of morbidity and mortality. While antibiotic resistance is cited as a potential threat to efforts aimed at controlling the spread of this pathogen, it is not clear how drug resistance affects disease dynamics. The effect of mutational events that lead to antibiotic-resistant phenotypes may or may not have a predictable effect on the fitness of drug-resistant tuberculosis strains. Here, we review the literature on laboratory studies of the fitness of drug-resistant tuberculosis, we examine the evidence from cluster studies, and we consider the effect of drug resistance on disease dynamics in mathematical models. On the basis of these diverse lines of evidence, we conclude that the fitness estimates of drug-resistant M tuberculosis are quite heterogeneous and that this variation may preclude our ability to predict future trends of this pathogen. AU - Cohen, T. AU - Sommers, B. AU - Murray, M. IS - 1 KW - *Mycobacterium tuberculosis/drug effects/genetics/ Antitubercular Agents/*pharmacology Cluster Analysis Drug Resistance, Multiple, Bacterial Humans Molecular Epidemiology Prevalence Tuberculosis/*epidemiology L1 - file:///C:/Users/James/AppData/Local/Mendeley Ltd/Mendeley Desktop/Downloaded/Cohen-2003-The effect of drug resistance on th.pdf N1 - Cohen, Ted Sommers, Ben Murray, Megan eng K08 A1 01930-01/PHS HHS/ K08 AI055985-01A1/AI/NIAID NIH HHS/ R01 A10 46669-02/PHS HHS/ T32 AI07433/AI/NIAID NIH HHS/ Research Support, U.S. Gov't, P.H.S. Review 2002/12/31 04:00 Lancet Infect Dis. 2003 Jan;3(1):13-21. PY - 2003 SN - 1473-3099 (Print) 1473-3099 (Linking) SP - 13-21 ST - The effect of drug resistance on the fitness of Mycobacterium tuberculosis T2 - Lancet Infect Dis TI - The effect of drug resistance on the fitness of Mycobacterium tuberculosis UR - http://www.ncbi.nlm.nih.gov/pubmed/12505028 http://ac.els-cdn.com.ezp.lib.unimelb.edu.au/S1473309903004833/1-s2.0-S1473309903004833-main.pdf?_tid=4d149104-5c99-11e4-9286-00000aab0f02&acdnat=1414277602_43658d241c5d537be879b37fa047c33c VL - 3 ID - 3429 ER - TY - JOUR AB - BACKGROUND: The increasing global burden of tuberculosis (TB) is linked to human immunodeficiency virus (HIV) infection. METHODS: We reviewed data from notifications of TB cases, cohort treatment outcomes, surveys of Mycobacterium tuberculosis infection, and HIV prevalence in patients with TB and other subgroups. Information was collated from published literature and databases held by the World Health Organization (WHO), the Joint United Nations Programme on HIV/Acquired Immunodeficiency Syndrome (UNAIDS), the US Census Bureau, and the US Centers for Disease Control and Prevention. RESULTS: There were an estimated 8.3 million (5th-95th centiles, 7.3-9.2 million) new TB cases in 2000 (137/100,000 population; range, 121/100,000-151/100,000). Tuberculosis incidence rates were highest in the WHO African Region (290/100,000 per year; range, 265/100,000-331/100,000), as was the annual rate of increase in the number of cases (6%). Nine percent (7%-12%) of all new TB cases in adults (aged 15-49 years) were attributable to HIV infection, but the proportion was much greater in the WHO African Region (31%) and some industrialized countries, notably the United States (26%). There were an estimated 1.8 million (5th-95th centiles, 1.6-2.2 million) deaths from TB, of which 12% (226 000) were attributable to HIV. Tuberculosis was the cause of 11% of all adult AIDS deaths. The prevalence of M tuberculosis-HIV coinfection in adults was 0.36% (11 million people). Coinfection prevalence rates equaled or exceeded 5% in 8 African countries. In South Africa alone there were 2 million coinfected adults. CONCLUSIONS: The HIV pandemic presents a massive challenge to global TB control. The prevention of HIV and TB, the extension of WHO DOTS programs, and a focused effort to control HIV-related TB in areas of high HIV prevalence are matters of great urgency. AD - Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, England, UK. AN - 12742798 AU - Corbett, E. L. AU - Watt, C. J. AU - Walker, N. AU - Maher, D. AU - Williams, B. G. AU - Raviglione, M. C. AU - Dye, C. DA - May 12 KW - AIDS-Related Opportunistic Infections/*epidemiology/prevention & control HIV Seronegativity HIV Seropositivity/*complications/epidemiology Humans Incidence Prevalence Registries Tuberculosis/*epidemiology/mortality/prevention & control/transmission Tuberculosis, Pulmonary/epidemiology World Health N1 - 0003-9926 (Print) Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review PY - 2003 SP - 1009-21 ST - The growing burden of tuberculosis: global trends and interactions with the HIV epidemic T2 - Arch Intern Med TI - The growing burden of tuberculosis: global trends and interactions with the HIV epidemic UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12742798http://archinte.jamanetwork.com/data/Journals/INTEMED/5439/ira20017.pdf VL - 163 ID - 2430 ER - TY - JOUR AB - OBJECTIVE: To compare the benefits of tuberculosis (TB) treatment with TB and HIV prevention for the control of TB in regions with high HIV prevalence. DESIGN AND METHODS: A compartmental difference equation model of TB and HIV has been developed and fitted to time series and other published data using Bayesian methods. The model is used to compare the effectiveness of TB chemotherapy with three strategies for prevention: highly active antiretroviral therapy (HAART), the treatment of latent TB infection (TLTI) and the reduction of HIV transmission. RESULTS: Even where the prevalence of HIV infection is high, finding and curing active TB is the most effective way to minimize the number of TB cases and deaths over the next 10 years. HAART can be as effective, but only with very high levels of coverage and compliance. TLTI is comparatively ineffective over all time scales. Reducing HIV incidence is relatively ineffective in preventing TB and TB deaths over 10 years but is much more effective over 20 years. CONCLUSIONS: In countries where the spread of HIV has led to a substantial increase in the incidence of TB, TB control programmes should maintain a strong emphasis on the treatment of active TB. To ensure effective control of TB in the longer term, methods of TB prevention should be carried out in addition to, but not as a substitute for, treating active cases. AD - Faculty of Mathematical Studies, University of Southampton, Southampton, UK. AN - 14600522 AU - Currie, C. S. AU - Williams, B. G. AU - Cheng, R. C. AU - Dye, C. DA - Nov 21 DO - 10.1097/01.aids.0000096903.73209.ac [doi] DP - Nlm ET - 11/06 KW - AIDS-Related Opportunistic Infections/ epidemiology/prevention & control Antiretroviral Therapy, Highly Active Bayes Theorem Developing Countries Disease Outbreaks/ prevention & control Humans Incidence Kenya/epidemiology Models, Statistical Prevalence South Africa/epidemiology Time Factors Tuberculosis/ epidemiology/prevention & control Uganda/epidemiology LA - eng N1 - Currie, Christine S M Williams, Brian G Cheng, Russell C H Dye, Christopher England AIDS (London, England) AIDS. 2003 Nov 21;17(17):2501-8. PY - 2003 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0269-9370 (Print) 0269-9370 (Linking) SP - 2501-8 ST - Tuberculosis epidemics driven by HIV: is prevention better than cure? T2 - AIDS TI - Tuberculosis epidemics driven by HIV: is prevention better than cure? UR - http://graphics.tx.ovid.com/ovftpdfs/FPDDNCDCLFEDDD00/fs046/ovft/live/gv023/00002030/00002030-200311210-00013.pdf VL - 17 ID - 2431 ER - TY - JOUR AB - A decision analysis was conducted to evaluate the cost-effectiveness of programs in which the Amplified Mycobacterium Tuberculosis Direct test (MTD) (Gen-Probe) is used to rapidly exclude Mycobacterium tuberculosis complex as a cause of disease in smear-positive respiratory specimens. MTD sensitivity, specificity, and probability of inhibition for smear-positive specimens were estimated from literature reports. Costs and laboratory performance characteristics were determined from review of records and practices at an urban hospital in the mid-Atlantic United States. In the base case, 31.4% of smear-positive specimens were assumed to be culture positive for M. tuberculosis. Under these conditions, the marginal cost of the MTD testing program was estimated as $338 per smear-positive patient, or $494 per early exclusion of tuberculosis based on negative MTD results. By comparison, the cost of respiratory isolation ($27.77/day) and drugs ($5.66/day) averted by MTD testing was estimated at $201 per early tuberculosis exclusion. MTD testing was therefore not cost-effective in this scenario. Sensitivity analysis revealed that cost-effectiveness estimates are sensitive to the number of smear-positive specimens processed annually, the relative prevalence of M. tuberculosis in smear-positive specimens, and the marginal daily cost of respiratory isolation. A decision tool is therefore presented for assessing the cost-effectiveness of MTD under various combinations of those three variables. While routine MTD testing of smear-positive specimens is not expected to be cost-saving for most individual hospitals, centralized reference laboratories may be able to implement MTD in a cost-effective manner across a wide range of situations. AD - Johns Hopkins Bloomberg School of Public Health. Johns Hopkins Hospital. Johns Hopkins University School of Medicine, Baltimore, Maryland. AN - 12624014 AU - Dowdy, D. W. AU - Maters, A. AU - Parrish, N. AU - Beyrer, C. AU - Dorman, S. E. DA - Mar N1 - 22511020 0095-1137 Journal Article PY - 2003 RN - fulltext fulltext_1208 SP - 948-953 ST - Cost-effectiveness analysis of the gen-probe amplified mycobacterium tuberculosis direct test as used routinely on smear-positive respiratory specimens T2 - Journal of clinical microbiology TI - Cost-effectiveness analysis of the gen-probe amplified mycobacterium tuberculosis direct test as used routinely on smear-positive respiratory specimens UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12624014file://C:\literature_pdf\rm11132.pdf VL - 41 ID - 2432 ER - TY - JOUR AB - SETTING: Mycobacterium bovis bacille Calmette-Guerin (BCG) is provided to all infants born in Finland. OBJECTIVE: To analyze the cost-effectiveness of universal versus selective BCG immunization. DESIGN: A Markov model was developed to simulate rates of tuberculosis (TB) and non-tuberculous mycobacterial disease (NTM), and to examine the cost-effectiveness in terms of cost per case averted of three different strategies: universal BCG, selective BCG (10% of infants at higher TB risk than other infants) or no BCG immunization. RESULTS: In a cohort of 60,000 infants over 15 years, the model predicts five cases each of TB and NTM disease with universal immunization, 8-21 TB and 31 NTM cases with various strategies of selective immunization, and 25 TB and 34 NTM cases with no BCG immunization. BCG side-effects are predicted in 5, 0.5 and 0 infants, respectively. The cost per case averted for immunization strategies ranges from a cost of 38,311 US dollars to a savings of 323 dollars as selective immunization becomes more efficient at targeting infants at highest risk of TB. CONCLUSIONS: In a country with a low incidence of pediatric tuberculosis, selective BCG immunization is a more cost-effective strategy than universal BCG immunization for the prevention of tuberculosis, but results in an increase in NTM cases. AD - Infectious Disease Section, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA. AN - 12701831 AU - Hersh, A. L. AU - Tala-Heikkila, M. AU - Tala, E. AU - Tosteson, A. N. AU - Fordham von Reyn, C. DA - Jan KW - BCG Vaccine/administration & dosage/*economics Cohort Studies Cost of Illness Cost-Benefit Analysis Finland/epidemiology Humans Immunization Programs/*economics/organization & administration Incidence Infant Markov Chains Mass Immunization/economics *Patient Selection Tuberculosis/epidemiology/*prevention & control LA - eng N1 - Comparative Study Journal Article France the official journal of the International Union against Tuberculosis and Lung Disease PY - 2003 RN - fulltext fulltext_1208 SN - 1027-3719 (Print) SP - 22-29 ST - A cost-effectiveness analysis of universal versus selective immunization with Mycobacterium bovis bacille Calmette-Guerin in Finland T2 - International Journal of Tuberculosis and Lung Disease TI - A cost-effectiveness analysis of universal versus selective immunization with Mycobacterium bovis bacille Calmette-Guerin in Finland UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12701831 VL - 7 ID - 2433 ER - TY - JOUR AB - Recent data indicate that 10- to 14-mm Mycobacterium tuberculosis purified protein derivative (PPD) reactions are often due to prior infections with nontuberculous mycobacteria. Therefore, use of a 10-mm cutpoint to define latent tuberculosis infection (LTBI) results in false-positive diagnoses and unnecessary treatment for LTBI. A second skin test, Mycobacterium avium sensitin (MAS), has been shown to accurately identify false-positive PPD results.To compare the costs and accuracy of a single skin-test strategy (SST) with PPD alone with a dual skin-test strategy (DST) where 10- to 14-mm PPD results are also tested with MAS.A decision analytic model was developed to evaluate the two strategies. The model accounted for the costs of skin testing, the costs of LTBI treatment, the costs of undetected LTBI, and the sensitivity and specificity of each strategy.We estimated that DST saved $3 per subject tested compared to SST. Savings were due to a reduction in false-positive PPD results and consequent reduction in unnecessary treatment for LTBI of >60%. The DST strategy was associated with a minimal increase in undetected LTBI (6% vs 7%). Results were stable for a broad range of parameter values.DST is a promising approach to improving the specificity of LTBI testing when a 10-mm PPD cutpoint is used and would reduce costs and unnecessary drug treatment. AD - Stanford Center for Research in Disease Prevention (Hersh), Stanford University School of Medicine, Palo Alto, California, USA AN - 12657344 AU - Hersh, A. L. AU - Tosteson, A. N. AU - von Reyn, C. F. DA - Apr N1 - 22543442 0749-3797 Journal Article PY - 2003 RN - fulltext fulltext_1208 SP - 254-9 ST - Dual skin testing for latent tuberculosis infection. A decision analysis T2 - American Journal of Preventive Medicine TI - Dual skin testing for latent tuberculosis infection. A decision analysis UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12657344 VL - 24 ID - 2434 ER - TY - JOUR AB - We consider a model for a disease with a progressing and a quiescent exposed class and variable susceptibility to super-infection. The model exhibits backward bifurcations under certain conditions, which allow for both stable and unstable endemic states when the basic reproduction number is smaller than one. AD - Department of Mathematics, Polytechnic University, Brooklyn, NY 11201, USA. mayam@duke.poly.edu AN - 12750833 AU - Martcheva, M. AU - Thieme, H. R. DA - May DO - 10.1007/s00285-002-0181-7 [doi] DP - Nlm ET - 05/17 KW - HIV Infections Humans Malaria Models, Biological Schistosomiasis Superinfection/ microbiology/ parasitology Tuberculosis LA - eng N1 - Martcheva, Maia Thieme, Horst R Research Support, U.S. Gov't, Non-P.H.S. Germany Journal of mathematical biology J Math Biol. 2003 May;46(5):385-424. PY - 2003 RN - fulltext fulltext_1208 SN - 0303-6812 (Print) 0303-6812 (Linking) SP - 385-424 ST - Progression age enhanced backward bifurcation in an epidemic model with super-infection T2 - J Math Biol TI - Progression age enhanced backward bifurcation in an epidemic model with super-infection UR - http://www.springerlink.com/content/flqdyuk1j4qqpr3m/ VL - 46 ID - 2435 ER - TY - JOUR AB - Global eradication of tuberculosis (TB) is an international agenda. Thus understanding effects of treatment of TB in different settings is crucial. In previous work, we introduced the framework for a mathematical model of epidemic TB in demographically distinct, heterogeneous populations. Simulations showed the importance of genetic susceptibility in determining endemic prevalence levels. In the work presented here, we include treatment and investigate different strategies for treatment of latent and active TB disease in heterogeneous populations. We illustrate how the presence of a genetically susceptible subpopulation dramatically alters effects of treatment in the same way a core population does in the setting of sexually transmitted diseases. In addition, we evaluate treatment strategies that focus specifically on this subpopulation, and our results indicate that genetically susceptible subpopulations should be accounted for when designing treatment strategies to achieve the greatest reduction in disease prevalence. AD - Department of Microbiology and Immunology, The University of Michigan Medical School, University of Michigan at Ann Arbor, 6730 Medical Science II, MC 0620, Ann Arbor, MI 48109-0620, USA. AN - 12875819 AU - Murphy, B. M. AU - Singer, B. H. AU - Kirschner, D. DA - Aug 21 DO - S0022519303000389 [pii] DP - Nlm ET - 07/24 KW - Demography Disease Outbreaks Disease Progression Genetic Predisposition to Disease Humans Models, Statistical Mycobacterium tuberculosis Recurrence/prevention & control Tuberculosis/ drug therapy/ epidemiology/genetics World Health LA - eng N1 - Murphy, Brian M Singer, Benjamin H Kirschner, Denise 5 T32 AI07528/AI/NIAID NIH HHS/United States R01 HL62119/HL/NHLBI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England Journal of theoretical biology J Theor Biol. 2003 Aug 21;223(4):391-404. PY - 2003 RN - fulltext fulltext_1208 SN - 0022-5193 (Print) 0022-5193 (Linking) SP - 391-404 ST - On treatment of tuberculosis in heterogeneous populations T2 - J Theor Biol TI - On treatment of tuberculosis in heterogeneous populations UR - http://ac.els-cdn.com/S0022519303000389/1-s2.0-S0022519303000389-main.pdf?_tid=5f5a5b849f1d2b02fed9e32e89154e59&acdnat=1345014079_403666f84fb9ad7f79738dcc5575ac43 VL - 223 ID - 2436 ER - TY - JOUR AB - A mathematical model is presented to simulate the interaction between Human Immunodeficiency Virus (HIV) and Mycobacterium tuberculosis (MTB) infections in a closed environment. The dynamics is formulated through a compartmental system of non-linear ordinary differential equations. The stability of the trivial equilibrium point or absence of infections and the endemic basins are analyzed based on the threshold values for the HIV and MTB transmission coefficients. In order to deal with the estimation of the transmission coefficients of HIV and MTB infections we consider the incarcerated individuals in the Female Penitentiary of S?o Paulo State, Brazil. AU - Raimundo, Silvia Martorano AU - Engel, Alejandro B. AU - Yang, Hyun Mo AU - Bassanezi, Rodney Carlos DA - 2003/04/01 DO - 10.1080/02329290290027175 PY - 2003 RN - fulltext fulltext_1208 SN - 0232-9298 SP - 423-442 ST - An Approach to Estimating the Transmission Coefficients for AIDS and for Tuberculosis Using Mathematical Models T2 - Systems Analysis Modelling Simulation TI - An Approach to Estimating the Transmission Coefficients for AIDS and for Tuberculosis Using Mathematical Models UR - http://dx.doi.org/10.1080/02329290290027175http://www.tandfonline.com/doi/abs/10.1080/02329290290027175 VL - 43 Y2 - 2012/08/10 ID - 2437 ER - TY - JOUR AN - 10553 AU - Rust, P. KW - epidemiology infection mixture analysis models prevalence statistics tuberculosis N1 - TB Periodical PY - 2003 RN - fulltext fulltext_1208 SP - 194-197 ST - Standard errors in mixture studies of tuberculous infection prevalence T2 - Int.J.Tuberc.Lung Dis. TI - Standard errors in mixture studies of tuberculous infection prevalence UR - file://C:\literature_pdf\rm10553.pdf VL - 7 ID - 2438 ER - TY - JOUR AB - We introduce a spatial stochastic model for the spread of tuberculosis. After a primary infection, an individual may become sick (and infectious) through an endogenous reinfection or through an exogenous reinfection. We show that even in the absence of endogenous reinfection an epidemic is possible if the exogenous reinfection parameter is high enough. This is in sharp contrast with what happens for a mean field model corresponding to our spatial stochastic model. AD - LATP/CMI, Universite de Provence, 39 rue Joliot Curie, 13453 Marseille Cedex, France. schinazi@cmi.univ-mrs.fr AU - Schinazi, R. B. KW - Disease Outbreaks Disease Transmission, Infectious Humans Models, Statistical Recurrence Tuberculosis/transmission N1 - LR: 20081121; JID: 0376342; ppublish PY - 2003 RN - fulltext fulltext_1208 SN - 0022-5193 begin_of_the_skype_highlighting 0022-5193 end_of_the_skype_highlighting begin_of_the_skype_highlighting 0022-5193 begin_of_the_skype_highlighting 0022-5193 end_of_the_skype_highlighting end_of_the_skype_highlighting; 0022-5193 begin_of_the_skype_highlighting 0022-5193 end_of_the_skype_highlighting begin_of_the_skype_highlighting 0022-5193 begin_of_the_skype_highlighting 0022-5193 end_of_the_skype_highlighting end_of_the_skype_highlighting SP - 59-63 ST - On the role of reinfection in the transmission of infectious diseases T2 - Journal of theoretical biology TI - On the role of reinfection in the transmission of infectious diseases VL - 225 Y2 - Nov 7 ID - 2439 ER - TY - JOUR AB - OBJECTIVE: This study sought to determine the impact of the World Health Organization's directly observed treatment strategy (DOTS) compared with that of DOTS-plus on tuberculosis deaths, mainly in the developing world. DESIGN: Decision analysis with Monte Carlo simulation of a Markov decision tree. DATA SOURCES: People with smear positive pulmonary tuberculosis. DATA ANALYSIS: Analyses modelled different levels of programme effectiveness of DOTS and DOTS-plus, and high (10%) and intermediate (3%) proportions of primary multidrug resistant tuberculosis, while accounting for exogenous reinfection. MAIN OUTCOME MEASURE: The cumulative number of tuberculosis deaths per 100 000 population over 10 years. RESULTS: The model predicted that under DOTS, 276 people would die from tuberculosis (24 multidrug resistant and 252 not multidrug resistant) over 10 years under optimal implementation in an area with 3% primary multidrug resistant tuberculosis. Optimal implementation of DOTS-plus would result in four (1.5%) fewer deaths. If implementation of DOTS-plus were to result in a decrease of just 5% in the effectiveness of DOTS, 16% more people would die with tuberculosis than under DOTS alone. In an area with 10% primary multidrug resistant tuberculosis, 10% fewer deaths would occur under optimal DOTS-plus than under optimal DOTS, but 16% more deaths would occur if implementation of DOTS-plus were to result in a 5% decrease in the effectiveness of DOTS CONCLUSIONS: Under optimal implementation, fewer tuberculosis deaths would occur under DOTS-plus than under DOTS. If, however, implementation of DOTS-plus were associated with even minimal decreases in the effectiveness of treatment, substantially more patients would die than under DOTS. AD - Johns Hopkins University Center for Tuberculosis Research, 424 N Bond Street, Baltimore, MD 21231, USA. tsterls@jhmi.edu AN - 12637401 AU - Sterling, T. R. AU - Lehmann, H. P. AU - Frieden, T. R. DA - Mar 15 L1 - internal-pdf://1225460229/Sterling-2003-Impact of DOTS compared with DOT.pdf N1 - 22523683 1468-5833 Journal Article PY - 2003 RN - fulltext fulltext_1208 SP - 574 ST - Impact of DOTS compared with DOTS-plus on multidrug resistant tuberculosis and tuberculosis deaths: decision analysis T2 - British Medical Journal TI - Impact of DOTS compared with DOTS-plus on multidrug resistant tuberculosis and tuberculosis deaths: decision analysis UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12637401 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC151519/pdf/574.pdf VL - 326 ID - 2440 ER - TY - JOUR AB - Several recent studies have used proportions of tuberculosis cases sharing identical DNA fingerprint patterns (i.e., isolate clustering) to estimate the extent of disease attributable to recent transmission. Using a model of introduction and transmission of strains with different DNA fingerprint patterns, we show that the properties and interpretation of clustering statistics may differ substantially between settings. For some unindustrialized countries, where the annual risk for infection has changed little over time, 70% to 80% of all age groups may be clustered during a 3-year period, which underestimates the proportion of disease attributable to recent transmission. In contrast, for a typical industrialized setting (the Netherlands), clustering declines with increasing age (from 75% to 15% among young and old patients, respectively) and underestimates the extent of recent transmission only for young patients. We conclude that, in some settings, clustering is an unreliable indicator of the extent of recent transmission. AD - London School of Hygiene & Tropical Medicine, London, England. emilia.vynnycky@lshtm.ac.uk AN - 12603987 AU - Vynnycky, E. AU - Borgdorff, M. W. AU - Van Soolingen, D. AU - Fine, P. E. PY - 2003 RN - fulltext fulltext_1208 SP - 176-83. ST - Annual Mycobacterium tuberculosis Infection Risk and Interpretation of Clustering Statistics T2 - Emerg Infect Dis TI - Annual Mycobacterium tuberculosis Infection Risk and Interpretation of Clustering Statistics UR - http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=12603987 VL - 9 ID - 2441 ER - TY - JOUR AB - Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has dramatically increased the incidence of tuberculosis (TB) in subSaharan Africa, where up to 60% of TB patients are coinfected with HIV and each year 200,000 TB deaths are attributable to HIV coinfection. Now HIV threatens control of TB in Asia, Eastern Europe, and Latin America. Antiretroviral (ARV) drugs can prevent TB by preserving immunity, but cohort analysis shows that early therapy, plus high levels of coverage and compliance, will be needed to avert a significant fraction of TB cases. However, ARV drugs could enhance the treatment of TB, and TB programs provide an important entry point for the treatment of HIV/AIDS. AD - Communicable Diseases, World Health Organization, 1211 Geneva 27, Switzerland. williamsbg@who.int AU - Williams, B. G. AU - Dye, C. DO - 10.1126/science.1086845 KW - Acquired Immunodeficiency Syndrome/complications/drug therapy/immunology/mortality Africa South of the Sahara/epidemiology Anti-HIV Agents/therapeutic use Antitubercular Agents/therapeutic use CD4 Lymphocyte Count Cohort Studies Developing Countries Drug Therapy, Combination Female HIV Infections/complications/drug therapy/immunology/mortality HIV-1 HIV-2 Humans Incidence Male Survival Rate Tuberculosis/complications/drug therapy/epidemiology/prevention & control N1 - LR: 20070319; JID: 0404511; 0 (Anti-HIV Agents); 0 (Antitubercular Agents); 2003/08/14 [aheadofprint]; ppublish PY - 2003 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1095-9203; 0036-8075 SP - 1535-1537 ST - Antiretroviral drugs for tuberculosis control in the era of HIV/AIDS T2 - Science (New York, N.Y.) TI - Antiretroviral drugs for tuberculosis control in the era of HIV/AIDS UR - http://www.sciencemag.org/content/301/5639/1535.full.pdf VL - 301 Y2 - Sep 12 ID - 2442 ER - TY - JOUR AB - OBJECTIVE: To compare the cost-effectiveness of three diagnostic algorithms incorporating a new rapid test, FASTPlaqueTB, with the current National TB Control Programme (NTCP) algorithm for diagnosis of pulmonary tuberculosis in new smear-negative suspects in South Africa. DESIGN: A model of the outcome of patients screened using each diagnostic algorithm was established using published costs and performance data for each component of the algorithm. Direct health care provider costs associated with provision of each diagnostic strategy were determined. Overall performance, total cost, speed and accuracy of diagnosis were estimated for screening 1000 new TB suspects using each algorithm. RESULTS: The use of FASTPlaqueTB and culture algorithms enabled 28% more smear-negative TB patients to be diagnosed overall and was cheaper to implement than the NTCP algorithm (18,312-18,581 US dollars compared with 20,079 dollars). Fewer clinic visits were required to establish a diagnosis, reducing clinic workload and patient costs. FASTPlaqueTB enabled rapid and specific diagnosis of at least 50% of smear-negative TB patients within 2 days. CONCLUSIONS: The use of FASTPlaqueTB can assist in improving existing case detection strategies and may be cost-effectively integrated into the current diagnostic infrastructure, offering patients more rapid and reliable diagnosis whilst reducing the overall cost. AD - Biotec Laboratories Ltd., c/o National Health Laboratory Service, Cape Town, Western Cape, South Africa. alberth@mweb.co.za AN - 15139454 AU - Albert, H. DA - Feb ET - 05/14 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - *Algorithms Bacteriological Techniques/*economics Cost-Benefit Analysis Humans Mycobacterium tuberculosis/classification Predictive Value of Tests South Africa Sputum/*microbiology Time Factors Tuberculosis, Pulmonary/*diagnosis LA - eng M3 - Comparative Study N1 - Albert, H France Int J Tuberc Lung Dis. 2004 Feb;8(2):240-7. PY - 2004 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 240-7 ST - Economic analysis of the diagnosis of smear-negative pulmonary tuberculosis in South Africa: incorporation of a new rapid test, FASTPlaqueTB, into the diagnostic algorithm T2 - Int J Tuberc Lung Dis TI - Economic analysis of the diagnosis of smear-negative pulmonary tuberculosis in South Africa: incorporation of a new rapid test, FASTPlaqueTB, into the diagnostic algorithm UR - http://www.ncbi.nlm.nih.gov/pubmed/15139454 VL - 8 ID - 2443 ER - TY - JOUR AB - 'Hot zones' are areas that have >5% prevalence (or incidence) of multidrug-resistant tuberculosis (MDRTB). We present a new mathematical model (the amplifier model) that tracks the emergence and evolution of multiple (pre-MDR, MDR and post-MDR) strains of drug-resistant Mycobacterium tuberculosis. We reconstruct possible evolutionary trajectories that generated hot zones over the past three decades, and identify the key causal factors. Results are consistent with recently reported World Health Organization (WHO) data. Our analyses yield three important insights. First, paradoxically we found that areas with programs that successfully reduced wild-type pansensitive strains often evolved into hot zones. Second, some hot zones emerged even when MDR strains were substantially less fit (and thus less transmissible) than wild-type pansensitive strains. Third, levels of MDR are driven by case-finding rates, cure rates and amplification probabilities. To effectively control MDRTB in the hot zones, it is essential that the WHO specify a goal for minimizing the amplification probability. AD - Department of Biomathematics and UCLA AIDS Institute, David Geffen School of Medicine at the University of California, Los Angeles, 1100 Glendon Avenue, Penthouse 2, Westwood, California 90024, USA. sblower@mednet.ucla.edu AN - 15378053 AU - Blower, S. M. AU - Chou, T. DA - Oct DO - 10.1038/nm1102 [doi] nm1102 [pii] DP - Nlm ET - 09/21 KW - Biological Evolution Disease Outbreaks Epidemiologic Research Design Geography Humans Incidence Models, Biological Monte Carlo Method Mycobacterium tuberculosis/genetics/ pathogenicity Prevalence Tuberculosis, Multidrug-Resistant/ epidemiology/prevention & control World Health L1 - internal-pdf://2769125462/Blower-2004-Modeling the emergence of the 'hot.pdf LA - eng N1 - Blower, Sally M Chou, Tom R01 AI041935/AI/NIAID NIH HHS/United States Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. United States Nature medicine Nat Med. 2004 Oct;10(10):1111-6. Epub 2004 Sep 19. PY - 2004 RN - fulltext fulltext_1208 SN - 1078-8956 (Print) 1078-8956 (Linking) SP - 1111-6 ST - Modeling the emergence of the 'hot zones': tuberculosis and the amplification dynamics of drug resistance T2 - Nat Med TI - Modeling the emergence of the 'hot zones': tuberculosis and the amplification dynamics of drug resistance UR - http://www.nature.com/nm/journal/v10/n10/pdf/nm1102.pdf https://www.nature.com/articles/nm1102.pdf VL - 10 ID - 2444 ER - TY - JOUR AB - The reemergence of tuberculosis (TB) from the 1980s to the early 1990s instigated extensive researches on the mechanisms behind the transmission dynamics of TB epidemics. This article provides a detailed review of the work on the dynamics and control of TB. The earliest mathematical models describing the TB dynamics appeared in the 1960s and focused on the prediction and control strategies using simulation approaches. Most recently developed models not only pay attention to simulations but also take care of dynamical analysis using modern knowledge of dynamical systems. Questions addressed by these models mainly concentrate on TB control strategies, optimal vaccination policies, approaches toward the elimination of TB in the U.S.A., TB co-infection with HIV/AIDS, drug-resistant TB, responses of the immune system, impacts of demography, the role of public transportation systems, and the impact of contact patterns. Model formulations involve a variety of mathematical areas, such as ODEs (Ordinary Differential Equations) (both autonomous and non-autonomous systems), PDEs (Partial Differential Equations), system of difference equations, system of integro-differential equations, Markov chain model, and simulation models. AU - Castillo-Chavez, C. AU - Song, B. IS - 2 N1 - Castillo-Chavez, Carlos Song, Baojun eng 2004/09/01 00:00 Math Biosci Eng. 2004 Sep;1(2):361-404. PY - 2004 SN - 1547-1063 (Print) 1547-1063 (Linking) SP - 361-404 ST - Dynamical models of tuberculosis and their applications T2 - Math Biosci Eng TI - Dynamical models of tuberculosis and their applications UR - http://www.ncbi.nlm.nih.gov/pubmed/20369977 VL - 1 ID - 3918 ER - TY - JOUR AB - Background Tuberculosis (TB) notification rates among First Nations people in British Columbia, Canada, are higher than those among non-First Nations people, although rates are declining more rapidly in the First Nations population. The epidemiology of tuberculous infection and disease during the period 1926–2000 in this population was investigated.Methods The trend in the annual risk of infection (ARI) since 1926 was estimated using tuberculous meningitis mortality statistics and skin testing data. Risks of progression from infection to disease were estimated by fitting model predictions of disease incidence to TB notifications, using maximum likelihood methods. Infectious TB notifications were matched with ARI estimates to obtain the number of transmissions per infectious case over time.Results We estimate that the ARI decreased from more than 10% during the prechemotherapy era to less than 0.1% by 2000. The risks of primary, reactivation, and exogenous re-infection disease among adults aged 25–44 years were 22%, 0.1%, and 6%, respectively. The number of transmissions per infectious case decreased from 16 to 2 from the early 1970s to the late 1990s.Conclusions This study shows that the risk of infection among British Columbia First Nations people is decreasing, while the relative contribution of reactivation to disease incidence is increasing. Once infected, First Nations people may have a higher risk of developing disease than other populations. AU - Clark, Michael AU - Vynnycky, Emilia DA - June 1, 2004 DO - 10.1093/ije/dyh001 PY - 2004 RN - fulltext fulltext_1208 SP - 477-484 ST - The use of maximum likelihood methods to estimate the risk of tuberculous infection and disease in a Canadian First Nations population T2 - International Journal of Epidemiology TI - The use of maximum likelihood methods to estimate the risk of tuberculous infection and disease in a Canadian First Nations population UR - http://ije.oxfordjournals.org/content/33/3/477.abstract VL - 33 ID - 2445 ER - TY - JOUR AB - Mathematical models have recently been used to predict the future burden of multidrug-resistant tuberculosis (MDRTB). These models suggest the threat of multidrug resistance to TB control will depend on the relative 'fitness' of MDR strains and imply that if the average fitness of MDR strains is considerably less than that of drug-sensitive strains, the emergence of resistance will not jeopardize the success of tuberculosis control efforts. Multidrug resistance in M. tuberculosis is conferred by the sequential acquisition of a number of different single-locus mutations that have been shown to have heterogeneous phenotypic effects. Here we model the impact of initial fitness estimates on the emergence of MDRTB assuming that the relative fitness of MDR strains is heterogeneous. We find that even when the average relative fitness of MDR strains is low and a well-functioning control program is in place, a small subpopulation of a relatively fit MDR strain may eventually outcompete both the drug-sensitive strains and the less fit MDR strains. These results imply that current epidemiological measures and short-term trends in the burden of MDRTB do not provide evidence that MDRTB strains can be contained in the absence of specific efforts to limit transmission from those with MDR disease. AD - Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, Massachusetts 02115, USA. AN - 15378056 AU - Cohen, T. AU - Murray, M. DA - Oct DO - 10.1038/nm1110 [doi] nm1110 [pii] DP - Nlm ET - 09/21 KW - Disease Outbreaks Drug Resistance, Multiple, Bacterial/ genetics Humans Models, Biological Mycobacterium tuberculosis/genetics/ pathogenicity Species Specificity Time Factors Tuberculosis, Multidrug-Resistant/ epidemiology/prevention & control/transmission World Health L1 - internal-pdf://4026727844/Cohen-2004-Modeling epidemics of multidrug-res.pdf LA - eng N1 - Cohen, Ted Murray, Megan K08 AI055985-02/AI/NIAID NIH HHS/United States T32 AI007433-10/AI/NIAID NIH HHS/United States United States Nature medicine Nihms94735 Nat Med. 2004 Oct;10(10):1117-21. Epub 2004 Sep 19. PY - 2004 RN - fulltext fulltext_1208 SN - 1078-8956 (Print) 1078-8956 (Linking) SP - 1117-21 ST - Modeling epidemics of multidrug-resistant M. tuberculosis of heterogeneous fitness T2 - Nat Med TI - Modeling epidemics of multidrug-resistant M. tuberculosis of heterogeneous fitness UR - http://www.nature.com/nm/journal/v10/n10/pdf/nm1110.pdf https://www.nature.com/articles/nm1110.pdf VL - 10 ID - 2446 ER - TY - JOUR AB - The immune response to Mycobacterium tuberculosis (Mtb) infection is the formation of multicellular lesions, or granolomas, in the lung of the individual. However, the structure of the granulomas and the spatial distribution of the immune cells within is not well understood. In this paper we develop a mathematical model investigating the early and initial immune response to Mtb. The model consists of coupled reaction-diffusion-advection partial differential equations governing the dynamics of the relevant macrophage and bacteria populations and a bacteria-produced chemokine. Our novel application of mathematical concepts of internal states and internal velocity allows us to begin to study this unique immunological structure. Volume changes resulting from proliferation and death terms generate a velocity field by which all cells are transported within the forming granuloma. We present numerical results for two distinct infection outcomes: controlled and uncontrolled granuloma growth. Using a simplified model we are able to analytically determine conditions under which the bacteria population decreases, representing early clearance of infection, or grows, representing the initial stages of granuloma formation. AD - Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 49109, USA. AN - 14745511 AU - Gammack, D. AU - Doering, C. R. AU - Kirschner, D. E. DA - Feb DO - 10.1007/s00285-003-0232-8 [doi] DP - Nlm ET - 01/28 KW - Algorithms Cell Count Cell Death/immunology Cell Movement/immunology Chemokines/immunology Chemotaxis, Leukocyte/immunology Granuloma/immunology/microbiology/pathology Humans Immunity, Innate/immunology Macrophages/cytology/ immunology/microbiology Models, Immunological Mycobacterium tuberculosis/cytology/growth & development/immunology Phagocytosis/immunology Tuberculosis/ immunology/microbiology LA - eng N1 - Gammack, D Doering, C R Kirschner, D E HL6119/HL/NHLBI NIH HHS/United States HL68526/HL/NHLBI NIH HHS/United States Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Germany Journal of mathematical biology J Math Biol. 2004 Feb;48(2):218-42. Epub 2003 Aug 20. PY - 2004 RN - fulltext fulltext_1208 SN - 0303-6812 (Print) 0303-6812 (Linking) SP - 218-42 ST - Macrophage response to Mycobacterium tuberculosis infection T2 - J Math Biol TI - Macrophage response to Mycobacterium tuberculosis infection UR - http://www.springerlink.com/content/bn36wd4p4f6ypk0m/ VL - 48 ID - 2447 ER - TY - JOUR AB - Molecular epidemiological studies can provide novel insights into the transmission of infectious diseases such as tuberculosis. Typically, risk factors for transmission are identified using traditional hypothesis-driven statistical methods such as logistic regression. However, limitations become apparent in these approaches as the scope of these studies expand to include additional epidemiological and bacterial genomic data. Here we examine the use of Bayesian models to analyze tuberculosis epidemiology. We begin by exploring the use of Bayesian networks (BNs) to identify the distribution of tuberculosis patient attributes (including demographic and clinical attributes). Using existing algorithms for constructing BNs from observational data, we learned a BN from data about tuberculosis patients collected in San Francisco from 1991 to 1999. We verified that the resulting probabilistic models did in fact capture known statistical relationships. Next, we examine the use of newly introduced methods for representing and automatically constructing probabilistic models in structured domains. We use statistical relational models (SRMs) to model distributions over relational domains. SRMs are ideally suited to richly structured epidemiological data. We use a data-driven method to construct a statistical relational model directly from data stored in a relational database. The resulting model reveals the relationships between variables in the data and describes their distribution. We applied this procedure to the data on tuberculosis patients in San Francisco from 1991 to 1999, their Mycobacterium tuberculosis strains, and data on contact investigations. The resulting statistical relational model corroborated previously reported findings and revealed several novel associations. These models illustrate the potential for this approach to reveal relationships within richly structured data that may not be apparent using conventional statistical approaches. We show that Bayesian methods, in particular statistical relational models, are an important tool for understanding infectious disease epidemiology. AD - Computer Science Deptartment and UMIACS, University of Maryland, College Park, MD 20742, USA. getoor@cs.umd.edu AN - 15081074 AU - Getoor, L. AU - Rhee, J. T. AU - Koller, D. AU - Small, P. DA - Mar N1 - 0933-3657 Journal Article PY - 2004 RN - fulltext fulltext_1208 SP - 233-256 ST - Understanding tuberculosis epidemiology using structured statistical models T2 - Artificial Intelligence in Medicine TI - Understanding tuberculosis epidemiology using structured statistical models UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15081074http://ac.els-cdn.com/S0933365703001337/1-s2.0-S0933365703001337-main.pdf?_tid=26f9353e-6b36-11e2-b271-00000aab0f6c&acdnat=1359589290_10f521802b4cf63c00c720e01649cbab VL - 30 ID - 2448 ER - TY - JOUR AB - Population patterns of infection are determined largely by susceptibility to infection. Infection and vaccination induce an immune response that, typically, reduces susceptibility to subsequent infections. With a general epidemic model, we detect a 'reinfection threshold', above which reinfection is the principal type of transmission and, consequently, infection levels are much higher and vaccination fails. The model is further developed to address human tuberculosis (TB) and the impact of vaccination. The bacille Calmette-Guerin (BCG) is the only vaccine in current use against TB, and there is no consensus about its usefulness. Estimates of protection range from 0 to 80%, and this variability is aggravated by an association between low vaccine efficacy and high prevalence of the disease. We propose an explanation based on three postulates: (i) the potential for transmission varies between populations, owing to differences in socio-economic and environmental factors; (ii) exposure to mycobacteria induces an immune response that is partially protective against reinfection; and (iii) this protection is not significantly improved by BCG vaccination. These postulates combine to reproduce the observed trends, and this is attributed to a reinfection threshold intrinsic to the transmission dynamics. Finally, we demonstrate how reinfection thresholds can be manipulated by vaccination programmes, suggesting that they have a potentially powerful role in global control. AD - Instituto Gulbenkian de Ciencia, Apartado 14, 2781-901 Oeiras, Portugal. ggomes@igc.gulbenkian.pt AN - 15156920 AU - Gomes, M. G. AU - Franco, A. O. AU - Gomes, M. C. AU - Medley, G. F. DA - Mar 22 DO - 10.1098/rspb.2003.2606 ET - 05/26 J2 - Proceedings. Biological sciences / The Royal Society KW - BCG Vaccine/*immunology Disease Transmission, Infectious/*prevention & control Humans *Models, Biological Mycobacterium Infections/*immunology Tuberculosis/epidemiology/immunology/*transmission LA - eng M3 - Research Support, Non-U.S. Gov't N1 - Gomes, M Gabriela M Franco, Ana O Gomes, Manuel C Medley, Graham F England Proc Biol Sci. 2004 Mar 22;271(1539):617-23. PY - 2004 RN - fulltext fulltext_1208 SN - 0962-8452 (Print) 0962-8452 (Linking) SP - 617-23 ST - The reinfection threshold promotes variability in tuberculosis epidemiology and vaccine efficacy T2 - Proc Biol Sci TI - The reinfection threshold promotes variability in tuberculosis epidemiology and vaccine efficacy UR - http://www.ncbi.nlm.nih.gov/pubmed/15156920http://pubmedcentralcanada.ca/picrender.cgi?accid=PMC1691632&blobtype=pdf VL - 271 ID - 2449 ER - TY - JOUR AN - 13919 AU - Gomes, M. G. M. AU - White, L. J. AU - Medley, G. F. KW - immunity infection interventions models protection reinfection tuberculosis vaccination vaccine vaccine development N1 - IN FILE TB Intervention strategies Vaccine development No sub-heading Vacc dev - misc PY - 2004 RN - fulltext fulltext_1208 SP - 539-549 ST - Infection, reinfection, and vaccination under suboptimal immune protection: epidemiological perspectives T2 - J.Theor.Biol. TI - Infection, reinfection, and vaccination under suboptimal immune protection: epidemiological perspectives UR - file://C:\literature_pdf\rm13919.pdfhttp://ac.els-cdn.com/S0022519304000748/1-s2.0-S0022519304000748-main.pdf?_tid=a369897a-6b36-11e2-a468-00000aacb362&acdnat=1359589498_229e65e7b4d531f910339318b91df69b VL - 228 ID - 2450 ER - TY - JOUR AB - BACKGROUND: Moxifloxacin is a quinolone antimicrobial that has potent activity against Mycobacterium tuberculosis. To optimize moxifloxacin dose and dose regimen, pharmacodynamic antibiotic-exposure targets associated with maximal microbial kill and complete suppression of drug resistance in M. tuberculosis must be identified. METHODS: We used a novel in vitro pharmacodynamic infection model of tuberculosis in which we exposed M. tuberculosis to moxifloxacin with a pharmacokinetic half-life of decline similar to that encountered in humans. Data obtained from this model were mathematically modeled, and the drug-exposure breakpoint associated with the suppression of drug resistance was determined. Monte-Carlo simulations were performed to determine the probability that 10,000 clinical patients taking different doses of moxifloxacin would achieve or exceed the drug-exposure breakpoint needed to suppress resistance to moxifloxacin in M. tuberculosis. RESULTS: The ratio of the moxifloxacin-free (non-protein-bound) area under the concentration-time curve from 0 to 24 h to the minimum inhibitory concentration associated with complete suppression of the drug-resistant mutant population was 53. For patients taking moxifloxacin doses of 400, 600, or 800 mg/day, the calculated target-attainment rates to suppress drug resistance were 59%, 86%, and 93%, respectively. CONCLUSION: A moxifloxacin dose of 800 mg/day is likely to achieve excellent M. tuberculosis microbial kill and to suppress drug resistance. However, tolerability of this higher dose is still unknown. AD - Emerging Infections and Host Defense Section, Ordway Research Institute, Albany, New York 12208, USA. AN - 15478070 AU - Gumbo, T. AU - Louie, A. AU - Deziel, M. R. AU - Parsons, L. M. AU - Salfinger, M. AU - Drusano, G. L. DA - Nov 1 DO - JID32536 [pii] 10.1086/424849 [doi] DP - Nlm ET - 10/13 KW - Antitubercular Agents/administration & dosage/pharmacokinetics/ pharmacology/therapeutic use Aza Compounds/administration & dosage/ pharmacokinetics/ pharmacology/therapeutic use Colony Count, Microbial Drug Resistance, Bacterial Humans Microbial Sensitivity Tests Models, Biological Monte Carlo Method Mycobacterium tuberculosis/ drug effects/growth & development Quinolines/administration & dosage/ pharmacokinetics/ pharmacology/therapeutic use Tuberculosis/drug therapy/microbiology L1 - internal-pdf://0928176041/Gumbo-2004-Selection of a moxifloxacin dose th.pdf LA - eng N1 - Gumbo, Tawanda Louie, Arnold Deziel, Mark R Parsons, Linda M Salfinger, Max Drusano, George L Research Support, Non-U.S. Gov't United States The Journal of infectious diseases J Infect Dis. 2004 Nov 1;190(9):1642-51. Epub 2004 Sep 24. PY - 2004 RN - fulltext fulltext_1208 SN - 0022-1899 (Print) 0022-1899 (Linking) SP - 1642-51 ST - Selection of a moxifloxacin dose that suppresses drug resistance in Mycobacterium tuberculosis, by use of an in vitro pharmacodynamic infection model and mathematical modeling T2 - J Infect Dis TI - Selection of a moxifloxacin dose that suppresses drug resistance in Mycobacterium tuberculosis, by use of an in vitro pharmacodynamic infection model and mathematical modeling UR - http://jid.oxfordjournals.org/content/190/9/1642.full.pdf https://watermark.silverchair.com/190-9-1642.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAc8wggHLBgkqhkiG9w0BBwagggG8MIIBuAIBADCCAbEGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMyF8_epcQm4VNYrpDAgEQgIIBggsX4qnr8_dvV6PFHHMaK79tMwdbCBgxmUcnG9Mkpr5--AkWxyfm-tg4QaFZBWk6El4o6L0rexo7jSSA0Uolj2gXoiQWqFFCIr9_3kzZLtLFznpzSHcE7xJ47RD5BF6lOtSwY9l2ijXqz2bVjQJ5nL-7ZSKBf8LjhjGhHHc94u6C5lIakawUzBD-tEQ1qj-OdJ8G0Qlt9k6gvelh_NpzNYe2cjidd1aKdWu6tkptoz-CwwNIg5N2CjPBivzIln-ZQYrZT_XKxYj3J4oCFvSu0es2VVGG89ztsFcTymOhetdlTGimqi85tOtFxRBy8-jgjUF6RRDZgCenSqZl16FIJrv-2UN4kpSAvYLweepYk7SSOkjegO3g7olOAiBBOUVVy6-zL__Fe_DvicoFDPs5L8397nrTNHK0gpe8lGoSxl_ABJxVZWjWRt95AI6fZYbVOv-E_qJkgbUFTJ_QFIcleHrmo2xy9kwqNmgRMRRqprmmB4oSpIj0Xzt57OZ8SjWcWckf VL - 190 ID - 2451 ER - TY - JOUR AU - Guwatudde, D. AU - Debanne, S. M. AU - Diaz, M. AU - King, C. AU - Whalen, C. C. DO - 10.1016/j.ypmed.2004.04.008 KW - Tuberculosis preventive therapy Tuberculosis control Sub-Saharan Africa HIV-infection Deterministic model PY - 2004 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0091-7435 SP - 1036-1046 ST - A re-examination of the potential impact of preventive therapy on the public health problem of tuberculosis in contemporary sub-Saharan Africa T2 - Preventive Medicine TI - A re-examination of the potential impact of preventive therapy on the public health problem of tuberculosis in contemporary sub-Saharan Africa UR - http://www.sciencedirect.com/science/article/pii/S0091743504002117http://ac.els-cdn.com/S0091743504002117/1-s2.0-S0091743504002117-main.pdf?_tid=88ab7fb2ac53ae8c8768c7226bf2893a&acdnat=1345012430_531a7dd98abd3bed8080cd1e63a4eaa5 VL - 39 ID - 2452 ER - TY - JOUR AB - Two months of treatment with rifampin-pyrazinamide (RZ) and 9 months of treatment with isoniazid are both recommended for treatment of latent tuberculosis infection in adults without human immunodeficiency virus infection, but the relative cost-effectiveness of these 2 treatments is unknown. We used a Markov model to conduct a cost-effectiveness analysis to assess the impact on life expectancy and costs based on the results of a recent clinical trial that compared the rates of adverse events and completion of the 2 treatment regimens. Compared with no treatment, both regimens increased life expectancy by 1.2 years, but RZ cost 273 dollars more per patient. Sensitivity analyses showed that, assuming equal efficacy between the 2 regimens, there was no threshold completion rate for RZ at which the 2 treatments would be of equal net cost. Under most circumstances, treatment of latent tuberculosis infection with isoniazid is cost-saving than treatment with RZ. AU - Jasmer, R. M. AU - Snyder, D. C. AU - Saukkonen, J. J. AU - Hopewell, P. C. AU - Bernardo, J. AU - King, M. D. AU - Kawamura, L. M. AU - Daley, C. L. AU - Short-Course, Rifampin AU - Pyrazinamide for Tuberculosis Infection Study, Investigators DO - 10.1086/380966 IS - 3 KW - Adolescent Adult Antitubercular Agents/adverse effects/*economics/t Cost Savings Cost-Benefit Analysis Costs and Cost Analysis Humans Isoniazid/adverse effects/*economics/therapeutic u Pyrazinamide/adverse effects/*economics/therapeuti Rifampin/adverse effects/*economics/therapeutic us Tuberculosis/*drug therapy L1 - file:///C:/Users/James/AppData/Local/Mendeley Ltd/Mendeley Desktop/Downloaded/Jasmer-2004-Short-course rifampin and pyrazin1.pdf N1 - Jasmer, Robert M Snyder, David C Saukkonen, Jussi J Hopewell, Philip C Bernardo, John King, Mark D Kawamura, L Masae Daley, Charles L eng PY - 2004 SN - 1537-6591 (Electronic) 1058-4838 (Linking) SP - 363-369 ST - Short-course rifampin and pyrazinamide compared with isoniazid for latent tuberculosis infection: a cost-effectiveness analysis based on a multicenter clinical trial T2 - Clin Infect Dis TI - Short-course rifampin and pyrazinamide compared with isoniazid for latent tuberculosis infection: a cost-effectiveness analysis based on a multicenter clinical trial UR - http://www.ncbi.nlm.nih.gov/pubmed/14727206 http://cid.oxfordjournals.org/content/38/3/363.full.pdf http://cid.oxfordjournals.org/content/38/3/363.full.pdf#page=1&view=FitH http://cid.oxfordjournals.org/content/38/3/363.long VL - 38 ID - 3774 ER - TY - JOUR AB - This article estimates the risk of tuberculosis (TB) transmission on a typical commercial airliner using a simple one box model (OBM) and a sequential box model (SBM). We used input data derived from an actual TB exposure on an airliner, and we assumed a hypothetical scenario that a highly infectious TB source case (i.e., 108 infectious quanta per hour) travels as a passenger on an 8.7-hour flight. We estimate an average risk of TB transmission on the order of 1 chance in 1,000 for all passengers using the OBM. Applying the more realistic SBM, we show that the risk and incidence decrease sharply in a stepwise fashion in cabins downstream from the cabin containing the source case assuming some potential for airflow from more contaminated to less contaminated cabins. We further characterized spatial variability in the risk within the cabin by modeling a previously reported TB outbreak in an airplane to demonstrate that the TB cases occur most likely within close proximity of the source TB patient. AD - Environmental Sciences, University of Texas Health Science Center at Houston, School of Public Health, Houston, TX 77225, USA. gwangpyo.ko@uth.tmc.edu AN - 15078308 AU - Ko, G. AU - Thompson, K. M. AU - Nardell, E. A. DA - Apr DO - 10.1111/j.0272-4332.2004.00439.x [doi] RISK439 [pii] DP - Nlm ET - 04/14 KW - Aerospace Medicine Air Microbiology Aviation Humans Models, Biological Risk Risk Assessment Tuberculosis, Pulmonary/ transmission Ventilation LA - eng N1 - Ko, Gwangpyo Thompson, Kimberly M Nardell, Edward A United States Risk analysis : an official publication of the Society for Risk Analysis Risk Anal. 2004 Apr;24(2):379-88. PY - 2004 RN - fulltext fulltext_1208 SN - 0272-4332 (Print) 0272-4332 (Linking) SP - 379-88 ST - Estimation of tuberculosis risk on a commercial airliner T2 - Risk Anal TI - Estimation of tuberculosis risk on a commercial airliner UR - http://onlinelibrary.wiley.com/doi/10.1111/j.0272-4332.2004.00439.x/abstract VL - 24 ID - 2453 ER - TY - JOUR AB - A key issue for the study of tuberculosis is to understand why individuals infected with Mycobacterium tuberculosis (Mtb) experience different clinical outcomes. To better understand the dynamics of Mtb infection and immunity, we have previously developed a temporal mathematical model that qualitatively and quantitatively characterizes the cellular and cytokine control network during infection. In this work we extend that model to a two compartmental model to capture the important processes of cellular activation and priming that occur between the lung and the nearest draining lymph node. We are able to reproduce typical disease progression scenarios including primary infection, latency or clearance. Then we use the model to predict key processes determining these different disease trajectories (i.e. identify bifurcation parameters), suggesting directions for further basic science study and potential new treatment strategies. AD - Department of Microbiology and Immunology, University of Michigan Medical School, 6730 Medical Science Building II, Ann Arbor, MI 48109-0620, USA. simeonem@umich.edu AN - 15038983 AU - Marino, S. AU - Kirschner, D. E. DA - Apr 21 DO - 10.1016/j.jtbi.2003.11.023 [doi] S0022519303004429 [pii] DP - Nlm ET - 03/25 KW - Cytokines/immunology Dendritic Cells/immunology Disease Progression Humans Immunity/immunology Lung/ immunology Lymph Nodes/ immunology Lymphocytes/immunology Mathematics Models, Immunological Mycobacterium tuberculosis/ immunology Tuberculosis/drug therapy/ immunology LA - eng N1 - Marino, Simeone Kirschner, Denise E R01 HL68526/HL/NHLBI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England Journal of theoretical biology J Theor Biol. 2004 Apr 21;227(4):463-86. PY - 2004 RN - fulltext fulltext_1208 SN - 0022-5193 (Print) 0022-5193 (Linking) SP - 463-86 ST - The human immune response to Mycobacterium tuberculosis in lung and lymph node T2 - J Theor Biol TI - The human immune response to Mycobacterium tuberculosis in lung and lymph node UR - http://ac.els-cdn.com/S0022519303004429/1-s2.0-S0022519303004429-main.pdf?_tid=463df9c23cd467c72c7b22525a29a48e&acdnat=1345012650_2ba45ca5231c150bbe59251fbf62022d VL - 227 ID - 2454 ER - TY - JOUR AB - Mycobacterium tuberculosis (Mtb) is an extraordinarily successful human pathogen, one of the major causes of death by infectious disease worldwide. A key issue for the study of tuberculosis is to understand why individuals infected with Mtb experience different clinical outcomes. To better understand the dynamics of Mtb infection and immunity, we coupled nonhuman primate experiments with a mathematical model we previously developed that qualitatively and quantitatively captures important processes of cellular priming and activation. These processes occur between the lung and the nearest draining lymph node where the key cells mediating this process are the dendritic cells (DC). The nonhuman primate experiments consist of bacteria and cell numbers from tissues of 17 adult cynomolgus macaques (Macaca fascicularis) that were infected with Mtb strain Erdman (similar to25 CFU/animal via bronchoscope). The main result of this work is that delays in either DC migration to the draining lymph node or T cell trafficking to the site of infection can alter the outcome of Mtb infection, defining progression to primary disease or latent infection and reactivated tuberculosis. Our results also support the idea that the development of a new generation of treatment against Mtb should optimally elicit a fast DC turnover at the site of infection, as well as strong activation of DCs for maximal Ag presentation and production of key cytokines. This will induce the most protective T cell response. AD - Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA Univ Pittsburgh, Dept Mol Genet & Biochem, Sch Med, Pittsburgh, PA 15260 USA Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA AN - WOS:000222170900063 AU - Marino, S. AU - Pawar, S. AU - Fuller, C. L. AU - Reinhart, T. A. AU - Flynn, J. L. AU - Kirschner, D. E. DA - Jul 1 IS - 1 J2 - J Immunol KW - cd8(+) t-cells chemokine receptor expression necrosis-factor-alpha in-vivo interferon-gamma bronchoalveolar lavage sensitivity analysis ifn-gamma endogenous reactivation pulmonary tuberculosis LA - English N1 - 831cq Times Cited:71 Cited References Count:106 PY - 2004 SN - 0022-1767 SP - 494-506 ST - Dendritic cell trafficking and antigen presentation in the human immune response to Mycobacterium tuberculosis T2 - Journal of Immunology TI - Dendritic cell trafficking and antigen presentation in the human immune response to Mycobacterium tuberculosis UR - ://WOS:000222170900063 VL - 173 ID - 2231 ER - TY - JOUR AB - The importance of exogenous reinfection versus endogenous reactivation for the resurgence of tuberculosis (TB) has been a matter of ongoing debate. Previous mathematical models of TB give conflicting results on the possibility of multiple stable equilibria in the presence of reinfection, and hence the failure to control the disease even when the basic reproductive number is less than unity. The present study reconsiders the effect of exogenous reinfection, by extending previous studies to incorporate a generalized rate of reinfection as a function of the number of actively infected individuals. A mathematical model is developed to include all possible routes to the development of active TB (progressive primary infection, endogenous reactivation, and exogenous reinfection). The model is qualitatively analyzed to show the existence of multiple equilibria under realistic assumptions and plausible range of parameter values. Two examples, of unbounded and saturated incidence rates of reinfection, are given, and simulation results using estimated parameter values are presented. The results reflect exogenous reinfection as a major cause of TB emergence, especially in high prevalence areas, with important public health implications for controlling its spread. AD - Natl Res Council Canada, Inst Biodiagnost, Winnipeg, MB R3B 1Y6, Canada AN - WOS:000222829400006 AU - Moghadas, S. M. AU - Alexander, M. E. DA - Jun DO - Doi 10.1142/S0218339004001063 IS - 2 J2 - J Biol Syst KW - basic reproductive number epidemic models equilibria exogenous reinfection stability tuberculosis mycobacterium-tuberculosis epidemic model disease transmission backward bifurcation control strategies infection prevalence equilibria dynamics hiv LA - English N1 - 840am Times Cited:5 Cited References Count:39 PY - 2004 SN - 0218-3390 SP - 231-247 ST - Exogenous reinfection and resurgence of tuberculosis: A theoretical framework T2 - Journal of Biological Systems TI - Exogenous reinfection and resurgence of tuberculosis: A theoretical framework UR - ://WOS:000222829400006 VL - 12 ID - 4834 ER - TY - JOUR AB - The purposes of this study are to predict the future trend of drug-sensitive and resistant tuberculosis (TB) in Thailand, and to assess the impact of different control strategies on the generation of drug resistant TB, through the use of mathematical analysis. We assume that the present status of TB and the emergence of drug-resistant TB in Thailand are the consequence of past epidemics. Control strategies in the model are defined by specifying the value of the effective treatment rate (baseline value = 0.74) and the relative treatment efficacy (baseline value = 0.84). It is predicted that the total number of new TB cases would continue to decrease at the current level of intervention. Although a dramatic decline in the incidence rate of drug-sensitive cases is expected, drug-resistant cases are predicted to increase gradually, so that more than half of the TB strains would not be drug-sensitive after 2020. The prediction is not greatly altered by improving the interventions. They could, however, delay the emergence of drug-resistant strains for a few years. Our study demonstrates it would be impossible to avoid the continued emergence of drug-resistant TB in the future. It is pointed out that there are urgent needs to ensure adequate supervision and monitoring, to insure treatment of 100% of the targeted population with Directly Observed Therapy. AD - Department of Mathematics, Faculty of Science, Mahidol University, Bangkok, Thailand. Nishiurah@aol.com AN - 15689082 AU - Nishiura, H. AU - Patanarapelert, K. AU - Tang, I. M. DA - Sep DP - Nlm ET - 02/04 KW - Antibiotics, Antitubercular/pharmacology/therapeutic use Chemoprevention Communicable Disease Control Directly Observed Therapy Drug Resistance, Multiple, Bacterial Forecasting Humans Incidence Models, Theoretical Mycobacterium tuberculosis/ drug effects Rifampin/pharmacology/therapeutic use Thailand/epidemiology Tuberculosis, Multidrug-Resistant/drug therapy/ epidemiology/prevention & control L1 - internal-pdf://2935527750/27-3243.pdf LA - eng N1 - Nishiura, Hiroshi Patanarapelert, Kot Tang, I Ming Thailand The Southeast Asian journal of tropical medicine and public health Southeast Asian J Trop Med Public Health. 2004 Sep;35(3):649-56. PY - 2004 RN - fulltext fulltext_1208 SN - 0125-1562 (Print) 0125-1562 (Linking) SP - 649-56 ST - Predicting the future trend of drug-resistant tuberculosis in Thailand: assessing the impact of control strategies T2 - Southeast Asian J Trop Med Public Health TI - Predicting the future trend of drug-resistant tuberculosis in Thailand: assessing the impact of control strategies VL - 35 ID - 2455 ER - TY - JOUR AB - This paper is devoted to the construction of the mathematical model of the tuberculosis morbidity dynamics. The model takes into account the peculiarities of morbidity epidemiology and its control. The model is adjusted to the data collected in the Orlovskaya oblast. The results obtained will be used for the analysis of the epidemiological situation and designing the effective strategy of tuberculosis control. AD - Moscow Med Acad, IM Sechenov Res Inst Phthisiopulmon, Moscow 127994, Russia Russian Acad Sci, Inst Numer Math, Moscow 119991, Russia AN - WOS:000223636500004 AU - Perelman, M. I. AU - Marchuk, G. I. AU - Borisov, S. E. AU - Kazennykh, B. Y. AU - Avilov, K. K. AU - Karkach, A. S. AU - Romanyukha, A. A. DO - Doi 10.1163/1569398041974905 IS - 4 J2 - Russ J Numer Anal M KW - resistant impact hiv LA - English N1 - 850tu Times Cited:7 Cited References Count:8 PY - 2004 SN - 0927-6467 SP - 305-314 ST - Tuberculosis epidemiology in Russia: the mathematical model and data analysis T2 - Russian Journal of Numerical Analysis and Mathematical Modelling TI - Tuberculosis epidemiology in Russia: the mathematical model and data analysis UR - ://WOS:000223636500004 https://www.degruyter.com/view/j/rnam.2004.19.issue-4/1569398041974905/1569398041974905.xml VL - 19 ID - 4835 ER - TY - JOUR AB - To determine whether polymerase chain reaction (PCR) testing in the initial diagnosis of pulmonary tuberculosis (TB) is cost-effective in a low-prevalence population, an economic evaluation was carried out between the smear and culture (NOPCR) and smear, culture and PCR (+PCR) strategies. A decision tree model based on retrospective laboratory data was developed to assess the strategies of testing patients with suspicion of TB. Direct healthcare costs prior to confirmation of TB or nontuberculous mycobacteria by PCR or culture were included. Effectiveness was measured by the probability of correct treatment and isolation decisions. In the baseline situation NOPCR costs Euro 29.50 less than the +PCR strategy per patient tested. According to sensitivity analyses, reducing PCR test price, shortening test performance time or increasing the proportion of smear-positive patients in the tested population would contribute to cost savings with the +PCR strategy. Routine polymerase chain reaction testing of all specimens from suspected tuberculosis patients in a low-prevalence population was not cost-saving. When the polymerase chain reaction assay was applied only to smear-positive sputum specimens, the smear and culture strategy was clearly dominated by it, i.e. the polymerase chain reaction smear-positive sputum strategy was less costly and more effective in producing correct treatment decisions and isolations. AD - Dept of Pulmonary Diseases, Tampere University Hospital, Tampere, Finland. iiris.rajalahti@kolumbus.fi AN - 15065837 AU - Rajalahti, I. AU - Ruokonen, E. L. AU - Kotomaki, T. AU - Sintonen, H. AU - Nieminen, M. M. DA - Mar DP - Nlm ET - 04/07 J2 - The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology KW - Cost-Benefit Analysis Decision Trees Finland/epidemiology Health Care Costs/statistics & numerical data Humans Incidence Polymerase Chain Reaction/ economics Prevalence Specimen Handling Sputum/microbiology Tuberculosis, Pulmonary/ diagnosis/economics/epidemiology LA - eng N1 - Rajalahti, I Ruokonen, E L Kotomaki, T Sintonen, H Nieminen, M M Research Support, Non-U.S. Gov't Denmark Eur Respir J. 2004 Mar;23(3):446-51. PY - 2004 RN - fulltext fulltext_1208 SN - 0903-1936 (Print) 0903-1936 (Linking) SP - 446-51 ST - Economic evaluation of the use of PCR assay in diagnosing pulmonary TB in a low-incidence area T2 - Eur Respir J TI - Economic evaluation of the use of PCR assay in diagnosing pulmonary TB in a low-incidence area UR - http://erj.ersjournals.com/content/23/3/446.full.pdf VL - 23 ID - 2456 ER - TY - JOUR AB - Infection with Mycobacterium tuberculosis is a major world health problem. An estimated 2 billion people are presently infected and the disease causes approximately 3 million deaths per year. After bacteria are inhaled into the lung, a complex immune response is triggered leading to the formation of multicellular structures termed granulomas. It is believed that the collection of host granulomas either contain bacteria resulting in a latent infection or are unable to do so, leading to active disease. Thus, understanding granuloma formation and function is essential for improving both diagnosis and treatment of tuberculosis. Granuloma formation is a complex spatio-temporal system involving interactions of bacteria, specific immune cells, including macrophages, CD4+ and CD8+ T cells, as well as immune effectors such as chemokine and cytokines. To study this complex dynamical system we have developed an agent-based model of granuloma formation in the lung. This model combines continuous representations of chemokines with discrete agent representations of macrophages and T cells in a cellular automata-like environment. Our results indicate that key host elements involved in granuloma formation are chemokine diffusion, prevention of macrophage overcrowding within the granuloma, arrival time, location and number of T cells within the granuloma, and an overall host ability to activate macrophages. Interestingly, a key bacterial factor is its intracellular growth rate, whereby slow growth actually facilitates survival. AD - Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA. AN - 15501468 AU - Segovia-Juarez, J. L. AU - Ganguli, S. AU - Kirschner, D. DA - Dec 7 DO - 10.1016/j.jtbi.2004.06.031 ET - 10/27 J2 - Journal of theoretical biology KW - Chemokines/immunology Granuloma/*immunology Humans Lung/*immunology Lymphocyte Activation Macrophage Activation Macrophages/immunology *Models, Immunological *Mycobacterium tuberculosis T-Lymphocytes/immunology Tuberculosis/*immunology LA - eng M3 - Research Support, U.S. Gov't, P.H.S. N1 - Segovia-Juarez, Jose L Ganguli, Suman Kirschner, Denise R01HL68526/HL/NHLBI NIH HHS/ England J Theor Biol. 2004 Dec 7;231(3):357-76. PY - 2004 RN - fulltext fulltext_1208 SN - 0022-5193 (Print) 0022-5193 (Linking) SP - 357-76 ST - Identifying control mechanisms of granuloma formation during M. tuberculosis infection using an agent-based model T2 - J Theor Biol TI - Identifying control mechanisms of granuloma formation during M. tuberculosis infection using an agent-based model UR - http://www.ncbi.nlm.nih.gov/pubmed/15501468 VL - 231 ID - 2458 ER - TY - JOUR AB - the extent to which reinfection of latently infected individuals contributes to the dynamics of tuberculosis (TB) epidemics. In this study we present an epidemiological model of Mycobacterium tuberculosis infection that includes the process of reinfection. Using analysis and numerical simulations, we observe the effect that varying levels of reinfection has on the qualitative dynamics of the TB epidemic. We examine cases of the model both with and without treatment of actively infected individuals. Next, we consider a variation of the model describing a heterogeneous population, stratified by susceptibility to TB infection. Results show that a threshold level of reinfection exists in all cases of the model. Beyond this threshold, the dynamics of the model are described by a backward bifurcation. Uncertainty analysis of the parameters shows that this threshold is too high to be attained in a realistic epidemic. However, we show that even for sub-threshold levels of reinfection, including reinfection in the model changes dynamic behavior of the model. In particular, when reinfection is present the basic reproductive number, R(0), does not accurately describe the severity of an epidemic. AD - Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI 48109-0620. kirschne@umich.edu. AN - 20369961 AU - Singer, B. H. AU - Kirschner, D. E. DA - Jun IS - 1 N1 - Singer, Benjamin H Kirschner, Denise E eng 2004/06/01 00:00 Math Biosci Eng. 2004 Jun;1(1):81-93. PY - 2004 SN - 1547-1063 (Print) 1547-1063 (Linking) SP - 81-93 ST - Influence of backward bifurcation on interpretation of r(0) in a model of epidemic tuberculosis with reinfection T2 - Math Biosci Eng TI - Influence of backward bifurcation on interpretation of r(0) in a model of epidemic tuberculosis with reinfection UR - https://www.ncbi.nlm.nih.gov/pubmed/20369961 VL - 1 ID - 2259 ER - TY - JOUR AB - BACKGROUND: While the pathogenesis and epidemiology of tuberculosis are well studied, relatively little is known about the evolution of the infectious agent Mycobacterium tuberculosis, especially at the within-host level. The insertion sequence IS6110 is a genetic marker that is widely used to track the transmission of tuberculosis between individuals. This and other markers may also facilitate our understanding of the disease within patients. RESULTS: This article presents three lines of evidence supporting the action of positive selection on M. tuberculosis within patients. The arguments are based on a comparison between empirical findings from molecular epidemiology, and population genetic models of evolution. Under the hypothesis of neutrality of genotypes, 1) the mutation rate of the marker IS6110 is unusually high, 2) the time it takes for substitutions to occur within patients is too short, and 3) the amount of polymorphism within patients is too low. CONCLUSIONS: Empirical observations are explained by the action of positive selection during infection, or alternatively by very low effective population sizes. I discuss the possible roles of antibiotic treatment, the host immune system and extrapulmonary dissemination in creating opportunities for positive selection. AD - School of Biotechnology and Biomolecular Sciences, University of New South Wales, NSW 2052, Australia. m.tanaka@unsw.edu.au AN - 15355550 AU - Tanaka, M. M. DA - Sep 9 N1 - 1471-2148 Journal Article PY - 2004 RN - fulltext fulltext_1208 SP - 31 ST - Evidence for positive selection on Mycobacterium tuberculosis within patients T2 - Bio Med Central Evolutionary Biology TI - Evidence for positive selection on Mycobacterium tuberculosis within patients UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15355550 VL - 4 ID - 2459 ER - TY - JOUR AB - Developing effective tuberculosis (TB) vaccines is a high priority. We use mathematical models to predict the potential public health impact of new TB vaccines in high-incidence countries. We show that preexposure vaccines would be almost twice as effective as postexposure vaccines in reducing the number of new infections. Postexposure vaccines would initially have a substantially greater impact, compared to preexposure vaccines, on reducing the number of new cases of disease. However, the effectiveness of postexposure vaccines would diminish over time, whereas the effectiveness of preexposure vaccines would increase. Thus, after 20 to 30 years, post- or preexposure vaccination campaigns would be almost equally effective in terms of cumulative TB cases prevented. Even widely deployed and highly effective (50%-90% efficacy) pre- or postexposure vaccines would only be able to reduce the number of TB cases by one third. We discuss the health policy implications of our analyses. AD - University of California-San Francisco, San Francisco, California, USA. AN - 15498152 AU - Ziv, E. AU - Daley, C. L. AU - Blower, S. DA - Sep ET - 10/23 J2 - Emerging infectious diseases KW - Disease Outbreaks Health Policy Humans Incidence Models, Theoretical Public Health Time Factors Tuberculosis/immunology/*prevention & control Tuberculosis Vaccines/*immunology LA - eng M3 - Research Support, U.S. Gov't, P.H.S. Review N1 - Ziv, Elad Daley, Charles L Blower, Sally R01 AI041935/AI/NIAID NIH HHS/ Emerg Infect Dis. 2004 Sep;10(9):1529-35. PY - 2004 RN - fulltext fulltext_1208 SN - 1080-6040 (Print) 1080-6040 (Linking) SP - 1529-35 ST - Potential public health impact of new tuberculosis vaccines T2 - Emerg Infect Dis TI - Potential public health impact of new tuberculosis vaccines UR - http://www.ncbi.nlm.nih.gov/pubmed/15498152 VL - 10 ID - 2460 ER - TY - JOUR AB - As HIV/AIDS drugs are becoming more widely available in Southern Africa, we compared the effectiveness and cost effectiveness of different treatment options, using a Markov Monte Carlo simulation model based on published estimates of disease progression, treatment effectiveness and health care costs. Cost and outcome values were discounted. Quality of life was considered. Acceptability curves summarized uncertainties. Sensitivity analyses tested assumptions. Results showed that triple antiretroviral therapy (ARV) plus antibiotics would prolong life by 6.7 undiscounted years if provided 'late' (CD4 = 200 cells/microl) and by 9.8 years if provided 'early' (CD4 = 350 cells/microl). The incremental undiscounted costs per year of life gained, compared to no preventive therapy, were $17 for isoniazid plus cotrimoxazole started late, $244 for both antibiotics started early, $2454 for ARV plus antibiotics started late and $2784 for ARV plus both antibiotics started early. The discounted incremental costs per quality adjusted life year (QALY) gained were, respectively, $29 saving, $254, $4937 and $3057. Late ARV plus both antibiotics was the strategy most likely to be cost effective if society was willing to pay more than $2000 per life year gained. Cost-effectiveness estimates were sensitive to discounting and assumed treatment costs but were less sensitive to assumed treatment effectiveness. AD - School of Medicine, University of East Anglia, UK. m.bachmann@uea.ac.uk AN - 16338768 AU - Bachmann, M. O. DA - Feb DO - 10.1080/09540120500159334 DP - Nlm ET - 12/13 J2 - AIDS care KW - AIDS-Related Opportunistic Infections/drug therapy/economics/mortality Africa, Southern/epidemiology Anti-Infective Agents/administration & dosage Anti-Retroviral Agents/economics/ therapeutic use Antitubercular Agents/administration & dosage Cost-Benefit Analysis Drug Therapy, Combination HIV Infections/ drug therapy/economics/mortality Health Care Costs/ statistics & numerical data Humans Isoniazid/administration & dosage Markov Chains Models, Statistical Monte Carlo Method Quality-Adjusted Life Years Treatment Outcome Trimethoprim-Sulfamethoxazole Combination/administration & dosage Tuberculosis/complications/drug therapy/economics LA - eng N1 - Bachmann, M O England AIDS Care. 2006 Feb;18(2):109-20. PY - 2005 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0954-0121 (Print) 0954-0121 (Linking) SP - 109-20 ST - Effectiveness and cost effectiveness of early and late prevention of HIV/AIDS progression with antiretrovirals or antibiotics in Southern African adults T2 - AIDS Care TI - Effectiveness and cost effectiveness of early and late prevention of HIV/AIDS progression with antiretrovirals or antibiotics in Southern African adults UR - http://www.tandfonline.com/doi/pdf/10.1080/09540120500159334 VL - 18 ID - 2470 ER - TY - JOUR AB - OBJECTIVE: To assess the costs and health effects of tuberculosis control interventions in Africa and South East Asia in the context of the millennium development goals. DESIGN: Cost effectiveness analysis based on an epidemiological model. SETTING: Analyses undertaken for two regions classified by WHO according to their epidemiological grouping-Afr-E, countries in sub-Saharan Africa with very high adult and high child mortality, and Sear-D, countries in South East Asia with high adult and high child mortality. DATA SOURCES: Published studies, costing databases, expert opinion. MAIN OUTCOME MEASURES: Costs per disability adjusted life year (DALY) averted in 2000 international dollars (dollarsInt). RESULTS: Treatment of new cases of smear-positive tuberculosis in DOTS programmes cost dollarsInt6-8 per DALY averted in Afr-E and dollarsInt7 per DALY averted in Sear-D at coverage levels of 50-95%. In Afr-E, adding treatment of smear-negative and extra-pulmonary cases at a coverage level of 95% cost dollarsInt95 per DALY averted; the addition of DOTS-Plus treatment for multidrug resistant cases cost dollarsInt123. In Sear-D, these costs were dollarsInt52 and dollarsInt226, respectively. The full combination of interventions could reduce prevalence and mortality by over 50% in Sear-D between 1990 and 2010, and by almost 50% between 2000 and 2010 in Afr-E. CONCLUSIONS: DOTS treatment of new smear-positive cases is the first priority in tuberculosis control, including in countries with high HIV prevalence. DOTS treatment of smear-negative and extra-pulmonary cases and DOTS-Plus treatment of multidrug resistant cases are also highly cost effective. To achieve the millennium development goal for tuberculosis control, substantial extra investment is needed to increase case finding and implement interventions on a wider scale. AD - Institute for Medical Technology Assessment (iMTA), Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands. r.baltussen@erasmusmc.nl AN - 16282379 AU - Baltussen, R. AU - Floyd, K. AU - Dye, C. DA - Dec 10 DO - 10.1136/bmj.38645.660093.68 ET - 11/12 J2 - Bmj KW - Africa/epidemiology Antitubercular Agents/economics/therapeutic use Asia, Southeastern/epidemiology Communicable Disease Control/economics/methods Cost-Benefit Analysis *Developing Countries Humans Incidence Prevalence Program Evaluation Quality-Adjusted Life Years Tuberculosis/classification/economics/*prevention & control Tuberculosis, Multidrug-Resistant/epidemiology/prevention & control L1 - internal-pdf://1107758612/Baltussen-2005-Cost effectiveness analysis of.pdf LA - eng M3 - Research Support, Non-U.S. Gov't N1 - Baltussen, Rob Floyd, Katherine Dye, Christopher England Clinical research ed. BMJ. 2005 Dec 10;331(7529):1364. Epub 2005 Nov 10. PY - 2005 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1756-1833 (Electronic) 0959-535X (Linking) SP - 1364 ST - Cost effectiveness analysis of strategies for tuberculosis control in developing countries T2 - BMJ TI - Cost effectiveness analysis of strategies for tuberculosis control in developing countries UR - http://www.ncbi.nlm.nih.gov/pubmed/16282379http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1309642/pdf/bmj33101364.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1309642/pdf/bmj33101364.pdf VL - 331 ID - 2462 ER - TY - JOUR AB - BACKGROUND: The HIV epidemic has caused a dramatic increase in tuberculosis (TB) in East and southern Africa. Several strategies have the potential to reduce the burden of TB in high HIV prevalence settings, and cost and cost-effectiveness analyses can help to prioritize them when budget constraints exist. However, published cost and cost-effectiveness studies are limited. METHODS: Our objective was to compare the cost, affordability and cost-effectiveness of seven strategies for reducing the burden of TB in countries with high HIV prevalence. A compartmental difference equation model of TB and HIV and recent cost data were used to assess the costs (year 2003 USD prices) and effects (TB cases averted, deaths averted, DALYs gained) of these strategies in Kenya during the period 2004-2023. RESULTS: The three lowest cost and most cost-effective strategies were improving TB cure rates, improving TB case detection rates, and improving both together. The incremental cost of combined improvements to case detection and cure was below USD 15 million per year (7.5% of year 2000 government health expenditure); the mean cost per DALY gained of these three strategies ranged from USD 18 to USD 34. Antiretroviral therapy (ART) had the highest incremental costs, which by 2007 could be as large as total government health expenditures in year 2000. ART could also gain more DALYs than the other strategies, at a cost per DALY gained of around USD 260 to USD 530. Both the costs and effects of treatment for latent tuberculosis infection (TLTI) for HIV+ individuals were low; the cost per DALY gained ranged from about USD 85 to USD 370. Averting one HIV infection for less than USD 250 would be as cost-effective as improving TB case detection and cure rates to WHO target levels. CONCLUSION: To reduce the burden of TB in high HIV prevalence settings, the immediate goal should be to increase TB case detection rates and, to the extent possible, improve TB cure rates, preferably in combination. Realising the full potential of ART will require substantial new funding and strengthening of health system capacity so that increased funding can be used effectively. AD - School of Mathematics, University of Southampton, Southampton, SO17 1BJ, UK. christine.currie@soton.ac.uk AN - 16343345 AU - Currie, C. S. AU - Floyd, K. AU - Williams, B. G. AU - Dye, C. DO - 1471-2458-5-130 [pii] 10.1186/1471-2458-5-130 [doi] DP - Nlm ET - 12/14 KW - AIDS-Related Opportunistic Infections/ economics/epidemiology/ prevention & control Adolescent Adult Antiretroviral Therapy, Highly Active/utilization Antitubercular Agents/therapeutic use Cost of Illness Cost-Benefit Analysis Directly Observed Therapy Female Health Care Costs/ statistics & numerical data Health Services Accessibility Humans Kenya/epidemiology Middle Aged Models, Econometric Prevalence Quality-Adjusted Life Years Tuberculosis/ economics/epidemiology/ prevention & control LA - eng N1 - Currie, Christine S M Floyd, Katherine Williams, Brian G Dye, Christopher Comparative Study Research Support, Non-U.S. Gov't England BMC public health BMC Public Health. 2005 Dec 12;5:130. PY - 2005 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1471-2458 (Electronic) 1471-2458 (Linking) SP - 130 ST - Cost, affordability and cost-effectiveness of strategies to control tuberculosis in countries with high HIV prevalence T2 - BMC Public Health TI - Cost, affordability and cost-effectiveness of strategies to control tuberculosis in countries with high HIV prevalence UR - http://www.biomedcentral.com/1471-2458/5/130http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1361804/pdf/1471-2458-5-130.pdf VL - 5 ID - 2463 ER - TY - JOUR AB - The aim of the present study was to perform a cost-effectiveness analysis in young and middle-aged adults with latent tuberculosis (TB) infection in Germany. A Markov model simulated the progression of 20- and 40-yr-old close contacts of active TB cases over 20 yrs. Health and economic outcomes of isoniazid (INH) chemoprevention versus no intervention were compared. The analysis determined the incremental cost-effectiveness ratio in terms of cost per quality-adjusted life year and the difference between numbers of TB cases and of TB-related deaths. INH chemoprevention prevented 79% of expected TB cases in both age groups, and saved 9,482 and 9,142 in the lower and higher age groups, respectively, per case prevented. Quality-adjusted life expectancy was slightly extended by 8 days in the lower age group and 7 days in the higher age group, at a cost saving of 417 and 375, respectively, per person. Annual savings were 20,862 and 18,742 per 1,000 contacts, respectively. The number needed to be treated to prevent one TB case in the lower age group was 23 and 25 in the higher age group. The programme also prevented three TB-related deaths in the younger and two in the older cohort. The results are highly sensitive to treatment-cost assumptions. In conclusion, isoniazid chemoprevention in Germany is a highly cost-effective approach for reducing the burden of tuberculosis in recently converted young and middle-aged adults. AD - School of Public Health, c/o Institute for Medical Sociology, Heinrich Heine University, Post box 101007, D-40001 Dusseldorf, Germany. Roland.Diel@uni-duesseldorf.de AN - 16135730 AU - Diel, R. AU - Nienhaus, A. AU - Schaberg, T. DA - Sep KW - Adolescent Adult Antitubercular Agents/administration & dosage/economics/*therapeutic use Carrier State/*prevention & control/transmission Chemoprevention/economics Contact Tracing Cost-Benefit Analysis Germany *Health Care Costs Health Status Humans Isoniazid/administration & dosage/economics/*therapeutic use Markov Chains Middle Aged Quality-Adjusted Life Years Treatment Outcome Tuberculosis/mortality/*prevention & control/transmission N1 - 0903-1936 Journal Article PY - 2005 RN - fulltext fulltext_1208 SP - 465-473 ST - Cost-effectiveness of isoniazid chemoprevention in close contacts T2 - European Respiratory Journal TI - Cost-effectiveness of isoniazid chemoprevention in close contacts UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16135730 VL - 26 ID - 2464 ER - TY - JOUR AU - Gammack, D. AU - Ganguli, S. AU - Marino, S. AU - Segovia-Juarez, J. AU - Kirschner, D. E. PY - 2005 RN - fulltext fulltext_1208 SN - 1540-3459 SP - 312-345 ST - Understanding the immune response in tuberculosis using different mathematical models and biological scales T2 - Multiscale Modeling and Simulation TI - Understanding the immune response in tuberculosis using different mathematical models and biological scales VL - 3 ID - 2465 ER - TY - JOUR AB - The immune response to Mycobacterium tuberculosis infection (Mtb) is the formation of unique lesions, called granulomas. How well these granulomas form and function is a key issue that might explain why individuals experience different disease outcomes. The spatial structures of these granulomas are not well understood. In this paper, we use a metapopulation framework to develop a spatio-temporal model of the immune response to Mtb. Using this model, we are able to investigate the spatial organization of the immune response in the lungs to Mtb. We identify both host and pathogen factors that contribute to successful infection control. Additionally, we identify specific spatial interactions and mechanisms important for successful granuloma formation. These results can be further studied in the experimental setting. AD - Biosystems Group, University of California, San Francisco, 513 Parnassus Ave., San Francisco, CA 94143. sganguli@itsa.ucsf.edu. AN - 20369939 AU - Ganguli, S. AU - Gammack, D. AU - Kirschner, D. E. DO - 040579197 [pii] LA - eng N1 - Ganguli, Suman Gammack, David Kirschner, Denise E United States Mathematical biosciences and engineering : MBE Math Biosci Eng. 2005 Jul;2(3):535-60. PY - 2005 RN - fulltext fulltext_1208 SN - 1547-1063 (Print) 1547-1063 (Linking) SP - 535-560 ST - A metapopulation model of granuloma formation in the lung during infection with mycobacterium tuberculosis T2 - Mathematical Biosciences and Engineering TI - A metapopulation model of granuloma formation in the lung during infection with mycobacterium tuberculosis UR - http://www.ncbi.nlm.nih.gov/pubmed/20369939 VL - 2 ID - 2466 ER - TY - JOUR AB - In this paper, a nonlinear mathematical model is proposed for the transmission dynamics of HIV and a curable TB pathogen within a population of varying size. In the model, we have divided the population into four sub classes of susceptibles, TB infectives, HIV infectives and that of AIDS patients. The model exhibits four equillibria namely, a disease free, HIV free, TB free and a co?infection equilibrium. The model has been studied qualitatively using stability theory of nonlinear differential equations. It is shown that the positive co?infection equilibrium is always locally stable but it may become globally stable under certain conditions showing that the disease becomes endemic due to constant migration of the population into the habitat. A numerical study of the model is also performed to investigate the influence of certain key parameters on the spread of the disease. AU - Naresh, R. AU - Tripathi, A. DA - 2005/01/01 DO - 10.1080/13926292.2005.9637287 PY - 2005 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1392-6292 SP - 275-286 ST - Modelling and analysis of HIV‐TB co‐infection in a variable size population T2 - Mathematical Modelling and Analysis TI - Modelling and analysis of HIV‐TB co‐infection in a variable size population UR - http://www.tandfonline.com/doi/abs/10.1080/13926292.2005.9637287 VL - 10 Y2 - 2012/08/10 ID - 2467 ER - TY - JOUR AB - OBJECTIVE: To evaluate cost-effective screening and treatment strategies for healthcare workers (HCWs) at risk for tuberculosis exposure. DESIGN: A Markov model was developed to track three hypothetical cohorts of HCWs at low, moderate, and high risk for tuberculosis exposure. For those found to be tuberculin reactors at entry, the choice was for isoniazid treatment or no treatment. For those without tuberculin reactivity, the choice of screening intervals was 6 months, 1 year, 2 years, or 5 years. Outcomes measured were tuberculosis cases, death, life expectancy, and cost. Assumptions were derived from published data and analyses. RESULTS: Treatment of initial reactors with isoniazid in all three risk groups was associated with a net savings of $14,800 to $15,700 for each tuberculosis case prevented. For those without evidence of infection at entry, the most cost-effective screening interval was 1 year for high-risk groups, 2 years for moderate-risk groups, and 5 years for low-risk groups, with a net savings $0.20 to $26 per HCW per year. Screening at a more frequent interval was still cost-effective. CONCLUSIONS: For HCWs found to be tuberculin reactors, treatment of their latent infection is to their benefit and is associated with a net cost-savings. Regular tuberculin screening of HCWs can be cost-effective or result in a net cost-savings. Each institution could use its own skin test surveillance data to create an optimum screening program for its employees. However, for most HCWs, a 1-year screening interval would be a cost-effective and safe choice. AD - Santa Clara Valley Medical Center, San Jose, USA. AN - 15636292 AU - Salpeter, S. R. AU - Salpeter, E. E. DA - Dec DO - ICHE9433 [pii] 10.1086/502343 ET - 01/08 KW - Antitubercular Agents/therapeutic use Cost-Benefit Analysis *Decision Trees *Health Personnel Humans Isoniazid/therapeutic use Markov Chains *Mass Screening Risk Factors Tuberculin Test Tuberculosis/diagnosis/drug therapy/*economics LA - eng N1 - Salpeter, Shelley R Salpeter, Edwin E Evaluation Studies Research Support, Non-U.S. Gov't United States Infection control and hospital epidemiology : the official journal of the Society of Hospital Epidemiologists of America Infect Control Hosp Epidemiol. 2004 Dec;25(12):1056-61. PY - 2005 RN - fulltext fulltext_1208 SN - 0899-823X (Print) 0899-823X (Linking) SP - 1056-61 ST - Screening and treatment of latent tuberculosis among healthcare workers at low, moderate, and high risk for tuberculosis exposure: a cost-effectiveness analysis T2 - Infect Control Hosp Epidemiol TI - Screening and treatment of latent tuberculosis among healthcare workers at low, moderate, and high risk for tuberculosis exposure: a cost-effectiveness analysis UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15636292http://www.journals.uchicago.edu/doi/pdf/10.1086/502343http://www.jstor.org/stable/pdfplus/10.1086/502343.pdf?acceptTC=true VL - 25 ID - 2457 ER - TY - JOUR AB - BACKGROUND: We hypothesized that investments to improve the control of tuberculosis in selected high-incidence countries would prove to be cost saving for the United States by reducing the incidence of the disease among migrants. METHODS: Using decision analysis, we estimated tuberculosis-related morbidity, mortality, and costs among legal immigrants and refugees, undocumented migrants, and temporary visitors from Mexico after their entry into the United States. We assessed the current strategy of radiographic screening of legal immigrants plus current tuberculosis-control programs alone and with the addition of either U.S.-funded expansion of the strategy of directly observed treatment, short course (DOTS), in Mexico or tuberculin skin testing to screen legal immigrants from Mexico. We also examined tuberculosis-related outcomes among migrants from Haiti and the Dominican Republic using the same three strategies. RESULTS: As compared with the current strategy, expanding the DOTS program in Mexico at a cost to the United States of 34.9 million dollars would result in 2591 fewer cases of tuberculosis in the United States, with 349 fewer deaths from the disease and net discounted savings of 108 million dollars over a 20-year period. Adding tuberculin skin testing to radiographic screening of legal immigrants from Mexico would result in 401 fewer cases of tuberculosis in the United States but would cost an additional 329 million dollars. Expansion of the DOTS program would remain cost saving even if the initial investment were doubled, if the United States paid for all antituberculosis drugs in Mexico, or if the decline in the incidence of tuberculosis in Mexico was less than projected. A 9.4 million dollars investment to expand the DOTS program in Haiti and the Dominican Republic would result in net U.S. savings of 20 million dollars over a 20-year period. CONCLUSIONS: U.S.-funded efforts to expand the DOTS program in Mexico, Haiti, and the Dominican Republic could reduce tuberculosis-related morbidity and mortality among migrants to the United States, producing net cost savings for the United States. AD - Respiratory Epidemiology Unit, Montreal Chest Institute, McGill University, Montreal, QC, Canada. AN - 16148286 AU - Schwartzman, K. AU - Oxlade, O. AU - Barr, R. G. AU - Grimard, F. AU - Acosta, I. AU - Baez, J. AU - Ferreira, E. AU - Melgen, R. E. AU - Morose, W. AU - Salgado, A. C. AU - Jacquet, V. AU - Maloney, S. AU - Laserson, K. AU - Mendez, A. P. AU - Menzies, D. DA - Sep 8 DO - 353/10/1008 [pii] 10.1056/NEJMsa043194 [doi] DP - Nlm ET - 09/09 KW - Antitubercular Agents/economics/therapeutic use Cost Savings Decision Support Techniques Directly Observed Therapy/ economics Dominican Republic Emigration and Immigration Haiti Health Care Costs Humans Incidence International Cooperation Investments Lung/ radiography Markov Chains Mass Screening Mexico/epidemiology Models, Economic Radiography, Thoracic/economics Tuberculin Test/ economics Tuberculosis, Pulmonary/diagnosis/economics/mortality/ prevention & control United States/epidemiology LA - eng N1 - Schwartzman, Kevin Oxlade, Olivia Barr, R Graham Grimard, Franque Acosta, Ivelisse Baez, Jeannette Ferreira, Elizabeth Melgen, Ricardo Elias Morose, Willy Salgado, Arturo Cruz Jacquet, Vary Maloney, Susan Laserson, Kayla Mendez, Ariel Pablos Menzies, Dick Comparative Study Research Support, Non-U.S. Gov't United States The New England journal of medicine N Engl J Med. 2005 Sep 8;353(10):1008-20. PY - 2005 RN - fulltext fulltext_1208 SN - 1533-4406 (Electronic) 0028-4793 (Linking) SP - 1008-20 ST - Domestic returns from investment in the control of tuberculosis in other countries T2 - N Engl J Med TI - Domestic returns from investment in the control of tuberculosis in other countries UR - http://www.nejm.org/doi/pdf/10.1056/NEJMsa043194 VL - 353 ID - 2468 ER - TY - JOUR AB - Mathematical models are formulated to establish the conditions (restrictions) on the size of the area occupied required minimizing and thereafter eradicating tuberculosis. Both numerical and qualitative analyses of the model are done and the effect of variation in the area size and recruitment rate on the different epidemiological groups is investigated. The results of the analysis show that there exists a stable disease-free equilibrium point provided that the characteristic area is greater than the product of the probability of survival from the latent stage to the infectious stage and the number of latent infections produced by a typical infectious individual during his/her mean infectious period. The study recommends that the characteristic area per individual should be at least 0.25 square kilometres in order to minimize the tuberculosis incidence. AU - Ssematimba, A. AU - Mugisha, J. Y. T. AU - Luboobi, L. S. DO - 10.3844/jmssp.2005.217.224 IS - 3 PY - 2005 SP - 217-224 ST - Mathematical Model Mathematical Models for the Dynamics of Tuberculosis in Density-dependent Populations: The Case of Internally Displaced Peoples' Camps (IDPCs) in Uganda T2 - Journal of Mathematics and Statistics TI - Mathematical Model Mathematical Models for the Dynamics of Tuberculosis in Density-dependent Populations: The Case of Internally Displaced Peoples' Camps (IDPCs) in Uganda VL - 1 ID - 4934 ER - TY - JOUR AB - Epidemics of HIV/AIDS have increased the tuberculosis (TB) case-load by five or more times in East Africa and southern Africa. As HIV continues to spread, warnings have been issued of disastrous AIDS and TB epidemics in "new-wave" countries, including India, which accounts for 20% of all new TB cases arising in the world each year. Here we investigate whether, in the face of the HIV epidemic, India's Revised National TB Control Program (RNTCP) could halve TB prevalence and death rates in the period 1990-2015, as specified by the United Nations Millennium Development Goals. Using a mathematical model to capture the spatial and temporal variation in TB and HIV in India, we predict that, without the RNTCP, HIV would increase TB prevalence (by 1%), incidence (by 12%), and mortality rates (by 33%) between 1990 and 2015. With the RNTCP, however, we expect substantial reductions in prevalence (by 68%), incidence (by 41%), and mortality (by 39%) between 1990 and 2015. In India, 29% of adults but 72% of HIV-positive adults live in four large states in the south where, even with the RNTCP, mortality is expected to fall by only 15% between 1990 and 2015. Nationally, the RNTCP should be able to reverse the increases in TB burden due to HIV but, to ensure that TB mortality is reduced by 50% or more by 2015, HIV-infected TB patients should be provided with antiretroviral therapy in addition to the recommended treatment for TB. AD - World Health Organization, 20 Avenue Appia, Geneva 1212, Switzerland. AN - 15976029 AU - Williams, B. G. AU - Granich, R. AU - Chauhan, L. S. AU - Dharmshaktu, N. S. AU - Dye, C. DA - Jul 5 DO - 0501615102 [pii] 10.1073/pnas.0501615102 [doi] DP - Nlm ET - 06/25 KW - AIDS-Related Opportunistic Infections/ epidemiology Communicable Disease Control/ methods Demography Developing Countries Forecasting Hiv Humans Incidence India/epidemiology Models, Theoretical Prevalence Public Health Tuberculosis/ epidemiology/mortality/ prevention & control/transmission LA - eng N1 - Williams, B G Granich, R Chauhan, L S Dharmshaktu, N S Dye, C Comparative Study United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9619-24. Epub 2005 Jun 23. PY - 2005 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0027-8424 (Print) 0027-8424 (Linking) SP - 9619-24 ST - The impact of HIV/AIDS on the control of tuberculosis in India T2 - Proc Natl Acad Sci U S A TI - The impact of HIV/AIDS on the control of tuberculosis in India UR - http://www.pnas.org/content/102/27/9619.full.pdf VL - 102 ID - 2469 ER - TY - JOUR AB - In Eastern Europe and Central Asia (ECA) the control of tuberculosis, multidrug resistant tuberculosis (MDRTB) and human immunodeficiency virus (HIV) poses important public health challenges. We used system dynamics simulation to determine impact on cumulative HIV/AIDS, tuberculosis and HIV-associated-tuberculosis deaths, over 20 years, of harm-reduction programmes to reduce needle-sharing and injection-frequency amongst injecting drug users (IDUs) and multidrug resistant tuberculosis (MDRTB) control in a population with an explosive HIV epidemic in IDUs and high MDRTB prevalence. We estimate that the number of HIV-associated-deaths will decline by 30% with effective harm-reduction programmes but double if these are ineffective. In our model, effective MDRTB and HIV control reduces cumulative tuberculosis deaths by 54%, cumulative MDRTB deaths 15-fold and cumulative HIV-associated-tuberculosis-deaths 2-fold. Effective MDRTB control, without effective harm-reduction programmes, only reduce tuberculosis deaths by 22%. However, effective harm-reduction programme with a poor MDRTB control reduce cumulative tuberculosis deaths by 34%, MDRTB by 14% and HIV-associated-tuberculosis by 56%. Even with good control programmes for drug sensitive TB, neglecting harm reduction and MDRTB control will result in 50% more tuberculosis-related deaths than if both are effectively addressed. Effective harm-reduction programmes reduces cumulative deaths from tuberculosis more substantively than effective MDRTB control. Our finding have important policy implications for communicable disease policies in post-Soviet countries, which need to substantially change if they are to effectively address the emerging HIV and MDRTB epidemics. AD - Centre for Health Management, Tanaka Business School, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. r.atun@imperial.ac.uk AN - 16854499 AU - Atun, R. A. AU - Lebcir, R. M. AU - McKee, M. AU - Habicht, J. AU - Coker, R. J. DA - May DO - S0168-8510(06)00131-X [pii] 10.1016/j.healthpol.2006.05.021 [doi] DP - Nlm ET - 07/21 KW - Antitubercular Agents Communicable Disease Control/methods Drug Resistance, Multiple Estonia/epidemiology HIV Infections/mortality Harm Reduction Health Policy Humans Models, Theoretical Tuberculosis/ drug therapy/mortality/prevention & control L1 - internal-pdf://1028025318/1-s2.0-S016885100600131X-main.pdf LA - eng N1 - Atun, Rifat A Lebcir, Reda M McKee, Martin Habicht, Jarno Coker, Richard J Ireland Health policy (Amsterdam, Netherlands) Health Policy. 2007 May;81(2-3):207-17. Epub 2006 Jul 18. PY - 2006 RN - fulltext fulltext_1208 SN - 0168-8510 (Print) 0168-8510 (Linking) SP - 207-17 ST - Impact of joined-up HIV harm reduction and multidrug resistant tuberculosis control programmes in Estonia: System dynamics simulation model T2 - Health Policy TI - Impact of joined-up HIV harm reduction and multidrug resistant tuberculosis control programmes in Estonia: System dynamics simulation model UR - http://ac.els-cdn.com/S016885100600131X/1-s2.0-S016885100600131X-main.pdf?_tid=d83372b2-f0e6-11e1-8283-00000aab0f6b&acdnat=1346141185_688289afe364cf51bd4bcc42a92c9b70 VL - 81 ID - 2495 ER - TY - BOOK A2 - Kolchanov, N. A2 - Hofestadt, R. AB - Motivation: A mathematical model to describe the immune response and different chemotherapeutic regimens for the treatment of tuberculosis (TB) has been developed. The model can be used as a tool for predicting the course of the infectious process and outcomes in individuals infected with Mycobacterium tuberculosis (MBT). To identify what chemotherapeutic regimen is the best, one should clearly understand how different anti-TB drugs work. One of the most promising approaches to elaborate optimal anti-TB chemotherapeutic treatment/regimen is the gene-network technology. Results: The model proposed herein consists of a set of ordinary differential equations for the dynamics of diverse populations of bacteria, macrophages, T lymphocytes, dendrite cells as well as for various concentrations of cytokines and antibacterial drugs. Different treatment regimens in individuals with different variants of the course of disease (latent and acute infection) were simulated, and so were different rates of drug inactivation (rapid and slow acetylators). Different regimes of the model, which yield different outcomes, correspond to different chemotherapeutic regimens, which either give recovery (adequate chemotherapy) or delay recovery and contribute to the emergence of drug-resistant strains (inadequate chemotherapy). A further progression of the model will be connected with optimization of the treatment regimens for TB. To serve the purpose, we have reconstructed the gene network for the mechanisms of anti-TB drugs and for the mechanisms underlying the emergence of drug resistance developed by MBT due to mutation in separate target genes. AD - SRC VB Vector, Novosibirsk 633159, Russia. Bazhan, SI (reprint author), SRC VB Vector, Novosibirsk 633159, Russia. AN - WOS:000243858000020 AU - Bazhan, S. I. AU - Schwartz, Y. S. AU - Gainova, I. A. AU - Ananko, E. A. CY - Novosibirsk KW - mathematical model mycobacteria tuberculosis infection immune response treatment regimens LA - English N1 - ISI Document Delivery No.: BFQ57 Times Cited: 0 Cited Reference Count: 3 Bazhan, S., I Schwartz, Ya. Sh Gainova, I. A. Ananko, E. A. Proceedings Paper 5th International Conference on Bioinformatics of Genome Regulation and Structure Jul 16-22, 2006 Novosibirsk, RUSSIA Inst Cytol & Genet, Lab Theoret Genet, Inst Cytol & Genet, Siberian Branch Russian Acad Sci, Vavilov Soc Genet & Breeders, Russian Acad Sci, Sci Council Bioinformat, Siberian Branch, Russian Acad Sci, Siberian Branch, Novosibirsk State Univ, Dept Natl Sci, Chair Informat Biol Novoskibrisk 90, morskoi, prosp 2, 630090 novosibirsk, russia PB - Russian Acad Sci Siberian Branch PY - 2006 SN - 978-5-7692-0847-8 SP - 114-117 ST - A mathematical model of immune response in infection induced by Mycobacteria tuberculosis. Prediction of the disease course and outcomes at different treatment regimens T2 - Proceedings of the Fifth International Conference on Bioinformatics of Genome Regulation and Structure, Vol 2 TI - A mathematical model of immune response in infection induced by Mycobacteria tuberculosis. Prediction of the disease course and outcomes at different treatment regimens UR - ://WOS:000243858000020 ID - 6142 ER - TY - JOUR AB - OBJECTIVE: Newborns in a hospital nursery were exposed to a mother whose sputum was direct-smear negative for acid-fast bacilli but culture positive for Mycobacterium tuberculosis. Given the low risk for exposure, the high susceptibility of infants to M. tuberculosis infection, and the possibility of hepatotoxicity due to isoniazid therapy, a decision analysis model was used to determine whether administration of isoniazid prophylaxis against tuberculosis is preferable to no administration of prophylaxis. DESIGN: A decision analysis tree was constructed with software, using probabilities from the literature and costs from local health facilities. The expected values for each strategy were obtained, and sensitivity analyses were performed. RESULTS: For the strategy in which prophylaxis was administered under direct observation (DO), the probability for survival was 0.999980. For the strategy in which no prophylaxis was administered, the probability of survival was 0.999950, which corresponds to 3 more deaths per 100,000 patients than with the DO prophylaxis strategy. The incremental cost-effectiveness of the DO prophylaxis strategy was 21,710,000 US dollars per death prevented. Sensitivity analysis for survival showed that the DO prophylaxis strategy was preferable to the strategy in which no prophylaxis is given if the probability of infection was >0.0002, the probability of tuberculous disease in an infected infant who did not receive prophylaxis was greater than 0.12, the probability of dying from tuberculosis was greater than 0.025, the probability of hepatotoxicity was less than 0.004, and the probability of dying from hepatotoxicity was less than 0.04. For the strategy in which prophylaxis was administered under non-DO conditions (ie, by parents), the incremental cost-effectiveness was 929,500 US dollars per death prevented, which is approximately 5% of the incremental cost-effectiveness of the DO prophylaxis strategy. CONCLUSION: This model provides a structure for determining the preferable prophylaxis strategies for different risks of exposure to tuberculosis in a nursery. Administration of prophylaxis is preferable to no administration of prophylaxis, unless the probability of infection is extremely low. AD - Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30303, USA. fberkow@emory.edu AN - 16755481 AU - Berkowitz, F. E. AU - Severens, J. L. AU - Blumberg, H. M. DA - Jun DO - 10.1086/504359 DP - Nlm ET - 06/07 J2 - Infection control and hospital epidemiology : the official journal of the Society of Hospital Epidemiologists of America KW - Acquired Immunodeficiency Syndrome/complications Antibiotic Prophylaxis Antitubercular Agents/adverse effects/ therapeutic use Decision Support Techniques Decision Trees Disease Transmission, Infectious Drug Toxicity/chemically induced Humans Infant, Newborn Isoniazid/adverse effects/ therapeutic use Models, Biological Survival Analysis Tuberculosis/complications/ prevention & control/transmission LA - eng N1 - Berkowitz, Frank E Severens, Johan L Blumberg, Henry M United States Infect Control Hosp Epidemiol. 2006 Jun;27(6):604-11. Epub 2006 May 31. PY - 2006 RN - fulltext fulltext_1208 SN - 0899-823X (Print) 0899-823X (Linking) SP - 604-11 ST - Exposure to tuberculosis among newborns in a nursery: decision analysis for initiation of prophylaxis T2 - Infect Control Hosp Epidemiol TI - Exposure to tuberculosis among newborns in a nursery: decision analysis for initiation of prophylaxis UR - http://www.jstor.org/stable/pdfplus/10.1086/504359.pdf?acceptTC=true VL - 27 ID - 2471 ER - TY - JOUR AN - 17356 AU - Clark, M. AU - Cameron, D. W. KW - BCG complications disseminated extrapulmonary HIV immunodeficiency infants models tuberculosis vaccination N1 - IN FILE TB Intervention strategies BCG vaccination Safety BCG - complications PY - 2006 RN - fulltext fulltext_1208 SP - 1-12 ST - The benefits and risks of bacille Calmette-Gu‚rin vaccination among infants at high risk for both tuberculosis and severe combined immunodeficiency: assessment by Markov model T2 - BMC Pediatrics TI - The benefits and risks of bacille Calmette-Gu‚rin vaccination among infants at high risk for both tuberculosis and severe combined immunodeficiency: assessment by Markov model UR - file://C:\literature_pdf\rm17356.pdf VL - 6-5 ID - 2472 ER - TY - JOUR AB - In sub-Saharan Africa, where the emergence of HIV has caused dramatic increases in tuberculosis (TB) case notifications, new strategies for TB control are necessary. Isoniazid preventive therapy (IPT) for HIV-TB coinfected individuals reduces the reactivation of latent Mycobacterium tuberculosis infections and is being evaluated as a potential community-wide strategy for improving TB control. We developed a mathematical model of TB/HIV coepidemics to examine the impact of community-wide implementation of IPT for TB-HIV coinfected individuals on the dynamics of drug-sensitive and -resistant TB epidemics. We found that community-wide IPT will reduce the incidence of TB in the short-term but may also speed the emergence of drug-resistant TB. We conclude that community-wide IPT in areas of emerging HIV and drug-resistant TB should be coupled with diagnostic and treatment policies designed to identify and effectively treat the increasing proportion of patients with drug-resistant TB. AD - Division of Social Medicine and Health Inequalities, Brigham and Women's Hospital, One Brigham Circle, 1620 Tremont Street, Boston, MA 02120, USA. tcohen@hsph.harvard.edu AN - 16632605 AU - Cohen, T. AU - Lipsitch, M. AU - Walensky, R. P. AU - Murray, M. DA - May 2 DO - 0600349103 [pii] 10.1073/pnas.0600349103 [doi] DP - Nlm ET - 04/25 KW - AIDS-Related Opportunistic Infections/drug therapy/epidemiology/prevention & control Africa South of the Sahara/epidemiology Antitubercular Agents/ therapeutic use Comorbidity HIV Infections/complications/epidemiology Humans Isoniazid/ therapeutic use Models, Theoretical Tuberculosis, Multidrug-Resistant/drug therapy/epidemiology/etiology/prevention & control L1 - internal-pdf://3299365905/Cohen-2006-Beneficial and perverse effects of.pdf LA - eng N1 - Cohen, Ted Lipsitch, Marc Walensky, Rochelle P Murray, Megan 1R21 AI55825-01/AI/NIAID NIH HHS/United States K08 AI055985/AI/NIAID NIH HHS/United States K08 AI055985-04/AI/NIAID NIH HHS/United States K23 AI01794-05/AI/NIAID NIH HHS/United States T32 AI007433-10/AI/NIAID NIH HHS/United States Research Support, N.I.H., Extramural United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2006 May 2;103(18):7042-7. Epub 2006 Apr 21. PY - 2006 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0027-8424 (Print) 0027-8424 (Linking) SP - 7042-7 ST - Beneficial and perverse effects of isoniazid preventive therapy for latent tuberculosis infection in HIV-tuberculosis coinfected populations T2 - Proc Natl Acad Sci U S A TI - Beneficial and perverse effects of isoniazid preventive therapy for latent tuberculosis infection in HIV-tuberculosis coinfected populations UR - http://www.pnas.org/content/103/18/7042.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459015/pdf/zpq7042.pdf VL - 103 ID - 2473 ER - TY - JOUR AB - SETTING: Various methods have been used to estimate the prevalence of Mycobacterium tuberculosis infection from tuberculin survey data. All are complicated by prior sensitisation to environmental mycobacteria and bacille Calmette-Guerin (BCG) vaccination. Mixture analysis has recently been proposed as a means of overcoming misclassification and improving infection prevalence estimates. OBJECTIVE: To compare conventional and mixture model estimates of M. tuberculosis infection prevalence. DESIGN: Mixture models with two or three univariate normal components were fitted to the results of 53 909 tuberculin tests conducted in northern Malawi during 1980-1984. Data were stratified by BCG status, sex and age and corrected for digit preference. Prevalence estimates derived from mixture models were compared with those of conventional methods. RESULTS: The optimal model was age-dependent, with three- and one-component solutions preferred in younger and older age groups, respectively. In contrast with findings from elsewhere, a component corresponding to BCG vaccination was indistinguishable from that attributable to environmental mycobacterial exposure, and infection prevalence estimates in younger individuals with a BCG scar were inflated, irrespective of the method used. CONCLUSION: The validity of infection prevalence and incidence estimates based on mixture modelling is probably locale-dependent, and the assumptions underlying mixture models may not realistically reflect underlying immunological processes. AD - Department of Pharmacology, University of Liverpool, Liverpool, Merseyside, United Kingdom. gerrydavies@doctors.org.uk AN - 16964795 AU - Davies, G. R. AU - Fine, P. E. AU - Vynnycky, E. DA - Sep DP - Nlm ET - 09/13 KW - Adolescent Adult Aged Child Female Humans Malawi/epidemiology Male Middle Aged Prevalence Questionnaires Tuberculin Test/methods/ statistics & numerical data Tuberculosis/ diagnosis/ epidemiology LA - eng N1 - Davies, G R Fine, P E Vynnycky, E 079828/Wellcome Trust/United Kingdom Wellcome Trust/United Kingdom Research Support, Non-U.S. Gov't France The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Int J Tuberc Lung Dis. 2006 Sep;10(9):1023-9. PY - 2006 RN - fulltext fulltext_1208 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 1023-9 ST - Mixture analysis of tuberculin survey data from northern Malawi and critique of the method T2 - Int J Tuberc Lung Dis TI - Mixture analysis of tuberculin survey data from northern Malawi and critique of the method VL - 10 ID - 2474 ER - TY - JOUR AB - OBJECTIVES: To evaluate whether methodological optimization of serial sputum colony counting (SSCC) studies, a potentially important component in the drug development process for tuberculosis, could significantly improve their power. METHODS: Simulations were carried out using a model derived from a large SSCC dataset. Variance inflation factors (VIFs) were calculated for model parameters, focusing on the elimination rate constant likely to reflect 'sterilizing' activity and sampling schemes were optimized relative to a scheme of daily sampling during the initial phase of therapy. Corresponding sample sizes required for SSCC studies using different schemes were also computed. RESULTS: Published sampling schemes lacked efficiency with respect to the 'sterilizing' phase. Pragmatic optimized schemes yielding greatest precision were achieved using eleven sampling points around a skeleton of 0, 2, 7, 14 and 56 days. The standard error of the 'sterilizing' rate constant was reduced more than 4-fold, and sample size for realistic treatment effects was effectively halved. Even schemes with a restricted duration of sampling to avoid high proportions of missing data and those with fewer sampling points still achieved significant gains in precision. Sensitivity analysis suggested that such schemes should continue to perform well over the immediately foreseeable range of improvements in therapy. CONCLUSIONS: Methodological improvements in the design of SSCC studies could make them a powerful tool in Phase II development of anti-tuberculosis agents. AD - Wellcome Trust Centre for Clinical Tropical Medicine, University of Liverpool, Merseyside, UK. gdavies@doctors.org.uk AN - 16857690 AU - Davies, G. R. AU - Khoo, S. H. AU - Aarons, L. J. DA - Sep DO - dkl272 [pii] 10.1093/jac/dkl272 [doi] DP - Nlm ET - 07/22 KW - Antitubercular Agents/administration & dosage/ pharmacology/therapeutic use Colony Count, Microbial Computer Simulation Humans Models, Biological Predictive Value of Tests Sample Size Specimen Handling/methods/standards Sputum/ microbiology Tuberculosis, Pulmonary/drug therapy/ microbiology LA - eng N1 - Davies, G R Khoo, S H Aarons, L J GR067910MA/Wellcome Trust/United Kingdom Research Support, Non-U.S. Gov't England The Journal of antimicrobial chemotherapy J Antimicrob Chemother. 2006 Sep;58(3):594-600. Epub 2006 Jul 19. PY - 2006 RN - fulltext fulltext_1208 SN - 0305-7453 (Print) 0305-7453 (Linking) SP - 594-600 ST - Optimal sampling strategies for early pharmacodynamic measures in tuberculosis T2 - J Antimicrob Chemother TI - Optimal sampling strategies for early pharmacodynamic measures in tuberculosis UR - http://jac.oxfordjournals.org/content/58/3/594.full.pdf VL - 58 ID - 2475 ER - TY - JOUR AN - 15908 AU - Diel, R. AU - Nienhaus, A. AU - Lange, C. AU - Schaberg, T. KW - case-finding contacts costs epidemiology infection screening tuberculosis N1 - TB Tuberculosis control Case-finding No sub-heading PY - 2006 RN - fulltext fulltext_1208 SP - 35-44 ST - Cost-optimisation of screening for latent tuberculosis in close contacts T2 - Eur.Respir.J. TI - Cost-optimisation of screening for latent tuberculosis in close contacts UR - file://C:\literature_pdf\rm15908.pdf VL - 28 ID - 2476 ER - TY - JOUR AB - OBJECTIVE: To explore the potential impact of enhanced tuberculosis (TB) diagnostic techniques as a TB control strategy in an adult population with high HIV prevalence. DESIGN: A compartmental difference-equation model of TB/HIV was developed using parameter estimates from the literature. METHODS: The impact of five TB control interventions (rapid molecular testing, mycobacterial culture, community-wide and HIV-targeted active case finding, and highly active antiretroviral therapy) on TB incidence, prevalence, and mortality was modeled in a steady-state population with an HIV prevalence of 17% and annual TB incidence of 409 per 100 000. Sensitivity analyses assessed the influence of each model parameter on the interventions' mortality impact. RESULTS: Enhanced diagnostic techniques (rapid molecular testing or culture) are each projected to reduce TB prevalence and mortality by 20% or more, an impact similar to that of active case-finding in 33% of the general community and greater than the effect achievable by case-finding or antiretroviral treatment efforts in HIV-positive patients alone. The projected impact of enhanced diagnostics on TB incidence (< 10% reduction) is smaller. The impact of TB diagnostics is sensitive to the quality of existing diagnostic standards and the level of access to diagnostic services, but is robust across a wide range of population parameters including HIV and TB incidence. CONCLUSIONS: Enhanced TB diagnostic techniques may have substantial impact on TB morbidity and mortality in HIV-endemic regions. As TB rates continue to increase in these areas, enhanced diagnostic techniques merit further consideration as TB control strategies. AD - Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland 21231, USA. AN - 16514306 AU - Dowdy, D. W. AU - Chaisson, R. E. AU - Moulton, L. H. AU - Dorman, S. E. DA - Mar 21 DO - 10.1097/01.aids.0000216376.07185.cc [doi] 00002030-200603210-00015 [pii] DP - Nlm ET - 03/04 KW - AIDS-Related Opportunistic Infections/ diagnosis Adolescent Adult Anti-HIV Agents/therapeutic use Antiretroviral Therapy, Highly Active Bacterial Typing Techniques Communicable Disease Control DNA, Bacterial/analysis Developing Countries Disease Outbreaks HIV Infections/ complications/drug therapy Health Services Accessibility Humans Incidence Intervention Studies Middle Aged Models, Statistical Mycobacterium tuberculosis/genetics/isolation & purification Prevalence Tuberculosis/ diagnosis/epidemiology/virology LA - eng N1 - Dowdy, David W Chaisson, Richard E Moulton, Lawrence H Dorman, Susan E 5 T32 GMO7309/PHS HHS/United States K23 AI 51528/AI/NIAID NIH HHS/United States K24 AI16137/AI/NIAID NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England AIDS (London, England) AIDS. 2006 Mar 21;20(5):751-62. PY - 2006 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0269-9370 (Print) 0269-9370 (Linking) SP - 751-62 ST - The potential impact of enhanced diagnostic techniques for tuberculosis driven by HIV: a mathematical model T2 - AIDS TI - The potential impact of enhanced diagnostic techniques for tuberculosis driven by HIV: a mathematical model UR - http://graphics.tx.ovid.com/ovftpdfs/FPDDNCDCLFEDDD00/fs047/ovft/live/gv024/00002030/00002030-200603210-00015.pdf VL - 20 ID - 2477 ER - TY - JOUR AB - Antibiotic resistance is seen in both the hospital and community settings. Approaches are required to minimize the increase in resistant strains, such as good antibiotic stewardship and the limiting of antibiotic use to appropriate circumstances. There are instances when drug dose and/or schedule can be used to minimize the probability that mutants will take over the bacterial population. Over the past several years, significant advances have been made in understanding the relationship between drug concentrations and amplification of resistant mutant subpopulations. In this review, we examine the use of preclinical models for facilitating this understanding. We also use mathematical techniques, including Monte Carlo simulation, to bridge between the identification of exposures to minimize resistance and the examination of candidate drug doses to achieve this end. Examples are provided for Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus aureus, and Mycobacterium tuberculosis. In each instance, quinolone antimicrobials were examined. More investigations with other pathogens and drug classes are required. AD - Ordway Research Institute, Albany, NY 12208, USA. gdrusano@ordwayresearch.org AN - 16421797 AU - Drusano, G. L. AU - Louie, A. AU - Deziel, M. AU - Gumbo, T. DA - Feb 15 DO - CID36544 [pii] 10.1086/499046 [doi] DP - Nlm ET - 01/20 KW - Animals Anti-Infective Agents/pharmacokinetics/ pharmacology Bacterial Infections/ drug therapy Colony Count, Microbial Dose-Response Relationship, Drug Drug Resistance, Bacterial/ drug effects/ physiology Humans Mice Microbial Sensitivity Tests Models, Biological Monte Carlo Method L1 - internal-pdf://1649502949/Drusano-2006-The crisis of resistance_ identif.pdf LA - eng N1 - Drusano, G L Louie, Arnold Deziel, Mark Gumbo, Tawanda Review United States Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Clin Infect Dis. 2006 Feb 15;42(4):525-32. Epub 2006 Jan 3. PY - 2006 RN - fulltext fulltext_1208 SN - 1537-6591 (Electronic) 1058-4838 (Linking) SP - 525-32 ST - The crisis of resistance: identifying drug exposures to suppress amplification of resistant mutant subpopulations T2 - Clin Infect Dis TI - The crisis of resistance: identifying drug exposures to suppress amplification of resistant mutant subpopulations UR - http://cid.oxfordjournals.org/content/42/4/525.full.pdf https://watermark.silverchair.com/42-4-525.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAcowggHGBgkqhkiG9w0BBwagggG3MIIBswIBADCCAawGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMBJH3goF9hSba_DMrAgEQgIIBfXW1oY85-GXNdbaieNT-FJ0EXj2erYGCTn7r2oOktrJiSTcG_4c-BW0O9xyOM4PmhCwEDrQyAk4URyJglfIhG1W5qSmUn3qQyERy1hF8-7HPDcos8PVRWln8F0ZsdR0wR3IdscsA3yQk904B_FOgxSPlKOLOHr93vqC7t1Gmlk7m1WTyNqZZiS69tf_v7zKIOhH5YldUCWqj5gBwfSvf6svFqmlnPEJSCikJWGw97XLUbL8mLza1VCdoOjqNoVoS-NQ7gf3FIBhzHlxM9MnEDlNBF6qrtHsbstBercot4kpKrNLXCUN7auTKVTmUESA0vl8ArfjUuvB3YzSIsidf9MallbFogkrNkNEpRxJd2Ljjw3uixGZ3vNa-iklAy4KGahZuNGWCdJl9wbH7iPZRfOGR67hkzO8v4DU2WZVj8ogbF27EhMmMT0Es6v2L_6YfAw6ZE_gTQtnJ8Dw8iJL1LRYpTW-OT8g6aoX61xt5kz7x_pHO8EDEKcgvNfK0gQ VL - 42 ID - 2478 ER - TY - CPAPER AU - Hughes, Georgina R. AU - Currie, Christine S. M. AU - Corbett, Elizabeth L. C1 - 1218200 CY - Monterey, California PB - Winter Simulation Conference PY - 2006 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SP - 459-465 T2 - Proceedings of the 38th conference on Winter simulation TI - Modeling tuberculosis in areas of high HIV prevalence UR - http://dl.acm.org/citation.cfm?id=1218200 ID - 2479 ER - TY - JOUR AB - BACKGROUND: Implementation of the World Health Organization's DOTS strategy (Directly Observed Treatment Short-course therapy) can result in significant reduction in tuberculosis incidence. We estimated potential costs and benefits of DOTS expansion in Haiti from the government, and societal perspectives. METHODS: Using decision analysis incorporating multiple Markov processes (Markov modelling), we compared expected tuberculosis morbidity, mortality and costs in Haiti with DOTS expansion to reach all of the country, and achieve WHO benchmarks, or if the current situation did not change. Probabilities of tuberculosis related outcomes were derived from the published literature. Government health expenditures, patient and family costs were measured in direct surveys in Haiti and expressed in 2003 US$. RESULTS: Starting in 2003, DOTS expansion in Haiti is anticipated to cost $4.2 million and result in 63,080 fewer tuberculosis cases, 53,120 fewer tuberculosis deaths, and net societal savings of $131 million, over 20 years. Current government spending for tuberculosis is high, relative to the per capita income, and would be only slightly lower with DOTS. Societal savings would begin within 4 years, and would be substantial in all scenarios considered, including higher HIV seroprevalence or drug resistance, unchanged incidence following DOTS expansion, or doubling of initial and ongoing costs for DOTS expansion. CONCLUSION: A modest investment for DOTS expansion in Haiti would provide considerable humanitarian benefit by reducing tuberculosis-related morbidity, mortality and costs for patients and their families. These benefits, together with projected minimal Haitian government savings, argue strongly for donor support for DOTS expansion. AD - National tuberculosis control programme, Port-au-Prince, Haiti. varyj@yahoo.com AN - 16911786 AU - Jacquet, V. AU - Morose, W. AU - Schwartzman, K. AU - Oxlade, O. AU - Barr, G. AU - Grimard, F. AU - Menzies, D. DO - 1471-2458-6-209 [pii] 10.1186/1471-2458-6-209 [doi] DP - Nlm ET - 08/17 KW - Antitubercular Agents/ administration & dosage/economics Cost of Illness Directly Observed Therapy/ economics Drug Therapy, Combination Ethambutol/administration & dosage/economics Haiti/epidemiology Health Care Costs Humans Isoniazid/administration & dosage/economics Program Evaluation Pyrazinamide/administration & dosage/economics Rifampin/administration & dosage/economics Treatment Outcome Tuberculosis, Pulmonary/ drug therapy/ economics/epidemiology World Health Organization L1 - internal-pdf://3904429895/Jacquet-2006-Impact of DOTS expansion on tuber.pdf LA - eng N1 - Jacquet, Vary Morose, Willy Schwartzman, Kevin Oxlade, Olivia Barr, Graham Grimard, Franque Menzies, Dick Evaluation Studies Research Support, Non-U.S. Gov't England BMC public health BMC Public Health. 2006 Aug 15;6:209. PY - 2006 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1471-2458 (Electronic) 1471-2458 (Linking) SP - 209 ST - Impact of DOTS expansion on tuberculosis related outcomes and costs in Haiti T2 - BMC Public Health TI - Impact of DOTS expansion on tuberculosis related outcomes and costs in Haiti UR - http://www.biomedcentral.com/1471-2458/6/209http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1590025/pdf/1471-2458-6-209.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1590025/pdf/1471-2458-6-209.pdf VL - 6 ID - 2480 ER - TY - JOUR AU - Joshi, Rajani R. AU - Raghuvanshi, Meenakshi AU - Pandya, Pranav DO - doi:10.1142/S0218339006001891 PY - 2006 RN - fulltext fulltext_1208 SP - 463-489 ST - YAGYOPATHY VERSUS ORAL AND IV DRUG ADMINISTRATION: EVALUATION FOR PULMONARY TUBERCULOSIS USING COMPARTMENT MODELING T2 - Journal of Biological Systems TI - YAGYOPATHY VERSUS ORAL AND IV DRUG ADMINISTRATION: EVALUATION FOR PULMONARY TUBERCULOSIS USING COMPARTMENT MODELING UR - http://www.worldscientific.com/doi/abs/10.1142/S0218339006001891 VL - 14 ID - 2481 ER - TY - JOUR AB - PURPOSE: Assess the costs and cost-effectiveness of an incentive-based tuberculosis (TB) program designed to promote adolescents' compliance with treatment for latent TB infection (LTBI). METHODS: Randomized controlled trial. Adolescents between the ages of 11 and 19 years who were referred to one of two participating clinics after being screened for TB and receiving a positive diagnosis indicating LTBI (n = 794) were assigned to one of four groups: usual care, peer counseling, contingency contracting, and combined peer counseling/contingency contracting. Primary outcome variables were completion of isoniazid preventive therapy (IPT), total treatment costs, and lifetime TB-related costs per quality-adjusted life year (QALY) in each of the four study groups (three treatment, one control). Cost effectiveness was evaluated using a five-stage Markov model and a Monte Carlo simulation with 10,000 trials. RESULTS: Average costs were 199 dollars for usual care (UC), 277 dollars for peer counseling (PC), 326 dollars for contingency contracting (CC), and 341 dollars for PC + CC combined. The differences among these groups were all significant at the p = .001 level. Only the PC + CC group improved the rate of IPT completion (83.8%) relative to usual care (75.9%) (p = .051), with an overall incremental CE ratio of 209 dollars per QALY relative to usual care. CONCLUSION: Incentives combined with peer counseling are a cost-effective strategy for helping adolescents to complete care when combined with peer counseling. AD - Department of Health Services, UCLA School of Public Health, Los Angeles, California 90024, USA. kominski@ucla.edu AN - 17185207 AU - Kominski, G. F. AU - Varon, S. F. AU - Morisky, D. E. AU - Malotte, C. K. AU - Ebin, V. J. AU - Coly, A. AU - Chiao, C. DA - Jan DO - 10.1016/j.jadohealth.2006.08.012 DP - Nlm ET - 12/23 J2 - The Journal of adolescent health : official publication of the Society for Adolescent Medicine KW - Adolescent Antitubercular Agents/therapeutic use Child Contracts Cost-Benefit Analysis Counseling/economics/ methods Female Health Care Costs Humans Isoniazid/therapeutic use Logistic Models Los Angeles Male Markov Chains Monte Carlo Method Motivation Patient Compliance/psychology Peer Group Quality-Adjusted Life Years Reward Tuberculosis/economics/ prevention & control LA - eng N1 - Kominski, Gerald F Varon, Sepideh Farivar Morisky, Donald E Malotte, C Kevin Ebin, Vicki J Coly, Astou Chiao, Chi R01-55770/PHS HHS/United States T32 HS00046/HS/AHRQ HHS/United States Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S. United States J Adolesc Health. 2007 Jan;40(1):61-8. Epub 2006 Oct 27. PY - 2006 RN - fulltext fulltext_1208 SN - 1879-1972 (Electronic) 1054-139X (Linking) SP - 61-8 ST - Costs and cost-effectiveness of adolescent compliance with treatment for latent tuberculosis infection: results from a randomized trial T2 - J Adolesc Health TI - Costs and cost-effectiveness of adolescent compliance with treatment for latent tuberculosis infection: results from a randomized trial UR - http://ac.els-cdn.com/S1054139X06003089/1-s2.0-S1054139X06003089-main.pdf?_tid=90d79c56-f1d4-11e1-a0a1-00000aab0f01&acdnat=1346243286_cc1761d7767c3933366d4866b5dee7d3 VL - 40 ID - 2507 ER - TY - JOUR AB - This work elaborates on the effects of cytotoxic lymphocytes (CTLs) and other immune mechanisms in determining whether a TB-infected individual will develop active or latent TB. It answers one intriguing question: why do individuals infected with Mycobacterium tuberculosis (Mtb) experience different clinical outcomes? In addressing this question, we have developed a model that captures the effects of CTLs and the combined effects of CD4+ helper T cells (Th1 and Th2) immune response mechanisms to TB infection. The occurrence of active or latent infection is shown to depend on a number of factors that include effector function and levels of CTLs. We use the model to predict disease progression scenarios, including primary, latency or clearance. Model analysis shows that occurrence of active disease is much attributed to the Mtb pathogen ability to persist outside the intracellular environment and that high levels of CTLs result in latent TB, while low levels of CTLs result in active TB. This is attributed to the CTLs' ability to directly kill infected macrophages and the bacteria inside the infected macrophages. The study suggests directions for further basic studies and potential new treatment strategies. AD - Department of Applied Mathematics, National University of Science and Technology, PO Box AC939 Ascot, Bulawayo, Zimbabwe. gmagombedze@nust.ac.zw. AN - 20361838 AU - Magombedze, G. AU - Garira, W. AU - Mwenje, E. DA - Oct DP - Nlm ET - 10/01 LA - eng N1 - Magombedze, Gesham Garira, Winston Mwenje, Eddie United States Mathematical biosciences and engineering : MBE Math Biosci Eng. 2006 Oct;3(4):661-82. PY - 2006 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1547-1063 (Print) 1547-1063 (Linking) SP - 661-82 ST - Modelling the human immune response mechanisms to mycobacterium tuberculosis infection in the lungs T2 - Math Biosci Eng TI - Modelling the human immune response mechanisms to mycobacterium tuberculosis infection in the lungs VL - 3 ID - 2482 ER - TY - JOUR AU - Magombedze, Gesham AU - Garira, Winston AU - Mwenje, Eddie DO - doi:10.1142/S0218339006001945 PY - 2006 RN - fulltext fulltext_1208 SP - 509-553 ST - MATHEMATICAL MODELING OF CHEMOTHERAPY OF HUMAN TB INFECTION T2 - Journal of Biological Systems TI - MATHEMATICAL MODELING OF CHEMOTHERAPY OF HUMAN TB INFECTION UR - http://www.worldscientific.com/doi/abs/10.1142/S0218339006001945 VL - 14 ID - 2483 ER - TY - JOUR AB - The spread of tuberculosis is studied through two models which include fast and slow progression to the infected class. For each model, Lyapunov functions are used to show that when the basic reproduction number is less than or equal to one, the disease-free equilibrium is globally asymptotically stable, and when it is greater than one there is an endemic equilibrium which is globally asymptotically stable. AD - Department of Mathematics, Wilfrid Laurier University, 75 University Ave West, Waterloo, ON, N2L 3C5, Canada. cmccluskey@wlu.ca. AN - 20361835 AU - McCluskey, C. C. DA - Oct DP - Nlm ET - 10/01 LA - eng N1 - McCluskey, C Connell United States Mathematical biosciences and engineering : MBE Math Biosci Eng. 2006 Oct;3(4):603-14. PY - 2006 RN - fulltext fulltext_1208 SN - 1547-1063 (Print) 1547-1063 (Linking) SP - 603-14 ST - Lyapunov functions for tuberculosis models with fast and slow progression T2 - Math Biosci Eng TI - Lyapunov functions for tuberculosis models with fast and slow progression VL - 3 ID - 2484 ER - TY - JOUR AB - BACKGROUND: Between April 2001 and March 2004, the Directly Observed Therapy-Short course (DOTS) program was successfully implemented by the National Tuberculosis control program, with assistance from the Canadian Lung Association, in three provinces of Ecuador, where 52% of the population of the country reside. METHODS: Markov modelling was used to project TB-related morbidity, mortality and costs if the former TB control program (status quo) had continued or if the newly expanded DOTS program is maintained over 20 years. Extensive sensitivity analyses were used to determine the effect on projected outcomes of varying key assumptions. RESULTS: If DOTS is maintained over the next 20 years, we predict that 18,760 cases and 15,812 TB-related deaths will be prevented, resulting in societal savings of dollars 203 million and government savings of dollars 7.1 million (all costs in dollars US). These findings were robust in extensive sensitivity analyses. Given the initial investment of dollars 3 million for DOTS implementation, this would mean a cost of dollars 190 per life saved. CONCLUSIONS: Implementation of DOTS could yield very substantial public health and economic benefits for Ecuador. These results demonstrate the benefits from Canadian government support for DOTS implementation in low- and middle-income countries. AD - Respiratory Epidemiology & Clinical Research Unit, Montreal Chest Institute, McGill University, QC, Canada. AN - 16512320 AU - Oxlade, O. AU - Vaca, J. AU - Romero, E. AU - Schwartzman, K. AU - Graham, B. AU - Hernandez, L. AU - Tannenbaum, T. AU - Menzies, D. DA - Jan-Feb DP - Nlm ET - 03/04 KW - Canada Communicable Disease Control/ economics Cost Savings Cost of Illness Cost-Benefit Analysis Decision Support Techniques Directly Observed Therapy/ economics Ecuador/epidemiology Forecasting Humans Markov Chains Program Development Program Evaluation Quality-Adjusted Life Years Risk Assessment Time Factors Tuberculosis/ drug therapy/ economics/epidemiology/mortality LA - eng N1 - Oxlade, Olivia Vaca, Judyth Romero, Elizabeth Schwartzman, Kevin Graham, Brian Hernandez, Lucero Tannenbaum, Terry Menzies, Dick Evaluation Studies Research Support, Non-U.S. Gov't Canada Canadian journal of public health. Revue canadienne de sante publique Can J Public Health. 2006 Jan-Feb;97(1):14-9. PY - 2006 RN - fulltext fulltext_1208 SN - 0008-4263 (Print) 0008-4263 (Linking) SP - 14-9 ST - The long-term health and economic benefits of DOTS implementation in Ecuador T2 - Can J Public Health TI - The long-term health and economic benefits of DOTS implementation in Ecuador VL - 97 ID - 2485 ER - TY - JOUR AB - BACKGROUND: Immigrants to the U.S. are required to undergo overseas screening for tuberculosis (TB), but the value of evaluation and treatment following entry to the U.S. is not well understood. We determined the cost-effectiveness of domestic follow-up of immigrants identified as tuberculosis suspects through overseas screening. METHODS: Using a stochastic simulation for tuberculosis reactivation, transmission, and follow-up for a hypothetical cohort of 1000 individuals, we calculated the incremental cost-effectiveness of follow-up and evaluation interventions. We utilized published literature, California Reports of Verified Cases of Tuberculosis (RVCTs), demographic estimates from the California Department of Finance, Medicare reimbursement, and Medi-Cal reimbursement rates. Our target population was legal immigrants to the United States, our time horizon is twenty years, and our perspective was that of all domestic health-care payers. We examined the intervention to offer latent tuberculosis therapy to infected individuals, to increase the yield of domestic evaluation, and to increase the starting and completion rates of LTBI therapy with INH (isoniazid). Our outcome measures were the number of cases averted, the number of deaths averted, the incremental dollar cost (year 2004), and the number of quality-adjusted life-years saved. RESULTS: Domestic follow-up of B-notification patients, including LTBI treatment for latently infected individuals, is highly cost-effective, and at times, cost-saving. B-notification follow-up in California would reduce the number of new tuberculosis cases by about 6-26 per year (out of a total of approximately 3000). Sensitivity analysis revealed that domestic follow-up remains cost-effective when the hepatitis rates due to INH therapy are over fifteen times our best estimates, when at least 0.4 percent of patients have active disease and when hospitalization of cases detected through domestic follow-up is no less likely than hospitalization of passively detected cases. CONCLUSION: While the current immigration screening program is unlikely to result in a large change in case rates, domestic follow-up of B-notification patients, including LTBI treatment, is highly cost-effective. If as many as three percent of screened individuals have active TB, and early detection reduces the rate of hospitalization, net savings may be expected. AD - California Department of Health Services, Tuberculosis Control Branch, 850 Marina Bay Parkway, Building P, Second Floor, Richmond, CA 94804, USA. tporco@dhs.ca.gov AN - 16784541 AU - Porco, T. C. AU - Lewis, B. AU - Marseille, E. AU - Grinsdale, J. AU - Flood, J. M. AU - Royce, S. E. DO - 1471-2458-6-157 [pii] 10.1186/1471-2458-6-157 [doi] DP - Nlm ET - 06/21 KW - Adult Aged Antitubercular Agents/therapeutic use California/epidemiology Cohort Studies Communicable Disease Control/ economics/methods Contact Tracing/economics Cost-Benefit Analysis Disease Notification/ economics Emigration and Immigration Humans Isoniazid/therapeutic use Mass Screening/economics Middle Aged Population Surveillance Program Evaluation Prospective Studies Quality-Adjusted Life Years Treatment Outcome Tuberculosis, Pulmonary/ economics/epidemiology/ prevention & control LA - eng N1 - Porco, Travis C Lewis, Bryan Marseille, Elliot Grinsdale, Jennifer Flood, Jennifer M Royce, Sarah E Comparative Study Evaluation Studies Research Support, U.S. Gov't, P.H.S. England BMC public health BMC Public Health. 2006 Jun 19;6:157. PY - 2006 RN - fulltext fulltext_1208 SN - 1471-2458 (Electronic) 1471-2458 (Linking) SP - 157 ST - Cost-effectiveness of tuberculosis evaluation and treatment of newly-arrived immigrants T2 - BMC Public Health TI - Cost-effectiveness of tuberculosis evaluation and treatment of newly-arrived immigrants UR - http://www.biomedcentral.com/1471-2458/6/157 VL - 6 ID - 2486 ER - TY - JOUR AB - A theoretical framework to assess the transmission dynamics of Tuberculosis (TB) is developed. Once infected with Mycobacterium tuberculosis, individuals can either develop active TB or remain infected for the rest of their life unless endogenous reactivation or exogenous re-infection occurs. The effects of vaccination and treatment Of active TB cases suggest that even if these control strategies could have a significant effect on reducing TB incidence, the exogenous re-infection and the endogenous reactivation, mainly due to H-TV infection, will still increase the incidence of TB. AD - Univ Sao Paulo, Fac Med, Disciplina Informat Med, Inst Oscar Freire, BR-01246903 Sao Paulo, Brazil Univ Estadual Campinas, UNICAMP, IMECC, Dept Matemat Aplicada, Campinas, SP, Brazil AN - WOS:000241398400002 AU - Raimundo, S. M. AU - Yang, H. M. DA - Oct-Dec DO - 10.1080/08898480600950457 IS - 4 J2 - Math Popul Stud KW - endogenous reactivation exogenous re-infection mathematical modeling mycobacterium tuberculosis backward bifurcation epidemic model LA - English N1 - 096sz Times Cited:7 Cited References Count:18 PY - 2006 SN - 0889-8480 SP - 181-203 ST - Transmission of tuberculosis with exogenous re-infection and endogenous reactivation T2 - Mathematical Population Studies TI - Transmission of tuberculosis with exogenous re-infection and endogenous reactivation UR - ://WOS:000241398400002 VL - 13 ID - 4838 ER - TY - JOUR AB - BACKGROUND: Despite the existence of effective drug treatments, tuberculosis (TB) causes 2 million deaths annually worldwide. Effective treatment is complicated by multidrug-resistant TB (MDR TB) strains that respond only to second-line drugs. We projected the health benefits and cost-effectiveness of using drug susceptibility testing and second-line drugs in a lower-middle-income setting with high levels of MDR TB. METHODS AND FINDINGS: We developed a dynamic state-transition model of TB. In a base case analysis, the model was calibrated to approximate the TB epidemic in Peru, a setting with a smear-positive TB incidence of 120 per 100,000 and 4.5% MDR TB among prevalent cases. Secondary analyses considered other settings. The following strategies were evaluated: first-line drugs administered under directly observed therapy (DOTS), locally standardized second-line drugs for previously treated cases (STR1), locally standardized second-line drugs for previously treated cases with test-confirmed MDR TB (STR2), comprehensive drug susceptibility testing and individualized treatment for previously treated cases (ITR1), and comprehensive drug susceptibility testing and individualized treatment for all cases (ITR2). Outcomes were costs per TB death averted and costs per quality-adjusted life year (QALY) gained. We found that strategies incorporating the use of second-line drug regimens following first-line treatment failure were highly cost-effective compared to strategies using first-line drugs only. In our base case, standardized second-line treatment for confirmed MDR TB cases (STR2) had an incremental cost-effectiveness ratio of 720 dollars per QALY (8,700 dollars per averted death) compared to DOTS. Individualized second-line drug treatment for MDR TB following first-line failure (ITR1) provided more benefit at an incremental cost of 990 dollars per QALY (12,000 dollars per averted death) compared to STR2. A more aggressive version of the individualized treatment strategy (ITR2), in which both new and previously treated cases are tested for MDR TB, had an incremental cost-effectiveness ratio of 11,000 dollars per QALY (160,000 dollars per averted death) compared to ITR1. The STR2 and ITR1 strategies remained cost-effective under a wide range of alternative assumptions about treatment costs, effectiveness, MDR TB prevalence, and transmission. CONCLUSIONS: Treatment of MDR TB using second-line drugs is highly cost-effective in Peru. In other settings, the attractiveness of strategies using second-line drugs will depend on TB incidence, MDR burden, and the available budget, but simulation results suggest that individualized regimens would be cost-effective in a wide range of situations. AD - Department of Health Policy and Management, Harvard School of Public Health, Harvard University, Boston, Massachusetts, United States of America. resch@fas.harvard.edu AU - Resch, S. C. AU - Salomon, J. A. AU - Murray, M. AU - Weinstein, M. C. DO - 10.1371/journal.pmed.0030241 KW - Antitubercular Agents/administration & dosage/classification/therapeutic use Budgets Cost-Benefit Analysis Developing Countries Directly Observed Therapy/economics Disease Outbreaks Disease Transmission, Infectious/economics/prevention & control Drug Costs Health Care Costs Health Policy Humans Income Microbial Sensitivity Tests/economics Models, Economic Mycobacterium tuberculosis/drug effects/isolation & purification Peru/epidemiology Quality-Adjusted Life Years Treatment Failure Treatment Outcome Tuberculosis, Multidrug-Resistant/drug therapy/economics/microbiology/mortality/prevention & control/transmission Value of Life L1 - internal-pdf://3194378282/Resch-2006-Cost-effectiveness of treating mult.pdf N1 - LR: 20100429; GR: T32 AI07433-12/AI/NIAID NIH HHS/United States; JID: 101231360; 0 (Antitubercular Agents); CIN: PLoS Med. 2006 Dec;3(12):e539; author reply e549. PMID: 17194204; CIN: PLoS Med. 2006 Dec;3(12):e542. PMID: 17194207; OID: NLM: PMC1483913; 2005/07/06 [received]; 2006/03/24 [accepted]; ppublish PY - 2006 RN - fulltext fulltext_1208 SN - 1549-1676; 1549-1277 SP - e241 ST - Cost-effectiveness of treating multidrug-resistant tuberculosis T2 - PLoS medicine TI - Cost-effectiveness of treating multidrug-resistant tuberculosis UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1483913/pdf/pmed.0030241.pdf VL - 3 Y2 - Jul ID - 2487 ER - TY - JOUR AB - Through a rationale used in thermodynamics some "states" or "compartments" in the natural history of Tuberculosis are defined. Based oil macroscopic changes observed in the total system an attempt is made to quantify the dynamics of these changes in the following "states": "virgin of infection", "infected" and "sick". A new way to calculate the risk of becoming infected by Tuberculosis, following the laws which govern the variation of the contents in a system of compartments, is presented. A sketch showing the relationships among the considered "states", the equations of the dynamics of them and a formula to calculate the risk of infection is also presented. AD - USP, Dept Social Med, Fac Med Ribeirao Preto, Ribeirao Preto, SP, Brazil. Ruffino-Netto, A (reprint author), USP, Dept Social Med, Fac Med Ribeirao Preto, Ribeirao Preto, SP, Brazil. AN - WOS:000237699700004 AU - Ruffino-Netto, A. DA - Apr IS - 2 J2 - Rev. Saude Publica KW - tuberculosis epidemiometric models uberculosis, risk of infection epidemiology epidemiological model sensitivity Public, Environmental & Occupational Health LA - Portuguese M3 - Article; Proceedings Paper N1 - ISI Document Delivery No.: 044VA Times Cited: 0 Cited Reference Count: 18 Ruffino-Netto, A 28th annual meeting of the sociedade-brasileira-para-o-progresso-da-ciencia 1976 Brasilia, brazil Soc brasileira progresso cien 0 Revista de saude publica Sao paulo PY - 2006 SN - 0034-8910 SP - 207-217 ST - Epidemiometric models in tuberculosis - definition of "states" and risk of infection T2 - Revista De Saude Publica TI - Epidemiometric models in tuberculosis - definition of "states" and risk of infection UR - ://WOS:000237699700004 VL - 40 ID - 6125 ER - TY - JOUR AB - BACKGROUND: Development of new, effective, and affordable tuberculosis (TB) therapies has been identified as a critical priority for global TB control. As new candidates emerge from the global TB drug pipeline, the potential impacts of novel, shorter regimens on TB incidence and mortality have not yet been examined. METHODS AND FINDINGS: We used a mathematical model of TB to evaluate the expected benefits of shortening the duration of effective chemotherapy for active pulmonary TB. First, we considered general relationships between treatment duration and TB dynamics. Next, as a specific example, we calibrated the model to reflect the current situation in the South-East Asia region. We found that even with continued and rapid progress in scaling up the World Health Organization's DOTS strategy of directly observed, short-course chemotherapy, the benefits of reducing treatment duration would be substantial. Compared to a baseline of continuing DOTS coverage at current levels, and with currently available tools, a 2-mo regimen introduced by 2012 could prevent around 20% (range 13%-28%) of new cases and 25% (range 19%-29%) of TB deaths in South-East Asia between 2012 and 2030. If effective treatment with existing drugs expands rapidly, overall incremental benefits of shorter regimens would be lower, but would remain considerable (13% [range 8%-19%] and 19% [range 15%-23%] reductions in incidence and mortality, respectively, between 2012 and 2030). A ten-year delay in the introduction of new drugs would erase nearly three-fourths of the total expected benefits in this region through 2030. CONCLUSIONS: The introduction of new, shorter treatment regimens could dramatically accelerate the reductions in TB incidence and mortality that are expected under current regimens-with up to 2- or 3-fold increases in rates of decline if shorter regimens are accompanied by enhanced case detection. Continued progress in reducing the global TB burden will require a balanced approach to pursuing new technologies while promoting wider implementation of proven strategies. AD - Department of Population and International Health, Harvard School of Public Health, Boston, Massachusetts, United States of America. jsalomon@hsph.harvard.edu AN - 16866578 AU - Salomon, J. A. AU - Lloyd-Smith, J. O. AU - Getz, W. M. AU - Resch, S. AU - Sanchez, M. S. AU - Porco, T. C. AU - Borgdorff, M. W. DA - Aug DO - 05-PLME-RA-0399R2 [pii] 10.1371/journal.pmed.0030273 [doi] DP - Nlm ET - 07/27 KW - Antitubercular Agents/administration & dosage/ therapeutic use Asia, Southeastern/epidemiology Communicable Disease Control/ trends Directly Observed Therapy Drug Administration Schedule Drug Design Humans Incidence Models, Theoretical Patient Compliance Recurrence/prevention & control Tuberculosis/ drug therapy/epidemiology/prevention & control World Health Organization LA - eng N1 - Salomon, Joshua A Lloyd-Smith, James O Getz, Wayne M Resch, Stephen Sanchez, Maria S Porco, Travis C Borgdorff, Martien W T32 AI007433-10/AI/NIAID NIH HHS/United States Research Support, Non-U.S. Gov't United States PLoS medicine PLoS Med. 2006 Aug;3(8):e273. PY - 2006 RN - fulltext fulltext_1208 SN - 1549-1676 (Electronic) 1549-1277 (Linking) SP - e273 ST - Prospects for advancing tuberculosis control efforts through novel therapies T2 - PLoS Med TI - Prospects for advancing tuberculosis control efforts through novel therapies UR - http://www.plosmedicine.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.0030273&representation=PDF VL - 3 ID - 2488 ER - TY - JOUR AN - 15740 AU - Shrestha, R. K. AU - Mugisha, B. AU - Bunnell, R. AU - Mermin, J. AU - Hitimana-Lukanika, C. AU - Odeke, R. AU - Madra, P. AU - Adatu, F. AU - Blandford, J. M. KW - Africa cost effectiveness HIV isoniazid preventive therapy tuberculin testing Uganda Preventive Therapy TB and HIV N1 - TB Periodical PY - 2006 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SP - 656-662 ST - Cost-effectiveness of including tuberculin skin testing in an IPT program for HIV-infected persons in Uganda T2 - International Journal of Tuberculosis and Lung Disease TI - Cost-effectiveness of including tuberculin skin testing in an IPT program for HIV-infected persons in Uganda UR - file://C:\literature_pdf\rm15740.pdf VL - 10 ID - 2489 ER - TY - JOUR AB - Tuberculosis is the number one cause of death due to infectious disease in the world today. Understanding the dynamics of the immune response is crucial to elaborating differences between individuals who contain infection vs those who suffer active disease. Key cells in an adaptive immune response to intracellular pathogens include CD8(+) T cells. Once stimulated, these cells provide a number of different effector functions, each aimed at clearing or containing the pathogen. To explore the role of CD8(+) T cells in an integrative way, we synthesize both published and unpublished data to build and test a mathematical model of the immune response to Mycobacterium tuberculosis in the lung. The model is then used to perform a series of simulations mimicking experimental situations. Selective deletion of CD8(+) T cell subsets suggests a differential contribution for CD8(+) T cell effectors that are cytotoxic as compared with those that produce IFN-gamma. We also determined the minimum levels of effector memory cells of each T cell subset (CD4(+) and CD8(+)) in providing effective protection following vaccination. AD - Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, 48109, USA. AN - 16547267 AU - Sud, D. AU - Bigbee, C. AU - Flynn, J. L. AU - Kirschner, D. E. DA - Apr 01 IS - 7 KW - Animals CD8-Positive T-Lymphocytes/*immunology/metabolism Cells, Cultured Interleukin-10/pharmacology Kinetics Macrophages/drug effects/metabolism Mice Mycobacterium tuberculosis/*immunology Tuberculosis/*immunology/metabolism/*microbiology N1 - Sud, Dhruv Bigbee, Carolyn Flynn, Joanne L Kirschner, Denise E eng AI37859/AI/NIAID NIH HHS/ R01 HL62119/HL/NHLBI NIH HHS/ R01 HL68526/HL/NHLBI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2006/03/21 09:00 J Immunol. 2006 Apr 1;176(7):4296-314. PY - 2006 SN - 0022-1767 (Print) 0022-1767 (Linking) SP - 4296-314 ST - Contribution of CD8+ T cells to control of Mycobacterium tuberculosis infection T2 - J Immunol TI - Contribution of CD8+ T cells to control of Mycobacterium tuberculosis infection UR - https://www.ncbi.nlm.nih.gov/pubmed/16547267 VL - 176 ID - 2232 ER - TY - JOUR AB - Infection with Mycobacterium tuberculosis (Mtb) is characterized by localized, roughly spherical lesions within which the pathogen interacts with host cells. Containment of the infection or progression of disease depends on the behavior of individual cells, which, in turn, depends on the local molecular environment and on contact with neighboring cells. Modeling can help us understand the nonlinear interactions that drive the overall dynamics in this system. Early events in infection are particularly important, as are spatial effects and inherently stochastic processes. We describe a model of early Mycobacterium infection using the CyCells simulator, which was designed to capture these effects. We relate CyCells simulations of the model to several experimental observations of individual components of the response to Mtb. AD - Department of Computer Science, University of New Mexico, P.O. Box 5800 MS 1423, Albuquerque, NM 87185-1423, USA. cewarr@sandia.gov AN - 17086496 AU - Warrender, C. AU - Forrest, S. AU - Koster, F. DA - Nov DO - 10.1007/s11538-006-9103-y [doi] DP - Nlm ET - 11/07 KW - Computer Simulation Humans Interferon-gamma/immunology Interleukin-10/immunology Macrophages, Alveolar/immunology/microbiology Models, Biological Mycobacterium tuberculosis/ physiology T-Lymphocytes/immunology/microbiology Tuberculosis/immunology/ microbiology Tumor Necrosis Factor-alpha/immunology LA - eng N1 - Warrender, Christina Forrest, Stephanie Koster, Frederick P20 GM066283/GM/NIGMS NIH HHS/United States R-1P20RR18754/RR/NCRR NIH HHS/United States U54 AI057156/AI/NIAID NIH HHS/United States Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. United States Bulletin of mathematical biology Bull Math Biol. 2006 Nov;68(8):2233-61. Epub 2006 May 20. PY - 2006 RN - fulltext fulltext_1208 SN - 0092-8240 (Print) 0092-8240 (Linking) SP - 2233-61 ST - Modeling intercellular interactions in early Mycobacterium infection T2 - Bull Math Biol TI - Modeling intercellular interactions in early Mycobacterium infection UR - http://www.springerlink.com/content/f698424230324675/ VL - 68 ID - 2490 ER - TY - JOUR AB - The aim of the present study was to compare the direct costs of three models for detection of latent tuberculosis infection (LTBI) in routine clinical practice in Switzerland. Comparison of the overall costs of screening for LTBI, including medical and radiological examination, and preventive treatment associated with three screening models was carried out. Model 1 relies only on the tuberculin skin test (TST) according to the current national guidelines, model 2 relies on T-SPOT.TB (Oxford Immunotec, Oxford, UK) only and model 3 relies on TST followed by confirmation of positive results by T-SPOT.TB. Costs were taken directly from the clinic's figures. Clinical assumptions were based on the 267 patients who were referred to the clinic over the study period. Model 3 was found to be the most cost-effective. Using only the skin test (model 1) was the least cost-effective. If only one test for LTBI is to be used, then model 2 (using T-SPOT.TB only) is cheaper than using the TST (model 1). Screening for latent tuberculosis infection by tuberculin skin test followed by confirmation with T-SPOT.TB is less costly than screening with tuberculin skin test alone, as it allows a reduction in the number of people who receive preventive treatment. In groups with a high proportion of negative tuberculin skin tests, screening with T-SPOT.TB test only may be the most cost-effective. AD - University Medical Policlinic, Rue du Bugnon 44, 1011 Lausanne, Switzerland. AU - Wrighton-Smith, P. AU - Zellweger, J. P. DO - 10.1183/09031936.06.00005906 KW - Cost-Benefit Analysis Decision Support Techniques Humans Interferon-gamma/metabolism Mass Screening/economics/methods Mycobacterium tuberculosis/metabolism Public Health/methods Reagent Kits, Diagnostic Sensitivity and Specificity Switzerland Tuberculin Test/economics/methods Tuberculosis/diagnosis N1 - LR: 20081121; JID: 8803460; 0 (Reagent Kits, Diagnostic); 82115-62-6 (Interferon-gamma); 2006/04/12 [aheadofprint]; 2006/05/31 [aheadofprint]; ppublish PY - 2006 RN - fulltext fulltext_1208 SN - 0903-1936; 0903-1936 SP - 45-50 ST - Direct costs of three models for the screening of latent tuberculosis infection T2 - The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology TI - Direct costs of three models for the screening of latent tuberculosis infection VL - 28 Y2 - Jul ID - 2491 ER - TY - BILL AB - BACKGROUND: San Francisco has the highest rate of tuberculosis (TB) in the U.S. with recurrent outbreaks among the homeless and marginally housed. It has been shown for syndromic data that when exact geographic coordinates of individual patients are used as the spatial base for outbreak detection, higher detection rates and accuracy are achieved compared to when data are aggregated into administrative regions such as zip codes and census tracts. We examine the effect of varying the spatial resolution in the TB data within the San Francisco homeless population on detection sensitivity, timeliness, and the amount of historical data needed to achieve better performance measures. METHODS AND FINDINGS: We apply a variation of space-time permutation scan statistic to the TB data in which a patient's location is either represented by its exact coordinates or by the centroid of its census tract. We show that the detection sensitivity and timeliness of the method generally improve when exact locations are used to identify real TB outbreaks. When outbreaks are simulated, while the detection timeliness is consistently improved when exact coordinates are used, the detection sensitivity varies depending on the size of the spatial scanning window and the number of tracts in which cases are simulated. Finally, we show that when exact locations are used, smaller amount of historical data is required for training the model. CONCLUSION: Systematic characterization of the spatio-temporal distribution of TB cases can widely benefit real time surveillance and guide public health investigations of TB outbreaks as to what level of spatial resolution results in improved detection sensitivity and timeliness. Trading higher spatial resolution for better performance is ultimately a tradeoff between maintaining patient confidentiality and improving public health when sharing data. Understanding such tradeoffs is critical to managing the complex interplay between public policy and public health. This study is a step forward in this direction. AD - MITRE Corporation, McLean, Virginia, United States of America. bhiggs100@yahoo.com AN - 18074010 DA - Jan 1 KW - Disease Outbreaks Population Surveillance Humans Tuberculosis Prevalence San Francisco Sensitivity and Specificity LB - p02029 M1 - 12 PY - 2007 RN - fulltext fulltext_1208 SP - e1284 ST - Early detection of tuberculosis outbreaks among the San Francisco homeless: trade-offs between spatial resolution and temporal scale T2 - PLoS ONE TI - Early detection of tuberculosis outbreaks among the San Francisco homeless: trade-offs between spatial resolution and temporal scale UR - http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0001284 VL - 2 ID - 2506 ER - TY - BILL AB - OBJECTIVE: To model the effect of socio-economic deprivation and a few transmission-related indicators of the tuberculosis (TB) incidence at small area level, to discuss the potential of each indicator in targeting places for developing preventive action. METHODS: Ecological spatial study of TB incidence in Olinda, a city in the north-east of Brazil, during the period 1996-2000. Three socio-economic indicators (mean number of inhabitants per household; percentage of heads of household with <1 year's formal education; percentage of heads of households with monthly income lower than the minimum wage) and two transmission-related indicators (number of cases of retreatment; number of households with more than one case during the period under study), all calculated per census tract, were used. We adopted four different full hierarchical Bayesian models to estimate the relative risk of the occurrence of TB via Markov chain Monte Carlo. RESULTS: The best specified model includes all the selected covariates and the spatially structured random effect. The gain in goodness-of-fit statistic when the spatial structure was included confirms the clustered spatial pattern of disease and poverty. In this model, the covariates within the non-zero credibility interval were the number of persons per house, the number of cases of retreatment and the number of households with more than one case (all with relative risk > or = 1.8) in each census tract. CONCLUSIONS: The possibility to estimate in the same framework both the contribution of covariates at ecological level and the spatial pattern should be encouraged in epidemiology, and may help with establishing Epidemiological Surveillance Systems on a territorial basis, that allows rational planning of interventions and improvement of the Control Programme effectiveness. AD - Aggeu Magalhães Research Centre, Oswaldo Cruz Foundation, Recife, Brazil. wayner@cpqam.fiocruz.br AN - 17286622 DA - Mar 1 KW - Bayes Theorem Income Humans Risk Factors Brazil Urban Health Population Surveillance Models: Statistical Residence Characteristics Tuberculosis: Pulmonary Incidence Socioeconomic Factors Psychosocial Deprivation LB - p02031 M1 - 3 PY - 2007 RN - fulltext fulltext_1208 SP - 323-30 ST - Tuberculosis in intra-urban settings: a Bayesian approach T2 - Trop Med Int Health TI - Tuberculosis in intra-urban settings: a Bayesian approach UR - http://www3.interscience.wiley.com/journal/118506949/abstract VL - 12 ID - 2511 ER - TY - JOUR AU - Adetunde, I. A. IS - 9 PY - 2007 SP - 943-946 ST - The mathematical models of the dynamical behaviour of tuberculosis disease in the Upper East Region of the northern part of Ghana: a case study of Bawku T2 - Research Journal of Applied Sciences TI - The mathematical models of the dynamical behaviour of tuberculosis disease in the Upper East Region of the northern part of Ghana: a case study of Bawku UR - http://docsdrive.com/pdfs/medwelljournals/rjasci/2007/943-946.pdf VL - 2 ID - 4935 ER - TY - JOUR AB - Mathematical models for the population dynamics of de novo resistant Mycobacterium tuberculosis within individuals are studied. The models address the use of one or two antimicrobial drugs for treating latent tuberculosis (TB). They consider the effect of varying individual immune response strength on the dynamics for the appearance of resistant bacteria. From the analysis of the models, equilibria and local stabilities are determined. For assessing temporal dynamics and global stability for sensitive and drug-resistant bacteria, numerical simulations are used. Results indicate that for a low bacteria load that is characteristic of latent TB and for small reduction in an immune response, the use of a single drug is capable of curing the infection before the appearance of drug resistance. However, for severe immune deficiency, the use of two drugs will provide a larger time period before the emergence of resistance. Therefore, in this case, two-drugs treatment will be more efficient in controlling the infection. AD - Division Academica de Ciencias Basicas, Universidad Juarez Autonoma de Tabasco, Cunduacan 86690, Tabasco, Mexico. AN - 17060491 AU - Alavez-Ramirez, J. AU - Castellanos, J. R. AU - Esteva, L. AU - Flores, J. A. AU - Fuentes-Allen, J. L. AU - Garcia-Ramos, G. AU - Gomez, G. AU - Lopez-Estrada, J. DA - Mar DO - 10.1093/imammb/dql026 ET - 2006/10/25 IS - 1 J2 - Mathematical medicine and biology : a journal of the IMA KW - Algorithms Anti-Bacterial Agents/*pharmacology/therapeutic use Computer Simulation *Drug Resistance, Microbial Drug Therapy, Combination Granuloma/drug therapy/microbiology Humans Isoniazid/pharmacology/therapeutic use *Models, Biological Mycobacterium tuberculosis/*drug effects/growth & development Rifampin/pharmacology/therapeutic use Tuberculosis, Pulmonary/drug therapy/*microbiology L1 - internal-pdf://0462474380/Alavez-Ramirez IMA.pdf LA - eng N1 - Alavez-Ramirez, Justino Castellanos, J Rogelio Avendano Esteva, Lourdes Flores, Jose Antonio Fuentes-Allen, Jose Luis Garcia-Ramos, Gisela Gomez, Guillermo Lopez-Estrada, Jesus England Math Med Biol. 2007 Mar;24(1):35-56. Epub 2006 Oct 23. PY - 2007 RN - fulltext fulltext_1208 SN - 1477-8599 (Print) 1477-8599 (Linking) SP - 35-56 ST - Within-host population dynamics of antibiotic-resistant M. tuberculosis T2 - Math Med Biol TI - Within-host population dynamics of antibiotic-resistant M. tuberculosis UR - http://www.ncbi.nlm.nih.gov/pubmed/17060491 http://imammb.oxfordjournals.org/content/24/1/35 VL - 24 ID - 144 ER - TY - JOUR AB - Contact tracing (also known as partner notification) is a primary means of controlling infectious diseases such as tuberculosis (TB), human immunodeficiency virus (HIV), and sexually transmitted diseases (STDs). However, little work has been done to determine the optimal level of investment in contact tracing. In this paper, we present a methodology for evaluating the appropriate level of investment in contact tracing. We develop and apply a simulation model of contact tracing and the spread of an infectious disease among a network of individuals in order to evaluate the cost and effectiveness of different levels of contact tracing. We show that contact tracing is likely to have diminishing returns to scale in investment: incremental investments in contact tracing yield diminishing reductions in disease prevalence. In conjunction with a cost-effectiveness threshold, we then determine the optimal amount that should be invested in contact tracing. We first assume that the only incremental disease control is contact tracing. We then extend the analysis to consider the optimal allocation of a budget between contact tracing and screening for exogenous infection, and between contact tracing and screening for endogenous infection. We discuss how a simulation model of this type, appropriately tailored, could be used as a policy tool for determining the appropriate level of investment in contact tracing for a specific disease in a specific population. We present an example application to contact tracing for chlamydia control. AD - Department of Management Science and Engineering, Stanford University, Stanford, CA 94305-4026, USA. armbruster@stanford.edu AN - 18074967 AU - Armbruster, B. AU - Brandeau, M. L. DA - Dec DP - Nlm ET - 12/14 J2 - Health care management science KW - Chlamydia Infections/epidemiology/transmission Contact Tracing/ economics/utilization Cost-Benefit Analysis Humans Mass Screening United States/epidemiology LA - eng N1 - Armbruster, Benjamin Brandeau, Margaret L PY - 2007 RN - fulltext fulltext_1208 SN - 1386-9620 (Print) 1386-9620 (Linking) SP - 341-55 ST - Contact tracing to control infectious disease: when enough is enough T2 - Health Care Manag Sci TI - Contact tracing to control infectious disease: when enough is enough UR - http://www.springerlink.com/content/f7171782467075v1/fulltext.pdf VL - 10 ID - 2493 ER - TY - JOUR AB - We used a system dynamics simulation model of the transmission dynamics of drug-sensitive tuberculosis (DSTB), multidrug-resistant tuberculosis (MDRTB) and HIV to estimate the impact of coverage with highly active antiretroviral therapy (HAART) and different cure rates for MDRTB in settings of explosive HIV epidemics and high MDRTB levels. Population coverage levels at 0%, 25%, 50%, 75% and 100% for HAART, and 5% and 80% of MDRTB treatment cure rates were simulated over a 10-year period and cumulative deaths from tuberculosis and HIV-associated tuberculosis were estimated for populations with latent tuberculosis, DSTB, MDRTB, HIV and HIV-associated tuberculosis. Depending on levels of HAART population coverage, increasing MDRTB cure rates from 5% to 80% reduces cumulative tuberculosis deaths by 1% and 13%. High population coverage with HAART (75% or higher), allied with high MDRTB cure rates, reduces cumulative deaths by 60%, with limited impact below this level. High coverage with HAART is required to substantially reduce the number of deaths from tuberculosis. AD - Centre for Health Management, Tanaka Business School, Imperial College London, South Kensington Campus, London, UK. r.atun@imperial.ac.uk AN - 17509178 AU - Atun, R. A. AU - Lebcir, R. M. AU - Drobniewski, F. AU - McKee, M. AU - Coker, R. J. DA - Apr DO - 10.1258/095646207780659024 [doi] DP - Nlm ET - 05/19 KW - AIDS-Related Opportunistic Infections/drug therapy/ prevention & control Antiretroviral Therapy, Highly Active/ utilization Disease Transmission, Infectious/ prevention & control HIV Infections/ drug therapy Humans Models, Biological Russia/epidemiology Tuberculosis, Multidrug-Resistant/epidemiology/ prevention & control L1 - internal-pdf://4034003261/095646207780659024.pdf LA - eng N1 - Atun, Rifat A Lebcir, Reda M Drobniewski, Francis McKee, Martin Coker, Richard J Research Support, Non-U.S. Gov't England International journal of STD & AIDS Int J STD AIDS. 2007 Apr;18(4):267-73. PY - 2007 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0956-4624 (Print) 0956-4624 (Linking) SP - 267-73 ST - High coverage with HAART is required to substantially reduce the number of deaths from tuberculosis: system dynamics simulation T2 - Int J STD AIDS TI - High coverage with HAART is required to substantially reduce the number of deaths from tuberculosis: system dynamics simulation UR - http://ijsa.rsmjournals.com/content/18/4/267http://ijsa.rsmjournals.com/content/18/4/267.full.pdf VL - 18 ID - 2494 ER - TY - JOUR AB - A mathematical model of the spread of tuberculosis taking into account the impact of the antituberculosis programs was considered. The singularity of the proposed model lies in making explicit discrimination between the detected and overlooked patients and taking into account their migration. Studies demonstrated insufficiency of the standard accounting form of the regional Russian antituberculosis institutions. Proposed was a submodel enabling objective estimation of the patient detection system on the basis of individualized database. These estimates corroborated the assumption of a substantial nonuniformity of the Russian regions in terms of tuberculosis morbidity and efficiency of patient detection. For example, the rates of patient detection can differ by the factor of five through six. The model can be used to forecast the tuberculosis morbidity and efficiency of the antituberculosis programs. AD - Russian Acad Sci, Inst Numer Math, Moscow, Russia AN - WOS:000249805000015 AU - Avilov, K. K. AU - Romanyukha, A. A. DA - Sep DO - 10.1134/S0005117907090159 IS - 9 J2 - Automat Rem Contr+ KW - risks LA - English N1 - 215jq Times Cited:7 Cited References Count:15 PY - 2007 SN - 0005-1179 SP - 1604-1617 ST - Mathematical modeling of tuberculosis propagation and patient detection T2 - Automation and Remote Control TI - Mathematical modeling of tuberculosis propagation and patient detection UR - ://WOS:000249805000015 VL - 68 ID - 4840 ER - TY - JOUR AB - BACKGROUND: Extensively drug-resistant (XDR) tuberculosis has spread among hospitalised patients in South Africa, but the epidemic-level effect of hospital-based infection control strategies remains unknown. We modelled the plausible effect of rapidly available infection control strategies on the overall course of the XDR tuberculosis epidemic in a rural area of South Africa. METHODS: We investigated the effect of administrative, environmental, and personal infection control measures on the epidemic trajectory of XDR tuberculosis in the rural community of Tugela Ferry. Assessments were done with a mathematical model incorporating over 2 years of longitudinal inpatient and community-based data. The model simulated inpatient airborne tuberculosis transmission, community tuberculosis transmission, and the effect of HIV and antiretroviral therapy. FINDINGS: If no new interventions are introduced, about 1300 cases of XDR tuberculosis are predicted to occur in the area of Tugela Ferry by the end of 2012, more than half of which are likely to be nosocomially transmitted. Mask use alone would avert fewer than 10% of cases in the overall epidemic, but could prevent a large proportion of cases of XDR tuberculosis in hospital staff. The combination of mask use with reduced hospitalisation time and a shift to outpatient therapy could prevent nearly a third of XDR tuberculosis cases. Supplementing this approach with improved ventilation, rapid drug resistance testing, HIV treatment, and tuberculosis isolation facilities could avert 48% of XDR tuberculosis cases (range 34-50%) by the end of 2012. However, involuntary detention could result in an unexpected rise in incidence due to restricted isolation capacity. INTERPRETATION: A synergistic combination of available nosocomial infection control strategies could prevent nearly half of XDR tuberculosis cases, even in a resource-limited setting. XDR tuberculosis transmission will probably continue in the community, indicating the need to develop and implement parallel community-based programmes. AD - Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA. sanjay.basu@yale.edu AN - 17964351 AU - Basu, S. AU - Andrews, J. R. AU - Poolman, E. M. AU - Gandhi, N. R. AU - Shah, N. S. AU - Moll, A. AU - Moodley, P. AU - Galvani, A. P. AU - Friedland, G. H. DA - Oct 27 DO - S0140-6736(07)61636-5 [pii] 10.1016/S0140-6736(07)61636-5 [doi] DP - Nlm ET - 10/30 KW - Cross Infection/ prevention & control/transmission Hospitals, District Humans Models, Theoretical Rural Health South Africa/epidemiology Tuberculosis, Multidrug-Resistant/epidemiology/ prevention & control/transmission L1 - internal-pdf://1337477870/Basu-2007-Prevention of nosocomial transmissio.pdf LA - eng N1 - Basu, Sanjay Andrews, Jason R Poolman, Eric M Gandhi, Neel R Shah, N Sarita Moll, Anthony Moodley, Prashini Galvani, Alison P Friedland, Gerald H 5 T32 GM07205-32/GM/NIGMS NIH HHS/United States R01 AI068932/AI/NIAID NIH HHS/United States R01 AI072706/AI/NIAID NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England Lancet Lancet. 2007 Oct 27;370(9597):1500-7. PY - 2007 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1474-547X (Electronic) 0140-6736 (Linking) SP - 1500-7 ST - Prevention of nosocomial transmission of extensively drug-resistant tuberculosis in rural South African district hospitals: an epidemiological modelling study T2 - Lancet TI - Prevention of nosocomial transmission of extensively drug-resistant tuberculosis in rural South African district hospitals: an epidemiological modelling study UR - http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(07)61636-5/fulltexthttp://ac.els-cdn.com/S0140673607616365/1-s2.0-S0140673607616365-main.pdf?_tid=e27df51c-f0e6-11e1-879f-00000aacb35e&acdnat=1346141203_b98aeedbc04189a4bb89b46e525174b1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711808/pdf/nihms-35061.pdf VL - 370 ID - 2496 ER - TY - JOUR AB - We propose that microbes that have developed persistent relationships with human hosts have evolved cross-signalling mechanisms that permit homeostasis that conforms to Nash equilibria and, more specifically, to evolutionarily stable strategies. This implies that a group of highly diverse organisms has evolved within the changing contexts of variation in effective human population size and lifespan, shaping the equilibria achieved, and creating relationships resembling climax communities. We propose that such ecosystems contain nested communities in which equilibrium at one level contributes to homeostasis at another. The model can aid prediction of equilibrium states in the context of further change: widespread immunodeficiency, changing population densities, or extinctions. AD - Department of Medicine, New York University School of Medicine, New York, New York 10016, USA. martin.blaser@med.nyu.edu AN - 17943121 AU - Blaser, M. J. AU - Kirschner, D. DO - nature06198 [pii] 10.1038/nature06198 KW - *Bacterial Physiological Phenomena Helicobacter pylori/immunology/physiology *Host-Pathogen Interactions Humans *Models, Biological Mycobacterium tuberculosis/immunology/physiology Salmonella typhi/immunology/physiology LA - eng N1 - Blaser, Martin J Kirschner, Denise Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Nature Nature. 2007 Oct 18;449(7164):843-9. PY - 2007 RN - fulltext fulltext_1208 SN - 1476-4687 (Electronic) 0028-0836 (Linking) SP - 843-849 ST - The equilibria that allow bacterial persistence in human hosts T2 - Nature TI - The equilibria that allow bacterial persistence in human hosts UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17943121 VL - 449 ID - 2497 ER - TY - JOUR AB - Infection with Mycobacterium tuberculosis leads to tuberculosis (TB) disease by one of the three possible routes: primary progression after a recent infection; re-activation of a latent infection; or exogenous re-infection of a previously infected individual. Recent studies show that optimal TB control strategies may vary depending on the predominant route to disease in a specific population. It is therefore important for public health policy makers to understand the relative frequency of each type of TB within specific epidemiological scenarios. Although molecular epidemiologic tools have been used to estimate the relative contribution of recent transmission and re-activation to the burden of TB disease, it is not possible to use these techniques to distinguish between primary disease and re-infection on a population level. Current estimates of the contribution of re-infection therefore rely on mathematical models which identify the parameters most consistent with epidemiological data; these studies find that exogenous re-infection is important only when TB incidence is high. A basic assumption of these models is that people in a population are all equally likely to come into contact with an infectious case. However, theoretical studies demonstrate that the social and spatial structure can strongly influence the dynamics of infectious disease transmission. Here, we use a network model of TB transmission to evaluate the impact of non-homogeneous mixing on the relative contribution of re-infection over realistic epidemic trajectories. In contrast to the findings of previous models, our results suggest that re-infection may be important in communities where the average disease incidence is moderate or low as the force of infection can be unevenly distributed in the population. These results have important implications for the development of TB control strategies. AD - Division of Social Medicine and Health Inequalities, Brigham and Women's Hospital, One Brigham Circle, Boston, MA 02120, USA tcohen@hsph.harvard.edu AN - 17251134 AU - Cohen, T. AU - Colijn, C. AU - Finklea, B. AU - Murray, M. DA - Jun 22 DO - PJ25346278M18447 [pii] 10.1098/rsif.2006.0193 [doi] DP - Nlm ET - 01/26 KW - Cluster Analysis Disease Outbreaks/prevention & control Europe/epidemiology Humans Models, Biological Tuberculosis, Pulmonary/ epidemiology/prevention & control/ transmission LA - eng N1 - Cohen, Ted Colijn, Caroline Finklea, Bryson Murray, Megan K08 AI055985-05/AI/NIAID NIH HHS/United States England Journal of the Royal Society, Interface / the Royal Society J R Soc Interface. 2007 Jun 22;4(14):523-31. PY - 2007 RN - fulltext fulltext_1208 SN - 1742-5689 (Print) 1742-5662 (Linking) SP - 523-31 ST - Exogenous re-infection and the dynamics of tuberculosis epidemics: local effects in a network model of transmission T2 - J R Soc Interface TI - Exogenous re-infection and the dynamics of tuberculosis epidemics: local effects in a network model of transmission UR - http://rsif.royalsocietypublishing.org/content/4/14/523.full.pdf VL - 4 ID - 2498 ER - TY - JOUR AB - Tuberculosis is a disease of global importance: over 2 million deaths are attributed to this infectious disease each year. Even in areas where tuberculosis is in decline, there are sporadic outbreaks which are often attributed either to increased host susceptibility or increased strain transmissibility and virulence. Using two mathematical models, we explore the role of the contact structure of the population, and find that in declining epidemics, localized outbreaks may occur as a result of contact heterogeneity even in the absence of host or strain variability. We discuss the implications of this finding for tuberculosis control in low incidence settings. AD - Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. ccolijn@hsph.harvard.edu AN - 17540410 AU - Colijn, C. AU - Cohen, T. AU - Murray, M. DA - Aug 21 DO - S0022-5193(07)00197-X [pii] 10.1016/j.jtbi.2007.04.015 [doi] DP - Nlm ET - 06/02 KW - Antitubercular Agents/therapeutic use Communicable Disease Control Disease Outbreaks Disease Susceptibility Disease Transmission, Infectious Humans Incidence Models, Biological Models, Statistical Mycobacterium tuberculosis Tuberculosis, Pulmonary/drug therapy/ epidemiology/transmission World Health LA - eng N1 - Colijn, Caroline Cohen, Ted Murray, Megan K08 AI055985-05/AI/NIAID NIH HHS/United States Netherlands Journal of theoretical biology Nihms94733 J Theor Biol. 2007 Aug 21;247(4):765-74. Epub 2007 Apr 27. PY - 2007 RN - fulltext fulltext_1208 SN - 0022-5193 (Print) 0022-5193 (Linking) SP - 765-74 ST - Emergent heterogeneity in declining tuberculosis epidemics T2 - J Theor Biol TI - Emergent heterogeneity in declining tuberculosis epidemics UR - http://ac.els-cdn.com/S002251930700197X/1-s2.0-S002251930700197X-main.pdf?_tid=701971423bef0a352e3f5d824a965769&acdnat=1345012153_4a5156ce5fbcc81695d4f605ae8bcb3a VL - 247 ID - 2499 ER - TY - JOUR AB - Tuberculosis is a leading cause of infectious mortality. Although anti-biotic treatment is available and there is vaccine, tuberculosis levels are rising in many areas of the world. The recent emergence of drug-resistant of TB is alarming, as are the potential effects of HIV on TB epidemics. Mathematical models have been used to study tuberculosis in the past and have influenced policy; there is renewed opportunity for mathematical models to contribute today. Here we review and compare the mathematical models of tuberculosis dynamics in the literature. We present two models of our own: a spatial stochastic individual-based model and a set of delay differential equations encapsulating the same biological assumptions. We compare two different assumptions about partial immunity and explore the effect of preventative treatments. We argue that seemingly subtle differences in model assumptions can have significant effects on biological conclusions. AD - Harvard Univ, Sch Publ Hlth, Kresge Bldg,677 Huntington Ave, Boston, MA 02138 USA Infect Dis Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA AN - WOS:000261596200008 AU - Colijn, C. AU - Cohen, T. AU - Murray, M. DO - Doi 10.1142/9789812708779_0008 KW - intrinsic transmission dynamics drug-resistant tuberculosis mycobacterium-tuberculosis amplification dynamics reinfection threshold exogenous reinfection epidemiological model published literature epidemics infection LA - English N1 - Bip52 Times Cited:3 Cited References Count:60 PY - 2007 SP - 123-+ ST - Mathematical Models of Tuberculosis: Accomplishments and Future Challenges T2 - Biomat 2006 TI - Mathematical Models of Tuberculosis: Accomplishments and Future Challenges UR - ://WOS:000261596200008 http://www.worldscientific.com/doi/abs/10.1142/9789812708779_0008 ID - 4837 ER - TY - JOUR AB - Tuberculosis still remains as a serious public health problem. Thinking about more efficient interventions for its combat and control WHO advocates that DOTS (Directly Observed Short-time Treatment Strategy) can improve cure rates and case detection. In this context, mathematical modeling can be used to evaluate the behavior of tuberculosis under DOTS, supplying informations to optimal action strategies. The model presented in this work, describes the dynamic of 4 individuals groups: susceptibles, never before infected; latently-infected or cured of TB under chemotherapy; infectious individuals with pulmonary TB and sputum smear positive; and noninfectious with pulmonary TB but sputum-smear negative or extra-pulmonary TB. Individuals, who complete treatment successfull, are cured of tuberculosis but remain infected and individuals, who do not complete treatment, continue with the illness (infectious or noninfectious). The model, as considered here allows us to evaluate the effect of improve cure rates and case detection. The Effective Reproductive Rate (R(0)(e)) was found for this model and used as epidemiological measure of severity of an epidemics. If R(0)(e) > 1, an epidemics occurs and if R(0)(e) < 1, it is eradicated. The time-dependent uncertainty analysis is presented using the Monte Carlo Method. AD - Comes, PD Univ Fed Fluminense, Inst Comp, Rua Passo Patria 156,Bloco E Salsa 301 Sao Doming, BR-24210240 Niteroi, RJ, Brazil Univ Fed Fluminense, Inst Comp, Rua Passo Patria 156,Bloco E Salsa 301 Sao Doming, BR-24210240 Niteroi, RJ, Brazil Univ Fed Fluminense, Inst Comp, BR-24210240 Niteroi, RJ, Brazil AN - WOS:000261596200010 AU - Comes, P. D. AU - Leal-Toledo, R. C. P. AU - Cunha, C. E. C. KW - transmission sensitivity uncertainty example model LA - English N1 - Bip52 Times Cited:0 Cited References Count:25 PY - 2007 SP - 161-180 ST - Dynamics of Tuberculosis under Dots Strategy T2 - Biomat 2006 TI - Dynamics of Tuberculosis under Dots Strategy UR - ://WOS:000261596200010 ID - 4841 ER - TY - JOUR AB - OBJECTIVES: To assess the cost-effectiveness of the new QuantiFERON-TB Gold In-Tube (QFT-G) [Cellestis; Carnegie, VIC, Australia] assay for screening and treating of persons who have had close contact with tuberculosis (TB) patients and are suspected of having latent tuberculosis infection (LTBI) [hereafter called close-contacts] in Germany. METHODS: The health and economic outcomes of isoniazid treatment of 20-year-old close-contacts were compared in a Markov model over a period of 20 years, using two different cutoff values for the tuberculin skin test (TST), the QFT-G assay alone, or the QFT-G assay as a confirmatory test for the TST results. RESULTS: QFT-G assay-based treatment led to cost savings of $542.9 and 3.8 life-days gained per LTBI case. TST-based treatment at a 10-mm induration size cutoff gained $177.4 and 2.0 life-days gained per test-positive contact. When the cutoff induration size for the TST was reduced to 5 mm, the incremental cost-effectiveness ratio fell below the willingness-to-pay threshold ($30,170 per life-years gained) but resulted in unnecessary treatment of 77% of contacts owing to false-positive TST results. Combination with the 5-mm induration size TST cutoff value compared to the results of the QFT-G assay alone reduced the total costs per 1,000 contacts by 1.8% to $222,869. The number treated to prevent 1 TB case was 22 for the two QFT-G assay-based procedures, 40 for the TST at a cutoff induration size of 10 mm, and 96 for the TST at a cutoff induration size of 5 mm. When the sensitivity rates of the TST and the QFT-G assay were compounded, the QFT-G assay strategy alone was slightly less costly (0.6%) than the two-step approach. CONCLUSIONS: Using the QFT-G assay, but especially combining the QFT-G assay following the TST screening of close-contacts at a cutoff induration size of 5 mm before LTBI treatment is highly cost-effective in reducing the disease burden of TB. AD - School of Public Health, c/o Institute for Medical Sociology, Heinrich Heine University, Post Box 101007, D-40001 Dusseldorf, Germany. Roland.Diel@uni-duesseldorf.de AU - Diel, R. AU - Nienhaus, A. AU - Loddenkemper, R. DO - 10.1378/chest.06-2728 KW - Adult Antitubercular Agents/therapeutic use Carrier State/diagnosis Cost-Benefit Analysis/statistics & numerical data False Positive Reactions Female Germany Humans Interferon-gamma/blood Isoniazid/therapeutic use Male Markov Chains Mass Screening/economics/methods Models, Theoretical Sensitivity and Specificity Tuberculin Test/economics/methods Tuberculosis/diagnosis/drug therapy N1 - LR: 20081121; JID: 0231335; 0 (Antitubercular Agents); 54-85-3 (Isoniazid); 82115-62-6 (Interferon-gamma); ppublish PY - 2007 RN - fulltext fulltext_1208 SN - 0012-3692; 0012-3692 SP - 1424-1434 ST - Cost-effectiveness of interferon-gamma release assay screening for latent tuberculosis infection treatment in Germany T2 - Chest TI - Cost-effectiveness of interferon-gamma release assay screening for latent tuberculosis infection treatment in Germany VL - 131 Y2 - May ID - 2500 ER - TY - JOUR AB - The aim of the present study was to assess the cost-effectiveness of the new T-SPOT.TB assay versus the tuberculin skin test (TST) for screening contacts for latent tuberculosis (TB) infection in Switzerland. Health and economic outcomes of isoniazid treatment of 20- and 40-yr-old close contacts were compared in a Markov model over a 20-yr period following screening with TST only (at three cut-off values) and T-SPOT.TB alone or in combination with the TST. T-SPOT.TB-based treatment was cost-effective at (Euro)11,621 and (Euro)23,692 per life-year-gained (LYG) in the younger and older age group, respectively. No TST-based programmes were cost-effective, except at a 15-mm cut-off in the younger group only, where the cost-effectiveness ((Euro)26,451.LYG(-1)) fell just below the willingness-to-pay threshold. Combination of the TST with T-SPOT.TB slightly reduced the total cost compared with the T-SPOT.TB alone by 4.4 and 5.0% in the younger and older groups respectively. The number of contacts treated to avoid one case of TB decreased from 50 (95% confidence interval 32-106) with the TST (10-mm cut-off) to 18 (95%CI 11-43) if T-SPOT.TB was used. Using T-SPOT.TB alone or in combination with the tuberculin skin test for screening of close contacts before latent tuberculosis infection treatment is highly cost-effective in reducing the disease burden of tuberculosis. AD - School of Public Health, University of Dusseldorf, Germany. Roland.Diel@uni-duesseldorf.de AN - 17504793 AU - Diel, R. AU - Wrighton-Smith, P. AU - Zellweger, J. P. DA - Aug DO - 10.1183/09031936.00145906 DP - Nlm ET - 05/17 J2 - The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology KW - Adult Antitubercular Agents/therapeutic use Carrier State Cost-Benefit Analysis Decision Support Techniques False Positive Reactions Female Humans Interferon-gamma/ blood Male Markov Chains Mass Screening/ economics/methods Probability Sensitivity and Specificity Software Switzerland/epidemiology Tuberculin Test/ economics/methods Tuberculosis/ diagnosis/ drug therapy/epidemiology LA - eng N1 - Diel, R Wrighton-Smith, P Zellweger, J-P Switzerland Eur Respir J. 2007 Aug;30(2):321-32. Epub 2007 May 15. PY - 2007 RN - fulltext fulltext_1208 SN - 0903-1936 (Print) 0903-1936 (Linking) SP - 321-32 ST - Cost-effectiveness of interferon-gamma release assay testing for the treatment of latent tuberculosis T2 - Eur Respir J TI - Cost-effectiveness of interferon-gamma release assay testing for the treatment of latent tuberculosis UR - http://erj.ersjournals.com/content/30/2/321.full.pdf VL - 30 ID - 6684 ER - TY - JOUR AB - Recognizing that tuberculosis (TB) is still the leading cause of human death from a curable infection, the international health community has set ambitious targets for disease control. One target is to eliminate TB by 2050; that is, to cut the annual incidence of new cases to less than 1 per million population. National TB control programmes are working to eliminate TB mainly by intensifying efforts to find and cure patients with active disease. Here, we use mathematical modelling to show that, while most TB patients can be cured with present drug regimens, the 2050 target is far more likely to be achieved with a combination of diagnostics, drugs and vaccines that can detect and treat both latent infection and active disease. We find that the coupling of control methods is particularly effective because treatments for latent infection and active disease act in synergy. This synergistic effect offers new perspectives on the cost-effectiveness of treating latent TB infection and the impact of possible new TB vaccines. Our results should be a stimulus to those who develop, manufacture and implement new technology for TB control, and to their financial donors. AD - HIV/AIDS, Tuberculosis and Malaria, World Health Organization, Avenue Appia 20, 1211 Geneva 27, Switzerland. dyec@who.int AN - 17690054 AU - Dye, C. AU - Williams, B. G. DA - Jun 6 DO - N502JJ12W45R6403 [pii] 10.1098/rsif.2007.1138 [doi] DP - Nlm ET - 08/11 KW - Antitubercular Agents/therapeutic use Computer Simulation Endemic Diseases Humans Models, Biological Tuberculosis/drug therapy/ prevention & control/transmission World Health LA - eng N1 - Dye, Christopher Williams, Brian G Research Support, Non-U.S. Gov't England Journal of the Royal Society, Interface / the Royal Society J R Soc Interface. 2008 Jun 6;5(23):653-62. PY - 2007 RN - fulltext fulltext_1208 SN - 1742-5689 (Print) 1742-5662 (Linking) SP - 653-62 ST - Eliminating human tuberculosis in the twenty-first century T2 - J R Soc Interface TI - Eliminating human tuberculosis in the twenty-first century UR - http://rsif.royalsocietypublishing.org/content/5/23/653.full.pdf VL - 5 ID - 2527 ER - TY - JOUR AN - 17502 AU - Eilers, P. H. C. AU - Borgdorff, M. W. KW - epidemiology mixture analysis models penalized likelihood risk of infection smoothing statistics N1 - TB Transmission, pathogenesis, and epidemiology Infection with tubercle bacilli Predict epi: risk of infection Risk of infection - models PY - 2007 RN - fulltext fulltext_1208 SP - 5444-5451 ST - Non-parametric log-concave mixtures T2 - Comp.Stat.Data Analysis TI - Non-parametric log-concave mixtures UR - file://C:\literature_pdf\rm17502.pdf VL - 51 ID - 2502 ER - TY - JOUR AB - OBJECTIVE: We undertook a decision analysis to evaluate the economic and health effects and incremental cost-effectiveness of using targeted tuberculin skin testing, compared with universal screening or no screening, before kindergarten. METHODS: We constructed a decision tree to determine the costs and clinical outcomes of using targeted testing compared with universal screening or no screening. Baseline estimates for input parameters were taken from the medical literature and from California health jurisdiction data. Sensitivity analyses were performed to determine plausible ranges of associated outcomes and costs. We surveyed California health jurisdictions to determine the prevalence of mandatory universal tuberculin skin testing. RESULTS: In our base-case scenario, the cost to prevent an additional case of tuberculosis by using targeted testing, compared with no screening, was $524,897. The cost to prevent an additional case by using universal screening, compared with targeted testing, was $671,398. The incremental cost of preventing a case through screening remained above $100,000 unless the prevalence of tuberculin skin testing positivity increased to >10%. More than 51% of children entering kindergarten in California live where tuberculin skin testing is mandatory. CONCLUSIONS: The cost to prevent a case of tuberculosis by using either universal screening or targeted testing of kindergarteners is high. If targeted testing replaced universal tuberculin skin testing in California, then $1.27 million savings per year would be generated for more cost-effective strategies to prevent tuberculosis. Improving the positive predictive value of the risk factor tool or applying it to groups with higher prevalence of latent tuberculosis would make its use more cost-effective. Universal tuberculin skin testing should be discontinued, and targeted testing should be considered only when the prevalence of risk factor positivity and the prevalence of tuberculin skin testing positivity among risk factor-positive individuals are high enough to meet acceptable thresholds for cost-effectiveness. AD - Department of Pediatrics, University of California San Francisco, 3333 California St, San Francisco, CA 94118, USA. flahermanv@peds.ucsf.edu AN - 17606566 AU - Flaherman, V. J. AU - Porco, T. C. AU - Marseille, E. AU - Royce, S. E. DA - Jul DO - 10.1542/peds.2006-2168 DP - Nlm ET - 07/04 J2 - Pediatrics KW - California Child Child, Preschool Cost-Benefit Analysis Costs and Cost Analysis Humans Mass Screening/economics Risk Factors Sensitivity and Specificity Tuberculin Test/ economics Tuberculosis/diagnosis/ economics/prevention & control LA - eng N1 - Flaherman, Valerie J Porco, Travis C Marseille, Elliot Royce, Sarah E KL2 RR024130/RR/NCRR NIH HHS/United States Research Support, N.I.H., Extramural United States Pediatrics. 2007 Jul;120(1):90-9. PY - 2007 RN - fulltext fulltext_1208 SN - 1098-4275 (Electronic) 0031-4005 (Linking) SP - 90-9 ST - Cost-effectiveness of alternative strategies for tuberculosis screening before kindergarten entry T2 - Pediatrics TI - Cost-effectiveness of alternative strategies for tuberculosis screening before kindergarten entry UR - http://pediatrics.aappublications.org/content/120/1/90.full.pdf VL - 120 ID - 2503 ER - TY - JOUR AB - One-third of the world population (approximately 2 billion individuals) is currently infected with Mycobacterium tuberculosis, the vast majority harboring a latent infection. As the risk of reactivation is around 10% in a lifetime, it follows that 200 million of these will eventually develop active pulmonary disease. Only therapeutic or post-exposure interventions can tame this vast reservoir of infection. Treatment of latent infections can reduce the risk of reactivation, and there is accumulating evidence that combination with post-exposure vaccines can reduce the risk of reinfection. Here we develop mathematical models to explore the potential of these post-exposure interventions to control tuberculosis on a global scale. Intensive programs targeting recent infections appear generally effective, but the benefit is potentially greater in intermediate prevalence scenarios. Extending these strategies to longer-term persistent infections appears more beneficial where prevalence is low. Finally, we consider that susceptibility to reinfection is altered by therapy, and explore its epidemiological consequences. When we assume that therapy reduces susceptibility to subsequent reinfection, catastrophic dynamics are observed. Thus, a bipolar outcome is obtained, where either small or large reductions in prevalence levels result, depending on the rate of detection and treatment of latent infections. By contrast, increased susceptibility after therapy may induce an increase in disease prevalence and does not lead to catastrophic dynamics. These potential outcomes are silent unless a widespread intervention is implemented. AD - Instituto Gulbenkian de Ciencia, Apartado 14, 2781-901 Oeiras Cedex, Portugal. ggomes@igc.gulbenkian.pt AN - 17669435 AU - Gomes, G. AU - Rodrigues, P. AU - Hilker, F. M. AU - Mantilla-Beniers, N. B. AU - Muehlen, M. AU - Cristina Paulo, A. AU - Medley, G. F. DA - Oct 21 DO - S0022-5193(07)00284-6 [pii] 10.1016/j.jtbi.2007.06.005 [doi] DP - Nlm ET - 08/03 KW - Antitubercular Agents/therapeutic use Carrier State/immunology Humans Models, Biological Recurrence/prevention & control Tuberculosis/ immunology/ prevention & control/transmission Tuberculosis Vaccines LA - eng N1 - Gabriela M Gomes, M Rodrigues, Paula Hilker, Frank M Mantilla-Beniers, Natalia B Muehlen, Marion Cristina Paulo, Ana Medley, Graham F Research Support, Non-U.S. Gov't Netherlands Journal of theoretical biology J Theor Biol. 2007 Oct 21;248(4):608-17. Epub 2007 Jul 4. PY - 2007 RN - fulltext fulltext_1208 SN - 0022-5193 (Print) 0022-5193 (Linking) SP - 608-17 ST - Implications of partial immunity on the prospects for tuberculosis control by post-exposure interventions T2 - J Theor Biol TI - Implications of partial immunity on the prospects for tuberculosis control by post-exposure interventions UR - http://ac.els-cdn.com/S0022519307002846/1-s2.0-S0022519307002846-main.pdf?_tid=5839d379ca81b25a7b73afd9055a8d60&acdnat=1345012345_79ffbc04fe99446b4f36cf19900f8c40 VL - 248 ID - 2504 ER - TY - JOUR AB - Isoniazid, administered as part of combination antituberculosis therapy, is responsible for most of the early bactericidal activity (EBA) of the regimen. However, the emergence of Mycobacterium tuberculosis resistance to isoniazid is a major problem. We examined the relationship between isoniazid exposure and M. tuberculosis microbial kill, as well as the emergence of resistance, in our in vitro pharmacodynamic model of tuberculosis. Since single-nucleotide polymorphisms of the N-acetyltransferase-2 gene lead to two different clearances of isoniazid from serum in patients, we simulated the isoniazid concentration-time profiles encountered in both slow and fast acetylators. Both microbial kill and the emergence of resistance during monotherapy were associated with the ratio of the area under the isoniazid concentration-time curve from 0 to 24 h (AUC(0-24)) to the isoniazid MIC. The time in mutant selection window hypothesis was rejected. Next, we utilized the in vitro relationship between the isoniazid AUC(0-24)/MIC ratio and microbial kill, the distributions of isoniazid clearance in populations with different percentages of slow and fast acetylators, and the distribution of isoniazid MICs for isonazid-susceptible M. tuberculosis clinical isolates in Monte Carlo simulations to calculate the EBA expected for approximately 10,000 patients treated with 300 mg of isoniazid. For those patient populations in which the proportion of fast acetylators and the isoniazid MICs were high, the average EBA of the standard dose was approximately 0.3 log(10) CFU/ml/day and was thus suboptimal. Our approach, which utilizes preclinical pharmacodynamics and the genetically determined multimodal distributions of serum clearances, is a preclinical tool that may be able to predict the EBAs of various doses of new antituberculosis drugs. AD - Division of Infectious Diseases, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9113, USA. Tawanda.Gumbo@UTSouthwestern.edu AN - 17438043 AU - Gumbo, T. AU - Louie, A. AU - Liu, W. AU - Brown, D. AU - Ambrose, P. G. AU - Bhavnani, S. M. AU - Drusano, G. L. DA - Jul DO - AAC.00185-07 [pii] 10.1128/AAC.00185-07 [doi] DP - Nlm ET - 04/18 KW - Antitubercular Agents/pharmacokinetics/ pharmacology Area Under Curve Colony Count, Microbial Computer Simulation Dose-Response Relationship, Drug Drug Resistance, Bacterial/genetics Ethnic Groups/ classification Humans Isoniazid/pharmacokinetics/ pharmacology Microbial Sensitivity Tests Models, Biological Monte Carlo Method Mutation Mycobacterium tuberculosis/ drug effects/genetics/isolation & purification Pharmacogenetics Time Factors L1 - internal-pdf://0062309846/Gumbo-2007-Isoniazid bactericidal activity and.pdf LA - eng N1 - Gumbo, Tawanda Louie, Arnold Liu, Weiguo Brown, David Ambrose, Paul G Bhavnani, Sujata M Drusano, George L Research Support, Non-U.S. Gov't United States Antimicrobial agents and chemotherapy Antimicrob Agents Chemother. 2007 Jul;51(7):2329-36. Epub 2007 Apr 16. PY - 2007 RN - fulltext fulltext_1208 SN - 0066-4804 (Print) 0066-4804 (Linking) SP - 2329-36 ST - Isoniazid bactericidal activity and resistance emergence: integrating pharmacodynamics and pharmacogenomics to predict efficacy in different ethnic populations T2 - Antimicrob Agents Chemother TI - Isoniazid bactericidal activity and resistance emergence: integrating pharmacodynamics and pharmacogenomics to predict efficacy in different ethnic populations UR - http://aac.asm.org/content/51/7/2329.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1913269/pdf/0185-07.pdf VL - 51 ID - 2505 ER - TY - JOUR AB - OBJECTIVE: To review the transmission models of tuberculosis in heterogeneous population. DATA SOURCES: The data used in this review were adopted mainly from the studies of models of tuberculosis reported from 1995 to 2006. STUDY SELECTION: Relevant literature on transmission models of tuberculosis in heterogeneous populations are referenced. RESULTS: Casual/random factors and genetic factors are the main reasons for epidemics of tuberculosis in recent years. Mass public transport is playing the primary role in casually close contact which can facilitate the transmission of tuberculosis. Genetic susceptibility not only varies endemic prevalence levels, but also drastically alters the effects of treatment for tuberculosis patients. Detailed studies further exhibit that casual contact and genetic factor are responsible for over 30% - 40% of the total new cases in recent years. The prevalence of tuberculosis could double (from 33% to 60%) if a genetically susceptible phenotype is present in only 30% of the population. And some challenges have emerged along with these exciting results. CONCLUSIONS: Casual/random contact, public transport and genetic susceptibility are responsible for most new tuberculosis cases and a wide variation in endemic tuberculosis levels between regions. Hence, the transmission model of tuberculosis in a heterogeneous population can provide more clues to underlying mechanism of tuberculosis transmission than in a homogeneous population. However, many challenges remain for us in understanding transmission of disease. AD - School of InformatioEineering, Beijing University of Posts and Telecommunications, Beijing 100876, China. AN - 17711744 AU - Jia, Z. W. AU - Li, X. W. AU - Feng, D. AU - Cao, W. C. DA - Aug 05 DP - NLM ET - 2007/08/23 IS - 15 J2 - Chinese medical journal KW - Cluster Analysis Genetic Predisposition to Disease Humans Models, Theoretical Tuberculosis/*transmission LA - eng N1 - Jia, Zhong-wei Li, Xiao-wen Feng, Dan Cao, Wu-chun Journal Article Research Support, Non-U.S. Gov't Review China Chin Med J (Engl). 2007 Aug 5;120(15):1360-5. PY - 2007 SN - 0366-6999 (Print) 0366-6999 SP - 1360-5 ST - Transmission models of tuberculosis in heterogeneous population T2 - Chin Med J (Engl) TI - Transmission models of tuberculosis in heterogeneous population VL - 120 ID - 2923 ER - TY - JOUR AB - This paper presents a mathematical model to evaluate the impact of different latent periods on the epidemic of tuberculosis. Analysis results show that the disease-free equilibrium P-0 is globally asymptotically stable and disease is eliminated from population if R-0 <= 1. However, the roof of stability of the unique endemic equilibrium P* is still a challege. Numerical simulation demonstrates that P* is globally asymptotically stable if R-0 > 1. AD - Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, 20 Dong Da St,Fengtai Dist, Beijing 100071, Peoples R China Beijing Univ Posts & Telecommun, Beijing 100871, Peoples R China Chinese Acad Sci, Inst Remote Sensing Applicat, Beijing 100864, Peoples R China North Univ China, Taiyuan, Peoples R China AN - WOS:000250429200081 AU - Jia, Z. W. AU - Li, X. W. AU - Jin, Z. AU - Feng, D. AU - Cao, W. C. DO - 10.1109/Snpd.2007.63 KW - infection therapy LA - English N1 - Bgt70 Times Cited:0 Cited References Count:15 PY - 2007 SP - 422-+ ST - A model for tuberculosis with various latent periods T2 - Snpd 2007: Eighth Acis International Conference on Software Engineering, Artificial Intelligence, Networking, and Parallel/Distributed Computing, Vol 1, Proceedings TI - A model for tuberculosis with various latent periods UR - ://WOS:000250429200081 ID - 4842 ER - TY - JOUR AB - This paper considers an SEIT epidemic model that incorporates proportion recruitment and with vertical transmission. BY means of Lyapunov function and LaSalle's invariant set theorem, we proved the global asymptotical stable results of the disease-free equilibrium and the endenzic equilibrium with the help of numerical simulations. AD - North Univ China, Dept Math, Taiyuan 030051, Peoples R China Yuncheng Univ, Dept Math, Yuncheng 044000, Peoples R China AN - WOS:000250717100094 AU - Ma, C. AU - Zhang, F. Q. AU - Jin, Z. DO - 10.1109/Snpd.2007.337 KW - dynamics populations epidemic LA - English N1 - Bgu85 Times Cited:1 Cited References Count:15 PY - 2007 SP - 508-+ ST - Global stability of a tuberculosis model with vertical transmission T2 - Snpd 2007: Eighth Acis International Conference on Software Engineering, Artificial Intelligence, Networking, and Parallel/Distributed Computing, Vol 3, Proceedings TI - Global stability of a tuberculosis model with vertical transmission UR - ://WOS:000250717100094 ID - 4843 ER - TY - JOUR AB - The Global Plan to Stop TB 2006-2015 is a road map for policy-makers and managers of national programmes. It sets out the key actions needed to achieve the targets of the Millennium Development Goals relating to tuberculosis (T13): to halve the prevalence and deaths by 2015 relative to 1990 levels and to save 14 million lives. Developed by a broad coalition of partners, the plan presents a model approach combining interventions that can feasibly be supplied on the ground. The main areas of activity set out in the plan are: scaling up interventions to control tuberculosis; promoting the research and development of improved diagnostics, drugs and vaccines; and engaging in related activities for advocacy, communications and social mobilization. Scenarios for the planning process were developed; these looked at issues both globally and in seven epidemiological regions. The scenarios made ambitious but realistic assumptions about the pace of scale-up and implementation coverage of the activities. A mathematical model was used to estimate the impact of scaling up current interventions based on data from studies of tuberculosis biology and from experience with tuberculosis control in diverse settings. The estimated costs of the activities set out in the Global Plan were based on implementing interventions and researching and developing drugs, diagnostics and vaccines; these costs were US$ 56 billion over 10 years. When translated into cost per disability adjusted life year averted, these costs compare favourably with those of other public health interventions. This approach to planning for global tuberculosis control is a valuable example of developing plans to improve global health that has relevance for other health issues. AD - Koek, I WHO, Stop TB Dept, CH-1211 Geneva, Switzerland WHO, Stop TB Dept, CH-1211 Geneva, Switzerland WHO, Stop TB Dept, CH-1211 Geneva, Switzerland WHO, Dept Immunizat, CH-1211 Geneva, Switzerland WHO, Special Programme Res & Training Trop Dis, CH-1211 Geneva, Switzerland Stop TB Partnership, Working Grp New Drugs, New York, NY USA AN - ISI:000246790400008 AU - Maher, D. AU - Dye, C. AU - Floyd, K. AU - Pantoja, A. AU - Lonnroth, K. AU - Reid, A. AU - Nathanson, E. AU - Pennas, T. AU - Fruth, U. AU - Cunningham, J. AU - Ignatius, H. AU - Raviglione, M. C. AU - Koek, I. AU - Espinal, M. DA - May DO - Doi 10.2471/Blt.06.037820 J2 - B World Health Organ KW - public-health stop tb impact model LA - English N1 - 172FV Times Cited:31 Cited References Count:27 PY - 2007 RN - fulltext fulltext_1208 SN - 0042-9686 SP - 341-347 ST - Planning to improve global health: the next decade of tuberculosis control T2 - Bulletin of the World Health Organization TI - Planning to improve global health: the next decade of tuberculosis control UR - ://000246790400008http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2636650/pdf/06-037820.pdf VL - 85 ID - 2508 ER - TY - JOUR AB - The immune response to Mycobacterium tuberculosis (Mtb) infection is complex. Experimental evidence has revealed that tumor necrosis factor (TNF) plays a major role in host defense against Mtb in both active and latent phases of infection. TNF-neutralizing drugs used to treat inflammatory disorders have been reported to increase the risk of tuberculosis (TB), in accordance with animal studies. The present study takes a computational approach toward characterizing the role of TNF in protection against the tubercle bacillus in both active and latent infection. We extend our previous mathematical models to investigate the roles and production of soluble (sTNF) and transmembrane TNF (tmTNF). We analyze effects of anti-TNF therapy in virtual clinical trials (VCTs) by simulating two of the most commonly used therapies, anti-TNF antibody and TNF receptor fusion, predicting mechanisms that explain observed differences in TB reactivation rates. The major findings from this study are that bioavailability of TNF following anti-TNF therapy is the primary factor for causing reactivation of latent infection and that sTNF--even at very low levels--is essential for control of infection. Using a mathematical model, it is possible to distinguish mechanisms of action of the anti-TNF treatments and gain insights into the role of TNF in TB control and pathology. Our study suggests that a TNF-modulating agent could be developed that could balance the requirement for reduction of inflammation with the necessity to maintain resistance to infection and microbial diseases. Alternatively, the dose and timing of anti-TNF therapy could be modified. Anti-TNF therapy will likely lead to numerous incidents of primary TB if used in areas where exposure is likely. AD - Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA. AN - 17953477 AU - Marino, S. AU - Sud, D. AU - Plessner, H. AU - Lin, P. L. AU - Chan, J. AU - Flynn, J. L. AU - Kirschner, D. E. C2 - PMC2041971 DA - Oct DO - 10.1371/journal.pcbi.0030194 DP - NLM ET - 2007/10/24 IS - 10 J2 - PLoS computational biology KW - Animals Antitubercular Agents/*pharmacokinetics/therapeutic use Computational Biology/*methods Granuloma/metabolism Humans Models, Statistical Models, Theoretical Mycobacterium Infections/drug therapy Mycobacterium tuberculosis/metabolism Sensitivity and Specificity Signal Transduction T-Lymphocytes/drug effects/microbiology Tuberculosis/*drug therapy Tumor Necrosis Factor-alpha/antagonists & inhibitors/*metabolism L1 - internal-pdf://3820148719/Marino-2007-Differences in reactivation of tub.pdf LA - eng N1 - 1553-7358 Marino, Simeone Sud, Dhruv Plessner, Hillarie Lin, Philana Ling Chan, John Flynn, JoAnne L Kirschner, Denise E R01 HL071241/HL/NHLBI NIH HHS/United States HL68526/HL/NHLBI NIH HHS/United States R01 LM009027/LM/NLM NIH HHS/United States DAIT-BAA-05-10/PHS HHS/United States LMHL68526/PHS HHS/United States HL71241/HL/NHLBI NIH HHS/United States R01 HL106804/HL/NHLBI NIH HHS/United States R01 EB012579/EB/NIBIB NIH HHS/United States R01 HL068526/HL/NHLBI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States PLoS Comput Biol. 2007 Oct;3(10):1909-24. Epub 2007 Aug 22. PY - 2007 SN - 1553-734x SP - 1909-24 ST - Differences in reactivation of tuberculosis induced from anti-TNF treatments are based on bioavailability in granulomatous tissue T2 - PLoS Comput Biol TI - Differences in reactivation of tuberculosis induced from anti-TNF treatments are based on bioavailability in granulomatous tissue UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2041971/pdf/pcbi.0030194.pdf VL - 3 ID - 2145 ER - TY - JOUR AB - SETTING: Rio de Janeiro, Brazil, is a middle-income setting with an estimated 1% adult human immunodeficiency virus (HIV) seroprevalence. OBJECTIVE: To examine the cost-effectiveness of DOTS in Rio de Janeiro. DESIGN: Cost-effectiveness analysis based on cost data and an epidemiological model based on programmatic outcomes from the Health Department in Rio de Janeiro, cost data from the retail market sector and epidemiological data from published studies. RESULTS: The 10-year cost of a tuberculosis program treating a population of 262 000 based on self-administered therapy (SAT) was estimated to be $580 271 compared to $1047 886 for DOTS. The largest portion of the DOTS budget was for staff costs and costs incurred by patients, both at 28%. For SAT, the largest percentage of the budget was allocated to medication costs, at 34%. Upgrading from SAT to DOTS averted 1558 cases of tuberculosis (TB, uncertainty range [UR] 1418-1704) and 143 TB deaths (UR 131-155). The incremental cost effectiveness ratio (ICER) for DOTS was $300 per case averted (UR $289-$312) and $3270 per death averted (UR $3123-$3435). In terms of disability adjusted life years (DALYs), DOTS saved 5426 DALYs (UR 4908-5961). The ICER for DOTS was $86 per DALY saved (UR $74-$100). CONCLUSIONS: DOTS is a highly cost-effective intervention in Brazil. AD - Johns Hopkins School of Medicine, Baltimore, USA. mohanci@yahoo.com AN - 17217126 AU - Mohan, C. I. AU - Bishai, D. AU - Cavalcante, S. AU - Chaisson, R. E. DA - Jan IS - 1 KW - Antitubercular Agents/*therapeutic use Brazil/epidemiology Cost-Benefit Analysis Directly Observed Therapy/*economics Female HIV Seropositivity/epidemiology Humans Male Prevalence Tuberculosis/*drug therapy/epidemiology Urban Population N1 - Mohan, C I Bishai, D Cavalcante, S Chaisson, R E eng 45432/PHS HHS/ Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. France 2007/01/16 09:00 Int J Tuberc Lung Dis. 2007 Jan;11(1):27-32. PY - 2007 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 27-32 ST - The cost-effectiveness of DOTS in urban Brazil T2 - Int J Tuberc Lung Dis TI - The cost-effectiveness of DOTS in urban Brazil UR - https://www.ncbi.nlm.nih.gov/pubmed/17217126 VL - 11 ID - 2256 ER - TY - JOUR AB - We apply the techniques of Lie's symmetry analysis to a caricature of the simplified multistrain model of Castillo-Chavez and Feng [C. Castillo-Chavez, Z. Feng, To treat or not to treat: The case of tuberculosis, J. Math. Biol. 35 (1997) 629-656] for the transmission of tuberculosis and the coupled two-stream vector-based model of Feng and Velasco-Hernandez [Z. Feng, JX Velasco-Hernandez, Competitive exclusion in a vector-host model for the dengue fever, J. Math. Biol. 35 (1997) 523-544] to identify the combinations of parameters which lead to the existence of nontrivial symmetries. In particular we identify those combinations which lead to the possibility of the linearization of the system and provide the corresponding solutions. Many instances of additional symmetry are analyzed. (c) 2007 Elsevier Inc. All rights reserved. AD - Univ Perugia, Dipartimento Matemat & Informat, I-06123 Perugia, Italy. Univ KwaZulu Natal, Sch Math Sci, ZA-4000 Durban, South Africa. Nucci, MC (reprint author), Univ Perugia, Dipartimento Matemat & Informat, I-06123 Perugia, Italy. nucci@unipg.it; leachp@ukzn.ac.za AN - WOS:000247325900029 AU - Nucci, M. C. AU - Leach, P. G. L. DA - Sep DO - 10.1016/j.jmaa.2007.02.061 IS - 1 J2 - J. Math. Anal. Appl. KW - Lie group analysis mathematical epidemiology configurational invariants Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: 179YG Times Cited: 8 Cited Reference Count: 16 Nucci, M. C. Leach, P. G. L. Nucci, Maria Clara/B-3588-2012 Nucci, Maria Clara/0000-0003-1453-0988 8 0 1 Academic press inc elsevier science San diego PY - 2007 SN - 0022-247X SP - 430-449 ST - Lie integrable cases of the simplified multistrain/two-stream model for tuberculosis and dengue fever T2 - Journal of Mathematical Analysis and Applications TI - Lie integrable cases of the simplified multistrain/two-stream model for tuberculosis and dengue fever UR - ://WOS:000247325900029 VL - 333 ID - 6041 ER - TY - JOUR AB - This paper presents mathematical models for tuberculosis and its dynamics under the implementation of the direct observation therapy strategy (DOTS) in Nigeria. The models establish conditions for the eradication of tuberculosis in Nigeria based on the fraction of detected infectious individuals placed under DOTS for treatment. Both numerical and qualitative analysis of the models were carried out and the effect of the fraction of detected cases of active TB on the various epidemiological classes is investigated. The results showed that, provided that the fraction of detected infectious individuals exceeded a critical value, there exists a globally stable disease free equilibrium. However, if this critical detection level is not reached, the disease-free equilibrium will be unstable even with the very high probability successful treatment under DOTS. The results showed that DOTS expansion in Nigeria must include significant increase in the detection rate of infectious individuals; otherwise the effect in reducing the incidence in Nigeria will not be achieved disregarding the tremendous efforts in any other direction, and the huge number of undetected cases will make DOTS insignificant with respect to tuberculosis control. AD - Univ Benin, Dept Math, Benin, Edo State, Nigeria Univ Limerick, Dept Math & Stat, MACSI, Limerick, Ireland AN - WOS:000207833200006 AU - Okuonghae, D. AU - Korobeinikov, A. DO - 10.1051/mmnp:2008013 IS - 1 J2 - Math Model Nat Pheno KW - tuberculosis mathematical model dots prevention and control case detection global stability basic reproduction number LA - English N1 - V15wx Times Cited:7 Cited References Count:33 PY - 2007 SN - 0973-5348 SP - 113-128 ST - Dynamics of Tuberculosis: The effect of Direct Observation Therapy Strategy (DOTS) in Nigeria T2 - Mathematical Modelling of Natural Phenomena TI - Dynamics of Tuberculosis: The effect of Direct Observation Therapy Strategy (DOTS) in Nigeria UR - ://WOS:000207833200006 VL - 2 ID - 4844 ER - TY - JOUR AB - There is increasing recognition that reinfection is an important component of TB transmission. Moreover, it has been shown that partial immunity has significant epidemiological consequences, particularly in what concerns disease prevalence and effectiveness of control measures. We address the problem of drug resistance as a competition between two types of strains of Mycobacterium tuberculosis: those that are sensitive to anti-tuberculosis drugs and those that are resistant. Our objective is to characterise the role of reinfection in the transmission of drug-resistant tuberculosis. The long-term behaviour of our model reflects how reinfection modifies the conditions for coexistence of sensitive and resistant strains. This sets the scene for discussing how strain prevalence is affected by different control strategies. It is shown that intervention effectiveness is highly sensitive to the baseline epidemiological setting. (c) 2006 Elsevier Inc. All rights reserved. AD - Inst Gulbenkian Ciencias, P-2781901 Oeiras, Portugal. Univ Nova Lisboa, Fac Ciencias & Tecnol, P-2825114 Caparica, Portugal. Fac Ciencias Lisboa, P-1649003 Lisbon, Portugal. Ctr Matemat Aplicacoes Fundamentais, P-1649003 Lisbon, Portugal. Rodrigues, P (reprint author), Inst Gulbenkian Ciencias, Apartado 14, P-2781901 Oeiras, Portugal. pcpr@igc.gulbenkian.pt; ggomes@igc.gulbenkian.pt; carlota@ptmat.fc.ul.pt AN - WOS:000244907800007 AU - Rodrigues, P. AU - Gomes, M. G. M. AU - Rebelo, C. DA - Mar DO - 10.1016/j.tpb.2006.10.004 IS - 2 J2 - Theor. Popul. Biol. KW - reinfection drug resistance tuberculosis control strategies coexistence stability mathematical models mycobacterium-tuberculosis antibiotic-resistance threshold transmission strategies framework emergence epidemics dynamics fitness Environmental Sciences & Ecology Evolutionary Biology Genetics & Heredity L1 - internal-pdf://2378446066/1-s2.0-S0040580906001316-main.pdf LA - English M3 - Article N1 - ISI Document Delivery No.: 146AV Times Cited: 38 Cited Reference Count: 32 Rodrigues, Paula Gomes, M. Gabriela M. Rebelo, Carlota Gomes, Gabriela/H-7218-2014; Rebelo, Carlota/M-2582-2015 Gomes, Gabriela/0000-0002-1454-4979; Rebelo, Carlota/0000-0001-5818-8892; Paticio, Paula/0000-0001-6766-4336 39 1 10 Academic press inc elsevier science San diego PY - 2007 SN - 0040-5809 SP - 196-212 ST - Drug resistance in tuberculosis - a reinfection model T2 - Theoretical Population Biology TI - Drug resistance in tuberculosis - a reinfection model UR - ://WOS:000244907800007 VL - 71 ID - 6073 ER - TY - JOUR AB - A combination of continuous and categorical tests, none of which is a gold standard, is often available for classification of subject status in epidemiologic studies. For example, tuberculosis (TB) molecular epidemiology uses select mycobacterial DNA sequences to provide clues about which cases of active TB are likely clustered, implying recent transmission between these cases, versus reactivation of previously acquired infection. The proportion of recently transmitted cases is important to public health, as different control methods are implemented as transmission rates increase. Standard typing methods include IS6110 restriction fragment length polymorphism (IS6110 RFLP), but recently developed polymerase chain reaction based genotyping modalities, including mycobacterial interspersed repetitive unit-variable-number tandem repeat and spoligotyping provide quicker results. In addition, it has recently been suggested that results from IS6110 RFLP can be used to create a continuous measure of genetic relatedness, called the nearest genetic distance. Whichever method is used, estimation of cluster rates is rendered difficult by the lack of a gold standard method for classifying cases as clustered or not. Since many of these methods are relatively new, their properties have not been extensively investigated. Misclassification errors subsequently lead to sub-optimal estimation of risk factors for clustering. Here we show how Bayesian latent class models can be used in such situations, for example to simultaneously analyse Mycobacterium tuberculosis DNA data from all three of the above methods. Using the data collected at the Public Health Unit in Montreal, we estimate the proportion of clustered cases and the operating characteristics of each method using information from all three methods combined, including both continuous and dichotomous measures from IS6110 RFLP. A misclassification-adjusted regression model provides estimates of the effects of risk factors on the clustering probabilities. We also discuss how one must carefully interpret any inferences that arise from a combination of continuous and dichotomous tests. AD - Department of Epidemiology and Biostatistics, McGill University, 1020 Pine Avenue West, Montreal, Que., Canada H3A 1A2. AN - 17437254 AU - Scott, A. N. AU - Joseph, L. AU - Belisle, P. AU - Behr, M. A. AU - Schwartzman, K. DA - Jan 15 DO - 10.1002/sim.2899 [doi] DP - Nlm ET - 04/18 KW - Analysis of Variance Bayes Theorem Cluster Analysis DNA Fingerprinting Female Humans Male Molecular Epidemiology/ methods Mycobacterium tuberculosis/ genetics Tuberculosis/ epidemiology/ microbiology LA - eng N1 - Scott, Allison N Joseph, Lawrence Belisle, Patrick Behr, Marcel A Schwartzman, Kevin England Statistics in medicine Stat Med. 2008 Jan 15;27(1):140-56. PY - 2007 RN - fulltext fulltext_1208 SN - 0277-6715 (Print) 0277-6715 (Linking) SP - 140-56 ST - Bayesian modelling of tuberculosis clustering from DNA fingerprint data T2 - Stat Med TI - Bayesian modelling of tuberculosis clustering from DNA fingerprint data UR - http://onlinelibrary.wiley.com.ez.lshtm.ac.uk/store/10.1002/sim.2899/asset/2899_ftp.pdf?v=1&t=h5w29req&s=302abd98afe554aacc48977400af05ce6136728f VL - 27 ID - 2543 ER - TY - JOUR AN - 17660 AU - Shrestha, R. K. AU - Mugisha, B. AU - Bunnell, R. AU - Mermin, J. AU - Odeke, R. AU - Madra, P. AU - Hitimana-Lukanika, C. AU - Adatu-Engwau, F. AU - Blandford, J. M. KW - adults cost effectiveness decision analysis HIV prevention tuberculosis Uganda N1 - TB Periodical PY - 2007 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SP - 747-754 ST - Cost-utility of tuberculosis prevention among HIV-infected adults in Kampala, Uganda T2 - Int.J.Tuberc.Lung Dis. TI - Cost-utility of tuberculosis prevention among HIV-infected adults in Kampala, Uganda UR - file://C:\literature_pdf\rm17660.pdf VL - 11 ID - 2509 ER - TY - JOUR AB - Recent new methods in Bayesian simulation have provided ways of evaluating posterior distributions in the presence of analytically or computationally intractable likelihood functions. Despite representing a substantial methodological advance, existing methods based on rejection sampling or Markov chain Monte Carlo can be highly inefficient and accordingly require far more iterations than may be practical to implement. Here we propose a sequential Monte Carlo sampler that convincingly overcomes these inefficiencies. We demonstrate its implementation through an epidemiological study of the transmission rate of tuberculosis. AD - School of Mathematics and Statistics, University of New South Wales, Sydney, NSW 2052, Australia. scott.sisson@unsw.edu.au AN - 17264216 AU - Sisson, S. A. AU - Fan, Y. AU - Tanaka, M. M. DA - Feb 6 DO - 0607208104 [pii] 10.1073/pnas.0607208104 [doi] DP - Nlm ET - 02/01 KW - Algorithms Animals Bayes Theorem Computer Simulation/statistics & numerical data Humans Likelihood Functions Models, Statistical Monte Carlo Method Tuberculosis/epidemiology/transmission LA - eng N1 - Sisson, S A Fan, Y Tanaka, Mark M Research Support, Non-U.S. Gov't United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1760-5. Epub 2007 Jan 30. PY - 2007 RN - fulltext fulltext_1208 SN - 0027-8424 (Print) 0027-8424 (Linking) SP - 1760-5 ST - Sequential Monte Carlo without likelihoods T2 - Proc Natl Acad Sci U S A TI - Sequential Monte Carlo without likelihoods UR - http://www.pnas.org/content/104/6/1760.full.pdf VL - 104 ID - 2510 ER - TY - JOUR AB - Background: Tuberculosis ( TB) remains a major cause of mortality in developing countries, and in these countries diabetes prevalence is increasing rapidly. Diabetes increases the risk of TB. Our aim was to assess the potential impact of diabetes as a risk factor for incident pulmonary tuberculosis, using India as an example. Methods: We constructed an epidemiological model using data on tuberculosis incidence, diabetes prevalence, population structure, and relative risk of tuberculosis associated with diabetes. We evaluated the contribution made by diabetes to both tuberculosis incidence, and to the difference between tuberculosis incidence in urban and rural areas. Results: In India in 2000 there were an estimated 20.7 million adults with diabetes, and 900,000 incident adult cases of pulmonary tuberculosis. Our calculations suggest that diabetes accounts for 14.8% ( uncertainty range 7.1% to 23.8%) of pulmonary tuberculosis and 20.2% ( 8.3% to 41.9%) of smear- positive ( i. e. infectious) tuberculosis. We estimate that the increased diabetes prevalence in urban areas is associated with a 15.2% greater smear- positive tuberculosis incidence in urban than rural areas - over a fifth of the estimated total difference. Conclusion: Diabetes makes a substantial contribution to the burden of incident tuberculosis in India, and the association is particularly strong for the infectious form of tuberculosis. The current diabetes epidemic may lead to a resurgence of tuberculosis in endemic regions, especially in urban areas. This potentially carries a risk of global spread with serious implications for tuberculosis control and the achievement of the United Nations Millennium Development Goals. AD - Unwin, N Univ Newcastle Upon Tyne, Inst Hlth & Soc, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England Univ Newcastle Upon Tyne, Inst Hlth & Soc, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England Univ Newcastle Upon Tyne, Inst Hlth & Soc, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England MRC, Epidemiol Unit, Cambridge, England WHO, Dept Chron Dis & Hlth Promot, CH-1211 Geneva, Switzerland AN - ISI:000250030800001 AU - Stevenson, C. R. AU - Forouhi, N. G. AU - Roglic, G. AU - Williams, B. G. AU - Lauer, J. A. AU - Dye, C. AU - Unwin, N. DA - Sep 6 DO - Artn 234 Doi 10.1186/1471-2458-7-234 J2 - Bmc Public Health KW - impaired glucose-tolerance temporal-changes southern india prevalence population burden risk LA - English N1 - 218QU Times Cited:46 Cited References Count:33 PY - 2007 RN - fulltext fulltext_1208 SN - 1471-2458 ST - Diabetes and tuberculosis: the impact of the diabetes epidemic on tuberculosis incidence T2 - Bmc Public Health TI - Diabetes and tuberculosis: the impact of the diabetes epidemic on tuberculosis incidence UR - ://000250030800001http://www.biomedcentral.com/1471-2458/7/234 VL - 7 ID - 2512 ER - TY - JOUR AB - BACKGROUND: In many communities where TB occurs at high incidence, the major force driving the epidemic is transmission. It is plausible that the typical long delay from the onset of infectious disease to diagnosis and commencement of treatment is almost certainly the major factor contributing to the high rate of transmission. METHODOLOGY/PRINCIPAL FINDINGS: This study is confined to communities which are epidemiologically relatively isolated and which have low HIV incidence. The consequences of delays to diagnosis are analyzed and the existence of a threshold delay value is demonstrated. It is shown that unless a sufficient number of cases are detected before this threshold, the epidemic will escalate. The method used for the analysis avoids the standard computer integration of systems of differential equations since the intention is to present a line of reasoning that reveals the essential dynamics of an epidemic in an intuitively clear way that is nevertheless quantitatively realistic. CONCLUSIONS/SIGNIFICANCE: The analysis presented here shows that typical delays to diagnosis present a major obstacle to the control of a TB epidemic. Control can be achieved by optimizing the rapid identification of TB cases together with measures to increase the threshold value. A calculated and aggressive program is therefore necessary in order to bring about a reduction in the prevalence of TB in a community by decreasing the time to diagnosis in all its ramifications. Intervention strategies to increase the threshold value relative to the time to diagnosis and which thereby decrease disease incidence are discussed. AD - Division of Molecular Biology and Human Genetics, MRC Center for Molecular and Cellular Biology, Faculty of Health Sciences, Stellenbosch University, Cape Town, Western Cape, Republic of South Africa. AN - 17712405 AU - Uys, P. W. AU - Warren, R. M. AU - van Helden, P. D. DO - 10.1371/journal.pone.0000757 ET - 08/23 J2 - PloS one KW - Disease Susceptibility HIV Infections/epidemiology Humans Mycobacterium tuberculosis/pathogenicity South Africa/epidemiology Time Factors Tuberculosis, Pulmonary/*diagnosis/*epidemiology/transmission LA - eng M3 - Research Support, Non-U.S. Gov't N1 - Uys, Pieter W Warren, Robin M van Helden, Paul D PLoS One. 2007 Aug 22;2(8):e757. PY - 2007 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e757 ST - A threshold value for the time delay to TB diagnosis T2 - PLoS One TI - A threshold value for the time delay to TB diagnosis UR - http://www.ncbi.nlm.nih.gov/pubmed/17712405 VL - 2 ID - 2513 ER - TY - JOUR AB - Over 50% of the global burden of tuberculosis occurs in South East Asia and the Western Pacific. Since 1950, notification rates in high-income countries in these settings have declined slowly and have remained over ten-fold greater than those in Western populations. The reasons for the slow decline are poorly understood. Using an age-structured model describing the incidence of Mycobacterium tuberculosis infection and disease applied to notification data from Hong Kong, we illustrate that in Hong Kong, a high prevalence of M. tuberculosis infection among older individuals and a high risk of disease through reactivation (e.g. up to 17-fold greater than that estimated for infected males in the United Kingdom) may explain this slow decline. If this feature of the epidemiology of tuberculosis is widespread, the WHO directly observed treatment short-course (DOTS) strategy may have a smaller impact in Asia in the short term than has been implied by recent predictions, all of which have been based on disease risk estimates derived from Western Europe. As a result, it may be difficult to meet the targets for tuberculosis control, which have been prescribed by the UN Millennium Development Goals. AD - Modelling and Economics Unit, Health Protection Agency Centre for Infections, Colindale, London, UK. emilia.vynnycky@hpa.org.uk AN - 17678555 AU - Vynnycky, E. AU - Borgdorff, M. W. AU - Leung, C. C. AU - Tam, C. M. AU - Fine, P. E. DA - Jul DO - S0950268807008552 [pii] 10.1017/S0950268807008552 [doi] DP - Nlm ET - 08/07 KW - Adult Age Factors Aged Communicable Disease Control/methods Hong Kong/epidemiology Humans Incidence Male Middle Aged Recurrence Risk Factors Tuberculosis/ epidemiology LA - eng N1 - Vynnycky, E Borgdorff, M W Leung, C C Tam, C M Fine, P E M Medical Research Council/United Kingdom Research Support, Non-U.S. Gov't England Epidemiology and infection Epidemiol Infect. 2008 Jul;136(7):943-52. Epub 2007 Aug 3. PY - 2007 RN - fulltext fulltext_1208 SN - 0950-2688 (Print) 0950-2688 (Linking) SP - 943-52 ST - Limited impact of tuberculosis control in Hong Kong: attributable to high risks of reactivation disease T2 - Epidemiol Infect TI - Limited impact of tuberculosis control in Hong Kong: attributable to high risks of reactivation disease UR - http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=1872696 VL - 136 ID - 2547 ER - TY - JOUR AB - BACKGROUND: Resistance to commonly used antituberculosis drugs is emerging worldwide. Conventional drug-susceptibility testing (DST) methods are slow and demanding. Alternative, rapid DST methods would permit the early detection of drug resistance and, in turn, arrest tuberculosis transmission. METHODS: A cost-effectiveness analysis of 5 DST methods was performed in the context of a clinical trial that compared rapid with conventional DST methods. The methods under investigation were direct phage-replication assay (FASTPlaque-Response; Biotech), direct amplification and reverse hybridization of the rpoB gene (INNO-LiPA; Innogenetics), indirect colorimetric minimum inhibitory concentration assay (MTT; ICN Biomedicals), and direct proportion method on Lowenstein-Jensen medium. These were compared with the widely used indirect proportion method on Lowenstein-Jensen medium. RESULTS: All alternative DST methods were found to be cost-effective, compared with other health care interventions. DST methods also generate substantial cost savings in settings of high prevalence of multidrug-resistant tuberculosis. Excluding the effects of transmission, the direct proportion method on Lowenstein-Jensen medium was the most cost-effective alternative DST method for patient groups with prevalences of multidrug-resistant tuberculosis of 2%, 5%, 20%, and 50% (cost in US$2004, $94, $36, $8, and $2 per disability-adjusted life year, respectively). CONCLUSION: Alternative, rapid methods for DST are cost-effective and should be considered for use by national tuberculosis programs in middle-income countries. AD - Instituto de Medicina Tropical Alexander Von Humboldt, Lima, Peru. AN - 18636955 AU - Acuna-Villaorduna, C. AU - Vassall, A. AU - Henostroza, G. AU - Seas, C. AU - Guerra, H. AU - Vasquez, L. AU - Morcillo, N. AU - Saravia, J. AU - O'Brien, R. AU - Perkins, M. D. AU - Cunningham, J. AU - Llanos-Zavalaga, L. AU - Gotuzzo, E. DA - Aug 15 DO - 10.1086/590010 ET - 07/19 KW - Antitubercular Agents/*pharmacology Bacterial Proteins/genetics Colorimetry Cost-Benefit Analysis *Drug Resistance, Multiple, Bacterial Gene Amplification Humans Income/classification Microbial Sensitivity Tests/economics/methods Mycobacteriophages/physiology Mycobacterium tuberculosis/*drug effects/genetics/growth & development Nucleic Acid Hybridization Peru Quality-Adjusted Life Years Reagent Kits, Diagnostic Sensitivity and Specificity Time Factors Tuberculosis, Multidrug-Resistant/*diagnosis/epidemiology/microbiology Tuberculosis, Pulmonary/diagnosis/epidemiology/microbiology L1 - internal-pdf://2381178956/Acuna-Villaordu-2008-Cost-effectiveness analys.pdf LA - eng N1 - Acuna-Villaorduna, Carlos Vassall, Anna Henostroza, German Seas, Carlos Guerra, Humberto Vasquez, Lucy Morcillo, Nora Saravia, Juan O'Brien, Richard Perkins, Mark D Cunningham, Jane Llanos-Zavalaga, Luis Gotuzzo, Eduardo Clinical Trial, Phase III Research Support, Non-U.S. Gov't United States Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Clin Infect Dis. 2008 Aug 15;47(4):487-95. PY - 2008 RN - fulltext fulltext_1208 SN - 1537-6591 (Electronic) 1058-4838 (Linking) SP - 487-95 ST - Cost-effectiveness analysis of introduction of rapid, alternative methods to identify multidrug-resistant tuberculosis in middle-income countries T2 - Clin Infect Dis TI - Cost-effectiveness analysis of introduction of rapid, alternative methods to identify multidrug-resistant tuberculosis in middle-income countries UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18636955http://www.journals.uchicago.edu/doi/pdf/10.1086/590010http://cid.oxfordjournals.org/content/47/4/487.full.pdf https://watermark.silverchair.com/47-4-487.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAckwggHFBgkqhkiG9w0BBwagggG2MIIBsgIBADCCAasGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMWZ-80ve7n9SxLa_YAgEQgIIBfC7za9ITklwoc9o8BLCv_eoI-rR-kEBW0qBov1QDuNaWTlJ8PZUpnJYBzfBwSTKjlRHzJ8QNGXxVIRhXQgqNaBwQxaH8ZHnyg5BPVxAh-K9BBUbCu1n8u0BM4spC-d8-aSrUzKwlaZA19olwd9mgzlBWT8BQqmzX3DWB-Upbkkjfua0T7bM9SPgi66l89VVGEFVA4DHuIdY0QBETrmOmuToX2OoV6JnGFNqP9C_mHbtHMatno9yGgxn1RPg6d8DhpwjCNHJFJG11e7VAJnIOiA4C4Vz1_xj06fXdf-SZ7w4B8fLSgo1Z3uq-5Z8mPJNccltC3l5N3yzAjsA_EKCYwsEsHUFzgAsj_HMiADENRFLiXiyryrzUfxJJBG70_sS8GHty20xbnehXSF9O86lLgpHI7BhfVUfYJ1rKC8pczNQ477eKgOepN-LcDohQNAiRe1uI5de7ZQhFRtxfpAaOc_QLKboDqKqkSdJuMuAOSvO-it1lo8liYxmJOHfn VL - 47 ID - 2514 ER - TY - JOUR AB - We present a simple mathematical model with six compartments for the interaction between HIV and TB epidemics. Using data from a township near Cape Town, South Africa, where the prevalence of HIV is above 20% and where the TB notification rate is close to 2,000 per 100,000 per year, we estimate some of the model parameters and study how various control measures might change the course of these epidemics. Condom promotion, increased TB detection and TB preventive therapy have a clear positive effect. The impact of antiretroviral therapy on the incidence of HIV is unclear and depends on the extent to which it reduces sexual transmission. However, our analysis suggests that it will greatly reduce the TB notification rate. AD - Institut de Recherche pour le Developpement, 32 avenue Henri Varagnat, 93143 Bondy, France. bacaer@bondy.ird.fr AN - 18414866 AU - Bacaer, N. AU - Ouifki, R. AU - Pretorius, C. AU - Wood, R. AU - Williams, B. DA - Oct DO - 10.1007/s00285-008-0177-z ET - 04/17 KW - Antiretroviral Therapy, Highly Active Antitubercular Agents/therapeutic use Comorbidity Condoms Disease Notification Disease Outbreaks/prevention & control Disease Transmission, Infectious/prevention & control HIV Infections/drug therapy/*epidemiology Humans Isoniazid/therapeutic use *Models, Biological Prevalence South Africa/epidemiology Tuberculosis/drug therapy/*epidemiology LA - eng N1 - Bacaer, Nicolas Ouifki, Rachid Pretorius, Carel Wood, Robin Williams, Brian Germany Journal of mathematical biology J Math Biol. 2008 Oct;57(4):557-93. Epub 2008 Apr 15. PY - 2008 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0303-6812 (Print) 0303-6812 (Linking) SP - 557-93 ST - Modeling the joint epidemics of TB and HIV in a South African township T2 - J Math Biol TI - Modeling the joint epidemics of TB and HIV in a South African township UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18414866http://www.springerlink.com/content/b7242x4625711ug8/fulltext.pdf VL - 57 ID - 2515 ER - TY - JOUR AB - Extensively drug-resistant tuberculosis (XDR TB) has emerged as a threat to TB control efforts in several high-burden areas, generating international concern. XDR TB is now found in every region of the world, but appears most worrisome in the context of HIV and in resource-limited settings with congregate hospital wards. Here, we examine the emergence and transmission dynamics of the disease, incorporating the mathematical modelling literature related to airborne infection and epidemiological studies related to the operations of TB control programmes in resource-limited settings. We find that while XDR TB may present many challenges in the setting of resource constraints, the central problems highlighted by the emergence of XDR TB are those that have plagued TB programmes for years. These include a slow rate of case detection that permits prolonged infectiousness, the threat of airborne infection in enclosed spaces, the problem of inadequate treatment delivery and treatment completion, and the need to develop health systems that can address the combination of TB and poverty. Mathematical models of TB transmission shed light on the idea that community-based therapy and rapid detection systems may be beneficial in resource-limited settings, while congregate hospital wards are sites for major structural reform. AU - Basu, S. AU - Galvani, A. P. DO - 10.1017/S0950268808000964 10.1017/S0950268808000964. Epub 2008 Jul 7. ET - 07/09 IS - 12 KW - *Models, Theoretical Extensively Drug-Resistant Tuberculosis/epidemiolo Humans Rural Health South Africa/epidemiology control/*transmission L1 - internal-pdf://2730768699/Basu-2008-The transmission and control of XDR.pdf LA - eng PY - 2008 SN - 0950-2688 (Print) 0950-2688 (Linking) SP - 1585-1598 ST - The transmission and control of XDR TB in South Africa: an operations research and mathematical modelling approach T2 - Epidemiol Infect TI - The transmission and control of XDR TB in South Africa: an operations research and mathematical modelling approach UR - http://www.ncbi.nlm.nih.gov/pubmed/18606028 http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=2634260 https://www.cambridge.org/core/services/aop-cambridge-core/content/view/3CA94C1FC0E08456FCFF953B638F295C/S0950268808000964a.pdf/div-class-title-the-transmission-and-control-of-xdr-tb-in-south-africa-an-operations-research-and-mathematical-modelling-approach-div.pdf VL - 136 ID - 3919 ER - TY - JOUR AB - BACKGROUND: Emerging research suggests that genetically distinct strains of Mycobacterium tuberculosis may modulate the immune system differently. This may be of importance in high-burden settings where > or =1 genetic group of M. tuberculosis confers significant morbidity. METHODS: A dynamic mathematical model was constructed to evaluate how different degrees of cross-immunity among M. tuberculosis groups could affect epidemics of drug-resistant tuberculosis (TB). RESULTS: Simulated populations with immunogenically distinct TB strain groups experienced a heightened risk of drug-resistant TB, compared with populations without such strain diversity, even when the same rates of case detection and treatment success were achieved. The highest risks of infection were observed in populations in which HIV was prevalent. Drug-resistant strains with very low transmission fitness could still propagate in environments with reduced cross-immunity among different strain groups, even after common targets for case detection and treatment success are reached. CONCLUSIONS: It is possible that the propagation of drug-resistant strains could depend not only on the rate of development of resistance and the fitness of the drug-resistant strains but, also, on the diversity of the strains in the region. The risk of infection with drug-resistant strains could be amplified in locations where there is reduced cross-immunity between originating strain groups. This amplification may be most profound during the first few decades of TB treatment expansion. AD - Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA. sanjay.basu@yale.edu AN - 18816192 AU - Basu, S. AU - Orenstein, E. AU - Galvani, A. P. DA - Nov 15 DO - 10.1086/592508 [doi] DP - Nlm ET - 09/26 KW - AIDS-Related Opportunistic Infections/epidemiology/ immunology/microbiology Computer Simulation Disease Outbreaks Disease Progression HIV Infections/complications Models, Theoretical Mycobacterium tuberculosis/genetics/ immunology Risk Assessment Tuberculosis, Multidrug-Resistant/complications/epidemiology/ immunology/transmission L1 - internal-pdf://1066362079/Basu-2008-The theoretical influence of immunit.pdf LA - eng N1 - Basu, Sanjay Orenstein, Evan Galvani, Alison P Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. United States The Journal of infectious diseases J Infect Dis. 2008 Nov 15;198(10):1502-13. PY - 2008 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0022-1899 (Print) 0022-1899 (Linking) SP - 1502-13 ST - The theoretical influence of immunity between strain groups on the progression of drug-resistant tuberculosis epidemics T2 - J Infect Dis TI - The theoretical influence of immunity between strain groups on the progression of drug-resistant tuberculosis epidemics UR - http://jid.oxfordjournals.org/content/198/10/1502.full.pdf https://watermark.silverchair.com/198-10-1502.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAdIwggHOBgkqhkiG9w0BBwagggG_MIIBuwIBADCCAbQGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMij7ru7s6F3k_DsN9AgEQgIIBhWKfi0LKfOvH-2OWfFngqPN8NWuvizyxg2nhupaw8nP0KovK--SfpeYKkD7CNSemAXaQIumULPPZeuIa0kBW0RhnpPDWWtqxTFXexYo3hP7Juh7wR2ZRFht5vcgqUgEaETCbzuus5fyAh27xBS7fYVtVzZ7DizsOi_5PSNyeIPD0JIMxIXrm1MMZyyGA-ze0Wy_xqG_Rdnmkbo5eYcxqCeTKfYwao1gKXn8ONPNNhioNAGmrMt60ILFNblA9EhF_yujGj22m1eCs1tJakxMkWbZBwAsZr-Sk-h4Hk4UWapsWHgFDWhidvxFoIJuGO3ujaMjQFLj_HfeExOZ6X8iN0FrQCRRszYtxvsQoQAU8zlCknVx6461AprjA4RSGqQ-1XpYtljiYdP6mzbIRVUoNeGivrBN_msJj1fTc5yvpaja0BOO_6ieDy3O8r8M_6i63bDisi5o3HDO8j7H2Hj_ReyUOvUFk8xfeqGM08MfCNv9o-4mzkZCJCg0NkmGq5fzNjN5arcGH VL - 198 ID - 2516 ER - TY - JOUR AB - Epidemic control strategies alter the spread of the disease in the host population. In this paper, we describe and discuss mathematical models that can be used to explore the potential of pre-exposure and post-exposure vaccines currently under development in the control of tuberculosis. A model with bacille Calmette-Guerin (BCG) vaccination for the susceptibles and treatment for the infectives is first presented. The epidemic thresholds known as the basic reproduction numbers and equilibria for the models are determined and stabilities are investigated. The reproduction numbers for the models are compared to assess the impact of the vaccines currently under development. The centre manifold theory is used to show the existence of backward bifurcation when the associated reproduction number is less than unity and that the unique endemic equilibrium is locally asymptotically stable when the associated reproduction number is greater than unity. From the study we conclude that the pre-exposure vaccine currently under development coupled with chemoprophylaxis for the latently infected and treatment of infectives is more effective when compared to the post-exposure vaccine currently under development for the latently infected coupled with treatment of the infectives. AD - Modelling Biomedical Systems Research Group, Department of Applied Mathematics, National University of Science and Technology, P.O. Box AC 939 Ascot, Bulawayo, Zimbabwe. cpbhunu1762@nust.ac.zw AN - 18644386 AU - Bhunu, C. P. AU - Garira, W. AU - Mukandavire, Z. AU - Magombedze, G. DA - Oct 7 DO - S0022-5193(08)00309-3 [pii] 10.1016/j.jtbi.2008.06.023 [doi] DP - Nlm ET - 07/23 KW - Antitubercular Agents/therapeutic use Basic Reproduction Number Carrier State/drug therapy Computational Biology Disease Outbreaks/prevention & control Humans Models, Biological Tuberculosis/ epidemiology/ prevention & control/therapy Tuberculosis Vaccines/therapeutic use LA - eng N1 - Bhunu, C P Garira, W Mukandavire, Z Magombedze, G Research Support, Non-U.S. Gov't Netherlands Journal of theoretical biology J Theor Biol. 2008 Oct 7;254(3):633-49. Epub 2008 Jul 1. PY - 2008 RN - fulltext fulltext_1208 SN - 1095-8541 (Electronic) 0022-5193 (Linking) SP - 633-49 ST - Modelling the effects of pre-exposure and post-exposure vaccines in tuberculosis control T2 - J Theor Biol TI - Modelling the effects of pre-exposure and post-exposure vaccines in tuberculosis control UR - http://ac.els-cdn.com/S0022519308003093/1-s2.0-S0022519308003093-main.pdf?_tid=9cd3afbb621724c7f1c7b776db347970&acdnat=1345011996_6faf58a30be5ee9615d3855da6ebe4a6 VL - 254 ID - 2517 ER - TY - JOUR AB - A tuberculosis model which incorporates treatment of infectives and chemoprophylaxis is presented. The model assumes that latently infected individuals develop active disease as a result of endogenous re-activation, exogenous re-infection and disease relapse, though a small fraction is assumed to develop active disease soon after infection. We start by formulating and analyzing a TB model without any intervention strategy that we extend to incorporate chemoprophylaxis and treatment of infectives. The epidemic thresholds known as reproduction numbers and equilibria for the models are determined, and stabilities analyzed. The reproduction numbers for the models are compared to assess the possible community benefits achieved by treatment of infectives, chemoprophylaxis and a holistic approach of these intervention strategies. The study shows that treatment of infectives is more effective in the first years of implementation (approximately 10 years) as treatment results in clearing active TB immediately and there after chemoprophylaxis will do better in controlling the number of infectives due to reduced progression to active TB. AD - Modelling Biomedical Systems Research Group, Department of Applied Mathematics, National University of Science and Technology, P.O. Box 939 Ascot, Bulawayo, Zimbabwe. cpbhunu1762@nust.ac.zw AN - 18231839 AU - Bhunu, C. P. AU - Garira, W. AU - Mukandavire, Z. AU - Zimba, M. DA - May DO - 10.1007/s11538-008-9295-4 [doi] DP - Nlm ET - 01/31 KW - Antitubercular Agents/therapeutic use Carrier State/drug therapy/prevention & control/transmission Humans Mathematics Models, Biological Recurrence Tuberculosis, Pulmonary/ drug therapy/prevention & control/ transmission LA - eng N1 - Bhunu, C P Garira, W Mukandavire, Z Zimba, M Research Support, Non-U.S. Gov't United States Bulletin of mathematical biology Bull Math Biol. 2008 May;70(4):1163-91. Epub 2008 Jan 30. PY - 2008 RN - fulltext fulltext_1208 SN - 0092-8240 (Print) 0092-8240 (Linking) SP - 1163-91 ST - Tuberculosis transmission model with chemoprophylaxis and treatment T2 - Bull Math Biol TI - Tuberculosis transmission model with chemoprophylaxis and treatment UR - http://www.springerlink.com/content/f553q1508h5073g8/ VL - 70 ID - 2518 ER - TY - JOUR AB - Mathematical models that describe the global spread of infectious diseases such as influenza, severe acute respiratory syndrome (SARS), and tuberculosis (TB) often consider a sample of international airports as a network supporting disease spread. However, there is no consensus on how many cities should be selected or on how to select those cities. Using airport flight data that commercial airlines reported to the Official Airline Guide (OAG) in 2000, we have examined the network characteristics of network samples obtained under different selection rules. In addition, we have examined different size samples based on largest flight volume and largest metropolitan populations. We have shown that although the bias in network characteristics increases with the reduction of the sample size, a relatively small number of areas that includes the largest airports, the largest cities, the most-connected cities, and the most central cities is enough to describe the dynamics of the global spread of influenza. The analysis suggests that a relatively small number of cities (around 200 or 300 out of almost 3000) can capture enough network information to adequately describe the global spread of a disease such as influenza. Weak traffic flows between small airports can contribute to noise and mask other means of spread such as the ground transportation. AD - RTI International, Research Triangle Park, North Carolina, United States of America. bobashev@rti.org AN - 18776932 AU - Bobashev, G. AU - Morris, R. J. AU - Goedecke, D. M. DO - 10.1371/journal.pone.0003154 [doi] DP - Nlm ET - 09/09 KW - Aircraft Aviation Communicable Diseases/ epidemiology/transmission Disease Outbreaks Geography Humans Influenza, Human/epidemiology/transmission Models, Theoretical Severe Acute Respiratory Syndrome/transmission Travel Tuberculosis/epidemiology/transmission LA - eng N1 - Bobashev, Georgiy Morris, Robert J Goedecke, D Michael U01GM070698/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural United States PloS one PLoS One. 2008 Sep 8;3(9):e3154. PY - 2008 RN - fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e3154 ST - Sampling for global epidemic models and the topology of an international airport network T2 - PLoS One TI - Sampling for global epidemic models and the topology of an international airport network UR - http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0003154&representation=PDF VL - 3 ID - 2519 ER - TY - JOUR AU - Cohen, T. AU - Colijn, C. AU - Finklea, B. AU - Wright, A. AU - Zignol, M. AU - Pym, A. AU - Murray, M. L1 - internal-pdf://2445009922/Cohen-2008-Are Survey-Based Estimates of the B.pdf PY - 2008 RN - fulltext fulltext_1208 SP - e2363 ST - Are Survey-Based Estimates of the Burden of Drug Resistant TB Too Low? Insight from a Simulation Study T2 - PLoS One TI - Are Survey-Based Estimates of the Burden of Drug Resistant TB Too Low? Insight from a Simulation Study UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408555/pdf/pone.0002363.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408555/pdf/pone.0002363.pdf VL - 3 ID - 2520 ER - TY - JOUR AB - While bacillus Calmette-Guerin vaccination plays an important role in reducing the morbidity of tuberculosis (TB) infection during childhood, new tuberculosis vaccines are necessary to disrupt the transmission of disease and improve global control of this pathogen. Growing evidence of the presence of meaningful Mycobacterium tuberculosis strain diversity, coupled with the possibility that new vaccines may differentially protect against infection or disease with circulating M. tuberculosis strains, suggest that these vaccines may have complicated effects on disease dynamics. We use a mathematical model to explore the potential effects of strain diversity on the performance of vaccines and find that vaccines offer great promise for improving tuberculosis control, but the expected benefits of mass vaccination will be eroded if strain replacement with M. tuberculosis variants that are not effectively targeted by vaccines occurs. Determining the likelihood of strain replacement will require additional knowledge of the strain specificities of current vaccine candidates, and an improved understanding of the mechanisms of strain interaction, which are responsible for maintaining the diversity of M. tuberculosis within communities. AD - Division of Global Health Equity, Brigham and Women's Hospital, Boston MA 02115, USA. tcohen@hsph.harvard.edu AN - 18849476 AU - Cohen, T. AU - Colijn, C. AU - Murray, M. DA - Oct 21 DO - 0808746105 [pii] 10.1073/pnas.0808746105 [doi] DP - Nlm ET - 10/14 KW - Models, Biological Tuberculosis/immunology Tuberculosis Vaccines/ classification/ immunology LA - eng N1 - Cohen, Ted Colijn, Caroline Murray, Megan K08 AI055985-06/AI/NIAID NIH HHS/United States Research Support, N.I.H., Extramural United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16302-7. Epub 2008 Oct 10. PY - 2008 RN - fulltext fulltext_1208 SN - 1091-6490 (Electronic) 0027-8424 (Linking) SP - 16302-7 ST - Modeling the effects of strain diversity and mechanisms of strain competition on the potential performance of new tuberculosis vaccines T2 - Proc Natl Acad Sci U S A TI - Modeling the effects of strain diversity and mechanisms of strain competition on the potential performance of new tuberculosis vaccines UR - http://www.pnas.org/content/105/42/16302.full.pdf VL - 105 ID - 2521 ER - TY - JOUR AB - Technologies for strain differentiation and typing have made it possible to detect genetic diversity of pathogens, both within individual hosts and within communities. Coinfection of a host by more than one pathogen strain may affect the relative frequency of these strains at the population level through complex within- and between-host interactions; in infectious diseases that have a long latent period, interstrain competition during latency is likely to play an important role in disease dynamics. We show that SEIR models that include a class of latently coinfected individuals can have markedly different long-term dynamics than models without coinfection, and that coinfection can greatly facilitate the stable coexistence of strains. We demonstrate these dynamics using a model relevant to tuberculosis in which people may experience latent coinfection with both drug sensitive and drug resistant strains. Using this model, we show that the existence of a latent coinfected state allows the possibility that disease control interventions that target latency may facilitate the emergence of drug resistance. AD - Department of Engineering Mathematics, University of Bristol, Bristol, UK. ccolijn@gmail.com AN - 19082663 AU - Colijn, C. AU - Cohen, T. AU - Murray, M. DA - Jan DO - 10.1007/s11538-008-9361-y [doi] DP - Nlm ET - 12/17 KW - Basic Reproduction Number Biodiversity Communicable Diseases/drug therapy/ microbiology Drug Resistance, Bacterial/genetics Host-Pathogen Interactions/drug effects/immunology Humans Incidence Infectious Disease Incubation Period Models, Biological Mycobacterium/drug effects/genetics/immunology Nonlinear Dynamics Selection, Genetic Species Specificity Tuberculosis/drug therapy/immunology/microbiology Virus Latency/physiology L1 - internal-pdf://1123055917/Colijn-2008-Latent coinfection and the mainten.pdf LA - eng N1 - Colijn, Caroline Cohen, Ted Murray, Megan K08 AI055985-06/AI/NIAID NIH HHS/United States United States Bulletin of mathematical biology Nihms94718 Bull Math Biol. 2009 Jan;71(1):247-63. Epub 2008 Dec 10. PY - 2008 RN - fulltext fulltext_1208 SN - 1522-9602 (Electronic) 0092-8240 (Linking) SP - 247-63 ST - Latent coinfection and the maintenance of strain diversity T2 - Bull Math Biol TI - Latent coinfection and the maintenance of strain diversity UR - http://www.springerlink.com/content/y426974338578126/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652765/pdf/nihms-94718.pdf VL - 71 ID - 2562 ER - TY - JOUR AB - BACKGROUND: Numerous studies of interferon-gamma release assays (IGRAs) and tuberculin skin testing (TST) to assess latent tuberculosis infection have been published without a framework to understand the extent to which these two tests should agree. Analyzing the causes of variability in agreement levels is crucial. METHODS: A mathematical model of agreement between dichotomous tests was used to understand variations in the level of agreement between IGRA and TST results. The effect of cut-off point selection on agreement was also explored using the model. Model-based predictions are illustrated using published literature. RESULTS: Analyses of IGRAs and TST that depart from model predictions are an indication that surrogates of prevalence of Mycobacterium tuberculosis infection may have been improperly measured or analyzed. For fixed prevalence, the extent of agreement between tests depends upon cut-off point selection. Changing cut-off points while holding prevalence constant may lead to increasing, decreasing or even no change in agreement. CONCLUSIONS: Researchers have recognized that experimental error, clinical risk and prevalence of non-tuberculous mycobacteria contribute to study-to-study variability. In the present study, we show that paradoxical findings in certain IGRA studies can be explained by the proposed mathematical model. Re-analysis of existing studies may lead to overlooked hypotheses. Future IGRA studies will require epidemiologically well-characterized populations. AD - Global Tuberculosis Institute, New Jersey Medical School, Newark, New Jersey, USA. davidoal@umdnj.edu AN - 18230247 AU - Davidow, A. L. AU - Affouf, M. DA - Feb DP - Nlm ET - 01/31 KW - Humans Interferon-gamma/ secretion Research Design Sensitivity and Specificity Tuberculin Test Tuberculosis/ diagnosis LA - eng N1 - Davidow, A L Affouf, M France The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Int J Tuberc Lung Dis. 2008 Feb;12(2):152-9. PY - 2008 RN - fulltext fulltext_1208 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 152-9 ST - Making sense of agreement among interferon-gamma release assays and tuberculosis skin testing T2 - Int J Tuberc Lung Dis TI - Making sense of agreement among interferon-gamma release assays and tuberculosis skin testing VL - 12 ID - 2522 ER - TY - JOUR AB - South Africa has high rates of tuberculosis (TB), including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Expanding access to culture and drug susceptibility testing (DST) for TB diagnosis may help control this epidemic, but the potential impact of existing and novel TB diagnostics is uncertain. By fitting to World Health Organization epidemiological estimates, we developed a compartmental difference-equation model of the TB/HIV epidemic among South African adults. Performing culture and DST in 37% of new cases and 85% of previously treated cases was projected to save 47,955 lives (17.2% reduction in TB mortality, 95% simulation interval (S.I.) 8.9-24.4%), avert 7,721 MDR-TB cases (14.1% reduction, 95% S.I. 5.3-23.8%), and prevent 46.6% of MDR-TB deaths (95% S.I. 32.6-56.0%) in South Africa over 10 years. Used alone, expanded culture and DST did not reduce XDR-TB incidence, but they enhanced the impact of transmission-reduction strategies, such as respiratory isolation. In South Africa, expanding TB culture and DST could substantially reduce TB, and particularly MDR-TB, mortality. Control of XDR-TB will require additional interventions, the impact of which may be enhanced by improved TB diagnosis. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Suite W6508, Baltimore, MD 21205, USA. AN - 18695217 AU - Dowdy, D. W. AU - Chaisson, R. E. AU - Maartens, G. AU - Corbett, E. L. AU - Dorman, S. E. DA - Aug 12 DO - 0800965105 [pii] 10.1073/pnas.0800965105 [doi] DP - Nlm ET - 08/13 KW - Disease Outbreaks Drug Resistance, Multiple, Bacterial Female HIV Infections/complications/ diagnosis/ mortality/transmission Humans Male Models, Theoretical Retrospective Studies South Africa/epidemiology Time Factors Tuberculosis/complications/ diagnosis/ mortality/transmission World Health Organization L1 - internal-pdf://3950028845/Dowdy-2008-Impact of enhanced tuberculosis dia.pdf LA - eng N1 - Dowdy, David W Chaisson, Richard E Maartens, Gary Corbett, Elizabeth L Dorman, Susan E 074644/Wellcome Trust/United Kingdom K23 AI51528/AI/NIAID NIH HHS/United States K24 AI01637/AI/NIAID NIH HHS/United States T32 GMO7309/PHS HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11293-8. Epub 2008 Aug 11. PY - 2008 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1091-6490 (Electronic) 0027-8424 (Linking) SP - 11293-8 ST - Impact of enhanced tuberculosis diagnosis in South Africa: a mathematical model of expanded culture and drug susceptibility testing T2 - Proc Natl Acad Sci U S A TI - Impact of enhanced tuberculosis diagnosis in South Africa: a mathematical model of expanded culture and drug susceptibility testing UR - http://www.pnas.org/content/105/32/11293.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2516234/pdf/zpq11293.pdf VL - 105 ID - 2523 ER - TY - JOUR AB - SETTING: The potential cost-effectiveness of improved diagnostic tests for tuberculosis (TB) in resource-limited settings is unknown. OBJECTIVE: To estimate the incremental cost-effectiveness of a hypothetical new point-of-care TB diagnostic test in South Africa, Brazil and Kenya. DESIGN: Decision-analysis model, adding four diagnostic interventions (sputum smear microscopy, new test, smear plus new test and smear plus TB culture) to a baseline of existing infrastructure without smear. RESULTS: Adding sputum smear was estimated to be more cost-effective (incremental cost per disability-adjusted life year [DALY] of $86 [South Africa], $131 [Brazil], $38 (Kenya]) than a new TB diagnostic with 70% sensitivity, 95% specificity and price of $20 per test ($198 [South Africa], $275 [Brazil], $84 [Kenya]). However, compared to sputum smear, smear plus new test averted 46-49% more DALYs per 1000 TB suspects (321 vs. 215 [South Africa], 243 vs. 166 [Brazil], 790 vs. 531 [Kenya]), at an incremental cost of $170 (Kenya) to $625 (Brazil) per DALY averted. Cost-effectiveness was most sensitive to the specificity and price of the new test, the baseline TB case detection rate and the discount rate. CONCLUSION: Novel diagnostic tests for TB are potentially highly cost-effective. Cost-effectiveness is maximized by high-specificity, low-cost tests deployed to regions with poor infrastructure. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. david.w.dowdy@gmail.com AN - 18713499 AU - Dowdy, D. W. AU - O'Brien, M. A. AU - Bishai, D. DA - Sep ET - 08/21 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Brazil Cost-Benefit Analysis Decision Support Techniques Diagnostic Tests, Routine/*economics/methods Humans Kenya Models, Economic Sensitivity and Specificity South Africa Tuberculosis/*diagnosis/drug therapy/economics LA - eng M3 - Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't N1 - Dowdy, D W O'Brien, M A Bishai, D 5 T32 GM07309/GM/NIGMS NIH HHS/ France Int J Tuberc Lung Dis. 2008 Sep;12(9):1021-9. PY - 2008 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 1021-9 ST - Cost-effectiveness of novel diagnostic tools for the diagnosis of tuberculosis T2 - Int J Tuberc Lung Dis TI - Cost-effectiveness of novel diagnostic tools for the diagnosis of tuberculosis UR - http://www.ncbi.nlm.nih.gov/pubmed/18713499 VL - 12 ID - 2525 ER - TY - JOUR AB - Using fuzzy set theory, we created a system, that assesses a herb's usefulness for the treatment of tuberculosis, based on ethnobotanical data. We analysed two systems which contain different amount of inputs. The first system contains four inputs, the second one contains six inputs. We used the Takagi-Sugeno-Kanga model. Mamdani model is poor at representation as it needs more fuzzy rules than that of TSK to model a real world system where accuracy is demanded. It has been employed a fuzzy controller, and a fuzzy model, in successfully solving difficult control and modelling problems in practice. It is implemented in the Fuzzy Logic Toolbox in Matlab. The data for inputs are gathered in the database named SOPAT (selection of plants against tuberculosis), which is part of a project coordinated by the Oxford International Biomedical Centre. In this database there could be up to one million plant species. It would be cumbersome to select a remedy from one (or some) of these species looking at the data base one-by-one. By means of the fuzzy set theory this remedy can be chosen very quickly. AD - Section of Physics and Applied Mathematics, Faculty of Chemistry, Silesian University of Technology, Ks M Strzody 9, Gliwice, Poland. gmdudek@polsl.pl AN - 18773936 AU - Dudek, G. AU - Grzywna, Z. J. AU - Willcox, M. L. DA - Dec DO - S0303-2647(08)00178-0 [pii] 10.1016/j.biosystems.2008.05.038 [doi] DP - Nlm ET - 09/09 KW - Algorithms Antitubercular Agents/ classification Databases, Factual Ethnobotany Fuzzy Logic Models, Biological Plants, Medicinal/ classification LA - eng N1 - Dudek, Gabriela Grzywna, Zbigniew J Willcox, Merlin L Comparative Study Research Support, Non-U.S. Gov't Ireland Bio Systems Biosystems. 2008 Dec;94(3):285-9. Epub 2008 Aug 19. PY - 2008 RN - fulltext fulltext_1208 SN - 1872-8324 (Electronic) 0303-2647 (Linking) SP - 285-9 ST - Classification of antituberculosis herbs for remedial purposes by using fuzzy sets T2 - Biosystems TI - Classification of antituberculosis herbs for remedial purposes by using fuzzy sets UR - http://ac.els-cdn.com/S0303264708001780/1-s2.0-S0303264708001780-main.pdf?_tid=60b5fc21b1e4026d50b5c1d377ffa514&acdnat=1345012294_d85e1d01b0a71e7a5bd6ff4083250257 VL - 94 ID - 2526 ER - TY - JOUR AB - BACKGROUND: The current understanding of airborne tuberculosis (TB) transmission is based on classic 1950s studies in which guinea pigs were exposed to air from a tuberculosis ward. Recently we recreated this model in Lima, Peru, and in this paper we report the use of molecular fingerprinting to investigate patient infectiousness in the current era of HIV infection and multidrug-resistant (MDR) TB. METHODS AND FINDINGS: All air from a mechanically ventilated negative-pressure HIV-TB ward was exhausted over guinea pigs housed in an airborne transmission study facility on the roof. Animals had monthly tuberculin skin tests, and positive reactors were removed for autopsy and organ culture for M. tuberculosis. Temporal exposure patterns, drug susceptibility testing, and DNA fingerprinting of patient and animal TB strains defined infectious TB patients. Relative patient infectiousness was calculated using the Wells-Riley model of airborne infection. Over 505 study days there were 118 ward admissions of 97 HIV-positive pulmonary TB patients. Of 292 exposed guinea pigs, 144 had evidence of TB disease; a further 30 were tuberculin skin test positive only. There was marked variability in patient infectiousness; only 8.5% of 118 ward admissions by TB patients were shown by DNA fingerprinting to have caused 98% of the 125 characterised cases of secondary animal TB. 90% of TB transmission occurred from inadequately treated MDR TB patients. Three highly infectious MDR TB patients produced 226, 52, and 40 airborne infectious units (quanta) per hour. CONCLUSIONS: A small number of inadequately treated MDR TB patients coinfected with HIV were responsible for almost all TB transmission, and some patients were highly infectious. This result highlights the importance of rapid TB drug-susceptibility testing to allow prompt initiation of effective treatment, and environmental control measures to reduce ongoing TB transmission in crowded health care settings. TB infection control must be prioritized in order to prevent health care facilities from disseminating the drug-resistant TB that they are attempting to treat. AD - Department of Infectious Diseases and Immunity, Imperial College London, United Kingdom. rod.escombe@imperial.ac.uk AN - 18798687 AU - Escombe, A. R. AU - Moore, D. A. AU - Gilman, R. H. AU - Pan, W. AU - Navincopa, M. AU - Ticona, E. AU - Martinez, C. AU - Caviedes, L. AU - Sheen, P. AU - Gonzalez, A. AU - Noakes, C. J. AU - Friedland, J. S. AU - Evans, C. A. DA - Sep 30 J2 - PLoS medicine L1 - internal-pdf://3320319453/Escombe-2008-The infectiousness of tuberculosi.pdf LA - eng N1 - T35A107646/PHS HHS/United States Wellcome Trust/United Kingdom Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United States PY - 2008 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1549-1676 (Electronic) SP - e188 ST - The infectiousness of tuberculosis patients coinfected with HIV T2 - PLoS Med TI - The infectiousness of tuberculosis patients coinfected with HIV UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18798687http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2535657/pdf/pmed.0050188.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2535657/pdf/pmed.0050188.pdf VL - 5 ID - 2528 ER - TY - JOUR AB - Minisatellites are highly variable tandem repeats used for over 20 years in humans for DNA fingerprinting. In prokaryotes fingerprinting techniques exploiting VNTR (variable number of tandem repeats) polymorphisms have become widely used recently in bacterial typing. However although many investigations into the mechanisms underlying minisatellite variation in humans have been performed, relatively little is known about the processes that mediate bacterial minisatellite polymorphism. An understanding of this is important since it will influence how the results from VNTR experiments are interpreted. The minisatellites of Mycobacterium tuberculosis are well characterized since they are some of the few polymorphic loci in what is otherwise a very homogeneous organism. Using VNTR results from a well-defined and characterized set of M. tuberculosis strains we show that the repeats at a locus are likely to evolve by stepwise contraction or expansion in the number of repeats. A stochastic continuous-time population mathematical model was developed to simulate the evolution of the repeats. This allowed estimation of the tendency of the repeats to increase or decrease and the rate at which they change. The majority of loci tend to lose rather than gain repeats. All of the loci mutate extremely slowly, with an average rate of 2.3 x 10(-8), which is 350 times slower than that of a set of VNTR repeats with similar diversity observed experimentally in Escherichia coli. This suggests that the VNTR profile of a strain of M. tuberculosis will be indicative of its clonal lineage and will be unlikely to vary in epidemiologically-related strains. AD - Statistics Unit, Statistics, Modelling and Bioinformatics Department, Centre for Infections, Health Protection Agency, 61 Colindale Avenue, London NW9 5EQ, UK. AN - 18458805 AU - Grant, A. AU - Arnold, C. AU - Thorne, N. AU - Gharbia, S. AU - Underwood, A. DA - Jun DO - 10.1007/s00239-008-9104-6 [doi] DP - Nlm ET - 05/07 KW - Evolution, Molecular Minisatellite Repeats Models, Genetic Mutation Mycobacterium tuberculosis/classification/ genetics LA - eng N1 - Grant, Andrew Arnold, Catherine Thorne, Nicola Gharbia, Saheer Underwood, Anthony Research Support, Non-U.S. Gov't Germany Journal of molecular evolution J Mol Evol. 2008 Jun;66(6):565-74. Epub 2008 May 6. PY - 2008 RN - fulltext fulltext_1208 SN - 0022-2844 (Print) 0022-2844 (Linking) SP - 565-74 ST - Mathematical modelling of Mycobacterium tuberculosis VNTR loci estimates a very slow mutation rate for the repeats T2 - J Mol Evol TI - Mathematical modelling of Mycobacterium tuberculosis VNTR loci estimates a very slow mutation rate for the repeats UR - http://www.springerlink.com/content/j2j4v867632868gu/ VL - 66 ID - 2529 ER - TY - JOUR AB - Knowing how to control a pathogen that infects more than one host species is of increasing importance because the incidence of such infections grows with continuing environmental change. Of concern are infections transmitted from wildlife to humans or livestock. To determine which options are available to control a pathogen in these circumstances, we analyze the pathogen invasion matrix for the multihost susceptible-infected-susceptible model. We highlight the importance of both community structure and the column sum or row sum index, an indicator of both force of infection and community stability. We derive a set of guidelines for constructing culling strategies and suggest a hybrid strategy that has the advantages of both the bottom-up and the top-down approaches, which we study in some detail. The analysis holds for an arbitrary number of host species, enabling the analysis of large-scale ecological systems and systems with spatial dimensions. We test the robustness of our methods by making two changes in the structure of the underlying dynamic model, adding direct competition and introducing frequency-dependent infection transmission. In particular, we show that the introduction of an additional host can eliminate the pathogen rather than eliminate the resident host. The discussion is illustrated with a reference to bovine tuberculosis. AD - Department of Computing Science and Mathematics, University of Stirling, Stirling FK9 4LA, Scotland, United Kingdom. j.v.greenman@stir.ac.uk AN - 18771403 AU - Greenman, J. V. AU - Hoyle, A. S. DA - Oct DO - 10.1086/590967 DP - NLM ET - 2008/09/06 IS - 4 J2 - The American naturalist KW - Animals Cattle Disease Reservoirs *Host-Pathogen Interactions Humans Models, Biological Mustelidae Tuberculosis, Bovine/immunology/*microbiology LA - eng N1 - 1537-5323 Greenman, J V Hoyle, A S Journal Article United States Am Nat. 2008 Oct;172(4):576-84. doi: 10.1086/590967. PY - 2008 SN - 0003-0147 SP - 576-84 ST - Exclusion of generalist pathogens in multihost communities T2 - Am Nat TI - Exclusion of generalist pathogens in multihost communities VL - 172 ID - 2945 ER - TY - JOUR AB - We conducted a decision analysis to assess and compare four algorithms for amplified Mycobacterium tuberculosis direct (MTD) testing of respiratory specimens in terms of cost-effectiveness. The most cost-effective strategy was one in which smear-positive specimens but not smear-negative specimens were diluted prior to MTD testing. AD - Johns Hopkins University Center for Tuberculosis Research, 1550 Orleans Street, Room 1M-06, Baltimore, MD 21231, USA. AN - 18799694 AU - Guerra, R. L. AU - Hooper, N. M. AU - Baker, J. F. AU - Alborz, R. AU - Armstrong, D. T. AU - Kiehlbauch, J. A. AU - Conde, M. B. AU - Dorman, S. E. DA - Nov DO - JCM.01682-08 [pii] 10.1128/JCM.01682-08 ET - 09/19 KW - Cost-Benefit Analysis Humans Mycobacterium tuberculosis/genetics/*isolation & purification Nucleic Acid Amplification Techniques/*economics/*methods Tuberculosis, Pulmonary/*diagnosis/microbiology LA - eng N1 - Guerra, Renata L Hooper, Nancy M Baker, James F Alborz, Roya Armstrong, Derek T Kiehlbauch, Julia A Conde, Marcus B Dorman, Susan E D43 TW05574-01/TW/FIC NIH HHS/United States K23AI51528/AI/NIAID NIH HHS/United States U19AI45432/AI/NIAID NIH HHS/United States U2R TW006883/TW/FIC NIH HHS/United States Research Support, N.I.H., Extramural United States Journal of clinical microbiology J Clin Microbiol. 2008 Nov;46(11):3811-2. Epub 2008 Sep 17. PY - 2008 RN - fulltext fulltext_1208 SN - 1098-660X (Electronic) 0095-1137 (Linking) SP - 3811-2 ST - Cost-effectiveness of different strategies for amplified Mycobacterium tuberculosis direct testing for cases of pulmonary tuberculosis T2 - J Clin Microbiol TI - Cost-effectiveness of different strategies for amplified Mycobacterium tuberculosis direct testing for cases of pulmonary tuberculosis UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18799694http://jcm.asm.org/cgi/reprint/46/11/3811.pdfhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2576624/pdf/1682-08.pdf VL - 46 ID - 2530 ER - TY - JOUR AB - The resurgence of multi-drug-resistant tuberculosis in some parts of Europe and North America calls for a mathematical study to assess the impact of the emergence and spread of such strain on the global effort to effectively control the burden of tuberculosis. This paper presents a deterministic compartmental model for the transmission dynamics of two strains of tuberculosis, a drug-sensitive (wild) one and a multi-drug-resistant strain. The model allows for the assessment of the treatment of people infected with the wild strain. The qualitative analysis of the model reveals the following. The model has a disease-free equilibrium, which is locally asymptotically stable if a certain threshold, known as the effective reproduction number, is less than unity. Further, the model undergoes a backward bifurcation, where the disease-free equilibrium coexists with a stable endemic equilibrium. One of the main novelties of this study is the numerical illustration of tri-stable equilibria, where the disease-free equilibrium coexists with two stable endemic equilibrium when the aforementioned threshold is less than unity, and a bi-stable setup, involving two stable endemic equilibria, when the effective reproduction number is greater than one. This, to our knowledge, is the first time such dynamical features have been observed in TB dynamics. Finally, it is shown that the backward bifurcation phenomenon in this model arises due to the exogenous re-infection property of tuberculosis. AD - Department of Mathematics, University of Manitoba, Winnipeg, Manitoba, Canada. gumelab@cc.umanitoba.ca AN - 18616351 AU - Gumel, A. B. AU - Song, B. DA - Jul DP - Nlm ET - 07/12 KW - Algorithms Antitubercular Agents/therapeutic use Disease Outbreaks Drug Resistance, Bacterial Humans Mathematics Models, Statistical Models, Theoretical Mycobacterium tuberculosis/ metabolism Pharmaceutical Preparations Tuberculosis/microbiology/ transmission Tuberculosis, Multidrug-Resistant/ epidemiology/transmission LA - eng N1 - Gumel, Abba B Song, Baojun United States Mathematical biosciences and engineering : MBE Math Biosci Eng. 2008 Jul;5(3):437-55. PY - 2008 RN - fulltext fulltext_1208 SN - 1547-1063 (Print) 1547-1063 (Linking) SP - 437-55 ST - Existence of multiple-stable equilibria for a multi-drug-resistant model of Mycobacterium tuberculosis T2 - Math Biosci Eng TI - Existence of multiple-stable equilibria for a multi-drug-resistant model of Mycobacterium tuberculosis VL - 5 ID - 2531 ER - TY - JOUR AB - This paper presents two new theoretical frameworks to investigate the impact of immigration on the transmission dynamics of tuberculosis. For the basic model, we present new analysis on the existence and stability of equilibria. Then, we use numerical simulations of the model to illustrate the behavior of the system. We apply the model to Canadian reported data on tuberculosis and observe a good agreement between the model prediction and the data. For the extended model, which incorporated the recruitment of the latent and infectious in immigrants to the basic model, we find that the usual threshold condition does not apply and a unique equilibrium exists for all parameter values. This indicates that the disease does not disappear and becomes endemic in host areas. This finding is also supported by numerical simulations with the extended model. Our study suggests that immigrants have a considerable influence on the overall transmission dynamics behavior of tuberculosis. AD - School of Information Engineering, Beijing University of Posts and Telecommunications, 10 Xitucheng Road, Beijing 100876, PR China. AN - 18255113 AU - Jia, Z. W. AU - Tang, G. Y. AU - Jin, Z. AU - Dye, C. AU - Vlas, S. J. AU - Li, X. W. AU - Feng, D. AU - Fang, L. Q. AU - Zhao, W. J. AU - Cao, W. C. DA - May DO - S0040-5809(07)00136-0 [pii] 10.1016/j.tpb.2007.12.007 [doi] DP - Nlm ET - 02/08 KW - Emigration and Immigration Humans Models, Theoretical Tuberculosis/ epidemiology LA - eng N1 - Jia, Zhong-Wei Tang, Gong-You Jin, Zhen Dye, Christopher Vlas, Sake J Li, Xiao-Wen Feng, Dan Fang, Li-Qun Zhao, Wen-Juan Cao, Wu-Chun Research Support, Non-U.S. Gov't United States Theoretical population biology Theor Popul Biol. 2008 May;73(3):437-48. Epub 2007 Dec 27. PY - 2008 RN - fulltext fulltext_1208 SN - 1096-0325 (Electronic) 0040-5809 (Linking) SP - 437-48 ST - Modeling the impact of immigration on the epidemiology of tuberculosis T2 - Theor Popul Biol TI - Modeling the impact of immigration on the epidemiology of tuberculosis UR - http://ac.els-cdn.com/S0040580907001360/1-s2.0-S0040580907001360-main.pdf?_tid=6f3c9e5c3d75a3967a221ea8398403ca&acdnat=1345012518_7316eb0e4e39d2e662facb8eb34c462b VL - 73 ID - 2532 ER - TY - JOUR AB - BACKGROUND: Nearly the entire population of Japan has been vaccinated with Bacillus Calmette-Guerin (BCG), which causes a false-positive result in the tuberculin skin test (TST). The interferon-gamma release assay QuantiFERON-TB Gold (QFT) is a new alternative to the TST that can be used to screen for latent tuberculosis infection and active tuberculosis, as it has no cross-reactivity with BCG. METHODS: We constructed a Markov model to evaluate the cost effectiveness of the QFT for tuberculosis contact screening. The target population is a hypothetical cohort of 1000 immunocompetent 20-year-old individuals who have had contact with sputum-smear-positive pulmonary tuberculosis patients. The analysis was conducted from a societal perspective over the lifetime of a contact. We compared the QFT-alone strategy with the TST followed by QFT (TST/QFT) strategy and the TST-alone strategy. RESULTS: In a base-case analysis, the QFT-alone strategy was dominant ($US 471.54; 28.1099 quality-adjusted life-years [QALYs]), compared with the TST/QFT strategy ($US 500.55; 28.1087 QALYs) and the TST-alone strategy ($US573.98; 28.1079 QALYs). The incremental cost-effectiveness ratio of the QFT-alone strategy was a cost saving of $US23 043.5/QALY gained compared with the TST/QFT strategy. On one-way sensitivity analysis, TST specificity and the prevalence of tuberculosis/latent tuberculosis infection affected the cost effectiveness. The probabilistic analysis showed that the QFT-alone strategy has a 95% chance of being cost effective at a threshold ratio of $US2.10/QALY gained, compared with the TST/QFT strategy. CONCLUSION: The QFT-alone strategy is the most cost effective for tuberculosis contact screening in Japan. AD - Katsushika City Public Health Center, Tokyo, Japan. a-kowada@city.katsushika.lg.jp AN - 18652520 AU - Kowada, A. AU - Takahashi, O. AU - Shimbo, T. AU - Ohde, S. AU - Tokuda, Y. AU - Fukui, T. DP - Nlm ET - 07/26 J2 - Molecular diagnosis & therapy KW - Adult Aged Antitubercular Agents/therapeutic use BCG Vaccine/diagnostic use/ economics Carrier State/diagnosis Contact Tracing Cost-Benefit Analysis False Positive Reactions Humans Interferon-gamma/ blood Markov Chains Mass Screening/ economics/methods Middle Aged Models, Theoretical Sensitivity and Specificity Tuberculin Test/ economics/methods Tuberculosis/ diagnosis/drug therapy LA - eng N1 - Kowada, Akiko Takahashi, Osamu Shimbo, Takuro Ohde, Sachiko Tokuda, Yasuharu Fukui, Tsuguya New Zealand Mol Diagn Ther. 2008;12(4):235-51. PY - 2008 RN - fulltext fulltext_1208 SN - 1177-1062 (Print) 1177-1062 (Linking) SP - 235-51 ST - Cost effectiveness of interferon-gamma release assay for tuberculosis contact screening in Japan T2 - Mol Diagn Ther TI - Cost effectiveness of interferon-gamma release assay for tuberculosis contact screening in Japan VL - 12 ID - 2533 ER - TY - JOUR AB - BACKGROUND: Tuberculosis (TB) in prisons is a major health problem in countries of high and intermediate TB endemicity such as Brazil. For operational reasons, TB control strategies in prisons cannot be compared through population based intervention studies. METHODOLOGY/PRINCIPAL FINDINGS: A mathematical model is proposed to simulate the TB dynamics in prison and evaluate the potential impact on active TB prevalence of several intervention strategies. The TB dynamics with the ongoing program was simulated over a 10 year period in a Rio de Janeiro prison (TB prevalence 4.6 %). Then, a simulation of the DOTS strategy reaching the objective of 70 % of bacteriologically-positive cases detected and 85 % of detected cases cured was performed; this strategy reduced only to 2.8% the average predicted TB prevalence after 5 years. Adding TB detection at entry point to DOTS strategy had no major effect on the predicted active TB prevalence. But, adding further a yearly X-ray mass screening of inmates reduced the predicted active TB prevalence below 1%. Furthermore, according to this model, after applying this strategy during 2 years (three annual screenings), the TB burden would be reduced and the active TB prevalence could be kept at a low level by associating X-ray screening at entry point and DOTS. CONCLUSIONS/SIGNIFICANCE: We have shown that X-ray mass screenings should be considered to control TB in highly endemic prison. Prisons with different levels of TB prevalence could be examined thanks to this model which provides a rational tool for public health deciders. AD - U 707, INSERM, Paris, France. j.legrand@imperial.ac.uk AN - 18461123 AU - Legrand, J. AU - Sanchez, A. AU - Le Pont, F. AU - Camacho, L. AU - Larouze, B. DO - 10.1371/journal.pone.0002100 [doi] DP - Nlm ET - 05/08 KW - Brazil/epidemiology Crowding/ physiopathology Humans Mass Screening Models, Statistical Prisoners/ statistics & numerical data Prisons/standards/ statistics & numerical data Radiography, Thoracic Tuberculosis/epidemiology/ prevention & control/radiography/transmission LA - eng N1 - Legrand, Judith Sanchez, Alexandra Le Pont, Francoise Camacho, Luiz Larouze, Bernard Research Support, Non-U.S. Gov't United States PloS one PLoS One. 2008 May 7;3(5):e2100. PY - 2008 RN - fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e2100 ST - Modeling the impact of tuberculosis control strategies in highly endemic overcrowded prisons T2 - PLoS One TI - Modeling the impact of tuberculosis control strategies in highly endemic overcrowded prisons UR - http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0002100&representation=PDF VL - 3 ID - 2534 ER - TY - JOUR AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD), lung cancer, and tuberculosis are three leading causes of death in China, where prevalences of smoking and solid-fuel use are also high. We aimed to predict the effects of risk-factor trends on COPD, lung cancer, and tuberculosis. METHODS: We used representative data sources to estimate past trends in smoking and household solid-fuel use and to construct a range of future scenarios. We obtained the aetiological effects of risk factors on diseases from meta-analyses of epidemiological studies and from large studies in China. We modelled future COPD and lung cancer mortality and tuberculosis incidence, taking into account the accumulation of hazardous effects of risk factors on COPD and lung cancer over time, and dependency of the risk of tuberculosis infection on the prevalence of disease. We quantified the sensitivity of our results to methods and data choices. FINDINGS: If smoking and solid-fuel use remain at current levels between 2003 and 2033, 65 million deaths from COPD and 18 million deaths from lung cancer are predicted in China; 82% of COPD deaths and 75% of lung cancer deaths will be attributable to the combined effects of smoking and solid-fuel use. Complete gradual cessation of smoking and solid-fuel use by 2033 could avoid 26 million deaths from COPD and 6.3 million deaths from lung cancer; interventions of intermediate magnitude would reduce deaths by 6-31% (COPD) and 8-26% (lung cancer). Complete cessation of smoking and solid-fuel use by 2033 would reduce the projected annual tuberculosis incidence in 2033 by 14-52% if 80% DOTS coverage is sustained, 27-62% if 50% coverage is sustained, or 33-71% if 20% coverage is sustained. INTERPRETATION: Reducing smoking and solid-fuel use can substantially lower predictions of COPD and lung cancer burden and would contribute to effective tuberculosis control in China. AD - Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. AN - 18835640 AU - Lin, H. H. AU - Murray, M. AU - Cohen, T. AU - Colijn, C. AU - Ezzati, M. DA - Oct 25 DO - 10.1016/S0140-6736(08)61345-8 ET - 10/07 J2 - Lancet KW - Air Pollution, Indoor/*adverse effects China/epidemiology Female Humans Lung Neoplasms/epidemiology/*etiology/mortality Male Meta-Analysis as Topic Prevalence Pulmonary Disease, Chronic Obstructive/epidemiology/*etiology/mortality Risk Factors Smoking/*adverse effects/epidemiology Tuberculosis/epidemiology/*etiology LA - eng M3 - Research Support, Non-U.S. Gov't N1 - Lin, Hsien-Ho Murray, Megan Cohen, Ted Colijn, Caroline Ezzati, Majid K08 AI055985-06/AI/NIAID NIH HHS/ England Lancet. 2008 Oct 25;372(9648):1473-83. Epub 2008 Oct 3. PY - 2008 RN - fulltext fulltext_1208 SN - 1474-547X (Electronic) 0140-6736 (Linking) SP - 1473-83 ST - Effects of smoking and solid-fuel use on COPD, lung cancer, and tuberculosis in China: a time-based, multiple risk factor, modelling study T2 - Lancet TI - Effects of smoking and solid-fuel use on COPD, lung cancer, and tuberculosis in China: a time-based, multiple risk factor, modelling study UR - http://www.ncbi.nlm.nih.gov/pubmed/18835640http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652750/pdf/nihms-94728.pdf VL - 372 ID - 2535 ER - TY - JOUR AB - Case detection of an infectious individual and differentiation of infectiveness of a treated patient during two different stages of treatment are recognized as among key factors for the successful control and management of tuberculosis (TB) transmission. In this paper, a dynamic compartmental model is developed that incorporates these factors, and proofs are provided to show that the model's global dynamics are completely characterized by the control reproduction number, and in particular the disease eradication condition in terms of the case detection fraction is obtained, along with some numerical simulations. AD - Xian Jiaotong Univ, Sch Sci, Xian 710049, Peoples R China York Univ, Ctr Dis Modeling, Toronto, ON M3J 1P3, Canada York Univ, Dept Math & Stat, Toronto, ON M3J 1P3, Canada AN - WOS:000261427900016 AU - Liu, L. J. AU - Zhou, Y. C. AU - Wu, J. H. DO - 10.1216/Rmj-2008-38-5-1541 IS - 5 J2 - Rocky Mt J Math KW - tb model case detection relapse treatment m. tuberculosis mycobacterium-tuberculosis drug-resistance infection transmission reinfection epidemics LA - English N1 - Sp. Iss. SI 379wv Times Cited:9 Cited References Count:20 PY - 2008 SN - 0035-7596 SP - 1541-1559 ST - Global Dynamics in a Tb Model Incorporating Case Detection and Two Treatment Stages T2 - Rocky Mountain Journal of Mathematics TI - Global Dynamics in a Tb Model Incorporating Case Detection and Two Treatment Stages UR - ://WOS:000261427900016 https://projecteuclid.org/euclid.rmjm/1222088604 VL - 38 ID - 4846 ER - TY - JOUR AB - A co-epidemic arises when the spread of one infectious disease stimulates the spread of another infectious disease. Recently, this has happened with human immunodeficiency virus (HIV) and tuberculosis (TB). We develop two variants of a coepidemic model of two diseases. We calculate the basic reproduction number (R(0)), the disease-free equilibrium, and the quasi-disease-free equilibria, which we de. ne as the existence of one disease along with the complete eradication of the other disease, and the co-infection equilibria for specific conditions. We determine stability criteria for the disease-free and quasi-disease-free equilibria. We present an illustrative numerical analysis of the HIV-TB co-epidemics in India that we use to explore the effects of hypothetical prevention and treatment scenarios. Our numerical analysis demonstrates that exclusively treating HIV or TB may reduce the targeted epidemic, but can subsequently exacerbate the other epidemic. Our analyses suggest that coordinated treatment efforts that include highly active antiretroviral therapy for HIV, latent TB prophylaxis, and active TB treatment may be necessary to slow the HIV-TB co-epidemic. However, treatment alone may not be sufficient to eradicate both diseases. Increased disease prevention efforts (for example, those that promote condom use) may also be needed to extinguish this co-epidemic. Our simple model of two synergistic infectious disease epidemics illustrates the importance of including the effects of each disease on the transmission and progression of the other disease. AD - Yale Univ, Sch Management, New Haven, CT 06520 USA Los Alamos Natl Lab, Los Alamos, NM 87545 USA Stanford Univ, Dept Management Sci & Engn, Stanford, CA 94305 USA AN - WOS:000263565300004 AU - Long, E. F. AU - Vaidya, N. K. AU - Brandeau, M. L. DA - Nov-Dec DO - 10.1287/opre.1080.0571 IS - 6 J2 - Oper Res KW - united-states india impact therapy models transmission populations prevention hiv/aids driven LA - English N1 - 410gk Times Cited:17 Cited References Count:41 PY - 2008 SN - 0030-364x SP - 1366-1381 ST - Controlling Co-Epidemics: Analysis of HIV and Tuberculosis Infection Dynamics T2 - Operations Research TI - Controlling Co-Epidemics: Analysis of HIV and Tuberculosis Infection Dynamics UR - ://WOS:000263565300004 VL - 56 ID - 4847 ER - TY - JOUR AB - Molecular techniques such as IS6110-RFLP typing and spacer oligonucleotide typing (spoligotyping) have aided in understanding the transmission patterns of Mycobacterium tuberculosis. The degree of clustering of isolates on the basis of genotypes is informative of the extent of transmission in a given geographic area. We analyzed 130 published data sets of M. tuberculosis isolates, each representing a sample of bacterial isolates from a specific geographic region, typed with either or both of the IS6110-RFLP and spoligotyping methods. We explored common features and differences among these samples. Using population models, we found that the presence of large clusters (typically associated with recent transmission) as well as a large number of singletons (genotypes found exactly once in the data set) is consistent with an expanding infectious population. We also estimated the mutation rate of spoligotype patterns relative to IS6110 patterns and found the former rate to be about 10-26% of the latter. This study illustrates the utility of examining the full distribution of genotype cluster sizes from a given region, in the light of population genetic models. AU - Luciani, F. AU - Francis, A. R. AU - Tanaka, M. M. DO - 10.1016/j.meegid.2007.12.004 10.1016/j.meegid.2007.12.004. Epub 2008 Feb 1. IS - 2 KW - *Genotype *Oligonucleotides/chemistry Bacterial Typing Techniques/*methods Cluster Analysis DNA, Bacterial/analysis/genetics Evolution, Molecular Genetics, Population Models, Genetic Mutation Mycobacterium tuberculosis/*genetics/isolation & p Polymorphism, Restriction Fragment Length L1 - file:///C:/Users/James/AppData/Local/Mendeley Ltd/Mendeley Desktop/Downloaded/Luciani-2008-Interpreting genotype cluster siz.pdf PY - 2008 SN - 1567-1348 (Print) 1567-1348 (Linking) SP - 182-190 ST - Interpreting Genotype Cluster Sizes of Mycobacterium tuberculosis Isolates Typed with IS6110 and Spoligotyping T2 - Infect Genet Evol TI - Interpreting Genotype Cluster Sizes of Mycobacterium tuberculosis Isolates Typed with IS6110 and Spoligotyping UR - http://www.ncbi.nlm.nih.gov/pubmed/18243064 http://ac.els-cdn.com/S1567134807001980/1-s2.0-S1567134807001980-main.pdf?_tid=eb5abfc6-d108-11e4-9f77-00000aacb35d&acdnat=1427079876_82a807901e0a64a1115dc893a52728ab VL - 8 ID - 4115 ER - TY - JOUR AU - Magombedze, Gesham AU - Garira, Winston AU - Mwenje, Eddie DO - doi:10.1142/S0218339008002551 PY - 2008 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SP - 357-394 ST - IN-VIVO MATHEMATICAL STUDY OF CO-INFECTION DYNAMICS OF HIV-1 AND MYCOBACTERIUM TUBERCULOSIS T2 - Journal of Biological Systems TI - IN-VIVO MATHEMATICAL STUDY OF CO-INFECTION DYNAMICS OF HIV-1 AND MYCOBACTERIUM TUBERCULOSIS UR - http://www.worldscientific.com/doi/abs/10.1142/S0218339008002551 VL - 16 ID - 2536 ER - TY - JOUR AB - BACKGROUND: Recent approval of interferon-gamma release assays that are more specific for Mycobacterium tuberculosis has given new options for the diagnosis of latent tuberculosis infection (LTBI). OBJECTIVE: To assess the cost-effectiveness of Quanti-FERON-TB Gold (QFT-G) vs. the tuberculin skin test (TST) in diagnosing LTBI in contacts of active TB cases using a decision analytic Markov model. METHODS: Three screening strategies--TST alone, QFT-G alone and sequential screening of TST then QFT-G--were evaluated. The model was further stratified according to ethnicity and bacille Calmette-Guerin (BCG) vaccination status. Data sources included published studies and empirical data. Results were reported in terms of the incremental net monetary benefit (INMB) of each strategy compared with the baseline strategy of TST-based screening in all contacts. RESULTS: The most economically attractive strategy was to administer QFT-G in BCG-vaccinated contacts, and to reserve TST for all others (INMB CA$3.70/contact). The least cost-effective strategy was QFT-G for all contacts, which resulted in an INMB of CA$-11.50 per contact. Assuming a higher prevalence of recent infection, faster conversion of QFT-G, a higher rate of TB reactivation, reduction in utility or greater adherence to preventive treatment resulted in QFT-G becoming cost-effective in more subgroups. CONCLUSIONS: Selected use of QFT-G appears to be cost-effective if used in a targeted fashion. AD - University of British Columbia, Vancouver, British Columbia, Canada. carlo.marra@ubc.ca AU - Marra, F. AU - Marra, C. A. AU - Sadatsafavi, M. AU - Moran-Mendoza, O. AU - Cook, V. AU - Elwood, R. K. AU - Morshed, M. AU - Brunham, R. C. AU - Fitzgerald, J. M. KW - Adolescent Adult BCG Vaccine Canada Clinical Laboratory Techniques/economics Contact Tracing Cost-Benefit Analysis Humans Interferon-gamma/blood Markov Chains Middle Aged Sensitivity and Specificity Tuberculin Test/economics Tuberculosis/diagnosis Vaccination N1 - LR: 20111117; JID: 9706389; 0 (BCG Vaccine); 82115-62-6 (Interferon-gamma); ppublish PY - 2008 RN - fulltext fulltext_1208 SN - 1027-3719; 1027-3719 SP - 1414-1424 ST - Cost-effectiveness of a new interferon-based blood assay, QuantiFERON-TB Gold, in screening tuberculosis contacts T2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease TI - Cost-effectiveness of a new interferon-based blood assay, QuantiFERON-TB Gold, in screening tuberculosis contacts VL - 12 Y2 - Dec ID - 2537 ER - TY - JOUR AB - A method for estimating the parameters of a model describing the main specifics of tuberculosis transmission in Russia is constructed in the paper. The method presented here allows one to take into account the difference of social and economic characteristics in the regions and the quality of work of antituberculous centers. The dynamics of the main epidemiological indices under possible changes of both socioeconomic characteristics and the quality of work of antituberculous centers is simulated. The results obtained show that an improvement in economic conditions may positively influence the epidemic situation diminishing the prevalence of disease. Regions with high epidemiological indices are the most sensitive to changes. AD - [Melnichenko, O. A.; Romanyukha, A. A.] Moscow MV Lomonosov State Univ, Dept Numer Math & Cybernet, Moscow 119992, Russia. Melnichenko, OA (reprint author), Moscow MV Lomonosov State Univ, Dept Numer Math & Cybernet, Moscow 119992, Russia. AN - WOS:000257264100004 AU - Melnichenko, O. A. AU - Romanyukha, A. A. DO - 10.1515/rjnamm.2008.004 IS - 1 J2 - Russ. J. Numer. Anal. Math. Model KW - Engineering Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: 320VV Times Cited: 2 Cited Reference Count: 7 Melnichenko, O. A. Romanyukha, A. A. 2 1 4 Walter de gruyter & co Berlin PY - 2008 SN - 0927-6467 SP - 63-75 ST - A model of tuberculosis epidemiology: estimation of parameters and analysis of factors influencing the dynamics of an epidemic process T2 - Russian Journal of Numerical Analysis and Mathematical Modelling TI - A model of tuberculosis epidemiology: estimation of parameters and analysis of factors influencing the dynamics of an epidemic process UR - ://WOS:000257264100004 VL - 23 ID - 6026 ER - TY - JOUR AB - BACKGROUND: Numerous patient and healthcare system-related delays contribute to the overall delay experienced by patients from onset of TB symptoms to diagnosis and treatment. Such delays are critical as infected individuals remain untreated in the community, providing more opportunities for transmission of the disease and adversely affecting the epidemic. METHODOLOGY/PRINCIPAL FINDINGS: We present an analysis of the factors that contribute to the overall delay in TB diagnosis and treatment, in a resource-poor setting. Impact on the distribution of diagnostic delay times was assessed for various factors, the sensitivity of the diagnostic method being found to be the most significant. A linear relationship was found between the sensitivity of the test and the predicted mean delay time, with an increase in test sensitivity resulting in a reduced mean delay time and a reduction in the drop-out rate. CONCLUSIONS/SIGNIFICANCE: The results show that in a developing country a number of delay factors, particularly the low sensitivity of the initial sputum smear microscopy test, potentially increase total diagnostic delay times experienced by TB patients significantly. The results reinforce the urgent need for novel diagnostic methods, both for smear positive and negative TB, that are highly sensitive, accessible and point of care, in order to reduce mean delay times. AD - DST/NRF Centre of Excellence for Epidemiological Modelling and Analysis (SACEMA), Stellenbosch University, Western Cape, Republic of South Africa. AN - 18398459 AU - Millen, S. J. AU - Uys, P. W. AU - Hargrove, J. AU - van Helden, P. D. AU - Williams, B. G. DO - 10.1371/journal.pone.0001933 [doi] DP - Nlm ET - 04/10 KW - Antitubercular Agents/therapeutic use Community Health Services/organization & administration Computer Simulation Developing Countries Health Services Accessibility Humans Patient Acceptance of Health Care Probability Risk Factors Sensitivity and Specificity Time Factors Tuberculosis/ diagnosis/ transmission LA - eng N1 - Millen, Stephen J Uys, Pieter W Hargrove, John van Helden, Paul D Williams, Brian G Research Support, Non-U.S. Gov't United States PloS one PLoS One. 2008 Apr 9;3(4):e1933. PY - 2008 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e1933 ST - The effect of diagnostic delays on the drop-out rate and the total delay to diagnosis of tuberculosis T2 - PLoS One TI - The effect of diagnostic delays on the drop-out rate and the total delay to diagnosis of tuberculosis UR - http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0001933&representation=PDF VL - 3 ID - 2538 ER - TY - JOUR AB - SETTING: The expansion of culture has been proposed to aid tuberculosis (TB) control in developing countries. OBJECTIVES: To examine the cost and cost-effectiveness at the Zambian National TB Reference Laboratory of homemade and commercially produced Lowenstein-Jensen culture (HLJ and CLJ) as well as automated and manually read liquid culture (AMGIT and MMGIT). DESIGN: Costs were estimated from the provider's perspective and based on the average monthly throughput. Cost-effectiveness estimates were based on yield during the study period. RESULTS: All techniques show comparable costs per culture (between US$28 and $32). Costs per Mycobacterium tuberculosis specimen detected were respectively US$197, $202, $312 and $340 for MMGIT, AMGIT, CLJ and HLJ. When modelled for the maximum throughput, costs were above US$95 per M. tuberculosis specimen detected for all techniques. When only performed among smear-negative specimens, costs per additionally identified M. tuberculosis would be US$487 for MMGIT and higher for other methods. CONCLUSION: Based on cost-effectiveness grounds, liquid media compare well with conventional solid media, especially where yield of MGIT is substantially higher than that of LJ media. The results indicate high overall costs per culture; the expansion of culture to decentralised levels with lower throughputs may result in even higher costs. AD - Health Economics and Financing Programme, Department of Public Health and Policy, London School of Hygiene & Tropical Medicine, London, UK. dirk.mueller@lshtm.ac.uk AN - 18812051 AU - Mueller, D. H. AU - Mwenge, L. AU - Muyoyeta, M. AU - Muvwimi, M. W. AU - Tembwe, R. AU - McNerney, R. AU - Godfrey-Faussett, P. AU - Ayles, H. M. DA - Oct ET - 09/25 KW - Bacteriological Techniques/*economics Cost-Benefit Analysis/*methods Costs and Cost Analysis Culture Media/economics Developing Countries Humans Mycobacterium tuberculosis/*isolation & purification Tuberculosis, Pulmonary/*diagnosis Zambia LA - eng N1 - Mueller, D H Mwenge, L Muyoyeta, M Muvwimi, M W Tembwe, R McNerney, R Godfrey-Faussett, P Ayles, H M Research Support, Non-U.S. Gov't France The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Int J Tuberc Lung Dis. 2008 Oct;12(10):1196-202. PY - 2008 RN - fulltext fulltext_1208 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 1196-202 ST - Costs and cost-effectiveness of tuberculosis cultures using solid and liquid media in a developing country T2 - Int J Tuberc Lung Dis TI - Costs and cost-effectiveness of tuberculosis cultures using solid and liquid media in a developing country UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18812051 VL - 12 ID - 2539 ER - TY - JOUR AB - We apply singularity analysis to a caricature of the simplified multistrain model of Castillo-Chavez and Feng (J Math Biol 35 (1997) 629-656) for the transmission of tuberculosis and the coupled two-stream vector-based model of Feng and Velasco-Hernandez (J Math Biol 35 (1997) 523-544) to identify values of the parameters for which the system of nonlinear first-order ordinary differential equations describing the model are integrable. A number of combinations of parameters for which the system is integrable are identified. We compare them with the results we obtained by a symmetry analysis in an earlier paper (J Math Anal Appl 333 (2007) 430-449. AD - [Nucci, M. C.] Univ Perugia, Dipartimento Matemat & Informat, I-06123 Perugia, Italy. [Leach, P. G. L.] Univ KwaZulu Natal, Sch Math Sci, ZA-4000 Durban, South Africa. Nucci, MC (reprint author), Univ Perugia, Dipartimento Matemat & Informat, I-06123 Perugia, Italy. nucci@unipg.it; leachp@nu.ac.za AN - WOS:000256889500003 AU - Nucci, M. C. AU - Leach, P. G. L. DA - Mar DO - 10.2991/jnmp.2008.15.1.3 IS - 1 J2 - J. Nonlinear Math. Phys. KW - ordinary differential-equations configurational invariants symmetries painleve Mathematics Physics L1 - internal-pdf://2961992493/Nucci-2008-Singularity analysis and integrabil.pdf LA - English M3 - Article N1 - ISI Document Delivery No.: 315OO Times Cited: 1 Cited Reference Count: 16 Nucci, M. C. Leach, P. G. L. Nucci, Maria Clara/B-3588-2012 Nucci, Maria Clara/0000-0003-1453-0988 1 0 2 Atlantis press Paris PY - 2008 SN - 1402-9251 SP - 22-34 ST - Singularity analysis and integrability of a simplified multistrain model for the transmission of tuberculosis and dengue fever T2 - Journal of Nonlinear Mathematical Physics TI - Singularity analysis and integrability of a simplified multistrain model for the transmission of tuberculosis and dengue fever UR - ://WOS:000256889500003 http://www.tandfonline.com/doi/pdf/10.2991/jnmp.2008.15.1.3?needAccess=true VL - 15 ID - 6014 ER - TY - JOUR AU - Okuonghae, Daniel AU - Aihie, Vincent DO - doi:10.1142/S0218339008002344 PY - 2008 RN - fulltext fulltext_1208 SP - 1-31 ST - CASE DETECTION AND DIRECT OBSERVATION THERAPY STRATEGY (DOTS) IN NIGERIA: ITS EFFECT ON TB DYNAMICS T2 - Journal of Biological Systems TI - CASE DETECTION AND DIRECT OBSERVATION THERAPY STRATEGY (DOTS) IN NIGERIA: ITS EFFECT ON TB DYNAMICS UR - http://www.worldscientific.com/doi/abs/10.1142/S0218339008002344 VL - 16 ID - 2540 ER - TY - JOUR AB - To aid the creation of novel antituberculosis (antiTB) compounds, Bayesian models were derived and validated on a data set of 3779 compounds which have been measured for minimum inhibitory concentration (MIC) in the Mycobacterium tuberculosis H37Rv strain. The model development and validation involved exploring six different training sets and 15 fingerprint types which resulted in a total of 90 models, with active compounds defined as those with MIC < 5 microM. The best model was derived using Extended Class Fingerprints of maximum diameter 12 (ECFP_12) and a few global descriptors on a training set derived using Functional Class Fingerprints of maximum diameter 4 (FCFP_4). This model demonstrated very good discriminant ability in general, with excellent discriminant statistics for the training set (total accuracy: 0.968; positive recall: 0.967) and a good predictive ability for the test set (total accuracy: 0.869; positive recall: 0.789). The good predictive ability was maintained when the model was applied to a well-separated test set of 2880 compounds derived from a commercial database (total accuracy: 0.73; positive recall: 0.72). The model revealed several conserved substructures present in the active and inactive compounds which are believed to have incremental and detrimental effects on the MIC, respectively. Strategies for enhancing the repertoire of antiTB compounds with the model, including virtual screening of large databases and combinatorial library design, are proposed. AD - Novartis Institute for Tropical Diseases, 10 Biopolis Road, #05-01 Chromos 138670, Singapore. AN - 19053518 AU - Prathipati, P. AU - Ma, N. L. AU - Keller, T. H. DA - Dec DO - 10.1021/ci800143n [doi] 10.1021/ci800143n [pii] DP - Nlm ET - 12/05 KW - Antitubercular Agents/ chemistry/ pharmacology Bayes Theorem Computer Simulation Databases, Factual Drug Design Drug Discovery/ statistics & numerical data Models, Chemical Mycobacterium tuberculosis/drug effects Quantitative Structure-Activity Relationship LA - eng N1 - Prathipati, Philip Ma, Ngai Ling Keller, Thomas H Validation Studies United States Journal of chemical information and modeling J Chem Inf Model. 2008 Dec;48(12):2362-70. PY - 2008 RN - fulltext fulltext_1208 SN - 1549-9596 (Print) 1549-9596 (Linking) SP - 2362-70 ST - Global Bayesian models for the prioritization of antitubercular agents T2 - J Chem Inf Model TI - Global Bayesian models for the prioritization of antitubercular agents UR - http://pubs.acs.org/doi/abs/10.1021/ci800143n VL - 48 ID - 2541 ER - TY - JOUR AB - During most infections, the population of immune cells known as macrophages are key to taking up and killing bacteria as an integral part of the immune response. However, during infection with Mycobacterium tuberculosis (Mtb), host macrophages serve as the preferred environment for mycobacterial growth. Further, killing of Mtb by macrophages is impaired unless they become activated. Activation is induced by stimulation from bacterial antigens and inflammatory cytokines derived from helper T cells. The key macrophage-activating cytokines in Mtb infection are tumor necrosis factor-alpha (TNF) and interferon (IFN)-gamma. Due to differences in cellular sources and secretion pathways for TNF and IFN-gamma, the possibility of heterogeneous cytokine distributions exists, suggesting that the timing of macrophage activation from these signals may affect activation kinetics and thus impact the outcome of Mtb infection. Here we use a mathematical model to show that negative feedback from production of nitric oxide (the key mediator of mycobacterial killing) that typically optimizes macrophage responses to activating stimuli may reduce effective killing of Mtb. Statistical sensitivity analysis predicts that if TNF and IFN-gamma signals precede infection, the level of negative feedback may have a strong effect on how effectively macrophages kill Mtb. However, this effect is relaxed when IFN-gamma or TNF+IFN-gamma signals are received coincident with infection. Under these conditions, the model suggests that negative feedback induces fast responses and an initial overshoot of nitric oxide production for given doses of TNF and IFN-gamma, favoring killing of Mtb. Together, our results suggest that direct entry of macrophages into a granuloma site (and not distal to it) from lung vascular sources represents a preferred host strategy for mycobacterial control. We examine implications of these results in establishment of latent Mtb infection. (c) 2008 Elsevier Ltd. All rights reserved. AD - Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA AN - WOS:000256212500003 AU - Ray, J. C. J. AU - Wang, J. AU - Chan, J. AU - Kirschner, D. E. DA - May 7 DO - 10.1016/j.jtbi.2008.01.010 IS - 1 J2 - J Theor Biol KW - mathematical model cytokine immune system response time feedback nf-kappa-b necrosis-factor-alpha murine peritoneal-macrophages toll-like receptors interferon-gamma nitric-oxide oxidative stress iron-metabolism gene-expression reactive oxygen LA - English N1 - 305ya Times Cited:16 Cited References Count:64 PY - 2008 SN - 0022-5193 SP - 24-38 ST - The timing of TNF and IFN-gamma signaling affects macrophage activation strategies during Mycobacterium tuberculosis infection T2 - Journal of Theoretical Biology TI - The timing of TNF and IFN-gamma signaling affects macrophage activation strategies during Mycobacterium tuberculosis infection UR - ://WOS:000256212500003 VL - 252 ID - 2240 ER - TY - JOUR AB - OBJECTIVE AND DESIGN: The increased risk for tuberculosis in HIV-infected people has fueled a worldwide resurgence of tuberculosis. A major hindrance to controlling tuberculosis is the long treatment duration, leading to default, jeopardizing cure, and generating drug resistance. We investigated how tuberculosis is impacted by reducing treatment duration alone or combined with enhanced case detection and/or cure under different HIV prevalence levels. METHODS: Our model includes HIV stages I-IV and was calibrated to long-term tuberculosis and HIV data from Kenya. Benefits were assessed in terms of absolute and relative reductions in new tuberculosis cases and deaths. RESULTS: Compared with present-day strategies, at 3-20% HIV prevalence we attain a 6-20% decrease in incidence and mortality in 25 years when reducing treatment duration alone; benefits exceed 300% when combined with increased detection and cure. Benefits vary substantially according to HIV status and prevalence. Challenges arise because in absolute terms the number of infected people and deaths increases dramatically with increasing HIV prevalence, and because the relative efficacy of tuberculosis control policies displays a nonlinear pattern whereby they become less effective on a per capita basis at HIV prevalence levels greater than 15%. Benefits of reducing treatment duration may even be reversed at extreme HIV prevalence levels. Benefits of increasing cure versus detection increase as HIV prevalence increases. CONCLUSION: Reducing tuberculosis treatment duration, alone or in combination with other control strategies, can provide enormous benefits at high HIV prevalence. Tuberculosis control policies need to account for HIV levels because the efficacy of different interventions varies substantially with HIV prevalence. AD - Department of Environmental Science, policy and Management, University of California, Berkeley, California 94720-3114, USA. msanchez@nature.berkeley.edu AN - 18453856 AU - Sanchez, M. S. AU - Lloyd-Smith, J. O. AU - Porco, T. C. AU - Williams, B. G. AU - Borgdorff, M. W. AU - Mansoer, J. AU - Salomon, J. A. AU - Getz, W. M. DA - May 11 DO - 10.1097/QAD.0b013e3282f7cb4b ET - 05/06 J2 - Aids KW - AIDS-Related Opportunistic Infections/diagnosis/*drug therapy/epidemiology/prevention & control Antitubercular Agents/*administration & dosage/therapeutic use Drug Administration Schedule HIV Infections/epidemiology Humans Kenya/epidemiology Models, Biological Prevalence Treatment Outcome Tuberculosis/diagnosis/*drug therapy/epidemiology/prevention & control L1 - internal-pdf://1361299546/Sanchez-2008-Impact of HIV on novel therapies.pdf LA - eng M3 - Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't N1 - Sanchez, Maria S Lloyd-Smith, James O Porco, Travis C Williams, Brian G Borgdorff, Martien W Mansoer, John Salomon, Joshua A Getz, Wayne M England London, England AIDS. 2008 May 11;22(8):963-72. PY - 2008 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1473-5571 (Electronic) 0269-9370 (Linking) SP - 963-72 ST - Impact of HIV on novel therapies for tuberculosis control T2 - AIDS TI - Impact of HIV on novel therapies for tuberculosis control UR - http://www.ncbi.nlm.nih.gov/pubmed/18453856http://graphics.tx.ovid.com/ovftpdfs/FPDDNCGCICCHEG00/fs046/ovft/live/gv025/00002030/00002030-200805110-00007.pdf http://ovidsp.tx.ovid.com/ovftpdfs/FPDDNCIBLEEJED00/fs046/ovft/live/gv025/00002030/00002030-200805110-00007.pdf VL - 22 ID - 2542 ER - TY - JOUR AB - This paper addresses the synergistic interaction between HIV and mycobacterium tuberculosis using a deterministic model, which incorporates many of the essential biological and epidemiological features of the two dis- eases. In the absence of TB infection, the model (HIV-only model) is shown to have a globally asymptotically stable, disease-free equilibrium whenever the associated reproduction number is less than unity and has a unique endemic equilibrium whenever this number exceeds unity. On the other hand, the model with TB alone (TB-only model) undergoes the phenomenon of back- ward bifurcation, where the stable disease-free equilibrium co-exists with a stable endemic equilibrium when the associated reproduction threshold is less than unity. The analysis of the respective reproduction thresholds shows that the use of a targeted HIV treatment (using anti-retroviral drugs) strategy can lead to effective control of HIV provided it reduces the relative infectiousness of individuals treated (in comparison to untreated HIV-infected individuals) below a certain threshold. The full model, with both HIV and TB, is simulated to evaluate the impact of the various treatment strategies. It is shown that the HIV-only treatment strategy saves more cases of the mixed infection than the TB-only strategy. Further, for low treatment rates, the mixed-only strategy saves the least number of cases (of HIV, TB, and the mixed infection) in comparison to the other strategies. Thus, this study shows that if resources are limited, then targeting such resources to treating one of the diseases is more beneficial in reducing new cases of the mixed infection than targeting the mixed infection only diseases. Finally, the universal strategy saves more cases of the mixed infection than any of the other strategies. AD - Department of Mathematics, University of Manitoba, Winnipeg, Manitoba, R3T 2N2, Canada. AN - 18193936 AU - Sharomi, O. AU - Podder, C. N. AU - Gumel, A. B. AU - Song, B. DA - Jan DP - Nlm ET - 01/16 KW - Comorbidity Computer Simulation Disease Outbreaks/ prevention & control/ statistics & numerical data HIV Infections/ epidemiology/ prevention & control/transmission Humans Models, Biological Proportional Hazards Models Risk Assessment/ methods Risk Factors Treatment Outcome Tuberculosis/ epidemiology/ prevention & control/transmission LA - eng N1 - Sharomi, Oluwaseun Podder, Chandra N Gumel, Abba B Song, Baojun Research Support, Non-U.S. Gov't United States Mathematical biosciences and engineering : MBE Math Biosci Eng. 2008 Jan;5(1):145-74. PY - 2008 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1547-1063 (Print) 1547-1063 (Linking) SP - 145-74 ST - Mathematical analysis of the transmission dynamics of HIV/TB coinfection in the presence of treatment T2 - Math Biosci Eng TI - Mathematical analysis of the transmission dynamics of HIV/TB coinfection in the presence of treatment VL - 5 ID - 2544 ER - TY - JOUR AB - BACKGROUND: Travelers to countries with high tuberculosis incidence can acquire infection during travel. We sought to compare four screening interventions for travelers from low-incidence countries, who visit countries with varying tuberculosis incidence. METHODS: Decision analysis model: We considered hypothetical cohorts of 1,000 travelers, 21 years old, visiting Mexico, the Dominican Republic, or Haiti for three months. Travelers departed from and returned to the United States or Canada; they were born in the United States, Canada, or the destination countries. The time horizon was 20 years, with 3% annual discounting of future costs and outcomes. The analysis was conducted from the health care system perspective. Screening involved tuberculin skin testing (post-travel in three strategies, with baseline pre-travel tests in two), or chest radiography post-travel (one strategy). Returning travelers with tuberculin conversion (one strategy) or other evidence of latent tuberculosis (three strategies) were offered treatment. The main outcome was cost (in 2005 US dollars) per tuberculosis case prevented. RESULTS: For all travelers, a single post-trip tuberculin test was most cost-effective. The associated cost estimate per case prevented ranged from $21,406 for Haitian-born travelers to Haiti, to $161,196 for US-born travelers to Mexico. In all sensitivity analyses, the single post-trip tuberculin test remained most cost-effective. For US-born travelers to Haiti, this strategy was associated with cost savings for trips over 22 months. Screening was more cost-effective with increasing trip duration and infection risk, and less so with poorer treatment adherence. CONCLUSION: A single post-trip tuberculin skin test was the most cost-effective strategy considered, for travelers from the United States or Canada. The analysis did not evaluate the use of interferon-gamma release assays, which would be most relevant for travelers who received BCG vaccination after infancy, as in many European countries. Screening decisions should reflect duration of travel, tuberculosis incidence, and commitment to treat latent infection. AD - Respiratory Epidemiology Unit, Montreal Chest Institute, 3650 St, Urbain St,, Montreal, Quebec, H2X 2P4, Canada. michael_tan325@yahoo.com AN - 18534007 AU - Tan, M. AU - Menzies, D. AU - Schwartzman, K. DO - 10.1186/1471-2458-8-201 DP - Nlm ET - 06/07 J2 - BMC public health KW - Adult Canada/epidemiology Cost-Benefit Analysis Decision Support Techniques Disease Outbreaks/ prevention & control Dominican Republic Haiti Humans Incidence Markov Chains Mass Chest X-Ray/economics/statistics & numerical data Mass Screening/ economics/statistics & numerical data Mexico Skin Tests/economics/statistics & numerical data Travel/ statistics & numerical data Tuberculin Test Tuberculosis, Pulmonary/ epidemiology United States/epidemiology LA - eng N1 - Tan, Michael Menzies, Dick Schwartzman, Kevin England BMC Public Health. 2008 Jun 5;8:201. PY - 2008 RN - fulltext fulltext_1208 SN - 1471-2458 (Electronic) 1471-2458 (Linking) SP - 201 ST - Tuberculosis screening of travelers to higher-incidence countries: a cost-effectiveness analysis T2 - BMC Public Health TI - Tuberculosis screening of travelers to higher-incidence countries: a cost-effectiveness analysis UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2443799/pdf/1471-2458-8-201.pdf VL - 8 ID - 2545 ER - TY - JOUR AB - BACKGROUND: Contacts of patients with active tuberculosis ("TB contacts") with a tuberculin skin test (TST) size > or = 5 mm are currently recommended treatment for latent TB infection (LTBI). Knowing the cost-effectiveness of LTBI therapy for specific TB contact subpopulations may improve the use of limited resources by reducing the treatment of persons at low TB risk. OBJECTIVE: To evaluate the cost-effectiveness of LTBI therapy for different TB contact populations defined by important risk factors, and to propose an optimal policy based on different recommendation for each subgroup of contacts. METHODS: A 6-year Markov decision analytic model simulating the quality-adjusted life years (QALYs), number of active TB cases prevented, and costs for hypothetical cohorts of Canadian TB contacts defined by TST size, age group (< 10 y/o or above), ethnicity, closeness of contact, and Bacillus Calmette-Guerin (BCG) vaccination status. RESULTS: For the majority of subgroups, the current policy of preventive therapy in those with positive TST was the most cost-effective. Nevertheless, our analysis determined that LTBI treatment is not cost-effective in nonhousehold Canadian-born (nonaboriginal) or foreign-born contacts age > or = 10 y/o. On the other hand, empirical treatment without screening of all non-BCG-vaccinated household contacts age < 10 y/o appeared cost-effective. Such an optimal approach would result in an incremental net monetary benefit of $25 for each contact investigated for a willingness-to-pay of $50,000/QALY. Results were robust to several alternative assumptions considered in sensitivity analyses. CONCLUSIONS: The current practice of LTBI treatment for TB contacts with a TST size > or = 5 mm is cost-effective. A customized approach based on excluding low risk groups from screening and providing treatment to high risk contacts without screening could improve the performance of the program. AD - Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. AN - 18489519 AU - Tan, M. C. AU - Marra, C. A. AU - Sadatsafavi, M. AU - Marra, F. AU - Moran-Mendoza, O. AU - Moadebi, S. AU - Elwood, R. K. AU - FitzGerald, J. M. DA - Sep-Oct DO - 10.1111/j.1524-4733.2008.00334.x DP - Nlm ET - 05/21 J2 - Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research KW - Adolescent Adult Antitubercular Agents/ economics/therapeutic use British Columbia/epidemiology Child Child, Preschool Contact Tracing/ economics Cost-Benefit Analysis Female Humans Infant Infant, Newborn Male Markov Chains Models, Economic Quality-Adjusted Life Years Risk Factors Sensitivity and Specificity Tuberculin Test Tuberculosis, Pulmonary/drug therapy/ economics/epidemiology/transmission Young Adult LA - eng N1 - Tan, Michael C Marra, Carlo A Sadatsafavi, Mohsen Marra, Fawziah Moran-Mendoza, Onofre Moadebi, Susanne Elwood, R Kevin FitzGerald, J Mark United States Value Health. 2008 Sep-Oct;11(5):842-52. Epub 2008 Jul 15. PY - 2008 RN - fulltext fulltext_1208 SN - 1524-4733 (Electronic) 1098-3015 (Linking) SP - 842-52 ST - Cost-effectiveness of LTBI treatment for TB contacts in British Columbia T2 - Value Health TI - Cost-effectiveness of LTBI treatment for TB contacts in British Columbia UR - http://onlinelibrary.wiley.com/store/10.1111/j.1524-4733.2008.00334.x/asset/j.1524-4733.2008.00334.x.pdf?v=1&t=h6gegr4a&s=6e1abd0fd1fb12eaef44bdb058379457bdea0270 VL - 11 ID - 2546 ER - TY - JOUR AB - In a significant number of instances, an episode of tuberculosis can be attributed to a reinfection event. Because reinfection is more likely in high incidence regions than in regions of low incidence, more tuberculosis (TB) cases due to reinfection could be expected in high-incidence regions than in low-incidence regions. Empirical data from regions with various incidence rates appear to confirm the conjecture that, in fact, the incidence rate due to reinfection only, as a proportion of all cases, correlates with the logarithm of the incidence rate, rather than with the incidence rate itself. A theoretical model that supports this conjecture is presented. A Markov model was used to obtain a relationship between incidence and reinfection rates. It was assumed in this model that the rate of reinfection is a multiple, rho (the reinfection factor), of the rate of first-time infection, lambda. The results obtained show a relationship between the proportion of cases due to reinfection and the rate of incidence that is approximately logarithmic for a range of values of the incidence rate typical of those observed in communities across the globe. A value of rho is determined such that the relationship between the proportion of cases due to reinfection and the logarithm of the incidence rate closely correlates with empirical data. From a purely theoretical investigation, it is shown that a simple relationship can be expected between the logarithm of the incidence rates and the proportions of cases due to reinfection after a prior episode of TB. This relationship is sustained by a rate of reinfection that is higher than the rate of first-time infection and this latter consideration underscores the great importance of monitoring recovered TB cases for repeat disease episodes, especially in regions where TB incidence is high. Awareness of this may assist in attempts to control the epidemic. AD - DST/NRF Centre of Excellence for Excellence in Epidemiological Modelling and Analysis (SACEMA), Stellenbosch University, Stellenbosch, Western Cape 7602, Republic of South Africa. edserve@iafrica.com AN - 18577502 AU - Uys, P. W. AU - van Helden, P. D. AU - Hargrove, J. W. DA - Jan 6 DO - N48G734P015PV1JW [pii] 10.1098/rsif.2008.0184 [doi] DP - Nlm ET - 06/26 KW - Computer Simulation Humans Incidence Markov Chains Models, Theoretical Recurrence Tuberculosis/ epidemiology/ transmission LA - eng N1 - Uys, Pieter W van Helden, Paul D Hargrove, John W England Journal of the Royal Society, Interface / the Royal Society J R Soc Interface. 2009 Jan 6;6(30):11-5. PY - 2008 RN - fulltext fulltext_1208 SN - 1742-5689 (Print) 1742-5662 (Linking) SP - 11-5 ST - Tuberculosis reinfection rate as a proportion of total infection rate correlates with the logarithm of the incidence rate: a mathematical model T2 - J R Soc Interface TI - Tuberculosis reinfection rate as a proportion of total infection rate correlates with the logarithm of the incidence rate: a mathematical model UR - http://rsif.royalsocietypublishing.org/content/6/30/11.full.pdf VL - 6 ID - 2582 ER - TY - JOUR AB - OBJECTIVE: Tumor necrosis factor (TNF) blockade increases the risk of tuberculosis (TB). The purpose of this study was to use Markov modeling to examine the contributions of reactivation of latent tuberculous infection (LTBI) and the progression of new infection with Mycobacterium tuberculosis to active TB due to TNF blockade. These 2 pathogenic mechanisms cannot otherwise be readily distinguished. METHODS: Monte Carlo simulation was used to represent the range of reported values for the incidence of TB associated with infliximab (TNF monoclonal antibody) and etanercept (soluble TNF receptor) therapy. Iterative methods were then used to identify for each pair of incidence rates the Markov model parameters that most accurately represented the distribution of time to onset of TB as reported to the Food and Drug Administration. RESULTS: Modeling revealed an apparent median monthly rate of reactivation of LTBI by infliximab treatment of 20.8%, which was 12.1 times that with etanercept treatment (P<0.001). In contrast, both drugs appeared to pose a high risk of progression of new M tuberculosis infection to active TB. Progression of new infection appeared to cause nearly half of the etanercept-associated cases; it became the predominant cause of infliximab-associated cases only after the first year. CONCLUSION: Despite sharing a common therapeutic target, infliximab and etanercept differ markedly in the rates at which they reactivate LTBI. Confirmation of these findings will require the application of molecular epidemiologic tools to studies of TB in future biologics registries. Hidden Markov modeling and Monte Carlo simulation are powerful tools for revealing otherwise hidden aspects of the pathogenesis of TB. AD - PPD Inc., Washington, DC 20005, USA. robert.wallis@columbia.ppdi.com AN - 18383389 AU - Wallis, R. S. DA - Apr DO - 10.1002/art.23285 [doi] DP - Nlm ET - 04/03 KW - Antibodies, Monoclonal/ adverse effects Carrier State/immunology Humans Immunocompromised Host Immunoglobulin G/ adverse effects Immunologic Factors/ adverse effects Incidence Models, Theoretical Monte Carlo Method Receptors, Tumor Necrosis Factor Rheumatic Diseases/drug therapy Tuberculosis/ chemically induced/epidemiology/ immunology Tumor Necrosis Factor-alpha/ antagonists & inhibitors LA - eng N1 - Wallis, Robert S United States Arthritis and rheumatism Arthritis Rheum. 2008 Apr;58(4):947-52. PY - 2008 RN - fulltext fulltext_1208 SN - 0004-3591 (Print) 0004-3591 (Linking) SP - 947-52 ST - Mathematical modeling of the cause of tuberculosis during tumor necrosis factor blockade T2 - Arthritis Rheum TI - Mathematical modeling of the cause of tuberculosis during tumor necrosis factor blockade UR - http://onlinelibrary.wiley.com/store/10.1002/art.23285/asset/23285_ftp.pdf?v=1&t=h5w2ch1j&s=5239a0816f96e987fece13b26966f1ff1563b8ac VL - 58 ID - 2548 ER - TY - JOUR AB - This article describes the population pharmacokinetics of rifampin in South African pulmonary tuberculosis patients. Three datasets containing 2,913 rifampin plasma concentration-time data points, collected from 261 South African pulmonary tuberculosis patients aged 18 to 72 years and weighing 28.5 to 85.5 kg and receiving regular daily treatment that included administration of rifampin (450 to 600 mg) for at least 10 days, were pooled. A compartmental pharmacokinetic model was developed using nonlinear mixed-effects modeling. Variability in the shape of the absorption curve was described using a flexible transit compartment model, in which a delay in the onset of absorption and a gradually changing absorption rate were modeled as the passage of drug through a chain of hypothetical compartments, ultimately reaching the absorption compartment. A previously described implementation was extended to allow its application to multiple-dosing data. The typical population estimate of oral clearance was 19.2 liters x h(-1), while the volume of distribution was estimated to be 53.2 liters. Interindividual variability was estimated to be 52.8% for clearance and 43.4% for volume of distribution. Interoccasional variability was estimated for CL/F (22.5%) and mean transit time during absorption (67.9%). The use of single-drug formulations was found to increase both the mean transit time (by 104%) and clearance (by 23.6%) relative to fixed-dose-combination use. A strong correlation between clearance and volume of distribution suggested substantial variability in bioavailability, which could have clinical implications, given the dependence of treatment effectiveness on exposure. The final model successfully described rifampin pharmacokinetics in the population studied and is suitable for simulation in this context. AD - Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. AN - 18391026 AU - Wilkins, J. J. AU - Savic, R. M. AU - Karlsson, M. O. AU - Langdon, G. AU - McIlleron, H. AU - Pillai, G. AU - Smith, P. J. AU - Simonsson, U. S. DA - Jun DO - AAC.00461-07 [pii] 10.1128/AAC.00461-07 [doi] DP - Nlm ET - 04/09 KW - Absorption Adolescent Adult Aged Antibiotics, Antitubercular/administration & dosage/ pharmacokinetics/therapeutic use Biological Availability Female Humans Male Metabolic Clearance Rate Middle Aged Models, Biological Rifampin/administration & dosage/ pharmacokinetics/therapeutic use South Africa Tuberculosis, Pulmonary/blood/ drug therapy/microbiology LA - eng N1 - Wilkins, Justin J Savic, Radojka M Karlsson, Mats O Langdon, Grant McIlleron, Helen Pillai, Goonaseelan Smith, Peter J Simonsson, Ulrika S H Research Support, Non-U.S. Gov't United States Antimicrobial agents and chemotherapy Antimicrob Agents Chemother. 2008 Jun;52(6):2138-48. Epub 2008 Apr 7. PY - 2008 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1098-6596 (Electronic) 0066-4804 (Linking) SP - 2138-48 ST - Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption T2 - Antimicrob Agents Chemother TI - Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption UR - http://aac.asm.org/content/52/6/2138.full.pdf VL - 52 ID - 2549 ER - TY - JOUR AB - Tuberculosis (TB) incidence rates vary substantially from regions to regions and from countries to countries. In countries such as Canada where TB incidence rate is low, increasing immigration trends may have significant impact on the TB transmission patterns in these countries. In this study we formulate a deterministic epidemiological model of TB transmission in two demographically distinct populations: Canadian born and foreign born populations, in order to investigate the effects of this demographic distinction on the short-term incidence and long-term transmission dynamics, and with special emphasis on the impact of immigration latent TB cases on the overall TB incidence rate in the whole population. AD - Department of Mathematics, Xi'an Jiaotong University, Xi'an 710049, China. zhouyc@mail.xjtu.edu.cn AN - 18656210 AU - Zhou, Y. AU - Khan, K. AU - Feng, Z. AU - Wu, J. DA - Sep 21 DO - S0022-5193(08)00271-3 [pii] 10.1016/j.jtbi.2008.05.026 [doi] DP - Nlm ET - 07/29 KW - Canada/epidemiology Disease Outbreaks Emigration and Immigration Forecasting Humans Incidence Models, Biological Models, Statistical Mycobacterium tuberculosis Tuberculosis/ epidemiology/transmission LA - eng N1 - Zhou, Yicang Khan, Kamran Feng, Zhilan Wu, Jianhong Research Support, Non-U.S. Gov't Netherlands Journal of theoretical biology J Theor Biol. 2008 Sep 21;254(2):215-28. Epub 2008 May 29. PY - 2008 RN - fulltext fulltext_1208 SN - 1095-8541 (Electronic) 0022-5193 (Linking) SP - 215-28 ST - Projection of tuberculosis incidence with increasing immigration trends T2 - J Theor Biol TI - Projection of tuberculosis incidence with increasing immigration trends UR - http://ac.els-cdn.com/S0022519308002713/1-s2.0-S0022519308002713-main.pdf?_tid=b394a83f5356d185ed29f48e419e68c9&acdnat=1345013792_8d9963f2787708670586453b53dfa93a VL - 254 ID - 2550 ER - TY - BILL AB - Bacterial persistent infections are responsible for a significant amount of the human morbidity and mortality. Unlike acute bacterial infections, it is very difficult to treat persistent bacterial infections (e.g. tuberculosis). Knowledge about the location of pathogenic bacteria during persistent infection will help to treat such conditions by designing novel drugs which can reach such locations. In this study, events of bacterial persistent infections were analyzed using game theory. A game was defined where the pathogen and the host are the two players with a conflict of interest. Criteria for the establishment of Nash equilibrium were calculated for this game. This theoretical model, which is very simple and heuristic, predicts that during persistent infections pathogenic bacteria stay in both intracellular and extracellular compartments of the host. The result of this study implies that a bacterium should be able to survive in both intracellular and extracellular compartments of the host in order to cause persistent infections. This explains why persistent infections are more often caused by intracellular pathogens like Mycobacterium and Salmonella. Moreover, this prediction is in consistence with the results of previous experimental studies. AD - Centre for Infectious Disease Research and Biosafety Laboratories, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India. sandeep@mcbl.iisc.ernet.in AN - 19401783 DA - Jan 1 KW - Models: Biological Game Theory Bacteria Extracellular Space Intracellular Space Humans Bacterial Infections Host-Pathogen Interactions LB - p31798 M1 - 4 PY - 2009 RN - fulltext fulltext_1208 SP - e5383 ST - Location of pathogenic bacteria during persistent infections: insights from an analysis using game theory T2 - PLoS ONE TI - Location of pathogenic bacteria during persistent infections: insights from an analysis using game theory UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=19401783 VL - 4 ID - 2567 ER - TY - BILL AB - The Global Plan to Stop TB calls for significant financial resources to meet the Millennium Development Goals for tuberculosis. However, it is unclear whether the economic benefits of TB control exceed the costs. Using an epidemiological model, we find that the economic benefits of the Global Plan relative to sustained DOTS (a commonly used treatment method) were unambiguously greater than the incremental costs in all nine high-burden countries in Africa and in Afghanistan, Pakistan, and Russia. Benefit-cost ratios of sustaining DOTS at current levels relative to having no DOTS exceeded 1 in all twenty-two high-burden, TB-endemic countries and sub-Saharan Africa. AD - Resources for the Future, Washington, D.C., USA. ramanan@rff.org AN - 19567413 DA - Jan 1 KW - Africa South of the Sahara Directly Observed Therapy Cost-Benefit Analysis Tuberculosis Humans Health Care Costs LB - p30434 M1 - 4 PY - 2009 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SP - w730-42 ST - Global investments in TB control: economic benefits T2 - Health Aff (Millwood) TI - Global investments in TB control: economic benefits UR - http://content.healthaffairs.org/content/28/4/w730.longhttp://content.healthaffairs.org/content/28/4/w730.full.pdf VL - 28 ID - 2575 ER - TY - JOUR AB - The Bill and Melinda Gates Foundation supports an ambitious portfolio of novel vaccines, drug regimens, and diagnostic tools for tuberculosis (TB). We elicited the expected efficacies and improvements of the novel interventions in discussions with the foundations managing their development. Using an age-structured mathematical model of TB, we explored the potential benefits of novel interventions under development and those not yet in the portfolio, focusing on the WHO Southeast Asia region. Neonatal vaccination with the portfolio vaccine decreases TB incidence by 39% to 52% by 2050. Drug regimens that shorten treatment duration and are efficacious against drug-resistant strains reduce incidence by 10-27%. New diagnostics reduce incidence by 13-42%. A triple combination of a portfolio vaccine, drug regimen, and diagnostics reduces incidence by 71%. A short mass vaccination catch-up campaign, not yet in the portfolio, to augment the triple combination, accelerates the decrease, preventing >30% more cases by 2050 than just the triple combination. New vaccines and drug regimens targeted at the vast reservoir of latently infected people, not in the portfolio, would reduce incidence by 37% and 82%, respectively. The combination of preventive latent therapy and a 2-month drug treatment regimen reduces incidence by 94%. Novel technologies in the pipeline would achieve substantial reductions in TB incidence, but not the Stop TB Partnership target for elimination. Elimination will require new delivery strategies, such as mass vaccination campaigns, and new products targeted at latently infected people. AD - Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. AN - 19666590 AU - Abu-Raddad, L. J. AU - Sabatelli, L. AU - Achterberg, J. T. AU - Sugimoto, J. D. AU - Longini, I. M., Jr. AU - Dye, C. AU - Halloran, M. E. DA - Aug 18 DO - 0901720106 [pii] 10.1073/pnas.0901720106 [doi] DP - Nlm ET - 08/12 KW - Antitubercular Agents/ therapeutic use Asia, Southeastern Combined Modality Therapy/methods Disease Progression Humans Immunization Programs Models, Theoretical Prevalence Public Health Reproducibility of Results Time Factors Tuberculosis/diagnosis/drug therapy/ epidemiology/prevention & control Tuberculosis Vaccines/ therapeutic use World Health LA - eng N1 - Abu-Raddad, Laith J Sabatelli, Lorenzo Achterberg, Jerusha T Sugimoto, Jonathan D Longini, Ira M Jr Dye, Christopher Halloran, M Elizabeth T32 HD007543-10/HD/NICHD NIH HHS/United States Research Support, Non-U.S. Gov't United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13980-5. Epub 2009 Aug 3. PY - 2009 RN - fulltext fulltext_1208 SN - 1091-6490 (Electronic) 0027-8424 (Linking) SP - 13980-5 ST - Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics T2 - Proc Natl Acad Sci U S A TI - Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics UR - http://www.pnas.org/content/106/33/13980.full.pdf VL - 106 ID - 2551 ER - TY - JOUR AB - BACKGROUND: A mathematical model was designed to explore the impact of three strategies for better tuberculosis case finding. Strategies included: (1) reducing the number of tuberculosis patients who do not seek care; (2) reducing diagnostic delay; and (3) engaging non-DOTS providers in the referral of tuberculosis suspects to DOTS services in the Indonesian health system context. The impact of these strategies on tuberculosis mortality and treatment outcome was estimated using a mathematical model of the Indonesian health system. METHODS: The model consists of multiple compartments representing logical movement of a respiratory symptomatic (tuberculosis suspect) through the health system, including patient- and health system delays. Main outputs of the model are tuberculosis death rate and treatment outcome (i.e. full or partial cure). We quantified the model parameters for the Jogjakarta province context, using a two round Delphi survey with five Indonesian tuberculosis experts. RESULTS: The model validation shows that four critical model outputs (average duration of symptom onset to treatment, detection rate, cure rate, and death rate) were reasonably close to existing available data, erring towards more optimistic outcomes than are actually reported. The model predicted that an intervention to reduce the proportion of tuberculosis patients who never seek care would have the biggest impact on tuberculosis death prevention, while an intervention resulting in more referrals of tuberculosis suspects to DOTS facilities would yield higher cure rates. This finding is similar for situations where the alternative sector is a more important health resource, such as in most other parts of Indonesia. CONCLUSION: We used mathematical modeling to explore the impact of Indonesian health system interventions on tuberculosis treatment outcome and deaths. Because detailed data were not available regarding the current Indonesian population, we relied on expert opinion to quantify the parameters. The fact that the model output showed similar results to epidemiological data suggests that the experts had an accurate understanding of this subject, thereby reassuring the quality of our predictions. The model highlighted the potential effectiveness of active case finding of tuberculosis patients with limited access to DOTS facilities in the developing country setting. AD - Department of Public Health, Faculty of Medicine, Gadjah Mada University, Jogjakarta, Indonesia. risandono.ahmad@gmail.com AN - 19505296 AU - Ahmad, R. A. AU - Mahendradhata, Y. AU - Cunningham, J. AU - Utarini, A. AU - de Vlas, S. J. DO - 1471-2334-9-87 [pii] 10.1186/1471-2334-9-87 [doi] DP - Nlm ET - 06/10 KW - Computer Simulation Delphi Technique Humans Indonesia/epidemiology Models, Theoretical Outcome Assessment (Health Care) Patient Acceptance of Health Care Tuberculosis/ epidemiology/prevention & control LA - eng N1 - Ahmad, Riris A Mahendradhata, Yodi Cunningham, Jane Utarini, Adi de Vlas, Sake J Research Support, Non-U.S. Gov't England BMC infectious diseases BMC Infect Dis. 2009 Jun 8;9:87. PY - 2009 RN - fulltext fulltext_1208 SN - 1471-2334 (Electronic) 1471-2334 (Linking) SP - 87 ST - How to optimize tuberculosis case finding: explorations for Indonesia with a health system model T2 - BMC Infect Dis TI - How to optimize tuberculosis case finding: explorations for Indonesia with a health system model UR - http://www.biomedcentral.com/1471-2334/9/87 VL - 9 ID - 2552 ER - TY - JOUR AB - BACKGROUND: BCG vaccine protects against the severe forms of tuberculosis (TB) in children. Several low-prevalence countries are reviewing their policy, usually shifting from universal vaccination to vaccination of infants in high-risk groups only. We combined an epidemiologic analysis with a cost-effectiveness analysis to evaluate the cost-effectiveness of targeted strategies. METHODS: We fitted a static model to the data to estimate vaccine efficacy and risk of disease. We applied our method to the Dutch situation, analyzing severe TB cases in high-risk group children age 0-5, between 1996 and 2003. We considered the current strategy targeting immigrant children from high-incidence countries, and a proposed strategy additionally targeting children from 3 lower-incidence, but higher-immigration, countries. RESULTS: In the absence of vaccination, the annual risk of developing severe TB for a child in the current target group is 3/100,000, while BCG vaccination reduces this risk by 73%. Therefore about 9000 children would need to be vaccinated to prevent 1 case. Vaccinating children from high-incidence countries would then cost about Euro 4,500 per discounted disability-adjusted life year averted. In the extended target group, the risk of disease is somewhat lower with a similar vaccine effectiveness, so costs are raised. CONCLUSIONS: The current Dutch BCG strategy, as well as the proposed inclusion of immigrant children from Turkey, Surinam and former Yugoslavia, is on average cost-effective. However, the low number of both vaccinated and unvaccinated severe TB cases leads to broad confidence intervals on vaccine efficacy, highlighting the difficulty associated with decision-making in low-prevalence settings. AD - Department of Infectious Diseases Epidemiology, National Institute for Public Health and the Environment, Bilthoven, The Netherlands. hester.korthals.altes@rivm.nl AN - 19295437 AU - Altes, H. K. AU - Dijkstra, F. AU - Lugner, A. AU - Cobelens, F. AU - Wallinga, J. DO - 10.1097/EDE.0b013e31819e3c1a ET - 03/20 KW - BCG Vaccine/*therapeutic use Child, Preschool Cost-Benefit Analysis Humans Immunization Programs/*economics/methods/organization & administration Infant Infant, Newborn Netherlands/epidemiology *Severity of Illness Index Tuberculosis/epidemiology/physiopathology/*prevention & control LA - eng N1 - Altes, Hester Korthals Dijkstra, Frederika Lugner, Anna Cobelens, Frank Wallinga, Jacco United States Epidemiology (Cambridge, Mass.) Epidemiology. 2009 Jul;20(4):562-8. PY - 2009 RN - fulltext fulltext_1208 SN - 1531-5487 (Electronic) 1044-3983 (Linking) SP - 562-568 ST - Targeted BCG vaccination against severe tuberculosis in low-prevalence settings: epidemiologic and economic assessment T2 - Epidemiology TI - Targeted BCG vaccination against severe tuberculosis in low-prevalence settings: epidemiologic and economic assessment UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19295437http://graphics.tx.ovid.com/ovftpdfs/FPDDNCGCAGHAJF00/fs047/ovft/live/gv024/00001648/00001648-200907000-00015.pdf VL - 20 ID - 2553 ER - TY - JOUR AB - The strengths and limitations of using homogeneous mixing and heterogeneous mixing epidemic models are explored in the context of the transmission dynamics of tuberculosis. The focus is on three types of models: a standard incidence homogeneous mixing model, a non-homogeneous mixing model that incorporates 'household' contacts, and an age-structured model. The models are parameterized using demographic and epidemiological data and the patterns generated from these models are compared. Furthermore, the effects of population growth, stochasticity, clustering of contacts, and age structure on disease dynamics are explored. This framework is used to asses the possible causes for the observed historical decline of tuberculosis notifications. AD - School of Science and Technology, Universidad Metropolitana, San Juan 00928-1150, Puerto Rico. juan.p.aparicio@gmail.com AN - 19364150 AU - Aparicio, J. P. AU - Castillo-Chavez, C. DA - Apr DP - Nlm ET - 04/15 KW - Age Distribution Biometry/ methods Computer Simulation Data Interpretation, Statistical Disease Outbreaks/ statistics & numerical data Humans Incidence Models, Biological Population Dynamics Proportional Hazards Models Risk Assessment/methods Risk Factors Survival Analysis Survival Rate Tuberculosis/ mortality LA - eng N1 - Aparicio, Juan Pablo Castillo-Chavez, Carlos Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United States Mathematical biosciences and engineering : MBE Math Biosci Eng. 2009 Apr;6(2):209-37. PY - 2009 RN - fulltext fulltext_1208 SN - 1547-1063 (Print) 1547-1063 (Linking) SP - 209-37 ST - Mathematical modelling of tuberculosis epidemics T2 - Math Biosci Eng TI - Mathematical modelling of tuberculosis epidemics VL - 6 ID - 2554 ER - TY - JOUR AB - Extensively drug-resistant tuberculosis (XDR TB) has been detected in most provinces of South Africa, particularly in the KwaZulu-Natal province where several hundred cases have been reported since 2004. We analyzed the transmission dynamics of XDR TB in the region using mathematical models, and observed that nosocomial transmission clusters of XDR TB may emerge into community-based epidemics under the public health conditions of many South African communities. The effective reproductive number of XDR TB in KwaZulu-Natal may be around 2. Intensified community-based case finding and therapy appears critical to curtailing transmission. In the setting of delayed disease presentation and high system demand, improved diagnostic approaches may need to be employed in community-based programs rather than exclusively at tertiary hospitals. Using branching process mathematics, we observed that early, community-based drug-susceptibility testing and effective XDR therapy could help curtail ongoing transmission and reduce the probability of XDR TB epidemics in neighboring territories. AD - Tugela Ferry Care and Research Collaboration, Tugela Ferry, KwaZulu-Natal 3010, South Africa. sanjay.basu@yale.edu AN - 19365076 AU - Basu, S. AU - Friedland, G. H. AU - Medlock, J. AU - Andrews, J. R. AU - Shah, N. S. AU - Gandhi, N. R. AU - Moll, A. AU - Moodley, P. AU - Sturm, A. W. AU - Galvani, A. P. DA - May 5 DO - 0812472106 [pii] 10.1073/pnas.0812472106 [doi] DP - Nlm ET - 04/15 KW - Disease Outbreaks/ prevention & control Humans Models, Biological South Africa/epidemiology Tuberculosis, Multidrug-Resistant/ epidemiology/ prevention & control/transmission L1 - internal-pdf://0349054559/Basu-2009-Averting epidemics of extensively dr.pdf LA - eng N1 - Basu, Sanjay Friedland, Gerald H Medlock, Jan Andrews, Jason R Shah, N Sarita Gandhi, Neel R Moll, Anthony Moodley, Prashini Sturm, A Willem Galvani, Alison P R36/PHS HHS/United States T32/PHS HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2009 May 5;106(18):7672-7. Epub 2009 Apr 13. PY - 2009 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1091-6490 (Electronic) 0027-8424 (Linking) SP - 7672-7 ST - Averting epidemics of extensively drug-resistant tuberculosis T2 - Proc Natl Acad Sci U S A TI - Averting epidemics of extensively drug-resistant tuberculosis UR - http://www.pnas.org/content/106/18/7672.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2678614/pdf/zpq7672.pdf VL - 106 ID - 2555 ER - TY - JOUR AB - The evolution of Mycobacterium tuberculosis presents several challenges for public health. HIV and resistance to antimycobacterial medications have evolutionary implications for how Mycobacterium tuberculosis will evolve, as these factors influence the host environment and transmission dynamics of tuberculosis strains. We present an evolutionary invasion analysis of tuberculosis that characterizes the direction of tuberculosis evolution in the context of different natural and human-driven selective pressures, including changes in tuberculosis treatment and HIV prevalence. We find that the evolution of tuberculosis virulence can be affected by treatment success rates, the relative transmissibility of emerging strains, the rate of reactivation from latency among hosts, and the life expectancy of hosts. We find that the virulence of tuberculosis strains may also increase as a consequence of rising HIV prevalence, requiring faster case detection strategies in areas where the epidemics of HIV and tuberculosis collide. AD - Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College Street, New Haven, CT 06520, USA. sanjay.basu@yale.edu AN - 19172358 AU - Basu, S. AU - Galvani, A. P. DO - 10.1007/s11538-009-9394-x KW - *Biological Evolution Drug Resistance, Bacterial/genetics HIV Infections/complications Humans Mathematical Concepts Mutation Mycobacterium tuberculosis/drug effects/genetics/*pathogenicity Selection, Genetic Tuberculosis/complications/drug therapy/*microbiology Virulence/genetics LA - eng N1 - Basu, Sanjay Galvani, Alison P United States Bulletin of mathematical biology Bull Math Biol. 2009 Jul;71(5):1073-88. Epub 2009 Jan 27. PY - 2009 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1522-9602 (Electronic) 0092-8240 (Linking) SP - 1073-1088 ST - The evolution of tuberculosis virulence T2 - Bulletin of Mathematical Biology TI - The evolution of tuberculosis virulence UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19172358http://www.springerlink.com/content/a214u21283449170/http://www.springerlink.com/content/a214u21283449170/?MUD=MP https://link.springer.com/article/10.1007%2Fs11538-009-9394-x VL - 71 ID - 2556 ER - TY - JOUR AB - BACKGROUND: Isoniazid preventive treatment (IPT) has been recommended for human immunodeficiency virus (HIV) infected individuals. OBJECTIVE/DESIGN: We used a mathematical model to simulate the benefits and risks of preventive treatment delivered through antiretroviral (ARV) clinics using clinical data from Botswana. RESULTS: Preventive treatment was found to reduce the incidence of tuberculosis (TB) by at least 12 cases per 100000 population per year versus the scenario without such treatment over a 50-year simulation. Isoniazid (INH) resistant TB was observed to increase by <1% per year, even when using pessimistic assumptions about resistance emergence. The use of tuberculin skin testing had little impact as a screening procedure, while secondary treatment was observed to nearly double the impact of a preventive treatment program. Regardless of whether or not preventive treatment was implemented, INH-resistant TB rose in the context of increasing HIV prevalence, but was minimally amplified by preventive treatment itself. CONCLUSIONS: IPT programs implemented through ARV clinics may be effective at reducing TB incidence. The resistance contribution of IPT appears unlikely to supersede its overall incidence and mortality benefits. AD - Department of Epidemiology & Public Health, Yale University School of Medicine, New Haven, Connecticut, USA. sanjay.basu@yale.edu AN - 19383201 AU - Basu, S. AU - Maru, D. AU - Poolman, E. AU - Galvani, A. DA - May ET - 04/23 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Anti-Retroviral Agents/*therapeutic use Antitubercular Agents/*therapeutic use Botswana/epidemiology Drug Therapy, Combination HIV Infections/complications/epidemiology/*prevention & control Hospitals, Special Humans Incidence Mass Screening/methods Models, Theoretical *Practice Guidelines as Topic Prevalence Primary Prevention/*standards Secondary Prevention/*standards Treatment Outcome Tuberculosis/epidemiology/*prevention & control L1 - internal-pdf://0848659591/s21.pdf LA - eng M3 - Comparative Study N1 - Basu, S Maru, D Poolman, E Galvani, A France Int J Tuberc Lung Dis. 2009 May;13(5):652-8. PY - 2009 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 652-8 ST - Primary and secondary tuberculosis preventive treatment in HIV clinics: simulating alternative strategies T2 - Int J Tuberc Lung Dis TI - Primary and secondary tuberculosis preventive treatment in HIV clinics: simulating alternative strategies UR - http://www.ncbi.nlm.nih.gov/pubmed/19383201 VL - 13 ID - 2557 ER - TY - JOUR AB - A two strain tuberculosis model with treatment which allows TB patients with the drug sensitive of strain Mycobacterium tuberculosis to be cured is presented. The model is further extended to incorporate quarantine for active TB cases with multi?drug resistant TB strains. The model assumes that latently infected individuals develop active disease as a result of endogenous activation and exogenous reinfection. Qualitative analysis of the model including positivity, boundedness and persistence of solutions are presented. The thresholds and equilibria quantities for the models are determined and stability of the solution is analyzed. From the study we conclude that quarantine of the multi?drug resistant tuberculosis cases reduces the multi?drug resistant tuberculosis induced reproduction number to values below unit, thus this intervention strategy can control the development of multi?drug resistant tuberculosis epidemic. Also effective chemoprophylaxis and treatment of infectives result in a reduction of multi?drug resistant tuberculosis cases since most multi?drug resistant tuberculosis cases are a result of inappropriate treatment. AU - Bhunu, C. P. AU - Garira, W. DA - 2009/01/01 DO - 10.3846/1392-6292.2009.14.291-312 L1 - internal-pdf://0181572430/Bhunu-2009-A two strain tuberculosis transmiss.pdf PY - 2009 RN - fulltext fulltext_1208 SN - 1392-6292 SP - 291-312 ST - A two strain tuberculosis transmission model with therapy and quarantine T2 - Mathematical Modelling and Analysis TI - A two strain tuberculosis transmission model with therapy and quarantine UR - http://www.tandfonline.com/doi/abs/10.3846/1392-6292.2009.14.291-312 http://www.tandfonline.com/doi/pdf/10.3846/1392-6292.2009.14.291-312?needAccess=true VL - 14 Y2 - 2012/08/10 ID - 2558 ER - TY - JOUR AB - An HIV/AIDS and TB coinfection model which considers antiretroviral therapy for the AIDS cases and treatment of all forms of TB, i.e., latent and active forms of TB, is presented. We begin by presenting an HIV/AIDS-TB coinfection model and analyze the TB and HIV/AIDS submodels separately without any intervention strategy. The TB-only model is shown to exhibit backward bifurcation when its corresponding reproduction number is less than unity. On the other hand, the HIV/AIDS-only model has a globally asymptotically stable disease-free equilibrium when its corresponding reproduction number is less than unity. We proceed to analyze the full HIV-TB coinfection model and extend the model to incorporate antiretroviral therapy for the AIDS cases and treatment of active and latent forms of TB. The thresholds and equilibria quantities for the models are determined and stabilities analyzed. From the study we conclude that treatment of AIDS cases results in a significant reductions of numbers of individuals progressing to active TB. Further, treatment of latent and active forms of TB results in delayed onset of the AIDS stage of HIV infection. AD - Modeling Biomedical Systems Research Group, Department of Applied Mathematics, National University of Science and Technology, P.O. Box AC 939 Ascot, Bulawayo, Zimbabwe. cpbhunu1762@nust.ac.zw AN - 19475456 AU - Bhunu, C. P. AU - Garira, W. AU - Mukandavire, Z. DA - Oct DO - 10.1007/s11538-009-9423-9 [doi] DP - Nlm ET - 05/29 KW - AIDS-Related Opportunistic Infections/drug therapy/epidemiology Acquired Immunodeficiency Syndrome/ complications/drug therapy/ epidemiology/transmission Algorithms Anti-Retroviral Agents/therapeutic use Antitubercular Agents/therapeutic use Basic Reproduction Number Computer Simulation HIV Infections/ complications/drug therapy/ epidemiology/transmission HIV Seropositivity/drug therapy/epidemiology/transmission Humans Models, Biological Tuberculosis/ complications/drug therapy/ epidemiology/transmission LA - eng N1 - Bhunu, C P Garira, W Mukandavire, Z Research Support, N.I.H., Extramural United States Bulletin of mathematical biology Bull Math Biol. 2009 Oct;71(7):1745-80. Epub 2009 May 28. PY - 2009 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1522-9602 (Electronic) 0092-8240 (Linking) SP - 1745-80 ST - Modeling HIV/AIDS and tuberculosis coinfection T2 - Bull Math Biol TI - Modeling HIV/AIDS and tuberculosis coinfection UR - http://www.springerlink.com/content/d3g7732k83772416/ VL - 71 ID - 2559 ER - TY - JOUR AB - This paper deals with the global properties of a tuberculosis model with mass action incidence and two differential infectivity. The direct Lyapunov method enables us to prove that the considered model is globally stable: There is always a globally asymptotically stable equilibrium state. Depending on the value of the basic reproduction number R-0, this state can be either endemic (R-0 > 1), or infection-free (R-0 <= 1). Numerical results are provided to illustrate analytical results. (C) 2009 Elsevier B.V. All rights reserved. AD - Univ Douala, Fac Sci, Dept Math & Comp Sci, Lab Appl Math, Douala, Cameroon Univ Yaounde 1, Dept Math & Phys, Natl High Sch Polytech, Yaounde, Cameroon AN - WOS:000266896800033 AU - Bowong, S. AU - Tewa, J. J. DA - Nov DO - 10.1016/j.cnsns.2009.02.017 IS - 11 J2 - Commun Nonlinear Sci KW - lyapunov functions stability epidemiological models tuberculosis global asymptotic stability heterogeneous populations disease transmission lyapunov functions systems dynamics seir LA - English N1 - 457al Times Cited:23 Cited References Count:33 PY - 2009 SN - 1007-5704 SP - 4010-4021 ST - Mathematical analysis of a tuberculosis model with differential infectivity T2 - Communications in Nonlinear Science and Numerical Simulation TI - Mathematical analysis of a tuberculosis model with differential infectivity UR - ://WOS:000266896800033 VL - 14 ID - 4849 ER - TY - JOUR AB - OBJECTIVE: To assess the cost-effectiveness of screening for latent tuberculosis infection (LTBI) using a commercially available detection test and treating individuals at high risk for human immunodeficiency virus (HIV) infection in a middle-income country. DESIGN: We developed a Markov model to evaluate the cost per LTBI case detected, TB case averted and quality-adjusted life year (QALY) gained for a cohort of 1000 individuals at high risk for HIV infection over 20 years. Baseline model inputs for LTBI prevalence were obtained from published literature and cross-sectional data from tuberculosis (TB) screening using QuantiFERON-TB Gold In-Tube (QFT-GIT) testing among sex workers and illicit drug users at high risk for HIV recruited through street outreach in Tijuana, Mexico. Costs are reported in 2007 US dollars. Future costs and QALYs were discounted at 3% per year. Sensitivity analyses were performed to evaluate model robustness. RESULTS: Over 20 years, we estimate the program would prevent 78 cases of active TB and 55 TB-related deaths. The incremental cost per case of LTBI detected was US$730, cost per active TB averted was US$529 and cost per QALY gained was US$108. CONCLUSIONS: In settings of endemic TB and escalating HIV incidence, targeting LTBI screening and treatment among high-risk groups may be highly cost-effective. AD - Division of Global Public Health, School of Medicine, University of California San Diego, San Diego, California 92093-0507, USA. jlburgos@ucsd.edu AU - Burgos, J. L. AU - Kahn, J. G. AU - Strathdee, S. A. AU - Valencia-Mendoza, A. AU - Bautista-Arredondo, S. AU - Laniado-Laborin, R. AU - Castaneda, R. AU - Deiss, R. AU - Garfein, R. S. KW - Comorbidity Cost-Benefit Analysis HIV Infections/epidemiology Humans Markov Chains Mass Screening/economics Mexico/epidemiology Monte Carlo Method Quality-Adjusted Life Years Tuberculosis/diagnosis/economics/epidemiology/therapy N1 - LR: 20110517; GR: R01 DA019829/DA/NIDA NIH HHS/United States; GR: R01 DA019829-03/DA/NIDA NIH HHS/United States; GR: R01 DA023877-02S2/DA/NIDA NIH HHS/United States; GR: R01 DA023877-S1/DA/NIDA NIH HHS/United States; GR: T32 A107384/PHS HHS/United States; GR: T32 AI007384-17/AI/NIAID NIH HHS/United States; GR: T32 AI007384-18/AI/NIAID NIH HHS/United States; GR: T32 DA023356-04/DA/NIDA NIH HHS/United States; JID: 9706389; NIHMS136277; OID: NLM: NIHMS136277; OID: NLM: PMC2763545; ppublish PY - 2009 RN - fulltext fulltext_1208 SN - 1027-3719; 1027-3719 SP - 962-968 ST - Targeted screening and treatment for latent tuberculosis infection using QuantiFERON-TB Gold is cost-effective in Mexico T2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease TI - Targeted screening and treatment for latent tuberculosis infection using QuantiFERON-TB Gold is cost-effective in Mexico UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763545/pdf/nihms136277.pdf VL - 13 Y2 - Aug ID - 2560 ER - TY - JOUR AB - Background: Tuberculosis (TB) remains an important public health problem in Canadian Aboriginal (First Nations and Inuit) communities. The objectives of this study were to predict future disease burden and set feasible targets for the elimination of TB in the First Nations population, using retrospective data and an epidemic model. Methods: Reported TB incidence data (1974-2002), previously published TB meningitis data from the pre-chemotherapy era, and previous estimates of disease risk following infection were used to estimate a trend in the annual risk of infection from 1929 to 2002, and the age-specific prevalence of infection in 2002. A state-transfer, compartmental model was then developed to predict future disease burden. Two scenarios were simulated, with different disease risk parameters. Results: The estimated prevalence of infection in 2002 was 20.9% in scenario 1 and 25.5% in scenario 2. Predicted incidence rates in 2015 were 16.8 per 100 000 and 11.7 per 100 000 for the two scenarios, respectively. The incidence of disease was not tower than 1 per 100 000 for either scenario in 2034, the arbitrarily chosen last year of the model. Conclusions: The goal of eliminating TB among Aboriginal peoples in Canada is a feasible one, but will only be achieved with continued investment in programs designed to control and prevent transmission. Reactivation disease cases may occur for a number of years to come, making rapid elimination a difficult goal. (C) 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. AD - [Clark, Michael] Childrens Hosp Eastern Ontario, Dept Pediat, Ottawa, ON K1H 8L1, Canada. [Cameron, D. William] Univ Ottawa, Dept Med, Div Infect Dis, Ottawa, ON, Canada. Clark, M (reprint author), Childrens Hosp Eastern Ontario, Dept Pediat, 401 Smyth Rd, Ottawa, ON K1H 8L1, Canada. mclar018@uottawa.ca AN - WOS:000264707200018 AU - Clark, M. AU - Cameron, D. W. DA - Mar DO - 10.1016/j.ijid.2008.06.021 IS - 2 J2 - Int. J. Infect. Dis. KW - Tuberculosis model Canada mycobacterium-tuberculosis control strategies tubercle-bacilli calmette-guerin annual risk infection meningitis children alberta disease Infectious Diseases LA - English M3 - Article N1 - ISI Document Delivery No.: 426KM Times Cited: 4 Cited Reference Count: 33 Clark, Michael Cameron, D. William Cameron, Bill/0000-0002-0090-3539 4 0 5 Elsevier sci ltd Oxford PY - 2009 SN - 1201-9712 SP - 220-226 ST - Tuberculosis elimination in the Canadian First Nations population: assessment by a state-transfer, compartmental epidemic model T2 - International Journal of Infectious Diseases TI - Tuberculosis elimination in the Canadian First Nations population: assessment by a state-transfer, compartmental epidemic model UR - ://WOS:000264707200018 VL - 13 ID - 5935 ER - TY - JOUR AB - Recent reports of extensively drug-resistant TB in South Africa have renewed concerns that antibiotic resistance may undermine progress in TB control. We review three major questions for which mathematical models elucidate the epidemiology and control of drug-resistant TB. How is multiple drug-resistant Mycobacterium tuberculosis selected for in individuals exposed to combination chemotherapy? What factors determine the prevalence of drug-resistant TB? Which interventions to prevent the spread of drug-resistant TB are effective and feasible? Models offer insight into the acquisition and amplification of drug resistance, reveal the importance of distinguishing the intrinsic and extrinsic determinants of the reproductive capacity of drug-resistant M. tuberculosis, and demonstrate the cost effectiveness of interventions for drug-resistant TB. These models also highlight knowledge gaps for which new research will improve our ability to project trends of drug resistance and develop more effective policies for its control. AD - Division of Global Health Equity, Brigham and Women's Hospital, Boston, MA, USA and Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. tcohen@hsph.harvard.edu. AN - 20477283 AU - Cohen, T. AU - Dye, C. AU - Colijn, C. AU - Williams, B. AU - Murray, M. DA - Feb DO - 10.1586/17476348.3.1.67 ET - 2009/02/01 IS - 1 J2 - Expert review of respiratory medicine LA - eng N1 - Cohen, Ted Dye, Christopher Colijn, Caroline Williams, Brian Murray, Megan England Expert Rev Respir Med. 2009 Feb;3(1):67-79. doi: 10.1586/17476348.3.1.67. PY - 2009 SN - 1747-6356 (Electronic) 1747-6348 (Linking) SP - 67-79 ST - Mathematical models of the epidemiology and control of drug-resistant TB T2 - Expert Rev Respir Med TI - Mathematical models of the epidemiology and control of drug-resistant TB UR - http://www.ncbi.nlm.nih.gov/pubmed/20477283 VL - 3 ID - 4501 ER - TY - JOUR AB - Metabolism is central to cell physiology, and metabolic disturbances play a role in numerous disease states. Despite its importance, the ability to study metabolism at a global scale using genomic technologies is limited. In principle, complete genome sequences describe the range of metabolic reactions that are possible for an organism, but cannot quantitatively describe the behaviour of these reactions. We present a novel method for modeling metabolic states using whole cell measurements of gene expression. Our method, which we call E-Flux (as a combination of flux and expression), extends the technique of Flux Balance Analysis by modeling maximum flux constraints as a function of measured gene expression. In contrast to previous methods for metabolically interpreting gene expression data, E-Flux utilizes a model of the underlying metabolic network to directly predict changes in metabolic flux capacity. We applied E-Flux to Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). Key components of mycobacterial cell walls are mycolic acids which are targets for several first-line TB drugs. We used E-Flux to predict the impact of 75 different drugs, drug combinations, and nutrient conditions on mycolic acid biosynthesis capacity in M. tuberculosis, using a public compendium of over 400 expression arrays. We tested our method using a model of mycolic acid biosynthesis as well as on a genome-scale model of M. tuberculosis metabolism. Our method correctly predicts seven of the eight known fatty acid inhibitors in this compendium and makes accurate predictions regarding the specificity of these compounds for fatty acid biosynthesis. Our method also predicts a number of additional potential modulators of TB mycolic acid biosynthesis. E-Flux thus provides a promising new approach for algorithmically predicting metabolic state from gene expression data. AD - Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America. C.Colijn@bristol.ac.uk AN - 19714220 AU - Colijn, C. AU - Brandes, A. AU - Zucker, J. AU - Lun, D. S. AU - Weiner, B. AU - Farhat, M. R. AU - Cheng, T. Y. AU - Moody, D. B. AU - Murray, M. AU - Galagan, J. E. DA - Aug DO - 10.1371/journal.pcbi.1000489 [doi] DP - Nlm ET - 08/29 KW - Algorithms Cluster Analysis Computational Biology/methods Fatty Acids/chemistry Gene Expression Profiling/ methods Gene Expression Regulation Gene Expression Regulation, Bacterial Genome, Bacterial Metabolic Networks and Pathways/genetics Models, Biological Models, Statistical Mycobacterium tuberculosis/ metabolism Mycolic Acids/ chemistry Reproducibility of Results Software LA - eng N1 - Colijn, Caroline Brandes, Aaron Zucker, Jeremy Lun, Desmond S Weiner, Brian Farhat, Maha R Cheng, Tan-Yun Moody, D Branch Murray, Megan Galagan, James E 1U19AI076217/AI/NIAID NIH HHS/United States HHSN 26620040000IC/PHS HHS/United States R01 071155/PHS HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States PLoS computational biology PLoS Comput Biol. 2009 Aug;5(8):e1000489. Epub 2009 Aug 28. PY - 2009 RN - fulltext fulltext_1208 SN - 1553-7358 (Electronic) 1553-734X (Linking) SP - e1000489 ST - Interpreting expression data with metabolic flux models: predicting Mycobacterium tuberculosis mycolic acid production T2 - PLoS Comput Biol TI - Interpreting expression data with metabolic flux models: predicting Mycobacterium tuberculosis mycolic acid production UR - http://www.ploscompbiol.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pcbi.1000489&representation=PDF VL - 5 ID - 2561 ER - TY - JOUR AB - BACKGROUND: Interferon gamma release assays (IGRAs) offer alternatives to tuberculin skin tests (TSTs) for diagnosing latent tuberculosis infection (LTBI). Unlike TSTs, IGRAs require only a single patient visit and are not affected by prior BCG vaccination, providing greater specificity. Of 2 Food and Drug Administration-approved IGRAs, the newer QuantiFERON-TB Gold in Tube test (QFT-GIT) requires less manual processing time than the QuantiFERON-TB Gold test (QFT-G). We compared the cost-effectiveness of the QFT-G, QFT-GIT, and TST for detecting LTBI in new health care workers (HCWs). METHODS: A Markov state-transition decision analytic model using the societal perspective and lifetime horizon was constructed to compare costs and quality-adjusted life-years (QALYs) associated with the 3 strategies for hypothetical 35-year-old HCWs with or without prior BCG vaccination. Direct and indirect costs and probabilities were based on manufacturer data, national Veterans Health Administration records, and the published literature. Future costs and QALYs were discounted at 3% per year. RESULTS: Both IGRAs were more effective and less costly than the TST, whether or not the HCW had been vaccinated with BCG previously. The incremental cost-effectiveness ratio of the QFT-G compared with the QFT-GIT was $14,092/QALY for non-BCG-vaccinated HCWs and $103,047/QALY for BCG-vaccinated HCWs. There was no prevalence of LTBI at which the TST became the most effective or least costly strategy. If the sensitivity of the QFT-GIT exceeds that of the QFT-G, then the QFT-GIT is the most effective and least costly strategy. CONCLUSION: Use of the QFT-G and QFT-GIT leads to superior clinical outcomes and lower costs than the TST and should be considered in screening non-BCG-vaccinated and BCG-vaccinated new HCWs for LTBI. AD - Division of Infectious Diseases, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Box 670560, Cincinnati, OH 45267, USA. deperiom@hotmail.com AU - de Perio, M. A. AU - Tsevat, J. AU - Roselle, G. A. AU - Kralovic, S. M. AU - Eckman, M. H. DO - 10.1001/archinternmed.2008.524 KW - Antigens, Bacterial Cost-Benefit Analysis Enzyme-Linked Immunosorbent Assay Female Health Personnel Humans Interferon-gamma/blood/secretion Leukocytes/metabolism Male Mass Screening Sensitivity and Specificity Tuberculin Test/economics Tuberculosis/diagnosis/economics N1 - LR: 20090729; JID: 0372440; 0 (Antigens, Bacterial); 82115-62-6 (Interferon-gamma); CIN: Arch Intern Med. 2009 Jul 27;169(14):1336; author reply 1336-7. PMID: 19636037; ppublish PY - 2009 RN - fulltext fulltext_1208 SN - 1538-3679; 0003-9926 SP - 179-187 ST - Cost-effectiveness of interferon gamma release assays vs tuberculin skin tests in health care workers T2 - Archives of Internal Medicine TI - Cost-effectiveness of interferon gamma release assays vs tuberculin skin tests in health care workers UR - http://archinte.jamanetwork.com/article.aspx?articleid=414724 VL - 169 Y2 - Jan 26 ID - 2563 ER - TY - JOUR AB - OBJECTIVES: There is only limited economic data in head-to head comparison between a whole blood QuantiFERON TB Gold in tube (QFT) and the tuberculin skin test (TST) when screening and treating for latent tuberculosis infection (LTBI), and no published study to date that takes into account the predictive value of the two tests. METHODS: Health and economic outcomes of isoniazid preventive treatment (IPT) of close contacts were compared in a decision tree model to perform a cost-benefit analysis with respect to isoniazid related hepatotoxicity and early post-exposure TB over a 2-y period, using the QFT or TST alone or QFT as a confirmatory test for TST results. RESULTS: Cost of screening and treating for using the QFT alone amounted to euro215.79 per close contact, less than that of dual step-testing (euro227.89) or using TST alone (euro232.58). Savings amounted to euro12,200 or euro16,791 per 1000 close contacts, respectively. QFT based procedures were most sensitive to low compliance with IPT or increasing price. Costs of dual step screening was mostly influenced by cost of treating TB disease. When the progression rate for QFT was lowered to that for the TST in a sensitivity analysis, the relationship between the strategies remained robust. In addition, costs of the QFT strategy decreased to euro165.1, and those of the dual step strategy to euro218.4. CONCLUSION: IPT on the basis of using the QFT assay alone produces less cost and reduces more TB cases than other strategies in a low-incidence setting. These data have implications for the rational implementation of screening strategies in contact investigation. AD - Department of Pneumology, Medical School Hannover (MHH), Carl-Neuberg-Str.1, 30625 Hannover, Germany. Diel.Roland@mhh-hannover.de AU - Diel, R. AU - Schaberg, T. AU - Loddenkemper, R. AU - Welte, T. AU - Nienhaus, A. DO - 10.1016/j.rmed.2009.07.008 KW - Antitubercular Agents/economics/therapeutic use Cost-Benefit Analysis Epidemiologic Methods Germany Humans Isoniazid/economics/therapeutic use Latent Tuberculosis/economics/prevention & control Tuberculin Test/economics/methods N1 - JID: 8908438; 0 (Antitubercular Agents); 54-85-3 (Isoniazid); 2009/06/10 [received]; 2009/07/03 [revised]; 2009/07/10 [accepted]; 2009/08/13 [aheadofprint]; ppublish PY - 2009 RN - fulltext fulltext_1208 SN - 1532-3064; 0954-6111 SP - 1838-1853 ST - Enhanced cost-benefit analysis of strategies for LTBI screening and INH chemoprevention in Germany T2 - Respiratory medicine TI - Enhanced cost-benefit analysis of strategies for LTBI screening and INH chemoprevention in Germany UR - http://ac.els-cdn.com/S0954611109002285/1-s2.0-S0954611109002285-main.pdf?_tid=983026d6-6b36-11e2-b95a-00000aacb35d&acdnat=1359589480_2444bddb27af2d8dcf3910d59109b1c7 VL - 103 Y2 - Dec ID - 2564 ER - TY - JOUR AB - OBJECTIVE: To investigate whether short-term annual declines of 5-10% in the incidence of tuberculosis (TB) can be sustained over the long term by maintaining high case detection rates (CDRs). METHODS: We constructed a compartmental difference-equation model of a TB epidemic in a hypothetical population of constant size with a treatment success rate of 85%. The impact of CDR on TB incidence was then investigated by generating an equilibrium population with no TB case detection and increasing the smear-positive CDR under two scenarios: (i) rapid expansion by 10% per year to a CDR of 80% after 8 years, and (ii) gradual expansion by 1% per year to a CDR of 90% after 90 years. The model was applied in two hypothetical populations: one without HIV and the other with a stable HIV incidence representative of the African Region. The CDR for smear-negative TB was assumed to be a constant fraction of the smear-positive CDR. FINDINGS: In the absence of a TB control programme, the projected annual incidence of TB was 513 cases per 100 000 population, with a point prevalence of 1233 per 100 000 and an annual TB-specific mortality rate of 182 per 100 000. Immediately increasing the TB CDR from 0% to 70% caused a 74% reduction in TB incidence within 10 years. However, once case detection stabilized at any constant level < 80%, projected TB incidence also stabilized. Ten years after a CDR of 70% was reached, the annual decline in TB incidence was < 1.5%, regardless of how rapidly case detection was scaled up and despite wide variation of all model parameters. CONCLUSION: While improved CDRs have a dramatic short-term effect on TB incidence, maintaining those rates, even at current target levels, may not reduce long-term incidence by more than 1-2% per year. TB control programmes and researchers should vigorously pursue improvements in case detection, regardless of current CDRs. AD - Center for Tuberculosis Research, Johns Hopkins University, 1550 Orleans Street, Baltimore, MD 21221, USA. AN - 19551238 AU - Dowdy, D. W. AU - Chaisson, R. E. DA - Apr ET - 06/25 J2 - Bulletin of the World Health Organization KW - Disease Outbreaks HIV Infections/epidemiology/microbiology Humans *Models, Biological Sputum/microbiology Tuberculosis/*epidemiology/microbiology/therapy/virology LA - eng M3 - Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't N1 - Dowdy, David W Chaisson, Richard E K24 AI 01637/AI/NIAID NIH HHS/ T32 GM07309/GM/NIGMS NIH HHS/ Switzerland Bull World Health Organ. 2009 Apr;87(4):296-304. PY - 2009 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1564-0604 (Electronic) 0042-9686 (Linking) SP - 296-304 ST - The persistence of tuberculosis in the age of DOTS: reassessing the effect of case detection T2 - Bull World Health Organ TI - The persistence of tuberculosis in the age of DOTS: reassessing the effect of case detection UR - http://www.ncbi.nlm.nih.gov/pubmed/19551238http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672581/pdf/08-054510.pdf VL - 87 ID - 2565 ER - TY - JOUR AB - BACKGROUND: Culture of Mycobacterium tuberculosis currently represents the closest "gold standard" for diagnosis of tuberculosis (TB), but operational data are scant on the impact and cost-effectiveness of TB culture for human immunodeficiency (HIV-) infected individuals in resource-limited settings. METHODOLOGY/PRINCIPAL FINDINGS: We recorded costs, laboratory results, and dates of initiating TB therapy in a centralized TB culture program for HIV-infected patients in Rio de Janeiro, Brazil, constructing a decision-analysis model to estimate the incremental cost-effectiveness of TB culture from the perspective of a public-sector TB control program. Of 217 TB suspects presenting between January 2006 and March 2008, 33 (15%) had culture-confirmed active tuberculosis; 23 (70%) were smear-negative. Among smear-negative, culture-positive patients, 6 (26%) began TB therapy before culture results were available, 11 (48%) began TB therapy after culture result availability, and 6 (26%) did not begin TB therapy within 180 days of presentation. The cost per negative culture was US$17.52 (solid media)-$23.50 (liquid media). Per 1,000 TB suspects and compared with smear alone, TB culture with solid media would avert an estimated eight TB deaths (95% simulation interval [SI]: 4, 15) and 37 disability-adjusted life years (DALYs) (95% SI: 13, 76), at a cost of $36 (95% SI: $25, $50) per TB suspect or $962 (95% SI: $469, $2642) per DALY averted. Replacing solid media with automated liquid culture would avert one further death (95% SI: -1, 4) and eight DALYs (95% SI: -4, 23) at $2751 per DALY (95% SI: $680, dominated). The cost-effectiveness of TB culture was more sensitive to characteristics of the existing TB diagnostic system than to the accuracy or cost of TB culture. CONCLUSIONS/SIGNIFICANCE: TB culture is potentially effective and cost-effective for HIV-positive patients in resource-constrained settings. Reliable transmission of culture results to patients and integration with existing systems are essential. AD - Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. AN - 19129940 AU - Dowdy, D. W. AU - Lourenco, M. C. AU - Cavalcante, S. C. AU - Saraceni, V. AU - King, B. AU - Golub, J. E. AU - Bishai, D. AU - Durovni, B. AU - Chaisson, R. E. AU - Dorman, S. E. DO - 10.1371/journal.pone.0004057 ET - 01/09 J2 - PloS one KW - AIDS-Related Opportunistic Infections/*diagnosis Bacteriological Techniques/*economics Brazil Cost-Benefit Analysis HIV Infections/*complications Humans Mycobacterium tuberculosis/*isolation & purification Tuberculosis/*diagnosis LA - eng M3 - Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't N1 - Dowdy, David W Lourenco, Maria C Cavalcante, Solange C Saraceni, Valeria King, Bonnie Golub, Jonathan E Bishai, David Durovni, Betina Chaisson, Richard E Dorman, Susan E 5 T32 GMO7309/PHS HHS/ K23 AI 51528/AI/NIAID NIH HHS/ K24 AI 16137/AI/NIAID NIH HHS/ PLoS One. 2008;3(12):e4057. Epub 2008 Dec 29. PY - 2009 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e4057 ST - Impact and cost-effectiveness of culture for diagnosis of tuberculosis in HIV-infected Brazilian adults T2 - PLoS One TI - Impact and cost-effectiveness of culture for diagnosis of tuberculosis in HIV-infected Brazilian adults UR - http://www.ncbi.nlm.nih.gov/pubmed/19129940http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614861/pdf/pone.0004057.pdf VL - 3 ID - 2524 ER - TY - JOUR AB - The growing number of reports of antibiotic resistance worldwide has led to fears that some lethal human pathogens, such as Mycobacterium tuberculosis, will soon become untreatable. Here, we show that, although this is possible, it is not inevitable. The World Health Organization has recently reported more cases of multidrug-resistant tuberculosis than ever before, but a new analysis of trend data for 10 groups of countries shows how and why the spread of multidrug-resistant tuberculosis can be reversed by good treatment practices. We find that multidrug-resistant tuberculosis is not self-sustaining in 9 out of the 10 settings and conclude that multidrug-resistant tuberculosis can be set on a path-albeit a slow path-to elimination. This result applies even to countries such as Estonia and Latvia, which have exceptionally high prevalence rates of multidrug-resistant tuberculosis. AD - Dye, C WHO, Off HIV AIDS TB Malaria & Neglected Trop Dis, CH-1211 Geneva 27, Switzerland WHO, Off HIV AIDS TB Malaria & Neglected Trop Dis, CH-1211 Geneva 27, Switzerland WHO, Off HIV AIDS TB Malaria & Neglected Trop Dis, CH-1211 Geneva 27, Switzerland STIAS, S African Ctr Epidemiol Modelling & Anal, ZA-7602 Stellenbosch, South Africa AN - ISI:000277196700001 AU - Dye, C. AU - Williams, B. G. DA - Oct 21 DO - ARTN 3ra8 DOI 10.1126/scitranslmed.3000346 J2 - Sci Transl Med KW - mycobacterium-tuberculosis drug-resistance mutations emergence epidemics dynamics cohort period risks L1 - internal-pdf://0619070107/3ra8.full.pdf LA - English N1 - 590AW Times Cited:3 Cited References Count:34 PY - 2009 RN - fulltext fulltext_1208 SN - 1946-6234 ST - Slow Elimination of Multidrug-Resistant Tuberculosis T2 - Science Translational Medicine TI - Slow Elimination of Multidrug-Resistant Tuberculosis UR - ://000277196700001http://stm.sciencemag.org/content/1/3/3ra8 VL - 1 ID - 2566 ER - TY - JOUR AB - BACKGROUND: Because metabolism is fundamental in sustaining microbial life, drugs that target pathogen-specific metabolic enzymes and pathways can be very effective. In particular, the metabolic challenges faced by intracellular pathogens, such as Mycobacterium tuberculosis, residing in the infected host provide novel opportunities for therapeutic intervention. RESULTS: We developed a mathematical framework to simulate the effects on the growth of a pathogen when enzymes in its metabolic pathways are inhibited. Combining detailed models of enzyme kinetics, a complete metabolic network description as modeled by flux balance analysis, and a dynamic cell population growth model, we quantitatively modeled and predicted the dose-response of the 3-nitropropionate inhibitor on the growth of M. tuberculosis in a medium whose carbon source was restricted to fatty acids, and that of the 5'-O-(N-salicylsulfamoyl) adenosine inhibitor in a medium with low-iron concentration. CONCLUSION: The predicted results quantitatively reproduced the experimentally measured dose-response curves, ranging over three orders of magnitude in inhibitor concentration. Thus, by allowing for detailed specifications of the underlying enzymatic kinetics, metabolic reactions/constraints, and growth media, our model captured the essential chemical and biological factors that determine the effects of drug inhibition on in vitro growth of M. tuberculosis cells. AD - Biotechnology HPC Software Applications Institute, Telemedicine and Advanced Technology Research Center, U,S, Army Medical Research and Materiel Command, Ft, Detrick, MD 21702, USA. xfang@bioanalysis.org AN - 19754970 AU - Fang, X. AU - Wallqvist, A. AU - Reifman, J. DO - 1752-0509-3-92 [pii] 10.1186/1752-0509-3-92 [doi] DP - Nlm ET - 09/17 KW - Bacterial Proteins/ metabolism Cell Proliferation/drug effects Cell Survival/drug effects Computer Simulation Models, Biological Mycobacterium tuberculosis/drug effects/ metabolism Nitro Compounds/ administration & dosage Propionic Acids/ administration & dosage Signal Transduction/drug effects/ physiology Succinate Dehydrogenase/ antagonists & inhibitors Systems Biology/ methods LA - eng N1 - Fang, Xin Wallqvist, Anders Reifman, Jaques Research Support, U.S. Gov't, Non-P.H.S. England BMC systems biology BMC Syst Biol. 2009 Sep 15;3:92. PY - 2009 RN - fulltext fulltext_1208 SN - 1752-0509 (Electronic) 1752-0509 (Linking) SP - 92 ST - A systems biology framework for modeling metabolic enzyme inhibition of Mycobacterium tuberculosis T2 - BMC Syst Biol TI - A systems biology framework for modeling metabolic enzyme inhibition of Mycobacterium tuberculosis UR - http://www.biomedcentral.com/1752-0509/3/92http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759933/pdf/1752-0509-3-92.pdf VL - 3 ID - 2568 ER - TY - JOUR AB - OBJECTIVE: People who live under fragile living conditions may stay overnight in Internet cafes in urban areas. An outbreak of tuberculosis (TB), the routes of which were possibly related to such a facility, has been reported. The purpose of this study was to use a mathematical model to quantify the public health risk of TB infection in such a facility. METHODS: The reproduction number for airborne infection in an enclosed space (R (A)) was estimated using a Wells-Riley model. First, we estimated R (A) for the TB infection based on the report of the TB outbreak in the Internet cafe. Second, TB infectious dose, number of days of exposure, and air-exchange rate in the facility were varied to estimate the effect of TB risk settings and environmental factors. RESULTS: We assumed that TB patients and 59 susceptible subjects stayed for 150 days in a room where the air-exchange rate was five per hour. Using the estimated median R (A) of 44.14, the TB infection rate was 74.6%. This result was similar to the epidemiological report that the TB infection rate among employees in the Internet cafe was 70%. The median R (A) increased linearly as the number of days of exposure increased. The slope of the change in median R (A) divided by the change in the number of days of exposure increased exponentially as air-exchange rate decreased; thus air ventilation in a facility may be essential to prevent TB infection. CONCLUSIONS: Appropriate air ventilation in facilities such as Internet cafes is needed as part of a TB-control program in metropolitan areas. AD - Basic Clinical Science and Public Health, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193, Japan, furuya@is.icc.u-tokai.ac.jp AN - 19568853 AU - Furuya, H. AU - Nagamine, M. AU - Watanabe, T. DA - Mar DO - 10.1007/s12199-008-0062-9 [doi] DP - Nlm ET - 07/02 LA - eng N1 - Furuya, Hiroyuki Nagamine, Michiko Watanabe, Tetsu Japan Environmental health and preventive medicine Environ Health Prev Med. 2009 Mar;14(2):96-102. Epub 2008 Nov 20. PY - 2009 RN - fulltext fulltext_1208 SN - 1342-078X (Print) 1342-078X (Linking) SP - 96-102 ST - Use of a mathematical model to estimate tuberculosis transmission risk in an Internet cafe T2 - Environ Health Prev Med TI - Use of a mathematical model to estimate tuberculosis transmission risk in an Internet cafe UR - http://www.springerlink.com/content/y4p35w852t3768vl/ VL - 14 ID - 2569 ER - TY - JOUR AB - Policies regarding the use of the Bacille Calmette-Guerin (BCG) vaccine for tuberculosis vary greatly throughout the international community. In several countries, consideration of discontinuing universal vaccination programs is currently under way. The arguments against mass vaccination are that the effectiveness of BCG in preventing tuberculosis is uncertain and that BCG vaccination can interfere with the detection and treatment of latent tuberculosis. In this work, we pose a dynamical systems model for the population-level dynamics of tuberculosis in order to study the trade-off which occurs between vaccination and detection/treatment of latent tuberculosis. We assume that latent infection in vaccinated individuals is completely undetectable. For the case of a country with very low levels of tuberculosis, we establish analytic thresholds, via stability analysis and the basic reproductive number, which determine the optimal vaccination policy, given the effectiveness of the vaccine and the detection/treatment rate of latent tuberculosis. The results of this work suggest that it is unlikely that a country detects and treats latent tuberculosis at a high enough rate to justify the discontinuation of mass vaccination from this perspective. AD - Department of Mathematics, Purdue University, West Lafayette, IN 47907-2067, USA. gerberry@math.purdue.edu AN - 19733577 AU - Gerberry, D. J. DA - Dec 21 DO - S0022-5193(09)00409-3 [pii] 10.1016/j.jtbi.2009.08.029 [doi] DP - Nlm ET - 09/08 KW - BCG Vaccine Health Policy Humans Latent Tuberculosis/ diagnosis Mass Vaccination Mathematics Models, Theoretical Program Evaluation Tuberculosis/ prevention & control World Health LA - eng N1 - Gerberry, David J England Journal of theoretical biology J Theor Biol. 2009 Dec 21;261(4):548-60. Epub 2009 Sep 4. PY - 2009 RN - fulltext fulltext_1208 SN - 1095-8541 (Electronic) 0022-5193 (Linking) SP - 548-60 ST - Trade-off between BCG vaccination and the ability to detect and treat latent tuberculosis T2 - J Theor Biol TI - Trade-off between BCG vaccination and the ability to detect and treat latent tuberculosis UR - http://ac.els-cdn.com/S0022519309004093/1-s2.0-S0022519309004093-main.pdf?_tid=6bfa50d3f1b770ab01fcb7f24051a839&acdnat=1345012389_7a7e0c6069b2a2bc442ddf8e87662ebe VL - 261 ID - 2570 ER - TY - JOUR AB - Few tools exist to assess replication of chronic pathogens during infection. This has been a considerable barrier to understanding latent tuberculosis, and efforts to develop new therapies generally assume that the bacteria are very slowly replicating or nonreplicating during latency. To monitor Mycobacterium tuberculosis replication within hosts, we exploit an unstable plasmid that is lost at a steady, quantifiable rate from dividing cells in the absence of antibiotic selection. By applying a mathematical model, we calculate bacterial growth and death rates during infection of mice. We show that during chronic infection, the cumulative bacterial burden-enumerating total live, dead and removed organisms encountered by the mouse lung-is substantially higher than estimates from colony-forming units. Our data show that M. tuberculosis replicates throughout the course of chronic infection of mice and is restrained by the host immune system. This approach may also shed light on the replication dynamics of other chronic pathogens. AD - Division of Allergy and Infectious Diseases, University of Washington Medical Center, 1959 Northeast Pacific Street, Box 356523, Seattle, Washington 98195, USA. AN - 19182798 AU - Gill, W. P. AU - Harik, N. S. AU - Whiddon, M. R. AU - Liao, R. P. AU - Mittler, J. E. AU - Sherman, D. R. DA - Feb DO - nm.1915 [pii] 10.1038/nm.1915 [doi] DP - Nlm ET - 02/03 KW - Animals Base Sequence Colony Count, Microbial DNA Primers Mice Mice, Inbred C57BL Mycobacterium tuberculosis/ growth & development Plasmids Polymerase Chain Reaction Tuberculosis/ microbiology/physiopathology LA - eng N1 - Gill, Wendy P Harik, Nada S Whiddon, Molly R Liao, Reiling P Mittler, John E Sherman, David R R01 AI047744-05/AI/NIAID NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Nature medicine Nihms152087 Nat Med. 2009 Feb;15(2):211-4. Epub 2009 Feb 1. PY - 2009 RN - fulltext fulltext_1208 SN - 1546-170X (Electronic) 1078-8956 (Linking) SP - 211-4 ST - A replication clock for Mycobacterium tuberculosis T2 - Nat Med TI - A replication clock for Mycobacterium tuberculosis UR - http://www.nature.com.ez.lshtm.ac.uk/nm/journal/v15/n2/pdf/nm.1915.pdf VL - 15 ID - 2571 ER - TY - JOUR AB - Little information exists on the pulmonary pharmacology of antituberculosis drugs. We used population pharmacokinetic modeling and Monte Carlo simulation to describe and explore the pulmonary pharmacokinetics and pharmacodynamics of rifampin (RIF; rifampicin). A population pharmacokinetic model that adequately described the plasma, epithelial lining fluid (ELF), and alveolar cell (AC) concentrations of RIF in a population of 34 human volunteers was made by use of the nonparametric adaptive grid (NPAG) algorithm. The estimated concentrations correlated well with the measured concentrations, and there was little bias and good precision. The results obtained with the NPAG algorithm were then imported into Matlab software to perform a 10,000-subject Monte Carlo simulation. The ability of RIF to suppress the development of drug resistance and to induce a sufficient bactericidal effect against Mycobacterium tuberculosis was evaluated by calculating the proportion of subjects achieving specific target values for the maximum concentration of drug (C(max))/MIC ratio and the area under the concentration-time curve from time zero to 24 h (AUC(0-24))/MIC ratio, respectively. At the lowest MIC (0.01 mg/liter), after the administration of one 600-mg oral dose, the rates of target attainment for C(max)/MIC (> or =175) were 95% in ACs, 48.8% in plasma, and 35.9% in ELF. Under the same conditions, the target attainment results for the killing effect were 100% in plasma (AUC(0-24)/MIC > or = 271) but only 54.5% in ELF (AUC(0-24)/MIC > or = 665). The use of a 1,200-mg RIF dose was associated with better results for target attainment. The overall results suggest that the pulmonary concentrations obtained with the standard RIF dose are too low in most subjects. This work supports the need to evaluate higher doses of RIF for the treatment of patients with tuberculosis. AD - Hospices Civils de Lyon, Hopital Antoine Charial, Service Pharmaceutique, ADCAPT, 40 Avenue de la Table de Pierre, Francheville, France. sylvain.goutelle@chu-lyon.fr AN - 19380594 AU - Goutelle, S. AU - Bourguignon, L. AU - Maire, P. H. AU - Van Guilder, M. AU - Conte, J. E., Jr. AU - Jelliffe, R. W. DA - Jul DO - AAC.01520-08 [pii] 10.1128/AAC.01520-08 [doi] DP - Nlm ET - 04/22 KW - Algorithms Antitubercular Agents/ pharmacokinetics Computer Simulation Female Humans Lung/ metabolism Male Monte Carlo Method Prospective Studies Rifampin/ pharmacokinetics L1 - internal-pdf://2336466970/Goutelle-2009-Population modeling and Monte Ca.pdf LA - eng N1 - Goutelle, Sylvain Bourguignon, Laurent Maire, Pascal H Van Guilder, Michael Conte, John E Jr Jelliffe, Roger W EB005803/EB/NIBIB NIH HHS/United States Research Support, N.I.H., Extramural United States Antimicrobial agents and chemotherapy Antimicrob Agents Chemother. 2009 Jul;53(7):2974-81. Epub 2009 Apr 20. PY - 2009 RN - fulltext fulltext_1208 SN - 1098-6596 (Electronic) 0066-4804 (Linking) SP - 2974-81 ST - Population modeling and Monte Carlo simulation study of the pharmacokinetics and antituberculosis pharmacodynamics of rifampin in lungs T2 - Antimicrob Agents Chemother TI - Population modeling and Monte Carlo simulation study of the pharmacokinetics and antituberculosis pharmacodynamics of rifampin in lungs UR - http://aac.asm.org/content/53/7/2974.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704682/pdf/1520-08.pdf VL - 53 ID - 2572 ER - TY - JOUR AB - For some diseases, the transmission of infection can cause spatial clustering of disease cases. This clustering has an impact on how one estimates the rate of the spread of the disease and on the design of control strategies. It is, however, difficult to assess such clustering, (local effects on transmission), using traditional statistical methods. A stochastic Markov-chain model that takes into account possible local or more dispersed global effects on the risk of contracting disease is introduced in the context of the transmission dynamics of tuberculosis. The model is used to analyse TB notifications collected in the Asembo and Gem Divisions of Nyanza Province in western Kenya by the Kenya Ministry of Health/National Leprosy and Tuberculosis Program and the Centers for Disease Control and Prevention. The model shows evidence of a pronounced local effect that is significantly greater than the global effect. We discuss a number of variations of the model which identify how this local effect depends on factors such as age and gender. Zoning/clustering of villages is used to identify the influence that zone size has on the model's ability to distinguish local and global effects. An important possible use of the model is in the design of a community randomised trial where geographical clusters of people are divided into two groups and the effectiveness of an intervention policy is assessed by applying it to one group but not the other. Here the model can be used to take the effect of case clustering into consideration in calculating the minimum difference in an outcome variable (e.g. disease prevalence) that can be detected with statistical significance. It thereby gauges the potential effectiveness of such a trial. Such a possible application is illustrated with the given time/spatial TB data set. AD - Warwick Business School, University of Warwick, University Road, Coventry, Warwickshire CV4 7AL, UK. kathryn.hoad@wbs.ac.uk AN - 19563744 AU - Hoad, K. A. AU - van't Hoog, A. H. AU - Rosen, D. AU - Marston, B. AU - Nyabiage, L. AU - Williams, B. G. AU - Dye, C. AU - Cheng, R. C. DA - Apr DO - S0025-5564(09)00021-2 [pii] 10.1016/j.mbs.2009.01.002 [doi] DP - Nlm ET - 07/01 KW - Age Factors Female Humans Kenya/epidemiology Male Markov Chains Models, Immunological Mycobacterium tuberculosis/ immunology Sex Factors Space-Time Clustering Tuberculosis/epidemiology/immunology/ transmission LA - eng N1 - Hoad, K A van't Hoog, A H Rosen, D Marston, B Nyabiage, L Williams, B G Dye, C Cheng, R C H Research Support, Non-U.S. Gov't United States Mathematical biosciences Math Biosci. 2009 Apr;218(2):98-104. Epub 2009 Jan 19. PY - 2009 RN - fulltext fulltext_1208 SN - 1879-3134 (Electronic) 0025-5564 (Linking) SP - 98-104 ST - Modelling local and global effects on the risk of contracting Tuberculosis using stochastic Markov-chain models T2 - Math Biosci TI - Modelling local and global effects on the risk of contracting Tuberculosis using stochastic Markov-chain models UR - http://ac.els-cdn.com/S0025556409000212/1-s2.0-S0025556409000212-main.pdf?_tid=77817aaa05622369ca0d29b39ce4a269&acdnat=1345012489_4856d1ca7ba758754fdd87eb5d14dd13 VL - 218 ID - 2573 ER - TY - JOUR AB - RATIONALE: Isoniazid given daily for 9 months is the standard treatment for latent tuberculosis infection (LTBI), but its effectiveness is limited by poor completion rates. Shorter course regimens and regimens using directly observed therapy result in improved adherence but have higher upfront costs. OBJECTIVES: To evaluate the costs and cost-effectiveness of regimens for the treatment of LTBI. METHODS: We used a computerized Markov model to estimate total societal costs and benefits associated with four regimens for the treatment of LTBI: self-administered isoniazid daily for 9 months, directly observed isoniazid twice-weekly for 9 months, directly observed isoniazid plus rifapentine once weekly for 3 months, and self-administered rifampin daily for 4 months. In the base-case analysis, subjects were assumed to have newly positive tuberculin skin tests after recent exposure to infectious tuberculosis. MEASUREMENTS AND MAIN RESULTS: We determined the costs of treatment, quality-adjusted life-years gained, and cases of active tuberculosis prevented. In the base-case analysis, rifampin dominated (less costly with increased benefits) all other regimens except isoniazid plus rifapentine, which was more effective at a cost $48,997 per quality-adjusted life year gained. Isoniazid plus rifapentine dominated all regimens at a relative risk of disease 5.2 times the baseline estimate, or with completion rates less than 34% for isoniazid or 37% for rifampin. Rifampin could be 17% less efficacious than self-administered isoniazid and still be cost-saving compared with this regimen. CONCLUSIONS: In our model, rifampin is cost-saving compared with the standard therapy of self-administered isoniazid. Isoniazid plus rifapentine is cost-saving for extremely high-risk patients and is cost-effective for lower-risk patients. AD - Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. AU - Holland, D. P. AU - Sanders, G. D. AU - Hamilton, C. D. AU - Stout, J. E. DO - 10.1164/rccm.200901-0153OC KW - Antitubercular Agents/administration & dosage/economics Cost-Benefit Analysis Directly Observed Therapy/economics Drug Administration Schedule Drug Therapy, Combination Humans Isoniazid/administration & dosage/economics Markov Chains Rifampin/administration & dosage/analogs & derivatives/economics Tuberculosis/drug therapy N1 - LR: 20100923; GR: 1-U54 AI057157/AI/NIAID NIH HHS/United States; JID: 9421642; 0 (Antitubercular Agents); 13292-46-1 (Rifampin); 54-85-3 (Isoniazid); 61379-65-5 (rifapentine); OID: NLM: PMC2689913; 2009/03/19 [aheadofprint]; ppublish PY - 2009 RN - fulltext fulltext_1208 SN - 1535-4970; 1073-449X SP - 1055-1060 ST - Costs and cost-effectiveness of four treatment regimens for latent tuberculosis infection T2 - American journal of respiratory and critical care medicine TI - Costs and cost-effectiveness of four treatment regimens for latent tuberculosis infection VL - 179 Y2 - Jun 1 ID - 2574 ER - TY - THES AB - In this thesis, a mathematical model describing the interaction between HIV and TB in the presence of TB superinfection is presented. The model takes into account two strains of Mycobacterium tuberculosis (MTB), where one strain is drug-sensitive and the other is resistant to at least one of the first-line anti-tuberculosis drugs. The impact of TB superinfection on the incidence and prevalence of TB in HIV-negative and HIVTB coinfected individuals is evaluated. Various control measures such as condom use, antiretroviral therapy, isoniazid preventive therapy and increased TB detection are studied using this model. Numerical results show that TB superinfection increases the prevalence and incidence of TB and its impact is more in HIV-negative than HIV-TB coinfected individuals. The results also show that TB superinfection promotes strain coexistence and increases the associated HIV mortality. Increased condom use was found to have a high positive impact towards the control of the two epidemics. Antiretroviral therapy decreases the TB notification rate and its impact on HIV prevalence increases with the coverage and efficacy. Isoniazid preventive therapy has a clear effect on the TB prevalence. Finally, increased TB detection was found to have a less impact on the TB incidence in HIV-TB coinfected individuals AU - Kajunguri, D. L1 - internal-pdf://3487199912/kajunguri_modelling_2009.pdf PB - University of Stellenbosch PY - 2009 ST - MODELLING THE IMPACT OF TB SUPERINFECTION ON THE DYNAMICS OF HIV-TB COINFECTION TI - MODELLING THE IMPACT OF TB SUPERINFECTION ON THE DYNAMICS OF HIV-TB COINFECTION VL - MSc ID - 4936 ER - TY - JOUR AB - The aim of this paper is to describe the development and use of a computer simulation model that can be used as a Decision Support System (DSS) to tackle the critical public health issues of HIV and HIV-related tuberculosis in the Russian Federation. This country has recently witnessed an explosion of HIV infections and a worrying spread of the Multi-Drug Resistant form of Tuberculosis (MDRTB). The conclusions drawn are that a high population coverage with Highly Active Anti-Retroviral Treatment (HAART) (75% or higher), allied with high MDRTB cure rates, reduces cumulative deaths by 60%, with limited impact below this level. This research offers a simulation model that can be applied as a DSS by public health officials to inform policy making. By doing so, ways of controlling the spread of HIV and MDRTB and reduce mortality from these serious public health threats is provided. AD - Business School, University of Hertfordshire, Hatfield, Herts, AL 10 9AB, UK. M.R.Lebcir@Herts.ac.uk AN - 19505866 AU - Lebcir, R. M. AU - Choudrie, J. AU - Atun, R. A. AU - Coker, R. J. DO - G86453764772W185 [pii] DP - Nlm ET - 06/10 KW - AIDS-Related Opportunistic Infections/ drug therapy/mortality/transmission Antiretroviral Therapy, Highly Active/ utilization Antitubercular Agents/administration & dosage/ therapeutic use Computer Simulation Decision Support Systems, Clinical/ organization & administration Directly Observed Therapy Humans Models, Biological Russia/epidemiology Tuberculosis, Multidrug-Resistant/drug therapy/mortality/transmission Tuberculosis, Pulmonary/ drug therapy/mortality/transmission LA - eng N1 - Lebcir, Reda M Choudrie, Jyoti Atun, Rifat A Coker, Richard J Switzerland International journal of electronic healthcare Int J Electron Healthc. 2009;5(1):14-32. PY - 2009 RN - fulltext fulltext_1208 SN - 1741-8453 (Print) 1741-8453 (Linking) SP - 14-32 ST - Using a decision support systems computer simulation model to examine HIV and tuberculosis: the Russian Federation T2 - Int J Electron Healthc TI - Using a decision support systems computer simulation model to examine HIV and tuberculosis: the Russian Federation UR - https://www.inderscienceonline.com/doi/abs/10.1504/IJEH.2009.02627?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed VL - 5 ID - 2576 ER - TY - JOUR AB - A tuberculosis (TB) model with two latent periods, short-term latent period (E(1)) and long-term latent period (E(2)), and fast and slow progressions is analyzed. The stability of the unique endemic equilibrium of the model is proved. It turns out that the disease-free equilibrium is globally asymptotically stable if the basic reproduction number R(0) <= 1, and the endemic equilibrium is globally asymptotically stable if R(0) > 1. AD - Liu, LJ Xi An Jiao Tong Univ, Dept Math, Xian 710049, Peoples R China Xi An Jiao Tong Univ, Dept Math, Xian 710049, Peoples R China Xi An Jiao Tong Univ, Dept Math, Xian 710049, Peoples R China Mem Univ Newfoundland, Dept Math & Stat, St John, NF A1C 5S7, Canada AN - WOS:000279191500009 AU - Liu, L. J. DA - Sep DO - 10.1142/S1793524509000480 IS - 3 J2 - Int J Biomath KW - tb model endemic equilibrium globally stability lyapunov function transmission epidemiology infection LA - English N1 - 616el Times Cited:3 Cited References Count:14 PY - 2009 SN - 1793-5245 SP - 357-362 ST - Global Stability in a Tuberculosis Model Incorporating Two Latent Periods T2 - International Journal of Biomathematics TI - Global Stability in a Tuberculosis Model Incorporating Two Latent Periods UR - ://WOS:000279191500009 VL - 2 ID - 2198 ER - TY - JOUR AB - We provide the complete classification of all global analytic first integrals of the simplified multistrain/two-stream model for tuberculosis and dengue fever that can be written as (x) over dot = x(beta(1) - b - gamma(1) - beta(1)x - (beta(1) - nu)y), (y) over dot = y(beta(2) - b - gamma(2) - (beta(2) + nu)x - beta(2)y), with beta(1), beta(2), b, gamma(1), gamma(2), nu is an element of R. AD - [Llibre, Jaume] Univ Autonoma Barcelona, Dept Matemat, E-08193 Barcelona, Spain. [Valls, Claudia] Inst Super Tecn, Dept Matemat, P-1049001 Lisbon, Portugal. Llibre, J (reprint author), Univ Autonoma Barcelona, Dept Matemat, E-08193 Barcelona, Spain. jllibre@mat.uab.cat; cvalls@math.ist.utl.pt AN - WOS:000274916800009 AU - Llibre, J. AU - Valls, C. DA - Dec DO - 10.1142/s1402925109000510 IS - 4 J2 - J. Nonlinear Math. Phys. KW - Analytic first integral multistrain/two-stream model tuberculosis dengue fever transmission Mathematics Physics LA - English M3 - Article N1 - ISI Document Delivery No.: 560QI Times Cited: 4 Cited Reference Count: 9 Llibre, Jaume Valls, Claudia Valls, Claudia/H-5040-2015; Llibre, Jaume/F-4225-2016 Llibre, Jaume/0000-0002-9511-5999; Valls, Claudia/0000-0001-8279-1229 MCYT/FEDER [MTM 2008-03437]; CICYT [2009SGR 410]; FCT through CAMGDS, Lisbon The first author has been supported by the grants MCYT/FEDER MTM 2008-03437 and CICYT grant number 2009SGR 410. The second author has been partially supported by FCT through CAMGDS, Lisbon. 4 0 2 Atlantis press Paris PY - 2009 SN - 1402-9251 SP - 505-516 ST - GLOBAL ANALYTIC FIRST INTEGRALS FOR THE SIMPLIFIED MULTISTRAIN/TWO-STREAM MODEL FOR TUBERCULOSIS AND DENGUE FEVER T2 - Journal of Nonlinear Mathematical Physics TI - GLOBAL ANALYTIC FIRST INTEGRALS FOR THE SIMPLIFIED MULTISTRAIN/TWO-STREAM MODEL FOR TUBERCULOSIS AND DENGUE FEVER UR - ://WOS:000274916800009 VL - 16 ID - 5883 ER - TY - JOUR AB - The emergence of antibiotic resistance in Mycobacterium tuberculosis has raised the concern that pathogen strains that are virtually untreatable may become widespread. The acquisition of resistance to antibiotics results in a longer duration of infection in a host, but this resistance may come at a cost through a decreased transmission rate. This raises the question of whether the overall fitness of drug-resistant strains is higher than that of sensitive strains--essential information for predicting the spread of the disease. Here, we directly estimate the transmission cost of drug resistance, the rate at which resistance evolves, and the relative fitness of resistant strains. These estimates are made by using explicit models of the transmission and evolution of sensitive and resistant strains of M. tuberculosis, using approximate Bayesian computation, and molecular epidemiology data from Cuba, Estonia, and Venezuela. We find that the transmission cost of drug resistance relative to sensitivity can be as low as 10%, that resistance evolves at rates of approximately 0.0025-0.02 per case per year, and that the overall fitness of resistant strains is comparable with that of sensitive strains. Furthermore, the contribution of transmission to the spread of drug resistance is very high compared with acquired resistance due to treatment failure (up to 99%). Estimating such parameters directly from in vivo data will be critical to understanding and responding to antibiotic resistance. For instance, projections using our estimates suggest that the prevalence of tuberculosis may decline with successful treatment, but the proportion of cases associated with resistance is likely to increase. AD - School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW 2052, Australia. AN - 19706556 AU - Luciani, F. AU - Sisson, S. A. AU - Jiang, H. AU - Francis, A. R. AU - Tanaka, M. M. DA - Aug 25 DO - 0902437106 [pii] 10.1073/pnas.0902437106 ET - 08/27 KW - Algorithms Antitubercular Agents/*therapeutic use Bayes Theorem Cuba/epidemiology Drug Resistance, Multiple, Bacterial Estonia/epidemiology Humans Models, Theoretical Mycobacterium tuberculosis/*drug effects Tuberculosis, Multidrug-Resistant/*drug therapy/epidemiology/transmission Venezuela/epidemiology L1 - internal-pdf://0465276404/Luciani-2009-The epidemiological fitness cost.pdf LA - eng N1 - Luciani, Fabio Sisson, Scott A Jiang, Honglin Francis, Andrew R Tanaka, Mark M Research Support, Non-U.S. Gov't United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14711-5. Epub 2009 Aug 13. PY - 2009 RN - fulltext fulltext_1208 SN - 1091-6490 (Electronic) SP - 14711-14715 ST - The epidemiological fitness cost of drug resistance in Mycobacterium tuberculosis T2 - Proc Natl Acad Sci U S A TI - The epidemiological fitness cost of drug resistance in Mycobacterium tuberculosis UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19706556http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2732896/pdf/zpq14711.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2732896/pdf/zpq14711.pdf VL - 106 ID - 2577 ER - TY - JOUR AB - Natural infection with Mycobacterium tuberculosis, as well as cross-immune reactions with the constituent of standard vaccines, attenuated M. bovis, and other species of mycobacteria confer partial immunity to subsequent M. tuberculosis infection, It has been shown in the past that the immune response to mycobacteria found naturally in the environment reduces the benefit of vaccination as assessed by means of vaccine efficacy. In this paper we show that efficacy is a poor measure of the potential success of new anti-tuberculous vaccines due to its inability to account for the relative weight of reinfection in disease dynamics. We advocate instead the use of vaccine effectiveness when evaluating the impact of new control methods against infections that confer partial immunity. Through the study of a simple model that incorporates cross-reactive responses to environmental mycobacteria (EM) and reinfection, we show how the particulars of the relation between EM abundance and vaccine effectiveness depend on the degree of protection conferred respectively by natural infection, vaccination and EM. The relative importance of reinfection as a transmission mechanism comes Lip as the most important source of variability in vaccine effectiveness. Our results suggest that control efforts should be placed in reducing the importance of reinfection through diminishing transmission rates. Vaccines that overcome preexisting immunity to other mycobacteria will still have varying degrees of success depending on the underlying rate of TB transmission. (C) 2009 Elsevier Inc. All rights reserved. AD - Univ Nacl Autonoma Mexico, Inst Fis, Mexico City 04510, DF, Mexico Gulbenkian Inst Sci, P-2781901 Oeiras, Portugal Univ Lisbon, Ctr Matemat & Aplicacoes Fundamentais, P-1649003 Lisbon, Portugal AN - WOS:000265736600006 AU - Mantilla-Beniers, N. B. AU - Gomes, M. G. M. DA - Mar-May DO - 10.1016/j.tpb.2009.01.006 IS - 2-3 J2 - Theor Popul Biol KW - epidemiology disease ecology tuberculosis reinfection vaccine efficacy effectiveness intervention effectiveness bcg environmental mycobacteria cross-immunity bovis bcg vaccination exogenous reinfection environmental mycobacteria recurrent tuberculosis northern malawi heterologous immunity infectious-diseases prior exposure efficacy epidemiology LA - English N1 - 440yw Times Cited:2 Cited References Count:39 PY - 2009 SN - 0040-5809 SP - 142-152 ST - Mycobacterial ecology as a modulator of tuberculosis vaccine success T2 - Theoretical Population Biology TI - Mycobacterial ecology as a modulator of tuberculosis vaccine success UR - ://WOS:000265736600006 VL - 75 ID - 4853 ER - TY - JOUR AB - We formulate and analyze a deterministic mathematical model which incorporates some basic epidemiological features of the co-dynamics of malaria and tuberculosis. Two sub-models, namely: malaria-only and TB-only sub-models are considered first of all. Sufficient conditions for the local stability of the steady states are presented. Global stability of the disease-free steady state does not hold because the two sub-models exhibit backward bifurcation. The dynamics of the dual malaria-TB only sub-model is also analyzed. It has different dynamics to that of malaria-only and TB-only sub-models: the dual malaria-TB only model has no positive endemic equilibrium whenever R(MT)(d) < 1, - its disease free equilibrium is globally asymptotically stable whenever the reproduction number for dual malaria-TB co-infection only R(MT)(d) < 1 - it does not exhibit the phenomenon of backward bifurcation. Graphical representations of this phenomenon is shown, while numerical simulations of the full model are carried out in order to determine whether the two diseases will co-exist whenever their partial reproductive numbers exceed unity. Finally, we perform sensitivity analysis on the key parameters that drive the disease dynamics in order to determine their relative importance to disease transmission. AD - Dar es Salaam Inst Technol, Dar Es Salaam, Tanzania Univ Dar Es Salaam, Dept Math, Dar Es Salaam, Tanzania AN - WOS:000271091400008 AU - Mtisi, E. AU - Rwezaura, H. AU - Tchuenche, J. M. DA - Nov DO - 10.3934/dcdsb.2009.12.827 IS - 4 J2 - Discrete Cont Dyn-B KW - malaria-tb model co-dynamics basic reproduction number equilibrium stability sensitivity model hiv transmission coinfection bifurcation strategies vaccines diseases burden LA - English N1 - 510ma Times Cited:16 Cited References Count:40 PY - 2009 SN - 1531-3492 SP - 827-864 ST - A Mathematical Analysis of Malaria and Tuberculosis Co-Dynamics T2 - Discrete and Continuous Dynamical Systems-Series B TI - A Mathematical Analysis of Malaria and Tuberculosis Co-Dynamics UR - ://WOS:000271091400008 VL - 12 ID - 4854 ER - TY - JOUR AB - In this paper, the cumulative effect of ecological factors in the habitat on the spread of tuberculosis (TB) in human population is modeled and analyzed. The total human population is divided into two classes, susceptibles and infectives. It is assumed that TB is not only spread by direct contacts with infectives in the population but also indirectly by bacteria which are emitted by infectives in the habitat. It is assumed further that bacteria survive due to conducive ecological factors such as flower pots, plants, grasses, human clothes, etc. in the habitat. The cumulative density of ecological factors in the habitat is assumed to be governed by a population density dependent logistic model. The analysis of the model shows that as parameters governing the conducive ecological factors in the habitat increase, the spread of TB increases. The same result is also found with the increase in the parameter governing the survival and accumulation of bacteria in the habitat. It is further found that due to immigration of the population TB becomes more endemic. A numerical study of the model is also carried out to support the analytical results. AD - [Naresh, Ram; Pandey, Surabhi] Harcourt Butler Technol Inst, Dept Math, Kanpur 208002, Uttar Pradesh, India. [Shukla, J. B.] Ctr Modelling Environm & Dev, Kanpur 208017, Uttar Pradesh, India. [Shukla, J. B.] LNM Indian Inst Technol Jaipur, Jaipur 303012, Rajasthan, India. Naresh, R (reprint author), Harcourt Butler Technol Inst, Dept Math, Kanpur 208002, Uttar Pradesh, India. ramntripathi@yahoo.com; psurabhi_81@yahoo.co.in; jbs@iitk.ac.in AN - WOS:000279191500008 AU - Naresh, R. AU - Pandey, S. AU - Shukla, J. B. DA - Sep DO - 10.1142/s1793524509000728 IS - 3 J2 - Int. J. Biomath. KW - Mycobacterium tuberculosis ecological density bacterial population stability simulation Mathematical & Computational Biology LA - English M3 - Article N1 - ISI Document Delivery No.: 616EL Times Cited: 3 Cited Reference Count: 23 Naresh, Ram Pandey, Surabhi Shukla, J. B. 3 0 4 World scientific publ co pte ltd Singapore PY - 2009 SN - 1793-5245 SP - 339-355 ST - MODELING THE CUMULATIVE EFFECT OF ECOLOGICAL FACTORS IN THE HABITAT ON THE SPREAD OF TUBERCULOSIS T2 - International Journal of Biomathematics TI - MODELING THE CUMULATIVE EFFECT OF ECOLOGICAL FACTORS IN THE HABITAT ON THE SPREAD OF TUBERCULOSIS UR - ://WOS:000279191500008 http://www.worldscientific.com/doi/abs/10.1142/S1793524509000728 VL - 2 ID - 5903 ER - TY - JOUR AB - A nonlinear mathematical model is proposed to study the effect of tuberculosis on the spread of HIV infection in a logistically growing human population. The host population is divided into four sub classes of susceptibles, TB infectives, HIV infectives (with or without TB) and that of AIDS patients. The model exhibits four equilibria namely, a disease free, HIV free, TB free and an endemic equilibrium. The model has been studied qualitatively using stability theory of nonlinear differential equations and computer simulation. We have found a threshold parameter R 0 which is if less than one, the disease free equilibrium is locally asymptotically stable otherwise for R 0 > 1 , at least one of the infections will be present in the population. It is shown that the positive endemic equilibrium is always locally stable but it may become globally stable under certain conditions showing that the disease becomes endemic. It is found that as the number of TB infectives decreases due to recovery, the number of HIV infectives also decreases and endemic equilibrium tends to TB free equilibrium. It is also observed that number of AIDS individuals decreases if TB is not associated with HIV infection. A numerical study of the model is also performed to investigate the influence of certain key parameters on the spread of the disease. AU - Naresh, Ram AU - Sharma, Dileep AU - Tripathi, Agraj DO - 10.1016/j.mcm.2009.05.033 KW - HIV/AIDS epidemic PY - 2009 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0895-7177 SP - 1154-1166 ST - Modelling the effect of tuberculosis on the spread of HIV infection in a population with density-dependent birth and death rate T2 - Mathematical and Computer Modelling TI - Modelling the effect of tuberculosis on the spread of HIV infection in a population with density-dependent birth and death rate UR - http://www.sciencedirect.com/science/article/pii/S0895717709002131http://ac.els-cdn.com/S0895717709002131/1-s2.0-S0895717709002131-main.pdf?_tid=91543dc8067263b6b14d2bc42dec2019&acdnat=1345012911_4304f0798d5c14dfd87464c2a818a108 VL - 50 ID - 2578 ER - TY - JOUR AB - Epidemics such as tuberculosis (TB), can be represented by a finite number of states and transition rules that govern the spread of the disease in each discrete time step. This paper Uses a graph theoretic approach to investigate TB interactions in a community where infectives are categorized. A threshold value, alpha = 1 - 1/n, for 'reasonable' infectives is proposed. The results show that ail epidemic will not ensue as long as the threshold is Surpassed. Simulations presented show that unreasonable infectives can amplify the epidemic. (C) 2009 Elsevier B.V. All rights reserved. AD - [Nyabadza, Farai] Univ Stellenbosch, S African Ctr Epidemiol Modelling & Anal, ZA-7600 Stellenbosch, South Africa. [Mukwembi, Simon; Rodrigues, Bernardo Gabriel] Univ KwaZulu Natal, Sch Math Sci, Durban, South Africa. Nyabadza, F (reprint author), Univ Stellenbosch, S African Ctr Epidemiol Modelling & Anal, 19 Jonkershoek Rd, ZA-7600 Stellenbosch, South Africa. nyabadzaf@sun.ac.za AN - WOS:000265016600004 AU - Nyabadza, F. AU - Mukwembi, S. AU - Rodrigues, B. G. DA - May DO - 10.1016/j.physa.2009.01.039 IS - 10 J2 - Physica A KW - Tuberculosis Graph Contacts Transition States heterogeneous populations transmission dynamics complex networks epidemic reinfection tb Physics LA - English M3 - Article N1 - ISI Document Delivery No.: 430VC Times Cited: 2 Cited Reference Count: 17 Nyabadza, Farai Mukwembi, Simon Rodrigues, Bernardo Gabriel Rodrigues, Bernardo/0000-0002-1349-0219; Nyabadza, Farai/0000-0003-3468-5581 Sacema The first author acknowledges, with thanks, the support of SACEMA (DST/NRF Centre of Excellence in Epidemiological Modelling and Analysis) and the University of KwaZulu-Natal for the research visit that they fully funded during which this work was done. The second and third authors acknowledge, with gratitude, the financial support of the University of KwaZulu-Natal. 2 0 Elsevier science bv Amsterdam PY - 2009 SN - 0378-4371 SP - 1995-2000 ST - A tuberculosis model: The case of 'reasonable' and 'unreasonable' infectives T2 - Physica a-Statistical Mechanics and Its Applications TI - A tuberculosis model: The case of 'reasonable' and 'unreasonable' infectives UR - ://WOS:000265016600004 VL - 388 ID - 5922 ER - TY - JOUR AD - [Pareek, Manish; White, Peter J.; Garnett, Geoffrey P.] Univ London Imperial Coll Sci Technol & Med, MRC Ctr Outbreak Anal & Modelling, Dept Infect Dis Epidemiol, London, England. [White, Peter J.] Ctr Infect, Hlth Protect Agcy, Modelling & Econ Unit, London, England. [Pareek, Manish; Lalvani, Ajit] Univ London Imperial Coll Sci Technol & Med, TB Res Unit, Dept Resp Med, London, England. AN - WOS:000273714700037 AU - Pareek, M. AU - White, P. J. AU - Lalvani, A. AU - Garnett, G. P. DA - Dec IS - 6 J2 - J. Infect. KW - Infectious Diseases LA - English M3 - Meeting Abstract N1 - ISI Document Delivery No.: 545EG Times Cited: 0 Cited Reference Count: 0 Pareek, Manish White, Peter J. Lalvani, Ajit Garnett, Geoffrey P. 0 1 2 W b saunders co ltd London PY - 2009 SN - 0163-4453 SP - S442-S442 ST - MODELLING THE HEALTH IMPACT AND COST-EFFECTIVENESS OF SCREENING NEW ENTRANTS TO THE UK FOR LATENT TUBERCULOSIS INFECTION T2 - Journal of Infection TI - MODELLING THE HEALTH IMPACT AND COST-EFFECTIVENESS OF SCREENING NEW ENTRANTS TO THE UK FOR LATENT TUBERCULOSIS INFECTION UR - ://WOS:000273714700037 VL - 59 ID - 5882 ER - TY - JOUR AB - A stochastic individual-based model of the spread of tuberculosis is considered. The model is based on a system of stochastic recurrent equations with integer-valued variables and discrete time. Individuals differ by the duration of different states of their disease (noninfectious, infectious, in remission) and by values of the parameters describing their life time distribution. Monte Carlo methods are used for numerical experiments based on the model. The dynamics of the number of individuals depending on the variation of the parameters of the model is studied. AD - [Pertsev, N. V.; Leonenko, V. N.] Russian Acad Sci, Siberian Branch, Sobolev Inst Math, Omsk 644099, Russia. Pertsev, NV (reprint author), Russian Acad Sci, Siberian Branch, Sobolev Inst Math, Omsk 644099, Russia. AN - WOS:000269370000004 AU - Pertsev, N. V. AU - Leonenko, V. N. DO - 10.1515/rjnamm.2009.021 IS - 4 J2 - Russ. J. Numer. Anal. Math. Model KW - Engineering Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: 488SL Times Cited: 3 Cited Reference Count: 11 Pertsev, N. V. Leonenko, V. N. Leonenko, Vasiliy/E-8752-2013; Pertsev, Nikolay/F-8086-2013 Pertsev, Nikolay/0000-0002-5674-7096 Russian Foundation for Basic Research [09-01-00098-a] The work was supported by the Russian Foundation for Basic Research (09-01-00098-a). 3 1 4 Walter de gruyter & co Berlin PY - 2009 SN - 0927-6467 SP - 341-360 ST - Stochastic individual-based model of spread of tuberculosis T2 - Russian Journal of Numerical Analysis and Mathematical Modelling TI - Stochastic individual-based model of spread of tuberculosis UR - ://WOS:000269370000004 VL - 24 ID - 5953 ER - TY - JOUR AB - Heterogeneity in susceptibility and infectivity is inherent to infectious disease transmission in nature. Here we are concerned with the formulation of mathematical models that capture the essence of heterogeneity while keeping a simple structure suitable of analytical treatment. We explore the consequences of host heterogeneity in the susceptibility to infection for epidemiological models for which immunity conferred by infection is partially protective, known as susceptible-infected-recovered-infected (SIRI) models. We analyze the impact of heterogeneity on disease prevalence and contrast the susceptibility profiles of the subpopulations at risk for primary infection and reinfection. We present a systematic study in the case of two frailty groups. We predict that the average rate of reinfection may be higher than the average rate of primary infection, which may seem paradoxical given that primary infection induces life-long partial protection. Infection generates a selection mechanism whereby fit individuals remain in S and frail individuals are transferred to R. If this effect is strong enough we have a scenario where, on average, the rate of reinfection is higher than the rate of primary infection even though each individual has a risk reduction following primary infection. This mechanism may explain high rates of tuberculosis reinfection recently reported. Finally, the enhanced benefits of vaccination strategies that target the high-risk groups are quantified. AD - Instituto Gulbenkian de Ciencia, Apartado 14, 2781-901 Oeiras, Portugal. pcpr@igc.gulbenkian.pt AN - 19306886 AU - Rodrigues, P. AU - Margheri, A. AU - Rebelo, C. AU - Gomes, M. G. DA - Jul 21 DO - S0022-5193(09)00126-X [pii] 10.1016/j.jtbi.2009.03.013 [doi] DP - Nlm ET - 03/25 KW - Communicable Diseases/epidemiology/ immunology/transmission Disease Susceptibility Endemic Diseases Humans Immunization Programs/organization & administration Immunologic Memory Models, Biological Recurrence Risk Assessment/methods Tuberculosis/epidemiology/immunology/prevention & control/transmission LA - eng N1 - Rodrigues, Paula Margheri, Alessandro Rebelo, Carlota Gomes, M Gabriela M Research Support, Non-U.S. Gov't England Journal of theoretical biology J Theor Biol. 2009 Jul 21;259(2):280-90. Epub 2009 Mar 21. PY - 2009 RN - fulltext fulltext_1208 SN - 1095-8541 (Electronic) 0022-5193 (Linking) SP - 280-90 ST - Heterogeneity in susceptibility to infection can explain high reinfection rates T2 - J Theor Biol TI - Heterogeneity in susceptibility to infection can explain high reinfection rates UR - http://ac.els-cdn.com/S002251930900126X/1-s2.0-S002251930900126X-main.pdf?_tid=0e76250e4b0924442f25d4e7f94d036f&acdnat=1345013156_bb0915944646b87f81a0b0a2e026cb6c VL - 259 ID - 2579 ER - TY - JOUR AB - Tuberculosis (TB) is the leading cause of death among individuals infected with the human immunodeficiency virus (HIV). The study of the joint dynamics of HIV and TB present formidable mathematical challenges due to the fact that the models of transmission are quite distinct. Furthermore, although there is overlap in the populations at risk of HIV and TB infections, the magnitude of the proportion of individuals at risk for both diseases is not known. Here, we consider a highly simplified deterministic model that incorporates the joint dynamics of TB and HIV, a model that is quite hard to analyze. We compute independent reproductive numbers for TB (R1) and HIV (R2) and the overall reproductive number for the system, R=max{R1, R2}. The focus is naturally (given the highly simplified nature of the framework) on the qualitative analysis of this model. We find that if R < 1 then the disease-free equilibrium is locally asymptotically stable. The TB-only equilibrium ET is locally asymptotically stable if R1 < 1 and R2 < 1. However, the symmetric condition, R1 < 1 and R2 > 1, does not necessarily guarantee the stability of the HIV-only equilibrium EH, and it is possible that TB can coexist with HIV when R2 > 1. In other words, in the case when R1 < 1 and R2 > 1 (or when R1 > 1 and R2 > 1), we are able to find a stable HIV/TB coexistence equilibrium. Moreover, we show that the prevalence level of TB increases with R2 > 1 under certain conditions. Through simulations, we find that i) the increased progression rate from latent to active TB in co-infected individuals may play a significant role in the rising prevalence of TB; and ii) the increased progression rates from HIV to AIDS have not only increased the prevalence level of HIV while decreasing TB prevalence, but also generated damped oscillations in the system. AD - Department of Mathematics and Statistics, Box 41042, Texas Tech University, Lubbock, TX 79409, USA. lih-ing.roeger@ttu.edu AN - 19835430 AU - Roeger, L. I. AU - Feng, Z. AU - Castillo-Chavez, C. DA - Oct DO - 10.3934/mbe.2009.6.815. DP - Nlm ET - 10/20 KW - Comorbidity HIV Infections/ complications/epidemiology Humans Mathematical Concepts Models, Biological Risk Factors Time Factors Tuberculosis, Pulmonary/ complications/epidemiology LA - eng PY - 2009 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1547-1063 (Print) 1547-1063 (Linking) SP - 815-37 ST - Modeling TB and HIV co-infections T2 - Math Biosci Eng TI - Modeling TB and HIV co-infections VL - 6 ID - 2580 ER - TY - JOUR AB - OBJECTIVE: Kenya is heralded as an example of declining HIV in Africa, while its tuberculosis (TB) numbers continue rising. We conducted a comparative investigation of TB-HIV co-dynamics in Africa to determine the likelihood of reported trends. METHODS AND RESULTS: Our mathematical modeling analysis exposes the notable incongruence of reported trends in Kenya because TB-HIV co-dynamics, tightly knit worldwide and most dramatically in sub-Saharan Africa, suggest that declining HIV trends should trigger reductions in TB trends. Moreover, a continental-scale analysis of TB-HIV trends places Kenya as an outlier in eastern and southern Africa, and shows TB outpacing HIV in western central Africa. We further investigate which TB processes across HIV stages have greater potential to reduce TB incidence via a sensitivity analysis. CONCLUSIONS: There are two parsimonious explanations: an unaccounted improvement in TB case detection has occurred, or HIV is not declining as reported. The TB-HIV mismatch could be compounded by surveillance biases due to spatial heterogeneity in disease dynamics. Results highlight the need to re-evaluate trends of both diseases in Kenya, and identify the most critical epidemiological factors at play. Substantial demographic changes have occurred in Kenya, including rapid urbanization accompanied by poor living conditions, which could disproportionately increase TB incidence. Other possible contributors include immune reconstitution due to the recent delivery of antiretrovirals, and an increased presence of the virulent Beijing/W TB genotype. Results support the importance of integrating information from closely interacting epidemics, because this approach provides critical insights unobtainable when components of generalized epidemics are considered individually. AD - Department of Environmental Science, Policy and Management, University of California, 137 Mulford Hall, Berkeley, CA 94720-3112, USA. msanchez@nature.berkeley.edu AN - 21352748 AU - Sanchez, M. S. AU - Lloyd-Smith, J. O. AU - Williams, B. G. AU - Porco, T. C. AU - Ryan, S. J. AU - Borgdorff, M. W. AU - Mansoer, J. AU - Dye, C. AU - Getz, W. M. DA - Mar DO - S1755-4365(08)00003-0 [pii] 10.1016/j.epidem.2008.08.001 [doi] DP - Nlm ET - 03/01 KW - Anti-Retroviral Agents/therapeutic use HIV Infections/drug therapy/ epidemiology Humans Kenya/epidemiology Models, Biological Prevalence Sentinel Surveillance Tuberculosis/diagnosis/ epidemiology/prevention & control LA - eng N1 - Sanchez, Maria S Lloyd-Smith, James O Williams, Brian G Porco, Travis C Ryan, Sadie J Borgdorff, Martien W Mansoer, John Dye, Christopher Getz, Wayne M Comparative Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Netherlands Epidemics Epidemics. 2009 Mar;1(1):14-20. Epub 2008 Nov 6. PY - 2009 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1878-0067 (Electronic) 1878-0067 (Linking) SP - 14-20 ST - Incongruent HIV and tuberculosis co-dynamics in Kenya: interacting epidemics monitor each other T2 - Epidemics TI - Incongruent HIV and tuberculosis co-dynamics in Kenya: interacting epidemics monitor each other UR - http://ac.els-cdn.com/S1755436508000030/1-s2.0-S1755436508000030-main.pdf?_tid=d70a98b54da4304818c4ac65a058feac&acdnat=1345013202_c90577b411728ebebe90e509ba017b8c VL - 1 ID - 2581 ER - TY - JOUR AB - The long-term persistence of Mycobacterium tuberculosis in communities with high tuberculosis prevalence is a serious problem aggravated by the presence of drug-resistant tuberculosis strains. Drug resistance in an individual patient is often discovered only after a long delay, particularly if the diagnosis is based on current culture-based drug sensitivity testing methods. During such delays, the patient may transmit tuberculosis to his or her contacts. Rapid diagnosis of drug resistance would be expected to reduce this transmission and hence to decrease the prevalence of drug-resistant strains. To investigate this quantitatively, a mathematical model was constructed, assuming a homogeneous population structure typical of communities in South Africa where tuberculosis incidence is high. Computer simulations performed with this model showed that current control strategies will not halt the spread of multidrug-resistant tuberculosis in such communities. The simulations showed that the rapid diagnosis of drug resistance can be expected to reduce the incidence of drug-resistant cases provided the additional measure of screening within the community is implemented. AD - Faculty of Health Sciences, MRC Center for Molecular and Cellular Biology, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Tygerberg, South Africa. pieter@edserve.co.za AN - 19297604 AU - Uys, P. W. AU - Warren, R. AU - van Helden, P. D. AU - Murray, M. AU - Victor, T. C. DA - May DO - JCM.02289-08 [pii] 10.1128/JCM.02289-08 [doi] DP - Nlm ET - 03/20 KW - Computer Simulation Drug Resistance, Multiple, Bacterial Humans Microbial Sensitivity Tests Models, Theoretical Mycobacterium tuberculosis/ drug effects/genetics/ isolation & purification South Africa Time Factors Tuberculosis, Multidrug-Resistant/ diagnosis/ microbiology/transmission L1 - internal-pdf://1495523986/Uys-2009-Potential of rapid diagnosis for cont.pdf LA - eng N1 - Uys, Pieter W Warren, Robin van Helden, Paul D Murray, Megan Victor, Thomas C Research Support, Non-U.S. Gov't United States Journal of clinical microbiology J Clin Microbiol. 2009 May;47(5):1484-90. Epub 2009 Mar 18. PY - 2009 RN - fulltext fulltext_1208 SN - 1098-660X (Electronic) 0095-1137 (Linking) SP - 1484-90 ST - Potential of rapid diagnosis for controlling drug-susceptible and drug-resistant tuberculosis in communities where Mycobacterium tuberculosis infections are highly prevalent T2 - J Clin Microbiol TI - Potential of rapid diagnosis for controlling drug-susceptible and drug-resistant tuberculosis in communities where Mycobacterium tuberculosis infections are highly prevalent UR - http://jcm.asm.org/content/47/5/1484.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681859/pdf/2289-08.pdf VL - 47 ID - 2583 ER - TY - JOUR AB - BACKGROUND: The incidence of tuberculosis (TB) in The Netherlands has been declining for many years. For the purpose of planning future TB-control activities we estimated the number of TB patients in The Netherlands up to 2030. METHODS: Statistical modelling for 5-year age groups up to 2030 distinguishing among Dutch TB patients infected by a Dutch source (survival model), non-Dutch patients (projection of the proportion of culture-positive patients among first generation immigrants) and Dutch patients infected by a non-Dutch source (fixed relation with the number of non-Dutch patients). RESULTS: The number of TB patients is expected to decline to 877 in 2030. After 2010 declines may slow due to an increase in non-Dutch TB patients. This increase cancels out the decrease of Dutch TB patients infected by a Dutch source. In 2030, 85% of all TB patients are expected to be non-Dutch. In the four largest counties and the rest of The Netherlands, this will be 89 and 76%, respectively. CONCLUSION: The decrease in TB incidence observed over many years may stall from 2010 onwards because of an estimated increase in non-Dutch TB patients. Given their disproportionate burden, future TB-control activities should prioritize the health of first-generation immigrants. Enhanced TB control in the countries of origin and new diagnostic tests to identify those at high risk of developing active TB could help in reducing further the TB incidence in the Netherlands. Future TB-control efforts must be organized in a flexible way to be able to incorporate changing epidemiological situations. AD - KNCV Tuberculosis Foundation, 2514 JD Den Haag, The Hague, The Netherlands. vanlethf@kncvtbc.nl AN - 19357241 AU - van Leth, F. AU - Kalisvaart, N. A. AU - Erkens, C. G. AU - Borgdoff, M. W. DA - Aug DO - ckp042 [pii] 10.1093/eurpub/ckp042 [doi] DP - Nlm ET - 04/10 KW - Adolescent Adult Aged Female Forecasting Humans Life Tables Male Middle Aged Netherlands/epidemiology Tuberculosis/ epidemiology/ethnology Young Adult LA - eng N1 - van Leth, Frank Kalisvaart, Nico A Erkens, Connie G M Borgdoff, Martien W England European journal of public health Eur J Public Health. 2009 Aug;19(4):424-7. Epub 2009 Apr 8. PY - 2009 RN - fulltext fulltext_1208 SN - 1464-360X (Electronic) 1101-1262 (Linking) SP - 424-7 ST - Projection of the number of patients with tuberculosis in the Netherlands in 2030 T2 - Eur J Public Health TI - Projection of the number of patients with tuberculosis in the Netherlands in 2030 UR - http://eurpub.oxfordjournals.org/content/19/4/424.full.pdf VL - 19 ID - 2584 ER - TY - BILL AB - We consider a four-compartment tuberculosis model including exogenous reinfection. We derive sufficient conditions, in terms of the parameters of the system, which guarantee the occurrence of backward bifurcation. We also discuss the global stability of the endemic state by using a generalization of the Poincaré-Bendixson criterion. An application is given for the case of Internally Displaced People's Camps in North Uganda. The study suggests how important it is to provide qualitative indications on the threshold value of the population density in the area occupied by the camps, in order to possibly eradicate the disease. AD - a Department of Mathematics and Applications , University of Naples Federico II , via Cintia , I-80126 , Naples , Italy. AN - 22881205 DA - Nov 1 LB - p31787 M1 - 6 PY - 2010 RN - fulltext fulltext_1208 SP - 571-93 ST - Analysis of a tuberculosis model with a case study in Uganda T2 - J Biol Dyn TI - Analysis of a tuberculosis model with a case study in Uganda UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=22881205 VL - 4 ID - 2590 ER - TY - JOUR AB - In this paper we consider the fractional order model with two immune effectors interacting with two strain antigen. The systems may explain the recurrence of some diseases e.g. tuberculosis (TB). The stability of equilibrium points are studied. Numerical solutions of this model are given. Using integer order system the system oscillates. Using fractional order system the system converges to a stable internal equilibrium. Ulam-Hyers stability of the system has been studied. AD - Mathematics Department, Damietta Faculty of Science, Mansoura University, 34517, New Damietta, Egypt. halaelsaka@yahoo.com. AN - 21106113 AU - Ahmed el, S. M. AU - El-Saka, H. A. DO - 1753-4631-4-6 [pii] 10.1186/1753-4631-4-6 [doi] DP - Nlm ET - 11/26 LA - eng N1 - Ahmed, El-Sayed M El-Saka, Hala A United States Nonlinear biomedical physics Nonlinear Biomed Phys. 2010 Nov 25;4:6. PY - 2010 RN - fulltext fulltext_1208 SN - 1753-4631 (Electronic) 1753-4631 (Linking) SP - 6 ST - On modeling two immune effectors two strain antigen interaction T2 - Nonlinear Biomed Phys TI - On modeling two immune effectors two strain antigen interaction UR - http://www.nonlinearbiomedphys.com/content/pdf/1753-4631-4-6.pdf VL - 4 ID - 2585 ER - TY - JOUR AB - Smoking has long being associated with tuberculosis. We present a tuberculosis dynamics model taking into account the fact that some people in the population are smoking in order to assess the effects of smoking on tuberculosis transmission. The epidemic thresholds known as the reproduction numbers and equilibria for the model are determined and stabilities analyzed. Qualitative analysis of the model including positivity and persistence of solutions are presented. The model is numerically analyzed to assess the effects of smoking on the transmission dynamics of tuberculosis. Numerical simulations of the model show that smoking enhances tuberculosis transmission, progression to active disease and in a population of smokers, tuberculosis cannot be controlled even when treatment success is assumed to be as high as 88%. Further, analysis of the reproduction numbers indicates that the number of active tuberculosis cases increases as the number of smokers increase. AD - Department of Applied Mathematics, Modelling Biomedical Systems Research Group, National University of Science and Technology, Ascot, Bulawayo, Zimbabwe. cpbhunu@gmail.com AN - 20725798 AU - Bhunu, C. P. AU - Mushayabasa, S. AU - Tchuenche, J. M. DA - Jun DO - 10.1007/s11538-010-9568-6 [doi] DP - Nlm ET - 08/21 KW - Antitubercular Agents/therapeutic use Basic Reproduction Number Computer Simulation Humans Models, Immunological Mycobacterium tuberculosis/ immunology Smoking/adverse effects/ immunology Tuberculosis/drug therapy/ immunology/ transmission LA - eng N1 - Bhunu, C P Mushayabasa, S Tchuenche, J M United States Bulletin of mathematical biology Bull Math Biol. 2011 Jun;73(6):1333-57. Epub 2010 Aug 20. PY - 2010 RN - fulltext fulltext_1208 SN - 1522-9602 (Electronic) 0092-8240 (Linking) SP - 1333-57 ST - A theoretical assessment of the effects of smoking on the transmission dynamics of tuberculosis T2 - Bull Math Biol TI - A theoretical assessment of the effects of smoking on the transmission dynamics of tuberculosis UR - http://www.springerlink.com/content/4n410216p3555249/ VL - 73 ID - 2611 ER - TY - JOUR AB - Background: Prior infection with one strain TB has been linked with diminished likelihood of re-infection by a new strain. This paper attempts to determine the role of declining prevalence of drug-susceptible TB in enabling future epidemics of MDR-TB. Methods: A computer simulation of MDR-TB epidemics was developed using an agent-based model platform programmed in NetLogo (See http://mdr.tbtools.org/). Eighty-one scenarios were created, varying levels of treatment quality, diagnostic accuracy, microbial fitness cost, and the degree of immunogenicity elicited by drug-susceptible TB. Outcome measures were the number of independent MDR-TB cases per trial and the proportion of trials resulting in MDR-TB epidemics for a 500 year period after drug therapy for TB is introduced. Results: MDR-TB epidemics propagated more extensively after TB prevalence had fallen. At a case detection rate of 75%, improving therapeutic compliance from 50% to 75% can reduce the probability of an epidemic from 45% to 15%. Paradoxically, improving the case-detection rate from 50% to 75% when compliance with DOT is constant at 75% increases the probability of MDR-TB epidemics from 3% to 45%. Conclusions: The ability of MDR-TB to spread depends on the prevalence of drug-susceptible TB. Immunologic protection conferred by exposure to drug-susceptible TB can be a crucial factor that prevents MDR-TB epidemics when TB treatment is poor. Any single population that successfully reduces its burden of drug-susceptible TB will have reduced herd immunity to externally or internally introduced strains of MDR-TB and can experience heightened vulnerability to an epidemic. Since countries with good TB control may be more vulnerable, their self interest dictates greater promotion of case detection and DOTS implementation in countries with poor control to control their risk of MDR-TB. AD - Stanford Univ, Sch Humanities & Sci, Stanford, CA 94305 USA Johns Hopkins Sch Med, Dept Med, Div Infect Dis, Baltimore, MD USA Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA AN - WOS:000282053100016 AU - Bishai, J. D. AU - Bishai, W. R. AU - Bishai, D. M. DA - Sep 22 DO - ARTN e12843 10.1371/journal.pone.0012843 IS - 9 J2 - Plos One KW - resistant mycobacterium-tuberculosis exogenous reinfection united-states transmission emergence dynamics russia model patterns fitness L1 - internal-pdf://1603501073/Bishai-2010-Heightened Vulnerability to MDR-TB.pdf LA - English N1 - 653ac Times Cited:7 Cited References Count:37 PY - 2010 SN - 1932-6203 ST - Heightened Vulnerability to MDR-TB Epidemics after Controlling Drug-Susceptible TB T2 - Plos One TI - Heightened Vulnerability to MDR-TB Epidemics after Controlling Drug-Susceptible TB UR - ://WOS:000282053100016 http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0012843&type=printable VL - 5 ID - 4856 ER - TY - JOUR AB - SETTING: Bleach sedimentation is a method used to increase the diagnostic yield of sputum microscopy for countries with a high prevalence of human immunodeficiency virus (HIV) infection and limited resources. OBJECTIVES: To compare the relative cost-effectiveness of different microscopy approaches in diagnosing tuberculosis (TB) in Kenya. METHODS: An analytical decision tree model including cost and effectiveness measures of 10 combinations of direct (D) and overnight bleach (B) sedimentation microscopy was constructed. Data were drawn from the evaluation of the bleach sedimentation method on two specimens (first on the spot [1] and second morning [2]) from 644 TB suspects in a peripheral health clinic. Incremental cost per smear-positive detected case was measured. Costs included human resources and materials using a micro-costing evaluation. RESULTS: All bleach-based microscopy approaches detected significantly more cases (between 23.3% for B1 and 25.9% for B1+B2) than the conventional D1+D2 approach (21.0%). Cost per tested case ranged between respectively euro 2.7 and euro 4.5 for B1 and B1+D2+B2. B1 and B1+B2 were the most cost-effective approaches. D1+B2 and D1+B1 were good alternatives to avoid using approaches exclusively based on bleach sedimentation microscopy. CONCLUSIONS: Among several effective microscopy approaches used, including sodium hypochlorite sedimentation, only some resulted in a limited increase in the laboratory workload and would be most suitable for programmatic implementation. AD - Epicentre, Paris, France. maryline.bonnet@geneva.msf.org AN - 20392349 AU - Bonnet, M. AU - Tajahmady, A. AU - Hepple, P. AU - Ramsay, A. AU - Githui, W. AU - Gagdnidze, L. AU - Guerin, P. J. AU - Varaine, F. DA - May DP - Nlm ET - 04/16 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Centrifugation Cost-Benefit Analysis Decision Trees Humans Kenya/epidemiology Microscopy/economics/ methods Sodium Hypochlorite/ chemistry Sputum/ microbiology Time Factors Tuberculosis, Pulmonary/ diagnosis/epidemiology LA - eng N1 - Bonnet, M Tajahmady, A Hepple, P Ramsay, A Githui, W Gagdnidze, L Guerin, P J Varaine, F Research Support, Non-U.S. Gov't France Int J Tuberc Lung Dis. 2010 May;14(5):571-7. PY - 2010 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1815-7920 (Electronic) 1027-3719 (Linking) SP - 571-7 ST - Added value of bleach sedimentation microscopy for diagnosis of tuberculosis: a cost-effectiveness study T2 - Int J Tuberc Lung Dis TI - Added value of bleach sedimentation microscopy for diagnosis of tuberculosis: a cost-effectiveness study VL - 14 ID - 2587 ER - TY - JOUR AB - This paper deals with the problem of optimal control for the transmission dynamics of tuberculosis (TB). A tuberculosis model which incorporates the essential biological and epidemiological features of the disease such as exogenous reinfection and chemoprophylaxis of latently infected individuals, and treatment of the infectious is developed and rigorously analyzed. Based on this continuous model, the tuberculosis control is formulated and solved as an optimal control theory problem, indicating how a control term on the chemoprophylaxis should be introduced in the population to reduce the number of individuals with active TB. The feedback control law has been proved to be capable of reducing the number of individuals with active TB. An advantage is that the proposed scheme accounts for the energy wasted by the controller and the closed-loop performance on tracking. Numerical results show the performance of the optimization strategy. AD - Univ Douala, Fac Sci, Dept Math & Comp Sci, Lab Appl Math, Douala, Cameroon UPMC UMMISCO, IRD, UMI 209, Bondy, France Projet MASAIE INRIA Grand Est, Paris, France AN - WOS:000281012800012 AU - Bowong, S. DA - Sep DO - 10.1007/s11071-010-9683-9 IS - 4 J2 - Nonlinear Dynam KW - epidemiological models tuberculosis optimal control riccati equation exogenous reinfection backward bifurcation model systems hiv synchronization vaccination evolution diseases relapse LA - English N1 - 639yj Times Cited:18 Cited References Count:59 PY - 2010 SN - 0924-090x SP - 729-748 ST - Optimal control of the transmission dynamics of tuberculosis T2 - Nonlinear Dynamics TI - Optimal control of the transmission dynamics of tuberculosis UR - ://WOS:000281012800012 VL - 61 ID - 4857 ER - TY - JOUR AB - Tuberculosis (TB) is the leading cause of death among individuals infected with the hepatitis B virus (HBV). The study of the joint dynamics of HBV and TB present formidable mathematical challenges due to the fact that the models of transmission are quite distinct. We formulate and analyze a deterministic mathematical model which incorporates of the co-dynamics of hepatitis B and tuberculosis. Two sub-models, namely: HBV-only and TB-only sub-models are considered first of all. Unlike the HBV-only sub-model, which has a globally-asymptotically stable disease-free equilibrium whenever the associated reproduction number is less than unity, the TB-only sub-model undergoes the phenomenon of backward bifurcation, where a stable disease-free equilibrium co-exists with a stable endemic equilibrium, for a certain range of the associated reproduction number less than unity. Thus, for TB, the classical requirement of having the associated reproduction number to be less than unity, although necessary, is not sufficient for its elimination. It is also shown, that the full HBV-TB co-infection model undergoes a backward bifurcation phenomenon. Through simulations, we mainly find that i) the two diseases will co-exist whenever their partial reproductive numbers exceed unity; (ii) the increased progression rate due to exogenous reinfection from latent to active TB in co-infected individuals may play a significant role in the rising prevalence of TB; and (iii) the increased progression rates from acute stage to chronic stage of HBV infection have increased the prevalence levels of HBV and TB prevalences. AD - Univ Douala, Lab Appl Math, Dept Math & Comp Sci, Fac Sci, Douala, Cameroon Postdam Inst Climate Impact Res PIK, D-14412 Potsdam, Germany Humboldt Univ, Dept Phys, D-12489 Berlin, Germany UPMC, UMI 209, IRD, UMMISCO,Projet MASAIE INRIA Grand Est, Bondy, France AN - WOS:000286884800010 AU - Bowong, S. AU - Kurths, J. DO - 10.1051/mmnp/20105610 IS - 6 J2 - Math Model Nat Pheno KW - nonlinear dynamical systems epidemiological models tuberculosis hepatitis b stability highly endemic areas virus-infection transmission dynamics mathematical-analysis backward bifurcations exogenous reinfection disease burden hiv vaccination prevalence LA - English N1 - 2 715la Times Cited:2 Cited References Count:64 PY - 2010 SN - 0973-5348 SP - 196-242 ST - Modelling Tuberculosis and Hepatitis B Co-infections T2 - Mathematical Modelling of Natural Phenomena TI - Modelling Tuberculosis and Hepatitis B Co-infections UR - ://WOS:000286884800010 VL - 5 ID - 4859 ER - TY - JOUR AB - We propose a method based on synchronization to identify the parameters and to estimate the underlying variables for an epidemic model from real data. We suggest an adaptive synchronization method based on observer approach with an effective guidance parameter to update rule design only from real data. In order, to validate the identifiability and estimation results, numerical simulations of a tuberculosis (TB) model using real data of the region of Center in Cameroon are performed to estimate the parameters and variables. This study shows that some tools of synchronization of nonlinear systems can help to deal with the parameter and state estimation problem in the field of epidemiology. We exploit the close link between mathematical modelling, structural identifiability analysis, synchronization, and parameter estimation to obtain biological insights into the system modelled. (C) 2010 Elsevier B.V. All rights reserved. AD - Univ Douala, Fac Sci, Dept Math & Comp Sci, Lab Appl Math, Douala, Cameroon Postdam Inst Climate Impact Res PIK, D-14412 Potsdam, Germany Humboldt Univ, Dept Phys, D-12489 Berlin, Germany AN - WOS:000283344200003 AU - Bowong, S. AU - Kurths, J. DA - Oct 4 DO - 10.1016/j.physleta.2010.09.008 IS - 44 J2 - Phys Lett A KW - epidemiological models parameter identification adaptive synchronization tuberculosis systems dynamics LA - English N1 - 669jr Times Cited:11 Cited References Count:30 PY - 2010 SN - 0375-9601 SP - 4496-4505 ST - Parameter estimation based synchronization for an epidemic model with application to tuberculosis in Cameroon T2 - Physics Letters A TI - Parameter estimation based synchronization for an epidemic model with application to tuberculosis in Cameroon UR - ://WOS:000283344200003 VL - 374 ID - 4860 ER - TY - JOUR AB - This paper deals with the global analysis of a dynamical model for the spread of tuberculosis with a general contact rate The model exhibits the traditional threshold behavior We prove that when the basic reproduction ratio is less than unity, then the disease-free equilibrium is globally asymptotically stable and when the basic reproduction ratio is great than unity, a unique endemic equilibrium exists and is globally asymptotically stable under certain conditions. The stability of equilibria is derived through the use of Lyapunov stability theory and LaSalle's invariant set theorem. Numerical simulations are provided to illustrate the theoretical results (C) 2010 Elsevier B V All rights reserved AD - Univ Douala, Fac Sci, Dept Math & Comp Sci, Lab Appl Math, Douala, Cameroon Postdam Inst Climate Impact Res PIK, D-14412 Potsdam, Germany Univ Yaounde, Dept Math & Phys, Natl Adv Sch Engn, Yaounde, Cameroon IRD UPMC UMMISCO, UMI 209, Project MASAIE INRIA Grand Est, Bondy, France LIRIMA, Project GRIMCAPE, Yaounde, Cameroon AN - WOS:000278723500044 AU - Bowong, S. AU - Tewa, J. J. DA - Nov DO - 10.1016/j.cnsns.2010.01.007 IS - 11 J2 - Commun Nonlinear Sci KW - dynamical systems epidemiological models general contact rate tuberculosis global stability lyapunov functions heterogeneous populations epidemiologic models lyapunov functions stability analysis seir strategies systems sir LA - English N1 - 610hw Times Cited:12 Cited References Count:46 PY - 2010 SN - 1007-5704 SP - 3621-3631 ST - Global analysis of a dynamical model for transmission of tuberculosis with a general contact rate T2 - Communications in Nonlinear Science and Numerical Simulation TI - Global analysis of a dynamical model for transmission of tuberculosis with a general contact rate UR - ://WOS:000278723500044 VL - 15 ID - 4861 ER - TY - JOUR AB - BACKGROUND: Mathematical models of tuberculosis (TB) transmission have been used to characterize disease dynamics, investigate the potential effects of public health interventions, and prioritize control measures. While previous work has addressed the mathematical description of TB natural history, the impact of demography on the behaviour of TB models has not been assessed. METHODS: A simple model of TB transmission, with alternative assumptions about survivorship, is used to explore the effect of age structure on the prevalence of infection, disease, basic reproductive ratio and the projected impact of control interventions. We focus our analytic arguments on the differences between constant and exponentially distributed lifespans and use an individual-based model to investigate the range of behaviour arising from realistic distributions of survivorship. RESULTS: The choice of age structure and natural (non-disease related) mortality strongly affects steady-state dynamics, parameter estimation and predictions about the effectiveness of control interventions. Since most individuals infected with TB develop an asymptomatic latent infection and never progress to active disease, we find that assuming a constant mortality rate results in a larger reproductive ratio and an overestimation of the effort required for disease control in comparison to using more realistic age-specific mortality rates. CONCLUSIONS: Demographic modelling assumptions should be considered in the interpretation of models of chronic infectious diseases such as TB. For simple models, we find that assuming constant lifetimes, rather than exponential lifetimes, produces dynamics more representative of models with realistic age structure. AD - Department of Epidemiology, Harvard School of Public Health, Brigham and Women's Hospital, Boston, Massachusetts, United States of America. ebrooks@hsph.harvard.edu AN - 20062531 AU - Brooks-Pollock, E. AU - Cohen, T. AU - Murray, M. DO - 10.1371/journal.pone.0008479 [doi] DP - Nlm ET - 01/12 KW - Humans Models, Theoretical Prevalence Tuberculosis/mortality/ transmission LA - eng N1 - Brooks-Pollock, Ellen Cohen, Ted Murray, Megan DP2 OD006663-01/OD/NIH HHS/United States U19 AI076217/AI/NIAID NIH HHS/United States Research Support, N.I.H., Extramural United States PloS one PLoS One. 2010 Jan 7;5(1):e8479. PY - 2010 RN - fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e8479 ST - The impact of realistic age structure in simple models of tuberculosis transmission T2 - PLoS One TI - The impact of realistic age structure in simple models of tuberculosis transmission UR - http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0008479&representation=PDF VL - 5 ID - 2588 ER - TY - JOUR AB - BACKGROUND: Mycobacterium tuberculosis is a particularly aggressive microorganism and the host's defense is based on the induction of cellular immunity, in which the creation of a granulomatous structure has an important role. METHODOLOGY: We present here a new 2D cellular automata model based on the concept of a multifunctional process that includes key factors such as the chemokine attraction of the cells; the role of innate immunity triggered by natural killers; the presence of neutrophils; apoptosis and necrosis of infected macrophages; the removal of dead cells by macrophages, which induces the production of foamy macrophages (FMs); the life cycle of the bacilli as a determinant for the evolution of infected macrophages; and the immune response. RESULTS: The results obtained after the inclusion of two degrees of tolerance to the inflammatory response triggered by the infection shows that the model can cover a wide spectrum, ranging from highly-tolerant (i.e. mice) to poorly-tolerant hosts (i.e. mini-pigs or humans). CONCLUSIONS: This model suggest that stopping bacillary growth at the onset of the infection might be difficult and the important role played by FMs in bacillary drainage in poorly-tolerant hosts together with apoptosis and innate lymphocytes. It also shows the poor ability of the cellular immunity to control the infection, provides a clear protective character to the granuloma, due its ability to attract a sufficient number of cells, and explains why an already infected host can be constantly reinfected. AD - Departamento de Matematica Aplicada, Facultad de Matematicas, Universidad Complutense de Madrid, Madrid, Spain. AN - 20886087 AU - Bru, A. AU - Cardona, P. J. DO - 10.1371/journal.pone.0012985 [doi] DP - Nlm ET - 10/05 KW - Animals Chemokines/immunology Granuloma/immunology/microbiology Host-Pathogen Interactions Humans Macrophages/immunology/microbiology Mice Models, Biological Models, Theoretical Mycobacterium tuberculosis/ chemistry/ growth & development/immunology/physiology Swine Swine, Miniature Tuberculosis/ immunology/ microbiology LA - eng N1 - Bru, Antonio Cardona, Pere-Joan Research Support, Non-U.S. Gov't United States PloS one PLoS One. 2010 Sep 23;5(9):e12985. PY - 2010 RN - fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e12985 ST - Mathematical modeling of tuberculosis bacillary counts and cellular populations in the organs of infected mice T2 - PLoS One TI - Mathematical modeling of tuberculosis bacillary counts and cellular populations in the organs of infected mice UR - http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0012985&representation=PDF VL - 5 ID - 2589 ER - TY - CHAP AB - A discrete tuberculosis model with different infectious compartments is formulated and studied. The basic reproduction number, of the model is defined. The global stability of the disease-free equilibrium is proved if R-0 < 1. The existence of endemic equilibrium and the persistence of TB is established if R-0 > 1. The main attention is paid on the influence of the infectivity proportion on the case number. The numerical simulations show that the infection cases increase as p increase. AD - [Cao, Hui; Zhou, Yicang] Xi An Jiao Tong Univ, Dept Math, Xian 710049, Peoples R China. Cao, H (reprint author), Xi An Jiao Tong Univ, Dept Math, Xian 710049, Peoples R China. caohui0103@163.com; zhouyc@mail.xjtu.edu.cn AN - WOS:000397260202044 AU - Cao, H. AU - Zhou, Y. C. AU - Ieee CY - New York KW - Discrete epidemic model Smear-positive Smear-negative Tuberculosis epidemic models time sis LA - English N1 - ISI Document Delivery No.: BH0ZM Times Cited: 0 Cited Reference Count: 11 Cao, Hui Zhou, Yicang Icbbe 2010 Proceedings Paper 4th International Conference on Bioinformatics and Biomedical Engineering (iCBBE) Jun 18-20, 2010 Chengdu, PEOPLES R CHINA IEEE Engn Med & Biol Soc, Sichuan Univ, Wuhan Univ Nsfc [10971163] The work was supported by NSFC # 10971163 345 e 47th st, new york, ny 10017 usa 2151-7614 PB - Ieee PY - 2010 SN - 978-1-4244-4713-8 ST - A Discrete Tuberculosis Model with Two Different Infectious Compartments T2 - 2010 4th International Conference on Bioinformatics and Biomedical Engineering T3 - International Conference on Bioinformatics and Biomedical Engineering TI - A Discrete Tuberculosis Model with Two Different Infectious Compartments UR - ://WOS:000397260202044 ID - 5850 ER - TY - JOUR AB - Endogenous infection and exogenous reinfection are two mechanisms responsible for the reactivation or regeneration of active tuberculosis (TB) in individuals who have experienced prior active TB infections. We provide a brief review of a classical reinfection model, introduce a more general model, and include some new results. We conclude with a snapshot on the use of reinfection models in the study of the evolution of TB. AD - Arizona State Univ, Computat Modeling Sci Ctr, POB 871904, Tempe, AZ 85287 USA Arizona State Univ, Sch human Evolut & Social Changes, Tempe, AZ 85287 USA Arizona State Univ, Sch Math & Stat, Tempe, AZ 85287 USA Santa Fe Inst, Santa Fe, NM 87501 USA Univ Nacl Salla, Inst Invest Energias Convencionales, RA-4400 Salla, Argentina AN - WOS:000290496200021 AU - Castillo-Chavez, C. AU - Wang, X. AU - Aparicio, J. P. AU - Feng, Z. DO - Doi 10.1142/9789814304900_0021 KW - brief epidemiologic history intrinsic transmission dynamics exogenous reinfection disease epidemics arcana models USA strategies age LA - English N1 - Buw21 Times Cited:0 Cited References Count:44 PY - 2010 SP - 304-+ ST - On the Dynamics of Reinfection: The Case of Tuberculosis T2 - Biomat 2009 TI - On the Dynamics of Reinfection: The Case of Tuberculosis UR - ://WOS:000290496200021 http://www.worldscientific.com/doi/abs/10.1142/9789814304900_0021 ID - 4862 ER - TY - JOUR AB - Prediction of metabolic changes that result from genetic or environmental perturbations has several important applications, including diagnosing metabolic disorders and discovering novel drug targets. A cardinal challenge in obtaining accurate predictions is the integration of transcriptional regulatory networks with the corresponding metabolic network. We propose a method called probabilistic regulation of metabolism (PROM) that achieves this synthesis and enables straightforward, automated, and quantitative integration of high-throughput data into constraint-based modeling, making it an ideal tool for constructing genome-scale regulatory-metabolic network models for less-studied organisms. PROM introduces probabilities to represent gene states and gene-transcription factor interactions. By using PROM, we constructed an integrated regulatory-metabolic network for the model organism, Escherichia coli, and demonstrated that our method based on automated inference is more accurate and comprehensive than the current state of the art, which is based on manual curation of literature. After validating the approach, we used PROM to build a genome-scale integrated metabolic-regulatory model for Mycobacterium tuberculosis, a critically important human pathogen. This study incorporated data from more than 1,300 microarrays, 2,000 transcription factor-target interactions regulating 3,300 metabolic reactions, and 1,905 KO phenotypes for E. coli and M. tuberculosis. PROM identified KO phenotypes with accuracies as high as 95%, and predicted growth rates quantitatively with correlation of 0.95. Importantly, PROM represents the successful integration of a top-down reconstructed, statistically inferred regulatory network with a bottom-up reconstructed, biochemically detailed metabolic network, bridging two important classes of systems biology models that are rarely combined quantitatively. AD - Center for Biophysics and Computational Biology, Institute for Genomic Biology, Department of Chemical and Biomolecular Engineering, University of Illinois, Urbana, IL 61801, USA. AN - 20876091 AU - Chandrasekaran, S. AU - Price, N. D. DA - Oct 12 DO - 1005139107 [pii] 10.1073/pnas.1005139107 [doi] DP - Nlm ET - 09/30 KW - Algorithms Computational Biology/ methods Escherichia coli/ genetics Gene Regulatory Networks/ genetics Genome, Bacterial/genetics Metabolic Networks and Pathways/ genetics Models, Genetic Mycobacterium tuberculosis/ genetics Systems Biology/ methods LA - eng N1 - Chandrasekaran, Sriram Price, Nathan D R00 CA126184-04/CA/NCI NIH HHS/United States Evaluation Studies Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2010 Oct 12;107(41):17845-50. Epub 2010 Sep 27. PY - 2010 RN - fulltext fulltext_1208 SN - 1091-6490 (Electronic) 0027-8424 (Linking) SP - 17845-50 ST - Probabilistic integrative modeling of genome-scale metabolic and regulatory networks in Escherichia coli and Mycobacterium tuberculosis T2 - Proc Natl Acad Sci U S A TI - Probabilistic integrative modeling of genome-scale metabolic and regulatory networks in Escherichia coli and Mycobacterium tuberculosis UR - http://www.pnas.org/content/107/41/17845.full.pdf VL - 107 ID - 2591 ER - TY - JOUR AB - The objective of this article is to characterize the risk of infection from airborne Mycobacterium tuberculosis bacilli exposure in commercial passenger trains based on a risk-based probabilistic transmission modeling. We investigated the tuberculosis (TB) infection risks among commercial passengers by inhaled aerosol M. tuberculosis bacilli and quantify the patterns of TB transmission in Taiwan High Speed Rail (THSR). A deterministic Wells-Riley mathematical model was used to account for the probability of infection risk from M. tuberculosis bacilli by linking the cough-generated aerosol M. tuberculosis bacilli concentration and particle size distribution. We found that (i) the quantum generation rate of TB was estimated with a lognormal distribution of geometric mean (GM) of 54.29 and geometric standard deviation (GSD) of 3.05 quantum/h at particle size euro75 000/YLG was when the prevalence of LTBI around TB was low (<5%) and TST specificity high (>90%). CONCLUSIONS: In France, for the diagnosis of LTBI after close contact with TB, the TST is more expensive and less effective than QFT. Although it is more expensive, QFT is more effective and cost-effective than TST+QFT under a wide range of realistic test performance scenarios. AD - Institut National de la Sante et de la Recherche Medicale (INSERM) U795, Faculte de Medecine, Lille, France. sylvie.burban@yahoo.fr AN - 20202306 AU - Deuffic-Burban, S. AU - Atsou, K. AU - Viget, N. AU - Melliez, H. AU - Bouvet, E. AU - Yazdanpanah, Y. DA - Apr DP - Nlm ET - 03/06 KW - Adult BCG Vaccine Computer Simulation Contact Tracing Cost-Benefit Analysis Decision Support Techniques Decision Trees France Health Care Costs Humans Interferon-gamma/ analysis Latent Tuberculosis/ diagnosis/ economics/immunology Life Expectancy Mass Screening/ economics/methods Predictive Value of Tests Reagent Kits, Diagnostic/ economics Tuberculin Test/ economics LA - eng N1 - Deuffic-Burban, S Atsou, K Viget, N Melliez, H Bouvet, E Yazdanpanah, Y Comparative Study Evaluation Studies Research Support, Non-U.S. Gov't France The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Int J Tuberc Lung Dis. 2010 Apr;14(4):471-81. PY - 2010 RN - fulltext fulltext_1208 SN - 1815-7920 (Electronic) 1027-3719 (Linking) SP - 471-81 ST - Cost-effectiveness of QuantiFERON-TB test vs. tuberculin skin test in the diagnosis of latent tuberculosis infection T2 - Int J Tuberc Lung Dis TI - Cost-effectiveness of QuantiFERON-TB test vs. tuberculin skin test in the diagnosis of latent tuberculosis infection VL - 14 ID - 2595 ER - TY - JOUR AB - Tuberculosis (TB) granulomas are organized collections of immune cells comprised of macrophages, lymphocytes and other cells that form in the lung as a result of immune response to Mycobacterium tuberculosis (Mtb) infection. Formation and maintenance of granulomas are essential for control of Mtb infection and are regulated in part by a pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF). To characterize mechanisms that control TNF availability within a TB granuloma, we developed a multi-scale two compartment partial differential equation model that describes a granuloma as a collection of immune cells forming concentric layers and includes TNF/TNF receptor binding and trafficking processes. We used the results of sensitivity analysis as a tool to identify experiments to measure critical model parameters in an artificial experimental model of a TB granuloma induced in the lungs of mice following injection of mycobacterial antigen-coated beads. Using our model, we then demonstrated that the organization of immune cells within a TB granuloma as well as TNF/TNF receptor binding and intracellular trafficking are two important factors that control TNF availability and may spatially coordinate TNF-induced immunological functions within a granuloma. Further, we showed that the neutralization power of TNF-neutralizing drugs depends on their TNF binding characteristics, including TNF binding kinetics, ability to bind to membrane-bound TNF and TNF binding stoichiometry. To further elucidate the role of TNF in the process of granuloma development, our modeling and experimental findings on TNF-associated molecular scale aspects of the granuloma can be incorporated into larger scale models describing the immune response to TB infection. Ultimately, these modeling and experimental results can help identify new strategies for TB disease control/therapy. AD - Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA. AN - 20463877 AU - Fallahi-Sichani, M. AU - Schaller, M. A. AU - Kirschner, D. E. AU - Kunkel, S. L. AU - Linderman, J. J. DA - May DO - 10.1371/journal.pcbi.1000778 [doi] DP - Nlm ET - 05/14 KW - Algorithms Animals Apoptosis/physiology Computer Simulation Dendritic Cells/immunology Granuloma/immunology/ metabolism/microbiology/pathology Lymphocytes/immunology Macrophages/immunology Mice Mice, Inbred CBA Models, Biological Mycobacterium tuberculosis Protein Binding Receptors, Tumor Necrosis Factor/metabolism Tuberculin/metabolism Tuberculosis/immunology/ metabolism/pathology Tumor Necrosis Factor-alpha/antagonists & inhibitors/ metabolism LA - eng N1 - Fallahi-Sichani, Mohammad Schaller, Matthew A Kirschner, Denise E Kunkel, Steven L Linderman, Jennifer J PY - 2010 RN - fulltext fulltext_1208 SN - 1553-7358 (Electronic) 1553-734X (Linking) SP - e1000778 ST - Identification of key processes that control tumor necrosis factor availability in a tuberculosis granuloma T2 - PLoS Comput Biol TI - Identification of key processes that control tumor necrosis factor availability in a tuberculosis granuloma UR - http://www.ploscompbiol.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pcbi.1000778&representation=PDF VL - 6 ID - 2596 ER - TY - JOUR AB - A two-strain tuberculosis model with general contact rate which allows tuberculosis patients with the drug-sensitive Mycobacterium tuberculosis strain to be treated is presented. The model includes both drug-sensitive and drug-resistant strains. A detailed qualitative analysis about positivity, boundedness, existence, uniqueness and global stability of the equilibria of this model is carried out. Analytical results of the model show that the quantities R(1) and R(2), which represent the basic reproduction numbers of the sensitive and resistant strains, respectively, provide the threshold conditions which determine the competitive outcomes of the two strains. Numerical simulations are also conducted to confirm and extend the analytic results. AD - Lanzhou Univ Technol, Inst Appl Math, Lanzhou 730050, Gansu, Peoples R China Lanzhou Univ, Hosp 1, Dept Pediat, Lanzhou 730000, Peoples R China AN - WOS:000290323800001 AU - Huo, H. F. AU - Dang, S. J. AU - Li, Y. N. DO - Artn 293747 10.1155/2010/293747 J2 - Abstr Appl Anal KW - nonlinear incidence rate epidemic model heterogeneous populations global stability transmission dynamics L1 - internal-pdf://1217555451/Huo-2010-Stability of a Two-Strain Tuberculosi.pdf LA - English N1 - 760ks Times Cited:6 Cited References Count:34 PY - 2010 SN - 1085-3375 ST - Stability of a Two-Strain Tuberculosis Model with General Contact Rate T2 - Abstract and Applied Analysis TI - Stability of a Two-Strain Tuberculosis Model with General Contact Rate UR - ://WOS:000290323800001 http://downloads.hindawi.com/journals/aaa/2010/293747.pdf ID - 4864 ER - TY - JOUR AB - BACKGROUND: The prevalence of tuberculosis (TB) in the elderly is higher than that in the general population, and elderly populations are considered a high-risk group. Currently, annual TB screening of Bacille Calmette-Guerin (BCG)-vaccinated people aged over 65 years is performed by an annual chest x-ray examination (CXR) in Japan. Interferon-gamma release assays (QuantiFERON-TB Gold and QuantiFERON-TB Gold In-Tube [QFT]) are new alternatives to the tuberculin skin test to diagnose latent TB infection (LTBI) that have no cross-reactivity with the BCG vaccine. We evaluated the cost effectiveness of QFT versus CXR versus no screening in BCG-vaccinated elderly populations. METHODS: We constructed a Markov model to evaluate the cost effectiveness of QFT, CXR, and no screening. The target population was a hypothetical cohort of 1000 immunocompetent 65-year-olds, using a societal perspective and a lifetime horizon. All costs and clinical benefits were discounted at a fixed annual rate of 3%. RESULTS: In the base-case analysis, a no-screening strategy resulted in the lowest cost ($US303.51; 14.6475 quality-adjusted life-years [QALYs]) compared with CXR ($US393.22; 14.6477 QALYs) and QFT ($US525.45; 14.6516 QALYs) [year 2008 values]. The sensitivity of QFT, as well as the prevalence of TB and LTBI, influenced the cost effectiveness; when the sensitivity of QFT was higher than 0.89, QFT became more cost effective than providing no screening. As the prevalence of LTBI and TB increased, the QFT strategy became progressively more cost effective. CONCLUSIONS: Providing no routine TB screening is currently the most cost-effective strategy for BCG-vaccinated elderly populations in Japan. There appears to be little role for CXR in TB screening of elderly populations. These findings may be applicable to other countries with intermediate and high TB risks when choosing optimal TB screening of elderly populations. AD - Bunkyo City Public Health Center, Bunkyo City, Tokyo, Japan. Akiko_Kowada@city.bunkyo.lg.jp AN - 20799765 AU - Kowada, A. AU - Deshpande, G. A. AU - Takahashi, O. AU - Shimbo, T. AU - Fukui, T. DA - Aug 1 DO - 10.2165/11538610-000000000-00000 10.2165/11538610-000000000-00000. DP - Nlm ET - 08/31 J2 - Molecular diagnosis & therapy KW - Aged Aged, 80 and over BCG Vaccine/administration & dosage Cost-Benefit Analysis Female Humans Immunologic Tests/ economics Interferon-gamma/ analysis/ immunology Japan Latent Tuberculosis/ diagnosis/immunology/radiography Male Mass Chest X-Ray/ economics Mass Screening/economics Tuberculosis, Pulmonary/ diagnosis/immunology/radiography LA - eng PY - 2010 RN - fulltext fulltext_1208 SN - 1177-1062 (Print) 1177-1062 (Linking) SP - 229-36 ST - Cost effectiveness of interferon-gamma release assay versus chest X-ray for tuberculosis screening of BCG-vaccinated elderly populations T2 - Mol Diagn Ther TI - Cost effectiveness of interferon-gamma release assay versus chest X-ray for tuberculosis screening of BCG-vaccinated elderly populations VL - 14 ID - 2597 ER - TY - JOUR AB - The explosive increase in the number of people infected with tuberculosis (TB), multi drug resistant tuberculosis (MDRTB), and injecting drug users (IDU) HIV/AIDS has become a serious public health challenge in Russia. The World Health Organization is recommending policies including simultaneous use of highly active antiretroviral therapy (HAART) to treat HIV/AIDS and second line drugs to treat MDRTB. We developed a System Dynamics simulation model to represent the dynamic transmission of TB, MDRTB and human immunodeficiency virus (HIV). The model simulated scenarios regarding MDRTB cure rate and HAART coverage, that is the HIV/AIDS population covered by HAART. The results over a 20-year period indicate that reduction in TB and HIV-associated TB deaths would be negligible for HAART coverage up to 50%. The reduction is only significant for HAART coverage of 70% and above. Similarly, high MDRTB cure rate reduces significantly deaths from TB and MDRTB and this reduction is more important as the HAART coverage is increased. Journal of the Operational Research Society (2010) 61, 1238-1248. doi: 10.1057/jors.2009.90 Published online 5 August 2009 AD - Univ Hertfordshire, Sch Business, Hatfield AL10 9AB, Herts, England Univ London Imperial Coll Sci Technol & Med, London, England London Sch Hyg & Trop Med, London WC1, England AN - WOS:000280099900004 AU - Lebcir, R. M. AU - Atun, R. A. AU - Coker, R. J. DA - Aug DO - 10.1057/jors.2009.90 IS - 8 J2 - J Oper Res Soc KW - health service hiv tuberculosis haart system dynamics russia human-immunodeficiency-virus health-care developing-countries incubation period eastern-europe aids treatment public-health samara oblast model transmission LA - English N1 - 628fl Times Cited:4 Cited References Count:33 PY - 2010 SN - 0160-5682 SP - 1238-1248 ST - System Dynamic simulation of treatment policies to address colliding epidemics of tuberculosis, drug resistant tuberculosis and injecting drug users driven HIV in Russia T2 - Journal of the Operational Research Society TI - System Dynamic simulation of treatment policies to address colliding epidemics of tuberculosis, drug resistant tuberculosis and injecting drug users driven HIV in Russia UR - ://WOS:000280099900004 https://link.springer.com/article/10.1057%2Fjors.2009.90 VL - 61 ID - 4852 ER - TY - BOOK A2 - Jiang, Y. A2 - Song, Q. K. A2 - Chen, L. S. A2 - Tan, Y. S. AB - The paper studies the applicability of the impulsive strategy for the stable eradication of tuberculosis (TB). We formulate an infection-age-structured TB model with impulsive drug-treatment. In the model, infected class includes latent, infected with drug-sensitive TB and infected with drug-resistant TB. We look at the effects of impulsive period T and drug-treatment proportion rho on TB dynamics. AD - [Liu, Helong; Li, Lianbing] Xinyang Normal Univ, Coll Math & Informat Sci, Xinyang 464000, Peoples R China. Liu, HL (reprint author), Xinyang Normal Univ, Coll Math & Informat Sci, Xinyang 464000, Peoples R China. liuhelong2004@yahoo.com.cn AN - WOS:000280408600135 AU - Liu, H. L. AU - Li, L. B. CY - Liverpool KW - tuberculosis infection age impulsive period infection-free state stability tuberculosis LA - English N1 - ISI Document Delivery No.: BPZ09 Times Cited: 0 Cited Reference Count: 7 Liu, Helong Li, Lianbing Proceedings Paper 7th Conference on Biological Dynamic System and Stability of Differential Equation May 14-16, 2010 Chongqing, PEOPLES R CHINA 113, academic house, mill lane, wavertree technology park, liverpool, l13 4 ah, england PB - World Acad Union-World Acad Press PY - 2010 SN - 978-1-84626-029-2 SP - 648-653 ST - An Age-Infection-Structured TB Model with Delay and Impulsive Effects T2 - Proceedings of the 7th Conference on Biological Dynamic System and Stability of Differential Equation, Vols I and Ii TI - An Age-Infection-Structured TB Model with Delay and Impulsive Effects UR - ://WOS:000280408600135 ID - 5876 ER - TY - JOUR AB - The statistical data of tuberculosis (TB) cases show seasonal fluctuations in many countries. A TB model incorporating seasonality is developed and the basic reproduction ratio R(0) is defined. It is shown that the disease-free equilibrium is globally asymptotically stable and the disease eventually disappears if R(0)<1, and there exists at least one positive periodic solution and the disease is uniformly persistent if R(0)>1. Numerical simulations indicate that there may be a unique positive periodic solution which is globally asymptotically stable if R(0)>1. Parameter values of the model are estimated according to demographic and epidemiological data in China. The simulation results are in good accordance with the seasonal variation of the reported cases of active TB in China. AD - Department of Mathematics, Xi'an Jiaotong University, Xi'an 710049, China. lujuliu@gmail.com AN - 20063125 AU - Liu, L. AU - Zhao, X. Q. AU - Zhou, Y. DA - May DO - 10.1007/s11538-009-9477-8 [doi] DP - Nlm ET - 01/12 KW - Basic Reproduction Number China/epidemiology Computer Simulation Humans Models, Biological Mycobacterium tuberculosis/ growth & development Seasons Tuberculosis/ epidemiology/microbiology LA - eng N1 - Liu, Luju Zhao, Xiao-Qiang Zhou, Yicang United States Bulletin of mathematical biology Bull Math Biol. 2010 May;72(4):931-52. Epub 2010 Jan 9. PY - 2010 RN - fulltext fulltext_1208 SN - 1522-9602 (Electronic) 0092-8240 (Linking) SP - 931-52 ST - A tuberculosis model with seasonality T2 - Bull Math Biol TI - A tuberculosis model with seasonality UR - http://www.springerlink.com/content/ch168155037172u8/ VL - 72 ID - 2598 ER - TY - JOUR AB - This paper describes a mathematical model for tuberculosis (TB) and discusses its dynamic behavior. The model is novel in that it combines multi-drug resistant TB (MDR-TB) with undetected TB cases. The basic reproduction number, R-0, is calculated. The result shows that the disease-free equilibrium is globally asymptotically stable if R-0 <= 1, and is unstable if R-0 > 1. When R-0 > 1, there also exists a locally asymptotically stable endemic equilibrium. Simulations confirm the analysis, and exhibit that undetected TB cases play an important role. AD - S China Univ Technol, SCUT CUHK Joint Ctr Automat Sci & Engn, Guangzhou 510460, Guangdong, Peoples R China AN - WOS:000290460300159 AU - Liu, Y. Q. AU - Sun, Z. D. DO - Doi 10.1109/Ccdc.2010.5498120 J2 - Chin Cont Decis Conf KW - mycobacterium-tuberculosis transmission dynamics coinfection equilibria diseases LA - English N1 - Buv61 Times Cited:0 Cited References Count:21 Chinese Control and Decision Conference PY - 2010 SN - 1948-9439 SP - 792-797 ST - A New Model for MDR-TB Infection with Undetected TB Cases T2 - 2010 Chinese Control and Decision Conference, Vols 1-5 TI - A New Model for MDR-TB Infection with Undetected TB Cases UR - ://WOS:000290460300159 http://ieeexplore.ieee.org/document/5498120/?reload=true ID - 4865 ER - TY - JOUR AB - Modeling the interaction of Tuberculosis (TB) and AIDS (HIV) drugs in the treatment of the TB/HIV co-infection shows that the treatment of Mtb (Mycobacterium tuberculosis) and AIDS improves. The administration of HIV drugs without TB drugs during co-infection favors the treatment of HIV, but the patient will eventually die of the Mtb opportunistic infection. Reducing the interaction of TB and HIV drugs and increasing the performance (efficiency of inhibition) of Reverse Transcriptase Inhibitors (RTIs) in CD4+ T cells improves the treatment of HIV and leads to the preferential replication of HIV particles in macrophages. The simultaneous administration of TB and HIV drugs is to be recommended for it prevents patients from dying of the Mtb opportunistic infection. AD - [Magombedze, Gesham; Garira, Winston] Natl Univ Sci & Technol, Dept Appl Math, Modeling Biomed Syst Res Grp, Ascot, Bulawayo, Zimbabwe. [Mwenje, Eddie] Natl Univ Sci & Technol, Dept Appl Biol, Modeling Biomed Syst Res Grp, Ascot, Bulawayo, Zimbabwe. Magombedze, G (reprint author), Natl Univ Sci & Technol, Dept Appl Math, Modeling Biomed Syst Res Grp, POB AC 939, Ascot, Bulawayo, Zimbabwe. gmagombedze@gmail.com AN - WOS:000274168800002 AU - Magombedze, G. AU - Garira, W. AU - Mwenje, E. C7 - Pii 918914817 DO - 10.1080/08898480903467241 IS - 1 J2 - Math. Popul. Stud. KW - AIDS co-infection highly active anti-retroviral therapy (HAART) Mycobacterium tuberculosis TB chemotherapy mycobacterium-tuberculosis infection tumor-necrosis-factor hiv-related tuberculosis host immune-response t-cells antituberculosis drugs granuloma-formation healthy-volunteers fusion inhibitors entry inhibitors Demography Mathematics Mathematical Methods In Social Sciences LA - English M3 - Article N1 - ISI Document Delivery No.: 550XX Times Cited: 4 Cited Reference Count: 61 Magombedze, Gesham Garira, Winston Mwenje, Eddie Garira, Winston/N-8804-2016 Garira, Winston/0000-0001-8909-2236; Magombedze, Gesham/0000-0003-2745-3475 South African DST/NRF Center of Excellence in Epidemiological Modeling and Analysis (SACEMA) Gesham Magombedze acknowledges the financial support of the South African DST/NRF Center of Excellence in Epidemiological Modeling and Analysis (SACEMA). 4 0 Taylor & francis inc Philadelphia PY - 2010 SN - 0889-8480 SP - 12-64 ST - Modeling the TB/HIV-1 Co-Infection and the Effects of Its Treatment T2 - Mathematical Population Studies TI - Modeling the TB/HIV-1 Co-Infection and the Effects of Its Treatment UR - ://WOS:000274168800002 VL - 17 ID - 5871 ER - TY - JOUR AB - We aimed to evaluate the incremental cost-effectiveness of engaging private practitioners (PPs) to refer tuberculosis (TB) suspects to public health centers in Jogjakarta, Indonesia. Effectiveness was assessed for TB suspects notified between May 2004 and April 2005. Private practitioners referred 1,064 TB suspects, of which 57.5% failed to reach a health center. The smear-positive rate among patients reaching a health center was 61.8%. Two hundred eighty (280) out of a total of 1,306 (21.4%) new smear-positive cases were enrolled through the PPs strategy. The incremental cost-effectiveness ratio per smear-positive case successfully treated for the PPs strategy was US$351.66 (95% CI 322.84-601.33). On the basis of an acceptability curve using the National TB control program's willingness-to-pay threshold (US$448.61), we estimate the probability that the PPs strategy is cost-effective at 66.8%. The strategy of engaging PPs was incrementally cost-effective, although under specific conditions, most importantly a well-functioning public directly observed treatment, short-course (DOTS) program. AD - Department of Public Health, Faculty of Medicine, Gadjah Mada University, Jogjakarta, Indonesia. yodi_mahendradhata@yahoo.co.uk AN - 20519613 AU - Mahendradhata, Y. AU - Probandari, A. AU - Ahmad, R. A. AU - Utarini, A. AU - Trisnantoro, L. AU - Lindholm, L. AU - van der Werf, M. J. AU - Kimerling, M. AU - Boelaert, M. AU - Johns, B. AU - Van der Stuyft, P. DA - Jun DO - 82/6/1131 [pii] 10.4269/ajtmh.2010.09-0447 ET - 06/04 KW - Antitubercular Agents/*administration & dosage/*therapeutic use Cost-Benefit Analysis Directly Observed Therapy Humans Indonesia/epidemiology Physician's Practice Patterns/*economics Referral and Consultation Tuberculosis/*drug therapy/*epidemiology LA - eng N1 - Mahendradhata, Yodi Probandari, Ari Ahmad, Riris A Utarini, Adi Trisnantoro, Laksono Lindholm, Lars van der Werf, Marieke J Kimerling, Michael Boelaert, Marleen Johns, Benjamin Van der Stuyft, Patrick Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United States The American journal of tropical medicine and hygiene Am J Trop Med Hyg. 2010 Jun;82(6):1131-9. PY - 2010 RN - fulltext fulltext_1208 SN - 1476-1645 (Electronic) 0002-9637 (Linking) SP - 1131-1139 ST - The incremental cost-effectiveness of engaging private practitioners to refer tuberculosis suspects to DOTS services in Jogjakarta, Indonesia T2 - American Journal of Tropcial Medicine and Hygiene TI - The incremental cost-effectiveness of engaging private practitioners to refer tuberculosis suspects to DOTS services in Jogjakarta, Indonesia UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20519613http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877424/pdf/tropmed-82-1131.pdf VL - 82 ID - 2599 ER - TY - JOUR AB - Tuberculosis (TB) is one of the earliest recorded human diseases and still one of the deadliest worldwide. Its causative agent is the bacteria Mycobacterium tuberculosis (Mtb). Cytokine-mediated macrophage activation is a necessary step in control of bacterial growth, and early immunologic events in lymph node and lung are crucial to the outcome of infection, although the factors that influence these environments and the immune response are poorly understood. Our goal is to build the next-generation two-compartmental model of the immune response to provide a gateway to more spatial and mechanistic investigations of M. tuberculosis infection in the LN and lung. Crucial immune factors emerge that affect macrophage populations and inflammation, namely TNF-dependent recruitment and apoptosis, and IL-10 levels. Surprisingly, bacterial load plays a less important role than TNF in increasing the population of infected macrophages and inflammation. Using a mathematical model, it is possible to distinguish the effects of pro-inflammatory (TNF) and anti-inflammatory (IL-10) cytokines on the spectrum of phagocyte populations (macrophages and dendritic cells) in the lung and lymph node. Our results suggest that TNF is a major mediator of recruitment of phagocytes to the lungs. In contrast, IL-10 plays a role in balancing the dominant macrophage phenotype in LN and lung. AD - Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA. simeonem@umich.edu AN - 20510249 AU - Marino, S. AU - Myers, A. AU - Flynn, J. L. AU - Kirschner, D. E. DA - Aug 21 DO - S0022-5193(10)00241-9 [pii] 10.1016/j.jtbi.2010.05.012 [doi] DP - Nlm ET - 06/01 KW - Animals Cell Polarity Dendritic Cells/immunology/microbiology Humans Immunomodulation/immunology Interleukin-10/ immunology Lung/ immunology/microbiology/pathology Lymph Nodes/ immunology/microbiology/pathology Macrophages/cytology/immunology/microbiology Mice Mice, Inbred C57BL Models, Immunological Mycobacterium tuberculosis/immunology Phagocytes/cytology/ immunology Reproducibility of Results T-Lymphocytes/immunology/microbiology Tuberculosis/ immunology Tumor Necrosis Factor-alpha/ immunology LA - eng N1 - Marino, Simeone Myers, Amy Flynn, JoAnne L Kirschner, Denise E HL092853/HL/NHLBI NIH HHS/United States LM00902701/LM/NLM NIH HHS/United States N01 AI050018/AI/NIAID NIH HHS/United States N01 AI50018/AI/NIAID NIH HHS/United States R01 HL071241-08/HL/NHLBI NIH HHS/United States R01 LM009027-03/LM/NLM NIH HHS/United States R01HL71241/HL/NHLBI NIH HHS/United States R33 HL092853-03/HL/NHLBI NIH HHS/United States Research Support, N.I.H., Extramural England Journal of theoretical biology Nihms217396 J Theor Biol. 2010 Aug 21;265(4):586-98. Epub 2010 May 25. PY - 2010 RN - fulltext fulltext_1208 SN - 1095-8541 (Electronic) 0022-5193 (Linking) SP - 586-98 ST - TNF and IL-10 are major factors in modulation of the phagocytic cell environment in lung and lymph node in tuberculosis: a next-generation two-compartmental model T2 - J Theor Biol TI - TNF and IL-10 are major factors in modulation of the phagocytic cell environment in lung and lymph node in tuberculosis: a next-generation two-compartmental model UR - http://ac.els-cdn.com/S0022519310002419/1-s2.0-S0022519310002419-main.pdf?_tid=18a5b01be8b035d5b65dbe99b6609ef6&acdnat=1345012718_f9a3f6428d4664f7ba74c5aa29b37038 VL - 265 ID - 2600 ER - TY - JOUR AU - Okuonghae, D. AU - Aihie, V. U. DO - doi:10.1142/S0218339010003160 PY - 2010 RN - fulltext fulltext_1208 SP - 17-54 ST - OPTIMAL CONTROL MEASURES FOR TUBERCULOSIS MATHEMATICAL MODELS INCLUDING IMMIGRATION AND ISOLATION OF INFECTIVE T2 - Journal of Biological Systems TI - OPTIMAL CONTROL MEASURES FOR TUBERCULOSIS MATHEMATICAL MODELS INCLUDING IMMIGRATION AND ISOLATION OF INFECTIVE UR - http://www.worldscientific.com/doi/abs/10.1142/S0218339010003160 VL - 18 ID - 2601 ER - TY - JOUR AB - This paper presents qualitative and quantitative study of a TB mathematical model to test results from a survey carried out in Benin City, Nigeria. The purpose of the survey was to determine factors that could enhance the case detection rate of tuberculosis. Results from the survey identified four key factors that must be combined for an effective control of TB and increase the case detection rate: effective awareness programme, active cough identification, associated cost factor for treatment of identified cases and effective treatment. The overall effect of these factors on the basic reproduction number under treatment, R(T), of the TB model was considered. In all, a serious concentration on tuberculosis awareness programmes and active cough identification as a marker for someone having TB was shown to significantly reduce the value of the reproduction number, hereby reducing the severity of the disease in the presence of treatment. AD - Department of Mathematics, University of Benin, P.M.B. 1154, Benin City, Edo State, Nigeria. danny.okuonghae@corpus-christi.oxon.org AN - 20937288 AU - Okuonghae, D. AU - Omosigho, S. E. DA - Jan 21 DO - S0022-5193(10)00527-8 [pii] 10.1016/j.jtbi.2010.09.044 [doi] DP - Nlm ET - 10/13 KW - Basic Reproduction Number Computer Simulation Humans Models, Biological Nigeria/epidemiology Tuberculosis/ diagnosis/ epidemiology/therapy Uncertainty LA - eng N1 - Okuonghae, D Omosigho, S E England Journal of theoretical biology J Theor Biol. 2011 Jan 21;269(1):31-45. Epub 2010 Oct 15. PY - 2010 RN - fulltext fulltext_1208 SN - 1095-8541 (Electronic) 0022-5193 (Linking) SP - 31-45 ST - Analysis of a mathematical model for tuberculosis: What could be done to increase case detection T2 - J Theor Biol TI - Analysis of a mathematical model for tuberculosis: What could be done to increase case detection UR - http://ac.els-cdn.com/S0022519310005278/1-s2.0-S0022519310005278-main.pdf?_tid=8fadaf066889020abe397627114b1c58&acdnat=1345012976_71255e4ac825a88815d9584230c81981 VL - 269 ID - 2641 ER - TY - JOUR AD - [Ou, S. -C.] Leader Univ, Dept Comp Sci & Informat Engn, Taipei, Taiwan. [Chung, C. -Y.; Chung, H. -Y.] Natl Cent Univ, Dept Elect Engn, Taipei, Taiwan. AN - WOS:000279630200294 AU - Ou, S. C. AU - Chung, C. Y. AU - Chung, H. Y. DA - Jul J2 - Int. J. Infect. Dis. KW - Infectious Diseases LA - English M3 - Meeting Abstract N1 - ISI Document Delivery No.: 622AK Times Cited: 0 Cited Reference Count: 0 Ou, S. -C. Chung, C. -Y. Chung, H. -Y. Chung, Hung-Yuan/H-8055-2012 Chung, Hung-Yuan/0000-0002-1787-173X 0 2 Elsevier sci ltd Oxford PY - 2010 SN - 1201-9712 SP - S93-S93 ST - Liapunov functions and computer simulation applied to biomathematic model of dynamic system for tuberculosis T2 - International Journal of Infectious Diseases TI - Liapunov functions and computer simulation applied to biomathematic model of dynamic system for tuberculosis UR - ://WOS:000279630200294 VL - 14 ID - 5822 ER - TY - CHAP A2 - Zhu, R. B. A2 - Zhang, Y. C. A2 - Liu, B. X. A2 - Liu, C. F. AB - According the World Health Organization, one third of the world's population is infected with tuberculosis (TB), leading to between two and three million deaths each year. TB is now the second most common cause of death from infectious disease in the world after human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Tuberculosis is a leading cause of infectious mortality. Although anti-biotic treatment is available and there is vaccine, tuberculosis levels are rising in many areas of the world. Mathematical models have been used to study tuberculosis in the past and have influenced policy; the spread of HIV and the emergence of drug-resistant TB strains motivate the use of mathematical models today In the recent year, the Biomathmetics has become the main important trend of research dirction which has applied to the epidemic models of disease mechanism, spreading, regulation, and stategy of disease preventing in the field of medical and public health. The papers will apply Lyapunov stability function V (x) to construct a dynamic mathematics models for tuberculosis and to meet the above-mentioned TB disease mechanism,spreading regulation, and stategy of disease preventing in the medical field. The theory of Lyapunov stability function is a general rule and method to examine and determine the stability characteristics of a dynamic system. There are two functions of Lyapunov theory: (a) the Lyapunov indirect method which solves the dynamics differential equations of the constructing system then determines its stability properties, and (b) the Lyapunov direct method which determine the system stability directly via constructing a Lyapunov Energy Function V(x) of the dynamic mathematic model for tuberculosis. Here we will analyse the complex dynamic mathematic model of tuberculosis epidemic and determine its stability property by using the popular Matlab/Simulink software and relative software packages. AD - [Ou, Shih-Ching] Leader Univ, Dept Comp Sci & Informat Engn, Tainan 709, Taiwan. [Chung, Hung-Yuan; Chung, Chun-Yen] Natl Cent Univ, Dept Elect Engn, Jhongli 32001, Taiwan. Ou, SC (reprint author), Leader Univ, Dept Comp Sci & Informat Engn, Tainan 709, Taiwan. chunyen911@gmail.com AN - WOS:000289612900057 AU - Ou, S. C. AU - Chung, H. Y. AU - Chung, C. Y. CY - Berlin KW - Tuberculosis Biomathmetics Lyapunov LA - English N1 - ISI Document Delivery No.: BUK24 Times Cited: 0 Cited Reference Count: 6 Ou, Shih-Ching Chung, Hung-Yuan Chung, Chun-Yen Proceedings Paper International Conference on Information Computing and Applications Oct 15-18, 2010 Tangshan, PEOPLES R CHINA Hebei Polytechn Univ, Hebei Scene Stat Soc, Natl Sci Fdn, Hunan Inst Engn financial support of the National Science Council,Taiwan [NSC 98-2221-E-426-007] The authors wish to thank the financial support of the National Science Council,Taiwan, under Contract NSC 98-2221-E-426-007. Heidelberger platz 3, d-14197 berlin, germany 0302-9743 PB - Springer-Verlag Berlin PY - 2010 SN - 978-3-642-16166-7 SP - 447-+ ST - A Biomathematic Models for Tuberculosis Using Lyapunov Stability Functions T2 - Information Computing and Applications T3 - Lecture Notes in Computer Science TI - A Biomathematic Models for Tuberculosis Using Lyapunov Stability Functions UR - ://WOS:000289612900057 VL - 6377 ID - 5866 ER - TY - JOUR AB - The model herein aims to explore the dynamics of the spread of tuberculosis (TB) in an informal settlement or township. The population is divided into households of various sizes and also based on commuting status. The model dynamics distinguishes between three distinct social patterns: the exposure of commuters during travel, random diurnal interaction and familial exposure at night. Following the general SLIR models, the population is further segmented into susceptible (S), exposed/latently infected (L), active/infectious (I), and recovered (R) individuals. During the daytime, commuters travel on public transport, while non-commuters randomly interact in the community to mimic chance encounters with infectious persons. At night, each family interacts and sleeps together in the home. The risk of exposure to TB is based on the proximity, duration, and frequency of encounters with infectious persons. The model is applied to a hypothetical population to explore the effects of different intervention strategies including vaccination, wearing of masks during the commute, prophylactic treatment of latent infections and more effective case-finding and treatment. The most important findings of the model are: (1) members of larger families are responsible for more disease transmissions than those from smaller families, (2) daily commutes on public transport provide ideal conditions for transmission of the disease, (3) improved diagnosis and treatment has the greatest impact on the spread of the disease, and (4) detecting TB at the first clinic visit, when patients are still smear negative, is key. (C) 2010 Elsevier Ltd. All rights reserved. AD - Univ Nebraska, Dept Chem & Biomol Engn, Lincoln, NE 68588 USA Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE 68198 USA AN - WOS:000278721200003 AU - Pienaar, E. AU - Fluitt, A. M. AU - Whitney, S. E. AU - Freifeld, A. G. AU - Viljoen, H. J. DA - Apr DO - 10.1016/j.compbiolchem.2010.03.003 IS - 2 J2 - Comput Biol Chem KW - mathematical model tuberculosis multiple cluster urban community commute drug-resistant tuberculosis exogenous reinfection infectious-diseases south-africa epidemics dynamics efficacy population prevalence protection L1 - internal-pdf://1884756587/Pienaar-2010-A model of tuberculosis transmiss.pdf LA - English N1 - 610hb Times Cited:7 Cited References Count:36 PY - 2010 SN - 1476-9271 SP - 86-96 ST - A model of tuberculosis transmission and intervention strategies in an urban residential area T2 - Computational Biology and Chemistry TI - A model of tuberculosis transmission and intervention strategies in an urban residential area UR - ://WOS:000278721200003 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039429/pdf/nihms266749.pdf VL - 34 ID - 4866 ER - TY - JOUR AB - The complex web of interactions between the host immune system and the pathogen determines the outcome of any infection. A computational model of this interaction network, which encodes complex interplay among host and bacterial components, forms a useful basis for improving the understanding of pathogenesis, in filling knowledge gaps and consequently to identify strategies to counter the disease. We have built an extensive model of the Mycobacterium tuberculosis host-pathogen interactome, consisting of 75 nodes corresponding to host and pathogen molecules, cells, cellular states or processes. Vaccination effects, clearance efficiencies due to drugs and growth rates have also been encoded in the model. The system is modelled as a Boolean network. Virtual deletion experiments, multiple parameter scans and analysis of the system's response to perturbations, indicate that disabling processes such as phagocytosis and phagolysosome fusion or cytokines such as TNF-alpha and IFN-gamma, greatly impaired bacterial clearance, while removing cytokines such as IL-10 alongside bacterial defence proteins such as SapM greatly favour clearance. Simulations indicate a high propensity of the pathogen to persist under different conditions. AD - Bioinformatics Centre, Indian Institute of Science, Bangalore - 560012, India. nchandra@serc.iisc.ernet.in. AN - 20174680 AU - Raman, K. AU - Bhat, A. G. AU - Chandra, N. DA - Mar DO - 10.1039/b912129c [doi] DP - Nlm ET - 02/23 KW - Computer Simulation Cytokines/genetics Gene Knockout Techniques Host-Pathogen Interactions/genetics/immunology/ physiology Humans Immune System Phenomena Models, Biological Mycobacterium tuberculosis/genetics/immunology/ physiology Signal Transduction Systems Biology/ methods Tuberculosis/immunology/metabolism/ microbiology Virulence Factors LA - eng N1 - Raman, Karthik Bhat, Ashwini Gurudas Chandra, Nagasuma Research Support, Non-U.S. Gov't England Molecular bioSystems Mol Biosyst. 2010 Mar;6(3):516-30. Epub 2009 Dec 14. PY - 2010 RN - fulltext fulltext_1208 SN - 1742-2051 (Electronic) 1742-2051 (Linking) SP - 516-30 ST - A systems perspective of host-pathogen interactions: predicting disease outcome in tuberculosis T2 - Mol Biosyst TI - A systems perspective of host-pathogen interactions: predicting disease outcome in tuberculosis UR - http://pubs.rsc.org/en/Content/ArticleLanding/2010/MB/b912129c VL - 6 ID - 2602 ER - TY - JOUR AB - RATIONALE: Isoniazid preventive therapy is effective in reducing the risk of tuberculosis (TB) in persons living with HIV (PLWH); however, screening must exclude TB disease before initiating therapy. Symptom screening alone may be insufficient to exclude TB disease in PLWH because some PLWH with TB disease have no symptoms. The addition of chest radiography (CXR) may improve disease detection. OBJECTIVES: The objective of the present analysis was to compare the costs and effects of the addition of CXR to the symptom screening process against the costs and effects of symptom screening alone. METHODS: Using data from Botswana, a decision analytic model was used to compare a "Symptom only" policy against a "Symptom+CXR" policy. The outcomes of interest were cost, death, and isoniazid- and multidrug-resistant TB in a hypothetical cohort of 10,000 PLWH. MEASUREMENTS AND MAIN RESULTS: The Symptom+CXR policy prevented 16 isoniazid- and 0.3 multidrug-resistant TB cases; however, because of attrition from the screening process, there were 98 excess cases of TB, 15 excess deaths, and an additional cost of U.S. $127,100. The Symptom+CXR policy reduced deaths only if attrition was close to zero; however, to eliminate attrition the cost would be U.S. $2.8 million per death averted. These findings did not change in best- and worst-case scenario analyses. CONCLUSIONS: In Botswana, a policy with symptom screening only preceding isoniazid-preventive therapy initiation prevents more TB and TB-related deaths, and uses fewer resources, than a policy that uses both CXR and symptom screening. AD - Division of TB Elimination, Centers for Disease Control and Prevention/PHS, 1600 Clifton Rd., Atlanta, GA 30333, USA. tts0@cdc.gov AN - 21148723 AU - Samandari, T. AU - Bishai, D. AU - Luteijn, M. AU - Mosimaneotsile, B. AU - Motsamai, O. AU - Postma, M. AU - Hubben, G. DA - Apr 15 DO - 201004-0620OC [pii] 10.1164/rccm.201004-0620OC ET - 12/15 KW - Antitubercular Agents/economics/therapeutic use Botswana/epidemiology Cost-Benefit Analysis Drug Resistance, Multiple, Bacterial Health Care Costs/*statistics & numerical data Humans Isoniazid/economics/therapeutic use Mass Chest X-Ray/*economics Models, Economic Tuberculosis, Pulmonary/drug therapy/economics/*prevention & control/radiography L1 - internal-pdf://0776974818/Samandari-2010-Costs and consequences of addit.pdf LA - eng N1 - Samandari, Taraz Bishai, David Luteijn, Michiel Mosimaneotsile, Barudi Motsamai, Oaitse Postma, Maarten Hubben, Gijs R24 HD042854-09/HD/NICHD NIH HHS/United States Research Support, U.S. Gov't, P.H.S. United States American journal of respiratory and critical care medicine Am J Respir Crit Care Med. 2011 Apr 15;183(8):1103-11. Epub 2010 Dec 10. PY - 2010 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1535-4970 (Electronic) 1073-449X (Linking) SP - 1103-11 ST - Costs and consequences of additional chest x-ray in a tuberculosis prevention program in Botswana T2 - Am J Respir Crit Care Med TI - Costs and consequences of additional chest x-ray in a tuberculosis prevention program in Botswana UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21148723http://ajrccm.atsjournals.org/content/183/8/1103.longhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159079/pdf/AJRCCM18381103.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159079/pdf/AJRCCM18381103.pdf VL - 183 ID - 2644 ER - TY - CHAP A2 - Gumel, A. B. A2 - Lenhart, S. AB - Curtailing the public health crises generated by the TB/HIV co-pandemic poses many challenges, including monitoring difficulties that complicate our ability to accurately predict the efficacy of public health interventions. Unfortunately, the dire and urgent need to inform policy makers on the individual and population benefits to be obtained from different disease control measures may result in our prioritizing predicting per se, over conducting in-depth system studies that can maximize our ability to properly address the question(s) posed. In this chapter we illustrate these difficulties and exemplify how analytical studies can be used not only as a powerful predictive tool that can help guide public health policy, but also as a means of gaining important insight into the system's functioning that, in turn, can help the monitoring of pandemics. We present in detail the mathematical, statistical and computational approach and methodology behind our recent research focused on evaluating the potential public health benefits to be derived from reducing TB treatment duration from the standard 6- to 8-month treatments to a 2-month treatment in areas of high HIV prevalence. Because of the considerable uncertainties and spatial and temporal heterogeneity in parameter values we conducted a calibration to historical TB/HIV trends that increased the validity of our predictive results for high HIV prevalence areas. Unexpectedly, our calibration unveiled incongruent epidemiological patterns between the two interacting diseases in Kenya, which led us to evaluate reported TB/HIV co-dynamics for the whole of Africa with a new statistic that quantifies the relative change in TB numbers as compared to HIV numbers. Our initial analysis of pan-African patterns placed Kenya as an outlier. However, Kenyan TB and HIV estimates have since been revised, and now the relative change in the co-dynamics of the two diseases place Kenya in a more intermediate position. We additionally conducted a sensitivity analysis to evaluate which parameters had a greater influence on the output variables of choice. In this chapter we briefly explain the results of our model predictions and of our sensitivity analysis focusing on the general approach and methods because many of the lessons learned related to the reasoning and steps we followed, and not exclusively to the results of our investigation. Thus, here our final conclusions and recommendations are geared towards the analytical process more than the public health implications of our studies. Most importantly, this study taught us the power of contrasting trends of interacting diseases in global disease monitoring and control. This is particularly so for such a complex co-pandemic as TB/HIV, where our analysis of the joint co-dynamics provided important insights into the individual epidemiology of each disease. AD - [Sanchez, Maria S.] Univ Calif Berkeley, Dept Environm Sci Policy & Management, Berkeley, CA 94720 USA. Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. WHO, Stop TB Dept, CH-1211 Geneva 27, Switzerland. Sanchez, MS (reprint author), Univ Calif Berkeley, Dept Environm Sci Policy & Management, Berkeley, CA 94720 USA. AN - WOS:000294873400007 AU - Sanchez, M. S. AU - Lloyd-Smith, J. O. AU - Williams, B. G. AU - Getz, W. M. CY - Providence KW - active antiretroviral therapy sub-saharan africa tuberculosis-control hiv-infection mycobacterium-tuberculosis control strategies south-africa high-rates kenya transmission LA - English N1 - ISI Document Delivery No.: BWU51 Times Cited: 0 Cited Reference Count: 96 Sanchez, Maria S. Lloyd-Smith, James O. Williams, Brian G. Getz, Wayne M. Proceedings Paper US-African-Advanced-Study-Institute Conference on Mathematical Modeling of Infectious Diseases in Africa DIMACS Workshop on Mathematical Modeling of Infectious Diseases in Africa Jun 11-22, 2007 Jun 25-27, 2007 African Inst Math Sci, Muizenberg, SOUTH AFRICA S African Ctr Epidemiol Model Anal, Stellenbosch, SOUTH AFRICA AIMS, DIMACS, US Natl Sci Fdn, SACEMA NIH-NIDA; James S. McDonnell Foundation 21st Century Science Initiative; Global Alliance for TB Drug Development; SACEMA; South African Center for Epidemiological Modeling and Analysis We thank anonymous reviewers and David Bangsberg, Jason Barbour, Frank Cobelens, Kathryn DeRiemer, Judy Hahn, John Hargrove, Philip Hopewell, Gwynne Oosterbaan, Perry de Valpine, Francois Venter, Suzanne Verver, and members of Wayne Getzs lab, for their help and orientation. We would especially like to thank the Kenyan public health authorities and all persons participating in the data collection. This research was supported by NIH-NIDA (MSS and WMG), the James S. McDonnell Foundation 21st Century Science Initiative (WMG), the Global Alliance for TB Drug Development (WMG), and SACEMA, the South African Center for Epidemiological Modeling and Analysis (WMG). P.o. box 6248, providence, ri 02940 usa 1052-1798 PB - Amer Mathematical Soc PY - 2010 SN - 978-0-8218-4384-0 SP - 135-+ ST - Using mathematical models to monitor and evaluate the impact of public health interventions on epidemics: the case of the TB/HIV co-pandemic in Africa T2 - Modeling Paradigms and Analysis of Disease Transmission Models T3 - DIMACS-Series in Discrete Mathematics and Theoretical Computer Science TI - Using mathematical models to monitor and evaluate the impact of public health interventions on epidemics: the case of the TB/HIV co-pandemic in Africa UR - ://WOS:000294873400007 VL - 75 ID - 5872 ER - TY - JOUR AB - Up to now, the effects of having heterogeneous networks of contacts have been studied mostly for diseases which are not persistent in time, i.e., for diseases where the infectious period can be considered very small compared to the lifetime of an individual. Moreover, all these previous results have been obtained for closed populations, where the number of individuals does not change during the whole duration of the epidemics. Here, we go one step further and analyze, both analytically and numerically, a radically different kind of diseases: those that are persistent and can last for an individual's lifetime. To be more specific, we particularize to the case of tuberculosis' (TB) infection dynamics, where the infection remains latent for a period of time before showing up and spreading to other individuals. We introduce an epidemiological model for TB-like persistent infections taking into account the heterogeneity inherent to the population structure. This sort of dynamics introduces new analytical and numerical challenges that we are able to sort out. Our results show that also for persistent diseases the epidemic threshold depends on the ratio of the first two moments of the degree distribution so that it goes to zero in a class of scale-free networks when the system approaches the thermodynamic limit. AD - Institute for Biocomputation and Physics of Complex Systems (BIFI), University of Zaragoza, Zaragoza 50009, Spain. AN - 20866298 AU - Sanz, J. AU - Floria, L. M. AU - Moreno, Y. DA - May DO - 10.1103/PhysRevE.81.056108 IS - 5 Pt 2 N1 - Sanz, J Floria, L M Moreno, Y eng 2010/09/28 06:00 Phys Rev E Stat Nonlin Soft Matter Phys. 2010 May;81(5 Pt 2):056108. Epub 2010 May 25. PY - 2010 SN - 1550-2376 (Electronic) 1539-3755 (Linking) SP - 056108 ST - Spreading of persistent infections in heterogeneous populations T2 - Phys Rev E Stat Nonlin Soft Matter Phys TI - Spreading of persistent infections in heterogeneous populations UR - https://www.ncbi.nlm.nih.gov/pubmed/20866298 VL - 81 ID - 2250 ER - TY - JOUR AB - Background: Several diseases, many of which nowadays pandemic, consist of multifactorial pathologies. Paradigmatic examples come from the immune response to pathogens, in which cases the effects of different infections combine together, yielding complex mutual feedback, often a positive one that boosts infection progression in a scenario that can easily become lethal. HIV is one such infection, which weakens the immune system favouring the insurgence of opportunistic infections, amongst which Tuberculosis (TB). The treatment with antiretroviral therapies has shown effective in reducing mortality. An in-depth understanding of complex systems, like the one consisting of HIV, TB and related therapies, is an open great challenge, on the boundaries of bioinformatics, computational and systems biology. Results: We present a simplified formalisation of the highly dynamic system consisting of HIV, TB and related therapies, at the cellular level. The progression of the disease (AIDS) depends hence on interactions between viruses, cells, chemokines, the high mutation rate of viruses, the immune response of individuals and the interaction between drugs and infection dynamics. We first discuss a deterministic model of dual infection (HIV and TB) which is able to capture the long-term dynamics of CD4 T cells, viruses and Tumour Necrosis Factor (TNF). We contrast this model with a stochastic approach which captures intrinsic fluctuations of the biological processes. Furthermore, we also integrate automated reasoning techniques, i.e. probabilistic model checking, in our formal analysis. Beyond numerical simulations, model checking allows general properties (effectiveness of anti-HIV therapies) to be verified against the models by means of an automated procedure. Our work stresses the growing importance and flexibility of model checking techniques in bioinformatics. In this paper we i) describe HIV as a complex case of infectious diseases; ii) provide a number of different formal descriptions that suitably account for aspects of interests; iii) suggest that the integration of different models together with automated reasoning techniques can improve the understanding of infections and therapies through formal analysis methodologies. Conclusion: We argue that the described methodology suitably supports the study of viral infections in a formal, automated and expressive manner. We envisage a long-term contribution of this kind of approaches to clinical Bioinformatics and Translational Medicine. AD - [Sorathiya, Anil; Lio, Pietro] Univ Cambridge, Comp Lab, Cambridge CB3 0FD, England. [Bracciali, Andrea] Univ Pisa, Dept Comp Sci, I-56127 Pisa, Italy. Sorathiya, A (reprint author), Univ Cambridge, Comp Lab, William Gates Bldg,15 JJ Thomson Ave, Cambridge CB3 0FD, England. anilkumar.sorathiya@cl.cam.ac.uk; braccia@di.unipi.it; pietro.lio@cl.cam.ac.uk AN - WOS:000277537900046 AU - Sorathiya, A. AU - Bracciali, A. AU - Lio, P. C7 - S67 DO - 10.1186/1471-2105-11-s1-s67 J2 - BMC Bioinformatics KW - immunodeficiency-virus type-1 necrosis-factor-alpha mycobacterium-tuberculosis immune-system in-vivo infection dynamics expression receptor cells Biochemistry & Molecular Biology Biotechnology & Applied Microbiology Mathematical & Computational Biology LA - English M3 - Article N1 - ISI Document Delivery No.: 594KZ Times Cited: 3 Cited Reference Count: 43 Sorathiya, Anil Bracciali, Andrea Lio, Pietro Bracciali, Andrea/0000-0003-1451-9260 Ec The authors wish to thank the anonymous referees for their helpful comments on a previous version of this paper. This project is partially supported by EC IST SOCIALNETS and WADA projects. 3 1 4 Biomed central ltd London PY - 2010 SN - 1471-2105 SP - 11 ST - Formal reasoning on qualitative models of coinfection of HIV and Tuberculosis and HAART therapy T2 - Bmc Bioinformatics TI - Formal reasoning on qualitative models of coinfection of HIV and Tuberculosis and HAART therapy UR - ://WOS:000277537900046 VL - 11 ID - 5863 ER - TY - JOUR AB - High tuberculosis (TB) prevalence in Papua New Guinea (PNG) is a serious public health concern. The epidemic in this region is exacerbated by the presence of drug-resistant TB strains as well as HIV infection. This presents a public health threat not only locally but also to Australia due to the high potential for cross-border transmission between PNG's Western Province and the Australian Torres Strait Islands. We present two mathematical models of TB in the Western Province: a simple model of the underlying TB dynamics, and a detailed model which accounts for the additional effects of HIV and drug resistance. The detailed model is used to make quantitative predictions about the impact of expanding the TB case detection rate under the Directly Observed Treatment, Short-course treatment regimen. This paper provides a framework for future investigation into the economic costs and public health benefits of potential TB interventions in this region, with the eventual aim of providing recommendations to guide policy makers in both PNG and Australia. AD - Australian Natl Univ, Natl Ctr Epidemiol & Populat Hlth, Canberra, ACT 0200, Australia Univ Western Australia, Perth, WA 6009, Australia AN - WOS:000291051300003 AU - Thomas, E. G. AU - Barrington, H. E. AU - Lokuge, K. M. AU - Mercer, G. N. DA - Jul DO - 10.1017/S1446181111000587 IS - 1 J2 - Anziam J KW - tuberculosis drug resistant hiv papua new guinea mathematical model intrinsic transmission dynamics multidrug-resistant mycobacterium-tuberculosis strategies epidemic cost tb L1 - internal-pdf://2251111410/Thomas-2010-Modelling the Spread of Tuberculos.pdf LA - English N1 - 769xj Times Cited:5 Cited References Count:48 PY - 2010 SN - 1446-1811 SP - 26-45 ST - Modelling the Spread of Tuberculosis, Including Drug Resistance and Hiv: A Case Study in Papua New Guinea's Western Province T2 - Anziam Journal TI - Modelling the Spread of Tuberculosis, Including Drug Resistance and Hiv: A Case Study in Papua New Guinea's Western Province UR - ://WOS:000291051300003 https://www.cambridge.org/core/services/aop-cambridge-core/content/view/C2BBAFB69AC59AEB25B63E95C1C471F3/S1446181111000587a.pdf/div-class-title-modelling-the-spread-of-tuberculosis-including-drug-resistance-and-hiv-a-case-study-in-papua-new-guinea-s-western-province-div.pdf VL - 52 ID - 4880 ER - TY - JOUR AB - BACKGROUND: Indian guidelines recommend routine referral for HIV testing of all tuberculosis (TB) patients in the nine states with the highest HIV prevalence, and selective referral for testing elsewhere. We assessed the clinical impact and cost-effectiveness of alternative HIV testing referral strategies among TB patients in India. METHODS AND FINDINGS: We utilized a computer model of HIV and TB disease to project outcomes for patients with active TB in India. We compared life expectancy, cost, and cost-effectiveness for three HIV testing referral strategies: 1) selective referral for HIV testing of those with increased HIV risk, 2) routine referral of patients in the nine highest HIV prevalence states with selective referral elsewhere (current standard), and 3) routine referral of all patients for HIV testing. TB-related data were from the World Health Organization. HIV prevalence among TB patients was 9.0% in the highest prevalence states, 2.9% in the other states, and 4.9% overall. The selective referral strategy, beginning from age 33.50 years, had a projected discounted life expectancy of 16.88 years and a mean lifetime HIV/TB treatment cost of US$100. The current standard increased mean life expectancy to 16.90 years with additional per-person cost of US$10; the incremental cost-effectiveness ratio was US$650/year of life saved (YLS) compared to selective referral. Routine referral of all patients for HIV testing increased life expectancy to 16.91 years, with an incremental cost-effectiveness ratio of US$730/YLS compared to the current standard. For HIV-infected patients cured of TB, receiving antiretroviral therapy increased survival from 4.71 to 13.87 years. Results were most sensitive to the HIV prevalence and the cost of second-line antiretroviral therapy. CONCLUSIONS: Referral of all patients with active TB in India for HIV testing will be both effective and cost-effective. While effective implementation of this strategy would require investment, routine, voluntary HIV testing of TB patients in India should be recommended. AD - Division of General Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. luhler@partners.org AU - Uhler, L. M. AU - Kumarasamy, N. AU - Mayer, K. H. AU - Saxena, A. AU - Losina, E. AU - Muniyandi, M. AU - Stoler, A. W. AU - Lu, Z. AU - Walensky, R. P. AU - Flanigan, T. P. AU - Bender, M. A. AU - Freedberg, K. A. AU - Swaminathan, S. AU - investigators, Cepac International DO - 10.1371/journal.pone.0012747 KW - Adult Anti-HIV Agents/economics/therapeutic use Antitubercular Agents/therapeutic use Cost-Benefit Analysis Female HIV Infections/complications/diagnosis/drug therapy/economics Health Care Costs Humans India Male Middle Aged Tuberculosis/complications/drug therapy N1 - GR: K24 AI062476/AI/NIAID NIH HHS/United States; GR: R01 AI058736/AI/NIAID NIH HHS/United States; JID: 101285081; 0 (Anti-HIV Agents); 0 (Antitubercular Agents); OID: NLM: PMC2940842; 2010/04/29 [received]; 2010/08/20 [accepted]; 2010/09/16 [epublish]; epublish PY - 2010 RN - fulltext fulltext_1208 SN - 1932-6203; 1932-6203 SP - e12747 ST - Cost-effectiveness of HIV testing referral strategies among tuberculosis patients in India T2 - PloS one TI - Cost-effectiveness of HIV testing referral strategies among tuberculosis patients in India UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940842/pdf/pone.0012747.pdf VL - 5 Y2 - Sep 16 ID - 2603 ER - TY - JOUR AB - BACKGROUND: There is good evidence that diabetes is a risk factor for pulmonary tuberculosis. In England, the rates of both diabetes and tuberculosis vary markedly by ethnic group. OBJECTIVE: To estimate the proportion of incident cases of pulmonary tuberculosis attributable to diabetes (population attributable fraction, PAF) for Asian, black and white men and women aged > or = 15 years in England. METHODS: An epidemiological model was constructed using data on the incidence of tuberculosis, the prevalence of diabetes, the population structure for 2005 and the age-specific relative risk of tuberculosis associated with diabetes from a large cohort study. RESULTS: The estimated PAF of diabetes for pulmonary tuberculosis is highest for Asian men (19.6%, 95% CI 10.9% to 33.1%) and women (14.2%, 95% CI 7.1% to 26.5%). The PAF for all ages is similar in white and black men (6.9%, 95% CI 3.1% to 12.4% and 7.4%, 95% CI 4.6% to 12.9%, respectively) and women (8.2%, 95% CI 3.0% to 15.6% and 8.9%, 95% CI 5.3% to 15.6%, respectively). The similarity of these overall figures, despite a higher prevalence of diabetes in the black population, reflects a much younger mean age of pulmonary tuberculosis in the black population. Overall, of 3461 new cases of pulmonary tuberculosis in England in 2005, 384 (202-780) were estimated to be attributable to diabetes. CONCLUSION: Given the nature of the data available, considerable uncertainty surrounds these estimates. Nonetheless, they highlight the potential importance of diabetes as a risk factor for pulmonary tuberculosis, particularly in groups at high risk of both diseases. Further research to examine the implications of these findings for tuberculosis control is urgently needed. AD - Institute of Health and Society, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. AN - 20421330 AU - Walker, C. AU - Unwin, N. DA - Jul DO - 10.1136/thx.2009.128223 IS - 7 KW - Adolescent Adult African Continental Ancestry Group/statistics & numerical data Age Distribution Aged Asian Continental Ancestry Group/statistics & numerical data Diabetes Complications/ethnology Diabetes Mellitus/*ethnology England/epidemiology Epidemiologic Methods European Continental Ancestry Group/statistics & numerical data Female Humans Male Middle Aged Opportunistic Infections/complications/*ethnology Sex Distribution Tuberculosis, Pulmonary/complications/*ethnology Young Adult N1 - Walker, Caron Unwin, Nigel eng England 2010/04/28 06:00 Thorax. 2010 Jul;65(7):578-81. doi: 10.1136/thx.2009.128223. Epub 2010 Apr 26. PY - 2010 SN - 1468-3296 (Electronic) 0040-6376 (Linking) SP - 578-81 ST - Estimates of the impact of diabetes on the incidence of pulmonary tuberculosis in different ethnic groups in England T2 - Thorax TI - Estimates of the impact of diabetes on the incidence of pulmonary tuberculosis in different ethnic groups in England UR - https://www.ncbi.nlm.nih.gov/pubmed/20421330 VL - 65 ID - 2251 ER - TY - CHAP A2 - Michael, E. A2 - Spear, R. C. AB - Despite the infectious agent that causes tuberculosis having been discovered in 1882, many aspects of the natural history and transmission dynamics of TB are still not fully understood. This is reflected in differences in the structures of mathematical models of TB, which in turn produce differences in the predicted impacts of interventions. Gaining a greater understanding of TB transmission dynamics requires further empirical laboratory and field work, mathematical modelling and interaction between them. Modelling can be used to quantify uncertainty due to different gaps in our knowledge to help identify research priorities. Fortunately, the present moment is an exciting time for TB epidemiology, with rapid progress being made in applying new mathematical modelling techniques, new tools for TB diagnosis and genetic analysis and a growing interest in developing more-effective public-health interventions. AD - [White, Peter J.] Hlth Protect Agcy Ctr Infect, Modelling & Econ Unit, London NW9 5EQ, England. [White, Peter J.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Infect Dis Epidemiol, MRC Ctr Outbreak Anal & Modelling, London W2 1PG, England. White, PJ (reprint author), Hlth Protect Agcy Ctr Infect, Modelling & Econ Unit, 61 Colindale Ave, London NW9 5EQ, England. peter.white@hpa.org.uk AN - WOS:000277148900009 AU - White, P. J. AU - Garnett, G. P. CY - Berlin KW - drug-resistant tuberculosis intrinsic transmission dynamics public-health impact new-york-city mycobacterium-tuberculosis exogenous reinfection molecular epidemiology heterogeneous populations amplification dynamics recurrent tuberculosis LA - English N1 - ISI Document Delivery No.: BOO44 Times Cited: 7 Cited Reference Count: 131 White, Peter J. Garnett, Geoff P. Article; Book Chapter Garnett, Geoffrey/A-9312-2008 Heidelberger platz 3, d-14197 berlin, germany 0065-2598 PB - Springer-Verlag Berlin PY - 2010 SN - 978-1-4419-6063-4 SP - 127-140 ST - Adv.Exp.Med.Biol. T2 - Modelling Parasite Transmission and Control T3 - Advances in Experimental Medicine and Biology TI - Mathematical Modelling of the Epidemiology of Tuberculosis UR - ://WOS:000277148900009 VL - 673 ID - 5873 ER - TY - JOUR AB - HIV has increased the incidence of tuberculosis (TB) by up to sevenfold in African countries, but antiretroviral therapy (ART) reduces the incidence of AIDS-related TB. We use a mathematical model to investigate the short-term and long-term impacts of ART on the incidence of TB, assuming that people are tested for HIV once a year, on average, and start ART at a fixed time after HIV seroconversion or at a fixed CD4(+) cell count. We fit the model to trend data on HIV prevalence and TB incidence in nine countries in sub-Saharan Africa. If HIV-positive people start ART within 5 y of seroconversion, the incidence of AIDS-related TB in 2015 will be reduced by 48% (range: 37-55%). Long-term reductions depend sensitively on the delay to starting ART. If treatment is started 5, 2, or 1 y after HIV seroconversion, or as soon as people test positive, the incidence in 2050 will be reduced by 66% (range: 57-80%), 95% (range: 93-96%), 97.7% (range: 96.9-98.2%) and 98.4% (range: 97.8-98.9%), respectively. In the countries considered here, early ART could avert 0.71 +/- 0.36 [95% confidence interval (CI)] million of 3.4 million cases of TB between 2010 and 2015 and 5.8 +/- 2.9 (95% CI) million of 15 million cases between 2015 and 2050. As more countries provide ART at higher CD4(+) cell counts, the impact on TB should be investigated to test the predictions of this model. AD - South African Centre for Epidemiological Modelling and Analysis, Stellenbosch 7600, South Africa. briangerardwilliams@gmail.com AN - 20974976 AU - Williams, B. G. AU - Granich, R. AU - De Cock, K. M. AU - Glaziou, P. AU - Sharma, A. AU - Dye, C. DA - Nov 9 DO - 1005660107 [pii] 10.1073/pnas.1005660107 [doi] DP - Nlm ET - 10/27 KW - Acquired Immunodeficiency Syndrome/ complications/drug therapy Africa/epidemiology Anti-Retroviral Agents/ therapeutic use HIV Seropositivity Humans Incidence Models, Statistical Time Factors Tuberculosis/drug therapy/epidemiology/etiology/ prevention & control LA - eng N1 - Williams, Brian G Granich, Reuben De Cock, Kevin M Glaziou, Philippe Sharma, Abhishek Dye, Christopher United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19485-9. Epub 2010 Oct 25. PY - 2010 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1091-6490 (Electronic) 0027-8424 (Linking) SP - 19485-9 ST - Antiretroviral therapy for tuberculosis control in nine African countries T2 - Proc Natl Acad Sci U S A TI - Antiretroviral therapy for tuberculosis control in nine African countries UR - http://www.pnas.org/content/107/45/19485.full.pdf VL - 107 ID - 2604 ER - TY - JOUR AB - BACKGROUND: Tuberculosis transmission is determined by contact between infectious and susceptible individuals. A recent study reported a 4% annual risk of child tuberculosis infection in a southern African township. A model was used to explore the interactions between prevalence of adult tuberculosis infection, adult-to-child contacts, and household ventilation, which could result in such a high annual risk of tuberculosis infection. METHODS: Number of residents per household and tuberculosis incidence were derived from a household census and community tuberculosis registers. Using the Wells-Riley equation and probability analyses of contact between infectious adults with tuberculosis and preschool children, we estimated the annual risk of tuberculosis infection within and outside of the home. RESULTS: There was a mean of 2.2 adults per child-containing household with a 1.35% annual adult smear-positive tuberculosis notification rate. The maximal household annual risk of tuberculosis infection was 3%, which was primarily determined by the number of resident adults. Transmission risk outside the home increased with increasing number of households visited. Transmission probabilities were sensitive to exposure time, ventilation, and period of adult infectivity. The benefits of increased ventilation were greatest when the period of infectivity was reduced. Similar reductions in household transmission could be achieved by increasing ventilation from 2 to 6 air changes/hour or by separating child and adult sleeping areas. CONCLUSIONS: The annual risk of tuberculosis infection of preschool children predominantly results from infectious residents in the home. However, even with limited social interactions, a substantial proportion of transmissions may occur from nonresident adults. The benefits of increased ventilation are maximized when the period of infectivity is reduced by prompt treatment of source cases. AD - Desmond Tutu HIV Centre, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Faculty of Health Sciences, Cape Town, South Africa. robin.wood@hiv-research.org.za AN - 20604716 AU - Wood, R. AU - Johnstone-Robertson, S. AU - Uys, P. AU - Hargrove, J. AU - Middelkoop, K. AU - Lawn, S. D. AU - Bekker, L. G. DA - Aug 15 DO - 10.1086/655129 [doi] DP - Nlm ET - 07/08 KW - Adolescent Adult Child Child, Preschool Community-Acquired Infections/ epidemiology/ transmission Family Health Humans Infant Infant, Newborn Models, Statistical Prevalence Risk Assessment South Africa/epidemiology Tuberculosis/ epidemiology/ transmission LA - eng N1 - Wood, Robin Johnstone-Robertson, Simon Uys, Pieter Hargrove, John Middelkoop, Keren Lawn, Stephen D Bekker, Linda-Gail 1U19AI53217-01/AI/NIAID NIH HHS/United States A1058736-01A1/PHS HHS/United States R01 AI058736-01A1/AI/NIAID NIH HHS/United States Wellcome Trust/United Kingdom Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Nihms208805 Clin Infect Dis. 2010 Aug 15;51(4):401-8. PY - 2010 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1537-6591 (Electronic) 1058-4838 (Linking) SP - 401-8 ST - Tuberculosis transmission to young children in a South African community: modeling household and community infection risks T2 - Clin Infect Dis TI - Tuberculosis transmission to young children in a South African community: modeling household and community infection risks UR - http://cid.oxfordjournals.org/content/51/4/401.full.pdf VL - 51 ID - 2605 ER - TY - JOUR AB - BACKGROUND: Hong Kong is an affluent subtropical city with a well-developed healthcare infrastructure but an intermediate TB burden. Declines in notification rates through the 1960s and 1970s have slowed since the 1980s to the current level of around 82 cases per 100 000 population. We studied the transmission dynamics of TB in Hong Kong to explore the factors underlying recent trends in incidence. METHODOLOGY/PRINCIPAL FINDINGS: We fitted an age-structured compartmental model to TB notifications in Hong Kong between 1968 and 2008. We used the model to quantify the proportion of annual cases due to recent transmission versus endogenous reactivation of latent infection, and to project trends in incidence rates to 2018. The proportion of annual TB notifications attributed to endogenous reactivation increased from 46% to 70% between 1968 and 2008. Age-standardized notification rates were projected to decline to approximately 56 per 100 000 in 2018. CONCLUSIONS/SIGNIFICANCE: Continued intermediate incidence of TB in Hong Kong is driven primarily by endogenous reactivation of latent infections. Public health interventions which focus on reducing transmission may not lead to substantial reductions in disease burden associated with endogenous reactivation of latent infections in the short- to medium-term. While reductions in transmission with socio-economic development and public health interventions will lead to declines in TB incidence in these regions, a high prevalence of latent infections may hinder substantial declines in burden in the longer term. These findings may therefore have important implications for the burden of TB in developing regions with higher levels of transmission currently. AD - Department of Community Medicine and School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. AN - 20454620 AU - Wu, P. AU - Lau, E. H. AU - Cowling, B. J. AU - Leung, C. C. AU - Tam, C. M. AU - Leung, G. M. DO - 10.1371/journal.pone.0010468 ET - 05/11 LA - eng N1 - Wu, Peng Lau, Eric H Y Cowling, Benjamin J Leung, Chi-Chiu Tam, Cheuk-Ming Leung, Gabriel M 1 U54 GM088558/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural United States PloS one PLoS One. 2010 May 3;5(5):e10468. PY - 2010 RN - fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e10468 ST - The transmission dynamics of tuberculosis in a recently developed chinese city T2 - PLoS One TI - The transmission dynamics of tuberculosis in a recently developed chinese city UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20454620http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862741/pdf/pone.0010468.pdf VL - 5 ID - 2606 ER - TY - JOUR AU - Yang, H. M. AU - Raimundo, S. M. DO - doi:10.1186/1742-4682-7-41 ET - 8 November PY - 2010 RN - fulltext fulltext_1208 ST - Assessing the effects of multiple infections and long latency in the dynamics of tuberculosis T2 - Theoretical Biology and Medical Modelling TI - Assessing the effects of multiple infections and long latency in the dynamics of tuberculosis UR - http://www.tbiomed.com/content/pdf/1742-4682-7-41.pdf VL - 7 ID - 2607 ER - TY - JOUR AB - Two tuberculosis (TB) models with incomplete treatment are investigated. It is assumed that the treated individuals may enter either the latent compartment due to the remainder of Mycobacterium tuberculosis or the infectious compartment due to the treatment failure. The first model is a simple one with treatment failure reflecting the current TB treatment fact in most countries with high tuberculosis incidence. The second model refines the simple one by dividing the latent compartment into slow and fast two kinds of progresses. This improvement can be used to describe the case that the latent TB individuals have been infected with some other chronic diseases (such as HIV and diabetes) which may weaken the immunity of infected individuals and shorten the latent period of TB. Both of the two models assume mass action incidence and exponential distributions of transfers between different compartments. The basic reproduction numbers of the two models are derived and their intuitive epidemiological interpretations are given. The global dynamics of two models are all proved by using Liapunov functions. At last, some strategies to control the spread of tuberculosis are discussed. (C) 2010 Elsevier Ltd. All rights reserved. AD - Xi An Jiao Tong Univ, Dept Appl Math, Xian 710049, Peoples R China AF Engn Univ, Dept Appl Math & Phys, Xian 710051, Peoples R China Henan Univ Sci & Technol, Dept Math, Luoyang 471003, Peoples R China AN - WOS:000285445800010 AU - Yang, Y. L. AU - Li, J. Q. AU - Ma, Z. E. AU - Liu, L. J. DA - Jan-Dec DO - 10.1016/j.chaos.2010.09.002 IS - 1-12 J2 - Chaos Soliton Fract KW - sei epidemic model drug-resistance transmission reinfection dynamics LA - English N1 - 696mp Times Cited:9 Cited References Count:23 PY - 2010 SN - 0960-0779 SP - 79-85 ST - Global stability of two models with incomplete treatment for tuberculosis T2 - Chaos Solitons & Fractals TI - Global stability of two models with incomplete treatment for tuberculosis UR - ://WOS:000285445800010 VL - 43 ID - 4868 ER - TY - BOOK A2 - Jiang, Y. A2 - Song, Q. K. A2 - Chen, L. S. A2 - Tan, Y. S. AB - A tuberculosis model with incomplete treatment is investigated. It is assumed that the treated individuals may enter the susceptible compartment due to complete treatment, or enter the latent compartment due to the existence of tubercle bacillus for incomplete treatment, even enter the infectious compartment due to the failure of treatment. The basic reproduction number is obtained, and it has been shown that the dynamics of the model is determined by its basic reproduction number. If the basic reproduction number is less than or equal to one, there exists only the disease-free equilibrium which is globally asymptotically stable, and the disease dies cut eventually. If the basic reproduction number is greater than one, besides the unstable disease-free equilibrium, there exists a unique endemic equilibrium, and the disease is uniformly persistent. AD - [Yang, Yali] Xi An Jiao Tong Univ, Dept Appl Math, Xian 710049, Peoples R China. Yang, YL (reprint author), Xi An Jiao Tong Univ, Dept Appl Math, Xian 710049, Peoples R China. yylhgr@126.com AN - WOS:000280408600083 AU - Yang, Y. L. AU - Li, J. Q. AU - Yang, Y. S. CY - Liverpool KW - tuberculosis treatment equilibrium global stability uniform persistence LA - English N1 - ISI Document Delivery No.: BPZ09 Times Cited: 0 Cited Reference Count: 10 Yang, Yali Li, Jianquan Yang, Youshe Proceedings Paper 7th Conference on Biological Dynamic System and Stability of Differential Equation May 14-16, 2010 Chongqing, PEOPLES R CHINA 113, academic house, mill lane, wavertree technology park, liverpool, l13 4 ah, england PB - World Acad Union-World Acad Press PY - 2010 SN - 978-1-84626-029-2 SP - 397-400 ST - Qualitative Analysis of A Tuberculosis Model with Incomplete Treatment T2 - Proceedings of the 7th Conference on Biological Dynamic System and Stability of Differential Equation, Vols I and Ii TI - Qualitative Analysis of A Tuberculosis Model with Incomplete Treatment UR - ://WOS:000280408600083 ID - 5875 ER - TY - CHAP A2 - Sivaloganathan, S. AB - Tuberculosis (TB) is a contagious disease. It has been a leading cause of death throughout the world. TB has kept being a focus of public health and epidemiological modeling. Based on the fact that most epidemiological data is compiled in certain time interval, discrete TB transmission models are formulated and studied. The basic reproductive number is defined to investigate the dynamical behavior under simple assumptions. The global stability condition of the disease free equilibrium is obtained. The existence of the endemic equilibrium is established. The existence of the periodic solution and the stability of the endemic equilibrium are investigated numerically. The discrete TB model with time dependent model is used to describe the seasonal fluctuation of the monthly reported TB cases in China. The discrete TB model with immigration is applied to simulate the impact of immigration to TB infection in Canada. AD - [Zhou, Yicang; Cao, Hui] Xi An Jiao Tong Univ, Dept Math, Sch Sci, Xian 710049, Peoples R China. Zhou, YC (reprint author), Xi An Jiao Tong Univ, Dept Math, Sch Sci, Xian 710049, Peoples R China. zhouyc@mail.xjtu.edu.cn; caohui0103@163.com AN - WOS:000289584200005 AU - Zhou, Y. C. AU - Cao, H. CY - Providence KW - infectious-diseases epidemic model health system china LA - English N1 - ISI Document Delivery No.: BUK19 Times Cited: 5 Cited Reference Count: 36 Zhou, Yicang Cao, Hui Proceedings Paper Society-for-Mathematical-Biology Conference Jul 29-aug 02, 2008 Toronto, CANADA Fields Inst, Pacif Inst Math Sci, Natl Sci Fdn China, Soc Math Biol P.o. box 6248, providence, ri 02940 usa 1069-5265 PB - Amer Mathematical Soc PY - 2010 SN - 978-0-8218-4845-6 SP - 83-112 ST - Discrete Tuberculosis Models and Their Application T2 - New Perspectives in Mathematical Biology T3 - Fields Institute Communications TI - Discrete Tuberculosis Models and Their Application UR - ://WOS:000289584200005 VL - 57 ID - 5874 ER - TY - JOUR AB - BACKGROUND: Detailed analysis of the dynamic interactions among biological, environmental, social, and economic factors that favour the spread of certain diseases is extremely useful for designing effective control strategies. Diseases like tuberculosis that kills somebody every 15 seconds in the world, require methods that take into account the disease dynamics to design truly efficient control and surveillance strategies. The usual and well established statistical approaches provide insights into the cause-effect relationships that favour disease transmission but they only estimate risk areas, spatial or temporal trends. Here we introduce a novel approach that allows figuring out the dynamical behaviour of the disease spreading. This information can subsequently be used to validate mathematical models of the dissemination process from which the underlying mechanisms that are responsible for this spreading could be inferred. METHODOLOGY/PRINCIPAL FINDINGS: The method presented here is based on the analysis of the spread of tuberculosis in a Brazilian endemic city during five consecutive years. The detailed analysis of the spatio-temporal correlation of the yearly geo-referenced data, using different characteristic times of the disease evolution, allowed us to trace the temporal path of the aetiological agent, to locate the sources of infection, and to characterize the dynamics of disease spreading. Consequently, the method also allowed for the identification of socio-economic factors that influence the process. CONCLUSIONS/SIGNIFICANCE: The information obtained can contribute to more effective budget allocation, drug distribution and recruitment of human skilled resources, as well as guiding the design of vaccination programs. We propose that this novel strategy can also be applied to the evaluation of other diseases as well as other social processes. AD - Departamento de Fisica, Universidade Federal de Pernambuco, Cidade Universitaria, Recife, Pernambuco, Brazil. rita.zorzenon@gmail.com AN - 21152440 AU - Zorzenon dos Santos, R. M. AU - Amador, A. AU - de Souza, W. V. AU - de Albuquerque, M. F. AU - Ponce Dawson, S. AU - Ruffino-Netto, A. AU - Zarate-Blades, C. R. AU - Silva, C. L. DO - 10.1371/journal.pone.0014140 [doi] DP - Nlm ET - 12/15 KW - Brazil/epidemiology Geography Humans Incidence Population Density Population Dynamics Population Surveillance/ methods Socioeconomic Factors Tuberculosis/epidemiology/ prevention & control/ transmission LA - eng N1 - Zorzenon dos Santos, Rita M Amador, Ana de Souza, Wayner V de Albuquerque, Maria Fatima P M Ponce Dawson, Silvina Ruffino-Netto, Antonio Zarate-Blades, Carlos R Silva, Celio L Research Support, Non-U.S. Gov't United States PloS one PLoS One. 2010 Nov 30;5(11):e14140. PY - 2010 RN - fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e14140 ST - A dynamic analysis of tuberculosis dissemination to improve control and surveillance T2 - PLoS One TI - A dynamic analysis of tuberculosis dissemination to improve control and surveillance UR - http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0014140&representation=PDF VL - 5 ID - 2608 ER - TY - JOUR AB - A model is built and used to explore the effects of variations in transmission and/or progression on the decline of tuberculosis rates during the twentieth century. This study also makes use of available data generated over two significantly distinct spatial scales: one (global) involving the United States and the second (local) utilizing the tuberculosis data generated by the state of Massachusetts. AD - [Pablo Aparicio, Juan] Univ Nacl Salta, CONICET, Inst Invest Energias Convenc, Salta, Argentina. [Castillo-Chavez, Carlos] Santa Fe Inst, Santa Fe, NM 87501 USA. [Castillo-Chavez, Carlos] Arizona State Univ, Tempe, AZ 85287 USA. Aparicio, JP (reprint author), Univ Nacl Salta, CONICET, Inst Invest Energias Convenc, Salta, Argentina. juan.p.aparicio@gmail.com; cchavez@asu.edu AN - WOS:000337352200006 AU - Aparicio, J. P. AU - Castillo-Chavez, C. KW - brief epidemiologic history disease arcana transmission Mathematical & Computational Biology LA - English M3 - Proceedings Paper N1 - ISI Document Delivery No.: BA7BE Times Cited: 0 Cited Reference Count: 38 Pablo Aparicio, Juan Castillo-Chavez, Carlos Mondaini, RP 1st International Symposium on Mathematical and Computational Biology of the Society-for-Mathematical-Biology Jul 24-29, 2010 Rio de Janeiro, BRAZIL Soc Math Biol, Coordinat Improvement Higher Educ Personell Agcy, Board Trustees, Natl Res Council Sci & Technol Dev Agcy, Board Trustees, Fdn Res Support Rio de Janeiro State Agcy, Board Trustees National Science Foundation [NSF - DMS -0502349]; National Security Agency [NSA - H98230- 06-1-0097] JPA is a member of the CONICET.This project have been partially sup- ported by grants from the National Science Foundation (NSF - Grant DMS -0502349), the National Security Agency (NSA - Grant H98230- 06-1-0097), the Alfred T. Sloan Foundation and the Office of the Provost of Arizona State University. 0 1 World scientific publ co pte ltd Singapore 978-981-4343-42-8 PY - 2011 SP - 73-95 ST - ON THE USE OF MECHANISTIC AND DATA-DRIVEN MODELS IN POPULATION DYNAMICS: THE CASE OF TUBERCULOSIS IN THE US OVER THAT PAST TWO CENTURIES T2 - Biomat 2010: International Symposium on Mathematical and Computational Biology TI - ON THE USE OF MECHANISTIC AND DATA-DRIVEN MODELS IN POPULATION DYNAMICS: THE CASE OF TUBERCULOSIS IN THE US OVER THAT PAST TWO CENTURIES UR - ://WOS:000337352200006 ID - 5782 ER - TY - JOUR AB - OBJECTIVES: Almost 20% of people smoke tobacco worldwide--a percentage projected to rise in many poor countries. Smoking has been linked to increased individual risk of tuberculosis infection and mortality, but it remains unclear how these risks affect population-wide tuberculosis rates. DESIGN: We constructed a state transition, compartmental, mathematical model of tuberculosis epidemics to estimate the impact of alternative future smoking trends on tuberculosis control. We projected tuberculosis incidence, prevalence, and mortality in each World Health Organization region from 2010 to 2050, and incorporated changing trends in smoking, case detection, treatment success, and HIV prevalence. RESULTS: The model predicted that smoking would produce an excess of 18 million tuberculosis cases (standard error 16-20) and 40 million deaths from tuberculosis (39-41) between 2010 and 2050, if smoking trends continued along current trajectories. The effect of smoking was anticipated to increase the number of tuberculosis cases by 7% (274 million v 256 million) and deaths by 66% (101 million v 61 million), compared with model predictions that did not account for smoking. Smoking was also expected to delay the millennium development goal target to reduce tuberculosis mortality by half from 1990 to 2015. The model estimated that aggressive tobacco control (achieving a 1% decrease in smoking prevalence per year down to eradication) would avert 27 million smoking attributable deaths from tuberculosis by 2050. However, if the prevalence of smoking increased to 50% of adults (as observed in countries with high tobacco use), the model estimated that 34 million additional deaths from tuberculosis would occur by 2050. CONCLUSIONS: Tobacco smoking could substantially increase tuberculosis cases and deaths worldwide in coming years, undermining progress towards tuberculosis mortality targets. Aggressive tobacco control could avert millions of deaths from tuberculosis. AD - Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA. sanjay.basu@ucsf.edu AN - 21972295 AU - Basu, S. AU - Stuckler, D. AU - Bitton, A. AU - Glantz, S. A. DO - 10.1136/bmj.d5506. DP - Nlm ET - 10/06 KW - Adult Humans Models, Theoretical Prevalence Smoking/ adverse effects/epidemiology/prevention & control Tuberculosis/ epidemiology/mortality LA - eng PY - 2011 RN - fulltext fulltext_1208 SN - 1756-1833 (Electronic) 0959-535X (Linking) SP - d5506 ST - Projected effects of tobacco smoking on worldwide tuberculosis control: mathematical modelling analysis T2 - BMJ TI - Projected effects of tobacco smoking on worldwide tuberculosis control: mathematical modelling analysis UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186817/pdf/bmj.d5506.pdf VL - 343 ID - 2609 ER - TY - JOUR AB - Tuberculosis outbreaks originating in prisons, mines, or hospital wards can spread to the larger community. Recent proposals have targeted these high-transmission institutional amplifiers by improving case detection, treatment, or reducing the size of the exposed population. However, what effects these alternative proposals may have is unclear. We mathematically modeled these control strategies and found case detection and treatment methods insufficient in addressing epidemics involving common types of institutional amplifiers. Movement of persons in and out of amplifiers fundamentally altered the transmission dynamics of tuberculosis in a manner not effectively mitigated by detection or treatment alone. Policies increasing the population size exposed to amplifiers or the per-person duration of exposure within amplifiers potentially worsened incidence, even in settings with high rates of detection and treatment success. However, reducing the total population size entering institutional amplifiers significantly lowered tuberculosis incidence and the risk of propagating new drug-resistant tuberculosis strains. AD - Department of Medicine, University of California, Division of General Internal Medicine, San Francisco General Hospital, San Francisco, California 94143, USA. sanjay.basu@ucsf.edu AN - 21212197 AU - Basu, S. AU - Stuckler, D. AU - McKee, M. DA - Jan DO - 84/1/30 [pii] 10.4269/ajtmh.2011.10-0472 [doi] DP - Nlm ET - 01/08 KW - Africa/epidemiology Algorithms Communicable Disease Control/ methods Computer Simulation Epidemics/ prevention & control Europe/epidemiology Hospitals Humans Mining Models, Theoretical Prisons Tuberculosis/ epidemiology/prevention & control L1 - internal-pdf://1595374355/Basu-2011-Addressing institutional amplifiers.pdf LA - eng N1 - Basu, Sanjay Stuckler, David McKee, Martin Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States The American journal of tropical medicine and hygiene Am J Trop Med Hyg. 2011 Jan;84(1):30-7. PY - 2011 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1476-1645 (Electronic) 0002-9637 (Linking) SP - 30-7 ST - Addressing institutional amplifiers in the dynamics and control of tuberculosis epidemics T2 - Am J Trop Med Hyg TI - Addressing institutional amplifiers in the dynamics and control of tuberculosis epidemics UR - http://www.ajtmh.org/content/84/1/30.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005502/pdf/tropmed-84-030.pdf VL - 84 ID - 2610 ER - TY - JOUR AB - Complex biological systems exhibit a property of robustness at all levels of organization. Through different mechanisms, the system tries to sustain stress such as due to starvation or drug exposure. To explore whether reconfiguration of the metabolic networks is used as a means to achieve robustness, we have studied possible metabolic adjustments in Mtb upon exposure to isoniazid (INH), a front-line clinical drug. The redundancy in the genome of M. tuberculosis (Mtb) makes it an attractive system to explore if alternate routes of metabolism exist in the bacterium. While the mechanism of action of INH is well studied, its effect on the overall metabolism is not well characterized. Using flux balance analysis, inhibiting the fluxes flowing through the reactions catalyzed by Rv1484, the target of INH, significantly changes the overall flux profiles. At the pathway level, activation or inactivation of certain pathways distant from the target pathway, are seen. Metabolites such as NADPH are shown to reduce drastically, while fatty acids tend to accumulate. The overall biomass also decreases with increasing inhibition levels. Inhibition studies, pathway level clustering and comparison of the flux profiles with the gene expression data indicate the activation of folate metabolism, ubiquinone metabolism, and metabolism of certain amino acids. This analysis provides insights useful for target identification and designing strategies for combination therapy. Insights gained about the role of individual components of a system and their interactions will also provide a basis for reconstruction of whole systems through synthetic biology approaches. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11693-011-9075-6) contains supplementary material, which is available to authorized users. AD - Bioinformatics Centre, Indian Institute of Science, Bangalore, India. AN - 22132057 AU - Bhat, A. G. AU - Vashisht, R. AU - Chandra, N. DA - Dec DO - 10.1007/s11693-011-9075-6 [doi] 9075 [pii] DP - Nlm ET - 12/02 LA - eng N1 - Bhat, Ashwini G Vashisht, Rohit Chandra, Nagasuma Germany Systems and synthetic biology Syst Synth Biol. 2010 Dec;4(4):299-309. Epub 2011 Feb 26. PY - 2011 RN - fulltext fulltext_1208 SN - 1872-5333 (Electronic) 1872-5325 (Linking) SP - 299-309 ST - Modeling metabolic adjustment in Mycobacterium tuberculosis upon treatment with isoniazid T2 - Syst Synth Biol TI - Modeling metabolic adjustment in Mycobacterium tuberculosis upon treatment with isoniazid UR - http://www.springerlink.com/content/965qr26w05854550/ VL - 4 ID - 2586 ER - TY - JOUR AB - In recent years, bacteria have become resistant to antibiotics, leading to a decline in the effectiveness of antibiotics in treating infectious diseases. A mathematical model for multi-strain tuberculosis transmission dynamics to assess the burden of drug-sensitive, multidrug-resistant and extensively drug-resistant tuberculosis is formulated and analyzed. Each single strain submodel is shown to exhibit backward bifurcation when the threshold parameter is less than unity. Both analytical and numerical results show that resistance to drugs increase with increase in drug use, that is, active tuberculosis treatment results in a reduction of drug sensitive and increase in multidrug-resistant tuberculosis. Furthermore, use of second line drugs results in a decrease of the multidrug-resistant and increase of extensively drug resistant tuberculosis as most cases of multidrug resistant tuberculosis occur as a result of inappropriate, misuse or mismanaged treatment. Both the analytic results and numerical simulations suggest that quarantine of extensively drug resistant TB cases in addition to treatment of other forms of TB may be able to reduce the spread of the epidemic in poor resource-settings. (C) 2011 Elsevier Inc. All rights reserved. AD - Natl Univ Sci & Technol, Dept Appl Math, Modelling Biomed Syst Res Grp, Ascot, Bulawayo, Zimbabwe Univ Cambridge, Dept Vet Med, Cambridge CB3 0ES, England AN - WOS:000291407800044 AU - Bhunu, C. P. DA - Sep DO - 10.1016/j.apm.2011.03.037 IS - 9 J2 - Appl Math Model KW - multidrug-resistant tuberculosis extensively drug-resistant tuberculosis first line tuberculosis drugs second line tuberculosis drugs drug-resistant tuberculosis mycobacterium-tuberculosis exogenous reinfection south-africa emergence equilibria epidemics dynamics disease tb L1 - internal-pdf://0952434647/Bhunu 2011.pdf LA - English N1 - 774sw Times Cited:4 Cited References Count:47 PY - 2011 SN - 0307-904x SP - 4647-4660 ST - Mathematical analysis of a three-strain tuberculosis transmission model T2 - Applied Mathematical Modelling TI - Mathematical analysis of a three-strain tuberculosis transmission model UR - ://WOS:000291407800044 VL - 35 ID - 529 ER - TY - JOUR AB - Molecular epidemiologic studies may use genotypic clustering of isolates as an indicator of recent transmission. It has been shown that missing cases lead to underestimating clustering, and modelling studies suggested that they may also lead to underestimating odds ratios for clustering. Using a national, comprehensive database from the Netherlands covering 15 years between 1993 and 2007 and including over 12,000 patients and their isolates, the authors determined the effects of sampling at random, in time, and by geographic area. As expected, sampling reduced the observed clustering percentages. However, sampling did not reduce the observed odds ratios for clustering. The main explanations for this discrepancy with model outcomes were that a substantial proportion of clustered cases were found in large clusters and that risk factors for clustering tended to be-among clustered cases-also risk factors for large clusters. The authors conclude that, in settings where risk factors for clustering may be interpreted as risk factors for recent transmission, these risk factors are also associated with larger cluster sizes. As a result, odds ratios would show limited sampling bias. AD - Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Academic Medical Center, University of Amsterdam, the Netherlands. mborgdorff@ggd.amsterdam.nl AN - 21606233 AU - Borgdorff, M. W. AU - van den Hof, S. AU - Kalisvaart, N. AU - Kremer, K. AU - van Soolingen, D. DA - Jul 15 DO - kwr061 [pii] 10.1093/aje/kwr061 [doi] DP - Nlm ET - 05/25 KW - Adolescent Adult Child Cluster Analysis Female Humans Male Molecular Epidemiology Odds Ratio Risk Factors Sampling Studies Tuberculosis/ epidemiology LA - eng N1 - Borgdorff, Martien W van den Hof, Susan Kalisvaart, Nico Kremer, Kristin van Soolingen, Dick United States American journal of epidemiology Am J Epidemiol. 2011 Jul 15;174(2):243-51. Epub 2011 May 23. PY - 2011 RN - fulltext fulltext_1208 SN - 1476-6256 (Electronic) 0002-9262 (Linking) SP - 243-51 ST - Influence of sampling on clustering and associations with risk factors in the molecular epidemiology of tuberculosis T2 - Am J Epidemiol TI - Influence of sampling on clustering and associations with risk factors in the molecular epidemiology of tuberculosis UR - http://aje.oxfordjournals.org/content/174/2/243.full.pdf VL - 174 ID - 2612 ER - TY - JOUR AB - This paper deals with the problem of modeling and parameter estimation of a deterministic model of tuberculosis (abbreviated as TB for tubercle bacillus). We first propose and analyze a tuberculosis model without seasonality that incorporates the essential biological and epidemiological features of the disease. The model is shown to exhibit the phenomenon of backward bifurcation, where a stable disease-free equilibrium coexists with one or more stable endemic equilibria when the associated basic reproduction number is less than unity. The statistical data of new TB cases show seasonal fluctuations in many countries. Then, we extend the proposed TB model by incorporating seasonality. We propose a numerical study to estimate unknown parameters according to demographic and epidemiological data in Cameroon. Simulation results are in good accordance with the seasonal variation of the reported new cases of active TB in Cameroon. AD - Univ Douala, Fac Sci, Dept Math & Comp Sci, Lab Appl Math, Douala, Cameroon Postdam Inst Climate Impact Res PIK, D-14412 Potsdam, Germany Humboldt Univ, Dept Phys, D-12489 Berlin, Germany UPMC UMMISCO, UMI IRD 209, Project MASAIE INRIA Grand Est, Bondy, France LIRIMA, Project GRIMCAPE LIRIMA, Yaounde, Cameroon AN - WOS:000294467900014 AU - Bowong, S. AU - Kurths, J. DA - Jul DO - 10.1142/S0218127411029598 IS - 7 J2 - Int J Bifurcat Chaos KW - dynamical systems epidemiological models tuberculosis season pattern parameter estimation heterogeneous populations seasonality bifurcations diseases dynamics LA - English N1 - 814pa Times Cited:1 Cited References Count:36 PY - 2011 SN - 0218-1274 SP - 1999-2015 ST - Modeling and Parameter Estimation of Tuberculosis with Application to Cameroon T2 - International Journal of Bifurcation and Chaos TI - Modeling and Parameter Estimation of Tuberculosis with Application to Cameroon UR - ://WOS:000294467900014 VL - 21 ID - 4873 ER - TY - JOUR AB - Background. Tuberculosis (TB) often occurs among household contacts of people with active TB. It is unclear whether clustering of cases represents household transmission or shared household risk factors for TB. Methods. We used cross-sectional data from 764 households in Lima, Peru, to estimate the relative contributions of household and community transmission, the average time between cases, and the immunity afforded by a previous TB infection. Results. The distribution of cases per household suggests that almost 7 of 10 nonindex household cases were infected in the community rather than in the household. The average interval between household cases was 3.5 years. We observed a saturation effect in the number of cases per household and estimated that protective immunity conferred up to 35% reduction in the risk of disease. Conclusions. Cross-sectional household data can elucidate the natural history and transmission dynamics of TB. In this high-incidence setting, we found that the majority of cases were attributable to community transmission and that household contacts of case patients derive some immunity from household exposures. Screening of household contacts may be an effective method of detecting new TB cases if carried out over several years. AD - Department of Epidemiology, Harvard School of Public Health. AN - 21592987 AU - Brooks-Pollock, E. AU - Becerra, M. C. AU - Goldstein, E. AU - Cohen, T. AU - Murray, M. B. DO - jir162 [pii] 10.1093/infdis/jir162 LA - eng N1 - Brooks-Pollock, Ellen Becerra, Mercedes C Goldstein, Edward Cohen, Ted Murray, Megan B United States The Journal of infectious diseases J Infect Dis. 2011 Jun;203(11):1582-9. PY - 2011 RN - fulltext fulltext_1208 SN - 1537-6613 (Electronic) 0022-1899 (Linking) SP - 1582-1589 ST - Epidemiologic inference from the distribution of tuberculosis cases in households in Lima, Peru T2 - Journal of Infectious Diseases TI - Epidemiologic inference from the distribution of tuberculosis cases in households in Lima, Peru UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21592987http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096792/pdf/jir162.pdf VL - 203 ID - 2613 ER - TY - CHAP A2 - Ran, C. A2 - Yang, G. AB - The research will analyze the complex dynamic mathematic model of tuberculosis epidemic and determine its stability property by using the popular Matlab/Simulink software and relative software packages. Facing to the currently TB epidemic situation, in this project we will investgate the development of TB and its developing trend throught constructing the dynamic biomathematics system model of TB. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of [CEIS 2011] AD - [Chung, Chun-Yen; Chung, Hung-Yuan] Natl Cent Univ, Dept Elect Engn, Jhongli 32001, Taoyuan County, Taiwan. [Ou, Shih-Ching] Univ Kang Ning, Dept Digital Applicat, Tainan 709, Taiwan. Chung, CY (reprint author), Natl Cent Univ, Dept Elect Engn, Jhongli 32001, Taoyuan County, Taiwan. chunyen911@gmail.com AN - WOS:000300876503125 AU - Chung, C. Y. AU - Chung, H. Y. AU - Ou, S. C. CY - Amsterdam DO - 10.1016/j.proeng.2011.08.679 KW - tuberculosis Matlab mathematic intrinsic transmission dynamics LA - English N1 - ISI Document Delivery No.: BYZ94 Times Cited: 1 Cited Reference Count: 4 Chung, Chun-Yen Chung, Hung-Yuan Ou, Shih-Ching Proceedings Paper International Conference on Advanced in Control Engineering and Information Science (CEIS) Aug 18-19, 2011 Dali, PEOPLES R CHINA Chung, Hung-Yuan/H-8055-2012 Chung, Hung-Yuan/0000-0002-1787-173X Sara burgerhartstraat 25, po box 211, 1000 ae amsterdam, netherlands 1877-7058 PB - Elsevier Science Bv PY - 2011 ST - Computer Simulation Applied to a Bio-mathematic Model for Tuberculosis T2 - Ceis 2011 T3 - Procedia Engineering TI - Computer Simulation Applied to a Bio-mathematic Model for Tuberculosis UR - ://WOS:000300876503125 VL - 15 ID - 5772 ER - TY - JOUR AB - The emergence of drug resistance in M. tuberculosis undermines the efficacy of tuberculosis (TB) treatment in individuals and of TB control programs in populations. Multiple drug resistance is often attributed to sequential functional monotherapy, and standard initial treatment regimens have therefore been designed to include simultaneous use of four different antibiotics. Despite the widespread use of combination therapy, highly resistant M. tb strains have emerged in many settings. Here we use a stochastic birth-death model to estimate the probability of the emergence of multidrug resistance during the growth of a population of initially drug sensitive TB bacilli within an infected host. We find that the probability of the emergence of resistance to the two principal anti-TB drugs before initiation of therapy ranges from 10(-5) to 10(-4); while rare, this is several orders of magnitude higher than previous estimates. This finding suggests that multidrug resistant M. tb may not be an entirely "man-made" phenomenon and may help explain how highly drug resistant forms of TB have independently emerged in many settings. AD - Department of Engineering Mathematics, University of Bristol, Bristol, United Kingdom. AN - 21479171 AU - Colijn, C. AU - Cohen, T. AU - Ganesh, A. AU - Murray, M. DO - 10.1371/journal.pone.0018327 [doi] DP - Nlm ET - 04/12 KW - Humans Isoniazid/pharmacology/therapeutic use Probability Time Factors Tuberculosis, Multidrug-Resistant/diagnosis/ drug therapy L1 - internal-pdf://3240893575/Colijn-2011-Spontaneous emergence of multiple.pdf LA - eng N1 - Colijn, Caroline Cohen, Ted Ganesh, Ayalvadi Murray, Megan DP2 OD006663-01/OD/NIH HHS/United States DP2OD006663/OD/NIH HHS/United States U19AI076217/AI/NIAID NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States PloS one PLoS One. 2011 Mar 30;6(3):e18327. PY - 2011 RN - fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e18327 ST - Spontaneous emergence of multiple drug resistance in tuberculosis before and during therapy T2 - PLoS One TI - Spontaneous emergence of multiple drug resistance in tuberculosis before and during therapy UR - http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0018327&representation=PDF https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068161/pdf/pone.0018327.pdf VL - 6 ID - 2615 ER - TY - JOUR AB - Application of molecular dynamics simulation technique has become a conventional computational methodology to calculate significant processes at the molecular level. This computational methodology is particularly useful for analyzing the dynamics of protein-ligand systems. Several uses of molecular dynamics simulation makes possible evaluation of important structural features found at interface between a ligand and a protein, such as intermolecular hydrogen bonds, contact area and binding energy. Considering structure-based virtual screening, molecular dynamics simulations play a pivotal role in understanding the features that are important for ligand-binding affinity. This information could be employed to select higher-affinity ligands obtained in screening processes. Many protein targets such as enoyl-[acyl-carrier-protein] reductase (InhA), purine nucleoside phosphorylase (PNP), and shikimate kinase have been submitted to these simulations and will be analyzed here. All command files used in this review are available for download at http://azevedolab.net/md_75.html. AD - Instituto Nacional de Ciencia e Tecnologia em Tuberculose-CNPq-MCT, Faculdade de Biociencias, Laboratorio de Bioquimica Estrutural, Pontificia Universidade Catolica do Rio Grande do Sul, Porto Alegre - RS, Brazil. walter@azevedolab.net AN - 21366529 AU - de Azevedo, W. F., Jr. DO - BSP/CMC/E-Pub/2011/ 087 [pii] DP - Nlm ET - 03/04 KW - Bacterial Proteins/ chemistry/metabolism Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)/chemistry/metabolism Molecular Dynamics Simulation Mycobacterium tuberculosis/ enzymology/metabolism Phosphotransferases (Alcohol Group Acceptor)/chemistry/metabolism Purine-Nucleoside Phosphorylase/chemistry/metabolism LA - eng N1 - de Azevedo, W F Jr Research Support, Non-U.S. Gov't Review Netherlands Current medicinal chemistry Curr Med Chem. 2011;18(9):1353-66. PY - 2011 RN - fulltext fulltext_1208 SN - 1875-533X (Electronic) 0929-8673 (Linking) SP - 1353-66 ST - Molecular dynamics simulations of protein targets identified in Mycobacterium tuberculosis T2 - Curr Med Chem TI - Molecular dynamics simulations of protein targets identified in Mycobacterium tuberculosis VL - 18 ID - 2616 ER - TY - JOUR AB - In this work we propose an alternative model of the spread of tuberculosis (TB) and the emergence of drug resistance due to the treatment with antibiotics. We implement the simulations by an agent-based model computational approach where the spatial structure is taken into account. The spread of tuberculosis occurs according to probabilities defined by the interactions among individuals. The model was validated by reproducing results already known from the literature in which different treatment regimes yield the emergence of drug resistance. The different patterns of TB spread can be visualized at any time of the system evolution. The implementation details as well as some results of this alternative approach are discussed. AD - Univ Fed Fluminense, Dept Fis, Inst Ciencias Exatas ICEx, BR-27213350 Rio De Janeiro, Brazil Univ Guelph, Dept Math & Stat, Guelph, ON N1G 2W1, Canada Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Pret, BR-14040901 Sao Paulo, Brazil Natl Inst Sci & Technol Complex Syst, BR-14040901 Sao Paulo, Brazil AN - WOS:000292190200004 AU - de Espindola, A. L. AU - Bauch, C. T. AU - Cabella, B. C. T. AU - Martinez, A. S. DA - May DO - Artn P05003 10.1088/1742-5468/2011/05/P05003 J2 - J Stat Mech-Theory E KW - population dynamics (theory) epidemic modelling control strategies resistance epidemics LA - English N1 - 784ww Times Cited:5 Cited References Count:20 PY - 2011 SN - 1742-5468 ST - An agent-based computational model of the spread of tuberculosis T2 - Journal of Statistical Mechanics-Theory and Experiment TI - An agent-based computational model of the spread of tuberculosis UR - ://WOS:000292190200004 http://iopscience.iop.org/article/10.1088/1742-5468/2011/05/P05003/meta ID - 4874 ER - TY - JOUR AU - Dodd, Peter J. AU - White, Richard G. AU - Corbett, Elizabeth L. DO - 10.1371/journal.pone.0029130 IS - 12 L1 - file:///C:/Users/James/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Dodd, White, Corbett - 2011 - Periodic Active Case Finding for TB When to Look.pdf internal-pdf://0401618573/Dodd-2011-Periodic Active Case Finding for TB_.pdf PY - 2011 SP - e29130-e29130 ST - Periodic Active Case Finding for TB: When to Look? T2 - PLoS ONE TI - Periodic Active Case Finding for TB: When to Look? UR - http://dx.plos.org/10.1371/journal.pone.0029130 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245256/pdf/pone.0029130.pdf VL - 6 ID - 3195 ER - TY - JOUR AB - BACKGROUND: Undiagnosed and misdiagnosed tuberculosis (TB) drives the epidemic in India. Serological (antibody detection) TB tests are not recommended by any agency, but widely used in many countries, including the Indian private sector. The cost and impact of using serology compared with other diagnostic techniques is unknown. METHODS AND FINDINGS: Taking a patient cohort conservatively equal to the annual number of serological tests done in India (1.5 million adults suspected of having active TB), we used decision analysis to estimate costs and effectiveness of sputum smear microscopy (US$3.62 for two smears), microscopy plus automated liquid culture (mycobacterium growth indicator tube [MGIT], US$20/test), and serological testing (anda-tb ELISA, US$20/test). Data on test accuracy and costs were obtained from published literature. We adopted the perspective of the Indian TB control sector and an analysis frame of 1 year. Our primary outcome was the incremental cost per disability-adjusted life year (DALY) averted. We performed one-way sensitivity analysis on all model parameters, with multiway sensitivity analysis on variables to which the model was most sensitive. If used instead of sputum microscopy, serology generated an estimated 14,000 more TB diagnoses, but also 121,000 more false-positive diagnoses, 102,000 fewer DALYs averted, and 32,000 more secondary TB cases than microscopy, at approximately four times the incremental cost (US$47.5 million versus US$11.9 million). When added to high-quality sputum smears, MGIT culture was estimated to avert 130,000 incremental DALYs at an incremental cost of US$213 per DALY averted. Serology was dominated by (i.e., more costly and less effective than) MGIT culture and remained less economically favorable than sputum smear or TB culture in one-way and multiway sensitivity analyses. CONCLUSIONS: In India, sputum smear microscopy remains the most cost-effective diagnostic test available for active TB; efforts to increase access to quality-assured microscopy should take priority. In areas where high-quality microscopy exists and resources are sufficient, MGIT culture is more cost-effective than serology as an additional diagnostic test for TB. These data informed a recently published World Health Organization policy statement against serological tests. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America. AN - 21857810 AU - Dowdy, D. W. AU - Steingart, K. R. AU - Pai, M. DA - Aug DO - 10.1371/journal.pmed.1001074 ET - 08/23 J2 - PLoS medicine KW - Adult Antibodies, Bacterial/*blood Bacteriological Techniques/*economics Bias (Epidemiology) Cost-Benefit Analysis Decision Support Techniques Enzyme-Linked Immunosorbent Assay Humans India Microscopy/economics Mycobacterium/immunology/pathogenicity Sensitivity and Specificity Serologic Tests/*economics Sputum/*microbiology Tuberculosis/*diagnosis/microbiology LA - eng M3 - Comparative Study Research Support, Non-U.S. Gov't N1 - Dowdy, David W Steingart, Karen R Pai, Madhukar Canadian Institutes of Health Research/Canada PLoS Med. 2011 Aug;8(8):e1001074. Epub 2011 Aug 9. PY - 2011 RN - fulltext fulltext_1208 SN - 1549-1676 (Electronic) 1549-1277 (Linking) SP - e1001074 ST - Serological testing versus other strategies for diagnosis of active tuberculosis in India: a cost-effectiveness analysis T2 - PLoS Med TI - Serological testing versus other strategies for diagnosis of active tuberculosis in India: a cost-effectiveness analysis UR - http://www.ncbi.nlm.nih.gov/pubmed/21857810http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153451/pdf/pmed.1001074.pdf VL - 8 ID - 2618 ER - TY - JOUR AB - PURPOSE: The search for small molecules with activity against Mycobacterium tuberculosis (Mtb) increasingly uses high throughput screening and computational methods. Several public datasets from the Collaborative Drug Discovery Tuberculosis (CDD TB) database have been evaluated with cheminformatics approaches to validate their utility and suggest compounds for testing. METHODS: Previously reported Bayesian classification models were used to predict a set of 283 Novartis compounds tested against Mtb (containing aerobic and anaerobic hits) and to search FDA approved drugs. The Novartis compounds were also filtered with computational SMARTS alerts to identify potentially undesirable substructures. RESULTS: Using the Novartis compounds as a test set for the Bayesian models demonstrated a >4.0-fold enrichment over random screening for finding aerobic hits not in the computational models (N = 34). A 10-fold enrichment was observed for finding Mtb active compounds in the FDA drugs database. 85.9% of the Novartis compounds failed the Abbott SMARTS alerts, a value substantially higher than for known TB drugs. Higher levels of failures of SMARTS filters from different groups also correlate with the number of Lipinski violations. CONCLUSIONS: These computational approaches may assist in finding desirable leads for Tuberculosis drug discovery. AD - Collaborative Drug Discovery, 1633 Bayshore Highway, Suite 342, Burlingame, California 94010, USA. sekins@collaborativedrug.com AN - 21547522 AU - Ekins, S. AU - Freundlich, J. S. DA - Aug DO - 10.1007/s11095-011-0413-x [doi] DP - Nlm ET - 05/07 KW - Antitubercular Agents/chemistry/ pharmacology Bayes Theorem Computer Simulation Databases, Factual Drug Discovery/methods Models, Biological Mycobacterium tuberculosis/drug effects Small Molecule Libraries/chemistry/ pharmacology Tuberculosis/ drug therapy LA - eng N1 - Ekins, Sean Freundlich, Joel S United States Pharmaceutical research Pharm Res. 2011 Aug;28(8):1859-69. Epub 2011 Mar 10. PY - 2011 RN - fulltext fulltext_1208 SN - 1573-904X (Electronic) 0724-8741 (Linking) SP - 1859-69 ST - Validating new tuberculosis computational models with public whole cell screening aerobic activity datasets T2 - Pharm Res TI - Validating new tuberculosis computational models with public whole cell screening aerobic activity datasets UR - http://www.springerlink.com/content/58228876406x7556/ VL - 28 ID - 2619 ER - TY - JOUR AB - This paper deals with the problem of optimal control for the transmission dynamics of tuberculosis (TB). A TB model that considers the existence of a new class (mainly in the African context) is considered: the lost to follow up individuals. Based on the model formulated and studied in the work of Plaire Tchinda Mouofo, (2009), the TB control is formulated and solved as an optimal control theory problem using the Pontryagin's maximum principle (Pontryagin et al., 1992). This control strategy indicates how the control of the lost to follow up class can considerably influence the basic reproduction ratio so as to reduce the number of lost to follow up. Numerical results show the performance of the optimization strategy. AD - Laboratory of Applied Mathematics, University of Yaounde 1, Yaounde, Cameroon. yemvudu@yahoo.fr AN - 22007263 AU - Emvudu, Y. AU - Demasse, R. AU - Djeudeu, D. DO - 10.1155/2011/398476 [doi] DP - Nlm ET - 10/19 KW - Africa Algorithms Communicable Disease Control Follow-Up Studies Humans Lost to Follow-Up Models, Statistical Models, Theoretical Population Dynamics Poverty Public Health Tuberculosis/ therapy/ transmission World Health LA - eng N1 - Emvudu, Yves Demasse, Ramses Djeudeu, Dany United States Computational and mathematical methods in medicine Comput Math Methods Med. 2011;2011:398476. Epub 2011 Oct 11. PY - 2011 RN - fulltext fulltext_1208 SN - 1748-6718 (Electronic) 1748-670X (Linking) SP - 398476 ST - Optimal control of the lost to follow up in a tuberculosis model T2 - Comput Math Methods Med TI - Optimal control of the lost to follow up in a tuberculosis model UR - http://downloads.hindawi.com/journals/cmmm/2011/398476.pdf VL - 2011 ID - 2620 ER - TY - JOUR AB - Multiple immune factors control host responses to Mycobacterium tuberculosis infection, including the formation of granulomas, which are aggregates of immune cells whose function may reflect success or failure of the host to contain infection. One such factor is TNF-alpha. TNF-alpha has been experimentally characterized to have the following activities in M. tuberculosis infection: macrophage activation, apoptosis, and chemokine and cytokine production. Availability of TNF-alpha within a granuloma has been proposed to play a critical role in immunity to M. tuberculosis. However, in vivo measurement of a TNF-alpha concentration gradient and activities within a granuloma are not experimentally feasible. Further, processes that control TNF-alpha concentration and activities in a granuloma remain unknown. We developed a multiscale computational model that includes molecular, cellular, and tissue scale events that occur during granuloma formation and maintenance in lung. We use our model to identify processes that regulate TNF-alpha concentration and cellular behaviors and thus influence the outcome of infection within a granuloma. Our model predicts that TNF-alphaR1 internalization kinetics play a critical role in infection control within a granuloma, controlling whether there is clearance of bacteria, excessive inflammation, containment of bacteria within a stable granuloma, or uncontrolled growth of bacteria. Our results suggest that there is an interplay between TNF-alpha and bacterial levels in a granuloma that is controlled by the combined effects of both molecular and cellular scale processes. Finally, our model elucidates processes involved in immunity to M. tuberculosis that may be new targets for therapy. AD - Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA. AN - 21321109 AU - Fallahi-Sichani, M. AU - El-Kebir, M. AU - Marino, S. AU - Kirschner, D. E. AU - Linderman, J. J. DA - Mar 15 DO - jimmunol.1003299 [pii] 10.4049/jimmunol.1003299 [doi] DP - Nlm ET - 02/16 KW - Computational Biology/ methods Granuloma/ immunology/microbiology/pathology Humans Inflammation Mediators/chemistry/metabolism/physiology Ligands Models, Immunological Molecular Dynamics Simulation Mycobacterium tuberculosis/ growth & development/ immunology/pathogenicity Predictive Value of Tests Receptors, Tumor Necrosis Factor, Type I/chemistry/metabolism/ physiology Signal Transduction/immunology Tuberculosis, Pulmonary/ immunology/microbiology/pathology Tumor Necrosis Factor-alpha/chemistry/metabolism/physiology LA - eng N1 - Fallahi-Sichani, Mohammad El-Kebir, Mohammed Marino, Simeone Kirschner, Denise E Linderman, Jennifer J N01 AI50018/AI/NIAID NIH HHS/United States R33 HL092844-01/HL/NHLBI NIH HHS/United States R33 HL092844-03/HL/NHLBI NIH HHS/United States R33 HL092853-01/HL/NHLBI NIH HHS/United States R33HL092844/HL/NHLBI NIH HHS/United States R33HL092853/HL/NHLBI NIH HHS/United States Research Support, N.I.H., Extramural United States Journal of immunology (Baltimore, Md. : 1950) Nihms291818 J Immunol. 2011 Mar 15;186(6):3472-83. Epub 2011 Feb 14. PY - 2011 RN - fulltext fulltext_1208 SN - 1550-6606 (Electronic) 0022-1767 (Linking) SP - 3472-83 ST - Multiscale computational modeling reveals a critical role for TNF-alpha receptor 1 dynamics in tuberculosis granuloma formation T2 - J Immunol TI - Multiscale computational modeling reveals a critical role for TNF-alpha receptor 1 dynamics in tuberculosis granuloma formation UR - http://www.jimmunol.org/content/186/6/3472.full.pdf VL - 186 ID - 2622 ER - TY - JOUR AB - To establish itself within the host system, Mycobacterium tuberculosis (Mtb) has formulated various means of attacking the host system. One such crucial strategy is the exploitation of the iron resources of the host system. Obtaining and maintaining the required concentration of iron becomes a matter of contest between the host and the pathogen, both trying to achieve this through complex molecular networks. The extent of complexity makes it important to obtain a systems perspective of the interplay between the host and the pathogen with respect to iron homeostasis. We have reconstructed a systems model comprising 92 components and 85 protein-protein or protein-metabolite interactions, which have been captured as a set of 194 rules. Apart from the interactions, these rules also account for protein synthesis and decay, RBC circulation and bacterial production and death rates. We have used a rule-based modelling approach, Kappa, to simulate the system separately under infection and non-infection conditions. Various perturbations including knock-outs and dual perturbation were also carried out to monitor the behavioral change of important proteins and metabolites. From this, key components as well as the required controlling factors in the model that are critical for maintaining iron homeostasis were identified. The model is able to re-establish the importance of iron-dependent regulator (ideR) in Mtb and transferrin (Tf) in the host. Perturbations, where iron storage is increased, appear to enhance nutritional immunity and the analysis indicates how they can be harmful for the host. Instead, decreasing the rate of iron uptake by Tf may prove to be helpful. Simulation and perturbation studies help in identifying Tf as a possible drug target. Regulating the mycobactin (myB) concentration was also identified as a possible strategy to control bacterial growth. The simulations thus provide significant insight into iron homeostasis and also for identifying possible drug targets for tuberculosis. AD - Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India. AN - 21833436 AU - Ghosh, S. AU - Prasad, K. V. AU - Vishveshwara, S. AU - Chandra, N. DA - Oct DO - 10.1039/c1mb05093a [doi] DP - Nlm ET - 08/13 KW - Homeostasis Iron/ metabolism Models, Biological Mycobacterium tuberculosis/ metabolism LA - eng N1 - Ghosh, Soma Prasad, K V S Vishveshwara, Saraswathi Chandra, Nagasuma Research Support, Non-U.S. Gov't England Molecular bioSystems Mol Biosyst. 2011 Oct;7(10):2750-68. Epub 2011 Aug 11. PY - 2011 RN - fulltext fulltext_1208 SN - 1742-2051 (Electronic) 1742-2051 (Linking) SP - 2750-68 ST - Rule-based modelling of iron homeostasis in tuberculosis T2 - Mol Biosyst TI - Rule-based modelling of iron homeostasis in tuberculosis UR - http://pubs.rsc.org/en/Content/ArticleLanding/2011/MB/c1mb05093a VL - 7 ID - 2623 ER - TY - JOUR AB - OBJECTIVES: To measure the economic costs and benefits of scaling up tuberculosis (TB) control under the Revised National Tuberculosis Control Programme (RNTCP) in India. DESIGN: Modelling based on country-level programme and epidemiological data from 1997 to 2006. RESULTS: The scale-up of TB control in India has resulted in a total health benefit of 29.2 million disability-adjusted life years (DALYs), including 1.3 million deaths averted. In 2006, the burden of TB measured in terms of DALYs lost would have been 1.8 times higher in the absence of the programme. The total gain in economic well-being from TB control is estimated at US$88.1 billion over the 1997-2006 10-year period. Total public expenditure on TB control over this period amounted to US$768 million, with the RNTCP accounting for US$299 million and other health sector costs accounting for US$469 million. The cost of TB control averaged just US$26 per DALY gained over 1997-2006 and generated a return of US$115 per dollar spent. CONCLUSIONS: The scale-up of TB control has been a very cost-effective strategy for improving the health status of India's population, while the return on investment has been exceptional from a societal perspective. AD - World Health Organization, New Delhi, India. goodchildm@hotmail.com AN - 21333103 AU - Goodchild, M. AU - Sahu, S. AU - Wares, F. AU - Dewan, P. AU - Shukla, R. S. AU - Chauhan, L. S. AU - Floyd, K. DA - Mar DP - Nlm ET - 02/22 KW - Cost-Benefit Analysis Directly Observed Therapy/economics Humans India Models, Economic National Health Programs/ economics Quality-Adjusted Life Years Tuberculosis/economics/ prevention & control LA - eng N1 - Goodchild, M Sahu, S Wares, F Dewan, P Shukla, R S Chauhan, L S Floyd, K Research Support, Non-U.S. Gov't France The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Int J Tuberc Lung Dis. 2011 Mar;15(3):358-62. PY - 2011 RN - fulltext fulltext_1208 SN - 1815-7920 (Electronic) 1027-3719 (Linking) SP - 358-62 ST - A cost-benefit analysis of scaling up tuberculosis control in India T2 - Int J Tuberc Lung Dis TI - A cost-benefit analysis of scaling up tuberculosis control in India VL - 15 ID - 2624 ER - TY - JOUR AB - There is a critical need for improved and shorter tuberculosis (TB) treatment. Current in vitro models of TB, while valuable, are poor predictors of the antibacterial effect of drugs in vivo. Mathematical models may be useful to overcome the limitations of traditional approaches in TB research. The objective of this study was to set up a prototype mathematical model of TB treatment by rifampin, based on pharmacokinetic, pharmacodynamic and disease submodels. The full mathematical model can simulate the time-course of tuberculous disease from the first day of infection to the last day of therapy. Therapeutic simulations were performed with the full model to study the antibacterial effect of various dosage regimens of rifampin in lungs. The model reproduced some qualitative and quantitative properties of the bactericidal activity of rifampin observed in clinical data. The kill curves simulated with the model showed a typical biphasic decline in the number of extracellular bacteria consistent with observations in TB patients. Simulations performed with more simple pharmacokinetic/pharmacodynamic models indicated a possible role of a protected intracellular bacterial compartment in such a biphasic decline. This modeling effort strongly suggests that current dosage regimens of RIF may be further optimized. In addition, it suggests a new hypothesis for bacterial persistence during TB treatment. AD - Hospices Civils de Lyon, Groupement Hospitalier de Geriatrie, Service Pharmaceutique-ADCAPT, Francheville, France. sylvain.goutelle@chu-lyon.fr AN - 21605569 AU - Goutelle, S. AU - Bourguignon, L. AU - Jelliffe, R. W. AU - Conte, J. E., Jr. AU - Maire, P. DA - Aug 7 DO - S0022-5193(11)00255-4 [pii] 10.1016/j.jtbi.2011.05.013 [doi] DP - Nlm ET - 05/25 KW - Animals Antitubercular Agents/pharmacokinetics/pharmacology/ therapeutic use Mice Models, Theoretical Rifampin/pharmacokinetics/pharmacology/ therapeutic use Tuberculosis, Pulmonary/ drug therapy LA - eng N1 - Goutelle, Sylvain Bourguignon, Laurent Jelliffe, Roger W Conte, John E Jr Maire, Pascal England Journal of theoretical biology J Theor Biol. 2011 Aug 7;282(1):80-92. Epub 2011 May 18. PY - 2011 RN - fulltext fulltext_1208 SN - 1095-8541 (Electronic) 0022-5193 (Linking) SP - 80-92 ST - Mathematical modeling of pulmonary tuberculosis therapy: Insights from a prototype model with rifampin T2 - J Theor Biol TI - Mathematical modeling of pulmonary tuberculosis therapy: Insights from a prototype model with rifampin UR - http://ac.els-cdn.com/S0022519311002554/1-s2.0-S0022519311002554-main.pdf?_tid=876b5e7118fa0e117600e5bd358ef74d&acdnat=1345012412_e092be0a51c53045ce45abc61fdba41c VL - 282 ID - 2625 ER - TY - JOUR AB - Mathematical analysis is carried out for a tuberculosis (TB) model incorporating both latent and clinical stages, immigration and treatment. With immigration into the latent classes, we show that the model always has a unique endemic equilibrium and it is globally asymptotically stable. The global stability of the endemic equilibrium is proved using a global Lyapunov function. AU - Guo, h. AU - Li, M. Y. IS - 1 PY - 2011 SP - 1-18 ST - GLOBAL STABILITY OF THE ENDEMIC EQUILIBRIUM OF A TUBERCULOSIS MODEL WITH IMMIGRATION AND TREATMENT T2 - Canadian Applied Mathematics Quarterly TI - GLOBAL STABILITY OF THE ENDEMIC EQUILIBRIUM OF A TUBERCULOSIS MODEL WITH IMMIGRATION AND TREATMENT UR - http://www.math.ualberta.ca/ami/CAMQ/pdf_files/vol_19/19_1/19_1a.pdf VL - 19 ID - 4938 ER - TY - JOUR AB - Spread of tuberculosis (TB) due to the immigration from some developing countries with high TB incidence to developed countries poses an increasing challenge in the global TB control. Here a simple compartmental TB model with constant immigration, early and late latency is developed in order to investigate the impact of new immigrants with latent TB on the overall TB incidence, and to compare the difference contributed by different proportions of latently-infected new immigrants with high or low risk to develop active TB shortly after arrival. The global dynamics of the system is completely classified, numerical simulations are carried out for different scenarios, and potential applications to public health policy are discussed. AD - Centre for Disease Modeling, Department of Mathematics and Statistics, York University, 4700 Keele Street Toronto, ON, M3J 1P3, Canada. hguo@mathstat.yorku.ca AN - 21675805 AU - Guo, H. AU - Wu, J. DA - Jul DO - 10.3934/mbe.2011.8.695 DP - NLM ET - 2011/06/17 IS - 3 J2 - Mathematical biosciences and engineering : MBE KW - Canada/epidemiology Computer Simulation Disease Outbreaks/*statistics & numerical data Emigration and Immigration/*statistics & numerical data Humans Incidence *Models, Statistical Time Factors Tuberculosis/*epidemiology LA - eng N1 - 1551-0018 Guo, Hongbin Wu, Jianhong Journal Article Research Support, Non-U.S. Gov't United States Math Biosci Eng. 2011 Jul;8(3):695-709. doi: 10.3934/mbe.2011.8.695. PY - 2011 SN - 1547-1063 SP - 695-709 ST - Persistent high incidence of tuberculosis among immigrants in a low-incidence country: impact of immigrants with early or late latency T2 - Math Biosci Eng TI - Persistent high incidence of tuberculosis among immigrants in a low-incidence country: impact of immigrants with early or late latency VL - 8 ID - 2851 ER - TY - JOUR AB - Evidence of preferential mixing through selected social routes has been suggested for the transmission of tuberculosis (TB) infection in low burden settings. A realistic modelization of these contact routes is needed to appropriately assess the impact of individually targeted control strategies, such as contact network investigation of index cases and treatment of latent TB infection (LTBI). We propose an age-structured, socio-demographic individual based model (IBM) with a realistic, time-evolving structure of preferential contacts in a population. In particular, transmission within households, schools and workplaces, together with a component of casual, distance-dependent contacts are considered. We also compared the model against two other formulations having no social structure of contacts (homogeneous mixing transmission): a baseline deterministic model without age structure and an age-structured IBM. The socio-demographic IBM better fitted recent longitudinal data on TB epidemiology in Arkansas, USA, which serves as an example of a low burden setting. Inclusion of age structure in the model proved fundamental to capturing actual proportions of reactivated TB cases (as opposed to recently transmitted) as well as profiling age-group specific incidence. The socio-demographic structure additionally provides a prediction of TB transmission rates (the rate of infection in household contacts and the rate of secondary cases in household and workplace contacts). These results suggest that the socio-demographic IBM is an optimal choice for evaluating current control strategies, including contact network investigation of index cases, and the simulation of alternative scenarios, particularly for TB eradication targets. AD - Fondazione Bruno Kessler, Trento, Italy. guzzetta@fbk.eu AN - 21906603 AU - Guzzetta, G. AU - Ajelli, M. AU - Yang, Z. AU - Merler, S. AU - Furlanello, C. AU - Kirschner, D. DA - Nov 21 DO - S0022-5193(11)00435-8 [pii] 10.1016/j.jtbi.2011.08.032 [doi] DP - Nlm ET - 09/13 KW - Adolescent Adult Age Distribution Age Factors Aged Arkansas/epidemiology Child Child, Preschool Contact Tracing Endemic Diseases Epidemiologic Methods Humans Infant Infant, Newborn Interpersonal Relations Latent Tuberculosis/epidemiology Middle Aged Models, Biological Tuberculosis/epidemiology/prevention & control/ transmission Young Adult LA - eng N1 - Guzzetta, Giorgio Ajelli, Marco Yang, Zhenhua Merler, Stefano Furlanello, Cesare Kirschner, Denise R01 EB012579-04A1/EB/NIBIB NIH HHS/United States R01 HL106804-01/HL/NHLBI NIH HHS/United States R01-EB-012579-04/EB/NIBIB NIH HHS/United States R01-HL-106804-01/HL/NHLBI NIH HHS/United States R33 HL092853-01/HL/NHLBI NIH HHS/United States R33HL092853-01/HL/NHLBI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Journal of theoretical biology Nihms327860 J Theor Biol. 2011 Nov 21;289:197-205. Epub 2011 Sep 3. PY - 2011 RN - fulltext fulltext_1208 SN - 1095-8541 (Electronic) 0022-5193 (Linking) SP - 197-205 ST - Modeling socio-demography to capture tuberculosis transmission dynamics in a low burden setting T2 - J Theor Biol TI - Modeling socio-demography to capture tuberculosis transmission dynamics in a low burden setting UR - http://ac.els-cdn.com/S0022519311004358/1-s2.0-S0022519311004358-main.pdf?_tid=51cf6280baf7343d83850525bdaed5d3&acdnat=1345012454_66e6a3a6ba3270670d4232cc72803123 VL - 289 ID - 2626 ER - TY - JOUR AB - Tuberculosis (TB) is a growing problem worldwide, with an estimated third of the world's population currently infected. Of particular concern is the growing trend of dual epidemics of HIV and TB, with the associated multidrug-resistant TB (MDR-TB). Developed countries which had previously removed TB transmission from communities are being re-infected with the MDR-TB strains. In the USA, Centers for Disease Control & Prevention (2009) estimate that treatment of a single case of MDR-TB costs approximately USD$250,000, with a similar cost expected in Australia. TB is a complicated disease with different rates of progression to, and different aspects of, the clinically active disease. Approximately 5-10% of those infected with TB develop 'fast' TB, and are expected to progress to clinically active TB within 2 years [Porco et al. 2001]. The remainder have 'slow' TB, and remain latently infected, with 5-10% progressing to clinically active TB in 20 years [Blower et al. 1995]. Those with clinically active TB are further divided into extra-pulmonary (non-infectious) and pulmonary (able to infect others). Note those in the 'pulmonary' category may also have extra-pulmonary TB, but the reverse is not true. The control of TB spread is of paramount importance. The main intervention strategy adopted by the World Health Organisation (WHO) Stop TB program is the 'Directly Observed Treatment Short course' (DOTS) [World Health Organisation 2010]. Not all detection occurs under this program, but a significant amount of the treatment does, particularly for high burden countries. Therefore when considering interventions, we concentrate on the DOTS program, and do not consider other interventions here. We develop a population level model for TB transmission, with a focus on incorporating the WHO's DOTS (Directly Observed Treatment Short-course) intervention program. The population is divided into 6 compartments, with 4 describing different stages of the disease (susceptible, latently infected, extrapulmonary, and pulmonary), and 2 for the DOTS intervention program (detection and treatment). This work has applications worldwide, but here we focus on the Torres Strait region where there is a high proportion of multidrug-resistant TB (MDR-TB). In particular, estimates suggest Papua New Guinea (PNG) may have the highest proportion of MDR-TB in the world [Gilpin et al. 2008], and the Torres Strait Islands could potentially act as a gateway for MDR-TB into mainland Australia. A sensitivity analysis is important in terms of both data collection and refinement, and in the context of understanding and informing the control of TB. To perform the sensitivity analysis the model needs to be run many times with different parameter values. Latin hypercube sampling is used to efficiently cover the parameter space, in conjunction with partial rank correlation coefficient to determine which parameters most influence the disease dynamics. The results show the most important parameter for TB in Papua New Guinea (PNG) is the rate of progression from latent to clinically active TB. Therefore, data refinement should concentrate on determining this rate as accurately as possible. The most important intervention parameter is the detection rate for the DOTS intervention program. This suggests an increase in DOTS coverage by even a small margin will result in a significant decrease in the incidence and prevalence of TB in PNG and other high burden countries. AD - Australian Natl Univ, Natl Ctr Epidemiol & Populat Hlth, Canberra, ACT 0200, Australia AN - WOS:000314989300125 AU - Hickson, R. I. AU - Mercer, G. N. AU - Lokuge, M. KW - tuberculosis infectious disease control intervention dots sensitivity analysis transmission dynamics cost-effectiveness western province drug-resistance hiv strategies uncertainty countries papua tb LA - English N1 - Bdu79 Times Cited:2 Cited References Count:23 PY - 2011 SP - 926-932 ST - Sensitivity analysis of a model for tuberculosis T2 - 19th International Congress on Modelling and Simulation (Modsim2011) TI - Sensitivity analysis of a model for tuberculosis UR - ://WOS:000314989300125 ID - 4875 ER - TY - JOUR AB - Tuberculosis (TB) is a global emergency. The World Health Organization reports about 9.2 million new infections each year, with an average of 1.7 million people killed by the disease. The causative agent is Mycobacterium tuberculosis (Mtb), whose main target are the macrophages, important immune system cells. Macrophages and T cell populations are the main responsible for fighting the pathogen. A better understanding of the interaction between Mtb, macrophages and T cells will contribute to the design of strategies to control TB. The purpose of this study is to evaluate the impact of the response of T cells and macrophages in the control of Mtb. To this end, we propose a system of ordinary differential equations to model the interaction among non-infected macrophages, infected macrophages, T cells and Mtb bacilli. Model analysis reveals the existence of two equilibrium states, infection-free equilibrium and the endemically infected equilibrium which can represent a state of latent or active infection, depending on the amount of bacteria. AD - Departamento de Matematicas y Estadistica, Universidad de Narino, Pasto, Clle 18 - Cra 50, Colombia. edbargun@udenar.edu.co AN - 21936595 AU - Ibarguen-Mondragon, E. AU - Esteva, L. AU - Chavez-Galan, L. DA - Oct 01 DO - 10.3934/mbe.2011.8.973 IS - 4 KW - Basic Reproduction Number Computer Simulation Humans Immunity, Cellular/immunology Macrophages/*immunology/microbiology *Models, Immunological Mycobacterium tuberculosis/*immunology T-Lymphocytes/*immunology/microbiology Tuberculosis/*immunology/microbiology/prevention & control N1 - Ibarguen-Mondragon, Eduardo Esteva, Lourdes Chavez-Galan, Leslie eng Research Support, Non-U.S. Gov't 2011/09/23 06:00 Math Biosci Eng. 2011 Oct 1;8(4):973-86. doi: 10.3934/mbe.2011.8.973. PY - 2011 SN - 1551-0018 (Electronic) 1547-1063 (Linking) SP - 973-86 ST - A mathematical model for cellular immunology of tuberculosis T2 - Math Biosci Eng TI - A mathematical model for cellular immunology of tuberculosis UR - https://www.ncbi.nlm.nih.gov/pubmed/21936595 VL - 8 ID - 2235 ER - TY - JOUR AB - For pathogens that must be treated with combinations of antibiotics and acquire resistance through genetic mutation, knowledge of the order in which drug-resistance mutations occur may be important for determining treatment policies. Diagnostic specimens collected from patients are often available; this makes it possible to determine the presence of individual drug resistance-conferring mutations and combinations of these mutations. In most cases, these specimens are only available from a patient at a single point in time; it is very rare to have access to multiple specimens from a single patient collected over time as resistance accumulates to multiple drugs. Statistical methods that use branching trees have been successfully applied to such cross-sectional data to make inference on the ordering of events that occurred prior to sampling. Here, we propose a Bayesian approach to fitting branching tree models that has several advantages, including the ability to accommodate prior information regarding measurement error or cross resistance and the natural way it permits the characterization of uncertainty. Our methods are applied to a data set for drug-resistant TB in Peru; the goal of the analysis was to determine the order with which patients develop resistance to the drugs commonly used for treating TB in this setting. AD - Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA. aizu@hsph.harvard.edu AN - 21717491 AU - Izu, A. AU - Cohen, T. AU - Mitnick, C. AU - Murray, M. AU - De Gruttola, V. DA - Sep 30 DO - 10.1002/sim.4287 [doi] 10.1002/sim.4287. Epub 2011 Jun 30. DP - Nlm ET - 07/01 KW - Anti-Bacterial Agents/ pharmacology Bayes Theorem Computer Simulation Drug Resistance, Multiple, Bacterial Humans Models, Genetic Models, Statistical Mutation Mycobacterium tuberculosis/drug effects/ genetics Tuberculosis/drug therapy/ microbiology L1 - internal-pdf://0048581990/Izu-2011-Bayesian methods for fitting mixture.pdf LA - eng PY - 2011 RN - fulltext fulltext_1208 SN - 1097-0258 (Electronic) 0277-6715 (Linking) SP - 2708-20 ST - Bayesian methods for fitting mixture models that characterize branching tree processes: An application to development of resistant TB strains T2 - Stat Med TI - Bayesian methods for fitting mixture models that characterize branching tree processes: An application to development of resistant TB strains UR - http://onlinelibrary.wiley.com.ez.lshtm.ac.uk/store/10.1002/sim.4287/asset/sim4287.pdf?v=1&t=h5w1m62j&s=09334abd6f823c09c5f187f158f8e5341cba1933 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219798/pdf/nihms321244.pdf VL - 30 ID - 2627 ER - TY - JOUR AB - Children with tuberculosis present with high rates of disseminated disease and tuberculous (TB) meningitis due to poor cell-mediated immunity. Recommended isoniazid doses vary from 5 mg/kg/day to 15 mg/kg/day. Antimicrobial pharmacokinetic/pharmacodynamic studies have demonstrated that the ratio of the 0- to 24-h area under the concentration-time curve (AUC(0-24)) to the MIC best explains isoniazid microbial kill. The AUC(0-24)/MIC ratio associated with 80% of maximal kill (80% effective concentration [EC(80)]), considered the optimal effect, is 287.2. Given the pharmacokinetics of isoniazid encountered in children 10 years old or younger, with infants as a special group, and given the differences in penetration of isoniazid into phagocytic cells, epithelial lining fluid, and subarachnoid space during TB meningitis, we performed 10,000 patient Monte Carlo simulations to determine how well isoniazid doses of between 2.5 and 40 mg/kg/day would achieve or exceed the EC(80). None of the doses examined achieved the EC(80) in >/=90% of children. Doses of 5 mg/kg were universally inferior; doses of 10 to 15 mg/kg/day were adequate only under the very limited circumstances of children who were slow acetylators and had disease limited to pneumonia. Each of the three disease syndromes, acetylation phenotype, and being an infant required different doses to achieve adequate AUC(0-24)/MIC exposures in an acceptable proportion of children. We conclude that current recommended doses for children are likely suboptimal and that isoniazid doses in children are best individualized based on disease process, age, and acetylation status. AD - Department of Paediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa. AN - 21098246 AU - Jeena, P. M. AU - Bishai, W. R. AU - Pasipanodya, J. G. AU - Gumbo, T. C2 - PMC3028779 DA - Feb DO - 10.1128/aac.00763-10 DP - NLM ET - 2010/11/26 IS - 2 J2 - Antimicrobial agents and chemotherapy KW - Animals Antitubercular Agents/*administration & dosage/pharmacokinetics/pharmacology Area Under Curve Cerebrospinal Fluid/metabolism Child Child, Preschool *Computer Simulation Dose-Response Relationship, Drug Humans Immunity, Cellular Infant Isoniazid/*administration & dosage/pharmacokinetics/pharmacology Mice Microbial Sensitivity Tests Models, Biological *Monte Carlo Method Mycobacterium tuberculosis/*drug effects Phagocytes/metabolism Treatment Outcome Tuberculosis/*drug therapy/microbiology Tuberculosis, Meningeal/drug therapy/microbiology LA - eng N1 - 1098-6596 Jeena, Prakash M Bishai, William R Pasipanodya, Jotam G Gumbo, Tawanda Howard Hughes Medical Institute/United States Journal Article Research Support, Non-U.S. Gov't United States Antimicrob Agents Chemother. 2011 Feb;55(2):539-45. doi: 10.1128/AAC.00763-10. Epub 2010 Nov 22. PY - 2011 SN - 0066-4804 SP - 539-45 ST - In silico children and the glass mouse model: clinical trial simulations to identify and individualize optimal isoniazid doses in children with tuberculosis T2 - Antimicrob Agents Chemother TI - In silico children and the glass mouse model: clinical trial simulations to identify and individualize optimal isoniazid doses in children with tuberculosis VL - 55 ID - 2134 ER - TY - JOUR AB - In order to better predict epidemic of tuberculosis (TB) and evaluate the effect of TB control strategies, we added the effect of transmission from permanent residents to migrants to our previous TB model. We simulated the behavior of TB transmission by the extended model. The numerical simulation indicated that the basic reproductive numbers must be less than one in both permanent residents and migrants in order to eliminate the disease from total population. We also evaluated the Canada's TB screening strategy and observe that TB is sensitive to the strategy. Our study suggests that immigrants have a considerable influence on the overall transmission dynamics behavior of tuberculosis. The effective TB control measures should incorporate migrant as well the permanent residents. AD - National Institute on Drug Dependence, Peking University, Beijing, China National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China. AN - 21342483 AU - Jia, Z. AU - Cheng, S. AU - Jia, X. DA - Feb 5 DO - 10.1111/j.1756-5391.2011.01116.x [doi] 10.1111/j.1756-5391.2011.01116.x. DP - Nlm ET - 02/24 LA - Eng PY - 2011 RN - fulltext fulltext_1208 SN - 1756-5391 (Electronic) 1756-5391 (Linking) ST - A Mathematical model for evaluating tuberculosis screening strategies T2 - J Evid Based Med TI - A Mathematical model for evaluating tuberculosis screening strategies UR - http://onlinelibrary.wiley.com/doi/10.1111/j.1756-5391.2011.01116.x/abstract ID - 2628 ER - TY - JOUR AB - BACKGROUND: Currently, an annual chest X-ray examination (CXR) for detection of active tuberculosis (TB) in employees aged >/=40 years is recommended in the guidelines of the Japan Industrial Safety and Health Law. Interferon-gamma release assays are new alternatives to the tuberculin skin test for detecting Mycobacterium tuberculosis infection, with higher specificity than the tuberculin skin test and without cross-reactivity with the Bacille Calmette-Guerin vaccine. This study aimed to assess the cost-effectiveness of employee TB screening using QuantiFERON-TB Gold In-Tube (QFT) versus CXR. METHODS: Markov models were constructed. The target population was a hypothetical cohort of immunocompetent 40-year-old individuals, using a societal perspective and a lifetime horizon. All costs and clinical benefits were discounted at a fixed annual rate of 3%. RESULTS: In a base-case analysis, the QFT strategy was the most cost-effective ($US 262.84; 22.87049 quality-adjusted life-years [QALYs]) compared with no screening ($448.38; 22.85452 QALYs) and CXR ($543.50; 22.85453 QALYs) [year 2009 values]. CONCLUSION: The QFT strategy is currently robust for screening Bacille Calmette-Guerin- vaccinated employees in Japan. There appears to be little role for CXR. These findings may be applicable to other countries in terms of choosing optimal TB screening for employees. AD - Public Health Promotion Division, Tamagawa District Administration Office, City of Setagaya, Tokyo, Japan. Kowada101@mb.city.setagaya.tokyo.jp AN - 21839543 AU - Kowada, A. DA - Dec DO - 10.1016/j.ajic.2011.04.329 DP - Nlm ET - 08/16 J2 - American journal of infection control KW - Adult Cost-Benefit Analysis Female Health Personnel Humans Interferon-gamma Release Tests/ economics/methods Japan Male Occupational Health Radiography, Thoracic/ economics/methods Tuberculosis/ diagnosis X-Rays LA - eng N1 - Kowada, Akiko United States Am J Infect Control. 2011 Dec;39(10):e67-72. Epub 2011 Aug 12. PY - 2011 RN - fulltext fulltext_1208 SN - 1527-3296 (Electronic) 0196-6553 (Linking) SP - e67-72 ST - Cost-effectiveness of interferon-gamma release assay versus chest X-ray for tuberculosis screening of employees T2 - Am J Infect Control TI - Cost-effectiveness of interferon-gamma release assay versus chest X-ray for tuberculosis screening of employees UR - http://ac.els-cdn.com/S0196655311007255/1-s2.0-S0196655311007255-main.pdf?_tid=991548c8-f1d4-11e1-902d-00000aab0f01&acdnat=1346243300_adc9202a2f12935cc68bcb3623f56bdd VL - 39 ID - 2630 ER - TY - JOUR AN - 21440954 AU - Kowada, A. AU - Deshpande, G. A. AU - Takahashi, O. AU - Shimbo, T. AU - Fukui, T. DA - Jun DO - 10.1016/j.jhin.2011.01.026 DP - Nlm ET - 03/29 J2 - The Journal of hospital infection KW - Adult Cost-Benefit Analysis Health Personnel Humans Immunologic Tests/ economics Incidence Interferon-gamma/ biosynthesis Latent Tuberculosis/diagnosis/epidemiology/immunology/radiography Markov Chains Mass Chest X-Ray/ economics Mass Screening/ economics Middle Aged Mycobacterium tuberculosis/immunology Tuberculosis, Pulmonary/ diagnosis/epidemiology/immunology/radiography LA - eng N1 - Kowada, A Deshpande, G A Takahashi, O Shimbo, T Fukui, T Letter England J Hosp Infect. 2011 Jun;78(2):152-4. Epub 2011 Mar 26. PY - 2011 RN - fulltext fulltext_1208 SN - 1532-2939 (Electronic) 0195-6701 (Linking) SP - 152-4 ST - Cost-effectiveness analysis of interferon-gamma release assays versus chest X-ray for annual tuberculosis screening of healthcare workers T2 - J Hosp Infect TI - Cost-effectiveness analysis of interferon-gamma release assays versus chest X-ray for annual tuberculosis screening of healthcare workers UR - http://ac.els-cdn.com/S0195670111000909/1-s2.0-S0195670111000909-main.pdf?_tid=9495ff54-f1d4-11e1-bda6-00000aab0f01&acdnat=1346243292_bc75a6a0ca9018638c484814e10f3c09 VL - 78 ID - 2631 ER - TY - JOUR AU - Li, Xue-Zhi AU - Bhattacharya, Souvik AU - Yang, Jun-Yuan AU - Martcheva, Maia DO - doi:10.1142/S0218339011003889 PY - 2011 RN - fulltext fulltext_1208 SP - 205-236 ST - A TUBERCULOSIS (TB) MODEL WITH UNDETECTED COMPARTMENT: AN APPLICATION TO CHINA T2 - Journal of Biological Systems TI - A TUBERCULOSIS (TB) MODEL WITH UNDETECTED COMPARTMENT: AN APPLICATION TO CHINA UR - http://www.worldscientific.com/doi/abs/10.1142/S0218339011003889 VL - 19 ID - 2632 ER - TY - JOUR AB - Efforts to stimulate technological innovation in the diagnosis of tuberculosis (TB) have resulted in the recent introduction of several novel diagnostic tools. As these products come to market, policy makers must make difficult decisions about which of the available tools to implement. This choice should depend not only on the test characteristics (e.g., sensitivity and specificity) of the tools, but also on how they will be used within the existing health care infrastructure. Accordingly, policy makers choosing between diagnostic strategies must decide: 1) What is the best combination of tools to select? 2)Who should be tested with the new tools? and 3)Will these tools complement or replace existing diagnostics? The best choice of diagnostic strategy will likely vary between settings with different epidemiology (e.g., levels of TB incidence, human immunodeficiency virus co-infection and drug-resistant TB) and structural and resource constraints (e.g., existing diagnostic pathways, human resources and laboratory capacity). We propose a joint modelling framework that includes a tuberculosis (TB) transmission component (a dynamic epidemiological model) and a health system component (an operational systems model) to support diagnostic strategy decisions. This modelling approach captures the complex feedback loops in this system: new diagnostic strategies alter the demands on and performance of health systems that impact TB transmission dynamics which, in turn, result in further changes to demands on the health system. We demonstrate the use of a simplified model to support the rational choice of a diagnostic strategy based on health systems requirements, patient outcomes and population-level TB impact. AD - Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan. AN - 21740663 AU - Lin, H. H. AU - Langley, I. AU - Mwenda, R. AU - Doulla, B. AU - Egwaga, S. AU - Millington, K. A. AU - Mann, G. H. AU - Murray, M. AU - Squire, S. B. AU - Cohen, T. DA - Aug DO - 10.5588/ijtld.11.0062 ET - 07/12 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Antitubercular Agents/therapeutic use *Bacteriological Techniques/economics Computer Simulation *Decision Support Techniques Feedback Health Care Costs Health Policy Health Resources/economics/utilization Humans Policy Making Predictive Value of Tests Prognosis Sensitivity and Specificity Sputum/microbiology Time Factors Tuberculosis/*diagnosis/drug therapy/economics/epidemiology/transmission LA - eng M3 - Research Support, Non-U.S. Gov't N1 - Lin, H-H Langley, I Mwenda, R Doulla, B Egwaga, S Millington, K A Mann, G H Murray, M Squire, S B Cohen, T France Int J Tuberc Lung Dis. 2011 Aug;15(8):996-1004. PY - 2011 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1815-7920 (Electronic) 1027-3719 (Linking) SP - 996-1004 ST - A modelling framework to support the selection and implementation of new tuberculosis diagnostic tools T2 - Int J Tuberc Lung Dis TI - A modelling framework to support the selection and implementation of new tuberculosis diagnostic tools UR - http://www.ncbi.nlm.nih.gov/pubmed/21740663 VL - 15 ID - 2634 ER - TY - JOUR AB - RATIONALE: To improve the effectiveness of tuberculosis (TB) control programs in the United States by identifying cost-effective priorities for screening for latent tuberculosis infection (LTBI). OBJECTIVES: To estimate the cost-effectiveness of LTBI screening using the tuberculin skin test (TST)and interferon-g release assays (IGRAs). METHODS: A Markov model of screening for LTBI with TST and IGRA in risk-groups considered in current LTBI screening guidelines. MEASUREMENTS AND MAIN RESULTS: In all risk-groups, TST and IGRA screening resulted in increased mean life expectancy, ranging from 0.03-0.24 life-months per person screened. IGRA screening resulted in greater life expectancy gains than TST. Screening always cost more than not screening, but IGRA was cost-saving compared with TST in some groups. Four patterns of cost-effectiveness emerged, related to four risk categories. (1) Individuals at highest risk of TB reactivation (close contacts and those infected with HIV): the incremental cost-effectiveness ratio (ICER) of IGRA compared with TST was less than $100,000 per quality-adjusted life year (QALY) gained. (2) The foreign-born: IGRA was cost-saving compared with TST and cost-effective compared with no screening (ICER ,$100,000 per QALY gained). (3) Vulnerable populations (e.g., homeless, drug user, or former prisoner): the ICER of TST screening was approximately $100,000-$150,000 per QALY gained, but IGRA was not cost-effective. (4) Medical comorbidities (e.g., diabetes): the ICER of screening with TST or IGRA was greater than $100,000 per QALY. CONCLUSIONS: LTBI screening guidelines could make progress toward TB elimination by prioritizing screening for close contacts, those infected with HIV, and the foreign-born regardless of time living in the United States. For these groups, IGRA screening was more cost-effective than TST screening. AD - HIV Epidemiology and Outcomes Research Unit, Boston Medical Center, Section of Infectious Disease, Evans Biomedical Research Center, 650 Albany St. Rm 647, Boston, MA 02118, USA. benjamin.linas@bmc.org AN - 21562129 AU - Linas, B. P. AU - Wong, A. Y. AU - Freedberg, K. A. AU - Horsburgh, C. R., Jr. DO - 201101-0181OC [pii] 10.1164/rccm.201101-0181OC KW - Adolescent Adult Aged Aged, 80 and over Child Contact Tracing/economics/methods Cost Savings Cost-Benefit Analysis Female Humans Incidence Interferon-gamma/secretion Latent Tuberculosis/diagnosis/*epidemiology/therapy Male *Mass Screening/economics/methods/standards Middle Aged *Models, Economic Morbidity/trends Practice Guidelines as Topic Prevalence Quality-Adjusted Life Years Retrospective Studies Tuberculin Test/*economics United States/epidemiology Young Adult LA - eng N1 - Linas, Benjamin P Wong, Angela Y Freedberg, Kenneth A Horsburgh, C Robert Jr K01AI073193/AI/NIAID NIH HHS/United States K24AI062476/AI/NIAID NIH HHS/United States R37AI42006/AI/NIAID NIH HHS/United States Comparative Study Research Support, N.I.H., Extramural United States American journal of respiratory and critical care medicine Am J Respir Crit Care Med. 2011 Sep 1;184(5):590-601. PY - 2011 RN - fulltext fulltext_1208 SN - 1535-4970 (Electronic) 1073-449X (Linking) SP - 590-601 ST - Priorities for screening and treatment of latent tuberculosis infection in the United States T2 - American journal of respiratory and critical care medicine TI - Priorities for screening and treatment of latent tuberculosis infection in the United States UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21562129http://ajrccm.atsjournals.org/content/184/5/590.long VL - 184 ID - 2635 ER - TY - JOUR AB - A deterministic model is developed to describe the effects of vaccination and treatment on the spread of tuberculosis. It is shown that the basic reproduction number characterizes the disease transmission dynamics: if R 0 ≤ 1 , there exists only the disease-free equilibrium which is globally asymptotically stable, and if R 0 > 1 then there is a disease endemic equilibrium and the disease persists. Global stability of the endemic equilibrium is also discussed. Analysis of the dependence of R 0 on the vaccination rate, vaccine efficacy and treatment rate shows that the spread of tuberculosis can be controlled if the vaccine rate or the efficacy or the treatment rate reaches a certain threshold. AU - Liu, Junli AU - Zhang, Tailei DO - 10.1016/j.mcm.2011.03.033 KW - Tuberculosis Vaccination Treatment Lyapunov function Global stability PY - 2011 RN - fulltext fulltext_1208 SN - 0895-7177 SP - 836-845 ST - Global stability for a tuberculosis model T2 - Mathematical and Computer Modelling TI - Global stability for a tuberculosis model UR - http://www.sciencedirect.com/science/article/pii/S0895717711001932http://ac.els-cdn.com/S0895717711001932/1-s2.0-S0895717711001932-main.pdf?_tid=6e401a810ebafd6a2b564ba57d5e7e04&acdnat=1345012593_1c343b0c8216062a71c1fa8ef9a99469 VL - 54 ID - 2636 ER - TY - JOUR AB - This paper presents a novel mathematical model with multidrug-resistant (MDR) and undetected TB cases. The theoretical analysis indicates that the disease-free equilibrium is globally asymptotically stable if R(0) < 1; otherwise, the system may exist a locally asymptotically stable endemic equilibrium. The model is also used to simulate and predict TB epidemic in Guangdong. The results imply that our model is in agreement with actual data and the undetected rate plays vital role in the TB trend. Our model also implies that TB cannot be eradicated from population if it continues to implement current TB control strategies. AD - Jia, ZW Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China S China Univ Technol, Coll Automat Sci & Engn, Guangzhou 510640, Guangdong, Peoples R China N Univ China, Dept Math, Taiyuan 030051, Peoples R China AntiTB Res Inst Guangdong Prov, Guangzhou 510630, Guangdong, Peoples R China AN - WOS:000293568100001 AU - Liu, Y. Q. AU - Sun, Z. D. AU - Sun, G. Q. AU - Zhong, Q. AU - Jiang, L. AU - Zhou, L. AU - Qiao, Y. P. AU - Jia, Z. W. DO - Artn 296905 10.1155/2011/296905 J2 - Discrete Dyn Nat Soc L1 - internal-pdf://0733788662/Liu-2011-Modeling Transmission of Tuberculosis.pdf LA - English N1 - 803fv Times Cited:0 Cited References Count:10 PY - 2011 SN - 1026-0226 ST - Modeling Transmission of Tuberculosis with MDR and Undetected Cases T2 - Discrete Dynamics in Nature and Society TI - Modeling Transmission of Tuberculosis with MDR and Undetected Cases UR - ://WOS:000293568100001 http://downloads.hindawi.com/journals/ddns/2011/296905.pdf ID - 4876 ER - TY - JOUR AB - The majority of individuals infected with Mycobacterium tuberculosis (Mtb) bacilli develop latent infection. Mtb becomes dormant and phenotypically drug resistant when it encounters multiple stresses within the host, and expresses a set of genes, known as the dormancy regulon, in vivo. These genes are expressed in vitro in response to nitric oxide (NO), hypoxia (oxygen deprivation), and nutrient starvation. The occurrence and reactivation of latent tuberculosis (TB) is not clearly understood. The ability of the pathogen to enter and exit from different states is associated with its ability to cause persistent infection. During infection it is not known whether the organism is in a persistent slow replicating state or a dormant non-replicating state, with the latter ultimately causing a latent infection with the potential to reactivate to active disease. We collected gene expression data for Mtb bacilli under different stress conditions that simulate latency or dormancy. Time course experiments were selected and differentially expressed gene profiles were determined at each time point. A mathematical model was then developed to show the dynamics of Mtb latency based on the profile of differentially expressed genes. Analysis of the time course data show the dynamics of latency occurrence in vitro and the mathematical model reveals all possible scenarios of Mtb latency development with respect to the different conditions that may be produced by the immune response in vivo. The mathematical model provides a biological explanation of how Mtb latency occurs based on observed gene expression changes in in vitro latency models. AD - University of Cape Town, Institute of Infectious Disease and Molecular Medicine, Department of Clinical Laboratory Sciences, Cape Town, South Africa. gesham.magombedze@uct.ac.za AN - 21968442 AU - Magombedze, G. AU - Mulder, N. DA - Jan 7 DO - S0022-5193(11)00489-9 [pii] 10.1016/j.jtbi.2011.09.025 [doi] DP - Nlm ET - 10/05 KW - Gene Expression Regulation, Bacterial/drug effects/genetics Genes, Bacterial Humans Latent Tuberculosis/ microbiology Models, Biological Mycobacterium tuberculosis/drug effects/genetics/ growth & development Nitric Oxide/pharmacology Oxygen/pharmacology Stress, Physiological/genetics LA - eng N1 - Magombedze, Gesham Mulder, Nicola Research Support, Non-U.S. Gov't England Journal of theoretical biology J Theor Biol. 2012 Jan 7;292:44-59. Epub 2011 Sep 29. PY - 2011 RN - fulltext fulltext_1208 SN - 1095-8541 (Electronic) 0022-5193 (Linking) SP - 44-59 ST - A mathematical representation of the development of Mycobacterium tuberculosis active, latent and dormant stages T2 - J Theor Biol TI - A mathematical representation of the development of Mycobacterium tuberculosis active, latent and dormant stages UR - http://ac.els-cdn.com/S0022519311004899/1-s2.0-S0022519311004899-main.pdf?_tid=d54d8d90a3eba9c169d9501e63fde212&acdnat=1345012620_a88a65a3fb97213412ab8f9ff9770d74 VL - 292 ID - 2675 ER - TY - JOUR AB - SETTING: No cost-effectiveness studies of testing for latent tuberculosis infection have incorporated both targeted testing and the use of interferon-gamma release assays (IGRAs) in heterogeneous populations. OBJECTIVE: To examine the cost-effectiveness of universal vs. targeted and sequential testing strategies and the use of tuberculin skin testing (TST) vs. IGRAs. DESIGN: Using a decision-analytic model, incremental cost-effectiveness ratios were calculated in 2009 among nine potential strategies for screening recruits. A societal perspective was taken over a 20-year analytic horizon, discounting future costs at 3% annually. Sensitivity analyses were conducted to determine how changes in assumptions affected the estimates. RESULTS: Targeted strategies cost over US$250 000 per case prevented, whereas universal testing strategies cost over US$700 000 per incremental case prevented in base case and most sensitivity analyses. CONCLUSION: Targeted testing offered the best value in this population, although it was still relatively expensive compared to no testing. Sequential testing with both TST and IGRAs provided a poor incremental value compared to targeted and universal testing strategies. Targeted testing using TST was slightly more cost-effective than targeted testing using either QuantiFERON(R)-TB Gold In-Tube or T-SPOT(R).TB, but these estimates were very sensitive to changes in model assumptions. AD - Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. james.mancuso@us.army.mil AU - Mancuso, J. D. AU - Niebuhr, D. W. AU - Frick, K. D. AU - Keep, L. W. AU - Anderson, K. M. DO - 10.5588/ijtld.10.0542 N1 - JID: 9706389; ppublish PY - 2011 RN - fulltext fulltext_1208 SN - 1815-7920; 1027-3719 SP - 1223-30, i ST - Cost-effectiveness analysis of targeted and sequential screening strategies for latent tuberculosis T2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease TI - Cost-effectiveness analysis of targeted and sequential screening strategies for latent tuberculosis VL - 15 Y2 - Sep ID - 2637 ER - TY - JOUR AB - Tuberculosis is a worldwide health problem with 2 billion people infected with Mycobacterium tuberculosis (Mtb, the bacteria causing TB). The hallmark of infection is the emergence of organized structures of immune cells forming primarily in the lung in response to infection. Granulomas physically contain and immunologically restrain bacteria that cannot be cleared. We have developed several models that spatially characterize the dynamics of the host-mycobacterial interaction, and identified mechanisms that control granuloma formation and development. In particular, we published several agent-based models (ABMs) of granuloma formation in TB that include many subtypes of T cell populations, macrophages as well as key cytokine and chemokine effector molecules. These ABM studies emphasize the important role of T-cell related mechanisms in infection progression, such as magnitude and timing of T cell recruitment, and macrophage activation. In these models, the priming and recruitment of T cells from the lung draining lymph node (LN) was captured phenomenologically. In addition to these ABM studies, we have also developed several multi-organ models using ODEs to examine trafficking of cells between, for example, the lung and LN. While we can predict temporal dynamic behaviors, those models are not coupled to the spatial aspects of granuloma. To this end, we have developed a multi-organ model that is hybrid: an ABM for the lung compartment and a non-linear system of ODE representing the lymph node compartment. This hybrid multi-organ approach to study TB granuloma formation in the lung and immune priming in the LN allows us to dissect protective mechanisms that cannot be achieved using the single compartment or multi-compartment ODE system. The main finding of this work is that trafficking of important cells known as antigen presenting cells from the lung to the lymph node is a key control mechanism for protective immunity: the entire spectrum of infection outcomes can be regulated by key immune cell migration rates. Our hybrid multi-organ implementation suggests that effector CD4+ T cells can rescue the system from a persistent infection and lead to clearance once a granuloma is fully formed. This could be effective as an immunotherapy strategy for latently infected individuals. (C) 2011 Elsevier Ltd. All rights reserved. AD - [Marino, Simeone; Kirschner, Denise] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [El-Kebir, Mohammed] Vrije Univ Amsterdam, Ctr Integrat Bioinformat VU, NL-1081 HV Amsterdam, Netherlands. [El-Kebir, Mohammed] Ctr Wiskunde & Informat, Life Sci Grp, NL-1098 XG Amsterdam, Netherlands. Marino, S (reprint author), Univ Michigan, Sch Med, Dept Microbiol & Immunol, 1150 W Med Ctr Dr,6730 MSB2, Ann Arbor, MI 48109 USA. simeonem@umich.edu AN - WOS:000291371100006 AU - Marino, S. AU - El-Kebir, M. AU - Kirschner, D. DA - Jul DO - 10.1016/j.jtbi.2011.03.022 IS - 1 J2 - J. Theor. Biol. KW - Agent-based model Mtb Multi-organ models Cell trafficking human immune-response mycobacterium-tuberculosis dendritic cells antigen presentation sensitivity-analysis lymph-node pulmonary tuberculosis interferon-gamma gene-expression in-vivo Life Sciences & Biomedicine - Other Topics Mathematical & Computational Biology LA - English M3 - Article N1 - ISI Document Delivery No.: 774FR Times Cited: 37 Cited Reference Count: 75 Marino, Simeone El-Kebir, Mohammed Kirschner, Denise El-Kebir, Mohammed/0000-0002-1468-2407 National Institute of Health (NIH) [R33HL092844, R33HL092853, N01 AI50018] This work was supported by National Institute of Health (NIH) Grants R33HL092844, R33HL092853, and N01 AI50018 awarded to DK. We thank reviewers for helpful comments. 38 3 8 Academic press ltd- elsevier science ltd London PY - 2011 SN - 0022-5193 SP - 50-62 ST - A hybrid multi-compartment model of granuloma formation and T cell priming in Tuberculosis T2 - Journal of Theoretical Biology TI - A hybrid multi-compartment model of granuloma formation and T cell priming in Tuberculosis UR - ://WOS:000291371100006 VL - 280 ID - 5733 ER - TY - JOUR AB - Tuberculosis (TB) is a deadly infectious disease caused by Mycobacterium tuberculosis (Mtb). No available vaccine is reliable and, although treatment exists, approximately 2 million people still die each year. The hallmark of TB infection is the granuloma, a self-organizing structure of immune cells forming in the lung and lymph nodes in response to bacterial invasion. Protective immune mechanisms play a role in granuloma formation and maintenance; these act over different time/length scales (e. g., molecular, cellular, and tissue scales). The significance of specific immune factors in determining disease outcome is still poorly understood, despite incredible efforts to establish several animal systems to track infection progression and granuloma formation. Mathematical and computational modeling approaches have recently been applied to address open questions regarding host-pathogen interaction dynamics, including the immune response to Mtb infection and TB granuloma formation. This provides a unique opportunity to identify factors that are crucial to a successful outcome of infection in humans. These modeling tools not only offer an additional avenue for exploring immune dynamics at multiple biological scales but also complement and extend knowledge gained via experimental tools. We review recent modeling efforts in capturing the immune response to Mtb, emphasizing the importance of a multiorgan and multiscale approach that has tuneable resolution. Together with experimentation, systems biology has begun to unravel key factors driving granuloma formation and protective immune response in TB. (C) 2010 John Wiley & Sons, Inc. WIREs Syst Biol Med 2011 3 479-489 DOI: 10.1002/wsbm.131 AD - [Marino, Simeone; Kirschner, Denise E.] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Linderman, Jennifer J.] Univ Michigan, Dept Chem Engn, Coll Engn, Ann Arbor, MI 48109 USA. Kirschner, DE (reprint author), Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. kirschne@umich.edu AN - WOS:000291821300008 AU - Marino, S. AU - Linderman, J. J. AU - Kirschner, D. E. DA - Jul-Aug DO - 10.1002/wsbm.131 IS - 4 J2 - Wiley Interdiscip. Rev.-Syst. Biol KW - mycobacterium-tuberculosis lymph-node antigen presentation cynomolgus macaques t-cells granuloma-formation systems biology dendritic cells infection macrophages Research & Experimental Medicine LA - English M3 - Article N1 - ISI Document Delivery No.: 779ZS Times Cited: 27 Cited Reference Count: 57 Marino, Simeone Linderman, Jennifer J. Kirschner, Denise E. Nih [r33hl092844, r33hl092853, n01 ai50018] This work was supported by grants from the NIH: R33HL092844, R33HL092853, and N01 AI50018. 28 0 10 Wiley-blackwell Hoboken 1939-005x PY - 2011 SN - 1939-5094 SP - 479-489 ST - A multifaceted approach to modeling the immune response in tuberculosis T2 - Wiley Interdisciplinary Reviews-Systems Biology and Medicine TI - A multifaceted approach to modeling the immune response in tuberculosis UR - ://WOS:000291821300008 VL - 3 ID - 5737 ER - TY - JOUR AU - Mellor, Georgina R. AU - Currie, Christine S. M. AU - Corbett, Elizabeth L. C1 - 2000499 DO - 10.1145/2000494.2000499 PY - 2011 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1049-3301 SP - 1-17 ST - Incorporating household structure into a discrete-event simulation model of tuberculosis and HIV T2 - ACM Trans. Model. Comput. Simul. TI - Incorporating household structure into a discrete-event simulation model of tuberculosis and HIV UR - http://dl.acm.org/citation.cfm?doid=2000494.2000499 VL - 21 ID - 2638 ER - TY - JOUR AB - Individuals living with HIV experience a much higher risk of progression from latent M. tuberculosis infection to active tuberculosis (TB) disease relative to individuals with intact immune systems. A several-month daily course of a single drug during latent infection (i.e. isoniazid preventive therapy (IPT)) has proved in clinical trials to substantially reduce an HIV-infected individual's risk of TB disease. As a result of these findings and ongoing studies, the World Health Organization has produced strong guidelines for implementing IPT on a community-wide scale for individuals with HIV at risk of TB disease. To date, there has been limited use of IPT at a community-wide level. In this paper, we present a new co-network model for HIV and TB co-epidemics to address questions about how the population-level impact of community-wide IPT may differ from the individual-level impact of IPT offered to selected individuals. In particular, we examine how the effect of clustering of contacts within high-TB incidence communities may affect the rates of re-infection with TB and how this clustering modifies the expected population-level effects of IPT. We find that populations with clustering of respiratory contacts experience aggregation of TB cases and high numbers of re-infection events. While, encouragingly, the overall population-level effects of community-wide IPT appear to be sustained regardless of network structure, we find that in populations where these contacts are highly clustered, there is dramatic heterogeneity in the impact of IPT: in some sub-regions of these populations, TB is nearly eliminated, while in others, repeated re-infection almost completely undermines the effect of IPT. Our findings imply that as IPT programmes are brought to scale, we should expect local heterogeneity of effectiveness as a result of the complex patterns of disease transmission within communities. AD - Bristol Centre for Complexity Sciences, University of Bristol, Bristol, UK. harriet.l.mills@gmail.com AN - 21508012 AU - Mills, H. L. AU - Cohen, T. AU - Colijn, C. DA - Oct 7 DO - rsif.2011.0160 [pii] 10.1098/rsif.2011.0160 [doi] DP - Nlm ET - 04/22 KW - Africa South of the Sahara/epidemiology Antitubercular Agents/administration & dosage/therapeutic use Computer Simulation Contact Tracing/ methods Endemic Diseases HIV Infections/ complications/epidemiology Humans Isoniazid/ administration & dosage/ therapeutic use Models, Biological Time Factors Tuberculosis/epidemiology/ prevention & control LA - eng N1 - Mills, H L Cohen, T Colijn, C DP2 OD006663-01/OD/NIH HHS/United States U54 GM088558-01/GM/NIGMS NIH HHS/United States England Journal of the Royal Society, Interface / the Royal Society J R Soc Interface. 2011 Oct 7;8(63):1510-20. Epub 2011 Apr 20. PY - 2011 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1742-5662 (Electronic) 1742-5662 (Linking) SP - 1510-20 ST - Modelling the performance of isoniazid preventive therapy for reducing tuberculosis in HIV endemic settings: the effects of network structure T2 - J R Soc Interface TI - Modelling the performance of isoniazid preventive therapy for reducing tuberculosis in HIV endemic settings: the effects of network structure UR - http://rsif.royalsocietypublishing.org.ez.lshtm.ac.uk/content/8/63/1510.full.pdf VL - 8 ID - 2639 ER - TY - JOUR AB - Mathematical models have facilitated our understanding of infectious diseases dynamics and proved useful tools to compare control scenarios when interventional studies are not feasible or ethical. Here, we summarize evidence linking social, economic and biologic determinants to tuberculosis (TB) and review modeling approaches that have been used to understand their contribution to the epidemic dynamics of TB. Specifically, we find evidence for associations between smoking, indoor air pollution, diabetes mellitus, alcohol, nutritional status, crowding, migration, aging and economic trends, and the occurrence of TB infection and/or disease. We outline some methodological problems inherent to the study of these associations; these include study design issues, reverse causality and misclassification of both exposure and outcomes. We then go on to review two existing approaches to modeling the impact of determinants and the effect of interventions: the population attributable fraction model, which estimates the proportion of the TB burden that would be averted if exposure to a risk factor were eliminated from the population, and deterministic epidemic models that capture transmission dynamics and the indirect effects of interventions. We conclude by defining research priorities in both the study of specific determinants and the development of appropriate models to assess the impact of addressing these determinants. AD - Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. mmurray@hsph.harvard.edu AN - 21740661 AU - Murray, M. AU - Oxlade, O. AU - Lin, H. H. DA - Jun DO - 10.5588/ijtld.10.0535 ET - 07/16 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - *Environment Epidemiologic Research Design Humans *Models, Theoretical Population Surveillance Risk Assessment Risk Factors *Socioeconomic Factors Tuberculosis/*epidemiology/transmission LA - eng M3 - Review N1 - Murray, M Oxlade, O Lin, H-H France Int J Tuberc Lung Dis. 2011 Jun;15 Suppl 2:S64-70. PY - 2011 RN - fulltext fulltext_1208 SN - 1815-7920 (Electronic) 1027-3719 (Linking) SP - S64-70 ST - Modeling social, environmental and biological determinants of tuberculosis T2 - Int J Tuberc Lung Dis TI - Modeling social, environmental and biological determinants of tuberculosis UR - http://www.ncbi.nlm.nih.gov/pubmed/21740661 VL - 15 Suppl 2 ID - 2640 ER - TY - JOUR AB - This article seeks to elucidate effects of early-life influences on later-life tuberculosis outcomes using a dynamic computer simulation model. To illustrate the value of such a model, three research questions are considered: 1) If we implemented an intervention capable of reducing infection rates to varying degrees, what would the impact be on tuberculosis prevalence by age? 2) If there were a temporary increase in the rate of infection, what would the impact be on tuberculosis outcomes for the population? 3) If a fixed number of recently infected individuals were targeted for prophylactic treatment, who should be chosen to maximize impact?. AD - Univ Saskatchewan, Dept Comp Sci, Coll Arts & Sci, Saskatoon, SK S7H 5C9, Canada Univ Saskatchewan, Toronto, ON, Canada Wellesley Inst, Toronto, ON, Canada Univ N Carolina, Chapel Hill, NC 27515 USA Saskatchewan TB Control, Saskatoon, SK, Canada AN - WOS:000287704500002 AU - Osgood, N. D. AU - Mahamoud, A. AU - Lich, K. H. AU - Tian, Y. A. AU - Al-Azem, A. AU - Hoeppner, V. H. DO - Pii 933916938 10.1080/15427609.2011.549692 IS - 1 J2 - Res Hum Dev KW - exogenous reinfection british adults health epidemiology childhood dynamics diseases models risks LA - English N1 - 726fk Times Cited:6 Cited References Count:34 PY - 2011 SN - 1542-7609 SP - 26-47 ST - Estimating the Relative Impact of Early-Life Infection Exposure on Later-Life Tuberculosis Outcomes in a Canadian Sample T2 - Research in Human Development TI - Estimating the Relative Impact of Early-Life Infection Exposure on Later-Life Tuberculosis Outcomes in a Canadian Sample UR - ://WOS:000287704500002 VL - 8 ID - 4877 ER - TY - JOUR AB - Background. Simulation models are useful in policy planning for tuberculosis (TB) control. To accurately assess interventions, important modifiers of the epidemic should be accounted for in evaluative models. Improvements in population health were associated with the declining TB epidemic in the pre–antibiotic era and may be relevant today. The objective of this study was to develop and validate a TB transmission model that accounted for changes in population health. Methods. We developed a deterministic TB transmission model, using reported data from the pre–antibiotic era in England. Change in adjusted life expectancy, used as a proxy for general health, was used to determine the rate of change of key epidemiological parameters. Predicted outcomes included risk of TB infection and TB mortality. The model was validated in the setting of the Netherlands and then applied to modern Peru. Results. The model, developed in the setting of England, predicted TB trends in the Netherlands very accurately. The R2 value for correlation between observed and predicted data was 0.97 and 0.95 for TB infection and mortality, respectively. In Peru, the predicted decline in incidence prior to the expansion of “Directly Observed Treatment Short Course” (The DOTS strategy) was 3.7% per year (observed = 3.9% per year). After DOTS expansion, the predicted decline was very similar to the observed decline of 5.8% per year. Conclusions. We successfully developed and validated a TB model, which uses a proxy for population health to estimate changes in key epidemiology parameters. Population health contributed significantly to improvement in TB outcomes observed in Peru. Changing population health should be incorporated into evaluative models for global TB control. AU - Oxlade, Olivia AU - Schwartzman, Kevin AU - Benedetti, Andrea AU - Pai, Madhukar AU - Heymann, Jody AU - Menzies, Dick DA - January/February 2011 DO - 10.1177/0272989x10369001 PY - 2011 RN - fulltext fulltext_1208 SP - 53-68 ST - Developing a Tuberculosis Transmission Model That Accounts for Changes in Population Health T2 - Medical Decision Making TI - Developing a Tuberculosis Transmission Model That Accounts for Changes in Population Health UR - http://mdm.sagepub.com/content/31/1/53.abstracthttp://mdm.sagepub.com/content/31/1/53 VL - 31 ID - 2642 ER - TY - JOUR AB - Continuous differential equations are often applied to small populations with little time spent on understanding uncertainty brought about by small-population effects. Despite large numbers of individuals being latently infected with Mycobacterium tuberculosis (TB), progression from latent infection to observable disease is a relatively rare event. For small communities, this means case counts are subject to stochasticity, and deterministic models may not be appropriate tools for interpreting transmission trends. Furthermore, the nonlinear nature of the underlying dynamics means that fluctuations are autocorrelated, which can invalidate standard statistical analyses which assume independent fluctuations. Here we extend recent work using a system of differential equations to study the HIV-TB epidemic in Masiphumelele, a community near Cape Town in South Africa [Bacaer, et al., J. Mol. Biol. 57(4), 557-593] by studying the statistical properties of active TB events. We apply van Kampen's system-size (or population-size) expansion technique to obtain an approximation to a master equation describing the dynamics. We use the resulting Fokker-Planck equation and point-process theory to derive two-time correlation functions for active TB events. This method can be used to gain insight into the temporal aspect of cluster identification, which currently relies on DNA classification only. AD - SACEMA, c/o StIAS, DST/NRF Centre of Excellence in Epidemiological Modelling and Analysis, Stellenbosch University, 19 Jonkershoek Road, Stellenbosch 7600, South Africa. c.d.pretorius@gmail.com AN - 21056044 AU - Pretorius, C. AU - Dodd, P. AU - Wood, R. DA - Feb 7 DO - S0022-5193(10)00540-0 [pii] 10.1016/j.jtbi.2010.10.012 [doi] DP - Nlm ET - 2010/11/09 IS - 1 KW - Adolescent Adult Algorithms Cluster Analysis Computer Simulation HIV Infections/complications/ epidemiology Humans Latent Tuberculosis/complications/epidemiology Middle Aged Models, Biological Mycobacterium tuberculosis/genetics/isolation & purification Prevalence Residence Characteristics South Africa/epidemiology Stochastic Processes Tuberculosis/complications/ epidemiology/etiology Young Adult LA - eng N1 - Pretorius, Carel Dodd, Peter Wood, Robin England Journal of theoretical biology J Theor Biol. 2011 Feb 7;270(1):154-63. Epub 2010 Nov 4. PY - 2011 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1095-8541 (Electronic) 0022-5193 (Linking) SP - 154-63 ST - An investigation into the statistical properties of TB episodes in a South African community with high HIV prevalence T2 - J Theor Biol TI - An investigation into the statistical properties of TB episodes in a South African community with high HIV prevalence UR - http://ac.els-cdn.com/S0022519310005400/1-s2.0-S0022519310005400-main.pdf?_tid=4f17a03c8b15a53d6201c197ce418733&acdnat=1345013076_15964e48c8e46e9653029eaf2e692bf1 VL - 270 ID - 4474 ER - TY - JOUR AB - Over the past decade, numerous studies have identified tuberculosis patients in whom more than one distinct strain of Mycobacterium tuberculosis is present. While it has been shown that these mixed strain infections can reduce the probability of treatment success for individuals simultaneously harboring both drug-sensitive and drug-resistant strains, it is not yet known if and how this phenomenon impacts the long-term dynamics for tuberculosis within communities. Strain-specific differences in immunogenicity and associations with drug resistance suggest that a better understanding of how strains compete within hosts will be necessary to project the effects of mixed strain infections on the future burden of drug-sensitive and drug-resistant tuberculosis. In this paper, we develop a modeling framework that allows us to investigate mechanisms of strain competition within hosts and to assess the long-term effects of such competition on the ecology of strains in a population. These models permit us to systematically evaluate the importance of unknown parameters and to suggest priority areas for future experimental research. Despite the current scarcity of data to inform the values of several model parameters, we are able to draw important qualitative conclusions from this work. We find that mixed strain infections may promote the coexistence of drug-sensitive and drug-resistant strains in two ways. First, mixed strain infections allow a strain with a lower basic reproductive number to persist in a population where it would otherwise be outcompeted if has competitive advantages within a co-infected host. Second, some individuals progressing to phenotypically drug-sensitive tuberculosis from a state of mixed drug-sensitive and drug-resistant infection may retain small subpopulations of drug-resistant bacteria that can flourish once the host is treated with antibiotics. We propose that these types of mixed infections, by increasing the ability of low fitness drug-resistant strains to persist, may provide opportunities for compensatory mutations to accumulate and for relatively fit, highly drug-resistant strains of M. tuberculosis to emerge. AD - Division of Global Health Equity, Brigham and Women's Hospital, 641 Huntington Ave, 02115 Boston, MA, USA. rsergeev@partners.org AN - 21514304 AU - Sergeev, R. AU - Colijn, C. AU - Cohen, T. DA - Jul 7 DO - S0022-5193(11)00201-3 [pii] 10.1016/j.jtbi.2011.04.011 [doi] DP - Nlm ET - 04/26 KW - Anti-Bacterial Agents/therapeutic use Drug Resistance, Bacterial/drug effects/ immunology Humans Models, Theoretical Mutation Mycobacterium tuberculosis/genetics/ immunology Species Specificity Tuberculosis/drug therapy/ epidemiology/genetics/ immunology L1 - internal-pdf://1315802482/Sergeev-2011-Models to understand the populati.pdf LA - eng N1 - Sergeev, Rinat Colijn, Caroline Cohen, Ted DP2 OD006663-01/OD/NIH HHS/United States DP2OD006663/OD/NIH HHS/United States U54 GM088558-01/GM/NIGMS NIH HHS/United States U54GM088558/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural England Journal of theoretical biology Nihms290299 J Theor Biol. 2011 Jul 7;280(1):88-100. Epub 2011 Apr 16. PY - 2011 RN - fulltext fulltext_1208 SN - 1095-8541 (Electronic) 0022-5193 (Linking) SP - 88-100 ST - Models to understand the population-level impact of mixed strain M. tuberculosis infections T2 - J Theor Biol TI - Models to understand the population-level impact of mixed strain M. tuberculosis infections UR - http://ac.els-cdn.com/S0022519311002013/1-s2.0-S0022519311002013-main.pdf?_tid=7405d287e36e3e8cfc4ef3bd852a7036&acdnat=1345013619_4d9c2e52fd4fdd0ba38795899948628b https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111980/pdf/nihms290299.pdf VL - 280 ID - 2645 ER - TY - JOUR AB - BACKGROUND: It is believed that nonadherence is the proximate cause of multidrug-resistant tuberculosis (MDR-tuberculosis) emergence. The level of nonadherence associated with emergence of MDR-tuberculosis is unknown. Performance of a randomized controlled trial in which some patients are randomized to nonadherence would be unethical; therefore, other study designs should be utilized. METHODS: We performed hollow fiber studies for both bactericidal and sterilizing effect, with inoculum spiked with 0.5% rifampin- and isoniazid-resistant isogenic strains in some experiments. Standard therapy was administered daily for 28-56 days, with extents of nonadherence varying between 0% and 100%. Sizes of drug-resistant populations were compared using analysis of variance. We also explored the effect of pharmacokinetic variability on MDR-tuberculosis emergence using computer-aided clinical trial simulations of 10 000 Cape Town, South Africa, tuberculosis patients. RESULTS: Therapy failure was only encountered at extents of nonadherence >/=60%. Surprisingly, isoniazid- and rifampin-resistant populations did not achieve >/=1% proportion in any experiment and did not achieve a higher proportion with nonadherence. However, clinical trial simulations demonstrated that approximately 1% of tuberculosis patients with perfect adherence would still develop MDR-tuberculosis due to pharmacokinetic variability alone. CONCLUSIONS: These data, based on a preclinical model, demonstrate that nonadherence alone is not a sufficient condition for MDR-tuberculosis emergence. AD - Department of Medicine, University of Texas Southwestern Medical Center at Dallas, TX, USA. AN - 22021624 AU - Srivastava, S. AU - Pasipanodya, J. G. AU - Meek, C. AU - Leff, R. AU - Gumbo, T. DA - Dec 15 DO - jir658 [pii] 10.1093/infdis/jir658 [doi] DP - Nlm ET - 10/25 KW - Antitubercular Agents/ administration & dosage/ pharmacokinetics/pharmacology Computer Simulation Drug Resistance, Multiple, Bacterial Humans Isoniazid/administration & dosage/pharmacology Medication Adherence Models, Biological Monte Carlo Method Mycobacterium tuberculosis/ drug effects Pyrazinamide/administration & dosage/pharmacology Rifampin/administration & dosage/pharmacology Tuberculosis, Multidrug-Resistant/ drug therapy L1 - internal-pdf://1742794991/Srivastava-2011-Multidrug-resistant tuberculos.pdf LA - eng N1 - Srivastava, Shashikant Pasipanodya, Jotam G Meek, Claudia Leff, Richard Gumbo, Tawanda R01AI079497/AI/NIAID NIH HHS/United States Research Support, N.I.H., Extramural United States The Journal of infectious diseases J Infect Dis. 2011 Dec 15;204(12):1951-9. Epub 2011 Oct 21. PY - 2011 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1537-6613 (Electronic) 0022-1899 (Linking) SP - 1951-9 ST - Multidrug-resistant tuberculosis not due to noncompliance but to between-patient pharmacokinetic variability T2 - J Infect Dis TI - Multidrug-resistant tuberculosis not due to noncompliance but to between-patient pharmacokinetic variability UR - http://jid.oxfordjournals.org/content/204/12/1951.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209814/pdf/jir658.pdf VL - 204 ID - 2646 ER - TY - JOUR AB - For a two-patch transmission of tuberculosis (TB), the disease-free equilibrium and the basic reproduction rate R-0 are computed. The disease-free equilibrium is globally asymptotically stable when the basic reproduction rate is less than one. The model can have one or more endemic equilibria. The increased progression rate from latent to active TB in one population may play a significant role in the rising prevalence of TB in the other population. The increased migration from the first to the second population increases the prevalence level of TB in the second population and decreases the TB prevalence in the first population. AD - Univ Douala, Fac Sci, Douala, Cameroon Univ Yaounde 1, Natl Adv Sch Engn, Yaounde, Cameroon Univ Yaounde 1, Fac Sci, Yaounde, Cameroon Postdam Inst Climate Impact Res PIK, Potsdam, Germany Humboldt Univ, Berlin, Germany GRIMCAPE Yaounde, UMMISCO Yaounde, UMI IRD 209, Yaounde, Cameroon AN - WOS:000299684300003 AU - Tewa, J. J. AU - Bowong, S. AU - Mewoli, B. AU - Kurths, J. DO - 10.1080/08898480.2011.596757 IS - 3 J2 - Math Popul Stud KW - epidemiology lyapunov functions patches stability tuberculosis dynamics models LA - English N1 - 884de Times Cited:6 Cited References Count:15 PY - 2011 SN - 0889-8480 SP - 189-205 ST - Two-Patch Transmission of Tuberculosis T2 - Mathematical Population Studies TI - Two-Patch Transmission of Tuberculosis UR - ://WOS:000299684300003 VL - 18 ID - 4879 ER - TY - JOUR AB - Despite great efforts to control the spread of tuberculosis (TB), the disease remains stubbornly persistent, having infected one third of the world population, and causing more than 1.5 million deaths annually. To better understand the epidemiology of TB, past modeling efforts have sought to understand how TB prevention and control policies affect infection spread in the population. This paper describes a preliminary dynamic model to evaluate the role of current contact tracing policies in managing TB transmission. Through a novel representation of contact tracing dynamics, the model supports investigation of how TB outcomes are affected by changes to the breadth and timeliness of contact investigation. Model results suggest that while successful contact tracing is self-limiting, it plays a critical role in TB control. Results also suggest that expanded breadth of contact tracing offers diminishing returns, and underscores the desirability of highly targeted contact tracing and the desirability of richer models. AD - Univ Saskatchewan, 1437 Coll Dr, Saskatoon, SK S7N 0W0, Canada AN - WOS:000300520801060 AU - Tian, Y. AU - Alawami, F. AU - Al-Azem, A. AU - Osgood, N. AU - Hoeppner, V. AU - Dutchyn, C. J2 - Wint Simul C Proc KW - infection disease impact LA - English N1 - Byu80 Times Cited:2 Cited References Count:15 Winter Simulation Conference Proceedings PY - 2011 SN - 0891-7736 SP - 1362-1373 ST - A System Dynamics Model of Tuberculosis Diffusion with Respect to Contact Tracing Investigation T2 - Proceedings of the 2011 Winter Simulation Conference (Wsc) TI - A System Dynamics Model of Tuberculosis Diffusion with Respect to Contact Tracing Investigation UR - ://WOS:000300520801060 ID - 4881 ER - TY - JOUR AB - BACKGROUND: The development of a successful new tuberculosis (TB) vaccine would circumvent many limitations of current diagnostic and treatment practices. However, vaccine development is complex and costly. We aimed to assess the potential cost effectiveness of novel vaccines for TB control in a sub-Saharan African country--Zambia--relative to the existing strategy of directly observed treatment, short course (DOTS) and current level of bacille Calmette-Guerin (BCG) vaccination coverage. METHODS: We conducted a decision analysis model-based simulation from the societal perspective, with a 3% discount rate and all costs expressed in 2007 US dollars. Health outcomes and costs were projected over a 30-year period, for persons born in Zambia (population 11,478,000 in 2005) in year 1. Initial development costs for single vaccination and prime-boost strategies were prorated to the Zambian share (0.398%) of global BCG vaccine coverage for newborns. Main outcome measures were TB-related morbidity, mortality, and costs over a range of potential scenarios for vaccine efficacy. RESULTS: Relative to the status quo strategy, a BCG replacement vaccine administered at birth, with 70% efficacy in preventing rapid progression to TB disease after initial infection, is estimated to avert 932 TB cases and 422 TB-related deaths (prevention of 199 cases/100,000 vaccinated, and 90 deaths/100,000 vaccinated). This would result in estimated net savings of $3.6 million over 30 years for 468,073 Zambians born in year 1 of the simulation. The addition of a booster at age 10 results in estimated savings of $5.6 million compared to the status quo, averting 1,863 TB cases and 1,011 TB-related deaths (prevention of 398 cases/100,000 vaccinated, and of 216 deaths/100,000 vaccinated). With vaccination at birth alone, net savings would be realized within 1 year, whereas the prime-boost strategy would require an additional 5 years to realize savings, reflecting a greater initial development cost. CONCLUSIONS: Investment in an improved TB vaccine is predicted to result in considerable cost savings, as well as a reduction in TB morbidity and TB-related mortality, when added to existing control strategies. For a vaccine with waning efficacy, a prime-boost strategy is more cost-effective in the long term. AD - Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, Montreal, Canada. AN - 21269503 AU - Tseng, C. L. AU - Oxlade, O. AU - Menzies, D. AU - Aspler, A. AU - Schwartzman, K. DO - 10.1186/1471-2458-11-55 ET - 01/29 J2 - BMC public health KW - Adolescent Adult BCG Vaccine/economics/therapeutic use Child Child, Preschool Communicable Disease Control/*economics Cost of Illness Cost-Benefit Analysis Decision Support Techniques Directly Observed Therapy Health Care Costs/statistics & numerical data Health Expenditures/statistics & numerical data Humans Infant Infant, Newborn Mycobacterium tuberculosis/drug effects Tuberculosis/economics/*prevention & control Tuberculosis Vaccines/economics/*therapeutic use Young Adult Zambia LA - eng M3 - Research Support, Non-U.S. Gov't N1 - Tseng, Chia-Lin Oxlade, Olivia Menzies, Dick Aspler, Anne Schwartzman, Kevin Canadian Institutes of Health Research/Canada England BMC Public Health. 2011 Jan 26;11:55. PY - 2011 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1471-2458 (Electronic) 1471-2458 (Linking) SP - 55 ST - Cost-effectiveness of novel vaccines for tuberculosis control: a decision analysis study T2 - BMC Public Health TI - Cost-effectiveness of novel vaccines for tuberculosis control: a decision analysis study UR - http://www.ncbi.nlm.nih.gov/pubmed/21269503http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039588/pdf/1471-2458-11-55.pdf VL - 11 ID - 2647 ER - TY - JOUR AB - BACKGROUND: Despite consistently meeting international performance targets for tuberculosis case detection and treatment success, areas where tuberculosis is hyperendemic fail to achieve the predicted epidemiological impact. In this article, we explore the anomalous relationship between defined performance targets and actual reduction in tuberculosis transmission. METHODS: In areas where tuberculosis is endemic, poorly ventilated social gathering places such as shebeens (informal alcohol drinking places), minibus taxis, and clinic waiting rooms are all potential transmission hot spots. We modeled the transmission reduction achieved by removal of infectious persons in settings with different tuberculosis prevalence rates to demonstrate the concept of transmission elasticity. We then applied this concept to real-life data from a hyperendemic community in Cape Town, South Africa. RESULTS: In a hyperendemic area, reducing the number of infectious people by a given percentage results in a smaller percentage decrease in the annual risk of infection (ARI) compared with a nonendemic area; for example, removing 10% of infectious persons could result in as little as a 5% reduction in the ARI. With use of real-life data and removal of 60% of infectious individuals with tuberculosis, as would be achieved by meeting current performance targets of 70% case detection and 85% cure, the estimated ARI reduction is 50%. CONCLUSIONS: The relationship between the number of infectious people removed and the decrease in ARI is nonlinear. The concept of transmission elasticity has important implications for the formulation of universal performance targets, since hyperendemic areas would require more stringent targets to achieve comparable transmission reduction. AD - Department of Science and Technology/National Research Foundations Centre of Excellence in Epidemiological Modeling and Analysis, Westmead, Australia. AN - 21628479 AU - Uys, P. AU - Marais, B. J. AU - Johnstone-Robertson, S. AU - Hargrove, J. AU - Wood, R. DA - Jun 15 DO - cir229 [pii] 10.1093/cid/cir229 [doi] DP - Nlm ET - 06/02 KW - Disease Transmission, Infectious Endemic Diseases Humans Models, Statistical Prevalence South Africa/epidemiology Tuberculosis/diagnosis/drug therapy/ epidemiology/ transmission LA - eng N1 - Uys, Pieter Marais, Ben J Johnstone-Robertson, Simon Hargrove, John Wood, Robin United States Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Clin Infect Dis. 2011 Jun 15;52(12):1399-404. PY - 2011 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1537-6591 (Electronic) 1058-4838 (Linking) SP - 1399-404 ST - Transmission elasticity in communities hyperendemic for tuberculosis T2 - Clin Infect Dis TI - Transmission elasticity in communities hyperendemic for tuberculosis UR - http://cid.oxfordjournals.org/content/52/12/1399.full.pdf VL - 52 ID - 2648 ER - TY - JOUR AB - BACKGROUND: Xpert MTB/RIF (Xpert) is a promising new rapid diagnostic technology for tuberculosis (TB) that has characteristics that suggest large-scale roll-out. However, because the test is expensive, there are concerns among TB program managers and policy makers regarding its affordability for low- and middle-income settings. METHODS AND FINDINGS: We estimate the impact of the introduction of Xpert on the costs and cost-effectiveness of TB care using decision analytic modelling, comparing the introduction of Xpert to a base case of smear microscopy and clinical diagnosis in India, South Africa, and Uganda. The introduction of Xpert increases TB case finding in all three settings; from 72%-85% to 95%-99% of the cohort of individuals with suspected TB, compared to the base case. Diagnostic costs (including the costs of testing all individuals with suspected TB) also increase: from US$28-US$49 to US$133-US$146 and US$137-US$151 per TB case detected when Xpert is used "in addition to" and "as a replacement of" smear microscopy, respectively. The incremental cost effectiveness ratios (ICERs) for using Xpert "in addition to" smear microscopy, compared to the base case, range from US$41-$110 per disability adjusted life year (DALY) averted. Likewise the ICERS for using Xpert "as a replacement of" smear microscopy range from US$52-$138 per DALY averted. These ICERs are below the World Health Organization (WHO) willingness to pay threshold. CONCLUSIONS: Our results suggest that Xpert is a cost-effective method of TB diagnosis, compared to a base case of smear microscopy and clinical diagnosis of smear-negative TB in low- and middle-income settings where, with its ability to substantially increase case finding, it has important potential for improving TB diagnosis and control. The extent of cost-effectiveness gain to TB programmes from deploying Xpert is primarily dependent on current TB diagnostic practices. Further work is required during scale-up to validate these findings. AD - Department of Global Health, Amsterdam Institute of Global Health and Development, Academic Medical Center, Amsterdam, The Netherlands. AN - 22087078 AU - Vassall, A. AU - van Kampen, S. AU - Sohn, H. AU - Michael, J. S. AU - John, K. R. AU - den Boon, S. AU - Davis, J. L. AU - Whitelaw, A. AU - Nicol, M. P. AU - Gler, M. T. AU - Khaliqov, A. AU - Zamudio, C. AU - Perkins, M. D. AU - Boehme, C. C. AU - Cobelens, F. DA - Nov DO - 10.1371/journal.pmed.1001120 [doi] PMEDICINE-D-11-00805 [pii] DP - Nlm ET - 11/17 KW - Clinical Laboratory Techniques/ economics/methods Cohort Studies Cost-Benefit Analysis Humans India South Africa Tuberculosis, Pulmonary/ diagnosis/economics Uganda LA - eng N1 - Vassall, Anna van Kampen, Sanne Sohn, Hojoon Michael, Joy S John, K R den Boon, Saskia Davis, J Lucian Whitelaw, Andrew Nicol, Mark P Gler, Maria Tarcela Khaliqov, Anar Zamudio, Carlos Perkins, Mark D Boehme, Catharina C Cobelens, Frank Research Support, Non-U.S. Gov't United States PLoS medicine PLoS Med. 2011 Nov;8(11):e1001120. Epub 2011 Nov 8. PY - 2011 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1549-1676 (Electronic) 1549-1277 (Linking) SP - e1001120 ST - Rapid diagnosis of tuberculosis with the Xpert MTB/RIF assay in high burden countries: a cost-effectiveness analysis T2 - PLoS Med TI - Rapid diagnosis of tuberculosis with the Xpert MTB/RIF assay in high burden countries: a cost-effectiveness analysis UR - http://www.plosmedicine.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.1001120&representation=PDF VL - 8 ID - 2649 ER - TY - JOUR AB - We have developed a dynamic model for tuberculosis (TB) transmission in South Korea using a SEIR model with the time-dependent parameters. South Korea ranked the highest TB incidence among members of the Organization for Economic Cooperation and Development (OECD) in 2005 yr. The observed data from the Korea Center for Disease Control and Prevention (KCDC) shows a certain rise of active-TB incidence individuals after 2001 yr. Because of this sudden jump, we have considered two different periods for best fitting the model: prior to 2001 yr and posterior to 2001 yr. The least-squares fitting has been used for estimating model parameters to the observed data of active-TB incidence. Our model agrees well with the observed data. In this work, we also propose optimal treatment strategies of TB model in South Korea for the future. We have considered three control mechanisms representing distancing, case finding and case holding efforts. Optimal control programs have been proposed in various scenarios, in order to minimize the number of exposed and infectious individuals and the cost of implementing the control treatment. AD - Department of Mathematics, Ajou University, San 5, Woncheon-dong, Yeongtong-gu, Suwon, Kyungki-do 443-749, Republic of Korea. AN - 21439972 AU - Whang, S. AU - Choi, S. AU - Jung, E. DA - Jun 21 DO - S0022-5193(11)00149-4 [pii] 10.1016/j.jtbi.2011.03.009 [doi] DP - Nlm ET - 03/29 KW - Basic Reproduction Number Humans Incidence Life Expectancy Models, Biological Numerical Analysis, Computer-Assisted Population Dynamics Republic of Korea/epidemiology Time Factors Treatment Outcome Tuberculosis/epidemiology/ therapy/ transmission LA - eng N1 - Whang, Sungim Choi, Sunhwa Jung, Eunok Research Support, Non-U.S. Gov't England Journal of theoretical biology J Theor Biol. 2011 Jun 21;279(1):120-31. Epub 2011 Mar 30. PY - 2011 RN - fulltext fulltext_1208 SN - 1095-8541 (Electronic) 0022-5193 (Linking) SP - 120-31 ST - A dynamic model for tuberculosis transmission and optimal treatment strategies in South Korea T2 - J Theor Biol TI - A dynamic model for tuberculosis transmission and optimal treatment strategies in South Korea UR - http://ac.els-cdn.com/S0022519311001494/1-s2.0-S0022519311001494-main.pdf?_tid=2b58d8746001b36810a0dec94e9467ad&acdnat=1345013756_f141f171ce9ad067a44211f05f4555d3 VL - 279 ID - 2650 ER - TY - JOUR AB - This paper deals with the dynamic behaviors of a tuberculosis (TB) model with disease-related death rate. The stability of the system is discussed by stability theory. The conditions of existence for transcritical bifurcation and Saddle-Node bifurcation are derived by using bifurcation theory. Finally, the numerical verifications of analytic results are done. AD - Liaoning Shihua Univ, Sch Sci, Fushun 113001, Peoples R China AN - WOS:000323234701126 AU - Yi, N. AU - Liu, P. J2 - Chin Cont Decis Conf KW - epidemic model tuberculosis stability bifurcations LA - English N1 - Bgj71 Times Cited:0 Cited References Count:10 Chinese Control and Decision Conference PY - 2011 SN - 1948-9439 SP - 2104-2107 ST - The Analysis of Stability and Bifurcations for a Tuberculosis Model T2 - 2011 Chinese Control and Decision Conference, Vols 1-6 TI - The Analysis of Stability and Bifurcations for a Tuberculosis Model UR - ://WOS:000323234701126 ID - 4882 ER - TY - JOUR AB - Variable numbers of tandem repeats (VNTR) typing is widely used for studying the bacterial cause of tuberculosis. Knowledge of the rate of mutation of VNTR loci facilitates the study of the evolution and epidemiology of Mycobacterium tuberculosis. Previous studies have applied population genetic models to estimate the mutation rate, leading to estimates varying widely from around [Formula: see text] to [Formula: see text] per locus per year. Resolving this issue using more detailed models and statistical methods would lead to improved inference in the molecular epidemiology of tuberculosis. Here, we use a model-based approach that incorporates two alternative forms of a stepwise mutation process for VNTR evolution within an epidemiological model of disease transmission. Using this model in a Bayesian framework we estimate the mutation rate of VNTR in M. tuberculosis from four published data sets of VNTR profiles from Albania, Iran, Morocco and Venezuela. In the first variant, the mutation rate increases linearly with respect to repeat numbers (linear model); in the second, the mutation rate is constant across repeat numbers (constant model). We find that under the constant model, the mean mutation rate per locus is [Formula: see text] (95% CI: [Formula: see text],[Formula: see text])and under the linear model, the mean mutation rate per locus per repeat unit is [Formula: see text] (95% CI: [Formula: see text],[Formula: see text]). These new estimates represent a high rate of mutation at VNTR loci compared to previous estimates. To compare the two models we use posterior predictive checks to ascertain which of the two models is better able to reproduce the observed data. From this procedure we find that the linear model performs better than the constant model. The general framework we use allows the possibility of extending the analysis to more complex models in the future. AD - School of Mathematics and Statistics, University of New South Wales, Sydney, New South Wales, Australia. AN - 22761563 AU - Aandahl, R. Z. AU - Reyes, J. F. AU - Sisson, S. A. AU - Tanaka, M. M. DA - Jun DO - 10.1371/journal.pcbi.1002573 [doi] PCOMPBIOL-D-11-01614 [pii] DP - Nlm ET - 07/05 LA - eng N1 - Aandahl, R Zachariah Reyes, Josephine F Sisson, Scott A Tanaka, Mark M United States PLoS computational biology PLoS Comput Biol. 2012 Jun;8(6):e1002573. Epub 2012 Jun 28. PY - 2012 RN - fulltext fulltext_1208 SN - 1553-7358 (Electronic) 1553-734X (Linking) SP - e1002573 ST - A Model-Based Bayesian Estimation of the Rate of Evolution of VNTR Loci in Mycobacterium tuberculosis T2 - PLoS Comput Biol TI - A Model-Based Bayesian Estimation of the Rate of Evolution of VNTR Loci in Mycobacterium tuberculosis UR - http://www.ploscompbiol.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pcbi.1002573&representation=PDF VL - 8 ID - 2651 ER - TY - JOUR AB - Background: In sub-Saharan Africa, patients with advanced HIV experience high mortality during the first few months of antiretroviral therapy (ART), largely attributable to tuberculosis (TB). We evaluated the cost-effectiveness of TB diagnostic strategies to reduce this early mortality. Methods: We developed a decision analytic model to estimate the incremental cost, deaths averted, and cost-effectiveness of 3 TB diagnostic algorithms. The model base case represents current practice (symptoms screening, sputum smear, and chest radiography) in many resource-limited countries in sub-Saharan Africa. We compared the current practice with World Health Organization (WHO)-recommended practice with culture and WHO-recommended practice with the Xpert mycobacterium tuberculosis and resistance to rifampicin test and considered relevant medical costs from a health system perspective using the timeframe of the first 6 months of ART. We conducted univariate and probabilistic sensitivity analyses on all parameters in the model. Results: When considering TB diagnosis and treatment and ART costs, the cost per patient was $850 for current practice, $809 for the algorithm with Xpert test, and $879 for the algorithm with culture. Our results showed that both WHO-recommended algorithms avert more deaths among TB cases than does the current practice. The algorithm with Xpert test was least costly at reducing early mortality compared with the current practice. Sensitivity analyses indicated that cost-effectiveness findings were stable. Conclusions: Our analysis showed that culture or Xpert were cost-effective at reducing early mortality during the first 6 months of ART compared with the current practice. Thus, our findings provide support for ongoing efforts to expand TB diagnostic capacity. AU - Abimbola, Taiwo O. AU - Marston, Barbara J. AU - Date, Anand A. AU - Blandford, John M. AU - Sangrujee, Nalinee AU - Wiktor, Stefan Z. KW - HIV tuberculosis tuberculosis diagnosis cost cost-effectiveness sub-Saharan Africa 00126334-201205010-00016 PY - 2012 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1525-4135 SP - e1-e7 10.1097/QAI.0b013e318246538f ST - Cost-Effectiveness of Tuberculosis Diagnostic Strategies to Reduce Early Mortality Among Persons With Advanced HIV Infection Initiating Antiretroviral Therapy T2 - JAIDS Journal of Acquired Immune Deficiency Syndromes TI - Cost-Effectiveness of Tuberculosis Diagnostic Strategies to Reduce Early Mortality Among Persons With Advanced HIV Infection Initiating Antiretroviral Therapy UR - http://journals.lww.com/jaids/Fulltext/2012/05010/Cost_Effectiveness_of_Tuberculosis_Diagnostic.16.aspxhttp://graphics.tx.ovid.com/ovftpdfs/FPDDNCDCLFEDDD00/fs047/ovft/live/gv024/00126334/00126334-201205010-00016.pdf http://ovidsp.tx.ovid.com/ovftpdfs/FPDDNCDCAHCKLO00/fs047/ovft/live/gv024/00126334/00126334-201205010-00016.pdf VL - 60 ID - 2652 ER - TY - JOUR AB - SETTING: The seasonality of tuberculosis (TB) incidence suggests that the risk of infection or development of disease has a seasonal component.OBJECTIVE: To investigate factors associated with seasonal patterns of TB disease in the Netherlands by splitting notifications according to origin (natives vs. non-natives) and disease site (pulmonary TB [PTB] vs. extra-pulmonary TB [EPTB]). We focus on the presence of a seasonal peak, as much debate has centred on factors enhancing transmission vs. disease development.DESIGN: Monthly notifications were derived from culture sample dates of all cases between 1993 and 2008. We fitted seasonal autoregressive integrated moving average (SARIMA) models to the time series. Seasonal decomposition revealed seasonal trends. To assess the seasonality of the peak, we repeated the analysis omitting December (trough) notifications.RESULTS: TB notifications show a seasonal pattern, with a peak in spring and a trough in winter, which is present in both PTB and EPTB and in both natives and non-natives. However, when excluding December notifications, seasonality only holds in non-native EPTB and non-native TB notifications.CONCLUSION: A seasonal peak in TB notifications (March-June) is apparent in non-natives, but is absent in natives. This peak is driven by the seasonality of EPTB notifications, which are highest in June-July. The contribution of winter crowding is discussed. Vitamin D deficiency, enhancing disease development at the end of winter-early spring, seems the most likely factor explaining the yearly peak in EPTB. AN - 22410705 AU - Altes, H. K. AU - Kremer, K. AU - Erkens, C. AU - van Soolingen, D. AU - Wallinga, J. DO - ijtld110680 [pii] 10.5588/ijtld.11.0680 LA - Eng N1 - Journal article The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Int J Tuberc Lung Dis. 2012 Mar 9. PY - 2012 RN - fulltext fulltext_1208 SN - 1815-7920 (Electronic) 1027-3719 (Linking) ST - Tuberculosis seasonality in the Netherlands differs between natives and non-natives: a role for vitamin D deficiency? T2 - International Journal of Tuberculosis and Lung Disease TI - Tuberculosis seasonality in the Netherlands differs between natives and non-natives: a role for vitamin D deficiency? UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22410705 ID - 2653 ER - TY - JOUR AB - Background: In settings with high tuberculosis (TB) prevalence, 15–30% of HIV-infected individuals initiating antiretroviral therapy (ART) have undiagnosed TB. Such patients are usually screened by symptoms and sputum smear, which have poor sensitivity. Objective: To project the clinical and economic outcomes of using Xpert MTB/RIF(Xpert), a rapid TB/rifampicin-resistance diagnostic, to screen individuals initiating ART. Design: We used a microsimulation model to evaluate the clinical impact and cost-effectiveness of alternative TB screening modalities – in all patients or only symptomatic patients – for hypothetical cohorts of individuals initiating ART in South Africa (mean CD4 cell count = 171 cells/μl; TB prevalence 22%). We simulated no active screening and four diagnostic strategies, smear microscopy (sensitivity 23%); smear and culture (sensitivity, 100%); one Xpert sample (sensitivity in smear-negative TB: 43%); two Xpert samples (sensitivity in smear-negative TB: 62%). Outcomes included projected life expectancy, lifetime costs (2010 US$), and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs less than $7100 (South African gross domestic product per capita) were considered very cost-effective. Results: Compared with no screening, life expectancy in TB-infected patients increased by 1.6 months using smear in symptomatic patients and by 6.6 months with two Xpert samples in all patients. At 22% TB prevalence, the ICER of smear for all patients was $2800 per year of life saved (YLS), and of Xpert (two samples) for all patients was $5100/YLS. Strategies involving one Xpert sample or symptom screening were less efficient. Conclusion: Model-based analysis suggests that screening all individuals initiating ART in South Africa with two Xpert samples is very cost-effective. AU - Andrews, Jason R. AU - Lawn, Stephen D. AU - Rusu, Corina AU - Wood, Robin AU - Noubary, Farzad AU - Bender, Melissa A. AU - Horsburgh, C. Robert AU - Losina, Elena AU - Freedberg, Kenneth A. AU - Walensky, Rochelle P. KW - antiretroviral therapy cost-effectiveness diagnostics HIV tuberculosis 00002030-201205150-00010 L1 - internal-pdf://0889838638/Andrews-2012-The cost-effectiveness of routine.pdf PY - 2012 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0269-9370 SP - 987-995 10.1097/QAD.0b013e3283522d47 ST - The cost-effectiveness of routine tuberculosis screening with Xpert MTB/RIF prior to initiation of antiretroviral therapy: a model-based analysis T2 - AIDS TI - The cost-effectiveness of routine tuberculosis screening with Xpert MTB/RIF prior to initiation of antiretroviral therapy: a model-based analysis UR - http://journals.lww.com/aidsonline/Fulltext/2012/05150/The_cost_effectiveness_of_routine_tuberculosis.10.aspxhttp://graphics.tx.ovid.com/ovftpdfs/FPDDNCDCLFEDDD00/fs047/ovft/live/gv024/00002030/00002030-201205150-00010.pdf http://ovidsp.tx.ovid.com/ovftpdfs/FPDDNCIBLEEJED00/fs047/ovft/live/gv024/00002030/00002030-201205150-00010.pdf VL - 26 ID - 2654 ER - TY - JOUR AB - Multi-drug therapy is the standard-of-care treatment for tuberculosis. Despite this, virtually all studies of the pharmacodynamics (PD) of mycobacterial drugs employed for the design of treatment protocols are restricted to single agents. In this report, mathematical models and in vitro experiments with Mycobacterium marinum and five antimycobacterial drugs are used to quantitatively evaluate the pharmaco-, population and evolutionary dynamics of two-drug antimicrobial chemotherapy regimes. Time kill experiments with single and pairs of antibiotics are used to estimate the parameters and evaluate the fit of Hill-function-based PD models. While Hill functions provide excellent fits for the PD of each single antibiotic studied, rifampin, amikacin, clarithromycin, streptomycin and moxifloxacin, two-drug Hill functions with a unique interaction parameter cannot account for the PD of any of the 10 pairs of these drugs. If we assume two antibiotic-concentration dependent functions for the interaction parameter, one for sub-MIC and one for supra-MIC drug concentrations, the modified biphasic Hill function provides a reasonably good fit for the PD of all 10 pairs of antibiotics studied. Monte Carlo simulations of antibiotic treatment based on the experimentally-determined PD functions are used to evaluate the potential microbiological efficacy (rate of clearance) and evolutionary consequences (likelihood of generating multi-drug resistance) of these different drug combinations as well as their sensitivity to different forms of non-adherence to therapy. These two-drug treatment simulations predict varying outcomes for the different pairs of antibiotics with respect to the aforementioned measures of efficacy. In summary, Hill functions with biphasic drug-drug interaction terms provide accurate analogs for the PD of pairs of antibiotics and M. marinum. The models, experimental protocols and computer simulations used in this study can be applied to evaluate the potential microbiological and evolutionary efficacy of two-drug therapy for any bactericidal antibiotics and bacteria that can be cultured in vitro. AD - Department of Biology, Emory University, Atlanta, Georgia, United States of America. pankoma@emory.edu AN - 22253599 AU - Ankomah, P. AU - Levin, B. R. DA - Jan DO - 10.1371/journal.ppat.1002487 [doi] PPATHOGENS-D-11-01392 [pii] DP - Nlm ET - 01/19 KW - Amikacin/administration & dosage/pharmacokinetics Anti-Infective Agents/ administration & dosage/pharmacokinetics Clarithromycin/administration & dosage/pharmacokinetics Computer Simulation Dose-Response Relationship, Drug Drug Combinations Drug Interactions/physiology Drug Resistance, Multiple/drug effects/physiology Humans Microbial Sensitivity Tests Models, Biological Models, Theoretical Mycobacterium Infections, Nontuberculous/ drug therapy/metabolism Mycobacterium marinum/ drug effects/growth & development/physiology Rifampin/administration & dosage/pharmacokinetics Tuberculosis/drug therapy/metabolism L1 - internal-pdf://2281433836/Ankomah-2012-Two-drug antimicrobial chemothera.pdf LA - eng N1 - Ankomah, Peter Levin, Bruce R PY - 2012 RN - fulltext fulltext_1208 SN - 1553-7374 (Electronic) 1553-7366 (Linking) SP - e1002487 ST - Two-drug antimicrobial chemotherapy: a mathematical model and experiments with Mycobacterium marinum T2 - PLoS Pathog TI - Two-drug antimicrobial chemotherapy: a mathematical model and experiments with Mycobacterium marinum UR - http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1002487&representation=PDF https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257304/pdf/ppat.1002487.pdf VL - 8 ID - 2655 ER - TY - JOUR AB - ABSTRACT: BACKGROUND: Formulation and evaluation of public health policy commonly employs science-based mathematical models. For instance, epidemiological dynamics of TB is dominated, in general, by flow between actively and latently infected populations. Thus modelling is central in planning public health intervention. However, models are highly uncertain because they are based on observations that are geographically and temporally distinct from the population to which they are applied. AIMS: We aim to demonstrate the advantages of info-gap theory, a non-probabilistic approach to severe uncertainty when worst cases cannot be reliably identified and probability distributions are unreliable or unavailable. Info-gap is applied here to mathematical modelling of epidemics and analysis of public health decision-making. METHODS: Applying info-gap robustness analysis to tuberculosis/HIV (TB/HIV) epidemics, we illustrate the critical role of incorporating uncertainty in formulating recommendations for interventions. Robustness is assessed as the magnitude of uncertainty that can be tolerated by a given intervention. We illustrate the methodology by exploring interventions that alter the rates of diagnosis, cure, relapse and HIV infection. RESULTS: We demonstrate several policy implications. Equivalence among alternative rates of diagnosis and relapse are identified. The impact of initial TB and HIV prevalence on the robustness to uncertainty is quantified. In some configurations, increased aggressiveness of intervention improves the predicted outcome but also reduces the robustness to uncertainty. Similarly, predicted outcomes may be better at larger target times, but may also be more vulnerable to model error. CONCLUSIONS: The info-gap framework is useful for managing model uncertainty and is attractive when uncertainties on model parameters are extreme. When a public health model underlies guidelines, info-gap decision theory provides valuable insight into the confidence of achieving agreed-upon goals. AD - Division of Infectious Diseases, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. nzetola@gmail.com. AN - 23249291 AU - Ben-Haim, Y. AU - Dacso, C. C. AU - Zetola, N. M. DO - 10.1186/1471-2458-12-1091 10.1186/1471-2458-12-1091. DP - Nlm ET - 12/20 J2 - BMC public health LA - eng PY - 2012 SN - 1471-2458 (Electronic) 1471-2458 (Linking) SP - 1091 ST - Info-gap management of public health Policy for TB with HIV-prevalence and epidemiological uncertainty T2 - BMC Public Health TI - Info-gap management of public health Policy for TB with HIV-prevalence and epidemiological uncertainty UR - http://www.biomedcentral.com/1471-2458/12/1091 VL - 12 ID - 2656 ER - TY - JOUR AU - Bhunu, C. P. AU - Mushayabasa, S. AU - Smith, R. J. PY - 2012 SP - 4173–4185 ST - Assessing the effects of poverty in tuberculosis transmission dynamics T2 - Applied Mathematical Modelling TI - Assessing the effects of poverty in tuberculosis transmission dynamics VL - 36 ID - 4792 ER - TY - JOUR AB - A deterministic model of tuberculosis without and with seasonality is designed and analyzed into its transmission dynamics. We first present and analyze a tuberculosis model without seasonality, which incorporates the essential biological and epidemiological features of the disease. The model is shown to exhibit the phenomenon of backward bifurcation, where a stable disease-free equilibrium coexists with one or more stable endemic equilibria when the associated basic reproduction number is less than unity. The statistical data of tuberculosis (TB) cases show seasonal fluctuations in many countries. Then, the extension of our TB model by incorporating seasonality is developed and the basic reproduction ratio is defined. Parameter values of the model are estimated according to demographic and epidemiological data in Cameroon. The simulation results are in good accordance with the seasonal variation of the reported cases of active TB in Cameroon. AD - Univ Douala, Fac Sci, Dept Math & Comp Sci, Lab Appl Math, Douala, Cameroon Postdam Inst Climate Impact Res PIK, D-14412 Potsdam, Germany Humboldt Univ, Dept Phys, D-12489 Berlin, Germany AN - WOS:000299085800028 AU - Bowong, S. AU - Kurths, J. DA - Feb DO - 10.1007/s11071-011-0127-y IS - 3 J2 - Nonlinear Dynam KW - tuberculosis mathematical models backward bifurcation stability seasonal pattern infectious-diseases heterogeneous populations exogenous reinfection backward bifurcation epidemic model systems vaccination hiv LA - English N1 - 876cw Times Cited:10 Cited References Count:59 PY - 2012 SN - 0924-090x SP - 2027-2051 ST - Modeling and analysis of the transmission dynamics of tuberculosis without and with seasonality T2 - Nonlinear Dynamics TI - Modeling and analysis of the transmission dynamics of tuberculosis without and with seasonality UR - ://WOS:000299085800028 VL - 67 ID - 4872 ER - TY - JOUR AB - Although diseases such as influenza, tuberculosis and SARS are transmitted through an environmentally mediated mechanism, most modeling work on these topics is based on the concepts of infectious contact and direct transmission. In this paper we use a paradigm model to show that environmental transmission appears like direct transmission in the case where the pathogen persists little time in the environment. Furthermore, we formulate conditions for the validity of this modeling approximation and we illustrate them numerically for the cases of cholera and influenza. According to our results based on recently published parameter estimates, the direct transmission approximation fails for both cholera and influenza. While environmental transmission is typically chosen over direct transmission in modeling cholera, this is not the case for influenza. AD - Unite d'Epidemiologie des Maladies Emergentes, Institut Pasteur, 75724, Paris, France, romulus.breban@pasteur.fr. AN - 22382994 AU - Breban, R. DA - Mar 1 DO - 10.1007/s00285-012-0520-2 [doi] DP - Nlm ET - 03/03 LA - Eng N1 - Breban, Romulus Journal of mathematical biology J Math Biol. 2012 Mar 1. PY - 2012 RN - fulltext fulltext_1208 SN - 1432-1416 (Electronic) 0303-6812 (Linking) ST - Role of environmental persistence in pathogen transmission: a mathematical modeling approach T2 - J Math Biol TI - Role of environmental persistence in pathogen transmission: a mathematical modeling approach UR - http://www.springerlink.com/content/0665x60018j71243/ ID - 2657 ER - TY - JOUR AB - Age plays an important role in the transmission of some infectious diseases. A discrete SEIT model with age-structure is formulated and studied. The basic reproduction number, R 0 , of the model is defined. It is proved that R 0 = 1 is a threshold to determine the disease extinction or persistence. The disease-free equilibrium is globally stable (unstable) if R 0 < 1 (if R 0 > 1 ). There exists an endemic equilibrium, and the system is uniformly persistent if R 0 > 1 . The numerical simulation demonstrates that the endemic equilibrium may be globally asymptotically stable. The model is applied to describe tuberculosis (TB) transmission in China. The total number of the population, the incidence rate, the prevalent rate and its age structure match the statistical data well. AU - Cao, Hui AU - Zhou, Yicang DO - 10.1016/j.mcm.2011.08.017 KW - The discrete epidemic model Age structure The reproduction number Persistence Tuberculosis PY - 2012 RN - fulltext fulltext_1208 SN - 0895-7177 SP - 385-395 ST - The discrete age-structured SEIT model with application to tuberculosis transmission in China T2 - Mathematical and Computer Modelling TI - The discrete age-structured SEIT model with application to tuberculosis transmission in China UR - http://www.sciencedirect.com/science/article/pii/S0895717711004973http://ac.els-cdn.com/S0895717711004973/1-s2.0-S0895717711004973-main.pdf?_tid=b65602f0816ab609a42cfd7d29e713ae&acdnat=1345012081_5cbd0b42f5c3d8599432f3d0cf273413 VL - 55 ID - 2658 ER - TY - JOUR AB - In this paper, a discrete mathematical model is formulated to describe tuberculosis (TB) progression from latent infection to active disease. The data of national TB epidemiology surveys in China are taken to estimate the TB progression rate for children aged 0-14 years. The progression rate obtained in this paper gives a detailed and better estimate of TB progression rate among children. AD - a Department of Applied Mathematics , Xi'an Jiaotong University , Xi'an , 710049 , People's Republic of China. AN - 22873611 AU - Cao, H. AU - Zhou, Y. AU - Brauer, F. DO - 10.1080/17513758.2012.677483 LA - eng N1 - Cao, Hui Zhou, Yicang Brauer, Fred England Journal of biological dynamics J Biol Dyn. 2012 Mar;6(2):663-73. PY - 2012 RN - fulltext fulltext_1208 SN - 1751-3766 (Electronic) 1751-3758 (Linking) SP - 663-673 ST - Estimates of tuberculosis progression rate of children in China T2 - Journal of Biological Dynamics TI - Estimates of tuberculosis progression rate of children in China UR - http://www.ncbi.nlm.nih.gov/pubmed/22873611http://www.tandfonline.com/doi/pdf/10.1080/17513758.2012.677483 VL - 6 ID - 2659 ER - TY - JOUR AB - Although annual data are commonly used to model linear trends and changes in trends of disease incidence, monthly data could provide additional resolution for statistical inferences. Because monthly data may exhibit seasonal patterns, we need to consider seasonally adjusted models, which can be theoretically complex and computationally intensive. We propose a combination of methods to reduce the complexity of modeling seasonal data and to provide estimates for a change in trend when the timing and magnitude of the change are unknown. To assess potential changes in trend, we first used autoregressive integrated moving average (ARIMA) models to analyze the residuals and forecast errors, followed by multiple ARIMA intervention models to estimate the timing and magnitude of the change. Because the variable corresponding to time of change is not a statistical parameter, its confidence bounds cannot be estimated by intervention models. To model timing of change and its credible interval, we developed a Bayesian technique. We avoided the need for computationally intensive simulations by deriving a closed form for the posterior distribution of the time of change. Using a combination of ARIMA and Bayesian methods, we estimated the timing and magnitude of change in trend for tuberculosis cases in the United States. Published 2012. This article is a US Government work and is in the public domain in the USA. AD - Division of Tuberculosis Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers forDisease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30329, USA. mchen1@cdc.gov AN - 22415632 AU - Chen, M. P. AU - Shang, N. AU - Winston, C. A. AU - Becerra, J. E. DA - Nov 30 DO - 10.1002/sim.5343 10.1002/sim.5343. Epub 2012 Mar 13. DP - Nlm ET - 03/15 J2 - Statistics in medicine LA - eng PY - 2012 SN - 1097-0258 (Electronic) 0277-6715 (Linking) SP - 3278-84 ST - A Bayesian analysis of the 2009 decline in tuberculosis morbidity in the United States T2 - Stat Med TI - A Bayesian analysis of the 2009 decline in tuberculosis morbidity in the United States UR - http://onlinelibrary.wiley.com/store/10.1002/sim.5343/asset/sim5343.pdf?v=1&t=he8t0plh&s=eab7ed2ff636eb614739563026c0fe256575842c VL - 31 ID - 2661 ER - TY - JOUR AB - Days to positivity in automated liquid mycobacterial culture have been shown to correlate with mycobacterial load and have been proposed as a useful biomarker for treatment responses in tuberculosis. However, there is currently no quantitative method or model to analyze the change in days to positivity with time on treatment. The objectives of this study were to describe the decline in numbers of mycobacteria in sputum collected once weekly for 8 weeks from patients on treatment for tuberculosis using days to positivity in liquid culture. One hundred forty-four patients with smear-positive pulmonary tuberculosis were recruited from a tuberculosis clinic in Cape Town, South Africa. A nonlinear mixed-effects repeated-time-to-event modeling approach was used to analyze the time-to-positivity data. A biexponential model described the decline in the estimated number of bacteria in patients' sputum samples, while a logistic model with a lag time described the growth of the bacteria in liquid culture. At baseline, the estimated number of rapidly killed bacteria is typically 41 times higher than that of those that are killed slowly. The time to kill half of the rapidly killed bacteria was about 1.8 days, while it was 39 days for slowly killed bacteria. Patients with lung cavitation had higher bacterial loads than patients without lung cavitation. The model successfully described the increase in days to positivity as treatment progressed, differentiating between bacteria that are killed rapidly and those that are killed slowly. Our model can be used to analyze similar data from studies testing new drug regimens. AD - Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa. AN - 23183433 AU - Chigutsa, E. AU - Patel, K. AU - Denti, P. AU - Visser, M. AU - Maartens, G. AU - Kirkpatrick, C. M. AU - McIlleron, H. AU - Karlsson, M. O. DA - Feb DO - 10.1128/aac.01876-12 10.1128/AAC.01876-12. Epub 2012 Nov 26. DP - Nlm ET - 11/28 J2 - Antimicrobial agents and chemotherapy LA - eng PY - 2012 SN - 1098-6596 (Electronic) 0066-4804 (Linking) SP - 789-95 ST - A time-to-event pharmacodynamic model describing treatment response in patients with pulmonary tuberculosis using days to positivity in automated liquid mycobacterial culture T2 - Antimicrob Agents Chemother TI - A time-to-event pharmacodynamic model describing treatment response in patients with pulmonary tuberculosis using days to positivity in automated liquid mycobacterial culture UR - http://aac.asm.org/content/57/2/789.full.pdf VL - 57 ID - 2695 ER - TY - JOUR AB - The study will apply Lyapunov principle to construct a dynamic model for tuberculosis (TB). The Lyapunov principle is commonly used to examine and determine the stability of a dynamic system. To simulate the transmissions of vector-borne diseases and discuss the related health policies effects on vector-borne diseases, the authors combine the multi-agent-based system, social network and compartmental model to develop an epidemic simulation model. In the identity level, the authors use the multi-agent-based system and the mirror identity concept to describe identities with social network features such as daily visits, long-distance movement, high degree of clustering, low degree of separation and local clustering. The research will analyse the complex dynamic mathematic model of TB epidemic and determine its stability property by using the popular Matlab/Simulink software and relative software packages. Facing the current TB epidemic situation, the development of TB and its developing trend through constructing a dynamic bio-mathematical system model of TB is investigated. After simulating the development of epidemic situation with the solution of the SMIR epidemic model, the authors will come up with a good scheme to control epidemic situation to analyse the parameter values of a model that influence epidemic situation evolved. The authors will try to find the quarantining parameters that are the most important factors to control epidemic situation. The SMIR epidemic model and the results via numerical analysis may offer effective prevention with reference to controlling epidemic situation of TB. AD - Department of Electrical Engineering, National Central University, Jhongli, City Taoyuan County 32001, Taiwan. hychung@ee.ncu.edu.tw AN - 23101874 AU - Chung, H. Y. AU - Chung, C. Y. AU - Ou, S. C. DA - Oct DO - 10.1049/iet-syb.2011.0078 DP - NLM ET - 2012/10/30 IS - 5 J2 - IET systems biology KW - Computer Simulation Disease Outbreaks/*statistics & numerical data Humans *Models, Biological *Models, Statistical *Population Dynamics Prevalence Tuberculosis/*epidemiology/*transmission LA - eng N1 - Chung, H-Y Chung, C-Y Ou, S-C Journal Article Research Support, Non-U.S. Gov't England IET Syst Biol. 2012 Oct;6(5):196-206. doi: 10.1049/iet-syb.2011.0078. PY - 2012 SN - 1751-8849 (Print) 1751-8849 SP - 196-206 ST - Analysis of a bio-dynamic model via Lyapunov principle and small-world network for tuberculosis T2 - IET Syst Biol TI - Analysis of a bio-dynamic model via Lyapunov principle and small-world network for tuberculosis VL - 6 ID - 2940 ER - TY - JOUR AB - OBJECTIVE: To investigate the factors influencing the performance and cost-efficacy of periodic rounds of active case finding (ACF) for TB. METHODS: A mathematical model of TB dynamics and periodic ACF (PACF) in the HIV era, simplified by assuming constant prevalence of latent TB infection, is analyzed for features that control intervention outcome, measured as cases averted and cases found. Explanatory variables include baseline TB incidence, interval between PACF rounds, and different routine and PACF case-detection rates among HIV-infected and uninfected TB cases. FINDINGS: PACF can be cost-saving over a 10 year time frame if the cost-per-round is lower than a threshold proportional to initial incidence and cost-per-case-treated. More cases are averted at higher baseline incidence rates, when more potent PACF strategies are used, intervals between PACF rounds are shorter, and when the ratio of HIV-negative to positive TB cases detected is higher. More costly approaches, e.g. radiographic screening, can be as cost-effective as less costly alternatives if PACF case-detection is higher and/or implementation less frequent. CONCLUSION: Periodic ACF can both improve control and save medium-term health care costs in high TB burden settings. Greater costs of highly effective PACF at frequent (e.g. yearly) intervals may be offset by higher numbers of cases averted in populations with high baseline TB incidence, higher prevalence of HIV-uninfected cases, higher costs per-case-treated, and more effective routine case-detection. Less intensive approaches may still be cost-neutral or cost-saving in populations lacking one or more of these key determinants. AD - London School of Hygiene and Tropical Medicine, London, United Kingdom. peter.dodd@lshtm.ac.uk AN - 22216182 AU - Dodd, P. J. AU - White, R. G. AU - Corbett, E. L. DO - 10.1371/journal.pone.0029130 [doi] PONE-D-11-12349 [pii] DP - Nlm ET - 01/05 KW - HIV Infections/complications Health Care Costs Humans Incidence Models, Theoretical Prevalence Tuberculosis/complications/ diagnosis/epidemiology LA - eng N1 - Dodd, Peter J White, Richard G Corbett, Elizabeth L 091769/Wellcome Trust/United Kingdom G0802414/Medical Research Council/United Kingdom Research Support, Non-U.S. Gov't United States PloS one PLoS One. 2011;6(12):e29130. Epub 2011 Dec 22. PY - 2012 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e29130 ST - Periodic active case finding for TB: when to look? T2 - PLoS One TI - Periodic active case finding for TB: when to look? UR - http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0029130&representation=PDF VL - 6 ID - 2617 ER - TY - JOUR AB - Rationale: Tuberculosis (TB) is characterized by a subclinical phase (symptoms absent or not considered abnormal); prediagnostic phase (symptoms noticed but diagnosis not pursued); and clinical phase (care actively sought). Diagnostic capacity during these phases is limited. Objectives: To estimate the population-level impact of TB case-finding strategies in the presence of subclinical and prediagnostic disease. Methods: We created a mathematical epidemic model of TB, calibrated to global incidence. We then introduced three prototypical diagnostic interventions: increased sensitivity of diagnosis in the clinical phase by 20% ("passive"); early diagnosis during the prediagnostic phase at a rate of 10% per year ("enhanced"); and population-based diagnosis of 5% of undiagnosed prevalent cases per year ("active"). Measurements and Main Results: If the subclinical phase was ignored, as in most models, the passive strategy was projected to reduce TB incidence by 18% (90% uncertainty range [UR], 11-32%) by year 10, compared with 23% (90% UR, 14-35%) for the enhanced strategy and 18% (90% UR, 11-28%) for the active strategy. After incorporating a subclinical phase into the model, consistent with population-based prevalence surveys, the active strategy still reduced 10-year TB incidence by 16% (90% UR, 11-28%), but the passive and enhanced strategies' impact was attenuated to 11% (90% UR, 8-25%) and 6% (90% UR, 4-13%), respectively. The degree of attenuation depended strongly on the transmission rate during the subclinical phase. Conclusions: Subclinical disease may limit the impact of current diagnostic strategies for TB. Active detection of undiagnosed prevalent cases may achieve greater population-level TB control than increasing passive case detection. AD - 615 North Wolfe Street, E6531, Baltimore, MD 21205. ddowdy@jhsph.edu. AN - 23262515 AU - Dowdy, D. W. AU - Basu, S. AU - Andrews, J. R. DA - Mar 1 DO - 10.1164/rccm.201207-1217OC 10.1164/rccm.201207-1217OC. Epub 2012 Dec 21. DP - Nlm ET - 12/25 J2 - American journal of respiratory and critical care medicine LA - eng PY - 2012 SN - 1535-4970 (Electronic) 1073-449X (Linking) SP - 543-51 ST - Is passive diagnosis enough?: the impact of subclinical disease on diagnostic strategies for tuberculosis T2 - Am J Respir Crit Care Med TI - Is passive diagnosis enough?: the impact of subclinical disease on diagnostic strategies for tuberculosis UR - http://ajrccm.atsjournals.org/content/187/5/543.full.pdf VL - 187 ID - 2696 ER - TY - JOUR AB - The importance of high-incidence "hotspots" to population-level tuberculosis (TB) incidence remains poorly understood. TB incidence varies widely across countries, but within smaller geographic areas (e.g., cities), TB transmission may be more homogeneous than other infectious diseases. We constructed a steady-state compartmental model of TB in Rio de Janeiro, replicating nine epidemiological variables (e.g., TB incidence) within 1% of their observed values. We estimated the proportion of TB transmission originating from a high-incidence hotspot (6.0% of the city's population, 16.5% of TB incidence) and the relative impact of TB control measures targeting the hotspot vs. the general community. If each case of active TB in the hotspot caused 0.5 secondary transmissions in the general community for each within-hotspot transmission, the 6.0% of people living in the hotspot accounted for 35.3% of city-wide TB transmission. Reducing the TB transmission rate (i.e., number of secondary infections per infectious case) in the hotspot to that in the general community reduced city-wide TB incidence by 9.8% in year 5, and 29.7% in year 50-an effect similar to halving time to diagnosis for the remaining 94% of the community. The importance of the hotspot to city-wide TB control depended strongly on the extent of TB transmission from the hotspot to the general community. High-incidence hotspots may play an important role in propagating TB epidemics. Achieving TB control targets in a hotspot containing 6% of a city's population can have similar impact on city-wide TB incidence as achieving the same targets throughout the remaining community. AD - Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205. AN - 22645356 AU - Dowdy, D. W. AU - Golub, J. E. AU - Chaisson, R. E. AU - Saraceni, V. DA - May 29 DO - 10.1073/pnas.1203517109 ET - 05/31 J2 - Proceedings of the National Academy of Sciences of the United States of America LA - Eng N1 - Proc Natl Acad Sci U S A. 2012 May 29. PY - 2012 RN - fulltext fulltext_1208 SN - 1091-6490 (Electronic) 0027-8424 (Linking) ST - Heterogeneity in tuberculosis transmission and the role of geographic hotspots in propagating epidemics T2 - Proc Natl Acad Sci U S A TI - Heterogeneity in tuberculosis transmission and the role of geographic hotspots in propagating epidemics UR - http://www.ncbi.nlm.nih.gov/pubmed/22645356 ID - 2662 ER - TY - JOUR AB - Background & objectives: New diagnostic tests for tuberculosis, especially those based on nucleic acid amplification, offer the possibility of early and accurate diagnosis of active TB. In this study we use mathematical modelling to explore the potential epidemiological impact of these new tests, with particular reference to India. Methods: A behavioural model of patient-doctor interactions embedded in an epidemiological model of Mycobacterium tuberculosis transmission, linked to field data, was used to investigate the effects of early diagnosis in preventing future TB cases. Results: New diagnostic tests for active TB will have a bigger impact sooner where: disease incidence is high and most cases are due to recent infection; advances in test technology (test sensitivity, specificity, etc.) are combined with early diagnosis; new tests have not only better technical specifications than current tests, but also compensate for the misuse of existing tests; health system delays are long compared with patient delays, assuming the former are more amenable to change. Interpretation & conclusions: New diagnostic tests will certainly improve TB control, but the highest impact will be obtained by applying tests with higher sensitivity and specificity early in the infectious period. Refined behavioural and epidemiological models should be able to investigate the mechanisms by which early diagnosis could be achieved, in addition to the consequent epidemiological effects. AD - HIV/AIDS, Tuberculosis, Malaria & Neglected Tropical Diseases Cluster, World Health Organization, Geneva, Switzerland. AN - 22771607 AU - Dye, C. DA - May DO - IndianJMedRes_2012_135_5_737_97762 [pii] DP - Nlm ET - 07/10 LA - eng N1 - Dye, Christopher India The Indian journal of medical research Indian J Med Res. 2012 May;135(5):737-44. PY - 2012 RN - fulltext fulltext_1208 SN - 0971-5916 (Print) SP - 737-44 ST - The potential impact of new diagnostic tests on tuberculosis epidemics T2 - Indian J Med Res TI - The potential impact of new diagnostic tests on tuberculosis epidemics UR - http://www.ijmr.org.in/article.asp?issn=0971-5916;year=2012;volume=135;issue=5;spage=737;epage=744;aulast=Dye VL - 135 ID - 2663 ER - TY - JOUR AB - BACKGROUND: Methods for determining cost-effectiveness of different treatments are well established, unlike appraisal of non-drug interventions, including novel diagnostics and biomarkers. OBJECTIVE: The authors develop and validate a new health economic model by comparing cost-effectiveness of tuberculin skin test (TST); blood test, interferon-gamma release assay (IGRA) and TST followed by IGRA in conditional sequence, in screening healthcare workers for latent or active tuberculosis (TB). DESIGN: The authors focus on healthy life years gained as the benefit metric, rather than quality-adjusted life years given limited data to estimate quality adjustments of life years with TB and complications of treatment, like hepatitis. Healthy life years gained refer to the number of TB or hepatitis cases avoided and the increase in life expectancy. The authors incorporate disease and test parameters informed by systematic meta-analyses and clinical practice. Health and economic outcomes of each strategy are modelled as a decision tree in Markov chains, representing different health states informed by epidemiology. Cost and effectiveness values are generated as the individual is cycled through 20 years of the model. Key parameters undergo one-way and Monte Carlo probabilistic sensitivity analyses. SETTING: Screening healthcare workers in secondary and tertiary care. RESULTS: IGRA is the most effective strategy, with incremental costs per healthy life year gained of pound10 614- pound20 929, base case, pound8021- pound18 348, market costs TST pound45, IGRA pound90, IGRA specificities of 99%-97%; mean (5%, 95%), pound12 060 ( pound4137- pound38 418) by Monte Carlo analysis. CONCLUSIONS: Incremental costs per healthy life year gained, a conservative estimate of benefit, are comparable to the pound20 000- pound30 000 NICE band for IGRA alone, across wide differences in disease and test parameters. Health gains justify IGRA costs, even if IGRA tests cost three times TST. This health economic model offers a powerful tool for appraising non-drug interventions in the market and under development. AD - Centre for Health Leadership and Enterprise, Judge Business School, University of Cambridge, Cambridge, UK. AN - 22382118 AU - Eralp, M. N. AU - Scholtes, S. AU - Martell, G. AU - Winter, R. AU - Exley, A. R. DO - 10.1136/bmjopen-2011-000630 DP - Nlm ET - 03/03 J2 - BMJ open LA - eng N1 - Eralp, Merve Nazli Scholtes, Stefan Martell, Geraldine Winter, Robert Exley, Andrew Robert England BMJ Open. 2012 Mar 1;2(2):e000630. Print 2012. PY - 2012 RN - fulltext fulltext_1208 SN - 2044-6055 (Electronic) SP - e000630 ST - Screening of healthcare workers for tuberculosis: development and validation of a new health economic model to inform practice T2 - BMJ Open TI - Screening of healthcare workers for tuberculosis: development and validation of a new health economic model to inform practice UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293131/pdf/bmjopen-2011-000630.pdf VL - 2 ID - 2664 ER - TY - JOUR AB - SETTING: Standard treatment for latent tuberculosis infection (LTBI) is 9 months daily isoniazid (9INH). An alternative is 4 months daily rifampin (4RMP), associated with better completion and less toxicity; however, its efficacy remains uncertain. OBJECTIVES: To assess the cost-effectiveness of these regimens for treating LTBI in human immunodeficiency virus negative persons, using results from a recent clinical trial, plus different scenarios for 4RMP efficacy, and to estimate the costs of an adequately powered noninferiority trial and resulting savings from substitution with 4RMP. DESIGN: A decision-analysis model tracked TB contacts and lower-risk tuberculin reactors receiving 9INH, 4RMP or no treatment. For different 4RMP efficacy scenarios, we estimated the cost-effectiveness, sample size and cost of non-inferiority trials, and potential cost savings substituting 4RMP for 9INH for 10 years in Canada. RESULTS: With an assumed 4RMP efficacy of 60%, 9INH was more effective but slightly more expensive. Above a threshold efficacy of 69%, 4RMP was cheaper and more effective than 9INH. If the true efficacy of 4RMP is >/=75%, a trial powered to detect non-inferiority with a lower limit of 60% estimated efficacy (~20 000 subjects) may lead to cost savings within 10 years, even with the extreme assumption that Canada bears the entire cost. CONCLUSION: 4RMP may be a reasonable alternative to 9INH. Costs of a large-scale non-inferiority trial may be offset by subsequent savings. AD - Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, Montreal, Quebec, Canada. AN - 22283892 AU - Esfahani, K. AU - Aspler, A. AU - Menzies, D. AU - Schwartzman, K. DA - Oct DO - 10.5588/ijtld.10.0575 DP - Nlm ET - 01/31 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Adult Antitubercular Agents/ administration & dosage/adverse effects/ economics Brazil Canada Cost-Benefit Analysis Decision Support Techniques Drug Administration Schedule Drug Costs Female Humans Isoniazid/ administration & dosage/adverse effects/ economics Latent Tuberculosis/diagnosis/ drug therapy/ economics/microbiology Male Middle Aged Models, Economic Research Design Rifampin/ administration & dosage/adverse effects/ economics Saudi Arabia Time Factors Treatment Outcome Young Adult LA - eng N1 - Esfahani, K Aspler, A Menzies, D Schwartzman, K Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't France Int J Tuberc Lung Dis. 2011 Oct;15(10):1340-6. PY - 2012 RN - fulltext fulltext_1208 SN - 1815-7920 (Electronic) 1027-3719 (Linking) SP - 1340-6 ST - Potential cost-effectiveness of rifampin vs. isoniazid for latent tuberculosis: implications for future clinical trials T2 - Int J Tuberc Lung Dis TI - Potential cost-effectiveness of rifampin vs. isoniazid for latent tuberculosis: implications for future clinical trials VL - 15 ID - 2621 ER - TY - JOUR AB - In this work we present an agent-based model for the spread of tuberculosis where the individuals can be infected with either drug-susceptible or drug-resistant strains and can also receive a treatment. The dynamics of the model and the role of each one of the parameters are explained. The whole set of parameters is explored to check their importance in the numerical simulation results. The model captures the beneficial impact of the adequate treatment on the prevalence of tuberculosis. Nevertheless, depending on the treatment parameters range, it also captures the emergence of drug resistance. Drug resistance emergence is particularly likely to occur for parameter values corresponding to less efficacious treatment, as usually found in developing countries. AD - Univ Fed Fluminense Volta Redonda, Dept Fis, Inst Ciencias Exatas ICEx, BR-27213250 Niteroi, RJ, Brazil Natl Inst Sci & Technol Complex Syst, Rio De Janeiro, Brazil Univ Guelph, Dept Math & Stat, Guelph, ON N1G 2K1, Canada Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, BR-14040901 Sao Paulo, Brazil AN - WOS:000305905500006 AU - Espindola, A. L. AU - Girardi, D. AU - Penna, T. J. P. AU - Bauch, C. T. AU - Martinez, A. S. AU - Cabella, B. C. T. DA - Jun DO - Artn 1250046 10.1142/S0129183112500465 IS - 6 J2 - Int J Mod Phys C KW - computational epidemiology tuberculosis cellular automata stochastic models control strategies epidemics LA - English N1 - 967kd Times Cited:1 Cited References Count:15 PY - 2012 SN - 0129-1831 ST - Exploration of the Parameter Space in an Agent-Based Model of Tuberculosis Spread: Emergence of Drug Resistance in Developing Vs Developed Countries T2 - International Journal of Modern Physics C TI - Exploration of the Parameter Space in an Agent-Based Model of Tuberculosis Spread: Emergence of Drug Resistance in Developing Vs Developed Countries UR - ://WOS:000305905500006 http://www.worldscientific.com/doi/abs/10.1142/S0129183112500465 VL - 23 ID - 271 ER - TY - JOUR AB - Increased rates of tuberculosis (TB) reactivation have been reported in humans treated with TNF-alpha (TNF)-neutralizing drugs, and higher rates are observed with anti-TNF Abs (e.g., infliximab) as compared with TNF receptor fusion protein (etanercept). Mechanisms driving differential reactivation rates and differences in drug action are not known. We use a computational model of a TB granuloma formation that includes TNF/TNF receptor dynamics to elucidate these mechanisms. Our analyses yield three important insights. First, drug binding to membrane-bound TNF critically impairs granuloma function. Second, a higher risk of reactivation induced from Ab-type treatments is primarily due to differences in TNF/drug binding kinetics and permeability. Apoptotic and cytolytic activities of Abs and pharmacokinetic fluctuations in blood concentration of drug are not essential to inducing TB reactivation. Third, we predict specific host factors that, if augmented, would improve granuloma function during anti-TNF therapy. Our findings have implications for the development of safer anti-TNF drugs to treat inflammatory diseases. AD - Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA. AN - 22379032 AU - Fallahi-Sichani, M. AU - Flynn, J. L. AU - Linderman, J. J. AU - Kirschner, D. E. C2 - PMC3311778 C6 - NIHMS352958 DA - Apr 01 DO - 10.4049/jimmunol.1103298 DP - NLM ET - 2012/03/02 IS - 7 J2 - Journal of immunology (Baltimore, Md. : 1950) KW - Adalimumab Antibodies, Monoclonal/*adverse effects/blood/pharmacokinetics Antibodies, Monoclonal, Humanized/adverse effects/blood/pharmacokinetics Antirheumatic Agents/*adverse effects/blood/classification/pharmacokinetics Apoptosis/drug effects Certolizumab Pegol *Computer Simulation Cytotoxicity, Immunologic Etanercept Humans Immunoglobulin Fab Fragments/adverse effects/blood Immunoglobulin G/adverse effects/blood Infliximab Latent Tuberculosis/immunology/*physiopathology *Models, Biological Mycobacterium tuberculosis/*growth & development/immunology Permeability Polyethylene Glycols/adverse effects/pharmacokinetics Protein Binding Receptors, Tumor Necrosis Factor/blood/*drug effects/physiology Risk Tuberculoma/immunology/microbiology/*physiopathology Tuberculosis, Pulmonary/immunology/physiopathology Tumor Necrosis Factor-alpha/*antagonists & inhibitors/physiology LA - eng N1 - 1550-6606 Fallahi-Sichani, Mohammad Flynn, JoAnne L Linderman, Jennifer J Kirschner, Denise E R01 HL106804-01/HL/NHLBI NIH HHS/United States 1R01 HL106804/HL/NHLBI NIH HHS/United States R01 EB012579-04A1/EB/NIBIB NIH HHS/United States R33HL092853/HL/NHLBI NIH HHS/United States R33 HL092853-03/HL/NHLBI NIH HHS/United States R33 HL092883/HL/NHLBI NIH HHS/United States R33 HL092853/HL/NHLBI NIH HHS/United States R33HL092844/HL/NHLBI NIH HHS/United States N01 AI050018/AI/NIAID NIH HHS/United States R01 HL71241/HL/NHLBI NIH HHS/United States R01 EB012579/EB/NIBIB NIH HHS/United States R33 HL092844-03/HL/NHLBI NIH HHS/United States R33 HL092844/HL/NHLBI NIH HHS/United States Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States J Immunol. 2012 Apr 1;188(7):3169-78. doi: 10.4049/jimmunol.1103298. Epub 2012 Feb 29. PY - 2012 SN - 0022-1767 SP - 3169-78 ST - Differential risk of tuberculosis reactivation among anti-TNF therapies is due to drug binding kinetics and permeability T2 - J Immunol TI - Differential risk of tuberculosis reactivation among anti-TNF therapies is due to drug binding kinetics and permeability VL - 188 ID - 2119 ER - TY - JOUR AB - The NF-kappaB signaling pathway is central to the body's response to many pathogens. Mathematical models based on cell culture experiments have identified important molecular mechanisms controlling the dynamics of NF-kappaB signaling, but the dynamics of this pathway have never been studied in the context of an infection in a host. Here, we incorporate these dynamics into a virtual infection setting. We build a multi-scale model of the immune response to the pathogen Mycobacterium tuberculosis (Mtb) to explore the impact of NF-kappaB dynamics occurring across molecular, cellular, and tissue scales in the lung. NF-kappaB signaling is triggered via tumor necrosis factor-alpha (TNF) binding to receptors on macrophages; TNF has been shown to play a key role in infection dynamics in humans and multiple animal systems. Using our multi-scale model, we predict the impact of TNF-induced NF-kappaB-mediated responses on the outcome of infection at the level of a granuloma, an aggregate of immune cells and bacteria that forms in response to infection and is key to containment of infection and clinical latency. We show how the stability of mRNA transcripts corresponding to NF-kappaB-mediated responses significantly controls bacterial load in a granuloma, inflammation level in tissue, and granuloma size. Because we incorporate intracellular signaling pathways explicitly, our analysis also elucidates NF-kappaB-associated signaling molecules and processes that may be new targets for infection control. AD - Department of Chemical Engineering, University of Michigan Ann Arbor, MI, USA. AN - 22685435 AU - Fallahi-Sichani, M. AU - Kirschner, D. E. AU - Linderman, J. J. C2 - PMC3368390 DO - 10.3389/fphys.2012.00170 KW - NF-kappaB signaling pathway granuloma multi-scale modeling systems biology tuberculosis tumor necrosis factor N1 - Fallahi-Sichani, Mohammad Kirschner, Denise E Linderman, Jennifer J eng R33 HL092853/HL/NHLBI NIH HHS/ R01 HL106804/HL/NHLBI NIH HHS/ R01 EB012579/EB/NIBIB NIH HHS/ R01 HL110811/HL/NHLBI NIH HHS/ R33 HL092844/HL/NHLBI NIH HHS/ Switzerland 2012/06/12 06:00 Front Physiol. 2012 Jun 6;3:170. doi: 10.3389/fphys.2012.00170. eCollection 2012. PY - 2012 SN - 1664-042X (Electronic) 1664-042X (Linking) SP - 170 ST - NF-kappaB Signaling Dynamics Play a Key Role in Infection Control in Tuberculosis T2 - Front Physiol TI - NF-kappaB Signaling Dynamics Play a Key Role in Infection Control in Tuberculosis UR - https://www.ncbi.nlm.nih.gov/pubmed/22685435 VL - 3 ID - 2238 ER - TY - JOUR AB - A nonlinear mathematical model is proposed and analyzed to study the dynamics of HIV, TB and co-infection. The basic reproduction number for each of the two diseases (HIV and TB) is obtained. Four equilibrium points are found, out of which one is disease free equilibrium while the remaining three equilibrium points are such that they are having at least one of the diseases HIV and / or TB is present. When the basic reproduction number of the two diseases is less than one then the disease free equilibrium point is stable. This provides a threshold for the control of diseases. When TB free equilibrium point exists then it is locally stable if the basic reproduction number of HIV is more than that of TB. A condition for local stability of HIV free equilibrium point is also obtained. There exist some situations in which bi-stability is possible, that is, both of the diseases persist. The conditions for global stability of these points are also established. The conditions for existence of endemic equilibrium point are explored and it was found that it remains unstable whenever the endemic equilibrium point exists. The instability of endemic equilibrium point is used to interpret that the co-infection is not long lasting. (C) 2012 Elsevier Inc. All rights reserved. AD - [Gakkhar, Sunita; Chavda, Nareshkumar] Indian Inst Technol Roorkee, Dept Math, Roorkee 247667, Uttar Pradesh, India. Chavda, N (reprint author), Indian Inst Technol Roorkee, Dept Math, Roorkee 247667, Uttar Pradesh, India. sungkfma@iitr.ernet.in; anchavda@yahoo.com AN - WOS:000302992700021 AU - Gakkhar, S. AU - Chavda, N. DA - May DO - 10.1016/j.amc.2012.03.004 IS - 18 J2 - Appl. Math. Comput. KW - Co-infection Basic reproduction number Stability tuberculosis infection driven spread impact Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: 928OP Times Cited: 4 Cited Reference Count: 16 Gakkhar, Sunita Chavda, Nareshkumar 4 0 5 Elsevier science inc New york PY - 2012 SN - 0096-3003 SP - 9261-9270 ST - A dynamical model for HIV-TB co-infection T2 - Applied Mathematics and Computation TI - A dynamical model for HIV-TB co-infection UR - ://WOS:000302992700021 VL - 218 ID - 5664 ER - TY - JOUR AB - National policies regarding the BCG vaccine for tuberculosis vary greatly throughout the international community and several countries are currently considering discontinuing universal vaccination. Detractors of BCG point to its uncertain effectiveness and its interference with the detection and treatment of latent tuberculosis infection (LTBI). In order to quantify the trade-off between vaccination and treatment of LTBI, a mathematical model was designed and calibrated to data from Brazil, Ghana, Germany, India, Mexico, Romania, the United Kingdom and the United States. Country-specific thresholds for when LTBI treatment outperforms mass vaccination were found and the consequences of policy changes were estimated. Our results suggest that vaccination outperforms LTBI treatment in all settings but with greatly reduced efficiency in low incidence countries. While national policy statements emphasize BCG’s interference with LTBI detection, we find that reinfection should be more determinant of a country’s proper policy choice. AU - Gerberry, D. J. AU - Milner, F. A. DB - Cambridge Core DO - 10.1051/mmnp/20127307 DP - Cambridge University Press ET - 06/06 IS - 3 KW - tuberculosis BCG vaccination mathematical modeling threshold analysis latent tuberculosis detection latent tuberculosis treatment PY - 2012 SN - 0973-5348 SP - 78-98 ST - Could changes in national tuberculosis vaccination policies be ill-informed ? T2 - Mathematical Modelling of Natural Phenomena TI - Could changes in national tuberculosis vaccination policies be ill-informed ? UR - https://www.cambridge.org/core/article/could-changes-in-national-tuberculosis-vaccination-policies-be-illinformed/EEF2BDF4E1023EEC613B4C04709CD5EA VL - 7 ID - 4931 ER - TY - JOUR AB - Recurrent episodes of tuberculosis (TB) can be due to relapse of latent infection or exogenous reinfection, and discrimination is crucial for control planning. Molecular genotyping of Mycobacterium tuberculosis isolates offers concrete opportunities to measure the relative contribution of reinfection in recurrent disease. Here, a mathematical model of TB transmission is fitted to data from 14 molecular epidemiology studies, enabling the estimation of relevant epidemiological parameters. Meta-analysis reveals that rates of reinfection after successful treatment are higher than rates of new TB, raising an important question about the underlying mechanism. We formulate two alternative mechanisms within our model framework: (i) infection increases susceptibility to reinfection or (ii) infection affects individuals differentially, thereby recruiting high-risk individuals to the group at risk for reinfection. The second mechanism is better supported by the fittings to the data, suggesting that reinfection rates are inflated through a population phenomenon that occurs in the presence of heterogeneity in individual risk of infection. As a result, rates of reinfection are higher when measured at the population level even though they might be lower at the individual level. Finally, differential host recruitment is modulated by transmission intensity, being less pronounced when incidence is high. AD - Instituto Gulbenkian de Ciencia, Apartado 14, 2781-901 Oeiras, Portugal. ggomes@igc.gulbenkian.pt AN - 22357260 AU - Gomes, M. G. AU - Aguas, R. AU - Lopes, J. S. AU - Nunes, M. C. AU - Rebelo, C. AU - Rodrigues, P. AU - Struchiner, C. J. DA - Jun 22 DO - rspb.2011.2712 [pii] 10.1098/rspb.2011.2712 [doi] DP - Nlm ET - 02/24 LA - eng N1 - Gomes, M Gabriela M Aguas, Ricardo Lopes, Joao S Nunes, Marta C Rebelo, Carlota Rodrigues, Paula Struchiner, Claudio J Research Support, Non-U.S. Gov't England Proceedings. Biological sciences / The Royal Society Proc Biol Sci. 2012 Jun 22;279(1737):2473-8. Epub 2012 Feb 22. PY - 2012 RN - fulltext fulltext_1208 SN - 1471-2954 (Electronic) 0962-8452 (Linking) SP - 2473-8 ST - How host heterogeneity governs tuberculosis reinfection? T2 - Proc Biol Sci TI - How host heterogeneity governs tuberculosis reinfection? UR - http://rspb.royalsocietypublishing.org/content/279/1737/2473.full.pdf VL - 279 ID - 2665 ER - TY - JOUR AB - About 90% of the people infected with Mycobacterium tuberculosis carry latent bacteria that are believed to get activated upon immune suppression. One of the fundamental challenges in the control of tuberculosis is therefore to understand molecular mechanisms involved in the onset of latency and/or reactivation. We have attempted to address this problem at the systems level by a combination of predicted functional protein:protein interactions, integration of functional interactions with large scale gene expression studies, predicted transcription regulatory network and finally simulations with a boolean model of the network. Initially a prediction for genome-wide protein functional linkages was obtained based on genome-context methods using a Support Vector Machine. This set of protein functional linkages along with gene expression data of the available models of latency was employed to identify proteins involved in mediating switch signals during dormancy. We show that genes that are up and down regulated during dormancy are not only coordinately regulated under dormancy-like conditions but also under a variety of other experimental conditions. Their synchronized regulation indicates that they form a tightly regulated gene cluster and might form a latency-regulon. Conservation of these genes across bacterial species suggests a unique evolutionary history that might be associated with M. tuberculosis dormancy. Finally, simulations with a boolean model based on the regulatory network with logical relationships derived from gene expression data reveals a bistable switch suggesting alternating latent and actively growing states. Our analysis based on the interaction network therefore reveals a potential model of M. tuberculosis latency. AD - Structural Biology Laboratory, Centre for DNA Fingerprinting and Diagnostics, Gruhakalpa, Nampally, Hyderabad, India. AN - 22448278 AU - Hegde, S. R. AU - Rajasingh, H. AU - Das, C. AU - Mande, S. S. AU - Mande, S. C. DO - 10.1371/journal.pone.0033893 [doi] PONE-D-11-23961 [pii] DP - Nlm ET - 03/27 LA - eng N1 - Hegde, Shubhada R Rajasingh, Hannah Das, Chandrani Mande, Sharmila S Mande, Shekhar C Research Support, Non-U.S. Gov't United States PloS one PLoS One. 2012;7(3):e33893. Epub 2012 Mar 20. PY - 2012 RN - fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e33893 ST - Understanding communication signals during mycobacterial latency through predicted genome-wide protein interactions and boolean modeling T2 - PLoS One TI - Understanding communication signals during mycobacterial latency through predicted genome-wide protein interactions and boolean modeling UR - http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0033893&representation=PDF VL - 7 ID - 2666 ER - TY - JOUR AB - Tuberculosis (TB) is a growing problem worldwide, especially with the emergence and high prevalence of multidrug-resistant strains. We develop a metapopulation model for TB spread, which is particularly suited to investigating transmission between areas of high and low prevalence. A case study of cross-border transmission in the Torres Strait region of Australia and Papua New Guinea (PNG) is considered and a sensitivity analysis is conducted. We find that only 6 of the 50 parameters analysed are important to the cumulative number of clinically active TB patients in the entire region. Of these, only the detection rate in PNG is found to be an important intervention parameter. We therefore give insight into the extent the area with the high burden of TB (PNG in the case study) is dominating the TB dynamics of the entire region. Furthermore, the sensitivity analysis results give insight into the data that most important to collect and refine, which is found to be data relating to the PNG parameters. AD - National Centre for Epidemiology and Population Health, Australian National University, Canberra, Australia. AN - 22496801 AU - Hickson, R. I. AU - Mercer, G. N. AU - Lokuge, K. M. DO - 10.1371/journal.pone.0034411 PONE-D-11-19467 [pii] L1 - internal-pdf://0159393492/Hickson-2012-A metapopulation model of tubercu.pdf LA - eng N1 - Hickson, Roslyn I Mercer, Geoffry N Lokuge, Kamalini M United States PloS one PLoS One. 2012;7(3):e34411. Epub 2012 Apr 4. PY - 2012 RN - fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e34411 ST - A metapopulation model of tuberculosis transmission with a case study from high to low burden areas T2 - PLoS One TI - A metapopulation model of tuberculosis transmission with a case study from high to low burden areas UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22496801http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319591/pdf/pone.0034411.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319591/pdf/pone.0034411.pdf VL - 7 ID - 2667 ER - TY - JOUR AB - We present a mathematical transmission model of tuberculosis in the USA. The model is calibrated to recent trends of declining incidence in the US-born and foreign-born populations and is used in assessing relative impacts of treatment of latently infected individuals on elimination time, where elimination is defined as annual incidence <1 case/million. Provided current control efforts are maintained, elimination in the US-born population can be achieved before the end of this century. However, elimination in the foreign-born population is unlikely in this timeframe even with higher rates of targeted testing and treatment of residents of and immigrants to the USA with latent tuberculosis infection. Cutting transmission of disease as an interim step would shorten the time to elimination in the US-born population but foreign-born rates would remain above the elimination target. AD - Division of Tuberculosis Elimination, U.S. Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA. ahill2@cdc.gov AN - 22233605 AU - Hill, A. N. AU - Becerra, J. AU - Castro, K. G. DA - Oct DO - 10.1017/s095026881100286x 10.1017/S095026881100286X. Epub 2012 Jan 11. DP - Nlm ET - 01/12 J2 - Epidemiology and infection KW - Humans Incidence Models, Statistical Tuberculosis/ epidemiology/prevention & control United States/epidemiology LA - eng PY - 2012 SN - 1469-4409 (Electronic) 0950-2688 (Linking) SP - 1862-72 ST - Modelling tuberculosis trends in the USA T2 - Epidemiol Infect TI - Modelling tuberculosis trends in the USA UR - http://journals.cambridge.org/download.php?file=%2FHYG%2FHYG140_10%2FS095026881100286Xa.pdf&code=e69da0c8eec17422533e435a6523a1b7 VL - 140 ID - 2668 ER - TY - JOUR AB - While in antiquity both leprosy and tuberculosis were prevalent in Europe, leprosy declined thereafter and, simultaneously, tuberculosis prevalence increased. Since both diseases are caused by mycobacterial infections, it has been suggested that there might be a causal relationship between both epidemics. Chaussinand observed the inverse prevalence of leprosy and tuberculosis and suggested that individuals with a latent tuberculosis infection are protected from acquiring leprosy. His cross-immunity hypothesis has been countered more recently by a co-infection hypothesis. The latter suggestion, proposed by Donoghue, states that people being infected with multi-bacillary leprosy are more susceptible to tuberculosis, which leads to increased mortality from the disease. This study utilizes mathematical modeling to explore the epidemiological consequences of the co-infection hypothesis for realistically confined parameter values. While the co-infection hypothesis appears plausible at first glance, a second thought reveals that it comprises also substantial consequences for tuberculosis epidemics: if co-infection raises the mortality rate above that of purely tuberculosis infected persons, then tuberculosis might as well be eradicated by leprosy. It is the specific interplay of both increased susceptibility towards tuberculosis and increased death rate when co-infected that determines the epidemiological fate. As a result of this analysis, it is shown that there is a large parameter region where the eventual disappearance of leprosy could indeed be explained by co-infection. This parameter region is considerably larger than that predicted by the cross-immunity hypothesis. This shows that the co-infection hypothesis should be considered a significant alternative to the cross-immunity hypothesis. The time scales at which the effects of co-infection are observed depend critically on the spatial distribution of the individuals but reach epidemiologically realistic values for rather immobile individuals with local interaction. AD - Center of High Performance Computing (ZIH), Technical University Dresden, 01062 Dresden, Germany. nadine.hohmann@tu-dresden.de AN - 23246805 AU - Hohmann, N. AU - Voss-Bohme, A. DA - Feb DO - 10.1016/j.mbs.2012.11.008 10.1016/j.mbs.2012.11.008. Epub 2012 Dec 13. DP - Nlm ET - 12/19 J2 - Mathematical biosciences LA - eng PY - 2012 SN - 1879-3134 (Electronic) 0025-5564 (Linking) SP - 225-37 ST - The epidemiological consequences of leprosy-tuberculosis co-infection T2 - Math Biosci TI - The epidemiological consequences of leprosy-tuberculosis co-infection UR - http://ac.els-cdn.com/S0025556412002283/1-s2.0-S0025556412002283-main.pdf?_tid=44cc1060-8c09-11e2-9bdf-00000aacb361&acdnat=1363198401_814dcb05fcde6861376376ea3cb88903 VL - 241 ID - 2697 ER - TY - JOUR AB - BACKGROUND: The optimal treatment for latent multiple-drug resistant tuberculosis infection remains unclear. In anticipation of future clinical trials, we modeled the expected performance of six potential regimens for treatment of latent multiple-drug resistant tuberculosis. METHODS: A computerized Markov model to analyze the total cost of treatment for six different regimens: Pyrazinamide/ethambutol, moxifloxacin monotherapy, moxifloxacin/pyrazinamide, moxifloxacin/ethambutol, moxifloxacin/ethionamide, and moxifloxacin/PA-824. Efficacy estimates were extrapolated from mouse models and examined over a wide range of assumptions. RESULTS: In the base-case, moxifloxacin monotherapy was the lowest cost strategy, but moxifloxacin/ethambutol was cost-effective at an incremental cost-effectiveness ratio of $21,252 per quality-adjusted life-year. Both pyrazinamide-containing regimens were dominated due to their toxicity. A hypothetical regimen of low toxicity and even modest efficacy was cost-effective compared to "no treatment." CONCLUSION: In our model, moxifloxacin/ethambutol was the preferred treatment strategy under a wide range of assumptions; pyrazinamide-containing regimens fared poorly because of high rates of toxicity. Although more data are needed on efficacy of treatments for latent MDR-TB infection, data on toxicity and treatment discontinuation, which are easier to obtain, could have a substantial impact on public health practice. AD - Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America. david.p.holland@duke.edu AN - 22272302 AU - Holland, D. P. AU - Sanders, G. D. AU - Hamilton, C. D. AU - Stout, J. E. DO - 10.1371/journal.pone.0030194 DP - Nlm ET - 01/25 J2 - PloS one KW - Animals Antitubercular Agents/ therapeutic use Aza Compounds/therapeutic use Cost-Benefit Analysis Decision Support Techniques Drug Therapy/economics/methods Drug Therapy, Combination Ethambutol/therapeutic use Humans Isoniazid/therapeutic use Markov Chains Mice Models, Theoretical Outcome Assessment (Health Care) Quality-Adjusted Life Years Quinolines/therapeutic use Rifampin/therapeutic use Tuberculosis, Multidrug-Resistant/ drug therapy L1 - internal-pdf://0724696808/Holland-2012-Strategies for treating latent mu.pdf LA - eng N1 - Holland, David P Sanders, Gillian D Hamilton, Carol D Stout, Jason E K01-A108372-01/PHS HHS/United States U54 AI057157/AI/NIAID NIH HHS/United States Research Support, N.I.H., Extramural United States PLoS One. 2012;7(1):e30194. Epub 2012 Jan 17. PY - 2012 RN - fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e30194 ST - Strategies for treating latent multiple-drug resistant tuberculosis: a decision analysis T2 - PLoS One TI - Strategies for treating latent multiple-drug resistant tuberculosis: a decision analysis UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260212/pdf/pone.0030194.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260212/pdf/pone.0030194.pdf VL - 7 ID - 2669 ER - TY - JOUR AB - In this paper, we investigate a SEILR tuberculosis model incorporating the effect of seasonal fluctuation, where the loss of sight class is considered. The basic reproduction number R(0) is defined. It is shown that the disease-free equilibrium is globally asymptotically stable and the disease eventually disappears if R(0) < 1, and there exists at least one positive periodic solution and the disease is uniformly persistent if R(0) > 1. Numerical simulations are provided to illustrate analytical results. AD - Department of Applied Mathematics, Xi'an Jiaotong University, Xi'an, 710049, China. huxinli1975@yahoo.com.cn AN - 22229399 AU - Hu, X. DA - Jan 01 DO - 10.3934/mbe.2012.9.111 DP - NLM ET - 2012/01/11 IS - 1 J2 - Mathematical biosciences and engineering : MBE KW - Antitubercular Agents/*therapeutic use Basic Reproduction Number Computer Simulation Humans *Models, Biological Mycobacterium tuberculosis/*growth & development Patient Dropouts Seasons Tuberculosis/*drug therapy/epidemiology/*microbiology LA - eng N1 - 1551-0018 Hu, Xinli Journal Article United States Math Biosci Eng. 2012 Jan 1;9(1):111-22. doi: 10.3934/mbe.2012.9.111. PY - 2012 SN - 1547-1063 SP - 111-22 ST - Threshold dynamics for a tuberculosis model with seasonality T2 - Math Biosci Eng TI - Threshold dynamics for a tuberculosis model with seasonality VL - 9 ID - 2734 ER - TY - JOUR AB - BACKGROUND: There is wide variation in the techniques deployed to diagnose tuberculosis in the UK, with little agreement on which tools or strategies are cost effective. This analysis therefore comprehensively evaluated the cost effectiveness of currently available diagnostic strategies for routine diagnosis of TB in the NHS. METHODS: The analysis compared strategies consisting of Nucleic Acid Amplification Techniques, culture and microscopy. A decision tree was used to estimate costs and Quality-Adjusted Life Years (QALYs) from a UK health service perspective. The sensitivity and specificity of each test determined the true and false positive and negative results in patients suspected of having active tuberculosis. These results led to either early, correct diagnosis or delayed diagnosis and the associated costs and QALYs. The presence of active tuberculosis combined with the side effects of treatment was associated with reduction in quality of life. Costs included were test costs, drug costs and the management of tuberculosis. Drug costs were based on generic UK list prices. Uncertainty in the model was explored through probabilistic and deterministic sensitivity analyses. RESULTS/CONCLUSIONS: The cost effective strategy at threshold of pound20,000 per QALY was a strategy using only sputum microscopy and culture routinely, meaning Nucleic Acid Amplification Techniques are not cost effective at baseline. When the prevalence of tuberculosis was increased, however, nucleic acid amplification became cost effective at the same threshold. Aside from the prevalence, the results were shown to be robust. At low tuberculosis prevalence, Nucleic Acid Amplification Techniques may not be cost effective but their potential in higher prevalence situations is considerable. AD - National Clinical Guidelines Centre, 180 Great Portland Street, London W1W 5QZ, UK. Ralph.hughes@rcplondon.ac.uk AN - 22137190 AU - Hughes, R. AU - Wonderling, D. AU - Li, B. AU - Higgins, B. DO - S0954-6111(11)00345-3 [pii] 10.1016/j.rmed.2011.10.005 KW - Cost-Benefit Analysis Decision Trees *Direct Service Costs Female Great Britain/epidemiology Humans Male *Microscopy/economics/methods National Health Programs/economics Nucleic Acid Amplification Techniques/*economics/methods Prevalence Quality-Adjusted Life Years Sensitivity and Specificity Tuberculosis/*diagnosis/*economics/genetics LA - eng N1 - Hughes, Ralph Wonderling, David Li, Bernadette Higgins, Bernard Comparative Study Review England Respiratory medicine Respir Med. 2012 Feb;106(2):300-7. Epub 2011 Dec 1. PY - 2012 RN - fulltext fulltext_1208 SN - 1532-3064 (Electronic) 0954-6111 (Linking) SP - 300-307 ST - The cost effectiveness of Nucleic Acid Amplification Techniques for the diagnosis of tuberculosis T2 - Respiratory medicine TI - The cost effectiveness of Nucleic Acid Amplification Techniques for the diagnosis of tuberculosis UR - http://www.ncbi.nlm.nih.gov/pubmed/22137190http://ac.els-cdn.com/S0954611111003453/1-s2.0-S0954611111003453-main.pdf?_tid=f0fb9cfc-6b2f-11e2-85ca-00000aacb35e&acdnat=1359586622_4d20eeb6452ae11ec466e6aa649b2371 VL - 106 ID - 2670 ER - TY - JOUR AB - BACKGROUND: Prisons are recognised internationally as institutions with very high tuberculosis (TB) burdens where transmission is predominantly determined by contact between infectious and susceptible prisoners. A recent South African court case described the conditions under which prisoners awaiting trial were kept. With the use of these data, a mathematical model was developed to explore the interactions between incarceration conditions and TB control measures. METHODS: Cell dimensions, cell occupancy, lock-up time, TB incidence and treatment delays were derived from court evidence and judicial reports. Using the Wells-Riley equation and probability analyses of contact between prisoners, we estimated the current TB transmission probability within prison cells, and estimated transmission probabilities of improved levels of case finding in combination with implementation of national and international minimum standards for incarceration. RESULTS: Levels of overcrowding (230%) in communal cells and poor TB case finding result in annual TB transmission risks of 90% per annum. Implementing current national or international cell occupancy recommendations would reduce TB transmission probabilities by 30% and 50%, respectively. Improved passive case finding, modest ventilation increase or decreased lock-up time would minimally impact on transmission if introduced individually. However, active case finding together with implementation of minimum national and international standards of incarceration could reduce transmission by 50% and 94%, respectively. CONCLUSIONS: Current conditions of detention for awaiting-trial prisoners are highly conducive for spread of drug-sensitive and drug-resistant TB. Combinations of simple well-established scientific control measures should be implemented urgently. AD - Desmond Tutu HIV Centre, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa. AN - 22272961 AU - Johnstone-Robertson, S. AU - Lawn, S. D. AU - Welte, A. AU - Bekker, L. G. AU - Wood, R. DA - Nov DP - Nlm ET - 01/26 LA - eng N1 - Johnstone-Robertson, Simon Lawn, Stephen D Welte, Alex Bekker, Linda-Gail Wood, Robin A1058736-01A1/PHS HHS/United States Wellcome Trust/United Kingdom Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. South Africa South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde S Afr Med J. 2011 Nov 1;101(11):809-13. PY - 2012 RN - fulltext fulltext_1208 SN - 0256-9574 (Print) 0256-9574 (Linking) SP - 809-13 ST - Tuberculosis in a South African prison - a transmission modelling analysis T2 - S Afr Med J TI - Tuberculosis in a South African prison - a transmission modelling analysis VL - 101 ID - 2629 ER - TY - JOUR AB - The introduction and scale-up of new tools for the diagnosis of Tuberculosis (TB) in developing countries has the potential to make a huge difference to the lives of millions of people living in poverty. To achieve this, policy makers need the information to make the right decisions about which new tools to implement and where in the diagnostic algorithm to apply them most effectively. These decisions are difficult as the new tools are often expensive to implement and use, and the health system and patient impacts uncertain, particularly in developing countries where there is a high burden of TB. The authors demonstrate that a discrete event simulation model could play a significant part in improving and informing these decisions. The feasibility of linking the discrete event simulation to a dynamic epidemiology model is also explored in order to take account of longer term impacts on the incidence of TB. Results from two diagnostic districts in Tanzania are used to illustrate how the approach could be used to improve decisions. AD - Clinical Group, Liverpool School of Tropical Medicine, Liverpool, UK, ivorlang@liv.ac.uk. AN - 22674467 AU - Langley, I. AU - Doulla, B. AU - Lin, H. H. AU - Millington, K. AU - Squire, B. DA - Sep DO - 10.1007/s10729-012-9201-3 [doi] DP - Nlm ET - 06/08 LA - eng N1 - Langley, Ivor Doulla, Basra Lin, Hsien-Ho Millington, Kerry Squire, Bertie Netherlands Health care management science Health Care Manag Sci. 2012 Sep;15(3):239-53. Epub 2012 Jun 7. PY - 2012 RN - fulltext fulltext_1208 SN - 1386-9620 (Print) 1386-9620 (Linking) SP - 239-53 ST - Modelling the impacts of new diagnostic tools for tuberculosis in developing countries to enhance policy decisions T2 - Health Care Manag Sci TI - Modelling the impacts of new diagnostic tools for tuberculosis in developing countries to enhance policy decisions UR - http://www.springerlink.com/content/u768lr018r04t135/fulltext.pdf VL - 15 ID - 2671 ER - TY - JOUR AB - BACKGROUND: Guidelines differ on screening recommendations for latent tuberculosis infection (LTBI) prior to immunosuppressive therapy. We aimed to determine the most cost-effective LTBI screening strategy before long-term steroid therapy in a child with new-onset idiopathic nephrotic syndrome. STUDY DESIGN: Markov state-transition model. SETTING & POPULATION: 5-year-old boy with new-onset idiopathic nephrotic syndrome. MODEL, PERSPECTIVE, & TIMEFRAME: The Markov model took a societal perspective over a lifetime horizon. INTERVENTION: 3 strategies were compared: universal tuberculin skin testing (TST), targeted screening using a risk-factor questionnaire, and no screening. A secondary model included the newer interferon gamma release assays (IGRAs), requiring only one visit and having greater specificity than TST. OUTCOMES: Marginal cost-effectiveness ratios (2010 US dollars) with effectiveness measured as quality-adjusted life-years (QALYs). RESULTS: At an LTBI prevalence of 1.1% (the average US childhood prevalence in our base case), a no-screening strategy dominated ($2,201; 29.3356 QALYs) targeted screening ($2,218; 29.3356 QALYs) and universal TST ($2,481; 29.3347 QALYs). At a prevalence >10.3%, targeted screening with a risk-factor questionnaire was the most cost-effective option. Higher than a prevalence of 58.5%, universal TST was preferred. In the secondary model, targeted screening with a questionnaire followed by IGRA testing was cost-effective compared with no screening in the base case when the LTBI prevalence was >4.9%. LIMITATIONS: There is no established gold standard for the diagnosis of LTBI. Results of any modeling task are limited by the accuracy of available data. CONCLUSIONS: Prior to starting steroid therapy, only patients in areas with a high prevalence of LTBI will benefit from universal TST. As more evidence becomes available about the use of IGRA testing in children, the assay may become a component of cost-effective screening protocols in populations with a higher burden of LTBI. AD - Division of Nephrology, The Children's Hospital of Philadelphia, Philadelphia, PA. AN - 22784996 AU - Laskin, B. L. AU - Goebel, J. AU - Starke, J. R. AU - Schauer, D. P. AU - Eckman, M. H. DA - Jul 9 DO - S0272-6386(12)00858-X [pii] 10.1053/j.ajkd.2012.06.004 [doi] DP - Nlm ET - 07/13 LA - Eng N1 - Laskin, Benjamin L Goebel, Jens Starke, Jeffrey R Schauer, Daniel P Eckman, Mark H American journal of kidney diseases : the official journal of the National Kidney Foundation Am J Kidney Dis. 2012 Jul 9. PY - 2012 RN - fulltext fulltext_1208 SN - 1523-6838 (Electronic) 0272-6386 (Linking) ST - Cost-Effectiveness of Latent Tuberculosis Screening Before Steroid Therapy for Idiopathic Nephrotic Syndrome in Children T2 - Am J Kidney Dis TI - Cost-Effectiveness of Latent Tuberculosis Screening Before Steroid Therapy for Idiopathic Nephrotic Syndrome in Children ID - 2672 ER - TY - JOUR AB - The purpose of this study was to examine tuberculosis (TB) population dynamics and to assess potential infection risk in Taiwan. A well-established mathematical model of TB transmission built on previous models was adopted to study the potential impact of TB transmission. A probabilistic risk model was also developed to estimate site-specific risks of developing disease soon after recent primary infection, exogenous reinfection, or through endogenous reactivation (latently infected TB) among Taiwan regions. Here, we showed that the proportion of endogenous reactivation (53-67%) was larger than that of exogenous reinfection (32-47%). Our simulations showed that as epidemic reaches a steady state, age distribution of cases would finally shift toward older age groups dominated by latently infected TB cases as a result of endogenous reactivation. A comparison of age-weighted TB incidence data with our model simulation output with 95% credible intervals revealed that the predictions were in an apparent agreement with observed data. The median value of overall basic reproduction number (R(0) ) in eastern Taiwan ranged from 1.65 to 1.72, whereas northern Taiwan had the lowest R(0) estimate of 1.50. We found that total TB incidences in eastern Taiwan had 25-27% probabilities of total proportion of infected population exceeding 90%, whereas there were 36-66% probabilities having exceeded 20% of total proportion of infected population attributed to latently infected TB. We suggested that our Taiwan-based analysis can be extended to the context of developing countries, where TB remains a substantial cause of elderly morbidity and mortality. AN - 22211354 AU - Liao, C. M. AU - Cheng, Y. H. AU - Lin, Y. J. AU - Hsieh, N. H. AU - Huang, T. L. AU - Chio, C. P. AU - Chen, S. C. AU - Ling, M. P. DA - Dec 28 DO - 10.1111/j.1539-6924.2011.01750.x [doi] 10.1111/j.1539-6924.2011.01750.x. DP - Nlm ET - 01/04 LA - Eng PY - 2012 RN - fulltext fulltext_1208 SN - 1539-6924 (Electronic) 0272-4332 (Linking) ST - A Probabilistic Transmission and Population Dynamic Model to Assess Tuberculosis Infection Risk T2 - Risk Anal TI - A Probabilistic Transmission and Population Dynamic Model to Assess Tuberculosis Infection Risk UR - http://onlinelibrary.wiley.com/doi/10.1111/j.1539-6924.2011.01750.x/abstract ID - 2633 ER - TY - JOUR AB - OBJECTIVE: The objective of this study was to link transmission dynamics with a probabilistic risk model to provide a mechanistically explicit assessment for estimating the multidrug-resistant tuberculosis (MDR TB) infection risk in regions of Taiwan. METHODS: A relative fitness (RF)-based MDR TB model was used to describe transmission, validated with disease data for the period 2006-2010. A dose-response model quantifying by basic reproduction number (R(0)) and total proportion of infected population was constructed to estimate the site-specific MDR TB infection risk. RESULTS: We found that the incidence rate of MDR TB was highest in Hwalien County (4.91 per 100,000 population) in eastern Taiwan, with drug-sensitive and multidrug-resistant R(0) estimates of 0.89 (95% CI 0.23-2.17) and 0.38 (95% CI 0.05-1.30), respectively. The predictions were in apparent agreement with observed data in the 95% credible intervals. Our simulation showed that the incidence of MDR TB will be falling by 2013-2016. Our results indicated that the selected regions of Taiwan had only approximately 1% probability of exceeding 50% of the population with infection attributed to MDR TB. CONCLUSIONS: Our study found that the ongoing control programs implemented in Taiwan may succeed in curing most patients with MDR TB and will reduce the TB incidence countrywide. AD - Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan. cmliao@ntu.edu.tw AN - 22818291 AU - Liao, C. M. AU - Lin, Y. J. DA - Oct DO - 10.1016/j.ijid.2012.06.001 10.1016/j.ijid.2012.06.001. Epub 2012 Jul 19. DP - Nlm ET - 07/24 J2 - International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases KW - Algorithms Antitubercular Agents/therapeutic use Communicable Disease Control Epidemics Female Humans Incidence Male Models, Statistical Mycobacterium tuberculosis Population Dynamics Risk Assessment Taiwan/epidemiology Tuberculosis, Multidrug-Resistant/epidemiology/prevention & control/ transmission LA - eng PY - 2012 SN - 1878-3511 (Electronic) 1201-9712 (Linking) SP - e739-47 ST - Assessing the transmission risk of multidrug-resistant Mycobacterium tuberculosis epidemics in regions of Taiwan T2 - Int J Infect Dis TI - Assessing the transmission risk of multidrug-resistant Mycobacterium tuberculosis epidemics in regions of Taiwan UR - http://ac.els-cdn.com/S1201971212011927/1-s2.0-S1201971212011927-main.pdf?_tid=4f1ab800-8c09-11e2-8539-00000aacb35e&acdnat=1363198418_13f7ed07000e13be8a134b0d6d671d53 VL - 16 ID - 2673 ER - TY - JOUR AB - OBJECTIVE: To estimate the impact of new tuberculosis diagnostics on tuberculosis transmission given the complex contextual factors that can lead to patient loss before diagnosis or treatment. METHODS: An epidemic model of tuberculosis specifying discrete steps along the tuberculosis diagnostic pathway was constructed. The model was calibrated to the epidemiology of tuberculosis and human immunodeficiency virus (HIV) infection in the United Republic of Tanzania and was used to assess the impact of a new diagnostic tool with 70% sensitivity for smear-negative pulmonary tuberculosis. The influence of contextual factors on the projected epidemic impact of the new diagnostic tool over the decade following introduction was explored. FINDINGS: With the use of smear microscopy, the incidence of tuberculosis will decline by an average of 3.94% per year. If the new tool is added, incidence will decline by an annual 4.25%. This represents an absolute change of 0.31 percentage points (95% confidence interval: 0.04-0.42). However, the annual decline in transmission with use of the new tool is less when existing strategies for the diagnosis of smear-negative cases have high sensitivity and when symptomatic individuals delay in seeking care. Other influential contextual factors include access to tuberculosis care, patient loss before diagnosis, initial patient default after diagnosis and treatment success rate. CONCLUSION: When implementing and scaling up the use of a new diagnostic tool, the operational context in which diagnosis and treatment take place needs to be considered. AD - Institute of Epidemiology and Preventive Medicine, National Taiwan University, 17 Xuzhou Road, 100 Taipei, Taiwan, China. AN - 23109741 AU - Lin, H. H. AU - Dowdy, D. AU - Dye, C. AU - Murray, M. AU - Cohen, T. DA - Oct 1 DO - 10.2471/blt.11.101436 10.2471/BLT.11.101436. Epub 2012 Jul 16. DP - Nlm ET - 10/31 J2 - Bulletin of the World Health Organization LA - eng PY - 2012 SN - 1564-0604 (Electronic) 0042-9686 (Linking) SP - 739-747A ST - The impact of new tuberculosis diagnostics on transmission: why context matters T2 - Bull World Health Organ TI - The impact of new tuberculosis diagnostics on transmission: why context matters UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471051/pdf/BLT.11.101436.pdf VL - 90 ID - 2674 ER - TY - JOUR AB - A tuberculosis (TB) transmission model involving migrant workers is proposed and investigated. The basic reproduction number R0 is calculated, and is shown to be a threshold parameter for the disease to persist or become extinct in the population. The existence and global attractivity of an endemic equilibrium, if R0 > 1, is also established under some technical conditions. A case study, based on the TB epidemiological and other statistical data in China, indicates that the disease spread can be controlled if effective measures are taken to reduce the reactivation rate of exposed/latent migrant workers. Impact of the migration rate and direction, as well as the duration of home visit stay, on the control of disease spread is also examined numerically. AD - School of Mathematics and Statistics, Henan University of Science and Technology, Luoyang, 471023, China. lujuliu@gmail.com AN - 23311422 AU - Liu, L. AU - Wu, J. AU - Zhao, X. Q. DA - Oct DO - 10.3934/mbe.2012.9.785 DP - NLM ET - 2013/01/15 IS - 4 J2 - Mathematical biosciences and engineering : MBE KW - China/epidemiology Computer Simulation Disease Outbreaks/*statistics & numerical data Disease Transmission, Infectious/*statistics & numerical data Emigration and Immigration/*statistics & numerical data Humans Incidence *Models, Statistical *Proportional Hazards Models Risk Factors Transients and Migrants/*statistics & numerical data Tuberculosis/*epidemiology/*transmission LA - eng N1 - 1551-0018 Liu, Luju Wu, Jianhong Zhao, Xiao-Qiang Journal Article Research Support, Non-U.S. Gov't United States Math Biosci Eng. 2012 Oct;9(4):785-807. doi: 10.3934/mbe.2012.9.785. PY - 2012 SN - 1547-1063 SP - 785-807 ST - The impact of migrant workers on the tuberculosis transmission: general models and a case study for China T2 - Math Biosci Eng TI - The impact of migrant workers on the tuberculosis transmission: general models and a case study for China VL - 9 ID - 2914 ER - TY - JOUR AB - One tuberculosis transmission model is formulated by incorporating exogenous reinfection, relapse, and two treatment stages of infectious TB cases. The global stability of the unique disease-free equilibrium is obtained by applying the comparison principle if the effective reproduction number for the full model is less than unity. The existence and stability of the boundary equilibria are given by introducing the invasion reproduction numbers. Furthermore, the existence and local stability of the endemic equilibrium are addressed under some conditions. AD - Henan Univ Sci & Technol, Sch Math & Stat, Luoyang 471003, Peoples R China Zhengzhou Univ, Sch Basic Studies, SIAS Int Coll, Zhengzhou 451150, Peoples R China AN - WOS:000303942200010 AU - Liu, L. J. AU - Gao, X. C. DA - Jul DO - Artn 1250031 10.1142/S1793524511001763 IS - 4 J2 - Int J Biomath KW - exogenous reinfection relapse the effective reproduction number the invasion reproduction number center manifold theory stability mycobacterium-tuberculosis mathematical-analysis drug-resistance global dynamics transmission population equilibria recurrence shanghai outcomes LA - English N1 - 941db Times Cited:1 Cited References Count:37 PY - 2012 SN - 1793-5245 ST - Qualitative Study for a Multi-Drug Resistant Tb Model with Exogenous Reinfection and Relapse T2 - International Journal of Biomathematics TI - Qualitative Study for a Multi-Drug Resistant Tb Model with Exogenous Reinfection and Relapse UR - ://WOS:000303942200010 http://www.worldscientific.com/doi/abs/10.1142/S1793524511001763 VL - 5 ID - 270 ER - TY - JOUR AB - The Mycobacterium tuberculosis bacilli's potency to cause persistent latent infection that is unresponsive to the current cocktail of TB drugs is strongly associated with its ability to adapt to changing intracellular environments, and tolerating, evading and subverting host defence mechanisms. We applied a combination of bioinformatics and mathematical modelling methods to enhance the understanding of TB latency dynamics. Analysis of time course microarray gene expression data was carried out and gene profiles for bacilli adaptation and survival in latency, simulated by hypoxia were determined. Reverse network engineering techniques were used to predict gene dependencies and regulatory interactions. Biochemical systems theory was applied to mathematically model the inferred gene regulatory networks. Significant regulatory genes involved in latency were determined by a combination of systems biology procedures and mathematical modelling of the inferred regulatory networks. Analysis of gene clusters of the inferred networks in the stationary and non-replicating phases of the bacilli predicted probable functions of some of the latency genes to be associated with latency genes of known functions. The systems biology approach and mathematical computational deletion experiments predicted key genes in the TB latency/dormancy program that may be possible TB drug targets. However, these gene candidates require experimental testing and validation. AD - National Institute for Mathematical and Biological Synthesis, 1534 White Ave., University of Tennessee, Knoxville, TN 37996-1527, USA. gmagombedze@nimbios.org AN - 23146828 AU - Magombedze, G. AU - Mulder, N. DA - Jan DO - 10.1016/j.meegid.2012.09.017 10.1016/j.meegid.2012.09.017. Epub 2012 Nov 10. DP - Nlm ET - 11/14 J2 - Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases LA - eng PY - 2012 SN - 1567-7257 (Electronic) 1567-1348 (Linking) SP - 267-83 ST - Understanding TB latency using computational and dynamic modelling procedures T2 - Infect Genet Evol TI - Understanding TB latency using computational and dynamic modelling procedures UR - http://ac.els-cdn.com/S1567134812003309/1-s2.0-S1567134812003309-main.pdf?_tid=543033f6-8c09-11e2-b4a8-00000aab0f6b&acdnat=1363198427_79819944fa90179478bc7af641821ecf VL - 13 ID - 2699 ER - TY - JOUR AB - BACKGROUND: Tuberculosis (TB) accounts of much of the morbidity and mortality associated with HIV. We evaluate the cost-effectiveness of different strategies to actively screen for TB disease in HIV positive individuals, where isoniazid preventative therapy (IPT) is given to those screening negative, and use value of information analysis (VOI) to identify future research priorities. METHODOLOGY/ PRINCIPAL FINDINGS: We built an individual sampling model to investigate the costs (2010 US Dollars) and consequences of screening for TB, and providing TB treatment or IPT in adults testing HIV positive in Sub-Saharan Africa. A systematic review and meta-analysis was conducted to assess performance of the nine different TB screening strategies evaluated. Probabilistic sensitivity analysis was conducted to incorporate decision uncertainty, and expected value of perfect information for the entire model and for groups of parameters was calculated. Screening all HIV infected individuals with sputum microscopy was the least costly strategy, with other strategies not cost-effective at WHO recommended thresholds. Screening those with TB symptoms with sputum microscopy and CXR would be cost-effective at a threshold ICER of $7,800 per quality-adjusted life year (QALY), but associated with significant uncertainty. VOI analysis suggests further information would be of value. CONCLUSIONS/ SIGNIFICANCE: Resource-constrained countries in sub-Saharan Africa wishing to scale up TB preventative services in their HIV infected populations should consider expanding laboratory facilities to enable increased screening for TB with sputum microscopy, whilst improved estimates of the TB prevalence in the population to be screened are needed, as it may influence the optimal strategy. AD - Division of Health Sciences, University of Warwick Medical School, Coventry, United Kingdom. AN - 22291958 AU - Maheswaran, H. AU - Barton, P. DO - 10.1371/journal.pone.0030457 ET - 02/01 J2 - PloS one LA - eng N1 - Maheswaran, Hendramoorthy Barton, Pelham PLoS One. 2012;7(1):e30457. Epub 2012 Jan 23. PY - 2012 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e30457 ST - Intensive Case Finding and Isoniazid Preventative Therapy in HIV Infected Individuals in Africa: Economic Model and Value of Information Analysis T2 - PLoS One TI - Intensive Case Finding and Isoniazid Preventative Therapy in HIV Infected Individuals in Africa: Economic Model and Value of Information Analysis UR - http://www.ncbi.nlm.nih.gov/pubmed/22291958http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3264596/pdf/pone.0030457.pdf VL - 7 ID - 2676 ER - TY - JOUR AB - Many agencies, such as the United Nations Program on HIV/AIDS (UNAIDS), the World Health Organization (WHO), the World Bank, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), and the Global Fund to Fight AIDS, Tuberculosis and Malaria, provide funding to prevent HIV/AIDS infections worldwide. These funds are allocated at multiple levels, resulting in a highly complicated distribution process. An oversight agency allocates funds to various national-level decision-makers who then allocate funds to regional-level decision-makers who in turn distribute the monies to local organizations, programs, or risk groups. Simple allocation techniques are often preferred by the decision-makers at each administrative level, but such methods can lead to sub-optimal allocation of funds. Thus, incentives could be provided to decisionmakers in order to encourage optimal allocation of HIV/AIDS prevention resources. We formulate an incentive-based resource allocation model that takes into consideration strategic interactions between decision-makers in a multiple-level resource-allocation process. We analyze each decision-maker's behavior at the equilibrium and summarize the results that characterize the optimal solution to the resource-allocation problem. Our intended audiences are technical experts, decision-makers, and policy-makers in governments who can make use of incentives to encourage effective decisions regarding HIV/AIDS policy modeling and budget allocation at local levels. AD - Department of Ophthalmology, University of Western Ontario, London, Ontario N6A 4V2, Canada. Monali.Malvankar@schulich.uwo.ca AN - 22457168 AU - Malvankar-Mehta, M. S. AU - Xie, B. DA - Dec DO - 10.1007/s10729-012-9194-y 10.1007/s10729-012-9194-y. Epub 2012 Mar 29. DP - Nlm ET - 03/30 J2 - Health care management science KW - Acquired Immunodeficiency Syndrome/prevention & control Algorithms Decision Making Efficiency, Organizational HIV Infections/ prevention & control Health Care Rationing/ organization & administration Humans International Agencies/ organization & administration Models, Theoretical Motivation World Health LA - eng PY - 2012 SN - 1386-9620 (Print) 1386-9620 (Linking) SP - 327-38 ST - Optimal incentives for allocating HIV/AIDS prevention resources among multiple populations T2 - Health Care Manag Sci TI - Optimal incentives for allocating HIV/AIDS prevention resources among multiple populations UR - http://download.springer.com/static/pdf/918/art%253A10.1007%252Fs10729-012-9194-y.pdf?auth66=1364494250_6683b3a8e48dc76cf0de0d0dd71994f2&ext=.pdf VL - 15 ID - 2677 ER - TY - JOUR AB - BACKGROUND: In Uganda, isoniazid plus ethambutol is used for 6 months (6HE) during the continuation treatment phase of new tuberculosis (TB) cases. However, the World Health Organization (WHO) recommends using isoniazid plus rifampicin for 4 months (4HR) instead of 6HE. We compared the impact of a continuation phase using 6HE or 4HR on total cost and expected mortality from the perspective of the Ugandan national health system. METHODOLOGY/PRINCIPAL FINDINGS: Treatment costs and outcomes were determined by decision analysis. Median daily drug price was US$0.115 for HR and US$0.069 for HE. TB treatment failure or relapse and mortality rates associated with 6HE vs. 4HR were obtained from randomized trials and systematic reviews for HIV-negative (46% of TB cases; failure/relapse -6HE: 10.4% vs. 4HR: 5.2%; mortality -6HE: 5.6% vs. 4HR: 3.5%) and HIV-positive patients (54% of TB cases; failure or relapse -6HE: 13.7% vs. 4HR: 12.4%; mortality -6HE: 16.6% vs. 4HR: 10.5%). When the initial treatment is not successful, retreatment involves an additional 8-month drug-regimen at a cost of $110.70. The model predicted a mortality rate of 13.3% for patients treated with 6HE and 8.8% for 4HR; average treatment cost per patient was predicted at $26.07 for 6HE and $23.64 for 4HR. These results were robust to the inclusion of MDR-TB as an additional outcome after treatment failure or relapse. CONCLUSIONS/SIGNIFICANCE: Combination therapy with 4HR in the continuation phase dominates 6HE as it is associated with both lower expected costs and lower expected mortality. These data support the WHO recommendation to transition to a continuation phase comprising 4HR. AD - Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda. ymanabe@jhmi.edu AN - 22723960 AU - Manabe, Y. C. AU - Hermans, S. M. AU - Lamorde, M. AU - Castelnuovo, B. AU - Mullins, C. D. AU - Kuznik, A. DO - 10.1371/journal.pone.0039187 DP - Nlm ET - 06/23 J2 - PloS one L1 - internal-pdf://2684320912/Manabe-2012-Rifampicin for continuation phase.pdf LA - eng N1 - Manabe, Yukari C Hermans, Sabine M Lamorde, Mohammed Castelnuovo, Barbara Mullins, C Daniel Kuznik, Andreas 1R25TW009340-01/TW/FIC NIH HHS/United States IR24TW008886-02/TW/FIC NIH HHS/United States N01AI90500C/AI/NIAID NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States PLoS One. 2012;7(6):e39187. Epub 2012 Jun 18. PY - 2012 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e39187 ST - Rifampicin for continuation phase tuberculosis treatment in Uganda: a cost-effectiveness analysis T2 - PLoS One TI - Rifampicin for continuation phase tuberculosis treatment in Uganda: a cost-effectiveness analysis UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377630/pdf/pone.0039187.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377630/pdf/pone.0039187.pdf VL - 7 ID - 2678 ER - TY - JOUR AB - BACKGROUND: WHO recommends isoniazid preventive therapy (IPT) for young children in close contact with an infectious tuberculosis (TB) case. No models have examined the cost effectiveness of this recommendation. METHODS: A decision analysis model was developed to estimate health and economic outcomes of five TB infection screening strategies in young household contacts. In the no-testing strategy, children received IPT based on age and reported exposure. Other strategies included testing for infection with a tuberculin skin test (TST), interferon gamma release assay (IGRA) or IGRA after TST. Markov modelling included age-specific disease states and probabilities while considering risk of re-infection in a high-burden country. RESULTS: Among the 0-2-year-old cohort, the no-testing strategy was most cost effective. The discounted societal cost of care per life year saved ranged from US$237 (no-testing) to US$538 (IGRA only testing). Among the 3-5-year-old cohort, strategies employing an IGRA after a negative TST were most effective, but were associated with significant incremental cost (incremental cost-effectiveness ratio >US$233 000), depending on the rate of Mycobacterium tuberculosis infection. CONCLUSION: Screening for M tuberculosis infection and provision of IPT in young children is a highly cost-effective intervention. Screening without testing for M tuberculosis infection is the most cost-effective strategy in 0-2-year-old children and the preferred strategy in 3-5-year-old children. Lack of testing capacity should therefore not be a barrier to IPT delivery. These findings highlight the cost effectiveness of contact tracing and IPT delivery in young children exposed to TB in high-burden countries. AD - Section on Retrovirology and Global Health, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA. AN - 22717944 AU - Mandalakas, A. M. AU - Hesseling, A. C. AU - Gie, R. P. AU - Schaaf, H. S. AU - Marais, B. J. AU - Sinanovic, E. DA - Jun 20 DO - thoraxjnl-2011-200933 [pii] 10.1136/thoraxjnl-2011-200933 [doi] DP - Nlm ET - 06/22 LA - Eng N1 - Mandalakas, Anna M Hesseling, Anneke C Gie, Robert P Schaaf, H S Marais, Ben J Sinanovic, Edina Thorax Thorax. 2012 Jun 20. PY - 2012 RN - fulltext fulltext_1208 SN - 1468-3296 (Electronic) 0040-6376 (Linking) ST - Modelling the cost-effectiveness of strategies to prevent tuberculosis in child contacts in a high-burden setting T2 - Thorax TI - Modelling the cost-effectiveness of strategies to prevent tuberculosis in child contacts in a high-burden setting UR - http://thorax.bmj.com/content/early/2012/06/19/thoraxjnl-2011-200933 ID - 2679 ER - TY - JOUR AB - We study a model of disease transmission with continuous age-structure for latently infected individuals and for infectious individuals. The model is very appropriate for tuberculosis. Key theorems, including asymptotic smoothness and uniform persistence, are proven by reformulating the system as a system of Volterra integral equations. The basic reproduction number R0 is calculated. For R0 < 1, the disease-free equilibrium is globally asymptotically stable. For R0 > 1, a Lyapunov functional is used to show that the endemic equilibrium is globally stable amongst solutions for which the disease is present. Finally, some special cases are considered. AD - Department of Mathematics, Wilfrid Laurier University, Waterloo, Ontario, Canada. ccmcc8@gmail.com AN - 23311424 AU - McCluskey, C. C. DA - Oct DO - 10.3934/mbe.2012.9.819 IS - 4 KW - Age Distribution Communicable Diseases/*epidemiology Computer Simulation Disease Outbreaks/*statistics & numerical data Disease Transmission, Infectious/*statistics & numerical data Humans *Models, Statistical *Proportional Hazards Models Risk Assessment Risk Factors N1 - McCluskey, C Connell eng Research Support, Non-U.S. Gov't 2013/01/15 06:00 Math Biosci Eng. 2012 Oct;9(4):819-41. doi: 10.3934/mbe.2012.9.819. PY - 2012 SN - 1551-0018 (Electronic) 1547-1063 (Linking) SP - 819-41 ST - Global stability for an SEI epidemiological model with continuous age-structure in the exposed and infectious classes T2 - Math Biosci Eng TI - Global stability for an SEI epidemiological model with continuous age-structure in the exposed and infectious classes UR - https://www.ncbi.nlm.nih.gov/pubmed/23311424 VL - 9 ID - 2245 ER - TY - JOUR AB - BACKGROUND: The Xpert MTB/RIF test enables rapid detection of tuberculosis (TB) and rifampicin resistance. The World Health Organization recommends Xpert for initial diagnosis in individuals suspected of having multidrug-resistant TB (MDR-TB) or HIV-associated TB, and many countries are moving quickly toward adopting Xpert. As roll-out proceeds, it is essential to understand the potential health impact and cost-effectiveness of diagnostic strategies based on Xpert. METHODS AND FINDINGS: We evaluated potential health and economic consequences of implementing Xpert in five southern African countries--Botswana, Lesotho, Namibia, South Africa, and Swaziland--where drug resistance and TB-HIV coinfection are prevalent. Using a calibrated, dynamic mathematical model, we compared the status quo diagnostic algorithm, emphasizing sputum smear, against an algorithm incorporating Xpert for initial diagnosis. Results were projected over 10- and 20-y time periods starting from 2012. Compared to status quo, implementation of Xpert would avert 132,000 (95% CI: 55,000-284,000) TB cases and 182,000 (97,000-302,000) TB deaths in southern Africa over the 10 y following introduction, and would reduce prevalence by 28% (14%-40%) by 2022, with more modest reductions in incidence. Health system costs are projected to increase substantially with Xpert, by US$460 million (294-699 million) over 10 y. Antiretroviral therapy for HIV represents a substantial fraction of these additional costs, because of improved survival in TB/HIV-infected populations through better TB case-finding and treatment. Costs for treating MDR-TB are also expected to rise significantly with Xpert scale-up. Relative to status quo, Xpert has an estimated cost-effectiveness of US$959 (633-1,485) per disability-adjusted life-year averted over 10 y. Across countries, cost-effectiveness ratios ranged from US$792 (482-1,785) in Swaziland to US$1,257 (767-2,276) in Botswana. Assessing outcomes over a 10-y period focuses on the near-term consequences of Xpert adoption, but the cost-effectiveness results are conservative, with cost-effectiveness ratios assessed over a 20-y time horizon approximately 20% lower than the 10-y values. CONCLUSIONS: Introduction of Xpert could substantially change TB morbidity and mortality through improved case-finding and treatment, with more limited impact on long-term transmission dynamics. Despite extant uncertainty about TB natural history and intervention impact in southern Africa, adoption of Xpert evidently offers reasonable value for its cost, based on conventional benchmarks for cost-effectiveness. However, the additional financial burden would be substantial, including significant increases in costs for treating HIV and MDR-TB. Given the fundamental influence of HIV on TB dynamics and intervention costs, care should be taken when interpreting the results of this analysis outside of settings with high HIV prevalence. AD - Center for Health Decision Sciences, Harvard School of Public Health, Boston, Massachusetts, United States of America. nmenzies@fas.harvard.edu AN - 23185139 AU - Menzies, N. A. AU - Cohen, T. AU - Lin, H. H. AU - Murray, M. AU - Salomon, J. A. DO - 10.1371/journal.pmed.1001347 10.1371/journal.pmed.1001347. Epub 2012 Nov 20. DP - Nlm ET - 11/28 J2 - PLoS medicine L1 - internal-pdf://2910167374/Menzies-2012-Population health impact and cost.pdf LA - eng PY - 2012 SN - 1549-1676 (Electronic) 1549-1277 (Linking) SP - e1001347 ST - Population health impact and cost-effectiveness of tuberculosis diagnosis with Xpert MTB/RIF: a dynamic simulation and economic evaluation T2 - PLoS Med TI - Population health impact and cost-effectiveness of tuberculosis diagnosis with Xpert MTB/RIF: a dynamic simulation and economic evaluation UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3502465/pdf/pmed.1001347.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3502465/pdf/pmed.1001347.pdf VL - 9 ID - 2680 ER - TY - JOUR AB - OBJECTIVE: We estimated the incremental cost and impact on diagnosis and treatment uptake of national rollout of Xpert MTB/RIF technology (Xpert) for the diagnosis of pulmonary TB above the cost of current guidelines for the years 2011 to 2016 in South Africa. METHODS: We parameterised a population-level decision model with data from national-level TB databases (n = 199,511) and implementation studies. The model follows cohorts of TB suspects from diagnosis to treatment under current diagnostic guidelines or an algorithm that includes Xpert. Assumptions include the number of TB suspects, symptom prevalence of 5.5%, annual suspect growth rate of 10%, and 2010 public-sector salaries and drug and service delivery costs. Xpert test costs are based on data from an in-country pilot evaluation and assumptions about when global volumes allowing cartridge discounts will be reached. RESULTS: At full scale, Xpert will increase the number of TB cases diagnosed per year by 30%-37% and the number of MDR-TB cases diagnosed by 69%-71%. It will diagnose 81% of patients after the first visit, compared to 46% currently. The cost of TB diagnosis per suspect will increase by 55% to USD 60-61 and the cost of diagnosis and treatment per TB case treated by 8% to USD 797-873. The incremental capital cost of the Xpert scale-up will be USD 22 million and the incremental recurrent cost USD 287-316 million over six years. CONCLUSION: Xpert will increase both the number of TB cases diagnosed and treated and the cost of TB diagnosis. These results do not include savings due to reduced transmission of TB as a result of earlier diagnosis and treatment initiation. AD - Health Economics and Epidemiology Research Office (HE2RO), Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. AN - 22693561 AU - Meyer-Rath, G. AU - Schnippel, K. AU - Long, L. AU - Macleod, W. AU - Sanne, I. AU - Stevens, W. AU - Pillay, S. AU - Pillay, Y. AU - Rosen, S. DO - 10.1371/journal.pone.0036966 PONE-D-11-25103 [pii] L1 - internal-pdf://3937058099/Meyer-Rath-2012-The Impact and Cost of Scaling.pdf LA - eng N1 - Meyer-Rath, Gesine Schnippel, Kathryn Long, Lawrence Macleod, William Sanne, Ian Stevens, Wendy Pillay, Sagie Pillay, Yogan Rosen, Sydney United States PloS one PLoS One. 2012;7(5):e36966. Epub 2012 May 31. PY - 2012 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e36966 ST - The Impact and Cost of Scaling up GeneXpert MTB/RIF in South Africa T2 - PLoS One TI - The Impact and Cost of Scaling up GeneXpert MTB/RIF in South Africa UR - http://www.ncbi.nlm.nih.gov/pubmed/22693561http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365041/pdf/pone.0036966.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365041/pdf/pone.0036966.pdf VL - 7 ID - 2681 ER - TY - JOUR AB - Tuberculosis (TB) remains a major global health problem. A possible risk factor for TB is diabetes (DM), which is predicted to increase dramatically over the next two decades, particularly in low and middle income countries, where TB is widespread. This study aimed to assess the strength of the association between TB and DM. We present a deterministic model for TB in a community in order to determine the impact of DM in the spread of the disease. The important mathematical features of the TB model are thoroughly investigated. The epidemic threshold known as the basic reproduction number and equilibria for the model are determined and stabilities analyzed. The model is numerically analyzed to assess the impact of DM on the transmission dynamics of TB. We perform sensitivity analysis on the key parameters that drive the disease dynamics in order to determine their relative importance to disease transmission and prevalence. Numerical simulations suggest that DM enhances the TB transmission and progression to active TB in a community. The results suggest that there is a need for increased attention to intervention strategies such as the chemoprophylaxis of TB latent individuals and treatment of active TB in people with DM, which may include testing for suspected diabetes, improved glucose control, and increased clinical and therapeutic monitoring in order to reduce the burden of the disease. AD - Univ Douala, Dept Math & Comp Sci, Fac Sci, Lab Appl Math, Douala, Cameroon Univ Yaounde I, Fac Sci, Dept Math, Yaounde, Cameroon Univ Yaounde I, Dept Math & Phys, Natl Adv Sch Engn Polytech, Yaounde, Cameroon Univ Yaounde I, LIRIMA, Project GRIMCAPE, Yaounde, Cameroon UMI 209 IRD UPMC UMMISCO, Bondy, France Abdus Salam Int Ctr Theoret Phys, I-34014 Trieste, Italy AN - WOS:000306248900009 AU - Moualeu, D. P. AU - Bowong, S. AU - Tewa, J. J. AU - Emvudu, Y. DO - 10.1051/mmnp/20127309 IS - 3 J2 - Math Model Nat Pheno KW - nonlinear dynamical systems epidemiological models diabetes tuberculosis stability bifurcation exogenous reinfection pulmonary tuberculosis mellitus model prevalence epidemics chemoprophylaxis LA - English N1 - 972am Times Cited:3 Cited References Count:49 PY - 2012 SN - 0973-5348 SP - 117-146 ST - Analysis of The Impact of Diabetes on The Dynamical Transmission of Tuberculosis T2 - Mathematical Modelling of Natural Phenomena TI - Analysis of The Impact of Diabetes on The Dynamical Transmission of Tuberculosis UR - ://WOS:000306248900009 VL - 7 ID - 4884 ER - TY - JOUR AB - A deterministic model for evaluating the impact of voluntary testing and treatment on the transmission dynamics of tuberculosis is formulated and analyzed. The epidemiological threshold, known as the reproduction number is derived and qualitatively used to investigate the existence and stability of the associated equilibrium of the model system. The disease-free equilibrium is shown to be locally-asymptotically stable when the reproductive number is less than unity, and unstable if this threshold parameter exceeds unity. It is shown, using the Centre Manifold theory, that the model undergoes the phenomenon of backward bifurcation where the stable disease-free equilibrium coexists with a stable endemic equilibrium when the associated reproduction number is less than unity. The analysis of the reproduction number suggests that voluntary tuberculosis testing and treatment may lead to effective control of tuberculosis. Furthermore, numerical simulations support the fact that an increase voluntary tuberculosis testing and treatment have a positive impact in controlling the spread of tuberculosis in the community. AD - Natl Univ Sci & Technol, Dept Appl Math, Modeling Biomed Syst Res Grp, Bulawayo, Zimbabwe Univ Zimbabwe, Dept Math, Harare, Zimbabwe AN - WOS:000303942200008 AU - Mushayabasa, S. AU - Bhunu, C. P. DA - Jul DO - Artn 1250029 10.1142/S1793524511001726 IS - 4 J2 - Int J Biomath KW - tb model case findings treatment reproductive number stability exogenous reinfection recurrent tuberculosis epidemiologic models hiv strains infection risk cohort sir LA - English N1 - 941db Times Cited:4 Cited References Count:43 PY - 2012 SN - 1793-5245 ST - Modeling the Impact of Voluntary Testing and Treatment on Tuberculosis Transmission Dynamics T2 - International Journal of Biomathematics TI - Modeling the Impact of Voluntary Testing and Treatment on Tuberculosis Transmission Dynamics UR - ://WOS:000303942200008 VL - 5 ID - 4885 ER - TY - JOUR AB - The epidemiological mechanisms behind the W-shaped age-specific influenza mortality during the Spanish influenza (H1N1) pandemic 1918-19 have yet to be fully clarified. The present study aimed to develop a formal hypothesis: tuberculosis (TB) was associated with the W-shaped influenza mortality from 1918-19. Three pieces of epidemiological information were assessed: (i) the epidemic records containing the age-specific numbers of cases and deaths of influenza from 1918-19, (ii) an outbreak record of influenza in a Swiss TB sanatorium during the pandemic, and (iii) the age-dependent TB mortality over time in the early 20th century. Analyzing the data (i), we found that the W-shaped pattern was not only seen in mortality but also in the age-specific case fatality ratio, suggesting the presence of underlying age-specific risk factor(s) of influenza death among young adults. From the data (ii), TB was shown to be associated with influenza death (P = 0.09), and there was no influenza death among non-TB controls. The data (iii) were analyzed by employing the age-period-cohort model, revealing harvesting effect in the period function of TB mortality shortly after the 1918-19 pandemic. These findings suggest that it is worthwhile to further explore the role of TB in characterizing the age-specific risk of influenza death. AD - Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 358GA Utrecht, The Netherlands. AN - 22848231 AU - Oei, W. AU - Nishiura, H. DO - 10.1155/2012/124861 10.1155/2012/124861. Epub 2012 Jul 17. DP - Nlm ET - 08/01 J2 - Computational and mathematical methods in medicine KW - Adolescent Adult Aged Aged, 80 and over Child Child, Preschool Cohort Studies Cytokines/metabolism Female Humans Influenza A Virus, H1N1 Subtype/ metabolism Influenza, Human/ complications/ mortality Male Middle Aged Models, Statistical Models, Theoretical Pandemics Risk Time Factors Tuberculosis/ complications/ mortality LA - eng PY - 2012 SN - 1748-6718 (Electronic) 1748-670X (Linking) SP - 124861 ST - The relationship between tuberculosis and influenza death during the influenza (H1N1) pandemic from 1918-19 T2 - Comput Math Methods Med TI - The relationship between tuberculosis and influenza death during the influenza (H1N1) pandemic from 1918-19 UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405656/pdf/CMMM2012-124861.pdf VL - 2012 ID - 2682 ER - TY - JOUR AB - Drug-resistant tuberculosis (TB) is a serious emerging problem in many low-resource countries. TB control programmes are uncertain of which drug susceptibility tests (DSTs) to use and when to test patients.Wepredicted the potential cost-effectiveness of different DST strategies, in settings with varying prevalence of drug resistance. Using decision analysis, we assessed the cost-effectiveness of conventional and rapid DSTs for previously diagnosed smear-positive TB cases. Five different time-points were considered for administering DSTs. Different initial drug resistance and HIV scenarios were also considered. All DST scenarios in the wide range of settings considered were found to be cost-effective. The strategy of performing a rapid DST that detects any form of isoniazid (INH) and rifampicin (RIF) resistance for all patients before the initiation of treatment was predicted to be the most cost- effective strategy. In a setting with moderate drug resistance, the cost per disability-adjusted life year gained was as low as US$744. Our findings support the roll-out of rapid drug susceptibility testing at the moment of diagnosis to detect any form of INH and RIF resistance in all countries with moderate or greater burdens of drug-resistant TB. AU - Oxlade, O. AU - Falzon, D. AU - Menzies, D. L1 - internal-pdf://1428777739/626.full.pdf LB - p28326 PY - 2012 RN - fulltext fulltext_1208 SP - 626-634 ST - The impact and cost-effectiveness of strategies to detect drug-resistant tuberculosis T2 - Europeran Respiratory Journal TI - The impact and cost-effectiveness of strategies to detect drug-resistant tuberculosis VL - 39 ID - 2683 ER - TY - JOUR AB - The resurgence of tuberculosis in the 1990s and the emergence of drug-resistant tuberculosis in the first decade of the 21st century increased the importance of epidemiological models for the disease. Due to slow progression of tuberculosis, the transmission dynamics and its long-term effects can often be better observed and predicted using simulations of epidemiological models. This study provides a review of earlier study on modeling different aspects of tuberculosis dynamics. The models simulate tuberculosis transmission dynamics, treatment, drug resistance, control strategies for increasing compliance to treatment, HIV/TB co-infection, and patient groups. The models are based on various mathematical systems, such as systems of ordinary differential equations, simulation models. and Markov Chain Monte Carlo methods. The inferences from the models are justified by case studies and statistical analysis of TB patient datasets. (C) 2012 Elsevier Inc. All rights reserved. AD - [Ozcaglar, Cagri; Shabbeer, Amina; Yener, Buelent; Bennett, Kristin P.] Rensselaer Polytech Inst, Dept Comp Sci, Troy, NY 12180 USA. [Bennett, Kristin P.] Rensselaer Polytech Inst, Dept Math Sci, Troy, NY 12180 USA. [Vandenberg, Scott L.] Siena Colloge, Dept Comp Sci, Loudonville, NY USA. Ozcaglar, C (reprint author), Rensselaer Polytech Inst, Dept Comp Sci, Troy, NY 12180 USA. ozcagc2@cs.rpi.edu; shabba@cs.rpi.edu; vandenberg@siena.edu; yener@cs.rpi.edu; bennek@rpi.edu AN - WOS:000303231000001 AU - Ozcaglar, C. AU - Shabbeer, A. AU - Vandenberg, S. L. AU - Yener, B. AU - Bennett, K. P. DA - Apr DO - 10.1016/j.mbs.2012.02.003 IS - 2 J2 - Math. Biosci. KW - Tuberculosis Epidemiological models Transmission Drug resistance Treatment Co-epidemics of HIV and tuberculosis drug-resistant tuberculosis approximate bayesian computation intrinsic transmission dynamics therapy strategy dots pulmonary tuberculosis heterogeneous populations exogenous reinfection antibiotic-resistance united-states age-structure Life Sciences & Biomedicine - Other Topics Mathematical & Computational Biology L1 - internal-pdf://1945561333/Ozcaglar-2012-Epidemiological models of Mycoba.pdf LA - English M3 - Review N1 - ISI Document Delivery No.: 931PE Times Cited: 17 Cited Reference Count: 113 Ozcaglar, Cagri Shabbeer, Amina Vandenberg, Scott L. Yener, Buelent Bennett, Kristin P. Nih [r01lm009731] We would like to thank Dr. Peter Kramer (Rensselaer Polytechnic Institute) and Dr. Ted Cohen (Harvard School of Public Health) for their assistance. We also thank two anonymous reviewers for their comments and suggestions. This study was supported by NIH R01LM009731. 19 2 26 Elsevier science inc New york PY - 2012 SN - 0025-5564 SP - 77-96 ST - Epidemiological models of Mycobacterium tuberculosis complex infections T2 - Mathematical Biosciences TI - Epidemiological models of Mycobacterium tuberculosis complex infections UR - ://WOS:000303231000001 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330831/pdf/nihms362471.pdf VL - 236 ID - 5671 ER - TY - JOUR AB - SETTING: A combination of environmental measurement and mathematical modelling may provide a more quantitative method to inform the tuberculosis (TB) screening process in non-household settings following diagnosis of an infectious case. OBJECTIVE: To explore different methods for environmental assessment and mathematical modelling to predict TB transmission risk and devise a tool for public health practitioners for use in TB investigations. DESIGN: Parameters including air flow, carbon dioxide (CO(2)) and airborne particles were measured over 3 working days in an office with a staff member with infectious TB. The Wells-Riley model was applied to predict transmission rates. RESULTS: The results suggested that poor ventilation and well-mixed air led to equal exposure of staff members to airborne TB bacilli. The model's prediction of attack rate (42%) supported the actual number of infections that occurred (50%). CONCLUSION: This study supports the use of environmental assessment and modelling as a tool for public health practitioners to determine the extent of TB exposure and to inform TB screening strategies. CO(2) and airborne particle profiles, both measured via a handheld device, provide the greatest practicality and amount of information that public health practitioners can use. Further studies will validate the level of screening required related to these measurements. AD - Healthy Infrastructure Research Centre, Civil, Environmental and Geomatic Engineering, University College London, London, UK; Department of Microbiology and Infectious Diseases, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK. AN - 22691609 AU - Pankhurst, L. J. AU - Anaraki, S. AU - Lai, K. M. DA - Aug DO - ijtld110572 [pii] 10.5588/ijtld.11.0572 [doi] DP - Nlm ET - 06/14 LA - eng N1 - Pankhurst, L J Anaraki, S Lai, K M France The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Int J Tuberc Lung Dis. 2012 Aug;16(8):1023-9. Epub 2012 Jun 11. PY - 2012 RN - fulltext fulltext_1208 SN - 1815-7920 (Electronic) 1027-3719 (Linking) SP - 1023-9 ST - Combining environmental assessment and contact investigations to make tuberculosis screening decisions T2 - Int J Tuberc Lung Dis TI - Combining environmental assessment and contact investigations to make tuberculosis screening decisions VL - 16 ID - 2684 ER - TY - JOUR AB - BACKGROUND: Regimens for isoniazid-based preventive therapy (IPT) for tuberculosis (TB) in HIV-infected individuals have not been widely adopted given concerns regarding efficacy, adherence and drug resistance. Further, the cost-effectiveness of IPT has not been studied in India. METHODS: We used an HIV/TB model to project TB incidence, life expectancy, cost and incremental cost-effectiveness of six months of isoniazid plus ethambutol (6EH), thirty-six months of isoniazid (36H) and no IPT for HIV-infected patients in India. Model input parameters included a median CD4 count of 324 cells/mm(3), and a rate ratio of developing TB of 0.35 for 6EH and 0.22 for 36H at three years as compared to no IPT. Results of 6EH and 36H were also compared to six months of isoniazid (6H), three months of isoniazid plus rifampin (3RH) and three months of isoniazid plus rifapentine (3RPTH). RESULTS: Projected TB incidence decreased in the 6EH and 36H regimens by 51% and 62% respectively at three-year follow-up compared to no IPT. Without IPT, projected life expectancy was 136.1 months at a lifetime per person cost of $5,630. 6EH increased life expectancy by 0.8 months at an additional per person cost of $100 (incremental cost-effectiveness ratio (ICER) of $1,490/year of life saved (YLS)). 36H further increased life expectancy by 0.2 months with an additional per person cost of $55 (ICER of $3,120/YLS). The projected clinical impact of 6EH was comparable to 6H and 3RH; however when compared to these other options, 6EH was no longer cost-effective given the high cost of ethambutol. Results were sensitive to baseline CD4 count and adherence. CONCLUSIONS: Three, six and thirty-six-month regimens of isoniazid-based therapy are effective in preventing TB. Three months of isoniazid plus rifampin and six-months of isoniazid are similarly cost-effective in India, and should be considered part of HIV care. AD - Section of Hospital Medicine, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois, USA. mpho@medicine.bsd.uchicago.edu AN - 22558301 AU - Pho, M. T. AU - Swaminathan, S. AU - Kumarasamy, N. AU - Losina, E. AU - Ponnuraja, C. AU - Uhler, L. M. AU - Scott, C. A. AU - Mayer, K. H. AU - Freedberg, K. A. AU - Walensky, R. P. DO - 10.1371/journal.pone.0036001 PONE-D-11-22038 [pii] L1 - internal-pdf://2572574902/Pho-2012-The cost-effectiveness of tuberculosi.pdf LA - eng N1 - Pho, Mai T Swaminathan, Soumya Kumarasamy, Nagalingeswaran Losina, Elena Ponnuraja, C Uhler, Lauren M Scott, Callie A Mayer, Kenneth H Freedberg, Kenneth A Walensky, Rochelle P D43-TW000237/TW/FIC NIH HHS/United States K24-AI062476/AI/NIAID NIH HHS/United States K24-AR057827/AR/NIAMS NIH HHS/United States R01 AI058736/AI/NIAID NIH HHS/United States R01-AI058736/AI/NIAID NIH HHS/United States R37 AI042006/AI/NIAID NIH HHS/United States T32 AI07433/AI/NIAID NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United States PloS one PLoS One. 2012;7(4):e36001. Epub 2012 Apr 30. PY - 2012 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e36001 ST - The cost-effectiveness of tuberculosis preventive therapy for HIV-infected individuals in southern India: a trial-based analysis T2 - PLoS One TI - The cost-effectiveness of tuberculosis preventive therapy for HIV-infected individuals in southern India: a trial-based analysis UR - http://www.ncbi.nlm.nih.gov/pubmed/22558301http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340407/pdf/pone.0036001.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340407/pdf/pone.0036001.pdf VL - 7 ID - 2685 ER - TY - JOUR AB - A new host-pathogen model is described that simulates HIV-MTB co-infection and treatment, with the objective of testing treatment strategies. The model includes CD4+ and CD8+ T cells, resting and activated macrophages, HIV and Mycobacterium tuberculosis (MTB). For TB presentation at various stages of HIV disease in a co-infected individual, combined treatment strategies were tested with different relative timings of treatment for each infection. The stages were early HIV disease, late HIV disease and AIDS. The main strategies were TB treatment followed by anti-retroviral therapy (ART) after delays of 15 days, 2 months and 6 months. ART followed by TB treatment was an additional strategy that was tested. Treatment was simulated with and without drug interaction. Simulation results were that TB treatment first followed by ART after a stage-dependent delay has the best outcome. During early HIV disease a 6 month delay is acceptable. During late HIV disease, a 2 month delay is best. During AIDS it is better to start ART after 15 days. However, drug interaction works against the benefits of early ART. These results agree with expert reviews and clinical trials. AD - Physics-Durban Academic Group (School of Chemistry and Physics), University of KwaZulu-Natal, Westville Campus, Durban, South Africa. AN - 23209581 AU - Ramkissoon, S. AU - Mwambi, H. G. AU - Matthews, A. P. DO - 10.1371/journal.pone.0049492 10.1371/journal.pone.0049492. Epub 2012 Nov 28. DP - Nlm ET - 12/05 J2 - PloS one LA - eng PY - 2012 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e49492 ST - Modelling HIV and MTB co-infection including combined treatment strategies T2 - PLoS One TI - Modelling HIV and MTB co-infection including combined treatment strategies UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509125/pdf/pone.0049492.pdf VL - 7 ID - 2687 ER - TY - JOUR AB - Incidence and mortality due to tuberculosis (TB) have been decreasing worldwide. Given that TB is a cosmopolitan disease, proper surveillance and evaluation are critical for controlling dissemination. Herein, mathematical modeling was performed in order to: 1) demonstrate a correlation between the incidence of TB in HIV-free patients in the US and Germany, and their corresponding mortality rates; 2) show the utility of the newly developed D-R algorithm for analyzing and predicting the incidence of TB in both countries; and 3) inform us on population death rates due to TB in HIV-negative patients. Using data published by the World Health Organization between 1990 and 2009, the relationship between incidence and mortality that could not be ascribed to HIV infection was evaluated. Using linear, quadratic and cubic curves, we found that a cubic function provided the best fit with the data in both the US (Y = 2.3588+2.2459X+61.1639X(2)-60.104X(3)) and Germany (Y = 1.9271+9.4967X+18.3824X(2)-10.350X(3)) where the correlation coefficient (R) between incidence and mortality was 0.995 and 0.993, respectively. Second, we demonstrated that fitted curves using the D-R model were equal to or better than those generated using the GM(1,1) algorithm as exemplified in the relative values for Sum of Squares of Error, Relative Standard Error, Mean Absolute Deviation, Average Relative Error, and Mean Absolute Percentage Error. Finally, future trends using both the D-R and the classic GM(1,1) models predicted a continued decline in infection and mortality rates of TB in HIV-negative patients rates extending to 2015 assuming no changes to diagnosis or treatment regimens are enacted. AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China. AN - 23077479 AU - Ren, Y. AU - Ding, F. AU - Suo, S. AU - Bu, R. E. AU - Zarlenga, D. S. AU - Ren, X. C2 - 3471926 DO - 10.1371/journal.pone.0042055 DP - NLM ET - 2012/10/19 IS - 10 J2 - PloS one LA - eng N1 - Ren, Yudong Ding, Fan Suo, Siqingaowa Bu, Ri-e Zarlenga, Dante S Ren, Xiaofeng Research Support, Non-U.S. Gov't United States PLoS One. 2012;7(10):e42055. doi: 10.1371/journal.pone.0042055. Epub 2012 Oct 15. PY - 2012 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e42055 ST - Incidence rates and deaths of tuberculosis in HIV-negative patients in the United States and Germany as analyzed by new predictive model for infection T2 - PLoS One TI - Incidence rates and deaths of tuberculosis in HIV-negative patients in the United States and Germany as analyzed by new predictive model for infection UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471926/pdf/pone.0042055.pdf VL - 7 ID - 4371 ER - TY - JOUR AB - Historically, dosing regimens for the treatment of tuberculosis (TB) have been proposed in an empirical manner. Dose selection has often been the result of efficacy trials in which drugs were administered regardless of the magnitude of the effect of demographic factors on drug disposition. This has created challenges for the prescription of fixed-dose combinations with novel therapeutic agents. The objectives of this investigation were to evaluate the impact of body weight on the overall systemic exposure to pyrazinamide (PZA) and to assess whether the use of one fixed dose, without adjustment according to weight, would ensure target exposure and safety requirements across the overall patient population. Using a population pharmacokinetic model, simulation scenarios were explored based on population demographics from clinical trials in TB patients and on historical hepatotoxicity data. The systemic drug exposure (area under the concentration-time curve [AUC]), peak concentrations (the maximum concentration of drug in serum [C(max)]), the time above the MIC (t > MIC), and the risk of hepatotoxicity were evaluated for the current weight-banded regimen and compared to fixed doses under the assumption that pharmacokinetic differences are the primary drivers of toxicity. Evaluation of the standard weight banding reveals that more than 50% of subjects in the weight range of 45 to 55 kg remain below the proposed target exposure to PZA. In contrast, the use of a fixed 1,500-mg dose resulted in a lower proportion of subjects under the target value, with a 0.2% average overall increase in the risk of hepatotoxicity. Our results strongly support the use of a fixed-dose regimen for PZA in coformulation or combination with novel therapeutic agents. AD - Clinical Pharmacology Modelling & Simulation, GlaxoSmithKline, Uxbridge, United Kingdom. AN - 22777045 AU - Sahota, T. AU - Della Pasqua, O. DA - Nov DO - 10.1128/aac.05988-11 10.1128/AAC.05988-11. Epub 2012 Jul 9. DP - Nlm ET - 07/11 J2 - Antimicrobial agents and chemotherapy LA - eng PY - 2012 SN - 1098-6596 (Electronic) 0066-4804 (Linking) SP - 5442-9 ST - Feasibility of a fixed-dose regimen of pyrazinamide and its impact on systemic drug exposure and liver safety in patients with tuberculosis T2 - Antimicrob Agents Chemother TI - Feasibility of a fixed-dose regimen of pyrazinamide and its impact on systemic drug exposure and liver safety in patients with tuberculosis UR - http://aac.asm.org/content/56/11/5442.full.pdf VL - 56 ID - 2688 ER - TY - JOUR AB - The emergence of highly drug-resistant tuberculosis (TB) and interactions between TB and HIV epidemics pose serious challenges for TB control. Previous researchers have presented several hypotheses for why HIV-coinfected TB patients may suffer an increased risk of drug-resistant TB (DRTB) compared to other TB patients. Although some studies have found a positive association between an individual's HIV status and his or her subsequent risk of multidrug-resistant TB (MDRTB), the observed individual-level relationship between HIV and DRTB varies substantially among settings. Here, we develop a modeling framework to explore the effect of HIV on the dynamics of DRTB. The model captures the acquisition of resistance to important classes of TB drugs, imposes fitness costs associated with resistance-conferring mutations, and allows for subsequent restoration of fitness because of compensatory mutations. Despite uncertainty in several key parameters, we demonstrate epidemic behavior that is robust over a range of assumptions. Whereas HIV facilitates the emergence of MDRTB within a community over several decades, HIV-seropositive individuals presenting with TB may, counterintuitively, be at lower risk of drug-resistant TB at early stages of the co-epidemic. This situation arises because many individuals with incident HIV infection will already harbor latent Mycobacterium tuberculosis infection acquired at an earlier time when drug resistance was less prevalent. We find that the rise of HIV can increase the prevalence of MDRTB within populations even as it lowers the average fitness of circulating MDRTB strains compared to similar populations unaffected by HIV. Preferential social mixing among individuals with similar HIV status and lower average CD4 counts among HIV-seropositive individuals further increase the expected burden of MDRTB. This model suggests that the individual-level association between HIV and drug-resistant forms of TB is dynamic, and therefore, cross-sectional studies that do not report a positive individual-level association will not provide assurance that HIV does not exacerbate the burden of resistant TB in the community. AD - Department of Medicine, Brigham and Women's Hospital, 641 Huntington Avenue, Boston, MA 02115, USA. rinat@theory.ioffe.ru AN - 22623743 AU - Sergeev, R. AU - Colijn, C. AU - Murray, M. AU - Cohen, T. DA - May 23 DO - 4/135/135ra67 [pii] 10.1126/scitranslmed.3003815 [doi] DP - Nlm ET - 05/25 L1 - internal-pdf://2602472098/Sergeev-2012-Modeling the dynamic relationship.pdf LA - eng N1 - Sergeev, Rinat Colijn, Caroline Murray, Megan Cohen, Ted DP2OD006663/OD/NIH HHS/United States U54 GM088558/GM/NIGMS NIH HHS/United States U54 GM088558-02/GM/NIGMS NIH HHS/United States U54GM088558./GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural United States Science translational medicine Nihms381285 Sci Transl Med. 2012 May 23;4(135):135ra67. PY - 2012 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1946-6242 (Electronic) 1946-6234 (Linking) SP - 135ra67 ST - Modeling the dynamic relationship between HIV and the risk of drug-resistant tuberculosis T2 - Sci Transl Med TI - Modeling the dynamic relationship between HIV and the risk of drug-resistant tuberculosis UR - http://stm.sciencemag.org/content/4/135/135ra67http://stm.sciencemag.org/content/4/135/135ra67.short http://stm.sciencemag.org/content/scitransmed/4/135/135ra67.full.pdf VL - 4 ID - 2689 ER - TY - JOUR AB - The spread of tuberculosis is studied through a two-patch epidemiological model. We assume that susceptible individuals can migrate between the twopatches, but not infective individuals. We compute the basic reproduction number R-0, the disease-free equilibrium, two boundaries endemic equilibria which we define as the existence of the disease in one sub-population while the disease dies out in other sub-population, and the endemic equilibrium when the disease persists in the two sub-populations for specific conditions. We also determine stability criteria for the disease-free equilibrium, boundaries endemic equilibria and the endemic equilibrium. Numerical results are provided to illustrate theoretical results. (C) 2011 Elsevier Inc. All rights reserved. AD - Univ Douala, Lab Appl Math, Dept Math & Comp Sci, Fac Sci, Douala, Cameroon Univ Yaounde 1, Dept Math & Phys, Natl Adv Sch Engn Polytech, Yaounde, Cameroon Univ Yaounde 1, Dept Math, Fac Sci, Yaounde, Cameroon IRD UPMC UMMISCO, UMI 209, Bondy, France Univ Yaounde 1, Project Team GRIMCAPE, LIRIMA, Yaounde, Cameroon AN - WOS:000301404600012 AU - Tewa, J. J. AU - Bowong, S. AU - Mewoli, B. DA - Jun DO - 10.1016/j.apm.2011.09.004 IS - 6 J2 - Appl Math Model KW - patches epidemiological models tuberculosis stability lyapunov functions drug-resistant tuberculosis heterogeneous populations exogenous reinfection disease transmission reproduction numbers epidemiologic models global properties stability equilibria systems LA - English N1 - 907ga Times Cited:7 Cited References Count:55 PY - 2012 SN - 0307-904x SP - 2466-2485 ST - Mathematical analysis of two-patch model for the dynamical transmission of tuberculosis T2 - Applied Mathematical Modelling TI - Mathematical analysis of two-patch model for the dynamical transmission of tuberculosis UR - ://WOS:000301404600012 VL - 36 ID - 4878 ER - TY - JOUR AB - The spread of tuberculosis is studied through a two-patch epidemiological system SE1 ... EnI which incorporates migrations from one patch to another just by susceptible individuals. Our model is consider with bilinear incidence and migration between two patches, where infected and infectious individuals cannot migrate from one patch to another, due to medical reasons. The existence and uniqueness of the associated endemic equilibria are discussed. Quadratic forms and Lyapunov functions are used to show that when the basic reproduction ratio is less than one, the disease-free equilibrium (DFE) is globally asymptotically stable, and when it is greater than one there exists in each case a unique endemic equilibrium (boundary equilibria and endemic equilibrium) which is globally asymptotically stable. Numerical simulation results are provided to illustrate the theoretical results. (C) 2012 Elsevier Inc. All rights reserved. AD - Univ Yaounde I, Dept Math & Phys, Natl Adv Sch Engn Polytech, Yaounde, Cameroon Univ Douala, Fac Sci, Dept Math & Comp Sci, Lab Appl Math, Douala, Cameroon UMI 209 IRD, Yaounde, Cameroon UPMC UMMISCO, Yaounde, Cameroon LIRIMA Project Team GRIMCAPE, Yaounde, Cameroon North West Univ, Dept Math Sci, Mmabatho, South Africa AN - WOS:000308571900005 AU - Tewa, J. J. AU - Bowong, S. AU - Noutchie, S. C. O. DA - Dec DO - 10.1016/j.apm.2012.01.026 IS - 12 J2 - Appl Math Model KW - patch tuberculosis staged progression lyapunov function quadratic forms global-stability transmission dynamics epidemics LA - English N1 - 002xi Times Cited:6 Cited References Count:35 PY - 2012 SN - 0307-904x SP - 5792-5807 ST - Mathematical analysis of a two-patch model of tuberculosis disease with staged progression T2 - Applied Mathematical Modelling TI - Mathematical analysis of a two-patch model of tuberculosis disease with staged progression UR - ://WOS:000308571900005 VL - 36 ID - 4887 ER - TY - JOUR AB - The relative contributions of transmission and reactivation of latent infection to TB cases observed clinically has been reported in many situations, but always with some uncertainty. Genotyped data from TB organisms obtained from patients have been used as the basis for heuristic distinctions between circulating (clustered strains) and reactivated infections (unclustered strains). Naive methods previously applied to the analysis of such data are known to provide biased estimates of the proportion of unclustered cases. The hypergeometric distribution, which generates probabilities of observing clusters of a given size as realized clusters of all possible sizes, is analyzed in this paper to yield a formal estimator for genotype cluster sizes. Subtle aspects of numerical stability, bias, and variance are explored. This formal estimator is seen to be stable with respect to the epidemiologically interesting properties of the cluster size distribution (the number of clusters and the number of singletons) though it does not yield satisfactory estimates of the number of clusters of larger sizes. The problem that even complete coverage of genotyping, in a practical sampling frame, will only provide a partial view of the actual transmission network remains to be explored. AD - The South African Department of Science and Technology/National Research Foundation (DST/NRF) Centre of Excellence in Epidemiological Modelling and Analysis, Faculty of Science, University of Stellenbosch, Stellenbosch, South Africa. carivs@sun.ac.za AN - 22479534 AU - van Schalkwyk, C. AU - Cule, M. AU - Welte, A. AU - van Helden, P. AU - van der Spuy, G. AU - Uys, P. DO - 10.1371/journal.pone.0034109 [doi] PONE-D-12-01538 [pii] DP - Nlm ET - 04/06 LA - eng N1 - van Schalkwyk, Cari Cule, Madeleine Welte, Alex van Helden, Paul van der Spuy, Gian Uys, Pieter United States PloS one PLoS One. 2012;7(3):e34109. Epub 2012 Mar 29. PY - 2012 RN - fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e34109 ST - Towards eliminating bias in cluster analysis of TB genotyped data T2 - PLoS One TI - Towards eliminating bias in cluster analysis of TB genotyped data UR - http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0034109&representation=PDF VL - 7 ID - 2690 ER - TY - JOUR AB - An epidemiological model is presented that considers five possible states of a population: susceptible (S), exposed (W), infectious (Y), in treatment (Z) and recovered (R). In certain instances transition rates (from one state to another) depend on the time spent in the state; therefore the states W, Y and Z depend on time and length of stay in that state - similar to age-structured models. The model is particularly amenable to describe delays of exposed persons to become infectious and re-infection of exposed persons. Other transitions that depend on state time include the case finding and diagnosis, increased death rate and treatment interruption. The mathematical model comprises of a set of partial differential and ordinary differential equations. Non-steady state solutions are first presented, followed by a bifurcation study of the stationary states. AD - Department of Social Policy, London School of Economics, London WC2A 2AE, United Kingdom. hviljoen1@unl.edu AN - 22340441 AU - Viljoen, S. AU - Pienaar, E. AU - Viljoen, H. J. DA - Feb DO - S1476-9271(11)00121-6 [pii] 10.1016/j.compbiolchem.2011.11.003 [doi] DP - Nlm ET - 02/22 KW - Humans Models, Biological Time Factors Tuberculosis/ epidemiology LA - eng N1 - Viljoen, S Pienaar, E Viljoen, H J England Computational biology and chemistry Comput Biol Chem. 2012 Feb;36:15-22. Epub 2011 Nov 28. PY - 2012 RN - fulltext fulltext_1208 SN - 1476-928X (Electronic) 1476-9271 (Linking) SP - 15-22 ST - A state-time epidemiology model of tuberculosis: importance of re-infection T2 - Comput Biol Chem TI - A state-time epidemiology model of tuberculosis: importance of re-infection UR - http://ac.els-cdn.com/S1476927111001216/1-s2.0-S1476927111001216-main.pdf?_tid=5011c39c1d26a4ee9d6e09071326109c&acdnat=1345013671_1c8d29149cf49c072abac5b18b3cc07f VL - 36 ID - 2691 ER - TY - JOUR AB - An epidemiological model of TB with infectivity in latent period and imperfect treatment is introduced. As presented, sustained oscillations are not possible and the endemic proportions either approach the disease-free equilibrium or an endemic equilibrium. The expanded model that stratified the infectious individuals according to their time-since-infection theta is also carried out. The global asymptotic stability of the infection-free state is established as well as local asymptotic stability of the endemic equilibrium. At the end, numerical simulations are presented to illustrate the results. AD - Li, XZ Xinyang Normal Univ, Dept Math, Xinyang 464000, Peoples R China Xinyang Normal Univ, Dept Math, Xinyang 464000, Peoples R China Xinyang Normal Univ, Dept Math, Xinyang 464000, Peoples R China AN - WOS:000303738200001 AU - Wang, J. AU - Gao, S. S. AU - Li, X. Z. DO - Artn 184918 10.1155/2012/184918 J2 - Discrete Dyn Nat Soc KW - intrinsic transmission dynamics global stability drug-resistance epidemic model tuberculosis reinfection hiv L1 - internal-pdf://0072663906/Wang-2012-A TB Model with Infectivity in Laten.pdf LA - English N1 - 938ms Times Cited:0 Cited References Count:26 PY - 2012 SN - 1026-0226 ST - A TB Model with Infectivity in Latent Period and Imperfect Treatment T2 - Discrete Dynamics in Nature and Society TI - A TB Model with Infectivity in Latent Period and Imperfect Treatment UR - ://WOS:000303738200001 http://downloads.hindawi.com/journals/ddns/2012/184918.pdf ID - 4888 ER - TY - JOUR AB - Researchers create a dynamic model that could resolve conflicting findings on the effects of HIV infection on drug-resistant tuberculosis. AD - South African Centre for Epidemiological Modelling and Analysis (SACEMA), Matieland, Stellenbosch 7602, South Africa. williamsbg@me.com AN - 22623735 AU - Williams, B. G. DA - May 23 DO - 10.1126/scitranslmed.3004079 DP - NLM ET - 2012/05/25 IS - 135 J2 - Science translational medicine KW - HIV Infections/*epidemiology Humans Tuberculosis, Multidrug-Resistant/*epidemiology L1 - internal-pdf://4040361059/Williams-2012-TB and HIV_ deadly liaison or ma.pdf LA - eng N1 - 1946-6242 Williams, Brian G Comment Journal Article United States Sci Transl Med. 2012 May 23;4(135):135fs15. doi: 10.1126/scitranslmed.3004079. PY - 2012 SN - 1946-6234 SP - 135fs15 ST - TB and HIV: deadly liaison or manageable threat? T2 - Sci Transl Med TI - TB and HIV: deadly liaison or manageable threat? UR - http://stm.sciencemag.org/content/scitransmed/4/135/135fs15.full.pdf VL - 4 ID - 2941 ER - TY - JOUR AB - BACKGROUND: Prisons of the former Soviet Union (FSU) have high rates of multidrug-resistant tuberculosis (MDR-TB) and are thought to drive general population tuberculosis (TB) epidemics. Effective prison case detection, though employing more expensive technologies, may reduce long-term treatment costs and slow MDR-TB transmission. METHODS AND FINDINGS: We developed a dynamic transmission model of TB and drug resistance matched to the epidemiology and costs in FSU prisons. We evaluated eight strategies for TB screening and diagnosis involving, alone or in combination, self-referral, symptom screening, mass miniature radiography (MMR), and sputum PCR with probes for rifampin resistance (Xpert MTB/RIF). Over a 10-y horizon, we projected costs, quality-adjusted life years (QALYs), and TB and MDR-TB prevalence. Using sputum PCR as an annual primary screening tool among the general prison population most effectively reduced overall TB prevalence (from 2.78% to 2.31%) and MDR-TB prevalence (from 0.74% to 0.63%), and cost US$543/QALY for additional QALYs gained compared to MMR screening with sputum PCR reserved for rapid detection of MDR-TB. Adding sputum PCR to the currently used strategy of annual MMR screening was cost-saving over 10 y compared to MMR screening alone, but produced only a modest reduction in MDR-TB prevalence (from 0.74% to 0.69%) and had minimal effect on overall TB prevalence (from 2.78% to 2.74%). Strategies based on symptom screening alone were less effective and more expensive than MMR-based strategies. Study limitations included scarce primary TB time-series data in FSU prisons and uncertainties regarding screening test characteristics. CONCLUSIONS: In prisons of the FSU, annual screening of the general inmate population with sputum PCR most effectively reduces TB and MDR-TB prevalence, doing so cost-effectively. If this approach is not feasible, the current strategy of annual MMR is both more effective and less expensive than strategies using self-referral or symptom screening alone, and the addition of sputum PCR for rapid MDR-TB detection may be cost-saving over time. AD - Stanford University School of Medicine, California, United States of America. AN - 23209384 AU - Winetsky, D. E. AU - Negoescu, D. M. AU - DeMarchis, E. H. AU - Almukhamedova, O. AU - Dooronbekova, A. AU - Pulatov, D. AU - Vezhnina, N. AU - Owens, D. K. AU - Goldhaber-Fiebert, J. D. DO - 10.1371/journal.pmed.1001348 10.1371/journal.pmed.1001348. Epub 2012 Nov 27. DP - Nlm ET - 12/05 J2 - PLoS medicine L1 - internal-pdf://3426037257/Winetsky-2012-Screening and rapid molecular di.pdf LA - eng PY - 2012 SN - 1549-1676 (Electronic) 1549-1277 (Linking) SP - e1001348 ST - Screening and rapid molecular diagnosis of tuberculosis in prisons in Russia and Eastern Europe: a cost-effectiveness analysis T2 - PLoS Med TI - Screening and rapid molecular diagnosis of tuberculosis in prisons in Russia and Eastern Europe: a cost-effectiveness analysis UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507963/pdf/pmed.1001348.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507963/pdf/pmed.1001348.pdf VL - 9 ID - 2692 ER - TY - JOUR AB - Because the latent period and the infectious period of tuberculosis (TB) are very long, it is not reasonable to consider the time as constant. So this paper formulates a mathematical model that divides the latent period and the infectious period into n-stages. For a general n-stage stage progression (SP) model with bilinear incidence, we analyze its dynamic behavior. First, we give the basic reproduction number R-0. Moreover, if R-0 <= 1, the disease-free equilibrium P-0 is globally asymptotically stable and the disease always dies out. If R-0 > 1, the unique endemic equilibrium P* is globally asymptotically stable and the disease persists at the endemic equilibrium. AD - [Xue, Yakui; Wang, Xiaohong] N Univ China, Dept Math, Taiyuan 030051, Shanxi, Peoples R China. Xue, YK (reprint author), N Univ China, Dept Math, Taiyuan 030051, Shanxi, Peoples R China. xyk5152@163.com AN - WOS:000309765200001 AU - Xue, Y. K. AU - Wang, X. H. C7 - 571469 DO - 10.1155/2012/571469 J2 - J. Appl. Math. KW - infectious-disease models beverton-holt equation nonlinear incidence lyapunov functions epidemic models realistic distributions hiv-infection dynamics transmission sir Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: 019UP Times Cited: 0 Cited Reference Count: 31 Xue, Yakui Wang, Xiaohong National Sciences Foundation of China [10471040]; National Sciences Foundation of Shanxi Province [2009011005-1] The work is supported by the National Sciences Foundation of China (10471040) and the National Sciences Foundation of Shanxi Province (2009011005-1). 0 1 7 Hindawi publishing corporation New york PY - 2012 SN - 1110-757X SP - 15 ST - Global Stability of a SLIT TB Model with Staged Progression T2 - Journal of Applied Mathematics TI - Global Stability of a SLIT TB Model with Staged Progression UR - ://WOS:000309765200001 ID - 5692 ER - TY - JOUR AB - In general, cellular immune response results in the suppression of mycobacterial infection, but does not completely eradicate it. This is the reason why the majority of cases (95%) limits proliferation of the bacilli and produces a long-lasting partial immunity, and 5% of infected individuals develop early progressive disease that occurs within 2-5 years of infection. One of the characteristics of Mycobacterium infection is the replication of the bacteria inside of alveolar macrophages. For this reason 5% of asymptomatic individuals have late disease, which is caused by endogenous reactivation as long as several decades after infection. We develop a simple mathematical model that describes the interaction between Mycobacterium tuberculosis and cellular immune response. The risk of tuberculosis reactivation is determined by granulomas formation on one side and cellular immune response to phagocytize bacteria and to destroy granuloma on other side. The model is analyzed in the initial phase of mycobacterial infection, and an associated risk of tuberculosis among tobacco smokers is established. AD - Univ Estadual Campinas, IMECC, Dept Matemat Aplicada, BR-13083859 Campinas, SP, Brazil. Yang, HM (reprint author), Univ Estadual Campinas, IMECC, Dept Matemat Aplicada, Praca Sergio Buarque de Holanda 651, BR-13083859 Campinas, SP, Brazil. hyunyang@ime.unicamp.br AN - WOS:000339419700021 AU - Yang, H. M. KW - endogenous reactivation cigarette-smoking latency smokers cells lung Mathematical & Computational Biology LA - English M3 - Proceedings Paper N1 - ISI Document Delivery No.: BA9HY Times Cited: 0 Cited Reference Count: 21 Yang, H. M. Mondaini, RP International Symposium on Mathematical and Computational Biology (BIOMAT) Nov 05-10, 2011 Santiago, CHILE Int Union Biol Sci 0 World scientific publ co pte ltd Singapore 978-981-4397-70-4 PY - 2012 SP - 309-330 ST - MATHEMATICAL MODELLING OF THE INTERACTION BETWEEN Mycobacterium Tuberculosis INFECTION AND CELLULAR IMMUNE RESPONSE T2 - Biomat 2011: International Symposium on Mathematical and Computational Biology TI - MATHEMATICAL MODELLING OF THE INTERACTION BETWEEN Mycobacterium Tuberculosis INFECTION AND CELLULAR IMMUNE RESPONSE UR - ://WOS:000339419700021 ID - 5698 ER - TY - JOUR AB - Two tuberculosis (TB) models with treatment and self-cure are investigated. It is assumed that the treated individuals may reenter either the latent compartment due to the remainder of Mycobacterium tuberculosis or the infectious compartment due to the treatment failure. On the other hand, infectious individuals with mild symptoms may reenter the latent compartment due to self-cure. After investigating a simple model with one latent compartment, a TB model with two latent compartments is studied to describe the slow and fast progression of the exposed individuals. The basic reproduction numbers of those two models are defined, and their epidemiological interpretation is given. Similar threshold dynamics is obtained for those two models: the disease dies out ultimately when the basic reproduction number is less than or equal to one; the unique endemic equilibrium is globally stable when the basic reproduction number is greater than one. The influence of treatment failure and self-cure on the basic reproduction number is also discussed. AD - [Yang, Yali] Shaanxi Normal Univ, Coll Math & Informat Sci, Xian 710062, Peoples R China. [Yang, Yali; Li, Jianquan] AF Engn Univ, Coll Sci, Xian 710051, Peoples R China. [Yang, Yali; Zhou, Yicang] Xi An Jiao Tong Univ, Dept Appl Math, Xian 710049, Peoples R China. Yang, YL (reprint author), Shaanxi Normal Univ, Coll Math & Informat Sci, Xian 710062, Peoples R China. yylhgr@126.com; jianq_li@263.net; zhouyc@mail.xjtu.edu.cn AN - WOS:000314235200017 AU - Yang, Y. L. AU - Li, J. Q. AU - Zhou, Y. C. DO - 10.1216/rmj-2012-42-4-1367 IS - 4 J2 - Rocky Mt. J. Math. KW - Tuberculosis treatment self-cure equilibrium global stability infectious-diseases dynamics Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: 080IN Times Cited: 4 Cited Reference Count: 17 Yang, Yali Li, Jianquan Zhou, Yicang Nature Science Foundation of Shaanxi Province of China [2012JQ1019]; Nature Science Foundation of China [11071256] This work was partially supported by the Nature Science Foundation of Shaanxi Province of China (No. 2012JQ1019) and the Nature Science Foundation of China (No. 11071256). 4 0 3 Rocky mt math consortium Tempe PY - 2012 SN - 0035-7596 SP - 1367-1386 ST - GLOBAL STABILITY OF TWO TUBERCULOSIS MODELS WITH TREATMENT AND SELF-CURE T2 - Rocky Mountain Journal of Mathematics TI - GLOBAL STABILITY OF TWO TUBERCULOSIS MODELS WITH TREATMENT AND SELF-CURE UR - ://WOS:000314235200017 VL - 42 ID - 5691 ER - TY - JOUR AB - In this manuscript we apply stochastic modeling to investigate the risk of reactivation of latent mycobacterial infections in patients undergoing treatment with tumor necrosis factor inhibitors. First, we review the perspective proposed by one of the authors in a previous work and which consists in predicting the occurrence of reactivation of latent tuberculosis infection or newly acquired tuberculosis during treatment; this is based on variational procedures on a simple set of parameters (e.g. rate of reactivation of a latent infection). Then, we develop a full analytical study of this approach through a Markov chain analysis and we find an exact solution for the temporal evolution of the number of cases of tuberculosis infection (re)activation. The analytical solution is compared with Monte Carlo simulations and with experimental data, showing overall excellent agreement. The generality of this theoretical framework allows to investigate also the case of non-tuberculous mycobacteria infections; in particular, we show that reactivation in that context plays a minor role. This may suggest that, while the screening for tuberculous is necessary prior to initiating biologics, when considering non-tuberculous mycobacteria only a watchful monitoring during the treatment is recommended. The framework outlined in this paper is quite general and could be extremely promising in further researches on drug-related adverse events. AD - Dipartimento di Fisica, Universita di Parma, Parma, Italy ; Istituto Nazionale di Fisica Nucleare, Gruppo Collegato di Parma, Parma, Italy. AN - 23383039 AU - Agliari, E. AU - Asti, L. AU - Barra, A. AU - Scrivo, R. AU - Valesini, G. AU - Wallis, R. S. DO - 10.1371/journal.pone.0055017 10.1371/journal.pone.0055017. Epub 2013 Jan 28. DP - Nlm ET - 02/06 J2 - PloS one LA - eng PY - 2013 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e55017 ST - Application of a stochastic modeling to assess the evolution of tuberculous and non-tuberculous mycobacterial infection in patients treated with tumor necrosis factor inhibitors T2 - PLoS One TI - Application of a stochastic modeling to assess the evolution of tuberculous and non-tuberculous mycobacterial infection in patients treated with tumor necrosis factor inhibitors UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557254/pdf/pone.0055017.pdf VL - 8 ID - 2693 ER - TY - JOUR AB - Current tuberculosis notification rates in South Africa are among the highest ever recorded. Although the human immunodeficiency virus epidemic has been a critical factor, the density of respiratory contacts in high-risk environments may be an important and underappreciated driver. Using a modified Wells-Riley model for airborne disease transmission, we estimated the risk of tuberculosis transmission on 3 modes of public transit (minibus taxis, buses, and trains) in Cape Town, South Africa, using exhaled carbon dioxide as a natural tracer gas to evaluate air exchange. Carbon dioxide measurements were performed between October and December of 2011. Environmental risk, reflected in the rebreathed fraction of air, was highest in minibus taxis and lowest in trains; however, the average number of passengers sharing an indoor space was highest in trains and lowest in minibus taxis. Among daily commuters, the annual risk of tuberculosis infection was projected to be 3.5%-5.0% and was highest among minibus taxi commuters. Assuming a duration of infectiousness of 1 year, the basic reproductive number attributable to transportation was more than 1 in all 3 modes of transportation. Given its poor ventilation and high respiratory contact rates, public transportation may play a critical role in sustaining tuberculosis transmission in South African cities. AN - 23423215 AU - Andrews, J. R. AU - Morrow, C. AU - Wood, R. DA - Mar 15 DO - 10.1093/aje/kws331 10.1093/aje/kws331. Epub 2013 Feb 18. DP - Nlm ET - 02/21 J2 - American journal of epidemiology LA - eng PY - 2013 SN - 1476-6256 (Electronic) 0002-9262 (Linking) SP - 556-61 ST - Modeling the role of public transportation in sustaining tuberculosis transmission in South Africa T2 - Am J Epidemiol TI - Modeling the role of public transportation in sustaining tuberculosis transmission in South Africa UR - http://aje.oxfordjournals.org/content/177/6/556.full.pdf VL - 177 ID - 2694 ER - TY - JOUR AB - We examine possible approximate solutions of both integer and noninteger systems of nonlinear differential equations describing tuberculosis disease population dynamics. The approximate solutions are obtained via the relatively new analytical technique, the homotopy decomposition method (HDM). The technique is described and illustrated with numerical example. The numerical simulations show that the approximate solutions are continuous functions of the noninteger-order derivative. The technique used for solving these problems is friendly, very easy, and less time consuming. AD - [Atangana, Abdon] Univ Orange Free State, Inst Groundwater Studies, Bloemfontein, South Africa. [Bildik, Necdet] Celal Bayar Univ, Dept Math, Fac Art & Sci, TR-45047 Manisa, Turkey. Atangana, A (reprint author), Univ Orange Free State, Inst Groundwater Studies, POB 9300, Bloemfontein, South Africa. abdonatangana@yahoo.fr AN - WOS:000321393100001 AU - Atangana, A. AU - Bildik, N. C7 - 759801 DO - 10.1155/2013/759801 J2 - Abstract Appl. Anal. KW - Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: 177RM Times Cited: 6 Cited Reference Count: 20 Atangana, Abdon Bildik, Necdet 6 0 7 Hindawi publishing corporation New york PY - 2013 SN - 1085-3375 SP - 8 ST - Approximate Solution of Tuberculosis Disease Population Dynamics Model T2 - Abstract and Applied Analysis TI - Approximate Solution of Tuberculosis Disease Population Dynamics Model UR - ://WOS:000321393100001 ID - 5584 ER - TY - JOUR AB - The WHO recommended intervention of Directly Observed Treatment, Short-course (DOTS) appears to have been less successful than expected in reducing the burden of TB in some high prevalence settings. One strategy for enhancing DOTS is incorporating active case-finding through screening contacts of TB patients as widely used in low-prevalence settings. Predictive models that incorporate population-level effects on transmission provide one means of predicting impacts of such interventions. We aim to identify all TB transmission modelling studies addressing contact tracing and to describe and critically assess their modelling assumptions, parameter choices and relevance to policy. We searched MEDLINE, SCOPUS, COMPENDEX, Google Scholar and Web of Science databases for relevant English language publications up to February 2012. Of the 1285 studies identified, only 5 studies met our inclusion criteria of models of TB transmission dynamics in human populations designed to incorporate contact tracing as an intervention. Detailed implementation of contact processes was only present in two studies, while only one study presented a model for a high prevalence, developing world setting. Some use of relevant data for parameter estimation was made in each study however validation of the predicted impact of interventions was not attempted in any of the studies. Despite a large body of literature on TB transmission modelling, few published studies incorporate contact tracing. There is considerable scope for future analyses to make better use of data and to apply individual based models to facilitate more realistic patterns of infectious contact. Combined with a focus on high burden settings this would greatly increase the potential for models to inform the use of contract tracing as a TB control policy. Our findings highlight the potential for collaborative work between clinicians, epidemiologists and modellers to gather data required to enhance model development and validation and hence better inform future public health policy. AD - School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Sydney, Australia. AN - 24023742 AU - Begun, M. AU - Newall, A. T. AU - Marks, G. B. AU - Wood, J. G. C2 - PMC3762785 DO - 10.1371/journal.pone.0072470 DP - NLM ET - 2013/09/12 IS - 9 J2 - PloS one KW - Animals *Contact Tracing Humans *Models, Theoretical Tuberculosis/*prevention & control/*transmission LA - eng N1 - 1932-6203 Begun, Matt Newall, Anthony T Marks, Guy B Wood, James G Journal Article Research Support, Non-U.S. Gov't Review United States PLoS One. 2013 Sep 4;8(9):e72470. doi: 10.1371/journal.pone.0072470. eCollection 2013. PY - 2013 SN - 1932-6203 SP - e72470 ST - Contact tracing of tuberculosis: a systematic review of transmission modelling studies T2 - PLoS One TI - Contact tracing of tuberculosis: a systematic review of transmission modelling studies VL - 8 ID - 1702 ER - TY - JOUR AB - This paper deals with the problem of optimal control of a deterministic model of tuberculosis (abbreviated as TB for tubercle bacillus). We first present and analyze an uncontrolled tuberculosis model which incorporates the essential biological and epidemiological features of the disease. The model is shown to exhibit the phenomenon of backward bifurcation, where a stable disease-free equilibrium co-exists with one or more stable endemic equilibria when the associated basic reproduction number is less than the unity. Based on this continuous model, the tuberculosis control is formulated and solved as an optimal control problem, indicating how control terms on the chemoprophylaxis and detection should be introduced in the population to reduce the number of individuals with active TB. Results provide a framework for designing the cost-effective strategies for TB with two intervention methods. (C) 2012 Elsevier B. V. All rights reserved. AD - Univ Douala, Fac Sci, Dept Math & Comp Sci, Douala, Cameroon Univ Le Havre, Lab Math Appl, Le Havre, France UPMC, UMMISCO, IRD, UMI 209, Bondy, France Univ Yaounde I, LIRIMA, Project Team GRIMCAPE, Yaounde, Cameroon AN - WOS:000313705300010 AU - Bowong, S. AU - Alaoui, A. M. A. DA - Jun DO - 10.1016/j.cnsns.2012.08.001 IS - 6 J2 - Commun Nonlinear Sci KW - tuberculosis mathematical models backward bifurcation stability optimal control exogenous reinfection backward bifurcation infectious-diseases model hiv vaccination LA - English N1 - 072ww Times Cited:4 Cited References Count:37 PY - 2013 SN - 1007-5704 SP - 1441-1453 ST - Optimal intervention strategies for tuberculosis T2 - Communications in Nonlinear Science and Numerical Simulation TI - Optimal intervention strategies for tuberculosis UR - ://WOS:000313705300010 VL - 18 ID - 4891 ER - TY - JOUR AB - This paper analyzes the dynamics of the spread of tuberculosis (TB) on complex metapopulation, that is, networks of populations connected by migratory flows whose configurations are described in terms of connectivity distribution of nodes (patches) and the conditional probabilities of connections among classes of nodes sharing the same degree. The migration and transmission processes occur simultaneously. For uncorrelated networks, we give a necessary and sufficient condition for the instability of the disease-free equilibrium. The existence of endemic equilibria is also discussed. Finally, the prevalence of the TB infection across the metapopulation as a function of the path connectivity is studied using numerical simulations. AD - Univ Douala, Fac Sci, Dept Math & Comp Sci, Lab Appl Math, Douala, Cameroon Univ Yaounde I, Natl Adv Sch Engn Polytech, Dept Math & Phys, Yaounde, Cameroon Postdam Inst Climate Impact Res PIK, D-14412 Potsdam, Germany AN - WOS:000323290100020 AU - Bowong, S. AU - Tewa, J. J. AU - Kurths, J. DA - Jul DO - Artn 1350128 10.1142/S0218127413501289 IS - 7 J2 - Int J Bifurcat Chaos KW - dynamical systems tuberculosis complex metapopulation uncorrelated networks basic reproduction number stability infectious-diseases epidemic models networks transmission populations systems LA - English N1 - 203ka Times Cited:1 Cited References Count:40 PY - 2013 SN - 0218-1274 ST - Dynamics of the Spread of Tuberculosis in Heterogeneous Complex Metapopulations T2 - International Journal of Bifurcation and Chaos TI - Dynamics of the Spread of Tuberculosis in Heterogeneous Complex Metapopulations UR - ://WOS:000323290100020 VL - 23 ID - 4892 ER - TY - JOUR AB - BACKGROUND: Tuberculosis (TB) is a serious public health issue in developing countries. Early prediction of TB epidemic is very important for its control and intervention. We aimed to develop an appropriate model for predicting TB epidemics and analyze its seasonality in China. METHODS: Data of monthly TB incidence cases from January 2005 to December 2011 were obtained from the Ministry of Health, China. A seasonal autoregressive integrated moving average (SARIMA) model and a hybrid model which combined the SARIMA model and a generalized regression neural network model were used to fit the data from 2005 to 2010. Simulation performance parameters of mean square error (MSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) were used to compare the goodness-of-fit between these two models. Data from 2011 TB incidence data was used to validate the chosen model. RESULTS: Although both two models could reasonably forecast the incidence of TB, the hybrid model demonstrated better goodness-of-fit than the SARIMA model. For the hybrid model, the MSE, MAE and MAPE were 38969150, 3406.593 and 0.030, respectively. For the SARIMA model, the corresponding figures were 161835310, 8781.971 and 0.076, respectively. The seasonal trend of TB incidence is predicted to have lower monthly incidence in January and February and higher incidence from March to June. CONCLUSIONS: The hybrid model showed better TB incidence forecasting than the SARIMA model. There is an obvious seasonal trend of TB incidence in China that differed from other countries. AD - School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China. AN - 23638635 AU - Cao, S. AU - Wang, F. AU - Tam, W. AU - Tse, L. A. AU - Kim, J. H. AU - Liu, J. AU - Lu, Z. C2 - PMC3653787 DA - May 02 DO - 10.1186/1472-6947-13-56 DP - NLM ET - 2013/05/04 J2 - BMC medical informatics and decision making KW - China/epidemiology Computer Simulation Disease Notification Humans Incidence *Models, Statistical Seasons Systems Integration Tuberculosis/diagnosis/*epidemiology/mortality LA - eng N1 - 1472-6947 Cao, Shiyi Wang, Feng Tam, Wilson Tse, Lap Ah Kim, Jean Hee Liu, Junan Lu, Zuxun Case Reports Journal Article Research Support, Non-U.S. Gov't England BMC Med Inform Decis Mak. 2013 May 2;13:56. doi: 10.1186/1472-6947-13-56. PY - 2013 SN - 1472-6947 SP - 56 ST - A hybrid seasonal prediction model for tuberculosis incidence in China T2 - BMC Med Inform Decis Mak TI - A hybrid seasonal prediction model for tuberculosis incidence in China VL - 13 ID - 1781 ER - TY - JOUR AB - In the study of complex patterns in biology, mathematical and computational models are emerging as important tools. In addition to experimental approaches, these modeling tools have recently been applied to address open questions regarding host-pathogen interaction dynamics, including the immune response to mycobacterial infection and tuberculous granuloma formation. We present an approach in which a computational model represents the interaction of the Mycobacterium infection with the innate immune system in zebrafish at a high level of abstraction. We use the Petri Net formalism to model the interaction between the key host elements involved in granuloma formation and infection dissemination. We define a qualitative model for the understanding and description of causal relations in this dynamic process. Complex processes involving cell-cell or cell-bacteria communication can be modeled at smaller scales and incorporated hierarchically into this main model; these are to be included in later elaborations. With the infection mechanism being defined on a higher level, lower-level processes influencing the host-pathogen interaction can be identified, modeled, and tested both quantitatively and qualitatively. This systems biology framework incorporates modeling to generate and test hypotheses, to perform virtual experiments, and to make experimentally verifiable predictions. Thereby it supports the unraveling of the mechanisms of tuberculosis infection. AD - Leiden Institute of Advanced Computer Science, Leiden University, Leiden, The Netherlands. AN - 23365620 AU - Carvalho, R. V. AU - Kleijn, J. AU - Meijer, A. H. AU - Verbeek, F. J. DO - 10.1155/2012/790482 10.1155/2012/790482. Epub 2012 Dec 9. DP - Nlm ET - 02/01 J2 - Computational and mathematical methods in medicine LA - eng PY - 2013 SN - 1748-6718 (Electronic) 1748-670X (Linking) SP - 790482 ST - Modeling innate immune response to early Mycobacterium infection T2 - Comput Math Methods Med TI - Modeling innate immune response to early Mycobacterium infection UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3529460/pdf/CMMM2012-790482.pdf VL - 2012 ID - 2660 ER - TY - CHAP A2 - Wang, C. K. A2 - Guo, J. AB - In order to simulate the transmissions of vector-borne diseases and discuss the related health policies effects on vector-borne diseases, we using compartmental model to develop an epidemic simulation models. The research will analyze the complex dynamic mathematic model of tuberculosis epidemic and determine its stability property by using the popular Matlab/Simulink software and relative software packages. Facing the current TB epidemic situation, the development of TB and its developing trend through constructing a dynamic bio-mathematic system model of TB is investigated. AD - [Chung, Chun-Yen] Kun Shan Univ, Dept Informat Engn, Tainan, Taiwan. [Chung, Hung-Yuan] Natl Cent Univ, Dept Elect Engn, Taoyuan, Taiwan. Chung, CY (reprint author), Kun Shan Univ, Dept Informat Engn, Tainan, Taiwan. cychung@mail.ksu.edu.tw; hychung@mail.ncu.edu.tw AN - WOS:000320567900320 AU - Chung, C. Y. AU - Chung, H. Y. CY - Durnten-Zurich DO - 10.4028/www.scientific.net/AMM.300-301.1658 KW - Tuberculosis biomathematics DOTS LA - English N1 - ISI Document Delivery No.: BFM85 Times Cited: 1 Cited Reference Count: 12 Chung, Chun-Yen Chung, Hung-Yuan Proceedings Paper 2nd International Conference on Mechatronics and Applied Mechanics (ICMAM2012) Dec 06-07, 2012 Dec 08-09, 2012 Hong Kong, PEOPLES R CHINA Taipei, PEOPLES R CHINA Kreuzstrasse 10, 8635 durnten-zurich, switzerland 1660-9336 PB - Trans Tech Publications Ltd PY - 2013 SN - 978-3-03785-651-2 SP - 1658-+ ST - Computer Simulation for New Theoretical model Constructed with Tuberculosis T2 - Mechatronics and Applied Mechanics Ii, Pts 1 and 2 T3 - Applied Mechanics and Materials TI - Computer Simulation for New Theoretical model Constructed with Tuberculosis UR - ://WOS:000320567900320 https://www.scientific.net/AMM.300-301.1658 VL - 300-301 ID - 5585 ER - TY - CHAP A2 - Wang, C. K. AB - In recent years, following malaria, tuberculosis, AIDS, Novel Influenza, and other infectious diseases, have an enormous impact on the entire globe, and directly and profoundly awaken the public, making them cognitive and alert regarding emerging and re-emerging infectious diseases. For some countries or developing regions, tuberculosis is still very serious, however, the public is still unclear TB development and change a variety of factors, therefore, need a model theory of tuberculosis. In view of this, the global epidemic, scientists and statisticians hope to further develop a complete inspection and data acquisition system and is committed to the existing monitoring system, and through the establishment of mathematical models and the spread of infectious diseases dynamics of quantitative methods to facilitate the practical application and control of epidemics, trends and cost-benefit assessment, and help build disease prevention policies, evaluation and revision. AD - [Chung, Chun-Yen] Kun Shan Univ, Dept Informat Engn, Tainan, Taiwan. [Chung, Hung-Yuan] Natl Cent Univ, Dept Elect Engn, Taoyuan, Taiwan. [Sung, Wen-Tsai] Natl Chin Yi Univ Technol, Dept Elect Engn, Taichung, Taiwan. Chung, CY (reprint author), Kun Shan Univ, Dept Informat Engn, Tainan, Taiwan. cychung@mail.ksu.edu.tw; hychung@mail.ncu.edu.tw; songchen@ncut.edu.tw AN - WOS:000335880300055 AU - Chung, C. Y. AU - Chung, H. Y. AU - Sung, W. T. CY - Durnten-Zurich DO - 10.4028/www.scientific.net/AMM.418.265 KW - Tuberculosis AIDS HIV LA - English N1 - ISI Document Delivery No.: BA4JZ Times Cited: 0 Cited Reference Count: 8 Chung, Chun-Yen Chung, Hung-Yuan Sung, Wen-Tsai Proceedings Paper International Conference on Applied Mechatronics and Android Robotics (ICAMAR 2013) Jul 13-14, 2013-2014 Taipei, TAIWAN Kreuzstrasse 10, 8635 durnten-zurich, switzerland 1660-9336 PB - Trans Tech Publications Ltd PY - 2013 SN - 978-3-03785-874-5 SP - 265-+ ST - Mathematical Models for the Dynamics Simulation of Tuberculosis T2 - Applied Mechatronics and Android Robotics T3 - Applied Mechanics and Materials TI - Mathematical Models for the Dynamics Simulation of Tuberculosis UR - ://WOS:000335880300055 https://www.scientific.net/AMM.418.265 VL - 418 ID - 5581 ER - TY - JOUR AB - Interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) are key anti- and pro-inflammatory mediators elicited during the host immune response to Mycobacterium tuberculosis (Mtb). Understanding the opposing effects of these mediators is difficult due to the complexity of processes acting across different spatial (molecular, cellular, and tissue) and temporal (seconds to years) scales. We take an in silico approach and use multi-scale agent based modeling of the immune response to Mtb, including molecular scale details for both TNF-alpha and IL-10. Our model predicts that IL-10 is necessary to modulate macrophage activation levels and to prevent host-induced tissue damage in a granuloma, an aggregate of cells that forms in response to Mtb. We show that TNF-alpha and IL-10 parameters related to synthesis, signaling, and spatial distribution processes control concentrations of TNF-alpha and IL-10 in a granuloma and determine infection outcome in the long-term. We devise an overall measure of granuloma function based on three metrics - total bacterial load, macrophage activation levels, and apoptosis of resting macrophages - and use this metric to demonstrate a balance of TNF-alpha and IL-10 concentrations is essential to Mtb infection control, within a single granuloma, with minimal host-induced tissue damage. Our findings suggest that a balance of TNF-alpha and IL-10 defines a granuloma environment that may be beneficial for both host and pathogen, but perturbing the balance could be used as a novel therapeutic strategy to modulate infection outcomes. AD - Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, USA. AN - 23869227 AU - Cilfone, N. A. AU - Perry, C. R. AU - Kirschner, D. E. AU - Linderman, J. J. C2 - PMC3711807 DO - 10.1371/journal.pone.0068680 DP - NLM ET - 2013/07/23 IS - 7 J2 - PloS one KW - Computational Biology Granuloma/metabolism/*pathology Humans Interleukin-10/metabolism/*physiology Macrophages/immunology Models, Theoretical Mycobacterium tuberculosis/*immunology Signal Transduction Tuberculosis/metabolism/*pathology Tumor Necrosis Factor-alpha/metabolism/*physiology LA - eng N1 - 1932-6203 Cilfone, Nicholas A Perry, Cory R Kirschner, Denise E Linderman, Jennifer J R01 EB012579/EB/NIBIB NIH HHS/United States R01 HL110811/HL/NHLBI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural United States PLoS One. 2013 Jul 15;8(7):e68680. doi: 10.1371/journal.pone.0068680. Print 2013. PY - 2013 SN - 1932-6203 SP - e68680 ST - Multi-scale modeling predicts a balance of tumor necrosis factor-alpha and interleukin-10 controls the granuloma environment during Mycobacterium tuberculosis infection T2 - PLoS One TI - Multi-scale modeling predicts a balance of tumor necrosis factor-alpha and interleukin-10 controls the granuloma environment during Mycobacterium tuberculosis infection VL - 8 ID - 1732 ER - TY - JOUR AB - OBJECTIVE: To investigate the impact of antiretroviral therapy (ART) on long-term population-level tuberculosis disease (TB) incidence in sub-Saharan Africa. METHODS: We used a mathematical model to consider the effect of different assumptions about life expectancy and TB risk during long-term ART under alternative scenarios for trends in population HIV incidence and ART coverage. RESULTS: All the scenarios we explored predicted that the widespread introduction of ART would initially reduce population-level TB incidence. However, many modelled scenarios projected a rebound in population-level TB incidence after around 20 years. This rebound was predicted to exceed the TB incidence present before ART scale-up if decreases in HIV incidence during the same period were not sufficiently rapid or if the protective effect of ART on TB was not sustained. Nevertheless, most scenarios predicted a reduction in the cumulative TB incidence when accompanied by a relative decline in HIV incidence of more than 10% each year. CONCLUSIONS: Despite short-term benefits of ART scale-up on population TB incidence in sub-Saharan Africa, longer-term projections raise the possibility of a rebound in TB incidence. This highlights the importance of sustaining good adherence and immunologic response to ART and, crucially, the need for effective HIV preventive interventions, including early widespread implementation of ART. AD - Centre for Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom ; TB Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom. AN - 24069418 AU - Dodd, P. J. AU - Knight, G. M. AU - Lawn, S. D. AU - Corbett, E. L. AU - White, R. G. C2 - PMC3775764 DO - 10.1371/journal.pone.0075466 DP - NLM ET - 2013/09/27 IS - 9 J2 - PloS one KW - Africa South of the Sahara/epidemiology Anti-HIV Agents/adverse effects/therapeutic use Antiretroviral Therapy, Highly Active/*adverse effects HIV Infections/*complications/drug therapy/epidemiology Humans Incidence *Models, Theoretical Public Health Surveillance Tuberculosis/*epidemiology/*etiology LA - eng N1 - 1932-6203 Dodd, Peter J Knight, Gwenan M Lawn, Stephen D Corbett, Elizabeth L White, Richard G 091769/Wellcome Trust/United Kingdom 100714/Wellcome Trust/United Kingdom 101113/Wellcome Trust/United Kingdom MR/J005088/1/Medical Research Council/United Kingdom G0802414/Medical Research Council/United Kingdom Wellcome Trust/United Kingdom Journal Article Research Support, Non-U.S. Gov't United States PLoS One. 2013 Sep 17;8(9):e75466. doi: 10.1371/journal.pone.0075466. eCollection 2013. PY - 2013 SN - 1932-6203 SP - e75466 ST - Predicting the long-term impact of antiretroviral therapy scale-up on population incidence of tuberculosis T2 - PLoS One TI - Predicting the long-term impact of antiretroviral therapy scale-up on population incidence of tuberculosis VL - 8 ID - 1694 ER - TY - JOUR AB - OBJECTIVE: To compare the population-level impact of two World Health Organization-endorsed strategies for improving the diagnosis of tuberculosis (TB): same-day microscopy and Xpert MTB/RIF (Cepheid, USA). METHODS: We created a compartmental transmission model of TB in a representative African community, fit to the regional incidence and mortality of TB and HIV. We compared the population-level reduction in TB burden over ten years achievable with implementation over two years of same-day microscopy, Xpert MTB/RIF testing, and the combination of both approaches. FINDINGS: Same-day microscopy averted an estimated 11.0% of TB incidence over ten years (95% uncertainty range, UR: 3.3%-22.5%), and prevented 11.8% of all TB deaths (95% UR: 7.7%-27.1%). Scaling up Xpert MTB/RIF to all centralized laboratories to achieve 75% population coverage had similar impact on incidence (9.3% reduction, 95% UR: 1.9%-21.5%) and greater effect on mortality (23.8% reduction, 95% UR: 8.6%-33.4%). Combining the two strategies (i.e., same-day microscopy plus Xpert MTB/RIF) generated synergistic effects: an 18.7% reduction in incidence (95% UR: 5.6%-39.2%) and 33.1% reduction in TB mortality (95% UR: 18.1%-50.2%). By the end of year ten, combining same-day microscopy and Xpert MTB/RIF could reduce annual TB mortality by 44% relative to the current standard of care. CONCLUSION: Scaling up novel diagnostic tests for TB and optimizing existing ones are complementary strategies that, when combined, may have substantial impact on TB epidemics in Africa. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. AN - 23950942 AU - Dowdy, D. W. AU - Davis, J. L. AU - den Boon, S. AU - Walter, N. D. AU - Katamba, A. AU - Cattamanchi, A. C2 - PMC3741313 DO - 10.1371/journal.pone.0070485 DP - NLM ET - 2013/08/21 IS - 8 J2 - PloS one KW - Africa Diagnostic Tests, Routine/methods Humans Incidence *Microscopy Mortality Mycobacterium tuberculosis *Reagent Kits, Diagnostic Sensitivity and Specificity Standard of Care Tuberculosis/*diagnosis/epidemiology LA - eng N1 - 1932-6203 Dowdy, David W Davis, J Lucian den Boon, Saskia Walter, Nicholas D Katamba, Achilles Cattamanchi, Adithya R21 AI101152/AI/NIAID NIH HHS/United States K23 HL094141/HL/NHLBI NIH HHS/United States P30 AI027763/AI/NIAID NIH HHS/United States K23 AI080147/AI/NIAID NIH HHS/United States KL2RR024130/RR/NCRR NIH HHS/United States Journal Article Research Support, N.I.H., Extramural United States PLoS One. 2013 Aug 12;8(8):e70485. doi: 10.1371/journal.pone.0070485. eCollection 2013. PY - 2013 SN - 1932-6203 SP - e70485 ST - Population-level impact of same-day microscopy and Xpert MTB/RIF for tuberculosis diagnosis in Africa T2 - PLoS One TI - Population-level impact of same-day microscopy and Xpert MTB/RIF for tuberculosis diagnosis in Africa VL - 8 ID - 2912 ER - TY - JOUR AB - Infectious disease models are important tools for understanding epidemiology and supporting policy decisions for disease control. In the case of tuberculosis (TB), such models have informed our understanding and control strategies for over 40 years, but the primary assumptions of these models--and their most urgent data needs--remain obscure to many TB researchers and control officers. The structure and parameter values of TB models are informed by observational studies and experiments, but the evidence base in support of these models remains incomplete. Speaking from the perspective of infectious disease modelers addressing the broader TB research and control communities, we describe the basic structure common to most TB models and present a 'wish list' that would improve the evidence foundation upon which these models are built. As a comprehensive TB research agenda is formulated, we argue that the data needs of infectious disease models--our primary long-term decision-making tools--should figure prominently. AU - Dowdy, D. W. AU - Dye, C. AU - Cohen, T. DO - 10.5588/ijtld.12.0573 10.5588/ijtld.12.0573. ET - 06/08 IS - 7 L1 - file:///C:/Users/James/AppData/Local/Mendeley Ltd/Mendeley Desktop/Downloaded/Dye Modellers wish list.pdf LA - eng PY - 2013 SN - 1815-7920 (Electronic) 1027-3719 (Linking) SP - 866-877 ST - Data Needs for Evidence-Based Decisions: a Tuberculosis Modeler's 'Wish List' T2 - Int J Tuberc Lung Dis TI - Data Needs for Evidence-Based Decisions: a Tuberculosis Modeler's 'Wish List' UR - http://www.ncbi.nlm.nih.gov/pubmed/23743307 VL - 17 ID - 3456 ER - TY - JOUR AB - Background: The potential population-level impact of private-sector initiatives for tuberculosis (TB) case finding in Southeast Asia remains uncertain. In 2011, the Indus Hospital TB Control Program in Karachi, Pakistan, undertook an aggressive case-finding campaign that doubled notification rates, providing an opportunity to investigate potential population-level effects. Methods: We constructed an age-structured compartmental model of TB in the intervention area. We fit the model using field and literature data, assuming that TB incidence equaled the estimated nationwide incidence in Pakistan (primary analysis), or 1.5 times greater (high-incidence scenario). We modeled the intervention as an increase in the rate of formal-sector TB diagnosis and evaluated the potential impact of sustaining this rate for five years. Results: In the primary analysis, the five-year intervention averted 24% (95% uncertainty range, UR: 18-30%) of five-year cumulative TB cases and 52% (95% UR: 45-57%) of cumulative TB deaths. Corresponding reductions in the high-incidence scenario were 12% (95% UR: 8-17%) and 27% (95% UR: 21-34%), although the absolute number of lives saved was higher. At the end of five years, TB notification rates in the primary analysis were below their 2010 baseline, incidence had dropped by 45%, and annual mortality had fallen by 72%. About half of the cumulative impact on incidence and mortality could be achieved with a one-year intervention. Conclusions: Sustained, multifaceted, and innovative approaches to TB case-finding in Asian megacities can have substantial community-wide epidemiological impact. AD - Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA Johns Hopkins Univ, Ctr TB Res, Baltimore, MD USA Interact Res & Dev, Karachi, Sindh, Pakistan Stop TB Partnership, Geneva, Switzerland Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA AN - WOS:000326019400118 AU - Dowdy, D. W. AU - Lotia, I. AU - Azman, A. S. AU - Creswell, J. AU - Sahu, S. AU - Khan, A. J. DA - Oct 16 DO - ARTN e77517 10.1371/journal.pone.0077517 IS - 10 J2 - Plos One KW - smear-positive tuberculosis mycobacterium-tuberculosis annual risk reinfection strategies infection tb microscopy bacilli relapse LA - English N1 - 239jr Times Cited:12 Cited References Count:32 PY - 2013 SN - 1932-6203 ST - Population-Level Impact of Active Tuberculosis Case Finding in an Asian Megacity T2 - Plos One TI - Population-Level Impact of Active Tuberculosis Case Finding in an Asian Megacity UR - ://WOS:000326019400118 VL - 8 ID - 4893 ER - TY - JOUR AB - The target for TB elimination is to reduce annual incidence to less than one case per million population by 2050. Meeting that target requires a 1,000-fold reduction in incidence in little more than 35 years. This can be achieved only by combining the effective treatment of active TB-early case detection and high cure rates to interrupt transmission-with methods to prevent new infections and to neutralize existing latent infections. Vigorous implementation of the WHO Stop TB Strategy is needed to achieve the former, facilitated by the effective supply of, and demand for, health services. The latter calls for new technology, including biomarkers of TB risk, diagnostics, drugs, and vaccines. An important milestone en route to elimination will be reached when there is less than 1 TB death per 100,000 population, marking entry into the elimination phase. This landmark can be reached by many countries within 1-2 decades. AD - Office of Health Information, World Health Organization, CH 1211 Geneva 27, Switzerland. dyec@who.int AN - 23244049 AU - Dye, C. AU - Glaziou, P. AU - Floyd, K. AU - Raviglione, M. DO - 10.1146/annurev-publhealth-031912-114431 ET - 2012/12/19 J2 - Annual review of public health L1 - internal-pdf://3633604237/Dye-2013-Prospects for tuberculosis eliminatio.pdf LA - eng N1 - Dye, Christopher Glaziou, Philippe Floyd, Katherine Raviglione, Mario Annu Rev Public Health. 2013;34:271-86. doi: 10.1146/annurev-publhealth-031912-114431. Epub 2012 Dec 14. PY - 2013 SN - 1545-2093 (Electronic) 0163-7525 (Linking) SP - 271-86 ST - Prospects for tuberculosis elimination T2 - Annu Rev Public Health TI - Prospects for tuberculosis elimination UR - http://www.ncbi.nlm.nih.gov/pubmed/23244049 http://www.annualreviews.org.ez.lshtm.ac.uk/doi/pdf/10.1146/annurev-publhealth-031912-114431 http://www.annualreviews.org/doi/pdf/10.1146/annurev-publhealth-031912-114431 VL - 34 ID - 4432 ER - TY - JOUR AB - Tuberculosis is a global health issue with annually about 1.5 million deaths and 2 billion infected people worldwide. Extra-pulmonary tuberculosis comprises 13% of all cases of which tuberculous meningitis is the most severe. It has a high mortality and is often diagnosed once irreversible neurological damage has already occurred. Development of diagnostic and treatment strategies requires a thorough understanding of the pathogenesis of tuberculous meningitis. This disease is characterized by the formation of a cerebral granuloma, which is a collection of immune cells that attempt to immunologically restrain, and physically contain bacteria. The cytokine tumor necrosis factor-alpha is known for its important role in granuloma formation. Because traditional experimental animal studies exploring tuberculous meningitis are difficult and expensive, another approach is needed to begin to address this important and significant disease outcome. Here, we present an in silico model capturing the unique immunological environment of the brain that allows us to study the key mechanisms driving granuloma formation in time. Uncertainty and sensitivity analysis reveals a dose-dependent effect of tumor necrosis factor-alpha on bacterial load and immune cell numbers thereby influencing the onset of tuberculous meningitis. Insufficient levels result in bacterial overgrowth, whereas high levels lead to uncontrolled inflammation being detrimental to the host. These findings have important implications for the development of immuno-modulating treatment strategies for tuberculous meningitis. AD - Department of Pediatric Infectious diseases and Immunology, VU University Medical Center, Amsterdam, The Netherlands. AN - 23542051 AU - El-Kebir, M. AU - van der Kuip, M. AU - van Furth, A. M. AU - Kirschner, D. E. C2 - PMC3821557 C6 - NIHMS470247 DA - Jul 07 DO - 10.1016/j.jtbi.2013.03.008 DP - NLM ET - 2013/04/02 J2 - Journal of theoretical biology KW - Bacterial Load *Computer Simulation Granuloma/*immunology Humans *Models, Immunological Mycobacterium tuberculosis/*immunology Tuberculosis, Meningeal/diagnosis/*immunology/mortality Tumor Necrosis Factor-alpha/*immunology LA - eng N1 - 1095-8541 El-Kebir, M van der Kuip, M van Furth, A M Kirschner, D E R01HL106804/HL/NHLBI NIH HHS/United States R01EB012579/EB/NIBIB NIH HHS/United States R01HL110811/HL/NHLBI NIH HHS/United States R01 HL106804/HL/NHLBI NIH HHS/United States R01 EB012579/EB/NIBIB NIH HHS/United States R01 HL110811/HL/NHLBI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England J Theor Biol. 2013 Jul 7;328:43-53. doi: 10.1016/j.jtbi.2013.03.008. Epub 2013 Mar 26. PY - 2013 SN - 0022-5193 SP - 43-53 ST - Computational modeling of tuberculous meningitis reveals an important role for tumor necrosis factor-alpha T2 - J Theor Biol TI - Computational modeling of tuberculous meningitis reveals an important role for tumor necrosis factor-alpha VL - 328 ID - 1804 ER - TY - JOUR AB - This paper deals with the problem of optimal control for the transmission dynamics of tuberculosis (TB). A TB model which considers the existence of a new class (mainly in the African context) is considered: the lost of sight individuals. Based on the model formulated and studied in Tewa and Bowong (Commun Nonlinear Sci Numer Simul 14:4010-4021, 2009), the TB control is formulated and solved as an optimal control theory problem using state-dependent Riccati equation. This control strategy indicates how the control of the class of lost of sight can considerably influence the basic reproduction ratio so as to reduce their number. Numerical results illustrate the performance of the optimization strategy. AD - Univ Yaounde I, Fac Sci, Dept Math, Lab Appl Math, Yaounde, Cameroon UMI 209 IRD & UPMC UMMISCO, Bondy, France Project Team GRIMCAPE, LIRIMA, Yaounde, Cameroon AN - WOS:000320665200001 AU - Emvudu, Y. AU - Demasse, R. AU - Djeudeu, D. DA - Jul DO - 10.1007/s40314-013-0002-1 IS - 2 J2 - Comput Appl Math KW - nonlinear dynamical systems tuberculosis models basic reproduction ratio optimal control lost of sight LA - English N1 - 167wd Times Cited:1 Cited References Count:24 PY - 2013 SN - 1807-0302 SP - 191-210 ST - Optimal control using state-dependent Riccati equation of lost of sight in a tuberculosis model T2 - Computational & Applied Mathematics TI - Optimal control using state-dependent Riccati equation of lost of sight in a tuberculosis model UR - ://WOS:000320665200001 VL - 32 ID - 4894 ER - TY - JOUR AB - Finding more effective vaccines against tuberculosis (TB) and improved preventive treatments against endogenous reactivation of latent TB is strategic to block transmission and reach the WHO goal of eliminating TB by 2050. Key related open questions in TB research include: i) what are the determinants of a strong memory response upon primary infection? ii) what is the role of cytokines towards protective memory response against a secondary infection? iii) what are the mechanisms responsible for the increased risk of reactivation in elderly individuals? To address these questions, we explored a computational model of the immune response to Mycobacterium tuberculosis including a mathematical description of immunosenescence and the generation and maintenance of immune memory. Sensitivity analysis techniques, together with extensive model characterization and in silico experiments, were applied to identify key mechanisms controlling TB reactivation and immunological memory. Key findings of this study are summarized by the following model predictions: i) increased strength and duration of memory protection is associated with higher levels of Tumor Necrosis Factor-[Formula: see text] (TNF) during primary infection; ii) production of TNF, but not of interferon-[Formula: see text], by memory T cells during secondary infection is a major determinant of effective protection; iii) impaired recruitment of CD4+ T cells may promote reactivation of latent TB infections in aging hosts. This study is a first attempt to consider the immune dynamics of a persistent infection throughout the lifetime of the host, taking into account immunosenescence and memory. While the model is TB specific, the results are applicable to other persistent bacterial infections and can aid in the development, evaluation and refinement of TB treatment and/or vaccine protocols. AD - Department of Statistics and Mathematics Applied to Economics, University of Pisa, Pisa, Italy. guzzetta@fbk.eu AN - 23580062 AU - Guzzetta, G. AU - Kirschner, D. C2 - PMC3620273 DO - 10.1371/journal.pone.0060425 DP - NLM ET - 2013/04/13 IS - 4 J2 - PloS one KW - Aging/*immunology Algorithms CD4-Positive T-Lymphocytes/immunology Computer Simulation Cytokines/genetics/immunology Gene Knockout Techniques Humans *Immunologic Memory/genetics Models, Immunological Mycobacterium tuberculosis/*immunology Tuberculosis/genetics/*immunology/*prevention & control Tuberculosis Vaccines/immunology LA - eng N1 - 1932-6203 Guzzetta, Giorgio Kirschner, Denise R01 EB012579/EB/NIBIB NIH HHS/United States R01 HL110811/HL/NHLBI NIH HHS/United States R01 HL106804/HL/NHLBI NIH HHS/United States R33 HL092853/HL/NHLBI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States PLoS One. 2013 Apr 8;8(4):e60425. doi: 10.1371/journal.pone.0060425. Print 2013. PY - 2013 SN - 1932-6203 SP - e60425 ST - The roles of immune memory and aging in protective immunity and endogenous reactivation of tuberculosis T2 - PLoS One TI - The roles of immune memory and aging in protective immunity and endogenous reactivation of tuberculosis VL - 8 ID - 1795 ER - TY - JOUR AB - We address the problem of long-term dynamics of tuberculosis (TB) and latent tuberculosis (LTB) in semiclosed communities. These communities are congregate settings with the potential for sustained daily contact for weeks, months, and even years between their members. Basic examples of these communities are prisons, but certain urban/rural communities, some schools, among others could possibly fit well into this definition. These communities present a sort of ideal conditions for TB spread. In order to describe key relevant dynamics of the disease in these communities, we consider a five compartments SEIR model with five possible routes toward TB infection: primary infection after a contact with infected and infectious individuals (fast TB), endogenous reactivation after a period of latency (slow TB), relapse by natural causes after a cure, exogenous reinfection of latently infected, and exogenous reinfection of recovered individuals. We discuss the possible existence of multiple endemic equilibrium states and the role that the two types of exogenous reinfections in the long-term dynamics of the disease could play. AD - Facultad de Ingenieria, Universidad del Desarrollo, Santiago 7620001, Chile. AN - 23762194 AU - Herrera, M. AU - Bosch, P. AU - Najera, M. AU - Aguilera, X. C2 - PMC3665242 DO - 10.1155/2013/648291 DP - NLM ET - 2013/06/14 J2 - Computational and mathematical methods in medicine KW - Communicable Diseases/epidemiology/mortality/transmission Computational Biology Endemic Diseases/statistics & numerical data Humans Latent Tuberculosis/epidemiology/mortality/transmission *Models, Biological Models, Statistical Prisons Recurrence Tuberculosis, Pulmonary/epidemiology/mortality/*transmission LA - eng N1 - 1748-6718 Herrera, Mauricio Bosch, Paul Najera, Manuel Aguilera, Ximena Journal Article Research Support, Non-U.S. Gov't United States Comput Math Methods Med. 2013;2013:648291. doi: 10.1155/2013/648291. Epub 2013 May 9. PY - 2013 SN - 1748-670x SP - 648291 ST - Modeling the spread of tuberculosis in semiclosed communities T2 - Comput Math Methods Med TI - Modeling the spread of tuberculosis in semiclosed communities VL - 2013 ID - 1753 ER - TY - JOUR AB - Tuberculosis (TB) transmission is a key factor for disease-control policy, but the timing and distribution of transmission and the role of social contacts remain obscure. We develop an agent-based simulation of a TB epidemic in a single population, and consider a hierarchically structured contact network in three levels, typical of airborne diseases. The parameters are adopted from the literature, and the model is calibrated to a setting of high TB incidence. We model the dynamics of transmission at the individual level, and study the timing of secondary infections from a single source throughout the duration of the disease. We compare the patterns of transmission among different networks and discuss implications. Sensitivity analysis of outputs indicates the robustness of the results to variations in the parameter values. AD - Univ Cincinnati, Dept Operat Business Analyt & Informat Syst, Cincinnati, OH 45221 USA Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA AN - WOS:000349838402048 AU - Kasaie, P. AU - Dowdy, D. W. AU - Kelton, W. D. J2 - Wint Simul C Proc KW - high-incidence area reinfection community dynamics LA - English N1 - Bc0yo Times Cited:4 Cited References Count:30 Winter Simulation Conference Proceedings PY - 2013 SN - 0891-7736 SP - 2227-2238 ST - An Agent-Based Simulation of a Tuberculosis Epidemic: Understanding the Timing of Transmission T2 - 2013 Winter Simulation Conference (Wsc) TI - An Agent-Based Simulation of a Tuberculosis Epidemic: Understanding the Timing of Transmission UR - ://WOS:000349838402048 ID - 4896 ER - TY - JOUR AB - Background: While the overall population prevalence of tuberculosis in Quebec has been declining for many years, tuberculosis is still disproportionately more prevalent among the immigrant and Inuit communities. As such, the aim of this study was to forecast the incidence of tuberculosis in the Province of Quebec over time in order to examine the possible impact of future preventative and treatment programs geared to reducing such disparities. Methods: A compartmental differential equation based on a Susceptible Exposed Latent Infectious Recovered (SELIR) model was simulated using the Euler method using Visual Basic for Applications in Excel. Demographic parameters were obtained from census data for the Province of Quebec and the model was fitted to past epidemiological data to extrapolate future values over the period 2015 to 2030. Results: The trend of declining tuberculosis rates will continue in the general population, falling by 42% by 2030. The incidence among immigrants will decrease but never vanish, and may increase in the future. Among the Inuit, the incidence is expected to increase, reaching a maximum and then stabilizing, although if re-infection is taken into account it may continue to increase. Tuberculosis among non-indigenous Canadian born persons will continue to decline, with the disease almost eradicated in that group in the mid 21st century. Conclusions: While the incidence of tuberculosis in the Province of Quebec is expected to decrease overall, certain populations will remain at risk. AD - Medmetr Inc, Montreal, PQ H3A 0A5, Canada McGill Univ, Montreal, PQ, Canada AN - WOS:000319770400001 AU - Klotz, A. AU - Harouna, A. AU - Smith, A. F. DA - Apr 27 DO - Artn 400 10.1186/1471-2458-13-400 J2 - Bmc Public Health KW - tuberculosis epidemiology forecasting quebec transmission dynamics immigration canada LA - English N1 - 155tf Times Cited:1 Cited References Count:16 PY - 2013 SN - 1471-2458 ST - Forecast analysis of the incidence of tuberculosis in the province of Quebec T2 - Bmc Public Health TI - Forecast analysis of the incidence of tuberculosis in the province of Quebec UR - ://WOS:000319770400001 VL - 13 ID - 4897 ER - TY - JOUR AB - Active tuberculosis (TB) in the UK predominantly affects the non-UK born, but is generally not manifest at the time of UK entry. Strategies to detect latent TB infection (LTBI) in this population are, therefore, important. To date, targeted screening has focused on TB risk estimates based on the incidence in the country of origin. Using TB incidence in the UK and migration data, we estimated the numbers needed to be tested and treated for LTBI to prevent one case of TB disease. Numbers were the lowest in Somalian and the highest in South African and Filipino migrants, which contrasts with TB rates in these countries. Targeting screening on the basis of incidence in the UK may thus improve effectiveness. AD - Tuberculosis Section, Public Health England, , London, UK. AN - 23828120 AU - Kruijshaar, M. E. AU - Abubakar, I. AU - Stagg, H. R. AU - Pedrazzoli, D. AU - Lipman, M. DA - Dec DO - 10.1136/thoraxjnl-2013-203254 DP - NLM ET - 2013/07/06 IS - 12 J2 - Thorax KW - Africa South of the Sahara/ethnology Bangladesh/ethnology Emigration and Immigration/*statistics & numerical data Humans Incidence Interferon-gamma Release Tests Latent Tuberculosis/*diagnosis Mass Screening Pakistan/ethnology Philippines/ethnology Tuberculosis, Pulmonary/*diagnosis/*ethnology/prevention & control United Kingdom/epidemiology Tuberculosis LA - eng N1 - 1468-3296 Kruijshaar, Michelle E Abubakar, Ibrahim Stagg, Helen R Pedrazzoli, Debora Lipman, Marc Journal Article England Thorax. 2013 Dec;68(12):1172-4. doi: 10.1136/thoraxjnl-2013-203254. Epub 2013 Jul 4. PY - 2013 SN - 0040-6376 SP - 1172-4 ST - Migration and tuberculosis in the UK: targeting screening for latent infection to those at greatest risk of disease T2 - Thorax TI - Migration and tuberculosis in the UK: targeting screening for latent infection to those at greatest risk of disease VL - 68 ID - 1740 ER - TY - JOUR AB - Tuberculosis (TB) is among the top ten causes of death worldwide. The impacts of potential control measures on TB infection in senior care facilities are poorly understood in Taiwan region. The purpose of this paper was to assess the impacts of potential control strategies for reducing the risk for TB infection among elderly in senior care facilities and to provide the suggestions for sound TB infection control measures that should be implemented in all senior care facilities with aged people suspected of having infectious TB. We proposed an integrated-level mathematical model, incorporating the TB transmission dynamics, the Wells-Riley mathematical equation, and the competing-risks model to quantify the potential spread of TB bacilli in senior care facilities. We found that individuals living in hospital-based nursing homes had much higher exposure to TB than those in long-term and domiciliary care facilities. We showed that the proposed combinations of engineering control measures (e.g., ventilation and ultraviolet germicidal irradiation) with personal protection (e.g., surgical mask) guarantee the provision of a reliable control strategy to decrease the transmission potential and spread rate of TB bacilli aerosols in senior care facilities in that the efficacies range from 45 to 90%. The introduction of appropriate TB transmission control measures may decrease TB annual incidence in senior care facilities by as much as 76-90% of tuberculin skin test (TST) conversion. Our study implicated that sound TB infection control measures, including diagnosis and prompt treatment of infectious cases should be prioritized. (c) 2012 Elsevier Ltd. All rights reserved. AD - [Liao, Chung-Min; Lin, Yi-Jun; Cheng, Yi-Hsien] Natl Taiwan Univ, Dept Bioenvironm Syst Engn, Taipei 10617, Taiwan. Liao, CM (reprint author), Natl Taiwan Univ, Dept Bioenvironm Syst Engn, Taipei 10617, Taiwan. cmliao@ntu.edu.tw AN - WOS:000314371900008 AU - Liao, C. M. AU - Lin, Y. J. AU - Cheng, Y. H. DA - Jan DO - 10.1016/j.buildenv.2012.08.008 J2 - Build. Environ. KW - Tuberculosis Transmission Senior care facilities Control measures Modeling Indoor air quality ultraviolet germicidal irradiation intrinsic transmission dynamics mycobacterium-tuberculosis nosocomial transmission airborne infection anthrax outbreak risk age ventilation settings Construction & Building Technology Engineering LA - English M3 - Article N1 - ISI Document Delivery No.: 082DG Times Cited: 8 Cited Reference Count: 63 Liao, Chung-Min Lin, Yi-Jun Cheng, Yi-Hsien 8 1 19 Pergamon-elsevier science ltd Oxford PY - 2013 SN - 0360-1323 SP - 66-75 ST - Modeling the impact of control measures on tuberculosis infection in senior care facilities T2 - Building and Environment TI - Modeling the impact of control measures on tuberculosis infection in senior care facilities UR - ://WOS:000314371900008 VL - 59 ID - 5591 ER - TY - CHAP AB - A TB transmission model with TB defaulters is presented in this paper. The global dynamics of the TB model is established by constructing proper Lyapunov functions. It is proved that the disease-free equilibrium is globally asymptotically stable if the basic reproduction number R-0 is below unity; and the unique endemic equilibrium is globally asymptotically stable if the basic reproduction number R-0 is above unity. AD - [Liu, Luju; Wu, Yusen] Henan Univ Sci & Technol, Sch Math & Stat, Luoyang 471003, Peoples R China. Liu, LJ (reprint author), Henan Univ Sci & Technol, Sch Math & Stat, Luoyang 471003, Peoples R China. lujuliu@gmail.com AN - WOS:000330345600092 AU - Liu, L. J. AU - Wu, Y. S. AU - Ieee CY - New York KW - Global dynamics tuberculosis transmission model TB defaulters the basic reproduction number Lyapunov function LA - English N1 - ISI Document Delivery No.: BJT90 Times Cited: 0 Cited Reference Count: 14 Liu, Luju Wu, Yusen Icamechs Proceedings Paper International Conference on Advanced Mechatronic Systems (ICAMechS) Sep 25-27, 2013 Luoyang, PEOPLES R CHINA IEEE, Henan Univ Sci & Technol 345 e 47th st, new york, ny 10017 usa 2325-0682 PB - Ieee PY - 2013 SN - 978-1-4799-2518-6; 978-1-4799-2519-3 SP - 477-481 ST - Global dynamics of a TB transmission model with TB defaulters T2 - 2013 International Conference on Advanced Mechatronic Systems T3 - International Conference on Advanced Mechatronic Systems TI - Global dynamics of a TB transmission model with TB defaulters UR - ://WOS:000330345600092 ID - 5582 ER - TY - JOUR AB - One problem associated with regimen-based development of anti-tuberculosis (anti-TB) drugs is the difficulty of a systematic and thorough in vivo evaluation of the large number of possible regimens that arise from consideration of multiple drugs tested together. A mathematical model capable of simulating the pharmacokinetics and pharmacodynamics of experimental combination chemotherapy of TB offers a way to mitigate this problem by extending the use of available data to investigate regimens that are not initially tested. In order to increase the available mathematical tools needed to support such a model for preclinical anti-TB drug development, we constructed a preliminary whole-body physiologically based pharmacokinetic (PBPK) model of rifampin in mice, using data from the literature. Interindividual variability was approximated using Monte Carlo (MC) simulation with assigned probability distributions for the model parameters. An MC sensitivity analysis was also performed to determine correlations between model parameters and plasma concentration to inform future model development. Model predictions for rifampin concentrations in plasma, liver, kidneys, and lungs, following oral administration, were generally in agreement with published experimental data from multiple studies. Sensitive model parameters included those descriptive of oral absorption, total clearance, and partitioning of rifampin between blood and muscle. This PBPK model can serve as a starting point for the integration of rifampin pharmacokinetics in mice into a larger mathematical framework, including the immune response to Mycobacterium tuberculosis infection, and pharmacokinetic models for other anti-TB drugs. AD - Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA. AN - 23357766 AU - Lyons, M. A. AU - Reisfeld, B. AU - Yang, R. S. AU - Lenaerts, A. J. DA - Jan 28 DO - 10.1128/aac.01567-12 DP - Nlm ET - 01/30 J2 - Antimicrobial agents and chemotherapy LA - Eng N1 - Lyons, Michael A Reisfeld, Brad Yang, Raymond S H Lenaerts, Anne J Antimicrob Agents Chemother. 2013 Jan 28. PY - 2013 SN - 1098-6596 (Electronic) 0066-4804 (Linking) ST - A Physiologically Based Pharmacokinetic Model of Rifampin in Mice T2 - Antimicrob Agents Chemother TI - A Physiologically Based Pharmacokinetic Model of Rifampin in Mice UR - http://aac.asm.org/content/early/2013/01/22/AAC.01567-12.full.pdf ID - 2698 ER - TY - JOUR AB - The demonstration of the efficacy of antiretroviral therapy (ART) for HIV prevention in heterosexual HIV serodiscordant couples has resulted in the call for widespread implementation of "Treatment as Prevention" (TasP) to confront the challenge of continued transmission of HIV. In addition, evidence of the possible effect of use of ART on decreasing the incidence of tuberculosis (TB) in persons living with HIV has also contributed further enthusiasm. Mathematical modeling studies evaluating the potential impact of TasP on the trajectory of the HIV and TB epidemics have inspired discussions about a possible future without AIDS. We present the evidence regarding the effect of ART on the incidence of HIV and TB, benefits and risks associated with embracing TasP, and the need for multicomponent prevention strategies and for further research to generate empiric data on the effect of TasP on HIV and TB at a population level. AD - ICAP, Mailman School of Public Health, Columbia University, New York, NY 10032, USA. mm3780@columbia.edu AN - 23764636 AU - McNairy, M. L. AU - Howard, A. A. AU - El-Sadr, W. M. DA - Jul DO - 10.1097/QAI.0b013e3182986fc6 DP - NLM ET - 2013/06/21 J2 - Journal of acquired immune deficiency syndromes (1999) KW - AIDS-Related Opportunistic Infections/drug therapy/*prevention & control Anti-HIV Agents/administration & dosage/*therapeutic use Family Characteristics Female HIV Infections/complications/drug therapy/*prevention & control/transmission HIV Seropositivity Heterosexuality Humans Incidence Male Models, Theoretical Risk Tuberculosis/complications/drug therapy/*prevention & control LA - eng N1 - 1944-7884 McNairy, Margaret L Howard, Andrea A El-Sadr, Wafaa M Journal Article United States J Acquir Immune Defic Syndr. 2013 Jul;63 Suppl 2:S200-7. doi: 10.1097/QAI.0b013e3182986fc6. PY - 2013 SN - 1525-4135 SP - S200-7 ST - Antiretroviral therapy for prevention of HIV and tuberculosis: a promising intervention but not a panacea T2 - J Acquir Immune Defic Syndr TI - Antiretroviral therapy for prevention of HIV and tuberculosis: a promising intervention but not a panacea VL - 63 Suppl 2 ID - 1749 ER - TY - JOUR AB - SETTING: Although a preventable and treatable disease, tuberculosis (TB) is among the top 10 causes of death worldwide. A consequence of inadequately treated drug-susceptible TB (DS-TB) is multidrug-resistant TB (MDR-TB). OBJECTIVES: To improve our understanding of the primary drivers of incidence and prevalence of DS- and MDR-TB in China. METHODS: The Tuberculosis Disease Transmission Model (TBDTM) uses historical and current disease epidemiology and transmission trends and treatment effectiveness, and accounts for annual changes to these to estimate future DS-TB and MDR-TB burden. RESULTS: The model shows that in China, by 2050, incidence, prevalence and mortality of DS-TB will decrease by 32%, 50% and 41%, respectively, whereas MDR-TB will increase by respectively 60%, 48% and 35%. Reduction in DS-TB is a result of high treatment and cure rates leading to a decrease in the prevalence of latent tuberculous infection (LTBI), while the increase in MDR-TB is attributed to inappropriate treatment, leading to high transmission of infection and increased LTBI prevalence. CONCLUSIONS: These results demonstrate a reduction in DS-TB in China over the next 40 years, while MDR-TB will increase. Improvements in the diagnosis and treatment of MDR-TB are needed to counter this threat. The TBDTM tool has potential value in public health practice by demonstrating the impact of interventions and estimating their cost-effectiveness. AD - Janssen Global Services, Raritan, New Jersey 08869, USA. mmehra@its.jnj.com AN - 23827732 AU - Mehra, M. AU - Cossrow, N. AU - Kambili, C. AU - Underwood, R. AU - Makkar, R. AU - Potluri, R. DA - Sep DO - 10.5588/ijtld.12.0959 DP - NLM ET - 2013/07/06 IS - 9 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Antitubercular Agents/therapeutic use China/epidemiology *Computer Simulation Drug Resistance, Multiple, Bacterial Humans Incidence *Models, Theoretical Prevalence Prognosis Time Factors Tuberculosis/diagnosis/drug therapy/*epidemiology/mortality/*transmission Tuberculosis, Multidrug-Resistant/epidemiology/transmission L1 - internal-pdf://0540804614/s10 (1).pdf LA - eng N1 - 1815-7920 Mehra, M Cossrow, N Kambili, C Underwood, R Makkar, R Potluri, R Journal Article France Int J Tuberc Lung Dis. 2013 Sep;17(9):1186-94. doi: 10.5588/ijtld.12.0959. Epub 2013 Jul 3. PY - 2013 SN - 1027-3719 SP - 1186-94 ST - Assessment of tuberculosis burden in China using a dynamic disease simulation model T2 - Int J Tuberc Lung Dis TI - Assessment of tuberculosis burden in China using a dynamic disease simulation model VL - 17 ID - 1741 ER - TY - JOUR AB - Tuberculosis (TB) control is especially difficult in settings of high HIV prevalence; HIV co-infection erodes host immunity and increases risk of progression to active TB. Studies have demonstrated that a 6-month (or longer) course of monotherapy with isoniazid [isoniazid preventive therapy (IPT)] can reduce this risk. The World Health Organization endorses IPT for symptom-free individuals with HIV/TB co-infection and has recommended expanding IPT to entire communities (community-wide IPT). Although previous reviews have not found a statistically significant elevated risk of isoniazid-resistant TB among individuals previously treated with IPT, community-wide IPT programs may nonetheless generate substantial selective pressure and increase the burden of drug-resistant TB (DRTB). We developed mathematical models to identify the conditions under which community-wide IPT interventions could increase the burden of isoniazid-resistant Mycobacterium tuberculosis, even when we assumed that IPT does not select for resistance among those treated with IPT. We found that in models that included any mechanism of interstrain competition (such as partial immunity conferred by a previous M. tuberculosis infection), community-wide IPT interventions conferred an indirect benefit to drug-resistant strains through selective suppression of drug-sensitive infections. This result suggests that the absence of an observed elevation in the risk of DRTB among those receiving IPT in small-scale studies of limited duration does not imply that the selective pressure imposed by community-wide IPT will not be substantial. Community-wide IPT may play an important role in TB control in these settings, and its rollout should be accompanied by interventions to detect and treat drug-resistant disease. AD - Bristol Centre for Complexity Sciences, University of Bristol, Bristol BS8 1TR, UK. AN - 23576815 AU - Mills, H. L. AU - Cohen, T. AU - Colijn, C. C2 - PMC3714172 C6 - NIHMS483301 DA - Apr 10 DO - 10.1126/scitranslmed.3005260 DP - NLM ET - 2013/04/12 IS - 180 J2 - Science translational medicine KW - Antitubercular Agents/*therapeutic use Humans Isoniazid/*therapeutic use Tuberculosis/*drug therapy Tuberculosis, Multidrug-Resistant L1 - internal-pdf://2148711745/Mills-2013-Community-wide isoniazid preventive.pdf LA - eng N1 - 1946-6242 Mills, Harriet L Cohen, Ted Colijn, Caroline DP2 OD006663/OD/NIH HHS/United States U54 GM088558/GM/NIGMS NIH HHS/United States DP2OD006663/OD/NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Sci Transl Med. 2013 Apr 10;5(180):180ra49. doi: 10.1126/scitranslmed.3005260. PY - 2013 SN - 1946-6234 SP - 180ra49 ST - Community-wide isoniazid preventive therapy drives drug-resistant tuberculosis: a model-based analysis T2 - Sci Transl Med TI - Community-wide isoniazid preventive therapy drives drug-resistant tuberculosis: a model-based analysis UR - http://stm.sciencemag.org/content/scitransmed/5/180/180ra49.full.pdf VL - 5 ID - 1797 ER - TY - JOUR AB - Effective tuberculosis (TB) control depends on case findings to discover infectious cases, investigation of contacts of those with TB, as well as appropriate treatment. Adherence and successful completion of the treatment are equally important. Unfortunately, due to a number of personal, psychosocial, economic, medical, and health service factors, a significant number of TB patients become irregular and default from treatment. In this paper, a mathematical model is developed to assess the impact of early therapy for latent TB and non-adherence on controlling TB transmission dynamics. Equilibrium states of the model are determined and their local stability is examined. With the aid of the center manifold theory, it is established that the model undergoes a backward bifurcation. Qualitative mathematical analysis of the model suggests that a high level of latent tuberculosis case findings, coupled with a decrease of defaulting rate, may be effective in controlling TB transmission dynamics in the community. Population-level effects of organized campaigns to improve early therapy and to guarantee successful completion of each treatment are evaluated through numerical simulations and presented in support of the analytical results. AD - Department of Mathematics, University of Zimbabwe, PO Box MP 167, Harare, Zimbabwe. steadymushaya@gmail.com AN - 23975671 AU - Mushayabasa, S. AU - Bhunu, C. P. C2 - PMC3758829 DA - Sep DO - 10.1007/s10867-013-9328-6 DP - NLM ET - 2013/08/27 IS - 4 J2 - Journal of biological physics KW - Asymptomatic Diseases Communicable Disease Control/*methods Endemic Diseases/prevention & control Humans Latent Tuberculosis/epidemiology/*prevention & control/*therapy *Models, Statistical Patient Compliance Time Factors LA - eng N1 - 1573-0689 Mushayabasa, S Bhunu, C P Journal Article Netherlands J Biol Phys. 2013 Sep;39(4):723-47. doi: 10.1007/s10867-013-9328-6. Epub 2013 Aug 23. PY - 2013 SN - 0092-0606 SP - 723-47 ST - Modeling the impact of early therapy for latent tuberculosis patients and its optimal control analysis T2 - J Biol Phys TI - Modeling the impact of early therapy for latent tuberculosis patients and its optimal control analysis VL - 39 ID - 1712 ER - TY - CHAP AB - This paper presents a model of tuberculosis transmission with vaccination by explicitely considering the total number of recovered individuals, either from natural recovery or due to vaccination. In this paper the endemic and nonendemic fixed points, basic reproduction number, and vaccination reproduction number are given. Some results regarding the stability of the fixed points and the relation to the basic reproduction numbers are analysed. At the end of this study, the numerical computation presented and it shows that vaccination is capable to reduce the number of laten and infectious populations. AD - [Nainggolan, J.] Univ Cenderawasih, Dept Math, Jayapura, Indonesia. [Supian, Sudradjat; Supriatna, A. K.; Anggriani, N.] Univ Padjadjaran, Dept Math, Padjadjaran, Indonesia. Nainggolan, J (reprint author), Univ Cenderawasih, Dept Math, Jayapura, Indonesia. jonn_cesil@yahoo.co.id AN - WOS:000318418000059 AU - Nainggolan, J. AU - Supian, S. AU - Supriatna, A. K. AU - Anggriani, N. AU - Iop CY - Bristol DO - 012059 10.1088/1742-6596/423/1/012059 L1 - internal-pdf://3706534958/Nainggolan-2013-Mathematical Model Of Tubercul.pdf LA - English N1 - ISI Document Delivery No.: BEW62 Times Cited: 1 Cited Reference Count: 16 Nainggolan, J. Supian, Sudradjat Supriatna, A. K. Anggriani, N. Scietech 2013 Proceedings Paper International Conference on Science and Engineering in Mathematics, Chemistry and Physics (ScieTech) Jan 24-25, 2013 Jakarta, INDONESIA Indonesian Government through Penelitian Hibah Kompetensi The authors thanks to Irfan Wahyudi for reading and revising the grammar. Part of the work is funded by the Indonesian Government through Penelitian Hibah Kompetensi 2013 to AKS. Dirac house, temple back, bristol bs1 6be, england 1742-6588 PB - Iop Publishing Ltd PY - 2013 ST - Mathematical Model Of Tuberculosis Transmission With Reccurent Infection And Vaccination T2 - 2013 International Conference on Science & Engineering in Mathematics, Chemistry and Physics T3 - Journal of Physics Conference Series TI - Mathematical Model Of Tuberculosis Transmission With Reccurent Infection And Vaccination UR - ://WOS:000318418000059 http://iopscience.iop.org/article/10.1088/1742-6596/423/1/012059/pdf VL - 423 ID - 5587 ER - TY - JOUR AB - BACKGROUND: Despite the progress made in the past decade, tuberculosis (TB) control still faces significant challenges. In many countries with declining TB incidence, the disease tends to concentrate in vulnerable populations that often have limited access to health care. In light of the limitations of the current case-finding approach and the global urgency to improve case detection, active case-finding (ACF) has been suggested as an important complementary strategy to accelerate tuberculosis control especially among high-risk populations. The present exercise aims to develop a model that can be used for county-level project planning. METHODS: A simple deterministic model was developed to calculate the number of estimated TB cases diagnosed and the associated costs of diagnosis. The model was designed to compare cost-effectiveness parameters, such as the cost per case detected, for different diagnostic algorithms when they are applied to different risk populations. The model was transformed into a web-based tool that can support national TB programmes and civil society partners in designing ACF activities. RESULTS: According to the model output, tuberculosis active case-finding can be a costly endeavor, depending on the target population and the diagnostic strategy. The analysis suggests the following: (1) Active case-finding activities are cost-effective only if the tuberculosis prevalence among the target population is high. (2) Extensive diagnostic methods (e.g. X-ray screening for the entire group, use of sputum culture or molecular diagnostics) can be applied only to very high-risk groups such as TB contacts, prisoners or people living with human immunodeficiency virus (HIV) infection. (3) Basic diagnostic approaches such as TB symptom screening are always applicable although the diagnostic yield is very limited. The cost-effectiveness parameter was sensitive to local diagnostic costs and the tuberculosis prevalence of target populations. CONCLUSIONS: The prioritization of appropriate target populations and careful selection of cost-effective diagnostic strategies are critical prerequisites for rational active case-finding activities. A decision to conduct such activities should be based on the setting-specific cost-effectiveness analysis and programmatic assessment. A web-based tool was developed and is available to support national tuberculosis programmes and partners in the formulation of cost-effective active case-finding activities at the national and subnational levels. AU - Nishikiori, N. AU - Van Weezenbeek, C. DO - 10.1186/1471-2458-13-97 10.1186/1471-2458-13-97. KW - *Decision Support Techniques *Health Priorities Algorithms Cambodia/epidemiology Cost-Benefit Analysis Humans Internet Mass Screening/*economics/methods Regional Health Planning/*methods Risk Assessment Tuberculosis, Pulmonary/*diagnosis/economics/epide Vietnam/epidemiology L1 - file:///C:/Users/James/AppData/Local/Mendeley Ltd/Mendeley Desktop/Downloaded/Nishikiori-2013-Target prioritization and stra.pdf PY - 2013 SN - 1471-2458 (Electronic) 1471-2458 (Linking) SP - 97-97 ST - Target prioritization and strategy selection for active case-finding of pulmonary tuberculosis: a tool to support country-level project planning T2 - BMC Public Health TI - Target prioritization and strategy selection for active case-finding of pulmonary tuberculosis: a tool to support country-level project planning UR - https://www.ncbi.nlm.nih.gov/pubmed/23374118 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602078/pdf/1471-2458-13-97.pdf VL - 13 ID - 3998 ER - TY - JOUR AB - Tuberculosis (TB) continues to present an insurmountable health burden in the Western Cape Province of South Africa. TB dynamics in adults is different from that in children, with the former determining the latter. Because the dynamics of TB are largely dependent on age, planning for interventions requires reasonable and realistic projections of the incidence across ages. It is thus important to model the dynamics of TB using mathematical models as predictive tools. We considered a TB compartmental model that is age dependent and whose parameters are set as functions of age. The model was fitted to the TB incidence data from the Cape Town metropole. The effective contact rate, a function of both age and time, was changed to fit the model to the notification rates of active TB disease cases. Our simulations illustrate that age structure plays an important role in the dynamics of TB. Projections on the future of the epidemic were made for each age group. The projected results show that TB incidence is likely to increase in the lower age groups of the population. It is clearly evident that even very simple models when applied to limited data can actually give valuable insights. Our results show that the age groups who have the highest incidence rates of active TB disease have the highest contribution in the transmission of TB. Furthermore, interventions should be targeted in the age group 25-34 years. AD - Univ Stellenbosch, Dept Math Sci, ZA-7600 Stellenbosch, South Africa Univ Stellenbosch, DST NRF Ctr Excellence Epidemiol Modelling & Anal, ZA-7600 Stellenbosch, South Africa AN - WOS:000327880200013 AU - Nyabadza, F. AU - Winkler, D. DA - Sep-Oct DO - ARTN 2012-0106 10.1590/sajs.2013/20120106 IS - 9-10 J2 - S Afr J Sci KW - simulation age-specific model incidence tuberculosis data exogenous reinfection south-africa transmission dynamics impact transition infection community burden risks LA - English N1 - 264lx Times Cited:0 Cited References Count:22 PY - 2013 SN - 0038-2353 ST - A simulation age-specific tuberculosis model for the Cape Town metropole T2 - South African Journal of Science TI - A simulation age-specific tuberculosis model for the Cape Town metropole UR - ://WOS:000327880200013 VL - 109 ID - 4898 ER - TY - JOUR AB - The effect of difference in susceptibility on the dynamics of tuberculosis is an ongoing study. Several genes in TB co-receptors (e.g. HLA and non-HLA) have been correlated with susceptibility and resistance to tuberculosis and rate of progression to active TB. In this paper, we present a novel mathematical model that distinguishes between susceptibility amongst the population. The model classifies the susceptibles as having no, partial or full natural resistance to tuberculosis and the latently infecteds as rapid, normal or very slow (or no) progressors to active TB depending on the genes. The goal of this paper is to investigate the impact of such heterogeneity on the spread of tuberculosis and to identify key parameters that could be used in understanding these heterogeneities more fully. We derived the reproduction number R-T for the model and examine the relative contributions to R-T from the three latently infected classes as well as the infectious classes. The effect of treatment under the heterogeneity is also examined. (C) 2013 Elsevier Inc. All rights reserved. AD - Univ Benin, Dept Math, Benin, Edo State, Nigeria AN - WOS:000320568200017 AU - Okuonghae, D. DA - Jun 1 DO - 10.1016/j.apm.2013.01.039 IS - 10-11 J2 - Appl Math Model KW - tuberculosis mathematical model genetic heterogeneity treatment self cure therapy strategy dots d-receptor gene pulmonary tuberculosis mycobacterium-tuberculosis exogenous reinfection hla association resistance dynamics nigeria LA - English N1 - 166oz Times Cited:3 Cited References Count:48 PY - 2013 SN - 0307-904x SP - 6786-6808 ST - A mathematical model of tuberculosis transmission with heterogeneity in disease susceptibility and progression under a treatment regime for infectious cases T2 - Applied Mathematical Modelling TI - A mathematical model of tuberculosis transmission with heterogeneity in disease susceptibility and progression under a treatment regime for infectious cases UR - ://WOS:000320568200017 VL - 37 ID - 4899 ER - TY - JOUR AB - BACKGROUND: Routinely collected data from tuberculosis surveillance system can be used to investigate and monitor the irregularities and abrupt changes of the disease incidence. We aimed at using a Hidden Markov Model in order to detect the abnormal states of pulmonary tuberculosis in Iran. METHODS: Data for this study were the weekly number of newly diagnosed cases with sputum smear-positive pulmonary tuberculosis reported between April 2005 and March 2011 throughout Iran. In order to detect the unusual states of the disease, two Hidden Markov Models were applied to the data with and without seasonal trends as baselines. Consequently, the best model was selected and compared with the results of Serfling epidemic threshold which is typically used in the surveillance of infectious diseases. RESULTS: Both adjusted R-squared and Bayesian Information Criterion (BIC) reflected better goodness-of-fit for the model with seasonal trends (0.72 and -1336.66, respectively) than the model without seasonality (0.56 and -1386.75). Moreover, according to the Serfling epidemic threshold, higher values of sensitivity and specificity suggest a higher validity for the seasonal model (0.87 and 0.94, respectively) than model without seasonality (0.73 and 0.68, respectively). CONCLUSION: A two-state Hidden Markov Model along with a seasonal trend as a function of the model parameters provides an effective warning system for the surveillance of tuberculosis. AD - Dept. of Mathematics and Statistics, School of Health Management and Information Sciences, Tehran University of Medical Sciences, Tehran, Iran. AN - 23304666 AU - Rafei, A. AU - Pasha, E. AU - Jamshidi Orak, R. DP - Nlm ET - 01/11 J2 - Iranian journal of public health LA - eng N1 - Rafei, A Pasha, E Jamshidi Orak, R Iran Iran J Public Health. 2012;41(10):87-96. Epub 2012 Oct 1. PY - 2013 SN - 2251-6085 (Print) 2251-6085 (Linking) SP - 87-96 ST - Tuberculosis surveillance using a hidden markov model T2 - Iran J Public Health TI - Tuberculosis surveillance using a hidden markov model UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494236/pdf/ijph-41-87.pdf VL - 41 ID - 2686 ER - TY - JOUR AB - BACKGROUND: Use of Xpert MTB/RIF is being scaled up throughout South Africa for improved diagnosis of tuberculosis (TB). A large proportion of HIV-infected patients with possible TB are Xpert-negative on their initial test, and the existing diagnostic algorithm calls for these patients to have sputum culture (Xpert followed by culture (X/C)). We modelled the costs and impact of an alternative diagnostic algorithm in which these cultures are replaced with a second Xpert test (Xpert followed by Xpert (X/X)). METHODS: An existing population-level decision model was used. Costs were estimated from Xpert implementation studies and public sector price and salary data. The number of patients requiring diagnosis was estimated from the literature, as were rates of TB treatment uptake and loss to follow-up. TB and HIV positivity rates were estimated from the national TB register and laboratory databases. RESULTS: At national programme scale in 2014, X/X (R969 million/year) is less expensive than X/C R1 095 million/year), potentially saving R126 million/year (US$17.4 million). However, because Xpert is less sensitive than culture, X/X diagnoses 2% fewer TB cases. This is partly offset by higher expected treatment uptake with X/X due to the faster availability of results, resulting in 1% more patients initiating treatment under X/X than X/C. The cost per TB patient initiated on treatment under X/X is R2 682, which is 12% less than under X/C (R3 046). CONCLUSIONS: Modifying the diagnostic algorithm from X/C to X/X could provide rapid results, simplify diagnostic processes, improve HIV/TB treatment outcomes, and generate cost savings. AD - Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa. kschnippel@heroza.org AN - 23374320 AU - Schnippel, K. AU - Meyer-Rath, G. AU - Long, L. AU - Stevens, W. S. AU - Sanne, I. AU - Rosen, S. DA - Feb DO - 10.7196/samj.6182 10.7196/samj.6182. DP - Nlm ET - 02/05 J2 - South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde LA - eng PY - 2013 SN - 0256-9574 (Print) 0256-9574 (Linking) SP - 101-6 ST - Diagnosing Xpert MTB/RIF negative TB: impact and cost of alternative algorithms for South Africa T2 - S Afr Med J TI - Diagnosing Xpert MTB/RIF negative TB: impact and cost of alternative algorithms for South Africa UR - http://www.samj.org.za/index.php/samj/article/view/6182 VL - 103 ID - 2700 ER - TY - JOUR AB - SETTING: A large randomized controlled trial recently showed that for treating latent tuberculous infection (LTBI) in persons at high risk of progression to tuberculosis (TB) disease, a 12-dose regimen of weekly rifapentine plus isoniazid (3HP) administered as directly observed treatment (DOT) can be as effective as 9 months of daily self-administered isoniazid (9H). OBJECTIVES: To assess the cost-effectiveness of 3HP compared to 9H. DESIGN: A computational model was designed to simulate individuals with LTBI treated with 9H or 3HP. Costs and health outcomes were estimated to determine the incremental costs per active TB case prevented and per quality-adjusted life year (QALY) gained by 3HP compared to 9H. RESULTS: Over a 20-year period, treatment of LTBI with 3HP rather than 9H resulted in 5.2 fewer cases of TB and 25 fewer lost QALYs per 1000 individuals treated. From the health system and societal perspectives, 3HP would cost respectively US$21,525 and $4294 more per TB case prevented, and respectively $4565 and $911 more per QALY gained. CONCLUSIONS: 3HP may be a cost-effective alternative to 9H, particularly if the cost of rifapentine decreases, the effectiveness of 3HP can be maintained without DOT, and 3HP treatment is limited to those with a high risk of progression to TB disease. AD - Division of Tuberculosis Elimination, National Center for HIV/AIDS, Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA; Steven M Teutsch Prevention Effectiveness Fellowship Program, Office of Surveillance, Epidemiology and Laboratory Sciences, CDC, Atlanta, Georgia, USA; Department of Mathematics and Statistics, Mount Holyoke College, South Hadley, Massachusetts, USA. AN - 24200264 AU - Shepardson, D. AU - Marks, S. M. AU - Chesson, H. AU - Kerrigan, A. AU - Holland, D. P. AU - Scott, N. AU - Tian, X. AU - Borisov, A. S. AU - Shang, N. AU - Heilig, C. M. AU - Sterling, T. R. AU - Villarino, M. E. AU - Mac Kenzie, W. R. C2 - PMC5451112 C6 - HHSPA859232 DA - Dec DO - 10.5588/ijtld.13.0423 DP - NLM ET - 2013/11/10 IS - 12 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Antitubercular Agents/*administration & dosage/adverse effects/*economics Computer Simulation Cost-Benefit Analysis Directly Observed Therapy/economics Drug Administration Schedule *Drug Costs Drug Therapy, Combination Hospital Costs Humans Isoniazid/*administration & dosage/adverse effects/*economics Latent Tuberculosis/diagnosis/*drug therapy/*economics Models, Economic Quality-Adjusted Life Years Rifampin/administration & dosage/adverse effects/*analogs & derivatives/economics Time Factors Treatment Outcome United States L1 - internal-pdf://4211452893/Shepardson-2013-Cost-effectiveness of a 12-dos.pdf LA - eng N1 - 1815-7920 Shepardson, D Marks, S M Chesson, H Kerrigan, A Holland, D P Scott, N Tian, X Borisov, A S Shang, N Heilig, C M Sterling, T R Villarino, M E Mac Kenzie, W R CC999999/Intramural CDC HHS/United States Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S. France Int J Tuberc Lung Dis. 2013 Dec;17(12):1531-7. doi: 10.5588/ijtld.13.0423. PY - 2013 SN - 1027-3719 SP - 1531-7 ST - Cost-effectiveness of a 12-dose regimen for treating latent tuberculous infection in the United States T2 - Int J Tuberc Lung Dis TI - Cost-effectiveness of a 12-dose regimen for treating latent tuberculous infection in the United States UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451112/pdf/nihms859232.pdf VL - 17 ID - 1667 ER - TY - JOUR AB - We apply optimal control theory to a tuberculosis model given by a system of ordinary differential equations. Optimal control strategies are proposed to minimize the cost of interventions, considering reinfection and post-exposure interventions. They depend on the parameters of the model and reduce effectively the number of active infectious and persistent latent individuals. The time that the optimal controls are at the upper bound increase with the transmission coefficient. A general explicit expression for the basic reproduction number is obtained and its sensitivity with respect to the model parameters is discussed. Numerical results show the usefulness of the optimization strategies. AD - CIDMA - Center for Research and Development in Mathematics and Applications, Department of Mathematics, University of Aveiro, 3810-193 Aveiro, Portugal. cjoaosilva@ua.pt AN - 23707607 AU - Silva, C. J. AU - Torres, D. F. DA - Aug DO - 10.1016/j.mbs.2013.05.005 DP - NLM ET - 2013/05/28 IS - 2 J2 - Mathematical biosciences KW - Epidemics/economics/prevention & control Humans Latency Period (Psychology) Models, Biological Secondary Prevention Tuberculosis/economics/*epidemiology/prevention & control Tuberculosis Vaccines/economics/therapeutic use Epidemic model Optimal control theory Treatment strategies Tuberculosis LA - eng N1 - 1879-3134 Silva, Cristiana J Torres, Delfim F M Journal Article Research Support, Non-U.S. Gov't United States Math Biosci. 2013 Aug;244(2):154-64. doi: 10.1016/j.mbs.2013.05.005. Epub 2013 May 22. PY - 2013 SN - 0025-5564 SP - 154-64 ST - Optimal control for a tuberculosis model with reinfection and post-exposure interventions T2 - Math Biosci TI - Optimal control for a tuberculosis model with reinfection and post-exposure interventions VL - 244 ID - 1767 ER - TY - JOUR AB - Novel diagnostic tests hold promise for improving tuberculosis (TB) control, but their epidemiologic impact remains uncertain. Using data from the World Health Organization (2011-2012), we developed a transmission model to evaluate the deployment of 3 hypothetical TB diagnostic tests in Southeast Asia under idealized scenarios of implementation. We defined diagnostics by their sensitivity for smear-negative TB and proportion of patients testing positive who initiate therapy ("point-of-care amenability"), with tests of increasing point-of-care amenability having lower sensitivity. Implemented in the public sector (35% of care-seeking attempts), each novel test reduced TB incidence by 7%-9% (95% uncertainty range: 4%-13%) and mortality by 20%-22% (95% uncertainty range: 14%-27%) after 10 years. If also deployed in the private sector (65% of attempts), these tests reduced incidence by 13%-16%, whereas a perfect test (100% sensitivity and treatment initiation) reduced incidence by 20%. Annually detecting 20% of prevalent TB cases through targeted screening (70% smear-negative sensitivity, 85% treatment initiation) also reduced incidence by 19%. Sensitivity and point-of-care amenability are equally important considerations when developing novel diagnostic tests for TB. Novel diagnostics can substantially reduce TB incidence and mortality in Southeast Asia but are unlikely to transform TB control unless they are deployed actively and in the private sector. AN - 24100953 AU - Sun, A. Y. AU - Pai, M. AU - Salje, H. AU - Satyanarayana, S. AU - Deo, S. AU - Dowdy, D. W. C2 - PMC3858106 DA - Dec 15 DO - 10.1093/aje/kwt210 DP - NLM ET - 2013/10/09 IS - 12 J2 - American journal of epidemiology KW - Asia, Southeastern/epidemiology Computer Simulation Diagnostic Techniques and Procedures/*statistics & numerical data HIV Infections/epidemiology Humans Incidence Life Expectancy Mass Screening *Point-of-Care Systems Prevalence Residence Characteristics Sensitivity and Specificity Time Factors Tuberculosis/*diagnosis/mortality/*prevention & control World Health Organization Southeast Asia diagnostic techniques and procedures epidemiologic methods theoretical models tuberculosis LA - eng N1 - 1476-6256 Sun, Amanda Y Pai, Madhukar Salje, Henrik Satyanarayana, Srinath Deo, Sarang Dowdy, David W R21 AI101152/AI/NIAID NIH HHS/United States 123291/Canadian Institutes of Health Research/Canada 1R21AI101152/AI/NIAID NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Am J Epidemiol. 2013 Dec 15;178(12):1740-9. doi: 10.1093/aje/kwt210. Epub 2013 Oct 7. PY - 2013 SN - 0002-9262 SP - 1740-9 ST - Modeling the impact of alternative strategies for rapid molecular diagnosis of tuberculosis in Southeast Asia T2 - Am J Epidemiol TI - Modeling the impact of alternative strategies for rapid molecular diagnosis of tuberculosis in Southeast Asia VL - 178 ID - 1687 ER - TY - JOUR AB - SETTING: In-patient hospitals in South Africa and Uganda. OBJECTIVE: To evaluate the cost-effectiveness of a lateral-flow urine lipoarabinomannan (LAM) test when added to existing strategies for tuberculosis (TB) diagnosis in human immunodeficiency virus infected adults (CD4(+) T-cell counts < 100 cells/l) with symptoms of active TB. DESIGN: Decision-analytic cost-utility model, with the primary outcome being the incremental cost-effectiveness ratio, expressed in 2010 US dollars per disability-adjusted life year (DALY) averted from the perspective of a public sector TB control program. RESULTS AND CONCLUSION: For every 1000 patients tested, adding lateral-flow urine LAM generated 80 incremental appropriate anti-tuberculosis treatments and averted 224 DALYs. Estimated cost utility was US$353 per DALY averted (95% uncertainty range $192$1161) in South Africa and $86 per DALY averted (95% uncertainty range $49$239) in Uganda, reflecting the lower treatment costs in Uganda. Cost utility was most sensitive to assay specificity, cost of anti-tuberculosis treatment, life expectancy after TB cure and cohort TB prevalence, but did not rise above $1500 per DALY averted in South Africa under any one-way sensitivity analysis. The probability of acceptability was >99.8% at a per-DALY willingness-to-pay threshold equal to the per capita gross domestic product in South Africa ($7275) and Uganda ($509). AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. AN - 23485389 AU - Sun, D. AU - Dorman, S. AU - Shah, M. AU - Manabe, Y. C. AU - Moodley, V. M. AU - Nicol, M. P. AU - Dowdy, D. W. DA - Apr DO - 10.5588/ijtld.12.0627 10.5588/ijtld.12.0627. ET - 03/15 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease LA - eng PY - 2013 SN - 1815-7920 (Electronic) 1027-3719 (Linking) SP - 552-8 ST - Cost utility of lateral-flow urine lipoarabinomannan for tuberculosis diagnosis in HIV-infected African adults T2 - Int J Tuberc Lung Dis TI - Cost utility of lateral-flow urine lipoarabinomannan for tuberculosis diagnosis in HIV-infected African adults UR - http://www.ncbi.nlm.nih.gov/pubmed/23485389 VL - 17 ID - 2701 ER - TY - JOUR AB - Tuberculosis (TB) is a potentially fatal disease spread by an airborne pathogen infecting approximately one third of the globe. For decades, contact tracing (CT) has served a key role in the control of TB and many other notifiable communicable diseases. Unfortunately, CT is a labor-intensive and time-consuming process and is often conducted by a small and overworked nursing staff. To help improve the effectiveness of CT, we introduce a detailed, individual-based model of CT for the Canadian province of Saskatchewan. The model captures the detailed operation of TB CT, including loss to follow-up, and prophylactic and case treatment. This representation is used to assess the impact on active TB cases and TB infection prevalence of differential scoping, speed, prioritization of the CT process, and reduced loss to follow-up. Scenario results are broadly consistent with--but provide many additional insights beyond--our previously reported findings using an aggregate model. In the context of a stylized northern community, findings suggest that age- and ethnicity-prioritized schemes could improve CT effectiveness compared to unprioritized schemes by dramatically reducing TB infection and preventing on average roughly 11% (p < .0001) of active TB cases over a period of 20 years. Reducing loss to follow-up to 10% could yield 5.4% (p = .02) TB cases prevented on average with lower prevalence of TB infection, but improving the CT speed does not yield significant improvement in TB outcomes. Finally, although the work emphasized the value of social network analysis, we found that caution should be exercised in directly translating social network analysis-observed associations into prioritization recommendations. AD - 1University of Saskatchewan, Saskatoon, Saskatchewan, Canada. AN - 24084405 AU - Tian, Y. AU - Osgood, N. D. AU - Al-Azem, A. AU - Hoeppner, V. H. DA - Oct DO - 10.1177/1090198113493910 DP - NLM ET - 2013/10/23 IS - 1 Suppl J2 - Health education & behavior : the official publication of the Society for Public Health Education KW - Contact Tracing/*methods/statistics & numerical data Humans Latent Tuberculosis/diagnosis/therapy Lost to Follow-Up Models, Organizational Models, Theoretical Prevalence Program Evaluation/methods Risk Saskatchewan/epidemiology Tuberculosis/epidemiology/*prevention & control/therapy/transmission agent-based modeling contact tracing individual-based modeling infection control scale-free network tuberculosis LA - eng N1 - 1552-6127 Tian, Yuan Osgood, Nathaniel D Al-Azem, Assaad Hoeppner, Vernon H Journal Article Research Support, Non-U.S. Gov't United States Health Educ Behav. 2013 Oct;40(1 Suppl):98S-110S. doi: 10.1177/1090198113493910. PY - 2013 SN - 1090-1981 SP - 98s-110s ST - Evaluating the effectiveness of contact tracing on tuberculosis outcomes in Saskatchewan using individual-based modeling T2 - Health Educ Behav TI - Evaluating the effectiveness of contact tracing on tuberculosis outcomes in Saskatchewan using individual-based modeling VL - 40 ID - 1677 ER - TY - JOUR AB - BACKGROUND: High costs are a limitation to scaling up the Xpert MTB/RIF assay (Xpert) for the diagnosis of tuberculosis in resource-constrained settings. A triaging strategy in which a sensitive but not necessarily highly specific rapid test is used to select patients for Xpert may result in a more affordable diagnostic algorithm. To inform the selection and development of particular diagnostics as a triage test we explored combinations of sensitivity, specificity and cost at which a hypothetical triage test will improve affordability of the Xpert assay. METHODS: In a decision analytical model parameterized for Uganda, India and South Africa, we compared a diagnostic algorithm in which a cohort of patients with presumptive TB received Xpert to a triage algorithm whereby only those with a positive triage test were tested by Xpert. FINDINGS: A triage test with sensitivity equal to Xpert, 75% specificity, and costs of US$5 per patient tested reduced total diagnostic costs by 42% in the Uganda setting, and by 34% and 39% respectively in the India and South Africa settings. When exploring triage algorithms with lower sensitivity, the use of an example triage test with 95% sensitivity relative to Xpert, 75% specificity and test costs $5 resulted in similar cost reduction, and was cost-effective by the WHO willingness-to-pay threshold compared to Xpert for all in Uganda, but not in India and South Africa. The gain in affordability of the examined triage algorithms increased with decreasing prevalence of tuberculosis among the cohort. CONCLUSIONS: A triage test strategy could potentially improve the affordability of Xpert for TB diagnosis, particularly in low-income countries and with enhanced case-finding. Tests and markers with lower accuracy than desired of a diagnostic test may fall within the ranges of sensitivity, specificity and cost required for triage tests and be developed as such. AD - Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam, The Netherlands ; Department of Global Health, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. Social and Mathematical Epidemiology Group (SAME), Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom. KNCV Tuberculosis Foundation, The Hague, The Netherlands. Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. New Jersey Medical School-UMDNJ, Department of Medicine, Newark, New Jersey, United States of America. Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, United States of America. AN - 24367555 AU - van't Hoog, A. H. AU - Cobelens, F. AU - Vassall, A. AU - van Kampen, S. AU - Dorman, S. E. AU - Alland, D. AU - Ellner, J. C2 - PMC3867409 DO - 10.1371/journal.pone.0082786 DP - NLM ET - 2013/12/25 IS - 12 J2 - PloS one KW - Algorithms Cost-Benefit Analysis Decision Support Techniques Humans India South Africa Triage/*economics Tuberculosis/*diagnosis Uganda L1 - internal-pdf://3544886813/van't Hoog-2013-Optimal triage test characteri.pdf LA - eng N1 - 1932-6203 van't Hoog, Anna H Cobelens, Frank Vassall, Anna van Kampen, Sanne Dorman, Susan E Alland, David Ellner, Jerrold HHSN272200900050C/PHS HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States PLoS One. 2013 Dec 18;8(12):e82786. doi: 10.1371/journal.pone.0082786. eCollection 2013. PY - 2013 SN - 1932-6203 SP - e82786 ST - Optimal triage test characteristics to improve the cost-effectiveness of the Xpert MTB/RIF assay for TB diagnosis: a decision analysis T2 - PLoS One TI - Optimal triage test characteristics to improve the cost-effectiveness of the Xpert MTB/RIF assay for TB diagnosis: a decision analysis UR - http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0082786&type=printable VL - 8 ID - 1628 ER - TY - JOUR AB - A coepidemic arises when the spread of one infectious disease stimulates the spread of another infectious disease. Recently, this has happened with human immunodeficiency virus (HIV) and tuberculosis (TB). The density of individuals infected with latent tuberculosis is structured by age since latency. The host population is divided into five subclasses of susceptibles, latent TB, active TB (without HIV), HIV infectives (without TB), and coinfection class (infected by both TB and HIV). The model exhibits three boundary equilibria, namely, disease free equilibrium, TB dominated equilibrium, and HIV dominated equilibrium. We discuss the local or global stabilities of boundary equilibria. We prove the persistence of our model. Our simple model of two synergistic infectious disease epidemics illustrates the importance of including the effects of each disease on the transmission and progression of the other disease. We simulate the dynamic behaviors of our model and give medicine explanations. AD - Yuncheng Univ, Dept Appl Math, Yuncheng 044000, Shanxi, Peoples R China AN - WOS:000317218900001 AU - Wang, X. Y. AU - Yang, J. Y. AU - Zhang, F. Q. DO - Artn 429567 10.1155/2013/429567 J2 - J Appl Math KW - tuberculosis infection persistence spread era LA - English N1 - 121bz Times Cited:1 Cited References Count:19 PY - 2013 SN - 1110-757x ST - Dynamic of a TB-HIV Coinfection Epidemic Model with Latent Age T2 - Journal of Applied Mathematics TI - Dynamic of a TB-HIV Coinfection Epidemic Model with Latent Age UR - ://WOS:000317218900001 ID - 4900 ER - TY - JOUR AB - The global tuberculosis (TB) control plan has historically emphasized passive case finding (PCF) as the most practical approach for identifying TB suspects in high burden settings. The success of this approach in controlling TB depends on infectious individuals recognizing their symptoms and voluntarily seeking diagnosis rapidly enough to reduce onward transmission. It now appears, at least in some settings, that more intensified case-finding (ICF) approaches may be needed to control TB transmission; these more aggressive approaches for detecting as-yet undiagnosed cases obviously require additional resources to implement. Given that TB control programs are resource constrained and that the incremental yield of ICF is expected to wane over time as the pool of undiagnosed cases is depleted, a tool that can help policymakers to identify when to implement or suspend an ICF intervention would be valuable. In this article, we propose dynamic case-finding policies that allow policymakers to use existing observations about the epidemic and resource availability to determine when to switch between PCF and ICF to efficiently use resources to optimize population health. Using mathematical models of TB/HIV coepidemics, we show that dynamic policies strictly dominate static policies that prespecify a frequency and duration of rounds of ICF. We also find that the use of a diagnostic tool with better sensitivity for detecting smear-negative cases (e.g., Xpert MTB/RIF) further improves the incremental benefit of these dynamic case-finding policies. AD - Department of Epidemiology and the Center for Communicable Disease Dynamics, Harvard School of Public Health, Boston, MA 02115, USA. reza.yaesoubi@gmail.com AN - 23690585 AU - Yaesoubi, R. AU - Cohen, T. C2 - PMC3677479 DA - Jun 04 DO - 10.1073/pnas.1218770110 DP - NLM ET - 2013/05/22 IS - 23 J2 - Proceedings of the National Academy of Sciences of the United States of America KW - *Decision Support Techniques Epidemics/*prevention & control Epidemiological Monitoring HIV Infections/*epidemiology Humans Models, Theoretical Prevalence Public Health/*methods Public Policy Tuberculosis/*diagnosis/*epidemiology/*prevention & control approximate dynamic programming cost-effectiveness dynamic resource allocation mathematical model screening LA - eng N1 - 1091-6490 Yaesoubi, Reza Cohen, Ted DP2 OD006663/OD/NIH HHS/United States U54 GM088558/GM/NIGMS NIH HHS/United States DP2OD006663/OD/NIH HHS/United States U54GM088558/GM/NIGMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural United States Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9457-62. doi: 10.1073/pnas.1218770110. Epub 2013 May 20. PY - 2013 SN - 0027-8424 SP - 9457-62 ST - Identifying dynamic tuberculosis case-finding policies for HIV/TB coepidemics T2 - Proc Natl Acad Sci U S A TI - Identifying dynamic tuberculosis case-finding policies for HIV/TB coepidemics VL - 110 ID - 1770 ER - TY - JOUR AB - In this paper, we study a tuberculosis model with healthy education and treatment. The analysis of the model is presented in terms of the TB epidemic threshold . It is shown that the model has multiple equilibria and using the center manifold theory, the model exhibits the phenomenon of backward bifurcation where a stable disease-free equilibrium co-exists with a stable endemic equilibrium for a certain defined range of . We perform sensitivity analysis of on the parameters to determine their relative importance to TB transmission and prxevalence. Numerical simulations are presented to illustrate the results. AD - Xinyang Normal Univ, Coll Math & Informat Sci, Xinyang 464000, Herts, Peoples R China Shandong Univ Sci & Technol, Coll Sci, Qingdao 266510, Shandong, Peoples R China Xinyang Normal Univ, Coll Math & Informat Sci, Xinyang 464000, Henan, Peoples R China Shandong Univ Sci & Technol, Coll Sci, Qingdao 266510, Shandong, Peoples R China AN - WOS:000320665200004 AU - Zhou, X. Y. AU - Shi, X. Y. AU - Cheng, H. D. DA - Jul DO - 10.1007/s40314-013-0008-8 IS - 2 J2 - Comput Appl Math KW - tuberculosis model local stability backward bifurcation sensitivity analysis mathematical-model drug-resistance transmission reinfection dynamics malaria LA - English N1 - 167wd Times Cited:1 Cited References Count:20 PY - 2013 SN - 1807-0302 SP - 245-260 ST - Modelling and stability analysis for a tuberculosis model with healthy education and treatment T2 - Computational & Applied Mathematics TI - Modelling and stability analysis for a tuberculosis model with healthy education and treatment UR - ://WOS:000320665200004 https://link.springer.com/article/10.1007%2Fs40314-013-0008-8 VL - 32 ID - 4901 ER - TY - JOUR AB - Exact computational methods for inference in population genetics are intuitively preferable to approximate analyses. We reconcile two starkly different estimates of the reproductive number of tuberculosis from previous studies that used the same genotyping data and underlying model. This demonstrates the value of approximate analyses in validating exact methods. AD - School of Mathematics and Statistics, University of New South Wales, Sydney, NSW 2052 Australia. AN - 24496011 AU - Aandahl, R. Z. AU - Stadler, T. AU - Sisson, S. A. AU - Tanaka, M. M. C2 - PMC3982679 DA - Apr DO - 10.1534/genetics.113.158808 DP - NLM ET - 2014/02/06 IS - 4 J2 - Genetics KW - Bayes Theorem Computational Biology/*methods Likelihood Functions Mycobacterium tuberculosis/physiology Tuberculosis/*epidemiology/genetics/*microbiology/transmission Is6110 Mycobacterium tuberculosis approximate Bayesian computation reproductive number summary statistics LA - eng N1 - 1943-2631 Aandahl, R Zachariah Stadler, Tanja Sisson, Scott A Tanaka, Mark M Journal Article Research Support, Non-U.S. Gov't United States Genetics. 2014 Apr;196(4):1227-30. doi: 10.1534/genetics.113.158808. Epub 2014 Feb 4. PY - 2014 SN - 0016-6731 SP - 1227-30 ST - Exact vs. approximate computation: reconciling different estimates of Mycobacterium tuberculosis epidemiological parameters T2 - Genetics TI - Exact vs. approximate computation: reconciling different estimates of Mycobacterium tuberculosis epidemiological parameters VL - 196 ID - 1598 ER - TY - JOUR AB - Tuberculosis is a bacterial disease caused by Mycobacterium tuberculosis (TB). The risk for TB infection greatly increases with HIV infection; TB disease occurs in 7-10% of patients with HIV infection each year, increasing the potential for transmission of drug-resistant Mycobacterium tuberculosis strains. In this paper a deterministic model is presented and studied for the transmission of TB-HIV/AIDS co-infection. Optimal control theory is then applied to investigate optimal strategies for controlling the spread of the disease using treatment of infected individuals with TB as the system control variables. Various combination strategies were examined so as to investigate the impact of the controls on the spread of the disease. And incremental cost-effectiveness ratio (ICER) was used to investigate the cost effectiveness of all the control strategies. Our results show that the implementation of the combination strategy involving the prevention of treatment failure in drug-sensitive TB infectious individuals and the treatment of individuals with drug-resistant TB is the most cost-effective control strategy. Similar results were obtained with different objective functionals involving the minimization of the number of individuals with drug-sensitive TB-only and drug-resistant TB-only with the efforts involved in applying the control. AD - Department of Mathematics and Statistics, Austin Peay State University, Clarksville, TN, USA. Electronic address: fbagusto@gmail.com. Department of Mathematical Sciences, Federal University of Technology Akure, Nigeria. AN - 24704209 AU - Agusto, F. B. AU - Adekunle, A. I. DA - May DO - 10.1016/j.biosystems.2014.03.006 DP - NLM ET - 2014/04/08 J2 - Bio Systems KW - Acquired Immunodeficiency Syndrome/*prevention & control Coinfection/*prevention & control/*transmission Communicable Disease Control/economics/*methods Computer Simulation Cost-Benefit Analysis Drug Resistance, Bacterial/physiology Humans *Models, Biological Tuberculosis/*prevention & control Cost effectiveness Drug resistant strain Hiv/aids Optimality system Stability Tuberculosis L1 - internal-pdf://1223328376/1-s2.0-S0303264714000409-main.pdf LA - eng N1 - 1872-8324 Agusto, F B Adekunle, A I Journal Article Ireland Biosystems. 2014 May;119:20-44. doi: 10.1016/j.biosystems.2014.03.006. Epub 2014 Apr 2. PY - 2014 SN - 0303-2647 SP - 20-44 ST - Optimal control of a two-strain tuberculosis-HIV/AIDS co-infection model T2 - Biosystems TI - Optimal control of a two-strain tuberculosis-HIV/AIDS co-infection model VL - 119 ID - 1550 ER - TY - JOUR AB - BACKGROUND: Population models of tuberculosis transmission have not accounted for social contact structure and the role of the environment in which tuberculosis is transmitted. METHODS: We utilized extensions to the Wells-Riley model of tuberculosis transmission, using exhaled carbon dioxide as a tracer gas, to describe transmission patterns in an endemic community. Drawing upon social interaction data and carbon dioxide measurements from a South African township, we created an age-structured model of tuberculosis transmission in households, public transit, schools, and workplaces. We fit the model to local data on latent tuberculosis prevalence by age. RESULTS: Most tuberculosis infections (84%) were estimated to occur outside of one's own household. Fifty percent of infections among young adults (ages 15-19) occurred in schools, due to high contact rates and poor ventilation. Despite lower numbers of contacts in workplaces, assortative mixing among adults with high rates of smear-positive tuberculosis contributed to transmission in this environment. Households and public transit were important sites of transmission between age groups. CONCLUSIONS: Consistent with molecular epidemiologic estimates, a minority of tuberculosis transmission was estimated to occur within households, which may limit the impact of contact investigations. Further work is needed to investigate the role of schools in tuberculosis transmission. AD - Division of Infectious Diseases, Massachusetts General Hospital, Boston. Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa. AN - 24610874 AU - Andrews, J. R. AU - Morrow, C. AU - Walensky, R. P. AU - Wood, R. C2 - PMC4133578 DA - Aug 15 DO - 10.1093/infdis/jiu138 DP - NLM ET - 2014/03/13 IS - 4 J2 - The Journal of infectious diseases KW - Adolescent Child Child, Preschool Contact Tracing/*methods Environment Family Characteristics Humans Infant Infant, Newborn Latent Tuberculosis/epidemiology/transmission Models, Theoretical Prevalence Schools Social Behavior South Africa/epidemiology Tuberculosis/*epidemiology/*transmission Workplace Young Adult epidemiology mathematical models social contacts tuberculosis L1 - internal-pdf://1687597113/Andrews-2014-Integrating social contact and en.pdf LA - eng N1 - 1537-6613 Andrews, Jason R Morrow, Carl Walensky, Rochelle P Wood, Robin T32AI007433/AI/NIAID NIH HHS/United States R01 AI093269/AI/NIAID NIH HHS/United States R01 AI058736/AI/NIAID NIH HHS/United States K01 AI104411/AI/NIAID NIH HHS/United States T32 AI007433/AI/NIAID NIH HHS/United States U01 AI069519/AI/NIAID NIH HHS/United States U01 AI069924/AI/NIAID NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States J Infect Dis. 2014 Aug 15;210(4):597-603. doi: 10.1093/infdis/jiu138. Epub 2014 Mar 8. PY - 2014 SN - 0022-1899 SP - 597-603 ST - Integrating social contact and environmental data in evaluating tuberculosis transmission in a South African township T2 - J Infect Dis TI - Integrating social contact and environmental data in evaluating tuberculosis transmission in a South African township UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133578/pdf/jiu138.pdf VL - 210 ID - 1578 ER - TY - JOUR AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, Maryland, 21205 azman@jhu.edu, ddowdy1@jhmi.edu, URL: http://www.w3.org/1999/xlink. AN - 25198998 AU - Azman, A. S. AU - Dowdy, D. W. DA - Aug DO - 10.5588/ijtld.14.0386 DP - NLM ET - 2014/09/10 IS - 8 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Antitubercular Agents/*therapeutic use Female Humans Male *Models, Theoretical Mycobacterium tuberculosis/*pathogenicity Tuberculosis/*prevention & control LA - eng N1 - 1815-7920 Azman, Andrew S Dowdy, David W Comment Editorial France Int J Tuberc Lung Dis. 2014 Aug;18(8):883. doi: 10.5588/ijtld.14.0386. PY - 2014 SN - 1027-3719 SP - 883 ST - Bold thinking for bold results: modeling the elimination of tuberculosis T2 - Int J Tuberc Lung Dis TI - Bold thinking for bold results: modeling the elimination of tuberculosis VL - 18 ID - 1918 ER - TY - JOUR AB - Background: Current approaches are unlikely to achieve the aggressive global tuberculosis (TB) control targets set for 2035 and beyond. Active case finding (ACF) may be an important tool for augmenting existing strategies, but the cost-effectiveness of ACF remains uncertain. Program evaluators can often measure the cost of ACF per TB case detected, but how this accessible measure translates into traditional metrics of cost-effectiveness, such as the cost per disability-adjusted life year (DALY), remains unclear. Methods: We constructed dynamic models of TB in India, China, and South Africa to explore the medium-term impact and cost-effectiveness of generic ACF activities, conceptualized separately as discrete (2-year) campaigns and as continuous activities integrated into ongoing TB control programs. Our primary outcome was the cost per DALY, measured in relationship to the cost per TB case actively detected and started on treatment. Results: Discrete campaigns costing up to $1,200 (95% uncertainty range [UR] 850–2,043) per case actively detected and started on treatment in India, $3,800 (95% UR 2,706–6,392) in China, and $9,400 (95% UR 6,957–13,221) in South Africa were all highly cost-effective (cost per DALY averted less than per capita gross domestic product). Prolonged integration was even more effective and cost-effective. Short-term assessments of ACF dramatically underestimated potential longer term gains; for example, an assessment of an ACF program at 2 years might find a non-significant 11% reduction in prevalence, but a 10-year evaluation of that same intervention would show a 33% reduction. Conclusions: ACF can be a powerful and highly cost-effective tool in the fight against TB. Given that short-term assessments may dramatically underestimate medium-term effectiveness, current willingness to pay may be too low. ACF should receive strong consideration as a basic tool for TB control in most high-burden settings, even when it may cost over $1,000 to detect and initiate treatment for each extra case of active TB. AU - Azman, A. S. AU - Golub, J. E. AU - Dowdy, D. W. IS - 216 KW - Mathematical Modeling Screening Cost-Effectiveness Active Case Finding Tuberculosis TB PY - 2014 ST - How much is tuberculosis screening worth? Estimating the value of active case finding for tuberculosis in South Africa, China, and India T2 - BMC Medicine TI - How much is tuberculosis screening worth? Estimating the value of active case finding for tuberculosis in South Africa, China, and India UR - https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0216-0 VL - 12 ID - 4939 ER - TY - JOUR AB - Timely vaccinations of children in developing countries are important for reducing morbidity and mortality, which are Millennium Development Goals. However, a majority of children do not possess vaccination cards compiling information on timing. We investigated the benefits of vaccination cards for the uptake of immunizations against diphtheria, pertussis and tetanus (DPT), polio, tuberculosis (BCG), and measles using data on over 200,000 Indian children from the District Level Health and Facility Survey 3. Methodological issues such as whether parents of children with higher morbidity levels may have them vaccinated were investigated. The results from the models for DPT, polio, measles, and BCG vaccinations showed significant beneficial effects of maternal education, household possessions, and access to health care facilities. Moreover, models for children's ages at the time of vaccination showed significant interactions between maternal education and access to and availability of health care facilities. Finally, models for child morbidity due to diarrhea, cough, and fever showed that timely vaccinations against DPT, access to piped water, and cooking with electricity or natural gas were associated with lower morbidity. Overall, issuing paper or electronic vaccination cards to children is likely to enhance timely uptake of various immunizations thereby reducing child morbidity. AD - University of Maryland School of Public Policy, College Park, MD, USA. AN - 23670874 AU - Bhargava, A. AU - Guntupalli, A. M. AU - Lokshin, M. AU - Howard, L. L. DA - May DO - 10.1002/hec.2939 DP - NLM ET - 2013/05/15 IS - 5 J2 - Health economics KW - Child, Preschool Cooking/methods Female Health Services Accessibility/statistics & numerical data Humans *Immunization Schedule India/epidemiology Infant Infant, Newborn Male Models, Statistical Patient Acceptance of Health Care/*statistics & numerical data Socioeconomic Factors Vaccination/*statistics & numerical data Water Supply/statistics & numerical data childhood vaccinations economic development health care services morbidity simultaneity L1 - internal-pdf://3876901557/Bhargava-2014-Modeling the effects of immuniza.pdf LA - eng N1 - 1099-1050 Bhargava, Alok Guntupalli, Aravinda M Lokshin, Michael Howard, Larry L Journal Article England Health Econ. 2014 May;23(5):606-20. doi: 10.1002/hec.2939. Epub 2013 May 14. PY - 2014 SN - 1057-9230 SP - 606-20 ST - Modeling the effects of immunizations timing on child health outcomes in India T2 - Health Econ TI - Modeling the effects of immunizations timing on child health outcomes in India UR - http://onlinelibrary.wiley.com/store/10.1002/hec.2939/asset/hec2939.pdf?v=1&t=ja0y66r0&s=4f1dad4982be5733aa7dce396ac50d77e0e8e2d9 VL - 23 ID - 1777 ER - TY - JOUR AB - BACKGROUND: Tuberculosis remains the leading cause of death in South Africa. A number of potential new TB vaccine candidates have been identified and are currently in clinical trials. One such candidate is MVA85A. This study aimed to estimate the cost-effectiveness of adding the MVA85A vaccine as a booster to the BCG vaccine in children from the perspective of the South African government. METHODS: The cost-effectiveness was assessed by employing Decision Analytic Modelling, through the use of a Markov model. The model compared the existing strategy of BCG vaccination to a new strategy in which infants receive BCG and a booster vaccine, MVA85A, at 4 months of age. The costs and outcomes of the two strategies are estimated through modelling the vaccination of a hypothetical cohort of newborns and following them from birth through to 10 years of age, employing 6-monthly cycles. RESULTS: The results of the cost-effectiveness analysis indicate that the MVA85A strategy is both more costly and more effective - there are fewer TB cases and deaths from TB than BCG alone. The South African government would need to spend an additional USD 1,105 for every additional TB case averted and USD 284,017 for every additional TB death averted. The threshold analysis shows that, if the efficacy of the MVA85A vaccine was 41.3% (instead of the current efficacy of 17.3%), the two strategies would have the same cost but more cases of TB and more deaths from TB would be prevented by adding the MVA85A vaccine to the BCG vaccine. In this case, the government chould consider the MVA85A strategy. CONCLUSIONS: At the current level of efficacy, the MVA85A vaccine is neither effective nor cost-effective and, therefore, not a good use of limited resources. Nevertheless, this study contributes to developing a standardized Markov model, which could be used, in the future, to estimate the potential cost-effectiveness of new TB vaccines compared to the BCG vaccine, in children between the ages of 0-10 years. It also provides an indicative threshold of vaccine efficacy, which could guide future development. AD - Health Economics Unit, School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925 Cape Town, South Africa. AN - 25242892 AU - Channing, L. AU - Sinanovic, E. C2 - PMC4169661 DO - 10.1186/1478-7547-12-20 DP - NLM ET - 2014/09/23 J2 - Cost effectiveness and resource allocation : C/E KW - BCG vaccine Childhood TB Cost-effectiveness analysis Markov modelling New TB vaccine South Africa Tuberculosis LA - eng N1 - Channing, Liezl Sinanovic, Edina Journal Article England Cost Eff Resour Alloc. 2014 Sep 16;12:20. doi: 10.1186/1478-7547-12-20. eCollection 2014. PY - 2014 SN - 1478-7547 (Print) 1478-7547 SP - 20 ST - Modelling the cost-effectiveness of a new infant vaccine to prevent tuberculosis disease in children in South Africa T2 - Cost Eff Resour Alloc TI - Modelling the cost-effectiveness of a new infant vaccine to prevent tuberculosis disease in children in South Africa VL - 12 ID - 1902 ER - TY - JOUR AB - A mathematical control model for the transmission dynamics of tuberculosis (TB) in South Korea is developed on the basis of the reported active-TB and relapse-TB incidence data. In this work, optimal control theory is used to propose optimal TB prevention and control strategy and rearrange the government TB budget for the best TB elimination plan. The impact of distancing, case finding, and/or case holding controls are investigated when the number of infected and infectious individuals are minimized, while the intervention costs are kept low. The implementation of optimal control measures shows that the distancing control, such as isolation of infectious people, early TB patient detection, and educational program/campaign for healthy control, is the most effective control factor for the prevention of TB transmission in South Korea. AD - Department of Mathematics, Konkuk University, Seoul , 143-701, Republic of Korea, ssunhwa.choi@gmail.com. AN - 24849770 AU - Choi, S. AU - Jung, E. DA - Jul DO - 10.1007/s11538-014-9962-6 DP - NLM ET - 2014/05/23 IS - 7 J2 - Bulletin of mathematical biology KW - Computer Simulation Humans Incidence *Models, Immunological Mycobacterium tuberculosis/*immunology Republic of Korea/epidemiology Tuberculosis/epidemiology/immunology/*prevention & control LA - eng N1 - 1522-9602 Choi, Sunhwa Jung, Eunok Journal Article Research Support, Non-U.S. Gov't United States Bull Math Biol. 2014 Jul;76(7):1566-89. doi: 10.1007/s11538-014-9962-6. Epub 2014 May 22. PY - 2014 SN - 0092-8240 SP - 1566-89 ST - Optimal tuberculosis prevention and control strategy from a mathematical model based on real data T2 - Bull Math Biol TI - Optimal tuberculosis prevention and control strategy from a mathematical model based on real data VL - 76 ID - 2018 ER - TY - JOUR AD - [Cilfone, Nicholas A.; Pienaar, Elsje; Linderman, Jennifer J.] Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. [Kirschner, Denise E.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. AN - WOS:000337000403599 AU - Cilfone, N. A. AU - Pienaar, E. AU - Kirschner, D. E. AU - Linderman, J. J. DA - Jan IS - 2 J2 - Biophys. J. KW - Biophysics LA - English M3 - Meeting Abstract N1 - ISI Document Delivery No.: AI6QE Times Cited: 1 Cited Reference Count: 0 Cilfone, Nicholas A. Pienaar, Elsje Kirschner, Denise E. Linderman, Jennifer J. 58th Annual Meeting of the Biophysical-Society Feb 15-19, 2014 San Francisco, CA Biophys Soc 1 0 4 Cell press Cambridge 1542-0086 PY - 2014 SN - 0006-3495 SP - 644A-644A ST - Computational Modeling of Granuloma Formation in Tuberculosis Yields Insights into both Infection and Treatment T2 - Biophysical Journal TI - Computational Modeling of Granuloma Formation in Tuberculosis Yields Insights into both Infection and Treatment UR - ://WOS:000337000403599 VL - 106 ID - 5475 ER - TY - JOUR AD - Division of Medical Microbiology and Institute for Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. helen.cox@uct.ac.za. AN - 24903782 AU - Cox, H. S. DA - May DO - 10.5588/ijtld.14.0235 DP - NLM ET - 2014/06/07 IS - 5 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Antitubercular Agents/*therapeutic use *Coinfection Epidemics/*prevention & control HIV Infections/*epidemiology Humans *Models, Theoretical Tuberculosis/*prevention & control LA - eng N1 - 1815-7920 Cox, Helen S Comment Editorial France Int J Tuberc Lung Dis. 2014 May;18(5):507. doi: 10.5588/ijtld.14.0235. PY - 2014 SN - 1027-3719 SP - 507 ST - The benefits and risks of mathematical modelling in tuberculosis T2 - Int J Tuberc Lung Dis TI - The benefits and risks of mathematical modelling in tuberculosis VL - 18 ID - 1999 ER - TY - JOUR AB - BACKGROUND: The 2050 Millennium Development Goals (MDG) for tuberculosis (TB) aim for elimination of TB as a public health issue. We used a mathematical modelling approach to evaluate the feasibility of this target in a low-prevalence setting with immigration-related strategies directed at latent tuberculosis. METHODS: We used a stochastic individual-based model to simulate tuberculosis disease among immigrants to Victoria, Australia; a representative low-transmission setting. A variety of screening and treatment approaches aimed at preventing reactivation of latent infection were applied to evaluate overall tuberculosis incidence reduction and rates of multidrug resistant disease. RESULTS: Without additional intervention, tuberculosis incidence was predicted to reach 34.5 cases/million by 2050. Strategies involving the introduction of an available screening/treatment combination reduced TB incidence to between 16.9-23.8 cases/million, and required screening of 136-427 new arrivals for each case of TB prevented. Limiting screening to higher incidence regions of origin was less effective but more efficient. CONCLUSIONS: Public health strategies targeting latent tuberculosis infection in immigrants may substantially reduce tuberculosis incidence in a low prevalence region. However, immigration-focused strategies cannot achieve the 2050 MDG and alternative or complementary approaches are required. AD - Victorian Infectious Diseases Service, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Victoria; Department of Microbiology and Immunology, University of Melbourne, Victoria; AN - 24494951 AU - Denholm, J. T. AU - McBryde, E. S. DA - Feb DO - 10.1111/1753-6405.12161 DP - NLM ET - 2014/02/06 IS - 1 J2 - Australian and New Zealand journal of public health KW - Adult Antitubercular Agents/therapeutic use Australia Communicable Disease Control/methods Computer Simulation *Emigrants and Immigrants *Emigration and Immigration Humans Incidence Latent Tuberculosis/diagnosis/ethnology/microbiology/*prevention & control/transmission Mass Screening/*methods *Models, Theoretical Predictive Value of Tests Prevalence Public Health *Residence Characteristics Risk Factors Victoria/epidemiology immigration latent tuberculosis infection mathematical model screening L1 - internal-pdf://4113673269/Denholm-2014-Can Australia eliminate TB_ Model.pdf LA - eng N1 - 1753-6405 Denholm, Justin T McBryde, Emma S Journal Article Australia Aust N Z J Public Health. 2014 Feb;38(1):78-82. doi: 10.1111/1753-6405.12161. PY - 2014 SN - 1326-0200 SP - 78-82 ST - Can Australia eliminate TB? Modelling immigration strategies for reaching MDG targets in a low-transmission setting T2 - Aust N Z J Public Health TI - Can Australia eliminate TB? Modelling immigration strategies for reaching MDG targets in a low-transmission setting UR - http://onlinelibrary.wiley.com/store/10.1111/1753-6405.12161/asset/azph12161.pdf?v=1&t=jab7hm6v&s=8a1019a36dd5b926a6f74e5d026385e768750045 VL - 38 ID - 1599 ER - TY - JOUR AB - BACKGROUND: Extrapulmonary tuberculosis (EPTB) and most pediatric TB cannot be diagnosed using sputum-based assays. The epidemiological impact of different strategies to diagnose EPTB and pediatric TB is unclear. METHODS: We developed a dynamic epidemic model of TB in a hypothetical population with epidemiological characteristics similar to India. We evaluated the impact of four alternative diagnostic test platforms on adult EPTB and pediatric TB mortality over 10 years: (1) Nucleic acid amplification test optimized for diagnosis of EPTB ("NAAT-EPTB"); (2) NAAT optimized for pediatric TB ("NAAT-Peds"); (3) more deployable NAAT for sputum-based diagnosis of adult pulmonary TB ("point-of-care (POC) sputum NAAT"); and (4) more deployable NAAT capable of diagnosing all forms of TB using non-invasive, non-sputum specimens ("POC non-sputum NAAT"). RESULTS: NAAT-EPTB lowered adult EPTB mortality by a projected 7.6% (95% uncertainty range [UR]: 6.5-8.8%). NAAT-Peds lowered pediatric TB mortality by 6.8% (UR: 4.9-8.4%). POC sputum NAAT, though only able to diagnose pulmonary TB, reduced projected pediatric TB deaths by 13.3% (UR: 4.6-15.7%) and adult EPTB deaths by 8.4% (UR 2.0-9.3%) simply by averting transmission of disease. POC non-sputum NAAT had the greatest effect, lowering pediatric TB mortality by 34.7% (UR: 26.8-38.7), and adult EPTB mortality by 38.5% (UR: 30.7-41.2). The relative impact of a POC sputum NAAT (i.e., enhanced deployability) versus NAAT-EPTB (i.e., enhanced ability to specifically diagnose TB-NSP) on adult EPTB mortality depends most strongly on factors that influence transmission, with settings of higher transmission (e.g., higher per-person transmission rate, lower diagnostic rate) favoring POC sputum NAAT. CONCLUSION: Although novel tests for pediatric TB and EPTB are likely to reduce TB mortality, major reductions in pediatric and EPTB incidence and mortality also require better diagnostic tests for adult pulmonary TB that reach a larger population. AD - Beth Israel Deaconess Medical Center, Boston, USA. claudia.denkinger@mail.mcgill.ca. AN - 25186052 AU - Denkinger, C. M. AU - Kampmann, B. AU - Ahmed, S. AU - Dowdy, D. W. C2 - PMC4168123 DA - Sep 03 DO - 10.1186/1471-2334-14-477 DP - NLM ET - 2014/09/05 J2 - BMC infectious diseases KW - Adult Child Child, Preschool Diagnostic Tests, Routine/instrumentation/*methods Female Humans Incidence India Infant Male Models, Theoretical Pediatrics Sputum/microbiology Tuberculosis, Pulmonary/*diagnosis/microbiology/mortality LA - eng N1 - 1471-2334 Denkinger, Claudia M Kampmann, Beate Ahmed, Syed Dowdy, David W R21 AI101152/AI/NIAID NIH HHS/United States 1R21AI101152/AI/NIAID NIH HHS/United States MOP 123291/Canadian Institutes of Health Research/Canada MR/K011944/1/Medical Research Council/United Kingdom Evaluation Studies Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England BMC Infect Dis. 2014 Sep 3;14:477. doi: 10.1186/1471-2334-14-477. PY - 2014 SN - 1471-2334 SP - 477 ST - Modeling the impact of novel diagnostic tests on pediatric and extrapulmonary tuberculosis T2 - BMC Infect Dis TI - Modeling the impact of novel diagnostic tests on pediatric and extrapulmonary tuberculosis VL - 14 ID - 1924 ER - TY - JOUR AB - BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is resistant to both rifampicin (RIF) and isoniazid (INH). Whereas many TB diagnostics detect RIF-resistance, few detect INH-monoresistance, which is common and may increase risk of acquired MDR-TB. Whether inclusion of INH-resistance in a first-line rapid test for TB would have an important impact on MDR-TB rates remains uncertain. METHODS: WE DEVELOPED A TRANSMISSION MODEL TO EVALUATE THREE TESTS IN A POPULATION SIMILAR TO THAT OF INDIA: a rapid molecular test for TB, the same test plus RIF-resistance detection ("TB+RIF"), and detection of RIF and INH-resistance ("TB+RIF/INH"). Our primary outcome was the prevalence of INH-resistant and MDR-TB at ten years. RESULTS: Compared to the TB test alone and assuming treatment of all diagnosed MDR cases, the TB+RIF test reduced the prevalence of MDR-TB among all TB cases from 5.5% to 3.8% (30.6% reduction, 95% uncertainty range, UR: 17-54%). Despite using liberal assumptions about the impact of INH-monoresistance on treatment outcomes and MDR-TB acquisition, expansion from TB+RIF to TB+RIF/INH lowered this prevalence only from 3.8% to 3.6% further (4% reduction, 95% UR: 3-7%) and INH-monoresistant TB from 15.8% to 15.1% (4% reduction, 95% UR: (-8)-19%). CONCLUSION: When added to a rapid test for TB plus RIF-resistance, detection of INH-resistance has minimal impact on transmission of TB, MDR-TB, and INH-monoresistant TB. AD - Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America ; McGill International TB Centre & Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada. McGill International TB Centre & Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada ; Respiratory Epidemiology & Clinical Research Unit, Montreal Chest Institute, Montreal, Montreal, Quebec, Canada. Department of Epidemiology, Bloomberg School of Public Health, Baltimore, Maryland, United States of America ; Center for Tuberculosis Research, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America. AN - 24404155 AU - Denkinger, C. M. AU - Pai, M. AU - Dowdy, D. W. C2 - PMC3880287 DO - 10.1371/journal.pone.0084197 DP - NLM ET - 2014/01/10 IS - 1 J2 - PloS one KW - *Antitubercular Agents/pharmacology/therapeutic use Diagnostic Tests, Routine *Drug Resistance, Multiple, Bacterial/drug effects Humans Incidence India/epidemiology *Isoniazid/pharmacology/therapeutic use Microbial Sensitivity Tests Models, Statistical Mortality *Mycobacterium tuberculosis/drug effects Patient Outcome Assessment Population Surveillance *Rifampin/pharmacology/therapeutic use Tuberculosis, Multidrug-Resistant/diagnosis/drug therapy/*epidemiology/*transmission L1 - internal-pdf://3379116124/Denkinger-2014-Do we need to detect isoniazid.pdf LA - eng N1 - 1932-6203 Denkinger, Claudia M Pai, Madhukar Dowdy, David W 1R21AI101152/AI/NIAID NIH HHS/United States MOP 123291/Canadian Institutes of Health Research/Canada Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States PLoS One. 2014 Jan 3;9(1):e84197. doi: 10.1371/journal.pone.0084197. eCollection 2014. PY - 2014 SN - 1932-6203 SP - e84197 ST - Do we need to detect isoniazid resistance in addition to rifampicin resistance in diagnostic tests for tuberculosis? T2 - PLoS One TI - Do we need to detect isoniazid resistance in addition to rifampicin resistance in diagnostic tests for tuberculosis? UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880287/pdf/pone.0084197.pdf VL - 9 ID - 2910 ER - TY - JOUR AB - BACKGROUND: Confirmation of a diagnosis of tuberculosis in children (aged <15 years) is challenging; under-reporting can result even when children do present to health services. Direct incidence estimates are unavailable, and WHO estimates build on paediatric notifications, with adjustment for incomplete surveillance by the same factor as adult notifications. We aimed to estimate the incidence of infection and disease in children, the prevalence of infection, and household exposure in the 22 countries with a high burden of the disease. METHODS: Within a mechanistic mathematical model, we combined estimates of adult tuberculosis prevalence in 2010, with aspects of the natural history of paediatric tuberculosis. In a household model, we estimated household exposure and infection. We accounted for the effects of age, BCG vaccination, and HIV infection. Additionally, we tested sensitivity to key structural assumptions by repeating all analyses without variation in BCG efficacy by latitude. FINDINGS: The median number of children estimated to be sharing a household with an individual with infectious tuberculosis in 2010 was 15,319,701 (IQR 13,766,297-17,061,821). In 2010, the median number of Mycobacterium tuberculosis infections in children was 7,591,759 (5,800,053-9,969,780), and 650,977 children (424,871-983,118) developed disease. Cumulative exposure meant that the median number of children with latent infection in 2010 was 53,234,854 (41,111,669-68,959,804). The model suggests that 35% (23-54) of paediatric cases of tuberculosis in the 15 countries reporting notifications by age in 2010 were detected. India is predicted to account for 27% (22-33) of the total burden of paediatric tuberculosis in the 22 countries. The predicted proportion of tuberculosis burden in children for each country correlated with incidence, varying between 4% and 21%. INTERPRETATION: Our model has shown that the incidence of paediatric tuberculosis is higher than the number of notifications, particularly in young children. Estimates of current household exposure and cumulative infection suggest an enormous opportunity for preventive treatment. FUNDING: UNITAID and the US Agency for International Development. AD - Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK. Electronic address: p.j.dodd@shef.ac.uk. Global Alliance for TB Drug Development, New York, NY, USA. TESS Development Advisors, Geneva, Switzerland. Department of Paediatric Infectious Diseases, Imperial College London, London, UK. AN - 25103518 AU - Dodd, P. J. AU - Gardiner, E. AU - Coghlan, R. AU - Seddon, J. A. DA - Aug DO - 10.1016/s2214-109x(14)70245-1 DP - NLM ET - 2014/08/12 IS - 8 J2 - The Lancet. Global health KW - Adolescent Child Child, Preschool *Cost of Illness Developing Countries Female Humans Incidence Infant Models, Theoretical Prevalence Tuberculosis/*epidemiology LA - eng N1 - 2214-109x Dodd, Peter J Gardiner, Elizabeth Coghlan, Renia Seddon, James A Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England Lancet Glob Health. 2014 Aug;2(8):e453-9. doi: 10.1016/S2214-109X(14)70245-1. Epub 2014 Jul 8. PY - 2014 SN - 2214-109x SP - e453-9 ST - Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study T2 - Lancet Glob Health TI - Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study VL - 2 ID - 1941 ER - TY - JOUR AB - Most models of infectious diseases, including tuberculosis (TB), do not provide results customized to local conditions. We created a dynamic transmission model to project TB incidence, TB mortality, multidrug-resistant (MDR) TB prevalence, and incremental costs over 5 years after scale-up of nine alternative diagnostic strategies. A corresponding web-based interface allows users to specify local costs and epidemiology. In settings with little capacity for up-front investment, same-day microscopy had the greatest impact on TB incidence and became cost-saving within 5 years if delivered at $10/test. With greater initial investment, population-level scale-up of Xpert MTB/RIF or microcolony-based culture often averted 10 times more TB cases than narrowly-targeted strategies, at minimal incremental long-term cost. Xpert for smear-positive TB had reasonable impact on MDR-TB incidence, but at substantial price and little impact on overall TB incidence and mortality. This user-friendly modeling framework improves decision-makers' ability to evaluate the local impact of TB diagnostic strategies. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States. Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, United States. School of Health and Related Research, University of Sheffield, Sheffield, United Kingdom. Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States. AN - 24898755 AU - Dowdy, D. W. AU - Andrews, J. R. AU - Dodd, P. J. AU - Gilman, R. H. C2 - PMC4082287 DA - Jun 04 DO - 10.7554/eLife.02565 DP - NLM ET - 2014/06/06 J2 - eLife KW - Antibiotics, Antitubercular/*economics Computational Biology/*methods Decision Making Diagnostic Tests, Routine/*economics HIV Infections/complications Humans Incidence Internet Models, Economic Mycobacterium tuberculosis Probability Treatment Outcome Tuberculosis/complications/*diagnosis/therapy Tuberculosis, Multidrug-Resistant/complications/*diagnosis/therapy diagnostic techniques and procedures economic models epidemiology global health infectious disease transmission none tuberculosis L1 - internal-pdf://3101116177/Dowdy-2014-A user-friendly, open-source tool t.pdf LA - eng N1 - 2050-084x Dowdy, David W Andrews, Jason R Dodd, Peter J Gilman, Robert H R21 AI101152/AI/NIAID NIH HHS/United States MOP 271997/Canadian Institutes of Health Research/Canada R21AI101152/AI/NIAID NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Elife. 2014 Jun 4;3. doi: 10.7554/eLife.02565. PY - 2014 SN - 2050-084x ST - A user-friendly, open-source tool to project impact and cost of diagnostic tests for tuberculosis T2 - Elife TI - A user-friendly, open-source tool to project impact and cost of diagnostic tests for tuberculosis UR - https://cdn.elifesciences.org/articles/02565/elife-02565-v2.pdf VL - 3 ID - 2002 ER - TY - JOUR AB - BACKGROUND: The potential epidemiological impact of isoniazid preventive therapy (IPT), delivered at levels that could be feasibly scaled up among people living with HIV (PLHIV) in modern, moderate-burden settings, remains uncertain. METHODS: We used routine surveillance and implementation data from a cluster-randomized trial of IPT among HIV-infected clinic patients with good access to antiretroviral therapy in Rio de Janeiro, Brazil, to populate a parsimonious transmission model of tuberculosis (TB)/HIV. We modeled IPT delivery as a constant process capturing a proportion of the eligible population every year. We projected feasible reductions in TB incidence and mortality in the general population and among PLHIV specifically at the end of 5 years after implementing an IPT program. RESULTS: Data on time to IPT fit an exponential curve well, suggesting that IPT was delivered at a rate covering 20% (95% confidence interval: 16% to 24%) of the 2500 eligible individuals each year. By the end of year 5 after modeled program rollout, IPT had reduced TB incidence by 3.0% [95% uncertainty range (UR): 1.6% to 7.2%] in the general population and by 15.6% (95% UR: 15.5% to 36.5%) among PLHIV. Corresponding reductions in TB mortality were 4.0% (95% UR: 2.2% to 10.3%) and 14.3% (14.6% to 33.7%). Results were robust to wide variations in parameter values on sensitivity analysis. CONCLUSIONS: TB screening and IPT delivery can substantially reduce TB incidence and mortality among PLHIV in urban, moderate-burden settings. In such settings, IPT can be an important component of a multi-faceted strategy to feasibly reduce the burden of TB in PLHIV. AD - *Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; daggerDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; double daggerSubsecretariat for Primary Care, Surveillance, and Health Promotion, Municipal Health Secretariat, Rio de Janeiro, Brazil; section signDepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; ||Program of Scientific Computing, Fiocruz, Rio de Janeiro, Brazil; paragraph signEvandro Chagas Institute of Clinical Research, Fiocruz, Rio de Janeiro, Brazil; and #Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. AN - 24853308 AU - Dowdy, D. W. AU - Golub, J. E. AU - Saraceni, V. AU - Moulton, L. H. AU - Cavalcante, S. C. AU - Cohn, S. AU - Pacheco, A. G. AU - Chaisson, R. E. AU - Durovni, B. C2 - PMC4257469 DA - Aug 15 DO - 10.1097/QAI.0000000000000219 IS - 5 KW - Adolescent Adult Anti-HIV Agents/*therapeutic use Antitubercular Agents/administration & dosage/*pharmacology Brazil/epidemiology HIV Infections/complications/*drug therapy/transmission Humans Isoniazid/administration & dosage/*pharmacology Middle Aged Tuberculosis/*prevention & control/transmission Urban Population Young Adult N1 - Dowdy, David W Golub, Jonathan E Saraceni, Valeria Moulton, Lawrence H Cavalcante, Solange C Cohn, Silvia Pacheco, Antonio G Chaisson, Richard E Durovni, Betina eng UL1 TR001079/TR/NCATS NIH HHS/ P30 AI094189/AI/NIAID NIH HHS/ AI1066994/AI/NIAID NIH HHS/ AI001637/AI/NIAID NIH HHS/ K01 AI066994/AI/NIAID NIH HHS/ K24 AI001637/AI/NIAID NIH HHS/ Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2014/05/24 06:00 J Acquir Immune Defic Syndr. 2014 Aug 15;66(5):552-8. doi: 10.1097/QAI.0000000000000219. PY - 2014 SN - 1944-7884 (Electronic) 1525-4135 (Linking) SP - 552-8 ST - Impact of isoniazid preventive therapy for HIV-infected adults in Rio de Janeiro, Brazil: an epidemiological model T2 - J Acquir Immune Defic Syndr TI - Impact of isoniazid preventive therapy for HIV-infected adults in Rio de Janeiro, Brazil: an epidemiological model UR - https://www.ncbi.nlm.nih.gov/pubmed/24853308 VL - 66 ID - 2244 ER - TY - JOUR AB - The landscape of diagnostic testing for tuberculosis (TB) is changing rapidly, and stakeholders need urgent guidance on how to develop, deploy and optimize TB diagnostics in a way that maximizes impact and makes best use of available resources. When decisions must be made with only incomplete or preliminary data available, modelling is a useful tool for providing such guidance. Following a meeting of modelers and other key stakeholders organized by the TB Modelling and Analysis Consortium, we propose a conceptual framework for positioning models of TB diagnostics. We use that framework to describe modelling priorities in four key areas: Xpert((R)) MTB/RIF scale-up, target product profiles for novel assays, drug susceptibility testing to support new drug regimens, and the improvement of future TB diagnostic models. If we are to maximize the impact and cost-effectiveness of TB diagnostics, these modelling priorities should figure prominently as targets for future research. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. Department of Infectious Disease Epidemiology and TB Modelling Group, London School of Hygiene & Tropical Medicine, London, UK. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. Department of Epidemiology and Biostatistics & McGill International TB Centre, McGill University, Montreal, Quebec, Canada. Department of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Center, Amsterdam, The Netherlands. SAME Modelling and Economics, Department of Global Health and Development, London School of Hygiene & Tropical Medicine, London, UK. Center for Health Decision Science, Harvard School of Public Health, Boston, Massachusetts, USA. Department of Clinical Sciences and Centre for Applied Health Research & Delivery, Liverpool School of Tropical Medicine, Liverpool, UK. AN - 25189546 AU - Dowdy, D. W. AU - Houben, R. AU - Cohen, T. AU - Pai, M. AU - Cobelens, F. AU - Vassall, A. AU - Menzies, N. A. AU - Gomez, G. B. AU - Langley, I. AU - Squire, S. B. AU - White, R. C2 - PMC4436823 DA - Sep DO - 10.5588/ijtld.13.0851 DP - NLM ET - 2014/09/06 IS - 9 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Antitubercular Agents/therapeutic use Bacteriological Techniques/*economics/standards Biomedical Research/economics Cost-Benefit Analysis *Health Care Costs Health Priorities/economics Humans Microbial Sensitivity Tests/economics Models, Economic Practice Guidelines as Topic Predictive Value of Tests Prognosis Tuberculosis/*diagnosis/drug therapy/economics/microbiology LA - eng N1 - 1815-7920 Dowdy, D W Houben, R Cohen, T Pai, M Cobelens, F Vassall, A Menzies, N A Gomez, G B Langley, I Squire, S B White, R TB MAC meeting participants MR/J005088/1/Medical Research Council/United Kingdom Congresses Research Support, Non-U.S. Gov't France Int J Tuberc Lung Dis. 2014 Sep;18(9):1012-8. doi: 10.5588/ijtld.13.0851. PY - 2014 SN - 1027-3719 SP - 1012-8 ST - Impact and cost-effectiveness of current and future tuberculosis diagnostics: the contribution of modelling T2 - Int J Tuberc Lung Dis TI - Impact and cost-effectiveness of current and future tuberculosis diagnostics: the contribution of modelling VL - 18 ID - 1923 ER - TY - JOUR AB - Tuberculosis is an old disease which co-exists with humans. It claims for over 10 million new infections and deaths annually. According to the World Health Organization TB facts, about one-third of the world's population has latent TB, and drug resistant strains have been found in all countries surveyed.(1,2) With rapid spread of multi-drug resistance, TB has become a global public health challenge. Understanding the dynamics of TB infection and the interplay between confounding factors involved in the emergence and spread of drug-resistance is crucial for addressing this growing challenge. While mathematical models have contributed to enhance our understanding of the TB infection mechanisms and control,(3-6) the perplexity of this disease calls for application of more advanced and computationally sophisticated methods. 7 Here, we propose an agent-based modelling computational system as a general framework to study TB infection and interrelated processes. This framework includes two strains of TB, namely drug-sensitive and drug-resistant, and encapsulates principal mechanisms of latent, endogenous, exogenous, and relapse infection. This paper is concerned with the development of this framework both epidemiologically and computationally, with methodologies for model implementation. Using this model, we provide a new pathway towards evaluating treatment strategies for curtailing TB drug-resistant infection. AD - [Espindola, Aquino L.] Univ Fed Fluminense, Dept Fis, Inst Ciencias Exatas ICEx, BR-27213145 Volta Redonda, Brazil. [Martinez, Alexandre Souto] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, BR-14040901 Sao Paulo, Brazil. [Moghadas, Seyed M.] York Univ, Agent Based Modelling Lab, Toronto, ON M3J 1P3, Canada. Espindola, AL (reprint author), Univ Fed Fluminense, Dept Fis, Inst Ciencias Exatas ICEx, BR-27213145 Volta Redonda, Brazil. moghadas@yorku.ca AN - WOS:000358137000022 AU - Espindola, A. L. AU - Martinez, A. S. AU - Moghadas, S. M. J2 - BIOMAT-Int. S. Math. Comput. Biol. KW - exogenous reinfection control strategies transmission epidemics dynamics Mathematical & Computational Biology LA - English M3 - Proceedings Paper N1 - ISI Document Delivery No.: BD1LK Times Cited: 0 Cited Reference Count: 25 Espindola, Aquino L. Martinez, Alexandre Souto Moghadas, Seyed M. Mondaini, RP International Symposium on Mathematical and Computational Biology (BIOMAT) Nov 04-08, 2013 Fields Inst Res Math Sci, Toronto, CANADA Martinez, Alexandre/B-4539-2008 Martinez, Alexandre/0000-0002-4395-0511 0 2 World scientific publ co pte ltd Singapore 978-981-4602-21-1 PY - 2014 SP - 374-388 ST - AN AGENT-BASED MODELLING FRAMEWORK FOR TUBERCULOSIS INFECTION WITH DRUG-RESISTANCE T2 - Biomat 2013: International Symposium on Mathematical and Computational Biology TI - AN AGENT-BASED MODELLING FRAMEWORK FOR TUBERCULOSIS INFECTION WITH DRUG-RESISTANCE UR - ://WOS:000358137000022 ID - 5479 ER - TY - JOUR AB - Despite current control efforts, global tuberculosis (TB) incidence is decreasing slowly. New regimens that can shorten treatment hold promise for improving treatment completion and success, but their impact on population-level transmission remains unclear. Earlier models projected that a four-month regimen could reduce TB incidence by 10% but assumed that an entire course of therapy must be completed to derive any benefit. We constructed a dynamic transmission model of TB disease calibrated to global estimates of incidence, prevalence, mortality, and treatment success. To account for the efficacy of partial treatment, we used data from clinical trials of early short-course regimens to estimate relapse rates among TB patients who completed one-third, one-half, two-thirds, and all of their first-line treatment regimens. We projected population-level incidence and mortality over 10 years, comparing standard six-month therapy to hypothetical shorter-course regimens with equivalent treatment success but fewer defaults. The impact of hypothetical four-month regimens on TB incidence after 10 years was smaller than estimated in previous modeling analyses (1.9% [95% uncertainty range 0.6-3.1%] vs. 10%). Impact on TB mortality was larger (3.5% at 10 years) but still modest. Transmission impact was most sensitive to the proportion of patients completing therapy: four-month therapy led to greater incidence reductions in settings where 25% of patients leave care ("default") over six months. Our findings remained robust under one-way variation of model parameters. These findings suggest that novel regimens that shorten treatment duration may have only a modest effect on TB transmission except in settings of very low treatment completion. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America; Medical Scientist Training Program, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America. TB Modelling Group, TB Centre and Centre for the Mathematical Modelling of Infectious Diseases, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom. Department of Global Health, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. AN - 24816692 AU - Fofana, M. O. AU - Knight, G. M. AU - Gomez, G. B. AU - White, R. G. AU - Dowdy, D. W. C2 - PMC4015982 DO - 10.1371/journal.pone.0096389 DP - NLM ET - 2014/05/13 IS - 5 J2 - PloS one KW - Algorithms Antitubercular Agents/*therapeutic use Disease Progression Drug Administration Schedule Humans *Models, Theoretical Outcome Assessment (Health Care)/*methods Recurrence Time Factors Tuberculosis/*drug therapy/prevention & control/transmission LA - eng N1 - 1932-6203 Fofana, Mariam O Knight, Gwenan M Gomez, Gabriela B White, Richard G Dowdy, David W T32 GM007309/GM/NIGMS NIH HHS/United States MR/J005088/1/Medical Research Council/United Kingdom U2GPS0008111/PHS HHS/United States PEPFAR/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States PLoS One. 2014 May 9;9(5):e96389. doi: 10.1371/journal.pone.0096389. eCollection 2014. PY - 2014 SN - 1932-6203 SP - e96389 ST - Population-level impact of shorter-course regimens for tuberculosis: a model-based analysis T2 - PLoS One TI - Population-level impact of shorter-course regimens for tuberculosis: a model-based analysis VL - 9 ID - 2025 ER - TY - JOUR AB - OBJECTIVE: To evaluate the cost-effectiveness of the Three I's for HIV/TB (human immunodeficiency virus/tuberculosis): antiretroviral therapy (ART), intensified TB case finding (ICF), isoniazid preventive treatment (IPT), and TB infection control (IC). METHODS: Using a 3-year decision-analytic model, we estimated the cost-effectiveness of a base scenario (55% ART coverage at CD4 count 350 cells/mm(3)) and 19 strategies that included one or more of the following: 1) 90% ART coverage, 2) IC and 3) ICF using four-symptom screening and 6- or 36-month IPT. The TB diagnostic algorithm included 1) sputum smear microscopy with chest X-ray, and 2) Xpert(R) MTB/RIF. RESULTS: In resource-constrained settings with a high burden of HIV and TB, the most cost-effective strategies under both diagnostic algorithms included 1) 55% ART coverage and IC, 2) 55% ART coverage, IC and 36-month IPT, and 3) expanded ART at 90% coverage with IC and 36-month IPT. The latter averted more TB cases than other scenarios with increased ART coverage, IC, 6-month IPT and/or IPT for tuberculin skin test positive individuals. The cost-effectiveness results did not change significantly under the sensitivity analyses. CONCLUSION: Expanded ART to 90% coverage, IC and a 36-month IPT strategy averted most TB cases and is among the cost-effective strategies. AD - Joint United Nations Programme on HIV/AIDS, Geneva, Switzerland. US Centers for Disease Control and Prevention, Atlanta, Georgia, USA. South African Centre for Epidemiological Modelling and Analysis, University of Stellenbosch, Cape Town, South Africa. Independent Consultant, Huntingdon, UK. AN - 25216828 AU - Gupta, S. AU - Abimbola, T. AU - Date, A. AU - Suthar, A. B. AU - Bennett, R. AU - Sangrujee, N. AU - Granich, R. C2 - PMC4886505 C6 - HHSPA785776 DA - Oct DO - 10.5588/ijtld.13.0571 DP - NLM ET - 2014/09/14 IS - 10 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Algorithms Antitubercular Agents/therapeutic use CD4 Lymphocyte Count *Cost-Benefit Analysis Drug Resistance, Bacterial HIV Infections/*drug therapy/microbiology Humans Isoniazid/therapeutic use *Models, Economic Mycobacterium tuberculosis/drug effects Radiography Rifampin/therapeutic use Sensitivity and Specificity Tuberculosis/diagnosis/economics/*prevention & control L1 - internal-pdf://2672718028/Gupta-2014-Cost-effectiveness of the Three I's.pdf LA - eng N1 - 1815-7920 Gupta, S Abimbola, T Date, A Suthar, A B Bennett, R Sangrujee, N Granich, R CC999999/Intramural CDC HHS/United States Journal Article France Int J Tuberc Lung Dis. 2014 Oct;18(10):1159-65. doi: 10.5588/ijtld.13.0571. PY - 2014 SN - 1027-3719 SP - 1159-65 ST - Cost-effectiveness of the Three I's for HIV/TB and ART to prevent TB among people living with HIV T2 - Int J Tuberc Lung Dis TI - Cost-effectiveness of the Three I's for HIV/TB and ART to prevent TB among people living with HIV UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886505/pdf/nihms785776.pdf VL - 18 ID - 1911 ER - TY - JOUR AB - A new model for the transmission dynamics of Mycobacterium tuberculosis and bovine tuberculosis in a community, consisting of humans and African buffalos, is presented. The buffalo-only component of the model exhibits the phenomenon of backward bifurcation, which arises due to the reinfection of exposed and recovered buffalos, when the associated reproduction number is less than unity. This model has a unique endemic equilibrium, which is globally asymptotically stable for a special case, when the reproduction number exceeds unity. Uncertainty and sensitivity analyses, using data relevant to the dynamics of the two diseases in the Kruger National Park, show that the distribution of the associated reproduction number is less than unity (hence, the diseases would not persist in the community). Crucial parameters that influence the dynamics of the two diseases are also identified. Both the buffalo-only and the buffalo-human model exhibit the same qualitative dynamics with respect to the local and global asymptotic stability of their respective disease-free equilibrium, as well as with respect to the backward bifurcation phenomenon. Numerical simulations of the buffalo-human model show that the cumulative number of Mycobacterium tuberculosis cases in humans (buffalos) decreases with increasing number of bovine tuberculosis infections in humans (buffalo). AD - Department of Mathematics and Applied Mathematics, University of Pretoria, Pretoria 0002, South Africa. Department of Mathematics, University of Manitoba, Winnipeg, MB, Canada R3T 2N2. AN - 25254065 AU - Hassan, A. S. AU - Garba, S. M. AU - Gumel, A. B. AU - Lubuma, J. M. C2 - PMC4165569 DO - 10.1155/2014/912306 DP - NLM ET - 2014/09/26 J2 - Computational and mathematical methods in medicine KW - Animals Basic Reproduction Number Buffaloes Cattle Computer Simulation Disease Outbreaks Geography Humans Models, Theoretical Reproducibility of Results Species Specificity Tuberculosis/*epidemiology/microbiology/transmission Tuberculosis, Bovine/*epidemiology/microbiology/transmission LA - eng N1 - 1748-6718 Hassan, A S Garba, S M Gumel, A B Lubuma, J M-S Journal Article Research Support, Non-U.S. Gov't United States Comput Math Methods Med. 2014;2014:912306. doi: 10.1155/2014/912306. Epub 2014 Sep 2. PY - 2014 SN - 1748-670x SP - 912306 ST - Dynamics of Mycobacterium and bovine tuberculosis in a human-buffalo population T2 - Comput Math Methods Med TI - Dynamics of Mycobacterium and bovine tuberculosis in a human-buffalo population VL - 2014 ID - 1897 ER - TY - JOUR AB - SETTING: The global target of tuberculosis (TB) elimination by 2050 requires new approaches. Active case finding plus mass prophylactic treatment has been disappointing. We consider mass full anti-tuberculosis treatment as an approach to TB elimination in Kiribati, a Pacific Island nation, with a persistent epidemic of high TB incidence. OBJECTIVE: To construct a mathematical model to predict whether mass treatment with a full course of anti-tuberculosis drugs might eliminate TB from the defined population of the Republic of Kiribati. METHODS: We constructed a seven-state compartmental model of the life cycle of Mycobacterium tuberculosis in which active TB disease arises from the progression of infection, reinfection, reactivation and relapse, while distinguishing infectious from non-infectious disease. We evaluated the effects of 5-yearly mass treatment using a range of parameter values to generate outcomes in uncertainty analysis. RESULTS: Assuming population-wide treatment effectiveness for latent tuberculous infection and active TB of 90%, annual TB incidence is expected to fall sharply at each 5-yearly round of treatment, approaching elimination in two decades. The model showed that the incidence rate is sensitive to the relapse rate after successful treatment of TB. CONCLUSION: Mass treatment may help to eliminate TB, at least for discrete or geographically isolated populations. AD - Centre for International Health, Department of Preventive and Social Medicine, Faculty of Medicine, University of Otago, Dunedin, New Zealand; HIV/AIDS, Tuberculosis, Malaria & Neglected Tropical Diseases Cluster, World Health Organization, Geneva, Switzerland; Public Health Division, Secretariat of the Pacific Community, Noumea Cedex, New Caledonia; National Tuberculosis Control Programme, Ministry of Health and Medical Services, Republic of Kiribati; International Union Against Tuberculosis and Lung Disease, Paris, France; *South African Centre for Epidemiological Modelling and Analysis, Cape Town, South Africa; Medecins Sans Frontieres, Brussels Operational Centre, Luxembourg, Belgium; Sydney Emerging Infectious Disease and Biosecurity Institute and Centre for Research Excellence in Tuberculosis, University of Sydney, Sydney, New South Wales, Australia; AN - 25199002 AU - Hill, P. C. AU - Dye, C. AU - Viney, K. AU - Tabutoa, K. AU - Kienene, T. AU - Bissell, K. AU - Williams, B. G. AU - Zachariah, R. AU - Marais, B. J. AU - Harries, A. D. DA - Aug DO - 10.5588/ijtld.14.0007 DP - NLM ET - 2014/09/10 IS - 8 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Adolescent Adult Aged Antitubercular Agents/administration & dosage/*therapeutic use Child Child, Preschool Disease Progression Female Humans Incidence Infant Latent Tuberculosis/drug therapy/epidemiology/microbiology Male Micronesia/epidemiology Middle Aged *Models, Theoretical Mycobacterium tuberculosis/*pathogenicity Recurrence Time Factors Tuberculosis/epidemiology/microbiology/*prevention & control Young Adult LA - eng N1 - 1815-7920 Hill, P C Dye, C Viney, K Tabutoa, K Kienene, T Bissell, K Williams, B G Zachariah, R Marais, B J Harries, A D 001/World Health Organization/International Journal Article France Int J Tuberc Lung Dis. 2014 Aug;18(8):899-904. doi: 10.5588/ijtld.14.0007. PY - 2014 SN - 1027-3719 SP - 899-904 ST - Mass treatment to eliminate tuberculosis from an island population T2 - Int J Tuberc Lung Dis TI - Mass treatment to eliminate tuberculosis from an island population VL - 18 ID - 1917 ER - TY - JOUR AB - Existing approaches to tuberculosis (TB) control have been no more than partially successful in areas with high human immunodeficiency virus (HIV) prevalence. In the context of increasingly constrained resources, mathematical modelling can augment understanding and support policy for implementing those strategies that are most likely to bring public health and economic benefits. In this paper, we present an overview of past and recent contributions of TB modelling in this key area, and suggest a way forward through a modelling research agenda that supports a more effective response to the TB-HIV epidemic, based on expert discussions at a meeting convened by the TB Modelling and Analysis Consortium. The research agenda identified high-priority areas for future modelling efforts, including 1) the difficult diagnosis and high mortality of TB-HIV; 2) the high risk of disease progression; 3) TB health systems in high HIV prevalence settings; 4) uncertainty in the natural progression of TB-HIV; and 5) combined interventions for TB-HIV. Efficient and rapid progress towards completion of this modelling agenda will require co-ordination between the modelling community and key stakeholders, including advocates, health policy makers, donors and national or regional finance officials. A continuing dialogue will ensure that new results are effectively communicated and new policy-relevant questions are addressed swiftly. AD - TB Modelling Group, TB Centre, and Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine (LSHTM), London, UK. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. Department of Global Health and Development, LSHTM, London, UK. Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. Division of Medical Microbiology and Institute of Infectious Diseases and Molecular Medicine, University of Cape Town and National Health Laboratory Service, South Africa. Joint United Nations Programme on HIV/AIDS, World Health Organization (WHO), Geneva, Switzerland. Oxford-Emergent Tuberculosis Consortium, Wokingham, UK. Intellectual Ventures Laboratory, Bellevue, Washington, USA. HIV, TB Malaria and Neglected Tropical Diseases Cluster, WHO, Geneva, Switzerland. Bill and Melinda Gates Foundation, Seattle, Washington, USA. AN - 24903784 AU - Houben, R. M. AU - Dowdy, D. W. AU - Vassall, A. AU - Cohen, T. AU - Nicol, M. P. AU - Granich, R. M. AU - Shea, J. E. AU - Eckhoff, P. AU - Dye, C. AU - Kimerling, M. E. AU - White, R. G. C2 - PMC4436821 DA - May DO - 10.5588/ijtld.13.0773 DP - NLM ET - 2014/06/07 IS - 5 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Anti-HIV Agents/therapeutic use Antitubercular Agents/*therapeutic use *Coinfection Decision Support Techniques Epidemics/*prevention & control HIV Infections/diagnosis/drug therapy/*epidemiology Health Priorities Health Services Accessibility Health Services Needs and Demand Humans *Models, Theoretical Needs Assessment Prevalence Treatment Outcome Tuberculosis/diagnosis/epidemiology/*prevention & control/transmission LA - eng N1 - 1815-7920 Houben, R M G J Dowdy, D W Vassall, A Cohen, T Nicol, M P Granich, R M Shea, J E Eckhoff, P Dye, C Kimerling, M E White, R G TB MAC TB-HIV meeting participants 001/World Health Organization/International 091769/Wellcome Trust/United Kingdom Journal Article Research Support, Non-U.S. Gov't Review France Int J Tuberc Lung Dis. 2014 May;18(5):509-14. doi: 10.5588/ijtld.13.0773. PY - 2014 SN - 1027-3719 SP - 509-14 ST - How can mathematical models advance tuberculosis control in high HIV prevalence settings? T2 - Int J Tuberc Lung Dis TI - How can mathematical models advance tuberculosis control in high HIV prevalence settings? VL - 18 ID - 1998 ER - TY - JOUR AB - Trials of isoniazid preventive therapy (IPT) for people living with HIV in southern Africa have shown high rates of tuberculosis disease immediately after cessation of therapy. This could be due to the lack of cure following preventive therapy or reinfection with rapid progression to disease. Using a model fitted to trial data, we estimate the degree to which preventive therapies cure latent Mycobacterium tuberculosis infection in HIV-infected individuals in high-tuberculosis-burden settings. We identified randomized controlled trials that compared IPT to placebo or alternative regimen in HIV-positive, tuberculin skin test positive individuals. A mathematical model describing tuberculosis transmission in a closed cohort of HIV-positive, M. tuberculosis infected, antiretroviral therapy naive individuals following completion of preventive therapy (or placebo) was fitted to posttherapy tuberculosis rates to estimate the annual risk of M. tuberculosis reinfection and the proportion of individuals whose latent infection was cured after therapy. Three trials met our inclusion criteria. Estimated annual risks of reinfection ranged between 3.7 and 4.9%. Our results suggest 6 mo of isoniazid cured in a small proportion [estimated proportion cured = 0% (interquartile range 0-30.9%)]. The proportion cured for 3-mo regimens containing rifampicin or rifapentine was 19-100%. IPT alone does not cure existing infections in the majority of HIV-infected individuals. In high-incidence settings, continuous IPT should be integrated with HIV care. Where the risk of reinfection is lower, preventive therapy with more curative drugs should be preferred for HIV-positive individuals to achieve durable patient benefit. AD - TB Modelling Group, Department of Infectious Disease Epidemiology, TB Centre, and Department of Clinical Research, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom. AN - 24706842 AU - Houben, R. M. AU - Sumner, T. AU - Grant, A. D. AU - White, R. G. C2 - PMC3986199 DA - Apr 08 DO - 10.1073/pnas.1317660111 DP - NLM ET - 2014/04/08 IS - 14 J2 - Proceedings of the National Academy of Sciences of the United States of America KW - Africa, Southern/epidemiology Antitubercular Agents/*therapeutic use Controlled Clinical Trials as Topic HIV Infections/*complications/epidemiology Humans Latent Tuberculosis/complications/*drug therapy/epidemiology/microbiology Mycobacterium tuberculosis/isolation & purification Placebos LA - eng N1 - 1091-6490 Houben, Rein M G J Sumner, Tom Grant, Alison D White, Richard G MR/J005088/1/Medical Research Council/United Kingdom Journal Article Research Support, Non-U.S. Gov't United States Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5325-30. doi: 10.1073/pnas.1317660111. Epub 2014 Mar 24. PY - 2014 SN - 0027-8424 SP - 5325-30 ST - Ability of preventive therapy to cure latent Mycobacterium tuberculosis infection in HIV-infected individuals in high-burden settings T2 - Proc Natl Acad Sci U S A TI - Ability of preventive therapy to cure latent Mycobacterium tuberculosis infection in HIV-infected individuals in high-burden settings VL - 111 ID - 1548 ER - TY - JOUR AB - Threat of co-epidemic HIV-111 is a major problem that must be faced by countries around the world. In 2011, approximately about one-third of the 34 million people living with HIV worldwide is infected with latent TB. Persons co-infected with TB and HIV are 21-34 times more likely to develop active TB disease than persons without HIV. In this paper, we develop a simple co-epidemic model of HIV-TB. We calculate the basic reproduction ratio at the disease-free equilibrium, and the quasidisease-free equilibrium, which we define as the existence of one disease along with the complete eradication of the other disease, and the co-infection equilibrium for specific conditions. Using this model, we study co-epidemic HIV-TB in Indonesia based on demography data in 2009 to explore the effects of hypothetical prevention and treatment scenarios. Our simple model of coepidemic HIV-TB describes the importance of including the effects of HIV on 113 and vice versa on the transmission and progression of the HIV and TB epidemic. AD - Intistut Teknol Bandung, Dept Math, Bandung, Indonesia Nusa Cendana Univ, Dept Math, Kupang, Indonesia Diponegoro Univ, Dept Math, Semarang, Indonesia AN - WOS:000342294800012 AU - Jafaruddin AU - Sutimin AU - Ariyanto DO - 10.1063/1.4866534 J2 - Aip Conf Proc KW - model dynamic co-epidemic of hiv-tb, and basic reproduction number tuberculosis LA - English N1 - Bb2tj Times Cited:1 Cited References Count:9 AIP Conference Proceedings PY - 2014 SN - 0094-243x SP - 61-65 ST - A Model Dynamic for Effect Latent Population to Co-epidemic of HIV-TB T2 - Symposium on Biomathematics (Symomath 2013) TI - A Model Dynamic for Effect Latent Population to Co-epidemic of HIV-TB UR - ://WOS:000342294800012 VL - 1587 ID - 4902 ER - TY - JOUR AB - There has been an increasing interest in the analysis of spatially distributed multivariate binary data motivated by a wide range of research problems. Two types of correlations are usually involved: the correlation between the multiple outcomes at one location and the spatial correlation between the locations for one particular outcome. The commonly used regression models only consider one type of correlations while ignoring or modeling inappropriately the other one. To address this limitation, we adopt a Bayesian nonparametric approach to jointly modeling multivariate spatial binary data by integrating both types of correlations. A multivariate probit model is employed to link the binary outcomes to Gaussian latent variables; and Gaussian processes are applied to specify the spatially correlated random effects. We develop an efficient Markov chain Monte Carlo algorithm for the posterior computation. We illustrate the proposed model on simulation studies and a multidrug-resistant tuberculosis case study. AD - Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia, U.S.A. AN - 24975716 AU - Kang, J. AU - Zhang, N. AU - Shi, R. C2 - PMC4433053 C6 - NIHMS688272 DA - Dec DO - 10.1111/biom.12198 DP - NLM ET - 2014/07/01 IS - 4 J2 - Biometrics KW - Algorithms *Bayes Theorem Computer Simulation Data Interpretation, Statistical Humans *Models, Statistical *Multivariate Analysis Peru/epidemiology *Population Density Population Surveillance/*methods Prevalence Reproducibility of Results Sensitivity and Specificity Spatio-Temporal Analysis Tuberculosis, Multidrug-Resistant/*epidemiology Bayesian methods Drug resistance Gaussian processes Spatially distributed multivariate binary data L1 - internal-pdf://3255626134/Kang-2014-A Bayesian nonparametric model for s.pdf LA - eng N1 - 1541-0420 Kang, Jian Zhang, Nanhua Shi, Ran R01 MH105561/MH/NIMH NIH HHS/United States Journal Article United States Biometrics. 2014 Dec;70(4):981-92. doi: 10.1111/biom.12198. Epub 2014 Jun 27. PY - 2014 SN - 0006-341x SP - 981-92 ST - A Bayesian nonparametric model for spatially distributed multivariate binary data with application to a multidrug-resistant tuberculosis (MDR-TB) study T2 - Biometrics TI - A Bayesian nonparametric model for spatially distributed multivariate binary data with application to a multidrug-resistant tuberculosis (MDR-TB) study UR - http://onlinelibrary.wiley.com/store/10.1111/biom.12198/asset/biom12198.pdf?v=1&t=jab8au6o&s=2cd58621a639d183af49414f84cd0449a4c17b97 VL - 70 ID - 1978 ER - TY - JOUR AB - RATIONALE: Household contact tracing has recently been endorsed for global tuberculosis (TB) control, but its potential population-level impact remains uncertain. OBJECTIVES: To project the maximum impact of household contact tracing for TB in a moderate-burden setting. METHODS: We developed a stochastic, agent-based simulation model of a simplified TB epidemic, calibrated to a setting of moderate TB incidence. We used data from the literature to generate "community-driven" and "household-driven" scenarios in which 22 and 50% of TB transmission occurred within the household, respectively. In each scenario, we simulated an intervention in which the household members are screened and treated for TB at the time of an index patient's active TB diagnosis. MEASUREMENTS AND MAIN RESULTS: By the time of TB diagnosis, 75 to 95% of initial household infections had already occurred, but only 1.5 to 3.0% of contacts had sufficient time to progress to active TB. With 100% sensitive tracing of all contacts for 5 consecutive years, TB incidence declined by 10 to 15%, with a mean year-over-year decline of 2% per year. Effects were sustained for many years after stopping the intervention. Providing preventive therapy with contact tracing nearly doubled this impact (17-27% decline in incidence). Impact was proportional to sensitivity and coverage; thus, if 50% of contacts were screened with a 50% sensitive test, TB incidence declined by only 0.5% per year. CONCLUSIONS: Household contact tracing is unlikely to transform TB epidemiology in isolation but has the potential, especially with provision of preventive therapy, to augment a comprehensive package of interventions that could substantially reduce the population-level burden of TB. AD - 1 Department of Operations, Business Analytics, and Information Systems, College of Business, University of Cincinnati, Cincinnati, Ohio. AN - 24559425 AU - Kasaie, P. AU - Andrews, J. R. AU - Kelton, W. D. AU - Dowdy, D. W. DA - Apr 01 DO - 10.1164/rccm.201310-1846OC DP - NLM ET - 2014/02/25 IS - 7 J2 - American journal of respiratory and critical care medicine KW - Computer Simulation *Contact Tracing Family Characteristics Humans Incidence Models, Theoretical Tuberculosis, Pulmonary/diagnosis/epidemiology/prevention & control/*transmission LA - eng N1 - 1535-4970 Kasaie, Parastu Andrews, Jason R Kelton, W David Dowdy, David W Evaluation Studies Journal Article Research Support, Non-U.S. Gov't United States Am J Respir Crit Care Med. 2014 Apr 1;189(7):845-52. doi: 10.1164/rccm.201310-1846OC. PY - 2014 SN - 1073-449x SP - 845-52 ST - Timing of tuberculosis transmission and the impact of household contact tracing. An agent-based simulation model T2 - Am J Respir Crit Care Med TI - Timing of tuberculosis transmission and the impact of household contact tracing. An agent-based simulation model VL - 189 ID - 1590 ER - TY - JOUR AB - In this paper, we present a deterministic non-linear mathematical model for the transmission dynamics of HIV and TB co-infection and analyze it in the presence of screening and treatment. The equilibria of the model are computed and stability of these equilibria is discussed. The basic reproduction numbers corresponding to both HIV and TB are found and we show that the disease-free equilibrium is stable only when the basic reproduction numbers for both the diseases are less than one. When both the reproduction numbers are greater than one, the co-infection equilibrium point may exist. The co-infection equilibrium is found to be locally stable whenever it exists. The TB-only and HIV-only equilibria are locally asymptotically stable under some restriction on parameters. We present numerical simulation results to support the analytical findings. We observe that screening with proper counseling of HIV infectives results in a significant reduction of the number of individuals progressing to HIV. Additionally, the screening of TB reduces the infection prevalence of TB disease. The results reported in this paper clearly indicate that proper screening and counseling can check the spread of HIV and TB diseases and effective control strategies can be formulated around 'screening with proper counseling'. AD - School of Mathematics and Computer Applications, Thapar University, Patiala, 147004, Punjab, India, navjotkaur@thapar.edu. AN - 24664795 AU - Kaur, N. AU - Ghosh, M. AU - Bhatia, S. S. C2 - PMC4049375 DA - Mar DO - 10.1007/s10867-014-9342-3 DP - NLM ET - 2014/03/26 IS - 2 J2 - Journal of biological physics KW - Acquired Immunodeficiency Syndrome/diagnosis/therapy/*transmission Coinfection/diagnosis/therapy/*transmission Humans *Models, Statistical Nonlinear Dynamics Tuberculosis/diagnosis/therapy/*transmission LA - eng N1 - 1573-0689 Kaur, Navjot Ghosh, Mini Bhatia, S S Journal Article Research Support, Non-U.S. Gov't Netherlands J Biol Phys. 2014 Mar;40(2):139-66. doi: 10.1007/s10867-014-9342-3. Epub 2014 Mar 25. PY - 2014 SN - 0092-0606 SP - 139-66 ST - The role of screening and treatment in the transmission dynamics of HIV/AIDS and tuberculosis co-infection: a mathematical study T2 - J Biol Phys TI - The role of screening and treatment in the transmission dynamics of HIV/AIDS and tuberculosis co-infection: a mathematical study VL - 40 ID - 1564 ER - TY - JOUR AB - OBJECTIVES: According to the Korea Centers for Disease Control and Prevention, new active tuberculosis (TB) cases have increased since 2001. Some key factors explain and characterize the transmission dynamics of Korean TB infection, such as a higher ratio of latent individuals and a new reporting system implemented in 2001, among others. METHODS: We propose a mathematical TB model that includes exogenous reinfection to gain a better understanding of the recent trend for TB incidence. We divide the simulation time window into two periods, 1970-2000 and 2001-2012, according to the implementation date of a new TB detection system. RESULTS: Two sets of parameters, including the transmission rate, the latent period, the recovery rate, and the proportion of exogenous reinfection, are estimated using the least-squares method and calibrated to data on the incidence of active TB. CONCLUSION: Among some key parameters in the model, the case finding effort turned out to be the most significant impacting component on the reduction in the active TB cases. AD - Department of Applied Mathematics, Kyung-Hee University, Yongin, Korea. AN - 24955311 AU - Kim, S. AU - Choe, S. AU - Kim, J. AU - Nam, S. AU - Shin, Y. AU - Lee, S. C2 - PMC4064633 DA - Feb DO - 10.1016/j.phrp.2014.01.002 DP - NLM ET - 2014/06/24 IS - 1 J2 - Osong public health and research perspectives KW - Exogeneous reinfection Korea Tuberculosis Tuberculosis control measures LA - eng N1 - Kim, Sara Choe, Seoyun Kim, Junseong Nam, Sanga Shin, Yeon Lee, Sunmi Journal Article Korea (South) Osong Public Health Res Perspect. 2014 Feb;5(1):40-5. doi: 10.1016/j.phrp.2014.01.002. Epub 2014 Feb 5. PY - 2014 SN - 2210-9099 (Print) 2210-9099 SP - 40-5 ST - What does a mathematical model tell about the impact of reinfection in korean tuberculosis infection? T2 - Osong Public Health Res Perspect TI - What does a mathematical model tell about the impact of reinfection in korean tuberculosis infection? VL - 5 ID - 1985 ER - TY - JOUR AB - The use of multi-scale mathematical and computational models to study complex biological processes is becoming increasingly productive. Multi-scale models span a range of spatial and/or temporal scales and can encompass multi-compartment (e.g., multi-organ) models. Modeling advances are enabling virtual experiments to explore and answer questions that are problematic to address in the wet-lab. Wet-lab experimental technologies now allow scientists to observe, measure, record, and analyze experiments focusing on different system aspects at a variety of biological scales. We need the technical ability to mirror that same flexibility in virtual experiments using multi-scale models. Here we present a new approach, tuneable resolution, which can begin providing that flexibility. Tuneable resolution involves fine- or coarse-graining existing multi-scale models at the user's discretion, allowing adjustment of the level of resolution specific to a question, an experiment, or a scale of interest. Tuneable resolution expands options for revising and validating mechanistic multi-scale models, can extend the longevity of multi-scale models, and may increase computational efficiency. The tuneable resolution approach can be applied to many model types, including differential equation, agent-based, and hybrid models. We demonstrate our tuneable resolution ideas with examples relevant to infectious disease modeling, illustrating key principles at work. AD - Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA. AN - 24810243 AU - Kirschner, D. E. AU - Hunt, C. A. AU - Marino, S. AU - Fallahi-Sichani, M. AU - Linderman, J. J. C2 - PMC4102180 C6 - NIHMS580049 DA - Jul-Aug DO - 10.1002/wsbm.1270 DP - NLM ET - 2014/05/09 IS - 4 J2 - Wiley interdisciplinary reviews. Systems biology and medicine KW - Algorithms Animals Communicable Diseases Computational Biology/*methods Computer Simulation Cytokines/metabolism Humans Immune System/physiology Models, Biological Mycobacterium tuberculosis Systems Biology/*methods Tuberculosis/physiopathology LA - eng N1 - 1939-005x Kirschner, Denise E Hunt, C Anthony Marino, Simeone Fallahi-Sichani, Mohammad Linderman, Jennifer J R01 GM096040/GM/NIGMS NIH HHS/United States R01 HL 110811/HL/NHLBI NIH HHS/United States R01 HL106804/HL/NHLBI NIH HHS/United States R01 EB012579/EB/NIBIB NIH HHS/United States R01 HL110811/HL/NHLBI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Review United States Wiley Interdiscip Rev Syst Biol Med. 2014 Jul-Aug;6(4):289-309. doi: 10.1002/wsbm.1270. Epub 2014 May 9. PY - 2014 SN - 1939-005x SP - 289-309 ST - Tuneable resolution as a systems biology approach for multi-scale, multi-compartment computational models T2 - Wiley Interdiscip Rev Syst Biol Med TI - Tuneable resolution as a systems biology approach for multi-scale, multi-compartment computational models VL - 6 ID - 2027 ER - TY - JOUR AB - To help reach the target of tuberculosis (TB) disease elimination by 2050, vaccine development needs to occur now. We estimated the impact and cost-effectiveness of potential TB vaccines in low- and middle-income countries using an age-structured transmission model. New vaccines were assumed to be available in 2024, to prevent active TB in all individuals, to have a 5-y to lifetime duration of protection, to have 40-80% efficacy, and to be targeted at "infants" or "adolescents/adults." Vaccine prices were tiered by income group (US $1.50-$10 per dose), and cost-effectiveness was assessed using incremental cost per disability adjusted life year (DALY) averted compared against gross national income per capita. Our results suggest that over 2024-2050, a vaccine targeted to adolescents/adults could have a greater impact than one targeted at infants. In low-income countries, a vaccine with a 10-y duration and 60% efficacy targeted at adolescents/adults could prevent 17 (95% range: 11-24) million TB cases by 2050 and could be considered cost-effective at $149 (cost saving to $387) per DALY averted. If targeted at infants, 0.89 (0.42-1.58) million TB cases could be prevented at $1,692 ($634-$4,603) per DALY averted. This profile targeted at adolescents/adults could be cost-effective at $4, $9, and $20 per dose in low-, lower-middle-, and upper-middle-income countries, respectively. Increased investments in adult-targeted TB vaccines may be warranted, even if only short duration and low efficacy vaccines are likely to be feasible, and trials among adults should be powered to detect low efficacies. AD - TB Modelling Group, TB Centre, Centre for the Mathematical Modelling of Infectious Diseases, Faculty of Epidemiology and Population Health, and. Department of Global Health and Development, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; and. Global Tuberculosis, World Health Organization, CH 1211 Geneva 27, Switzerland. TB Modelling Group, TB Centre, Centre for the Mathematical Modelling of Infectious Diseases, Faculty of Epidemiology and Population Health, and richard.white@lshtm.ac.uk. AN - 25288770 AU - Knight, G. M. AU - Griffiths, U. K. AU - Sumner, T. AU - Laurence, Y. V. AU - Gheorghe, A. AU - Vassall, A. AU - Glaziou, P. AU - White, R. G. C2 - PMC4217399 DA - Oct 28 DO - 10.1073/pnas.1404386111 DP - NLM ET - 2014/10/08 IS - 43 J2 - Proceedings of the National Academy of Sciences of the United States of America KW - Adolescent Adult Calibration *Cost-Benefit Analysis Developing Countries/*economics Humans *Income Infant Models, Economic Tuberculosis/economics/immunology/mortality/prevention & control Tuberculosis Vaccines/*economics Uncertainty epidemiology mathematical modeling threshold analysis LA - eng N1 - 1091-6490 Knight, Gwenan M Griffiths, Ulla K Sumner, Tom Laurence, Yoko V Gheorghe, Adrian Vassall, Anna Glaziou, Philippe White, Richard G ORCID: http://orcid.org/0000-0003-4410-6635 001/World Health Organization/International MR/J005088/1/Medical Research Council/United Kingdom U2GPS0008111/PHS HHS/United States PEPFAR/United States Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15520-5. doi: 10.1073/pnas.1404386111. Epub 2014 Oct 6. PY - 2014 SN - 0027-8424 SP - 15520-5 ST - Impact and cost-effectiveness of new tuberculosis vaccines in low- and middle-income countries T2 - Proc Natl Acad Sci U S A TI - Impact and cost-effectiveness of new tuberculosis vaccines in low- and middle-income countries VL - 111 ID - 1886 ER - TY - JOUR AB - BACKGROUND: Several promising new diagnostic methods and algorithms for tuberculosis have been endorsed by WHO. National tuberculosis programmes now face the decision on which methods to implement and where to place them in the diagnostic algorithm. METHODS: We used an integrated model to assess the effects of different algorithms of Xpert MTB/RIF and light-emitting diode (LED) fluorescence microscopy in Tanzania. To understand the effects of new diagnostics from the patient, health system, and population perspective, the model incorporated and linked a detailed operational component and a transmission component. The model was designed to represent the operational and epidemiological context of Tanzania and was used to compare the effects and cost-effectiveness of different diagnostic options. FINDINGS: Among the diagnostic options considered, we identified three strategies as cost effective in Tanzania. Full scale-up of Xpert would have the greatest population-level effect with the highest incremental cost: 346 000 disability-adjusted life-years (DALYs) averted with an additional cost of US$36.9 million over 10 years. The incremental cost-effectiveness ratio (ICER) of Xpert scale-up ($169 per DALY averted, 95% credible interval [CrI] 104-265) is below the willingness-to-pay threshold ($599) for Tanzania. Same-day LED fluorescence microscopy is the next most effective strategy with an ICER of $45 (95% CrI 25-74), followed by LED fluorescence microscopy with an ICER of $29 (6-59). Compared with same-day LED fluorescence microscopy and Xpert full rollout, targeted use of Xpert in presumptive tuberculosis cases with HIV infection, either as an initial diagnostic test or as a follow-on test to microscopy, would produce DALY gains at a higher incremental cost and therefore is dominated in the context of Tanzania. INTERPRETATION: For Tanzania, this integrated modelling approach predicts that full rollout of Xpert is a cost-effective option for tuberculosis diagnosis and has the potential to substantially reduce the national tuberculosis burden. It also estimates the substantial level of funding that will need to be mobilised to translate this into clinical practice. This approach could be adapted and replicated in other developing countries to inform rational health policy formulation. AD - Liverpool School of Tropical Medicine, Liverpool, UK. Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taiwan. Electronic address: hsienho@ntu.edu.tw. National Tuberculosis and Leprosy Programme, Dar es Salaam, Tanzania. Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taiwan. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Division of Global Health Equity, Brigham and Women's Hospital, Boston, MA, USA. AN - 25304634 AU - Langley, I. AU - Lin, H. H. AU - Egwaga, S. AU - Doulla, B. AU - Ku, C. C. AU - Murray, M. AU - Cohen, T. AU - Squire, S. B. DA - Oct DO - 10.1016/s2214-109x(14)70291-8 DP - NLM ET - 2014/10/12 IS - 10 J2 - The Lancet. Global health KW - Algorithms Antitubercular Agents/pharmacology Cost-Benefit Analysis Drug Resistance, Bacterial Government Programs/economics Humans Microscopy, Fluorescence/*economics/*instrumentation Models, Econometric Rifampin/pharmacology Sputum/*microbiology Tanzania Time Factors Tuberculosis/*diagnosis L1 - internal-pdf://3649702241/PIIS2214109X14702918.pdf LA - eng N1 - 2214-109x Langley, Ivor Lin, Hsien-Ho Egwaga, Saidi Doulla, Basra Ku, Chu-Chang Murray, Megan Cohen, Ted Squire, S Bertel Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England Lancet Glob Health. 2014 Oct;2(10):e581-91. doi: 10.1016/S2214-109X(14)70291-8. PY - 2014 SN - 2214-109x SP - e581-91 ST - Assessment of the patient, health system, and population effects of Xpert MTB/RIF and alternative diagnostics for tuberculosis in Tanzania: an integrated modelling approach T2 - Lancet Glob Health TI - Assessment of the patient, health system, and population effects of Xpert MTB/RIF and alternative diagnostics for tuberculosis in Tanzania: an integrated modelling approach VL - 2 ID - 1882 ER - TY - JOUR AB - A two-patch model, SEi1,...,EinIiLi, i = 1,2, is used to analyze the spread of tuberculosis, with an arbitrary number n of latently infected compartments in each patch. A fraction of infectious individuals that begun their treatment will not return to the hospital for the examination of sputum. This fact usually occurs in sub-Saharan Africa, due to many reasons. The model incorporates migrations from one patch to another. The existence and uniqueness of the associated equilibria are discussed. A Lyapunov function is used to show that when the basic reproduction ratio is less than one, the disease-free equilibrium is globally and asymptotically stable. When it is greater than one, there exists at least one endemic equilibrium. The local stability of endemic equilibria can be illustrated using numerical simulations. Numerical simulation results are provided to illustrate the theoretical results and analyze the influence of lost sight individuals. AD - Univ Yaounde I, Dept Math, Fac Sci, Yaounde 8390, Cameroon Univ Yaounde I, Dept Math & Phys, Natl Adv Sch Engn, UMMISCO,Team Project GRIMCAPE,LIRIMA, Yaounde 8390, Cameroon Cheikh Anta Diop Univ, Natl Adv Sch Engn, UMMISCO, Dakar 5085, Senegal Univ Douala, Dept Math & Comp Sci, Fac Sci, UMMISCO,Team Project GRIMCAPE,LIRIMA, Douala 24157, Cameroon North West Univ, MaSIM Focus Area, ZA-2735 Mafikeng, South Africa AN - WOS:000343425700001 AU - Laohombe, A. AU - Eya, I. N. AU - Tewa, J. J. AU - Bah, A. AU - Bowong, S. AU - Noutchie, S. C. O. DO - Artn 263780 10.1155/2014/263780 J2 - Abstr Appl Anal KW - global-stability transmission LA - English N1 - Ar2nx Times Cited:0 Cited References Count:25 PY - 2014 SN - 1085-3375 ST - Mathematical Analysis of a General Two-Patch Model of Tuberculosis Disease with Lost Sight Individuals T2 - Abstract and Applied Analysis TI - Mathematical Analysis of a General Two-Patch Model of Tuberculosis Disease with Lost Sight Individuals UR - ://WOS:000343425700001 ID - 4903 ER - TY - JOUR AB - A mathematical model is presented of the growth and death of bacilli in a granuloma. The granuloma is treated with isoniazid (INH), a drug that inhibits the synthesis of mycolic acids (MA). Since MA is an essential component of cell walls, the organisms fail to reach maturity if deficient in MA. Cell wall turnover is a well-known feature of bacteria, at the exterior surface material sloughs off to foil attacks by hosts or other organisms, simultaneously synthesizing products for new cell wall assembly. Thus cell wall thickness is maintained in a dynamic equilibrium (Doyle et al., 1988). Presumably cell death is a result of loss in cell wall due to autolysis in combination with stinted replenishing. The mathematical model presented here uses differential equations to predict the effects of intracellular INH on cell wall thickness and cell viability. This analysis purposely distinguishes intracellular INH concentration from the concentration in the plasma. The concentration in the plasma depends only on the dosing. The intracellular INH concentration, however, depends on diffusion through the cell walls of the bacteria. This paper addresses the complex interactions between intracellular INH, cell wall thickness, and the rate of cell wall synthesis. AD - Material Science and Manufacturing, CSIR, Pretoria 0001, South Africa. Preclinical Drug Development Platform, North-West University, Potchefstroom 2520, South Africa. Department of Chemical and Biomolecular Engineering, Univerity of Nebraska-Lincoln, Lincoln, NE 68588, USA. Preclinical Drug Development Platform, North-West University, Potchefstroom 2520, South Africa; Department of Chemical and Biomolecular Engineering, Univerity of Nebraska-Lincoln, Lincoln, NE 68588, USA. AN - 25093828 AU - Lemmer, Y. AU - Grobler, A. AU - Moody, C. AU - Viljoen, H. DA - Dec 21 DO - 10.1016/j.jtbi.2014.07.024 DP - NLM ET - 2014/08/06 J2 - Journal of theoretical biology KW - Cell Wall/*drug effects/physiology Diffusion Granuloma/*microbiology Isoniazid/*pharmacology *Models, Biological Mycobacterium tuberculosis/*drug effects Tuberculosis/*drug therapy Cell wall Drug resistance Efflux pumps Mathematical model Mycolic acid LA - eng N1 - 1095-8541 Lemmer, Yolandy Grobler, Anne Moody, Clint Viljoen, Hendrik Journal Article Research Support, Non-U.S. Gov't England J Theor Biol. 2014 Dec 21;363:367-73. doi: 10.1016/j.jtbi.2014.07.024. Epub 2014 Aug 2. PY - 2014 SN - 0022-5193 SP - 367-73 ST - A model of isoniazid treatment of tuberculosis T2 - J Theor Biol TI - A model of isoniazid treatment of tuberculosis VL - 363 ID - 1944 ER - TY - JOUR AB - Understanding how seasonality shapes the dynamics of tuberculosis (TB) is essential in determining risks of transmission and drug resistance in (sub)tropical regions. We developed a relative fitness-based multidrug-resistant (MDR) TB model incorporated with seasonality and a probabilistic assessment model to assess infection risk in Taiwan regions. The model accurately captures the seasonal transmission and population dynamics of TB incidence during 2006-2008 and MDR TB in high TB burden areas during 2006-2010 in Taiwan. There is ~3% probability of having exceeded 50% of the population infected attributed to MDR TB. Our model not only provides insight into the understanding of the interactions between seasonal dynamics of TB and environmental factors but is also capable of predicting the seasonal patterns of TB incidence associated with MDR TB infection risk. A better understanding of the mechanisms of TB seasonality will be critical in predicting the impact of public control programmes. AD - Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan, ROC. AN - 23676258 AU - Lin, Y. J. AU - Liao, C. M. DA - Feb DO - 10.1017/s0950268813001040 DP - NLM ET - 2013/05/17 IS - 2 J2 - Epidemiology and infection KW - Epidemics/*statistics & numerical data Humans Incidence Models, Statistical Population Dynamics Risk Assessment Risk Factors Seasons Taiwan/epidemiology Tuberculosis, Multidrug-Resistant/*epidemiology/transmission Tuberculosis, Pulmonary/*epidemiology/prevention & control/transmission L1 - internal-pdf://2599965735/Lin-2014-Seasonal dynamics of tuberculosis epi.pdf LA - eng N1 - 1469-4409 Lin, Y-J Liao, C-M Journal Article Research Support, Non-U.S. Gov't England Epidemiol Infect. 2014 Feb;142(2):358-70. doi: 10.1017/S0950268813001040. Epub 2013 May 16. PY - 2014 SN - 0950-2688 SP - 358-70 ST - Seasonal dynamics of tuberculosis epidemics and implications for multidrug-resistant infection risk assessment T2 - Epidemiol Infect TI - Seasonal dynamics of tuberculosis epidemics and implications for multidrug-resistant infection risk assessment UR - https://www.cambridge.org/core/services/aop-cambridge-core/content/view/9B7A21D40D18254FEB006E8E78D23C55/S0950268813001040a.pdf/div-class-title-seasonal-dynamics-of-tuberculosis-epidemics-and-implications-for-multidrug-resistant-infection-risk-assessment-div.pdf VL - 142 ID - 1773 ER - TY - JOUR AB - A TB transmission model which incorporates treatment interruptions and two latent periods is presented. The threshold parameter known as the control reproduction number and the equilibria for the model are determined, and the global asymptotical stabilities of the equilibria are studied by constructing the proper Lyapunov functions. The reproduction numbers and numerical simulations show that treatment of active TB cases always helps to control the TB epidemic, while treatment interruptions may have a negative, positive, or no effect on combating TB epidemic. AD - School of Mathematics and Statistics, Henan University of Science and Technology, Luoyang 471023, China. College of Science, China University of Petroleum, Qingdao, Shandong 266580, China. AN - 24963343 AU - Liu, L. AU - Wang, Y. C2 - PMC4055065 DO - 10.1155/2014/932186 DP - NLM ET - 2014/06/26 J2 - Computational and mathematical methods in medicine KW - Algorithms Antitubercular Agents/therapeutic use Basic Reproduction Number Computer Simulation Humans Medical Informatics/*methods Models, Theoretical Time Factors Tuberculosis/*drug therapy/*epidemiology/transmission LA - eng N1 - 1748-6718 Liu, Luju Wang, Yan Journal Article Research Support, Non-U.S. Gov't United States Comput Math Methods Med. 2014;2014:932186. doi: 10.1155/2014/932186. Epub 2014 May 22. PY - 2014 SN - 1748-670x SP - 932186 ST - A mathematical study of a TB Model with treatment interruptions and two latent periods T2 - Comput Math Methods Med TI - A mathematical study of a TB Model with treatment interruptions and two latent periods VL - 2014 ID - 1981 ER - TY - JOUR AB - BACKGROUND: Tuberculosis remains a high burden for Human society despite considerable investments in its control. Unique features in the history of infection and transmission dynamics of tuberculosis pose serious limitations on the direct interpretation of surveillance data and call for models that incorporate latent processes and simulate specific interventions. METHODS: A transmission model was adjusted to the dataset of active tuberculosis cases reported in Portugal between 2002 and 2009. We estimated key transmission parameters from the data (i.e. time to diagnosis, treatment length, default proportion, proportion of pulmonary TB cases). Using the adjusted model to the Portuguese case, we estimated the total burden of tuberculosis in Portugal. We further performed sensitivity analysis to heterogeneities in susceptibility to infection and exposure intensity. RESULTS: We calculated a mean time to diagnose of 2.81 months and treatment length of 8.80 months in Portugal. The proportion defaulting treatment was calculated as 0.04 and the proportion of pulmonary cases as 0.75. Using these values, we estimated a TB burden of 1.6 million infected persons, corresponding to more than 15% of the Portuguese population. We further described the sensitivity of these estimates to heterogeneity. CONCLUSIONS: We showed that the model reproduces well the observed dynamics of the Portuguese data, thus demonstrating its adequacy for devising control strategies for TB and predicting the effects of interventions. AD - Instituto Gulbenkian de Ciencia, Apartado 14, 2781-901 Oeiras, Portugal. j.sollari.lopes@gmail.com. AN - 24941996 AU - Lopes, J. S. AU - Rodrigues, P. AU - Pinho, S. T. AU - Andrade, R. F. AU - Duarte, R. AU - Gomes, M. G. C2 - PMC4069091 DA - Jun 18 DO - 10.1186/1471-2334-14-340 DP - NLM ET - 2014/06/20 J2 - BMC infectious diseases KW - Humans Models, Theoretical Portugal/epidemiology Tuberculosis/diagnosis/*epidemiology/therapy/*transmission LA - eng N1 - 1471-2334 Lopes, Joao Sollari Rodrigues, Paula Pinho, Suani T R Andrade, Roberto F S Duarte, Raquel Gomes, M Gabriela M Journal Article Research Support, Non-U.S. Gov't England BMC Infect Dis. 2014 Jun 18;14:340. doi: 10.1186/1471-2334-14-340. PY - 2014 SN - 1471-2334 SP - 340 ST - Interpreting measures of tuberculosis transmission: a case study on the Portuguese population T2 - BMC Infect Dis TI - Interpreting measures of tuberculosis transmission: a case study on the Portuguese population VL - 14 ID - 2906 ER - TY - CHAP A2 - Ibrahim, H. A2 - Zulkepli, J. A2 - Aziz, N. A2 - Ahmad, N. A2 - Rahman, S. A. AB - The optimally of singular control for SEIR model of Tuberculosis is analyzed. There are controls that correspond to time of the vaccination and treatment schedule. The optimally of singular control is obtained by differentiate a switching function of the model. The result shows that vaccination and treatment control are singular. AD - [Marpaung, Faridawaty; Rangkuti, Yulita M.; Sinaga, Marlina S.] Univ Negeri Medan UNIMED, Fac Math & Nat Sci, Dept Math, Medan 20221, Sumatera Utara, Indonesia. Marpaung, F (reprint author), Univ Negeri Medan UNIMED, Fac Math & Nat Sci, Dept Math, Medan 20221, Sumatera Utara, Indonesia. farida2008.unim@gmail.com; yulitamolliq@yahoo.com; lin_2508@yahoo.co.id AN - WOS:000346073300023 AU - Marpaung, F. AU - Rangkuti, Y. M. AU - Sinaga, M. S. CY - Melville DO - 10.1063/1.4903577 KW - SEIR model Optimal singular control Switching function Tuberculosis LA - English N1 - ISI Document Delivery No.: BB7WT Times Cited: 0 Cited Reference Count: 5 Marpaung, Faridawaty Rangkuti, Yulita M. Sinaga, Marlina S. Icoqsia 2014 Proceedings Paper 3rd International Conference on Quantitative Sciences and Its Applications (ICOQSIA) Aug 12-14, 2014 Kedah, MALAYSIA Unive Utara Malaysia, Sch Quantitat Sci 2 huntington quadrangle, ste 1no1, melville, ny 11747-4501 usa 0094-243x PB - Amer Inst Physics PY - 2014 SN - 978-0-7354-1274-3 SP - 153-159 ST - The Analysis of Optimal Singular Controls for SEIR Model of Tuberculosis T2 - International Conference on Quantitative Sciences and Its Applications T3 - AIP Conference Proceedings TI - The Analysis of Optimal Singular Controls for SEIR Model of Tuberculosis UR - ://WOS:000346073300023 VL - 1635 ID - 5482 ER - TY - JOUR AB - Tuberculosis (TB) is a common lethal infectious disease usually caused by Mycobacterium tuberculosis. According to the WHO, TB to date, claims the second largest number of victims due to a single infectious agent right after HIV/AIDS. Although a widespread implementation of control measures focus on case finding and short-course chemotherapy, the global burden of TB has increased over the past two decades. A deterministic TB model with a demographic structure for the population living in a multi-patch environment (cities, towns, regions or countries, etc.) is formulated. The basic reproduction number R-0 is computed. A sensitivity analysis of the model parameters is performed to estimate the most influential parameters in TB dynamics. Using the iterative Gauss-Newton method to solve the inverse problem of parameter identification, estimability of parameters have been studied, and estimable unknown parameters have been computed using real data of TB in Cameroon, subdivided into four regions. Numerical simulations showed the model to reproduce the TB dynamics in Cameroon and predict a short term increase in the number of TB active cases over next years. AD - Zuse Inst Berlin, Computat Syst Biol Grp, D-14195 Berlin, Germany Univ Douala, Dept Math & Comp Sci, Douala, Cameroon UPMC UMMISCO, UMI IRD 209, Bondy, France Univ Yaounde I, LIRIMA, Project Team GRIMCAPE, Yaounde, Cameroon Postdam Inst Climate Impact Res PIK, D-14412 Potsdam, Germany AN - WOS:000358137000021 AU - Moualeu, D. P. AU - Bowong, S. AU - Kurths, J. J2 - Biomat Int S Math Co KW - dynamic-models epidemics transmission systems hiv LA - English N1 - Bd1lk Times Cited:0 Cited References Count:28 BIOMAT-International Symposium on Mathematical and Computational Biology PY - 2014 SP - 352-373 ST - Parameter Estimation of a Tuberculosis Model in a Patchy Environment: Case of Cameroon T2 - Biomat 2013: International Symposium on Mathematical and Computational Biology TI - Parameter Estimation of a Tuberculosis Model in a Patchy Environment: Case of Cameroon UR - ://WOS:000358137000021 ID - 4904 ER - TY - JOUR AB - A general compartmental model of disease transmission is studied. The generality comes from the fact that new infections may enter any of the infectious classes and that there is an ordering of the infectious classes so that individuals can be permitted (or not) to pass from one class to the next. The model includes staged progression, differential infectivity, and combinations of the two as special cases. The exact etiology of feline infectious peritonitis and its connection to coronavirus is unclear, with two competing theories - mutation process vs multiple virus strains. We apply the model to each of these theories, showing that in either case, one should expect traditional threshold dynamics. A further application to tuberculosis with multiple progression routes through latency is also presented. (C) 2014 Elsevier Inc. All rights reserved. AD - [Nadeau, Julie; McCluskey, C. Connell] Wilfrid Laurier Univ, Dept Math, Waterloo, ON N2L 3C5, Canada. McCluskey, CC (reprint author), Wilfrid Laurier Univ, Dept Math, Waterloo, ON N2L 3C5, Canada. julie.nadeau7@gmail.com; ccmcc8@gmail.com AN - WOS:000332402400044 AU - Nadeau, J. AU - McCluskey, C. C. DA - Mar DO - 10.1016/j.amc.2013.12.124 J2 - Appl. Math. Comput. KW - Global stability Lyapunov function Epidemiology Feline infectious peritonitis Tuberculosis transmission dynamics Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: AC3FY Times Cited: 2 Cited Reference Count: 11 Nadeau, Julie McCluskey, C. Connell 2 0 11 Elsevier science inc New york 1873-5649 PY - 2014 SN - 0096-3003 SP - 473-483 ST - Global stability for an epidemic model with applications to feline infectious peritonitis and tuberculosis T2 - Applied Mathematics and Computation TI - Global stability for an epidemic model with applications to feline infectious peritonitis and tuberculosis UR - ://WOS:000332402400044 VL - 230 ID - 5461 ER - TY - CHAP A2 - Arimura, H. A2 - Nuraini, N. AB - This paper deals with the mathematical analysis of the spread of tuberculosis with vaccination in a two-strain model. The vaccination reproduction ratio (R-rs.) and equilibria quantities for the models are determined and stability of the solution is analyzed. We prove that if the vaccination reproduction ratio R-rs < 1 the disease free equilibrium is locally and asymptotically stable on the nonnegative Pliant and if R-rs > I of the other equilibria is locally and asymptotically stable. At the end of this study, the numerical computation presented and it shows that vaccination and treatment capable to reduce the number of exposed and infected compartments. AD - [Nainggolan, J.; Supian, S.; Supriatna, A. K.; Anggriani, N.] Univ Padjadjaran, Dept Math, Jatinangor, Indonesia. Nainggolan, J (reprint author), Univ Padjadjaran, Dept Math, Jatinangor, Indonesia. jonn_cesil@yahoo.co.id AN - WOS:000342294800014 AU - Nainggolan, J. AU - Supian, S. AU - Supriatna, A. K. AU - Anggriani, N. CY - Melville DO - 10.1063/1.4866536 KW - Tuberculosis model vaccination drug resistant stability the vaccination reproduction ratio LA - English N1 - ISI Document Delivery No.: BB2TJ Times Cited: 0 Cited Reference Count: 8 Nainggolan, J. Supian, S. Supriatna, A. K. Anggriani, N. Symomath 2013 Proceedings Paper Symposium on Biomathematics (Symomath) Oct 27-29, 2013 Inst Teknologi Bandung, Bandung, INDONESIA Ctr Math Modelling & Simulat, Inst Res & Commun Serv, Indonesian Biomathemat Soc 2 huntington quadrangle, ste 1no1, melville, ny 11747-4501 usa 0094-243x PB - Amer Inst Physics PY - 2014 SN - 978-0-7354-1219-4 SP - 70-73 ST - Mathematical Model of Tuberculosis Transmission in A Two-Strain with Vaccination T2 - Symposium on Biomathematics T3 - AIP Conference Proceedings TI - Mathematical Model of Tuberculosis Transmission in A Two-Strain with Vaccination UR - ://WOS:000342294800014 http://aip.scitation.org/doi/abs/10.1063/1.4866536 VL - 1587 ID - 5488 ER - TY - JOUR AB - This paper presents a model of tuberculosis (TB) transmission with vaccination by explicitely considering the total number of recovered individuals, either from natural recovery or due to vaccination. This research needs to be studied because of the treatment of TB has not yet to control TB globally. Based on this continuous model, the TB control is formulated and solved as an optimal control theory problem, indicating how an optimal control term in the population to reduce the number of individuals with active TB. The method used by the numerical analysis. Control model on treatment to reduce actively infected individual populations. The end of this study determined numerically solution of optimal control model of TB treatment approach Principle Pontryagin Maximum by using C# programming. AU - Nainggolan, J. AU - Supian, Sudradjat AU - Supriatna, A. K. AU - Anggriani, N. AU - Detiatrimargini DA - // DO - 10.1166/asl.2014.5281 IS - 1 PY - 2014 SP - 51-55 ST - Optimal Control Solution of a Tuberculosis Transmission Model with Recurrent Infection and Vaccination Using C# Programming T2 - Advanced Science Letters TI - Optimal Control Solution of a Tuberculosis Transmission Model with Recurrent Infection and Vaccination Using C# Programming UR - http://www.ingentaconnect.com/content/asp/asl/2014/00000020/00000001/art00011 https://doi.org/10.1166/asl.2014.5281 VL - 20 ID - 4928 ER - TY - JOUR AB - To achieve the post-2015 global tuberculosis target of 90% reduction in tuberculosis incidence by 2035, the present rate of decline must accelerate. Among factors that hinder tuberculosis control, malnutrition and diabetes are key challenges. We review available data to describe the complex relationship between tuberculosis, diabetes, and nutritional status. Additionally, we review past trends, present burden, and available future global projections for diabetes, overweight and obesity, as well as undernutrition and food insecurity. Using a mathematical model, we estimate the potential effect of these factors on tuberculosis burden up to 2035. Great potential exists for reduction of worldwide tuberculosis burden by combination of improved prevention and care of diabetes with reduction of undernutrition. To achieve this combination will require joint efforts and strong cross-programme links, enabling synergistic effects of public health policies that promote good nutrition and optimum clinical care for tuberculosis and diabetes. AU - Odone, Anna AU - Houben, Rein M. G. J. AU - White, Richard G. AU - Lönnroth, Knut DO - 10.1016/S2213-8587(14)70164-0 IS - 9 L1 - file:///C:/Users/James/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Odone et al. - 2014 - The effect of diabetes and undernutrition trends on reaching 2035 global tuberculosis targets.pdf PY - 2014 SP - 754-764 ST - The effect of diabetes and undernutrition trends on reaching 2035 global tuberculosis targets T2 - The Lancet Diabetes & Endocrinology TI - The effect of diabetes and undernutrition trends on reaching 2035 global tuberculosis targets UR - http://www.ncbi.nlm.nih.gov/pubmed/25194888 http://linkinghub.elsevier.com/retrieve/pii/S2213858714701640 VL - 2 ID - 3310 ER - TY - JOUR AB - A stochastic model for the spread of tuberculosis is proposed taking into account the reproduction and seasonal immigration of individuals. The system of difference equations majorating the system of equations for mathematical expectations of sizes of considered cohorts of individuals is studied. Conditions for the parameters of the model are obtained so that under those conditions the sizes of cohorts of a afflicted individuals do not exceed the given mean level. The results of numerical experiments are presented for the study of dynamics of mean sizes of cohorts of individuals subject to parameters of immigration in inflow. AD - [Pertsev, Nikolay V.; Leonenko, Vasiliy N.] Sobolev Inst Math, Novosibirsk, Russia. Pertsev, NV (reprint author), Sobolev Inst Math, Novosibirsk, Russia. AN - WOS:000343882200003 AU - Pertsev, N. V. AU - Leonenko, V. N. DA - Oct DO - 10.1515/rnam-2014-0023 IS - 5 J2 - Russ. J. Numer. Anal. Math. Model KW - Stochastic recurrence equations mathematical modelling Monte-Carlo methods epidemiology tuberculosis chain-binomial model hiv-infection Engineering Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: AR9GW Times Cited: 0 Cited Reference Count: 8 Pertsev, Nikolay V. Leonenko, Vasiliy N. Leonenko, Vasiliy/E-8752-2013 Siberian Branch of the RAS [47] The work was partly supported by the Interdisciplinary Integration Project No. 47 of the Siberian Branch of the RAS (2012-2014). 0 1 2 Walter de gruyter gmbh Berlin 1569-3988 PY - 2014 SN - 0927-6467 SP - 285-295 ST - Analysis of a stochastic model for the spread of tuberculosis with regard to reproduction and seasonal immigration of individuals T2 - Russian Journal of Numerical Analysis and Mathematical Modelling TI - Analysis of a stochastic model for the spread of tuberculosis with regard to reproduction and seasonal immigration of individuals UR - ://WOS:000343882200003 VL - 29 ID - 5391 ER - TY - JOUR AB - There is a large body of literature describing molecular level interactions between Mycobacterium tuberculosis (Mtb) and macrophages. Macrophages initiate a range of anti-bacterial mechanisms in response to infection, and Mtb is capable of surviving and circumventing many of these responses. We apply a computational approach to ask: what are the effects on the cellular level of these opposing interactions? The model considers the interplay between bacterial killing and the pathogen's interference with macrophage function. The results reveal an oscillating balance between host and pathogen, but the balance is transient and varies in length, indicating that stochasticity in the bacterial population or host response could contribute to the diverse incubation periods observed in exposed individuals. The model captures host and strain variation and gives new insight into host-pathogen compatibility and co-evolution. AD - Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, SE-58185 Linkoping, Sweden. Electronic address: epienaar@umich.edu. Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, SE-58185 Linkoping, Sweden. AN - 24112967 AU - Pienaar, E. AU - Lerm, M. DA - Feb 07 DO - 10.1016/j.jtbi.2013.09.029 DP - NLM ET - 2013/10/12 J2 - Journal of theoretical biology KW - Colony Count, Microbial *Host-Pathogen Interactions/immunology Humans Immunity Macrophages/immunology/*microbiology/*pathology Microbial Viability *Models, Biological Mycobacterium tuberculosis/growth & development/pathogenicity/*physiology Tuberculosis/microbiology/pathology Virulence 6kDa early secreted antigenic target. Esat-6 IFN-gamma release assay Igra Individual-based model Macrophage function Mtb Mycobacterium tuberculosis Rns Ros Tb Tst Tuberculosis Variable disease outcomes reactive nitrogen species reactive oxygen species tuberculin skin test LA - eng N1 - 1095-8541 Pienaar, Elsje Lerm, Maria Journal Article Research Support, Non-U.S. Gov't England J Theor Biol. 2014 Feb 7;342:23-32. doi: 10.1016/j.jtbi.2013.09.029. Epub 2013 Oct 7. PY - 2014 SN - 0022-5193 SP - 23-32 ST - A mathematical model of the initial interaction between Mycobacterium tuberculosis and macrophages T2 - J Theor Biol TI - A mathematical model of the initial interaction between Mycobacterium tuberculosis and macrophages VL - 342 ID - 1684 ER - TY - JOUR AD - [Pierotti, F.; Trieste, L.; Turchetti, G.] Scuola Super Sant Anna, Pisa, Italy. AN - WOS:000346917301534 AU - Pierotti, F. AU - Trieste, L. AU - Turchetti, G. DA - Nov IS - 7 J2 - Value Health KW - Business & Economics Health Care Sciences & Services LA - English M3 - Meeting Abstract N1 - ISI Document Delivery No.: AX4QT Times Cited: 0 Cited Reference Count: 0 Pierotti, F. Trieste, L. Turchetti, G. 0 1 2 Elsevier science inc New york 1524-4733 PY - 2014 SN - 1098-3015 SP - A551-A551 ST - DIFFERENT STRATEGIES FOR LATENT TB ASSESSMENT IN PATIENTS UNDERGOING ANTI-TNF TREATMENT: AN ECONOMIC MODEL T2 - Value in Health TI - DIFFERENT STRATEGIES FOR LATENT TB ASSESSMENT IN PATIENTS UNDERGOING ANTI-TNF TREATMENT: AN ECONOMIC MODEL UR - ://WOS:000346917301534 VL - 17 ID - 5380 ER - TY - JOUR AB - In this paper we study a model for HIV and TB coinfection. We consider the integer order and the fractional order versions of the model. Let alpha is an element of [0.78, 1.0] be the order of the fractional derivative, then the integer order model is obtained for alpha = 1.0. The model includes vertical transmission for HIV and treatment for both diseases. We compute the reproduction number of the integer order model and HIV and TB submodels, and the stability of the disease free equilibrium. We sketch the bifurcation diagrams of the integer order model, for variation of the average number of sexual partners per person and per unit time, and the tuberculosis transmission rate. We analyze numerical results of the fractional order model for different values of alpha, including alpha = 1. The results show distinct types of transients, for variation of alpha. Moreover, we speculate, from observation of the numerical results, that the order of the fractional derivative may behave as a bifurcation parameter for the model. We conclude that the dynamics of the integer and the fractional order versions of the model are very rich and that together these versions may provide a better understanding of the dynamics of HIV and TB coinfection. (C) 2014 Elsevier Inc. All rights reserved. AD - [Pinto, Carla M. A.] Polytech Porto, Sch Engn, P-4200072 Oporto, Portugal. [Carvalho, Ana R. M.] Univ Porto, Fac Sci, P-4440452 Oporto, Portugal. Pinto, CMA (reprint author), Polytech Porto, Sch Engn, Rua Dr Antonio Bernardino de Almeida 431, P-4200072 Oporto, Portugal. cap@isep.ipp.pt; up200802541@fc.up.pt AN - WOS:000340563000004 AU - Pinto, C. M. A. AU - Carvalho, A. R. M. DA - Sep DO - 10.1016/j.amc.2014.05.061 J2 - Appl. Math. Comput. KW - HIV Tuberculosis (TB) Coinfection Integer model Fractional model Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: AN4MV Times Cited: 10 Cited Reference Count: 25 Pinto, Carla M. A. Carvalho, Ana R. M. Pinto, Carla/0000-0002-0729-1133 Fundacao Gulbenkian, through Premio Gulbenkian de Apoio a Investigacao; Polytechnic of Porto, through the PAPRE Programa de Apoio a Publicacao em Revistas Cientificas de Elevada Qualidade; European Regional Development Fund through the program COMPETE; Portuguese Government through the FCT - Fundacao para a Ciencia e a Tecnologia [PEst-C/MAT/UI0144/2013] Authors wish to thank Fundacao Gulbenkian, through Premio Gulbenkian de Apoio a Investigacao 2003, and the Polytechnic of Porto, through the PAPRE Programa de Apoio a Publicacao em Revistas Cientificas de Elevada Qualidade for financial support. The authors were partially funded by the European Regional Development Fund through the program COMPETE and by the Portuguese Government through the FCT - Fundacao para a Ciencia e a Tecnologia under the project PEst-C/MAT/UI0144/2013. 10 0 9 Elsevier science inc New york 1873-5649 PY - 2014 SN - 0096-3003 SP - 36-46 ST - New findings on the dynamics of HIV and TB coinfection models T2 - Applied Mathematics and Computation TI - New findings on the dynamics of HIV and TB coinfection models UR - ://WOS:000340563000004 VL - 242 ID - 5404 ER - TY - CHAP A2 - Baleanu, D. A2 - Machado, J. A. T. AB - In this paper we study a fractional order model for HIV and TB coinfection. We consider vertical transmission for HIV and treatment for both diseases. We analyze numerical results of the proposed model for different values of the order of the fractional derivative. The results are in agreement with the integer order model and reveal that we can extend the dynamical evolution up to new types of transients. AD - [Pinto, Carla M. A.] Univ Porto, Sch Engn, Polytech Porto, Ctr Math, Rua Dr Antonio Bernardino de Almeida,431, P-4200072 Oporto, Portugal. [Pinto, Carla M. A.] GECAD Knowledge Engn & Decis Support Res Ctr, P-4200072 Oporto, Portugal. [Carvalho, Ana R. M.] Univ Porto, Fac Sci, P-4440452 Oporto, Portugal. Pinto, CMA (reprint author), Univ Porto, Sch Engn, Polytech Porto, Ctr Math, Rua Dr Antonio Bernardino de Almeida,431, P-4200072 Oporto, Portugal. cap@isep.ipp.pt; up200802541@fc.up.pt AN - WOS:000411493600014 AU - Pinto, C. M. A. AU - Carvalho, A. R. M. CY - New York KW - HIV Tuberculosis (TB) fractional order model coinfection LA - English N1 - ISI Document Delivery No.: BI3WT Times Cited: 0 Cited Reference Count: 24 Pinto, Carla M. A. Carvalho, Ana R. M. Icfda Proceedings Paper International Conference on Fractional Differentiation and its Applications (ICFDA) Jun 23-25, 2014 Catania, ITALY Univ Studi Catania, Home Ind & Bldg Automat Syst, Schneider Elect, IEEE Italian Chapters, IEEE Instrumentat & Measurement Soc, Nucl & Plasma Sci Soc, IEEE Control Syst Soc, Circuits & Syst Soc Fundacao Gulbenkian, through Premio Gulbenkian de Apoio a Investigacao; Polytechnic of Porto, through the PAPRE Programa de Apoio a Publicacao em Revistas Cient ificas de Elevada Qualidade Authors which to thank Fundacao Gulbenkian, through Premio Gulbenkian de Apoio a Investigacao 2003, and the Polytechnic of Porto, through the PAPRE Programa de Apoio a Publicacao em Revistas Cient ificas de Elevada Qualidade for financial support. 345 e 47th st, new york, ny 10017 usa 2471-612x PB - Ieee PY - 2014 SN - 978-1-4799-2591-9 ST - Fractional dynamics of a model for HIV and TB coinfection T2 - 2014 International Conference on Fractional Differentiation and Its Applications T3 - International Conference on Fractional Differentiation and Its Applications TI - Fractional dynamics of a model for HIV and TB coinfection UR - ://WOS:000411493600014 ID - 5499 ER - TY - JOUR AB - OBJECTIVES: Reliable estimates of the joint burden of HIV and tuberculosis epidemics are crucial to planning strategic global and national tuberculosis responses. Prior to the Global Tuberculosis Report 2013, the Global Tuberculosis Programme (GTB) released estimates for tuberculosis-HIV incidence at the global level only. Neither GTB nor United Nations Programme on HIV/AIDS (UNAIDS) published country specific estimates for tuberculosis-HIV mortality. We used a regression approach that combined all available data from GTB and UNAIDS in order to estimate tuberculosis-HIV incidence and mortality at country level. METHODS: A regression method was devised to relate CD4 dynamics (based on national Spectrum files) to an increased relative risk (RR) of tuberculosis disease. The objective function is based on least squares and incorporates all available country-level estimates of tuberculosis-HIV incidence. Global regression parameters, obtained from averaging results over countries with population survey estimates for tuberculosis-HIV burden, were applied to countries with no survey tuberculosis-HIV incidence estimates. RESULTS: The method produced results that are in reasonably close agreement with existing GTB estimates for global tuberculosis-HIV burden. It estimated that tuberculosis-HIV accounts for 12.6% of global tuberculosis incidence, 21.3% of all tuberculosis deaths, and 20% of all HIV deaths as estimated by the Spectrum AIDS Impact Module (AIM). Regional estimates show the highest absolute incidence burden in East and Southeast Asia, and the highest per capita burden in sub-Saharan Africa, where between 12.5% (Central sub-Saharan Africa) and 60.6% (Southern sub-Saharan Africa) of all tuberculosis disease occurs in people living with HIV (PLWH). Tuberculosis mortality follows a similar pattern, except that a disproportionate percentage of global tuberculosis deaths (12.1%) relative to global incidence (8.7%) occurred in Southern sub-Saharan Africa. CONCLUSION: The disaggregation of tuberculosis incidence using a regression method on RR of tuberculosis disease and all available data on HIV burden (from UNAIDS) and tuberculosis-HIV testing (survey, sentinel and routine surveillance data) produces results that closely match GTB estimates for 2011. The tuberculosis-HIV incidence and mortality results were published in the Global Tuberculosis Report 2013. Several limitations of and potential improvements to the process are suggested. AD - aFutures Institute, Glastonbury, Connecticut, 06033, USA bGlobal TB Programme, World Health Organization, 20 avenue Appia, 1211 Geneva 27, Switzerland cHealth Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, S1 4DA, UK dTB Modelling Group, TB Centre, London School of Hygiene and Tropical Medicine, UK. *Philippe Glaziou, Peter J. Dodd and Richard White contributed equally to the writing of this article. AN - 25406751 AU - Pretorius, C. AU - Glaziou, P. AU - Dodd, P. J. AU - White, R. AU - Houben, R. C2 - PMC4247264 DA - Nov DO - 10.1097/qad.0000000000000484 DP - NLM ET - 2014/11/20 J2 - AIDS (London, England) KW - *Epidemiologic Methods Global Health HIV Infections/*complications/*epidemiology Humans Incidence Regression Analysis Survival Analysis Time Factors Tuberculosis/*epidemiology/*mortality LA - eng N1 - 1473-5571 Pretorius, Carel Glaziou, Philippe Dodd, Peter J White, Richard Houben, Rein 001/World Health Organization/International MR/J005088/1/Medical Research Council/United Kingdom Journal Article Research Support, Non-U.S. Gov't England AIDS. 2014 Nov;28 Suppl 4:S477-87. doi: 10.1097/QAD.0000000000000484. PY - 2014 SN - 0269-9370 SP - S477-87 ST - Using the TIME model in Spectrum to estimate tuberculosis-HIV incidence and mortality T2 - Aids TI - Using the TIME model in Spectrum to estimate tuberculosis-HIV incidence and mortality VL - 28 Suppl 4 ID - 1855 ER - TY - JOUR AB - OBJECTIVE(S): Many countries are considering expanding HIV treatment following recent findings emphasizing the effects of antiretroviral therapy (ART) on reducing HIV transmission in addition to already established survival benefits. Given the close interaction of tuberculosis (TB) and HIV epidemics, ART expansion could have important ramifications for TB burden. Previous studies suggest a wide range of possible TB impacts following ART expansion. We used three independently developed TB-HIV models to estimate the TB-related impact of expanding ART in South Africa. DESIGN: We considered two dimensions of ART expansion--improving coverage of pre-ART and ART services, and expanding CD4-based ART eligibility criteria (from CD4 <350 to CD4 <500 or all HIV-positive). METHODS: Three independent mathematical models were calibrated to the same data pertaining to the South African HIV-TB epidemic, and used to assess standardized ART policy changes. Key TB impact indicators were projected from 2014 to 2033. RESULTS: Compared with current eligibility and coverage, cumulative TB incidence was projected to decline by 6-30% over the period 2014-2033 if ART eligibility were expanded to all HIV positive individuals, and by 28-37% if effective ART coverage were additionally increased to 80%. Overall, expanding ART was estimated to avert one TB case for each 10-13 additional person-years of ART. All models showed that TB incidence and mortality reductions would grow over time, but would stabilize towards the end of the projection period. CONCLUSION: ART expansion could substantially reduce TB incidence and mortality in South Africa and could provide a platform for collaborative HIV-TB programs to effectively halt HIV-associated TB. AD - aFutures Institute, Glastonbury, Connecticut bCenter for Health Decision Science, Harvard School of Public Health cDepartment of Global Health and Population, Harvard School of Public Health dDivision of Global Health Equity, Brigham and Women's Hospital eDepartment of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA fMRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology gDepartment of Infectious Disease Epidemiology, Imperial College London hDepartment of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. *Carel Pretorius and Nicolas A. Menzies contributed equally to the writing of this article. AN - 24468944 AU - Pretorius, C. AU - Menzies, N. A. AU - Chindelevitch, L. AU - Cohen, T. AU - Cori, A. AU - Eaton, J. W. AU - Fraser, C. AU - Gopalappa, C. AU - Hallett, T. B. AU - Salomon, J. A. AU - Stover, J. AU - White, R. G. AU - Dodd, P. J. DA - Jan DO - 10.1097/qad.0000000000000085 DP - NLM ET - 2014/01/29 J2 - AIDS (London, England) KW - Anti-Retroviral Agents/*administration & dosage Antitubercular Agents/*administration & dosage CD4 Lymphocyte Count Drug Therapy, Combination/methods HIV Infections/complications/*drug therapy/*epidemiology/transmission Health Policy Humans Incidence Models, Theoretical Secondary Prevention/methods South Africa/epidemiology Survival Analysis Treatment Outcome Tuberculosis/complications/*drug therapy/*epidemiology Viral Load LA - eng N1 - 1473-5571 Pretorius, Carel Menzies, Nicolas A Chindelevitch, Leonid Cohen, Ted Cori, Anne Eaton, Jeffrey W Fraser, Christophe Gopalappa, Chaitra Hallett, Timothy B Salomon, Joshua A Stover, John White, Richard G Dodd, Peter J MR/K010174/1/Medical Research Council/United Kingdom G0802414/Medical Research Council/United Kingdom MR/J005088/1/Medical Research Council/United Kingdom Journal Article Research Support, Non-U.S. Gov't England AIDS. 2014 Jan;28 Suppl 1:S25-34. doi: 10.1097/QAD.0000000000000085. PY - 2014 SN - 0269-9370 SP - S25-34 ST - The potential effects of changing HIV treatment policy on tuberculosis outcomes in South Africa: results from three tuberculosis-HIV transmission models T2 - Aids TI - The potential effects of changing HIV treatment policy on tuberculosis outcomes in South Africa: results from three tuberculosis-HIV transmission models VL - 28 Suppl 1 ID - 1609 ER - TY - JOUR AB - Despite the availability of effective treatment, tuberculosis (TB) remains a major global cause of mortality. Multidrug-resistant tuberculosis (MDR-TB) is a form of TB that is resistant to at least two drugs used for the treatment of TB, and originally is developed when a case of drug-susceptible TB is improperly or incompletely treated. This work is concerned with a mathematical model to evaluate the effect of MDR-TB on TB epidemic and its control. The model assessing the transmission dynamics of both drug-sensitive and drug-resistant TB includes slow TB (cases that result from endogenous reactivation of susceptible and resistant latent infections). We identify the steady states of the model to analyse their stability. We establish threshold conditions for possible scenarios: elimination of sensitive and resistant strains and coexistence of both. We find that the effective reproductive number is composed of two critical values, relative reproductive number for drug-sensitive and drug-resistant strains. Our results imply that the potential for the spreading of the drug-resistant strain should be evaluated within the context of several others factors. We have also found that even the considerably less fit drug-resistant strains can lead to a high MDR-TB incidence, because the treatment is less effective against them. AD - Univ Sao Paulo, Fac Med, Disciplina Informat Med, BR-05405000 Sao Paulo, Brazil LIM01 HCFMUSP, BR-05405000 Sao Paulo, Brazil Univ Estadual Campinas, IMECC, DMA, Campinas, SP, Brazil Univ Turin, Dipartimento Matemat Giuseppe Peano, I-10123 Turin, Italy AN - WOS:000332763800013 AU - Raimundo, S. M. AU - Yang, H. M. AU - Venturino, E. DA - Aug DO - 10.3934/rnbe.2014.11.971 IS - 4 J2 - Math Biosci Eng KW - mdr-tb drug resistance treatment mathematical models equilibria mycobacterium-tuberculosis exogenous reinfection infection model emergence transmission dynamics disease hiv evolution L1 - internal-pdf://0768538237/2014_mbe_raimundo.pdf LA - English N1 - Ac8dr Times Cited:5 Cited References Count:46 PY - 2014 SN - 1547-1063 SP - 971-993 ST - Theoretical Assessment of the Relative Incidences of Sensitive and Resistant Tuberculosis Epidemic in Presence of Drug Treatment T2 - Mathematical Biosciences and Engineering TI - Theoretical Assessment of the Relative Incidences of Sensitive and Resistant Tuberculosis Epidemic in Presence of Drug Treatment UR - ://WOS:000332763800013 VL - 11 ID - 4905 ER - TY - CHAP A2 - Ibrahim, H. A2 - Zulkepli, J. A2 - Aziz, N. A2 - Ahmad, N. A2 - Rahman, S. A. AB - In this work, Vaccination (V), Susceptible (S), infected (I), and Recovered (R) (VSIR) model for transmission of Tuberculosis in North Sumatera is modified. An exposed class is adopted to VSIR model so called VSEIR to determine the probability of people who infectious before infected. This model is written in ordinary differential equation (ODEs) in live classes. Determination the equilibrium point and stability analysis of the model is discussed to determine the dynamic behaviour of systems. A simulation is also discussed to see the suitable model to North Sumatera data The simulation of VSEIR model indicates Tuberculosis has not endemic in North Sumatera AD - [Rangkuti, Yulita M.; Sinaga, Marlina S.; Marpaung, F.] Univ Negeri Medan UNIMED, Fac Math & Nat Sci, Dept Math, Medan 20221, Sumatera Utara, Indonesia. [Side, Syafruddin] Univ Negen Malcasar UNM, Fac Math & Nat Sci, Dept Math, Sulawesi Selatan 90245, Indonesia. Rangkuti, YM (reprint author), Univ Negeri Medan UNIMED, Fac Math & Nat Sci, Dept Math, Medan 20221, Sumatera Utara, Indonesia. AN - WOS:000346073300030 AU - Rangkuti, Y. M. AU - Sinaga, M. S. AU - Marpaung, F. AU - Side, S. CY - Melville DO - 10.1063/1.4903584 KW - VSEIR model Stability analysis equilibrium analysis Tuberculois LA - English N1 - ISI Document Delivery No.: BB7WT Times Cited: 1 Cited Reference Count: 7 Rangkuti, Yulita M. Sinaga, Marlina S. Marpaung, F. Side, Syafruddin Icoqsia 2014 Proceedings Paper 3rd International Conference on Quantitative Sciences and Its Applications (ICOQSIA) Aug 12-14, 2014 Kedah, MALAYSIA Unive Utara Malaysia, Sch Quantitat Sci side, syafruddin/0000-0002-5111-7220 Dircktorat Jenderal Pcndidikan Tinggi (DIKTI) Indonesia [062/UN33.8/LL/2014] We gratefully acknowledge, the financial support received from Dircktorat Jenderal Pcndidikan Tinggi (DIKTI) Indonesia with no. 062/UN33.8/LL/2014. 2 huntington quadrangle, ste 1no1, melville, ny 11747-4501 usa 0094-243x PB - Amer Inst Physics PY - 2014 SN - 978-0-7354-1274-3 SP - 201-208 ST - A VSEIR Model for Transmission of Tuberculosis (TB) Disease in North Sumatera, Indonesia T2 - International Conference on Quantitative Sciences and Its Applications T3 - AIP Conference Proceedings TI - A VSEIR Model for Transmission of Tuberculosis (TB) Disease in North Sumatera, Indonesia UR - ://WOS:000346073300030 VL - 1635 ID - 5483 ER - TY - JOUR AB - We propose and analyze an optimal control problem where the control system is a mathematical model for tuberculosis that considers reinfection. The control functions represent the fraction of early latent and persistent latent individuals that are treated. Our aim was to study how these control measures should be implemented, for a certain time period, in order to reduce the number of active infected individuals, while minimizing the interventions implementation costs. The optimal intervention is compared along different epidemiological scenarios, by varying the transmission coefficient. The impact of variation of the risk of reinfection, as a result of acquired immunity to a previous infection for treated individuals on the optimal controls and associated solutions, is analyzed. A cost-effectiveness analysis is done, to compare the application of each one of the control measures, separately or in combination. AD - Department of Mathematics and Center of Mathematics and Applications, New University of Lisbon, 2829-516, Caparica, Portugal, pcpr@fct.unl.pt. AN - 25245395 AU - Rodrigues, P. AU - Silva, C. J. AU - Torres, D. F. DA - Oct DO - 10.1007/s11538-014-0028-6 DP - NLM ET - 2014/09/24 IS - 10 J2 - Bulletin of mathematical biology KW - Cost-Benefit Analysis/statistics & numerical data Humans Infection Control/*economics/methods Latent Tuberculosis/economics/prevention & control/transmission Mathematical Concepts Models, Economic Tuberculosis/economics/*prevention & control/transmission LA - eng N1 - 1522-9602 Rodrigues, Paula Silva, Cristiana J Torres, Delfim F M Journal Article Research Support, Non-U.S. Gov't United States Bull Math Biol. 2014 Oct;76(10):2627-45. doi: 10.1007/s11538-014-0028-6. Epub 2014 Sep 23. PY - 2014 SN - 0092-8240 SP - 2627-45 ST - Cost-effectiveness analysis of optimal control measures for tuberculosis T2 - Bull Math Biol TI - Cost-effectiveness analysis of optimal control measures for tuberculosis VL - 76 ID - 1900 ER - TY - JOUR AB - BACKGROUND: India has announced a goal of universal access to quality tuberculosis (TB) diagnosis and treatment. A number of novel diagnostics could help meet this important goal. The rollout of one such diagnostic, Xpert MTB/RIF (Xpert) is being considered, but if Xpert is used mainly for people with HIV or high risk of multidrug-resistant TB (MDR-TB) in the public sector, population-level impact may be limited. METHODS AND FINDINGS: We developed a model of TB transmission, care-seeking behavior, and diagnostic/treatment practices in India and explored the impact of six different rollout strategies. Providing Xpert to 40% of public-sector patients with HIV or prior TB treatment (similar to current national strategy) reduced TB incidence by 0.2% (95% uncertainty range [UR]: -1.4%, 1.7%) and MDR-TB incidence by 2.4% (95% UR: -5.2%, 9.1%) relative to existing practice but required 2,500 additional MDR-TB treatments and 60 four-module GeneXpert systems at maximum capacity. Further including 20% of unselected symptomatic individuals in the public sector required 700 systems and reduced incidence by 2.1% (95% UR: 0.5%, 3.9%); a similar approach involving qualified private providers (providers who have received at least some training in allopathic or non-allopathic medicine) reduced incidence by 6.0% (95% UR: 3.9%, 7.9%) with similar resource outlay, but only if high treatment success was assured. Engaging 20% of all private-sector providers (qualified and informal [providers with no formal medical training]) had the greatest impact (14.1% reduction, 95% UR: 10.6%, 16.9%), but required >2,200 systems and reliable treatment referral. Improving referrals from informal providers for smear-based diagnosis in the public sector (without Xpert rollout) had substantially greater impact (6.3% reduction) than Xpert scale-up within the public sector. These findings are subject to substantial uncertainty regarding private-sector treatment patterns, patient care-seeking behavior, symptoms, and infectiousness over time; these uncertainties should be addressed by future research. CONCLUSIONS: The impact of new diagnostics for TB control in India depends on implementation within the complex, fragmented health-care system. Transformative strategies will require private/informal-sector engagement, adequate referral systems, improved treatment quality, and substantial resources. Please see later in the article for the Editors' Summary. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America. Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America. Indian School of Business, Hyderabad, India. Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada; McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada. Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America. Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada; McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada; Montreal Chest Institute, McGill University Health Centre, Montreal, Quebec, Canada. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America; Center for Tuberculosis Research, Johns Hopkins University, Baltimore, Maryland, United States of America. AN - 25025235 AU - Salje, H. AU - Andrews, J. R. AU - Deo, S. AU - Satyanarayana, S. AU - Sun, A. Y. AU - Pai, M. AU - Dowdy, D. W. C2 - PMC4098913 DA - Jul DO - 10.1371/journal.pmed.1001674 DP - NLM ET - 2014/07/16 IS - 7 J2 - PLoS medicine KW - Humans India/epidemiology Models, Theoretical Tuberculosis, Multidrug-Resistant/*diagnosis/epidemiology/*transmission Tuberculosis, Pulmonary/*diagnosis/epidemiology/*transmission L1 - internal-pdf://3116842897/Salje-2014-The importance of implementation st.pdf LA - eng N1 - 1549-1676 Salje, Henrik Andrews, Jason R Deo, Sarang Satyanarayana, Srinath Sun, Amanda Y Pai, Madhukar Dowdy, David W MOP 123291/Canadian Institutes of Health Research/Canada Journal Article Research Support, Non-U.S. Gov't United States PLoS Med. 2014 Jul 15;11(7):e1001674. doi: 10.1371/journal.pmed.1001674. eCollection 2014 Jul. PY - 2014 SN - 1549-1277 SP - e1001674 ST - The importance of implementation strategy in scaling up Xpert MTB/RIF for diagnosis of tuberculosis in the Indian health-care system: a transmission model T2 - PLoS Med TI - The importance of implementation strategy in scaling up Xpert MTB/RIF for diagnosis of tuberculosis in the Indian health-care system: a transmission model UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4098913/pdf/pmed.1001674.pdf VL - 11 ID - 2904 ER - TY - JOUR AB - This paper describes a method for incorporating a diffusion field modeling oxygen usage and dispersion in a multi-scale model of Mycobacterium tuberculosis (Mtb) infection mediated granuloma formation. We implemented this method over a floating-point field to model oxygen dynamics in host tissue during chronic phase response and Mtb persistence. The method avoids the requirement of satisfying the Courant-Friedrichs-Lewy (CFL) condition, which is necessary in implementing the explicit version of the finite-difference method, but imposes an impractical bound on the time step. Instead, diffusion is modeled by a matrix-based, steady state approximate solution to the diffusion equation. Presented in figure 1 is the evolution of the diffusion profiles of a containment granuloma over time. AN - 25569958 AU - Sershen, C. L. AU - Plimpton, S. J. AU - May, E. E. DO - 10.1109/embc.2014.6943590 DP - NLM ET - 2015/01/09 J2 - Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference KW - Diffusion Granuloma/metabolism/*microbiology Host-Pathogen Interactions Humans Models, Biological Mycobacterium tuberculosis/*physiology Oxygen/*metabolism Systems Biology Tuberculosis/metabolism/*microbiology LA - eng N1 - Sershen, Cheryl L Plimpton, Steven J May, Elebeoba E K25HL075105/HL/NHLBI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. United States Conf Proc IEEE Eng Med Biol Soc. 2014;2014:306-9. doi: 10.1109/EMBC.2014.6943590. PY - 2014 SN - 1557-170X (Print) 1557-170x SP - 306-9 ST - A method for modeling oxygen diffusion in an agent-based model with application to host-pathogen infection T2 - Conf Proc IEEE Eng Med Biol Soc TI - A method for modeling oxygen diffusion in an agent-based model with application to host-pathogen infection VL - 2014 ID - 1496 ER - TY - JOUR AB - In this paper we propose a system of ordinary differential equations to model the interaction among non-infected macrophages, infected macrophages, T cells and Mtb bacilli. Model analysis reveals the "existence of infection-free equilibrium and the endemically infected equilibrium. And we analyze the dynamics of this model, characterize the optimal controls related to drug therapy, and discuss a quadratic control and a linear control. The quadratic control allows for a weaker treatment that more effectively than the linear control. AD - [Shi, Ruiqing; Li, Yang] Shanxi Normal Univ, Sch Math & Comp Sci, Linfen 041004, Peoples R China. [Tang, Sanyi] Shaanxi Normal Univ, Coll Math & Informat Sci, Xian 710062, Peoples R China. Shi, RQ (reprint author), Shanxi Normal Univ, Sch Math & Comp Sci, Linfen 041004, Peoples R China. shirq1979@163.com; 769050041@qq.com; sanyitang219@hotmail.com AN - WOS:000336890900014 AU - Shi, R. Q. AU - Li, Y. AU - Tang, S. Y. DA - Apr IS - 2 J2 - Taiwan. J. Math. KW - mycobacterium-tuberculosis infection chemotherapy cancer cells Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: AI5FN Times Cited: 1 Cited Reference Count: 24 Shi, Ruiqing Li, Yang Tang, Sanyi Postdoctoral Science Foundation of China [2011M501428]; Young Science Funds of Shanxi [2013021002-2]; National Natural Science Foundation of China [11171199, 81161120403] The first author is supported by Postdoctoral Science Foundation of China (No. 2011M501428) and Young Science Funds of Shanxi (No. 2013021002-2). The third author is supported by National Natural Science Foundation of China (No. 11171199, 81161120403). 1 0 6 Mathematical soc rep china Hsinchu 2224-6851 PY - 2014 SN - 1027-5487 SP - 575-597 ST - A MATHEMATICAL MODEL WITH OPTIMAL CONTROLS FOR CELLULAR IMMUNOLOGY OF TUBERCULOSIS T2 - Taiwanese Journal of Mathematics TI - A MATHEMATICAL MODEL WITH OPTIMAL CONTROLS FOR CELLULAR IMMUNOLOGY OF TUBERCULOSIS UR - ://WOS:000336890900014 VL - 18 ID - 5448 ER - TY - JOUR AB - BACKGROUND: New first-line drug regimens for treatment of tuberculosis (TB) are in clinical trials: emergence of resistance is a key concern. Because population-level data on resistance cannot be collected in advance, epidemiological models are important tools for understanding the drivers and dynamics of resistance before novel drug regimens are launched. METHODS: We developed a transmission model of TB after launch of a new drug regimen, defining drug-resistant TB (DR-TB) as resistance to the new regimen. The model is characterized by (1) the probability of acquiring resistance during treatment, (2) the transmission fitness of DR-TB relative to drug-susceptible TB (DS-TB), and (3) the probability of treatment success for DR-TB versus DS-TB. We evaluate the effect of each factor on future DR-TB prevalence, defined as the proportion of incident TB that is drug-resistant. RESULTS: Probability of acquired resistance was the strongest predictor of the DR-TB proportion in the first 5 years after the launch of a new drug regimen. Over a longer term, however, the DR-TB proportion was driven by the resistant population's transmission fitness and treatment success rates. Regardless of uncertainty in acquisition probability and transmission fitness, high levels (>10%) of drug resistance were unlikely to emerge within 50 years if, among all cases of TB that were detected, 85% of those with DR-TB could be appropriately diagnosed as such and then successfully treated. CONCLUSIONS: Short-term surveillance cannot predict long-term drug resistance trends after launch of novel first-line TB regimens. Ensuring high treatment success of drug-resistant TB through early diagnosis and appropriate second-line therapy can mitigate many epidemiological uncertainties and may substantially slow the emergence of drug-resistant TB. AD - Department of Epidemiology , Johns Hopkins School of Public Health , Baltimore, Maryland. TB Modelling Group, Department of Infectious Disease Epidemiology , London School of Hygiene and Tropical Medicine , United Kingdom. Division of Global Health Equity , Brigham and Women's Hospital , Boston, Massachusetts. Amsterdam Institute for Global Health and Development , The Netherlands. AN - 25734143 AU - Shrestha, S. AU - Knight, G. M. AU - Fofana, M. AU - Cohen, T. AU - White, R. G. AU - Cobelens, F. AU - Dowdy, D. W. C2 - PMC4281792 DA - Sep DO - 10.1093/ofid/ofu073 DP - NLM ET - 2015/03/04 IS - 2 J2 - Open forum infectious diseases KW - Mycobacterium tuberculosis TB drug regimens TB drug resistance TB mathematical model L1 - internal-pdf://0781244049/Shrestha-2014-Drivers and trajectories of resi.pdf LA - eng N1 - Shrestha, Sourya Knight, Gwenan M Fofana, Mariam Cohen, Ted White, Richard G Cobelens, Frank Dowdy, David W MR/J005088/1/Medical Research Council/United Kingdom T32 GM007309/GM/NIGMS NIH HHS/United States Journal Article United States Open Forum Infect Dis. 2014 Aug 30;1(2):ofu073. doi: 10.1093/ofid/ofu073. eCollection 2014 Sep. PY - 2014 SN - 2328-8957 (Print) 2328-8957 SP - ofu073 ST - Drivers and trajectories of resistance to new first-line drug regimens for tuberculosis T2 - Open Forum Infect Dis TI - Drivers and trajectories of resistance to new first-line drug regimens for tuberculosis UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281792/pdf/ofu073.pdf VL - 1 ID - 1445 ER - TY - JOUR AB - Tuberculosis (TB) and human immunodeficiency virus (HIV) can be considered a deadly human syndemic. In this paper, we formulate a model for TB and HIV transmission dynamics. The model considers both TB and acquired immune deficiency syndrome (AIDS) treatment for individuals with only one of the two infectious diseases or both. The basic reproduction number and equilibrium points are determined and stability is analyzed. Through simulations, we show that TB treatment for individuals with only TB infection reduces the number of individuals that become coinfected with TB and HIV/AIDS and reduces the diseases (TB and AIDS) induced deaths. Analogously, the treatment of individuals with only AIDS also reduces the number of coinfected individuals. Further, TB treatment for coinfected individuals in the active and latent stage of TB disease implies a decrease of the number of individuals that passes from HIV-positive to AIDS. AD - Univ Aveiro, Dept Math, Ctr Res & Dev Math & Applicat CIDMA, P-3810193 Aveiro, Portugal AN - WOS:000339180200001 AU - Silva, C. J. AU - Torres, D. F. M. DO - Artn 248407 10.1155/2014/248407 J2 - J Appl Math KW - tuberculosis transmission coinfection dynamics LA - English N1 - Al5nj Times Cited:1 Cited References Count:16 PY - 2014 SN - 1110-757x ST - Modeling TB-HIV Syndemic and Treatment T2 - Journal of Applied Mathematics TI - Modeling TB-HIV Syndemic and Treatment UR - ://WOS:000339180200001 ID - 4906 ER - TY - JOUR AB - BACKGROUND: Multi-drug resistant tuberculosis (MDR TB) is a major health challenge in India that is gaining increasing public attention, but the implications of India's evolving MDR TB epidemic are poorly understood. As India's MDR TB epidemic is transitioning from a treatment-generated to transmission-generated epidemic, we sought to evaluate the potential effectiveness of the following two disease control strategies on reducing the prevalence of MDR TB: a) improving treatment of non-MDR TB; b) shortening the infectious period between the activation of MDR TB and initiation of effective MDR treatment. METHODS AND FINDINGS: We developed a dynamic transmission microsimulation model of TB in India. The model followed individuals by age, sex, TB status, drug resistance status, and treatment status and was calibrated to Indian demographic and epidemiologic TB time trends. The main effectiveness measure was reduction in the average prevalence reduction of MDR TB over the ten years after control strategy implementation. We find that improving non-MDR cure rates to avoid generating new MDR cases will provide substantial non-MDR TB benefits but will become less effective in reducing MDR TB prevalence over time because more cases will occur from direct transmission--by 2015, the model estimates 42% of new MDR cases are transmission-generated and this proportion continues to rise over time, assuming equal transmissibility of MDR and drug-susceptible TB. Strategies that disrupt MDR transmission by shortening the time between MDR activation and treatment are projected to provide greater reductions in MDR prevalence compared with improving non-MDR treatment quality: implementing MDR diagnostic improvements in 2017 is expected to reduce MDR prevalence by 39%, compared with 11% reduction from improving non-MDR treatment quality. CONCLUSIONS: As transmission-generated MDR TB becomes a larger driver of the MDR TB epidemic in India, rapid and accurate MDR TB diagnosis and treatment will become increasingly effective in reducing MDR TB cases compared to non-MDR TB treatment improvements. AD - Department of Management Science and Engineering, Stanford University Stanford, Stanford, California, United States of America. Division of General Medical Disciplines, Department of Medicine, Stanford University Stanford, Stanford, California, United States of America; Center for Health Policy and the Center for Primary Care and Outcomes Research, Stanford University, Stanford, California, United States of America. Center for Health Policy and the Center for Primary Care and Outcomes Research, Stanford University, Stanford, California, United States of America. AN - 24608234 AU - Suen, S. C. AU - Bendavid, E. AU - Goldhaber-Fiebert, J. D. C2 - 3946521 DO - 10.1371/journal.pone.0089822 ET - 2014/03/13 IS - 3 J2 - PloS one KW - Adolescent Adult Aged Antitubercular Agents/therapeutic use Child Child, Preschool Female Humans India/epidemiology Male Middle Aged Tuberculosis, Multidrug-Resistant/*drug therapy/*epidemiology Young Adult L1 - internal-pdf://4088996213/Suen-2014-Disease control implications of Indi.pdf M3 - Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. N1 - Suen, Sze-Chuan Bendavid, Eran Goldhaber-Fiebert, Jeremy D eng K01 AG037593/AG/NIA NIH HHS/ K01 AG037593-01A1/AG/NIA NIH HHS/ K01-AI084582/AI/NIAID NIH HHS/ P30 AG017253/AG/NIA NIH HHS/ PLoS One. 2014 Mar 7;9(3):e89822. doi: 10.1371/journal.pone.0089822. eCollection 2014. PY - 2014 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e89822 ST - Disease control implications of India's changing multi-drug resistant tuberculosis epidemic T2 - PLoS One TI - Disease control implications of India's changing multi-drug resistant tuberculosis epidemic UR - http://www.ncbi.nlm.nih.gov/pubmed/24608234 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946521/pdf/pone.0089822.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946521/pdf/pone.0089822.pdf VL - 9 ID - 4650 ER - TY - JOUR AB - We present a mathematical model to simulate tuberculosis (TB) transmission in highly endemic regions of the Asia-Pacific, where epidemiology does not appear to be primarily driven by HIV-coinfection. The ten-compartment deterministic model captures many of the observed phenomena important to disease dynamics, including partial and temporary vaccine efficacy, declining risk of active disease following infection, the possibility of reinfection both during the infection latent period and after treatment, multidrug resistant TB (MDR-TB) and de novo resistance during treatment. We found that the model could not be calibrated to the estimated incidence rate without allowing for reinfection during latency, and that even in the presence of a moderate fitness cost and a lower value of R0, MDR-TB becomes the dominant strain at equilibrium. Of the modifiable programmatic parameters, the rate of detection and treatment commencement was the most important determinant of disease rates with each respective strain, while vaccination rates were less important. Improved treatment of drug-susceptible TB did not result in decreased rates of MDR-TB through prevention of de novo resistance, but rather resulted in a modest increase in MDR-TB through strain replacement. This was due to the considerably greater relative contribution of community transmission to MDR-TB incidence, by comparison to de novo amplification of resistance in previously susceptible strains. AD - Burnet Institute, 89 Commercial Road, Melbourne 3004, Australia; Victorian Infectious Diseases Service at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia; Department of Medicine (Royal Melbourne Hospital/Western Hospital), University of Melbourne, Victoria 3010, Australia. Electronic address: jtrauer@burnet.edu.au. Victorian Infectious Diseases Service at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia; Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia. Electronic address: justin.denholm@mh.org.au. Burnet Institute, 89 Commercial Road, Melbourne 3004, Australia; Victorian Infectious Diseases Service at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia; Department of Medicine (Royal Melbourne Hospital/Western Hospital), University of Melbourne, Victoria 3010, Australia. Electronic address: emma.mcbryde@mh.org.au. AN - 24878110 AU - Trauer, J. M. AU - Denholm, J. T. AU - McBryde, E. S. DA - Oct 07 DO - 10.1016/j.jtbi.2014.05.023 DP - NLM ET - 2014/06/01 J2 - Journal of theoretical biology KW - Antitubercular Agents/therapeutic use Asia/epidemiology Humans Models, Theoretical Pacific Islands/epidemiology Tuberculosis/drug therapy/*epidemiology BCG vaccine Disease Transmission-Infectious Latent tuberculosis Models-Theoretical Tuberculosis-Multidrug Resistant L1 - internal-pdf://1717568844/1-s2.0-S0022519314002963-main.pdf LA - eng N1 - 1095-8541 Trauer, James M Denholm, Justin T McBryde, Emma S Journal Article Research Support, Non-U.S. Gov't England J Theor Biol. 2014 Oct 7;358:74-84. doi: 10.1016/j.jtbi.2014.05.023. Epub 2014 May 27. PY - 2014 SN - 0022-5193 SP - 74-84 ST - Construction of a mathematical model for tuberculosis transmission in highly endemic regions of the Asia-Pacific T2 - J Theor Biol TI - Construction of a mathematical model for tuberculosis transmission in highly endemic regions of the Asia-Pacific VL - 358 ID - 2008 ER - TY - JOUR AD - [Triplette, M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Dowdy, D.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Chaisson, L. H.; Merrifield, C.; Rudoy, I.; Cattamanchi, A.; Nahid, P.; Davis, J. L.] Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA USA. [Higashi, J.] TB Control Unit, San Francisco, CA USA. matt.triplette@ucsf.edu AN - WOS:000209838201714 AU - Triplette, M. AU - Dowdy, D. AU - Chaisson, L. H. AU - Higashi, J. AU - Merrifield, C. AU - Rudoy, I. AU - Cattamanchi, A. AU - Nahid, P. AU - Davis, J. L. J2 - Am. J. Respir. Crit. Care Med. KW - General & Internal Medicine Respiratory System LA - English M3 - Meeting Abstract N1 - ISI Document Delivery No.: V45TF Times Cited: 0 Cited Reference Count: 0 Triplette, M. Dowdy, D. Chaisson, L. H. Higashi, J. Merrifield, C. Rudoy, I. Cattamanchi, A. Nahid, P. Davis, J. L. 0 Amer thoracic soc New york 1535-4970 PY - 2014 SN - 1073-449X SP - 1 ST - Modeling The Clinical And Economic Impact Of Xpert Mtb/rif For Ambulatory Evaluation Of Pulmonary Tuberculosis In The United States T2 - American Journal of Respiratory and Critical Care Medicine TI - Modeling The Clinical And Economic Impact Of Xpert Mtb/rif For Ambulatory Evaluation Of Pulmonary Tuberculosis In The United States UR - ://WOS:000209838201714 VL - 189 ID - 5500 ER - TY - JOUR AB - BACKGROUND: To inform the choice of an appropriate screening and diagnostic algorithm for tuberculosis (TB) screening initiatives in different epidemiological settings, we compare algorithms composed of currently available methods. METHODS: Of twelve algorithms composed of screening for symptoms (prolonged cough or any TB symptom) and/or chest radiography abnormalities, and either sputum-smear microscopy (SSM) or Xpert MTB/RIF (XP) as confirmatory test we model algorithm outcomes and summarize the yield, number needed to screen (NNS) and positive predictive value (PPV) for different levels of TB prevalence. RESULTS: Screening for prolonged cough has low yield, 22% if confirmatory testing is by SSM and 32% if XP, and a high NNS, exceeding 1000 if TB prevalence is ://WOS:000341014300009 VL - 7 ID - 5422 ER - TY - JOUR AD - TB Modelling Group, TB Centre and CMMID Faculty of Epidemiology & Population Health London School of Hygiene & Tropical Medicine London, UK.richard.white@lshtm.ac.uk. TB Modelling Group, TB Centre and CMMID Faculty of Epidemiology & Population Health London School of Hygiene & Tropical Medicine London, UK. AN - 24670689 AU - White, R. G. AU - Houben, R. M. DA - Apr DO - 10.5588/ijtld.14.0156 DP - NLM ET - 2014/03/29 IS - 4 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - *Communicable Disease Control *Emigrants and Immigrants *Emigration and Immigration Humans Latent Tuberculosis/*prevention & control *Models, Theoretical *Residence Characteristics LA - eng N1 - 1815-7920 White, Richard G Houben, Rein M G J Comment Editorial Research Support, Non-U.S. Gov't France Int J Tuberc Lung Dis. 2014 Apr;18(4):380. doi: 10.5588/ijtld.14.0156. PY - 2014 SN - 1027-3719 SP - 380 ST - Towards elimination in industrialised countries: expanding diagnosis and treatment of LTBI among immigrants T2 - Int J Tuberc Lung Dis TI - Towards elimination in industrialised countries: expanding diagnosis and treatment of LTBI among immigrants VL - 18 ID - 1562 ER - TY - JOUR AB - The basic reproduction number is a key parameter in mathematical modelling of transmissible diseases. From the stability analysis of the disease free equilibrium, by applying Routh-Hurwitz criteria, a threshold is obtained, which is called the basic reproduction number. However, the application of spectral radius theory on the next generation matrix provides a different expression for the basic reproduction number, that is, the square root of the previously found formula. If the spectral radius of the next generation matrix is defined as the geometric mean of partial reproduction numbers, however the product of these partial numbers is the basic reproduction number, then both methods provide the same expression. In order to show this statement, dengue transmission modelling incorporating or not the transovarian transmission is considered as a case study. Also tuberculosis transmission and sexually transmitted infection modellings are taken as further examples. AD - UNICAMP - IMECC - DMA, Praca Sergio Buarque de Holanda, 651, CEP: 13083-859 Campinas, SP, Brazil. Electronic address: hyunyang@ime.unicamp.br. AN - 25305542 AU - Yang, H. M. DA - Dec DO - 10.1016/j.biosystems.2014.10.002 DP - NLM ET - 2014/10/12 J2 - Bio Systems KW - Basic Reproduction Number/*statistics & numerical data Communicable Diseases/epidemiology/transmission Dengue/*epidemiology/*transmission Disease Transmission, Infectious/statistics & numerical data Humans *Models, Theoretical Compartmental modelling Geometric mean Partial reproduction numbers Routh-Hurwitz criteria Stability analysis of disease free equilibrium LA - eng N1 - 1872-8324 Yang, Hyun Mo Journal Article Ireland Biosystems. 2014 Dec;126:52-75. doi: 10.1016/j.biosystems.2014.10.002. Epub 2014 Oct 8. PY - 2014 SN - 0303-2647 SP - 52-75 ST - The basic reproduction number obtained from Jacobian and next generation matrices - A case study of dengue transmission modelling T2 - Biosystems TI - The basic reproduction number obtained from Jacobian and next generation matrices - A case study of dengue transmission modelling VL - 126 ID - 1880 ER - TY - JOUR AB - Tuberculosis (TB) is an infectious disease with a peculiar feature: Upon infection with the causative agent, Mycobacterium Tuberculosis (MTB), most hosts enter a latent state during which no transmission of MTB to new hosts occurs. Only a fraction of latently infected hosts develop TB disease and can potentially infect new hosts. At first glance, this seems like a waste of transmission potential and therefore an evolutionary suboptimal strategy for MTB. It might be that the human immune response keeps MTB in check in most hosts, thereby preventing it from achieving its evolutionary optimum. Another possible explanation is that long latency and progression to disease in only a fraction of hosts are evolutionary beneficial to MTB by allowing it to persist better in small host populations. Given that MTB has co-evolved with human hosts for millenia or longer, it likely encountered small host populations for a large share of its evolutionary history and had to evolve strategies of persistence. Here, we use a mathematical model to show that indeed, MTB persistence is optimal for an intermediate duration of latency and level of activation. The predicted optimal level of activation is above the observed value, suggesting that human co-evolution has lead to host immunity, which keeps MTB below its evolutionary optimum. AD - Institute of Bioinformatics, University of Georgia, Athens, Georgia, United States of America. Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia, United States of America. AN - 25157958 AU - Zheng, N. AU - Whalen, C. C. AU - Handel, A. C2 - PMC4144956 DO - 10.1371/journal.pone.0105721 DP - NLM ET - 2014/08/27 IS - 8 J2 - PloS one KW - Biological Evolution Humans Latent Tuberculosis/immunology/*microbiology/mortality Models, Biological Mycobacterium tuberculosis/immunology/*physiology Stochastic Processes LA - eng N1 - 1932-6203 Zheng, Nibiao Whalen, Christopher C Handel, Andreas TW006900/TW/FIC NIH HHS/United States Journal Article Research Support, N.I.H., Extramural United States PLoS One. 2014 Aug 26;9(8):e105721. doi: 10.1371/journal.pone.0105721. eCollection 2014. PY - 2014 SN - 1932-6203 SP - e105721 ST - Modeling the potential impact of host population survival on the evolution of M. tuberculosis latency T2 - PLoS One TI - Modeling the potential impact of host population survival on the evolution of M. tuberculosis latency VL - 9 ID - 1931 ER - TY - JOUR AB - INTRODUCTION: The field of diagnostics for active tuberculosis (TB) is rapidly developing. TB diagnostic modeling can help to inform policy makers and support complicated decisions on diagnostic strategy, with important budgetary implications. Demand for TB diagnostic modeling is likely to increase, and an evaluation of current practice is important. We aimed to systematically review all studies employing mathematical modeling to evaluate cost-effectiveness or epidemiological impact of novel diagnostic strategies for active TB. METHODS: Pubmed, personal libraries and reference lists were searched to identify eligible papers. We extracted data on a wide variety of model structure, parameter choices, sensitivity analyses and study conclusions, which were discussed during a meeting of content experts. RESULTS & DISCUSSION: From 5619 records a total of 36 papers were included in the analysis. Sixteen papers included population impact/transmission modeling, 5 were health systems models, and 24 included estimates of cost-effectiveness. Transmission and health systems models included specific structure to explore the importance of the diagnostic pathway (n = 4), key determinants of diagnostic delay (n = 5), operational context (n = 5), and the pre-diagnostic infectious period (n = 1). The majority of models implemented sensitivity analysis, although only 18 studies described multi-way sensitivity analysis of more than 2 parameters simultaneously. Among the models used to make cost-effectiveness estimates, most frequent diagnostic assays studied included Xpert MTB/RIF (n = 7), and alternative nucleic acid amplification tests (NAATs) (n = 4). Most (n = 16) of the cost-effectiveness models compared new assays to an existing baseline and generated an incremental cost-effectiveness ratio (ICER). CONCLUSION: Although models have addressed a small number of important issues, many decisions regarding implementation of TB diagnostics are being made without the full benefits of insight from mathematical models. Further models are needed that address a wider array of diagnostic and epidemiological settings, that explore the inherent uncertainty of models and that include additional epidemiological data on transmission implications of false-negative diagnosis and the pre-diagnostic period. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America. TB Modelling Group, TB Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom. Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America. AN - 25340701 AU - Zwerling, A. AU - White, R. G. AU - Vassall, A. AU - Cohen, T. AU - Dowdy, D. W. AU - Houben, R. M. C2 - PMC4207742 DO - 10.1371/journal.pone.0110558 DP - NLM ET - 2014/10/24 IS - 10 J2 - PloS one KW - Cost-Benefit Analysis *Diagnostic Techniques and Procedures/economics Health Planning Guidelines Humans Models, Theoretical *Practice Patterns, Physicians' Tuberculosis, Pulmonary/*diagnosis Uncertainty LA - eng N1 - 1932-6203 Zwerling, Alice White, Richard G Vassall, Anna Cohen, Ted Dowdy, David W Houben, Rein M G J G0802414/Medical Research Council/United Kingdom MR/J005088/1/Medical Research Council/United Kingdom Canadian Institutes of Health Research/Canada Medical Research Council/United Kingdom Journal Article Meta-Analysis Research Support, Non-U.S. Gov't Review United States PLoS One. 2014 Oct 23;9(10):e110558. doi: 10.1371/journal.pone.0110558. eCollection 2014. PY - 2014 SN - 1932-6203 SP - e110558 ST - Modeling of novel diagnostic strategies for active tuberculosis - a systematic review: current practices and recommendations T2 - PLoS One TI - Modeling of novel diagnostic strategies for active tuberculosis - a systematic review: current practices and recommendations VL - 9 ID - 1874 ER - TY - JOUR AB - Late 19th century epidemics of tuberculosis (TB) in Western Canadian First Nations resulted in peak TB mortality rates more than six times the highest rates recorded in Europe. Using a mathematical modeling approach and historical TB mortality time series, we investigate potential causes of high TB mortality and rapid epidemic decline in First Nations from 1885 to 1940. We explore two potential causes of dramatic epidemic dynamics observed in this setting: first, we explore effects of famine prior to 1900 on both TB and population dynamics. Malnutrition is recognized as an individual-level risk factor for TB progression and mortality; its population-level effects on TB epidemics have not been explored previously. Second, we explore effects of heterogeneity in susceptibility to TB in two ways: modeling heterogeneity in susceptibility to infection, and heterogeneity in risk of developing disease once infected. Our results indicate that models lacking famine-related changes in TB parameters or heterogeneity result in an implausibly poor fit to both the TB mortality time series and census data; the inclusion of these features allows for the characteristic decline and rise in population observed in First Nations during this time period and confers improved fits to TB mortality data. AD - [Ackley, Sarah F.; Liu, Fengchen; Porco, Travis C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Ackley, Sarah F.; Porco, Travis C.] Univ Calif San Francisco, Proctor Fdn, San Francisco, CA 94143 USA. [Pepperell, Caitlin S.] Univ Wisconsin, Dept Med Infect Dis, Madison, WI 53706 USA. [Pepperell, Caitlin S.] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. Pepperell, CS (reprint author), Univ Wisconsin, Dept Med Infect Dis, Madison, WI 53706 USA. cspepper@medicine.wisc.edu AN - WOS:000364327000001 AU - Ackley, S. F. AU - Liu, F. C. AU - Porco, T. C. AU - Pepperell, C. S. C7 - e1237 DA - Sep DO - 10.7717/peerj.1237 J2 - PeerJ KW - Tuberculosis Mathematical model First Nations Malnutrition Genetic predisposition to disease Epidemics intrinsic transmission dynamics mycobacterium-tuberculosis hiv-infection united-states impact communities population mortality decline disease Science & Technology - Other Topics LA - English M3 - Article N1 - ISI Document Delivery No.: CV5QV Times Cited: 1 Cited Reference Count: 54 Ackley, Sarah F. Liu, Fengchen Porco, Travis C. Pepperell, Caitlin S. Pepperell, Caitlin/0000-0002-6324-1333 Models of Infectious Disease Agent Study (MIDAS) grant from the National Institute of General Medical Sciences at the National Institutes of Health [U01GM087728] This study was funded by a Models of Infectious Disease Agent Study (MIDAS) grant from the National Institute of General Medical Sciences at the National Institutes of Health to the University of California, San Francisco (Award Number U01GM087728). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 1 4 Peerj inc London PY - 2015 SN - 2167-8359 SP - 21 ST - Modeling historical tuberculosis epidemics among Canadian First Nations: effects of malnutrition and genetic variation T2 - PeerJ TI - Modeling historical tuberculosis epidemics among Canadian First Nations: effects of malnutrition and genetic variation UR - ://WOS:000364327000001 VL - 3 ID - 5266 ER - TY - JOUR AU - Agusto, F. B. AU - Cook, J. AU - Shelton, P. D. AU - Wickers, M. G. C7 - 828461 DO - 10.1155/2015/828461 L1 - internal-pdf://3354717783/Agusto-2015-Mathematical Model of MDR-TB and X.pdf PY - 2015 SP - 21 ST - Mathematical Model of MDR-TB and XDR-TB with Isolation and Lost to Follow-Up T2 - Abstract and Applied Analysis TI - Mathematical Model of MDR-TB and XDR-TB with Isolation and Lost to Follow-Up UR - http://dx.doi.org/10.1155/2015/828461 http://downloads.hindawi.com/journals/aaa/2015/828461.pdf VL - 2015 ID - 4932 ER - TY - JOUR AB - Tuberculosis is a major source of global mortality caused by infection, partly because of a tremendous ongoing burden of undiagnosed disease. Improved diagnostic technology may play an increasingly crucial part in global efforts to end tuberculosis, but the ability of diagnostic tests to curb tuberculosis transmission is dependent on multiple factors, including the time taken by a patient to seek health care, the patient's symptoms, and the patterns of transmission before diagnosis. Novel diagnostic assays for tuberculosis have conventionally been evaluated on the basis of characteristics such as sensitivity and specificity, using assumptions that probably overestimate the impact of diagnostic tests on transmission. We argue for a shift in focus to the evaluation of such tests' incremental value, defining outcomes that reflect each test's purpose (for example, transmissions averted) and comparing systems with the test against those without, in terms of those outcomes. Incremental value can also be measured in units of outcome per incremental unit of resource (for example, money or human capacity). Using a novel, simplified model of tuberculosis transmission that addresses some of the limitations of earlier tuberculosis diagnostic models, we demonstrate that the incremental value of any novel test depends not just on its accuracy, but also on elements such as patient behaviour, tuberculosis natural history and health systems. By integrating these factors into a single unified framework, we advance an approach to the evaluation of new diagnostic tests for tuberculosis that considers the incremental value at the population level and demonstrates how additional data could inform more-effective implementation of tuberculosis diagnostic tests under various conditions. AD - MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, Norfolk Place, London W2 1PG, UK. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. AN - 26633767 AU - Arinaminpathy, N. AU - Dowdy, D. DA - Dec 03 DO - 10.1038/nature16045 DP - NLM ET - 2015/12/04 IS - 7580 J2 - Nature KW - Cost-Benefit Analysis *Diagnostic Tests, Routine/economics/standards Health Resources/economics Humans Sensitivity and Specificity Time Factors Tuberculosis/*diagnosis/*prevention & control/transmission LA - eng N1 - 1476-4687 Arinaminpathy, Nimalan Dowdy, David MR/K010174/1/Medical Research Council/United Kingdom Journal Article Research Support, Non-U.S. Gov't England Nature. 2015 Dec 3;528(7580):S60-7. doi: 10.1038/nature16045. PY - 2015 SN - 0028-0836 SP - S60-7 ST - Understanding the incremental value of novel diagnostic tests for tuberculosis T2 - Nature TI - Understanding the incremental value of novel diagnostic tests for tuberculosis VL - 528 ID - 1143 ER - TY - JOUR AB - OBJECTIVE: To estimate tuberculosis (TB) incidence and case detection rate (CDR) using routine TB surveillance data only. METHODS: A mathematical model of the case detection process, representing competition between disease progression and case finding, is proposed. The model describes disease progression as a two-stage process (bacillary and non-bacillary TB), and so relates the proportion of bacillary TB cases on detection to the effectiveness of detection. Thus, given the annual numbers of newly detected TB cases stratified by bacillary status, the model estimates detection rates, incidence and CDR. Routine notification data from eight provinces in Russia, 2000-2011, were used for the study. RESULTS: Subnational level estimates of incidence and CDR were obtained. Incidence estimates varied by two-fold among the provinces; corrected CDR estimates varied by 1.5 times. The trend in the incidence estimates was similar to that in the World Health Organization estimates for the whole of Russia. The change in the trend in WHO CDR estimates in 2008-2009 was not supported by our estimates. CONCLUSION: The general approach that uses multistage models of disease progression and accordingly stratified notification data can be applied in various settings for the routine estimation of incidence and CDR. AD - *Institute for Numerical Mathematics, Russian Academy of Sciences, Moscow, daggerFederal Research Institute for Health Organization and Informatics, Ministry of Health of the Russian Federation, Moscow. *Institute for Numerical Mathematics, Russian Academy of Sciences, Moscow, double daggerLomonosov Moscow State University, Moscow, section signMoscow Institute of Physics and Technology (State University), Moscow. paragraph signMoscow Scientific and Clinical Center for Tuberculosis Control, Moscow Health Department, Moscow, Russia. daggerFederal Research Institute for Health Organization and Informatics, Ministry of Health of the Russian Federation, Moscow. *Institute for Numerical Mathematics, Russian Academy of Sciences, Moscow. AN - 25686136 AU - Avilov, K. K. AU - Romanyukha, A. A. AU - Borisov, S. E. AU - Belilovsky, E. M. AU - Nechaeva, O. B. AU - Karkach, A. S. DA - Mar DO - 10.5588/ijtld.14.0317 DP - NLM ET - 2015/02/17 IS - 3 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Humans Incidence Models, Theoretical Mycobacterium tuberculosis/*isolation & purification Population Surveillance Russia/epidemiology Tuberculosis/diagnosis/*epidemiology LA - eng N1 - 1815-7920 Avilov, K K Romanyukha, A A Borisov, S E Belilovsky, E M Nechaeva, O B Karkach, A S Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. France Int J Tuberc Lung Dis. 2015 Mar;19(3):288-94, i-x. doi: 10.5588/ijtld.14.0317. PY - 2015 SN - 1027-3719 SP - 288-94, i-x ST - An approach to estimating tuberculosis incidence and case detection rate from routine notification data T2 - Int J Tuberc Lung Dis TI - An approach to estimating tuberculosis incidence and case detection rate from routine notification data VL - 19 ID - 1459 ER - TY - JOUR AB - A dynamical model of TB for two age groups that incorporate vaccination of children at birth, behavior change in adult population, treatment of infectious children and adults is formulated and analyzed. Three types of control measures (vaccination, behavior change and anti-TB treatment strategies) are applied with separate rate for children and adults to analyze the solution of the controlled system by using the concept of optimal control theory. It is indicated that vaccination at birth and treatment for both age groups have impact in reducing the value of the reproduction number (R-o) whereas behavior modification does not have any impact on R-o. Pontryagin's Minimum Principle has been used to characterize the optimal level of controls applied on the model. It is shown that the optimal combination strategy of vaccination, behavior change and treatment for the two age groups can help to reduce the disease epidemic with minimum cost of interventions, in shorter possible time. AD - Mizan Teppi Univ, Dept Math, Teppi, Ethiopia Univ Addis Ababa, Dept Math, Addis Ababa, Ethiopia AN - WOS:000380493400002 AU - Aweke, T. D. AU - Kassa, S. M. DO - 10.1007/978-3-319-16121-1_2 LA - English N1 - Bf2rn Times Cited:0 Cited References Count:17 PY - 2015 SP - 15-38 ST - Impacts of Vaccination and Behavior Change in the Optimal Intervention Strategy for Controlling the Transmission of Tuberculosis T2 - Mathematics of Energy and Climate Change TI - Impacts of Vaccination and Behavior Change in the Optimal Intervention Strategy for Controlling the Transmission of Tuberculosis UR - ://WOS:000380493400002 ID - 4890 ER - TY - JOUR AB - Estimation of the true incidence of tuberculosis (TB) is challenging. The approach proposed by Styblo in 1985 is known to be inaccurate in the modern era where there is widespread availability of treatment for TB. This study re-examines the relationship of incidence to prevalence and other disease indicators that can be derived from surveys. We adapt a simple, previously published model that describes the epidemiology of TB in the presence of treatment to investigate a revised ratio-based approach to estimating incidence. We show that, following changes to treatment programmes for TB, the ratio of incidence to prevalence reaches an equilibrium value rapidly; long before other model indicators have stabilized. We also show that this ratio relies on few parameters but is strongly dependent on, and requires knowledge of, the efficacy and timeliness of treatment. AD - School of Public Health and Community Medicine,Faculty of Medicine,University of New South Wales,Sydney,NSW,Australia. Respiratory and Environmental Epidemiology,Woolcock Institute of Medical Research,Sydney,NSW,Australia. AN - 25234177 AU - Begun, M. AU - Newall, A. T. AU - Marks, G. B. AU - Wood, J. G. DA - May DO - 10.1017/s0950268814002428 DP - NLM ET - 2014/09/23 IS - 7 J2 - Epidemiology and infection KW - Antitubercular Agents/therapeutic use Humans Incidence *Models, Theoretical Prevalence Tuberculosis/drug therapy/*epidemiology/microbiology treatment LA - eng N1 - 1469-4409 Begun, M Newall, A T Marks, G B Wood, J G Journal Article Research Support, Non-U.S. Gov't England Epidemiol Infect. 2015 May;143(7):1556-65. doi: 10.1017/S0950268814002428. Epub 2014 Sep 19. PY - 2015 SN - 0950-2688 SP - 1556-65 ST - Revisiting Styblo's law: could mathematical models aid in estimating incidence from prevalence data? T2 - Epidemiol Infect TI - Revisiting Styblo's law: could mathematical models aid in estimating incidence from prevalence data? VL - 143 ID - 1906 ER - TY - JOUR AB - A discrete tuberculosis model with direct progression and treatment of latently infected individuals is presented. The model does not consider the drug-resistant TB, and it assumes that latently infected individuals develop the active disease only because of being endogenous reactive, and a small fraction of infected individuals is assumed to develop the active disease soon after infection. The global stability of a disease-free equilibrium, the persistence of system, and the local stability of endemic equilibrium are discussed. The basic reproductive numbers with different control measures are determined and analyzed, and we give the critical value of probability of successful detection and treatment of infectious individuals. If a treatment only of infectious individuals cannot control TB transmission, the treatment of latent TB individuals should be carried out, and we give the critical value of the probability of treatment of infectious individuals. Numerical simulations are done to demonstrate the complex dynamics of the model. AD - Shaanxi Univ Sci & Technol, Dept Math, Xian 710021, Peoples R China AN - WOS:000355615300002 AU - Cao, H. AU - Tan, H. W. DA - Jun 3 DO - ARTN 165 10.1186/s13662-015-0505-8 J2 - Adv Differ Equ-Ny KW - discrete tb model direct progression treatment strategies basic reproduction number i-s models epidemic model global stability dynamics time sis populations immigration strategies L1 - internal-pdf://0346978294/Cao-2015-The discrete tuberculosis transmissio.pdf LA - English N1 - Cj6ph Times Cited:1 Cited References Count:45 PY - 2015 SN - 1687-1847 ST - The discrete tuberculosis transmission model with treatment of latently infected individuals T2 - Advances in Difference Equations TI - The discrete tuberculosis transmission model with treatment of latently infected individuals UR - ://WOS:000355615300002 https://advancesindifferenceequations.springeropen.com/track/pdf/10.1186/s13662-015-0505-8?site=advancesindifferenceequations.springeropen.com ID - 4908 ER - TY - JOUR AU - Carvalho, Ana AU - Pinto, Carla M.A. DO - 10.1063/1.4912583 IS - 1 PY - 2015 SP - 350005 ST - Dynamics of coinfection of HIV/AIDS and tuberculosis with exogeneous reinfection T2 - AIP Conference Proceedings TI - Dynamics of coinfection of HIV/AIDS and tuberculosis with exogeneous reinfection UR - http://aip.scitation.org/doi/abs/10.1063/1.4912583 VL - 1648 ID - 4927 ER - TY - JOUR AB - Malaria, HIV, and tuberculosis (TB) collectively account for several million deaths each year, with all three ranking among the top ten killers in low-income countries. Despite being caused by very different organisms, malaria, HIV, and TB present a suite of challenges for mathematical modellers that are particularly pronounced in these infections, but represent general problems in infectious disease modelling, and highlight many of the challenges described throughout this issue. Here, we describe some of the unifying challenges that arise in modelling malaria, HIV, and TB, including variation in dynamics within the host, diversity in the pathogen, and heterogeneity in human contact networks and behaviour. Through the lens of these three pathogens, we provide specific examples of the other challenges in this issue and discuss their implications for informing public health efforts. AD - Center for Communicable Disease Dynamics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States. Office of the Director General, World Health Organization, Avenue Appia, 1211 Geneva 27, Switzerland. Department of Zoology, University of Oxford, Oxford OX1 3PS, United Kingdom. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States; Division of Global Health Equity, Brigham & Women's Hospital, Boston, MA 02115, United States. South African Centre for Epidemiological Modelling and Analysis, Stellenbosch, South Africa; Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa. Center for Communicable Disease Dynamics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States. Electronic address: cbuckee@hsph.harvard.edu. AN - 25843394 AU - Childs, L. M. AU - Abuelezam, N. N. AU - Dye, C. AU - Gupta, S. AU - Murray, M. B. AU - Williams, B. G. AU - Buckee, C. O. C2 - PMC4451070 C6 - NIHMS669047 DA - Mar DO - 10.1016/j.epidem.2015.02.002 DP - NLM ET - 2015/04/07 J2 - Epidemics KW - Genetic Variation HIV/genetics HIV Infections/*epidemiology/prevention & control/transmission Host-Pathogen Interactions/genetics Humans Malaria/*epidemiology/prevention & control/transmission Models, Statistical Mycobacterium tuberculosis/genetics Tuberculosis, Pulmonary/*epidemiology/prevention & control/transmission Hiv Malaria Modelling Tuberculosis LA - eng N1 - 1878-0067 Childs, Lauren M Abuelezam, Nadia N Dye, Christopher Gupta, Sunetra Murray, Megan B Williams, Brian G Buckee, Caroline O R01 MH087328/MH/NIMH NIH HHS/United States R01MH087328-03/MH/NIMH NIH HHS/United States AWARDNIAID AI 007433/PHS HHS/United States U54 GM088558/GM/NIGMS NIH HHS/United States U54GM088558/GM/NIGMS NIH HHS/United States T32 AI007433/AI/NIAID NIH HHS/United States 001/World Health Organization/International Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Netherlands Epidemics. 2015 Mar;10:102-7. doi: 10.1016/j.epidem.2015.02.002. Epub 2015 Feb 16. PY - 2015 SN - 1878-0067 SP - 102-7 ST - Modelling challenges in context: lessons from malaria, HIV, and tuberculosis T2 - Epidemics TI - Modelling challenges in context: lessons from malaria, HIV, and tuberculosis VL - 10 ID - 1400 ER - TY - JOUR AB - HIV has fuelled increasing tuberculosis (TB) incidence in sub-Saharan Africa. Better control of TB in this region may be achieved directly through TB programme improvements and indirectly through expanded use of antiretroviral therapy (ART) among those with HIV. We used a mathematical model of TB and HIV in South Africa to examine the potential epidemiological impact in scenarios involving improvements in three dimensions of TB programmes: coverage, diagnosis and treatment effectiveness, as well as expanded ART use through broadened eligibility. We projected the effect of alternative scenarios on TB prevalence, incidence and TB-related mortality over 20 years. Of the three dimensions of TB programme improvement, expanding coverage would produce the greatest reduction in TB burden. Compared with current performance, combined TB programme improvements were projected to decrease TB incidence by 30% over 5 years and 46% over 20 years, and decrease TB-related mortality by 45% over 5 years and 69% over 20 years. Expanded ART eligibility was projected to decrease TB incidence by 22% over 5 years and 45% over 20 years, and TB-related mortality by 22% over 5 years and 50% over 20 years. We found that over a 20-year horizon, TB-specific and HIV-specific programme changes contribute equally to incidence reductions, whereas the TB-specific changes produce a majority of the mortality benefits. An aggressive expansion of ART alongside traditional TB-specific control measures has the potential to greatly reduce TB burden, with the different elements of a combined approach having a synergistic effect in reducing long-term TB incidence and mortality. AD - Yale Univ, Dept Epidemiol Microbial Dis, Sch Publ Hlth, New Haven, CT 06520 USA Harvard Univ, TH Chan Sch Publ Hlth, Ctr Hlth Decis Sci, Boston, MA 02115 USA Harvard Univ, TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA Futures Inst, Glastonbury, CT USA AN - WOS:000353359900030 AU - Chindelevitch, L. AU - Menzies, N. A. AU - Pretorius, C. AU - Stover, J. AU - Salomon, J. A. AU - Cohen, T. DA - May 6 DO - ARTN 20150146 10.1098/rsif.2015.0146 IS - 106 J2 - J R Soc Interface KW - antiretroviral therapy hiv/aids mathematical model sub-saharan africa tuberculosis resistant mycobacterium-tuberculosis human-immunodeficiency-virus short-term risk antiretroviral therapy south-africa multidrug-resistant cost-effectiveness hiv-1-infected patients collaborative analysis pulmonary tuberculosis L1 - internal-pdf://0001235455/Chindelevitch-2015-Evaluating the potential im.pdf LA - English N1 - Cg5tx Times Cited:2 Cited References Count:71 PY - 2015 SN - 1742-5689 ST - Evaluating the potential impact of enhancing HIV treatment and tuberculosis control programmes on the burden of tuberculosis T2 - Journal of the Royal Society Interface TI - Evaluating the potential impact of enhancing HIV treatment and tuberculosis control programmes on the burden of tuberculosis UR - ://WOS:000353359900030 http://rsif.royalsocietypublishing.org/content/royinterface/12/106/20150146.full.pdf VL - 12 ID - 4909 ER - TY - JOUR AB - In this paper, we developed a dynamic model of smoking-tuberculosis (TB) transmission in South Korea, and investigated the effects of control strategies on the number of incidence of TB using optimal control theory. Model parameters regarding TB and smoking are estimated through least-squares fitting to real data. We considered three TB controls (distancing, case-finding, and case-holding) and two smoking controls (distancing and quitting), in order to minimize the number of exposed and infectious individuals and the cost of control. Numerical simulations for the various control strategies highlight that implementing the smoking controls, not with TB controls, can effectively reduce the incidence of TB transmission. AD - Department of Mathematics, Konkuk University, 120 Neungdong-ro, Gwngjin-gu, Seoul 143-701, Republic of Korea. Department of Liberal Arts, College of Engineering, Hongik University, 94 Wausan-ro, Mapo-gu, Seoul 121-791, Republic of Korea. Electronic address: sherwood@hongik.ac.kr. AN - 26025317 AU - Choi, S. AU - Jung, E. AU - Lee, S. M. DA - Sep 07 DO - 10.1016/j.jtbi.2015.05.022 DP - NLM ET - 2015/05/31 J2 - Journal of theoretical biology KW - Case-Control Studies Humans *Models, Theoretical Republic of Korea/epidemiology *Smoking Tuberculosis/epidemiology/*prevention & control Epidemic model Optimal control theory Parameter estimation LA - eng N1 - 1095-8541 Choi, Sunhwa Jung, Eunok Lee, Seok-Min Journal Article Research Support, Non-U.S. Gov't England J Theor Biol. 2015 Sep 7;380:256-70. doi: 10.1016/j.jtbi.2015.05.022. Epub 2015 May 27. PY - 2015 SN - 0022-5193 SP - 256-70 ST - Optimal intervention strategy for prevention tuberculosis using a smoking-tuberculosis model T2 - J Theor Biol TI - Optimal intervention strategy for prevention tuberculosis using a smoking-tuberculosis model VL - 380 ID - 1336 ER - TY - JOUR AB - Although almost a third of the world's population is infected with the bacterial pathogen Mycobacterium tuberculosis, our understanding of the functions of many immune factors involved in fighting infection is limited. Determining the role of the immunosuppressive cytokine IL-10 at the level of the granuloma has proven difficult because of lesional heterogeneity and the limitations of animal models. In this study, we take an in silico approach and, through a series of virtual experiments, we predict several novel roles for IL-10 in tuberculosis granulomas: 1) decreased levels of IL-10 lead to increased numbers of sterile lesions, but at the cost of early increased caseation; 2) small increases in early antimicrobial activity cause this increased lesion sterility; 3) IL-10 produced by activated macrophages is a major mediator of early antimicrobial activity and early host-induced caseation; and 4) increasing levels of infected macrophage derived IL-10 promotes bacterial persistence by limiting the early antimicrobial response and preventing lesion sterilization. Our findings, currently only accessible using an in silico approach, suggest that IL-10 at the individual granuloma scale is a critical regulator of lesion outcome. These predictions suggest IL-10-related mechanisms that could be used as adjunctive therapies during tuberculosis. AD - Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109; Broad Institute of MIT and Harvard, Cambridge, MA 02142; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109; and. Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219. Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109; linderma@umich.edu. AN - 25512604 AU - Cilfone, N. A. AU - Ford, C. B. AU - Marino, S. AU - Mattila, J. T. AU - Gideon, H. P. AU - Flynn, J. L. AU - Kirschner, D. E. AU - Linderman, J. J. C2 - PMC4283220 C6 - NIHMS642951 DA - Jan 15 DO - 10.4049/jimmunol.1400734 DP - NLM ET - 2014/12/17 IS - 2 J2 - Journal of immunology (Baltimore, Md. : 1950) KW - Animals Granuloma/genetics/immunology/microbiology Humans Interleukin-10/genetics/*immunology *Macrophage Activation Macrophages/*immunology Mycobacterium tuberculosis/*immunology Tuberculosis/genetics/*immunology LA - eng N1 - 1550-6606 Cilfone, Nicholas A Ford, Christopher B Marino, Simeone Mattila, Joshua T Gideon, Hannah P Flynn, JoAnne L Kirschner, Denise E Linderman, Jennifer J R01 AI094745/AI/NIAID NIH HHS/United States R01 EB012579/EB/NIBIB NIH HHS/United States R01 HL106804/HL/NHLBI NIH HHS/United States R01 HL110811/HL/NHLBI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States J Immunol. 2015 Jan 15;194(2):664-77. doi: 10.4049/jimmunol.1400734. Epub 2014 Dec 15. PY - 2015 SN - 0022-1767 SP - 664-77 ST - Computational modeling predicts IL-10 control of lesion sterilization by balancing early host immunity-mediated antimicrobial responses with caseation during mycobacterium tuberculosis infection T2 - J Immunol TI - Computational modeling predicts IL-10 control of lesion sterilization by balancing early host immunity-mediated antimicrobial responses with caseation during mycobacterium tuberculosis infection VL - 194 ID - 1523 ER - TY - JOUR AB - Biologically related processes operate across multiple spatiotemporal scales. For computational modeling methodologies to mimic this biological complexity, individual scale models must be linked in ways that allow for dynamic exchange of information across scales. A powerful methodology is to combine a discrete modeling approach, agent-based models (ABMs), with continuum models to form hybrid models. Hybrid multi-scale ABMs have been used to simulate emergent responses of biological systems. Here, we review two aspects of hybrid multi-scale ABMs: linking individual scale models and efficiently solving the resulting model. We discuss the computational choices associated with aspects of linking individual scale models while simultaneously maintaining model tractability. We demonstrate implementations of existing numerical methods in the context of hybrid multi-scale ABMs. Using an example model describing Mycobacterium tuberculosis infection, we show relative computational speeds of various combinations of numerical methods. Efficient linking and solution of hybrid multi-scale ABMs is key to model portability, modularity, and their use in understanding biological phenomena at a systems level. AD - Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA. Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA. AN - 26366228 AU - Cilfone, N. A. AU - Kirschner, D. E. AU - Linderman, J. J. C2 - PMC4564133 C6 - NIHMS699353 DA - Mar DO - 10.1007/s12195-014-0363-6 DP - NLM ET - 2015/09/15 IS - 1 J2 - Cellular and molecular bioengineering KW - Agent-Based Modeling Hybrid Modeling Linking Models Multi-Scale Modeling Numerical Implementation Tuneable Resolution LA - eng N1 - Cilfone, Nicholas A Kirschner, Denise E Linderman, Jennifer J R01 EB012579/EB/NIBIB NIH HHS/United States R01 HL110811/HL/NHLBI NIH HHS/United States Journal Article United States Cell Mol Bioeng. 2015 Mar;8(1):119-136. PY - 2015 SN - 1865-5025 (Print) 1865-5025 SP - 119-136 ST - Strategies for efficient numerical implementation of hybrid multi-scale agent-based models to describe biological systems T2 - Cell Mol Bioeng TI - Strategies for efficient numerical implementation of hybrid multi-scale agent-based models to describe biological systems VL - 8 ID - 1238 ER - TY - JOUR AB - Mathematical modelling can help to explain the nature and dynamics of infection transmissions, as well as support a policy for implementing those strategies that are most likely to bring public health and economic benefits. The paper addresses the application of optimal control strategies in a tuberculosis model. The model consists of a system of ordinary differential equations, which considers reinfection and post-exposure interventions. We propose a multiobjective optimization approach to find optimal control strategies for the minimization of active infectious and persistent latent individuals, as well as the cost associated to the implementation of the control strategies. Optimal control strategies are investigated for different values of the model parameters. The obtained numerical results cover a whole range of the optimal control strategies, providing valuable information about the tuberculosis dynamics and showing the usefulness of the proposed approach. AD - Univ Minho, Algoritmi R&D Ctr, P-4710057 Braga, Portugal Univ Aveiro, Dept Math, Ctr Res & Dev Math & Applicat CIDMA, P-3810193 Aveiro, Portugal AN - WOS:000360246700001 AU - Denysiuk, R. AU - Silva, C. J. AU - Torres, D. F. M. DA - Oct DO - 10.1080/10556788.2014.994704 IS - 5 J2 - Optim Method Softw KW - tuberculosis epidemic model treatment strategies optimal control theory multiobjective optimization exogenous reinfection postexposure interventions disease LA - English N1 - Cp9ws Times Cited:4 Cited References Count:32 PY - 2015 SN - 1055-6788 SP - 893-910 ST - Multiobjective approach to optimal control for a tuberculosis model T2 - Optimization Methods & Software TI - Multiobjective approach to optimal control for a tuberculosis model UR - ://WOS:000360246700001 VL - 30 ID - 4910 ER - TY - JOUR AD - [Fun, W. H.; Wu, D. B.; Cheong, Y. M.; Lee, K. K.] Monash Univ Malaysia, Subang Jaya, Malaysia. [Noordin, Mohamad N.] Natl Publ Hlth Lab, Sungai Buloh, Malaysia. AN - WOS:000354498504108 AU - Fun, W. H. AU - Wu, D. B. AU - Cheong, Y. M. AU - Noordin, N. M. AU - Lee, K. K. DA - May IS - 3 J2 - Value Health KW - Business & Economics Health Care Sciences & Services LA - English M3 - Meeting Abstract N1 - ISI Document Delivery No.: CI1IZ Times Cited: 0 Cited Reference Count: 0 Fun, W. H. Wu, D. B. Cheong, Y. M. Noordin, Mohamad N. Lee, K. K. 0 1 4 Elsevier science inc New york 1524-4733 PY - 2015 SN - 1098-3015 SP - A244-A244 ST - EVALUATION OF ECONOMIC IMPACT OF TUBERCULOSIS CONTROL IN MALAYSIA USING DYNAMIC TRANSMISSION MODEL T2 - Value in Health TI - EVALUATION OF ECONOMIC IMPACT OF TUBERCULOSIS CONTROL IN MALAYSIA USING DYNAMIC TRANSMISSION MODEL UR - ://WOS:000354498504108 VL - 18 ID - 5311 ER - TY - JOUR AB - The WHO recommends integrating interventions to address the devastating TB/HIV co-epidemics in South Africa, yet integration has been poorly implemented and TB/HIV control efforts need strengthening. Identifying infected individuals is particularly difficult in rural settings. We used mathematical modeling to predict the impact of community-based, integrated TB/HIV case finding and additional control strategies on South Africa's TB/HIV epidemics. We developed a model incorporating TB and HIV transmission to evaluate the effectiveness of integrating TB and HIV interventions in rural South Africa over 10 years. We modeled the impact of a novel screening program that integrates case finding for TB and HIV in the community, comparing it to status quo and recommended TB/HIV control strategies, including GeneXpert, MDR-TB treatment decentralization, improved first-line TB treatment cure rate, isoniazid preventive therapy, and expanded ART. Combining recommended interventions averted 27% of expected TB cases (95% CI 18-40%) 18% HIV (95% CI 13-24%), 60% MDR-TB (95% CI 34-83%), 69% XDR-TB (95% CI 34-90%), and 16% TB/HIV deaths (95% CI 12-29). Supplementing these interventions with annual community-based TB/HIV case finding averted a further 17% of TB cases (44% total; 95% CI 31-56%), 5% HIV (23% total; 95% CI 17-29%), 8% MDR-TB (68% total; 95% CI 40-88%), 4% XDR-TB (73% total; 95% CI 38-91%), and 8% TB/HIV deaths (24% total; 95% CI 16-39%). In addition to increasing screening frequency, we found that improving TB symptom questionnaire sensitivity, second-line TB treatment delays, default before initiating TB treatment or ART, and second-line TB drug efficacy were significantly associated with even greater reductions in TB and HIV cases. TB/HIV epidemics in South Africa were most effectively curtailed by simultaneously implementing interventions that integrated community-based TB/HIV control strategies and targeted drug-resistant TB. Strengthening existing TB and HIV treatment programs is needed to further reduce disease incidence. AD - Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, United States of America; Center for Infectious Disease Modeling and Analysis, Yale School of Public Health, New Haven, CT, United States of America. Anderson School of Management, University of California Los Angeles, Los Angeles, CA, United States of America. Department of Medicine, Section of Infectious Diseases, AIDS Program, Yale University School of Medicine, New Haven, CT, United States of America. Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, United States of America; Department of Medicine, Section of Infectious Diseases, AIDS Program, Yale University School of Medicine, New Haven, CT, United States of America. Department of Medicine, Section of Infectious Diseases, AIDS Program, Yale University School of Medicine, New Haven, CT, United States of America; Church of Scotland Hospital, Tugela Ferry, KwaZulu-Natal, South Africa. Department of Biostatistics, Yale University, New Haven, CT, United States of America; Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, United States of America; Program in Computational Biology and Informatics, Yale University, New Haven, CT, United States of America. Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, United States of America; Center for Infectious Disease Modeling and Analysis, Yale School of Public Health, New Haven, CT, United States of America; Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, United States of America; Program in Computational Biology and Informatics, Yale University, New Haven, CT, United States of America. AN - 25938501 AU - Gilbert, J. A. AU - Long, E. F. AU - Brooks, R. P. AU - Friedland, G. H. AU - Moll, A. P. AU - Townsend, J. P. AU - Galvani, A. P. AU - Shenoi, S. V. C2 - PMC4418809 DO - 10.1371/journal.pone.0126267 DP - NLM ET - 2015/05/06 IS - 5 J2 - PloS one KW - Adolescent Adult Anti-HIV Agents/therapeutic use Antitubercular Agents/therapeutic use HIV Infections/*drug therapy/*epidemiology Humans Middle Aged South Africa/epidemiology Tuberculosis/*drug therapy/*epidemiology Young Adult L1 - internal-pdf://1739715361/Gilbert-2015-Integrating Community-Based Inter.pdf LA - eng N1 - 1932-6203 Gilbert, Jennifer A Long, Elisa F Brooks, Ralph P Friedland, Gerald H Moll, Anthony P Townsend, Jeffrey P Galvani, Alison P Shenoi, Sheela V 1K23AI089260/AI/NIAID NIH HHS/United States K23 AI089260/AI/NIAID NIH HHS/United States P30 MH062294/MH/NIMH NIH HHS/United States 5U01GM105627/GM/NIGMS NIH HHS/United States R01DA015612/DA/NIDA NIH HHS/United States R01DA025932/DA/NIDA NIH HHS/United States 1U01GH000524-01/GH/CGH CDC HHS/United States 2U01GM087719/GM/NIGMS NIH HHS/United States R24TW007988/TW/FIC NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S. United States PLoS One. 2015 May 4;10(5):e0126267. doi: 10.1371/journal.pone.0126267. eCollection 2015. PY - 2015 SN - 1932-6203 SP - e0126267 ST - Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa T2 - PLoS One TI - Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418809/pdf/pone.0126267.pdf VL - 10 ID - 1369 ER - TY - JOUR AB - Granulomas play a centric role in tuberculosis (TB) infection progression. Multiple granulomas usually develop within a single host. These granulomas are not synchronized in size or bacteria load, and will follow different trajectories over time. How the fate of individual granulomas influence overall infection outcome at host scale is not understood, although computational models have been developed to predict single granuloma behavior. Here we present a within-host population model that tracks granulomas in two key organs during Mycobacteria tuberculosis (Mtb) infection: lung and lymph nodes (LN). We capture various time courses of TB progression, including latency and reactivation. The model predicts that there is no steady state; rather it is a continuous process of progressing to active disease over differing time periods. This is consistent with recently posed ideas suggesting that latent TB exists as a spectrum of states and not a single state. The model also predicts a dual role for granuloma development in LNs during Mtb infection: in early phases of infection granulomas suppress infection by providing additional antigens to the site of immune priming; however, this induces a more rapid reactivation at later stages by disrupting immune responses. We identify mechanisms that strongly correlate with better host-level outcomes, including elimination of uncontained lung granulomas by inducing low levels of lung tissue damage and inhibition of bacteria dissemination within the lung. AD - 6775 Medical Science Building II, Ann Arbor, MI 48109-5620, United States. changgon@umich.edu. AN - 25811559 AU - Gong, C. AU - Linderman, J. J. AU - Kirschner, D. C2 - PMC4447319 C6 - NIHMS686391 DA - Jun DO - 10.3934/mbe.2015.12.625 DP - NLM ET - 2015/03/27 IS - 3 J2 - Mathematical biosciences and engineering : MBE KW - Computer Simulation Granuloma, Respiratory Tract/*physiopathology Humans Latent Tuberculosis/*physiopathology Lung/*physiopathology *Models, Biological *Population Dynamics Prognosis Tuberculosis, Pulmonary/*physiopathology LA - eng N1 - 1551-0018 Gong, Chang Linderman, Jennifer J Kirschner, Denise R01 EB012579/EB/NIBIB NIH HHS/United States R01 HL106804/HL/NHLBI NIH HHS/United States R01 HL110811/HL/NHLBI NIH HHS/United States R01 HL 110811/HL/NHLBI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural United States Math Biosci Eng. 2015 Jun;12(3):625-42. doi: 10.3934/mbe.2015.12.625. PY - 2015 SN - 1547-1063 SP - 625-42 ST - A population model capturing dynamics of tuberculosis granulomas predicts host infection outcomes T2 - Math Biosci Eng TI - A population model capturing dynamics of tuberculosis granulomas predicts host infection outcomes VL - 12 ID - 1409 ER - TY - JOUR AB - Comprehensive assessment of the effectiveness of contact investigations for tuberculosis (TB) control is still lacking. In this study, we use a computational model, calibrated against notification data from Arkansas during the period 2001-2011, that reproduces independent data on key features of TB transmission and epidemiology. The model estimates that the Arkansas contact investigations program has avoided 18.6% (12.1-25.9%) of TB cases and 23.7% (16.4-30.6%) of TB deaths that would have occurred during 2001-2014 if passive diagnosis alone were implemented. If contacts of sputum smear-negative cases had not been included in the program, the percentage reduction would have been remarkably lower. In addition, we predict that achieving national targets for performance indicators of contact investigation programs has strong potential to further reduce TB transmission and burden. However, contact investigations are expected to have limited effectiveness on avoiding reactivation cases of latent infections over the next 60 years. AD - Fondazione Bruno Kessler, via Sommarive 18, 38123 Povo (TN), Italy; Trento RISE, via Sommarive 18, 38123 Povo (TN), Italy. Electronic address: guzzetta@fbk.eu. Fondazione Bruno Kessler, via Sommarive 18, 38123 Povo (TN), Italy. School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI40109-2029, USA. Arkansas Department of Health, Slot 8, 4815 West Markham Street, Little Rock, AR 72205, USA; University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, USA. University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA. AN - 26051196 AU - Guzzetta, G. AU - Ajelli, M. AU - Yang, Z. AU - Mukasa, L. N. AU - Patil, N. AU - Bates, J. H. AU - Kirschner, D. E. AU - Merler, S. C2 - PMC4522372 C6 - NIHMS697517 DA - Sep 07 DO - 10.1016/j.jtbi.2015.05.031 DP - NLM ET - 2015/06/09 J2 - Journal of theoretical biology KW - Arkansas/epidemiology *Contact Tracing Humans Models, Theoretical Prevalence Tuberculosis/epidemiology/*prevention & control Contact tracing Mathematical model Process assessment (Health Care) LA - eng N1 - 1095-8541 Guzzetta, Giorgio Ajelli, Marco Yang, Zhenhua Mukasa, Leonard N Patil, Naveen Bates, Joseph H Kirschner, Denise E Merler, Stefano R01HL106804/HL/NHLBI NIH HHS/United States R01EB012579/EB/NIBIB NIH HHS/United States R01HL110811/HL/NHLBI NIH HHS/United States R01 HL106804/HL/NHLBI NIH HHS/United States R01 EB012579/EB/NIBIB NIH HHS/United States R01 HL110811/HL/NHLBI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Validation Studies England J Theor Biol. 2015 Sep 7;380:238-46. doi: 10.1016/j.jtbi.2015.05.031. Epub 2015 Jun 5. PY - 2015 SN - 0022-5193 SP - 238-46 ST - Effectiveness of contact investigations for tuberculosis control in Arkansas T2 - J Theor Biol TI - Effectiveness of contact investigations for tuberculosis control in Arkansas VL - 380 ID - 1326 ER - TY - JOUR AB - RATIONALE, AIMS AND OBJECTIVES: Design and implement a concurrent campaign of influenza immunization and tuberculosis (TB) screening for health care workers (HCWs) that can reduce the number of clinic visits for each HCW. METHOD: A discrete-event simulation model was developed to support issues of resource allocation decisions in planning and operations phases. RESULTS: The campaign was compressed to100 days in 2010 and further compressed to 75 days in 2012 and 2013. With more than 5000 HCW arrivals in 2011, 2012 and 2013, the 14-day goal of TB results was achieved for each year and reduced to about 4 days in 2012 and 2013. CONCLUSION: Implementing a concurrent campaign allows less number of visiting clinics and the compressing of campaign length allows earlier immunization. The support of simulation modelling can provide useful evaluations of different configurations. AD - Department of Industrial and Systems Engineering, University of Washington, Seattle, WA, USA. Seattle Children's Hospital, Seattle, WA, USA. Department of Lab Medicine, University of Washington, Seattle, WA, USA. AN - 26009843 AU - Heim, J. A. AU - Huang, H. AU - Zabinsky, Z. B. AU - Dickerson, J. AU - Wellner, M. AU - Astion, M. AU - Cruz, D. AU - Vincent, J. AU - Jack, R. DA - Aug DO - 10.1111/jep.12377 DP - NLM ET - 2015/05/27 IS - 4 J2 - Journal of evaluation in clinical practice KW - Computer Simulation Decision Making Health Services Research Humans Influenza Vaccines/*administration & dosage Influenza, Human/*prevention & control Mass Screening/*methods Program Development Quality Improvement Tuberculosis/*prevention & control Washington clinical guidelines health care LA - eng N1 - 1365-2753 Heim, Joseph A Huang, Hao Zabinsky, Zelda B Dickerson, Jane Wellner, Monica Astion, Michael Cruz, Doris Vincent, Jeanne Jack, Rhona Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England J Eval Clin Pract. 2015 Aug;21(4):727-34. doi: 10.1111/jep.12377. Epub 2015 May 26. PY - 2015 SN - 1356-1294 SP - 727-34 ST - Design and implementation of a combined influenza immunization and tuberculosis screening campaign with simulation modelling T2 - J Eval Clin Pract TI - Design and implementation of a combined influenza immunization and tuberculosis screening campaign with simulation modelling UR - http://onlinelibrary.wiley.com/doi/10.1111/jep.12377/abstract VL - 21 ID - 1339 ER - TY - JOUR AD - TB Modelling Group, TB Centre and CMMID, Faculty of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, London, UK. AN - 25686128 AU - Houben, R. M. AU - White, R. G. DA - Mar DO - 10.5588/ijtld.15.0037 DP - NLM ET - 2015/02/17 IS - 3 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - *Cost of Illness Humans Periodicals as Topic Tuberculosis/*economics/pathology World Health Organization LA - eng N1 - 1815-7920 Houben, Rein M G J White, Richard G J005088/1/Medical Research Council/United Kingdom U2GPS0008111/PEPFAR/United States Editorial Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. France Int J Tuberc Lung Dis. 2015 Mar;19(3):255. doi: 10.5588/ijtld.15.0037. PY - 2015 SN - 1027-3719 SP - 255 ST - To improve our tuberculosis burden estimates we need to learn from each other T2 - Int J Tuberc Lung Dis TI - To improve our tuberculosis burden estimates we need to learn from each other VL - 19 ID - 1460 ER - TY - JOUR AB - BACKGROUND: In the last 20 years, China ramped up a DOTS (directly observed treatment, short-course)-based tuberculosis (TB) control program with 80% population coverage, achieving the 2015 Millennium Development Goal of a 50% reduction in TB prevalence and mortality. Recently, the World Health Organization developed the End TB Strategy, with an overall goal of a 90% reduction in TB incidence and a 95% reduction in TB deaths from 2015-2035. As the TB burden shifts to older individuals and China's overall population ages, it is unclear if maintaining the current DOTS strategy will be sufficient for China to reach the global targets. METHODS: We developed an individual-based computational model of TB transmission, implementing realistic age demographics and fitting to country-level data of age-dependent prevalence over time. We explored the trajectory of TB burden if the DOTS strategy is maintained or if new interventions are introduced using currently available and soon-to-be-available tools. These interventions include increasing population coverage of DOTS, reducing time to treatment, increasing treatment success, and active case finding among elders > 65 years old. We also considered preventative therapy in latently infected elders, a strategy limited by resource constraints and the risk of adverse events. RESULTS: Maintenance of the DOTS strategy reduces TB incidence and mortality by 42% (95% credible interval, 27-59%) and 41% (5-64%), respectively, between 2015 and 2035. A combination of all feasible interventions nears the 2035 mortality target, reducing TB incidence and mortality by 59% (50-76%) and 83% (73-94%). Addition of preventative therapy for elders would enable China to nearly reach both the incidence and mortality targets, reducing incidence and mortality by 84% (78-93%) and 92% (86-98%). CONCLUSIONS: The current decline in incidence is driven by two factors: maintaining a low level of new infections in young individuals and the aging out of older latently infected individuals who contribute incidence due to reactivation disease. While further reducing the level of new infections has a modest effect on burden, interventions that limit reactivation have a greater impact on TB burden. Tools that make preventative therapy more feasible on a large scale and in elders will help China achieve the global targets. AD - Institute for Disease Modeling, 1555 132nd Ave NE, Bellevue, WA, 98005, USA. ghuynh@intven.com. Institute for Disease Modeling, 1555 132nd Ave NE, Bellevue, WA, 98005, USA. dklein@intven.com. China Office, The Bill & Melinda Gates Foundation, Beijing, 100027, China. daniel.chin@gatesfoundation.org. Institute for Disease Modeling, 1555 132nd Ave NE, Bellevue, WA, 98005, USA. bwagner@intven.com. Institute for Disease Modeling, 1555 132nd Ave NE, Bellevue, WA, 98005, USA. peckhoff@intven.com. Chinese Center for Disease Control and Prevention, Beijing, 102206, China. sdlirenzhong@163.com. Chinese Center for Disease Control and Prevention, Beijing, 102206, China. wanglx@chinatb.org. AN - 25896465 AU - Huynh, G. H. AU - Klein, D. J. AU - Chin, D. P. AU - Wagner, B. G. AU - Eckhoff, P. A. AU - Liu, R. AU - Wang, L. C2 - PMC4424583 DA - Apr 21 DO - 10.1186/s12916-015-0341-4 DP - NLM ET - 2015/04/22 J2 - BMC medicine KW - Adolescent Adult Aged China/epidemiology Directly Observed Therapy/*methods Female Humans Incidence Male Middle Aged Models, Theoretical Prevalence Treatment Outcome Tuberculosis/*epidemiology/*prevention & control/transmission World Health Organization Young Adult LA - eng N1 - 1741-7015 Huynh, Grace H Klein, Daniel J Chin, Daniel P Wagner, Bradley G Eckhoff, Philip A Liu, Renzhong Wang, Lixia Journal Article Research Support, Non-U.S. Gov't England BMC Med. 2015 Apr 21;13:88. doi: 10.1186/s12916-015-0341-4. PY - 2015 SN - 1741-7015 SP - 88 ST - Tuberculosis control strategies to reach the 2035 global targets in China: the role of changing demographics and reactivation disease T2 - BMC Med TI - Tuberculosis control strategies to reach the 2035 global targets in China: the role of changing demographics and reactivation disease VL - 13 ID - 1378 ER - TY - JOUR AB - Drug-resistant tuberculosis (TB) has increased at an alarming rate in the WHO European Region. Of the 27 countries worldwide with a high burden of multidrug resistant-TB (MDR-TB), 15 are in the European Region. An estimated 78,000 new cases of MDR-TB occur annually in the Region, of which approximately 10% are extensively drug-resistant (XDR)-TB. In response, the WHO Regional Office for Europe developed a Consolidated Action Plan to Prevent and Combat Multidrug- and Extensively Drug-resistant Tuberculosis (2011-2015). Our objective was to analyse the cost-effectiveness of implementing the plan, with the expected achievements of diagnosing 85% of estimated MDR-TB cases and treating at least 75% successfully. A transmission model, using epidemiological data reported to WHO was developed to calculate expected achievements. WHO-CHOICE database was used for cost analyses. The highly cost-effective plan is expected to prevent the emergence of 250,000 new MDR-TB and 13,000 XDR-TB patients respectively, saving US$7 billion and 120,000 lives. The plan and accompanying Resolution were fully endorsed by the sixty-first session of the WHO Regional Committee for Europe in 2011. Member States need to continuously improve health system performance and address TB determinants. Research and development of new medicines, tools and patient-friendly services are also crucial. AD - WHO Regional Office for Europe, UN City, Marmorvej 51, DK-2100 Copenhagen O, Denmark. WHO Regional Office for Europe, UN City, Marmorvej 51, DK-2100 Copenhagen O, Denmark. Electronic address: daram@who.int. AN - 25829287 AU - Jakab, Z. AU - Acosta, C. D. AU - Kluge, H. H. AU - Dara, M. DA - Jun DO - 10.1016/j.tube.2015.02.027 DP - NLM ET - 2015/04/02 J2 - Tuberculosis (Edinburgh, Scotland) KW - Communicable Disease Control/economics Cost Savings Cost-Benefit Analysis Europe Extensively Drug-Resistant Tuberculosis/economics/prevention & control Gross Domestic Product Health Planning/economics Humans Tuberculosis, Multidrug-Resistant/economics/*prevention & control Extensively drug-resistant-TB Multidrug resistant-TB WHO European Region LA - eng N1 - 1873-281x Jakab, Zsuzsanna Acosta, Colleen D Kluge, Hans H Dara, Masoud 001/World Health Organization/International Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Scotland Tuberculosis (Edinb). 2015 Jun;95 Suppl 1:S212-6. doi: 10.1016/j.tube.2015.02.027. Epub 2015 Mar 6. PY - 2015 SN - 1472-9792 SP - S212-6 ST - Consolidated Action Plan to Prevent and Combat Multidrug- and Extensively Drug-resistant Tuberculosis in the WHO European Region 2011-2015: Cost-effectiveness analysis T2 - Tuberculosis (Edinb) TI - Consolidated Action Plan to Prevent and Combat Multidrug- and Extensively Drug-resistant Tuberculosis in the WHO European Region 2011-2015: Cost-effectiveness analysis VL - 95 Suppl 1 ID - 2900 ER - TY - JOUR AB - After decades on the decline, it is believed that the emergence of HIV is responsible for an increase in the tuberculosis prevalence. The leading infectious disease in the world, tuberculosis is also the leading cause of death among HIV-positive individuals. Each disease progresses through several stages. The current model suggests modeling these stages through a time-since-infection tracking transmission rate function, which, when considering co-infection, introduces a double-age structure in the PDE system. The basic and invasion reproduction numbers for each disease are calculated and the basic ones established as threshold for the disease progression. Numerical results confirm the calculations and a simple treatment scenario suggests the importance of time-since-infection when introducing disease control and treatment in the model. AD - Mathematics Department, Purdue University, 150 N. University Street, West Lafayette, IN 47907-2067, United States. georgi-kapitanov@uiowa.edu. AN - 25811330 AU - Kapitanov, G. DA - Feb DO - 10.3934/mbe.2015.12.23 DP - NLM ET - 2015/03/27 IS - 1 J2 - Mathematical biosciences and engineering : MBE KW - Algorithms Basic Reproduction Number *Coinfection Computer Simulation Disease Progression HIV Infections/complications/*epidemiology/transmission Humans Models, Theoretical Prevalence Time Factors Tuberculosis/complications/*epidemiology/transmission LA - eng N1 - 1551-0018 Kapitanov, Georgi Journal Article United States Math Biosci Eng. 2015 Feb;12(1):23-40. doi: 10.3934/mbe.2015.12.23. PY - 2015 SN - 1547-1063 SP - 23-40 ST - A double age-structured model of the co-infection of tuberculosis and HIV T2 - Math Biosci Eng TI - A double age-structured model of the co-infection of tuberculosis and HIV VL - 12 ID - 1410 ER - TY - JOUR AB - In any setting, a proportion of incident active tuberculosis (TB) reflects recent transmission ("recent transmission proportion"), whereas the remainder represents reactivation. Appropriately estimating the recent transmission proportion has important implications for local TB control, but existing approaches have known biases, especially where data are incomplete. We constructed a stochastic individual-based model of a TB epidemic and designed a set of simulations (derivation set) to develop two regression-based tools for estimating the recent transmission proportion from five inputs: underlying TB incidence, sampling coverage, study duration, clustered proportion of observed cases, and proportion of observed clusters in the sample. We tested these tools on a set of unrelated simulations (validation set), and compared their performance against that of the traditional 'n-1' approach. In the validation set, the regression tools reduced the absolute estimation bias (difference between estimated and true recent transmission proportion) in the 'n-1' technique by a median [interquartile range] of 60% [9%, 82%] and 69% [30%, 87%]. The bias in the 'n-1' model was highly sensitive to underlying levels of study coverage and duration, and substantially underestimated the recent transmission proportion in settings of incomplete data coverage. By contrast, the regression models' performance was more consistent across different epidemiological settings and study characteristics. We provide one of these regression models as a user-friendly, web-based tool. Novel tools can improve our ability to estimate the recent TB transmission proportion from data that are observable (or estimable) by public health practitioners with limited available molecular data. AD - Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD, United States of America. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, United States of America. Department of Operations, Business Analytics, and Information Systems, University of Cincinnati, Cincinnati, OH, United States of America. AN - 26679499 AU - Kasaie, P. AU - Mathema, B. AU - Kelton, W. D. AU - Azman, A. S. AU - Pennington, J. AU - Dowdy, D. W. C2 - PMC4683006 DO - 10.1371/journal.pone.0144137 DP - NLM ET - 2015/12/19 IS - 12 J2 - PloS one KW - Data Collection Humans Incidence Stochastic Processes Tuberculosis/epidemiology/*transmission LA - eng N1 - 1932-6203 Kasaie, Parastu Mathema, Barun Kelton, W David Azman, Andrew S Pennington, Jeff Dowdy, David W P30 AI094189/AI/NIAID NIH HHS/United States P30AI094189/AI/NIAID NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States PLoS One. 2015 Dec 17;10(12):e0144137. doi: 10.1371/journal.pone.0144137. eCollection 2015. PY - 2015 SN - 1932-6203 SP - e0144137 ST - A Novel Tool Improves Existing Estimates of Recent Tuberculosis Transmission in Settings of Sparse Data Collection T2 - PLoS One TI - A Novel Tool Improves Existing Estimates of Recent Tuberculosis Transmission in Settings of Sparse Data Collection VL - 10 ID - 1131 ER - TY - JOUR AB - BACKGROUND: Multidrug-resistant (MDR) tuberculosis can be acquired through de-novo mutation during tuberculosis treatment or through transmission from other individuals with active MDR tuberculosis. Understanding the balance between these two mechanisms is essential when allocating resources for MDR tuberculosis. We aimed to create a dynamic transmission model of an MDR tuberculosis epidemic to estimate the contributions of treatment-related acquisition and person-to-person transmission of resistance to incident MDR tuberculosis cases. METHODS: In this modelling analysis, we constructed a dynamic transmission model of an MDR tuberculosis epidemic, allowing for both treatment-related acquisition and person-to-person transmission of resistance. We used national tuberculosis notification data to inform Bayesian estimates of the proportion of each country's 2013 MDR tuberculosis incidence that resulted from MDR transmission rather than treatment-related MDR acquisition. FINDINGS: Global estimates of 3.5% MDR tuberculosis prevalence among new tuberculosis notifications and 20.5% among re-treatment notifications translate into an estimate that resistance transmission rather than acquisition accounts for a median 95.9% (95% uncertainty range [UR] 68.0-99.6) of all incident MDR tuberculosis, and 61.3% (16.5-95.2) of incident MDR tuberculosis in previously treated individuals. The estimated proportion of MDR tuberculosis resulting from transmission varied substantially with different countries' notification data-ranging from 48% (95% UR 30-75) in Bangladesh to 99% (91-100) in Uzbekistan. Estimates were most sensitive to estimates of the transmissibility of MDR strains, the probability of acquiring MDR during tuberculosis treatment, and the responsiveness of MDR tuberculosis to first-line treatment. INTERPRETATION: Notifications of MDR prevalence from most high-burden settings are consistent with most incident MDR tuberculosis resulting from transmission rather than new treatment-related acquisition of resistance. Merely improving the treatment of drug-susceptible tuberculosis is unlikely to greatly reduce future MDR tuberculosis incidence. Improved diagnosis and treatment of MDR tuberculosis-including new tests and drug regimens-should be highly prioritised. FUNDING: National Institutes of Health and the Bill & Melinda Gates Foundation. AD - Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: ekendal2@jhmi.edu. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. AN - 26597127 AU - Kendall, E. A. AU - Fofana, M. O. AU - Dowdy, D. W. C2 - PMC4684734 C6 - NIHMS740710 DA - Dec DO - 10.1016/s2213-2600(15)00458-0 DP - NLM ET - 2015/11/26 IS - 12 J2 - The Lancet. Respiratory medicine KW - *Epidemics Humans *Models, Statistical Tuberculosis, Multidrug-Resistant/*epidemiology/*transmission Tuberculosis, Pulmonary/*epidemiology/*transmission L1 - internal-pdf://2601437407/Kendall-2015-Burden of transmitted multidrug r.pdf LA - eng N1 - 2213-2619 Kendall, Emily A Fofana, Mariam O Dowdy, David W L30 AI113489/AI/NIAID NIH HHS/United States T32 AI007291/AI/NIAID NIH HHS/United States T32 GM007309/GM/NIGMS NIH HHS/United States 5T32AI007291-24/AI/NIAID NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Lancet Respir Med. 2015 Dec;3(12):963-72. doi: 10.1016/S2213-2600(15)00458-0. Epub 2015 Nov 18. PY - 2015 SN - 2213-2600 SP - 963-72 ST - Burden of transmitted multidrug resistance in epidemics of tuberculosis: a transmission modelling analysis T2 - Lancet Respir Med TI - Burden of transmitted multidrug resistance in epidemics of tuberculosis: a transmission modelling analysis UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684734/pdf/nihms740710.pdf VL - 3 ID - 1154 ER - TY - JOUR AB - As an emergent infectious disease outbreak unfolds, public health response is reliant on information on key epidemiological quantities, such as transmission potential and serial interval. Increasingly, transmission models fit to incidence data are used to estimate these parameters and guide policy. Some widely used modelling practices lead to potentially large errors in parameter estimates and, consequently, errors in model-based forecasts. Even more worryingly, in such situations, confidence in parameter estimates and forecasts can itself be far overestimated, leading to the potential for large errors that mask their own presence. Fortunately, straightforward and computationally inexpensive alternatives exist that avoid these problems. Here, we first use a simulation study to demonstrate potential pitfalls of the standard practice of fitting deterministic models to cumulative incidence data. Next, we demonstrate an alternative based on stochastic models fit to raw data from an early phase of 2014 West Africa Ebola virus disease outbreak. We show not only that bias is thereby reduced, but that uncertainty in estimates and forecasts is better quantified and that, critically, lack of model fit is more readily diagnosed. We conclude with a short list of principles to guide the modelling response to future infectious disease outbreaks. AU - King, A. A. AU - Domenech de Celles, M. AU - Magpantay, F. M. AU - Rohani, P. DO - 10.1098/rspb.2015.0347 10.1098/rspb.2015.0347. IS - 1806 KW - *Disease Outbreaks *Models, Theoretical Africa, Western/epidemiology Bias (Epidemiology) Communicable Diseases, Emerging/*epidemiology/viro Ebola virus disease Ebolavirus/*physiology Hemorrhagic Fever, Ebola/*epidemiology/virology Humans emerging infectious disease forecast L1 - file:///C:/Users/James/AppData/Local/Mendeley Ltd/Mendeley Desktop/Downloaded/ebola_avoidable_errors_supp.pdf file:///C:/Users/James/AppData/Local/Mendeley Ltd/Mendeley Desktop/Downloaded/ebola_avoidable_errors.pdf PY - 2015 SN - 1471-2954 (Electronic) 0962-8452 (Linking) SP - 20150347-20150347 ST - Avoidable errors in the modelling of outbreaks of emerging pathogens, with special reference to Ebola T2 - Proc Biol Sci TI - Avoidable errors in the modelling of outbreaks of emerging pathogens, with special reference to Ebola UR - https://www.ncbi.nlm.nih.gov/pubmed/25833863 VL - 282 ID - 3505 ER - TY - JOUR AB - BACKGROUND: Drug resistance poses a serious challenge for the control of tuberculosis in many settings. It is well established that the expected future trend in resistance depends on the reproductive fitness of drug-resistant Mycobacterium tuberculosis. However, the variability in fitness between strains with different resistance-conferring mutations has been largely ignored when making these predictions. METHODS: We developed a novel approach for incorporating the variable fitness costs of drug resistance-conferring mutations and for tracking this distribution of fitness costs over time within a transmission model. We used this approach to describe the effects of realistic fitness cost distributions on the future prevalence of drug-resistant tuberculosis. RESULTS: The shape of the distribution of fitness costs was a strong predictor of the long-term prevalence of resistance. While, as expected, lower average fitness costs of drug resistance-conferring mutations were associated with more severe epidemics of drug-resistant tuberculosis, fitness distributions with greater variance also led to higher levels of drug resistance. For example, compared to simulations in which the fitness cost of resistance was fixed, introducing a realistic amount of variance resulted in a 40% increase in prevalence of drug-resistant tuberculosis after 20 years. CONCLUSIONS: The differences in the fitness costs associated with drug resistance-conferring mutations are a key determinant of the future burden of drug-resistant tuberculosis. Future studies that can better establish the range of fitness costs associated with drug resistance-conferring mutations will improve projections and thus facilitate better public health planning efforts. AD - Tuberculosis Modelling Group, Centre for the Mathematical Modelling of Infectious Diseases, Tuberculosis Centre, Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Public Health, London School of Hygiene and Tropical Medicine. Department of Mathematics, Imperial College London, United Kingdom. Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland. Amsterdam Institute for Global Health and Development, Academic Medical Center KNCV Tuberculosis Foundation, The Hague, The Netherlands. Department of Epidemiology of Microbial Diseases, School of Public Health, Yale University, New Haven, Connecticut. AN - 26409276 AU - Knight, G. M. AU - Colijn, C. AU - Shrestha, S. AU - Fofana, M. AU - Cobelens, F. AU - White, R. G. AU - Dowdy, D. W. AU - Cohen, T. C2 - PMC4583567 DA - Oct 15 DO - 10.1093/cid/civ579 DP - NLM ET - 2015/09/27 J2 - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America KW - Antitubercular Agents/pharmacology/therapeutic use Drug Resistance, Multiple, Bacterial/*genetics *Genetic Fitness Humans Models, Molecular *Mutation Mycobacterium tuberculosis/drug effects/*genetics Prevalence Tuberculosis, Multidrug-Resistant/*epidemiology/microbiology United States antibiotic resistance fitness costs mathematical modeling tuberculosis L1 - internal-pdf://3405386988/Knight-2015-The Distribution of Fitness Costs.pdf LA - eng N1 - 1537-6591 Knight, Gwenan M Colijn, Caroline Shrestha, Sourya Fofana, Mariam Cobelens, Frank White, Richard G Dowdy, David W Cohen, Ted T32 GM007309/GM/NIGMS NIH HHS/United States MR/J005088/1/Medical Research Council/United Kingdom U2GPS0008111/PHS HHS/United States PEPFAR/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United States Clin Infect Dis. 2015 Oct 15;61Suppl 3:S147-54. doi: 10.1093/cid/civ579. PY - 2015 SN - 1058-4838 SP - S147-54 ST - The Distribution of Fitness Costs of Resistance-Conferring Mutations Is a Key Determinant for the Future Burden of Drug-Resistant Tuberculosis: A Model-Based Analysis T2 - Clin Infect Dis TI - The Distribution of Fitness Costs of Resistance-Conferring Mutations Is a Key Determinant for the Future Burden of Drug-Resistant Tuberculosis: A Model-Based Analysis UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4583567/pdf/civ579.pdf VL - 61Suppl 3 ID - 1220 ER - TY - JOUR AB - BACKGROUND: South Africa has one of the highest per capita rates of tuberculosis (TB) incidence in the world. In 2012, the South African government produced a National Strategic Plan (NSP) to control the spread of TB with the ambitious aim of zero new TB infections and deaths by 2032, and a halving of the 2012 rates by 2016. METHODS: We used a transmission model to investigate whether the NSP targets could be reached if immediate scale up of control methods had happened in 2014. We explored the potential impact of four intervention portfolios; 1) "NSP" represents the NSP strategy, 2) "WHO" investigates increasing antiretroviral therapy eligibility, 3) "Novel Strategies" considers new isoniazid preventive therapy strategies and HIV "Universal Test and Treat" and 4) "Optimised" contains the most effective interventions. FINDINGS: We find that even with this scale-up, the NSP targets are unlikely to be achieved. The portfolio that achieved the greatest impact was "Optimised", followed closely by "NSP". The "WHO" and "Novel Strategies" had little impact on TB incidence by 2050. Of the individual interventions explored, the most effective were active case finding and reductions in pre-treatment loss to follow up which would have a large impact on TB burden. CONCLUSION: Use of existing control strategies has the potential to have a large impact on TB disease burden in South Africa. However, our results suggest that the South African TB targets are unlikely to be reached without new technologies. Despite this, TB incidence could be dramatically reduced by finding and starting more TB cases on treatment. AD - TB Modelling Group, Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; TB Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom. School of Health and Related Research, University of Sheffield, Sheffield, United Kingdom. TB Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom. TB Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom; Aurum Institute, Johannesburg, South Africa; School of Public Health, University of Witwatersrand, Johannesburg, South Africa. AN - 25849558 AU - Knight, G. M. AU - Dodd, P. J. AU - Grant, A. D. AU - Fielding, K. L. AU - Churchyard, G. J. AU - White, R. G. C2 - PMC4388715 DO - 10.1371/journal.pone.0122514 DP - NLM ET - 2015/04/08 IS - 4 J2 - PloS one KW - Anti-HIV Agents/therapeutic use Antitubercular Agents/therapeutic use HIV Infections/complications/drug therapy Humans Incidence Isoniazid/therapeutic use *Models, Theoretical South Africa/epidemiology Tuberculosis/complications/epidemiology/*prevention & control LA - eng N1 - 1932-6203 Knight, Gwenan M Dodd, Peter J Grant, Alison D Fielding, Katherine L Churchyard, Gavin J White, Richard G MR/K012126/1/Medical Research Council/United Kingdom MR/J005088/1/Medical Research Council/United Kingdom Journal Article Research Support, Non-U.S. Gov't United States PLoS One. 2015 Apr 7;10(4):e0122514. doi: 10.1371/journal.pone.0122514. eCollection 2015. PY - 2015 SN - 1932-6203 SP - e0122514 ST - Tuberculosis prevention in South Africa T2 - PLoS One TI - Tuberculosis prevention in South Africa VL - 10 ID - 1399 ER - TY - JOUR AB - BACKGROUND: A 4-month first-line treatment regimen for tuberculosis disease (TB) is expected to have a direct impact on patient outcomes and societal costs, as well as an indirect impact on Mycobacterium tuberculosis transmission. We aimed to estimate this combined impact in a high TB-burden country: South Africa. METHOD: An individual based M. tb transmission model was fitted to the TB burden of South Africa using a standard TB natural history framework. We measured the impact on TB burden from 2015-2035 of introduction of a non-inferior 4-month regimen replacing the standard 6-month regimen as first-line therapy. Impact was measured with respect to three separate baselines (Guidelines, Policy and Current), reflecting differences in adherence to TB and HIV treatment guidelines. Further scenario analyses considered the variation in treatment-related parameters and resistance levels. Impact was measured in terms of differences in TB burden and Disability Adjusted Life Years (DALYs) averted. We also examined the highest cost at which the new regimen would be cost-effective for several willingness-to-pay thresholds. RESULTS: It was estimated that a 4-month regimen would avert less than 1% of the predicted 6 million person years with TB disease in South Africa between 2015 and 2035. A similarly small impact was seen on deaths and DALYs averted. Despite this small impact, with the health systems and patient cost savings from regimen shortening, the 4-month regimen could be cost-effective at $436 [NA, 5983] (mean [range]) per month at a willingness-to-pay threshold of one GDP per capita ($6,618). CONCLUSION: The introduction of a non-inferior 4-month first-line TB regimen into South Africa would have little impact on the TB burden. However, under several scenarios, it is likely that the averted societal costs would make such a regimen cost-effective in South Africa. AD - Centre for Mathematical Modelling of Infectious Diseases, TB Centre, TB Modeling Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom. Amsterdam Institute for Global Health and Development and Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom. School of Health and Related Research, University of Sheffield, Sheffield, United Kingdom. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America. Global Alliance for TB Drug Development, New York, United States of America. KNCV Tuberculosis Foundation, The Hague, The Netherlands. AN - 26717007 AU - Knight, G. M. AU - Gomez, G. B. AU - Dodd, P. J. AU - Dowdy, D. AU - Zwerling, A. AU - Wells, W. A. AU - Cobelens, F. AU - Vassall, A. AU - White, R. G. C2 - PMC4696677 DO - 10.1371/journal.pone.0145796 DP - NLM ET - 2015/12/31 IS - 12 J2 - PloS one KW - Antitubercular Agents/*economics/*therapeutic use Cost-Benefit Analysis Health Care Costs Humans Models, Economic Mycobacterium tuberculosis/drug effects Quality-Adjusted Life Years Radionuclide Imaging South Africa Tuberculosis/diagnostic imaging/*drug therapy/*economics L1 - internal-pdf://3628682469/Knight-2015-The Impact and Cost-Effectiveness.pdf LA - eng N1 - 1932-6203 Knight, Gwenan M Gomez, Gabriela B Dodd, Peter J Dowdy, David Zwerling, Alice Wells, William A Cobelens, Frank Vassall, Anna White, Richard G MR/J005088/1/Medical Research Council/United Kingdom Journal Article Research Support, Non-U.S. Gov't United States PLoS One. 2015 Dec 30;10(12):e0145796. doi: 10.1371/journal.pone.0145796. eCollection 2015. PY - 2015 SN - 1932-6203 SP - e0145796 ST - The Impact and Cost-Effectiveness of a Four-Month Regimen for First-Line Treatment of Active Tuberculosis in South Africa T2 - PLoS One TI - The Impact and Cost-Effectiveness of a Four-Month Regimen for First-Line Treatment of Active Tuberculosis in South Africa UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696677/pdf/pone.0145796.pdf VL - 10 ID - 1116 ER - TY - JOUR AB - Various forms of preventive and prophylactic antimicrobial therapies have been proposed to combat HIV (e.g. pre-exposure prophylaxis), tuberculosis (e.g. isoniazid preventive therapy) and malaria (e.g. intermittent preventive treatment). However, the potential population-level effects of preventative therapy (PT) on the prevalence of drug resistance are not well understood. PT can directly affect the rate at which resistance is acquired among those receiving PT. It can also indirectly affect resistance by altering the rate at which resistance is acquired through treatment for active disease and by modifying the level of competition between transmission of drug-resistant and drug-sensitive pathogens. We propose a general mathematical model to explore the ways in which PT can affect the long-term prevalence of drug resistance. Depending on the relative contributions of these three mechanisms, we find that increasing the level of coverage of PT may result in increases, decreases or non-monotonic changes in the overall prevalence of drug resistance. These results demonstrate the complexity of the relationship between PT and drug resistance in the population. Care should be taken when predicting population-level changes in drug resistance from small pilot studies of PT or estimates based solely on its direct effects. AD - Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06520, USA agkunkel@gmail.com. Department of Mathematics, Imperial College, London SW7 2AZ, UK. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA. Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06520, USA. AN - 25918446 AU - Kunkel, A. AU - Colijn, C. AU - Lipsitch, M. AU - Cohen, T. C2 - PMC4424438 DA - Jun 05 DO - 10.1098/rstb.2014.0306 DP - NLM ET - 2015/04/29 IS - 1670 J2 - Philosophical transactions of the Royal Society of London. Series B, Biological sciences KW - Antibiotic Prophylaxis/adverse effects/*methods/trends Communicable Disease Control/*methods/trends Computer Simulation Drug Resistance, Microbial/*genetics Humans Infection/*drug therapy/*epidemiology *Models, Theoretical Prevalence antibiotic resistance competition indirect effects mathematical model preventive prophylaxis L1 - internal-pdf://2498823734/Kunkel-2015-How could preventive therapy affec.pdf LA - eng N1 - 1471-2970 Kunkel, Amber Colijn, Caroline Lipsitch, Marc Cohen, Ted T32AI007535/AI/NIAID NIH HHS/United States R01AI112438/AI/NIAID NIH HHS/United States U54 GM088558/GM/NIGMS NIH HHS/United States R01 AI112438/AI/NIAID NIH HHS/United States U54GM088558/GM/NIGMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Philos Trans R Soc Lond B Biol Sci. 2015 Jun 5;370(1670):20140306. doi: 10.1098/rstb.2014.0306. PY - 2015 SN - 0962-8436 SP - 20140306 ST - How could preventive therapy affect the prevalence of drug resistance? Causes and consequences T2 - Philos Trans R Soc Lond B Biol Sci TI - How could preventive therapy affect the prevalence of drug resistance? Causes and consequences UR - http://rstb.royalsocietypublishing.org/content/royptb/370/1670/20140306.full.pdf VL - 370 ID - 1376 ER - TY - JOUR AD - [Leccese, P. A.] Univ Colorado, Sch Med, Denver, CO USA. [Leccese, P. A.; Dowdy, D.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Makamure, B.] Biomed Res & Training Inst, Harare, Zimbabwe. [Metcalfe, J. Z.] UCSF, San Francisco, CA USA. paul.leccese@ucdenver.edu AN - WOS:000377582803576 AU - Leccese, P. A. AU - Dowdy, D. AU - Makamure, B. AU - Metcalfe, J. Z. J2 - Am. J. Respir. Crit. Care Med. KW - General & Internal Medicine Respiratory System LA - English M3 - Meeting Abstract N1 - ISI Document Delivery No.: DO2AW Times Cited: 0 Cited Reference Count: 0 Leccese, P. A. Dowdy, D. Makamure, B. Metcalfe, J. Z. International Conference of the American-Thoracic-Society (ATS) May 15-20, 2015 Denver, CO Amer Thorac Soc 0 Amer thoracic soc New york 1535-4970 PY - 2015 SN - 1073-449X SP - 2 ST - A Cost-Consequence Model Comparing Xpert Mtb/rif And Microscopic Observation Drug Susceptibility Testing For The Diagnosis Of Suspected Drug-Resistant Pulmonary Tuberculosis In Adults In Harare, Zimbabwe T2 - American Journal of Respiratory and Critical Care Medicine TI - A Cost-Consequence Model Comparing Xpert Mtb/rif And Microscopic Observation Drug Susceptibility Testing For The Diagnosis Of Suspected Drug-Resistant Pulmonary Tuberculosis In Adults In Harare, Zimbabwe UR - ://WOS:000377582803576 VL - 191 ID - 5353 ER - TY - JOUR AB - It is unclear if current programmes in China can achieve the post-2015 global targets for tuberculosis - 50% reduction, in incidence and a 75% reduction in mortality by 2025. Chinese policy-makers need to maintain the recent decline in the prevalence of tuberculosis, while revising control policies to cope with an epidemic of drug-resistant tuberculosis and the effects of ongoing health reform. Health reforms are expected to shift patients from tuberculosis dispensaries to designated hospitals. We developed a mathematical model of tuberculosis control in China to help set appropriate targets and prioritize interventions that might be implemented in the next 10 years. This model indicates that, even under the most optimistic scenario - improved treatment in tuberculosis dispensaries, introduction of a new effective regimen for the treatment of drug-susceptible tuberculosis and optimal care of cases of multidrug-resistant tuberculosis - the current global targets for tuberculosis are unlikely to be reached. However, reductions in the incidence of multidrug-resistant tuberculosis should be feasible. We conclude that a shift of patients from tuberculosis dispensaries to designated hospitals is likely to hamper efforts at tuberculosis control if cure rates in the designated hospitals cannot be maintained at a high level. Our results can inform the planning of tuberculosis control in China. AD - [Lin, Hsien-Ho] Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei 100, Taiwan. [Wang, Lixia; Zhang, Hui; Ruan, Yunzhou] Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. [Chin, Daniel P.] Bill & Melinda Gates Fdn, China Off, Beijing, Peoples R China. [Dye, Christopher] WHO, Off Director Gen, CH-1211 Geneva, Switzerland. Lin, HH (reprint author), Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Rm706,17 Xuzhou Rd, Taipei 100, Taiwan. hsienho@ntu.edu.tw AN - WOS:000365244500016 AU - Lin, H. H. AU - Wang, L. X. AU - Zhang, H. AU - Ruan, Y. Z. AU - Chin, D. P. AU - Dye, C. DA - Nov DO - 10.2471/blt.15.154492 IS - 11 J2 - Bull. World Health Organ. KW - resistant tuberculosis national-survey prevalence prospects Public, Environmental & Occupational Health L1 - internal-pdf://2355473896/Lin-2015-Tuberculosis control in China_ use of.pdf LA - English M3 - Article N1 - ISI Document Delivery No.: CW8JB Times Cited: 7 Cited Reference Count: 20 Lin, Hsien-Ho Wang, Lixia Zhang, Hui Ruan, Yunzhou Chin, Daniel P. Dye, Christopher Dye, Christopher/0000-0002-2957-1793 Bill & Melinda Gates Foundation This work was supported by the Bill & Melinda Gates Foundation. 7 0 4 World health organization Geneva 27 1564-0604 PY - 2015 SN - 0042-9686 SP - 790-798 ST - Tuberculosis control in China: use of modelling to develop targets and policies T2 - Bulletin of the World Health Organization TI - Tuberculosis control in China: use of modelling to develop targets and policies UR - ://WOS:000365244500016 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622160/pdf/BLT.15.154492.pdf VL - 93 ID - 5251 ER - TY - JOUR AB - Approximately one third of the world's population is infected with Mycobacterium tuberculosis. Limited information about how the immune system fights M. tuberculosis and what constitutes protection from the bacteria impact our ability to develop effective therapies for tuberculosis. We present an in vivo systems biology approach that integrates data from multiple model systems and over multiple length and time scales into a comprehensive multi-scale and multi-compartment view of the in vivo immune response to M. tuberculosis. We describe computational models that can be used to study (a) immunomodulation with the cytokines tumor necrosis factor and interleukin 10, (b) oral and inhaled antibiotics, and AD - Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA. linderma@umich.edu. AN - 25924949 AU - Linderman, J. J. AU - Cilfone, N. A. AU - Pienaar, E. AU - Gong, C. AU - Kirschner, D. E. C2 - PMC4436084 C6 - NIHMS686333 DA - May DO - 10.1039/c4ib00295d DP - NLM ET - 2015/05/01 IS - 5 J2 - Integrative biology : quantitative biosciences from nano to macro KW - Administration, Inhalation Administration, Oral Animals Anti-Bacterial Agents/administration & dosage Biomarkers Computational Biology Computer Simulation Cytokines/metabolism Drug Delivery Systems Drug Design Granuloma/drug therapy Humans Immune System Interleukin-10/metabolism Macrophages/drug effects Mycobacterium tuberculosis Programming Languages Systems Biology Tuberculosis/*therapy Tumor Necrosis Factor-alpha LA - eng N1 - 1757-9708 Linderman, Jennifer J Cilfone, Nicholas A Pienaar, Elsje Gong, Chang Kirschner, Denise E R01 EB012579/EB/NIBIB NIH HHS/United States R01 HL110811/HL/NHLBI NIH HHS/United States R01 HL 110811/HL/NHLBI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England Integr Biol (Camb). 2015 May;7(5):591-609. doi: 10.1039/c4ib00295d. Epub 2015 Apr 30. PY - 2015 SN - 1757-9694 SP - 591-609 ST - A multi-scale approach to designing therapeutics for tuberculosis T2 - Integr Biol (Camb) TI - A multi-scale approach to designing therapeutics for tuberculosis VL - 7 ID - 1372 ER - TY - JOUR AB - Tuberculosis (TB) is a global health problem responsible for ~2 million deaths per year. Current antibiotic treatments are lengthy and fraught with compliance and resistance issues. There is a crucial need for additional approaches to provide a cost-effective means of exploring the design space for potential therapies. We discuss the use of mathematical and computational models in virtual experiments and virtual clinical trials both to develop new hypotheses regarding the disease and to provide a cost-effective means of discovering new treatment strategies. AD - Department of Chemical Engineering, Univ. of Michigan, Ann Arbor, MI. Phone 734-763-0679. Department of Microbiology and Immunology, Univ. of Michigan Medical School, Ann Arbor, MI. Phone 734-647-7722. AN - 26904139 AU - Linderman, J. J. AU - Kirschner, D. E. C2 - PMC4758993 C6 - NIHMS573700 DA - Spring DO - 10.1016/j.ddmod.2014.02.006 DP - NLM ET - 2016/02/24 J2 - Drug discovery today. Disease models L1 - internal-pdf://2595841047/Linderman-2015-In silico models of M. tubercul.pdf LA - eng N1 - Linderman, Jennifer J Kirschner, Denise E R01 EB012579/EB/NIBIB NIH HHS/United States R01 HL106804/HL/NHLBI NIH HHS/United States R01 HL110811/HL/NHLBI NIH HHS/United States Journal Article Netherlands Drug Discov Today Dis Models. 2015 Spring;15:37-41. Epub 2014 May 9. PY - 2015 SN - 1740-6757 (Print) 1740-6757 SP - 37-41 ST - In silico models of M. tuberculosis infection provide a route to new therapies T2 - Drug Discov Today Dis Models TI - In silico models of M. tuberculosis infection provide a route to new therapies UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758993/pdf/nihms573700.pdf VL - 15 ID - 1055 ER - TY - JOUR AB - BACKGROUND: TB in India presents the challenges of a complex disease in a complex healthcare system. Mathematical models, offering a framework for capturing such complexities, have proven useful in exploring strategies for the control of TB. As the use of such techniques develops in future, it is important to understand what aspects of the healthcare system are most critical for models to faithfully capture. METHODS: We ask what type of intervention should be prioritized for the control of TB, amongst: improved diagnosis of TB per visit to a healthcare provider; improved treatment success; and increased identification of TB cases in the community? Using simple mathematical models, calibrated to the national TB epidemic in India, we explore how the relative importance of each of these interventions is affected by different assumptions for the patient pathway in careseeking, thus outlining aspects of the healthcare system that may matter most for the transmission dynamics of TB. RESULTS: We illustrate that, under a range of plausible parameter assumptions, it is possible to generate conditions under which a case-finding intervention would be prioritized over improvement of diagnosis and treatment, and vice versa. Key data needs include: the proportion of patients not contacting the healthcare system, and the mean patient delay before first seeking care. CONCLUSIONS: For mathematical models addressing strategic priorities for TB control, it is important to adequately quantify the dynamics of careseeking. We outline ways in which these data gaps may be addressed, and questions for future work. AD - Public Health Foundation of India, New Delhi, India. Public Health Foundation of India, New Delhi, India Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College, London, UK nim.pathy@imperial.ac.uk. AN - 25733561 AU - Mandal, S. AU - Arinaminpathy, N. DA - Mar DO - 10.1093/inthealth/ihv004 DP - NLM ET - 2015/03/04 IS - 2 J2 - International health KW - *Delivery of Health Care Epidemics Government Programs Humans India/epidemiology Medical Assistance *Models, Theoretical *Patient Acceptance of Health Care Tuberculosis/epidemiology/prevention & control/*transmission India Modelling Tuberculosis LA - eng N1 - 1876-3405 Mandal, Sandip Arinaminpathy, Nimalan MR/K010174/1/Medical Research Council/United Kingdom Journal Article Research Support, Non-U.S. Gov't England Int Health. 2015 Mar;7(2):114-20. doi: 10.1093/inthealth/ihv004. PY - 2015 SN - 1876-3405 SP - 114-20 ST - Transmission modeling and health systems: the case of TB in India T2 - Int Health TI - Transmission modeling and health systems: the case of TB in India VL - 7 ID - 1447 ER - TY - JOUR AB - Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), induces formation of granulomas, structures in which immune cells and bacteria colocalize. Macrophages are among the most abundant cell types in granulomas and have been shown to serve as both critical bactericidal cells and targets for M. tuberculosis infection and proliferation throughout the course of infection. Very little is known about how these processes are regulated, what controls macrophage microenvironment-specific polarization and plasticity, or why some granulomas control bacteria and others permit bacterial dissemination. We take a computational-biology approach to investigate mechanisms that drive macrophage polarization, function, and bacterial control in granulomas. We define a "macrophage polarization ratio" as a metric to understand how cytokine signaling translates into polarization of single macrophages in a granuloma, which in turn modulates cellular functions, including antimicrobial activity and cytokine production. Ultimately, we extend this macrophage ratio to the tissue scale and define a "granuloma polarization ratio" describing mean polarization measures for entire granulomas. Here we coupled experimental data from nonhuman primate TB granulomas to our computational model, and we predict two novel and testable hypotheses regarding macrophage profiles in TB outcomes. First, the temporal dynamics of granuloma polarization ratios are predictive of granuloma outcome. Second, stable necrotic granulomas with low CFU counts and limited inflammation are characterized by short NF-kappaB signal activation intervals. These results suggest that the dynamics of NF-kappaB signaling is a viable therapeutic target to promote M1 polarization early during infection and to improve outcome. AD - Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA. Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, USA. Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA kirschne@umich.edu. AN - 25368116 AU - Marino, S. AU - Cilfone, N. A. AU - Mattila, J. T. AU - Linderman, J. J. AU - Flynn, J. L. AU - Kirschner, D. E. C2 - PMC4288886 DA - Jan DO - 10.1128/iai.02494-14 DP - NLM ET - 2014/11/05 IS - 1 J2 - Infection and immunity KW - Animals Computer Simulation Disease Models, Animal Granuloma/*immunology/*microbiology/pathology Macaca fascicularis Macrophages/*immunology/*microbiology NF-kappa B/immunology Tuberculosis/*immunology/*microbiology/pathology LA - eng N1 - 1098-5522 Marino, Simeone Cilfone, Nicholas A Mattila, Joshua T Linderman, Jennifer J Flynn, JoAnne L Kirschner, Denise E R01 HL 110811/HL/NHLBI NIH HHS/United States R01 HL106804/HL/NHLBI NIH HHS/United States R01 EB012579/EB/NIBIB NIH HHS/United States R01 HL 106804/HL/NHLBI NIH HHS/United States R01 HL110811/HL/NHLBI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. United States Infect Immun. 2015 Jan;83(1):324-38. doi: 10.1128/IAI.02494-14. Epub 2014 Nov 3. PY - 2015 SN - 0019-9567 SP - 324-38 ST - Macrophage polarization drives granuloma outcome during Mycobacterium tuberculosis infection T2 - Infect Immun TI - Macrophage polarization drives granuloma outcome during Mycobacterium tuberculosis infection VL - 83 ID - 1867 ER - TY - CHAP AB - Tuberculosis remains one of the world's deadliest infectious diseases. About one-third of the world's population is infected with tuberculosis bacteria. Understanding the dynamics of transmission at different spatial scales is critical to progress in its control. We present an agent-based model for tuberculosis epidemics in Barcelona, which has an observatory on this disease. Our model considers high heterogeneity within the population, including risk factors for developing an active disease, and it tracks the individual behavior once diagnosed. We incorporated the immunodeficiency and smoking/alcoholism, as well as the individual's origin (foreigner or not) for its contagion and infection as risks factors. We implemented the model in Netlogo, a useful tool for interaction with physicians. However, the platform has some computational limitations, and we propose a solution to overcome them. AD - [Montanola-Sales, Cristina; Francesc Gilabert-Navarro, Joan; Casanovas-Garcia, Josep] Univ Politecn Cataluna, Barcelona Sch Informat, BarcelonaTech, Barcelona Supercomp Ctr,inLab FIB, ES-08034 Barcelona, Spain. [Prats, Clara; Lopez, Daniel; Valls, Joaquim] Univ Politecn Cataluna, BarcelonaTech, Dept Fis & Engn Nucl, Castelldefels 08860, Spain. [Joan Cardona, Pere; Vilaplana, Cristina] Univ Autonoma Barcelona, Unitat TB Expt, Fundacio Inst Invest Ciencies Salut Germans Trias, CIBERES, Badalona, Spain. Montanola-Sales, C (reprint author), Univ Politecn Cataluna, Barcelona Sch Informat, BarcelonaTech, Barcelona Supercomp Ctr,inLab FIB, ES-08034 Barcelona, Spain. cristina.montanola@upc.edu; cescgina@gmail.com; josepk@fib.upc.edu; clara.prats@upc.edu; daniel.lopez-codina@upc.edu; quim.valls@upc.edu; pj.cardona@gmail.com; cvilaplana@gmail.com AN - WOS:000399133901021 AU - Montanola-Sales, C. AU - Gilabert-Navarro, J. F. AU - Casanovas-Garcia, J. AU - Prats, C. AU - Lopez, D. AU - Valls, J. AU - Cardona, P. J. AU - Vilaplana, C. AU - Ieee CY - New York LA - English N1 - ISI Document Delivery No.: BH2QZ Times Cited: 0 Cited Reference Count: 18 Montanola-Sales, Cristina Francesc Gilabert-Navarro, Joan Casanovas-Garcia, Josep Prats, Clara Lopez, Daniel Valls, Joaquim Joan Cardona, Pere Vilaplana, Cristina Wsc Proceedings Paper Winter Simulation Conference (WSC) Dec 06-09, 2015 Huntington Beach, CA TB PROGRAM OF THE CIBER ENFERMEDADES RESPIRATORIAS, within the Spanish National Plan I+ D+ I; ISCIII-Subdireccion General de Evaluacion; European Funds for Regional Development (FEDER); Secretaria d'Universitats i Recerca de la Generalitat de Catalunya; [CP13/00174]; [PIO11/01702]; [PI14/01038] This study was funded by the projects and contracts CP13/00174; PIO11/01702; PI14/01038 and the TB PROGRAM OF THE CIBER ENFERMEDADES RESPIRATORIAS, within the Spanish National Plan I+ D+ I co-funded by the ISCIII-Subdireccion General de Evaluacion and the European Funds for Regional Development (FEDER) and partially supported by the Secretaria d'Universitats i Recerca de la Generalitat de Catalunya. Thanks to Pau Fonseca i Casas for his comments on the statistical analysis. 345 e 47th st, new york, ny 10017 usa 0891-7736 PB - Ieee PY - 2015 SN - 978-1-4673-9743-8 SP - 1295-1306 ST - MODELING TUBERCULOSIS IN BARCELONA. A SOLUTION TO SPEED-UP AGENT-BASED SIMULATIONS T2 - 2015 Winter Simulation Conference T3 - Winter Simulation Conference Proceedings TI - MODELING TUBERCULOSIS IN BARCELONA. A SOLUTION TO SPEED-UP AGENT-BASED SIMULATIONS UR - ://WOS:000399133901021 ID - 5367 ER - TY - JOUR AB - This paper considers the optimal control of tuberculosis through education, diagnosis campaign and chemoprophylaxis of latently infected. A mathematical model which includes important components such as undiagnosed infectious, diagnosed infectious, latently infected and lost-sight infectious is formulated. The model combines a frequency dependent and a density dependent force of infection for TB transmission. Through optimal control theory and numerical simulations, a cost-effective balance of two different intervention methods is obtained. Seeking to minimize the amount of money the government spends when tuberculosis remain endemic in the Cameroonian population, Pontryagin’s maximum principle is used to characterize the optimal control. The optimality system is derived and solved numerically using the forward–backward sweep method (FBSM). Results provide a framework for designing cost-effective strategies for diseases with multiple intervention methods. It comes out that combining chemoprophylaxis and education, the burden of TB can be reduced by 80% in 10years. AU - Moualeu, D. P. AU - Weiser, M. AU - Ehrig, R. AU - Deuflhard, P. DA - 2015/03/01/ DO - https://doi.org/10.1016/j.cnsns.2014.06.037 IS - 3 KW - Tuberculosis Optimal control Diagnosis campaign Nonlinear dynamical systems PY - 2015 SN - 1007-5704 SP - 986-1003 ST - Optimal control for a tuberculosis model with undetected cases in Cameroon T2 - Communications in Nonlinear Science and Numerical Simulation TI - Optimal control for a tuberculosis model with undetected cases in Cameroon UR - http://www.sciencedirect.com/science/article/pii/S1007570414003001 VL - 20 ID - 4925 ER - TY - JOUR AB - A deterministic model of tuberculosis in Cameroon is designed and analyzed with respect to its transmission dynamics. The model includes lack of access to treatment and weak diagnosis capacity as well as both frequency-and density-dependent transmissions. It is shown that the model is mathematically well-posed and epidemiologically reasonable. Solutions are non-negative and bounded whenever the initial values are non-negative. A sensitivity analysis of model parameters is performed and the most sensitive ones are identified by means of a state-of-the-art Gauss-Newton method. In particular, parameters representing the proportion of individuals having access to medical facilities are seen to have a large impact on the dynamics of the disease. The model predicts that a gradual increase of these parameters could significantly reduce the disease burden on the population within the next 15 years. AD - Leibniz Univ Hannover, Inst Hort Prod Syst, Hannover, Germany Zuse Inst Berlin, Dept Numer Math, Berlin, Germany Beijing Univ Technol, Beijing Ctr Sci & Engn Comp, Beijing, Peoples R China AN - WOS:000352845100025 AU - Moualeu-Ngangue, D. P. AU - Roblitz, S. AU - Ehrig, R. AU - Deuflhard, P. DA - Apr 13 DO - UNSP e0120607 10.1371/journal.pone.0120607 IS - 4 J2 - Plos One KW - disease transmission hiv reinfection epidemics therapy numbers impact tb LA - English N1 - Cf8xk Times Cited:3 Cited References Count:44 PY - 2015 SN - 1932-6203 ST - Parameter Identification in a Tuberculosis Model for Cameroon T2 - Plos One TI - Parameter Identification in a Tuberculosis Model for Cameroon UR - ://WOS:000352845100025 VL - 10 ID - 4911 ER - TY - JOUR AB - Tuberculosis (TB) is one of the most common infectious diseases and a leading cause of death in the world. Despite the full implementation of Revised National Tuberculosis Control Programme, the disease continues to be a leading cause of morality and economic burden in India. The basic reproduction is a fundamental key parameter that quantifies the spread of a disease. In this article, we present a Bayesian melding approach to estimate the basic reproduction number using a deterministic model of TB. We present a point estimate of the basic reproduction number of 35 states and union territories of India during 2006 to 2011. The basic reproduction number of TB for India is computed to be 0.92, which indicates the slow elimination of TB in India during 2006 to 2011. AD - Indian Inst Technol Mandi, Mandi 175001, Himachal Prades, India Univ Cambridge, Cambridge, England AN - WOS:000361489600005 AU - Narula, P. AU - Azad, S. AU - Lio, P. DA - Oct DO - 10.1177/1010539515595068 IS - 7 J2 - Asia-Pac J Public He KW - tuberculosis bayesian melding basic reproduction number indian states dynamics model impact population epidemics diseases delhi dots LA - English N1 - Cr6wt Times Cited:0 Cited References Count:29 PY - 2015 SN - 1010-5395 SP - 723-732 ST - Bayesian Melding Approach to Estimate the Reproduction Number for Tuberculosis Transmission in Indian States and Union Territories T2 - Asia-Pacific Journal of Public Health TI - Bayesian Melding Approach to Estimate the Reproduction Number for Tuberculosis Transmission in Indian States and Union Territories UR - ://WOS:000361489600005 VL - 27 ID - 4912 ER - TY - JOUR AB - BACKGROUND: Although tuberculosis is a major cause of morbidity and mortality worldwide, available funding falls far short of that required for effective control. Economic and spillover consequences of investments in the treatment of tuberculosis are unclear, particularly when steep gradients in the disease and response are linked by population movements, such as that between Papua New Guinea (PNG) and the Australian cross-border region. OBJECTIVE: To undertake an economic evaluation of Australian support for the expansion of basic Directly Observed Treatment, Short Course in the PNG border area of the South Fly from the current level of 14% coverage. METHODS: Both cost-utility analysis and cost-benefit analysis were applied to models that allow for population movement across regions with different characteristics of tuberculosis burden, transmission, and access to treatment. Cost-benefit data were drawn primarily from estimates published by the World Health Organization, and disease transmission data were drawn from a previously published model. RESULTS: Investing $16 million to increase basic Directly Observed Treatment, Short Course coverage in the South Fly generates a net present value of roughly $74 million for Australia (discounted 2005 dollars). The cost per disability-adjusted life-year averted and quality-adjusted life-year saved for PNG is $7 and $4.6, respectively. CONCLUSIONS: Where regions with major disparities in tuberculosis burden and health system resourcing are connected through population movements, investments in tuberculosis control are of mutual benefit, resulting in net health and economic gains on both sides of the border. These findings are likely to inform the case for appropriate investment in tuberculosis control globally. AD - Crawford School of Public Policy, The Australian National University, Canberra, ACT, Australia. School of Mathematical and Physical Sciences, University of Newcastle, Callaghan, New South Wales, Australia; IBM Research Australia, Melbourne, Victoria, Australia. Crawford School of Public Policy, The Australian National University, Canberra, ACT, Australia. Electronic address: tom.kompas@anu.edu.au. National Centre for Epidemiology and Population Health, The Australian National University, Canberra, Australia. AN - 25773553 AU - Nguyen, H. T. AU - Hickson, R. I. AU - Kompas, T. AU - Mercer, G. N. AU - Lokuge, K. M. DA - Mar DO - 10.1016/j.jval.2014.11.008 IS - 2 KW - Antitubercular Agents/*economics/therapeutic use Australia/epidemiology Cost-Benefit Analysis/*methods Humans Papua New Guinea/epidemiology Tuberculosis/drug therapy/*economics/*epidemiology Australia Dots Png cost-benefit analysis cost-utility analysis metapopulation model tuberculosis control N1 - Nguyen, Hoa Thi Minh Hickson, Roslyn I Kompas, Tom Mercer, Geoffry N Lokuge, Kamalini M eng Research Support, Non-U.S. Gov't 2015/03/17 06:00 Value Health. 2015 Mar;18(2):180-8. doi: 10.1016/j.jval.2014.11.008. Epub 2015 Jan 13. PY - 2015 SN - 1524-4733 (Electronic) 1098-3015 (Linking) SP - 180-8 ST - Strengthening tuberculosis control overseas: who benefits? T2 - Value Health TI - Strengthening tuberculosis control overseas: who benefits? UR - https://www.ncbi.nlm.nih.gov/pubmed/25773553 VL - 18 ID - 4924 ER - TY - JOUR AB - This work examines the global stability of the disease equilibria of three tuberculosis mathematical models that considered the effect of case detection vis a vis the implementation of the direct observation therapy strategy, factors that enhances the case detection rate and effect of heterogeneity in susceptibility and disease progression. Both linear and non-linear Lyapunov functions are constructed and used to show that the disease-free equilibrium is globally asymptotically stable when the corresponding effective reproduction number is less than or equal to one. However, under some special cases where the disease-induced death is insignificant, the endemic equilibrium is globally asymptotically stable when the effective reproduction number is greater than one. AD - [Okuonghae, D.] Univ Benin, Dept Math, Benin, Edo State, Nigeria. Okuonghae, D (reprint author), Univ Benin, Dept Math, Benin, Edo State, Nigeria. danny.okuonghae@corpus-christi.oxon.org AN - WOS:000213185600024 AU - Okuonghae, D. DA - Jun DO - 10.1007/s12190-014-0811-4 IS - 1-2 J2 - J. Appl. Math. Comput. KW - Tuberculosis Mathematical model Global stability Lyapunov Case detection Heterogeneity Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: V95GR Times Cited: 1 Cited Reference Count: 18 Okuonghae, D. 1 0 Springer heidelberg Heidelberg 1865-2085 PY - 2015 SN - 1598-5865 SP - 421-439 ST - Lyapunov functions and global properties of some tuberculosis models T2 - Journal of Applied Mathematics and Computing TI - Lyapunov functions and global properties of some tuberculosis models UR - ://WOS:000213185600024 VL - 48 ID - 5302 ER - TY - JOUR AB - Tuberculosis is a global disease with much significant impact. Well over two million deaths are recorded each year due to Mycobacterium tuberculosis. The work by Colijn et al. (J Theor Biol 247, 765-774, 2007) examined two mathematical models (delay differential equation and network models) that explored the role of the contact structure of the population and found that in declining epidemics, localized outbreaks may occur as a result of contact heterogeneities even in the absence of host or strain variability. In this work, we carry out several qualitative studies (including the use of Sturm sequences for obtaining conditions on bifurcations) on the differential equation model with a time delay in Ref. Colijn et al., J Theor Biol 247, 765-774 (2007), and explicitly obtain threshold conditions for disease eradication as well as existence of bifurcations depending on a critical delay value which characterize the duration of fast latency. Further analysis showed the existence of a transcritical bifurcation when the reproduction number was less than one with the disease-free equilibrium co-existing with just one endemic state that was shown to be stable; the period of fast latency and the reinfection progression rate were shown to be very significant in the dynamics of the disease viz a viz the individuals who progressed to active TB within 5 years of their infection. AD - Univ Benin, Dept Math, Benin, Edo State, Nigeria. Okuonghae, D (reprint author), Univ Benin, Dept Math, Benin, Edo State, Nigeria. danny.okuonghae@corpus-christi.oxon.org AN - WOS:000355632700005 AU - Okuonghae, D. DA - Apr DO - 10.1007/s12591-013-0190-6 IS - 2 J2 - Differ. Equat. Dyn. Syst. KW - Tuberculosis Mathematical model Treatment Self cure Delay Fast latency therapy strategy dots mycobacterium-tuberculosis immune-response dynamics transmission epidemics nigeria Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: CJ6VI Times Cited: 0 Cited Reference Count: 28 Okuonghae, D. 0 1 Springer india New delhi 0974-6870 PY - 2015 SN - 0971-3514 SP - 181-194 ST - A Note on Some Qualitative Properties of a Tuberculosis Differential Equation Model with a Time Delay T2 - Differential Equations and Dynamical Systems TI - A Note on Some Qualitative Properties of a Tuberculosis Differential Equation Model with a Time Delay UR - ://WOS:000355632700005 VL - 23 ID - 5321 ER - TY - JOUR AB - This work extends a mathematical model for the transmission dynamics of tuberculosis that examined the impact of certain factors on tuberculosis case detection (Okuonghae and Omosigho, 2011). The extended model now classifies the latently infected individuals by their level of tuberculosis awareness (as was done for the susceptible sub-population) and further expands the number of key factors that can positively affect the tuberculosis case detection rate. The effect of these identified factors on the associated reproduction number of the model is considered. It is shown that the system can undergo the phenomenon of backward bifurcation when the associated reproduction number of the model is less than unity; in a special case, the effect of exogenous re-infection on the backward bifurcation phenomenon is significantly dictated by the level of awareness of the latently infected individuals. Qualitative and quantitative analysis of the model showed the effect of key identified factors on the dynamics of tuberculosis while suggesting a serious concentration on tuberculosis awareness programmes, active case finding strategies and use of active cough identification for identifying likely TB cases and sustaining awareness campaigns over a long period of time. AD - Department of Mathematics, University of Benin Benin City, Nigeria. AN - 26858691 AU - Okuonghae, D. AU - Ikhimwin, B. O. C2 - PMC4726775 DO - 10.3389/fmicb.2015.01530 DP - NLM ET - 2016/02/10 J2 - Frontiers in microbiology KW - awareness level bifurcation mathematical model simulation tuberculosis LA - eng N1 - Okuonghae, Daniel Ikhimwin, Bernard O Journal Article Switzerland Front Microbiol. 2016 Jan 26;6:1530. doi: 10.3389/fmicb.2015.01530. eCollection 2015. PY - 2015 SN - 1664-302X (Print) 1664-302x SP - 1530 ST - Dynamics of a Mathematical Model for Tuberculosis with Variability in Susceptibility and Disease Progressions Due to Difference in Awareness Level T2 - Front Microbiol TI - Dynamics of a Mathematical Model for Tuberculosis with Variability in Susceptibility and Disease Progressions Due to Difference in Awareness Level VL - 6 ID - 1075 ER - TY - JOUR AB - BACKGROUND: Tuberculosis (TB) and under-nutrition are widespread in many low and middle-income countries. Momentum to prioritize under-nutrition has been growing at an international level, as demonstrated by the "Scaling Up Nutrition" movement. Low body mass index is an important risk factor for developing TB disease. The objective of this study was to project future trends in TB related outcomes under different scenarios for reducing under-nutrition in the adult population in the Central Eastern states of India. METHODS: A compartmental TB transmission model stratified by body mass index was parameterized using national and regional data from India. We compared TB related mortality and incidence under several scenarios that represented a range of policies and programs designed to reduce the prevalence of under-nutrition, based on the experience and observed trends in similar countries. RESULTS: The modeled nutrition intervention scenarios brought about reductions in TB incidence and TB related mortality in the Central Eastern Indian states ranging from 43% to 71% and 40% to 68% respectively, relative to the scenario of no nutritional intervention. Modest reductions in under-nutrition averted 4.8 (95% UR 0.5, 17.1) million TB cases and 1.6 (95% UR 0.5, 5.2) million TB related deaths over a period of 20 years of intervention, relative to the scenario of no nutritional intervention. Complete elimination of under-nutrition in the Central Eastern states averted 9.4 (95% UR 1.5, 30.6) million TB cases and 3.2 (95% UR 0.7-, 10.1) million TB related deaths, relative to the scenario of no nutritional intervention. CONCLUSION: Our study suggests that intervening on under-nutrition could have a substantial impact on TB incidence and mortality in areas with high prevalence of under-nutrition, even if only small gains in under-nutrition can be achieved. Focusing on under-nutrition may be an effective way to reduce both rates of TB and other diseases associated with under-nutrition. AD - Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America; Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Infectious Disease Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America. AN - 26046649 AU - Oxlade, O. AU - Huang, C. C. AU - Murray, M. C2 - PMC4457886 DO - 10.1371/journal.pone.0128187 DP - NLM ET - 2015/06/06 IS - 6 J2 - PloS one KW - Body Mass Index Female Humans Incidence India/epidemiology Malnutrition/prevention & control *Models, Theoretical Nutritional Status Risk Factors Survival Rate Tuberculosis, Pulmonary/*epidemiology/mortality LA - eng N1 - 1932-6203 Oxlade, Olivia Huang, Chuan-Chin Murray, Megan Canadian Institutes of Health Research/Canada Journal Article Research Support, Non-U.S. Gov't United States PLoS One. 2015 Jun 5;10(6):e0128187. doi: 10.1371/journal.pone.0128187. eCollection 2015. PY - 2015 SN - 1932-6203 SP - e0128187 ST - Estimating the Impact of Reducing Under-Nutrition on the Tuberculosis Epidemic in the Central Eastern States of India: A Dynamic Modeling Study T2 - PLoS One TI - Estimating the Impact of Reducing Under-Nutrition on the Tuberculosis Epidemic in the Central Eastern States of India: A Dynamic Modeling Study VL - 10 ID - 1327 ER - TY - JOUR AB - BACKGROUND: Tuberculosis (TB) programs must invest in a variety of TB specific activities in order to reach ambitious global targets. Uncertainty exists surrounding the potential impact of each of these activities. The objective of our study was to model different interventions and quantify their impact on epidemiologic outcomes and costs from the health system perspective. METHODS: Decision analysis was used to define the TB patient trajectory within the health system of three different countries. We considered up to seven different interventions that could affect either the natural history of TB, or patient trajectories within the health system. The expected impact of interventions were derived from published studies where possible. Epidemiologic outcomes and associated health system costs were projected for each scenario. RESULTS: With no specific intervention, TB related death rates are high and less than 10% of the population starts on correct treatment. Interventions that either prevent cases or affect all patients with TB disease early in their trajectory are expected to have the biggest impact, regardless of underlying epidemiologic characteristics of the setting. In settings with a private sector, improving diagnosis and appropriate treatment across all sectors is expected to have a major impact on outcomes. CONCLUSION: In all settings, the greatest benefit will come from early diagnosis of all forms of TB. Once this has been achieved more specific interventions, such as those targeting HIV, drug resistance or the private sector can be integrated to increase impact. AD - McGill University and the McGill International TB Centre, Montreal, Canada. olivia.oxlade@mcgill.ca. United States Agency for International Development, Washington, DC, USA. apiatek@usaid.gov. United States Agency for International Development, Washington, DC, USA. cvincent@usaid.gov. McGill University and the McGill International TB Centre, Montreal, Canada. dick.menzies@mcgill.ca. Montreal Chest Institute, 3650 St. Urbain St, Montreal, H2X 2P4, PQ, Canada. dick.menzies@mcgill.ca. AN - 25884339 AU - Oxlade, O. AU - Piatek, A. AU - Vincent, C. AU - Menzies, D. C2 - PMC4335678 DA - Feb 13 DO - 10.1186/s12889-015-1480-4 DP - NLM ET - 2015/04/18 J2 - BMC public health KW - Adult *Decision Support Techniques Delivery of Health Care/*economics Female Health Promotion/*methods Humans Internationality Male Middle Aged Public Health Tuberculosis/*epidemiology/*prevention & control L1 - internal-pdf://0603524548/Oxlade-2015-Modeling the impact of tuberculosi.pdf LA - eng N1 - 1471-2458 Oxlade, Olivia Piatek, Amy Vincent, Cheri Menzies, Dick Journal Article Research Support, U.S. Gov't, Non-P.H.S. England BMC Public Health. 2015 Feb 13;15:141. doi: 10.1186/s12889-015-1480-4. PY - 2015 SN - 1471-2458 SP - 141 ST - Modeling the impact of tuberculosis interventions on epidemiologic outcomes and health system costs T2 - BMC Public Health TI - Modeling the impact of tuberculosis interventions on epidemiologic outcomes and health system costs UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335678/pdf/12889_2015_Article_1480.pdf VL - 15 ID - 1383 ER - TY - JOUR AB - BACKGROUND: Diabetes increases the risk of tuberculosis incidence and the risk of adverse treatment outcomes in patients with tuberculosis. Because prevalence of diabetes is increasing in low-income and middle-income countries where the burden of tuberculosis is high, prevention of diabetes carries the potential to improve tuberculosis control worldwide. METHODS: We used dynamic tuberculosis transmission models to analyse the potential effect of diabetes on tuberculosis epidemiology in 13 countries with high tuberculosis burden. We used data for previous diabetes prevalence in each country and constructed scenarios to represent the potential ranges of future diabetes prevalence. The country-specific model was calibrated to the estimated trend of tuberculosis incidence. We estimated the tuberculosis burden that can be reduced by alternative scenarios of diabetes prevention. FINDINGS: If the prevalence of diabetes continues to rise as it has been in the past decade in the 13 countries (base case scenario), by 2035, the cumulative reduction in tuberculosis incidence would be 8.8% (95% credible interval [CrI] 4.0-15.8) and mortality would be 34.0% (30.3-39.6). Lowering the prevalence of diabetes by an absolute level of 6.6-13.8% could accelerate the decline of tuberculosis incidence by an absolute level of 11.5-25.2% and tuberculosis mortality by 8.7-19.4%. Compared with the base case scenario, stopping the rise of diabetes would avoid 6.0 million (95% CrI 5.1-6.9) incident cases and 1.1 million (1.0-1.3) tuberculosis deaths in 13 countries during 20 years. If interventions reduce diabetes incidence by 35% by 2025, 7.8 million (6.7-9.0) tuberculosis cases and 1.5 million (1.3-1.7) tuberculosis deaths could be averted by 2035. INTERPRETATION: The diabetes epidemic could substantially affect tuberculosis epidemiology in high burden countries. The communicable disease and non-communicable disease sectors need to move beyond conventional boundaries and link with each other to form a joint response to diabetes and tuberculosis. FUNDING: Taiwan National Science Council. AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. Department of Epidemiology and Biostatistics, University of British Columbia, Vancouver, Canada. MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address: fangct@ntu.edu.tw. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address: hsienho@ntu.edu.tw. AN - 25754415 AU - Pan, S. C. AU - Ku, C. C. AU - Kao, D. AU - Ezzati, M. AU - Fang, C. T. AU - Lin, H. H. DA - May DO - 10.1016/s2213-8587(15)00042-x DP - NLM ET - 2015/03/11 IS - 5 J2 - The lancet. Diabetes & endocrinology KW - Adult Diabetes Complications/*epidemiology Disease Transmission, Infectious/statistics & numerical data Female Global Health Humans Incidence Male Models, Biological Prevalence Risk Factors Sensitivity and Specificity Tuberculosis/*epidemiology/*prevention & control Young Adult LA - eng N1 - 2213-8595 Pan, Sung-Ching Ku, Chu-Chang Kao, Diana Ezzati, Majid Fang, Chi-Tai Lin, Hsien-Ho 100693/Wellcome Trust/United Kingdom Journal Article Research Support, Non-U.S. Gov't England Lancet Diabetes Endocrinol. 2015 May;3(5):323-30. doi: 10.1016/S2213-8587(15)00042-X. Epub 2015 Mar 6. PY - 2015 SN - 2213-8587 SP - 323-30 ST - Effect of diabetes on tuberculosis control in 13 countries with high tuberculosis: a modelling study T2 - Lancet Diabetes Endocrinol TI - Effect of diabetes on tuberculosis control in 13 countries with high tuberculosis: a modelling study VL - 3 ID - 1437 ER - TY - JOUR AB - Despite extensive studies on the interactions between Mycobacterium tuberculosis (M.tb) and macrophages, the mechanism by which pathogen evades anti-microbial responses and establishes persistence within the host cell remains unknown. In this study, we developed a four-dimensional ODE model to describe the dynamics of host-pathogen interactions in the early phase of macrophage infection. The aim was to characterize the role of host cellular regulators such as iron and lipids, in addition to the bactericidal effector molecule Nitric Oxide. Conditions for existence and stability of the equilibrium point were analysed by examining the behaviour of the model through numerical simulations. These computational investigations revealed that it was the ability of pathogen to interfere with iron and lipid homeostatic pathways of the host cell, which ensured a shift in balance towards pathogen survival and persistence. Interestingly, small perturbations in this equilibrium triggered the cell's bactericidal response, thereby producing an oscillatory dynamic for disease progression. AD - International Centre for Genetic Engineering and Biotechnology. Aruna Asaf Ali Marg 110 067, New Delhi, India. Electronic address: gabriele@icgeb.res.in. International Centre for Genetic Engineering and Biotechnology. Aruna Asaf Ali Marg 110 067, New Delhi, India; Translational Health Science and Technology Institute, Drug Discovery Research Centre, Plot No. 496, Phase-III, Udyog Vihar, Gurgaon 122016, Haryana, India. Electronic address: kanury@icgeb.res.in. Translational Health Science and Technology Institute, Drug Discovery Research Centre, Plot No. 496, Phase-III, Udyog Vihar, Gurgaon 122016, Haryana, India. Electronic address: samrat.chatterjee@thsti.res.in. AN - 25865521 AU - Pedruzzi, G. AU - Rao, K. V. AU - Chatterjee, S. DA - Jul 07 DO - 10.1016/j.jtbi.2015.03.031 DP - NLM ET - 2015/04/14 J2 - Journal of theoretical biology KW - Animals *Computer Simulation Host-Pathogen Interactions/*immunology Humans *Immune Evasion Macrophages/*immunology *Models, Immunological Mycobacterium tuberculosis/*physiology Differential equations Host-pathogen interaction Iron Lipids Nitric Oxide LA - eng N1 - 1095-8541 Pedruzzi, Gabriele Rao, Kanury V S Chatterjee, Samrat Journal Article England J Theor Biol. 2015 Jul 7;376:105-17. doi: 10.1016/j.jtbi.2015.03.031. Epub 2015 Apr 9. PY - 2015 SN - 0022-5193 SP - 105-17 ST - Mathematical model of mycobacterium-host interaction describes physiology of persistence T2 - J Theor Biol TI - Mathematical model of mycobacterium-host interaction describes physiology of persistence VL - 376 ID - 1395 ER - TY - JOUR AB - Tuberculosis (TB) is a leading cause of human mortality due to infectious disease. Treatment default is a relevant factor which reduces therapeutic success and increases the risk of resistant TB. In this work we analyze the relation between treatment default and treatment length along with its consequence on the disease spreading. We use a stylized model structure to explore, systematically, the effects of varying treatment duration and compliance. We find that shortening treatment alone may not reduce TB prevalence, especially in regions where transmission intensity is high, indicating the necessity of complementing this action with increased compliance. A family of default functions relating the proportion of defaulters to the treatment length is considered and adjusted to a particular dataset. We find that the epidemiological benefits of shorter treatment regimens are tightly associated with increases in treatment compliance and depend on the epidemiological background. AD - Instituto de Fisica, Universidade Federal da Bahia, Campus Universitario de Ondina, 40210-340, Salvador, Brazil. Electronic address: suani@ufba.br. Departamento de Matematica and Centro de Matematica e Aplicacoes, Universidade Nova de Lisboa, Quinta da Torre, 2829-516, Caparica, Portugal. Electronic address: pcpr@fct.unl.pt. Instituto de Fisica, Universidade Federal da Bahia, Campus Universitario de Ondina, 40210-340, Salvador, Brazil. Electronic address: randrade@ufba.br. Faculdade de Educacao, Universidade Federal da Grande Dourados, Rodovia Dourados, Itahum, km 12, 79804-070 - Dourados, Brazil. Electronic address: hiraldoserra@ufgd.edu.br. Instituto Gulbenkian de Ciencia, Oeiras, Portugal. Electronic address: jmlopes@igc.pt. Instituto Gulbenkian de Ciencia, Oeiras, Portugal. Electronic address: ggomes@igc.pt. AN - 26163050 AU - Pinho, S. T. AU - Rodrigues, P. AU - Andrade, R. F. AU - Serra, H. AU - Lopes, J. S. AU - Gomes, M. G. DA - Sep DO - 10.1016/j.tpb.2015.06.004 DP - NLM ET - 2015/07/15 J2 - Theoretical population biology KW - Antitubercular Agents/*administration & dosage Drug Administration Schedule Humans *Medication Adherence Models, Biological Tuberculosis/*drug therapy/*transmission Default Mathematical model Reinfection Treatment Tuberculosis LA - eng N1 - 1096-0325 Pinho, S T R Rodrigues, P Andrade, R F S Serra, H Lopes, J S Gomes, M G M Journal Article Research Support, Non-U.S. Gov't United States Theor Popul Biol. 2015 Sep;104:68-77. doi: 10.1016/j.tpb.2015.06.004. Epub 2015 Jul 7. PY - 2015 SN - 0040-5809 SP - 68-77 ST - Impact of tuberculosis treatment length and adherence under different transmission intensities T2 - Theor Popul Biol TI - Impact of tuberculosis treatment length and adherence under different transmission intensities VL - 104 ID - 1291 ER - TY - JOUR AB - High resolution tests for genetic variation reveal that individuals may simultaneously host more than one distinct strain of Mycobacterium tuberculosis. Previous studies find that this phenomenon, which we will refer to as "mixed infection", may affect the outcomes of treatment for infected individuals and may influence the impact of population-level interventions against tuberculosis. In areas where the incidence of TB is high, mixed infections have been found in nearly 20% of patients; these studies may underestimate the actual prevalence of mixed infection given that tests may not be sufficiently sensitive for detecting minority strains. Specific reasons for failing to detect mixed infections would include low initial numbers of minority strain cells in sputum, stochastic growth in culture and the physical division of initial samples into parts (typically only one of which is genotyped). In this paper, we develop a mathematical framework that models the study designs aimed to detect mixed infections. Using both a deterministic and a stochastic approach, we obtain posterior estimates of the prevalence of mixed infection. We find that the posterior estimate of the prevalence of mixed infection may be substantially higher than the fraction of cases in which it is detected. We characterize this bias in terms of the sensitivity of the genotyping method and the relative growth rates and initial population sizes of the different strains collected in sputum. AD - Imperial College London, United Kingdom. Electronic address: giacomo.plazzotta11@imperial.ac.uk. Brigham and Womens Hospital, Harvard School of Public Health, United States. Imperial College London, United Kingdom. AN - 25553967 AU - Plazzotta, G. AU - Cohen, T. AU - Colijn, C. DA - Mar 07 DO - 10.1016/j.jtbi.2014.12.009 DP - NLM ET - 2015/01/03 J2 - Journal of theoretical biology KW - Bacterial Typing Techniques/methods Bias (Epidemiology) Coinfection/*diagnosis/epidemiology Humans *Models, Biological Mycobacterium tuberculosis/*classification/isolation & purification Prevalence Research Design Specimen Handling/methods Sputum/microbiology Tuberculosis/*diagnosis/epidemiology/microbiology Estimates of the prevalence of mixed infection Majority and minority strain Posterior distribution of the prevalence of mixed infection Prevalence of mixed infection Study designs aimed to detect mixed infection LA - eng N1 - 1095-8541 Plazzotta, Giacomo Cohen, Ted Colijn, Caroline DP2 OD006663/OD/NIH HHS/United States D2OD006663/OD/NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England J Theor Biol. 2015 Mar 7;368:67-73. doi: 10.1016/j.jtbi.2014.12.009. Epub 2014 Dec 29. PY - 2015 SN - 0022-5193 SP - 67-73 ST - Magnitude and sources of bias in the detection of mixed strain M. tuberculosis infection T2 - J Theor Biol TI - Magnitude and sources of bias in the detection of mixed strain M. tuberculosis infection VL - 368 ID - 1505 ER - TY - JOUR AB - For millennia tuberculosis (TB) has shown a successful strategy to survive, making it one of the world's deadliest infectious diseases. This resilient behavior is based not only on remaining hidden in most of the infected population, but also by showing slow evolution in most sick people. The course of the disease within a population is highly related to its heterogeneity. Thus, classic epidemiological approaches with a top-down perspective have not succeeded in understanding its dynamics. In the past decade a few individual-based models were built, but most of them preserved a top-down view that makes it difficult to study a heterogeneous population. We propose an individual-based model developed with a bottom-up approach to studying the dynamics of pulmonary TB in a certain population, considered constant. Individuals may belong to the following classes: healthy, infected, sick, under treatment, and treated with a probability of relapse. Several variables and parameters account for their age, origin (native or immigrant), immunodeficiency, diabetes, and other risk factors (smoking and alcoholism). The time within each infection state is controlled, and sick individuals may show a cavitated disease or not that conditions infectiousness. It was implemented in NetLogo because it allows non-modelers to perform virtual experiments with a user-friendly interface. The simulation was conducted with data from Ciutat Vella, a district of Barcelona with an incidence of 67 TB cases per 100,000 inhabitants in 2013. Several virtual experiments were performed to relate the disease dynamics with the structure of the infected subpopulation (e.g., the distribution of infected times). Moreover, the short-term effect of health control policies on modifying that structure was studied. Results show that the characteristics of the population are crucial for the local epidemiology of TB. The developed user-friendly tool is ready to test control strategies of disease in any city in the short-term. AD - Departament de Fisica, Escola Superior d'Agricultura de Barcelona, Universitat Politecnica de Catalunya-BarcelonaTech Barcelona, Spain. Departament d'Estadistica i Investigacio Operativa, Facultat d'Informatica de Barcelona, Universitat Politecnica de Catalunya-BarcelonaTech, Barcelona Supercomputing Centre (BSC-CNS) Barcelona, Spain. Unitat de Tuberculosi Experimental, Fundacio Institut d'Investigacio en Ciencies de la Salut Germans Trias i Pujol, Universitat Autonoma de Barcelona Badalona, Spain. AN - 26793189 AU - Prats, C. AU - Montanola-Sales, C. AU - Gilabert-Navarro, J. F. AU - Valls, J. AU - Casanovas-Garcia, J. AU - Vilaplana, C. AU - Cardona, P. J. AU - Lopez, D. C2 - PMC4709466 DO - 10.3389/fmicb.2015.01564 DP - NLM ET - 2016/01/23 J2 - Frontiers in microbiology KW - HIV-tuberculosis contact tracing diagnosis delay epidemiology immigrant individual-based model risk factors tuberculosis LA - eng N1 - Prats, Clara Montanola-Sales, Cristina Gilabert-Navarro, Joan F Valls, Joaquim Casanovas-Garcia, Josep Vilaplana, Cristina Cardona, Pere-Joan Lopez, Daniel Journal Article Switzerland Front Microbiol. 2016 Jan 12;6:1564. doi: 10.3389/fmicb.2015.01564. eCollection 2015. PY - 2015 SN - 1664-302X (Print) 1664-302x SP - 1564 ST - Individual-Based Modeling of Tuberculosis in a User-Friendly Interface: Understanding the Epidemiological Role of Population Heterogeneity in a City T2 - Front Microbiol TI - Individual-Based Modeling of Tuberculosis in a User-Friendly Interface: Understanding the Epidemiological Role of Population Heterogeneity in a City VL - 6 ID - 1092 ER - TY - JOUR AB - Vaccine effect, as measured in clinical trials, may not accurately reflect population-level impact. Furthermore, little is known about how sensitive apparent or real vaccine impacts are to factors such as the risk of re-infection or the mechanism of protection. We present a dynamic compartmental model to simulate vaccination for endemic infections. Several measures of effectiveness are calculated to compare the real and apparent impact of vaccination, and assess the effect of a range of infection and vaccine characteristics on these measures. Although broadly correlated, measures of real and apparent vaccine effectiveness can differ widely. Vaccine impact is markedly underestimated when primary infection provides partial natural immunity, when coverage is high and when post-vaccination infectiousness is reduced. Despite equivalent efficacy, 'all or nothing' vaccines are more effective than 'leaky' vaccines, particularly in settings with high risk of re-infection and transmissibility. Latent periods result in greater real impacts when risk of re-infection is high, but this effect diminishes if partial natural immunity is assumed. Assessments of population-level vaccine effects against endemic infections from clinical trials may be significantly biased, and vaccine and infection characteristics should be considered when modelling outcomes of vaccination programs, as their impact may be dramatic. AD - Centre for Population Health, Burnet Institute, 85 Commercial Road, Melbourne 3004 Australia. Victorian Infectious Diseases Service, Royal Melbourne Hospital, Grattan Street, Parkville 3050 Australia. Department of Medicine (Royal Melbourne Hospital/Western Hospital), University of Melbourne, Victoria 3010 Australia. Department of Microbiology and Immunology, University of Melbourne, Victoria 3010 Australia. Victorian Tuberculosis Program, Melbourne Health, Melbourne, Victoria 3000 Australia. Centre for Epidemiology and Biostatistics, MSPGH, University of Melbourne, Victoria 3053 Australia. AN - 26482413 AU - Ragonnet, R. AU - Trauer, J. M. AU - Denholm, J. T. AU - Geard, N. L. AU - Hellard, M. AU - McBryde, E. S. C2 - PMC4611864 DA - Oct 20 DO - 10.1038/srep15468 DP - NLM ET - 2015/10/21 J2 - Scientific reports KW - *Communicable Disease Control Computer Simulation Humans *Immunization Programs *Models, Theoretical *Vaccination *Vaccines LA - eng N1 - 2045-2322 Ragonnet, Romain Trauer, James M Denholm, Justin T Geard, Nicholas L Hellard, Margaret McBryde, Emma S Journal Article Research Support, Non-U.S. Gov't England Sci Rep. 2015 Oct 20;5:15468. doi: 10.1038/srep15468. PY - 2015 SN - 2045-2322 SP - 15468 ST - Vaccination Programs for Endemic Infections: Modelling Real versus Apparent Impacts of Vaccine and Infection Characteristics T2 - Sci Rep TI - Vaccination Programs for Endemic Infections: Modelling Real versus Apparent Impacts of Vaccine and Infection Characteristics VL - 5 ID - 1198 ER - TY - JOUR AB - Transmission of the agent of tuberculosis, Mycobacterium tuberculosis, is dependent on social context. A discrete spatial model representing neighborhoods segregated by levels of crowding and immunocompetence is constructed and used to evaluate prevention strategies, based on a number of assumptions about the spatial dynamics of tuberculosis. A cellular automata model is used to (a) construct neighborhoods of different densities, (b) model stochastically local interactions among individuals, and (c) model the spread of tuberculosis within and across neighborhoods over time. Since infected people may become progressively sick but also heal through treatment, the transition among stages was modeled with transition probabilities. A moderate level of successful treatment (40%) dramatically reduced the number of infections across all neighborhoods. Increasing the treatment in neighborhoods of a lower socioeconomic level from 40% to 90% results in an additional decrease of approximately 25% in the number of infected individuals overall. In conclusion, we find that a combination of a moderate level of successful treatment across all areas with more focused treatment efforts in lower socioeconomic areas resulted in the least number of infections over time. AD - [Rehkopf, David] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Furumoto-Dawson, Alice] Univ Chicago, Program Global Environm, Chicago, IL 60637 USA. [Kiszewski, Anthony] Bentley Univ, Dept Nat & Appl Sci, Waltham, MA 02452 USA. [Awerbuch-Friedlander, Tamara] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. Awerbuch-Friedlander, T (reprint author), Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, 665 Huntington Ave,Room 1219, Boston, MA 02115 USA. tamara@hsph.harvard.edu AN - WOS:000362761900001 AU - Rehkopf, D. AU - Furumoto-Dawson, A. AU - Kiszewski, A. AU - Awerbuch-Friedlander, T. C7 - 583819 DO - 10.1155/2015/583819 J2 - Discrete Dyn. Nat. Soc. KW - intrinsic transmission dynamics united-states epidemics approximation homeless contacts disease risk Mathematics Science & Technology - Other Topics LA - English M3 - Article N1 - ISI Document Delivery No.: CT4FO Times Cited: 0 Cited Reference Count: 36 Rehkopf, David Furumoto-Dawson, Alice Kiszewski, Anthony Awerbuch-Friedlander, Tamara 0 1 4 Hindawi publishing corp New york 1607-887x PY - 2015 SN - 1026-0226 SP - 8 ST - Spatial Spread of Tuberculosis through Neighborhoods Segregated by Socioeconomic Position: A Stochastic Automata Model T2 - Discrete Dynamics in Nature and Society TI - Spatial Spread of Tuberculosis through Neighborhoods Segregated by Socioeconomic Position: A Stochastic Automata Model UR - ://WOS:000362761900001 ID - 5357 ER - TY - JOUR AB - Although estimated tuberculosis (TB) incidence is now falling globally, we are unlikely to achieve the Millennium Development Goal (MDG) TB targets without changing the emphasis of the global TB response in high human immunodeficiency virus prevalence settings. Two independent modelling exercises using South African data with different structures and assumptions conclude that, until new drugs, diagnostics and vaccines are available, a fully funded and accessible combination approach to anti-tuberculosis treatment and prevention, based on knowledge of local TB epidemiology and evidence-informed policy, is essential to accelerate progress towards zero new tuberculous infections, zero TB deaths and zero suffering from TB. AD - Joint United Nations Programme on HIV/AIDS Country Office, Pretoria, South Africa. London School of Hygiene & Tropical Medicine, London, UK. World Health Organization, Geneva, Switzerland. London School of Hygiene & Tropical Medicine, London, UK; Public Health England, London, UK. London School of Hygiene & Tropical Medicine, London, UK; The Aurum Institute, Johannesburg, South Africa; School of Public Health, University of Witwatersrand, Johannesburg, South Africa. National Department of Health, Pretoria, South Africa. AN - 25519784 AU - Reid, A. AU - Grant, A. D. AU - White, R. G. AU - Dye, C. AU - Vynnycky, E. AU - Fielding, K. AU - Churchyard, G. AU - Pillay, Y. DA - Jan DO - 10.5588/ijtld.14.0078 DP - NLM ET - 2014/12/19 IS - 1 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Anti-Retroviral Agents/pharmacology Antitubercular Agents/pharmacology Cluster Analysis Drug Therapy, Combination HIV Infections/complications/drug therapy/epidemiology Humans Incidence *Models, Theoretical Prevalence Tuberculosis/*drug therapy/*epidemiology/*prevention & control LA - eng N1 - 1815-7920 Reid, A Grant, A D White, R G Dye, C Vynnycky, E Fielding, K Churchyard, G Pillay, Y 001/World Health Organization/International MR/J005088/1/Medical Research Council/United Kingdom U2GPS000811/PHS HHS/United States Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. France Int J Tuberc Lung Dis. 2015 Jan;19(1):5-9. doi: 10.5588/ijtld.14.0078. PY - 2015 SN - 1027-3719 SP - 5-9 ST - Accelerating progress towards tuberculosis elimination: the need for combination treatment and prevention T2 - Int J Tuberc Lung Dis TI - Accelerating progress towards tuberculosis elimination: the need for combination treatment and prevention VL - 19 ID - 1520 ER - TY - JOUR AB - In this work we present an agent-based computational model to study the spreading of the tuberculosis (TB) disease on age-structured populations. The model proposed is a merge of two previous models: an agent-based computational model for the spreading of tuberculosis and a bit-string model for biological aging. The combination of TB with the population aging, reproduces the coexistence of health states, as seen in real populations. In addition, the universal exponential behavior of mortalities curves is still preserved. Finally, the population distribution as function of age shows the prevalence of TB mostly in elders, for high efficacy treatments. (C) 2015 Elsevier B.V. All rights reserved. AD - Univ Fed Fluminense, MCCT, BR-27213145 Volta Redonda, RJ, Brazil Univ Fed Fluminense, Inst Ciencias Exatas ICEx, Dept Fis, BR-27213145 Volta Redonda, RJ, Brazil CNPq, Natl Inst Sci & Technol Complex Syst, Brasilia, DF, Brazil AN - WOS:000352328100006 AU - Rodrigues, C. C. G. AU - Espindola, A. L. AU - Penna, T. J. P. DA - Jun 15 DO - 10.1016/j.physa.2015.02.027 J2 - Physica A KW - agent-based modeling computational epidemiology aging tuberculosis computer-simulation aging model epidemics transmission strategies LA - English N1 - Cf1sl Times Cited:2 Cited References Count:27 PY - 2015 SN - 0378-4371 SP - 52-59 ST - An agent-based computational model for tuberculosis spreading on age-structured populations T2 - Physica a-Statistical Mechanics and Its Applications TI - An agent-based computational model for tuberculosis spreading on age-structured populations UR - ://WOS:000352328100006 VL - 428 ID - 4914 ER - TY - JOUR AB - BACKGROUND: In India as elsewhere, multi-drug resistance (MDR) poses a serious challenge in the control of tuberculosis (TB). The End TB strategy, recently approved by the world health assembly, aims to reduce TB deaths by 95% and new cases by 90% between 2015 and 2035. A key pillar of this approach is early diagnosis of tuberculosis, including use of higher-sensitivity diagnostic testing and universal rapid drug susceptibility testing (DST). Despite limitations of current laboratory assays, universal access to rapid DST could become more feasible with the advent of new and emerging technologies. Here we use a mathematical model of TB transmission, calibrated to the TB epidemic in India, to explore the potential impact of a major national scale-up of rapid DST. To inform key parameters in a clinical setting, we take GeneXpert as an example of a technology that could enable such scale-up. We draw from a recent multi-centric demonstration study conducted in India that involved upfront Xpert MTB/RIF testing of all TB suspects. RESULTS: We find that widespread, public-sector deployment of high-sensitivity diagnostic testing and universal DST appropriately linked with treatment could substantially impact MDR-TB in India. Achieving 75% access over 3 years amongst all cases being diagnosed for TB in the public sector alone could avert over 180,000 cases of MDR-TB (95% CI 44187 - 317077 cases) between 2015 and 2025. Sufficiently wide deployment of Xpert could, moreover, turn an increasing MDR epidemic into a diminishing one. Synergistic effects were observed with assumptions of simultaneously improving MDR-TB treatment outcomes. Our results illustrate the potential impact of new and emerging technologies that enable widespread, timely DST, and the important effect that universal rapid DST in the public sector can have on the MDR-TB epidemic in India. AD - Central TB Division, Government of India, New Delhi, India. Foundation for Innovative New Diagnostics, New Delhi, India. World Health Organization, India Country Office, New Delhi, India. Bill and Melinda Gates Foundation, New Delhi, India. Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom. AN - 26132584 AU - Sachdeva, K. S. AU - Raizada, N. AU - Gupta, R. S. AU - Nair, S. A. AU - Denkinger, C. AU - Paramasivan, C. N. AU - Kulsange, S. AU - Thakur, R. AU - Dewan, P. AU - Boehme, C. AU - Arinaminpathy, N. C2 - PMC4488842 DO - 10.1371/journal.pone.0131438 DP - NLM ET - 2015/07/02 IS - 7 J2 - PloS one KW - Antitubercular Agents/therapeutic use Epidemics/*prevention & control Humans Incidence India/epidemiology *Microbial Sensitivity Tests Models, Theoretical Prevalence Tuberculosis, Multidrug-Resistant/diagnosis/drug therapy/epidemiology/microbiology/*prevention & control/transmission L1 - internal-pdf://4262491213/Sachdeva-2015-The Potential Impact of Up-Front.pdf LA - eng N1 - 1932-6203 Sachdeva, Kuldeep Singh Raizada, Neeraj Gupta, Radhey Shyam Nair, Sreenivas Achuthan Denkinger, Claudia Paramasivan, Chinnambedu Nainarappan Kulsange, Shubhangi Thakur, Rahul Dewan, Puneet Boehme, Catharina Arinaminpathy, Nimalan 001/World Health Organization/International MR/K010174/1/Medical Research Council/United Kingdom Journal Article Research Support, Non-U.S. Gov't United States PLoS One. 2015 Jul 1;10(7):e0131438. doi: 10.1371/journal.pone.0131438. eCollection 2015. PY - 2015 SN - 1932-6203 SP - e0131438 ST - The Potential Impact of Up-Front Drug Sensitivity Testing on India's Epidemic of Multi-Drug Resistant Tuberculosis T2 - PLoS One TI - The Potential Impact of Up-Front Drug Sensitivity Testing on India's Epidemic of Multi-Drug Resistant Tuberculosis UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488842/pdf/pone.0131438.pdf VL - 10 ID - 1307 ER - TY - JOUR AB - BACKGROUND: From 2012 through 2014, the United States experienced acute shortages and price escalations of several first-line anti-tuberculosis (TB) medications. Because secondary TB drug regimens are longer and adverse events occur more frequently with them, we sought to conservatively estimate the cost, to patients and the health care system, of TB treatment and medication adverse events from alternative regimens during drug shortages. METHODS: We assessed the cost of treatment for TB disease in the absence of isoniazid (INH), rifampin (RIF), or pyrazinamide (PZA), or both INH and RIF. We simulated adverse events based on published probabilities using a monthly discrete-time stochastic model. For total costs, we summed costs of medications, routine testing, and treatment of adverse events using procedural terminology codes. We report average cost ratios of TB treatment during drug shortages to standard TB treatment. RESULTS: The cost ratio of TB treatment without INH, RIF, or PZA to standard treatment was 1.7 (Range: 1.2, 2.3), 4.9 (Range: 3.2, 7.3), and 1.1 (Range: 0.7, 1.7) times higher, respectively. Without both INH and RIF, the cost ratio was 18.6 (Range: 10.0, 39.0) times higher. When the prices for INH, RIF and PZA were increased, the cost for standard treatment increased by a factor of 2.7 (Range: 1.9, 3.0). The percentage of patients experiencing at least one adverse event while taking standard therapy was 3.9% (Range: 1.3%, 11.8%). This percentage increased to 51.5% (Range: 20.1%, 83.8%) when RIF was unavailable, and increased to 82.5% (Range: 41.2%, 98.5%) when both INH and RIF were unavailable. CONCLUSIONS: Our conservative model illustrates that an interruption in first-line anti-TB medications leads to appreciable additional costs and adverse events for patients. The availability of these drugs in the United States should be ensured. Models that incorporate the effectiveness of alternative regimens, delays in treatment initiation, and TB transmission can provide broader perspectives on the impact of drug shortages. AD - Colby College, Department of Mathematics and Statistics, Waterville, Maine, United States of America; Francis I. Proctor Foundation, San Francisco, California, United States of America. California Department of Health Tuberculosis Control Branch, Richmond, California, United States of America; Centers for Disease Control and Prevention, Division of Tuberculosis Elimination, Atlanta, Georgia, United States of America. Francis I. Proctor Foundation, San Francisco, California, United States of America; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America. California Department of Health Tuberculosis Control Branch, Richmond, California, United States of America. AN - 26284924 AU - Scott, J. C. AU - Shah, N. AU - Porco, T. AU - Flood, J. C2 - PMC4540488 DO - 10.1371/journal.pone.0134597 DP - NLM ET - 2015/08/19 IS - 8 J2 - PloS one KW - Antitubercular Agents/*economics/*supply & distribution/therapeutic use Cohort Studies Humans *Models, Statistical Resource Allocation Stochastic Processes Tuberculosis/drug therapy United States LA - eng N1 - 1932-6203 Scott, James C Shah, Neha Porco, Travis Flood, Jennifer U01-GM087728/GM/NIGMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural United States PLoS One. 2015 Aug 18;10(8):e0134597. doi: 10.1371/journal.pone.0134597. eCollection 2015. PY - 2015 SN - 1932-6203 SP - e0134597 ST - Cost Resulting from Anti-Tuberculosis Drug Shortages in the United States: A Hypothetical Cohort Study T2 - PLoS One TI - Cost Resulting from Anti-Tuberculosis Drug Shortages in the United States: A Hypothetical Cohort Study VL - 10 ID - 1260 ER - TY - JOUR AB - INTRODUCTION: Case detection by passive case finding (PCF) strategy alone is inadequate for detecting all tuberculosis (TB) cases in high burden settings especially Sub-Saharan Africa. Alternative case detection strategies such as community Active Case Finding (ACF) and Household Contact Investigations (HCI) are effective but empirical evidence of their cost-effectiveness is sparse. The objective of this study was to determine whether adding ACF or HCI compared with standard PCF alone represent cost-effective alternative TB case detection strategies in urban Africa. METHODS: A static decision modeling framework was used to examine the costs and effectiveness of three TB case detection strategies: PCF alone, PCF+ACF, and PCF+HCI. Probability and cost estimates were obtained from National TB program data, primary studies conducted in Uganda, published literature and expert opinions. The analysis was performed from the societal and provider perspectives over a 1.5 year time-frame. The main effectiveness measure was the number of true TB cases detected and the outcome was incremental cost-effectiveness ratios (ICERs) expressed as cost in 2013 US$ per additional true TB case detected. RESULTS: Compared to PCF alone, the PCF+HCI strategy was cost-effective at US$443.62 per additional TB case detected. However, PCF+ACF was not cost-effective at US$1492.95 per additional TB case detected. Sensitivity analyses showed that PCF+ACF would be cost-effective if the prevalence of chronic cough in the population screened by ACF increased 10-fold from 4% to 40% and if the program costs for ACF were reduced by 50%. CONCLUSIONS: Under our baseline assumptions, the addition of HCI to an existing PCF program presented a more cost-effective strategy than the addition of ACF in the context of an African city. Therefore, implementation of household contact investigations as a part of the recommended TB control strategy should be prioritized. AD - Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia, United States of America; Department of Epidemiology and Biostatistics, School of Public Health, College of Health Sciences, Makerere University, Kampala, Uganda. Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia, United States of America. School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda. Department of Health Policy and Management, College of Public Health, University of Georgia, Athens, Georgia, United States of America. AN - 25658592 AU - Sekandi, J. N. AU - Dobbin, K. AU - Oloya, J. AU - Okwera, A. AU - Whalen, C. C. AU - Corso, P. S. C2 - PMC4319733 DO - 10.1371/journal.pone.0117009 DP - NLM ET - 2015/02/07 IS - 2 J2 - PloS one KW - Cost-Benefit Analysis Decision Support Techniques Family Characteristics Humans Mass Screening/*economics Prevalence Residence Characteristics Tuberculosis/*diagnosis/economics/epidemiology Uganda/epidemiology Urbanization L1 - internal-pdf://2770592853/Sekandi-2015-Cost-effectiveness analysis of co.pdf LA - eng N1 - 1932-6203 Sekandi, Juliet N Dobbin, Kevin Oloya, James Okwera, Alphonse Whalen, Christopher C Corso, Phaedra S Journal Article Research Support, Non-U.S. Gov't United States PLoS One. 2015 Feb 6;10(2):e0117009. doi: 10.1371/journal.pone.0117009. eCollection 2015. PY - 2015 SN - 1932-6203 SP - e0117009 ST - Cost-effectiveness analysis of community active case finding and household contact investigation for tuberculosis case detection in urban Africa T2 - PLoS One TI - Cost-effectiveness analysis of community active case finding and household contact investigation for tuberculosis case detection in urban Africa UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319733/pdf/pone.0117009.pdf VL - 10 ID - 1470 ER - TY - JOUR AB - This paper studies the transmission process of Tuberculosis (TB) via mycobacterium virus. Tuberculosis epidemical ways attacks when the weather changes from dry to rainy season. In this study, mathematical modeling of tuberculosis was constructed by using Susceptible-Infected-Recovered (SIR) model. Derived from a system of nonlinear differential equations, a mathematical modeling of the transmission process to the spread of tuberculosis involving vertical transmission process was formed. With some assumptions, the models generated by four-dimensional nonlinear dynamical system are reduced to three dimensions. In fact, when this model is plugin (or compared) to the theoretical model, it was more realistic and suitable for local situation. The results of simulation for SIR model successfully described and predicted the number of TB cases. AD - State Univ Makassar, Fac Math & Nat Sci, Dept Math, Parang Tambung, Sulawesi Selata, Indonesia. Side, S (reprint author), State Univ Makassar, Fac Math & Nat Sci, Dept Math, Parang Tambung, Sulawesi Selata, Indonesia. AN - WOS:000356753200003 AU - Side, S. DA - Feb DO - 10.1166/asl.2015.5840 IS - 2 J2 - Adv. Sci. Lett. KW - Tuberculosis SIR Model Non-Linear Differential Equation Science & Technology - Other Topics LA - English M3 - Proceedings Paper N1 - ISI Document Delivery No.: CL2DG Times Cited: 0 Cited Reference Count: 8 Side, Syafruddin 1st International Conference on Science and Technology Applications in Climate Change (STACLIM) Nov 17-18, 2014 Indonesia side, syafruddin/0000-0002-5111-7220 0 Amer scientific publishers Valencia 1936-7317 PY - 2015 SN - 1936-6612 SP - 137-139 ST - A Susceptible-Infected-Recovered Model and Simulation for Transmission of Tuberculosis T2 - Advanced Science Letters TI - A Susceptible-Infected-Recovered Model and Simulation for Transmission of Tuberculosis UR - ://WOS:000356753200003 VL - 21 ID - 5348 ER - TY - JOUR AB - We propose a population model for TB-HIV/AIDS coinfection transmission dynamics, which considers antiretroviral therapy for HIV infection and treatments for latent and active tuberculosis. The HIV-only and TB-only sub-models are analyzed separately, as well as the TB-HIV/AIDS full model. The respective basic reproduction numbers are computed, equilibria and stability are studied. Optimal control theory is applied to the TB-HIV/AIDS model and optimal treatment strategies for co-infected individuals with HIV and TB are derived. Numerical simulations to the optimal control problem show that non intuitive measures can lead to the reduction of the number of individuals with active TB and AIDS. AD - Univ Aveiro, Dept Math, Ctr Res & Dev Math & Applicat CIDMA, P-3810193 Aveiro, Portugal AN - WOS:000353474800033 AU - Silva, C. J. AU - Torres, D. F. M. DA - Sep DO - 10.3934/dcds.2015.35.4639 IS - 9 J2 - Discrete Cont Dyn-A KW - tuberculosis human immunodeficiency virus coinfection treatment equilibrium stability optimal control infectious-diseases tuberculosis model hiv-infection transmission dynamics LA - English N1 - Sp. Iss. SI Cg7hx Times Cited:9 Cited References Count:47 PY - 2015 SN - 1078-0947 SP - 4639-4663 ST - A Tb-Hiv/Aids Coinfection Model and Optimal Control Treatment T2 - Discrete and Continuous Dynamical Systems TI - A Tb-Hiv/Aids Coinfection Model and Optimal Control Treatment UR - ://WOS:000353474800033 VL - 35 ID - 4915 ER - TY - JOUR AB - The optimality singular controls of a VSEIR model of Tuberculosis are analyzed in this paper. There are controls that correspond to time- vary the vaccination and treatment schedules. A Hamiltonian (H) of the model is defined. The model is splited into separate one-dimensional problems, the so-called switching functions. The extreme occurs when a switching function disappears suddenly over an open interval. In which the derivatives of switching function must disappears suddenly and this typically allows computing such a control. The second-order of the function is not vanishing, which satisfied Legendre-Clebsh condition, and thus the controls of these kinds are called singular. In this work, our main emphasis is on a complete analysis of the optimum properties corresponding to trajectories. The result shows that vaccination control is singular, but treatment is not. This means that the model reached the optimality control for vaccination schedule, but not treatment schedule. AD - [Sinaga, Marlina Setia; Rangkuti, Yulita Molliq] Univ Negari Medan, UNIMED, Fac Math & Nat Sci, Dept Math, Medan 20221, North Sumatera, Indonesia. Sinaga, MS (reprint author), Univ Negari Medan, UNIMED, Fac Math & Nat Sci, Dept Math, Medan 20221, North Sumatera, Indonesia. lin_2508@yahoo.co.id; yulitamolliq@yahoo.com AN - WOS:000379385800013 AU - Sinaga, M. S. AU - Rangkuti, Y. M. KW - VSEIR model Singular control Legendre-Clebsh switch functional Computer Science Mathematics LA - English M3 - Proceedings Paper N1 - ISI Document Delivery No.: BF0SL Times Cited: 0 Cited Reference Count: 8 Sinaga, Marlina Setia Rangkuti, Yulita Molliq Majid, ZA 7th International Conference on Research and Education in Mathematics (ICREM) Aug 25-27, 2015 Kuala Lumpur, MALAYSIA Univ Putra Malaysia, Inst Math Res, IEEE Women Engn, Akademi Sains Malaysia, Bandung Inst Technol, Vietnam Acad Sci & Technol, Inst Math 0 Ieee New york 978-1-4673-7506-1 PY - 2015 SP - 61-65 ST - OPTIMAL SINGULAR CONTROLS FOR VSEIR MODEL OF TUBERCULOSIS T2 - 2015 International Conference on Research and Education in Mathematics (Icrem7) TI - OPTIMAL SINGULAR CONTROLS FOR VSEIR MODEL OF TUBERCULOSIS UR - ://WOS:000379385800013 ID - 5352 ER - TY - JOUR AB - SETTING: Inaccurate diagnosis and inaccessibility of care undercut the effectiveness of high-quality anti-tuberculosis treatment and select for resistance. Rapid diagnostic systems, such as Xpert((R)) MTB/RIF for tuberculosis (TB) diagnosis and drug susceptibility testing (DST), and programs that provide high-quality DOTS anti-tuberculosis treatment to patients in the unregulated private sector (public-private mix [PPM]), may help address these challenges, albeit at increased cost. OBJECTIVE/DESIGN: We extended a microsimulation model of TB in India calibrated to demographic, epidemiologic, and care trends to evaluate 1) replacing DST with Xpert; 2) replacing microscopy and culture with Xpert to diagnose multidrug-resistant TB (MDR-TB) and non-MDR-TB; 3) implementing nationwide PPM; and combinations of (3) with (1) or (2). RESULTS: PPM (assuming costs of $38/person) and Xpert improved health and increase costs relative to the status quo. PPM alone or with Xpert cost <1 gross domestic product/capita per quality-adjusted life-year gained relative to the next best intervention, and dominated Xpert interventions excluding PPM. CONCLUSIONS: While both PPM and Xpert are promising tools for combatting TB in India, PPM should be prioritized over Xpert, as private sector engagement is more cost-effective than Xpert alone and, if sufficient resources are available, would substantially increase the value of Xpert if both interventions are implemented together. AD - Department of Management Science and Engineering, Stanford University, Stanford, California, USA. Division of General Medical Disciplines, Department of Medicine, Stanford University, Stanford, California, USA; Center for Health Policy and the Center for Primary Care and Outcomes Research, Stanford University, Stanford, California, USA. Center for Health Policy and the Center for Primary Care and Outcomes Research, Stanford University, Stanford, California, USA. AN - 26260835 AU - Suen, S. C. AU - Bendavid, E. AU - Goldhaber-Fiebert, J. D. DA - Sep DO - 10.5588/ijtld.15.0158 IS - 9 L1 - internal-pdf://1617476121/s22.pdf N1 - Suen, S-C Bendavid, E Goldhaber-Fiebert, J D eng K01-AG037593-01A1/AG/NIA NIH HHS/ K01-AI084582/AI/NIAID NIH HHS/ R01-DA15612/DA/NIDA NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. France 2015/08/12 06:00 Int J Tuberc Lung Dis. 2015 Sep;19(9):1115-24, i-xv. doi: 10.5588/ijtld.15.0158. PY - 2015 SN - 1815-7920 (Electronic) 1027-3719 (Linking) SP - 1115-24, i-xv ST - Cost-effectiveness of improvements in diagnosis and treatment accessibility for tuberculosis control in India T2 - Int J Tuberc Lung Dis TI - Cost-effectiveness of improvements in diagnosis and treatment accessibility for tuberculosis control in India UR - http://www.ncbi.nlm.nih.gov/pubmed/26260835 VL - 19 ID - 4689 ER - TY - JOUR AB - BACKGROUND: Molecular resistance detection (MRD) of resistance to second-line anti-tuberculous drugs provides faster results than phenotypic tests, may shorten treatment and allow earlier separation among patients with and without second-line drug resistance. METHODS: In a decision-analytical model we simulated a cohort of patients diagnosed with TB in a setting where drug resistant TB is highly prevalent and requires initial hospitalization, to explore the potential benefits of a high-throughput MRD-assay for reducing potential nosocomial transmission of highly resistant strains, and total costs for diagnosis of drug resistance, treatment and hospitalization. In the base case scenario first-line drug resistance was diagnosed with WHO-endorsed molecular tests, and second-line drug resistance with culture and phenotypic methods. Three alternative scenarios were explored, each deploying high-throughput MRD allowing either detection of second-line mutations in cultured isolates, directly on sputum, or MRD with optimized markers. RESULTS: Compared to a base case scenario, deployment of high-throughput MRD reduced total costs by 17-21 %. The period during which nosocomial transmission may take place increased by 15 % compared to the base case if MRD had currently reported suboptimal sensitivity and required cultured isolates; increased by 7 % if direct sputum analysis were possible including in patients with smear-negative TB, and reduced by 24 % if the assay had improved markers, but was still performed on cultured isolates. Improved clinical sensitivity of the assay (additional markers) by more than 35 % would be needed to avoid compromising infection control. CONCLUSIONS: Further development of rapid second-line resistance testing should prioritize investment in optimizing markers above investments in a platform for direct analysis of sputum. AD - Department of Global Health, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. a.h.vanthoog@aighd.org. Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands. a.h.vanthoog@aighd.org. KIT Biomedical Research, Royal Tropical Institute, Amsterdam, The Netherlands. i.bergval@kit.nl. National Tuberculosis Reference Laboratory, National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia. marikushane@yahoo.com. KIT Biomedical Research, Royal Tropical Institute, Amsterdam, The Netherlands. s.sengstake@kit.nl. National Tuberculosis Reference Laboratory, National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia. asporusiko@yahoo.com. KIT Biomedical Research, Royal Tropical Institute, Amsterdam, The Netherlands. r.anthony@kit.nl. Department of Global Health, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. f.cobelens@aighd.org. Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands. f.cobelens@aighd.org. KNCV Tuberculosis Foundation, The Hague, The Netherlands. f.cobelens@aighd.org. AN - 26503434 AU - van't Hoog, A. H. AU - Bergval, I. AU - Tukvadze, N. AU - Sengstake, S. AU - Aspindzelashvili, R. AU - Anthony, R. M. AU - Cobelens, F. C2 - PMC4624169 DA - Oct 26 DO - 10.1186/s12879-015-1205-4 DP - NLM ET - 2015/10/28 J2 - BMC infectious diseases KW - Antitubercular Agents/therapeutic use Costs and Cost Analysis Cross Infection/drug therapy/prevention & control Drug Resistance, Multiple, Bacterial/*genetics Early Diagnosis Georgia (Republic) High-Throughput Screening Assays/economics/*methods Humans Infection Control Middle Aged *Mutation Mycobacterium tuberculosis/genetics/isolation & purification Sputum/microbiology Tuberculosis/drug therapy Tuberculosis, Multidrug-Resistant/diagnosis/drug therapy/economics/*genetics L1 - internal-pdf://3995536354/van't Hoog-2015-The potential of a multiplex h.pdf LA - eng N1 - 1471-2334 Van't Hoog, A H Bergval, I Tukvadze, N Sengstake, S Aspindzelashvili, R Anthony, R M Cobelens, F D43 TW007124/TW/FIC NIH HHS/United States Journal Article Research Support, Non-U.S. Gov't England BMC Infect Dis. 2015 Oct 26;15:473. doi: 10.1186/s12879-015-1205-4. PY - 2015 SN - 1471-2334 SP - 473 ST - The potential of a multiplex high-throughput molecular assay for early detection of first and second line tuberculosis drug resistance mutations to improve infection control and reduce costs: a decision analytical modeling study T2 - BMC Infect Dis TI - The potential of a multiplex high-throughput molecular assay for early detection of first and second line tuberculosis drug resistance mutations to improve infection control and reduce costs: a decision analytical modeling study UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624169/pdf/12879_2015_Article_1205.pdf VL - 15 ID - 1184 ER - TY - JOUR AB - A recent major cluster randomized trial of screening, active disease treatment, and mass isoniazid preventive therapy for 9 months during 2006-2011 among South African gold miners showed reduced individual-level tuberculosis incidence but no detectable population-level impact. We fitted a dynamic mathematical model to trial data and explored 1) factors contributing to the lack of population-level impact, 2) the best-achievable impact if all implementation characteristics were increased to the highest level achieved during the trial ("optimized intervention"), and 3) how tuberculosis might be better controlled with additional interventions (improving diagnostics, reducing treatment delay, providing isoniazid preventive therapy continuously to human immunodeficiency virus-positive people, or scaling up antiretroviral treatment coverage) individually and in combination. We found the following: 1) The model suggests that a small proportion of latent infections among human immunodeficiency virus-positive people were cured, which could have been a key factor explaining the lack of detectable population-level impact. 2) The optimized implementation increased impact by only 10%. 3) Implementing additional interventions individually and in combination led to up to 30% and 75% reductions, respectively, in tuberculosis incidence after 10 years. Tuberculosis control requires a combination prevention approach, including health systems strengthening to minimize treatment delay, improving diagnostics, increased antiretroviral treatment coverage, and effective preventive treatment regimens. AN - 25792607 AU - Vynnycky, E. AU - Sumner, T. AU - Fielding, K. L. AU - Lewis, J. J. AU - Cox, A. P. AU - Hayes, R. J. AU - Corbett, E. L. AU - Churchyard, G. J. AU - Grant, A. D. AU - White, R. G. C2 - PMC4388015 DA - Apr 15 DO - 10.1093/aje/kwu320 DP - NLM ET - 2015/03/21 IS - 8 J2 - American journal of epidemiology KW - Adult Antitubercular Agents/*therapeutic use Gold HIV Infections/complications Humans Isoniazid/*therapeutic use Middle Aged Mining *Models, Theoretical Public Health Practice/*statistics & numerical data South Africa Tuberculosis/complications/*prevention & control mass community-wide isoniazid preventive therapy mathematical model tuberculosis LA - eng N1 - 1476-6256 Vynnycky, Emilia Sumner, Tom Fielding, Katherine L Lewis, James J Cox, Andrew P Hayes, Richard J Corbett, Elizabeth L Churchyard, Gavin J Grant, Alison D White, Richard G 091769/Wellcome Trust/United Kingdom MR/K007467/1/Medical Research Council/United Kingdom Department of Health/United Kingdom 100714/Wellcome Trust/United Kingdom MR/K012126/1/Medical Research Council/United Kingdom 5U2GPS0008111/PHS HHS/United States G0802414/Medical Research Council/United Kingdom G0700837/Medical Research Council/United Kingdom Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Am J Epidemiol. 2015 Apr 15;181(8):619-32. doi: 10.1093/aje/kwu320. Epub 2015 Mar 19. PY - 2015 SN - 0002-9262 SP - 619-32 ST - Tuberculosis control in South African gold mines: mathematical modeling of a trial of community-wide isoniazid preventive therapy T2 - Am J Epidemiol TI - Tuberculosis control in South African gold mines: mathematical modeling of a trial of community-wide isoniazid preventive therapy VL - 181 ID - 1421 ER - TY - JOUR AB - BACKGROUND: This study explored the effect of screening and treatment of refugees for latent tuberculosis infection (LTBI) before entrance to the United States as a strategy for reducing active tuberculosis (TB). The purpose of this study was to estimate the costs and benefits of LTBI screening and treatment in United States bound refugees prior to arrival. METHODS: Costs were included for foreign and domestic LTBI screening and treatment and the domestic treatment of active TB. A decision tree with multiple Markov nodes was developed to determine the total costs and number of active TB cases that occurred in refugee populations that tested 55, 35, and 20 % tuberculin skin test positive under two models: no overseas LTBI screening and overseas LTBI screening and treatment. For this analysis, refugees that tested 55, 35, and 20 % tuberculin skin test positive were divided into high, moderate, and low LTBI prevalence categories to denote their prevalence of LTBI relative to other refugee populations. RESULTS: For a hypothetical 1-year cohort of 100,000 refugees arriving in the United States from regions with high, moderate, and low LTBI prevalence, implementation of overseas screening would be expected to prevent 440, 220, and 57 active TB cases in the United States during the first 20 years after arrival. The cost savings associated with treatment of these averted cases would offset the cost of LTBI screening and treatment for refugees from countries with high (net cost-saving: $4.9 million) and moderate (net cost-saving: $1.6 million) LTBI prevalence. For low LTBI prevalence populations, LTBI screening and treatment exceed expected future TB treatment cost savings (net cost of $780,000). CONCLUSIONS: Implementing LTBI screening and treatment for United States bound refugees from countries with high or moderate LTBI prevalence would potentially save millions of dollars and contribute to United States TB elimination goals. These estimates are conservative since secondary transmission from tuberculosis cases in the United States was not considered in the model. AD - Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, GA, USA. latewing@gmail.com. Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, GA, USA. zby5@cdc.gov. Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, GA, USA. ije7@cdc.gov. Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, GA, USA. msemple09@jcu.edu. Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, GA, USA. waz6@cdc.gov. Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, GA, USA. mzc4@cdc.gov. Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, GA, USA. bzp3@cdc.gov. AN - 26627449 AU - Wingate, L. T. AU - Coleman, M. S. AU - de la Motte Hurst, C. AU - Semple, M. AU - Zhou, W. AU - Cetron, M. S. AU - Painter, J. A. C2 - PMC4666176 DA - Dec 01 DO - 10.1186/s12889-015-2530-7 DP - NLM ET - 2015/12/03 J2 - BMC public health KW - *Cost Savings *Cost-Benefit Analysis Decision Trees Emigration and Immigration Female Humans Internationality *Latent Tuberculosis/diagnosis/economics/epidemiology/therapy Male Mass Screening/*economics/methods Prevalence *Refugees Tuberculosis United States L1 - internal-pdf://3136662147/Wingate-2015-A cost-benefit analysis of a prop.pdf LA - eng N1 - 1471-2458 Wingate, La'Marcus T Coleman, Margaret S de la Motte Hurst, Christopher Semple, Marie Zhou, Weigong Cetron, Martin S Painter, John A Journal Article England BMC Public Health. 2015 Dec 1;15:1201. doi: 10.1186/s12889-015-2530-7. PY - 2015 SN - 1471-2458 SP - 1201 ST - A cost-benefit analysis of a proposed overseas refugee latent tuberculosis infection screening and treatment program T2 - BMC Public Health TI - A cost-benefit analysis of a proposed overseas refugee latent tuberculosis infection screening and treatment program UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666176/pdf/12889_2015_Article_2530.pdf VL - 15 ID - 1146 ER - TY - JOUR AB - This paper concentrates on the tuberculosis data of China from January 2005 to December 2012. We set up a mathematical model to fit those data with the goodness of fit and obtain the optimal parameter values of the model. By the Chi-square test of the statistical inference, the optimal parameter values of the model are reasonable. We get the effective reproductive number of the disease for each year, and also investigate the preventive measures to control the tuberculosis. AD - College of Science, Zhongyuan University of Technology, Zhengzhou 450007, China; School of Mathematics and Statistics, Central China Normal University, Wuhan 430079, China. Electronic address: jinhuitao20@126.com. School of Information and Mathematics, Yangtze University, Jingzhou 434023, China. School of Mathematics and Statistics, Central China Normal University, Wuhan 430079, China. AN - 25451959 AU - Zhang, J. AU - Li, Y. AU - Zhang, X. DA - Jan 21 DO - 10.1016/j.jtbi.2014.10.019 DP - NLM ET - 2014/12/03 J2 - Journal of theoretical biology KW - China Humans *Models, Biological Tuberculosis/*epidemiology Chi-square test Effective reproductive number Goodness of fit Parameter estimation LA - eng N1 - 1095-8541 Zhang, Jinhui Li, Yong Zhang, Xinan Journal Article Research Support, Non-U.S. Gov't England J Theor Biol. 2015 Jan 21;365:159-63. doi: 10.1016/j.jtbi.2014.10.019. Epub 2014 Oct 24. PY - 2015 SN - 0022-5193 SP - 159-63 ST - Mathematical modeling of tuberculosis data of China T2 - J Theor Biol TI - Mathematical modeling of tuberculosis data of China VL - 365 ID - 1841 ER - TY - JOUR AB - This paper deals with the global analysis of a dynamical model for the spread of tuberculosis with isolation and incomplete treatment. The model exhibits the traditional threshold behavior. We prove that when the basic reproductive number is less than unity, the disease-free equilibrium is globally asymptotically stable. When the basic reproductive number is greater than unity, the disease-free equilibrium is unstable and a unique endemic equilibrium exists which is locally asymptotically stable and globally asymptotically stable when the disease-induced death rate is equal to zero. The stability of disease-free equilibrium is derived by using Lyapunov stability theory and LaSalle's invariant set theorem. The global stability of endemic equilibrium is proved by generalized Dulac-Bendixson criterion when the disease-induced death rate is equal to zero. Numerical simulations support our analytical results. AD - Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China Hubei Univ Educ, Sch Math & Stat, Wuhan 430205, Peoples R China AN - WOS:000361552800024 AU - Zhang, J. H. AU - Feng, G. T. DA - Oct DO - 10.1007/s40314-014-0177-0 IS - 3 J2 - Comput Appl Math KW - basic reproductive number global stability generalized dulac-bendixson criterion competitive-exclusion strategies infection epidemics dynamics LA - English N1 - Cr7tb Times Cited:2 Cited References Count:25 PY - 2015 SN - 0101-8205 SP - 1237-1249 ST - Global stability for a tuberculosis model with isolation and incomplete treatment T2 - Computational & Applied Mathematics TI - Global stability for a tuberculosis model with isolation and incomplete treatment UR - ://WOS:000361552800024 VL - 34 ID - 4916 ER - TY - JOUR AB - As novel diagnostics, therapies, and algorithms are developed to improve case finding, diagnosis, and clinical management of patients with TB, policymakers must make difficult decisions and choose among multiple new technologies while operating under heavy resource constrained settings. Mathematical modelling can provide helpful insight by describing the types of interventions likely to maximize impact on the population level and highlighting those gaps in our current knowledge that are most important for making such assessments. This review discusses the major contributions of TB transmission models in general, namely, the ability to improve our understanding of the epidemiology of TB. We focus particularly on those elements that are important to appropriately understand the role of TB diagnosis and treatment (i.e., what elements of better diagnosis or treatment are likely to have greatest population-level impact) and yet remain poorly understood at present. It is essential for modellers, decision-makers, and epidemiologists alike to recognize these outstanding gaps in knowledge and understand their potential influence on model projections that may guide critical policy choices (e.g., investment and scale-up decisions). AD - Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. AN - 26556559 AU - Zwerling, A. AU - Shrestha, S. AU - Dowdy, D. W. C2 - PMC4590968 DO - 10.1155/2015/907267 DP - NLM ET - 2015/11/12 J2 - Advances in medicine LA - eng N1 - Zwerling, Alice Shrestha, Sourya Dowdy, David W Journal Article Review United States Adv Med. 2015;2015:907267. doi: 10.1155/2015/907267. Epub 2015 Mar 15. PY - 2015 SN - 2356-6752 (Print) 2314-758x SP - 907267 ST - Mathematical Modelling and Tuberculosis: Advances in Diagnostics and Novel Therapies T2 - Adv Med TI - Mathematical Modelling and Tuberculosis: Advances in Diagnostics and Novel Therapies VL - 2015 ID - 1166 ER - TY - JOUR AB - The control of bovine tuberculosis (bTB) in cattle herds in the Republic of Ireland (ROI) is partially hindered by spill-back infection from wild badgers (Meles meles). The aim of this study was to determine the relative effects of interventions (combinations of culling and/or vaccination) on bTB dynamics in an Irish badger population. A spatial agent-based stochastic simulation model was developed to evaluate the effect of various control strategies for bovine tuberculosis in badgers: single control strategies (culling, selective culling, vaccination, and vaccine baits), and combined strategies (Test vaccinate/cull (TVC)), split area approaches using culling and vaccination, or selective culling and vaccination, and mixed scenarios where culling was conducted for five years and followed by vaccination or by a TVC strategy. The effect of each control strategy was evaluated over a 20-year period. Badger control was simulated in 25%, 50%, and 75% area (limited area strategy) or in the entire area (100%, wide area strategy). For endemic bTB, a culling strategy was successful in eradicating bTB from the population only if applied as an area-wide strategy. However, this was achieved only by risking the extinction of the badger population. Selective culling strategies (selective culling or TVC) mitigated this negative impact on the badger population's viability. Furthermore, both strategies (selective culling and TVC) allowed the badger population to recover gradually, in compensation for the population reduction following the initial use of removal strategies. The model predicted that vaccination can be effective in reducing bTB prevalence in badgers, when used in combination with culling strategies (i.e. TVC or other strategies). If fecundity was reduced below its natural levels (e.g. by using wildlife contraceptives), the effectiveness of vaccination strategies improved. Split-area simulations highlighted that interventions can have indirect effects (e.g. on population size) in non-treatment areas. Our model suggests that mixed control strategies could maintain infection prevalence to a low level for a considerable period even with a growing population. The model supported the hypothesis that culling strategies appeared to be the most effective method for the control of bTB in badgers using parameters, where available, from ROI, either singly or in combination with other strategies. In this model, the success of a vaccination strategy depended partially upon population density and the proportion of the population infected, therefore an initial culling program (to reduce density and/or remove infected badgers) followed by long-term vaccination may be effective in controlling bTB in badgers. AD - Quantitative Veterinary Epidemiology Group, Wageningen Institute of Animal Sciences, Wageningen University, P.O. Box 338, 6700 AH Wageningen, The Netherlands. Centre for Veterinary Epidemiology and Risk Analysis, UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland. Centre for Veterinary Epidemiology and Risk Analysis, UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland; Agri-food and Biosciences Institute, Stormont, Stoney Road, Belfast BT4 3SD, United Kingdom. Electronic address: andrew.byrne@afbini.gov.uk. AN - 26774448 AU - Abdou, M. AU - Frankena, K. AU - O'Keeffe, J. AU - Byrne, A. W. DA - Mar 01 DO - 10.1016/j.prevetmed.2015.12.012 DP - NLM ET - 2016/01/18 J2 - Preventive veterinary medicine KW - Animals Cattle *Computer Simulation Ireland *Mustelidae Population Control Seasons Tuberculosis, Bovine/microbiology/*prevention & control/transmission Vaccination/*veterinary Agent-based model Culling Meles meles Mycobacterium bovis Spatially-explicit model Vaccination LA - eng N1 - 1873-1716 Abdou, Marwa Frankena, Klaas O'Keeffe, James Byrne, Andrew W Journal Article Research Support, Non-U.S. Gov't Netherlands Prev Vet Med. 2016 Mar 1;125:19-30. doi: 10.1016/j.prevetmed.2015.12.012. Epub 2015 Dec 24. PY - 2016 SN - 0167-5877 SP - 19-30 ST - Effect of culling and vaccination on bovine tuberculosis infection in a European badger (Meles meles) population by spatial simulation modelling T2 - Prev Vet Med TI - Effect of culling and vaccination on bovine tuberculosis infection in a European badger (Meles meles) population by spatial simulation modelling VL - 125 ID - 1104 ER - TY - JOUR AB - BACKGROUND: Understanding the amount of tuberculosis managed by the private sector in India is crucial to understanding the true burden of the disease in the country, and thus globally. In the absence of quality surveillance data on privately treated patients, commercial drug sales data offer an empirical foundation for disease burden estimation. METHODS: We used a large, nationally representative commercial dataset on sales of 189 anti-tuberculosis products available in India to calculate the amount of anti-tuberculosis treatment in the private sector in 2013-14. We corrected estimates using validation studies that audited prescriptions against tuberculosis diagnosis, and estimated uncertainty using Monte Carlo simulation. To address implications for numbers of patients with tuberculosis, we explored varying assumptions for average duration of tuberculosis treatment and accuracy of private diagnosis. FINDINGS: There were 17.793 million patient-months (95% credible interval 16.709 million to 19.841 million) of anti-tuberculosis treatment in the private sector in 2014, twice as many as the public sector. If 40-60% of private-sector tuberculosis diagnoses are correct, and if private-sector tuberculosis treatment lasts on average 2-6 months, this implies that 1.19-5.34 million tuberculosis cases were treated in the private sector in 2014 alone. The midpoint of these ranges yields an estimate of 2.2 million cases, two to three times higher than currently assumed. INTERPRETATION: India's private sector is treating an enormous number of patients for tuberculosis, appreciably higher than has been previously recognised. Accordingly, there is a re-doubled need to address this burden and to strengthen surveillance. Tuberculosis burden estimates in India and worldwide require revision. FUNDING: Bill & Melinda Gates Foundation. AD - MRC Centre for Outbreak Analysis and Modelling, School of Public Health, Imperial College London, London, UK. Electronic address: nim.pathy@imperial.ac.uk. IMS Health, New Delhi, India. Central TB Division, Government of India, New Delhi, India. World Health Organization, India Country Office, New Delhi, India. Bill & Melinda Gates Foundation, New Delhi, India. AN - 27568356 AU - Arinaminpathy, N. AU - Batra, D. AU - Khaparde, S. AU - Vualnam, T. AU - Maheshwari, N. AU - Sharma, L. AU - Nair, S. A. AU - Dewan, P. C2 - PMC5067370 DA - Nov DO - 10.1016/s1473-3099(16)30259-6 DP - NLM ET - 2016/10/30 IS - 11 J2 - The Lancet. Infectious diseases KW - Antitubercular Agents/*economics/therapeutic use Humans India/epidemiology Pharmaceutical Preparations/*economics Private Sector/*economics Tuberculosis/diagnosis/drug therapy/epidemiology LA - eng N1 - 1474-4457 Arinaminpathy, Nimalan Batra, Deepak Khaparde, Sunil Vualnam, Thongsuanmung Maheshwari, Nilesh Sharma, Lokesh Nair, Sreenivas A Dewan, Puneet Journal Article United States Lancet Infect Dis. 2016 Nov;16(11):1255-1260. doi: 10.1016/S1473-3099(16)30259-6. Epub 2016 Aug 25. PY - 2016 SN - 1473-3099 SP - 1255-1260 ST - The number of privately treated tuberculosis cases in India: an estimation from drug sales data T2 - Lancet Infect Dis TI - The number of privately treated tuberculosis cases in India: an estimation from drug sales data VL - 16 ID - 835 ER - TY - JOUR AB - BACKGROUND: Timely diagnosis and treatment of latent tuberculosis infection (LTBI) through screening remains a key public health priority. Although globally it is recommended to screen people at high risk of developing TB, the economic evidence underpinning these recommendations is limited. This review critically appraised studies that had used a decision-analytical modelling framework to estimate the cost-effectiveness of interferon gamma release assays (IGRAs) compared to tuberculin skin test (TST) for detecting LTBI in high risk populations. METHODS: A comprehensive search of MEDLINE, EMBASE, NHS-EED was undertaken from 2009 up to June 2015. Studies were screened and extracted by independent reviewers. The study quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and the Philips' checklist, respectively. A narrative synthesis of the included studies was undertaken. RESULTS: Ten studies were included in this review. Two economic evaluations were conducted in a child population, six in an immunocompromised population and two in a recently arrived population from a country with a high incidence of TB. Most studies (n = 7) used a decision tree structure with Markov nodes. In general, all models were clearly described in terms of reporting quality, but were subject to limitations to structure and model inputs. Models have not elaborated on their setting or the perspective of the studies was not consistent with their analyses. Other concerns were related to derivation of prevalence, test accuracy and transition probabilities. CONCLUSION: Current methods available highlight limitations in the clinical effectiveness literature, model structures and assumptions, which impact on the robustness of the cost-effectiveness results. These models available are useful, but limited on the information that can be used to inform on future cost-effectiveness analysis. Until consideration is given on deriving the performance of tests used to identify LTBI that progresses to active TB, and the development of more comprehensive models, the economic benefit of LTBI testing with TST/IGRAs in high risk populations will remain unanswered. AD - Warwick Evidence, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, United Kingdom. Electronic address: p.auguste@warwick.ac.uk. Evidence in Communicable Disease Epidemiology and Control, Health Sciences, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, United Kingdom. Warwick Evidence, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, United Kingdom. AN - 27450009 AU - Auguste, P. AU - Tsertsvadze, A. AU - Court, R. AU - Pink, J. DA - Jul DO - 10.1016/j.tube.2016.04.007 DP - NLM ET - 2016/07/28 J2 - Tuberculosis (Edinburgh, Scotland) KW - Cost-effectiveness Decision-analytical modelling Latent tuberculosis Systematic review LA - eng N1 - 1873-281x Auguste, Peter Tsertsvadze, Alexander Court, Rachel Pink, Joshua Journal Article Review Scotland Tuberculosis (Edinb). 2016 Jul;99:81-91. doi: 10.1016/j.tube.2016.04.007. Epub 2016 Apr 20. PY - 2016 SN - 1472-9792 SP - 81-91 ST - A systematic review of economic models used to assess the cost-effectiveness of strategies for identifying latent tuberculosis in high-risk groups T2 - Tuberculosis (Edinb) TI - A systematic review of economic models used to assess the cost-effectiveness of strategies for identifying latent tuberculosis in high-risk groups VL - 99 ID - 907 ER - TY - JOUR AB - BACKGROUND: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB) [(Zopf 1883) Lehmann and Neumann 1896], is a major cause of morbidity and mortality. Nearly one-third of the world's population is infected with MTB; TB has an annual incidence of 9 million new cases and each year causes 2 million deaths worldwide. OBJECTIVES: To investigate the clinical effectiveness and cost-effectiveness of screening tests [interferon-gamma release assays (IGRAs) and tuberculin skin tests (TSTs)] in latent tuberculosis infection (LTBI) diagnosis to support National Institute for Health and Care Excellence (NICE) guideline development for three population groups: children, immunocompromised people and those who have recently arrived in the UK from high-incidence countries. All of these groups are at higher risk of progression from LTBI to active TB. DATA SOURCES: Electronic databases including MEDLINE, EMBASE, The Cochrane Library and Current Controlled Trials were searched from December 2009 up to December 2014. REVIEW METHODS: English-language studies evaluating the comparative effectiveness of commercially available tests used for identifying LTBI in children, immunocompromised people and recent arrivals to the UK were eligible. Interventions were IGRAs [QuantiFERON((R))-TB Gold (QFT-G), QuantiFERON((R))-TB Gold-In-Tube (QFT-GIT) (Cellestis/Qiagen, Carnegie, VA, Australia) and T-SPOT.TB (Oxford Immunotec, Abingdon, UK)]. The comparator was TST 5 mm or 10 mm alone or with an IGRA. Two independent reviewers screened all identified records and undertook a quality assessment and data synthesis. A de novo model, structured in two stages, was developed to compare the cost-effectiveness of diagnostic strategies. RESULTS: In total, 6687 records were screened, of which 53 unique studies were included (a further 37 studies were identified from a previous NICE guideline). The majority of the included studies compared the strength of association for the QFT-GIT/G IGRA with the TST (5 mm or 10 mm) in relation to the incidence of active TB or previous TB exposure. Ten studies reported evidence on decision-analytic models to determine the cost-effectiveness of IGRAs compared with the TST for LTBI diagnosis. In children, TST (>/= 5 mm) negative followed by QFT-GIT was the most cost-effective strategy, with an incremental cost-effectiveness ratio (ICER) of pound18,900 per quality-adjusted life-year (QALY) gained. In immunocompromised people, QFT-GIT negative followed by the TST (>/= 5 mm) was the most cost-effective strategy, with an ICER of approximately pound18,700 per QALY gained. In those recently arrived from high TB incidence countries, the TST (>/= 5 mm) alone was less costly and more effective than TST (>/= 5 mm) positive followed by QFT-GIT or T-SPOT.TB or QFT-GIT alone. LIMITATIONS: The limitations and scarcity of the evidence, variation in the exposure-based definitions of LTBI and heterogeneity in IGRA performance relative to TST limit the applicability of the review findings. CONCLUSIONS: Given the current evidence, TST (>/= 5 mm) negative followed by QFT-GIT for children, QFT-GIT negative followed by TST (>/= 5 mm) for the immunocompromised population and TST (>/= 5 mm) for recent arrivals were the most cost-effective strategies for diagnosing LTBI that progresses to active TB. These results should be interpreted with caution given the limitations identified. The evidence available is limited and more high-quality research in this area is needed including studies on the inconsistent performance of tests in high-compared with low-incidence TB settings; the prospective assessment of progression to active TB for those at high risk; the relative benefits of two-compared with one-step testing with different tests; and improved classification of people at high and low risk for LTBI. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014009033. FUNDING: The National Institute for Health Research Health Technology Assessment programme. AD - Warwick Evidence, Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK. Evidence in Communicable Disease Epidemiology and Control, Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK. Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK. Department of Mathematics and Information Sciences, Faculty of Engineering and Environment, Northumbria University, Newcastle upon Tyne, UK. AN - 27220068 AU - Auguste, P. AU - Tsertsvadze, A. AU - Pink, J. AU - Court, R. AU - Seedat, F. AU - Gurung, T. AU - Freeman, K. AU - Taylor-Phillips, S. AU - Walker, C. AU - Madan, J. AU - Kandala, N. B. AU - Clarke, A. AU - Sutcliffe, P. C2 - PMC4904187 DA - May DO - 10.3310/hta20380 DP - NLM ET - 2016/05/25 IS - 38 J2 - Health technology assessment (Winchester, England) LA - eng N1 - 2046-4924 Auguste, Peter Tsertsvadze, Alexander Pink, Joshua Court, Rachel Seedat, Farah Gurung, Tara Freeman, Karoline Taylor-Phillips, Sian Walker, Clare Madan, Jason Kandala, Ngianga-Bakwin Clarke, Aileen Sutcliffe, Paul WMCLAHRC-2014-1/Department of Health/United Kingdom Journal Article England Health Technol Assess. 2016 May;20(38):1-678. doi: 10.3310/hta20380. PY - 2016 SN - 1366-5278 SP - 1-678 ST - Accurate diagnosis of latent tuberculosis in children, people who are immunocompromised or at risk from immunosuppression and recent arrivals from countries with a high incidence of tuberculosis: systematic review and economic evaluation T2 - Health Technol Assess TI - Accurate diagnosis of latent tuberculosis in children, people who are immunocompromised or at risk from immunosuppression and recent arrivals from countries with a high incidence of tuberculosis: systematic review and economic evaluation VL - 20 ID - 960 ER - TY - JOUR AB - Drug resistance to tuberculosis (TB) has become more widespread over the past decade. As such, understanding the emergence and fitness of antibiotic-resistant subpopulations is crucial for the development of new interventions. Here we use a simple mathematical model to explain the differences in the response to isoniazid (INH) of Mycobacterium tuberculosis cells cultured under two growth rates in a chemostat. We obtain posterior distributions of model parameters consistent with data using a Markov chain Monte Carlo (MCMC) method. We explore the dynamics of diverse INH-resistant subpopulations consistent with these data in a multi-population model. We find that the simple model captures the qualitative behaviour of the cultures under both dilution rates and also present testable predictions about how diversity is maintained in such cultures. AD - Department of Mathematics, Imperial College London, South Kensington Campus, London SW7 2AZ, UK d.ayabina14@imperial.ac.uk. Public Health England, National Infection Service, Porton Down, Salisbury SP4 0JG, UK. Department of Mathematics, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. AN - 27807274 AU - Ayabina, D. AU - Hendon-Dunn, C. AU - Bacon, J. AU - Colijn, C. C2 - PMC5134024 DA - Nov DO - 10.1098/rsif.2016.0745 DP - NLM ET - 2016/11/04 IS - 124 J2 - Journal of the Royal Society, Interface KW - Drug Resistance, Bacterial/*drug effects Isoniazid/*pharmacology *Models, Biological Mycobacterium tuberculosis/*growth & development Mycobacterium tuberculosis competition diversity resistance L1 - internal-pdf://3416198083/Ayabina-2016-Diverse drug-resistant subpopulat.pdf LA - eng N1 - 1742-5662 Ayabina, Diepreye ORCID: http://orcid.org/0000-0002-7005-6734 Hendon-Dunn, Charlotte Bacon, Joanna Colijn, Caroline Journal Article England J R Soc Interface. 2016 Nov;13(124). pii: 20160745. PY - 2016 SN - 1742-5662 ST - Diverse drug-resistant subpopulations of Mycobacterium tuberculosis are sustained in continuous culture T2 - J R Soc Interface TI - Diverse drug-resistant subpopulations of Mycobacterium tuberculosis are sustained in continuous culture UR - http://rsif.royalsocietypublishing.org/content/royinterface/13/124/20160745.full.pdf VL - 13 ID - 829 ER - TY - JOUR AB - Background: Tuberculosis (TB) is a deadly infectious disease caused by Mycobacteria tuberculosis. Tuberculosis as a chronic and highly infectious disease is prevalent in almost every part of the globe. More than 95% of TB mortality occurs in low/middle income countries. In 2014, approximately 10 million people were diagnosed with active TB and two million died from the disease. In this study, our aim is to compare the predictive powers of the seasonal autoregressive integrated moving average (SARIMA) and neural network auto-regression (SARIMA-NNAR) models of TB incidence and analyse its seasonality in South Africa. Methods: TB incidence cases data from January 2010 to December 2015 were extracted from the Eastern Cape Health facility report of the electronic Tuberculosis Register (ERT. Net). A SARIMA model and a combined model of SARIMA model and a neural network auto-regression (SARIMA-NNAR) model were used in analysing and predicting the TB data from 2010 to 2015. Simulation performance parameters of mean square error (MSE), root mean square error (RMSE), mean absolute error (MAE), mean percent error (MPE), mean absolute scaled error (MASE) and mean absolute percentage error (MAPE) were applied to assess the better performance of prediction between the models. Results: Though practically, both models could predict TB incidence, the combined model displayed better performance. For the combined model, the Akaike information criterion (AIC), second-order AIC (AICc) and Bayesian information criterion (BIC) are 288.56, 308.31 and 299.09 respectively, which were lower than the SARIMA model with corresponding values of 329.02, 327.20 and 341.99, respectively. The seasonality trend of TB incidence was forecast to have a slightly increased seasonal TB incidence trend from the SARIMA-NNAR model compared to the single model. Conclusions: The combined model indicated a better TB incidence forecasting with a lower AICc. The model also indicates the need for resolute intervention to reduce infectious disease transmission with co-infection with HIV and other concomitant diseases, and also at festival peak periods. AD - Univ Ft Hare, Dept Stat, Biostat & Epidemiol Res Grp, PMB X1314, ZA-5700 Alice, South Africa Univ Ft Hare, Dept Stat, PMB X1314, ZA-5700 Alice, South Africa AN - WOS:000382462900012 AU - Azeez, A. AU - Obaromi, D. AU - Odeyemi, A. AU - Ndege, J. AU - Muntabayi, R. DA - Aug DO - ARTN 757 10.3390/ijerph13080757 IS - 8 J2 - Int J Env Res Pub He KW - autocorrelation co-infection neutral-network non-seasonality prediction united-states LA - English N1 - Du8kv Times Cited:0 Cited References Count:23 PY - 2016 SN - 1660-4601 ST - Seasonality and Trend Forecasting of Tuberculosis Prevalence Data in Eastern Cape, South Africa, Using a Hybrid Model T2 - International Journal of Environmental Research and Public Health TI - Seasonality and Trend Forecasting of Tuberculosis Prevalence Data in Eastern Cape, South Africa, Using a Hybrid Model UR - ://WOS:000382462900012 VL - 13 ID - 2212 ER - TY - JOUR AB - Infectious diseases and their transmission are good examples of complex systems, with several interacting and interdependent components. We develop an agent-based simulation of the living condition of a typical slum setting in Nigeria which is considered to have a higher incidence and prevalence of tuberculosis. We consider the epidemiology of the disease and create a dynamic model, incorporating both environmental conditions and immune suppressed health conditions that have been observed in previous studies to be associated with emergence of the disease. Based on the developed model, we observe the pattern of transmission and we compare the results obtained with the estimates provided by the World Health Organization (WHO) and other individual surveys carried out in the past. The results obtained showed that increasing the air changes per hour (ACH) reduces the number of new latent tuberculosis infections among close contacts. Incorporating 7 air changes per hour which is the recommended value for a bedroom had a significance impact in reducing the number of new latent infections. Furthermore, introducing about 13 air changes per hour which is the recommended value for a smoking environment had a further reduction in the number of new latent infections. The result obtained also showed that individuals living with both HIV and diabetes have the highest risk of progressing to the active tuberculosis disease. Finally, the results also revealed that close contacts of people living with the active tuberculosis disease have a higher risk of developing the latent tuberculosis infection. These insights are useful findings to support public health policies for tuberculosis management. AD - [Badmus, Oluyemi; Camorlinga, Sergio] Univ Winnipeg, Appl Comp Sci, Winnipeg, MB, Canada. Badmus, O (reprint author), Univ Winnipeg, Appl Comp Sci, Winnipeg, MB, Canada. badmuso-38@webmail.uwinnipeg.ca; s.camorlinga@uwinnipeg.ca AN - WOS:000389647000104 AU - Badmus, O. AU - Camorlinga, S. AU - Ieee KW - tuberculosis complex systems agent-based modelling Computer Science Engineering LA - English M3 - Proceedings Paper N1 - ISI Document Delivery No.: BG5PW Times Cited: 0 Cited Reference Count: 14 Badmus, Oluyemi Camorlinga, Sergio 10th Annual IEEE International Systems Conference (SysCon) Apr 18-21, 2016 Orlando, FL IEEE, IEEE Syst Council 0 Ieee New york 978-1-4673-9519-9 PY - 2016 SP - 678-684 ST - Complex System Modelling of the Spread of Tuberculosis in Nigeria T2 - 2016 Annual Ieee Systems Conference (Syscon) TI - Complex System Modelling of the Spread of Tuberculosis in Nigeria UR - ://WOS:000389647000104 ID - 5214 ER - TY - JOUR AB - Tuberculosis has been observed to thrive in conditions of poverty and there has been a long history of documented linkage between tuberculosis and poverty at the society and community level. This paper utilizes an agent-based model to incorporate three aspects of the conditions faced by the economically poorer and vulnerable individuals. The three aspects considered in the paper include undernutrition, poor living conditions (overcrowding, inadequate ventilation) and access to adequate health care facilities. The paper aims to understand the effects of poor living conditions on the emergence of latent tuberculosis infection among individuals exposed to the disease. Also, we consider the effect of undernutrition on the immune system response to control the progression from the latent tuberculosis infection to the active tuberculosis disease. Finally, the paper studies the effect on adequate access to proper health care as a factor on the emergence of tuberculosis. The results obtained indicate that malnutrition coupled with limited access to adequate health care increases the risk of emergence of the active tuberculosis disease and also that inadequate ventilation increases the risk of emergence of the latent tuberculosis infection (LTBI). AD - [Badmus, Oluyemi; Camorlinga, Sergio; Simpson, Orlando] Univ Winnipeg, Winnipeg, MB, Canada. Camorlinga, S (reprint author), Univ Winnipeg, Winnipeg, MB, Canada. badmus-o38@webmail.uwinnipeg; camorlinga@uwinnipeg.ca; simpson-o@webmail.uwinnipeg.ca AN - WOS:000381398000139 AU - Badmus, O. AU - Camorlinga, S. AU - Simpson, O. AU - Ieee KW - Computer Science Engineering LA - English M3 - Proceedings Paper N1 - ISI Document Delivery No.: BF4NB Times Cited: 0 Cited Reference Count: 8 Badmus, Oluyemi Camorlinga, Sergio Simpson, Orlando 3rd IEEE EMBS International Conference on Biomedical and Health Informatics (IEEE BHI) Feb 24-27, 2016 Las Vegas, NV IEEE EMBS, IEEE, Journal of Biomed & Hlth Informat, IEEE Commun Soc 0 2 Ieee New york 978-1-5090-2455-1 PY - 2016 SP - 561-564 ST - Poverty and the Emergence of Tuberculosis: An Agent-Based Modelling Approach T2 - 2016 3rd Ieee Embs International Conference on Biomedical and Health Informatics TI - Poverty and the Emergence of Tuberculosis: An Agent-Based Modelling Approach UR - ://WOS:000381398000139 ID - 5222 ER - TY - JOUR AB - BACKGROUND: Tuberculosis (TB) is the leading cause of death in South Africa. The burden of disease varies by age, with peaks in TB notification rates in the HIV-negative population at ages 0-5, 20-24, and 45-49 years. There is little variation between age groups in the rates in the HIV-positive population. The drivers of this age pattern remain unknown. METHODS: We developed an age-structured simulation model of Mycobacterium tuberculosis (Mtb) transmission in Cape Town, South Africa. We considered five states of TB progression: susceptible, infected (latent TB), active TB, treated TB, and treatment default. Latently infected individuals could be re-infected; a previous Mtb infection slowed progression to active disease. We further considered three states of HIV progression: HIV negative, HIV positive, on antiretroviral therapy. To parameterize the model, we analysed treatment outcomes from the Cape Town electronic TB register, social mixing patterns from a Cape Town community and used literature estimates for other parameters. To investigate the main drivers behind the age patterns, we conducted sensitivity analyses on all parameters related to the age structure. RESULTS: The model replicated the age patterns in HIV-negative TB notification rates of Cape Town in 2009. Simulated TB notification rate in HIV-negative patients was 1000/100,000 person-years (pyrs) in children aged <5 years and decreased to 51/100,000 in children 5-15 years. The peak in early adulthood occurred at 25-29 years (463/100,000 pyrs). After a subsequent decline, simulated TB notification rates gradually increased from the age of 30 years. Sensitivity analyses showed that the dip after the early adult peak was due to the protective effect of latent TB and that retreatment TB was mainly responsible for the rise in TB notification rates from the age of 30 years. CONCLUSION: The protective effect of a first latent infection on subsequent infections and the faster progression in previously treated patients are the key determinants of the age-structure of TB notification rates in Cape Town. AD - Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland. Desmond Tutu HIV Centre, Institute for Infectious Disease & Molecular Medicine, University of Cape Town, South Africa; Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam Institute for Global Health and Development,The Netherlands; Department of Internal Medicine, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda. Desmond Tutu HIV Centre, Institute for Infectious Disease & Molecular Medicine, University of Cape Town, South Africa. Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland; School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland. Electronic address: olivia.keiser@ispm.unibe.ch. Desmond Tutu HIV Centre, Institute for Infectious Disease & Molecular Medicine, University of Cape Town, South Africa; Department of Medicine, University of Cape Town,, South Africa; Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK. AN - 26972514 AU - Blaser, N. AU - Zahnd, C. AU - Hermans, S. AU - Salazar-Vizcaya, L. AU - Estill, J. AU - Morrow, C. AU - Egger, M. AU - Keiser, O. AU - Wood, R. C2 - PMC4791535 C6 - NIHMS732257 DA - Mar DO - 10.1016/j.epidem.2015.10.001 DP - NLM ET - 2016/03/15 J2 - Epidemics KW - Adolescent Adult Age Distribution Child Child, Preschool Female Humans Incidence Infant Male Middle Aged Models, Theoretical South Africa/epidemiology Tuberculosis/*epidemiology/*transmission Young Adult Cape Town Mathematical model Tuberculosis LA - eng N1 - 1878-0067 Blaser, Nello Zahnd, Cindy Hermans, Sabine Salazar-Vizcaya, Luisa Estill, Janne Morrow, Carl Egger, Matthias Keiser, Olivia Wood, Robin 5U01-AI069924-05/AI/NIAID NIH HHS/United States R01AI058736/AI/NIAID NIH HHS/United States R37 AI093269/AI/NIAID NIH HHS/United States R01AI093269/AI/NIAID NIH HHS/United States R01 AI093269/AI/NIAID NIH HHS/United States R01 AI058736/AI/NIAID NIH HHS/United States U01 AI069924/AI/NIAID NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Netherlands Epidemics. 2016 Mar;14:54-61. doi: 10.1016/j.epidem.2015.10.001. Epub 2015 Oct 20. PY - 2016 SN - 1878-0067 SP - 54-61 ST - Tuberculosis in Cape Town: An age-structured transmission model T2 - Epidemics TI - Tuberculosis in Cape Town: An age-structured transmission model VL - 14 ID - 1038 ER - TY - JOUR AB - BACKGROUND: No clear evidence on the comparative effectiveness of delamanid (DLM) and bedaquiline (BDQ) has been published. OBJECTIVE: This study aims to estimate the incremental effectiveness of DLM versus BDQ in patients with multidrug-resistant tuberculosis (MDR-TB). METHODS: We developed a Markov model based on a cohort with MDR-TB, which consisted of success, failure, loss to follow-up, and death. The cohort simulation was conducted assuming each patient was 36 years old and, lived until age 82, and that the cycle length was 1 year. Patients with an inadequate response to DLM, the background regimen, or BDQ for 2 years were transitioned through the next treatment sequence. We evaluated the incremental effectiveness of the drugs using the quality-adjusted life-year (QALY) resulting from this Markov model over a lifetime. RESULTS: The incremental effectiveness of DLM (13.96 QALYs) was greater by 2.44 QALYs per patient than the background regimen (11.52 QALY), while the incremental effectiveness of BDQ (10.40 QALY) was higher by 1.14 QALY per patient than the background regimen (9.26 QALY). Consequently, the incremental effectiveness of DLM was relatively more positive by 1.30 QALY than those of BDQ per patient over a lifetime. LIMITATIONS: This study is a simulation study. Therefore, the treatment sequence for patients may be different in the real world. CONCLUSIONS: Our lifetime simulated data found that DLM was relatively more favorable than BDQ. A Markov model can be considered an alternative approach when there is an absence of head-to-head clinical data. AD - Pharmaceutical Policy and Outcomes Research, Department of Pharmaceutical Industrial Science, School of Pharmacy, Sungkyunkwan University (SKKU), 300 Cheonchoen-dong, Jangan-gu, Suwon, Gyeonggi-do, 440-746, South Korea. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada. Pharmaceutical Policy and Outcomes Research, Department of Pharmaceutical Industrial Science, School of Pharmacy, Sungkyunkwan University (SKKU), 300 Cheonchoen-dong, Jangan-gu, Suwon, Gyeonggi-do, 440-746, South Korea. ekyung@skku.edu. AN - 27465204 AU - Byun, J. H. AU - Park, J. A. AU - Kang, H. R. AU - Shin, J. Y. AU - Lee, E. K. DA - Nov DO - 10.1007/s40261-016-0443-6 DP - NLM ET - 2016/10/22 IS - 11 J2 - Clinical drug investigation KW - Aged Diarylquinolines/*therapeutic use Female Humans Male Middle Aged Nitroimidazoles/*therapeutic use Oxazoles/*therapeutic use Quality-Adjusted Life Years Tuberculosis, Multidrug-Resistant/*drug therapy LA - eng N1 - 1179-1918 Byun, Ji-Hye Park, Jae-A Kang, Hye-Rim Shin, Ju-Young Lee, Eui-Kyung Comparative Study Journal Article New Zealand Clin Drug Investig. 2016 Nov;36(11):957-968. PY - 2016 SN - 1173-2563 SP - 957-968 ST - Comparison of Effectiveness Between Delamanid and Bedaquiline Among Patients with Multidrug-Resistant Tuberculosis: A Markov Model Simulation Study T2 - Clin Drug Investig TI - Comparison of Effectiveness Between Delamanid and Bedaquiline Among Patients with Multidrug-Resistant Tuberculosis: A Markov Model Simulation Study UR - https://link.springer.com/article/10.1007%2Fs40261-016-0443-6 VL - 36 ID - 2204 ER - TY - JOUR AB - Treatment failure after therapy of pulmonary tuberculosis (TB) infections is an important challenge, especially when it coincides with de novo emergence of multi-drug-resistant TB (MDR-TB). We seek to explore possible causes why MDR-TB has been found to occur much more often in patients with a history of previous treatment. We develop a mathematical model of the replication of Mycobacterium tuberculosis within a patient reflecting the compartments of macrophages, granulomas, and open cavities as well as parameterizing the effects of drugs on the pathogen dynamics in these compartments. We use this model to study the influence of patient adherence to therapy and of common retreatment regimens on treatment outcome. As expected, the simulations show that treatment success increases with increasing adherence. However, treatment occasionally fails even under perfect adherence due to interpatient variability in pharmacological parameters. The risk of generating MDR de novo is highest between 40% and 80% adherence. Importantly, our simulations highlight the double-edged effect of retreatment: On the one hand, the recommended retreatment regimen increases the overall success rate compared to re-treating with the initial regimen. On the other hand, it increases the probability to accumulate more resistant genotypes. We conclude that treatment adherence is a key factor for a positive outcome, and that screening for resistant strains is advisable after treatment failure or relapse. AD - Institute for Integrative Biology, ETH Zurich, Switzerland. Division of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America. Department of Pharmacy, Faculty of Health Sciences, Norwegian Arctic University (UiT), Tromso, Norway. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland & Institute of Medical Virology, Swiss National Center for Retroviruses, University of Zurich, Zurich, Switzerland. AN - 26967493 AU - Cadosch, D. AU - Abel Zur Wiesch, P. AU - Kouyos, R. AU - Bonhoeffer, S. C2 - PMC4788301 DA - Mar DO - 10.1371/journal.pcbi.1004749 DP - NLM ET - 2016/03/12 IS - 3 J2 - PLoS computational biology KW - Antitubercular Agents/*administration & dosage Computer Simulation Humans Medication Adherence/*statistics & numerical data *Models, Biological Models, Statistical Mycobacterium tuberculosis/drug effects/*physiology Risk Assessment/methods Treatment Outcome Tuberculosis, Multidrug-Resistant/*drug therapy/epidemiology/*microbiology Tuberculosis, Pulmonary/drug therapy/microbiology L1 - internal-pdf://1207815283/Cadosch-2016-The Role of Adherence and Retreat.pdf LA - eng N1 - 1553-7358 Cadosch, Dominique Abel Zur Wiesch, Pia Kouyos, Roger Bonhoeffer, Sebastian Journal Article Research Support, Non-U.S. Gov't United States PLoS Comput Biol. 2016 Mar 11;12(3):e1004749. doi: 10.1371/journal.pcbi.1004749. eCollection 2016 Mar. PY - 2016 SN - 1553-734x SP - e1004749 ST - The Role of Adherence and Retreatment in De Novo Emergence of MDR-TB T2 - PLoS Comput Biol TI - The Role of Adherence and Retreatment in De Novo Emergence of MDR-TB UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788301/pdf/pcbi.1004749.pdf VL - 12 ID - 1039 ER - TY - JOUR AB - BACKGROUND: We estimated the potential impact and cost-effectiveness of providing 3-doses of nonavalent human papillomavirus (HPV) vaccine (9vHPV) to females aged 13-18 years who had previously completed a series of quadrivalent HPV vaccine (4vHPV), a strategy we refer to as "additional 9vHPV vaccination." METHODS: We used 2 distinct models: (1) the simplified model, which is among the most basic of the published dynamic HPV models, and (2) the US HPV-ADVISE model, a complex, stochastic, individual-based transmission-dynamic model. RESULTS: When assuming no 4vHPV cross-protection, the incremental cost per quality-adjusted life-year (QALY) gained by additional 9vHPV vaccination was $146 200 in the simplified model and $108 200 in the US HPV-ADVISE model ($191 800 when assuming 4vHPV cross-protection). In 1-way sensitivity analyses in the scenario of no 4vHPV cross-protection, the simplified model results ranged from $70 300 to $182 000, and the US HPV-ADVISE model results ranged from $97 600 to $118 900. CONCLUSIONS: The average cost per QALY gained by additional 9vHPV vaccination exceeded $100 000 in both models. However, the results varied considerably in sensitivity and uncertainty analyses. Additional 9vHPV vaccination is likely not as efficient as many other potential HPV vaccination strategies, such as increasing primary 9vHPV vaccine coverage. AD - Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia. Centre de recherche du CHU de Quebec, Universite Laval, Axe Sante des populations et pratiques optimales en sante Centre de recherche du CHU de Quebec, Universite Laval, Axe Sante des populations et pratiques optimales en sante Departement de medecine sociale et preventive, Universite Laval, Quebec, Canada Department of Infectious Disease Epidemiology, Imperial College, London, United Kingdom. AN - 26908738 AU - Chesson, H. W. AU - Laprise, J. F. AU - Brisson, M. AU - Markowitz, L. E. C2 - PMC4857476 DA - Jun 01 DO - 10.1093/infdis/jiw046 DP - NLM ET - 2016/02/26 IS - 11 J2 - The Journal of infectious diseases KW - Adolescent Cost-Benefit Analysis Dose-Response Relationship, Immunologic Female Humans Immunogenicity, Vaccine Male Models, Immunological Papillomavirus Vaccines/chemistry/*economics/*immunology United States *cost-effectiveness analysis *disease transmission models *human papillomavirus *vaccine *vaccine impact LA - eng N1 - 1537-6613 Chesson, Harrell W Laprise, Jean-Francois Brisson, Marc Markowitz, Lauri E Comparative Study Journal Article United States J Infect Dis. 2016 Jun 1;213(11):1694-700. doi: 10.1093/infdis/jiw046. Epub 2016 Feb 9. PY - 2016 SN - 0022-1899 SP - 1694-700 ST - Impact and Cost-effectiveness of 3 Doses of 9-Valent Human Papillomavirus (HPV) Vaccine Among US Females Previously Vaccinated With 4-Valent HPV Vaccine T2 - J Infect Dis TI - Impact and Cost-effectiveness of 3 Doses of 9-Valent Human Papillomavirus (HPV) Vaccine Among US Females Previously Vaccinated With 4-Valent HPV Vaccine VL - 213 ID - 2933 ER - TY - JOUR AB - Mycobacterium tuberculosis has an unusual natural history in that the vast majority of its human hosts enter a latent state that is both non-infectious and devoid of any symptoms of disease. From the pathogen perspective, it seems counterproductive to relinquish reproductive opportunities to achieve a detente with the host immune response. However, a small fraction of latent infections reactivate to the disease state. Thus, latency has been argued to provide a safe harbour for future infections which optimizes the persistence of M. tuberculosis in human populations. Yet, if a pathogen begins interactions with humans as an active disease without latency, how could it begin to evolve latency properties without incurring an immediate reproductive disadvantage? We address this question with a mathematical model. Results suggest that the emergence of tuberculosis latency may have been enabled by a mechanism akin to cryptic genetic variation in that detrimental latency properties were hidden from natural selection until their expression became evolutionarily favoured. AD - School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia Evolution and Ecology Research Centre, University of New South Wales, Sydney 2052, Australia rebecca.chisholm@unsw.edu.au. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia Evolution and Ecology Research Centre, University of New South Wales, Sydney 2052, Australia. AN - 27194699 AU - Chisholm, R. H. AU - Tanaka, M. M. C2 - PMC4892801 DA - May 25 DO - 10.1098/rspb.2016.0499 DP - NLM ET - 2016/05/20 IS - 1831 J2 - Proceedings. Biological sciences KW - Asymptomatic Infections *Genetic Fitness Humans Models, Genetic Mycobacterium tuberculosis/*pathogenicity/*physiology Tuberculosis/*epidemiology/microbiology/transmission Virulence *adaptive dynamics *cryptic genetic variation *latency *niche construction *virulence LA - eng N1 - 1471-2954 Chisholm, Rebecca H Orcid: 0000-0002-7830-793x Tanaka, Mark M Journal Article Research Support, Non-U.S. Gov't England Proc Biol Sci. 2016 May 25;283(1831). pii: 20160499. doi: 10.1098/rspb.2016.0499. PY - 2016 SN - 0962-8452 ST - The emergence of latent infection in the early evolution of Mycobacterium tuberculosis T2 - Proc Biol Sci TI - The emergence of latent infection in the early evolution of Mycobacterium tuberculosis VL - 283 ID - 970 ER - TY - JOUR AB - Tuberculosis (TB) is caused by the Mycobacterium tuberculosis complex (MTBC), a wildly successful group of organisms and the leading cause of death resulting from a single bacterial pathogen worldwide. It is generally accepted that MTBC established itself in human populations in Africa and that animal-infecting strains diverged from human strains. However, the precise causal factors of TB emergence remain unknown. Here, we propose that the advent of controlled fire use in early humans created the ideal conditions for the emergence of TB as a transmissible disease. This hypothesis is supported by mathematical modeling together with a synthesis of evidence from epidemiology, evolutionary genetics, and paleoanthropology. AD - School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia; Evolution & Ecology Research Centre, University of New South Wales, Sydney 2052, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne 3004, Australia; Palaeontology, Geobiology and Earth Archives Research Centre, University of New South Wales, Sydney 2052, Australia. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia; Evolution & Ecology Research Centre, University of New South Wales, Sydney 2052, Australia; m.tanaka@unsw.edu.au. AN - 27457933 AU - Chisholm, R. H. AU - Trauer, J. M. AU - Curnoe, D. AU - Tanaka, M. M. C2 - PMC4987778 DA - Aug 09 DO - 10.1073/pnas.1603224113 DP - NLM ET - 2016/07/28 IS - 32 J2 - Proceedings of the National Academy of Sciences of the United States of America KW - cultural evolution epidemiology mathematical modeling pathogen evolution tuberculosis L1 - internal-pdf://0123500341/Chisholm-2016-Controlled fire use in early hum.pdf LA - eng N1 - 1091-6490 Chisholm, Rebecca H Trauer, James M Curnoe, Darren Tanaka, Mark M Journal Article United States Proc Natl Acad Sci U S A. 2016 Aug 9;113(32):9051-6. doi: 10.1073/pnas.1603224113. Epub 2016 Jul 25. PY - 2016 SN - 0027-8424 SP - 9051-6 ST - Controlled fire use in early humans might have triggered the evolutionary emergence of tuberculosis T2 - Proc Natl Acad Sci U S A TI - Controlled fire use in early humans might have triggered the evolutionary emergence of tuberculosis UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987778/pdf/pnas.201603224.pdf VL - 113 ID - 904 ER - TY - JOUR AB - BACKGROUND: No treatment regimens have been specifically designed for children, in whom tuberculosis is predominantly intracellular. Given their activity as monotherapy and their ability to penetrate many diseased anatomic sites that characterize disseminated tuberculosis, linezolid and moxifloxacin could be combined to form a regimen for this need. METHODS: We examined microbial kill of intracellular Mycobacterium tuberculosis (Mtb) by the combination of linezolid and moxifloxacin multiple exposures in a 7-by-7 mathematical matrix. We then used the hollow fiber system (HFS) model of intracellular tuberculosis to identify optimal dose schedules and exposures of moxifloxacin and linezolid in combination. We mimicked pediatric half-lives and concentrations achieved by each drug. We sampled the peripheral compartment on days 0, 7, 14, 21, and 28 for Mtb quantification, and compared the slope of microbial kill of Mtb by these regimens to the standard regimen of isoniazid, rifampin, and pyrazinamide, based on exponential decline regression. RESULTS: The full exposure-response surface identified linezolid-moxifloxacin zones of synergy, antagonism, and additivity. A regimen based on each of these zones was then used in the HFS model, with observed half-lives of 4.08 +/- 0.66 for linezolid and 3.80 +/- 1.34 hours for moxifloxacin. The kill rate constant was 0.060 +/- 0.012 per day with the moxifloxacin-linezolid regimen in the additivity zone vs 0.083 +/- 0.011 per day with standard therapy, translating to a bacterial burden half-life of 11.52 days vs 8.53 days, respectively. CONCLUSIONS: We identified doses and dose schedules of a linezolid and moxifloxacin backbone regimen that could be highly efficacious in disseminated tuberculosis in children. AD - Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas. Center for Tuberculosis Research, Department of Medicine Department of International Health, Johns Hopkins University School of Medicine, Baltimore, Maryland. Tuberculosis Research Center, Chennai, India. Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas Department of Medicine, University of Cape Town, Observatory, South Africa. AN - 27742639 AU - Deshpande, D. AU - Srivastava, S. AU - Nuermberger, E. AU - Pasipanodya, J. G. AU - Swaminathan, S. AU - Gumbo, T. C2 - PMC5064154 DA - Nov 01 DO - 10.1093/cid/ciw473 DP - NLM ET - 2016/10/16 IS - suppl 3 J2 - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America KW - Bliss independence additivity disseminated tuberculosis exposure-response surface hollow fiber system model LA - eng N1 - 1537-6591 Deshpande, Devyani Srivastava, Shashikant Nuermberger, Eric Pasipanodya, Jotam G Swaminathan, Soumya Gumbo, Tawanda R56 AI111985/AI/NIAID NIH HHS/United States Journal Article United States Clin Infect Dis. 2016 Nov 1;63(suppl 3):S88-S94. PY - 2016 SN - 1058-4838 SP - S88-s94 ST - Concentration-Dependent Synergy and Antagonism of Linezolid and Moxifloxacin in the Treatment of Childhood Tuberculosis: The Dynamic Duo T2 - Clin Infect Dis TI - Concentration-Dependent Synergy and Antagonism of Linezolid and Moxifloxacin in the Treatment of Childhood Tuberculosis: The Dynamic Duo VL - 63 ID - 850 ER - TY - JOUR AB - BACKGROUND: After infection with Mycobacterium tuberculosis, children are at an increased risk of progression to tuberculosis disease; a condition that can be challenging to diagnose. New estimation approaches for children have highlighted the gap between incidence and notifications of M tuberculosis, and suggest there are more cases of isoniazid-resistant and multidrug-resistant (MDR) disease than are identified. No work has yet quantified the burden of drug-resistant infection, or accounted for other types of drug resistance or sampling uncertainty. METHODS: We combined a mathematical model of tuberculosis in children with an analysis of drug-resistance patterns to produce country-level, regional, and global estimates of drug-resistant infection and disease. We determined drug resistance using data from the Global Project on Antituberculosis Drug Resistance Surveillance at WHO, from surveys and surveillance reported between 1988 and 2014. We combined 1000 sampled proportions for each country from a Bayesian approach with 10 000 sampled country estimates of tuberculosis disease incidence and M tuberculosis infection prevalence. We estimated the proportions of tuberculosis cases at a country level with isoniazid monoresistance, rifampicin monoresistance, multidrug resistance (MDR), fluoroquinolone-resistant multidrug resistance, second-line injectable-resistant multidrug resistance, and extensive multidrug resistance with resistance to both a fluoroquinolone and a second-line injectable (XDR). FINDINGS: We estimated that 850 000 children developed tuberculosis in 2014; 58 000 with isoniazid-monoresistant tuberculosis, 25 000 with MDR tuberculosis, and 1200 with XDR tuberculosis. We estimate 67 million children are infected with M tuberculosis; 5 million with isoniazid monoresistance, 2 million with MDR, and 100 000 with XDR. Africa and southeast Asia have the highest numbers of children with tuberculosis, but the WHO Eastern Mediterranean region, European region, and Western Pacific region also contribute substantially to the burden of drug-resistant tuberculosis because of their much higher proportions of resistance. INTERPRETATION: Far more drug-resistant tuberculosis occurs in children than is diagnosed, and there is a large pool of drug-resistant infection. This finding has implications for approaches to empirical treatment and preventive therapy in some regions of the world. FUNDING: UNITAID. AD - School of Health and Related Research, University of Sheffield, Sheffield, UK. Electronic address: p.j.dodd@sheffield.ac.uk. Global TB Programme, World Health Organization, Geneva, Switzerland. Department of Paediatric Infectious Diseases, Imperial College London, London, UK. AN - 27342768 AU - Dodd, P. J. AU - Sismanidis, C. AU - Seddon, J. A. DA - Oct DO - 10.1016/s1473-3099(16)30132-3 DP - NLM ET - 2016/06/28 IS - 10 J2 - The Lancet. Infectious diseases KW - Antitubercular Agents/*therapeutic use Child Child, Preschool *Global Health Humans Incidence Isoniazid/therapeutic use *Models, Theoretical Mycobacterium tuberculosis/isolation & purification Tuberculosis, Multidrug-Resistant/*drug therapy/epidemiology L1 - internal-pdf://2746646925/PIIS1473309916301323.pdf LA - eng N1 - 1474-4457 Dodd, Peter J Sismanidis, Charalambos Seddon, James A 001/World Health Organization/International Journal Article United States Lancet Infect Dis. 2016 Oct;16(10):1193-201. doi: 10.1016/S1473-3099(16)30132-3. Epub 2016 Jun 21. PY - 2016 SN - 1473-3099 SP - 1193-201 ST - Global burden of drug-resistant tuberculosis in children: a mathematical modelling study T2 - Lancet Infect Dis TI - Global burden of drug-resistant tuberculosis in children: a mathematical modelling study VL - 16 ID - 935 ER - TY - JOUR AB - In this work, we examine practical aspects of backward bifurcation for a data-based model of tuberculosis that incorporates multiple features which have previously been shown to produce backward bifurcation (e.g. exogenous reinfection and imperfect vaccination) and new considerations such as the treatment of latent TB infection (LTBI) and the BCG vaccine's interference with detecting LTBI. Understanding the interplay between these multiple factors and backward bifurcation is particularly timely given that new diagnostic tests for LTBI detection could dramatically increase rates of both LTBI detection and vaccination in the coming decades. By establishing analytic thresholds for the existence of backward bifurcation, we identify those aspects of TB's complicated pathology that make backward bifurcation more or less likely to occur. We also examine the magnitude of the backward bifurcation produced by the model and its sensitivity to various model parameters. We find that backward bifurcation is unlikely to occur. While increased vaccine coverage and/or increased detection and treatment of LTBI can push the threshold for backward bifurcation into the region of biological plausibility, the resulting bifurcations may still be too small to have any noticeable epidemiological impact. AD - Department of Mathematics, Xavier University 3800 Victory Parkway, Cincinnati, OH 45207, USA. Electronic address: david.gerberry@xavier.edu. AN - 26493359 AU - Gerberry, D. J. DA - Jan 07 DO - 10.1016/j.jtbi.2015.10.003 DP - NLM ET - 2015/10/24 J2 - Journal of theoretical biology KW - *Algorithms BCG Vaccine/*therapeutic use Humans Latent Tuberculosis/diagnosis/drug therapy/microbiology *Models, Theoretical Mycobacterium tuberculosis/*drug effects/physiology Time Factors Tuberculin Test/methods Tuberculosis/diagnosis/*drug therapy/microbiology Vaccination/methods Bcg Backward bifurcation LTBI treatment Mathematical modeling Tuberculosis LA - eng N1 - 1095-8541 Gerberry, David J Journal Article England J Theor Biol. 2016 Jan 7;388:15-36. doi: 10.1016/j.jtbi.2015.10.003. Epub 2015 Oct 19. PY - 2016 SN - 0022-5193 SP - 15-36 ST - Practical aspects of backward bifurcation in a mathematical model for tuberculosis T2 - J Theor Biol TI - Practical aspects of backward bifurcation in a mathematical model for tuberculosis VL - 388 ID - 1191 ER - TY - JOUR AB - South Africa has one of the highest burdens of TB worldwide, driven by the country's widespread prevalence of HIV, and further complicated by drug resistance. Active case finding within the community, particularly in rural areas where healthcare access is limited, can significantly improve diagnosis and treatment coverage in high-incidence settings. We evaluated the potential health and economic consequences of implementing community-based TB/HIV screening and linkage to care. Using a dynamic model of TB and HIV transmission over a time horizon of 10 years, we compared status quo TB/HIV control to community-based TB/HIV screening at frequencies of once every two years, one year, and six months. We also considered the impact of extending IPT from 36 months for TST positive and 12 months for TST negative or unknown patients (36/12) to lifetime use for all HIV-infected patients. We conducted a probabilistic sensitivity analysis to assess the effect of parameter uncertainty on the cost-effectiveness results. We identified four strategies that saved the most life years for a given outlay: status quo TB/HIV control with 36/12 months of IPT and TB/HIV screening strategies at frequencies of once every two years, one year, and six months with lifetime IPT. All of these strategies were very cost-effective at a threshold of $6,618 per life year saved (the per capita GDP of South Africa). Community-based TB/HIV screening with linkage to care is therefore very cost-effective in rural South Africa. AD - Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America. Center for Infectious Disease Modeling and Analysis, Yale School of Public Health, New Haven, Connecticut, United States of America. Department of Medicine, Section of Infectious Diseases, AIDS Program, Yale University School of Medicine, New Haven, Connecticut, United States of America. Church of Scotland Hospital, Tugela Ferry, KwaZulu-Natal, South Africa. Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut, United States of America. AN - 27906986 AU - Gilbert, J. A. AU - Shenoi, S. V. AU - Moll, A. P. AU - Friedland, G. H. AU - Paltiel, A. D. AU - Galvani, A. P. C2 - PMC5131994 DO - 10.1371/journal.pone.0165614 DP - NLM ET - 2016/12/03 IS - 12 J2 - PloS one KW - Adult Cost-Benefit Analysis/*economics Female HIV Infections/economics/*epidemiology/transmission Humans Male *Mass Screening Patient Acceptance of Health Care Rural Population South Africa/epidemiology Tuberculosis/economics/*epidemiology/transmission L1 - internal-pdf://0195594989/Gilbert-2016-Cost-Effectiveness of Community-B.pdf LA - eng N1 - 1932-6203 Gilbert, Jennifer A Shenoi, Sheela V Moll, Anthony P Friedland, Gerald H Paltiel, A David Galvani, Alison P K23 AI089260/AI/NIAID NIH HHS/United States R01 DA015612/DA/NIDA NIH HHS/United States Journal Article United States PLoS One. 2016 Dec 1;11(12):e0165614. doi: 10.1371/journal.pone.0165614. eCollection 2016. PY - 2016 SN - 1932-6203 SP - e0165614 ST - Cost-Effectiveness of Community-Based TB/HIV Screening and Linkage to Care in Rural South Africa T2 - PLoS One TI - Cost-Effectiveness of Community-Based TB/HIV Screening and Linkage to Care in Rural South Africa UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131994/pdf/pone.0165614.pdf VL - 11 ID - 806 ER - TY - JOUR AB - Background: Diseases occur in populations whose individuals differ in essential characteristics, such as exposure to the causative agent, susceptibility given exposure, and infectiousness upon infection in the case of infectious diseases. Discussion: Concepts developed in demography more than 30 years ago assert that variability between individuals affects substantially the estimation of overall population risk from disease incidence data. Methods that ignore individual heterogeneity tend to underestimate overall risk and lead to overoptimistic expectations for control. Concerned that this phenomenon is frequently overlooked in epidemiology, here we feature its significance for interpreting global data on human tuberculosis and predicting the impact of control measures. Summary: We show that population-wide interventions have the greatest impact in populations where all individuals face an equal risk. Lowering variability in risk has great potential to increase the impact of interventions. Reducing inequality, therefore, empowers health interventions, which in turn improves health, further reducing inequality, in a virtuous circle. AD - Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England Univ Porto, Ctr Invest Biodiversidade & Recursos Genet, CIBIO InBIO, Vila Do Conde, Portugal Univ Sao Paulo, Inst Matemat & Estat, Sao Paulo, Brazil Fiocruz MS, Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil Univ Fed Bahia, Inst Saude Colet, Salvador, BA, Brazil WHO, CH-1211 Geneva 27, Switzerland London Sch Hyg & Trop Med, London WC1, England Natl Inst Publ Hlth & Environm, Dept Infect Dis Epidemiol, POB 1, NL-3720 BA Bilthoven, Netherlands Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, NL-2300 RC Leiden, Netherlands AN - WOS:000372704000001 AU - Gomes, M. G. M. AU - Barreto, M. L. AU - Glaziou, P. AU - Medley, G. F. AU - Rodrigues, L. C. AU - Wallinga, J. AU - Squire, S. B. DA - Mar 22 DO - ARTN 132 10.1186/s12879-016-1464-8 J2 - Bmc Infect Dis KW - tuberculosis heterogeneity cohort selection social inequality intervention impact tuberculosis-control heterogeneity countries dynamics impact L1 - internal-pdf://3733143470/Gomes-2016-End TB strategy_ the need to reduce.pdf LA - English N1 - Dh3rk Times Cited:2 Cited References Count:19 PY - 2016 SN - 1471-2334 ST - End TB strategy: the need to reduce risk inequalities T2 - Bmc Infectious Diseases TI - End TB strategy: the need to reduce risk inequalities UR - ://WOS:000372704000001 https://bmcinfectdis.biomedcentral.com/track/pdf/10.1186/s12879-016-1464-8?site=bmcinfectdis.biomedcentral.com VL - 16 ID - 2188 ER - TY - JOUR AB - BACKGROUND: Despite improvements in treatment success rates for tuberculosis (TB), current six-month regimen duration remains a challenge for many National TB Programmes, health systems, and patients. There is increasing investment in the development of shortened regimens with a number of candidates in phase 3 trials. METHODS: We developed an individual-based decision analytic model to assess the cost-effectiveness of a hypothetical four-month regimen for first-line treatment of TB, assuming non-inferiority to current regimens of six-month duration. The model was populated using extensive, empirically-collected data to estimate the economic impact on both health systems and patients of regimen shortening for first-line TB treatment in South Africa, Brazil, Bangladesh, and Tanzania. We explicitly considered 'real world' constraints such as sub-optimal guideline adherence. RESULTS: From a societal perspective, a shortened regimen, priced at USD1 per day, could be a cost-saving option in South Africa, Brazil, and Tanzania, but would not be cost-effective in Bangladesh when compared to one gross domestic product (GDP) per capita. Incorporating 'real world' constraints reduces cost-effectiveness. Patient-incurred costs could be reduced in all settings. From a health service perspective, increased drug costs need to be balanced against decreased delivery costs. The new regimen would remain a cost-effective option, when compared to each countries' GDP per capita, even if new drugs cost up to USD7.5 and USD53.8 per day in South Africa and Brazil; this threshold was above USD1 in Tanzania and under USD1 in Bangladesh. CONCLUSION: Reducing the duration of first-line TB treatment has the potential for substantial economic gains from a patient perspective. The potential economic gains for health services may also be important, but will be context-specific and dependent on the appropriate pricing of any new regimen. AD - Amsterdam Institute for Global Health and Development and Department of Global Health, Academic Medical Center, University of Amsterdam, Trinity Building C, Pietersbergweg 17, Amsterdam, 1105 BM, The Netherlands. g.gomez@aighd.org. Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, UK. g.gomez@aighd.org. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA. Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Tuberculosis Scientific League, Rio de Janeiro, Brazil. Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, UK. Health Economics Unit, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa. McGill University, Montreal, Canada. BRAC Health Nutrition and Population Programme, BRAC Centre, Dhaka, Bangladesh. Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania. TB Modelling Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. Global Alliance for TB Drug Development, New York, USA. Present address: United States Agency for International Development, Washington, DC, USA. Amsterdam Institute for Global Health and Development and Department of Global Health, Academic Medical Center, University of Amsterdam, Trinity Building C, Pietersbergweg 17, Amsterdam, 1105 BM, The Netherlands. KNCV Tuberculosis Foundation, The Hague, Netherlands. AN - 27905897 AU - Gomez, G. B. AU - Dowdy, D. W. AU - Bastos, M. L. AU - Zwerling, A. AU - Sweeney, S. AU - Foster, N. AU - Trajman, A. AU - Islam, M. A. AU - Kapiga, S. AU - Sinanovic, E. AU - Knight, G. M. AU - White, R. G. AU - Wells, W. A. AU - Cobelens, F. G. AU - Vassall, A. C2 - PMC5131398 DA - Dec 01 DO - 10.1186/s12879-016-2064-3 DP - NLM ET - 2016/12/03 IS - 1 J2 - BMC infectious diseases KW - Antitubercular Agents/*economics Bangladesh Brazil Cost-Benefit Analysis Delivery of Health Care/economics Drug Costs Health Care Costs Health Expenditures Health Services/economics Humans Models, Theoretical South Africa Tanzania Treatment Outcome Tuberculosis/*drug therapy/*economics Cost-effectiveness Economic evaluation New technologies Tuberculosis LA - eng N1 - 1471-2334 Gomez, G B Dowdy, D W Bastos, M L Zwerling, A Sweeney, S Foster, N Trajman, A Islam, M A Kapiga, S Sinanovic, E Knight, G M White, R G Wells, W A Cobelens, F G Vassall, A Journal Article England BMC Infect Dis. 2016 Dec 1;16(1):726. PY - 2016 SN - 1471-2334 SP - 726 ST - Cost and cost-effectiveness of tuberculosis treatment shortening: a model-based analysis T2 - BMC Infect Dis TI - Cost and cost-effectiveness of tuberculosis treatment shortening: a model-based analysis VL - 16 ID - 807 ER - TY - JOUR AD - [Goodell, A. J.; Vreman, R.; Porco, T. C.; Kahn, J. G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shete, P. B.; Metcalfe, J.; Cattamanchi, A.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Barry, P. M.; Flood, J.] Calif Dept Publ Hlth, Richmond, CA USA. [Marks, S.] Ctr Dis Control & Prevent, Atlanta, GA USA. AN - WOS:000390749607613 AU - Goodell, A. J. AU - Shete, P. B. AU - Vreman, R. AU - Metcalfe, J. AU - Porco, T. C. AU - Barry, P. M. AU - Flood, J. AU - Marks, S. AU - Cattamanchi, A. AU - Kahn, J. G. J2 - Am. J. Respir. Crit. Care Med. KW - General & Internal Medicine Respiratory System LA - English M3 - Meeting Abstract N1 - ISI Document Delivery No.: EG0VE Times Cited: 0 Cited Reference Count: 0 Goodell, A. J. Shete, P. B. Vreman, R. Metcalfe, J. Porco, T. C. Barry, P. M. Flood, J. Marks, S. Cattamanchi, A. Kahn, J. G. International Conference of the American-Thoracic-Society (ATS) May 13-18, 2016 San Francisco, CA Amer Thorac Soc 0 Amer thoracic soc New york 1535-4970 PY - 2016 SN - 1073-449X SP - 1 ST - Prospects For Elimination: An Individual-Based Model To Assess Tb Control Strategies In California T2 - American Journal of Respiratory and Critical Care Medicine TI - Prospects For Elimination: An Individual-Based Model To Assess Tb Control Strategies In California UR - ://WOS:000390749607613 VL - 193 ID - 5212 ER - TY - JOUR AB - Mycobacterium tuberculosis is a global health concern, causing over one million deaths a year. Alveolar macrophages, as the primary host cell of this intracellular bacterium, play an important role in the course of disease. Vitamin D3 is known to have a potent effect on macrophage behavior during infection, modulating the production of pro- and anti-inflammatory cytokines and immune effector molecules. In a vitamin D3 deficient host, the immune systems response to infection is greatly impaired. We used a quantitative systems biology approach to model the intracellular effects of vitamin D3 and compared our simulation output to our in vitro model of mycobacterium infection of macrophages in the presence and absence of Vitamin D3. Our in silico model results agreed with the in vitro assay results of interleukin-10, an anti-inflammatory protein whose production is known to be influenced by vitamin D3. This model will provide a platform for further investigation of the effects of vitamin D3 deficiency on host immune response to infection. AN - 28268597 AU - Gough, M. AU - May, E. DA - Aug DO - 10.1109/EMBC.2016.7590980 KW - Cholecalciferol Cytokines Humans Interleukin-10 *Macrophages Mycobacterium tuberculosis N1 - Gough, Maya May, Elebeoba eng 2017/03/09 06:00 Conf Proc IEEE Eng Med Biol Soc. 2016 Aug;2016:1443-1446. doi: 10.1109/EMBC.2016.7590980. PY - 2016 SN - 1557-170X (Print) 1557-170X (Linking) SP - 1443-1446 ST - An in silico model of the effects of vitamin D3 on mycobacterium infected macrophage T2 - Conf Proc IEEE Eng Med Biol Soc TI - An in silico model of the effects of vitamin D3 on mycobacterium infected macrophage UR - https://www.ncbi.nlm.nih.gov/pubmed/28268597 VL - 2016 ID - 2178 ER - TY - JOUR AB - Alveolar macrophages play a large role in the innate immune response of the lung. However, when these highly immune-regulatory cells are unable to eradicate pathogens, the adaptive immune system, which includes activated macrophages and lymphocytes, particularly T cells, is called upon to control the pathogens. This collection of immune cells surrounds, isolates and quarantines the pathogen, forming a small tissue structure called a granuloma for intracellular pathogens like Mycobacterium tuberculosis (Mtb). In the present work we develop a mathematical model of the dynamics of a granuloma by a system of partial differential equations. The 'strength' of the adaptive immune response to infection in the lung is represented by a parameter alpha, the flux rate by which T cells and M1 macrophages that immigrated from the lymph nodes enter into the granuloma through its boundary. The parameter alpha is negatively correlated with the 'switching time', namely, the time it takes for the number of M1 type macrophages to surpass the number of infected, M2 type alveolar macrophages. Simulations of the model show that as alpha increases the radius of the granuloma and bacterial load in the granuloma both decrease. The model is used to determine the efficacy of potential host-directed therapies in terms of the parameter alpha, suggesting that, with fixed dosing level, an infected individual with a stronger immune response will receive greater benefits in terms of reducing the bacterial load. AD - Mathematical Biosciences Institute, The Ohio State University, Columbus, OH, United States of America. Center for Microbial Interface Biology & Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, United States of America. Mathematical Biosciences Institute & Department of Mathematics, The Ohio State University, Columbus, OH, United States of America. AN - 26986986 AU - Hao, W. AU - Schlesinger, L. S. AU - Friedman, A. C2 - PMC4795641 DO - 10.1371/journal.pone.0148738 DP - NLM ET - 2016/03/18 IS - 3 J2 - PloS one KW - Adaptive Immunity Algorithms *Computer Simulation Granuloma/complications/*immunology/microbiology/pathology Humans Immunity, Innate Lung/*immunology/microbiology/pathology Macrophages, Alveolar/*immunology/microbiology/pathology *Models, Immunological Mycobacterium tuberculosis/*immunology T-Lymphocytes/immunology/microbiology/pathology Tuberculosis/complications/*immunology/microbiology/pathology LA - eng N1 - 1932-6203 Hao, Wenrui Schlesinger, Larry S Friedman, Avner NIH AI059639/AI/NIAID NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United States PLoS One. 2016 Mar 17;11(3):e0148738. doi: 10.1371/journal.pone.0148738. eCollection 2016. PY - 2016 SN - 1932-6203 SP - e0148738 ST - Modeling Granulomas in Response to Infection in the Lung T2 - PLoS One TI - Modeling Granulomas in Response to Infection in the Lung VL - 11 ID - 1032 ER - TY - JOUR AB - BACKGROUND: The Bacillus Calmette-Guerin (BCG) vaccine is provided to over 100 million neonates annually to protect against childhood tuberculosis (TB). Recent BCG manufacturing interruptions highlight global supply risks. We estimated the potential impact of BCG shortfalls on global paediatric (<15 years) TB mortality. METHODS: A static mathematical model was employed to estimate the number of paediatric TB deaths avoided by usual levels of BCG coverage, and potential additional TB deaths in the first 15 years of life due to 1-year BCG supply shortfalls of 6.3 % (as occurred in 2015) to 27.6 % (as anticipated without mitigating action in 2015) assuming no catch-up campaigns. RESULTS: BCG coverage without shortfalls, estimated at 90 % globally, was estimated to avoid 117,132 (95 % uncertainty range (UR): 5049-306,911) TB deaths globally per birth cohort in the first 15 years of life. An estimated 11,713 (UR: 505-30,691) additional TB deaths would occur in the first 15 years of life per 10 % (26 million dose) annual supply shortfall. A 16.5 million dose (6.3 %) shortfall as reported at the close of 2015, reflecting 84 % global coverage, was estimated as associated with 7433 (95 % UR: 320-19,477) excess TB deaths in the affected cohort in the first 15 years. A possible 24,914 (UR: 1074-65,278) additional deaths were avoided due to prompt shortfall reduction measures in 2015. CONCLUSIONS: BCG shortages could greatly increase paediatric TB mortality. Although rapid action in 2015 minimised BCG shortfalls, avoiding a large number of potential additional deaths, the possible public health impact of even relatively small shortfalls highlights the critical importance of ensuring secure future manufacturing capacity and global BCG supply continuity. AD - TB Modelling Group, TB Centre and Centre for the Mathematical Modelling of Infectious Diseases, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. rebecca.harris@lshtm.ac.uk. School of Health and Related Research, University of Sheffield, 30 Regent Street, Sheffield, S1 4DA, UK. TB Modelling Group, TB Centre and Centre for the Mathematical Modelling of Infectious Diseases, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. AN - 27633883 AU - Harris, R. C. AU - Dodd, P. J. AU - White, R. G. C2 - PMC5025545 DA - Sep 15 DO - 10.1186/s12916-016-0685-4 DP - NLM ET - 2016/09/17 IS - 1 J2 - BMC medicine KW - Acute Disease Adolescent BCG Vaccine/*supply & distribution/*therapeutic use Child Child, Preschool Health Services Accessibility/*statistics & numerical data Humans Infant Infant, Newborn Mass Vaccination/standards/statistics & numerical data Meta-Analysis as Topic *Models, Theoretical Tuberculosis/*mortality/*prevention & control Uncertainty Bacillus Calmette-Guerin vaccine Mathematical model Mortality Mycobacterium tuberculosis Paediatric Shortage Shortfall Tuberculosis LA - eng N1 - 1741-7015 Harris, Rebecca C ORCID: http://orcid.org/0000-0002-2636-1520 Dodd, Peter J White, Richard G MR/J005088/1/Medical Research Council/United Kingdom Journal Article England BMC Med. 2016 Sep 15;14(1):138. doi: 10.1186/s12916-016-0685-4. PY - 2016 SN - 1741-7015 SP - 138 ST - The potential impact of BCG vaccine supply shortages on global paediatric tuberculosis mortality T2 - BMC Med TI - The potential impact of BCG vaccine supply shortages on global paediatric tuberculosis mortality VL - 14 ID - 867 ER - TY - JOUR AB - Mathematical models are useful for assessing the potential epidemiological impact of future tuberculosis (TB) vaccines. We conducted a systematic review of mathematical models estimating the epidemiological impact of future human TB vaccines. PubMed, Embase and WHO Global Health Library were searched, 3-stage manual sifted, and citation- and reference-tracked, identifying 23 papers. An adapted quality assessment tool was developed, with a resulting median study quality score of 20/28. The literature remains divided as to whether vaccines effective pre- or post-infection would provide greatest epidemiological impact. However, all-age or adolescent/adult targeted prevention of disease vaccines achieve greater and more rapid impact than neonatal vaccines. Mass campaigns alongside routine neonatal vaccination can have profound additional impact. Economic evaluations found TB vaccines overwhelmingly cost-effective, particularly when targeted to adolescents/adults. The variability of impact by setting, age group and vaccine characteristics must be accounted for in the development and delivery of future TB vaccines. AD - a TB Modelling Group , TB Centre and Centre for the Mathematical Modelling of Infectious Diseases, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine , London , UK. b National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, Imperial College London , London , UK. AN - 27448625 AU - Harris, R. C. AU - Sumner, T. AU - Knight, G. M. AU - White, R. G. C2 - PMC5137531 DA - Nov DO - 10.1080/21645515.2016.1205769 DP - NLM ET - 2016/07/28 IS - 11 J2 - Human vaccines & immunotherapeutics KW - Cost-Benefit Analysis Disease Transmission, Infectious/*prevention & control Humans *Models, Theoretical Tuberculosis/economics/*epidemiology/*prevention & control/transmission Tuberculosis Vaccines/*administration & dosage/economics/*immunology epidemiology infectious disease dynamics mathematical model systematic review theoretical models tuberculosis vaccines L1 - internal-pdf://4200810932/Harris-2016-Systematic review of mathematical.pdf LA - eng N1 - 2164-554x Harris, Rebecca C Sumner, Tom Knight, Gwenan M White, Richard G Journal Article Review United States Hum Vaccin Immunother. 2016 Nov;12(11):2813-2832. Epub 2016 Jul 22. PY - 2016 SN - 2164-5515 SP - 2813-2832 ST - Systematic review of mathematical models exploring the epidemiological impact of future TB vaccines T2 - Hum Vaccin Immunother TI - Systematic review of mathematical models exploring the epidemiological impact of future TB vaccines UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137531/pdf/khvi-12-11-1205769.pdf VL - 12 ID - 909 ER - TY - JOUR AD - Department of Clinical Research, and Tuberculosis Modelling Group, Tuberculosis Centre, London School of Hygiene & Tropical Medicine, London, UK. katherine.horton@lshtm.ac.uk. Tuberculosis Modelling Group, Tuberculosis Centre, and Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK. Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi. AN - 27046729 AU - Horton, K. C. AU - Houben, R. M. AU - White, R. G. AU - Corbett, E. L. DA - Mar DO - 10.5588/ijtld.15.1031 DP - NLM ET - 2016/04/06 IS - 3 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Anti-HIV Agents/*therapeutic use Antitubercular Agents/*therapeutic use Female HIV Infections/*epidemiology Humans Male Tuberculosis, Pulmonary/*drug therapy LA - eng N1 - 1815-7920 Horton, Katherine C Houben, Rein M G J White, Richard G Corbett, Elizabeth L Comment Letter France Int J Tuberc Lung Dis. 2016 Mar;20(3):425. doi: 10.5588/ijtld.15.1031. PY - 2016 SN - 1027-3719 SP - 425 ST - Time for men to count, too T2 - Int J Tuberc Lung Dis TI - Time for men to count, too VL - 20 ID - 1009 ER - TY - JOUR AB - BACKGROUND: Tuberculosis (TB) case notification rates are usually higher in men than in women, but notification data are insufficient to measure sex differences in disease burden. This review set out to systematically investigate whether sex ratios in case notifications reflect differences in disease prevalence and to identify gaps in access to and/or utilisation of diagnostic services. METHODS AND FINDINGS: In accordance with the published protocol (CRD42015022163), TB prevalence surveys in nationally representative and sub-national adult populations (age >/= 15 y) in low- and middle-income countries published between 1 January 1993 and 15 March 2016 were identified through searches of PubMed, Embase, Global Health, and the Cochrane Database of Systematic Reviews; review of abstracts; and correspondence with the World Health Organization. Random-effects meta-analyses examined male-to-female (M:F) ratios in TB prevalence and prevalence-to-notification (P:N) ratios for smear-positive TB. Meta-regression was done to identify factors associated with higher M:F ratios in prevalence and higher P:N ratios. Eighty-three publications describing 88 surveys with over 3.1 million participants in 28 countries were identified (36 surveys in Africa, three in the Americas, four in the Eastern Mediterranean, 28 in South-East Asia and 17 in the Western Pacific). Fifty-six surveys reported in 53 publications were included in quantitative analyses. Overall random-effects weighted M:F prevalence ratios were 2.21 (95% CI 1.92-2.54; 56 surveys) for bacteriologically positive TB and 2.51 (95% CI 2.07-3.04; 40 surveys) for smear-positive TB. M:F prevalence ratios were highest in South-East Asia and in surveys that did not require self-report of signs/symptoms in initial screening procedures. The summary random-effects weighted M:F ratio for P:N ratios was 1.55 (95% CI 1.25-1.91; 34 surveys). We intended to stratify the analyses by age, HIV status, and rural or urban setting; however, few studies reported such data. CONCLUSIONS: TB prevalence is significantly higher among men than women in low- and middle-income countries, with strong evidence that men are disadvantaged in seeking and/or accessing TB care in many settings. Global strategies and national TB programmes should recognise men as an underserved high-risk group and improve men's access to diagnostic and screening services to reduce the overall burden of TB more effectively and ensure gender equity in TB care. AD - Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom. Tuberculosis Modelling Group, Tuberculosis Centre, London School of Hygiene & Tropical Medicine, London, United Kingdom. Department of Public Health and Policy, University of Liverpool, Liverpool, United Kingdom. Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom. Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom. Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi. AN - 27598345 AU - Horton, K. C. AU - MacPherson, P. AU - Houben, R. M. AU - White, R. G. AU - Corbett, E. L. C2 - PMC5012571 DA - Sep DO - 10.1371/journal.pmed.1002119 DP - NLM ET - 2016/09/07 IS - 9 J2 - PLoS medicine KW - *Developing Countries *Disease Notification/statistics & numerical data Female *Global Burden of Disease/statistics & numerical data Humans Male Prevalence Sex Factors Sex Ratio Tuberculosis/*epidemiology/microbiology LA - eng N1 - 1549-1676 Horton, Katherine C MacPherson, Peter Houben, Rein M G J White, Richard G ORCID: http://orcid.org/0000-0003-4410-6635 Corbett, Elizabeth L MR/J005088/1/Medical Research Council/United Kingdom Journal Article Meta-Analysis Review United States PLoS Med. 2016 Sep 6;13(9):e1002119. doi: 10.1371/journal.pmed.1002119. eCollection 2016 Sep. PY - 2016 SN - 1549-1277 SP - e1002119 ST - Sex Differences in Tuberculosis Burden and Notifications in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis T2 - PLoS Med TI - Sex Differences in Tuberculosis Burden and Notifications in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis VL - 13 ID - 874 ER - TY - JOUR AB - BACKGROUND: The existing estimate of the global burden of latent TB infection (LTBI) as "one-third" of the world population is nearly 20 y old. Given the importance of controlling LTBI as part of the End TB Strategy for eliminating TB by 2050, changes in demography and scientific understanding, and progress in TB control, it is important to re-assess the global burden of LTBI. METHODS AND FINDINGS: We constructed trends in annual risk in infection (ARI) for countries between 1934 and 2014 using a combination of direct estimates of ARI from LTBI surveys (131 surveys from 1950 to 2011) and indirect estimates of ARI calculated from World Health Organisation (WHO) estimates of smear positive TB prevalence from 1990 to 2014. Gaussian process regression was used to generate ARIs for country-years without data and to represent uncertainty. Estimated ARI time-series were applied to the demography in each country to calculate the number and proportions of individuals infected, recently infected (infected within 2 y), and recently infected with isoniazid (INH)-resistant strains. Resulting estimates were aggregated by WHO region. We estimated the contribution of existing infections to TB incidence in 2035 and 2050. In 2014, the global burden of LTBI was 23.0% (95% uncertainty interval [UI]: 20.4%-26.4%), amounting to approximately 1.7 billion people. WHO South-East Asia, Western-Pacific, and Africa regions had the highest prevalence and accounted for around 80% of those with LTBI. Prevalence of recent infection was 0.8% (95% UI: 0.7%-0.9%) of the global population, amounting to 55.5 (95% UI: 48.2-63.8) million individuals currently at high risk of TB disease, of which 10.9% (95% UI:10.2%-11.8%) was isoniazid-resistant. Current LTBI alone, assuming no additional infections from 2015 onwards, would be expected to generate TB incidences in the region of 16.5 per 100,000 per year in 2035 and 8.3 per 100,000 per year in 2050. Limitations included the quantity and methodological heterogeneity of direct ARI data, and limited evidence to inform on potential clearance of LTBI. CONCLUSIONS: We estimate that approximately 1.7 billion individuals were latently infected with Mycobacterium tuberculosis (M.tb) globally in 2014, just under a quarter of the global population. Investment in new tools to improve diagnosis and treatment of those with LTBI at risk of progressing to disease is urgently needed to address this latent reservoir if the 2050 target of eliminating TB is to be reached. AD - TB Modelling Group, TB Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom. Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom. School of Health and Related Research, University of Sheffield, Sheffield, United Kingdom. AN - 27780211 AU - Houben, R. M. AU - Dodd, P. J. C2 - PMC5079585 DA - Oct DO - 10.1371/journal.pmed.1002152 DP - NLM ET - 2016/10/26 IS - 10 J2 - PLoS medicine KW - Antitubercular Agents/*pharmacology *Global Health Humans Incidence Isoniazid/*pharmacology Latent Tuberculosis/*epidemiology/microbiology Mycobacterium tuberculosis/drug effects/physiology Prevalence Risk Tuberculosis, Multidrug-Resistant/epidemiology/microbiology L1 - internal-pdf://1155543566/Houben-2016-The Global Burden of Latent Tuberc.pdf LA - eng N1 - 1549-1676 Houben, Rein M G J Dodd, Peter J ORCID: http://orcid.org/0000-0001-5825-9347 Journal Article Review United States PLoS Med. 2016 Oct 25;13(10):e1002152. doi: 10.1371/journal.pmed.1002152. eCollection 2016 Oct. PY - 2016 SN - 1549-1277 SP - e1002152 ST - The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling T2 - PLoS Med TI - The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079585/pdf/pmed.1002152.pdf VL - 13 ID - 837 ER - TY - JOUR AB - Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, predominantly affecting low- and middle-income countries (LMICs), where resources are limited. As such, countries need to be able to choose the most efficient interventions for their respective setting. Mathematical models can be valuable tools to inform rational policy decisions and improve resource allocation, but are often unavailable or inaccessible for LMICs, particularly in TB. We developed TIME Impact, a user-friendly TB model that enables local capacity building and strengthens country-specific policy discussions to inform support funding applications at the (sub-)national level (e.g. Ministry of Finance) or to international donors (e.g. the Global Fund to Fight AIDS, Tuberculosis and Malaria).TIME Impact is an epidemiological transmission model nested in TIME, a set of TB modelling tools available for free download within the widely-used Spectrum software. The TIME Impact model reflects key aspects of the natural history of TB, with additional structure for HIV/ART, drug resistance, treatment history and age. TIME Impact enables national TB programmes (NTPs) and other TB policymakers to better understand their own TB epidemic, plan their response, apply for funding and evaluate the implementation of the response.The explicit aim of TIME Impact's user-friendly interface is to enable training of local and international TB experts towards independent use. During application of TIME Impact, close involvement of the NTPs and other local partners also builds critical understanding of the modelling methods, assumptions and limitations inherent to modelling. This is essential to generate broad country-level ownership of the modelling data inputs and results. In turn, it stimulates discussions and a review of the current evidence and assumptions, strengthening the decision-making process in general.TIME Impact has been effectively applied in a variety of settings. In South Africa, it informed the first South African HIV and TB Investment Cases and successfully leveraged additional resources from the National Treasury at a time of austerity. In Ghana, a long-term TIME model-centred interaction with the NTP provided new insights into the local epidemiology and guided resource allocation decisions to improve impact. AD - TB Modelling Group, TB Centre, London School of Hygiene and Tropical Medicine, Keppel Street, WC1E 7HT, London, UK. rein.houben@lshtm.ac.uk. Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. rein.houben@lshtm.ac.uk. TB Modelling Group, TB Centre, London School of Hygiene and Tropical Medicine, Keppel Street, WC1E 7HT, London, UK. Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. Avenir Health, Glastonbury, CT, USA. National Tuberculosis Control Programme, Ghana Health Service, Accra, Ghana. Aurum Institute, Johannesburg, South Africa. National Department of Health, Pretoria, South Africa. KNCV Tuberculosis Foundation, The Hague, The Netherlands. USAID, Washington, DC, USA. AN - 27012808 AU - Houben, R. M. AU - Lalli, M. AU - Sumner, T. AU - Hamilton, M. AU - Pedrazzoli, D. AU - Bonsu, F. AU - Hippner, P. AU - Pillay, Y. AU - Kimerling, M. AU - Ahmedov, S. AU - Pretorius, C. AU - White, R. G. C2 - PMC4806495 DA - Mar 24 DO - 10.1186/s12916-016-0608-4 DP - NLM ET - 2016/03/26 J2 - BMC medicine KW - *Health Policy Health Resources Humans *Models, Theoretical *Policy Making South Africa/epidemiology Tuberculosis/*epidemiology Capacity building Mathematical modelling Policy support Tuberculosis L1 - internal-pdf://2281198700/Houben-2016-TIME Impact - a new user-friendly.pdf LA - eng N1 - 1741-7015 Houben, R M G J Lalli, M Sumner, T Hamilton, M Pedrazzoli, D Bonsu, F Hippner, P Pillay, Y Kimerling, M Ahmedov, S Pretorius, C White, R G MR/J005088/1/Medical Research Council/United Kingdom Medical Research Council/United Kingdom Letter Research Support, Non-U.S. Gov't England BMC Med. 2016 Mar 24;14:56. doi: 10.1186/s12916-016-0608-4. PY - 2016 SN - 1741-7015 SP - 56 ST - TIME Impact - a new user-friendly tuberculosis (TB) model to inform TB policy decisions T2 - BMC Med TI - TIME Impact - a new user-friendly tuberculosis (TB) model to inform TB policy decisions UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806495/pdf/12916_2016_Article_608.pdf VL - 14 ID - 1021 ER - TY - JOUR AB - BACKGROUND: The post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements. METHODS: 11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa. Models were calibrated with data on tuberculosis incidence and mortality in 2012. Representatives from national tuberculosis programmes and the advocacy community provided distinct country-specific intervention scenarios, which included screening for symptoms, active case finding, and preventive therapy. FINDINGS: Aggressive scale-up of any single intervention scenario could not achieve the post-2015 End TB Strategy targets in any country. However, the models projected that, in the South Africa national tuberculosis programme scenario, a combination of continuous isoniazid preventive therapy for individuals on antiretroviral therapy, expanded facility-based screening for symptoms of tuberculosis at health centres, and improved tuberculosis care could achieve a 55% reduction in incidence (range 31-62%) and a 72% reduction in mortality (range 64-82%) compared with 2015 levels. For India, and particularly for China, full scale-up of all interventions in tuberculosis-programme performance fell short of the 2025 targets, despite preventing a cumulative 3.4 million cases. The advocacy scenarios illustrated the high impact of detecting and treating latent tuberculosis. INTERPRETATION: Major reductions in tuberculosis burden seem possible with current interventions. However, additional interventions, adapted to country-specific tuberculosis epidemiology and health systems, are needed to reach the post-2015 End TB Strategy targets at country level. FUNDING: Bill and Melinda Gates Foundation. AD - TB Modelling Group, TB Centre, London School of Hygiene and Tropical Medicine, London, UK; Faculty of Epidemiology and Public Health, London School of Hygiene and Tropical Medicine, London, UK. Electronic address: rein.houben@lshtm.ac.uk. Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, USA. TB Modelling Group, TB Centre, London School of Hygiene and Tropical Medicine, London, UK; Faculty of Epidemiology and Public Health, London School of Hygiene and Tropical Medicine, London, UK. Institute for Disease Modeling, Seattle, WA, USA. Department of Infectious Disease Epidemiology, Imperial College London, London, UK; Public Health Foundation of India, Delhi NCR, India. Stanford Health Policy, Centers for Health Policy and Primary Care and Outcomes Research, Stanford University, Stanford, CA, USA. Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan. Public Health Foundation of India, Delhi NCR, India. Management Science and Engineering Dept, Stanford University, Stanford, CA, USA. Department of Medicine, Stanford University, Stanford, CA, USA. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. IRD, UMMISCO, Bondy, France. Department of Biology, Stanford University, Stanford, CA, USA; Johnson & Johnson Global Public Health, Raritan, NJ, USA. Department of Biology, Stanford University, Stanford, CA, USA. Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, GA, USA. The Burnet Institute, Melbourne, Australia; The Victorian Infectious Diseases Service, at the Peter Doherty Institute, Melbourne, Australia; Department of Microbiology and Immunology, the University of Melbourne at the Peter Doherty Institute, Melbourne, Australia. The Victorian Infectious Diseases Service, at the Peter Doherty Institute, Melbourne, Australia; Department of Microbiology and Immunology, the University of Melbourne at the Peter Doherty Institute, Melbourne, Australia. Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA. Avenir Health, Glastonbury, CT, USA. Department of Infectious Disease Epidemiology, Imperial College London, London, UK. Faculty of Epidemiology and Public Health, London School of Hygiene and Tropical Medicine, London, UK. Strategic Information Department, The Global Fund, Geneva, Switzerland. Department of Global Health, University of Amsterdam, Amsterdam, Netherlands; Amsterdam Institute for Global Health and Development, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. Stop TB Partnership, Geneva, Switzerland. Bill and Melinda Gates Foundation, China Office, Beijing, China. National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. Epidemiology and Research Division, National Tuberculosis Institute, Bangalore, India. World Health Organization, Country Office for India, New Delhi, India. The Bill & Melinda Gates Foundation, New Delhi, India. Aurum Institute. Johannesburg, South Africa. Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK. Aurum Institute. Johannesburg, South Africa; School of Public Health, University of Witwatersrand, Johannesburg, South Africa. National Department of Health, Pretoria, South Africa. Bill and Melinda Gates foundation, Seattle, WA, USA (currently KNCV Tuberculosisn Foundation, The Hague, Netherlands). Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, UK. AN - 27720688 AU - Houben, R. M. G. J. AU - Menzies, N. A. AU - Sumner, T. AU - Huynh, G. H. AU - Arinaminpathy, N. AU - Goldhaber-Fiebert, J. D. AU - Lin, H. H. AU - Wu, C. Y. AU - Mandal, S. AU - Pandey, S. AU - Suen, S. C. AU - Bendavid, E. AU - Azman, A. S. AU - Dowdy, D. W. AU - Bacaer, N. AU - Rhines, A. S. AU - Feldman, M. W. AU - Handel, A. AU - Whalen, C. C. AU - Chang, S. T. AU - Wagner, B. G. AU - Eckhoff, P. A. AU - Trauer, J. M. AU - Denholm, J. T. AU - McBryde, E. S. AU - Cohen, T. AU - Salomon, J. A. AU - Pretorius, C. AU - Lalli, M. AU - Eaton, J. W. AU - Boccia, D. AU - Hosseini, M. AU - Gomez, G. B. AU - Sahu, S. AU - Daniels, C. AU - Ditiu, L. AU - Chin, D. P. AU - Wang, L. AU - Chadha, V. K. AU - Rade, K. AU - Dewan, P. AU - Hippner, P. AU - Charalambous, S. AU - Grant, A. D. AU - Churchyard, G. AU - Pillay, Y. AU - Mametja, L. D. AU - Kimerling, M. E. AU - Vassall, A. AU - White, R. G. DA - Nov DO - 10.1016/s2214-109x(16)30199-1 DP - NLM ET - 2016/10/22 IS - 11 J2 - The Lancet. Global health L1 - internal-pdf://0126388932/PIIS2214109X16301991.pdf LA - eng N1 - 2214-109x Houben, Rein M G J Menzies, Nicolas A Sumner, Tom Huynh, Grace H Arinaminpathy, Nimalan Goldhaber-Fiebert, Jeremy D Lin, Hsien-Ho Wu, Chieh-Yin Mandal, Sandip Pandey, Surabhi Suen, Sze-Chuan Bendavid, Eran Azman, Andrew S Dowdy, David W Bacaer, Nicolas Rhines, Allison S Feldman, Marcus W Handel, Andreas Whalen, Christopher C Chang, Stewart T Wagner, Bradley G Eckhoff, Philip A Trauer, James M Denholm, Justin T McBryde, Emma S Cohen, Ted Salomon, Joshua A Pretorius, Carel Lalli, Marek Eaton, Jeffrey W Boccia, Delia Hosseini, Mehran Gomez, Gabriela B Sahu, Suvanand Daniels, Colleen Ditiu, Lucica Chin, Daniel P Wang, Lixia Chadha, Vineet K Rade, Kiran Dewan, Puneet Hippner, Piotr Charalambous, Salome Grant, Alison D Churchyard, Gavin Pillay, Yogan Mametja, L David Kimerling, Michael E Vassall, Anna White, Richard G MR/K010174/1/Medical Research Council/United Kingdom Journal Article England Lancet Glob Health. 2016 Nov;4(11):e806-e815. doi: 10.1016/S2214-109X(16)30199-1. Epub 2016 Oct 6. PY - 2016 SN - 2214-109x SP - e806-e815 ST - Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models T2 - Lancet Glob Health TI - Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models VL - 4 ID - 845 ER - TY - JOUR AB - A tuberculosis model with two kinds of treatment, that is, treatment at home and treatment in hospital, is constructed. Mathematical analyses show that the dynamics of model are determined by the basic reproduction number R-0. If R-0 < 1, then the disease free equilibrium is globally asymptotically stable. If R-0 > 1, the endemic equilibrium is globally asymptotically stable when patients who are not cured do not transfer from hospital to home. Numerical simulations are also given to support our theoretical results. Our results show that the treatment at home has great negative influence on the spread of the tuberculosis. (C) 2016 Elsevier Inc. All rights reserved. AD - Lanzhou Univ Technol, Dept Appl Math, Lanzhou 730050, Gansu, Peoples R China AN - WOS:000384853900039 AU - Huo, H. F. AU - Zou, M. X. DA - Nov DO - 10.1016/j.apm.2016.06.029 IS - 21-22 J2 - Appl Math Model KW - treatment tuberculosis equilibrium global stability general contact rate reproduction numbers global stability epidemic model reinfection latent LA - English N1 - Dy1km Times Cited:2 Cited References Count:21 PY - 2016 SN - 0307-904x SP - 9474-9484 ST - Modelling effects of treatment at home on tuberculosis transmission dynamics T2 - Applied Mathematical Modelling TI - Modelling effects of treatment at home on tuberculosis transmission dynamics UR - ://WOS:000384853900039 VL - 40 ID - 2189 ER - TY - JOUR AB - A two-strain tuberculosis (TB) transmission model incorporating antibiotic-generated TB resistant strains and long and variable waiting periods within the latently infected class is introduced. The mathematical analysis is carried out when the waiting periods are modeled via parametrically friendly gamma distributions, a reasonable alternative to the use of exponential distributed waiting periods or to integral equations involving ``arbitrary'' distributions. The model supports a globally-asymptotically stable disease-free equilibrium when the reproduction number is less than one and an endemic equilibriums, shown to be locally asymptotically stable, or l.a.s., whenever the basic reproduction number is greater than one. Conditions for the existence and maintenance of TB resistant strains are discussed. The possibility of exogenous re-infection is added and shown to be capable of supporting multiple equilibria; a situation that increases the challenges faced by public health experts. We show that exogenous re-infection may help established resilient communities of actively-TB infected individuals that cannot be eliminated using approaches based exclusively on the ability to bring the control reproductive number just below 1. AD - Department of Applied Mathematics, Faculty of Mathematical Sciences, University of Tabriz, Tabriz, Iran. email: azizeh.jabbari@gmail.com. AN - 27775384 AU - Jabbari, A. AU - Castillo-Chavez, C. AU - Nazari, F. AU - Song, B. AU - Kheiri, H. DA - Aug 01 DO - 10.3934/mbe.2016017 DP - NLM ET - 2016/10/25 IS - 4 J2 - Mathematical biosciences and engineering : MBE L1 - internal-pdf://0002550477/12588.pdf LA - eng N1 - 1551-0018 Jabbari, Azizeh Castillo-Chavez, Carlos Nazari, Fereshteh Song, Baojun Kheiri, Hossein Journal Article United States Math Biosci Eng. 2016 Aug 1;13(4):741-785. doi: 10.3934/mbe.2016017. PY - 2016 SN - 1547-1063 SP - 741-785 ST - A two-strain TB model with multiple latent stages T2 - Math Biosci Eng TI - A two-strain TB model with multiple latent stages VL - 13 ID - 839 ER - TY - CHAP A2 - Rusli, N. A2 - Zaimi, Wmkaw A2 - Khazali, K. A. M. A2 - Masnan, M. J. A2 - Daud, W. S. W. A2 - Abdullah, N. A2 - Yahya, Z. A2 - Amin, N. A. M. A2 - Aziz, N. H. A. A2 - AbuYusuf, Y. N. AB - The study of the threshold dynamic co-epidemic of the HIV-TB is important to understand how the disease is related, and how prevention and treatment is most effective. In this paper, the mathematical model can be used to provide insight into the dynamics of co-epidemic HIV-TB is the most effective. In particular, we examined the effects of re-infection of TB in the susceptible heterosexual population. We have obtained the effect re-infection TB in heterosexual population significant to the magnitude of the basic reproduction number. In a simulation model of the rate of transition from exposed to active TB is much shorter than the transition from individual latent HIV to individuals with HIV less attention. Co-epidemic HIV-TB in this paper describes the importance of including the re-infection TB and effects of HIV on TB and vice versa on the transmission and progression of the HIV and TB epidemic. AD - [Jafaruddin; Pangaribuan, Rapmaida M.; Ariyanto] Univ Nusa Cendana, Dept Math, Kupang, Indonesia. kasfar05071994@gmail.com; rapmaida_pangaribuan@yahoo.com; arirakatesa@gmail.com AN - WOS:000392693300042 AU - Jafaruddin AU - Pangaribuan, R. M. AU - Ariyanto CY - Melville DO - 030041 10.1063/1.4965161 LA - English N1 - ISI Document Delivery No.: BG8SJ Times Cited: 0 Cited Reference Count: 11 Jafaruddin Pangaribuan, Rapmaida M. Ariyanto Icomeia2016 Proceedings Paper 2nd International Conference on Mathematics, Engineering and Industrial Applications (ICoMEIA) Aug 10-12, 2016 Songkhla, THAILAND Univ Malaysia Perlis, Inst Engn Math, Thaksin Univ, Fac Sci 2 huntington quadrangle, ste 1no1, melville, ny 11747-4501 usa 0094-243x PB - Amer Inst Physics PY - 2016 SN - 978-0-7354-1433-4 ST - Threshold Dynamic for Quasi-Endemic Equilibrium from Co-Epidemic HIV-TB Model with Re-infection TB in Heterosexual population T2 - International Conference on Mathematics, Engineering and Industrial Applications 2016 T3 - AIP Conference Proceedings TI - Threshold Dynamic for Quasi-Endemic Equilibrium from Co-Epidemic HIV-TB Model with Re-infection TB in Heterosexual population UR - ://WOS:000392693300042 VL - 1775 ID - 5209 ER - TY - JOUR AB - The dominant approach to decision-making in public health policy for infectious diseases relies heavily on expert opinion, which often applies empirical evidence to policy questions in a manner that is neither systematic nor transparent. Although systematic reviews are frequently commissioned to inform specific components of policy (such as efficacy), the same process is rarely applied to the full decision-making process. Mathematical models provide a mechanism through which empirical evidence can be methodically and transparently integrated to address such questions. However, such models are often considered difficult to interpret. In addition, models provide estimates that need to be iteratively re-evaluated as new data or considerations arise. Using the case study of a novel diagnostic for tuberculosis, a framework for improved collaboration between public health decision-makers and mathematical modellers that could lead to more transparent and evidence-driven policy decisions for infectious diseases in the future is proposed. The framework proposes that policymakers should establish long-term collaborations with modellers to address key questions, and that modellers should strive to provide clear explanations of the uncertainty of model structure and outputs. Doing so will improve the applicability of models and clarify their limitations when used to inform real-world public health policy decisions. AD - National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, Imperial College London, 8(th) floor Commonwealth Building, Hammersmith Hospital Campus, Du Cane Road, London, W12 0HS, UK; TB Modelling Group, TB Centre, Centre for Mathematical Modelling, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK. Electronic address: g.knight@imperial.ac.uk. New Jersey Medical School - Rutgers, the State University of New Jersey, Newark, New Jersey, USA. Respiratory Epidemiology Clinical Research Unit, McGill University, Montreal, Quebec, Canada. New York City Department of Health and Mental Hygiene, Bureau of Tuberculosis Control, New York, New York, USA. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. Maricopa County Department of Public Health, Clinical Services, Phoenix, Arizona, USA. AN - 26546234 AU - Knight, G. M. AU - Dharan, N. J. AU - Fox, G. J. AU - Stennis, N. AU - Zwerling, A. AU - Khurana, R. AU - Dowdy, D. W. C2 - PMC4996966 C6 - NIHMS745187 DA - Jan DO - 10.1016/j.ijid.2015.10.024 DP - NLM ET - 2015/11/08 J2 - International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases KW - Communicable Diseases/*therapy *Decision Making Humans Models, Theoretical *Public Health Models Public health practice Tuberculosis theoretical L1 - internal-pdf://0129169391/Knight-2016-Bridging the gap between evidence.pdf LA - eng N1 - 1878-3511 Knight, Gwenan M Dharan, Nila J Fox, Gregory J Stennis, Natalie Zwerling, Alice Khurana, Renuka Dowdy, David W R21 AI101152/AI/NIAID NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review Canada Int J Infect Dis. 2016 Jan;42:17-23. doi: 10.1016/j.ijid.2015.10.024. Epub 2015 Nov 3. PY - 2016 SN - 1201-9712 SP - 17-23 ST - Bridging the gap between evidence and policy for infectious diseases: How models can aid public health decision-making T2 - Int J Infect Dis TI - Bridging the gap between evidence and policy for infectious diseases: How models can aid public health decision-making UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996966/pdf/nihms745187.pdf VL - 42 ID - 1173 ER - TY - JOUR AB - BACKGROUND: Long-term expatriates from low to high tuberculosis (TB) incidence countries get high rates of active TB and latent TB infection (LTBI). TB screening for expatriates is important for occupational health. Interferon-gamma release assays are more accurate than tuberculin skin test (TST). Rifapentine plus isoniazid for 3 months (3HP) is as effective as 9 months of isoniazid (9H) with a higher treatment-completion rate. METHODS: Decision trees and Markov models were constructed using a societal perspective on a lifetime horizon. The target population was a hypothetical cohort of 30 year-old expatriates. Seven strategies; TST with 3HP or 9H, QuantiFERON(R)-TB Gold In-Tube (QFT) with 3HP or 9H, T-SPOT(R).TB (TSPOT) with 3HP or 9H and chest X-ray examination (CXR) were modeled. The main outcome measure of effectiveness was quality-adjusted life-years (QALYs) gained. RESULTS: QFT with 3HP yielded the greatest benefits with the lowest cost ($US 674.8; 25.95660 QALYs [year 2012 values]). CXR was the least cost-effective ($US 13,666.8; 24.62917 QALYs). Cost-effectiveness was sensitive to adherence rate of 3HP and QFT specificity, but not to BCG vaccination rate. CONCLUSIONS: Entry LTBI screening using QFT treated with 3HP is recommended on the basis of cost effectiveness among long-term expatriates from low to high incidence countries. AD - General Affairs Department, Ota City Office, Tokyo, Japan. Electronic address: kowadaa@gmail.com. AN - 27238907 AU - Kowada, A. DA - Sep - Oct DO - 10.1016/j.tmaid.2016.05.010 DP - NLM ET - 2016/10/25 IS - 5 J2 - Travel medicine and infectious disease KW - Adult Computer Simulation Cost-Benefit Analysis Decision Trees Female Humans Incidence Interferon-gamma Release Tests/*economics Isoniazid/*therapeutic use Latent Tuberculosis/*diagnosis/microbiology/transmission Male Markov Chains Mass Screening Rifampin/*analogs & derivatives/therapeutic use *Travel *Cost-effectiveness *Expatriate *Interferon-gamma release assay *Latent tuberculosis infection *Rifapentine LA - eng N1 - 1873-0442 Kowada, Akiko Journal Article Netherlands Travel Med Infect Dis. 2016 Sep - Oct;14(5):489-498. doi: 10.1016/j.tmaid.2016.05.010. Epub 2016 May 26. PY - 2016 SN - 1477-8939 SP - 489-498 ST - Cost effectiveness of interferon-gamma release assay for tuberculosis screening using three months of rifapentine and isoniazid among long-term expatriates from low to high incidence countries T2 - Travel Med Infect Dis TI - Cost effectiveness of interferon-gamma release assay for tuberculosis screening using three months of rifapentine and isoniazid among long-term expatriates from low to high incidence countries VL - 14 ID - 842 ER - TY - JOUR AB - BACKGROUND: The global spread of the human immunodeficiency virus (HIV) is the main hypothesis behind tuberculosis (TB) positive trends in the last decades, according to modeling studies and World Health Organization Reports (WHO). On one hand, TB (WHO) reports do not explicitly consider a modeling approach, but cover country and global TB trends. On the other hand, modeling studies usually do not cover the scale of WHO reports, because of the amount of parameters estimated to describe TB natural history. Here we combined these two principal sources of TB studies covering TB High Burden Countries (HBCs) dynamics. Our main goals were: (i) to detect the endogenous component of TB dynamics since 1974 for TB HBCs; and (ii) to explore the HIV exogenous effects on TB models`parameters. METHODS AND FINDINGS: We explored the relationship between the TB per capita population rate of change (RI) and the infectious class size following an endogenous/exogenous framework. RI can be affected by intra-population processes (i.e. competition, predation) and exogenous variables like HIV. We found that TB dynamics had always a strong endogenous component, represented by a negative correlation between TB population size and RI, which was captured by the discrete logistic model. Moreover, we explored the HIV exogenous effects on TB models`parameters. We found that overall the TB+HIV logistic model was more parsimonious than TB model alone, principally in the African region. Our results showed that HIV affected principally TB carrying capacity, as expected by the known HIV effects on TB natural-history. We also tested if DOTS (Directly Observed Treatment Short-Course Strategy), poverty levels and BCG (Bacillus Calmette-Guerin) coverage explained the models residuals variances, but they did not. CONCLUSIONS: Since 1974, TB dynamics were categorized in distinct chronological domains, with different dynamics but nearly the same underlying mechanism: a negative relationship between RI and infected class size (i.e. self-limiting). In the last decades, not only HIV spread represented a new TB chronological domain, but it also has been pushing TB carrying capacity (K) to higher levels. TB has a complex natural-history and imposes real challenges to model its dynamics. Yet, we were able to explore and reveal the main drivers of TB dynamics for HBCs since 1974, through a simple approach. Based on our results, we suggest that the endogenous view should be considered as a plausible hypothesis to model and explain TB dynamics and that future World Health Organization reports could include the endogenous/exogenous framework as a supplement to help to decipher the main drivers of TB dynamics and other diseases. AD - Pontificia Universidad Catolica de Chile, Santiago, Chile. AN - 27093296 AU - Krsulovic, F. A. AU - Lima, M. C2 - PMC4836699 DO - 10.1371/journal.pone.0153710 DP - NLM ET - 2016/04/20 IS - 4 J2 - PloS one KW - Antitubercular Agents/therapeutic use HIV Infections/*complications Humans Tuberculosis/drug therapy/*epidemiology/*etiology World Health Organization L1 - internal-pdf://4245674206/Krsulovic-2016-Tuberculosis Epidemiology at th.pdf LA - eng N1 - 1932-6203 Krsulovic, Felipe Augusto Maurin Lima, Mauricio Journal Article Research Support, Non-U.S. Gov't United States PLoS One. 2016 Apr 19;11(4):e0153710. doi: 10.1371/journal.pone.0153710. eCollection 2016. PY - 2016 SN - 1932-6203 SP - e0153710 ST - Tuberculosis Epidemiology at the Country Scale: Self-Limiting Process and the HIV Effects T2 - PLoS One TI - Tuberculosis Epidemiology at the Country Scale: Self-Limiting Process and the HIV Effects UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836699/pdf/pone.0153710.pdf VL - 11 ID - 992 ER - TY - JOUR AB - BACKGROUND: New drugs for the treatment of tuberculosis (TB) are becoming available for the first time in over 40 y. Optimal strategies for introducing these drugs have not yet been established. The objective of this study was to compare different strategies for introducing the new TB drug bedaquiline based on patients' resistance patterns. METHODS AND FINDINGS: We created a Markov decision model to follow a hypothetical cohort of multidrug-resistant (MDR) TB patients under different bedaquiline use strategies. The explored strategies included making bedaquiline available to all patients with MDR TB, restricting bedaquiline usage to patients with MDR plus additional resistance and withholding bedaquiline introduction completely. We compared these strategies according to life expectancy, risks of acquired resistance, and the expected number and health outcomes of secondary cases. For our simulated cohort, the mean (2.5th, 97.5th percentile) life expectancy from time of initiation of MDR TB treatment at age 30 was 36.0 y (33.5, 38.7) assuming all patients with MDR TB received bedaquiline, 35.1 y (34.4, 35.8) assuming patients with pre-extensively drug-resistant (PreXDR) and extensively drug-resistant (XDR) TB received bedaquiline, and 34.9 y (34.6, 35.2) assuming only patients with XDR TB received bedaquiline. Although providing bedaquiline to all MDR patients resulted in the highest life expectancy for our initial cohort averaged across all parameter sets, for parameter sets in which bedaquiline conferred high risks of added mortality and only small reductions in median time to culture conversion, the optimal strategy would be to withhold use even from patients with the most extensive resistance. Across all parameter sets, the most liberal bedaquiline use strategies consistently increased the risk of bedaquiline resistance but decreased the risk of resistance to other MDR drugs. In almost all cases, more liberal bedaquiline use strategies reduced the expected number of secondary cases and resulting life years lost. The generalizability of our results is limited by the lack of available data about drug effects among individuals with HIV co-infection, drug interactions, and other sources of heterogeneity, as well as changing recommendations for MDR TB treatment. CONCLUSIONS: If mortality benefits can be empirically verified, our results provide support for expanding bedaquiline access to all patients with MDR TB. Such expansion could improve patients' health, protect background MDR TB drugs, and decrease transmission, but would likely result in greater resistance to bedaquiline. AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America. Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America. Department of Global Health, Academic Medical Center, Amsterdam, Netherlands. KNCV Tuberculosis Foundation, The Hague, Netherlands. AN - 27727274 AU - Kunkel, A. AU - Cobelens, F. G. AU - Cohen, T. C2 - PMC5058480 DA - Oct DO - 10.1371/journal.pmed.1002142 IS - 10 KW - Adult Antitubercular Agents/adverse effects/*therapeutic use Cohort Studies *Decision Support Techniques Diarylquinolines/*therapeutic use Drug Approval Health Policy Humans Life Expectancy Male Markov Chains Risk Assessment Tuberculosis, Multidrug-Resistant/*drug therapy/transmission L1 - internal-pdf://3333306856/Kunkel-2016-Tradeoffs in Introduction Policies.pdf N1 - Kunkel, Amber Cobelens, Frank G Cohen, Ted eng 2016/10/12 06:00 PLoS Med. 2016 Oct 11;13(10):e1002142. doi: 10.1371/journal.pmed.1002142. eCollection 2016 Oct. PY - 2016 SN - 1549-1676 (Electronic) 1549-1277 (Linking) SP - e1002142 ST - Tradeoffs in Introduction Policies for the Anti-Tuberculosis Drug Bedaquiline: A Model-Based Analysis T2 - PLoS Med TI - Tradeoffs in Introduction Policies for the Anti-Tuberculosis Drug Bedaquiline: A Model-Based Analysis UR - https://www.ncbi.nlm.nih.gov/pubmed/27727274 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058480/pdf/pmed.1002142.pdf VL - 13 ID - 2202 ER - TY - JOUR AB - OBJECTIVE: Extending the duration of isoniazid preventive therapy (IPT) among people living with HIV (PLHIV) may improve its effectiveness at both individual and population levels, but could also increase selective pressure in favor of isoniazid-resistant tuberculosis (TB) strains. The objective of this study was to determine the relative importance of these two effects. METHODS: Transmission dynamic model. DESIGN: We created a mathematical model of TB transmission incorporating HIV incidence and treatment, mixed strain latent TB infections, and four different phenotypes of TB drug resistance (pan-susceptible, isoniazid monoresistant, rifampicin monoresistant, and multidrug resistant). We used this model to project the effects of IPT duration on the incidence of isoniazid-sensitive and isoniazid-resistant TB as well as mortality among PLHIV. We evaluated the sensitivity of our baseline model, which was calibrated to data from Botswana, to different assumptions about the future trajectory of the TB epidemic. RESULTS: Our model suggests that, in the context of a declining TB epidemic such as that currently observed in Botswana, the incidence and mortality benefits of continuous IPT for PLHIV are likely to outweigh the potential resistance risks associated with long-duration IPT. However, should TB epidemics fail to remain in control, as was observed during the initial emergence of HIV, the selective pressure imposed by widespread use of continuous IPT on isoniazid-resistant TB incidence may erode its initial benefits. CONCLUSION: Resistance concerns are likely insufficient to rule out use of continuous IPT when coupled with effective TB treatment, case finding, and HIV control. AD - aDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts bDepartment of Epidemiology of Microbial Diseases cDepartment of Biostatistics, Yale School of Public Health dDepartment of Ecology and Evolutionary Biology, Yale University eDivision of Infectious Disease, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. AN - 27782966 AU - Kunkel, A. AU - Crawford, F. W. AU - Shepherd, J. AU - Cohen, T. C2 - PMC5089846 C6 - NIHMS814768 DA - Nov 13 DO - 10.1097/qad.0000000000001235 DP - NLM ET - 2016/10/27 IS - 17 J2 - AIDS (London, England) L1 - internal-pdf://3203685523/Kunkel-2016-Benefits of continuous isoniazid p.pdf LA - eng N1 - 1473-5571 Kunkel, Amber Crawford, Forrest W Shepherd, James Cohen, Ted KL2 TR000140/TR/NCATS NIH HHS/United States P30 MH062294/MH/NIMH NIH HHS/United States UL1 TR001863/TR/NCATS NIH HHS/United States T32 AI007535/AI/NIAID NIH HHS/United States R01 AI112438/AI/NIAID NIH HHS/United States Journal Article England AIDS. 2016 Nov 13;30(17):2715-2723. PY - 2016 SN - 0269-9370 SP - 2715-2723 ST - Benefits of continuous isoniazid preventive therapy may outweigh resistance risks in a declining tuberculosis/HIV coepidemic T2 - Aids TI - Benefits of continuous isoniazid preventive therapy may outweigh resistance risks in a declining tuberculosis/HIV coepidemic UR - http://ovidsp.tx.ovid.com/ovftpdfs/FPDDNCJCNFAOFC00/fs047/ovft/live/gv031/00002030/00002030-201611130-00017.pdf VL - 30 ID - 836 ER - TY - JOUR AB - In this paper, a delayed Tuberculosis infection model is formulated and investigated. We showed the existence of disease free equilibrium and endemic equilibrium points. We used La Salle-Lyapunov Invariance Principle to show that if the reproductive number R-0 < 1, the disease-free equilibrium of the model is globally asymptotically stable. Numerical simulations are then performed to illustrate the existence of the disease free equilibrium and the endemic equilibrium point for a given value of R0. Thus, when R-0 < 1, the disease dies out in the population. AD - Univ Philippines Baguio, Dept Math & Comp Sci, Baguio, Benguet, Philippines AN - WOS:000389508100111 AU - Lapaan, R. D. AU - Collera, J. A. AU - Addawe, J. M. DO - Unsp 080022 10.1063/1.4968161 J2 - Aip Conf Proc LA - English N1 - Bg5ix Times Cited:0 Cited References Count:7 AIP Conference Proceedings PY - 2016 SN - 0094-243x ST - Mathematical Analysis of Tuberculosis Transmission Model with Delay T2 - Proceeding of the 4th International Conference of Fundamental and Applied Sciences 2016 (ICFAS2016) TI - Mathematical Analysis of Tuberculosis Transmission Model with Delay UR - ://WOS:000389508100111 VL - 1787 ID - 2192 ER - TY - JOUR AD - [Lee, K. K.; Wu, D. B.; Cheong, Y. M.] Monash Univ Malaysia, Subang Jaya, Malaysia. [Fun, W. H.] Inst Hlth Syst Res, Setia Alam, Malaysia. [Noordin, Mohamad N.] Natl Publ Hlth Lab, Sungai Buloh, Malaysia. AN - WOS:000396606303107 AU - Lee, K. K. AU - Fun, W. H. AU - Wu, D. B. AU - Cheong, Y. M. AU - Noordin, N. M. DA - Nov IS - 7 J2 - Value Health KW - Business & Economics Health Care Sciences & Services LA - English M3 - Meeting Abstract N1 - ISI Document Delivery No.: EO3PI Times Cited: 0 Cited Reference Count: 0 Lee, K. K. Fun, W. H. Wu, D. B. Cheong, Y. M. Noordin, Mohamad N. 0 Elsevier science inc New york 1524-4733 PY - 2016 SN - 1098-3015 SP - A859-A859 ST - COST-EFFECTIVENESS ANALYSIS OF XPERT MTB/RIF ASSAY FOR DIAGNOSING TUBERCULOSIS IN MALAYSIA USING DYNAMIC TRANSMISSION MODEL T2 - Value in Health TI - COST-EFFECTIVENESS ANALYSIS OF XPERT MTB/RIF ASSAY FOR DIAGNOSING TUBERCULOSIS IN MALAYSIA USING DYNAMIC TRANSMISSION MODEL UR - ://WOS:000396606303107 VL - 19 ID - 5084 ER - TY - JOUR AB - An tuberculosis model with prevention effect and latent delay is investigated. To the best of our knowledge, it is the first work to introduce a nonlinear incidence rate to describe the prevention effect. The sharp threshold condition R-0 of our model is obtained. Meanwhile, we also derive the globally dynamics of system and illustrate the analytical results by numerical simulations. Finally, the influence of the prevention effect is discussed. AD - [Li, Jun; Ma, Mingju] Xidian Univ, Sch Math & Stat, Xian 710071, Peoples R China. Li, J (reprint author), Xidian Univ, Sch Math & Stat, Xian 710071, Peoples R China. lijun@xidian.edu.cn AN - WOS:000382681600001 AU - Li, J. AU - Ma, M. J. C7 - 220 DA - Aug DO - 10.1186/s13662-016-0934-z J2 - Adv. Differ. Equ. KW - disease ecology delay globally asymptotic stability Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: DV1LC Times Cited: 0 Cited Reference Count: 11 Li, Jun Ma, Mingju Xidian University [7214614503]; Chinese Universities Scientific Fund [7215614501] This research has been partially supported by the Ph.D. Fellowship of Xidian University (No. 7214614503) and Chinese Universities Scientific Fund (No. 7215614501). The authors are very grateful to the editor and the anonymous referees for their valuable comments and suggestions, which greatly improved the presentation of this work. 0 1 5 Springer international publishing ag Cham PY - 2016 SN - 1687-1847 SP - 13 ST - Impact of prevention in a tuberculosis model with latent delay T2 - Advances in Difference Equations TI - Impact of prevention in a tuberculosis model with latent delay UR - ://WOS:000382681600001 ID - 5111 ER - TY - JOUR AB - Understanding the transmission dynamics of infectious diseases is important for both biological research and public health applications. It has been widely demonstrated that statistical modeling provides a firm basis for inferring relevant epidemiological quantities from incidence and molecular data. However, the complexity of transmission dynamic models presents two challenges: (1) the likelihood function of the models is generally not computable, and computationally intensive simulation-based inference methods need to be employed, and (2) the model may not be fully identifiable from the available data. While the first difficulty can be tackled by computational and algorithmic advances, the second obstacle is more fundamental. Identifiability issues may lead to inferences that are driven more by prior assumptions than by the data themselves. We consider a popular and relatively simple yet analytically intractable model for the spread of tuberculosis based on classical IS6110 fingerprinting data. We report on the identifiability of the model, also presenting some methodological advances regarding the inference. Using likelihood approximations, we show that the reproductive value cannot be identified from the data available and that the posterior distributions obtained in previous work have likely been substantially dominated by the assumed prior distribution. Further, we show that the inferences are influenced by the assumed infectious population size, which generally has been kept fixed in previous work. We demonstrate that the infectious population size can be inferred if the remaining epidemiological parameters are already known with sufficient precision. AD - Helsinki Institute for Information Technology (HIIT) and Department of Computer Science, Aalto University, FI-00076 Aalto, Finland jarno.lintusaari@aalto.fi. Helsinki Institute for Information Technology (HIIT) and Department of Computer Science, Aalto University, FI-00076 Aalto, Finland Helsinki Institute for Information Technology (HIIT) and Department of Mathematics and Statistics, University of Helsinki, FI-00014 Helsinki, Finland. Helsinki Institute for Information Technology (HIIT) and Department of Computer Science, Aalto University, FI-00076 Aalto, Finland. Helsinki Institute for Information Technology (HIIT) and Department of Mathematics and Statistics, University of Helsinki, FI-00014 Helsinki, Finland. AN - 26739450 AU - Lintusaari, J. AU - Gutmann, M. U. AU - Kaski, S. AU - Corander, J. C2 - PMC4788128 DA - Mar DO - 10.1534/genetics.115.180034 DP - NLM ET - 2016/01/08 IS - 3 J2 - Genetics KW - Algorithms Alleles Bayes Theorem Communicable Diseases/*transmission Computer Simulation Humans Likelihood Functions *Models, Statistical Mutation Rate Mycobacterium tuberculosis/genetics/pathogenicity Population Density Tuberculosis/transmission approximate Bayesian computation identifiability intractable likelihood transmission dynamic models tuberculosis L1 - internal-pdf://3681082521/Lintusaari-2016-On the Identifiability of Tran.pdf LA - eng N1 - 1943-2631 Lintusaari, Jarno Gutmann, Michael U Kaski, Samuel Corander, Jukka Journal Article Research Support, Non-U.S. Gov't United States Genetics. 2016 Mar;202(3):911-8. doi: 10.1534/genetics.115.180034. Epub 2016 Jan 6. PY - 2016 SN - 0016-6731 SP - 911-8 ST - On the Identifiability of Transmission Dynamic Models for Infectious Diseases T2 - Genetics TI - On the Identifiability of Transmission Dynamic Models for Infectious Diseases UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788128/pdf/911.pdf VL - 202 ID - 1112 ER - TY - JOUR AB - In this article, a TB transmission model with treatment interruptions is established. The control reproduction numbers which completely determine the long behaviors of the TB model are explicitly given. By applying the comparison principle and constructing proper Lyapunov functions, the global asymptotic stability of equilibria is analyzed. The numerical simulations show that the treatment of active TB cases has always a positive effect on controlling the TB epidemic; while treatment interruptions may have a negative, positive or no effect on combating the TB epidemic. (C) 2016 All rights reserved. AD - Henan Univ Sci & Technol, Sch Math & Stat, Luoyang 471023, Peoples R China China Univ Petr, Coll Sci, Qingdao 266580, Peoples R China AN - WOS:000373507700013 AU - Liu, L. J. AU - Wang, Y. IS - 4 J2 - J Nonlinear Sci Appl KW - tb transmission model treatment interruptions the control reproduction number lyapunov function globally asymptotically stable differential-equations tuberculosis infection LA - English N1 - Di4zk Times Cited:0 Cited References Count:14 PY - 2016 SN - 2008-1898 SP - 1549-1563 ST - Analysis of a TB model with treatment interruptions T2 - Journal of Nonlinear Sciences and Applications TI - Analysis of a TB model with treatment interruptions UR - ://WOS:000373507700013 VL - 9 ID - 2193 ER - TY - JOUR AB - We establish a dynamical model for tuberculosis of humans and cows. For the model, we firstly give the basic reproduction number R 0. Furthermore, we discuss the dynamical behaviors of the model. By epidemiological investigation of tuberculosis among humans and livestock from 2007 to 2014 in Urumqi, Xinjiang, China, we estimate the parameters of the model and study the transmission trend of the disease in Urumqi, Xinjiang, China. The reproduction number in Urumqi for the model is estimated to be 0.1811 (95% confidence interval: 0.123-0.281). Finally, we perform some sensitivity analysis of several model parameters and give some useful comments on controlling the transmission of tuberculosis. AD - Department of Public Health, Xinjiang Medical University, Urumqi 830011, China. Urumqi Animal Disease Control and Diagnosis Center, Urumqi 830063, China. Department of Mathematics, Yuncheng University, Yuncheng 044000, China. Department of Medical Engineering and Technology, Xinjiang Medical University, Urumqi 830011, China. AN - 27525034 AU - Liu, S. AU - Li, A. AU - Feng, X. AU - Zhang, X. AU - Wang, K. C2 - PMC4976259 DO - 10.1155/2016/3410320 DP - NLM ET - 2016/08/16 J2 - Computational and mathematical methods in medicine KW - Animals Autopsy Basic Reproduction Number Cattle China Communicable Disease Control Dairying Humans Interferon-gamma/chemistry Models, Theoretical Quarantine Reproducibility of Results Sensitivity and Specificity Tuberculin/chemistry Tuberculosis/*epidemiology/*transmission/*veterinary LA - eng N1 - 1748-6718 Liu, Shan Li, Aiqiao Feng, Xiaomei Zhang, Xueliang Wang, Kai Orcid: 0000-0002-6224-8453 Journal Article United States Comput Math Methods Med. 2016;2016:3410320. doi: 10.1155/2016/3410320. Epub 2016 Jul 25. PY - 2016 SN - 1748-670x SP - 3410320 ST - A Dynamic Model of Human and Livestock Tuberculosis Spread and Control in Urumqi, Xinjiang, China T2 - Comput Math Methods Med TI - A Dynamic Model of Human and Livestock Tuberculosis Spread and Control in Urumqi, Xinjiang, China VL - 2016 ID - 886 ER - TY - JOUR AB - An important question, of whether the initiation of HIV treatment during ongoing TB treatment for HIV TB co-infected individuals is appropriate, still remains unanswered; initiating HIV treatment at or soon after the start of the TB treatment course has some advantages including fewer HIV-related deaths and a lower risk of HIV transmission as well as some disadvantages including occurrence of Immune Reconstitution Inflammatory Syndrome (IRIS) due to a high pill burden. In this study, we develop a mathematical model to explore the effects of early and late HIV treatment, during the TB treatment course, on new HIV infections, HIV-related deaths, and IRIS cases. Mathematical analyses of our model indicate that co-infection treatment programs alone cannot eradicate the diseases; additional interventions and/or treatments targeting individuals infected with a single disease are necessary for successful disease eradication. Numerical computations of the model solution demonstrate that outcomes of the treatment programs aiming to reduce the total burden of this co-infection depend highly on both the strength and initiation timing of antiretroviral therapy (ART). Based on our model, we also formulate an optimal control problem and solve it using Pontryagin's Maximum Principle and an efficient numerical iterative method. Our numerical results of an optimal HIV TB treatment protocol that yields a minimum burden from this co-infection indicates that each of the new HIV infections, HIV-related deaths and IRIS cases is important for achieving optimal benefits from the co-infection treatment programs. (C) 2016 Elsevier B.V. All rights reserved. AD - [Mallela, Abhishek; Vaidya, Naveen K.] Univ Missouri, Dept Math & Stat, Kansas City, MO 64110 USA. [Lenhart, Suzanne] Univ Tennessee, Dept Math, Knoxville, TN 37996 USA. Vaidya, NK (reprint author), Univ Missouri, Dept Math & Stat, Kansas City, MO 64110 USA. vaidyan@umkc.edu AN - WOS:000378957100014 AU - Mallela, A. AU - Lenhart, S. AU - Vaidya, N. K. DA - Dec DO - 10.1016/j.cam.2016.02.051 J2 - J. Comput. Appl. Math. KW - HIV TB Co-infection dynamics Mathematical modeling Treatment programs Optimal controls reconstitution inflammatory syndrome antiretroviral therapy transmission dynamics tuberculosis initiation infection populations virus Mathematics LA - English M3 - Article; Proceedings Paper N1 - ISI Document Delivery No.: DQ1JK Times Cited: 1 Cited Reference Count: 42 Mallela, Abhishek Lenhart, Suzanne Vaidya, Naveen K. 1st Annual Meeting of SIAM-Central-States-Section Apr 11-12, 2015 Missouri Univ Sci & Technol, Rolla, MO SIAM, Cent States Sect 1 2 111 Elsevier science bv Amsterdam 1879-1778 PY - 2016 SN - 0377-0427 SP - 143-161 ST - HIV-TB co-infection treatment: Modeling and optimal control theory perspectives T2 - Journal of Computational and Applied Mathematics TI - HIV-TB co-infection treatment: Modeling and optimal control theory perspectives UR - ://WOS:000378957100014 VL - 307 ID - 5079 ER - TY - JOUR AB - Identifying biomarkers for tuberculosis (TB) is an ongoing challenge in developing immunological correlates of infection outcome and protection. Biomarker discovery is also necessary for aiding design and testing of new treatments and vaccines. To effectively predict biomarkers for infection progression in any disease, including TB, large amounts of experimental data are required to reach statistical power and make accurate predictions. We took a two-pronged approach using both experimental and computational modeling to address this problem. We first collected 200 blood samples over a 2- year period from 28 non-human primates (NHP) infected with a low dose of Mycobacterium tuberculosis. We identified T cells and the cytokines that they were producing (single and multiple) from each sample along with monkey status and infection progression data. Machine learning techniques were used to interrogate the experimental NHP datasets without identifying any potential TB biomarker. In parallel, we used our extensive novel NHP datasets to build and calibrate a multi-organ computational model that combines what is occurring at the site of infection (e.g., lung) at a single granuloma scale with blood level readouts that can be tracked in monkeys and humans. We then generated a large in silico repository of in silico granulomas coupled to lymph node and blood dynamics and developed an in silico tool to scale granuloma level results to a full host scale to identify what best predicts Mycobacterium tuberculosis (Mtb) infection outcomes. The analysis of in silico blood measures identifies Mtb-specific frequencies of effector T cell phenotypes at various time points post infection as promising indicators of infection outcome. We emphasize that pairing wetlab and computational approaches holds great promise to accelerate TB biomarker discovery. AD - Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America. Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America. Robert H. Smith School of Business, University of Maryland, College Park, Maryland, United States of America. Department of Pediatrics, Children's Hospital of the University of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States of America. Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America. AN - 27065304 AU - Marino, S. AU - Gideon, H. P. AU - Gong, C. AU - Mankad, S. AU - McCrone, J. T. AU - Lin, P. L. AU - Linderman, J. J. AU - Flynn, J. L. AU - Kirschner, D. E. C2 - PMC4827839 DA - Apr DO - 10.1371/journal.pcbi.1004804 DP - NLM ET - 2016/04/12 IS - 4 J2 - PLoS computational biology KW - Algorithms Animals Biomarkers/blood CD4-Positive T-Lymphocytes/immunology/microbiology CD8-Positive T-Lymphocytes/immunology/microbiology Computational Biology Computer Simulation Cytokines/biosynthesis Databases, Factual Humans Lung/immunology/microbiology Macaca fascicularis Models, Immunological Mycobacterium tuberculosis/*immunology T-Lymphocytes/*immunology/*microbiology Tuberculosis, Pulmonary/blood/immunology/microbiology LA - eng N1 - 1553-7358 Marino, Simeone Gideon, Hannah P Gong, Chang Mankad, Shawn McCrone, John T Lin, Philana Ling Linderman, Jennifer J Flynn, JoAnne L Kirschner, Denise E R01 EB012579/EB/NIBIB NIH HHS/United States R01 HL110811/HL/NHLBI NIH HHS/United States Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United States PLoS Comput Biol. 2016 Apr 11;12(4):e1004804. doi: 10.1371/journal.pcbi.1004804. eCollection 2016 Apr. PY - 2016 SN - 1553-734x SP - e1004804 ST - Computational and Empirical Studies Predict Mycobacterium tuberculosis-Specific T Cells as a Biomarker for Infection Outcome T2 - PLoS Comput Biol TI - Computational and Empirical Studies Predict Mycobacterium tuberculosis-Specific T Cells as a Biomarker for Infection Outcome VL - 12 ID - 1003 ER - TY - JOUR AB - Tuberculosis (TB) is a world-wide health problem with approximately 2 billion people infected with Mycobacterium tuberculosis (Mtb, the causative bacterium of TB). The pathologic hallmark of Mtb infection in humans and Non-Human Primates (NHPs) is the formation of spherical structures, primarily in lungs, called granulomas. Infection occurs after inhalation of bacteria into lungs, where resident antigen-presenting cells (APCs), take up bacteria and initiate the immune response to Mtb infection. APCs traffic from the site of infection (lung) to lung-draining lymph nodes (LNs) where they prime T cells to recognize Mtb. These T cells, circulating back through blood, migrate back to lungs to perform their immune effector functions. We have previously developed a hybrid agent-based model (ABM, labeled GranSim) describing in silico immune cell, bacterial (Mtb) and molecular behaviors during tuberculosis infection and recently linked that model to operate across three physiological compartments: lung (infection site where granulomas form), lung draining lymph node (LN, site of generation of adaptive immunity) and blood (a measurable compartment). Granuloma formation and function is captured by a spatio-temporal model (i.e., ABM), while LN and blood compartments represent temporal dynamics of the whole body in response to infection and are captured with ordinary differential equations (ODEs). In order to have a more mechanistic representation of APC trafficking from the lung to the lymph node, and to better capture antigen presentation in a draining LN, this current study incorporates the role of dendritic cells (DCs) in a computational fashion into GranSim. RESULTS: The model was calibrated using experimental data from the lungs and blood of NHPs. The addition of DCs allowed us to investigate in greater detail mechanisms of recruitment, trafficking and antigen presentation and their role in tuberculosis infection. CONCLUSION: The main conclusion of this study is that early events after Mtb infection are critical to establishing a timely and effective response. Manipulating CD8+ and CD4+ T cell proliferation rates, as well as DC migration early on during infection can determine the difference between bacterial clearance vs. uncontrolled bacterial growth and dissemination. AD - Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. AN - 28989808 AU - Marino, S. AU - Kirschner, D. E. C2 - PMC5627612 DO - 10.3390/computation4040039 IS - 4 KW - agent-based model dendritic cells multi-compartmental model tuberculosis uncertainty and sensitivity analysis N1 - Marino, Simeone Kirschner, Denise E eng R01 AI123093/AI/NIAID NIH HHS/ R01 EB012579/EB/NIBIB NIH HHS/ R01 HL110811/HL/NHLBI NIH HHS/ U01 HL131072/HL/NHLBI NIH HHS/ Switzerland 2016/01/01 00:00 Computation (Basel). 2016;4(4). pii: 39. doi: 10.3390/computation4040039. Epub 2016 Oct 21. PY - 2016 SN - 2079-3197 (Print) 2079-3197 (Linking) ST - A Multi-Compartment Hybrid Computational Model Predicts Key Roles for Dendritic Cells in Tuberculosis Infection T2 - Computation (Basel) TI - A Multi-Compartment Hybrid Computational Model Predicts Key Roles for Dendritic Cells in Tuberculosis Infection UR - https://www.ncbi.nlm.nih.gov/pubmed/28989808 VL - 4 ID - 4818 ER - TY - JOUR AB - We investigate the interplay between Lie symmetry analysis and dynamical systems analysis. As an example, we take a toy model describing the spread of TB and dengue fever. We first undertake a comprehensive dynamical systems analysis including a discussion about local stability. For those regions in which such analyzes cannot be translated to global behavior, we undertake a Lie symmetry analysis. It is shown that the Lie analysis can be useful in providing information for systems where the (local) dynamical systems analysis breaks down. AD - [Massoukou, R. Y. M'pika; Govinder, K. S.] Univ KwaZulu Natal, Sch Math Stat & Comp Sci, Private Bag X54001, ZA-4000 Durban, South Africa. Massoukou, RYM (reprint author), Univ KwaZulu Natal, Sch Math Stat & Comp Sci, Private Bag X54001, ZA-4000 Durban, South Africa. rodrigue@aims.ac.za; govinder@ukzn.ac.za AN - WOS:000388486900022 AU - Massoukou, R. Y. M. AU - Govinder, K. S. C7 - 1640022 DA - Nov DO - 10.1142/s0217979216400221 IS - 28-29 J2 - Int. J. Mod. Phys. B KW - Epidemiological modeling dynamical systems symmetry analysis multistrain/two-stream model dengue-fever tuberculosis equation Physics LA - English M3 - Article; Proceedings Paper N1 - ISI Document Delivery No.: EC9TK Times Cited: 0 Cited Reference Count: 19 Massoukou, R. Y. M'pika Govinder, K. S. 3rd International Workshop on Nonlinear and Modern Mathematical Physics (NMMP) Apr 09-11, 2015 African Inst Math Sci, Cape Town, SOUTH AFRICA 0 1 World scientific publ co pte ltd Singapore 1793-6578 PY - 2016 SN - 0217-9792 SP - 13 ST - Symmetry analysis for hyperbolic equilibria using a TB/dengue fever model T2 - International Journal of Modern Physics B TI - Symmetry analysis for hyperbolic equilibria using a TB/dengue fever model UR - ://WOS:000388486900022 VL - 30 ID - 5082 ER - TY - JOUR AB - We study a model of disease transmission with continuous age-structure for latently infected individuals and for infectious individuals and with immigration of new individuals into the susceptible, latent and infectious classes. The model is very appropriate for tuberculosis. A Lyapunov functional is used to show that the unique endemic equilibrium is globally stable for all parameter values. AD - Department of Mathematics, Wilfrid Laurier University, Waterloo, Ontario, Canada. email: ccmcc8@gmail.com. AN - 27105982 AU - McCluskey, C. C. DA - Apr 01 DO - 10.3934/mbe.2015008 DP - NLM ET - 2016/04/24 IS - 2 J2 - Mathematical biosciences and engineering : MBE LA - eng N1 - 1551-0018 McCluskey, C Connell Journal Article United States Math Biosci Eng. 2016 Apr 1;13(2):381-400. doi: 10.3934/mbe.2015008. PY - 2016 SN - 1547-1063 SP - 381-400 ST - Global stability for an SEI model of infectious disease with age structure and immigration of infecteds T2 - Math Biosci Eng TI - Global stability for an SEI model of infectious disease with age structure and immigration of infecteds VL - 13 ID - 988 ER - TY - JOUR AB - BACKGROUND: In high incidence settings, the majority of Mycobacterium tuberculosis (M.tb) transmission occurs outside the household. Little is known about where people's indoor contacts occur outside the household, and how this differs between different settings. We estimate the number of contact hours that occur between adults and adult/youths and children in different building types in urban areas in Western Cape, South Africa, and Zambia. METHODS: Data were collected from 3206 adults using a cross-sectional survey, on buildings visited in a 24-h period, including building function, visit duration, and number of adults/youths and children (5-12 years) present. The mean numbers of contact hours per day by building function were calculated. RESULTS: Adults in Western Cape were more likely to visit workplaces, and less likely to visit shops and churches than adults in Zambia. Adults in Western Cape spent longer per visit in other homes and workplaces than adults in Zambia. More adults/youths were present at visits to shops and churches in Western Cape than in Zambia, and fewer at homes and hairdressers. More children were present at visits to shops in Western Cape than in Zambia, and fewer at schools and hairdressers. Overall numbers of adult/youth indoor contact hours were the same at both sites (35.4 and 37.6 h in Western Cape and Zambia respectively, p = 0.4). Child contact hours were higher in Zambia (16.0 vs 13.7 h, p = 0.03). Adult/youth and child contact hours were highest in workplaces in Western Cape and churches in Zambia. Compared to Zambia, adult contact hours in Western Cape were higher in workplaces (15.2 vs 8.0 h, p = 0.004), and lower in churches (3.7 vs 8.6 h, p = 0.002). Child contact hours were higher in other peoples' homes (2.8 vs 1.6 h, p = 0.03) and workplaces (4.9 vs 2.1 h, p = 0.003), and lower in churches (2.5 vs 6.2, p = 0.004) and schools (0.4 vs 1.5, p = 0.01). CONCLUSIONS: Patterns of indoor contact between adults and adults/youths and children differ between different sites in high M.tb incidence areas. Targeting public buildings with interventions to reduce M.tb transmission (e.g. increasing ventilation or UV irradiation) should be informed by local data. AD - TB Modelling Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. nicky.mccreesh@lshtm.ac.uk. TB Modelling Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. clare_looker@hotmail.com. TB Modelling Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. p.j.dodd@sheffield.ac.uk. Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK. p.j.dodd@sheffield.ac.uk. TB Modelling Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. idplumb@gmail.com. ZAMBART Project, School of Medicine, University of Zambia, Lusaka, Zambia. kshanaube@zambart.org.zm. ZAMBART Project, School of Medicine, University of Zambia, Lusaka, Zambia. Monde.Muyoyeta@cidrz.org. TB Department, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. Monde.Muyoyeta@cidrz.org. Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. faussettp@unaids.org. Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. lizcorbett04@gmail.com. HIV and TB Theme, Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi. lizcorbett04@gmail.com. ZAMBART Project, School of Medicine, University of Zambia, Lusaka, Zambia. helen@zambart.org.zm. Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. helen@zambart.org.zm. TB Modelling Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. richard.white@lshtm.ac.uk. AN - 26861444 AU - McCreesh, N. AU - Looker, C. AU - Dodd, P. J. AU - Plumb, I. D. AU - Shanaube, K. AU - Muyoyeta, M. AU - Godfrey-Faussett, P. AU - Corbett, E. L. AU - Ayles, H. AU - White, R. G. C2 - PMC4746903 DA - Feb 09 DO - 10.1186/s12879-016-1406-5 DP - NLM ET - 2016/02/11 J2 - BMC infectious diseases KW - Adult Child Child, Preschool Cross-Sectional Studies Female Humans Incidence Interpersonal Relations Male Mycobacterium tuberculosis *Residence Characteristics Schools South Africa/epidemiology Tuberculosis/*prevention & control/transmission Workplace Zambia/epidemiology LA - eng N1 - 1471-2334 McCreesh, Nicky Looker, Clare Dodd, Peter J Plumb, Ian D Shanaube, Kwame Muyoyeta, Monde Godfrey-Faussett, Peter Corbett, Elizabeth L Ayles, Helen White, Richard G Wellcome Trust/United Kingdom G0802414/Medical Research Council/United Kingdom Comparative Study Journal Article Research Support, Non-U.S. Gov't England BMC Infect Dis. 2016 Feb 9;16:71. doi: 10.1186/s12879-016-1406-5. PY - 2016 SN - 1471-2334 SP - 71 ST - Comparison of indoor contact time data in Zambia and Western Cape, South Africa suggests targeting of interventions to reduce Mycobacterium tuberculosis transmission should be informed by local data T2 - BMC Infect Dis TI - Comparison of indoor contact time data in Zambia and Western Cape, South Africa suggests targeting of interventions to reduce Mycobacterium tuberculosis transmission should be informed by local data VL - 16 ID - 1074 ER - TY - JOUR AB - When an individual is exposed to Mycobacterium tuberculosis (Mtb) three outcomes are possible: bacterial clearance, active disease, or latent infection. It is generally believed that most individuals exposed to Mtb become latently infected and carry the mycobacteria for life. How Mtb is maintained during this latent infection remains largely unknown. During an Mtb infection in mice, there is a phase of rapid increase in bacterial numbers in the murine lungs within the first 3 weeks, and then bacterial numbers either stabilize or increase slowly over the period of many months. It has been debated whether the relatively constant numbers of bacteria in the chronic infection result from latent (dormant, quiescent), non-replicating bacteria, or whether the observed Mtb cell numbers are due to balance between rapid replication and death. A recent study of mice, infected with a Mtb strain carrying an unstable plasmid, showed that during the chronic phase, Mtb was replicating at significant rates. Using experimental data from this study and mathematical modeling we investigated the limits of the rates of bacterial replication, death, and quiescence during Mtb infection of mice. First, we found that to explain the data the rates of bacterial replication and death could not be constant and had to decrease with time since infection unless there were large changes in plasmid segregation probability over time. While a decrease in the rate of Mtb replication with time since infection was expected due to depletion of host's resources, a decrease in the Mtb death rate was counterintuitive since Mtb-specific immune response, appearing in the lungs 3-4 weeks after infection, should increase removal of bacteria. Interestingly, we found no significant correlation between estimated rates of Mtb replication and death suggesting the decline in these rates was driven by independent mechanisms. Second, we found that the data could not be explained by assuming that bacteria do not die, suggesting that some removal of bacteria from lungs of these mice had to occur even though the total bacterial counts in these mice always increased over time. Third and finally, we showed that to explain the data the majority of bacterial cells (at least ~60%) must be replicating in the chronic phase of infection further challenging widespread belief of nonreplicating Mtb in latency. Our predictions were robust to some changes in the structure of the model, for example, when the loss of plasmid-bearing cells was mainly due to high fitness cost of the plasmid. Further studies should determine if more mechanistic models for Mtb dynamics are also able to accurately explain these data. AD - National Institute for Mathematical and Biological SynthesisKnoxville, TN, USA; Department of Biochemistry, Cellular and Molecular Biology, University of TennesseeKnoxville, TN, USA; Department of Mathematics, University of TennesseeKnoxville, TN, USA. National Institute for Mathematical and Biological SynthesisKnoxville, TN, USA; The College at the University of ChicagoChicago, IL, USA. National Institute for Mathematical and Biological SynthesisKnoxville, TN, USA; Departments of Chemistry and Mathematics, Maryville CollegeMaryville, TN, USA. National Institute for Mathematical and Biological SynthesisKnoxville, TN, USA; Department of Forestry, Wildlife and Fisheries, University of TennesseeKnoxville, TN, USA. National Institute for Mathematical and Biological SynthesisKnoxville, TN, USA; Department of Mathematics, University of TennesseeKnoxville, TN, USA; Department of Microbiology, University of TennesseeKnoxville, TN, USA. AN - 27379030 AU - McDaniel, M. M. AU - Krishna, N. AU - Handagama, W. G. AU - Eda, S. AU - Ganusov, V. V. C2 - PMC4906525 DO - 10.3389/fmicb.2016.00862 KW - Mycobacterium tuberculosis chronic infection death rate mathematical model mouse pathogenesis plasmid loss replication rate N1 - McDaniel, Margaret M Krishna, Nitin Handagama, Winode G Eda, Shigetoshi Ganusov, Vitaly V eng Switzerland 2016/07/06 06:00 Front Microbiol. 2016 Jun 14;7:862. doi: 10.3389/fmicb.2016.00862. eCollection 2016. PY - 2016 SN - 1664-302X (Print) 1664-302X (Linking) SP - 862 ST - Quantifying Limits on Replication, Death, and Quiescence of Mycobacterium tuberculosis in Mice T2 - Front Microbiol TI - Quantifying Limits on Replication, Death, and Quiescence of Mycobacterium tuberculosis in Mice UR - https://www.ncbi.nlm.nih.gov/pubmed/27379030 VL - 7 ID - 2209 ER - TY - JOUR AB - BACKGROUND: In response to rising TB notification rates in England, universal strain typing was introduced in 2010. We evaluated the acceptability, effectiveness and cost-effectiveness of the TB strain typing service (TB-STS). METHODS: We conducted a mixed-methods evaluation using routine laboratory, clinic and public health data. We estimated the effect of the TB-STS on detection of false positive Mycobacterium tuberculosis diagnoses (2010-2012); contact tracing yield (number of infections or active disease per pulmonary TB case); and diagnostic delay. We developed a deterministic age-structured compartmental model to explore the effectiveness of the TB-STS, which informed a cost-effectiveness analysis. RESULTS: Semi-structured interviews explored user experience. Strain typing identified 17 additional false positive diagnoses. The TB-STS had no significant effect on contact tracing yield or diagnostic delay. Mathematical modelling suggested increasing the proportion of infections detected would have little value in reducing TB incidence in the white UK-born population. However, in the non-white UK-born and non-UK-born populations, over 20 years, if detection of latent infection increases from 3% to 13% per year, then TB incidence would decrease by 11%; reducing diagnostic delay by one week could lead to 25% reduction in incidence. The current TB-STS was not predicted to be cost-effective over 20 years ( pound95 628/quality-adjusted life-years). Interviews found people had mixed experiences, but identified broader benefits, of the TB-STS. CONCLUSIONS: To reduce costs, improve efficiency and increase effectiveness, we recommend changes to the TB-STS, including discontinuing routine cluster investigations and focusing on reducing diagnostic delay across the TB programme. This evaluation of a complex intervention informs the future of strain typing in the era of rapidly advancing technologies. AD - Research Department of Infection and Population Health, University College London, London, UK. Modelling and Economics Unit, Public Health England, London, UK Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. Health Economics Research Group, Brunel University, London, UK. Department of Infectious Diseases, Public Health Service (GGD) Amsterdam, Amsterdam, The Netherlands Department of Clinical Epidemiology, Academic Medical Centre, University of Amsterdam, The Netherlands. Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, USA. George Elliot NHS Trust, Warwickshire, UK. Department of Infection and Tropical Medicine, Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UK. South Midlands and Hertfordshire Public Health England Centre, Herts, UK. Field Epidemiology Services, Public Health England, London, UK. Research Department of Infection, University College London, London, UK. Department of Respiratory Medicine, University Hospitals Leicester, Glenfield Hospital, Leicester. Research Department of Infection and Population Health, University College London, London, UK Clinical Trials Unit, Medical Research Council, London, UK. AN - 25882538 AU - Mears, J. AU - Vynnycky, E. AU - Lord, J. AU - Borgdorff, M. W. AU - Cohen, T. AU - Crisp, D. AU - Innes, J. A. AU - Lilley, M. AU - Maguire, H. AU - McHugh, T. D. AU - Woltmann, G. AU - Abubakar, I. AU - Sonnenberg, P. DA - Aug DO - 10.1136/thoraxjnl-2014-206480 DP - NLM ET - 2015/04/18 IS - 8 J2 - Thorax KW - Bacterial Typing Techniques/*economics Cost-Benefit Analysis England/epidemiology Health Services/economics/standards Humans Incidence Mycobacterium tuberculosis/*genetics/isolation & purification Population Surveillance/methods *Program Evaluation Prospective Studies *Public Health Tuberculosis, Pulmonary/*diagnosis/economics/epidemiology/*microbiology Tuberculosis LA - eng N1 - 1468-3296 Mears, J Vynnycky, E Lord, J Borgdorff, M W Cohen, T Crisp, D Innes, J A Lilley, M Maguire, H McHugh, T D Woltmann, G Abubakar, I Sonnenberg, P Journal Article England Thorax. 2016 Aug;71(8):734-41. doi: 10.1136/thoraxjnl-2014-206480. Epub 2015 Apr 16. PY - 2016 SN - 0040-6376 SP - 734-41 ST - The prospective evaluation of the TB strain typing service in England: a mixed methods study T2 - Thorax TI - The prospective evaluation of the TB strain typing service in England: a mixed methods study VL - 71 ID - 1386 ER - TY - JOUR AB - BACKGROUND: The post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess resource requirements and cost-effectiveness of strategies to achieve these targets in China, India, and South Africa. METHODS: We examined intervention scenarios developed in consultation with country stakeholders, which scaled up existing interventions to high but feasible coverage by 2025. Nine independent modelling groups collaborated to estimate policy outcomes, and we estimated the cost of each scenario by synthesising service use estimates, empirical cost data, and expert opinion on implementation strategies. We estimated health effects (ie, disability-adjusted life-years averted) and resource implications for 2016-35, including patient-incurred costs. To assess resource requirements and cost-effectiveness, we compared scenarios with a base case representing continued current practice. FINDINGS: Incremental tuberculosis service costs differed by scenario and country, and in some cases they more than doubled existing funding needs. In general, expansion of tuberculosis services substantially reduced patient-incurred costs and, in India and China, produced net cost savings for most interventions under a societal perspective. In all three countries, expansion of access to care produced substantial health gains. Compared with current practice and conventional cost-effectiveness thresholds, most intervention approaches seemed highly cost-effective. INTERPRETATION: Expansion of tuberculosis services seems cost-effective for high-burden countries and could generate substantial health and economic benefits for patients, although substantial new funding would be required. Further work to determine the optimal intervention mix for each country is necessary. FUNDING: Bill & Melinda Gates Foundation. AD - Department of Global Health and Population, Harvard T H Chan School of Public Health, Boston, MA, USA; Center for Health Decision Science, Harvard T H Chan School of Public Health, Boston, MA, USA. Electronic address: nmenzies@hsph.harvard.edu. Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands; Department of Global Health, Academic Medical Center, University of Amsterdam, Netherlands; Department of Global Health and Development, London School of Hygiene & Tropical Medicine, London, UK. Department of Global Health and Development, London School of Hygiene & Tropical Medicine, London, UK. Public Health Foundation of India, Delhi NCR, India. Health Economics Unit, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. Monitoring and Evaluation Unit, Geneva, Switzerland. School of Health Care Management and Key Laboratory of Health Economics and Policy Research of Ministry of Health, Shandong University, Jinan, China. Global TB Programme, Geneva, Switzerland. Department of Global Health and Population, Harvard T H Chan School of Public Health, Boston, MA, USA. Public Health Foundation of India, Delhi NCR, India; Department of Infectious Disease Epidemiology, Imperial College London, London, UK. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Department of Medicine, Stanford University, Stanford, CA, USA. Institute for Disease Modeling, Seattle, WA, USA. Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA. Victorian Tuberculosis Program at the Peter Doherty Institute, Melbourne, VIC, Australia; Department of Microbiology and Immunology, University of Melbourne, Melbourne, VIC, Australia. Stanford Health Policy, Centers for Health Policy and Primary Care and Outcomes Research, Stanford University, Stanford, CA, USA. Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, GA, USA. Institute for Disease Modeling, Seattle, WA, USA; Synthetic Neurobiology Group, Media Lab, Massachusetts Institute of Technology, Cambridge, MA, USA. TB Modelling Group, TB Centre, London School of Hygiene & Tropical Medicine, London, UK; Faculty of Epidemiology and Public Health, London School of Hygiene & Tropical Medicine, London, UK. Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan. Victorian Tuberculosis Program at the Peter Doherty Institute, Melbourne, VIC, Australia; Department of Microbiology and Immunology, University of Melbourne, Melbourne, VIC, Australia; Burnet Institute, Melbourne, VIC, Australia. Department of Global Health and Population, Harvard T H Chan School of Public Health, Boston, MA, USA; Center for Health Decision Science, Harvard T H Chan School of Public Health, Boston, MA, USA. Department of Management Science and Engineering, Stanford University, Stanford, CA, USA. Faculty of Epidemiology and Public Health, London School of Hygiene & Tropical Medicine, London, UK. Epidemiology and Research Division, National Tuberculosis Institute, Bangalore, India. Aurum Institute, Johannesburg, South Africa. Bill & Melinda Gates Foundation, Seattle, WA, USA. Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; Aurum Institute, Johannesburg, South Africa; School of Public Health, University of Witwatersrand, Johannesburg, South Africa. Stop TB Partnership, Geneva, Switzerland. Bill & Melinda Gates Foundation, New Delhi, India. Department of Infectious Disease Epidemiology, Imperial College London, London, UK. Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; School of Public Health, University of Witwatersrand, Johannesburg, South Africa; Africa Centre for Population Health, School of Nursing & Public Health, University of KwaZulu-Natal, Durban, South Africa. Strategic Information Department, The Global Fund, Geneva, Switzerland. National Department of Health, Pretoria, South Africa. Avenir Health, Glastonbury, CT, USA. World Health Organization Country Office for India, New Delhi, India. National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. KNCV Tuberculosis Foundation, The Hague, Netherlands. AN - 27720689 AU - Menzies, N. A. AU - Gomez, G. B. AU - Bozzani, F. AU - Chatterjee, S. AU - Foster, N. AU - Baena, I. G. AU - Laurence, Y. V. AU - Qiang, S. AU - Siroka, A. AU - Sweeney, S. AU - Verguet, S. AU - Arinaminpathy, N. AU - Azman, A. S. AU - Bendavid, E. AU - Chang, S. T. AU - Cohen, T. AU - Denholm, J. T. AU - Dowdy, D. W. AU - Eckhoff, P. A. AU - Goldhaber-Fiebert, J. D. AU - Handel, A. AU - Huynh, G. H. AU - Lalli, M. AU - Lin, H. H. AU - Mandal, S. AU - McBryde, E. S. AU - Pandey, S. AU - Salomon, J. A. AU - Suen, S. C. AU - Sumner, T. AU - Trauer, J. M. AU - Wagner, B. G. AU - Whalen, C. C. AU - Wu, C. Y. AU - Boccia, D. AU - Chadha, V. K. AU - Charalambous, S. AU - Chin, D. P. AU - Churchyard, G. AU - Daniels, C. AU - Dewan, P. AU - Ditiu, L. AU - Eaton, J. W. AU - Grant, A. D. AU - Hippner, P. AU - Hosseini, M. AU - Mametja, D. AU - Pretorius, C. AU - Pillay, Y. AU - Rade, K. AU - Sahu, S. AU - Wang, L. AU - Houben, Rmgj AU - Kimerling, M. E. AU - White, R. G. AU - Vassall, A. C2 - PMC5527122 C6 - NIHMS875777 DA - Nov DO - 10.1016/s2214-109x(16)30265-0 DP - NLM ET - 2016/10/22 IS - 11 J2 - The Lancet. Global health LA - eng N1 - 2214-109x Menzies, Nicolas A Gomez, Gabriela B Bozzani, Fiammetta Chatterjee, Susmita Foster, Nicola Baena, Ines Garcia Laurence, Yoko V Qiang, Sun Siroka, Andrew Sweeney, Sedona Verguet, Stephane Arinaminpathy, Nimalan Azman, Andrew S Bendavid, Eran Chang, Stewart T Cohen, Ted Denholm, Justin T Dowdy, David W Eckhoff, Philip A Goldhaber-Fiebert, Jeremy D Handel, Andreas Huynh, Grace H Lalli, Marek Lin, Hsien-Ho Mandal, Sandip McBryde, Emma S Pandey, Surabhi Salomon, Joshua A Suen, Sze-Chuan Sumner, Tom Trauer, James M Wagner, Bradley G Whalen, Christopher C Wu, Chieh-Yin Boccia, Delia Chadha, Vineet K Charalambous, Salome Chin, Daniel P Churchyard, Gavin Daniels, Colleen Dewan, Puneet Ditiu, Lucica Eaton, Jeffrey W Grant, Alison D Hippner, Piotr Hosseini, Mehran Mametja, David Pretorius, Carel Pillay, Yogan Rade, Kiran Sahu, Suvanand Wang, Lixia Houben, Rein M G J Kimerling, Michael E White, Richard G Vassall, Anna K01 AG037593/AG/NIA NIH HHS/United States MR/K010174/1/Medical Research Council/United Kingdom R01 AI093856/AI/NIAID NIH HHS/United States R01 AI112438/AI/NIAID NIH HHS/United States Journal Article England Lancet Glob Health. 2016 Nov;4(11):e816-e826. doi: 10.1016/S2214-109X(16)30265-0. Epub 2016 Oct 6. PY - 2016 SN - 2214-109x SP - e816-e826 ST - Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models T2 - Lancet Glob Health TI - Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models VL - 4 ID - 844 ER - TY - JOUR AB - Healthcare workers (HCWs) in low-incidence settings are often serially tested for latent TB infection (LTBI) with the QuantiFERON-TB Gold In-Tube (QFT) assay, which exhibits frequent conversions and reversions. The clinical impact of such variability on serial testing remains unknown. We used a microsimulation Markov model that accounts for major sources of variability to project diagnostic outcomes in a simulated North American HCW cohort. Serial testing using a single QFT with the recommended conversion cutoff (IFN-g > 0.35 IU/mL) resulted in 24.6% (95% uncertainty range, UR: 23.8-25.5) of the entire population testing false-positive over ten years. Raising the cutoff to > 1.0 IU/mL or confirming initial positive results with a (presumed independent) second test reduced this false-positive percentage to 2.3% (95% UR: 2.0-2.6%) or 4.1% (95% UR: 3.7-4.5%), but also reduced the proportion of true incident infections detected within the first year of infection from 76.5% (95% UR: 66.3-84.6%) to 54.8% (95% UR: 44.6-64.5%) or 61.5% (95% UR: 51.6-70.9%), respectively. Serial QFT testing of HCWs in North America may result in tremendous over-diagnosis and over-treatment of LTBI, with nearly thirty false-positives for every true infection diagnosed. Using higher cutoffs for conversion or confirmatory tests (for initial positives) can mitigate these effects, but will also diagnose fewer true infections. AD - Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA UCSF, Dept Med, San Francisco, CA USA FIND, TB & Hepatitis Programme, Geneva, Switzerland Stanford Univ, Dept Med, Palo Alto, CA 94304 USA KNCV, Evidence Team, The Hague, Netherlands McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada McGill Univ, McGill Int TB Ctr, Montreal, PQ, Canada AN - WOS:000380659100001 AU - Moses, M. W. AU - Zwerling, A. AU - Cattamanchi, A. AU - Denkinger, C. M. AU - Banaei, N. AU - Kik, S. V. AU - Metcalfe, J. AU - Pai, M. AU - Dowdy, D. DA - Jul 29 DO - ARTN 30781 10.1038/srep30781 J2 - Sci Rep-Uk KW - health-care workers gamma release assays united-states control program infection challenges reproducibility variability diagnosis LA - English N1 - Ds3by Times Cited:1 Cited References Count:31 PY - 2016 SN - 2045-2322 ST - Serial testing for latent tuberculosis using QuantiFERON-TB Gold In-Tube: A Markov model T2 - Scientific Reports TI - Serial testing for latent tuberculosis using QuantiFERON-TB Gold In-Tube: A Markov model UR - ://WOS:000380659100001 VL - 6 ID - 2213 ER - TY - JOUR AB - A deterministic model of tuberculosis (TB) in sub-Saharan Africa including undetected and lost-sight cases is presented and analyzed. The model is shown to exhibit the phenomenon of backward bifurcation, when a stable disease-free equilibrium co-exists with one or more stable endemic equilibrium points when the associated basic reproduction number (R-0) is less than unity. Analyzing the model obviously reveals that exogenous reinfection plays a key role on the existence of backward bifurcation. However, an analysis of the ranges of exogenous reinfection suggested that backward bifurcation occurs only for very high and unrealistic ranges of the exogenous reinfection rate. Random perturbation of reinfection rates was performed to gain insight into the role of this latter on the stability of the disease free equilibrium. (C) 2016 Published by Elsevier B.V. AD - Leibniz Univ Hannover, Fac Nat Sci, Vegetable Syst Modelling Sect, Inst Hort Prod Syst, Herrenhauser Str 2, D-30419 Hannover, Germany Univ Douala, Fac Sci, Dept Math & Comp Sci, POB 24157, Douala, Cameroon UMMISCO, IRD UPMC, UMI 209, Bondy, France Univ Yaounde I, Project Team GRIMCAPE, LIRIMA, Yaounde, Cameroon Univ Yaounde I, African Ctr Excellence Informat & Commun Technol, Yaounde, Cameroon AN - WOS:000377294900005 AU - Moualeu, D. P. AU - Yakam, A. N. AU - Bowong, S. AU - Temgoua, A. DA - Dec DO - 10.1016/j.cnsns.2016.04.012 J2 - Commun Nonlinear Sci KW - nonlinear dynamical systems tuberculosis mathematical models stability bifurcation backward bifurcation undiagnosed tuberculosis exogenous reinfection epidemic model hiv vaccination transmission prevalence stability impact LA - English N1 - Dn7ya Times Cited:0 Cited References Count:52 PY - 2016 SN - 1007-5704 SP - 48-63 ST - Analysis of a tuberculosis model with undetected and lost-sight cases T2 - Communications in Nonlinear Science and Numerical Simulation TI - Analysis of a tuberculosis model with undetected and lost-sight cases UR - ://WOS:000377294900005 VL - 41 ID - 2196 ER - TY - JOUR AB - BACKGROUND: Systematic screening is often proposed as a way to improve case finding for tuberculosis (TB), but the cost-effectiveness of specific strategies for systematic screening remains poorly studied. METHODS: We constructed a Markov-based decision analytic model to analyse the cost-effectiveness of triage testing for TB in Uganda, compared against passive case detection with Xpert MTB/RIF. We assumed a triage algorithm whereby all adults presenting to healthcare centres would be screened for cough, and those with cough of at least 2 weeks would receive the triage test, with positive triage results confirmed by Xpert MTB/RIF. We adopted the perspective of the TB control sector, using a primary outcome of the cost per year of life gained (YLG) over a lifetime time horizon. RESULTS: Systematic screening in a population with a 5% underlying prevalence of TB was estimated to cost US$610 per YLG (95% uncertainty range US$200-US$1859) with chest X-ray (CXR) (US$5 per test, specificity 0.67), or US$588 (US$221-US$1746) with C reactive protein (CRP) (US$3 per test, specificity 0.59). In addition to the cost and specificity of the triage test, cost-effectiveness was most sensitive to the underlying prevalence of TB, monthly risk of mortality in people with untreated TB and the proportion of patients with TB who would be treated in the absence of systematic screening. CONCLUSIONS: To optimise the cost-effectiveness of facility-based systematic screening of TB with a triage test, it must be carried out in a high-risk population, or use triage tests that are cheaper or more specific than CXR or CRP. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. Division of Pulmonary and Critical Care Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California, USA. Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland. Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam, The Netherlands. Department of Epidemiology & Biostatistics, McGill International TB Centre, McGill University, Montreal, Quebec, Canada. AN - 28588939 AU - Murray, M. AU - Cattamanchi, A. AU - Denkinger, C. AU - Van't Hoog, A. AU - Pai, M. AU - Dowdy, D. C2 - PMC5321327 on the utility of C reactive protein as a screening test for tuberculosis among people living with HIV. CD reports employment by FIND. DO - 10.1136/bmjgh-2016-000064 DP - NLM ET - 2017/06/08 IS - 2 J2 - BMJ global health L1 - internal-pdf://3774087730/Murray-2016-Cost-effectiveness of triage testi.pdf LA - eng N1 - Murray, Matthew Cattamanchi, Adithya Denkinger, Claudia Van't Hoog, Anja Pai, Madhukar Dowdy, David R21 AI106031/AI/NIAID NIH HHS/United States Journal Article England BMJ Glob Health. 2016 Sep 28;1(2):e000064. doi: 10.1136/bmjgh-2016-000064. eCollection 2016. PY - 2016 SN - 2059-7908 (Print) 2059-7908 SP - e000064 ST - Cost-effectiveness of triage testing for facility-based systematic screening of tuberculosis among Ugandan adults T2 - BMJ Glob Health TI - Cost-effectiveness of triage testing for facility-based systematic screening of tuberculosis among Ugandan adults UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321327/pdf/bmjgh-2016-000064.pdf VL - 1 ID - 2180 ER - TY - JOUR AB - The first integrals and exact solutions of mathematical models of epidemiology: a susceptible-infected-recovered-infected (SIRI) model and a tuberculosis model with demographic growth are analyzed. These models are represented by systems of first-order nonlinear ordinary differential equations, and this system is replaced by one which contains a second-order ordinary differential equation. The partial Lagrangian approach is then utilized to derive the first integrals of these models. Several cases arise. Then, we utilize the derived first integrals to construct exact solutions for the models under investigation and determine new solutions. The dynamic properties of these models are studied too. Copyright (C) 2016 John Wiley & Sons, Ltd. AD - [Naz, R.] Lahore Sch Econ, Ctr Math & Stat Sci, Lahore 53200, Pakistan. [Mahomed, K. S.] Univ Witwatersrand, Sch Comp Sci & Appl Math, DST NRF Ctr Excellence Math & Stat Sci, ZA-2050 Johannesburg, South Africa. [Naeem, I.] LUMS, Sch Sci & Engn, Dept Math, Lahore 54792, Pakistan. Naz, R (reprint author), Lahore Sch Econ, Ctr Math & Stat Sci, Lahore 53200, Pakistan. rehananaz_qau@yahoo.com AN - WOS:000385718900028 AU - Naz, R. AU - Mahomed, K. S. AU - Naeem, I. DA - Oct DO - 10.1002/mma.3903 IS - 15 J2 - Math. Meth. Appl. Sci. KW - symmetries Lie-group and Lie-algebra methods methods of ordinary differential equations epidemic model mathematical-models partial lagrangians lyapunov functions conservation-laws transmission singularity symmetries stability systems Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: DZ3BO Times Cited: 0 Cited Reference Count: 27 Naz, R. Mahomed, K. S. Naeem, I. Naz, Rehana/I-5254-2013; Naz, Rehana/N-3246-2017 Naz, Rehana/0000-0001-6232-4957; Naz, Rehana/0000-0001-6232-4957; Naeem, Imran/0000-0003-2929-7226 NRF of South Africa K. S. M. thanks the NRF of South Africa for research funding support. 0 1 4 Wiley-blackwell Hoboken 1099-1476 PY - 2016 SN - 0170-4214 SP - 4654-4666 ST - First integrals and exact solutions of the SIRI and tuberculosis models T2 - Mathematical Methods in the Applied Sciences TI - First integrals and exact solutions of the SIRI and tuberculosis models UR - ://WOS:000385718900028 VL - 39 ID - 5099 ER - TY - JOUR AB - One third of the world's population is affected by tuberculosis (TB). This pandemic presents several challenges to the health professionals. Hence, forecasting and controlling TB epidemics play an important role to deal with this disease. Transmission models are valuable tools for projecting and evaluating control strategies against TB, but lack capability to easily integrate noisy information from epidemiological data into projections and policy analysis. To overcome this shortcoming, a dynamical system for TB based on particle filtering algorithm was developed. We evaluated the effectiveness of different levels of particle filtering by running the particle filter to year 2000, then disabling it and judging the discrepancy of model predictions vs. observed data for the period 2000-2007. The successive results revealed similar patterns including a rise in force of infection during the 1990s, but considering successively larger sets of observations yielded smaller discrepancies between particle filtered projections and observed data. AD - [Oraji, Rahim; Osgood, Nathaniel D.] Univ Saskatchewan, Dept Comp Sci, Saskatoon, SK, Canada. [Hoeppner, Vernon H.] Univ Saskatchewan, Dept Med, Saskatoon, SK, Canada. [Safarishahrbijari, Anahita] Univ Saskatchewan, Dept Mech Engn, Saskatoon, SK, Canada. Oraji, R (reprint author), Univ Saskatchewan, Dept Comp Sci, Saskatoon, SK, Canada. rao519@mail.usask.ca; vernon.hoeppner@usask.ca; anahita.safari@usask.ca; nathaniel.osgood@usask.ca AN - WOS:000391422100071 AU - Oraji, R. AU - Hoeppner, V. H. AU - Safarishahrbijari, A. AU - Osgood, N. D. AU - Ieee DO - 10.1109/ichi.2016.70 KW - simulation system dynamics particle filtering tuberculosis tuberculosis outcomes dynamics Health Care Sciences & Services Medical Informatics LA - English M3 - Proceedings Paper N1 - ISI Document Delivery No.: BG7LO Times Cited: 0 Cited Reference Count: 13 Oraji, Rahim Hoeppner, Vernon H. Safarishahrbijari, Anahita Osgood, Nathaniel D. IEEE International Conference on Healthcare Informatics (ICHI) Oct 04-07, 2016 Chicago, IL IEEE, GE Digital, IEEE Comp Soc, NSF, Computers, Univ Illinois 0 Ieee New york 978-1-5090-6117-4 PY - 2016 SP - 392-398 ST - Combining Particle Filtering and Transmission Modeling for TB control T2 - 2016 Ieee International Conference on Healthcare Informatics (Ichi) TI - Combining Particle Filtering and Transmission Modeling for TB control UR - ://WOS:000391422100071 ID - 5210 ER - TY - JOUR AB - BACKGROUND: Tuberculosis (TB) remains a significant health problem in the Canadian Arctic. Substantial health system delays in TB diagnosis can occur, in part due to the lack of capacity for onsite microbiologic testing. A study recently evaluated the yield and impact of a rapid automated PCR test (Xpert(R)MTB/RIF) for the diagnosis of TB in Iqaluit (Nunavut). We conducted an economic analysis to evaluate the expected cost relative to the expected reduction in time to treatment initiation, with the addition of Xpert(R)MTB/RIF to the current diagnostic and treatment algorithms used in this setting. METHODS: A decision analysis model compared current microbiologic testing to a scenario where Xpert(R)MTB/RIF was added to the current diagnostic algorithm for active TB, and incorporated costs and clinical endpoints from the Iqaluit study. Several sensitivity analyses that considered alternative use were also considered. We estimated days to TB diagnosis and treatment initiation, health system costs, and the incremental cost per treatment day gained for each individual evaluated for possible TB. RESULTS: With the addition of Xpert(R)MTB/RIF, costs increased while days to TB treatment initiation were reduced. The incremental cost per treatment day gained (per individual investigated for TB) was $164 (95% uncertainty range $85, $452). In a sensitivity analysis that considered hospital discharge after a single negative Xpert(R)MTB/RIF, the Xpert(R)MTB/RIF scenario was cost saving. INTERPRETATION: Adding Xpert(R)MTB/RIF to the current diagnostic algorithm for TB in Nunavut appears to reduce time to diagnosis and treatment at reasonable cost. It may be especially well suited to overcome some of the other logistical barriers that are unique to this and other remote communities. AD - Respiratory Epidemiology and Clinical Research Unit, Department of Epidemiology, McGill University, Montreal, QC, Canada. McGill International Tuberculosis Centre, McGill University, Montreal, QC, Canada. Clinical Epidemiology, The Ottawa Hospital Research Institute, Ottawa, ON, Canada. Division of Respirology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada. AN - 26990299 AU - Oxlade, O. AU - Sugarman, J. AU - Alvarez, G. G. AU - Pai, M. AU - Schwartzman, K. C2 - PMC4798714 DO - 10.1371/journal.pone.0150119 IS - 3 KW - Antitubercular Agents/administration & dosage/economics/*therapeutic use Arctic Regions Cost of Illness Health Services Accessibility Humans Nunavut Probability Sensitivity and Specificity Tuberculosis/*diagnosis/drug therapy/economics L1 - internal-pdf://0693664899/Oxlade-2016-Xpert(R)MTB_RIF for the Diagnosis.pdf N1 - Oxlade, Olivia Sugarman, Jordan Alvarez, Gonzalo G Pai, Madhukar Schwartzman, Kevin eng MOP 89918/Canadian Institutes of Health Research/Canada Research Support, Non-U.S. Gov't 2016/03/19 06:00 PLoS One. 2016 Mar 18;11(3):e0150119. doi: 10.1371/journal.pone.0150119. eCollection 2016. PY - 2016 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e0150119 ST - Xpert(R)MTB/RIF for the Diagnosis of Tuberculosis in a Remote Arctic Setting: Impact on Cost and Time to Treatment Initiation T2 - PLoS One TI - Xpert(R)MTB/RIF for the Diagnosis of Tuberculosis in a Remote Arctic Setting: Impact on Cost and Time to Treatment Initiation UR - https://www.ncbi.nlm.nih.gov/pubmed/26990299 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4798714/pdf/pone.0150119.pdf VL - 11 ID - 2215 ER - TY - JOUR AB - The Immunology tuberculosis model that has been formulated by (Ibarguen, E., Esteva, L., & Chavez, L, 2011) in the form of a system of nonlinear differential equations first order. In this study, we used to Runge Kutta Fehlberg method and Adams Bashforth Moulton method. This study has been obtained numerical solution of the model. The results showed that the relative error obtained from the Adams Bashforth Moulton method is smaller when compared with the Runge Kutta Fehlber method. There are two methods has a high accuracy in solving systems of nonlinear differential equations. AD - [Pagalay, Usman; Muhlish] State Islamic Univ Maulana Malik Ibrahim Malang, Dept Math, Malang, Indonesia. Pagalay, U (reprint author), State Islamic Univ Maulana Malik Ibrahim Malang, Dept Math, Malang, Indonesia. usmanpagalay@yahoo.co.id AN - WOS:000389057300057 AU - Pagalay, U. AU - Muhlish DA - May IS - 5 J2 - J. Teknol. KW - Runge Kutta Fehlberg Adams Bashforth Moulton Immunology of Tuberculosis Models Engineering LA - English M3 - Article N1 - ISI Document Delivery No.: ED7OT Times Cited: 0 Cited Reference Count: 4 Pagalay, Usman Muhlish 0 Penerbit utm press Johor 2180-3722 PY - 2016 SN - 0127-9696 SP - 369-372 ST - NUMERICAL SOLUTION FOR IMMUNOLOGY TUBERCULOSIS MODEL USING RUNGE KUTTA FEHLBERG AND ADAMS BASHFORTH MOULTON METHOD T2 - Jurnal Teknologi TI - NUMERICAL SOLUTION FOR IMMUNOLOGY TUBERCULOSIS MODEL USING RUNGE KUTTA FEHLBERG AND ADAMS BASHFORTH MOULTON METHOD UR - ://WOS:000389057300057 VL - 78 ID - 5154 ER - TY - JOUR AB - Response to the 2014-2015 Ebola outbreak in West Africa overwhelmed the healthcare systems of Guinea, Liberia, and Sierra Leone, reducing access to health services for diagnosis and treatment for the major diseases that are endemic to the region: malaria, HIV/AIDS, and tuberculosis. To estimate the repercussions of the Ebola outbreak on the populations at risk for these diseases, we developed computational models for disease transmission and infection progression. We estimated that a 50% reduction in access to healthcare services during the Ebola outbreak exacerbated malaria, HIV/AIDS, and tuberculosis mortality rates by additional death counts of 6,269 (2,564-12,407) in Guinea; 1,535 (522-2,8780) in Liberia; and 2,819 (844-4,844) in Sierra Leone. The 2014-2015 Ebola outbreak was catastrophic in these countries, and its indirect impact of increasing the mortality rates of other diseases was also substantial. AN - 26886846 AU - Parpia, A. S. AU - Ndeffo-Mbah, M. L. AU - Wenzel, N. S. AU - Galvani, A. P. C2 - PMC4766886 DA - Mar DO - 10.3201/eid2203.150977 DP - NLM ET - 2016/02/18 IS - 3 J2 - Emerging infectious diseases KW - Acquired Immunodeficiency Syndrome/*mortality Adolescent Adult Child, Preschool Computer Simulation Cost of Illness *Disease Outbreaks Guinea/epidemiology HIV Infections/mortality *Health Services Accessibility Hemorrhagic Fever, Ebola/*epidemiology Humans Liberia/epidemiology Malaria/*mortality Middle Aged Models, Biological Sierra Leone/epidemiology Tuberculosis/*mortality Young Adult Ebola virus HIV/AIDS and other retroviruses healthcare malaria mathematical model mortality rate mycobacteria parasites parasitic tuberculosis and other mycobacteria vector-borne infections viruses zoonoses LA - eng N1 - 1080-6059 Parpia, Alyssa S Ndeffo-Mbah, Martial L Wenzel, Natasha S Galvani, Alison P U01 GM087719/GM/NIGMS NIH HHS/United States U01 GM105627/GM/NIGMS NIH HHS/United States 2 U01 GM087719/GM/NIGMS NIH HHS/United States 5 U01 GM105627/GM/NIGMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. United States Emerg Infect Dis. 2016 Mar;22(3):433-41. doi: 10.3201/eid2203.150977. PY - 2016 SN - 1080-6040 SP - 433-41 ST - Effects of Response to 2014-2015 Ebola Outbreak on Deaths from Malaria, HIV/AIDS, and Tuberculosis, West Africa T2 - Emerg Infect Dis TI - Effects of Response to 2014-2015 Ebola Outbreak on Deaths from Malaria, HIV/AIDS, and Tuberculosis, West Africa VL - 22 ID - 1063 ER - TY - JOUR AB - Infection of humans with Mycobacterium tuberculosis (Mtb) results in diverse outcomes that range from acute disease to establishment of persistence and to even clearance of the pathogen. These different outcomes represent the combined result of host heterogeneity on the one hand, and virulence properties of the infecting strain of pathogen on the other. From the standpoint of the host, the balance between PGE2, LXA4 and LTB4 represents at least one of the factors that dictates the eventual pathophysiology. We therefore built an ODE model to describe the host-pathogen interaction and studied the local stability properties of the system, to obtain the parametric conditions that lead to different disease outcomes. We then modulated levels of the pro- and anti-inflammatory lipid mediators to better understand the convergence between host phenotype and factors that relate to virulence properties of the pathogen. Global sensitivity analysis, using the variance-based method of extended Fourier Amplitude Sensitivity Test (eFAST), revealed that disease severity was indeed defined by combined effects of phenotypic variability at the level of both host and pathogen. Interestingly here, [PGE2] was found to act as a switch between bacterial clearance and acute disease. Our mathematical model suggests that development of more effective treatments for tuberculosis will be contingent upon a better understanding of how the intrinsic variability at the level of both host and pathogen contribute to influence the nature of interactions between these two entities. AD - International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg 110067, New Delhi, India. Electronic address: gabriele@icgeb.res.in. International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg 110067, New Delhi, India. Electronic address: phonimath@gmail.com. International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg 110067, New Delhi, India. Electronic address: kanury@icgeb.res.in. Translational Health Science and Technology Institute, Drug Discovery Research Centre, NCR Biotech Science Cluster, 3rd Milestone, Faridabad - Gurgaon Express Way, Faridabad 121001, Haryana, India. Electronic address: samrat.chatterjee@thsti.res.in. AN - 26551160 AU - Pedruzzi, G. AU - Das, P. N. AU - Rao, K. V. AU - Chatterjee, S. DA - Jan 21 DO - 10.1016/j.jtbi.2015.10.025 DP - NLM ET - 2015/11/10 J2 - Journal of theoretical biology KW - Apoptosis Computer Simulation Dinoprostone/*metabolism Humans Inflammation Leukotriene B4/*metabolism Lipoxins/*metabolism Macrophages/cytology/metabolism Models, Theoretical Mycobacterium Infections/*metabolism *Mycobacterium tuberculosis Necrosis Phenotype Treatment Outcome Virulence Differential equations Host-pathogen interaction Lxa(4):ltb(4) Mycobacterium tuberculosis Pge(2) LA - eng N1 - 1095-8541 Pedruzzi, Gabriele Das, Phonindra Nath Rao, Kanury Vs Chatterjee, Samrat Journal Article England J Theor Biol. 2016 Jan 21;389:159-70. doi: 10.1016/j.jtbi.2015.10.025. Epub 2015 Nov 6. PY - 2016 SN - 0022-5193 SP - 159-70 ST - Understanding PGE2, LXA4 and LTB4 balance during Mycobacterium tuberculosis infection through mathematical model T2 - J Theor Biol TI - Understanding PGE2, LXA4 and LTB4 balance during Mycobacterium tuberculosis infection through mathematical model VL - 389 ID - 1169 ER - TY - JOUR AB - Granulomas are a hallmark of tuberculosis. Inside granulomas, the pathogen Mycobacterium tuberculosis may enter a metabolically inactive state that is less susceptible to antibiotics. Understanding M. tuberculosis metabolism within granulomas could contribute to reducing the lengthy treatment required for tuberculosis and provide additional targets for new drugs. Two key adaptations of M. tuberculosis are a nonreplicating phenotype and accumulation of lipid inclusions in response to hypoxic conditions. To explore how these adaptations influence granuloma-scale outcomes in vivo, we present a multiscale in silico model of granuloma formation in tuberculosis. The model comprises host immunity, M. tuberculosis metabolism, M. tuberculosis growth adaptation to hypoxia, and nutrient diffusion. We calibrated our model to in vivo data from nonhuman primates and rabbits and apply the model to predict M. tuberculosis population dynamics and heterogeneity within granulomas. We found that bacterial populations are highly dynamic throughout infection in response to changing oxygen levels and host immunity pressures. Our results indicate that a nonreplicating phenotype, but not lipid inclusion formation, is important for long-term M. tuberculosis survival in granulomas. We used virtual M. tuberculosis knockouts to predict the impact of both metabolic enzyme inhibitors and metabolic pathways exploited to overcome inhibition. Results indicate that knockouts whose growth rates are below approximately 66% of the wild-type growth rate in a culture medium featuring lipid as the only carbon source are unable to sustain infections in granulomas. By mapping metabolite- and gene-scale perturbations to granuloma-scale outcomes and predicting mechanisms of sterilization, our method provides a powerful tool for hypothesis testing and guiding experimental searches for novel antituberculosis interventions. AD - Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, USA Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA. Department of Biomedical Engineering and High-Throughput Biology Center, Johns Hopkins University, Baltimore, Maryland, USA. Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, USA. Department of Biomedical Engineering and High-Throughput Biology Center, Johns Hopkins University, Baltimore, Maryland, USA joel.bader@jhu.edu kirschne@umich.edu. Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA joel.bader@jhu.edu kirschne@umich.edu. AN - 26975995 AU - Pienaar, E. AU - Matern, W. M. AU - Linderman, J. J. AU - Bader, J. S. AU - Kirschner, D. E. C2 - PMC4862722 DA - May DO - 10.1128/iai.01438-15 DP - NLM ET - 2016/03/16 IS - 5 J2 - Infection and immunity KW - *Adaptation, Physiological Animals Carbon/metabolism *Computer Simulation Disease Models, Animal Granuloma/*microbiology/*pathology Lipid Metabolism Metabolic Networks and Pathways/genetics Microbial Viability Mycobacterium tuberculosis/growth & development/*immunology/metabolism/*physiology Primates Rabbits Tuberculosis/microbiology/*pathology LA - eng N1 - 1098-5522 Pienaar, Elsje Matern, William M Linderman, Jennifer J Bader, Joel S Kirschner, Denise E R01 EB012579/EB/NIBIB NIH HHS/United States R01 HL106804/HL/NHLBI NIH HHS/United States R01 HL110811/HL/NHLBI NIH HHS/United States T32 GM007057/GM/NIGMS NIH HHS/United States Journal Article United States Infect Immun. 2016 Apr 22;84(5):1650-69. doi: 10.1128/IAI.01438-15. Print 2016 May. PY - 2016 SN - 0019-9567 SP - 1650-69 ST - Multiscale Model of Mycobacterium tuberculosis Infection Maps Metabolite and Gene Perturbations to Granuloma Sterilization Predictions T2 - Infect Immun TI - Multiscale Model of Mycobacterium tuberculosis Infection Maps Metabolite and Gene Perturbations to Granuloma Sterilization Predictions VL - 84 ID - 1036 ER - TY - JOUR AB - INTRODUCTION: In vaccine development, dose-response curves are commonly assumed to be saturating. Evidence from tuberculosis (TB) vaccine, H56+IC31 shows this may be incorrect. Mathematical modelling techniques may be useful in efficiently identifying the most immunogenic dose, but model calibration requires longitudinal data across multiple doses and time points. AIMS: We aimed to (i) generate longitudinal response data in mice for a wide range of H56+IC31 doses for use in future mathematical modelling and (ii) test whether a 'saturating' or 'peaked' dose-response curve, better fit the empirical data. METHODS: We measured IFN-gamma secretion using an ELISPOT assay in the splenocytes of mice who had received doses of 0, 0.1, 0.5, 1, 5 or 15mug H56+IC31. Mice were vaccinated twice (at day 0 and 15) and responses measured for each dose at 8 time points over a 56-day period following first vaccination. Summary measures Area Under the Curve (AUC), peak and day 56 responses were compared between dose groups. Corrected Akaike Information Criteria was used to test which dose-response curve best fitted empirical data, at different time ranges. RESULTS: (i) All summary measures for dose groups 0.1 and 0.5mug were higher than the control group (p<0.05). The AUC was higher for 0.1 than 15mug dose. (ii) There was strong evidence that the dose-response curve was peaked for all time ranges, and the best dose is likely to be lower than previous empirical experiments have evaluated. CONCLUSION: These results suggest that the highest, safe dose may not always optimal in terms of immunogenicity, as the dose-response curve may not saturate. Detailed longitudinal dose range data for TB vaccine H56+IC31 reveals response dynamics in mice that should now be used to identify optimal doses for humans using clinical data, using new data collection and mathematical modelling. AD - TB Modelling Group, CMMID, TB Centre, London School of Hygiene and Tropical Medicine, UK. Electronic address: sophie.rhodes@lshtm.ac.uk. Immunology and Infection Department, London School of Hygiene and Tropical Medicine, UK. TB Modelling Group, CMMID, TB Centre, London School of Hygiene and Tropical Medicine, UK; National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, Imperial College London, UK. TomegaVax, Portland, OR, United States. Statens Serum Institut, Copenhagen, Denmark. TB Modelling Group, CMMID, TB Centre, London School of Hygiene and Tropical Medicine, UK. AN - 27816373 AU - Rhodes, S. J. AU - Zelmer, A. AU - Knight, G. M. AU - Prabowo, S. A. AU - Stockdale, L. AU - Evans, T. G. AU - Lindenstrom, T. AU - White, R. G. AU - Fletcher, H. DA - Dec 07 DO - 10.1016/j.vaccine.2016.10.060 DP - NLM ET - 2016/11/07 IS - 50 J2 - Vaccine LA - eng N1 - 1873-2518 Rhodes, Sophie J Zelmer, Andrea Knight, Gwenan M Prabowo, Satria Arief Stockdale, Lisa Evans, Thomas G Lindenstrom, Thomas White, Richard G Fletcher, Helen Journal Article Netherlands Vaccine. 2016 Dec 7;34(50):6285-6291. doi: 10.1016/j.vaccine.2016.10.060. Epub 2016 Nov 2. PY - 2016 SN - 0264-410x SP - 6285-6291 ST - The TB vaccine H56+IC31 dose-response curve is peaked not saturating: Data generation for new mathematical modelling methods to inform vaccine dose decisions T2 - Vaccine TI - The TB vaccine H56+IC31 dose-response curve is peaked not saturating: Data generation for new mathematical modelling methods to inform vaccine dose decisions VL - 34 ID - 824 ER - TY - JOUR AB - The incidence of tuberculosis (TB) declined more than two-fold, compared with the national average, in the northeastern region of Poland in the period of 2003-2012. During that time, four programs of active case finding of TB were conducted as part of which a total of 944 homeless individuals were examined and 21 cases of active TB were detected. The objective of the present study was to find out whether the observed beneficial epidemiological trend could be a result of those programs. We addressed the issue of how the active case finding programs in the homeless community affected the TB incidence in the general population using a modified crisscross SIS-type (Susceptible - Infected - Susceptible) model which describes the dynamics of TB spread between the homeless and non-homeless populations. The values calculated from our model proved highly congruent with the actual epidemiological data. Our analysis showed a significant decline in TB incidence within 1 year of completion of each active case finding program. The model shows that each identified and cured case in the homeless community reduced the number of new cases in the general population by 3-4 within 1 year and by up to 20 within 5 years. AD - Family Medicine Unit, University of Warmia and Mazury in Olsztyn, 30 Warszawska St, 10-082, Olsztyn, Poland. jerzy.romaszko@uwm.edu.pl. Faculty of Mathematics and Computer Science, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland. Department of Biopharmacy, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland. Pulmonary Department, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland. AN - 26992399 AU - Romaszko, J. AU - Siemaszko, A. AU - Bodzioch, M. AU - Bucinski, A. AU - Doboszynska, A. DO - 10.1007/5584_2016_225 DP - NLM ET - 2016/03/20 J2 - Advances in experimental medicine and biology KW - *Epidemiology *Mathematical modeling *Poverty *Prophylaxis *Public health *Tuberculosis LA - eng N1 - Romaszko, J Siemaszko, A Bodzioch, M Bucinski, A Doboszynska, A Journal Article Research Support, Non-U.S. Gov't United States Adv Exp Med Biol. 2016;911:67-76. doi: 10.1007/5584_2016_225. PY - 2016 SN - 0065-2598 (Print) 0065-2598 SP - 67-76 ST - Active Case Finding Among Homeless People as a Means of Reducing the Incidence of Pulmonary Tuberculosis in General Population T2 - Adv Exp Med Biol TI - Active Case Finding Among Homeless People as a Means of Reducing the Incidence of Pulmonary Tuberculosis in General Population VL - 911 ID - 1031 ER - TY - JOUR AB - OBJECTIVES: The objective of this study was to estimate the cost-effectiveness of treating patients infected with HIV and simultaneously coinfected with tuberculosis (TB) and hepatitis C virus (HCV). METHODS: A mathematical model for HIV coinfection with TB and HCV is introduced. The model was designed to incorporate parameters of control for the coverage of care, which makes it useful for performing cost-effectiveness analysis of public policies. A cost-effectiveness analysis of early medical care of patients with TB and HCV coinfection, with coverage of 0 (basal), 25, 50, 75 and 100%, was performed for the whole cohort of patients and a special analysis was performed in a selected population with triple infection. RESULTS: The cost per resolved infection and the cost per year of life gained were found to be very cost-effective for the population with triple infection, for all different coverages. CONCLUSIONS: It is known that treating patients with HIV who are coinfected with TB or HCV implies high cost and low efficacy, but it is possible that the population with triple infections could achieve important benefits in terms of years of life gained. AD - Immunology Division, National Institute of Public Health, Cuernavaca, Mexico. AN - 27279355 AU - Sanchez-Gonzalez, G. DA - Oct DO - 10.1111/hiv.12372 DP - NLM ET - 2016/06/10 IS - 9 J2 - HIV medicine KW - Antitubercular Agents/administration & dosage/*economics Antiviral Agents/administration & dosage/*economics Cohort Studies Coinfection/*drug therapy *Cost-Benefit Analysis HIV Infections/complications/*drug therapy Hepatitis C, Chronic/complications/*drug therapy Humans Models, Theoretical Tuberculosis/complications/*drug therapy Hiv Hepatitis C Virus Tuberculosis LA - eng N1 - 1468-1293 Sanchez-Gonzalez, G Journal Article England HIV Med. 2016 Oct;17(9):674-82. doi: 10.1111/hiv.12372. Epub 2016 Jun 9. PY - 2016 SN - 1464-2662 SP - 674-82 ST - The cost-effectiveness of treating triple coinfection with HIV, tuberculosis and hepatitis C virus T2 - HIV Med TI - The cost-effectiveness of treating triple coinfection with HIV, tuberculosis and hepatitis C virus UR - http://onlinelibrary.wiley.com/doi/10.1111/hiv.12372/abstract VL - 17 ID - 951 ER - TY - JOUR AB - Mycobacterium tuberculosis associated granuloma formation can be viewed as a structural immune response that can contain and halt the spread of the pathogen. In several mammalian hosts, including non-human primates, Mtb granulomas are often hypoxic, although this has not been observed in wild type murine infection models. While a presumed consequence, the structural contribution of the granuloma to oxygen limitation and the concomitant impact on Mtb metabolic viability and persistence remains to be fully explored. We develop a multiscale computational model to test to what extent in vivo Mtb granulomas become hypoxic, and investigate the effects of hypoxia on host immune response efficacy and mycobacterial persistence. Our study integrates a physiological model of oxygen dynamics in the extracellular space of alveolar tissue, an agent-based model of cellular immune response, and a systems biology-based model of Mtb metabolic dynamics. Our theoretical studies suggest that the dynamics of granuloma organization mediates oxygen availability and illustrates the immunological contribution of this structural host response to infection outcome. Furthermore, our integrated model demonstrates the link between structural immune response and mechanistic drivers influencing Mtbs adaptation to its changing microenvironment and the qualitative infection outcome scenarios of clearance, containment, dissemination, and a newly observed theoretical outcome of transient containment. We observed hypoxic regions in the containment granuloma similar in size to granulomas found in mammalian in vivo models of Mtb infection. In the case of the containment outcome, our model uniquely demonstrates that immune response mediated hypoxic conditions help foster the shift down of bacteria through two stages of adaptation similar to the in vitro non-replicating persistence (NRP) observed in the Wayne model of Mtb dormancy. The adaptation in part contributes to the ability of Mtb to remain dormant for years after initial infection. AD - Department of Biomedical Engineering, University of Houston Houston, TX, USA. Center for Computing Research, Sandia National Laboratories Albuquerque, NM, USA. AN - 26913242 AU - Sershen, C. L. AU - Plimpton, S. J. AU - May, E. E. C2 - PMC4753379 DO - 10.3389/fcimb.2016.00006 DP - NLM ET - 2016/02/26 J2 - Frontiers in cellular and infection microbiology KW - Cell Hypoxia/immunology Computational Biology/*methods Granuloma/*immunology/microbiology/pathology Host-Pathogen Interactions/immunology Humans Models, Biological Mycobacterium tuberculosis/*immunology Oxygen/*metabolism Tuberculosis, Pulmonary/*immunology/microbiology/pathology Mycobacterium tuberculosis agent based model dormancy granuloma host-pathogen interactions lung diseases multiscale modeling systems biology LA - eng N1 - 2235-2988 Sershen, Cheryl L Plimpton, Steven J May, Elebeoba E K25 HL075105/HL/NHLBI NIH HHS/United States K25HL075105/HL/NHLBI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Switzerland Front Cell Infect Microbiol. 2016 Feb 15;6:6. doi: 10.3389/fcimb.2016.00006. eCollection 2016. PY - 2016 SN - 2235-2988 SP - 6 ST - Oxygen Modulates the Effectiveness of Granuloma Mediated Host Response to Mycobacterium tuberculosis: A Multiscale Computational Biology Approach T2 - Front Cell Infect Microbiol TI - Oxygen Modulates the Effectiveness of Granuloma Mediated Host Response to Mycobacterium tuberculosis: A Multiscale Computational Biology Approach VL - 6 ID - 1053 ER - TY - JOUR AB - Some of the most promising vaccines in the pipeline for tuberculosis (TB) target adolescents and adults. Unlike for childhood vaccines, high-coverage population-wide vaccination is significantly more challenging for adult vaccines. Here, we aimed to estimate the impact of vaccine delivery strategies that were targeted to high-incidence geographical 'hotspots' compared with randomly allocated vaccination. We developed a spatially explicit mathematical model of TB transmission that distinguished these hotspots from the general population. We evaluated the impact of targeted and untargeted vaccine delivery strategies in India--a country that bears more than 25% of global TB burden, and may be a potential early adopter of the vaccine. We collected TB notification data and conducted a demonstration study in the state of Gujarat to validate our estimates of heterogeneity in TB incidence. We then projected the impact of randomly vaccinating 8% of adults in a single mass campaign to a spatially targeted vaccination preferentially delivered to 80% of adults in the hotspots, with both strategies augmented by continuous adolescent vaccination. In consultation with vaccine developers, we considered a vaccine efficacy of 60%, and evaluated the population-level impact after 10 years of vaccination. Spatial heterogeneity in TB notification (per 100,000/year) was modest in Gujarat: 190 in the hotspots versus 125 in the remaining population. At this level of heterogeneity, the spatially targeted vaccination was projected to reduce TB incidence by 28% after 10 years, compared with a 24% reduction projected to achieve via untargeted vaccination--a 1.17-fold augmentation in the impact of vaccination by spatially targeting. The degree of the augmentation was robust to reasonable variation in natural history assumptions, but depended strongly on the extent of spatial heterogeneity and mixing between the hotspot and general population. Identifying high-incidence hotspots and quantifying spatial mixing patterns are critical to accurate estimation of the value of targeted intervention strategies. AD - Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD 21205, USA sourya@jhu.edu. Public Health Foundation of India, Delhi, India. Department of International Health, Johns Hopkins School of Public Health, Baltimore, MD 21205, USA. Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD 21205, USA. AN - 27009179 AU - Shrestha, S. AU - Chatterjee, S. AU - Rao, K. D. AU - Dowdy, D. W. C2 - PMC4843669 DA - Mar DO - 10.1098/rsif.2015.1016 DP - NLM ET - 2016/03/25 IS - 116 J2 - Journal of the Royal Society, Interface KW - Adolescent Adult Aged Aged, 80 and over Female Humans India Male Middle Aged *Tuberculosis/epidemiology/prevention & control/transmission Tuberculosis Vaccines/*administration & dosage *Vaccination mathematical model spatially targeted tuberculosis vaccine tuberculosis tuberculosis in India LA - eng N1 - 1742-5662 Shrestha, Sourya ORCID: http://orcid.org/0000-0002-6106-6834 Chatterjee, Susmita Rao, Krishna D Dowdy, David W Comparative Study Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't England J R Soc Interface. 2016 Mar;13(116). pii: 20151016. doi: 10.1098/rsif.2015.1016. PY - 2016 SN - 1742-5662 ST - Potential impact of spatially targeted adult tuberculosis vaccine in Gujarat, India T2 - J R Soc Interface TI - Potential impact of spatially targeted adult tuberculosis vaccine in Gujarat, India VL - 13 ID - 1024 ER - TY - JOUR AB - BACKGROUND: In HIV-uninfected individuals, isoniazid preventive therapy (IPT) has been associated with long-term protection against tuberculosis (TB). For HIV-infected/antiretroviral therapy (ART)-naive individuals, high TB rates have been observed following completion of IPT, consistent with a lack of 'cure' of infection. Recent trial data of IPT among HIV-infected individuals on ART in Khayelitsha, South Africa, have suggested that the effect of IPT persisted following completion of IPT. METHODS: Using mathematical modelling, we explored if this increased duration of protection may be due to an increased curative ability of IPT when given in combination with ART. The model was used to estimate the annual risk of infection and proportion of individuals whose latent infection was 'cured' by IPT, defined such that they must be reinfected to be at risk of disease. RESULTS: The estimated annual risk of infection was 4.0% (2.6-5.8) and the estimated proportion of individuals whose latent Mycobacterium tuberculosis infection was cured following IPT was 35.4% (2.4-76.4), higher than that previously estimated for HIV-infected/ART-naive individuals. Our results suggest that IPT can cure latent M. tuberculosis infection in approximately one-third of HIV-infected individuals on ART and therefore provide protection beyond the period of treatment. CONCLUSION: Among HIV-infected individuals on ART in low incidence settings, 12 months of IPT may provide additional long-term benefit. Among HIV-infected individuals on ART in high incidence settings, the durability of this protection will be limited because of continued risk of reinfection, and continuous preventive therapy together with improved infection control efforts will be required to provide long-term protection against TB. AD - aDepartment of Infectious Disease Epidemiology, TB Modelling Group, TB Centre, Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine bDepartment of Infection and Population Health, Centre for Infectious Disease Epidemiology, University College London, London, UK cDepartment of Medicine, Institute of Infectious Disease and Molecular Medicine, University of Cape Town dDivision of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa eTuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA fCentre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa gDepartment of Medicine, Imperial College London hThe Francis Crick Institute Mill Hill Laboratory, London, UK iInstitute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa. AN - 26950316 AU - Sumner, T. AU - Houben, R. M. AU - Rangaka, M. X. AU - Maartens, G. AU - Boulle, A. AU - Wilkinson, R. J. AU - White, R. G. DA - May 15 DO - 10.1097/qad.0000000000001078 DP - NLM ET - 2016/03/08 IS - 8 J2 - AIDS (London, England) LA - eng N1 - 1473-5571 Sumner, Tom Houben, Rein M G J Rangaka, Molebogeng X Maartens, Gary Boulle, Andrew Wilkinson, Robert J White, Richard G Journal Article England AIDS. 2016 May 15;30(8):1279-86. doi: 10.1097/QAD.0000000000001078. PY - 2016 SN - 0269-9370 SP - 1279-86 ST - Post-treatment effect of isoniazid preventive therapy on tuberculosis incidence in HIV-infected individuals on antiretroviral therapy T2 - Aids TI - Post-treatment effect of isoniazid preventive therapy on tuberculosis incidence in HIV-infected individuals on antiretroviral therapy VL - 30 ID - 1044 ER - TY - JOUR AB - In this paper, we presented a novel multi-strain TB model of variable-order fractional derivatives, which incorporates three strains: drug-sensitive, emerging multi-drug resistant (MDR) and extensively drug-resistant (XDR), as an extension for multi-strain TB model of nonlinear ordinary differential equations which developed in 2014 by Arino and Soliman [1]. Numerical simulations for this variable-order fractional model are the main aim of this work, where the variable-order fractional derivative is defined in the sense of Grunwald-Letnikov definition. Two numerical methods are presented for this model, the standard finite difference method (SFDM) and nonstandard finite difference method (NSFDM). Numerical comparison between SFDM and NSFDM is presented. It is concluded that, NSFDM preserves the positivity of the solutions and numerically stable in large regions than SFDM. AD - Department of Mathematics, Faculty of Science, Cairo University, Giza 12613, Egypt. Department of Mathematics, Faculty of Education, Sana'a University, Sana'a, Yemen. AN - 26966568 AU - Sweilam, N. H. AU - Al-Mekhlafi, S. M. C2 - PMC4767813 DA - Mar DO - 10.1016/j.jare.2015.06.004 DP - NLM ET - 2016/03/12 IS - 2 J2 - Journal of advanced research KW - Epidemic model Grunwald-Letnikov definition M/xdr-tb Nonstandard finite difference Tuberculosis Variable-order fractional L1 - internal-pdf://0605036004/Sweilam-2016-Numerical study for multi-strain.pdf internal-pdf://0616907574/Sweilam-2016-Numerical study for multi-strain1.pdf LA - eng N1 - Sweilam, Nasser H Al-Mekhlafi, Seham M Journal Article Egypt J Adv Res. 2016 Mar;7(2):271-83. doi: 10.1016/j.jare.2015.06.004. Epub 2015 Jun 27. PY - 2016 SN - 2090-1232 (Print) 2090-1224 SP - 271-83 ST - Numerical study for multi-strain tuberculosis (TB) model of variable-order fractional derivatives T2 - J Adv Res TI - Numerical study for multi-strain tuberculosis (TB) model of variable-order fractional derivatives UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767813/pdf/main.pdf VL - 7 ID - 1040 ER - TY - JOUR AB - In this paper, optimal control of a general nonlinear multi-strain tuberculosis (TB) model that incorporates three strains drug-sensitive, emerging multi-drug resistant and extensively drug-resistant is presented. The general multi-strain TB model is introduced as a fractional order multi-strain TB model. The fractional derivatives are described in the Caputo sense. An optimal control problem is formulated and studied theoretically using the Pontryagin maximum principle. Four controls variables are proposed to minimize the cost of interventions. Two simple-numerical methods are used to study the nonlinear fractional optimal control problem. The methods are the iterative optimal control method and the generalized Euler method. Comparative studies are implemented, and it is found that the iterative optimal control method is better than the generalized Euler method. Copyright (c) 2016 John Wiley & Sons, Ltd. AD - [Sweilam, N. H.] Cairo Univ, Dept Math, Fac Sci, Giza, Egypt. [AL-Mekhlafi, S. M.] Sanaa Univ, Dept Math, Fac Educ, Sanaa, Yemen. Sweilam, NH (reprint author), Cairo Univ, Dept Math, Fac Sci, Giza, Egypt. nsweilam@sci.cu.edu.eg AN - WOS:000387322700014 AU - Sweilam, N. H. AU - Al-Mekhlafi, S. M. DA - Dec DO - 10.1002/oca.2247 IS - 6 J2 - Optim. Control Appl. Methods KW - tuberculosis M XDR-TB pontryagin maximum principle caputo fractional derivatives fractional optimal control generalized Euler method Grunwald-Letnikovs definition tuberculosis derivatives chaos Automation & Control Systems Operations Research & Management Science Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: EB4EM Times Cited: 2 Cited Reference Count: 28 Sweilam, N. H. AL-Mekhlafi, S. M. 2 0 3 Wiley Hoboken 1099-1514 PY - 2016 SN - 0143-2087 SP - 1355-1374 ST - On the optimal control for fractional multi-strain TB model T2 - Optimal Control Applications & Methods TI - On the optimal control for fractional multi-strain TB model UR - ://WOS:000387322700014 http://onlinelibrary.wiley.com/doi/10.1002/oca.2247/abstract?systemMessage=Wiley+Online+Library+usage+report+download+page+will+be+unavailable+on+Friday+24th+November+2017+at+21%3A00+EST+%2F+02.00+GMT+%2F+10%3A00+SGT+%28Saturday+25th+Nov+for+SGT+ VL - 37 ID - 5078 ER - TY - JOUR AB - BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a major threat to global TB control. MDR-TB treatment regimens typically have a high pill burden, last 20 months or more and often lead to unsatisfactory outcomes. A 9-11 month regimen with seven antibiotics has shown high success rates among selected MDR-TB patients in different settings and is conditionally recommended by the World Health Organization. METHODS: We construct a transmission-dynamic model of TB to estimate the likely impact of a shorter MDR-TB regimen when applied in a low HIV prevalence region of Uzbekistan (Karakalpakstan) with high rates of drug resistance, good access to diagnostics and a well-established community-based MDR-TB treatment programme providing treatment to around 400 patients. The model incorporates acquisition of additional drug resistance and incorrect regimen assignment. It is calibrated to local epidemiology and used to compare the impact of shorter treatment against four alternative programmatic interventions. RESULTS: Based on empirical outcomes among MDR-TB patients and assuming no improvement in treatment success rates, the shorter regimen reduced MDR-TB incidence from 15.2 to 9.7 cases per 100,000 population per year and MDR-TB mortality from 3.0 to 1.7 deaths per 100,000 per year, achieving comparable or greater gains than the alternative interventions. No significant increase in the burden of higher levels of resistance was predicted. Effects are probably conservative given that the regimen is likely to improve success rates. CONCLUSIONS: In addition to benefits to individual patients, we find that shorter MDR-TB treatment regimens also have the potential to reduce transmission of resistant strains. These findings are in the epidemiological setting of treatment availability being an important bottleneck due to high numbers of patients being eligible for treatment, and may differ in other contexts. The high proportion of MDR-TB with additional antibiotic resistance simulated was not exacerbated by programmatic responses and greater gains may be possible in contexts where the regimen is more widely applicable. AD - School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. james.trauer@monash.edu. The Victorian Tuberculosis Program at the Peter Doherty Institute, Melbourne, Australia. james.trauer@monash.edu. Medecins sans Frontieres, Manson Unit, London, UK. National TB Institute, Ministry of Health, Tashkent, Uzbekistan. Ministry of Health, Nukus, Uzbekistan. The Victorian Tuberculosis Program at the Peter Doherty Institute, Melbourne, Australia. Global TB Programme, World Health Organization, Geneva, Switzerland. Medecins sans Frontieres Holland, Amsterdam, The Netherlands. James Cook University, Queensland, Australia. AN - 27855693 AU - Trauer, J. M. AU - Achar, J. AU - Parpieva, N. AU - Khamraev, A. AU - Denholm, J. T. AU - Falzon, D. AU - Jaramillo, E. AU - Mesic, A. AU - du Cros, P. AU - McBryde, E. S. C2 - PMC5114735 DA - Nov 18 DO - 10.1186/s12916-016-0723-2 DP - NLM ET - 2016/11/20 IS - 1 J2 - BMC medicine KW - Antitubercular Agents/*administration & dosage Directly Observed Therapy Drug Administration Schedule Drug Therapy, Combination Humans Prevalence Treatment Outcome Tuberculosis, Multidrug-Resistant/*drug therapy/*epidemiology/transmission Uzbekistan/epidemiology World Health Organization *Epidemiology *Extensively drug-resistant tuberculosis *Modelling *Multidrug-resistant tuberculosis *Public health *Treatment *Tuberculosis *Uzbekistan L1 - internal-pdf://1289778998/Trauer-2016-Modelling the effect of short-cour.pdf LA - eng N1 - 1741-7015 Trauer, James M Achar, Jay Parpieva, Nargiza Khamraev, Atadjan Denholm, Justin T Falzon, Dennis Jaramillo, Ernesto Mesic, Anita du Cros, Philipp McBryde, Emma S Journal Article Observational Study England BMC Med. 2016 Nov 18;14(1):187. PY - 2016 SN - 1741-7015 SP - 187 ST - Modelling the effect of short-course multidrug-resistant tuberculosis treatment in Karakalpakstan, Uzbekistan T2 - BMC Med TI - Modelling the effect of short-course multidrug-resistant tuberculosis treatment in Karakalpakstan, Uzbekistan UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114735/pdf/12916_2016_Article_723.pdf VL - 14 ID - 818 ER - TY - JOUR AB - Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) are major health problems in Western Province, Papua New Guinea. While comprehensive expansion of TB control programs is desirable, logistical challenges are considerable, and there is substantial uncertainty regarding the true disease burden. We parameterized our previously described mathematical model of Mycobacterium tuberculosis dynamics in Western Province, following an epidemiologic assessment. Five hypothetical scenarios representing alternative programmatic approaches during the period from 2013 to 2023 were developed with local staff. Bayesian uncertainty analyses were undertaken to explicitly acknowledge the uncertainty around key epidemiologic parameters, and an economic evaluation was performed. With continuation of existing programmatic strategies, overall TB incidence remained stable at 555 cases per 100,000 population per year (95% simulation interval (SI): 420, 807), but the proportion of incident cases attributable to MDR-TB increased from 16% to 35%. Comprehensive, provincewide strengthening of existing programs reduced incidence to 353 cases per 100,000 population per year (95% SI: 246, 558), with 46% being cases of MDR-TB, while incorporating programmatic management of MDR-TB into these programs reduced incidence to 233 cases per 100,000 population per year (95% SI: 198, 269) with 14% MDR-TB. Most economic costs were due to hospitalization during the intensive treatment phase. Broad scale-up of TB control activities in Western Province with incorporation of programmatic management of MDR-TB is vital if control is to be achieved. Community-based treatment approaches are important to reduce the associated economic costs. AN - 27199387 AU - Trauer, J. M. AU - Denholm, J. T. AU - Waseem, S. AU - Ragonnet, R. AU - McBryde, E. S. DA - Jun 15 DO - 10.1093/aje/kwv323 DP - NLM ET - 2016/05/21 IS - 12 J2 - American journal of epidemiology KW - Antitubercular Agents/economics/therapeutic use Bayes Theorem Communicable Disease Control/*statistics & numerical data Directly Observed Therapy/economics/statistics & numerical data Hospitalization/economics/statistics & numerical data Humans Models, Theoretical *Mycobacterium tuberculosis Papua New Guinea/epidemiology Tuberculosis/*economics/*epidemiology/therapy Tuberculosis, Multidrug-Resistant/economics/epidemiology/therapy Bayesian probability Papua New Guinea models, biological tuberculosis tuberculosis, multidrug-resistant L1 - internal-pdf://4214653412/Trauer-2016-Scenario Analysis for Programmatic.pdf LA - eng N1 - 1476-6256 Trauer, James M Denholm, Justin T Waseem, Saba Ragonnet, Romain McBryde, Emma S Journal Article United States Am J Epidemiol. 2016 Jun 15;183(12):1138-48. doi: 10.1093/aje/kwv323. Epub 2016 May 19. PY - 2016 SN - 0002-9262 SP - 1138-48 ST - Scenario Analysis for Programmatic Tuberculosis Control in Western Province, Papua New Guinea T2 - Am J Epidemiol TI - Scenario Analysis for Programmatic Tuberculosis Control in Western Province, Papua New Guinea UR - https://watermark.silverchair.com/kwv323.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAdIwggHOBgkqhkiG9w0BBwagggG_MIIBuwIBADCCAbQGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM3bbc2ChXYZVW8zHGAgEQgIIBhcyPuXcg2x76XXSa0mpO0H5EJktG7rusbZ1yfuVa9BN_9hS4d_9BWMKOqEYzrGkRmWDfC8CCaoMR9Pr31up8uQfyEI12J52kb5kR8k_63-ziI-pjka9bxI7lGQF1VbgKbqAXjGpS50HYKnB8b3mS463pGRsRvI8iC0aaJLH5UKoQK3C8WvLwMGerI52yPiXCQeX4UWkvrkRaFOk-MSdIhw73PYHAsbQmnkVjzneNzNxPdyV9aK2N9zb5ZjihZ-Z8m70nAps3Ie1IJDhyIOORYDJDm48ue3nEVBrB_DSJofXQxZhOrkFZJ9mNdZAoTosr32euVoidKgbmJB1XyaRVoxzSlgIhHymxmmhmwMPU834mWFUhxykLp-d8y3lbQ4pRInR5bQAWZJpejc-g2__pProg0oG2mnGcNdybTAbOQGiE2gcHsdZ2oOvN7ocN3LzNZ7lrEjGfu9Tv6kAn_FDp3M6SDdjjk6F2CVZV1I0TZVb0tHzpLGe2aJpSQ4D1c5pw6jXDdgcU VL - 183 ID - 967 ER - TY - JOUR AB - BACKGROUND: The aim of this study was to compare the cost effectiveness of the current Irish programme of universal BCG vaccination of infants versus a programme which considered selectively vaccinating high risk infants using decision analytical modelling. METHODS: The efficacy of the BCG vaccine was re-evaluated to inform a decision analytical model constructed to follow a birth cohort of vaccinated and unvaccinated infants over a 15 year time horizon. The number of life years gained (LYG) was the primary outcome measure and this was compared to the net cost of the vaccination strategies. RESULTS: In the base case analysis, the incremental cost effectiveness ratios (ICERs) for the universal strategy and selective strategy vs no vaccination were euro204,373/LYG and euro143,233/LYG respectively. When comparing the incremental difference in moving from the universal to the selective strategy, the selective strategy costs euro1,055,692 less per 4.8 life years lost per birth cohort. One way sensitivity analyses highlighted that a move from the universal to the selective strategy was particularly sensitive to the estimate of vaccine efficacy against deaths, the cost of administering the vaccine and the multiplier used to apportion risk of contracting tuberculosis. Probabilistic analysis suggested that a move from a universal based strategy to a selective based strategy could be deemed cost effective (probability of cost effectiveness is 76.8 %). CONCLUSION: The results of the study support the protective effect of the BCG vaccine in infants and quantified the cost effectiveness of the current BCG vaccination strategy and the decremental difference in moving to a selective strategy. This analysis highlights that the additional protection offered by the universal vaccination strategy is small compared to that of the selective strategy. Consideration should therefore be given to the implementation of a selective vaccination strategy, and diverting resources to improve TB case management and control. AD - National Centre for Pharmacoeconomics, St. James's Hospital, Dublin 8, Ireland. National Centre for Pharmacoeconomics, St. James's Hospital, Dublin 8, Ireland ; Department of Pharmacology & Therapeutics, Trinity Centre, St. James's Hospital, Dublin 8, Ireland. Health Protection Surveillance Centre, Dublin 1, Ireland ; National Immunisation Advisory Committee, Dublin 2, Ireland. National Immunisation Advisory Committee, Dublin 2, Ireland ; National Immunisation Office, Dublin 7, Ireland. National Immunisation Advisory Committee, Dublin 2, Ireland ; Department of Infectious Diseases, Our Lady's Childrens Hospital, Crumlin, Dublin 12, Ireland. National Centre for Pharmacoeconomics, St. James's Hospital, Dublin 8, Ireland ; Department of Maths & Statistics, Centre for Health Decision Sciences (CHeDS), University of Limerick, Limerick, Ireland. AN - 27413531 AU - Usher, C. AU - Adams, R. AU - Schmitz, S. AU - Kieran, J. AU - O'Flanagan, D. AU - O'Donnell, J. AU - Connolly, K. AU - Corcoran, B. AU - Butler, K. AU - Barry, M. AU - Walsh, C. C2 - PMC4942954 DO - 10.1186/s13690-016-0141-0 DP - NLM ET - 2016/07/15 J2 - Archives of public health = Archives belges de sante publique KW - BCG vaccine Cost effectiveness Neonatal vaccination Paediatric tuberculosis Vaccine efficacy L1 - internal-pdf://3427238334/Usher-2016-Evaluating the neonatal BCG vaccina.pdf LA - eng N1 - Usher, Cara Adams, Roisin Schmitz, Susanne Kieran, Jennifer O'Flanagan, Darina O'Donnell, Joan Connolly, Kevin Corcoran, Brenda Butler, Karina Barry, Michael Walsh, Cathal Journal Article England Arch Public Health. 2016 Jul 13;74:28. doi: 10.1186/s13690-016-0141-0. eCollection 2016. PY - 2016 SN - 0778-7367 (Print) 0778-7367 SP - 28 ST - Evaluating the neonatal BCG vaccination programme in Ireland T2 - Arch Public Health TI - Evaluating the neonatal BCG vaccination programme in Ireland UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942954/pdf/13690_2016_Article_141.pdf VL - 74 ID - 919 ER - TY - JOUR AB - BACKGROUND: Out-of-pocket (OOP) medical expenses often lead to catastrophic expenditure and impoverishment in low- and middle-income countries. Yet, there has been no systematic examination of which specific diseases and conditions (e.g., tuberculosis, cardiovascular disease) drive medical impoverishment, defined as OOP direct medical costs pushing households into poverty. METHODS: We used a cost and epidemiological model to propose an assessment of the burden of medical impoverishment in Ethiopia, i.e., the number of households crossing a poverty line due to excessive OOP direct medical expenses. We utilized disease-specific mortality estimates from the Global Burden of Disease study, epidemiological and cost inputs from surveys, and secondary data from the literature to produce a count of poverty cases due to OOP direct medical costs per specific condition. RESULTS: In Ethiopia, in 2013, and among 20 leading causes of mortality, we estimated the burden of impoverishment due to OOP direct medical costs to be of about 350,000 poverty cases. The top three causes of medical impoverishment were diarrhea, lower respiratory infections, and road injury, accounting for 75 % of all poverty cases. CONCLUSIONS: We present a preliminary attempt for the estimation of the burden of medical impoverishment by cause for high mortality conditions. In Ethiopia, medical impoverishment was notably associated with illness occurrence and health services utilization. Although currently used estimates are sensitive to health services utilization, a systematic breakdown of impoverishment due to OOP direct medical costs by cause can provide important information for the promotion of financial risk protection and equity, and subsequent design of health policies toward universal health coverage, reduction of direct OOP payments, and poverty alleviation. AD - Department of Global Health and Population, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA. verguet@hsph.harvard.edu. Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway. Department of Global Health and Population, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA. AN - 27769296 AU - Verguet, S. AU - Memirie, S. T. AU - Norheim, O. F. C2 - PMC5075208 DA - Oct 21 DO - 10.1186/s12916-016-0697-0 IS - 1 KW - Accidents, Traffic/mortality/statistics & numerical data Diarrhea/economics/epidemiology/mortality Ethiopia/epidemiology Financing, Personal/economics Health Expenditures/*statistics & numerical data Health Policy/*economics Humans Models, Economic Poverty/*statistics & numerical data Respiratory Tract Infections/economics/epidemiology/mortality Catastrophic health expenditure Direct medical payments Ethiopia Financial risk protection Medical impoverishment Out-of-pocket costs Poverty N1 - Verguet, Stephane Memirie, Solomon Tessema Norheim, Ole Frithjof eng England 2016/10/23 06:00 BMC Med. 2016 Oct 21;14(1):164. PY - 2016 SN - 1741-7015 (Electronic) 1741-7015 (Linking) SP - 164 ST - Assessing the burden of medical impoverishment by cause: a systematic breakdown by disease in Ethiopia T2 - BMC Med TI - Assessing the burden of medical impoverishment by cause: a systematic breakdown by disease in Ethiopia UR - https://www.ncbi.nlm.nih.gov/pubmed/27769296 VL - 14 ID - 2243 ER - TY - JOUR AB - The natural history of human infection with Mycobacterium tuberculosis (Mtb) is highly variable, as is the response to treatment of active tuberculosis. There is presently no direct means to identify individuals in whom Mtb infection has been eradicated, whether by a bactericidal immune response or sterilizing antimicrobial chemotherapy. Mathematical models can assist in such circumstances by measuring or predicting events that cannot be directly observed. The 3 models discussed in this review illustrate instances in which mathematical models were used to identify individuals with innate resistance to Mtb infection, determine the etiologic mechanism of tuberculosis in patients treated with tumor necrosis factor blockers, and predict the risk of relapse in persons undergoing tuberculosis treatment. These examples illustrate the power of various types of mathematic models to increase knowledge and thereby inform interventions in the present global tuberculosis epidemic. AD - The Aurum Institute Johannesburg, South Africa. AN - 27242697 AU - Wallis, R. S. C2 - PMC4869524 DO - 10.3389/fmicb.2016.00669 DP - NLM ET - 2016/06/01 J2 - Frontiers in microbiology KW - mathematical model reactivation relapse tuberculosis L1 - internal-pdf://0379842972/Wallis-2016-Mathematical Models of Tuberculosi.pdf LA - eng N1 - Wallis, Robert S Journal Article Switzerland Front Microbiol. 2016 May 17;7:669. doi: 10.3389/fmicb.2016.00669. eCollection 2016. PY - 2016 SN - 1664-302X (Print) 1664-302x SP - 669 ST - Mathematical Models of Tuberculosis Reactivation and Relapse T2 - Front Microbiol TI - Mathematical Models of Tuberculosis Reactivation and Relapse UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869524/pdf/fmicb-07-00669.pdf VL - 7 ID - 955 ER - TY - JOUR AB - Tuberculosis control and elimination remains a challenge for public health even in low-burden countries. New technology and novel approaches to case-finding, diagnosis, and treatment are causes for optimism but they need to be used cost-effectively. This in turn requires improved understanding of the epidemiology of TB and analysis of the effectiveness and cost-effectiveness of different interventions. We describe the contribution that mathematical modeling can make to understanding epidemiology and control of TB in different groups, guiding improved approaches to public health interventions. We emphasize that modeling is not a substitute for collecting data but rather is complementary to empirical research, helping determine what are the key questions to address to maximize the public-health impact of research, helping to plan studies, and making maximal use of available data, particularly from surveillance, and observational studies. We provide examples of how modeling and related empirical research inform policy and discuss how a combination of these approaches can be used to address current questions of key importance, including use of whole-genome sequencing, screening and treatment for latent infection, and combating drug resistance. AD - MRC Centre for Outbreak Analysis and Modelling and NIHR Health Protection Research Unit in Modelling Methodology, Imperial College London School of Public HealthLondon, UK; Modelling and Economics Unit, Centre for Infectious Disease Surveillance and Control, Public Health EnglandLondon, UK. TB Section, Respiratory Diseases Department, Centre for Infectious Disease Surveillance and Control, Public Health EnglandLondon, UK; Research Department of Infection and Population Health, University College LondonLondon, UK; MRC Clinical Trials Unit, University College LondonLondon, UK. AN - 27199896 AU - White, P. J. AU - Abubakar, I. C2 - PMC4853635 DO - 10.3389/fmicb.2016.00394 DP - NLM ET - 2016/05/21 J2 - Frontiers in microbiology KW - Mdr-tb cost-effectiveness health economics health systems latent TB infection migrants screening transmission L1 - internal-pdf://0582023995/White-2016-Improving Control of Tuberculosis i.pdf LA - eng N1 - White, Peter J Abubakar, Ibrahim MR/K010174/1/Medical Research Council/United Kingdom Journal Article Switzerland Front Microbiol. 2016 May 3;7:394. doi: 10.3389/fmicb.2016.00394. eCollection 2016. PY - 2016 SN - 1664-302X (Print) 1664-302x SP - 394 ST - Improving Control of Tuberculosis in Low-Burden Countries: Insights from Mathematical Modeling T2 - Front Microbiol TI - Improving Control of Tuberculosis in Low-Burden Countries: Insights from Mathematical Modeling UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4853635/pdf/fmicb-07-00394.pdf VL - 7 ID - 966 ER - TY - JOUR AB - The statistical data of monthly pulmonary tuberculosis (TB) incidence cases from January 2004 to December 2012 show the seasonality fluctuations in Shaanxi of China. A seasonality TB epidemic model with periodic varying contact rate, reactivation rate, and disease-induced death rate is proposed to explore the impact of seasonality on the transmission dynamics of TB. Simulations show that the basic reproduction number of time-averaged autonomous systems may underestimate or overestimate infection risks in some cases, which may be up to the value of period. The basic reproduction number of the seasonality model is appropriately given, which determines the extinction and uniform persistence of TB disease. If it is less than one, then the disease-free equilibrium is globally asymptotically stable; if it is greater than one, the system at least has a positive periodic solution and the disease will persist. Moreover, numerical simulations demonstrate these theorem results. AD - Science College, Air Force Engineering University, Xi'an, Shaanxi 710051, China; College of Mathematics and Information Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China; Centre for Disease Modelling, York University, Toronto, ON, Canada M3J 1P3. Science College, Air Force Engineering University, Xi'an, Shaanxi 710051, China. School of Mathematics and Statistics, Henan University of Science and Technology, Luoyang 471023, China. Institute of Tuberculosis Prevention and Treatment in Shaanxi, Xi'an, Shaanxi 710048, China. AN - 27042199 AU - Yang, Y. AU - Guo, C. AU - Liu, L. AU - Zhang, T. AU - Liu, W. C2 - PMC4793104 DO - 10.1155/2016/8713924 DP - NLM ET - 2016/04/05 J2 - Computational and mathematical methods in medicine KW - Algorithms *Basic Reproduction Number China Communicable Diseases/epidemiology Computer Simulation Epidemics Humans Incidence Models, Theoretical Mycobacterium tuberculosis *Seasons Software Time Factors Tuberculosis, Pulmonary/*epidemiology/*transmission LA - eng N1 - 1748-6718 Yang, Yali Orcid: 0000-0002-7944-3618 Guo, Chenping Orcid: 0000-0001-8713-9475 Liu, Luju Orcid: 0000-0003-4585-6999 Zhang, Tianhua Orcid: 0000-0002-6180-0381 Liu, Weiping Orcid: 0000-0002-5105-5031 Journal Article Research Support, Non-U.S. Gov't United States Comput Math Methods Med. 2016;2016:8713924. doi: 10.1155/2016/8713924. Epub 2016 Mar 2. PY - 2016 SN - 1748-670x SP - 8713924 ST - Seasonality Impact on the Transmission Dynamics of Tuberculosis T2 - Comput Math Methods Med TI - Seasonality Impact on the Transmission Dynamics of Tuberculosis VL - 2016 ID - 1011 ER - TY - JOUR AB - We formulate a mathematical model to explore the impact of vaccination and treatment on the transmission dynamics of tuberculosis (TB). We develop a technique to prove that the basic reproduction number is the threshold of global stability of the disease-free and endemic equilibria. We then incorporate a control term and evaluate the cost of control strategies, and then perform an optimal control analysis by Pontryagin's maximum principle. Our numerical simulations suggest that the maximum vaccination strategy should be enforced regardless of its efficacy. AD - Shaanxi Normal Univ, Coll Math & Informat Sci, Xian 710062, Peoples R China Air Force Engn Univ, Coll Sci, Xian 710051, Peoples R China York Univ, Ctr Dis Modelling, Toronto, ON M3J 1P3, Canada AN - WOS:000373424900016 AU - Yang, Y. L. AU - Tang, S. Y. AU - Ren, X. H. AU - Zhao, H. W. AU - Guo, C. P. DA - May DO - 10.3934/dcdsb.2016.21.1009 IS - 3 J2 - Discrete Cont Dyn-B KW - tuberculosis vaccination treatment basic reproduction number global stability pontryagin's maximum principle sensitivity-analysis transmission strategies epidemics LA - English N1 - Di3uv Times Cited:3 Cited References Count:21 PY - 2016 SN - 1531-3492 SP - 1009-1022 ST - Global Stability and Optimal Control for a Tuberculosis Model with Vaccination and Treatment T2 - Discrete and Continuous Dynamical Systems-Series B TI - Global Stability and Optimal Control for a Tuberculosis Model with Vaccination and Treatment UR - ://WOS:000373424900016 VL - 21 ID - 2190 ER - TY - JOUR AB - Unacceptable levels of Mycobacterium tuberculosis transmission are noted in high burden settings and a renewed focus on reducing person-to-person transmission in these communities is needed. We review recent developments in the understanding of airborne transmission. We outline approaches to measure transmission in populations and trials and describe the Wells-Riley equation, which is used to estimate transmission risk in indoor spaces. Present research priorities include the identification of effective strategies for tuberculosis infection control, improved understanding of where transmission occurs and the transmissibility of drug-resistant strains, and estimates of the effect of HIV and antiretroviral therapy on transmission dynamics. When research is planned and interventions are designed to interrupt transmission, resource constraints that are common in high burden settings-including shortages of health-care workers-must be considered. AD - Centre for Infectious Disease Epidemiology, Research Department of Infection and Population Health, University College London, London, UK; Wellcome Trust Africa Centre for Population Health, Mtubatuba, South Africa, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: t.yates@ucl.ac.uk. Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK; Tuberculosis Centre, London School of Hygiene & Tropical Medicine, London, UK; Karonga Prevention Study, Chilumba, Malawi. Tuberculosis Centre, London School of Hygiene & Tropical Medicine, London, UK; Tuberculosis Modelling Group, London School of Hygiene & Tropical Medicine, London, UK; National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, Imperial College London, London, UK. UCL Institute for Environmental Design and Engineering, Bartlett School of Environment, Energy and Resources, University College London, London, UK. Centre for Clinical Microbiology, University College London, London, UK. Division of Medicine, University College London, London, UK. Tuberculosis Centre, London School of Hygiene & Tropical Medicine, London, UK; Tuberculosis Modelling Group, London School of Hygiene & Tropical Medicine, London, UK. Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA. Department of Global Health, Academic Medical Center, Amsterdam, Netherlands; KNCV Tuberculosis Foundation, The Hague, Netherlands. Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK; Tuberculosis Centre, London School of Hygiene & Tropical Medicine, London, UK; The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. Tuberculosis Centre, London School of Hygiene & Tropical Medicine, London, UK; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK. Centre for Infectious Disease Epidemiology, Research Department of Infection and Population Health, University College London, London, UK; MRC Clinical Trials Unit at University College London, University College London, London, UK. AN - 26867464 AU - Yates, T. A. AU - Khan, P. Y. AU - Knight, G. M. AU - Taylor, J. G. AU - McHugh, T. D. AU - Lipman, M. AU - White, R. G. AU - Cohen, T. AU - Cobelens, F. G. AU - Wood, R. AU - Moore, D. A. AU - Abubakar, I. DA - Feb DO - 10.1016/s1473-3099(15)00499-5 DP - NLM ET - 2016/02/13 IS - 2 J2 - The Lancet. Infectious diseases KW - Air Microbiology Communicable Disease Control/*methods Cross Infection/*prevention & control Disease Transmission, Infectious Health Personnel Humans Mycobacterium tuberculosis Tuberculosis/*transmission LA - eng N1 - 1474-4457 Yates, Tom A Khan, Palwasha Y Knight, Gwenan M Taylor, Jonathon G McHugh, Timothy D Lipman, Marc White, Richard G Cohen, Ted Cobelens, Frank G Wood, Robin Moore, David A J Abubakar, Ibrahim MR/J005088/1/Medical Research Council/United Kingdom SRF-2011-04-001/Department of Health/United Kingdom Journal Article Research Support, Non-U.S. Gov't Review United States Lancet Infect Dis. 2016 Feb;16(2):227-38. doi: 10.1016/S1473-3099(15)00499-5. Epub 2016 Jan 26. PY - 2016 SN - 1473-3099 SP - 227-38 ST - The transmission of Mycobacterium tuberculosis in high burden settings T2 - Lancet Infect Dis TI - The transmission of Mycobacterium tuberculosis in high burden settings VL - 16 ID - 1070 ER - TY - JOUR AB - User-friendly models (UFMs) allow local decision makers to explore relationships and apply results from more detailed models of such outcomes as cost-effectiveness. When developing UFMs, modelers must decide which simplifications may be appropriate, enabling the UFM to retain accuracy while reducing complexity. We use the example of cost-effectiveness analysis (CEA) for novel shortened anti-tuberculosis treatment regimens across four settings to demonstrate how UFMs can allow decision makers to adapt published results to their local context. We simplified a complex model to produce a UFM that provides similar results, the ability to modify key parameter values, and receive customized results in seconds. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. Amsterdam Institute for Global Health and Development and Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Global Health and Development, London School of Hygiene & Tropical Medicine, London, UK. Amsterdam Institute for Global Health and Development and Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; KNCV Tuberculosis Foundation, The Hague, The Netherlands. AN - 26792481 AU - Zwerling, A. AU - Gomez, G. B. AU - Pennington, J. AU - Cobelens, F. AU - Vassall, A. AU - Dowdy, D. W. DA - Feb DO - 10.5588/ijtld.15.0415 DP - NLM ET - 2016/01/23 IS - 2 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Antitubercular Agents/*administration & dosage/*economics Computer Simulation Cost-Benefit Analysis *Decision Support Techniques Disability Evaluation Drug Administration Schedule *Drug Costs Drug Therapy, Combination Health Services Accessibility Humans Models, Economic Monte Carlo Method Patient Selection Time Factors Treatment Outcome Tuberculosis/diagnosis/*drug therapy/*economics/epidemiology LA - eng N1 - 1815-7920 Zwerling, A Gomez, G B Pennington, J Cobelens, F Vassall, A Dowdy, D W Journal Article Research Support, Non-U.S. Gov't France Int J Tuberc Lung Dis. 2016 Feb;20(2):257-60. doi: 10.5588/ijtld.15.0415. PY - 2016 SN - 1027-3719 SP - 257-60 ST - A simplified cost-effectiveness model to guide decision-making for shortened anti-tuberculosis treatment regimens T2 - Int J Tuberc Lung Dis TI - A simplified cost-effectiveness model to guide decision-making for shortened anti-tuberculosis treatment regimens VL - 20 ID - 1094 ER - TY - JOUR AB - Bovine tuberculosis (BTB) is an endemic zoonosis in Morocco caused by Mycobacterium bovis, which infects many domestic animals and is transmitted to humans through consumption of raw milk or from contact with infected animals. The prevalence of BTB in Moroccan cattle is estimated at 18%, and 33% at the individual and the herd level respectively, but the human M. bovis burden needs further clarification. The current control strategy based on test and slaughter should be improved through local context adaptation taking into account a suitable compensation in order to reduce BTB prevalence in Morocco and decrease the disease burden in humans and animals. We established a simple compartmental deterministic mathematical model for BTB transmission in cattle and humans to provide a general understanding of BTB, in particular regarding transmission to humans. Differential equations were used to model the different pathways between the compartments for cattle and humans. Scenarios of test and slaughter were simulated to determine the effects of varying the proportion of tested animals (p) on the time to elimination of BTB (individual animal prevalence of less than one in a thousand) in cattle and humans. The time to freedom from disease ranged from 75 years for p = 20% to 12 years for p = 100%. For p > 60% the time to elimination was less than 20 years. The cumulated cost was largely stable: for p values higher than 40%, cost ranged from 1.47 to 1.60 billion euros with a time frame of 12 to 32 years to reach freedom from disease. The model simulations also suggest that using a 2mm cut off instead of a 4mm cut off in the Single Intradermal Comparative Cervical Tuberculin skin test (SICCT) would result in cheaper and quicker elimination programs. This analysis informs Moroccan bovine tuberculosis control policy regarding time frame, range of cost and levels of intervention. However, further research is needed to clarify the national human-bovine tuberculosis ratio in Morocco. AD - Institut de Recherches en Elevage pour le Developpement, N'Djamena, Chad. Swiss Tropical and Public Health Institute, Basel, Switzerland. University of Basel, Basel, Switzerland. Institut Agronomique et Veterinaire Hassan II, Rabat, Morocco. AN - 28152056 AU - Abakar, M. F. AU - Yahyaoui Azami, H. AU - Justus Bless, P. AU - Crump, L. AU - Lohmann, P. AU - Laager, M. AU - Chitnis, N. AU - Zinsstag, J. C2 - PMC5289436 DA - Feb DO - 10.1371/journal.pntd.0005214 DP - NLM ET - 2017/02/06 IS - 2 J2 - PLoS neglected tropical diseases KW - Animals Cattle Humans Morocco/epidemiology Mycobacterium bovis/genetics/isolation & purification/physiology Prevalence Tuberculosis/epidemiology/microbiology/*transmission Tuberculosis, Bovine/epidemiology/microbiology/*transmission Zoonoses/epidemiology/microbiology/*transmission LA - eng N1 - 1935-2735 Abakar, Mahamat Fayiz Yahyaoui Azami, Hind Justus Bless, Philipp Crump, Lisa Lohmann, Petra Laager, Mirjam Chitnis, Nakul Zinsstag, Jakob Journal Article United States PLoS Negl Trop Dis. 2017 Feb 2;11(2):e0005214. doi: 10.1371/journal.pntd.0005214. eCollection 2017 Feb. PY - 2017 SN - 1935-2727 SP - e0005214 ST - Transmission dynamics and elimination potential of zoonotic tuberculosis in morocco T2 - PLoS Negl Trop Dis TI - Transmission dynamics and elimination potential of zoonotic tuberculosis in morocco VL - 11 ID - 754 ER - TY - JOUR AB - A model for tuberculosis (TB) that includes immigration of susceptible and infected individuals is presented and analyzed. Infected individuals are structured by time since infection to include a long and variable latency period, and individuals with active TB have an increased mortality rate. Two control problems are formulated and analyzed, minimizing the impact of infection by controlling infected immigrants and/or screening for detection and treatment of infected individuals before they develop active TB. AD - Bordeaux Univ, IMB, CNRS, UMR 5251, 3 Ter Pl Victoire, F-33000 Bordeaux, France Purdue Univ, Dept Math, 150 N Univ St, W Lafayette, IN 47907 USA Univ Trento, Dipartimento Matemat, I-38050 Povo, TN, Italy Arizona State Univ, Sch Math & Stat Sci, POB 871804, Tempe, AZ 85287 USA AN - WOS:000396675600004 AU - Ainseba, B. AU - Feng, Z. AU - Iannelli, M. AU - Milner, F. A. DO - 10.1137/15m1048719 IS - 1 J2 - Siam J Appl Math KW - tuberculosis mathematical modeling control partial differential equations arbitrarily distributed periods 2-strain tuberculosis model optimal vaccination endemic models age-structure infection dynamics diseases LA - English N1 - Eo4pa Times Cited:0 Cited References Count:37 PY - 2017 SN - 0036-1399 SP - 82-107 ST - Control Strategies for Tb Epidemics T2 - Siam Journal on Applied Mathematics TI - Control Strategies for Tb Epidemics UR - ://WOS:000396675600004 VL - 77 ID - 2186 ER - TY - JOUR AB - The use of stochastic models to study the dynamics of infectious diseases is an important tool to understand the epidemiological process. For several directly transmitted diseases, reinfection is a relevant process, which can be expressed by endogenous reactivation of the pathogen or by exogenous reinfection due to direct contact with an infected individual (with smaller reinfection rate sigmabeta than infection rate beta). In this paper, we examine the stochastic susceptible, infected, recovered, infected (SIRI) model simulating the endogenous reactivation by a spontaneous reaction, while exogenous reinfection by a catalytic reaction. Analyzing the mean-field approximations of a site and pairs of sites, and Monte Carlo (MC) simulations for the particular case of exogenous reinfection, we obtained continuous phase transitions involving endemic, epidemic, and no transmission phases for the simple approach; the approach of pairs is better to describe the phase transition from endemic phase (susceptible, infected, susceptible (SIS)-like model) to epidemic phase (susceptible, infected, and removed or recovered (SIR)-like model) considering the comparison with MC results; the reinfection increases the peaks of outbreaks until the system reaches endemic phase. For the particular case of endogenous reactivation, the approach of pairs leads to a continuous phase transition from endemic phase (SIS-like model) to no transmission phase. Finally, there is no phase transition when both effects are taken into account. We hope the results of this study can be generalized for the susceptible, exposed, infected, and removed or recovered (SEIR_{I}^{E}) model, for which the state exposed (infected but not infectious), describing more realistically transmitted diseases such as tuberculosis. In future work, we also intend to investigate the effect of network topology on phase transitions when the SIRI model describes both transmitted diseases (sigma<1) and social contagions (sigma>1). AD - Departamento de Fisica, Instituto Federal da Bahia-40110-150 Salvador, Brazil. Instituto de Fisica, Universidade Federal da Bahia-40210-340 Salvador, Brazil. AN - 28709290 AU - Barros, A. S. AU - Pinho, S. T. R. DA - Jun DO - 10.1103/PhysRevE.95.062135 IS - 6-1 N1 - Barros, Alessandro S Pinho, Suani T R eng 2017/07/16 06:00 Phys Rev E. 2017 Jun;95(6-1):062135. doi: 10.1103/PhysRevE.95.062135. Epub 2017 Jun 29. PY - 2017 SN - 2470-0053 (Electronic) 2470-0045 (Linking) SP - 062135 ST - Stochastic dynamics for reinfection by transmitted diseases T2 - Phys Rev E TI - Stochastic dynamics for reinfection by transmitted diseases UR - https://www.ncbi.nlm.nih.gov/pubmed/28709290 VL - 95 ID - 2173 ER - TY - JOUR AB - BACKGROUND: The majority of tuberculosis in migrants to Canada occurs due to reactivation of latent TB infection. Risk of tuberculosis in those with latent tuberculosis infection can be significantly reduced with treatment. Presently, only 2.4% of new migrants are flagged for post-landing surveillance, which may include latent tuberculosis infection screening; no other migrants receive routine latent tuberculosis infection screening. To aid in reducing the tuberculosis burden in new migrants to Canada, we determined the cost-effectiveness of using different latent tuberculosis infection interventions in migrants under post-arrival surveillance and in all new migrants. METHODS: A discrete event simulation model was developed that focused on a Canadian permanent resident cohort after arrival in Canada, utilizing a ten-year time horizon, healthcare system perspective, and 1.5% discount rate. Latent tuberculosis infection interventions were evaluated in the population under surveillance (N = 6100) and the total cohort (N = 260,600). In all evaluations, six different screening and treatment combinations were compared to the base case of tuberculin skin test screening followed by isoniazid treatment only in the population under surveillance. Quality adjusted life years, incident tuberculosis cases, and costs were recorded for each intervention and incremental cost-effectiveness ratios were calculated in relation to the base case. RESULTS: In the population under surveillance (N = 6100), using an interferon-gamma release assay followed by rifampin was dominant compared to the base case, preventing 4.90 cases of tuberculosis, a 4.9% reduction, adding 4.0 quality adjusted life years, and saving $353,013 over the ensuing ten-years. Latent tuberculosis infection screening in the total population (N = 260,600) was not cost-effective when compared to the base case, however could potentially prevent 21.8% of incident tuberculosis cases. CONCLUSIONS: Screening new migrants under surveillance with an interferon-gamma release assay and treating with rifampin is cost saving, but will not significantly impact TB incidence. Universal latent tuberculosis infection screening and treatment is cost-prohibitive. Research into using risk factors to target screening post-landing may provide alternate solutions. AD - Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada. Division of Respiratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada. British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada. AN - 29084227 AU - Campbell, J. R. AU - Johnston, J. C. AU - Sadatsafavi, M. AU - Cook, V. J. AU - Elwood, R. K. AU - Marra, F. C2 - PMC5662173 DO - 10.1371/journal.pone.0186778 IS - 10 N1 - Campbell, Jonathon R Johnston, James C Sadatsafavi, Mohsen Cook, Victoria J Elwood, R Kevin Marra, Fawziah eng 2017/10/31 06:00 PLoS One. 2017 Oct 30;12(10):e0186778. doi: 10.1371/journal.pone.0186778. eCollection 2017. PY - 2017 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e0186778 ST - Cost-effectiveness of post-landing latent tuberculosis infection control strategies in new migrants to Canada T2 - PLoS One TI - Cost-effectiveness of post-landing latent tuberculosis infection control strategies in new migrants to Canada UR - https://www.ncbi.nlm.nih.gov/pubmed/29084227 VL - 12 ID - 4211 ER - TY - JOUR AB - BACKGROUND: Contact tracing is a key element in England's 2015 collaborative TB strategy, although proposed indicators of successful contact tracing remain undescribed. METHODS: We conducted descriptive and multivariable analyses of contact tracing of TB cases in London between 1 July 2012 and 31 December 2015 using cohort review data from London's TB Register, identifying characteristics associated with improved indicators and yield. RESULTS: Of the pulmonary TB cases notified, 60% (2716/4561) had sufficient information for inclusion. Of these, 91% (2481/2716) had at least 1 contact (median: 4/case (IQR: 2-6)) identified, with 86% (10 251/11 981) of these contacts evaluated. 4.1% (177/4328), 1.3% (45/3421) and 0.70% (51/7264) of evaluated contacts of pulmonary smear-positive, pulmonary smear-negative and non-pulmonary cases, respectively, had active disease. Cases who were former prisoners or male were less likely to have at least one contact identified than those never imprisoned or female, respectively. Cases diagnosed at clinics with more directly observed therapy or social workers were more likely to have one or more contacts identified. Contacts screened at a different clinic to their index case or of male index cases were less likely to be evaluated than those screened at the same clinic or of women, respectively; yield of active disease was similar by sex. 10% (490/4850) of evaluated child contacts had latent TB infection. CONCLUSIONS: These are the first London-wide estimates of TB contact tracing indicators which are important for monitoring the strategy's success and informing risk assessment of index cases. Understanding why differences in indicators occur between groups could improve contact tracing outcomes. AD - TB Modelling Group, TB Centre and CMMID, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK. Statistics, Modelling and Economics Department, Public Health England, London, UK. Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London , UK. Respiratory Diseases Department, Public Health England, London, UK. Field Epidemiology Services, Public Health England, London, UK. Department of Infection and Population Health, University College London, London, UK. AN - 28389598 AU - Cavany, S. M. AU - Sumner, T. AU - Vynnycky, E. AU - Flach, C. AU - White, R. G. AU - Thomas, H. L. AU - Maguire, H. AU - Anderson, C. C2 - PMC5537523 DA - Aug DO - 10.1136/thoraxjnl-2016-209677 DP - NLM ET - 2017/04/09 IS - 8 J2 - Thorax KW - Adolescent Adult Child Contact Tracing/*methods Female Humans Incidence London/epidemiology Male Registries Retrospective Studies Tuberculin Test Tuberculosis/*diagnosis/epidemiology/transmission Young Adult Tuberculosis LA - eng N1 - 1468-3296 Cavany, Sean M Sumner, Tom Vynnycky, Emilia Flach, Clare White, Richard G Thomas, H Lucy Maguire, Helen Anderson, Charlotte Evaluation Studies Journal Article England Thorax. 2017 Aug;72(8):736-745. doi: 10.1136/thoraxjnl-2016-209677. Epub 2017 Apr 7. PY - 2017 SN - 0040-6376 SP - 736-745 ST - An evaluation of tuberculosis contact investigations against national standards T2 - Thorax TI - An evaluation of tuberculosis contact investigations against national standards VL - 72 ID - 702 ER - TY - JOUR AD - [Datta, Meenal; Chen, Wei; Xu, Lei; Jain, Rakesh] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Via, Laura; Barry, Clfton] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Baish, James] Bucknell Univ, Lewisburg, PA 17837 USA. AN - WOS:000397860000093 AU - Datta, M. AU - Via, L. AU - Chen, W. AU - Baish, J. AU - Xu, L. AU - Barry, C. AU - Jain, R. DA - Jan DO - 10.1158/1538-7445.epso16-b59 J2 - Cancer Res. KW - Oncology LA - English M3 - Meeting Abstract N1 - ISI Document Delivery No.: EQ1WJ Times Cited: 0 Cited Reference Count: 0 Datta, Meenal Via, Laura Chen, Wei Baish, James Xu, Lei Barry, Clfton Jain, Rakesh AACR Special Conference on Engineering and Physical Sciences in Oncology Jun 25-28, 2016 Boston, MA Amer Assoc Canc Res 0 Amer assoc cancer research Philadelphia 1538-7445 2 PY - 2017 SN - 0008-5472 SP - 2 ST - Mathematical Model of Oxygen Transport in Tuberculosis Granulomas T2 - Cancer Research TI - Mathematical Model of Oxygen Transport in Tuberculosis Granulomas UR - ://WOS:000397860000093 VL - 77 ID - 5059 ER - TY - JOUR AB - BACKGROUND: Tuberculosis in children is increasingly recognised as an important component of the global tuberculosis burden, with an estimated 1 million cases in 2015. Although younger children are vulnerable to severe forms of tuberculosis disease, no age-disaggregated estimates of paediatric tuberculosis mortality exist, and tuberculosis has never been included in official estimates of under-5 child mortality. We aimed to produce a global mortality burden estimate in children using a complementary approach not dependent on vital registration data. METHODS: In this mathematical modelling study, we estimated deaths in children younger than 5 years and those aged 5-14 years for 217 countries and territories using a case-fatality-based approach. We used paediatric tuberculosis notification data and HIV and antiretroviral treatment estimates to disaggregate the WHO paediatric tuberculosis incidence estimates by age, HIV, and treatment status. We then applied systematic review evidence on corresponding case-fatality ratios. FINDINGS: We estimated that 239 000 (95% uncertainty interval [UI] 194 000-298 000) children younger than 15 years died from tuberculosis worldwide in 2015; 80% (191 000, 95% UI 132 000-257 000) of these deaths were in children younger than 5 years. More than 70% (182 000, 140 000-239 000) of deaths occurred in the WHO southeast Asia and Africa regions. We estimated that 39 000 (17%, 23 000-73 000) paediatric tuberculosis deaths worldwide were in children with HIV infections, with 31 000 (36%, 19 000-59 000) in the WHO Africa region. More than 96% (230 000, 185 000-289 000) of all tuberculosis deaths occurred in children not receiving tuberculosis treatment. INTERPRETATION: Tuberculosis is a top ten cause of death in children worldwide and a key omission from previous analyses of under-5 mortality. Almost all these deaths occur in children not on tuberculosis treatment, implying substantial scope to reduce this burden. FUNDING: UNITAID, National Institutes of Health, and National Institute for Health Research. AD - School of Health and Related Research, University of Sheffield, Sheffield, UK. Electronic address: p.j.dodd@sheffield.ac.uk. Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. World Health Organization, Geneva, Switzerland. Centre for International Child Health, Department of Paediatrics, Imperial College London, London, UK. Boston University School of Public Health, Boston, MA, USA. AN - 28807188 AU - Dodd, P. J. AU - Yuen, C. M. AU - Sismanidis, C. AU - Seddon, J. A. AU - Jenkins, H. E. C2 - PMC5556253 DA - Sep DO - 10.1016/s2214-109x(17)30289-9 DP - NLM ET - 2017/08/16 IS - 9 J2 - The Lancet. Global health LA - eng N1 - 2214-109x Dodd, Peter J Yuen, Courtney M Sismanidis, Charalambos Seddon, James A Jenkins, Helen E K01 AI102944/AI/NIAID NIH HHS/United States Journal Article England Lancet Glob Health. 2017 Sep;5(9):e898-e906. doi: 10.1016/S2214-109X(17)30289-9. PY - 2017 SN - 2214-109x SP - e898-e906 ST - The global burden of tuberculosis mortality in children: a mathematical modelling study T2 - Lancet Glob Health TI - The global burden of tuberculosis mortality in children: a mathematical modelling study VL - 5 ID - 605 ER - TY - JOUR AB - Tuberculosis infection can result in clearance, latent infection, or active disease, with slow or fast progression. A four-dimensional model of in-host tuberculosis infection includes macrophages, T lymphocytes, tuberculosis bacteria, and their interactions. Changes in the infection rate, cell-mediated immunity rate, macrophage loss rate, and bacteria killing rate most affect disease outcomes. Simulations show that a periodic solution can occur. When the infected macrophage killing rate is constant, a backward bifurcation exists and the system is globally stable. AD - York Univ, Modelling Infect & Immun Lab, Ctr Dis Modelling, York Inst Hlth Res Math & Stat, Toronto, ON, Canada York Univ, Lab Appl & Ind Math, Ctr Dis Modelling, York Inst Hlth Res Math & Stat, Toronto, ON, Canada AN - WOS:000395719100004 AU - Du, Y. M. AU - Wu, J. H. AU - Heffernan, J. M. DO - 10.1080/08898480.2015.1054220 IS - 1 J2 - Math Popul Stud KW - active disease clearance latency latin hypercube sampling tuberculosis intrinsic transmission dynamics human immune-response endogenous reactivation disease transmission latent tuberculosis epidemiology sensitivity uncertainty mechanisms ratio LA - English N1 - Sp. Iss. S1 En0se Times Cited:0 Cited References Count:38 PY - 2017 SN - 0889-8480 SP - 37-63 ST - A simple in-host model for Mycobacterium tuberculosis that captures all infection outcomes T2 - Mathematical Population Studies TI - A simple in-host model for Mycobacterium tuberculosis that captures all infection outcomes UR - ://WOS:000395719100004 VL - 24 ID - 2187 ER - TY - JOUR AB - SETTING: Cape Town, South Africa. OBJECTIVE: To compare the diagnostic yield for smear/culture and Xpert(R) MTB/RIF algorithms and to investigate the mechanisms influencing tuberculosis (TB) yield. METHOD: We developed and validated an operational model of the TB diagnostic process, first with the smear/culture algorithm and then with the Xpert algorithm. We modelled scenarios by varying TB prevalence, adherence to diagnostic algorithms and human immunodeficiency virus (HIV) status. This enabled direct comparisons of diagnostic yield in the two algorithms to be made. RESULTS: Routine data showed that diagnostic yield had decreased over the period of the Xpert algorithm roll-out compared to the yield when the smear/culture algorithm was in place. However, modelling yield under identical conditions indicated a 13.3% increase in diagnostic yield from the Xpert algorithm compared to smear/culture. The model demonstrated that the extensive use of culture in the smear/culture algorithm and the decline in TB prevalence are the main factors contributing to not finding an increase in diagnostic yield in the routine data. CONCLUSION: We demonstrate the benefits of an operational model to determine the effect of scale-up of a new diagnostic algorithm, and recommend that policy makers use operational modelling to make appropriate decisions before new diagnostic algorithms are scaled up. AD - Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa. Centre for Applied Health Research and Delivery, Liverpool School of Tropical Medicine, Liverpool, UK. AN - 28284252 AU - Dunbar, R. AU - Naidoo, P. AU - Beyers, N. AU - Langley, I. DA - Apr 01 DO - 10.5588/ijtld.16.0432 DP - NLM ET - 2017/03/13 IS - 4 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease LA - eng N1 - 1815-7920 Dunbar, R Naidoo, P Beyers, N Langley, I Journal Article France Int J Tuberc Lung Dis. 2017 Apr 1;21(4):381-388. doi: 10.5588/ijtld.16.0432. PY - 2017 SN - 1027-3719 SP - 381-388 ST - Operational modelling: the mechanisms influencing TB diagnostic yield in an Xpert(R) MTB/RIF-based algorithm T2 - Int J Tuberc Lung Dis TI - Operational modelling: the mechanisms influencing TB diagnostic yield in an Xpert(R) MTB/RIF-based algorithm VL - 21 ID - 718 ER - TY - JOUR AB - In 2015, there were an estimated 10.4 million new (incident) Tuberculosis cases worldwide, of which 5.9 million (56%) were among men, 3.5 million (34%) among women and 1.0 million (10%) among children. People living with HIV accounted for 1.2 million (11%) of all new TB cases. Six countries accounted for 60% of the new cases: India, Indonesia, China, Nigeria, Pakistan and South Africa [3]. In this study we present a deterministic compartmental mathematical model for the dynamics of tuberculosis and incorporate parameters for slow and fast progression from latently infected tuberculosis to infectious tuberculosis using a modified SIS model to show the effect of HIV/AIDS on the spread of Tuberculosis. The disease free and endemic equilibrium states were established. The disease free equilibrium state was analyzed for stability using a modified version of Bellman and Cooke theorem [1]. AD - [Enagi, Abdullah Idris] Fed Univ Technol, Dept Math, Minna, Nigeria. [Bawa, Musa; Badegi, Yahya Aliyu] Ibrahim Badamasi Babangida Univ, Dept Math & Comp Sci, Lapai, Nigeria. [Sani, Abdullah Muhammad] Fed Univ, Dept Math, Birnin Kebbi, Nigeria. Enagi, AI (reprint author), Fed Univ Technol, Dept Math, Minna, Nigeria. enagi.idris@futminna.edu.ng; musa_bawa@yahoo.com; muhsangora@yahoo.com; aybadeggi@ibbu.edu.ng AN - WOS:000407995400001 AU - Enagi, A. I. AU - Bawa, M. AU - Sani, A. M. AU - Badegi, Y. A. IS - 2 J2 - Int. J. Math. Comput. Sci. KW - Equilibrium States Stability HIV/AIDS and Latent TB treatment Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: FE1RN Times Cited: 0 Cited Reference Count: 7 Enagi, Abdullah Idris Bawa, Musa Sani, Abdullah Muhammad Badegi, Yahya Aliyu 0 Lebanese univ Beirut 1814-0432 PY - 2017 SN - 1814-0424 SP - 85-95 ST - Stability Analysis of a Deterministic Compartmental Model of Tuberculosis with Effect of HIV/AIDS on the Progression from Latent Class to Infectious Class T2 - International Journal of Mathematics and Computer Science TI - Stability Analysis of a Deterministic Compartmental Model of Tuberculosis with Effect of HIV/AIDS on the Progression from Latent Class to Infectious Class UR - ://WOS:000407995400001 VL - 12 ID - 5043 ER - TY - JOUR AB - In Nigeria, the National Tuberculosis and Leprosy Control Program concentrates only on Infectious Tuberculosis treatment leaving the Latently infected ones on the waiting list at the mercy of their immune system. In this research we modeled the effect of combining Immunization with Latent Tuberculosis treatment in controlling the spread of Tuberculosis. We established the existence of equilibrium states and analyzed the Disease free equilibrium state for stability using Routh -Hurwitz Theorem. The disease free equilibrium state (i.e., the state of total eradication of Tuberculosis) will be stable if effort is intensified in bringing down both the contraction rate beta and the rate of break down to Infectious Tuberculosis tau. AD - [Enagi, Abdullah Idris; Akinwande, Ninuola Ifeoluwa] Fed Univ Technol, Dept Math, Minna, Nigeria. [Ibrahim, Mohammed Olanrewaju] Univ Illorin, Dept Math, Illorin, Nigeria. [Bawa, Musa; Wachin, Abdullahi A.] Ibrahim Badamasi Babangida Univ, Dept Math & Comp Sci, Lapai, Nigeria. Enagi, AI (reprint author), Fed Univ Technol, Dept Math, Minna, Nigeria. enagi.idris@futminna.edu.ng; moibraheem@yahoo.com; aninuola@gmail.com; musa_bawa@yahoo.com; aawachin@gmail.com AN - WOS:000407995400002 AU - Enagi, A. I. AU - Ibrahim, M. O. AU - Akinwande, N. I. AU - Bawa, M. AU - Wachin, A. A. IS - 2 J2 - Int. J. Math. Comput. Sci. KW - Vaccination Latent TB Treatment Infectious TB Treatment Equilibrium State Stability Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: FE1RN Times Cited: 0 Cited Reference Count: 7 Enagi, Abdullah Idris Ibrahim, Mohammed Olanrewaju Akinwande, Ninuola Ifeoluwa Bawa, Musa Wachin, Abdullahi A. 0 1 Lebanese univ Beirut 1814-0432 PY - 2017 SN - 1814-0424 SP - 97-106 ST - A Mathematical Model of Tuberculosis Control Incorporating Vaccination, Latency and Infectious Treatments (Case Study of Nigeria) T2 - International Journal of Mathematics and Computer Science TI - A Mathematical Model of Tuberculosis Control Incorporating Vaccination, Latency and Infectious Treatments (Case Study of Nigeria) UR - ://WOS:000407995400002 VL - 12 ID - 5044 ER - TY - JOUR AB - Background: The increasing rates of multidrug resistant TB (MDR-TB) have posed the question of whether control programs under enhanced directly observed treatment, short-course (DOTS-Plus) are sufficient or implemented optimally. Despite enhanced efforts on early case detection and improved treatment regimens, direct transmission of MDR-TB remains a major hurdle for global TB control. Methods: We developed an agent-based simulation model of TB dynamics to evaluate the effect of transmission reduction measures on the incidence of MDR-TB. We implemented a 15-day isolation period following the start of treatment in active TB cases. The model was parameterized with the latest estimates derived from the published literature. Results: We found that if high rates (over 90%) of TB case identification are achieved within 4 weeks of developing active TB, then a 15-day patient isolation strategy with 50% effectiveness in interrupting disease transmission leads to 10% reduction in the incidence of MDR-TB over 10 years. If transmission is fully prevented, the rise of MDR-TB can be halted within 10 years, but the temporal reduction of MDR-TB incidence remains below 20% in this period. Conclusions: The impact of transmission reduction measures on the TB incidence depends critically on the rates and timelines of case identification. The high costs and adverse effects associated with MDR-TB treatment warrant increased efforts and investments on measures that can interrupt direct transmission through early case detection. AD - Departamento de Fisica, Instituto de Ciencias Exatas-ICEx, Universidade Federal Fluminense, Volta Redonda, RJ, 27.213-145Brazil. Department of Mathematical and Statistical Sciences and Department of Public Health Sciences, University of Alberta, Edmonton, Alberta, Canada. Agent-Based Modelling Laboratory, York University, 4700 Keele St., Toronto, Ontario, M3J 1P3, Canada. Centre for Disease Modelling, Department of Mathematics and Statistics, York University, Toronto, ON, M3J 1P3, Canada. AN - 28338827 AU - Espindola, A. L. AU - Varughese, M. AU - Laskowski, M. AU - Shoukat, A. AU - Heffernan, J. M. AU - Moghadas, S. M. DA - Mar 01 DO - 10.1093/inthealth/ihw059 DP - NLM ET - 2017/03/25 IS - 2 J2 - International health KW - Antitubercular Agents/*therapeutic use Communicable Disease Control/*methods Developing Countries Disease Transmission, Infectious/*prevention & control Early Diagnosis Epidemics Humans Incidence Models, Theoretical Mycobacterium tuberculosis/isolation & purification Population Dynamics Tuberculosis, Multidrug-Resistant/*diagnosis/*prevention & control/transmission Agent-based modelling Case isolation Exogenous re-infection Multidrug resistant TB Relapse Transmission dynamics L1 - internal-pdf://1845801050/Espindola-2017-Strategies for halting the rise.pdf LA - eng N1 - 1876-3405 Espindola, Aquino L Varughese, Marie Laskowski, Marek Shoukat, Affan Heffernan, Jane M Moghadas, Seyed M Journal Article England Int Health. 2017 Mar 1;9(2):80-90. doi: 10.1093/inthealth/ihw059. PY - 2017 SN - 1876-3405 SP - 80-90 ST - Strategies for halting the rise of multidrug resistant TB epidemics: assessing the effect of early case detection and isolation T2 - Int Health TI - Strategies for halting the rise of multidrug resistant TB epidemics: assessing the effect of early case detection and isolation UR - https://watermark.silverchair.com/ihw059.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAdwwggHYBgkqhkiG9w0BBwagggHJMIIBxQIBADCCAb4GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMZSUgt4ajkTvEIuUXAgEQgIIBj6Ts_UyjBPf_2HyDSjNzX_wEriq9YMrC0snrBRg-QJbqRxIvdrxPNbBgq_SgIQ0nJ3AfBznAhDlNsuwuGYeJTXjwWEjfSy3jSZCrwWZeUqwExMZOiEBlC6x63socJUek08o2dNPRNQqvOjBaAsLeJL7Znqh1pdqBJoSftgmGg92H4ll1qgOkoGGojjZnCUJn0cvsN4kq_6D3b9F495EXmhMuiDeOVGmv5X15o0eqrKHVfcy44F2qLixja0_vpExYtzvpIvB3egff7kcI3ITAmvHHE2uKczPOYL-n9BMr-fp5oSzi_YmGdON7aOXwtMD8Q-iV1eiTZyEztkK2bnWN54xz96ZD_3icUUqjrL0N0yiZR_Jx3F66Ni1mYAn-Dt55KX2U5POw-mKfi3WNuGmtYan6pXzQ6SzNwnZGbK6NpFtSCvK0KsvZrnMz_Nuy-fY5G-DMPExfpcg9qCOAVib0qB97xv2DHOykKdE53-7gpA9dNdzoPrgE39J8Qeeb2G_y9fAkLTIlvZHbwmasCgqmZw VL - 9 ID - 710 ER - TY - JOUR AB - Among the several means by which heterogeneity can be modeled, Levins' (1969) meta-population approach preserves the most analytical tractability, a virtue to the extent that generality is desirable. When model populations are stratified, contacts among their respective sub-populations must be described. Using a simple meta-population model, Feng et al. (2015) showed that mixing among sub-populations, as well as heterogeneity in characteristics affecting sub-population reproduction numbers, must be considered when evaluating public health interventions to prevent or control infectious disease outbreaks. They employed the convex combination of preferential within- and proportional among-group contacts first described by Nold (1980) and subsequently generalized by Jacquez et al. (1988). As the utility of meta-population modeling depends on more realistic mixing functions, the authors added preferential contacts between parents and children and among co-workers (Glasser et al., 2012). Here they further generalize this function by including preferential contacts between grandparents and grandchildren, but omit workplace contacts. They also describe a general multi-level mixing scheme, provide three two-level examples, and apply two of them. In their first application, the authors describe age- and gender-specific patterns in face-to-face conversations (Mossong et al., 2008), proxies for contacts by which respiratory pathogens might be transmitted, that are consistent with everyday experience. This suggests that meta-population models with inter-generational mixing could be employed to evaluate prolonged school-closures, a proposed pandemic mitigation measure that could expose grandparents, and other elderly surrogate caregivers for working parents, to infectious children. In their second application, the authors use a meta-population SEIR model stratified by 7 age groups and 50 states plus the District of Columbia, to compare actual with optimal vaccination during the 2009-2010 influenza pandemic in the United States. They also show that vaccination efforts could have been adjusted month-to-month during the fall of 2009 to ensure maximum impact. Such applications inspire confidence in the reliability of meta-population modeling in support of public health policymaking. AD - Department of Mathematics, Purdue University, West Lafayette, IN, United States. National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, Atlanta, GA, United States. National Center for Immunization and Respiratory Diseases, CDC, Atlanta, GA, United States. National Center for Immunization and Respiratory Diseases, CDC, Atlanta, GA, United States . Electronic address: jglasser@cdc.gov. AN - 27671169 AU - Feng, Z. AU - Hill, A. N. AU - Curns, A. T. AU - Glasser, J. W. DA - May DO - 10.1016/j.mbs.2016.09.013 DP - NLM ET - 2016/09/28 J2 - Mathematical biosciences KW - Communicable Disease Control/*methods Humans Influenza, Human/*prevention & control/transmission *Models, Theoretical *Multilevel Analysis Designing or evaluating public health interventions Meta-population modeling Mixing functions LA - eng N1 - 1879-3134 Feng, Zhilan Hill, Andrew N Curns, Aaron T Glasser, John W Journal Article United States Math Biosci. 2017 May;287:93-104. doi: 10.1016/j.mbs.2016.09.013. Epub 2016 Sep 23. PY - 2017 SN - 0025-5564 SP - 93-104 ST - Evaluating targeted interventions via meta-population models with multi-level mixing T2 - Math Biosci TI - Evaluating targeted interventions via meta-population models with multi-level mixing VL - 287 ID - 860 ER - TY - JOUR AB - Several infectious diseases of global importance-e.g., HIV infection and tuberculosis (TB)-require prolonged treatment with combination antimicrobial regimens typically involving high-potency core agents coupled with additional companion drugs that protect against the de novo emergence of mutations conferring resistance to the core agents. Often, the most effective (or least toxic) companion agents are reused in sequential (first-line, second-line, etc.) regimens. We used a multistrain model of Mycobacterium tuberculosis transmission in Southeast Asia to investigate how this practice might facilitate the emergence of extensive drug resistance, i.e., resistance to multiple core agents. We calibrated this model to regional TB and drug resistance data using an approximate Bayesian computational approach. We report the proportion of data-consistent simulations in which the prevalence of pre-extensively drug-resistant (pre-XDR) TB-defined as resistance to both first-line and second-line core agents (rifampin and fluoroquinolones)-exceeds predefined acceptability thresholds (1 to 2 cases per 100,000 population by 2035). The use of pyrazinamide (the most effective companion agent) in both first-line and second-line regimens increased the proportion of simulations in which the prevalence exceeded the pre-XDR acceptability threshold by 7-fold compared to a scenario in which patients with pyrazinamide-resistant TB received an alternative drug. Model parameters related to the emergence and transmission of pyrazinamide-resistant TB and resistance amplification were among those that were the most strongly correlated with the projected pre-XDR prevalence, indicating that pyrazinamide resistance acquired during first-line treatment subsequently promotes amplification to pre-XDR TB under pyrazinamide-containing second-line treatment. These findings suggest that the appropriate use of companion drugs may be critical to preventing the emergence of strains resistant to multiple core agents. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. TB Modelling Group, TB Centre, Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. Department of Epidemiology of Microbial Diseases, School of Public Health, Yale University, New Haven, Connecticut, USA. Amsterdam Institute for Global Health and Development, Academic Medical Center, Amsterdam, Netherlands. KNCV Tuberculosis Foundation, The Hague, Netherlands. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA ddowdy@jhsph.edu. Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. AN - 27956422 AU - Fofana, M. O. AU - Shrestha, S. AU - Knight, G. M. AU - Cohen, T. AU - White, R. G. AU - Cobelens, F. AU - Dowdy, D. W. C2 - PMC5328532 DA - Mar DO - 10.1128/aac.00498-16 DP - NLM ET - 2016/12/14 IS - 3 J2 - Antimicrobial agents and chemotherapy KW - Antitubercular Agents/*therapeutic use Bayes Theorem Biological Availability Computer Simulation Drug Administration Schedule Drug Resistance, Multiple, Bacterial/*drug effects/physiology Extensively Drug-Resistant Tuberculosis/*drug therapy/microbiology Fluoroquinolones/therapeutic use Humans Microbial Sensitivity Tests *Models, Statistical Mycobacterium tuberculosis/drug effects/growth & development Pyrazinamide/*therapeutic use Rifampin/therapeutic use Tuberculosis, Pulmonary/*drug therapy/microbiology antimicrobial combinations mathematical modeling multidrug resistance pyrazinamide tuberculosis L1 - internal-pdf://1991227841/Fofana-2017-A Multistrain Mathematical Model T.pdf LA - eng N1 - 1098-6596 Fofana, Mariam O ORCID: http://orcid.org/0000-0002-2874-471X Shrestha, Sourya Knight, Gwenan M Cohen, Ted White, Richard G Cobelens, Frank Dowdy, David W Journal Article United States Antimicrob Agents Chemother. 2017 Feb 23;61(3). pii: e00498-16. doi: 10.1128/AAC.00498-16. Print 2017 Mar. PY - 2017 SN - 0066-4804 ST - A Multistrain Mathematical Model To Investigate the Role of Pyrazinamide in the Emergence of Extensively Drug-Resistant Tuberculosis T2 - Antimicrob Agents Chemother TI - A Multistrain Mathematical Model To Investigate the Role of Pyrazinamide in the Emergence of Extensively Drug-Resistant Tuberculosis UR - http://aac.asm.org/content/61/3/e00498-16.full.pdf VL - 61 ID - 799 ER - TY - JOUR AB - BACKGROUND: After steady decline since the 1990s, tuberculosis (TB) incidence in New York City (NYC) and the United States (US) has flattened. The reasons for this trend and the implications for the future trajectory of TB in the US remain unclear. METHODS: We developed a compartmental model of TB in NYC, parameterized with detailed epidemiological data. We ran the model under five alternative scenarios representing different explanations for recent declines in TB incidence. We evaluated each scenario's relative likelihood by comparing its output to available data. We used the most likely scenarios to explore drivers of TB incidence and predict future trajectories of the TB epidemic in NYC. FINDINGS: Demographic changes and declining TB transmission alone were insufficient to explain recent trends in NYC TB incidence. Only scenarios that assumed contemporary changes in TB dynamics among the foreign-born - a declining rate of reactivation or a decrease in imported subclinical TB - could accurately describe the trajectory of TB incidence since 2007. In those scenarios, the projected decline in TB incidence from 2015 to 2025 varied from minimal [2.0%/year (95% credible interval 0.4-3.5%)] to similar to 2005 to 2009 trends [4.4%/year (2.5-6.4%)]. The primary factor differentiating optimistic from pessimistic projections was the degree to which improvements in TB dynamics among the foreign-born continued into the coming decade. INTERPRETATION: Further progress against TB in NYC requires additional focus on the foreign-born population. Absent additional intervention in this group, TB incidence may not decline further. AD - Division of General Internal Medicine, Johns Hopkins University School of Medicine, 2024 Monument St., Baltimore, MD, USA 21205. Bureau of Tuberculosis Control, New York City Department of Health and Mental Hygiene, 42-09 28th St, 21st floor, Long Island City, NY, USA 11101. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St. Room E6531, Baltimore, MD, USA 21205. Division of Infectious Diseases, Johns Hopkins University School of Medicine, PCTB Suite 211, 725 N. Wolfe St., Baltimore, MD, USA 21205. AN - 29082351 AU - Fojo, A. T. AU - Stennis, N. L. AU - Azman, A. S. AU - Kendall, E. A. AU - Shrestha, S. AU - Ahuja, S. D. AU - Dowdy, D. W. C2 - PMC5659270 DA - Jul DO - 10.1016/S2468-2667(17)30119-6 IS - 7 KW - Health Resources Humans Mathematical Model New York City Tuberculosis United States N1 - Fojo, Anthony T Stennis, Natalie L Azman, Andrew S Kendall, Emily A Shrestha, Sourya Ahuja, Shama D Dowdy, David W eng K08 AI127908/AI/NIAID NIH HHS/ England 2017/10/31 06:00 Lancet Public Health. 2017 Jul;2(7):e323-e330. doi: 10.1016/S2468-2667(17)30119-6. PY - 2017 SN - 2468-2667 (Print) SP - e323-e330 ST - Current and future trends in tuberculosis incidence in New York City: a dynamic modelling analysis T2 - Lancet Public Health TI - Current and future trends in tuberculosis incidence in New York City: a dynamic modelling analysis UR - https://www.ncbi.nlm.nih.gov/pubmed/29082351 VL - 2 ID - 4822 ER - TY - JOUR AB - In this note, we investigate the global stability for a tuberculosis model with vaccination and treatment. The model exhibits the traditional threshold behavior. We prove that the basic reproduction number characterizes the global dynamics of the model, that is, the disease endemic equilibrium of the model is globally asymptotically stable whenever it exists, which accords with the corresponding conjecture presented in Liu and Zhang (2011). (C) 2017 Elsevier Ltd. All rights reserved. AD - [Gao, Da-peng; Huang, Nan-jing] Sichuan Univ, Dept Math, Chengdu 610064, Sichuan, Peoples R China. [Gao, Da-peng] China West Normal Univ, Sch Math & Informat, Nanchong 637009, Sichuan, Peoples R China. Huang, NJ (reprint author), Sichuan Univ, Dept Math, Chengdu 610064, Sichuan, Peoples R China. nanjinghuang@hotmail.com AN - WOS:000404324100024 AU - Gao, D. P. AU - Huang, N. J. DA - Nov DO - 10.1016/j.aml.2017.05.004 J2 - Appl. Math. Lett. KW - Tuberculosis Endemic equilibrium Basic reproduction number Lyapunov function Global stability Mathematics LA - English M3 - Article N1 - ISI Document Delivery No.: EY9NA Times Cited: 0 Cited Reference Count: 3 Gao, Da-peng Huang, Nan-jing National Natural Science Foundation of China [11371015, 11471230, 11671282]; Natural Science Foundation of Sichuan Provincial Education Department [14ZB0142] This work was supported by the National Natural Science Foundation of China (11371015, 11471230, 11671282) and the Natural Science Foundation of Sichuan Provincial Education Department (Grant No. 14ZB0142). 0 16 Pergamon-elsevier science ltd Oxford PY - 2017 SN - 0893-9659 SP - 163-168 ST - A note on global stability for a tuberculosis model T2 - Applied Mathematics Letters TI - A note on global stability for a tuberculosis model UR - ://WOS:000404324100024 VL - 73 ID - 4947 ER - TY - JOUR AB - Background In 2013, approximately 480,000 people developed active multidrug-resistant tuberculosis (MDR-TB), while only 97,000 started MDR-TB treatment. We sought to estimate the impact of improving access to MDR-TB diagnosis and treatment, under multiple diagnostic algorithm and treatment regimen scenarios, on ten-year projections of MDR-TB incidence and mortality. Methods We constructed a dynamic transmission model of an MDR-TB epidemic in an illustrative East/Southeast Asian setting. Using approximate Bayesian computation, we investigated a wide array of potential epidemic trajectories consistent with current notification data and known TB epidemiology. Results Despite an overall projected decline in TB incidence, data-consistent simulations suggested that MDR-TB incidence is likely to rise between 2015 and 2025 under continued 2013 treatment practices, although with considerable uncertainty (median 17% increase, 95% Uncertainty Range [UR] -38% to + 137%). But if, by 2017, all identified active TB patients with previously-treated TB could be tested for drug susceptibility, and 85% of those with MDR-TB could initiate MDR-appropriate treatment, then MDR-TB incidence in 2025 could be reduced by 26% (95% UR 4-52%) relative to projections under continued current practice. Also expanding this drug-susceptibility testing and appropriate MDR-TB treatment to treatment-naive as well as previously-treated TB cases, by 2020, could reduce MDR-TB incidence in 2025 by 29% (95% UR 6-55%) compared to continued current practice. If this diagnosis and treatment of all MDR-TB in known active TB cases by 2020 could be implemented via a novel second-line regimen with similar effectiveness and tolerability as current first-line therapy, a 54% (95% UR 20-74%) reduction in MDR-TB incidence compared to current-practice projections could be achieved by 2025. Conclusions Expansion of diagnosis and treatment of MDR-TB, even using current sub-optimal second-line regimens, is expected to significantly decrease MDR-TB incidence at the population level. Focusing MDR diagnostic efforts on previously-treated cases is an efficient first-step approach. AD - Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA Acad Med Ctr, Amsterdam Inst Global Hlth & Dev, Amsterdam, Netherlands AN - WOS:000396073700028 AU - Kendall, E. A. AU - Azman, A. S. AU - Cobelens, F. G. AU - Dowdy, D. W. DA - Mar 8 DO - ARTN e0172748 10.1371/journal.pone.0172748 IS - 3 J2 - Plos One KW - mycobacterium-tuberculosis treatment outcomes follow-up mathematical-model drug-resistance south-africa metaanalysis transmission disease reinfection L1 - internal-pdf://1898802826/Kendall-2017-MDR-TB treatment as prevention_ T.pdf LA - English N1 - En5vl Times Cited:0 Cited References Count:50 PY - 2017 SN - 1932-6203 ST - MDR-TB treatment as prevention: The projected population-level impact of expanded treatment for multidrug-resistant tuberculosis T2 - Plos One TI - MDR-TB treatment as prevention: The projected population-level impact of expanded treatment for multidrug-resistant tuberculosis UR - ://WOS:000396073700028 http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0172748&type=printable VL - 12 ID - 2181 ER - TY - JOUR AB - BACKGROUND: In May, 2016, WHO endorsed a 9 month regimen for multidrug-resistant tuberculosis that is cheaper and potentially more effective than the conventional, longer (20-24 month) therapy. We aimed to investigate the population-level implications of scaling up this new regimen. METHODS: In this population modelling analysis, we developed a dynamic transmission model to simulate the introduction of this short-course regimen as an instantaneous switch in 2016. We projected the corresponding percentage reduction in the incidence of multidrug-resistant tuberculosis by 2024 compared with continued use of longer therapy. In the primary analysis in a representative southeast Asian setting, we assumed that the short-course regimen would double treatment access (through savings in resources or capacity) and achieve long-term efficacy at levels seen in preliminary cohort studies. We then did extensive sensitivity analyses to explore a range of alternative scenarios. FINDINGS: Under the optimistic assumptions in the primary analysis, the incidence of multidrug-resistant tuberculosis in 2024 would be 3.3 (95% uncertainty range 2.2-5.6) per 100 000 population with the short-course regimen and 4.3 (2.9-7.6) per 100 000 population with continued use of longer therapy-ie, the short-course regimen could reduce incidence by 23% (10-38). Incidence would be reduced by 14% (4-28) if the new regimen affected only treatment effectiveness and by 11% (3-24) if it affected only treatment availability. Under more pessimistic assumptions, the short-course regimen would have minimal effect and even potential for harm-eg, when 30% of patients are ineligible for the new regimen because of second-line drug resistance, we projected a change in incidence of -2% (-20 to +28). The new regimen's effect was greater in settings with more ongoing transmission of multidrug-resistant tuberculosis, but results were otherwise similar across settings with different levels of tuberculosis incidence and prevalence of multidrug resistance. INTERPRETATION: The short-course regimen has potential to substantially lessen the multidrug-resistant tuberculosis epidemic, but this effect depends on its long-term efficacy, its ability to expand treatment access, and the role of second-line drug resistance. FUNDING: US National Institutes of Health and Bill & Melinda Gates Foundation. AD - Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: ekendal2@jhmi.edu. Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. AN - 27989591 AU - Kendall, E. A. AU - Fojo, A. T. AU - Dowdy, D. W. C2 - PMC5332590 DA - Mar DO - 10.1016/s2213-2600(16)30423-4 DP - NLM ET - 2016/12/19 IS - 3 J2 - The Lancet. Respiratory medicine L1 - internal-pdf://2949447161/Kendall-2017-Expected effects of adopting a 9.pdf LA - eng N1 - 2213-2619 Kendall, Emily A Fojo, Anthony T Dowdy, David W T32 AI007291/AI/NIAID NIH HHS/United States Journal Article England Lancet Respir Med. 2017 Mar;5(3):191-199. doi: 10.1016/S2213-2600(16)30423-4. Epub 2016 Dec 16. PY - 2017 SN - 2213-2600 SP - 191-199 ST - Expected effects of adopting a 9 month regimen for multidrug-resistant tuberculosis: a population modelling analysis T2 - Lancet Respir Med TI - Expected effects of adopting a 9 month regimen for multidrug-resistant tuberculosis: a population modelling analysis UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332590/pdf/main.pdf VL - 5 ID - 793 ER - TY - JOUR AB - BACKGROUND: Novel drug regimens are needed for tuberculosis (TB) treatment. New regimens aim to improve on characteristics such as duration, efficacy, and safety profile, but no single regimen is likely to be ideal in all respects. By linking these regimen characteristics to a novel regimen's ability to reduce TB incidence and mortality, we sought to prioritize regimen characteristics from a population-level perspective. METHODS AND FINDINGS: We developed a dynamic transmission model of multi-strain TB epidemics in hypothetical populations reflective of the epidemiological situations in India (primary analysis), South Africa, the Philippines, and Brazil. We modeled the introduction of various novel rifampicin-susceptible (RS) or rifampicin-resistant (RR) TB regimens that differed on six characteristics, identified in consultation with a team of global experts: (1) efficacy, (2) duration, (3) ease of adherence, (4) medical contraindications, (5) barrier to resistance, and (6) baseline prevalence of resistance to the novel regimen. We compared scale-up of these regimens to a baseline reflective of continued standard of care. For our primary analysis situated in India, our model generated baseline TB incidence and mortality of 157 (95% uncertainty range [UR]: 113-187) and 16 (95% UR: 9-23) per 100,000 per year at the time of novel regimen introduction and RR TB incidence and mortality of 6 (95% UR: 4-10) and 0.6 (95% UR: 0.3-1.1) per 100,000 per year. An optimal RS TB regimen was projected to reduce 10-y TB incidence and mortality in the India-like scenario by 12% (95% UR: 6%-20%) and 11% (95% UR: 6%-20%), respectively, compared to current-care projections. An optimal RR TB regimen reduced RR TB incidence by an estimated 32% (95% UR: 18%-46%) and RR TB mortality by 30% (95% UR: 18%-44%). Efficacy was the greatest determinant of impact; compared to a novel regimen meeting all minimal targets only, increasing RS TB treatment efficacy from 94% to 99% reduced TB mortality by 6% (95% UR: 1%-13%, half the impact of a fully optimized regimen), and increasing the efficacy against RR TB from 76% to 94% lowered RR TB mortality by 13% (95% UR: 6%-23%). Reducing treatment duration or improving ease of adherence had smaller but still substantial impact: shortening RS TB treatment duration from 6 to 2 mo lowered TB mortality by 3% (95% UR: 1%-6%), and shortening RR TB treatment from 20 to 6 mo reduced RR TB mortality by 8% (95% UR: 4%-13%), while reducing nonadherence to the corresponding regimens by 50% reduced TB and RR TB mortality by 2% (95% UR: 1%-4%) and 6% (95% UR: 3%-10%), respectively. Limitations include sparse data on key model parameters and necessary simplifications to model structure and outcomes. CONCLUSIONS: In designing clinical trials of novel TB regimens, investigators should consider that even small changes in treatment efficacy may have considerable impact on TB-related incidence and mortality. Other regimen improvements may still have important benefits for resource allocation and outcomes such as patient quality of life. AD - Johns Hopkins University School of Medicine, Division of Infectious Diseases, Baltimore, Maryland, United States of America. Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, Maryland, United States of America. Yale School of Public Health, Department of Epidemiology of Microbial Diseases, New Haven, Connecticut, United States of America. Johns Hopkins University School of Medicine, Division of Clinical Pharmacology, Baltimore, Maryland, United States of America. World Health Organization, Global TB Program, Geneva, Switzerland. Aurum Institute, Johannesburg, South Africa. University of California San Francisco, Division of Pulmonary and Critical Care Medicine, San Francisco, California, United States of America. Partners In Health, Boston, Massachusetts, United States of America. Brigham and Women's Hospital, Division of Global Health Equity, Boston, Massachusetts, United States of America. Bill and Melinda Gates Foundation, Seattle, Washington, United States of America. AN - 28045934 AU - Kendall, E. A. AU - Shrestha, S. AU - Cohen, T. AU - Nuermberger, E. AU - Dooley, K. E. AU - Gonzalez-Angulo, L. AU - Churchyard, G. J. AU - Nahid, P. AU - Rich, M. L. AU - Bansbach, C. AU - Forissier, T. AU - Lienhardt, C. AU - Dowdy, D. W. C2 - PMC5207633 (www.nih.gov) and by the Bill and Melinda Gates Foundation work order 10 (www.gatesfoundation.org). The NIH had no role in study design, data collection and analysis, or decision to publish. TF and CB are employees of the Bill and Melinda Gates Foundation and contributed as coauthors to framing of the study and review of the manuscript prior to publication; TF and CB did not have any role in the decision to fund this grant. DA - Jan DO - 10.1371/journal.pmed.1002202 IS - 1 KW - Antitubercular Agents/*therapeutic use Clinical Protocols *Epidemics Humans Incidence India/epidemiology *Models, Theoretical Tuberculosis/*drug therapy/*epidemiology/microbiology L1 - internal-pdf://0015386098/Kendall-2017-Priority-Setting for Novel Drug R.pdf N1 - Kendall, Emily A Shrestha, Sourya Cohen, Ted Nuermberger, Eric Dooley, Kelly E Gonzalez-Angulo, Lice Churchyard, Gavin J Nahid, Payam Rich, Michael L Bansbach, Cathy Forissier, Thomas Lienhardt, Christian Dowdy, David W eng T32 AI007291/AI/NIAID NIH HHS/ 2017/01/04 06:00 PLoS Med. 2017 Jan 3;14(1):e1002202. doi: 10.1371/journal.pmed.1002202. eCollection 2017 Jan. PY - 2017 SN - 1549-1676 (Electronic) 1549-1277 (Linking) SP - e1002202 ST - Priority-Setting for Novel Drug Regimens to Treat Tuberculosis: An Epidemiologic Model T2 - PLoS Med TI - Priority-Setting for Novel Drug Regimens to Treat Tuberculosis: An Epidemiologic Model UR - https://www.ncbi.nlm.nih.gov/pubmed/28045934 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207633/pdf/pmed.1002202.pdf VL - 14 ID - 2177 ER - TY - JOUR AB - BACKGROUND: India is considering the scale-up of the Xpert MTB/RIF assay for detection of tuberculosis (TB) and rifampicin resistance. We conducted an economic analysis to estimate the costs of different strategies of Xpert implementation in India. METHODS: Using a decision analytical model, we compared four diagnostic strategies for TB patients: (i) sputum smear microscopy (SSM) only; (ii) Xpert as a replacement for the rapid diagnostic test currently used for SSM-positive patients at risk of drug resistance (i.e. line probe assay (LPA)); (iii) Upfront Xpert testing for patients at risk of drug resistance; and (iv) Xpert as a replacement for SSM for all patients. RESULTS: The total costs associated with diagnosis for 100,000 presumptive TB cases were: (i) US$ 619,042 for SSM-only; (ii) US$ 575,377 in the LPA replacement scenario; (iii) US$ 720,523 in the SSM replacement scenario; and (iv) US$ 1,639,643 in the Xpert-for-all scenario. Total cohort costs, including treatment costs, increased by 46% from the SSM-only to the Xpert-for-all strategy, largely due to the costs associated with second-line treatment of a higher number of rifampicin-resistant patients due to increased drug-resistant TB (DR-TB) case detection. The diagnostic costs for an estimated 7.64 million presumptive TB patients would comprise (i) 19%, (ii) 17%, (iii) 22% and (iv) 50% of the annual TB control budget. Mean total costs, expressed per DR-TB case initiated on treatment, were lowest in the Xpert-for-all scenario (US$ 11,099). CONCLUSIONS: The Xpert-for-all strategy would result in the greatest increase of TB and DR-TB case detection, but would also have the highest associated costs. The strategy of using Xpert only for patients at risk for DR-TB would be more affordable, but would miss DR-TB cases and the cost per true DR-TB case detected would be higher compared to the Xpert-for-all strategy. As such expanded Xpert strategy would require significant increased TB control budget to ensure that increased case detection is followed by appropriate care. AD - Central TB Division, Government of India, New Delhi, India. Foundation for Innovative New Diagnostics, New Delhi, India. World Health Organization, Delhi, India. Foundation for Innovative New Diagnostics, Geneva, Switzerland. Additional DDG, Central TB Division, Ministry of Health and Family Welfare, New Delhi, India. Department of Global Health, Amsterdam Institute of Global Health and Development, Academic Medical Center, Amsterdam, The Netherlands. Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom. AN - 28880875 AU - Khaparde, S. AU - Raizada, N. AU - Nair, S. A. AU - Denkinger, C. AU - Sachdeva, K. S. AU - Paramasivan, C. N. AU - Salhotra, V. S. AU - Vassall, A. AU - van't Hoog, A. C2 - PMC5589184 DO - 10.1371/journal.pone.0184270 IS - 9 KW - Antibiotics, Antitubercular/*therapeutic use Biological Assay/*methods Humans India Rifampin/*therapeutic use Sputum/microbiology Tuberculosis/*diagnosis/*drug therapy Tuberculosis, Multidrug-Resistant L1 - internal-pdf://1399633114/Khaparde-2017-Scaling-up the Xpert MTB_RIF ass.pdf internal-pdf://1273816072/Khaparde-2017-Scaling-up the Xpert MTB_RIF as1.pdf N1 - Khaparde, Sunil Raizada, Neeraj Nair, Sreenivas Achuthan Denkinger, Claudia Sachdeva, Kuldeep Singh Paramasivan, Chinnambedu Nainarappan Salhotra, Virender Singh Vassall, Anna Hoog, Anja Van't eng 2017/09/08 06:00 PLoS One. 2017 Sep 7;12(9):e0184270. doi: 10.1371/journal.pone.0184270. eCollection 2017. PY - 2017 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e0184270 ST - Scaling-up the Xpert MTB/RIF assay for the detection of tuberculosis and rifampicin resistance in India: An economic analysis T2 - PLoS One TI - Scaling-up the Xpert MTB/RIF assay for the detection of tuberculosis and rifampicin resistance in India: An economic analysis UR - https://www.ncbi.nlm.nih.gov/pubmed/28880875 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589184/pdf/pone.0184270.pdf VL - 12 ID - 2171 ER - TY - JOUR AB - Tuberculosis (TB) is an ancient and deadly disease characterized by complex host-pathogen dynamics playing out over multiple time and length scales and physiological compartments. Mathematical and computational modeling can be used to integrate various types of experimental data and suggest new hypotheses, mechanisms, and therapeutic approaches to TB. Here, we offer a first-time comprehensive review of work on within-host TB models that describe the immune response to infection, including the formation of lung granulomas. The models include systems of ordinary and partial differential equations and agent-based models as well as hybrid and multi-scale models that are combinations of these. Many aspects of Mycobacterium tuberculosis infection, including host dynamics in the lung (typical site of infection for TB), granuloma formation, roles of cytokine and chemokine dynamics, and bacterial nutrient availability have been explored. Finally, we survey applications of these within-host models to TB therapy and prevention and suggest future directions to impact this global disease. AU - Kirschner, Denise AU - Pienaar, Elsje AU - Marino, Simeone AU - Linderman, Jennifer J. DA - 2017/06/01/ DO - https://doi.org/10.1016/j.coisb.2017.05.014 IS - Supplement C KW - Systems biology Simulations Granuloma Antibiotic treatment Sensitivity analysis Agent-based model PY - 2017 SN - 2452-3100 SP - 170-185 ST - A review of computational and mathematical modeling contributions to our understanding of Mycobacterium tuberculosis within-host infection and treatment T2 - Current Opinion in Systems Biology TI - A review of computational and mathematical modeling contributions to our understanding of Mycobacterium tuberculosis within-host infection and treatment UR - http://www.sciencedirect.com/science/article/pii/S2452310016300117 VL - 3 ID - 2179 ER - TY - JOUR AB - In this work, we explore epidemiological dynamics by the example of tuberculosis in Russian Federation. It has been shown that the epidemiological dynamics correlates linearly with the virulence of Mycobacterium tuberculosis during the period 1987-2012. To construct an appropriate model, we have analysed (using LogLet decomposition method) epidemiological World Health Organization (WHO) data (period 1980-2014) and obtained, as result of their integration, a curve approximated by a bi-logistic function. This fact allows a subdivision of the whole population into parts, each of them satisfies the Verhulst-like models with different constant virulences introduced into each subsystem separately. Such a subdivision could be interconnected with the heterogeneous structure of mycobacterial population that has a high ability of adaptation to the host and strong mutability. AD - Saint-Petersburg State University, Medical Faculty, Universitetskaya emb., 7/9, Saint-Petersburg, Russia. Saint-Petersburg State Research Institute of Phthisiopulmonology, Lygovsky avenue 2-4, Saint-Petersburg, Russia. Department of Theoretical Physics, Kursk State University, Radishcheva street 33, Kursk, Russia. AN - 28989789 AU - Lavrova, A. I. AU - Postnikov, E. B. AU - Manicheva, O. A. AU - Vishnevsky, B. I. C2 - PMC5627129 DA - Sep DO - 10.1098/rsos.171033 IS - 9 KW - Mycobacterium tuberculosis compartmental model mixed subpopulations virulence N1 - Lavrova, Anastasia I Postnikov, Eugene B Manicheva, Olga A Vishnevsky, Boris I eng England 2017/10/11 06:00 R Soc Open Sci. 2017 Sep 13;4(9):171033. doi: 10.1098/rsos.171033. eCollection 2017 Sep. PY - 2017 SN - 2054-5703 (Print) 2054-5703 (Linking) SP - 171033 ST - Bi-logistic model for disease dynamics caused by Mycobacterium tuberculosis in Russia T2 - R Soc Open Sci TI - Bi-logistic model for disease dynamics caused by Mycobacterium tuberculosis in Russia UR - https://www.ncbi.nlm.nih.gov/pubmed/28989789 VL - 4 ID - 4820 ER - TY - JOUR AB - Intense use of antibiotics for the treatment of diseases such as tuberculosis, malaria, Staphylococcus aureus or gonorrhea has led to rapidly increasing population levels of drug resistance. This has generally necessitated a switch to new drugs and the discontinuation of older ones, after which resistance often only declines slowly or even persists indefinitely. These long-term effects are usually ascribed to low fitness costs of resistance in absence of the drug. Here we show that structure in the host population, in particular heterogeneity in number of contacts, also plays an important role in the reversion dynamics. Host contact structure acts both during the phase of intense treatment, leading to non-random distributions of the resistant strain among the infected population, and after the discontinuation of the drug, by affecting the competition dynamics resulting in a mitigation of fitness advantages. As a consequence, we observe both a lower rate of reversion and a lower probability that reversion to sensitivity on the population level occurs after treatment is stopped. Our simulations show that the impact of heterogeneity in the host structure is maximal in the biologically most plausible parameter range, namely when fitness costs of resistance are small. AD - Institute for Integrative Biology, ETH Zurich, Zurich, Switzerland. Department of Civil and Environmental Engineering, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America. AN - 28827796 AU - Liechti, J. I. AU - Leventhal, G. E. AU - Bonhoeffer, S. C2 - PMC5602665 DA - Aug DO - 10.1371/journal.pcbi.1005704 DP - NLM ET - 2017/08/23 IS - 8 J2 - PLoS computational biology KW - Computational Biology Computer Simulation *Disease Transmission, Infectious Drug Resistance/*drug effects Host-Pathogen Interactions/*drug effects Humans *Models, Biological L1 - internal-pdf://0290088832/Liechti-2017-Host population structure impedes.pdf LA - eng N1 - 1553-7358 Liechti, Jonas I ORCID: http://orcid.org/0000-0003-3447-3060 Leventhal, Gabriel E ORCID: http://orcid.org/0000-0002-4463-166X Bonhoeffer, Sebastian ORCID: http://orcid.org/0000-0001-8052-3925 Journal Article United States PLoS Comput Biol. 2017 Aug 21;13(8):e1005704. doi: 10.1371/journal.pcbi.1005704. eCollection 2017 Aug. PY - 2017 SN - 1553-734x SP - e1005704 ST - Host population structure impedes reversion to drug sensitivity after discontinuation of treatment T2 - PLoS Comput Biol TI - Host population structure impedes reversion to drug sensitivity after discontinuation of treatment UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602665/pdf/pcbi.1005704.pdf VL - 13 ID - 594 ER - TY - JOUR AB - In this paper, we develop a mathematical model for a tuberculosis model with constant recruitment and varying total population size by incorporating stochastic perturbations. By constructing suitable stochastic Lyapunov functions, we establish sufficient conditions for the existence of an ergodic stationary distribution as well as extinction of the disease to the stochastic system. (C) 2016 Elsevier B.V. All rights reserved. AD - Northeast Normal Univ, Sch Math & Stat, Changchun 130024, Jilin, Peoples R China Yulin Normal Univ, Guangxi Univ Key Lab Complex Syst Optimizat & Big, Sch Math & Informat Sci, Yulin 537000, Guangxi, Peoples R China King Abdulaziz Univ, Fac Sci, Dept Math, Nonlinear Anal & Appl Math NAAM Res Grp, Jeddah 121589, Saudi Arabia China Univ Petr East China, Coll Sci, Qingdao 266580, Peoples R China Quaid I Azam Univ, Dept Math, Islamabad 45320, Pakistan AN - WOS:000392793500051 AU - Liu, Q. AU - Jiang, D. Q. AU - Shi, N. Z. AU - Hayat, T. AU - Alsaedi, A. DA - Mar 1 DO - 10.1016/j.physa.2016.11.053 J2 - Physica A KW - stochastic tuberculosis model stationary distribution extinction lyapunov function intrinsic transmission dynamics persistent high-incidence low-incidence country sis epidemic model exogenous reinfection control strategies environment immigrants vaccination extinction LA - English N1 - Ei8yg Times Cited:1 Cited References Count:34 PY - 2017 SN - 0378-4371 SP - 518-530 ST - Dynamics of a stochastic tuberculosis model with constant recruitment and varying total population size T2 - Physica a-Statistical Mechanics and Its Applications TI - Dynamics of a stochastic tuberculosis model with constant recruitment and varying total population size UR - ://WOS:000392793500051 VL - 469 ID - 2194 ER - TY - JOUR AB - This study first presents a mathematical model of TB transmission considering BCG vaccination compartment to investigate the transmission dynamics nowadays. Based on data reported by the National Bureau of Statistics of China, the basic reproduction number is estimated approximately as R0=1.1892. To reach the new End TB goal raised by WHO in 2015, considering the health system in China, we design a mixed vaccination strategy. Theoretical analysis indicates that the infectious population asymptotically tends to zero with the new vaccination strategy which is the combination of constant vaccination and pulse vaccination. We obtain that the control of TB is quicker to achieve with the mixed vaccination. The new strategy can make the best of current constant vaccination, and the periodic routine health examination provides an operable environment for implementing pulse vaccination in China. Numerical simulations are provided to illustrate the theoretical results and help to design the final mixed vaccination strategy once the new vaccine comes out. AD - College of Mathematics, Jilin University, Changchun 130012, China. email: siyu15@mails.jlu.edu.cn. AN - 28092959 AU - Liu, S. AU - Li, Y. AU - Bi, Y. AU - Huang, Q. DA - Jun 01 DO - 10.3934/mbe.2017039 DP - NLM ET - 2017/01/18 IS - 3 J2 - Mathematical biosciences and engineering : MBE LA - eng N1 - 1551-0018 Liu, Siyu Li, Yong Bi, Yingjie Huang, Qingdao Journal Article United States Math Biosci Eng. 2017 Jun 1;14(3):695-708. doi: 10.3934/mbe.2017039. PY - 2017 SN - 1547-1063 SP - 695-708 ST - Mixed vaccination strategy for the control of tuberculosis: A case study in China T2 - Math Biosci Eng TI - Mixed vaccination strategy for the control of tuberculosis: A case study in China VL - 14 ID - 773 ER - TY - JOUR AB - TB and HIV infection have the effect of deeply on assault the immune system, since they can afford to weaken host immune respone through a mechanism that has not been fully understood. HIV co-infection is the stongest risk factor for progression of M. tuberculosis to active TB disease in HIV individuals, as well as TB has been accelerated to progression HIV infection. In this paper we create a model of transmission co-infection TB in HIV community, dynamic system with ten compartments built in here. Dynamic analysis in this paper mentioned ranging from disease free equilibrium conditions, endemic equilibrium conditions, basic reproduction ratio, stability analysis and numerical simulation. Basic reproductive ratio were obtained from spectral radius the next generation matrix of the model. Numerical simulations are built to justify the results of the analysis and to see the changes in the dynamics of the population in each compartment. The sensitivity analysis indicates that the parameters affecting the population dynamics of TB in people with HIV infection is parameters rate of progression of individuals from the exposed TB class to the active TB, treatment rate of exposed TB individuals, treatment rate of infectious (active TB) individuals and probability of transmission of TB infection from an infective to a susceptible per contact per unit time. We can conclude that growing number of infections carried by infectious TB in people with HIV infection can lead to increased spread of disease or increase in endemic conditions. AD - Inst Teknol Bandung, Dept Math, Ganesha 10, Bandung 40132, Indonesia AN - WOS:000405094200012 AU - Lusiana, V. AU - Putra, S. AU - Nuraini, N. AU - Soewono, E. DO - Unsp 020012 10.1063/1.4978981 J2 - Aip Conf Proc LA - English N1 - Bi0qk Times Cited:0 Cited References Count:9 AIP Conference Proceedings PY - 2017 SN - 0094-243x ST - Mathematical Modeling of Transmission Co-infection Tuberculosis in HIV Community T2 - Symposium on Biomathematics (Symomath 2016) TI - Mathematical Modeling of Transmission Co-infection Tuberculosis in HIV Community UR - ://WOS:000405094200012 VL - 1825 ID - 4917 ER - TY - JOUR AB - BACKGROUND: Against the backdrop of renewed efforts to control tuberculosis (TB) worldwide, there is a need for improved methods to estimate the public health impact of TB programmes. Such methods should not only address the improved outcomes amongst those receiving care but should also account for the impact of TB services on reducing transmission. METHODS: Vital registration data in India are not sufficiently reliable for estimates of TB mortality. As an alternative approach, we developed a mathematical model of TB transmission dynamics and mortality, capturing the scale-up of DOTS in India, through the rollout of the Revised National TB Control Programme (RNTCP). We used available data from the literature to calculate TB mortality hazards amongst untreated TB; amongst cases treated under RNTCP; and amongst cases treated under non-RNTCP conditions. Using a Bayesian evidence synthesis framework, we combined these data with current estimates for the TB burden in India to calibrate the transmission model. We simulated the national TB epidemic in the presence and absence of the DOTS programme, measuring lives saved as the difference in TB deaths between these scenarios. RESULTS: From 1997 to 2016, India's RNTCP has saved 7.75 million lives (95% Bayesian credible interval 6.29-8.82 million). We estimate that 42% of this impact was due to the 'indirect' effects of the RNTCP in averting transmission as well as improving treatment outcomes. CONCLUSIONS: When expanding high-quality TB services, a substantial proportion of overall impact derives from preventive, as well as curative, benefits. Mathematical models, together with sufficient data, can be a helpful tool in estimating the true population impact of major disease control programmes. AD - Public Health Foundation of India, New Delhi, India. sandip.mandal@phfi.org. Epidemiology and Research Division, National Tuberculosis Institute, Bangalore, India. Public Health Foundation of India, New Delhi, India. Center for Disease Dynamics, Economics, and Policy, Washington, DC, USA. Princeton University, Princeton, NJ, USA. Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College, London, UK. AN - 28253922 AU - Mandal, S. AU - Chadha, V. K. AU - Laxminarayan, R. AU - Arinaminpathy, N. C2 - PMC5335816 DA - Mar 03 DO - 10.1186/s12916-017-0809-5 DP - NLM ET - 2017/03/04 IS - 1 J2 - BMC medicine KW - Bayes Theorem Humans Incidence India/epidemiology Models, Theoretical Prevalence Treatment Outcome Tuberculosis/epidemiology/*mortality/*prevention & control/transmission Deaths averted India Modelling Tuberculosis LA - eng N1 - 1741-7015 Mandal, Sandip Chadha, Vineet K Laxminarayan, Ramanan Arinaminpathy, Nimalan Journal Article England BMC Med. 2017 Mar 3;15(1):47. doi: 10.1186/s12916-017-0809-5. PY - 2017 SN - 1741-7015 SP - 47 ST - Counting the lives saved by DOTS in India: a model-based approach T2 - BMC Med TI - Counting the lives saved by DOTS in India: a model-based approach VL - 15 ID - 732 ER - TY - JOUR AB - In this paper, three-dimensional system of the tuberculosis (TB) model is reduced into a two-dimensional first- order and one-dimensional second-order differential equations. We use the method of Jacobi last multiplier to construct linear Lagrangians of systems of two first- order ordinary differential equations and nonlinear Lagrangian of the corresponding single second-order equation. The Noether's theorem is used for determining conservation laws. We apply the techniques of symmetry analysis to a model to identify the combinations of parameters which lead to the possibility of the linearization of the system and provide the corresponding solutions. AD - Univ Zululand, Sch Math Sci, Private Bag X1001, ZA-3886 Kwa Dlangezwa, Kwazulu Natal, South Africa AN - WOS:000395160400012 AU - Matadi, M. B. DA - Apr DO - Artn 1750042 10.1142/S1793524517500425 IS - 3 J2 - Int J Biomath KW - epidemics symmetry jacobi last multiplier and conservation laws LA - English N1 - Em2qj Times Cited:0 Cited References Count:14 PY - 2017 SN - 1793-5245 ST - Symmetry and conservation laws for tuberculosis model T2 - International Journal of Biomathematics TI - Symmetry and conservation laws for tuberculosis model UR - ://WOS:000395160400012 VL - 10 ID - 4918 ER - TY - JOUR AB - OBJECTIVES Multi-drug resistant tuberculosis (MDR-TB) is a threat to TB control. To guide TB control, it is essential to understand the extent to which and the circumstances in which MDR-TB will replace drug-susceptible TB (DS-TB) as the dominant phenotype. We examined the issue by presenting evidence from genomics, pharmacokinetics and epidemiology studies. We then synthesised this evidence into a mathematical model. METHODS Our model consider two TB strains, one with and one without MDR phenotype. We allowed that intrinsic transmissibility may be different between the two strains, as may the control response including detection rate, treatment failure and default rates. We explored the outcomes in terms of incidence of MDR-TB and time until MDR-TB surpasses DS-TB as the dominant strain. RESULTS AND CONCLUSIONS The ability of MDR-TB to dominate DS-TB was highly sensitive to the relative transmissibility of the resistant strain; however, MDR-TB could dominate even when its transmissibility was modestly reduced (to between 50% and 100% as transmissible as DS-TB strain). Our model suggest that it may take decades or more for strain replacement to occur. We also found that while amplification of resistance is the early cause of MDR-TB, this will rapidly give way to person-to-person transmission. AU - McBryde, Emma S. AU - Meehan, Michael T. AU - Doan, Tan N. AU - Ragonnet, Romain AU - Marais, Ben J. AU - Guernier, Vanina AU - Trauer, James M. DO - 10.1016/j.ijid.2017.01.031 IS - 0 KW - antibiotic resistance communicable disease control mathematical modelling tuberculosis L1 - file:///C:/Users/James/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/McBryde et al. - 2017 - The risk of global epidemic replacement with drug resistant M. tuberculosis strains.pdf PY - 2017 ST - The risk of global epidemic replacement with drug resistant M. tuberculosis strains T2 - International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases TI - The risk of global epidemic replacement with drug resistant M. tuberculosis strains UR - http://www.ncbi.nlm.nih.gov/pubmed/28163165 VL - 0 ID - 3367 ER - TY - JOUR AB - SETTING: Bedaquiline (BDQ) has been approved in India for the treatment of multidrug-resistant tuberculosis (MDR-TB), but is currently recommended for MDR-TB patients who have failed initial treatment with standard regimens. While some have argued that such deferred BDQ use allows a second line of defense with a potent drug, this strategy may not be optimal. OBJECTIVE: To compare several distinct scenarios of BDQ access and use, and their potential impact on the MDR-TB disease burden and the associated net economic benefit in India. METHOD: We used a state-transition model to carry out this evaluation. The scenarios differed in the timing and breadth of BDQ access. RESULTS: The simulations showed that a strategy reliant on reserving the use of BDQ for those who have failed other MDR-TB regimens is likely to result in worse treatment outcomes for patients and in inferior public health outcomes for communities, leading to reduced net monetary benefit. CONCLUSION: Our study suggests that deferring patient access to new drugs such as BDQ until front-line regimens have failed, in order to 'save' these drugs for later use, could be detrimental to patients and to public health, and could reduce the economic benefit of treating MDR-TB. AD - Janssen Global Commercial Strategy Organization, Raritan, New Jersey, USA. Johnson & Johnson Global Public Health, Raritan, New Jersey, USA. SmartAnalyst Inc, New York, New York, USA. Johnson & Johnson India Pvt Limited, Mumbai, India. AN - 28786799 AU - Mehra, M. AU - Kambili, C. AU - Potluri, R. AU - Rhines, A. AU - Singh, V. AU - Thomas, A. DA - Aug 01 DO - 10.5588/ijtld.16.0717 DP - NLM ET - 2017/08/09 IS - 8 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease L1 - internal-pdf://0415019637/s12.pdf LA - eng N1 - 1815-7920 Mehra, M Kambili, C Potluri, R Rhines, A Singh, V Thomas, A Journal Article France Int J Tuberc Lung Dis. 2017 Aug 1;21(8):902-909. doi: 10.5588/ijtld.16.0717. PY - 2017 SN - 1027-3719 SP - 902-909 ST - Modeling the impact of bedaquiline treatment strategies on the multidrug-resistant tuberculosis burden in India T2 - Int J Tuberc Lung Dis TI - Modeling the impact of bedaquiline treatment strategies on the multidrug-resistant tuberculosis burden in India VL - 21 ID - 612 ER - TY - JOUR AB - Modulation of host metabolic machinery by Mycobacterium tuberculosis is a well established phenomenon. In our earlier study (Mehrotra et al., 2014), we observed a marked increase in acetyl-CoA levels in cells bearing virulent M. tuberculosis infections compared to host cells harbouring avirulent infections. The difference was observed inspite of similar levels of total host cellular pyruvate in both infection types. The present study aimed in capturing the cause for such a phenomenon that defines the pathogenicity of M. tuberculosis. Through mathematical model, we dissected the relative importance of virulence mediated effect on Pyruvate dehydrogenase (PDH) activity, rate of acetyl-CoA consumption and mitochondrial pyruvate transporter (MPC) activity in causing the observed outcomes. Simulation results exhibit MPC to be the key regulatory junction perturbed by virulent strains of M. tuberculosis leading to alteration of mitochondrial metabolic flux and regulation of acetyl-CoA formation. As an experimental validation, drug mediated inhibition of MPC activity was sufficient to reduce virulent bacillary loads, pointing towards a possible mechanistic target for drug discovery. AD - International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India. International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India; Drug Discovery Research Centre, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad 121001, India. Drug Discovery Research Centre, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad 121001, India. Electronic address: samrat.chatterjee@thsti.res.in. AN - 28263840 AU - Mehrotra, P. AU - Rao, K. V. S. AU - Chatterjee, S. DA - May DO - 10.1016/j.biosystems.2017.02.003 DP - NLM ET - 2017/03/07 J2 - Bio Systems KW - Acetyl Coenzyme A/metabolism Acrylates/pharmacology Algorithms Anion Transport Proteins/*metabolism Cell Line, Tumor Host-Pathogen Interactions Humans Kinetics Macrophages/*metabolism/*microbiology Mitochondria/drug effects/metabolism Mitochondrial Membrane Transport Proteins/metabolism Mitochondrial Proteins/*metabolism *Models, Theoretical Mycobacterium tuberculosis/pathogenicity/*physiology Pyruvate Dehydrogenase Complex/metabolism Time Factors Tuberculosis/metabolism/microbiology Virulence Acetyl-CoA Host-pathogen interaction Ordinary differential equations Pyruvate LA - eng N1 - 1872-8324 Mehrotra, Parul Rao, Kanury V S Chatterjee, Samrat Journal Article Ireland Biosystems. 2017 May;155:1-9. doi: 10.1016/j.biosystems.2017.02.003. Epub 2017 Mar 2. PY - 2017 SN - 0303-2647 SP - 1-9 ST - A mathematical model predicting host mitochondrial pyruvate transporter activity to be a critical regulator of Mycobacterium tuberculosis pathogenicity T2 - Biosystems TI - A mathematical model predicting host mitochondrial pyruvate transporter activity to be a critical regulator of Mycobacterium tuberculosis pathogenicity VL - 155 ID - 726 ER - TY - JOUR AD - [Menzies, Nicolas A.] Harvard Univ, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Gomez, Gabriella B.; Vassall, Anna] London Sch Hyg & Trop Med, Dept Global Hlth & Dev, London, England. Menzies, NA (reprint author), Harvard Univ, Dept Global Hlth & Populat, Boston, MA 02115 USA. nmenzies@hsph.harvard.edu AN - WOS:000396341700026 AU - Menzies, N. A. AU - Gomez, G. B. AU - Vassall, A. DA - Mar IS - 3 J2 - Lancet Glob. Health KW - south-africa india china Public, Environmental & Occupational Health LA - English M3 - Letter N1 - ISI Document Delivery No.: EN9TE Times Cited: 0 Cited Reference Count: 2 Menzies, Nicolas A. Gomez, Gabriella B. Vassall, Anna 0 2 Elsevier sci ltd Oxford PY - 2017 SN - 2214-109X SP - E269-E269 ST - Modelling approaches for tuberculosis: are they realistic? T2 - Lancet Global Health TI - Modelling approaches for tuberculosis: are they realistic? UR - ://WOS:000396341700026 VL - 5 ID - 5027 ER - TY - JOUR AD - [Moghadas, Seyed M.] York Univ, Agent Based Modelling Lab, Toronto, ON M3J 1P3, Canada. Moghadas, SM (reprint author), York Univ, Agent Based Modelling Lab, Toronto, ON M3J 1P3, Canada. moghadas@yorku.ca AN - WOS:000395719100001 AU - Moghadas, S. M. DO - 10.1080/08898480.2015.1054222 IS - 1 J2 - Math. Popul. Stud. KW - drug-resistant tuberculosis south-africa Demography Mathematics Mathematical Methods In Social Sciences LA - English M3 - Article N1 - ISI Document Delivery No.: EN0SE Times Cited: 0 Cited Reference Count: 10 Moghadas, Seyed M. 0 1 Taylor & francis inc Philadelphia 1547-724x S1 PY - 2017 SN - 0889-8480 SP - 1-2 ST - Mathematical modeling of tuberculosis T2 - Mathematical Population Studies TI - Mathematical modeling of tuberculosis UR - ://WOS:000395719100001 VL - 24 ID - 5064 ER - TY - JOUR AB - We derive and analyze a tuberculosis (TB) model including exogenous re-infection and endogenous reactivation, and the re-infection among the treated individuals. The disease-free equilibrium and the existence criterion of endemic equilibrium are investigated. The basic reproduction number $$R_0 $$ R 0 is derived and it is found that the disease-free equilibrium is stable when $$R_0 <1$$ R 0 < 1 , unstable for $$R_0 >1$$ R 0 > 1 , and the system undergoes a transcritical bifurcation at the disease-free equilibrium when $$R_0 =1$$ R 0 = 1 . Furthermore, for $$R_0 <1$$ R 0 < 1 , there are two endemic equilibria, one of which is stable and other one is unstable, indicating the occurrence of backward bifurcation. The local stability analysis of the disease-free and the endemic equilibrium is shown. Also, we studied the sensitivity analysis of the system in refer to some crucial model parameters and the sensitivity indices of $$R_0$$ R 0 to parameters for the TB model are obtained. Using Pontryagin’s maximum principle, we have discussed about the optimal control of the disease. Various simulation works are given throughout the paper to support our analytical results. AU - Mondal, Prasanta Kumar AU - Kar, T. K. DA - June 01 DO - 10.1007/s40435-015-0176-z IS - 2 LB - Mondal2017 M3 - journal article PY - 2017 SN - 2195-2698 SP - 367-380 ST - Optimal treatment control and bifurcation analysis of a tuberculosis model with effect of multiple re-infections T2 - International Journal of Dynamics and Control TI - Optimal treatment control and bifurcation analysis of a tuberculosis model with effect of multiple re-infections UR - https://doi.org/10.1007/s40435-015-0176-z VL - 5 ID - 4926 ER - TY - JOUR AB - BACKGROUND: The transmission dynamics of Tuberculosis (TB) involve complex epidemiological and socio-economical interactions between individuals living in highly distinct regional conditions. The level of exogenous reinfection and first time infection rates within high-incidence settings may influence the impact of control programs on TB prevalence. The impact that effective population size and the distribution of individuals' residence times in different patches have on TB transmission and control are studied using selected scenarios where risk is defined by the estimated or perceive first time infection and/or exogenous re-infection rates. METHODS: This study aims at enhancing the understanding of TB dynamics, within simplified, two patch, risk-defined environments, in the presence of short term mobility and variations in reinfection and infection rates via a mathematical model. The modeling framework captures the role of individuals' 'daily' dynamics within and between places of residency, work or business via the average proportion of time spent in residence and as visitors to TB-risk environments (patches). As a result, the effective population size of Patch i (home of i-residents) at time t must account for visitors and residents of Patch i, at time t. RESULTS: The study identifies critical social behaviors mechanisms that can facilitate or eliminate TB infection in vulnerable populations. The results suggest that short-term mobility between heterogeneous patches contributes to significant overall increases in TB prevalence when risk is considered only in terms of direct new infection transmission, compared to the effect of exogenous reinfection. Although, the role of exogenous reinfection increases the risk that come from large movement of individuals, due to catastrophes or conflict, to TB-free areas. CONCLUSIONS: The study highlights that allowing infected individuals to move from high to low TB prevalence areas (for example via the sharing of treatment and isolation facilities) may lead to a reduction in the total TB prevalence in the overall population. The higher the population size heterogeneity between distinct risk patches, the larger the benefit (low overall prevalence) under the same "traveling" patterns. Policies need to account for population specific factors (such as risks that are inherent with high levels of migration, local and regional mobility patterns, and first time infection rates) in order to be long lasting, effective and results in low number of drug resistant cases. AD - Simon A. Levin Mathematical, Computational and Modeling Sciences Center, Arizona State University, Tempe, AZ, US. Department of Mathematical Sciences, University of Cincinnati, Cincinnati, OH, USA. Department of Mathematics and Physics, University of Puerto Rico, Cayey, PR, USA. Department of Mathematics & Center for Computational and Applied Mathematics, California State University, Fullerton, CA, USA. Simon A. Levin Mathematical, Computational and Modeling Sciences Center, Arizona State University, Tempe, AZ, US. amubayi@asu.edu. School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, US. amubayi@asu.edu. School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, US. Rector's Office, Yachay Tech University, Urcuqui, Ecuador. AN - 28129769 AU - Moreno, V. AU - Espinoza, B. AU - Barley, K. AU - Paredes, M. AU - Bichara, D. AU - Mubayi, A. AU - Castillo-Chavez, C. C2 - PMC5273827 DA - Jan 28 DO - 10.1186/s12976-017-0049-6 DP - NLM ET - 2017/01/29 IS - 1 J2 - Theoretical biology & medical modelling KW - Direct first time infection rate Exogenous re-infection Heterogeneity Metapopulation model Residence times Tuberculosis L1 - internal-pdf://3445412210/Moreno-2017-The role of mobility and health di.pdf LA - eng N1 - 1742-4682 Moreno, Victor Espinoza, Baltazar Barley, Kamal Paredes, Marlio Bichara, Derdei Mubayi, Anuj ORCID: http://orcid.org/0000-0003-3936-3055 Castillo-Chavez, Carlos R01 GM100471/GM/NIGMS NIH HHS/United States R01 LM012080/LM/NLM NIH HHS/United States Journal Article England Theor Biol Med Model. 2017 Jan 28;14(1):3. doi: 10.1186/s12976-017-0049-6. PY - 2017 SN - 1742-4682 SP - 3 ST - The role of mobility and health disparities on the transmission dynamics of Tuberculosis T2 - Theor Biol Med Model TI - The role of mobility and health disparities on the transmission dynamics of Tuberculosis UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5273827/pdf/12976_2017_Article_49.pdf VL - 14 ID - 759 ER - TY - JOUR AB - BACKGROUND: In North America, tuberculosis incidence is now very low and risk to healthcare workers has fallen. Indeed, recent cohort data question routine annual tuberculosis screening in this context. We compared the cost-effectiveness of three potential strategies for ongoing screening of North American healthcare workers at risk of exposure. The analysis did not evaluate the cost-effectiveness of screening at hiring, and considered only workers with negative baseline tests. METHODS: A decision analysis model simulated a hypothetical cohort of 1000 workers following negative baseline tests, considering duties, tuberculosis exposure, testing and treatment. Two tests were modelled, the tuberculin skin test (TST) and QuantiFERON(R)-TB-Gold In-Tube (QFT). Three screening strategies were compared: (1) annual screening, where workers were tested yearly; (2) targeted screening, where workers with high-risk duties (e.g. respiratory therapy) were tested yearly and other workers only after recognised exposure; and (3) post exposure-only screening, where all workers were tested only after recognised exposure. Workers with high-risk duties had 1% annual risk of infection, while workers with standard patient care duties had 0.3%. In an alternate higher-risk scenario, the corresponding annual risks of infection were 3% and 1%, respectively. We projected costs, morbidity, quality-adjusted survival and mortality over 20 years after hiring. The analysis used the healthcare system perspective and a 3% annual discount rate. RESULTS: Over 20 years, annual screening with TST yielded an expected 2.68 active tuberculosis cases/1000 workers, versus 2.83 for targeted screening and 3.03 for post-exposure screening only. In all cases, annual screening was associated with poorer quality-adjusted survival, i.e. lost quality-adjusted life years, compared to targeted or post-exposure screening only. The annual TST screening strategy yielded an incremental cost estimate of $1,717,539 per additional case prevented versus targeted TST screening, which in turn cost an incremental $426,678 per additional case prevented versus post-exposure TST screening only. With the alternate "higher-risk" scenario, the annual TST strategy cost an estimated $426,678 per additional case prevented versus the targeted TST strategy, which cost an estimated $52,552 per additional case prevented versus post-exposure TST screening only. In all cases, QFT was more expensive than TST, with no or limited added benefit. Sensitivity analysis suggested that, even with limited exposure recognition, annual screening was poorly cost-effective. CONCLUSIONS: For most North American healthcare workers, annual tuberculosis screening appears poorly cost-effective. Reconsideration of screening practices is warranted. AD - Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, Montreal, QC, Canada. Faculty of Medicine, McGill University, Montreal, QC, Canada. McGill International TB Centre, McGill University, Montreal, Quebec, Canada. Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, Montreal, QC, Canada. kevin.schwartzman@mcgill.ca. Faculty of Medicine, McGill University, Montreal, QC, Canada. kevin.schwartzman@mcgill.ca. McGill International TB Centre, McGill University, Montreal, Quebec, Canada. kevin.schwartzman@mcgill.ca. McGill University Health Centre, 1001 boulevard Decarie, Room D05.2511, Montreal, H4A 3J1, Quebec, Canada. kevin.schwartzman@mcgill.ca. Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA. AN - 28514962 AU - Mullie, G. A. AU - Schwartzman, K. AU - Zwerling, A. AU - N'Diaye, D. S. C2 - PMC5436424 DA - May 17 DO - 10.1186/s12916-017-0865-x IS - 1 KW - Adult Cost-Benefit Analysis Decision Support Techniques Female *Health Personnel Humans Incidence Latent Tuberculosis/*diagnosis/economics/epidemiology Male Mass Screening/economics Quality-Adjusted Life Years Tuberculin Test Cost-effectiveness Health personnel Latent tuberculosis Screening L1 - internal-pdf://0793847271/Mullie-2017-Revisiting annual screening for la.pdf N1 - Mullie, Guillaume A Schwartzman, Kevin Zwerling, Alice N'Diaye, Dieynaba S eng England 2017/05/19 06:00 BMC Med. 2017 May 17;15(1):104. doi: 10.1186/s12916-017-0865-x. PY - 2017 SN - 1741-7015 (Electronic) 1741-7015 (Linking) SP - 104 ST - Revisiting annual screening for latent tuberculosis infection in healthcare workers: a cost-effectiveness analysis T2 - BMC Med TI - Revisiting annual screening for latent tuberculosis infection in healthcare workers: a cost-effectiveness analysis UR - https://www.ncbi.nlm.nih.gov/pubmed/28514962 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436424/pdf/12916_2017_Article_865.pdf VL - 15 ID - 2175 ER - TY - JOUR AB - We design and analyze an unconditionally convergent nonstandard finite-difference method to study transmission dynamics of a mathematical model of HIV-TB co-infection. The dynamics of this model are studied using the qualitative theory of dynamical systems. These qualitative features of the continuous model are preserved by the numerical method that we propose in this paper. This method also preserves positivity of the solution which is one of the essential requirements when modelling epidemic diseases. Furthermore, we show that the numerical method is unconditionally stable. Competitive numerical results confirming theoretical investigations are provided. Comparisons are also made with other conventional approaches that are routinely used to solve these types of problems. AD - Univ theWestern Cape, Dept Math & Appl Math, Bellville, South Africa Stellenbosch Univ, DST NRF Ctr Excellence Epidemiol Modelling & Anal, Stellenbosch, South Africa Univ Pretoria, Fac Nat & Agr Sci, Dept Math & Appl Math, Pretoria, South Africa AN - WOS:000407382400008 AU - Obaid, H. A. AU - Ouifki, R. AU - Patidar, K. C. DO - 10.1080/10236198.2017.1318859 IS - 6 J2 - J Differ Equ Appl KW - hiv-tb co-infection dynamical systems nonstandard finite difference methods convergence and stability analysis autonomous dynamical-systems numerical-methods denominator functions equations schemes tuberculosis delay LA - English N1 - Fd2rl Times Cited:0 Cited References Count:34 PY - 2017 SN - 1023-6198 SP - 1105-1132 ST - A nonstandard finite difference method for solving a mathematical model of HIV-TB co-infection T2 - Journal of Difference Equations and Applications TI - A nonstandard finite difference method for solving a mathematical model of HIV-TB co-infection UR - ://WOS:000407382400008 VL - 23 ID - 4919 ER - TY - JOUR AB - BACKGROUND: There is an urgent need for improved estimations of the burden of tuberculosis (TB). OBJECTIVE: To develop a new quantitative method based on mathematical modelling, and to demonstrate its application to TB in India. DESIGN: We developed a simple model of TB transmission dynamics to estimate the annual incidence of TB disease from the annual risk of tuberculous infection and prevalence of smear-positive TB. We first compared model estimates for annual infections per smear-positive TB case using previous empirical estimates from China, Korea and the Philippines. We then applied the model to estimate TB incidence in India, stratified by urban and rural settings. RESULTS: Study model estimates show agreement with previous empirical estimates. Applied to India, the model suggests an annual incidence of smear-positive TB of 89.8 per 100 000 population (95%CI 56.8-156.3). Results show differences in urban and rural TB: while an urban TB case infects more individuals per year, a rural TB case remains infectious for appreciably longer, suggesting the need for interventions tailored to these different settings. CONCLUSIONS: Simple models of TB transmission, in conjunction with necessary data, can offer approaches to burden estimation that complement those currently being used. AD - Public Health Foundation of India, New Delhi. Epidemiology and Research Division, National Tuberculosis Institute, Bangalore, India. Public Health Foundation of India, New Delhi, Center for Disease Dynamics, Economics & Policy, Washington, DC, Princeton Environmental Institute, Princeton, New Jersey, USA. Public Health Foundation of India, New Delhi, Department of Infectious Disease Epidemiology, Imperial College London, London, UK. AN - 28284250 AU - Pandey, S. AU - Chadha, V. K. AU - Laxminarayan, R. AU - Arinaminpathy, N. C2 - PMC5347365 DA - Apr 01 DO - 10.5588/ijtld.16.0182 DP - NLM ET - 2017/03/13 IS - 4 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease LA - eng N1 - 1815-7920 Pandey, S Chadha, V K Laxminarayan, R Arinaminpathy, N Journal Article France Int J Tuberc Lung Dis. 2017 Apr 1;21(4):366-374. doi: 10.5588/ijtld.16.0182. PY - 2017 SN - 1027-3719 SP - 366-374 ST - Estimating tuberculosis incidence from primary survey data: a mathematical modeling approach T2 - Int J Tuberc Lung Dis TI - Estimating tuberculosis incidence from primary survey data: a mathematical modeling approach VL - 21 ID - 719 ER - TY - JOUR AB - OBJECTIVE: Pharmaceutical treatment of latent tuberculosis infection (LTBI) reduces the risk of progression to active tuberculosis (TB); however, poor adherence tempers the protective effect. We aimed to estimate the health burden of non-adherence, the maximum allowable cost of hypothetical new adherence interventions to be cost-effective and the potential value of existing adherence interventions for patients with low-risk LTBI in Canada. DESIGN: A microsimulation model of LTBI progression over 25 years. SETTING: General practice in Canada. PARTICIPANTS: Individuals with LTBI who are initiating drug therapy. INTERVENTIONS: A hypothetical intervention with a range of effectiveness was evaluated. Existing drug adherence interventions including peer support, two-way text messaging support, enhanced adherence counselling and adherence incentives were also evaluated. PRIMARY AND SECONDARY OUTCOME MEASURES: Simulation outcomes included healthcare costs, TB incidence, TB deaths and quality-adjusted life years (QALYs). Base case results were interpreted against a willingness-to-pay threshold of $C50 000/QALY. RESULTS: Compared with current adherence levels, full adherence to LTBI drug therapy could reduce new TB cases from 90.3 cases per 100 000 person-years to 35.9 cases per 100 000 person-years and reduce TB-related deaths from 7.9 deaths per 100 000 person-years to 3.1 deaths per 100 000 person-years. An intervention that increases relative adherence by 40% would bring the population near full adherence to drug therapy and could have a maximum allowable annual cost of approximately $C450 per person to be cost-effective. Based on estimates of effect sizes and costs of existing adherence interventions, we found that they yielded between 900 and 2400 additional QALYs per million people, reduced TB deaths by 5%-25% and were likely to be cost-effective over 25 years. CONCLUSION: Full adherence could reduce the number of future TB cases by nearly 60%, offsetting TB-related costs and health burden. Several existing interventions are could be cost-effective to help achieve this goal. AD - Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada. AN - 28918407 AU - Patel, A. R. AU - Campbell, J. R. AU - Sadatsafavi, M. AU - Marra, F. AU - Johnston, J. C. AU - Smillie, K. AU - Lester, R. T. C2 - PMC5640098 DA - Sep 15 DO - 10.1136/bmjopen-2016-015108 IS - 9 KW - adherence interventions burden of disease cost-effectiveness health economics public health tuberculosis International Health Society and WelTel, which develop and implement mobile health solutions. The remaining authors declare that they have no competing interests. L1 - internal-pdf://4027829007/Patel-2017-Burden of non-adherence to latent t.pdf N1 - Patel, Anik R Campbell, Jonathon R Sadatsafavi, Mohsen Marra, Fawziah Johnston, James C Smillie, Kirsten Lester, Richard T eng England 2017/09/18 06:00 BMJ Open. 2017 Sep 15;7(9):e015108. doi: 10.1136/bmjopen-2016-015108. PY - 2017 SN - 2044-6055 (Electronic) 2044-6055 (Linking) SP - e015108 ST - Burden of non-adherence to latent tuberculosis infection drug therapy and the potential cost-effectiveness of adherence interventions in Canada: a simulation study T2 - BMJ Open TI - Burden of non-adherence to latent tuberculosis infection drug therapy and the potential cost-effectiveness of adherence interventions in Canada: a simulation study UR - https://www.ncbi.nlm.nih.gov/pubmed/28918407 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640098/pdf/bmjopen-2016-015108.pdf VL - 7 ID - 2168 ER - TY - JOUR AB - This chapter reviews the use of mathematical and computational models to facilitate understanding of the epidemiology and evolution of Mycobacterium tuberculosis. First, we introduce general epidemiological models, and describe their use with respect to epidemiological dynamics of a single strain and of multiple strains of M. tuberculosis. In particular, we discuss multi-strain models that include drug sensitivity and drug resistance. Second, we describe models for the evolution of M. tuberculosis within and between hosts, and how the resulting diversity of strains can be assessed by considering the evolutionary relationships among different strains. Third, we discuss developments in integrating evolutionary and epidemiological models to analyse M. tuberculosis genetic sequencing data. We conclude the chapter with a discussion of the practical implications of modelling - particularly modelling strain diversity - for controlling the spread of tuberculosis, and future directions for research in this area. AD - Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland. School of Public Health and Community Medicine, UNSW Sydney, Sydney, NSW, Australia. School of Biotechnology & Biomolecular Sciences, and Evolution & Ecology Research Centre, UNSW Sydney, Sydney, NSW, Australia. m.tanaka@unsw.edu.au. AN - 29116641 AU - Pecerska, J. AU - Wood, J. AU - Tanaka, M. M. AU - Stadler, T. DO - 10.1007/978-3-319-64371-7_15 KW - Compartmental model Heterogeneity Molecular epidemiology Phylodynamics Phylogeny Population biology Strain variation N1 - Pecerska, Julija Wood, James Tanaka, Mark M Stadler, Tanja eng 2017/11/09 06:00 Adv Exp Med Biol. 2017;1019:281-307. doi: 10.1007/978-3-319-64371-7_15. PY - 2017 SN - 0065-2598 (Print) 0065-2598 (Linking) SP - 281-307 ST - Mathematical Models for the Epidemiology and Evolution of Mycobacterium tuberculosis T2 - Adv Exp Med Biol TI - Mathematical Models for the Epidemiology and Evolution of Mycobacterium tuberculosis UR - https://www.ncbi.nlm.nih.gov/pubmed/29116641 https://link.springer.com/chapter/10.1007%2F978-3-319-64371-7_15 VL - 1019 ID - 4814 ER - TY - JOUR AB - INTRODUCTION: Despite the close link between tuberculosis (TB) and poverty, most mathematical models of TB have not addressed underlying social and structural determinants. OBJECTIVE: To review studies employing mathematical modelling to evaluate the epidemiological impact of the structural determinants of TB. METHODS: We systematically searched PubMed and personal libraries to identify eligible articles. We extracted data on the modelling techniques employed, research question, types of structural determinants modelled and setting. RESULTS: From 232 records identified, we included eight articles published between 2008 and 2015; six employed population-based dynamic TB transmission models and two non-dynamic analytic models. Seven studies focused on proximal TB determinants (four on nutritional status, one on wealth, one on indoor air pollution, and one examined overcrowding, socio-economic and nutritional status), and one focused on macro-economic influences. CONCLUSIONS: Few modelling studies have attempted to evaluate structural determinants of TB, resulting in key knowledge gaps. Despite the challenges of modelling such a complex system, models must broaden their scope to remain useful for policy making. Given the intersectoral nature of the interrelations between structural determinants and TB outcomes, this work will require multidisciplinary collaborations. A useful starting point would be to focus on developing relatively simple models that can strengthen our knowledge regarding the potential effect of the structural determinants on TB outcomes. AD - TB Modelling Group, TB Centre and Centre for the Mathematical Modelling of Infectious Diseases, Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London. Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London. Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK. World Health Organization, Global Tuberculosis Programme, Geneva, Switzerland, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. World Health Organization, Global Tuberculosis Programme, Geneva, Switzerland. KNCV, Tuberculosis Foundation, The Hague, The Netherlands. AN - 28826444 AU - Pedrazzoli, D. AU - Boccia, D. AU - Dodd, P. J. AU - Lonnroth, K. AU - Dowdy, D. W. AU - Siroka, A. AU - Kimerling, M. E. AU - White, R. G. AU - Houben, Rmgj C2 - PMC5566999 DA - Sep 01 DO - 10.5588/ijtld.16.0906 DP - NLM ET - 2017/08/23 IS - 9 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease LA - eng N1 - 1815-7920 Pedrazzoli, D Boccia, D Dodd, P J Lonnroth, K Dowdy, D W Siroka, A Kimerling, M E White, R G Houben, R M G J Journal Article France Int J Tuberc Lung Dis. 2017 Sep 1;21(9):957-964. doi: 10.5588/ijtld.16.0906. PY - 2017 SN - 1027-3719 SP - 957-964 ST - Modelling the social and structural determinants of tuberculosis: opportunities and challenges T2 - Int J Tuberc Lung Dis TI - Modelling the social and structural determinants of tuberculosis: opportunities and challenges VL - 21 ID - 598 ER - TY - JOUR AB - Multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB) represent an important challenge for global tuberculosis (TB) control. The high rates of MDR/RR-TB observed among re-treatment cases can arise from diverse pathways: de novo amplification during initial treatment, inappropriate treatment of undiagnosed MDR/RR-TB, relapse despite appropriate treatment, or reinfection with MDR/RR-TB. Mathematical modelling allows quantification of the contribution made by these pathways in different settings. This information provides valuable insights for TB policy-makers, allowing better contextualised solutions. However, mathematical modelling outputs need to consider local data and be easily accessible to decision makers in order to improve their usefulness. We present a user-friendly web-based modelling interface, which can be used by people without technical knowledge. Users can input their own parameter values and produce estimates for their specific setting. This innovative tool provides easy access to mathematical modelling outputs that are highly relevant to national TB control programs. In future, the same approach could be applied to a variety of modelling applications, enhancing local decision making. AD - Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia. romain.ragonnet@burnet.edu.au. Burnet Institute, 85 Commercial Road, Melbourne, VIC, 3141, Australia. romain.ragonnet@burnet.edu.au. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia. Victorian Tuberculosis Program, Melbourne Health, Melbourne, Australia. School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute, Melbourne, Australia. Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, VIC, Australia. Marie Bashir Institute and the Centre for Research Excellence in Tuberculosis, University of Sydney, Sydney, Australia. Burnet Institute, 85 Commercial Road, Melbourne, VIC, 3141, Australia. Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Australia. AN - 28558651 AU - Ragonnet, R. AU - Trauer, J. M. AU - Denholm, J. T. AU - Marais, B. J. AU - McBryde, E. S. C2 - PMC5450394 DA - May 30 DO - 10.1186/s12879-017-2478-6 DP - NLM ET - 2017/06/01 IS - 1 J2 - BMC infectious diseases KW - Antitubercular Agents/therapeutic use Decision Making Drug Resistance, Bacterial/*drug effects Humans *Models, Theoretical Precision Medicine/methods Retreatment Rifampin/therapeutic use Tuberculosis/*drug therapy/microbiology Tuberculosis, Multidrug-Resistant/drug therapy User-Computer Interface Causal pathway Misdiagnosis Multidrug-resistant tuberculosis Re-treatment Tuberculosis User Interface L1 - internal-pdf://0707601559/Ragonnet-2017-A user-friendly mathematical mod.pdf LA - eng N1 - 1471-2334 Ragonnet, Romain ORCID: http://orcid.org/0000-0001-8520-2362 Trauer, James M Denholm, Justin T Marais, Ben J McBryde, Emma S Journal Article England BMC Infect Dis. 2017 May 30;17(1):374. doi: 10.1186/s12879-017-2478-6. PY - 2017 SN - 1471-2334 SP - 374 ST - A user-friendly mathematical modelling web interface to assist local decision making in the fight against drug-resistant tuberculosis T2 - BMC Infect Dis TI - A user-friendly mathematical modelling web interface to assist local decision making in the fight against drug-resistant tuberculosis UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450394/pdf/12879_2017_Article_2478.pdf VL - 17 ID - 658 ER - TY - JOUR AB - BACKGROUND: Globally 3.9% of new and 21% of re-treatment tuberculosis (TB) cases are multidrug-resistant or rifampicin-resistant (MDR/RR), which is often interpreted as evidence that drug resistance results mainly from poor treatment adherence. This study aims to assess the respective contributions of the different causal pathways leading to MDR/RR-TB at re-treatment. METHODS: We use a simple mathematical model to simulate progression between the different stages of disease and treatment for patients diagnosed with TB. The model is parameterised using region and country-specific TB disease burden data reported by the World Health Organization (WHO). The contributions of four separate causal pathways to MDR/RR-TB among re-treatment cases are estimated: I) initial drug-susceptible TB with resistance amplification during treatment; II) initial MDR/RR-TB inappropriately treated as drug-susceptible TB; III) MDR/RR-TB relapse despite appropriate treatment; and IV) re-infection with MDR/RR-TB. RESULTS: At the global level, Pathways I, II, III and IV contribute 38% (28-49, 95% Simulation Interval), 44% (36-52, 95% SI), 6% (5-7, 95% SI) and 12% (7-19, 95% SI) respectively to the burden of MDR/RR-TB among re-treatment cases. Pathway II is dominant in the Western Pacific (74%; 67-80 95% SI), Eastern Mediterranean (68%; 60-74 95% SI) and European (53%; 48-59 95% SI) regions, while Pathway I makes the greatest contribution in the American (53%; 40-66 95% SI), African (43%; 28-61 95% SI) and South-East Asian (50%; 40-59 95% SI) regions. CONCLUSIONS: Globally, failure to diagnose MDR/RR-TB at first presentation is the leading cause of the high proportion of MDR/RR-TB among re-treatment cases. These findings highlight the need for contextualised solutions to limit the impact and spread of MDR/RR-TB. AD - Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia. romain.ragonnet@burnet.edu.au. Centre for Population Health, Burnet Institute, 85 Commercial Road, Melbourne, 3141, VIC, Australia. romain.ragonnet@burnet.edu.au. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia. Centre for Population Health, Burnet Institute, 85 Commercial Road, Melbourne, 3141, VIC, Australia. Victorian Tuberculosis Program, Melbourne Health, Melbourne, Australia. School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute, Melbourne, Australia. Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, VIC, Australia. Marie Bashir Institute and the Centre for Research Excellence in Tuberculosis, University of Sydney, Sydney, Australia. Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Australia. AN - 28061832 AU - Ragonnet, R. AU - Trauer, J. M. AU - Denholm, J. T. AU - Marais, B. J. AU - McBryde, E. S. C2 - PMC5217596 DA - Jan 06 DO - 10.1186/s12879-016-2171-1 DP - NLM ET - 2017/01/08 IS - 1 J2 - BMC infectious diseases KW - Antitubercular Agents/*therapeutic use Humans *Models, Statistical Retreatment Rifampin/*therapeutic use Tuberculosis, Multidrug-Resistant/*drug therapy/epidemiology/microbiology Tuberculosis, Pulmonary/*drug therapy/epidemiology/microbiology World Health Organization Causal pathway Drug resistance amplification Inappropriate therapy Misdiagnosis Multidrug-resistant tuberculosis Re-treatment Tuberculosis L1 - internal-pdf://2703559381/Ragonnet-2017-High rates of multidrug-resistan.pdf LA - eng N1 - 1471-2334 Ragonnet, Romain Trauer, James M Denholm, Justin T Marais, Ben J McBryde, Emma S Journal Article England BMC Infect Dis. 2017 Jan 6;17(1):36. doi: 10.1186/s12879-016-2171-1. PY - 2017 SN - 1471-2334 SP - 36 ST - High rates of multidrug-resistant and rifampicin-resistant tuberculosis among re-treatment cases: where do they come from? T2 - BMC Infect Dis TI - High rates of multidrug-resistant and rifampicin-resistant tuberculosis among re-treatment cases: where do they come from? UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217596/pdf/12879_2016_Article_2171.pdf VL - 17 ID - 780 ER - TY - JOUR AB - SETTING: Isoniazid preventive therapy (IPT) is effective for preventing active tuberculosis (TB), although its mechanism of action is poorly understood and the optimal disease burden for IPT use has not been defined. OBJECTIVE: To describe the relationship between TB incidence and IPT effectiveness. METHODS: We constructed a model of TB transmission dynamics to investigate IPT effectiveness under various epidemiological settings. The model structure was intended to be highly adaptable to uncertainty in both input parameters and the mechanism of action of IPT. To determine the optimal setting for IPT use, we identified the lowest number needed to treat (NNT) with IPT to prevent one case of active TB. RESULTS: We found that the NNT as a function of TB incidence shows a 'U-shape', whereby IPT impact is greatest at an intermediate incidence and attenuated at both lower and higher incidence levels. This U-shape was observed over a broad range of parameter values; the optimal TB incidence was between 500 and 900 cases per 100 000 per year. CONCLUSIONS: TB burden is a critical factor to consider when making decisions about communitywide implementation of IPT. We believe that the total disease burden should not preclude programmatic application of IPT. AD - Department of Medicine, Royal Melbourne Hospital/Western Hospital, University of Melbourne, Parkville, Centre for Population Health, Burnet Institute, Melbourne, Australia. Department of Medicine, Royal Melbourne Hospital/Western Hospital, University of Melbourne, Parkville, Australia; Centre for Population Health, Burnet Institute, Melbourne, Victorian Tuberculosis Program, Melbourne Health, Melbourne, Victoria, Australia. Department of Medicine, Royal Melbourne Hospital/Western Hospital, University of Melbourne, Parkville, Centre for Population Health, Burnet Institute, Melbourne, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia. Department of Infectious Disease Epidemiology, TB Modelling Group, TB Centre, and Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, UK. Victorian Tuberculosis Program, Melbourne Health, Melbourne, Victoria, Australia; Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, Victoria, Australia. Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia, USA. AN - 28157466 AU - Ragonnet, R. AU - Trauer, J. M. AU - McBryde, E. S. AU - Houben, R. M. AU - Denholm, J. T. AU - Handel, A. AU - Sumner, T. C2 - PMC5166561 DA - Jan 01 DO - 10.5588/ijtld.16.0297 DP - NLM ET - 2017/02/06 IS - 1 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease LA - eng N1 - 1815-7920 Ragonnet, R Trauer, J M McBryde, E S Houben, R M G J Denholm, J T Handel, A Sumner, T Journal Article France Int J Tuberc Lung Dis. 2017 Jan 1;21(1):60-66. doi: 10.5588/ijtld.16.0297. PY - 2017 SN - 1027-3719 SP - 60-66 ST - Is IPT more effective in high-burden settings? Modelling the effect of tuberculosis incidence on IPT impact T2 - Int J Tuberc Lung Dis TI - Is IPT more effective in high-burden settings? Modelling the effect of tuberculosis incidence on IPT impact VL - 21 ID - 749 ER - TY - JOUR AB - Although different structures are used in modern tuberculosis (TB) models to simulate TB latency, it remains unclear whether they are all capable of reproducing the particular activation dynamics empirically observed. We aimed to determine which of these structures replicate the dynamics of progression accurately. We reviewed 88 TB-modelling articles and classified them according to the latency structure employed. We then fitted these different models to the activation dynamics observed from 1352 infected contacts diagnosed in Victoria (Australia) and Amsterdam (Netherlands) to obtain parameter estimates. Six different model structures were identified, of which only those incorporating two latency compartments were capable of reproducing the activation dynamics empirically observed. We found important differences in parameter estimates by age. We also observed marked differences between our estimates and the parameter values used in many previous models. In particular, when two successive latency phases are considered, the first period should have a duration that is much shorter than that used in previous studies. In conclusion, structures incorporating two latency compartments and age-stratification should be employed to accurately replicate the dynamics of TB latency. We provide a catalogue of parameter values and an approach to parameter estimation from empiric data for calibration of future TB-models. AD - Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Australia; Burnet Institute, Australia. Electronic address: romain.ragonnet@burnet.edu.au. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Australia; School of Population Health and Preventive Medicine, Monash University, Australia; Victorian Tuberculosis Program, Melbourne, Australia. Burnet Institute, Australia; School of Population Health and Preventive Medicine, Monash University, Australia. Australian Institute of Tropical Health and Medicine, James Cook University, Australia. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Australia; Victorian Tuberculosis Program, Melbourne, Australia; Royal Melbourne Hospital, Melbourne, Australia. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Australia. AN - 28641948 AU - Ragonnet, R. AU - Trauer, J. M. AU - Scott, N. AU - Meehan, M. T. AU - Denholm, J. T. AU - McBryde, E. S. DA - Jun 16 DO - 10.1016/j.epidem.2017.06.002 DP - NLM ET - 2017/06/24 J2 - Epidemics KW - Mathematical modelling Parameter estimation Risk of disease activation Tuberculosis latency LA - eng N1 - 1878-0067 Ragonnet, Romain Trauer, James M Scott, Nick Meehan, Michael T Denholm, Justin T McBryde, Emma S Journal Article Netherlands Epidemics. 2017 Jun 16. pii: S1755-4365(17)30017-8. doi: 10.1016/j.epidem.2017.06.002. PY - 2017 SN - 1878-0067 ST - Optimally capturing latency dynamics in models of tuberculosis transmission T2 - Epidemics TI - Optimally capturing latency dynamics in models of tuberculosis transmission ID - 637 ER - TY - JOUR AB - Tuberculosis (TB) is a disease that is infected by the bacteria Mycobacterium tuberculosis. The World Health Organization (WHO) recommends to implement the Baccilus Calmete Guerin (BCG) vaccine in toddler aged two to three months to be protected from the infection. This research explores the numerical simulation of forward-backward difference approximation method on the model of TB transmission considering this vaccination program. The model considers five compartments of sub-populations, i.e. susceptible, vaccinated, exposed, infected, and recovered human sub-populations. We consider here the vaccination as a control variable. The results of the simulation showed that vaccination can indeed reduce the number of infected human population. AD - Padjadjaran State Univ, Dept Math, Jl Raya Bandung Sumedang Km 21, Jatinangor 45363, Indonesia AN - WOS:000405094200020 AU - Rahmah, Z. AU - Subartini, B. AU - Djauhari, E. AU - Anggriani, N. AU - Supriatna, A. K. DO - Unsp 020020 10.1063/1.4978989 J2 - Aip Conf Proc LA - English N1 - Bi0qk Times Cited:0 Cited References Count:9 AIP Conference Proceedings PY - 2017 SN - 0094-243x ST - An Application of Forward-Backward Difference Approximation Method on the Optimal Control Problem in the Transmission of Tuberculosis Model T2 - Symposium on Biomathematics (Symomath 2016) TI - An Application of Forward-Backward Difference Approximation Method on the Optimal Control Problem in the Transmission of Tuberculosis Model UR - ://WOS:000405094200020 VL - 1825 ID - 4920 ER - TY - JOUR AB - In 1997, Castillo-Chavez and Feng developed a two-strain tuberculosis (TB) model, which is typical TB and resistant TB. Castillo-Chavez and Feng's model was then subsequently developed by Jung et al. (2002) by adding two control variables. In this work, Jung et al.'s model was modified by introducing a new control variable so that there are three controls, namely chemoprophylaxis and two treatment strategies, with the application of three different scenarios related to the objective functional form and control application. Pontryagin maximum principle was applied to derive the differential equations system as a condition that must be satisfied by the optimal control variables. Furthermore, the fourth-order Runge-Kutta method was exploited to determine the numerical solution of the optimal control problem. In this numerical solution, it is shown that the controls treated on TB transmission model provide a good effect because latent and infected individuals are decreasing, and the number of individuals that is treated effectively is increasing. AD - Bogor Agr Univ, Fac Math & Nat Sci, Dept Math, Bogor 16680, Indonesia AN - WOS:000406382200025 AU - Rayhan, S. N. AU - Bakhtiar, T. AU - Jaharuddin DO - Unsp 012025 10.1088/1755-1315/58/1/012025 J2 - Iop C Ser Earth Env L1 - internal-pdf://4088296526/Rayhan-2017-Two-strain Tuberculosis Transmissi.pdf LA - English N1 - Bi1mg Times Cited:0 Cited References Count:4 IOP Conference Series-Earth and Environmental Science PY - 2017 SN - 1755-1307 ST - Two-strain Tuberculosis Transmission Model under Three Control Strategies T2 - 3rd International Seminar on Sciences Sciences on Precision and Sustainable Agriculture (Iss-2016) TI - Two-strain Tuberculosis Transmission Model under Three Control Strategies UR - ://WOS:000406382200025 http://iopscience.iop.org/article/10.1088/1755-1315/58/1/012025/pdf VL - 58 ID - 4921 ER - TY - JOUR AB - In this paper, an SEIR epidemic model for an imperfect treatment disease with age-dependent latency and relapse is proposed. The model is well-suited to model tuberculosis. The basic reproduction number R-0 is calculated. We obtain the global behavior of the model in terms of R-0. If R-0 < 1, the disease-free equilibrium is globally asymptotically stable, whereas if R-0 > 1, a Lyapunov functional is used to show that the endemic equilibrium is globally stable amongst solutions for which the disease is present. AD - Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China Guizhou Educ Univ, Sch Math & Comp Sci, Guiyang 550018, Peoples R China AN - WOS:000402555000015 AU - Ren, S. J. DA - Oct-Dec DO - 10.3934/mbe.2017069 IS - 5-6 J2 - Math Biosci Eng KW - age-structure liapunov function tuberculosis infection equilibrium global stability mathematical-theory infectious classes epidemic model dynamics relapse endemicity diseases LA - English N1 - Sp. Iss. SI Ew5oe Times Cited:0 Cited References Count:33 PY - 2017 SN - 1547-1063 SP - 1337-1360 ST - Global Stability in a Tuberculosis Model of Imperfect Treatment with Age-Dependent Latency T2 - Mathematical Biosciences and Engineering TI - Global Stability in a Tuberculosis Model of Imperfect Treatment with Age-Dependent Latency UR - ://WOS:000402555000015 VL - 14 ID - 2197 ER - TY - JOUR AB - Macaques play a central role in the development of human tuberculosis (TB) vaccines. Immune and challenge responses differ across macaque and human subpopulations. We used novel immunostimulation/immunodynamic modeling methods in a proof-of-concept study to determine which macaque subpopulations best predicted immune responses in different human subpopulations. Data on gamma interferon (IFN-gamma)-secreting CD4+ T cells over time after recent Mycobacterium bovis BCG vaccination were available for 55 humans and 81 macaques. Human population covariates were baseline BCG vaccination status, time since BCG vaccination, gender, and the monocyte/lymphocyte cell count ratio. The macaque population covariate was the colony of origin. A two-compartment mathematical model describing the dynamics of the IFN-gamma T cell response after BCG vaccination was calibrated to these data using nonlinear mixed-effects methods. The model was calibrated to macaque and human data separately. The association between subpopulations and the BCG immune response in each species was assessed. The macaque subpopulations that best predicted immune responses in different human subpopulations were identified using Bayesian information criteria. We found that the macaque colony and the human baseline BCG status were significantly (P < 0.05) associated with the BCG-induced immune response. For humans who were BCG naive at baseline, Indonesian cynomolgus macaques and Indian rhesus macaques best predicted the immune response. For humans who had already been BCG vaccinated at baseline, Mauritian cynomolgus macaques best predicted the immune response. This work suggests that the immune responses of different human populations may be best modeled by different macaque colonies, and it demonstrates the potential utility of immunostimulation/immunodynamic modeling to accelerate TB vaccine development. AD - TB Modelling Group, CMMID, TB Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom Sophie.rhodes@lshtm.ac.uk. Public Health England, Porton Down, United Kingdom. TB Modelling Group, CMMID, TB Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom. Imperial College, London, United Kingdom. College of Health and Life Sciences, Department of Life Sciences, Brunel University, London, United Kingdom. The Jenner Institute, University of Oxford, Oxford, United Kingdom. TomegaVax, Portland, Oregon, USA. Immunology and Infection Department, London School of Hygiene and Tropical Medicine, London, United Kingdom. AN - 28077441 AU - Rhodes, S. J. AU - Sarfas, C. AU - Knight, G. M. AU - White, A. AU - Pathan, A. A. AU - McShane, H. AU - Evans, T. G. AU - Fletcher, H. AU - Sharpe, S. AU - White, R. G. C2 - PMC5339646 DA - Mar DO - 10.1128/cvi.00525-16 DP - NLM ET - 2017/01/13 IS - 3 J2 - Clinical and vaccine immunology : CVI KW - Adolescent Adult Animals BCG Vaccine/*administration & dosage/*immunology CD4-Positive T-Lymphocytes/*immunology Child Child, Preschool Drug Discovery/*methods Female *Healthy Volunteers Humans Infant Interferon-gamma/*secretion Macaca Male Middle Aged Models, Theoretical Mycobacterium bovis/*immunology Young Adult T-cell immunity bacillus Calmette-Guerin interferons mathematical modeling nonhuman primates tuberculosis tuberculosis vaccines LA - eng N1 - 1556-679x Rhodes, Sophie J Sarfas, Charlotte Knight, Gwenan M White, Andrew Pathan, Ansar A McShane, Helen Evans, Thomas G Fletcher, Helen ORCID: http://orcid.org/0000-0002-0435-1006 Sharpe, Sally White, Richard G Journal Article United States Clin Vaccine Immunol. 2017 Mar 6;24(3). pii: e00525-16. doi: 10.1128/CVI.00525-16. Print 2017 Mar. PY - 2017 SN - 1556-679x ST - Using Data from Macaques To Predict Gamma Interferon Responses after Mycobacterium bovis BCG Vaccination in Humans: a Proof-of-Concept Study of Immunostimulation/Immunodynamic Modeling Methods T2 - Clin Vaccine Immunol TI - Using Data from Macaques To Predict Gamma Interferon Responses after Mycobacterium bovis BCG Vaccination in Humans: a Proof-of-Concept Study of Immunostimulation/Immunodynamic Modeling Methods VL - 24 ID - 776 ER - TY - JOUR AB - Background: Substantial individual heterogeneity exists in the clinical manifestations and duration of active tuberculosis. We sought to link the individual-level characteristics of TB disease to observed population-level outcomes. Methods: We developed an individual-based, stochastic model of TB disease in a hypothetical cohort of patients with smear-positive TB. We conceptualized the disease process as consisting of two states - progression and recovery - including transitions between the two. We then used a Bayesian process to calibrate the model to clinical data from the pre-chemotherapy era, thus identifying the rates of progression and recovery (and probabilities of transition) consistent with observed population-level clinical outcomes. Results: Observed outcomes are consistent with slow rates of disease progression (median doubling time: 84 days, 95% uncertainty range 62-104) and a low, but nonzero, probability of transition from disease progression to recovery (median 16% per year, 95% uncertainty range 11%-21%). Other individual-level dynamics were less influential in determining observed outcomes. Conclusions: This simplified model identifies individual-level dynamics - including a long doubling time and low probability of immune recovery - that recapitulate population-level clinical outcomes of untreated TB patients. This framework may facilitate better understanding of the population-level impact of interventions acting at the individual host level. AD - Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health Baltimore, MD 21205, USA. Laboratorio de Investigacion en Enfermedades Infecciosas, Laboratorio de Investigacion y Desarrollo, Facultad de Ciencias y Filosofia, Universidad Peruana Cayetano Heredia Lima, 15026, Peru. Division of Infectious Diseases, The Johns Hopkins University School of Medicine Baltimore, MD 21205, USA. Laboratorio de Investigacion en Enfermedades Infecciosas, Laboratorio de Investigacion y Desarrollo, Facultad de Ciencias y Filosofia, Universidad Peruana Cayetano Heredia; Asociacion Benefica PRISMA. Department of International Health, The Johns Hopkins Bloomberg School of Public Health Baltimore, MD 21205, USA. Department of Epidemiology; Department of International Health The Johns Hopkins Bloomberg School of Public Health Baltimore, MD 21205, USA. AN - 29106638 AU - Salvatore, P. P. AU - Proano, A. AU - Kendall, E. A. AU - Gilman, R. H. AU - Dowdy, D. W. DA - Nov 02 DO - 10.1093/infdis/jix555 KW - Computer Simulation Disease Progression Markov Chains Mathematical Models Mycobacterium tuberculosis/growth and development Natural History Spontaneous Remission Symptom Threshold Theoretical Models Tuberculosis N1 - Salvatore, Phillip P Proano, Alvaro Kendall, Emily A Gilman, Robert H Dowdy, David W eng 2017/11/07 06:00 J Infect Dis. 2017 Nov 2. doi: 10.1093/infdis/jix555. PY - 2017 SN - 1537-6613 (Electronic) 0022-1899 (Linking) ST - Linking individual natural history to population outcomes in tuberculosis T2 - J Infect Dis TI - Linking individual natural history to population outcomes in tuberculosis UR - https://www.ncbi.nlm.nih.gov/pubmed/29106638 ID - 4812 ER - TY - JOUR AB - Recent and rapidly evolving progress on high-throughput measurement techniques and computational performance has led to the emergence of new disciplines, such as systems medicine and translational systems biology. At the core of these disciplines lies the desire to produce multiscale models: mathematical models that integrate multiple scales of biological organization, ranging from molecular, cellular and tissue models to organ, whole-organism and population scale models. Using such models, hypotheses can systematically be tested. In this review, we present state-of-the-art multiscale modelling of bacterial and fungal infections, considering both the pathogen and host as well as their interaction. Multiscale modelling of the interactions of bacteria, especially Mycobacterium tuberculosis, with the human host is quite advanced. In contrast, models for fungal infections are still in their infancy, in particular regarding infections with the most important human pathogenic fungi, Candida albicans and Aspergillus fumigatus. We reflect on the current availability of computational approaches for multiscale modelling of host-pathogen interactions and point out current challenges. Finally, we provide an outlook for future requirements of multiscale modelling. AD - Research Group Systems Biology and Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute Jena, Germany. Department of Cardiology, Linkoping University, Linkoping, Sweden. Integrative Systems Biology, Department of Biomedical Engineering, Linkoping University, Linkoping, Sweden. Cell Biology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. Leibniz-Institute for Natural Product Research and Infection Biology-Hans-Knoell-Institute, Jena, Germany. AN - 26857943 AU - Schleicher, J. AU - Conrad, T. AU - Gustafsson, M. AU - Cedersund, G. AU - Guthke, R. AU - Linde, J. C2 - PMC5439285 DA - Mar 01 DO - 10.1093/bfgp/elv064 DP - NLM ET - 2016/02/10 IS - 2 J2 - Briefings in functional genomics KW - *host-pathogen interaction *infection *mathematical modelling *multiscale modelling LA - eng N1 - 2041-2657 Schleicher, Jana Conrad, Theresia Gustafsson, Mika Cedersund, Gunnar Guthke, Reinhard Linde, Jorg Journal Article England Brief Funct Genomics. 2017 Mar 1;16(2):57-69. doi: 10.1093/bfgp/elv064. PY - 2017 SN - 2041-2649 SP - 57-69 ST - Facing the challenges of multiscale modelling of bacterial and fungal pathogen-host interactions T2 - Brief Funct Genomics TI - Facing the challenges of multiscale modelling of bacterial and fungal pathogen-host interactions VL - 16 ID - 1076 ER - TY - JOUR AB - BACKGROUND: Nearly 20,000 people were diagnosed with multi-drug and rifampicin-resistant tuberculosis (MDR/RR-TB) in South Africa in 2015, yet only one-half of the patients who start treatment are expected to have a successful outcome. There is increasing evidence of the effectiveness and safety of new drug regimens containing bedaquiline for MDR/RR-TB; however, whether they are affordable for high-burden, limited-resource settings is uncertain. OBJECTIVE: Our objective was to determine the incremental cost effectiveness of a bedaquiline-based regimen for MDR/RR-TB treatment in South Africa compared with the standard kanamycin-based regimen. METHODS: We established a Markov model for ambulatory treatment of MDR/RR-TB in a high-HIV prevalence setting, parameterized using clinical outcomes from the South African National TB Programme (SA NTP) before (2012-2014) and after (2015-2016) bedaquiline roll-out. The effectiveness of treatment was evaluated in disability-adjusted life-years (DALYs). Ingredient costs from the provider's perspective were collected in 2016 South African Rand and converted to $US, including bedaquiline at $US675.23 per 6-month treatment course. Culture conversion rates were derived from the phase IIb trial of bedaquiline, and disability adjustments were adapted from published literature. Costs and effectiveness were discounted at 3%. RESULTS: For non-bedaquiline regimens, the total expected cost over the 10-year time horizon for a patient with MDR/RR-TB was $US4439 with disability-adjusted survival of 5.1 years. Replacing capreomycin with bedaquiline in patients who failed MDR/RR-TB treatment and required treatment for extensively drug-resistant (XDR-TB) resulted in cost savings ($US4356; 1.8% less) and similar effectiveness (0.02 DALYs averted). As a result, the standard regimen (no bedaquiline) was dominated. Replacing kanamycin with bedaquiline to provide all patients with MDR/RR-TB access to bedaquiline cost $US4647 (4.3% more) and averted 0.17 DALYs compared with the no bedaquiline regimen. The incremental cost-effectiveness ratio was $US1242/DALY averted. CONCLUSION: Markov modelling indicates providing bedaquiline for all patients with MDR/RR-TB could increase the 24-month treatment success rate in South Africa from 56.3% using the current regimen to 60.6%, at a cost $US2.6 million over a 10-year horizon, less than 1% of the estimated $US425 million SA NTP annual budget. AD - Health Economics Unit, Faculty of Health Sciences, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. kschnipp@gmail.com. Clinical HIV Research Unit, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Department of Medicine, University of Colorado, Aurura, CO, USA. National TB Programme, South African National Department of Health, Pretoria, South Africa. Health Economics Unit, Faculty of Health Sciences, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. AN - 28980217 AU - Schnippel, K. AU - Firnhaber, C. AU - Conradie, F. AU - Ndjeka, N. AU - Sinanovic, E. DA - Oct 04 DO - 10.1007/s40258-017-0352-8 DP - NLM ET - 2017/10/06 J2 - Applied health economics and health policy LA - eng N1 - 1179-1896 Schnippel, Kathryn ORCID: http://orcid.org/0000-0003-0757-4325 Firnhaber, Cynthia Conradie, Francesca Ndjeka, Norbert Sinanovic, Edina Journal Article New Zealand Appl Health Econ Health Policy. 2017 Oct 4. doi: 10.1007/s40258-017-0352-8. PY - 2017 SN - 1175-5652 ST - Incremental Cost Effectiveness of Bedaquiline for the Treatment of Rifampicin-Resistant Tuberculosis in South Africa: Model-Based Analysis T2 - Appl Health Econ Health Policy TI - Incremental Cost Effectiveness of Bedaquiline for the Treatment of Rifampicin-Resistant Tuberculosis in South Africa: Model-Based Analysis UR - https://link.springer.com/article/10.1007%2Fs40258-017-0352-8 ID - 557 ER - TY - JOUR AB - BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa. METHODS: We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa. FINDINGS: The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12.4% (95% prediction interval 9.4-16.2) in India, 8.9% (4.5-11.7) in the Philippines, 32.5% (27.0-35.8) in Russia, and 5.7% (3.0-7.6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8.9% (95% prediction interval 5.1-12.9) in India, 9.0% (4.0-14.7) in the Philippines, 9.0% (4.8-14.2) in Russia, and 8.5% (2.5-14.7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040. INTERPRETATION: MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR tuberculosis. FUNDING: US Agency for International Development and US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination. AD - US Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: asharma4@cdc.gov. US Centers for Disease Control and Prevention, Atlanta, GA, USA. South Africa Medical Research Council, Pretoria, South Africa. University of Maryland Medical Center, Baltimore, MD, USA. Tropical Disease Foundation, Manila, Philippines. Vladimir Oblast Tuberculosis Dispensary, Vladimir, Russia. Orel Oblast Tuberculosis Dispensary, Orel, Russia. Central Tuberculosis Research Institute, Russian Academy of Medical Sciences, Moscow, Russia. Socios en Salud Sucursal, Lima, Peru. National Institute of Health, Lima, Peru. Riga East University Hospital Centre of Tuberculosis and Lung Diseases, Latvia. International Tuberculosis Research Center, Changwon and Yonsei University College of Medicine, Seoul, South Korea. Korean Institute of Tuberculosis, Seoul, South Korea. Tartu University Hospital, Tartu, Estonia. Ministry of Public Health, Bangkok, Thailand. Taiwan Centers for Disease Control, Taipei, Taiwan. AN - 28499828 AU - Sharma, A. AU - Hill, A. AU - Kurbatova, E. AU - van der Walt, M. AU - Kvasnovsky, C. AU - Tupasi, T. E. AU - Caoili, J. C. AU - Gler, M. T. AU - Volchenkov, G. V. AU - Kazennyy, B. Y. AU - Demikhova, O. V. AU - Bayona, J. AU - Contreras, C. AU - Yagui, M. AU - Leimane, V. AU - Cho, S. N. AU - Kim, H. J. AU - Kliiman, K. AU - Akksilp, S. AU - Jou, R. AU - Ershova, J. AU - Dalton, T. AU - Cegielski, P. C2 - PMC5599934 C6 - HHSPA877794 DA - Jul DO - 10.1016/s1473-3099(17)30247-5 DP - NLM ET - 2017/05/14 IS - 7 J2 - The Lancet. Infectious diseases KW - Antitubercular Agents/*therapeutic use Asia Extensively Drug-Resistant Tuberculosis/*drug therapy Humans *Models, Theoretical Mycobacterium tuberculosis/drug effects Risk Factors Russia South Africa L1 - internal-pdf://1789816453/1-s2.0-S1473309917302475-main.pdf LA - eng N1 - 1474-4457 Sharma, Aditya Hill, Andrew Kurbatova, Ekaterina van der Walt, Martie Kvasnovsky, Charlotte Tupasi, Thelma E Caoili, Janice C Gler, Maria Tarcela Volchenkov, Grigory V Kazennyy, Boris Y Demikhova, Olga V Bayona, Jaime Contreras, Carmen Yagui, Martin Leimane, Vaira Cho, Sang Nae Kim, Hee Jin Kliiman, Kai Akksilp, Somsak Jou, Ruwen Ershova, Julia Dalton, Tracy Cegielski, Peter Global Preserving Effective TB Treatment Study Investigators CC999999/Intramural CDC HHS/United States Journal Article United States Lancet Infect Dis. 2017 Jul;17(7):707-715. doi: 10.1016/S1473-3099(17)30247-5. Epub 2017 May 9. PY - 2017 SN - 1473-3099 SP - 707-715 ST - Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study T2 - Lancet Infect Dis TI - Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study VL - 17 ID - 669 ER - TY - JOUR AB - Models for the transmission dynamics of mycobacterium tuberculosis (TB) that incorporate exogenous re-infection are known to induce the phenomenon of backward bifurcation, a dynamic phenomenon associated with the existence of two stable attractors when the reproduction number of the model is less than unity. This study shows, by way of a counter example, that exogenous re-infection does not always cause backward bifurcation in TB transmission dynamics. In particular, it is shown that it is the transmission ability of the re-infected individuals, and not just the re-infection process, that causes the backward bifurcation phenomenon. When re-infected individuals do not transmit infection, the disease-free equilibrium of the model is shown to be globally-asymptotically stable (GAS) when the associated reproduction number is less than unity. The model has a unique endemic equilibrium whenever the reproduction threshold exceeds unity. It is shown, using a Lyapunov function, that the unique endemic equilibrium is GAS for the special case with no disease-induced mortality and no transmission by re-infected individuals. It is further shown that even if re-infected individuals do transmit infection, backward bifurcation only occurs if their transmissibility exceeds a certain threshold. Sensitivity analyses, with respect to the derived backward bifurcation threshold, show that the phenomenon of backward bifurcation is more likely to occur if the rates of re-infection and transmissibility of re-infected individuals are sufficiently high. Furthermore, it is likely to occur if the fraction of slow progressors (to active TB) is increased or if the rates of treatment (of symptomatic cases) and disease-induced mortality are increased. On the other hand, backward bifurcation is less likely to occur for increasing rates of endogenous re-activation of latent TB cases. AU - Sharomi, Oluwaseun Y. AU - Safi, Mohammad A. AU - Gumel, Abba B. AU - Gerberry, David J. DA - 2017/04/01/ DO - https://doi.org/10.1016/j.amc.2016.11.009 IS - Supplement C KW - Backward bifurcation Equilibria Reproduction number Re-infection Stability PY - 2017 SN - 0096-3003 SP - 322-335 ST - Exogenous re-infection does not always cause backward bifurcation in TB transmission dynamics T2 - Applied Mathematics and Computation TI - Exogenous re-infection does not always cause backward bifurcation in TB transmission dynamics UR - http://www.sciencedirect.com/science/article/pii/S0096300316306774 VL - 298 ID - 4923 ER - TY - JOUR AB - RATIONALE: There is substantial state-to-state heterogeneity in tuberculosis (TB) in the United States; better understanding this heterogeneity can inform effective response to TB at the state level, the level at which most TB control efforts are coordinated. OBJECTIVES: To characterize drivers of state-level heterogeneity in TB epidemiology in the four U.S. states that bear half the country's TB burden: California, Florida, New York, and Texas. METHODS: We constructed an individual-based model of TB in the four U.S. states and calibrated the model to state-specific demographic and age- and nativity-stratified TB incidence data. We used the model to infer differences in natural history of TB and in future projections of TB. MEASUREMENTS AND MAIN RESULTS: We found that differences in both demographic makeup (particularly the size and composition of the foreign-born population) and TB transmission dynamics contribute to state-level differences in TB epidemiology. The projected median annual rate of decline in TB incidence in the next decade was substantially higher in Texas (3.3%; 95% range, -5.6 to 10.9) than in California (1.7%; 95% range, -3.8 to 7.1), Florida (1.5%; 95% range, -7.4 to 14), and New York (1.9%; 95% range, -6.4 to 9.8). All scenarios projected a flattening of the decline in TB incidence by 2025 without additional resources or interventions. CONCLUSIONS: There is substantial state-level heterogeneity in TB epidemiology in the four states, which reflect both demographic factors and potential differences in the natural history of TB. These differences may inform resource allocation decisions in these states. AD - 1 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and. 2 Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia. AN - 28475845 AU - Shrestha, S. AU - Hill, A. N. AU - Marks, S. M. AU - Dowdy, D. W. DA - Oct 15 DO - 10.1164/rccm.201702-0377OC DP - NLM ET - 2017/05/06 IS - 8 J2 - American journal of respiratory and critical care medicine KW - Adult Age Factors Aged Aged, 80 and over California/epidemiology Female Florida/epidemiology Humans Incidence Male Middle Aged Models, Theoretical New York/epidemiology Population Surveillance Socioeconomic Factors Texas/epidemiology Tuberculosis/*epidemiology geographical heterogeneity in tuberculosis mathematical modeling of tuberculosis tuberculosis tuberculosis in the United States LA - eng N1 - 1535-4970 Shrestha, Sourya ORCID: http://orcid.org/0000-0002-6106-6834 Hill, Andrew N Marks, Suzanne M Dowdy, David W Comparative Study Journal Article United States Am J Respir Crit Care Med. 2017 Oct 15;196(8):1050-1059. doi: 10.1164/rccm.201702-0377OC. PY - 2017 SN - 1073-449x SP - 1050-1059 ST - Comparing Drivers and Dynamics of Tuberculosis in California, Florida, New York, and Texas T2 - Am J Respir Crit Care Med TI - Comparing Drivers and Dynamics of Tuberculosis in California, Florida, New York, and Texas VL - 196 ID - 677 ER - TY - JOUR AB - In this paper will be described Tuberculosis (TB) transmission using Susceptible- Exposed- Infected- Recovered (SEIR) model. SEIR model for transmission of TB were analyzed and performed simulations using data on the number of TB cases in South Sulawesi. The results showed that the levels of the basic reproduction ratio R0 <= 1 using the model of SEIR is, it means that the status of TB disease in South Sulawesi is at a stage that is not alarming, but based on simulation results using MatLab, predicted that the number of infection cases will continue to increase therefore government needs to take preventive measures to control and reduce the number of TB infections in South Sulawesi. AD - Univ Negeri Alakasar, Fac Math & Nat Sci, Dept Math, Makassar, Indonesia AN - WOS:000405092300004 AU - Side, S. AU - Mulbar, U. AU - Sidjara, S. AU - Sanusi, W. DO - Unsp 020004 10.1063/1.4980867 J2 - Aip Conf Proc LA - English N1 - Bi0qh Times Cited:0 Cited References Count:15 AIP Conference Proceedings PY - 2017 SN - 0094-243x ST - A SEIR model for Transmission of Tuberculosis T2 - 4th International Conference on Mathematical Sciences (Icms4): Mathematical Sciences: Championing the Way in a Problem Based and Data Driven Society TI - A SEIR model for Transmission of Tuberculosis UR - ://WOS:000405092300004 VL - 1830 ID - 4922 ER - TY - JOUR AB - We introduce delays in a tuberculosis (TB) model, representing the time delay on the diagnosis and commencement of treatment of individuals with active TB infection. The stability of the disease free and endemic equilibriums is investigated for any time delay. Corresponding optimal control problems, with time delays in both state and control variables, are formulated and studied. Although it is well-known that there is a delay between two to eight weeks between TB infection and reaction of body's immune system to tuberculin, delays for the active infected to be detected and treated, and delays on the treatment of persistent latent individuals due to clinical and patient reasons, which clearly justifies the introduction of time delays on state and control measures, our work seems to be the first to consider such time-delays for TB and apply time-delay optimal control to carry out the optimality analysis. AD - Center for Research and Development in Mathematics and Applications, Department of Mathematics, University of Aveiro, 3810-193 Aveiro, Portugal. email: cjoaosilva@ua.pt. AN - 27879136 AU - Silva, C. J. AU - Maurer, H. AU - Torres, D. F. DA - Feb 01 DO - 10.3934/mbe.2017021 DP - NLM ET - 2016/11/24 IS - 1 J2 - Mathematical biosciences and engineering : MBE LA - eng N1 - 1551-0018 Silva, Cristiana J Maurer, Helmut Torres, Delfim F M Journal Article United States Math Biosci Eng. 2017 Feb 1;14(1):321-337. doi: 10.3934/mbe.2017021. PY - 2017 SN - 1547-1063 SP - 321-337 ST - Optimal control of a tuberculosis model with state and control delays T2 - Math Biosci Eng TI - Optimal control of a tuberculosis model with state and control delays VL - 14 ID - 814 ER - TY - JOUR AB - Effective treatment for tuberculosis (TB) patients on first-line treatment involves triaging those with drug-resistant (DR) TB to appropriate treatment alternatives. Patients likely to have DR TB are identified using results from repeated inexpensive sputum-smear (SS) tests and expensive but definitive drug sensitivity tests (DST). Early DST may lead to high costs and unnecessary testing; late DST may lead to poor health outcomes and disease transmission. We use a partially observable Markov decision process (POMDP) framework to determine optimal DST timing. We develop policy-relevant structural properties of the POMDP model. We apply our model to TB in India to identify the patterns of SS test results that should prompt DST if transmission costs remain at status-quo levels. Unlike previous analyses of personalized treatment policies, we take a societal perspective and consider the effects of disease transmission. The inclusion of such effects can significantly alter the optimal policy. We find that an optimal DST policy could save India approximately $1.9 billion annually. AD - Daniel J. Epstein Department of Industrial and Systems Engineering, University of Southern California, CA, USA. ssuen@usc.edu. Department of Management Science and Engineering, Stanford University, Stanford, CA, USA. Stanford Health Policy, Centers for Health Policy and Primary Care and Outcomes Research, Stanford University, Stanford, CA, USA. AN - 28861650 AU - Suen, S. C. AU - Brandeau, M. L. AU - Goldhaber-Fiebert, J. D. DA - Aug 31 DO - 10.1007/s10729-017-9416-4 KW - Drug resistance Optimal testing Pomdp Tuberculosis L1 - internal-pdf://4070574621/Suen-2017-Optimal timing of drug sensitivity t.pdf N1 - Suen, Sze-Chuan Brandeau, Margaret L Goldhaber-Fiebert, Jeremy D eng Netherlands 2017/09/02 06:00 Health Care Manag Sci. 2017 Aug 31. doi: 10.1007/s10729-017-9416-4. PY - 2017 SN - 1386-9620 (Print) 1386-9620 (Linking) ST - Optimal timing of drug sensitivity testing for patients on first-line tuberculosis treatment T2 - Health Care Manag Sci TI - Optimal timing of drug sensitivity testing for patients on first-line tuberculosis treatment UR - https://www.ncbi.nlm.nih.gov/pubmed/28861650 https://link.springer.com/content/pdf/10.1007%2Fs10729-017-9416-4.pdf ID - 2170 ER - TY - JOUR AB - Importance: Testing for and treating latent tuberculosis infection (LTBI) is among the main strategies to achieve TB elimination in the United States. The best approach to testing among non-US born residents, particularly those with comorbid conditions, is uncertain. Objective: To estimate health outcomes, costs, and cost-effectiveness of LTBI testing and treatment among non-US born residents with and without medical comorbidities. Design, Setting, and Participants: Decision analytic tree and Markov cohort simulation model among non-US born residents with no comorbidities, with diabetes, with HIV infection, or with end-stage renal disease (ESRD) using a health care sector perspective with 3% annual discounting. Strategies compared included no testing, tuberculin skin test (TST), interferon gamma release assay (IGRA), confirm positive (initial TST, IGRA only for TST-positive results; both tests positive indicates LTBI), and confirm negative (initial IGRA, then TST for IGRA-negative; any test positive indicates LTBI). All strategies were coupled to treatment with 3 months of self-administered rifapentine and isoniazid. Main Outcomes and Measures: Number needed to test and treat to prevent 1 case of TB reactivation, discounted quality-adjusted life-years (QALYs), discounted lifetime medical costs, and incremental cost-effectiveness ratios (ICERs). Results: Improving health outcomes increased costs, with choice of test dependent on willingness to pay. Strategies ranked by ascending costs and benefits: no testing, confirm positive, TST, IGRA, and confirm negative. The ICERs varied by non-US born patient risk group: patients with no comorbidities, IGRA was likely cost-effective at $83000/QALY; patients with diabetes, both confirm positive ($53000/QALY) and IGRA ($120000/QALY) were likely cost-effective; patients with HIV, confirm negative was clearly preferred ($63000/QALY); and patients with ESRD, no testing was cost-effective. Increased LTBI prevalence and reduced return for TST reading improved IGRA's relative performance. In 10000 probabilistic simulations among non-US born patients with no comorbidities, with diabetes, and with HIV, some form of testing was virtually always cost-effective. These simulations highlight the uncertainty of test choice for non-US born patients with no comorbidities and non-US born patients with diabetes, but strategies including IGRA were preferred in over 60% of simulations for all non-US born populations except those with ESRD. Conclusions and Relevance: Testing for and treating LTBI among non-US born residents with and without selected comorbidities is likely cost-effective except among those with ESRD in whom competing risks of death limit benefits. Strategies including IGRA fell below a $100000/QALY willingness-to-pay threshold for non-US born patients with no comorbidities, patients with diabetes, and patients with HIV. AD - HIV Epidemiology & Outcomes Unit, Section of Infectious Diseases, Boston Medical Center, Boston, Massachusetts. Harvard T. H. Chan School of Public Health, Boston, Massachusetts. Center for Evidence-Based Medicine, Brown University, Providence, Rhode Island. Boston University School of Public Health, Boston, Massachusetts. Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia. AN - 29049814 AU - Tasillo, A. AU - Salomon, J. A. AU - Trikalinos, T. A. AU - Horsburgh, C. R., Jr. AU - Marks, S. M. AU - Linas, B. P. DA - Oct 16 DO - 10.1001/jamainternmed.2017.3941 N1 - Tasillo, Abriana Salomon, Joshua A Trikalinos, Thomas A Horsburgh, C Robert Jr Marks, Suzanne M Linas, Benjamin P eng 2017/10/20 06:00 JAMA Intern Med. 2017 Oct 16. doi: 10.1001/jamainternmed.2017.3941. PY - 2017 SN - 2168-6114 (Electronic) 2168-6106 (Linking) ST - Cost-effectiveness of Testing and Treatment for Latent Tuberculosis Infection in Residents Born Outside the United States With and Without Medical Comorbidities in a Simulation Model T2 - JAMA Intern Med TI - Cost-effectiveness of Testing and Treatment for Latent Tuberculosis Infection in Residents Born Outside the United States With and Without Medical Comorbidities in a Simulation Model UR - https://www.ncbi.nlm.nih.gov/pubmed/29049814 ID - 4815 ER - TY - JOUR AB - BACKGROUND: To reduce global tuberculosis (TB) burden, the active disease must be diagnosed quickly and accurately and patients should be treated and cured. In Ethiopia, TB diagnosis mainly relies on spot-morning-spot (SMS) sputum sample smear analysis using Ziehl-Neelsen staining techniques (ZN). Since 2014 targeted use of xpert has been implemented. New diagnostic techniques have higher sensitivity and are likely to detect more cases if routinely implemented. The objective of our study was to project the effects of alternative diagnostic algorithms on the patient, health system, and costs, and identify cost-effective algorithms that increase TB case detection in Addis Ababa, Ethiopia. METHODS: An observational quantitative modeling framework was applied using the Virtual Implementation approach. The model was designed to represent the operational and epidemiological context of Addis Ababa, the capital city of Ethiopia. We compared eight diagnostic algorithm with ZN microscopy, light emitting diode (LED) fluorescence microscopy and Xpert MTB/RIF. Interventions with an annualized cost per averted disability adjusted life year (DALY) of less than the Gross Domestic Product (GDP) per capita are considered cost-effective interventions. RESULTS: With a cost lower than the average per-capita GDP (US$690 for Ethiopia) for each averted disability adjusted life year (DALY), three of the modeled algorithms are cost-effective. Implementing them would have important patient, health system, and population-level effects in the context of Addis Ababa The full roll-out of Xpert MTB/RIF as the primary test for all presumptive TB cases would avert 91170 DALYs (95% credible interval [CrI] 54888 - 127448) with an additional health system cost of US$ 11.6 million over the next 10 years. The incremental cost-effectiveness ratio (ICER) is $370 per DALY averted. Same day LED fluorescence microscopy for all presumptive TB cases combined with Xpert MTB/RIF targeted to HIV-positive and High multidrug resistant (MDR) risk groups would avert 73600 DALYs( 95% CrI 48373 - 99214) with an additional cost of US$5.1 million over the next 10 years. The ICER is $169per DALY averted. Same-day LED fluorescence microscopy for all presumptive TB cases (and no Xpert MTB/RIF) would avert 43580 DALYs with a reduction cost of US$ 0.2 million over the next 10years. The ICER is $13 per DALY averted. CONCLUSIONS: The full roll-out of Xpert MTB/RIF is predicted to be the best option to substantially reduce the TB burden in Addis Ababa and is considered cost effective. However, the investment cost to implement this is far beyond the budget of the national TB control program. Targeted use of Xpert MTB/RIF for HIV positive and high MDR risk groups with same-day LED fluorescence microscopy for all other presumptive TB cases is an affordable alternative. AD - Addis Ababa City Government Health Bureau, Addis Ababa, Ethiopia. atabrish@gmail.com. KNCV Tuberculosis Foundation, Addis Ababa, Ethiopia. Department of Global Health, Academic Medical Center, Amsterdam Institute for Global Health and Development, University of Amsterdam, Amsterdam, the Netherlands. Addis Ababa University, Addis Ababa, Ethiopia. Liverpool School of Tropical Medicine, Pembroke, United Kingdom. AN - 28464797 AU - Tesfaye, A. AU - Fiseha, D. AU - Assefa, D. AU - Klinkenberg, E. AU - Balanco, S. AU - Langley, I. C2 - PMC5414345 DA - May 02 DO - 10.1186/s12879-017-2417-6 DP - NLM ET - 2017/05/04 IS - 1 J2 - BMC infectious diseases KW - *Algorithms Cost-Benefit Analysis Delivery of Health Care/economics Diagnosis, Computer-Assisted/economics/*methods Ethiopia Female HIV Infections/microbiology Humans Laboratories/economics Male Microscopy, Fluorescence/economics/methods Mycobacterium tuberculosis/drug effects Quality-Adjusted Life Years Sensitivity and Specificity Sputum/microbiology Tuberculosis, Multidrug-Resistant/diagnosis Tuberculosis, Pulmonary/*diagnosis Cost-effectiveness Diagnostics Modeling Tuberculosis L1 - internal-pdf://2162252594/Tesfaye-2017-Modeling the patient and health s.pdf LA - eng N1 - 1471-2334 Tesfaye, Abraham Fiseha, Daniel Assefa, Dawit Klinkenberg, Eveline Balanco, Silvia Langley, Ivor Journal Article England BMC Infect Dis. 2017 May 2;17(1):318. doi: 10.1186/s12879-017-2417-6. PY - 2017 SN - 1471-2334 SP - 318 ST - Modeling the patient and health system impacts of alternative xpert(R) MTB/RIF algorithms for the diagnosis of pulmonary tuberculosis in Addis Ababa, Ethiopia T2 - BMC Infect Dis TI - Modeling the patient and health system impacts of alternative xpert(R) MTB/RIF algorithms for the diagnosis of pulmonary tuberculosis in Addis Ababa, Ethiopia UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414345/pdf/12879_2017_Article_2417.pdf VL - 17 ID - 682 ER - TY - JOUR AB - BACKGROUND: Tuberculosis (TB) is now the world's leading infectious killer and major programmatic advances will be needed if we are to meet the ambitious new End TB Targets. Although mathematical models are powerful tools for TB control, such models must be flexible enough to capture the complexity and heterogeneity of the global TB epidemic. This includes simulating a disease that affects age groups and other risk groups differently, has varying levels of infectiousness depending upon the organ involved and varying outcomes from treatment depending on the drug resistance pattern of the infecting strain. RESULTS: We adopted sound basic principles of software engineering to develop a modular software platform for simulation of TB control interventions ("AuTuMN"). These included object-oriented programming, logical linkage between modules and consistency of code syntax and variable naming. The underlying transmission dynamic model incorporates optional stratification by age, risk group, strain and organ involvement, while our approach to simulating time-variant programmatic parameters better captures the historical progression of the epidemic. An economic model is overlaid upon this epidemiological model which facilitates comparison between new and existing technologies. A "Model runner" module allows for predictions of future disease burden trajectories under alternative scenario situations, as well as uncertainty, automatic calibration, cost-effectiveness and optimisation. The model has now been used to guide TB control strategies across a range of settings and countries, with our modular approach enabling repeated application of the tool without the need for extensive modification for each application. CONCLUSIONS: The modular construction of the platform minimises errors, enhances readability and collaboration between multiple programmers and enables rapid adaptation to answer questions in a broad range of contexts without the need for extensive re-programming. Such features are particularly important in simulating an epidemic as complex and diverse as TB. AD - School of Public Health and Preventive Medicine, Monash University, 99 Commercial Road, Melbourne, 3004, Australia. james.trauer@monash.edu. The Burnet Institute, 85 Commercial Road, Melbourne, 3004, Australia. Department of Medicine, Clinical Sciences Building, the Royal Melbourne Hospital, Parkville, 3050, Australia. Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, 4811, Australia. AN - 28784094 AU - Trauer, J. M. AU - Ragonnet, R. AU - Doan, T. N. AU - McBryde, E. S. C2 - PMC5547473 DA - Aug 07 DO - 10.1186/s12879-017-2648-6 DP - NLM ET - 2017/08/09 IS - 1 J2 - BMC infectious diseases KW - Disease transmission, infectious Global health Models, biological Software Tuberculosis Tuberculosis, multidrug-resistant L1 - internal-pdf://3435108505/Trauer-2017-Modular programming for tuberculos.pdf LA - eng N1 - 1471-2334 Trauer, James McCracken Ragonnet, Romain Doan, Tan Nhut McBryde, Emma Sue Journal Article England BMC Infect Dis. 2017 Aug 7;17(1):546. doi: 10.1186/s12879-017-2648-6. PY - 2017 SN - 1471-2334 SP - 546 ST - Modular programming for tuberculosis control, the "AuTuMN" platform T2 - BMC Infect Dis TI - Modular programming for tuberculosis control, the "AuTuMN" platform UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547473/pdf/12879_2017_Article_2648.pdf VL - 17 ID - 613 ER - TY - JOUR AB - BACKGROUND: The patterns of relative species abundance are commonly studied in ecology and epidemiology to provide insights into underlying dynamical processes. Molecular types (MVLA-types) of Mycobacterium bovis, the causal agent of bovine tuberculosis, are now routinely recorded in culture-confirmed bovine tuberculosis cases in Northern Ireland. In this study, we use ecological approaches and simulation modelling to investigate the distribution of relative abundances of MVLA-types and its potential drivers. We explore four biologically plausible hypotheses regarding the processes driving molecular type relative abundances: sampling and speciation; structuring of the pathogen population; historical changes in population size; and transmission heterogeneity (superspreading). RESULTS: Northern Irish herd-level MVLA-type surveillance shows a right-skewed distribution of MVLA-types, with a small number of types present at very high frequencies and the majority of types very rare. We demonstrate that this skew is too extreme to be accounted for by simple neutral ecological processes. Simulation results indicate that the process of MVLA-type speciation and the manner in which the MVLA-typing loci were chosen in Northern Ireland cannot account for the observed skew. Similarly, we find that pathogen population structure, assuming for example a reservoir of infection in a separate host, would drive the relative abundance distribution in the opposite direction to that observed, generating more even abundances of molecular types. However, we find that historical increases in bovine tuberculosis prevalence and/or transmission heterogeneity (superspreading) are both capable of generating the skewed MVLA-type distribution, consistent with findings of previous work examining the distribution of molecular types in human tuberculosis. CONCLUSION: Although the distribution of MVLA-type abundances does not fit classical neutral predictions, our simulations show that increases in pathogen population size and/or superspreading are consistent with the pattern observed, even in the absence of selective pressures acting on the system. AD - Boyd Orr Centre for Population and Ecosystem Health, Institute of Biodiversity and Animal Health, University of Glasgow, Glasgow, UK. hannah.trewby@glasgow.ac.uk. School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Belfast, UK. Veterinary Sciences Division, Agri-Food and Biosciences Institute, Stormont, Belfast, UK. School of Biological Sciences, Queen's University Belfast, Belfast, UK. Boyd Orr Centre for Population and Ecosystem Health, Institute of Biodiversity and Animal Health, University of Glasgow, Glasgow, UK. AN - 28830547 AU - Trewby, H. AU - Wright, D. M. AU - Skuce, R. A. AU - McCormick, C. AU - Mallon, T. R. AU - Presho, E. L. AU - Kao, R. R. AU - Haydon, D. T. AU - Biek, R. C2 - PMC5567634 DA - Aug 22 DO - 10.1186/s12917-017-1190-5 DP - NLM ET - 2017/08/24 IS - 1 J2 - BMC veterinary research KW - Bovine tuberculosis Multiple-locus variable number tandem repeats Neutral theory of biodiversity Population genetics Species abundance distributions LA - eng N1 - 1746-6148 Trewby, Hannah ORCID: http://orcid.org/0000-0001-8109-8107 Wright, David M Skuce, Robin A McCormick, Carl Mallon, Thomas R Presho, Eleanor L Kao, Rowland R Haydon, Daniel T Biek, Roman Journal Article England BMC Vet Res. 2017 Aug 22;13(1):268. doi: 10.1186/s12917-017-1190-5. PY - 2017 SN - 1746-6148 SP - 268 ST - Relative abundance of Mycobacterium bovis molecular types in cattle: a simulation study of potential epidemiological drivers T2 - BMC Vet Res TI - Relative abundance of Mycobacterium bovis molecular types in cattle: a simulation study of potential epidemiological drivers VL - 13 ID - 593 ER - TY - JOUR AB - BACKGROUND: In Canada, active tuberculosis (TB) disease rates remain disproportionately higher among the Indigenous population, especially among the Inuit in the north. We used mathematical modeling to evaluate how interventions might enhance existing TB control efforts in a region of Nunavut. METHODS: We developed a stochastic, agent-based model of TB transmission that captured the unique household and community structure. Evaluated interventions included: (i) rapid treatment of active cases; (ii) rapid contact tracing; (iii) expanded screening programs for latent TB infection (LTBI); and (iv) reduced household density. The outcomes of interest were incident TB infections and total diagnosed active TB disease over a 10- year time period. RESULTS: Model-projected incidence in the absence of additional interventions was highly variable (range: 33-369 cases) over 10 years. Compared to the 'no additional intervention' scenario, reducing the time between onset of active TB disease and initiation of treatment reduced both the number of new TB infections (47% reduction, relative risk of TB = 0.53) and diagnoses of active TB disease (19% reduction, relative risk of TB = 0.81). Expanding general population screening was also projected to reduce the burden of TB, although these findings were sensitive to assumptions around the relative amount of transmission occurring outside of households. Other potential interventions examined in the model (school-based screening, rapid contact tracing, and reduced household density) were found to have limited effectiveness. CONCLUSIONS: In a region of northern Canada experiencing a significant TB burden, more rapid treatment initiation in active TB cases was the most impactful intervention evaluated. Mathematical modeling can provide guidance for allocation of limited resources in a way that minimizes disease transmission and protects population health. AD - Dalla Lana School of Public Health, University of Toronto, University of Toronto, Toronto, ON, Canada. atuite@hsph.harvard.edu. Harvard T.H. Chan School of Public Health, 1633 Tremont Street, Boston, MA, 02120, United States. atuite@hsph.harvard.edu. Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada, Ottawa, ON, Canada. Nunavut Department of Health, Iqaluit, NU, Canada. Department of Population Medicine, University of Guelph, Guelph, ON, Canada. AN - 28086846 AU - Tuite, A. R. AU - Gallant, V. AU - Randell, E. AU - Bourgeois, A. C. AU - Greer, A. L. C2 - PMC5237134 DA - Jan 13 DO - 10.1186/s12889-016-3996-7 DP - NLM ET - 2017/01/15 IS - 1 J2 - BMC public health KW - Adolescent Adult Aged Aged, 80 and over Canada/epidemiology Child Child, Preschool Female Humans Incidence Infant Latent Tuberculosis/*epidemiology Male Middle Aged Models, Theoretical Nunavut/epidemiology Population Groups/*statistics & numerical data Risk Factors Tuberculosis/*epidemiology Young Adult Canada Latent TB infection Mathematical model Nunavut Public health Simulation Tb Tuberculosis LA - eng N1 - 1471-2458 Tuite, Ashleigh R Gallant, Victor Randell, Elaine Bourgeois, Annie-Claude Greer, Amy L Journal Article England BMC Public Health. 2017 Jan 13;17(1):73. doi: 10.1186/s12889-016-3996-7. PY - 2017 SN - 1471-2458 SP - 73 ST - Stochastic agent-based modeling of tuberculosis in Canadian Indigenous communities T2 - BMC Public Health TI - Stochastic agent-based modeling of tuberculosis in Canadian Indigenous communities VL - 17 ID - 774 ER - TY - JOUR AB - Sixty-three percent of the total active tuberculosis cases in Canada were diagnosed among foreign-born individuals, representing 20% of the total population. The majority of these cases occur from the reactivation of tuberculosis infections acquired prior to immigration. A preventive policy consisting of screening and treating new immigrants for latent tuberculosis infection is evaluated on its efficacy for reducing the total number of tuberculosis cases, using tuberculosis incidence data between 1986 and 1995 from the Canadian tuberculosis reporting system. The most effective intervention is to screen for and treat latent tuberculosis infection among arriving immigrants from countries of birth with a tuberculosis incidence rate greater than 15 cases per 100,000. AD - Univ Alberta, Dept Math & Stat Sci, 632 Cent Acad Bldg, Edmonton, AB T6G 2G1, Canada Univ Alberta, Sch Publ Hlth Sci, Edmonton, AB, Canada Univ Alberta, Fac Med & Dent, Edmonton, AB, Canada AN - WOS:000395719100003 AU - Varughese, M. AU - Long, R. AU - Li, M. Y. DO - 10.1080/08898480.2014.998546 IS - 1 J2 - Math Popul Stud KW - foreign-born population ordinary differential equations prevention screening tuberculosis intrinsic transmission dynamics foreign-born persons control strategies canada impact country epidemics rifampin assays costs LA - English N1 - Sp. Iss. S1 En0se Times Cited:0 Cited References Count:37 PY - 2017 SN - 0889-8480 SP - 21-36 ST - Efficacy of screening and treatment of latent tuberculosis infection T2 - Mathematical Population Studies TI - Efficacy of screening and treatment of latent tuberculosis infection UR - ://WOS:000395719100003 VL - 24 ID - 2200 ER - TY - JOUR AB - BACKGROUND: The economic burden on households affected by tuberculosis through costs to patients can be catastrophic. WHO's End TB Strategy recognises and aims to eliminate these potentially devastating economic effects. We assessed whether aggressive expansion of tuberculosis services might reduce catastrophic costs. METHODS: We estimated the reduction in tuberculosis-related catastrophic costs with an aggressive expansion of tuberculosis services in India and South Africa from 2016 to 2035, in line with the End TB Strategy. Using modelled incidence and mortality for tuberculosis and patient-incurred cost estimates, we investigated three intervention scenarios: improved treatment of drug-sensitive tuberculosis; improved treatment of multidrug-resistant tuberculosis; and expansion of access to tuberculosis care through intensified case finding (South Africa only). We defined tuberculosis-related catastrophic costs as the sum of direct medical, direct non-medical, and indirect costs to patients exceeding 20% of total annual household income. Intervention effects were quantified as changes in the number of households incurring catastrophic costs and were assessed by quintiles of household income. FINDINGS: In India and South Africa, improvements in treatment for drug-sensitive and multidrug-resistant tuberculosis could reduce the number of households incurring tuberculosis-related catastrophic costs by 6-19%. The benefits would be greatest for the poorest households. In South Africa, expanded access to care could decrease household tuberculosis-related catastrophic costs by 5-20%, but gains would be seen largely after 5-10 years. INTERPRETATION: Aggressive expansion of tuberculosis services in India and South Africa could lessen, although not eliminate, the catastrophic financial burden on affected households. FUNDING: Bill & Melinda Gates Foundation. AD - Department of Global Health and Population, Harvard T H Chan School of Public Health, Boston, MA, USA. Electronic address: verguet@hsph.harvard.edu. Department of Global Health and Population, Harvard T H Chan School of Public Health, Boston, MA, USA. Department of Global Health, Amsterdam Institute for Global Health and Development, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands; Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, UK. TB Modelling Group, TB Centre, London School of Hygiene and Tropical Medicine, London, UK; Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA. Health Economics Unit, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. Public Health Foundation of India, New Delhi, India. Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, UK. Global TB Programme, WHO, Geneva, Switzerland. Global TB Programme, WHO, Geneva, Switzerland; Department of Public Health Science, Karolinska Institutet, Stockholm, Sweden. AN - 29025634 AU - Verguet, S. AU - Riumallo-Herl, C. AU - Gomez, G. B. AU - Menzies, N. A. AU - Houben, Rmgj AU - Sumner, T. AU - Lalli, M. AU - White, R. G. AU - Salomon, J. A. AU - Cohen, T. AU - Foster, N. AU - Chatterjee, S. AU - Sweeney, S. AU - Baena, I. G. AU - Lonnroth, K. AU - Weil, D. E. AU - Vassall, A. C2 - PMC5640802 DA - Nov DO - 10.1016/s2214-109x(17)30341-8 DP - NLM ET - 2017/10/14 IS - 11 J2 - The Lancet. Global health L1 - internal-pdf://0597101547/Verguet-2017-Catastrophic costs potentially av.pdf LA - eng N1 - 2214-109x Verguet, Stephane Riumallo-Herl, Carlos Gomez, Gabriela B Menzies, Nicolas A Houben, Rein M G J Sumner, Tom Lalli, Marek White, Richard G Salomon, Joshua A Cohen, Ted Foster, Nicola Chatterjee, Susmita Sweeney, Sedona Baena, Ines Garcia Lonnroth, Knut Weil, Diana E Vassall, Anna Journal Article England Lancet Glob Health. 2017 Nov;5(11):e1123-e1132. doi: 10.1016/S2214-109X(17)30341-8. PY - 2017 SN - 2214-109x SP - e1123-e1132 ST - Catastrophic costs potentially averted by tuberculosis control in India and South Africa: a modelling study T2 - Lancet Glob Health TI - Catastrophic costs potentially averted by tuberculosis control in India and South Africa: a modelling study UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640802/pdf/main.pdf VL - 5 ID - 546 ER - TY - JOUR AB - Tuberculosis (TB) affects people globally and is being reconsidered as a serious public health problem in China. Reliable forecasting is useful for the prevention and control of TB. This study proposes a hybrid model combining autoregressive integrated moving average (ARIMA) with a nonlinear autoregressive (NAR) neural network for forecasting the incidence of TB from January 2007 to March 2016. Prediction performance was compared between the hybrid model and the ARIMA model. The best-fit hybrid model was combined with an ARIMA (3,1,0) x (0,1,1)12 and NAR neural network with four delays and 12 neurons in the hidden layer. The ARIMA-NAR hybrid model, which exhibited lower mean square error, mean absolute error, and mean absolute percentage error of 0.2209, 0.1373, and 0.0406, respectively, in the modelling performance, could produce more accurate forecasting of TB incidence compared to the ARIMA model. This study shows that developing and applying the ARIMA-NAR hybrid model is an effective method to fit the linear and nonlinear patterns of time-series data, and this model could be helpful in the prevention and control of TB. AD - Wuxi Medical School,Jiangnan University,Wuxi,Jiangsu,People's Republic of China. AN - 28115032 AU - Wang, K. W. AU - Deng, C. AU - Li, J. P. AU - Zhang, Y. Y. AU - Li, X. Y. AU - Wu, M. C. DA - Apr DO - 10.1017/s0950268816003216 DP - NLM ET - 2017/01/25 IS - 6 J2 - Epidemiology and infection KW - China/epidemiology Communicable Disease Control/organization & administration *Epidemiologic Methods Forecasting Humans Incidence Models, Statistical *Neural Networks (Computer) Time Factors Tuberculosis/*epidemiology/prevention & control Arima Nar hybrid model tuberculosis (TB) L1 - internal-pdf://1373039402/Wang-2017-Hybrid methodology for tuberculosis.pdf LA - eng N1 - 1469-4409 Wang, K W Deng, C Li, J P Zhang, Y Y Li, X Y Wu, M C Journal Article England Epidemiol Infect. 2017 Apr;145(6):1118-1129. doi: 10.1017/S0950268816003216. Epub 2017 Jan 24. PY - 2017 SN - 0950-2688 SP - 1118-1129 ST - Hybrid methodology for tuberculosis incidence time-series forecasting based on ARIMA and a NAR neural network T2 - Epidemiol Infect TI - Hybrid methodology for tuberculosis incidence time-series forecasting based on ARIMA and a NAR neural network UR - https://www.cambridge.org/core/services/aop-cambridge-core/content/view/E15300E2EA96782EC7F45EF3C650BF06/S0950268816003216a.pdf/div-class-title-hybrid-methodology-for-tuberculosis-incidence-time-series-forecasting-based-on-arima-and-a-nar-neural-network-div.pdf VL - 145 ID - 763 ER - TY - JOUR AB - Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a pulmonary pathogen of major global concern. A key feature of Mtb infection in primates is the formation of granulomas, dense cellular structures surrounding infected lung tissue. These structures serve as the main site of host-pathogen interaction in TB, and thus to effectively treat TB we must clarify mechanisms of granuloma formation and their function in disease. Fibrotic granulomas are associated with both good and bad disease outcomes. Fibrosis can serve to isolate infected tissue from healthy tissue, but it can also cause difficulty breathing as it leaves scars. Little is known about fibrosis in TB, and data from non-human primates is just beginning to clarify the picture. This work focuses on constructing a hybrid multi-scale model of fibrotic granuloma formation, in order to identify mechanisms driving development of fibrosis in Mtb infected lungs. We combine dynamics of molecular, cellular, and tissue scale models from previously published studies to characterize the formation of two common sub-types of fibrotic granulomas: peripherally fibrotic, with a cuff of collagen surrounding granulomas, and centrally fibrotic, with collagen throughout granulomas. Uncertainty and sensitivity analysis, along with large simulation sets, enable us to identify mechanisms differentiating centrally versus peripherally fibrotic granulomas. These findings suggest that heterogeneous cytokine environments exist within granulomas and may be responsible for driving tissue scale morphologies. Using this model we are primed to better understand the complex structure of granulomas, a necessity for developing successful treatments for TB. AD - Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, United States of America. Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, United States of America. Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, United States of America. Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, United States of America. Electronic address: kirschne@umich.edu. AN - 28642013 AU - Warsinske, H. C. AU - DiFazio, R. M. AU - Linderman, J. J. AU - Flynn, J. L. AU - Kirschner, D. E. C2 - PMC5576548 DA - Sep 21 DO - 10.1016/j.jtbi.2017.06.017 N1 - Warsinske, Hayley C DiFazio, Robert M Linderman, Jennifer J Flynn, JoAnne L Kirschner, Denise E eng R01 AI123093/AI/NIAID NIH HHS/ R01 HL110811/HL/NHLBI NIH HHS/ U01 HL131072/HL/NHLBI NIH HHS/ England 2017/06/24 06:00 J Theor Biol. 2017 Sep 21;429:1-17. doi: 10.1016/j.jtbi.2017.06.017. Epub 2017 Jun 20. PY - 2017 SN - 1095-8541 (Electronic) 0022-5193 (Linking) SP - 1-17 ST - Identifying mechanisms driving formation of granuloma-associated fibrosis during Mycobacterium tuberculosis infection T2 - J Theor Biol TI - Identifying mechanisms driving formation of granuloma-associated fibrosis during Mycobacterium tuberculosis infection UR - https://www.ncbi.nlm.nih.gov/pubmed/28642013 VL - 429 ID - 2176 ER - TY - JOUR AB - It is a daunting task to eradicate tuberculosis completely in Heng County due to a large transient population, human immunodeficiency virus/tuberculosis coinfection, and latent infection. Thus, a high-precision forecasting model can be used for the prevention and control of tuberculosis. In this study, four models including a basic autoregressive integrated moving average (ARIMA) model, a traditional ARIMA-generalized regression neural network (GRNN) model, a basic GRNN model, and a new ARIMA-GRNN hybrid model were used to fit and predict the incidence of tuberculosis. Parameters including mean absolute error (MAE), mean absolute percentage error (MAPE), and mean square error (MSE) were used to evaluate and compare the performance of these models for fitting historical and prospective data. The new ARIMA-GRNN model had superior fit relative to both the traditional ARIMA-GRNN model and basic ARIMA model when applied to historical data and when used as a predictive model for forecasting incidence during the subsequent 6 months. Our results suggest that the new ARIMA-GRNN model may be more suitable for forecasting the tuberculosis incidence in Heng County than traditional models. AD - Guangxi Key Laboratory of AIDS Prevention and Treatment and Guangxi Universities Key Laboratory of Prevention, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, China. Department of Infectious Diseases, Heng County Centers for Disease Control and Prevention, 16 Gongyuan Road, Heng County, China. Life Sciences Institute, Guangxi Medical University, 22 Shuangyong Road, Nanning, China. Geriatrics Digestion Department of Internal Medicine, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, China. AN - 28820678 AU - Wei, W. AU - Jiang, J. AU - Gao, L. AU - Liang, B. AU - Huang, J. AU - Zang, N. AU - Ning, C. AU - Liao, Y. AU - Lai, J. AU - Yu, J. AU - Qin, F. AU - Chen, H. AU - Su, J. AU - Ye, L. AU - Liang, H. DA - Sep DO - 10.4269/ajtmh.16-0648 DP - NLM ET - 2017/08/19 IS - 3 J2 - The American journal of tropical medicine and hygiene KW - China/epidemiology Computer Simulation Humans Incidence *Models, Biological *Models, Statistical *Neural Networks (Computer) Tuberculosis/*epidemiology L1 - internal-pdf://1127410833/Wei-2017-A New Hybrid Model Using an Autoregre.pdf LA - eng N1 - 1476-1645 Wei, Wudi Jiang, Junjun Gao, Lian Liang, Bingyu Huang, Jiegang Zang, Ning Ning, Chuanyi Liao, Yanyan Lai, Jingzhen Yu, Jun Qin, Fengxiang Chen, Hui Su, Jinming Ye, Li Liang, Hao Journal Article United States Am J Trop Med Hyg. 2017 Sep;97(3):799-805. doi: 10.4269/ajtmh.16-0648. Epub 2017 Aug 18. PY - 2017 SN - 0002-9637 SP - 799-805 ST - A New Hybrid Model Using an Autoregressive Integrated Moving Average and a Generalized Regression Neural Network for the Incidence of Tuberculosis in Heng County, China T2 - Am J Trop Med Hyg TI - A New Hybrid Model Using an Autoregressive Integrated Moving Average and a Generalized Regression Neural Network for the Incidence of Tuberculosis in Heng County, China VL - 97 ID - 602 ER - TY - JOUR AB - OBJECTIVE: To compare the cost-utility of microscopic observation drug-susceptibility assay (MODS) and Xpert(R) MTB/RIF implementation for tuberculosis (TB) diagnosis in rural northern Mozambique. METHODS: Stochastic transmission compartmental TB model from the healthcare provider perspective with parameter input from direct measurements, systematic literature reviews and expert opinion. MODS and Xpert(R) MTB/RIF were evaluated as replacement test of smear microscopy (SM) or as an add-on test after a negative SM. Costs were calculated in 2013 USD, effects in disability-adjusted life years (DALY). Willingness to pay threshold (WPT) was established at once the per capita Gross National Income of Mozambique. RESULTS: MODS as an add-on test to negative SM produced an incremental cost-effectiveness ratio (ICER) of 5647.89USD/DALY averted. MODS as a substitute for SM yielded an ICER of 5374.58USD/DALY averted. Xpert(R) MTB/RIF as an add-on test to negative SM yielded ICER of 345.71USD/DALY averted. Xpert(R) MTB/RIF as a substitute for SM obtained an ICER of 122.13USD/DALY averted. TB prevalence and risk of infection were the main factors impacting MODS and Xpert(R) MTB/RIF ICER in the one-way sensitivity analysis. In the probabilistic sensitivity analysis, Xpert(R) MTB/RIF was most likely to have an ICER below the WPT, whereas MODS was not. CONCLUSION: Our cost-utility analysis favours the implementation of Xpert(R) MTB/RIF as a replacement of SM for all TB suspects in this rural high TB/HIV prevalence African setting. AD - Department of Public Health, University of Barcelona, Barcelona, Spain. SolidarMed Mozambique, Ancuabe, Mozambique. Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain. Research Unit, Paediatrics Department, CAP Valldoreix, Mutua Terrassa Foundation, Mutua Terrassa University Hospital, Terrassa, Catalunya, Spain. SolidarMed Switzerland, Luzern, Switzerland. Provincial Health Directorate, Operational Research Nucleus of Pemba, Pemba, Mozambique. AN - 28380276 AU - Wikman-Jorgensen, P. E. AU - Llenas-Garcia, J. AU - Perez-Porcuna, T. M. AU - Hobbins, M. AU - Ehmer, J. AU - Mussa, M. A. AU - Ascaso, C. DA - Jun DO - 10.1111/tmi.12879 IS - 6 KW - Antibiotics, Antitubercular/pharmacology *Cost-Benefit Analysis Costs and Cost Analysis DNA, Bacterial/analysis *Drug Resistance, Bacterial Humans Microbial Sensitivity Tests/economics *Microscopy *Molecular Diagnostic Techniques/economics Mozambique *Mycobacterium tuberculosis/drug effects/genetics/growth & development Prevalence Quality-Adjusted Life Years Rifampin/*pharmacology Rural Population Sensitivity and Specificity Sputum Tuberculosis, Multidrug-Resistant/diagnosis/drug therapy/microbiology Tuberculosis, Pulmonary/*diagnosis/drug therapy/microbiology Mycobacterium tuberculosis Afrique subsaharienne Diagnostico Sub-Saharan Africa analyse cout-efficacite analisis de Coste-Efectividad cost-effectiveness analysis diagnosis diagnostic Africa subsahariana L1 - internal-pdf://0490263238/Wikman-Jorgense-2017-Microscopic observation d.pdf N1 - Wikman-Jorgensen, Philip E Llenas-Garcia, Jara Perez-Porcuna, Tomas M Hobbins, Michael Ehmer, Jochen Mussa, Manuel A Ascaso, Carlos eng Comparative Study England 2017/04/06 06:00 Trop Med Int Health. 2017 Jun;22(6):734-743. doi: 10.1111/tmi.12879. Epub 2017 May 2. PY - 2017 SN - 1365-3156 (Electronic) 1360-2276 (Linking) SP - 734-743 ST - Microscopic observation drug-susceptibility assay vs. Xpert(R) MTB/RIF for the diagnosis of tuberculosis in a rural African setting: a cost-utility analysis T2 - Trop Med Int Health TI - Microscopic observation drug-susceptibility assay vs. Xpert(R) MTB/RIF for the diagnosis of tuberculosis in a rural African setting: a cost-utility analysis UR - https://www.ncbi.nlm.nih.gov/pubmed/28380276 http://onlinelibrary.wiley.com/store/10.1111/tmi.12879/asset/tmi12879.pdf?v=1&t=ja9jg2z3&s=ff70b4f44dea265dce78f1ef5c623a4cb825f9fb VL - 22 ID - 2199 ER - TY - JOUR AB - Background: Treatment of multidrug-resistant tuberculosis (MDR-TB) is complex, lengthy, and involves a minimum of four drugs termed a background regimen (BR), that have not previously been prescribed or that have proven susceptible to patient sputum culture isolates. In recent years, promising new treatment options have emerged as add-on therapies to a BR. The aim of this study was to evaluate the long-term costs and effectiveness of adding the novel or group 5 interventions bedaquiline, delamanid, and linezolid to a background regimen (BR) of drugs for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis (MDR-TB), within their marketing authorisations, from a German healthcare cost-effectiveness perspective. Methods: A cohort-based Markov model was developed to simulate the incremental cost-effectiveness ratio of bedaquiline plus BR, delamanid plus BR, or linezolid plus BR versus BR alone in the treatment of MDR-TB, over a 10-year time horizon. Effectiveness of treatment was evaluated in Quality-Adjusted Life-Years (QALYs) and LifeYears Gained (LYG), using inputs from clinical trials for bedaquiline and delamanid and from a German observational study for linezolid. Cost data were obtained from German Drug Directory costs (epsilon/2015), published literature, and expert opinion. A 3% yearly discount rate was applied. Probabilistic and deterministic sensitivity analyses were conducted. Results: The total discounted costs per-patient were epsilon 85,575 for bedaquiline plus BR, epsilon 81,079 for delamanid plus BR, and epsilon 80,460 for linezolid plus BR, compared with a cost of epsilon 60,962 for BR alone. The total discounted QALYs per-patient were 5.95 for bedaquiline plus BR, 5.36 for delamanid plus BR, and 3.91 for linezolid plus BR, compared with 3.68 for BR alone. All interventions were therefore associated with higher QALYs and higher costs than BR alone, with incremental costs per QALY gained of epsilon 22,238 for bedaquiline, epsilon 38,703 for delamanid, and epsilon 87,484 for linezolid, versus BR alone. In a fully incremental analysis, bedaquiline plus BR was the most cost-effective treatment option at thresholds greater than epsilon 22,000 per QALY gained. In probabilistic analyses, the probability that bedaquiline plus BR was the most cost-effective treatment strategy at a willingness-to-pay threshold of epsilon 30,000 was 54.5%, compared with 22.9% for BR alone, 18.2% for delamanid plus BR, and 4.4% for linezolid. Conclusions: In Germany, the addition of bedaquiline, delamanid, or linezolid to a BR would result in QALY gains over BR alone. Based on this analysis, bedaquiline is likely to be the most cost-effective intervention for the treatment of MDRTB, when added to a BR regimen at thresholds greater than epsilon 22,000 per QALY. AD - Janssen Cilag GmbH, Hlth Econ & Market Access, Johnson & Johnson Pl 1, D-41470 Neuss, Germany Janssen Cilag Ltd, High Wycombe, Bucks, England PAREXEL Int, London, England AN - WOS:000396084900002 AU - Wirth, D. AU - Dass, R. AU - Hettle, R. DA - Mar 8 DO - ARTN 182 10.1186/s12913-017-2118-2 J2 - Bmc Health Serv Res KW - cost-effectiveness multidrug-resistant tuberculosis bedaquiline delamanid linezolid qaly lyg icer mdr-tb xdr-tb bedaquiline delamanid efficacy therapy safety tolerability outcomes cohort L1 - internal-pdf://0108879431/Wirth-2017-Cost-effectiveness of adding novel.pdf LA - English N1 - En5zs Times Cited:1 Cited References Count:51 PY - 2017 SN - 1472-6963 ST - Cost-effectiveness of adding novel or group 5 interventions to a background regimen for the treatment of multidrug-resistant tuberculosis in Germany T2 - Bmc Health Services Research TI - Cost-effectiveness of adding novel or group 5 interventions to a background regimen for the treatment of multidrug-resistant tuberculosis in Germany UR - ://WOS:000396084900002 https://bmchealthservres.biomedcentral.com/track/pdf/10.1186/s12913-017-2118-2?site=bmchealthservres.biomedcentral.com VL - 17 ID - 2183 ER - TY - JOUR AB - In the last 60 years, great progress has been made in controlling and preventing tuberculosis in China. However, the number of tuberculosis cases has increased dramatically in the last 25 years, mainly due to the lack of effective control measures of immigrating populations with tuberculosis. In order to explore the effective control and prevention measures we propose a deterministic model to study the transmission dynamics of tuberculosis in Guangdong province of China in this paper. The model consists of susceptible, exposed and infectious recovered subpopulations of immigrating populations from other provinces and the local population of Guangdong. We obtain the effective reproduction number. Based on the analysis, we also establish an optimal immune programming model, and get the optimal proportion of vaccine coverage with control of the effective reproduction number. Simulation is used to determine the validation and reliability. Our study demonstrates that the immigrating population from different provinces needs to be vaccinated according to the incidence rate of TB in their original provinces, and it is an effective way to prevent the outbreak of tuberculosis in Guangdong. AD - [Xu, Chuanqing; Wei, Xiaoxiao; Cui, Jingan; Wang, Xiaojing] Beijing Univ Civil Engn & Architecture, Sch Sci, Beijing 100044, Peoples R China. [Xu, Dashun] Southern Illinois Univ, Math Dept, Carbondale, IL 62901 USA. Cui, JA (reprint author), Beijing Univ Civil Engn & Architecture, Sch Sci, Beijing 100044, Peoples R China. cuijingan@bucea.edu.cn AN - WOS:000414207900001 AU - Xu, C. Q. AU - Wei, X. X. AU - Cui, J. A. AU - Wang, X. J. AU - Xu, D. S. C7 - 1750106 DA - Nov DO - 10.1142/s1793524517501066 IS - 8 J2 - Int. J. Biomath. KW - Tuberculosis vaccination immune cover SEIR model low-incidence country tuberculosis transmission disease transmission immigration dynamics migration impact Mathematical & Computational Biology LA - English M3 - Article N1 - ISI Document Delivery No.: FL4NT Times Cited: 0 Cited Reference Count: 21 Xu, Chuanqing Wei, Xiaoxiao Cui, Jingan Wang, Xiaojing Xu, Dashun NSFC [11371048]; Science Foundation of Beijing University of Architecture [00331614033]; Central Support Local Projects [21147515602]; science and technology program of Beijing Municipal Education Commission of China [KM201610016018]; [K2015004] This paper was supported by NSFC (11371048), Science Foundation of Beijing University of Architecture (00331614033), Project for Graduated Students (K2015004), Central Support Local Projects (21147515602), the science and technology program of Beijing Municipal Education Commission of China (KM201610016018). 0 World scientific publ co pte ltd Singapore 1793-7159 PY - 2017 SN - 1793-5245 SP - 18 ST - Mixing in regional-structure model about the influence of floating population and optimal control about TB in Guangdong province of China T2 - International Journal of Biomathematics TI - Mixing in regional-structure model about the influence of floating population and optimal control about TB in Guangdong province of China UR - ://WOS:000414207900001 http://www.worldscientific.com/doi/abs/10.1142/S1793524517501066 VL - 10 ID - 4944 ER - TY - JOUR AB - BACKGROUND AND OBJECTIVE: Tuberculosis (TB) remains a major public health challenge. China accounts for more than 10% of the global TB burden, and effective modelling of TB trends remains limited. METHODS: We used data drawn primarily from two Chinese nation-wide cross-sectional epidemiological surveys combined with data from China's National Disease Reporting Network to construct an eight-state Markov model that simulates TB prevalence. By adjusting the relevant parameters, we evaluated which characteristics have the greatest bearing upon prevalence and efficacy of the response measures. RESULTS: If current trends continue, the prevalence of TB in China will enter an 8-year period of decline from approximately 390 to 200 cases per 100 000 population and stabilize at 163 cases per 100 000 population, which is a figure well above the World Health Organization (WHO) goal of eliminating TB by 2050. We find that the proportion of notified cases in the population, the rate of progression from latent to active and the overall treatment success rate are the chief factors affecting disease progression. CONCLUSION: We suggest a 90-90-90 strategy, wherein the proportion of notified cases in the population reaches 90%, the risk of progression from latent to active is decreased by 90% compared with the current level and the overall treatment success rate is increased to 90%. This strategy could reduce TB prevalence to less than 10 cases per 100 000 population within 5 years and to 1.77 cases per 100 000 population within 50 years. AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Department of Neurobiology, Harvard University, Cambridge, Massachusetts, USA. Zhejiang Institute of Medical Care Information Technology, Hangzhou, China. Department of General Practice, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. AN - 28556405 AU - Xu, K. AU - Ding, C. AU - Mangan, C. J. AU - Li, Y. AU - Ren, J. AU - Yang, S. AU - Wang, B. AU - Ruan, B. AU - Sheng, J. AU - Li, L. DA - Oct DO - 10.1111/resp.13078 DP - NLM ET - 2017/05/31 IS - 7 J2 - Respirology (Carlton, Vic.) KW - Markov chains prevalence prevention and control proportion of notified cases tuberculosis LA - eng N1 - 1440-1843 Xu, Kaijin Ding, Cheng Mangan, Connor J Li, Yiping Ren, Jingjing Yang, Shigui Wang, Bing Ruan, Bing Sheng, Jifang Li, Lanjuan ORCID: http://orcid.org/0000-0001-6945-0593 Journal Article Australia Respirology. 2017 Oct;22(7):1423-1429. doi: 10.1111/resp.13078. Epub 2017 May 28. PY - 2017 SN - 1323-7799 SP - 1423-1429 ST - Tuberculosis in China: A longitudinal predictive model of the general population and recommendations for achieving WHO goals T2 - Respirology TI - Tuberculosis in China: A longitudinal predictive model of the general population and recommendations for achieving WHO goals UR - http://onlinelibrary.wiley.com/doi/10.1111/resp.13078/abstract VL - 22 ID - 659 ER - TY - JOUR AB - In this paper, a mathematical model describing tuberculosis transmission with incomplete treatment and continuous age structure for latently infected and infectious individuals is investigated. It is assumed in the model that the treated individuals may enter either the latent compartment due to the remainder of Mycobacterium tuberculosis or the infectious compartment due to the treatment failure. It is shown that the global transmission dynamics of the disease is fully determined by the basic reproduction number. The asymptotic smoothness of the semi-flow generated by the system is established. By analyzing the corresponding characteristic equations, the local stability of a disease-free steady state and an endemic steady state of the model is established. By using the persistence theory for infinite dimensional system, the uniform persistence of the system is established when the basic reproduction number is greater than unity. By means of suitable Lyapunov functionals and LaSalle's invariance principle, it is proven that if the basic reproduction number is less than unity, the disease-free steady state is globally asymptotically stable; if the basic reproduction number is greater than unity, the endemic steady state is globally asymptotically stable. AD - [Xu, Rui; Tian, Xiaohong] Shijiazhuang Mech Engn Coll, Inst Appl Math, Shijiazhuang 050003, Hebei, Peoples R China. [Zhang, Fengqin] Yuncheng Univ, Dept Appl Math, Yuncheng 044000, Shanxi, Peoples R China. Xu, R (reprint author), Shijiazhuang Mech Engn Coll, Inst Appl Math, Shijiazhuang 050003, Hebei, Peoples R China. rxu88@163.com AN - WOS:000408335100002 AU - Xu, R. AU - Tian, X. H. AU - Zhang, F. Q. C7 - 242 DA - Aug DO - 10.1186/s13662-017-1294-z J2 - Adv. Differ. Equ. KW - tuberculosis age structure stability Lyapunov functional LaSalle's invariance principle epidemic model drug-resistance stability vaccination reinfection diseases therapy relapse latency Mathematics L1 - internal-pdf://0012455603/Xu-2017-Global dynamics of a tuberculosis tran.pdf LA - English M3 - Article N1 - ISI Document Delivery No.: FE6QX Times Cited: 0 Cited Reference Count: 41 Xu, Rui Tian, Xiaohong Zhang, Fengqin National Natural Science Foundation of China [11371368, 11071254, 11371313]; Natural Science Foundation of Hebei Province [A2014506015]; Natural Science Foundation of Young Scientist of Hebei Province [A2013506012] The authors wish to thank the editor and the reviewers for their valuable comments and suggestions that greatly improved the presentation of this work. This work was supported by the National Natural Science Foundation of China (Nos. 11371368, 11071254, 11371313), the Natural Science Foundation of Hebei Province (No. A2014506015) and the Natural Science Foundation of Young Scientist of Hebei Province (No. A2013506012). 0 3 Springer international publishing ag Cham PY - 2017 SN - 1687-1847 SP - 34 ST - Global dynamics of a tuberculosis transmission model with age of infection and incomplete treatment T2 - Advances in Difference Equations TI - Global dynamics of a tuberculosis transmission model with age of infection and incomplete treatment UR - ://WOS:000408335100002 https://advancesindifferenceequations.springeropen.com/track/pdf/10.1186/s13662-017-1294-z?site=advancesindifferenceequations.springeropen.com ID - 4973 ER - TY - JOUR AB - In a model of tuberculosis with relapse, the basic reproduction number R-0 includes new and relapse infections. Lyapunov functions help to prove that the global dynamic is completely determined by R-0. Replicated Latin hypercube sampling shows that early diagnosis and treatment are more efficient when relapse cases are considered. AD - Air Force Engn Univ, Coll Sci, Xian 710051, Peoples R China Shaanxi Normal Univ, Coll Math & Informat Sci, Xian, Peoples R China York Univ, Ctr Dis Modelling, Toronto, ON, Canada Xian Univ Technol, Sch Sci, Xian, Peoples R China AN - WOS:000395719100002 AU - Yang, Y. L. AU - Wu, J. H. AU - Li, J. Q. AU - Xu, X. X. DO - 10.1080/08898480.2014.998550 IS - 1 J2 - Math Popul Stud KW - basic reproduction number equilibrium global stability partial rank correlation coefficient sensitivity analysis tuberculosis disease transmission sensitivity uncertainty dynamics example LA - English N1 - Sp. Iss. S1 En0se Times Cited:0 Cited References Count:20 PY - 2017 SN - 0889-8480 SP - 3-20 ST - Tuberculosis with relapse: A model T2 - Mathematical Population Studies TI - Tuberculosis with relapse: A model UR - ://WOS:000395719100002 VL - 24 ID - 2191 ER - TY - JOUR AB - Background: Untargeted active screening and treatment programmes for tuberculosis (TB) have not been shown to be more effective than passive screening and isoniazid preventive therapy (IPT) for reducing TB incidence. In this manuscript, we compare the efficacy of targeting screening and IPT on high-risk household contacts of diagnosed TB cases, with less-targeted active screening approaches in Lima, Peru. Methods: We conducted a population-based prospective cohort study within households of TB cases in Lima. We identified all adults diagnosed with incident pulmonary TB from 2009 through 2012 at 106 participating public health centres (HC) within our catchment area of approximately 3.3 million inhabitants. We estimated combined effects of community and household exposure on the risk of latent TB infection (LTBI) and incident TB disease. We used simulation modelling to assess the efficacy of TB screening programmes for reducing the risk of incident TB in these contacts. Results: Individuals with household exposure to TB are more likely to present with LTBI and TB disease than those without this exposure, despite wide variation in community exposure. Simulations suggest that more cases are prevented by 1000 administrations of IPT to tuberculin skin test (TST)-positive household contacts of identified TB cases (30, 95% CI = 16,47) than from blanket screening and treatment in the community (7, 95% CI = 2,17). Conclusions: Household exposure remains a major driver of incident TB risk among household contacts of identified TB cases. Targeting interventions on these individuals is likely to prevent more cases of TB than blanket screening of individuals in the community. AD - Department of Epidemiology. Center for Social Epidemiology and Population Health, University of Michigan School of Public Health, Ann Arbor, MI, USA. Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA. Partners In Health/Socios En Salud, Boston, MA, USA/Lima, Peru. Division of Global Health Equity, Brigham and Women's Hospital. Boston, MA, USA. Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA. AN - 29025111 AU - Zelner, J. AU - Murray, M. AU - Becerra, M. AU - Galea, J. AU - Lecca, L. AU - Calderon, R. AU - Yataco, R. AU - Zhang, Z. AU - Cohen, T. DA - Sep 13 DO - 10.1093/ije/dyx171 DP - NLM ET - 2017/10/13 J2 - International journal of epidemiology KW - Tuberculosis hierarchical modeling intervention targeting LA - eng N1 - 1464-3685 Zelner, Jon Murray, Megan Becerra, Mercedes Galea, Jerome Lecca, Leonid Calderon, Roger Yataco, Rosa Zhang, Zibiao Cohen, Ted Journal Article England Int J Epidemiol. 2017 Sep 13. doi: 10.1093/ije/dyx171. PY - 2017 SN - 0300-5771 ST - Protective effects of household-based TB interventions are robust to neighbourhood-level variation in exposure risk in Lima, Peru: a model-based analysis T2 - Int J Epidemiol TI - Protective effects of household-based TB interventions are robust to neighbourhood-level variation in exposure risk in Lima, Peru: a model-based analysis ID - 550 ER - TY - JOUR AB - Tuberculosis (TB), an air-borne infectious disease, is a major public-health problem in China. The reported number of the active tuberculosis cases is about one million each year. The morbidity data for 2005-2012 reflect that the difference in morbidity based on age group is significant, thus the role of age-structure on the transmission of TB needs to be further developed. In this work, based on the reported data and the observed morbidity characteristics, we propose a susceptible-exposed-infectious-recovered (SEIR) epidemic model with age groupings, involving three categories: children, the middle-aged, and senior to investigate the role of age on the transmission of tuberculosis in Mainland China from 2005 to 2016. Then, we evaluated the parameters by the Least Square method and simulated the model and it had good alignment with the reported infected TB data in Mainland China. Furthermore, we estimated the basic reproduction number R(0) of 1.7858, with an obtained 95% confidence interval for R(0) of (1.7752, 1.7963) by Latin hypercube sampling, and we completed a sensitivity analysis of R(0) in terms of some parameters. Our study demonstrates that diverse age groups have different effects on TB. Two effective measures were found that would help reach the goals of theWorld Health Organization (WHO) End TB Strategy: an increase in the recovery rate and the reduction in the infectious rate of the senior age group. AD - School of Public Health and Management, Ningxia Medical University, Yinchuan 750004, Ningxia, China. zhaoyuzy123@163.com. School of Mathematics and Computer Science, Ningxia Normal University, Guyuan 756000, Ningxia, China. zhaoyuzy123@163.com. School of Computer and Information Technology, Shanxi University, Taiyuan 030006, Shanxi, China. limingtao18@126.com. Complex Systems Research Center, Shanxi University, Taiyuan 030006, Shanxi, China. limingtao18@126.com. College of Science, University of Shanghai for Science and Technology, Shanghai 200093, China. sanling@usst.edu.cn. AN - 28991169 AU - Zhao, Y. AU - Li, M. AU - Yuan, S. DA - Oct 07 DO - 10.3390/ijerph14101192 DP - NLM ET - 2017/10/11 IS - 10 J2 - International journal of environmental research and public health KW - age group basic reproduction number data fitting global stability tuberculosis uncertainty and sensitivity analysis LA - eng N1 - 1660-4601 Zhao, Yu Li, Mingtao Yuan, Sanling Journal Article Switzerland Int J Environ Res Public Health. 2017 Oct 7;14(10). pii: E1192. doi: 10.3390/ijerph14101192. PY - 2017 SN - 1660-4601 ST - Analysis of Transmission and Control of Tuberculosis in Mainland China, 2005-2016, Based on the Age-Structure Mathematical Model T2 - Int J Environ Res Public Health TI - Analysis of Transmission and Control of Tuberculosis in Mainland China, 2005-2016, Based on the Age-Structure Mathematical Model VL - 14 ID - 554 ER - TY - JOUR AB - In this work we formulate a model for the population dynamics of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). Our main interest is to assess the impact of the competition among bacteria on the infection prevalence. For this end, we assume that Mtb population has two types of growth. The first one is due to bacteria produced in the interior of each infected macrophage, and it is assumed that is proportional to the number of infected macrophages. The second one is of logistic type due to the competition among free bacteria released by the same infected macrophages. The qualitative analysis and numerical results suggests the existence of forward, backward and S-shaped bifurcations when the associated reproduction number R-0 of the Mtb is less unity. In addition, qualitative analysis of the model shows that there may be up to three bacteria-present equilibria, two locally asymptotically stable, and one unstable. AD - [Ibarguen-Mondragon, Eduardo] Univ Narino, Dept Matemat & Estadist, Fac Ciencias Exactas & Nat, Calle 18 Cra 50, Pasto, Colombia. [Esteva, Lourdes] Univ Nacl Autonoma Mexico, Dept Matemat, Fac Ciencias, Mexico City 04510, DF, Mexico. [Mariela Burbano-Rosero, Edith] Univ Narino, Dept Biol, Fac Ciencias Exactas & Nat, Calle 18 Cra 50, Pasto, Colombia. Ibarguen-Mondragon, E (reprint author), Univ Narino, Dept Matemat & Estadist, Fac Ciencias Exactas & Nat, Calle 18 Cra 50, Pasto, Colombia. edbargun@udenar.edu.co; lesteva@cincias.unam.mx; marielaburbano@gmail.com AN - WOS:000412001800004 AU - Ibarguen-Mondragon, E. AU - Esteva, L. AU - Burbano-Rosero, E. M. DA - Apr DO - 10.3934/mbe.2018018 IS - 2 J2 - Math. Biosci. Eng. KW - Ordinary differential equations S-shaped bifurcation tuberculosis granuloma macrophages and T cells human immune-response life-span human macrophages drug-resistance t-cells infection dynamics antibiotics immunology mechanisms Mathematical & Computational Biology LA - English M3 - Article N1 - ISI Document Delivery No.: FI5DL Times Cited: 0 Cited Reference Count: 39 Ibarguen-Mondragon, Eduardo Esteva, Lourdes Mariela Burbano-Rosero, Edith Acuerdo [182-01/11/2016]; papiit-unam [in-112713] We want to thank anonymous referees for their valuable comments that helped us to improve the paper. E. Ibarguen-Mondragon and E. M. Burbano-Rosero acknowledge support from project approved by ACUERDO No 182-01/11/2016 (VIPRI-UDENAR). Lourdes Esteva acknowledges support from project IN-112713, PAPIIT-UNAM. 0 144 Amer inst mathematical sciences-aims Springfield 1551-0018 PY - 2018 SN - 1547-1063 SP - 407-428 ST - MATHEMATICAL MODEL FOR THE GROWTH OF MYCOBACTERIUM TUBERCULOSIS IN THE GRANULOMA T2 - Mathematical Biosciences and Engineering TI - MATHEMATICAL MODEL FOR THE GROWTH OF MYCOBACTERIUM TUBERCULOSIS IN THE GRANULOMA UR - ://WOS:000412001800004 VL - 15 ID - 4940 ER - TY - JOUR AB - Tuberculosis (TB) is returning to be a worldwide global public health threat. It is estimated that 9.6 million cases occurred in 2014, of which just two-thirds notified to public health authorities. The "missing cases" constitute a severe challenge for TB transmission control. TB is a severe disease in India, while, worldwide, the WHO estimates that one third of the entire world population is infected. Nowadays, incidence estimation relies increasingly more on notifications of new cases from routine surveillance. There is an urgent need for better estimates of the load of TB, in high-burden settings. We developed a simple model of TB transmission dynamics, using a dynamical system model, consisting of six classes of individuals. It contains the current medical epidemiologists' understanding of the spread of the Mycobacterium tuberculosis in humans, which is substantiated by field observations at the district level in India. The model incorporates the treatment options provided by the public and private sectors in India. Mathematically, an interesting feature of the system is that it exhibits a backward, or subcritical, bifurcation. One of the results of the investigation shows that the discrepancy between the diagnosis rates of the public and private sector does not seem to be the cause of the endemicity of the disease, and, unfortunately, even if they reached 100% of correct diagnosis, this would not be enough to achieve disease eradication. Several other approaches have been attempted on the basis of this model to indicate possible strategies that may lead to disease eradication, but the rather sad conclusion is that they unfortunately do not appear viable in practice. AD - [Pandey, Surabhi] Publ Hlth Fdn India, Plot 47,Sect 44, Gurgaon 122002, Haryana, India. [Venturino, Ezio] Univ Turin, Dipartimento Matemat Giuseppe Peano, Via Carlo Alberto 10, I-10123 Turin, Italy. Pandey, S (reprint author), Publ Hlth Fdn India, Plot 47,Sect 44, Gurgaon 122002, Haryana, India. surabhi.pandey@phfi.org; ezio.venturino@unito.it AN - WOS:000411999900011 AU - Pandey, S. AU - Venturino, E. DA - Feb DO - 10.3034/mbe.2n1.801.0 IS - 1 J2 - Math. Biosci. Eng. KW - Disease latency basic reproduction number public hospitalization private hospitalization backward bifurcation subcritical bifurcation pulmonary tuberculosis south-india dots transmission prevalence infection epidemic Mathematical & Computational Biology LA - English M3 - Article; Proceedings Paper N1 - ISI Document Delivery No.: FI5CU Times Cited: 0 Cited Reference Count: 31 Pandey, Surabhi Venturino, Ezio International Conference on Mathematical and Computational Epidemiology of Infectious Diseases - The Interplay between Models and Public Health Policies (Erice MathCompEpi) Aug 30-sep 05, 2015 Erice, ITALY project "Metodi numerici nelle scienze applicate" of the Dipartimento di Matematica "Giuseppe Peano" This work was undertaken when the first author visited the University of Torino, with a WWS2 grant, which is thankfully acknowledged. The research has also been partially supported by the project "Metodi numerici nelle scienze applicate" of the Dipartimento di Matematica "Giuseppe Peano". EV gratefully acknowledges very useful discussions with Antoine Perasso and Rafael Bravo de la Parra and the referees for their constructive comments. 0 17 Amer inst mathematical sciences-aims Springfield 1551-0018 Si PY - 2018 SN - 1547-1063 SP - 233-254 ST - A TB MODEL: IS DISEASE ERADICATION POSSIBLE IN INDIA? T2 - Mathematical Biosciences and Engineering TI - A TB MODEL: IS DISEASE ERADICATION POSSIBLE IN INDIA? UR - ://WOS:000411999900011 VL - 15 ID - 4941 ER -