TY - JOUR AN - 18014673 AU - Frost, W. H. C2 - 1563282 DA - Aug ET - 1937/08/01 J2 - American journal of public health and the nation's health LA - eng M1 - 8 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/18014673 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1563282/pdf/amjphnation01049-0029.pdf VL - 27 ID - 769 ER - TY - JOUR AN - 13458543 AU - Feldmann, F. M. C2 - 1551316 DA - Oct ET - 1957/10/01 J2 - American journal of public health and the nation's health LA - eng M1 - 10 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/13458543 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1551316/pdf/amjphnation01093-0004.pdf VL - 47 ID - 760 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 M1 - 6 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 - 972 ER - TY - JOUR AN - 14004185 AU - Waaler, H. AU - Geser, A. AU - Andersen, S. C2 - 1523050 DA - Jun ET - 1962/06/01 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/14004185 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1523050/pdf/amjphnation00492-0106.pdf VL - 52 ID - 1002 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 - 971 ER - TY - JOUR AN - 6018702 AU - Brogger, S. DA - Mar ET - 1967/03/01 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 M1 - 3 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 - 677 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 - 764 ER - TY - JOUR AN - 5582655 AU - Juchniewicz, M. AU - Olakowski, T. AU - Mardon, K. ET - 1967/01/01 KW - *Epidemiologic Methods Humans Models, Theoretical Poland Prognosis Retrospective Studies Tuberculosis/*prevention & control LA - pol M1 - 10 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 - 821 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 - 1967/11/01 KW - International Cooperation Models, Theoretical Systems Analysis Tuberculosis, Pulmonary/ prevention & control LA - eng M1 - 5 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 - 923 ER - TY - JOUR AN - 5710260 AU - Waaler, H. T. DA - Dec ET - 1968/12/01 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 - 1004 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 - 1005 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 - 782 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 - 970 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. C2 - 2427408 ET - 1969/01/01 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 M1 - 1 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/5309169 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2427408/pdf/bullwho00218-0087.pdf VL - 41 ID - 1008 ER - TY - JOUR AN - 4915929 AU - Revelle, C. AU - Male, J. DA - Sep DP - Nlm ET - 1970/09/01 KW - Costs and Cost Analysis Histological Techniques Humans Models, Theoretical Sputum/microbiology Tuberculin Test Tuberculosis/diagnosis/ prevention & control/radiography LA - eng M1 - 3 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 - 922 ER - TY - JOUR AN - 5425564 AU - Waaler, H. T. DA - Jun DP - Nlm ET - 1970/06/01 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 - 1006 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. C2 - 2427663 DP - Nlm ET - 1970/01/01 KW - Adolescent Adult Age Factors Aged BCG Vaccine Child Child, Preschool Humans Mathematics Middle Aged Models, Theoretical Time Factors Tuberculosis/ prevention & control LA - eng M1 - 1 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 - 1009 ER - TY - JOUR AU - Chorba, R.W. AU - Sanders, JL M1 - 2 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 - 694 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 - 752 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 - 973 ER - TY - BILL AN - 5077111 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 - 685 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 - 822 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 - 681 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 - 809 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 - 848 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 M1 - 6 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 - 933 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 - 720 ER - TY - JOUR AN - 4467941 AU - Waaler, H. AU - Rouillon, A. ET - 1974/01/01 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 M1 - 1 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 - 1003 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. C2 - 2366280 ET - 1974/01/01 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 M1 - 3 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/4549350 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2366280/pdf/bullwho00469-0048.pdf VL - 51 ID - 1007 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. C2 - 2366382 ET - 1975/01/01 J2 - Bulletin of the World Health Organization KW - BCG Vaccine Epidemiologic Methods Humans Japan *Models, Theoretical Tuberculosis/*epidemiology/mortality/prevention & control LA - eng M1 - 3 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/1084802 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2366382/pdf/bullwho00465-0076.pdf VL - 52 ID - 638 ER - TY - JOUR AN - 1185919 AU - Azuma, Y. DA - Jul ET - 1975/07/01 J2 - Kekkaku : [Tuberculosis] KW - Adolescent Adult Child Child, Preschool Humans Infant Infant, Newborn Japan Middle Aged *Models, Theoretical Tuberculosis, Pulmonary/*epidemiology LA - jpn M1 - 7 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 - 639 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 - 1975/04/01 KW - Epidemiologic Methods Humans Male Mathematics Models, Theoretical Naval Medicine Probability Tuberculin Test Tuberculosis, Pulmonary/ epidemiology United States LA - eng M1 - 4 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 - 932 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 - 975 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 - 1001 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 - 1976/09/01 KW - Cost-Benefit Analysis Health Services Humans Mass Screening Models, Theoretical Phenylketonurias/prevention & control Systems Analysis Tuberculin Test Tuberculosis/prevention & control LA - eng M1 - 3 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 - 692 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 - 919 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 - 974 ER - TY - JOUR AN - 1030279 AU - Sutherland, I. AU - Svandova, E. AU - Radhakrishna, S. ET - 1976/01/01 J2 - Bulletin of the International Union against Tuberculosis KW - Adolescent Adult Female Humans Male Middle Aged *Models, Biological Recurrence Risk *Tuberculosis, Pulmonary LA - eng M1 - 1 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 - 976 ER - TY - JOUR AN - 615153 AU - Nair, S. S. DA - Jul-Sep ET - 1977/07/01 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 - 889 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 - 633 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 - 968 ER - TY - JOUR AU - Sivaraman, V. AU - Umasankar, V. M1 - 1 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 - 959 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 - 1980/06/01 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 M1 - 3 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 - 872 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 - 708 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 - 879 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 - 1982/12/01 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 M1 - 4 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/6763793 http://ac.els-cdn.com/S0041387982800135/1-s2.0-S0041387982800135-main.pdf?_tid=5a366d31da488d96f9d9423663709bf6&acdnat=1345013641_fafdd63c26ae10575d849ec75af0d748 VL - 63 ID - 977 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 - 983 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 - 961 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 - 1987/12/01 KW - Adult Aged Epidemiologic Methods Humans Korea Middle Aged Models, Theoretical Probability Random Allocation Recurrence Taiwan Tuberculosis, Pulmonary/classification/ epidemiology LA - eng M1 - 4 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 - 945 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 - 1988/10/06 KW - Communicable Diseases/ etiology/transmission Health Resources Health Services Research Mass Screening/ organization & administration Models, Statistical LA - eng M1 - 6 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 - 835 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 - 1988/12/01 KW - History, Ancient History, Medieval Humans Illinois Models, Biological Social Environment Tuberculosis/history/ transmission LA - eng M1 - 4 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 - 871 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 - 1988/03/01 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 M1 - 2 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 - 930 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 - 1989/01/01 KW - Cohort Studies Computer Simulation Emigration and Immigration Forecasting Humans Italy/epidemiology Models, Theoretical Retrospective Studies Tuberculosis/ epidemiology LA - eng M1 - 1-3 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 - 618 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 - 1989/03/01 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 M1 - 1 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/2498217 http://ije.oxfordjournals.org.ez.lshtm.ac.uk/content/18/1/174.full.pdf VL - 18 ID - 817 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 - 1990/10/01 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 M1 - 4 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 - 766 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 - 1990/08/01 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 M1 - 8 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 - 888 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 - 642 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 - 1992/10/01 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 TB incidence by 2002. Public health officials could use this model to plan TB control programs to bring about a reduction in the increase. Even though TB control programs can help stem the projected increase, it will be very difficult for developing countries with high HIV prevalence to hold back the projected rise in TB incidence. Developing countries must take considerable appropriate action soon to prevent doubling of TB incidence as HIV prevalence nears 13% of adults. LA - eng M1 - 10 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 - 554 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 - 1992/08/21 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 LA - eng M1 - 5073 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 VL - 257 ID - 664 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 - 1992/02/01 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 M1 - 1 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 - 599 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 - 1993/07/01 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 M1 - 4 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 - 572 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 M1 - 9 M3 - doi: 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 - 583 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 - 1993/04/01 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 M1 - 4 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 - 892 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 - 717 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. C2 - 2486541 (TB) will occur worldwide, of which 8 million will be attributable to HIV infection. 30 million people are predicted to die of TB over the period, including 2.9 million attributable to HIV infection. Given a constant level of treatment availability, the numbers of new cases and deaths will both increase each year over the period. 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, however, are increasing due to the HIV epidemic and will account for the remaining 20.5% of the forecast increase in new cases. In the World Health Organization's Southeast Asia region and in Central and South America, 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. Finally, in the Western Pacific and Eastern Mediterranean regions, intervention strategies should reduce the age-specific incidence rates during the period, but population growth will fuel an increase in the total number of new cases until the year 2000. DP - Nlm ET - 1994/01/01 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 M1 - 2 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 - 562 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 - 1994/06/01 KW - Humans Models, Statistical Occupational Diseases/ epidemiology/ etiology Poisson Distribution Respiratory Protective Devices Risk Tuberculosis/ epidemiology/ transmission LA - eng M1 - 6 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 - 894 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 - 1994/04/01 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 M1 - 2 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 - 600 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 - 1995/08/01 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 M1 - 8 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 - 667 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 - 1995/02/01 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 M1 - 2 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 - 582 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 - 1995/08/23 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 M1 - 8 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 - 877 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=7780092 http://ac.els-cdn.com/0962847995905529/1-s2.0-0962847995905529-main.pdf?_tid=c07e572e-6b37-11e2-a32a-00000aacb360&acdnat=1359589977_76de43cdb6962b4403e18004d77ee7f5 VL - 76 ID - 924 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 - 1996/03/22 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 M1 - 1368 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 - 628 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 - 1996/07/26 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 LA - eng M1 - 5274 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 VL - 273 ID - 668 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 - 1996/12/18 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 LA - eng M1 - 23 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 VL - 276 ID - 675 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 - 878 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 - 1996/08/01 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 M1 - 4 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 - 895 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 - 1997/07/01 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 M1 - 1 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 - 684 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 - 1997/06/01 KW - Antitubercular Agents/*pharmacology *Drug Resistance, Microbial Humans *Models, Theoretical Tuberculosis/*drug therapy/epidemiology 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 - 688 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 - 1997/06/01 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 M1 - 7 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 - 570 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. C2 - 2627642 DA - Jul-Sep DP - Nlm ET - 1997/07/01 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 M1 - 3 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 - 773 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 - 1997/02/01 KW - Epidemiologic Methods France/epidemiology Humans Incidence Models, Theoretical Netherlands/epidemiology Risk Assessment Time Factors Tuberculosis/ epidemiology LA - eng M1 - 1 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 - 775 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 - 2000/05/24 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 LA - eng M1 - 6 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 - 1997 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 VL - 112 ID - 801 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. C2 - 1381230 DA - Dec DP - Nlm ET - 1998/02/07 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 M1 - 12 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 - 1997 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 - 840 ER - TY - JOUR AU - Marcus, Alexander M. AU - Rose, David N. AU - Sacks, Henry S. AU - Schechter, Clyde B. KW - Bacille Calmette-Guérin BCG health care worker isoniazid occupational health prevention tuberculin tuberculosis vaccination M1 - 2 M3 - doi: 10.1006/pmed.1996.0123 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 - 863 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 - 1997/05/26 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 M1 - 10 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 - 893 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 - 1997/12/31 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 M1 - 12 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 - 937 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 - 1997/06/15 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 M1 - 12 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 - 939 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 - 960 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 - 1998/01/24 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 M1 - 5 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 - 1997 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 - 995 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 M1 - 2 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.pdf http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808840/pdf/9363017.pdf VL - 119 ID - 996 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 - 1997/07/01 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 M1 - 1 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 - 1012 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 - 1998/09/02 KW - Disease Outbreaks Drug Resistance, Microbial Health Policy Humans Models, Biological Mycobacterium tuberculosis Tuberculosis/epidemiology/microbiology/ prevention & control LA - eng M1 - 9 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 - 666 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 - 1998/08/26 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 M1 - 2 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/9711046 http://www.sciencedirect.com/science/article/pii/S0025556498100160 VL - 151 ID - 689 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 - 1998/12/24 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 LA - eng M1 - 9144 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 - 568 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 - 1998/11/04 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 M1 - 10 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 - 763 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 M1 - 20 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 - 765 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 - 1998/04/04 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 LA - eng M1 - 3 N1 - Lipsitch, M Levin, B R GM-19182/GM/NIGMS NIH HHS/United States GM-33782/GM/NIGMS NIH HHS/United States Research Support, U.S. Gov't, P.H.S. 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):187-99. 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 - 845 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. C2 - 24946 DA - Nov 10 DP - Nlm ET - 1998/11/13 KW - Communicable Disease Control Humans Models, Biological Models, Theoretical Tuberculosis/ epidemiology/ prevention & control World Health Organization LA - eng M1 - 23 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 - 883 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 - 1998/10/02 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 M1 - 9 Suppl 1 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 - 884 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 - 1998/04/07 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 LA - eng M1 - 3 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 - 904 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 M1 - 2 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 - 910 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 - 1998/04/04 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 M1 - 3 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 - 928 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 - 1998/12/05 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 M1 - 10 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=9841583 http://annals.org/data/Journals/AIM/19920/0000605-199811150-00005.pdf VL - 129 ID - 929 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 - 1998/03/21 KW - Age Distribution Humans Incidence Models, Theoretical Prevalence Prospective Studies Retrospective Studies Tuberculosis/ epidemiology/transmission United States/epidemiology LA - eng M1 - 4 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 - 935 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 - 942 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. C2 - 2809528 DA - Oct ET - 1998/11/24 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 M1 - 2 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 - 997 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 - 553 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 - 1999/02/20 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 M1 - 4 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/10025480 http://aje.oxfordjournals.org/content/149/4/366.full.pdf VL - 149 ID - 781 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 - 1999/02/02 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 M1 - 1 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 - 575 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 - 862 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 - 906 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 - 1999/08/03 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 M1 - 2 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 - 962 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 - 963 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 - 1999/05/26 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 M1 - 2 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/10342699 http://ije.oxfordjournals.org/content/28/2/327.full.pdf VL - 28 ID - 998 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 - 1999/08/18 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 - 1025 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 - 629 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 - 2000/04/06 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 M1 - 3 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 - 691 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 - 2000/12/09 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 M1 - 6 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 - 711 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 - 2000/06/30 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 M1 - 4 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 - 713 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. C2 - 2640843 DA - Mar-Apr DP - Nlm ET - 2000/04/11 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 M1 - 2 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 - 721 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 - 2000/06/28 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 M1 - 3 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 - 742 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. C2 - 16690 DA - Jul 5 DO - 10.1073/pnas.140102797 [doi] 140102797 [pii] DP - Nlm ET - 2000/06/22 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 LA - eng M1 - 14 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 VL - 97 ID - 744 ER - TY - CHAP A2 - Portaels, F. A2 - Bastian, I. AU - Dye, C. AU - Williams, B. G. AU - Bastian, I. C3 - www CY - Dortrecht L1 - internal-pdf://Dye -2000 - Population dynamics and control of multidrug-resistant tuberculosis-4250904095/Dye -2000 - Population dynamics and control of multidrug-resistant tuberculosis.pdf 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 - 747 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 - 2000/06/01 KW - Disease Susceptibility Emigration and Immigration Endemic Diseases/statistics & numerical data Humans Models, Biological Tuberculosis/ epidemiology/prevention & control/ transmission LA - eng M1 - 3 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 - 761 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 - 2000/07/06 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 M1 - 1 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 - 802 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 - 2000/11/09 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 M1 - 5 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 - 814 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 - 2000/07/06 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 - 839 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 - 2001/02/24 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 M1 - 4 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 - 2000 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 - 841 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 - 2000/08/11 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 M1 - 3 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 - 849 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 - 2000/07/21 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 M1 - 5 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 - 851 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 - 2000/03/08 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 M1 - 1 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 - 880 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 - 2000/09/08 KW - Air Microbiology Air Pollution, Indoor/ analysis Humans Markov Chains Models, Statistical Occupational Exposure/analysis/prevention & control Tuberculosis/prevention & control/transmission Ventilation LA - eng M1 - 4 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 - 896 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 - 2000/09/21 KW - Cohort Studies Humans Likelihood Functions Models, Statistical Seasons Spain/epidemiology Time Factors Tuberculosis, Pulmonary/ epidemiology LA - eng M1 - 5 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 - 925 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 - 2000/03/11 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 M1 - 3 Pt 1 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 - 948 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=10716736 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC16274/pdf/pq003532.pdf VL - 97 ID - 981 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 - 982 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 - 2000/08/10 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 M1 - 3 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/10933272 http://aje.oxfordjournals.org/content/152/3/247.full.pdf VL - 152 ID - 999 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 - 2001/11/22 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 M1 - 11 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 - 662 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 - 2001/11/09 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 M1 - 10 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/11700248 http://aje.oxfordjournals.org/content/154/10/934.full.pdf VL - 154 ID - 671 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 - 2001/08/22 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 M1 - 7 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 - 676 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. C2 - 1087599 DA - Jan 7 DO - 10.1098/rspb.2000.1328 [doi] DP - Nlm ET - 2002/07/19 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 LA - eng M1 - 1462 N1 - Dye, C Espinal, M A England Proceedings. Biological sciences / The Royal Society Proc Biol Sci. 2001 Jan 7;268(1462):45-52. PY - 2001 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 VL - 268 ID - 741 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 - 762 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 - 819 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 - 2001/12/01 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 M1 - 4 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 - 824 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 - 2001/09/21 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 M1 - 3 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=11564856 http://www.springerlink.com/content/c7n6868776414512/fulltext.pdf VL - 78 ID - 907 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 - 2001/12/18 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 M1 - 5 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 - 592 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 - 915 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. C2 - 1088501 DA - Jul 29 DO - 10.1098/rstb.2001.0895 [doi] DP - Nlm ET - 2001/08/23 KW - Humans Prevalence Prisons Quality of Health Care Russia/epidemiology Survival Rate Treatment Outcome Tuberculosis/drug therapy/ epidemiology LA - eng M1 - 1411 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 - 955 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 M1 - 1 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=11293682 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869673/pdf/11293682.pdf VL - 126 ID - 1000 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/11160244 http://www.jimmunol.org/content/166/3/1951.full.pdf VL - 166 ID - 1014 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 - 2002/01/05 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 LA - eng M1 - 12 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 - 2001 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 - 613 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 - 2001/02/24 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 M1 - 4 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/11207156 http://aje.oxfordjournals.org/content/153/4/381.full.pdf VL - 153 ID - 1028 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 - 2002/06/08 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 M1 - 2 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 - 630 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 - 718 ER - TY - JOUR AB - Multidrug-resistant tuberculosis (MDR) is perceived as a growing hazard to human health worldwide. Judgments about the true scale of the problem, and strategies for containing it, need to come from a balanced appraisal of the epidemiological evidence. We conclude in this review that MDR is, and will probably remain, a locally severe problem; that epidemics can be prevented by fully exploiting the potential of standard short-course chemotherapy (SCC) based on cheap and safe first-line drugs; and that best-practice SCC may even reduce the incidence of MDR where it has already become endemic. On the basis of the available, imperfect data, we recommend a three-part response to the threat of MDR: widespread implementation of SCC as the cornerstone of good tuberculosis control, improved resistance testing and surveillance, and the careful introduction of second-line drugs after a sound evaluation of cost, effectiveness, and feasibility. AD - Communicable Diseases, World Health Organization, CH-1211 Geneva 27, Switzerland. dyec@who.int AN - 11896268 AU - Dye, Christopher AU - Williams, Brian G AU - Espinal, Marcos A AU - Raviglione, Mario C DA - Mar 15 KW - Mycobacterium tuberculosis Acquired Immunodeficiency Syndrome World Health HIV Infections Humans Drug Resistance: Multiple: Bacterial Incidence Tuberculosis: Multidrug-Resistant Antitubercular Agents Drug Therapy: Combination LB - p08170 M1 - 5562 PY - 2002 RN - fulltext fulltext_1208 SP - 2042-6 ST - Erasing the world's slow stain: strategies to beat multidrug-resistant tuberculosis T2 - Science TI - Erasing the world's slow stain: strategies to beat multidrug-resistant tuberculosis UR - http://www.sciencemag.org/cgi/content/full/295/5562/2042 http://www.sciencemag.org/content/295/5562/2042.full.pdf VL - 295 ID - 748 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 - 2002/07/02 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 M1 - 1 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 - 780 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 - 2002/10/22 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 - 881 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. C2 - 122226 DA - Feb 5 DO - 10.1073/pnas.022618299 ET - 2002/01/31 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 M1 - 3 M3 - Comparative Study Research Support, U.S. Gov't, P.H.S. N1 - Murray, Megan AI-01430-01/AI/NIAID NIH HHS/ Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1538-43. Epub 2002 Jan 29. 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/11818527 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC122226/pdf/pq0302001538.pdf VL - 99 ID - 588 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. C2 - 2730247 DA - Apr DO - 10.3201/eid0804.000444 [doi] DP - Nlm ET - 2002/04/25 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 M1 - 4 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 - 885 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 - 909 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 M1 - 01 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 - 594 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 - 2002/04/24 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 M1 - 2 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 - 943 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 - 2002/10/22 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 - 964 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 - 2002/04/05 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 M1 - 2 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 - 1020 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. C2 - 155390 DA - Jun DP - Nlm ET - 2003/05/20 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 M1 - 11 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 - 623 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 - 2003/11/06 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 M1 - 11 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 - 651 ER - TY - JOUR 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 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 - 661 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 M1 - 4 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 - 673 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 M1 - 9 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=12742798 http://archinte.jamanetwork.com/data/Journals/INTEMED/5439/ira20017.pdf VL - 163 ID - 1435 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 - 2003/11/06 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 M1 - 17 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 - 560 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 - 735 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 - 798 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 M1 - 3 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 - 799 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 - 2003/05/17 KW - HIV Infections Humans Malaria Models, Biological Schistosomiasis Superinfection/ microbiology/ parasitology Tuberculosis LA - eng M1 - 5 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 - 867 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 - 2003/07/24 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 M1 - 4 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 - 882 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 M1 - 4 M3 - doi: 10.1080/02329290290027175 N1 - doi: 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/10.1080/02329290290027175 http://www.tandfonline.com/doi/abs/10.1080/02329290290027175 VL - 43 Y2 - 2012/08/10 ID - 916 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 - 931 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 M1 - 1 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 - 944 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 M1 - 7389 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 VL - 326 ID - 967 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. M1 - 2 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 - 994 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 M1 - 5639 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 - 610 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 - 2004/05/14 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 M1 - 2 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 - 1418 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 - 2004/09/21 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 LA - eng M1 - 10 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 VL - 10 ID - 665 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 M1 - 3 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 - 697 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. C2 - 2652755 DA - Oct DO - 10.1038/nm1110 [doi] nm1110 [pii] DP - Nlm ET - 2004/09/21 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 LA - eng M1 - 10 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 VL - 10 ID - 703 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 - 2004/01/28 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 M1 - 2 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 - 771 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=15081074 http://ac.els-cdn.com/S0933365703001337/1-s2.0-S0933365703001337-main.pdf?_tid=26f9353e-6b36-11e2-b271-00000aab0f6c&acdnat=1359589290_10f521802b4cf63c00c720e01649cbab VL - 30 ID - 777 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. C2 - 1691632 DA - Mar 22 DO - 10.1098/rspb.2003.2606 ET - 2004/05/26 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 M1 - 1539 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/15156920 http://pubmedcentralcanada.ca/picrender.cgi?accid=PMC1691632&blobtype=pdf VL - 271 ID - 785 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.pdf http://ac.els-cdn.com/S0022519304000748/1-s2.0-S0022519304000748-main.pdf?_tid=a369897a-6b36-11e2-a468-00000aacb362&acdnat=1359589498_229e65e7b4d531f910339318b91df69b VL - 228 ID - 786 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 - 2004/10/13 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 LA - eng M1 - 9 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 VL - 190 ID - 792 ER - TY - JOUR AU - Guwatudde, D. AU - Debanne, S. M. AU - Diaz, M. AU - King, C. AU - Whalen, C. C. KW - Tuberculosis preventive therapy Tuberculosis control Sub-Saharan Africa HIV-infection Deterministic model M1 - 5 M3 - doi: 10.1016/j.ypmed.2004.04.008 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/S0091743504002117 http://ac.els-cdn.com/S0091743504002117/1-s2.0-S0091743504002117-main.pdf?_tid=88ab7fb2ac53ae8c8768c7226bf2893a&acdnat=1345012430_531a7dd98abd3bed8080cd1e63a4eaa5 VL - 39 ID - 571 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 - 2004/04/14 KW - Aerospace Medicine Air Microbiology Aviation Humans Models, Biological Risk Risk Assessment Tuberculosis, Pulmonary/ transmission Ventilation LA - eng M1 - 2 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 - 825 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 - 2004/03/25 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 M1 - 4 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 - 864 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 - 2005/02/04 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 LA - eng M1 - 3 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 - 897 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 - 2004/04/07 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 M1 - 3 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 - 918 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 - 2005/01/08 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 M1 - 12 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 - 2004 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/10.1086/502343 http://www.jstor.org/stable/pdfplus/10.1086/502343.pdf?acceptTC=true VL - 25 ID - 936 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 - 2004/10/27 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 M1 - 3 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 - 951 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 - 980 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 - 2004/10/23 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 M1 - 9 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 - 1027 ER - TY - JOUR AB - This study sought to determine the impact of an effective programme of multidrug resistant tuberculosis control (MDRTB) on a population that is witnessing an explosive HIV epidemic among injecting drug users (IDUs), where the prevalence of MDRTB is already high. A transmission model was constructed that represents the dynamics of the drug-susceptible tuberculosis (DSTB), MDRTB and HIV spread among the adult population of Samara Oblast, Russia: from official notifications of tuberculosis and of HIV infection, estimates of MDRTB derived from surveillance studies, population data from official regional statistics, data on transmission probabilities from peer-reviewed publications and informed estimates, and policy-makers' estimates of IDU populations. Two scenarios of programme effectiveness for MDRTB were modelled and run over a period of 10 years to predict cumulative deaths. In a population of 3.3 million with a high prevalence of MDRTB, an emerging epidemic of HIV among IDUs, and a functioning directly observed therapy-short course (DOTS) programme, the model predicts that under low cure rates for MDRTB the expected cumulative deaths from tuberculosis will reach 6303 deaths including 1900 deaths from MDRTB at 10 years. Under high cure rate for MDRTB 4465 deaths will occur including 134 deaths from MDRTB. At 10 years there is little impact on HIV-infected populations from the MDRTB epidemic, but as the HIV epidemic matures the impact becomes substantial. When the model is extended to 20 years cumulative deaths from MDRTB become very high if cure rates for MDRTB are low and cumulative deaths in the HIV-infected population, likewise, are profoundly affected. In the presence of an immature HIV epidemic failure to actively control MDRTB may result in approximately a third more deaths than if effective treatment is given. As the HIV epidemic matures then the impact of MDRTB grows substantially if MDRTB control strategies are ineffective. The epidemiological starting point for these scenarios is present in many regions within the former Soviet Union and this analysis suggests control of MDRTB should be an urgent priority. AD - Centre for Health Management, The Business School, Imperial College London, South Kensington Campus, London, UK. AN - 16105192 AU - Atun, R. A. AU - Lebcir, R. AU - Drobniewski, F. AU - Coker, R. J. DA - Aug DO - 10.1258/0956462054679124 [doi] DP - Nlm ET - 2005/08/18 KW - AIDS-Related Opportunistic Infections/ epidemiology Acquired Immunodeficiency Syndrome/complications/epidemiology/mortality Antitubercular Agents/ therapeutic use Computer Simulation Humans Tuberculosis, Multidrug-Resistant/ drug therapy/epidemiology/ prevention & control LA - eng M1 - 8 N1 - Atun, Rifat A Lebcir, Reda Drobniewski, Francis Coker, Richard J Research Support, Non-U.S. Gov't England International journal of STD & AIDS Int J STD AIDS. 2005 Aug;16(8):560-70. PY - 2005 RN - fulltext fulltext_1208 SN - 0956-4624 (Print) 0956-4624 (Linking) SP - 560-70 ST - Impact of an effective multidrug-resistant tuberculosis control programme in the setting of an immature HIV epidemic: system dynamics simulation model T2 - Int J STD AIDS TI - Impact of an effective multidrug-resistant tuberculosis control programme in the setting of an immature HIV epidemic: system dynamics simulation model UR - http://ijsa.rsmjournals.com/content/16/8/560 http://ijsa.rsmjournals.com/content/16/8/560.full.pdf VL - 16 ID - 635 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. C2 - 1309642 DA - Dec 10 DO - 10.1136/bmj.38645.660093.68 ET - 2005/11/12 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 LA - eng M1 - 7529 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/16282379 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1309642/pdf/bmj33101364.pdf VL - 331 ID - 546 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. C2 - 1361804 DO - 1471-2458-5-130 [pii] 10.1186/1471-2458-5-130 [doi] DP - Nlm ET - 2005/12/14 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/1471-2458/5/130 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1361804/pdf/1471-2458-5-130.pdf VL - 5 ID - 559 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 - 725 ER - TY - JOUR AU - Gammack, D. AU - Ganguli, S. AU - Marino, S. AU - Segovia-Juarez, J. AU - Kirschner, D.E. M1 - 2 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 - 772 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 - 774 ER - TY - JOUR AB - Abstract 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 M1 - 3 M3 - doi: 10.1080/13926292.2005.9637287 N1 - doi: 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 - 590 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 - 2005/09/09 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 M1 - 10 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 - 949 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. C2 - 1157104 DA - Jul 5 DO - 0501615102 [pii] 10.1073/pnas.0501615102 [doi] DP - Nlm ET - 2005/06/25 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 M1 - 27 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 - 611 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 - 2005/12/13 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 M1 - 2 N1 - Bachmann, M O England AIDS Care. 2006 Feb;18(2):109-20. PY - 2006 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 - 545 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 - 2006/06/07 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 M1 - 6 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 - 653 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 - 696 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. C2 - 1459015 DA - May 2 DO - 0600349103 [pii] 10.1073/pnas.0600349103 [doi] DP - Nlm ET - 2006/04/25 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 LA - eng M1 - 18 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 VL - 103 ID - 558 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 - 2006/09/13 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 M1 - 9 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 - 714 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 - 2006/07/22 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 M1 - 3 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 - 715 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 - 723 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 - 2006/03/04 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 M1 - 5 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 - 565 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 - 2006/01/20 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 LA - eng M1 - 4 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 VL - 42 ID - 738 ER - TY - CPAPER AU - Hughes, Georgina R. AU - Currie, Christine S. M. AU - Corbett, Elizabeth L. C1 - 1218200 CY - Monterey, California L1 - internal-pdf://Hughes_2006 DES simulation (conference)-3713912095/Hughes_2006 DES simulation (conference).pdf 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 - 573 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. C2 - 1590025 DO - 1471-2458-6-209 [pii] 10.1186/1471-2458-6-209 [doi] DP - Nlm ET - 2006/08/17 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 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/1471-2458/6/209 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1590025/pdf/1471-2458-6-209.pdf VL - 6 ID - 574 ER - TY - JOUR AU - JOSHI, RAJANI R. AU - RAGHUVANSHI, MEENAKSHI AU - PANDYA, PRANAV DO - doi:10.1142/S0218339006001891 M1 - 03 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 - 820 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 - 2006/10/01 LA - eng M1 - 4 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 - 578 ER - TY - JOUR AU - MAGOMBEDZE, GESHAM AU - GARIRA, WINSTON AU - MWENJE, EDDIE DO - doi:10.1142/S0218339006001945 M1 - 04 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 - 853 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 - 2006/10/01 LA - eng M1 - 4 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 - 870 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 - 2006/03/04 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 M1 - 1 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 - 903 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. C2 - 1559699 DO - 1471-2458-6-157 [pii] 10.1186/1471-2458-6-157 [doi] DP - Nlm ET - 2006/06/21 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 - 911 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 M1 - 7 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 VL - 3 Y2 - Jul ID - 921 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. C2 - 1523376 DA - Aug DO - 05-PLME-RA-0399R2 [pii] 10.1371/journal.pmed.0030273 [doi] DP - Nlm ET - 2006/07/27 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 M1 - 8 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 - 934 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 - 603 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 - 2006/11/07 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 M1 - 8 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 - 1011 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 M1 - 1 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 - 1022 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 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 LA - eng M1 - 1 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 - 622 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 - 2007/12/14 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 M1 - 4 N1 - Armbruster, Benjamin Brandeau, Margaret L DA-R01-15612/DA/NIDA NIH HHS/United States Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Netherlands Health Care Manag Sci. 2007 Dec;10(4):341-55. 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 - 634 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 - 2007/05/19 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 LA - eng M1 - 4 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/18/4/267 http://ijsa.rsmjournals.com/content/18/4/267.full.pdf VL - 18 ID - 543 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 - 2006/07/21 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 LA - eng M1 - 2-3 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 - 2007 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 - 637 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 - 2007/10/30 KW - Cross Infection/ prevention & control/transmission Hospitals, District Humans Models, Theoretical Rural Health South Africa/epidemiology Tuberculosis, Multidrug-Resistant/epidemiology/ prevention & control/transmission LA - eng M1 - 9597 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/fulltext http://ac.els-cdn.com/S0140673607616365/1-s2.0-S0140673607616365-main.pdf?_tid=e27df51c-f0e6-11e1-879f-00000aacb35e&acdnat=1346141203_b98aeedbc04189a4bb89b46e525174b1 VL - 370 ID - 547 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 - 663 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. C2 - 2373405 DA - Jun 22 DO - PJ25346278M18447 [pii] 10.1098/rsif.2006.0193 [doi] DP - Nlm ET - 2007/01/26 KW - Cluster Analysis Disease Outbreaks/prevention & control Europe/epidemiology Humans Models, Biological Tuberculosis, Pulmonary/ epidemiology/prevention & control/ transmission LA - eng M1 - 14 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 - 698 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. C2 - 2652758 DA - Aug 21 DO - S0022-5193(07)00197-X [pii] 10.1016/j.jtbi.2007.04.015 [doi] DP - Nlm ET - 2007/06/02 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 M1 - 4 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 - 706 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 M1 - 5 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 - 724 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 - 2007/05/17 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 M1 - 2 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 - 727 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 - 749 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 - 2007/07/04 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 M1 - 1 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 - 767 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 - 2007/08/03 KW - Antitubercular Agents/therapeutic use Carrier State/immunology Humans Models, Biological Recurrence/prevention & control Tuberculosis/ immunology/ prevention & control/transmission Tuberculosis Vaccines LA - eng M1 - 4 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 - 783 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. C2 - 1913269 DA - Jul DO - AAC.00185-07 [pii] 10.1128/AAC.00185-07 [doi] DP - Nlm ET - 2007/04/18 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 LA - eng M1 - 7 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 VL - 51 ID - 793 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 - 804 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 - 2006/12/23 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 M1 - 1 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 - 2007 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 - 826 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 US Agcy Int Dev, Infect Dis Div, Bur Global Hlth, Washington, DC 20523 USA WHO, Stop TB Partnership Secretariat, CH-1211 Geneva, Switzerland 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 M1 - 5 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 - ://000246790400008 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2636650/pdf/06-037820.pdf VL - 85 ID - 857 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 - 604 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. C2 - 1794282 DA - Feb 6 DO - 0607208104 [pii] 10.1073/pnas.0607208104 [doi] DP - Nlm ET - 2007/02/01 KW - Algorithms Animals Bayes Theorem Computer Simulation/statistics & numerical data Humans Likelihood Functions Models, Statistical Monte Carlo Method Tuberculosis/epidemiology/transmission LA - eng M1 - 6 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 - 958 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 - 965 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 - ://000250030800001 http://www.biomedcentral.com/1471-2458/7/234 VL - 7 ID - 969 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. C2 - 1942086 DO - 10.1371/journal.pone.0000757 ET - 2007/08/23 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 M1 - 8 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 - 1273 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 - 2008/07/19 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 LA - eng M1 - 4 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/10.1086/590010 http://cid.oxfordjournals.org/content/47/4/487.full.pdf VL - 47 ID - 619 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 - 2008/04/17 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 M1 - 4 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=18414866 http://www.springerlink.com/content/b7242x4625711ug8/fulltext.pdf VL - 57 ID - 544 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 - 2008/09/26 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 LA - eng M1 - 10 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 VL - 198 ID - 551 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 - 2008/07/23 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 M1 - 3 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 - 658 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 - 2008/01/31 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 M1 - 4 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 - 659 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. C2 - 2522280 DO - 10.1371/journal.pone.0003154 [doi] DP - Nlm ET - 2008/09/09 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 M1 - 9 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 - 669 ER - TY - JOUR AU - Cohen, T. AU - Colijn, C. AU - Finklea, B. AU - Wright, A. AU - Zignol, M. AU - Pym, A. AU - Murray, M. M1 - 6 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 VL - 3 ID - 699 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. C2 - 2570977 DA - Oct 21 DO - 0808746105 [pii] 10.1073/pnas.0808746105 [doi] DP - Nlm ET - 2008/10/14 KW - Models, Biological Tuberculosis/immunology Tuberculosis Vaccines/ classification/ immunology LA - eng M1 - 42 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 - 700 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 - 2008/01/31 KW - Humans Interferon-gamma/ secretion Research Design Sensitivity and Specificity Tuberculin Test Tuberculosis/ diagnosis LA - eng M1 - 2 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 - 712 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. C2 - 2516234 DA - Aug 12 DO - 0800965105 [pii] 10.1073/pnas.0800965105 [doi] DP - Nlm ET - 2008/08/13 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 LA - eng M1 - 32 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 VL - 105 ID - 564 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. C2 - 2614861 DO - 10.1371/journal.pone.0004057 ET - 2009/01/09 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 M1 - 12 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 - 2008 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/19129940 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614861/pdf/pone.0004057.pdf VL - 3 ID - 566 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 - 2008/08/21 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 M1 - 9 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 - 567 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 - 2008/09/09 KW - Algorithms Antitubercular Agents/ classification Databases, Factual Ethnobotany Fuzzy Logic Models, Biological Plants, Medicinal/ classification LA - eng M1 - 3 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 - 739 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. C2 - 3226985 DA - Jun 6 DO - N502JJ12W45R6403 [pii] 10.1098/rsif.2007.1138 [doi] DP - Nlm ET - 2007/08/11 KW - Antitubercular Agents/therapeutic use Computer Simulation Endemic Diseases Humans Models, Biological Tuberculosis/drug therapy/ prevention & control/transmission World Health LA - eng M1 - 23 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 - 2008 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 - 745 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 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=18798687 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2535657/pdf/pmed.0050188.pdf VL - 5 ID - 569 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 - 2008/05/07 KW - Evolution, Molecular Minisatellite Repeats Models, Genetic Mutation Mycobacterium tuberculosis/classification/ genetics LA - eng M1 - 6 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 - 790 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 - 2008/09/19 KW - Cost-Benefit Analysis Humans Mycobacterium tuberculosis/genetics/*isolation & purification Nucleic Acid Amplification Techniques/*economics/*methods Tuberculosis, Pulmonary/*diagnosis/microbiology LA - eng M1 - 11 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.pdf http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2576624/pdf/1682-08.pdf VL - 46 ID - 791 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 - 2008/07/12 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 M1 - 3 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 - 794 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 - 2008/02/08 KW - Emigration and Immigration Humans Models, Theoretical Tuberculosis/ epidemiology LA - eng M1 - 3 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 - 816 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 - 2008/07/26 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 M1 - 4 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 - 830 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. C2 - 2324198 DO - 10.1371/journal.pone.0002100 [doi] DP - Nlm ET - 2008/05/08 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 M1 - 5 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 - 836 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. C2 - 2652750 DA - Oct 25 DO - 10.1016/S0140-6736(08)61345-8 ET - 2008/10/07 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 M1 - 9648 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/18835640 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652750/pdf/nihms-94728.pdf VL - 372 ID - 843 ER - TY - JOUR AU - MAGOMBEDZE, GESHAM AU - GARIRA, WINSTON AU - MWENJE, EDDIE DO - doi:10.1142/S0218339008002551 M1 - 03 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 - 579 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 M1 - 12 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 - 866 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. C2 - 2276686 DO - 10.1371/journal.pone.0001933 [doi] DP - Nlm ET - 2008/04/10 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 M1 - 4 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 - 586 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 - 2008/09/25 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 M1 - 10 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 - 1181 ER - TY - JOUR AU - OKUONGHAE, DANIEL AU - AIHIE, VINCENT DO - doi:10.1142/S0218339008002344 M1 - 01 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 - 898 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 - 2008/12/05 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 M1 - 12 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 - 913 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 - 2008/05/06 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 LA - eng M1 - 8 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/18453856 http://graphics.tx.ovid.com/ovftpdfs/FPDDNCGCICCHEG00/fs046/ovft/live/gv025/00002030/00002030-200805110-00007.pdf VL - 22 ID - 597 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 - 2007/04/18 KW - Analysis of Variance Bayes Theorem Cluster Analysis DNA Fingerprinting Female Humans Male Molecular Epidemiology/ methods Mycobacterium tuberculosis/ genetics Tuberculosis/ epidemiology/ microbiology LA - eng M1 - 1 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 - 2008 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 - 950 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 - 2008/01/16 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 M1 - 1 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 - 602 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. C2 - 2443799 DO - 10.1186/1471-2458-8-201 DP - NLM ET - 2008/06/07 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 - 978 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 - 2008/05/21 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 M1 - 5 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 - 979 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. C2 - 2870882 DA - Jul DO - S0950268807008552 [pii] 10.1017/S0950268807008552 [doi] DP - Nlm ET - 2007/08/07 KW - Adult Age Factors Aged Communicable Disease Control/methods Hong Kong/epidemiology Humans Incidence Male Middle Aged Recurrence Risk Factors Tuberculosis/ epidemiology LA - eng M1 - 7 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 - 2008 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 - 993 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 - 2008/04/03 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 M1 - 4 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 - 1010 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. C2 - 2415769 DA - Jun DO - AAC.00461-07 [pii] 10.1128/AAC.00461-07 [doi] DP - Nlm ET - 2008/04/09 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 M1 - 6 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 - 609 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 - 2008/07/29 KW - Canada/epidemiology Disease Outbreaks Emigration and Immigration Forecasting Humans Incidence Models, Biological Models, Statistical Mycobacterium tuberculosis Tuberculosis/ epidemiology/transmission LA - eng M1 - 2 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 - 1026 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. C2 - 2720405 DA - Aug 18 DO - 0901720106 [pii] 10.1073/pnas.0901720106 [doi] DP - Nlm ET - 2009/08/12 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 M1 - 33 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 - 617 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. C2 - 2706250 DO - 1471-2334-9-87 [pii] 10.1186/1471-2334-9-87 [doi] DP - Nlm ET - 2009/06/10 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 - 620 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 - 2009/03/20 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=19295437 http://graphics.tx.ovid.com/ovftpdfs/FPDDNCGCAGHAJF00/fs047/ovft/live/gv024/00001648/00001648-200907000-00015.pdf VL - 20 ID - 624 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 - 2009/04/15 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 M1 - 2 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 - 631 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. C2 - 2678614 DA - May 5 DO - 0812472106 [pii] 10.1073/pnas.0812472106 [doi] DP - Nlm ET - 2009/04/15 KW - Disease Outbreaks/ prevention & control Humans Models, Biological South Africa/epidemiology Tuberculosis, Multidrug-Resistant/ epidemiology/ prevention & control/transmission LA - eng M1 - 18 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 VL - 106 ID - 548 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=19172358 http://www.springerlink.com/content/a214u21283449170/ http://www.springerlink.com/content/a214u21283449170/?MUD=MP VL - 71 ID - 549 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 - 2009/04/23 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 LA - eng M1 - 5 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 - 550 ER - TY - JOUR AB - Abstract 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 M1 - 3 M3 - doi: 10.3846/1392-6292.2009.14.291-312 N1 - doi: 10.3846/1392-6292.2009.14.291-312 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 VL - 14 Y2 - 2012/08/10 ID - 656 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 - 2009/05/29 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 M1 - 7 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 - 555 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 M1 - 8 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 - 683 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. C2 - 2726785 DA - Aug DO - 10.1371/journal.pcbi.1000489 [doi] DP - Nlm ET - 2009/08/29 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 M1 - 8 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 - 704 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. C2 - 2652765 DA - Jan DO - 10.1007/s11538-008-9361-y [doi] DP - Nlm ET - 2008/12/17 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 LA - eng M1 - 1 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 - 2009 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/ VL - 71 ID - 707 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 M1 - 2 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 - 719 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 M1 - 12 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 - 726 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. C2 - 2672581 DA - Apr ET - 2009/06/25 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 M1 - 4 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/19551238 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672581/pdf/08-054510.pdf VL - 87 ID - 563 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 LA - English M1 - 3 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 - ://000277196700001 http://stm.sciencemag.org/content/1/3/3ra8 VL - 1 ID - 746 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 - 756 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. C2 - 2759933 DO - 1752-0509-3-92 [pii] 10.1186/1752-0509-3-92 [doi] DP - Nlm ET - 2009/09/17 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/1752-0509/3/92 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759933/pdf/1752-0509-3-92.pdf VL - 3 ID - 759 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. C2 - 2684774 DA - Mar DO - 10.1007/s12199-008-0062-9 [doi] DP - Nlm ET - 2009/07/02 LA - eng M1 - 2 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 - 770 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 - 2009/09/08 KW - BCG Vaccine Health Policy Humans Latent Tuberculosis/ diagnosis Mass Vaccination Mathematics Models, Theoretical Program Evaluation Tuberculosis/ prevention & control World Health LA - eng M1 - 4 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 - 776 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. C2 - 2779834 DA - Feb DO - nm.1915 [pii] 10.1038/nm.1915 [doi] DP - Nlm ET - 2009/02/03 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 M1 - 2 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 - 779 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. C2 - 2704682 DA - Jul DO - AAC.01520-08 [pii] 10.1128/AAC.01520-08 [doi] DP - Nlm ET - 2009/04/22 KW - Algorithms Antitubercular Agents/ pharmacokinetics Computer Simulation Female Humans Lung/ metabolism Male Monte Carlo Method Prospective Studies Rifampin/ pharmacokinetics LA - eng M1 - 7 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 VL - 53 ID - 789 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 - 2009/07/01 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 M1 - 2 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 - 806 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 M1 - 11 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 - 807 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.long http://content.healthaffairs.org/content/28/4/w730.full.pdf VL - 28 ID - 576 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 - 2009/06/10 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 M1 - 1 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 VL - 5 ID - 834 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 - 2009/08/27 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 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=19706556 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2732896/pdf/zpq14711.pdf VL - 106 ID - 850 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 KW - HIV/AIDS epidemic TB infection Density-dependent Equilibrium points Reproductive number Stability M1 - 7–8 M3 - doi: 10.1016/j.mcm.2009.05.033 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/S0895717709002131 http://ac.els-cdn.com/S0895717709002131/1-s2.0-S0895717709002131-main.pdf?_tid=91543dc8067263b6b14d2bc42dec2019&acdnat=1345012911_4304f0798d5c14dfd87464c2a818a108 VL - 50 ID - 589 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 - 2009/03/25 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 M1 - 2 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 - 926 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 DP - Nlm ET - 2009/10/20 KW - Comorbidity HIV Infections/ complications/epidemiology Humans Mathematical Concepts Models, Biological Risk Factors Time Factors Tuberculosis, Pulmonary/ complications/epidemiology LA - eng M1 - 4 N1 - Roeger, Lih-Ing W Feng, Zhilan Castillo-Chavez, Carlos Research Support, U.S. Gov't, Non-P.H.S. United States Mathematical biosciences and engineering : MBE Math Biosci Eng. 2009 Oct;6(4):815-37. doi: 10.3934/mbe.2009.6.815. 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 - 595 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 - 2009/03/01 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 M1 - 1 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 - 598 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. C2 - 2610322 DA - Jan 6 DO - N48G734P015PV1JW [pii] 10.1098/rsif.2008.0184 [doi] DP - Nlm ET - 2008/06/26 KW - Computer Simulation Humans Incidence Markov Chains Models, Theoretical Recurrence Tuberculosis/ epidemiology/ transmission LA - eng M1 - 30 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 - 2009 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 - 987 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. C2 - 2681859 DA - May DO - JCM.02289-08 [pii] 10.1128/JCM.02289-08 [doi] DP - Nlm ET - 2009/03/20 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 LA - eng M1 - 5 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 VL - 47 ID - 988 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 - 2009/04/10 KW - Adolescent Adult Aged Female Forecasting Humans Life Tables Male Middle Aged Netherlands/epidemiology Tuberculosis/ epidemiology/ethnology Young Adult LA - eng M1 - 4 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 - 989 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. C2 - 3012021 DO - 1753-4631-4-6 [pii] 10.1186/1753-4631-4-6 [doi] DP - Nlm ET - 2010/11/26 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 - 621 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. C2 - 3065594 DA - Dec DO - 10.1007/s11693-011-9075-6 [doi] 9075 [pii] DP - Nlm ET - 2011/12/02 LA - eng M1 - 4 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 - 2010 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 - 655 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 - 2010/04/16 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 M1 - 5 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 - 556 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. C2 - 2797602 DO - 10.1371/journal.pone.0008479 [doi] DP - Nlm ET - 2010/01/12 KW - Humans Models, Theoretical Prevalence Tuberculosis/mortality/ transmission LA - eng M1 - 1 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 - 679 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. C2 - 2944881 DO - 10.1371/journal.pone.0012985 [doi] DP - Nlm ET - 2010/10/05 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 M1 - 9 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 - 680 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 - 682 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. C2 - 2955152 DA - Oct 12 DO - 1005139107 [pii] 10.1073/pnas.1005139107 [doi] DP - Nlm ET - 2010/09/30 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 M1 - 41 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 - 690 ER - TY - JOUR AB - SETTING: National Health Laboratory Services tuberculosis (TB) laboratory, South Africa. OBJECTIVES: To compare Mycobacterium Growth Indicator Tube (MGIT) with Lowenstein-Jensen (LJ) medium with regard to Mycobacterium tuberculosis yield, time to positive culture and contamination, and to assess MGIT cost-effectiveness. DESIGN: Sputum from gold miners was cultured on MGIT and LJ. We estimated cost per culture, and, for smear-negative samples, incremental cost per additional M. tuberculosis gained with MGIT using a decision-tree model. RESULTS: Among 1267 specimens, MGIT vs. LJ gave a higher yield of mycobacteria (29.7% vs. 22.8%), higher contamination (16.7% vs. 9.3%) and shorter time to positive culture (median 14 vs. 25 days for smear-negative specimens). Among smear-negative samples that were culture-positive on MGIT but negative/contaminated on LJ, 77.3% were non-tuberculous mycobacteria (NTM). Cost per culture on LJ, MGIT and MGIT+LJ was respectively US$12.35, US$16.62 and US$19.29. The incremental cost per additional M. tuberculosis identified by standard biochemical tests and microscopic cording was respectively US$504.08 and US$328.10 using MGIT vs. LJ, or US$160.80 and US$$109.07 using MGIT+LJ vs. LJ alone. CONCLUSION: MGIT gives higher yield and faster results at relatively high cost. The high proportion of NTM underscores the need for rapid speciation tests. Minimising contaminated cultures is key to cost-effectiveness. AD - Aurum Institute for Health Research, Johannesburg, South Africa. vchihota@auruminstitute.org AN - 20626948 AU - Chihota, V. N. AU - Grant, A. D. AU - Fielding, K. AU - Ndibongo, B. AU - van Zyl, A. AU - Muirhead, D. AU - Churchyard, G. J. DA - Aug ET - 2010/07/16 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Adult Aged Bacteriological Techniques/*economics/*standards Costs and Cost Analysis Culture Media/economics/*standards Follow-Up Studies Humans Middle Aged Mycobacterium fortuitum/growth & development/*isolation & purification Prevalence Reproducibility of Results Retrospective Studies South Africa/epidemiology Sputum/*microbiology Tuberculosis/*diagnosis/epidemiology/microbiology Young Adult LA - eng M1 - 8 M3 - Comparative Study N1 - Chihota, V N Grant, A D Fielding, K Ndibongo, B van Zyl, A Muirhead, D Churchyard, G J France Int J Tuberc Lung Dis. 2010 Aug;14(8):1024-31. PY - 2010 SN - 1815-7920 (Electronic) 1027-3719 (Linking) SP - 1024-31 ST - Liquid vs. solid culture for tuberculosis: performance and cost in a resource-constrained setting T2 - Int J Tuberc Lung Dis TI - Liquid vs. solid culture for tuberculosis: performance and cost in a resource-constrained setting UR - http://www.ncbi.nlm.nih.gov/pubmed/20626948 VL - 14 ID - 1420 ER - TY - JOUR AB - Mycobacterium tuberculosis (Mtb) is a widely diffused infection. However, in general, the human immune system is able to contain it. In this work, we propose a mathematical model which describes the early immune response to the Mtb infection in the lungs, also including the possible evolution of the infection in the formation of a granuloma. The model is based on coupled reaction-diffusion-transport equations with chemotaxis, which take into account the interactions among bacteria, macrophages and chemoattractant. The novelty of this approach is in the modeling of the velocity field, proportional to the gradient of the pressure developed between the cells, which makes possible to deal with a full multidimensional description and efficient numerical simulations. We perform a linear stability analysis of the model and propose a robust implicit-explicit scheme to deal with long time simulations. Both in one and two-dimensions, we find that there are threshold values in the parameters space, between a contained infection and the uncontrolled bacteria growth, and the generation of granuloma-like patterns can be observed numerically. AD - Istituto per le Applicazioni del Calcolo "M. Picone", CNR, c/o Dip. di Matematica, Universita di Roma "Tor Vergata", Via della Ricerca Scientifica, 1; I-00133 Roma, Italy. f.clarelli@iac.rm.cnr.it AN - 20462290 AU - Clarelli, F. AU - Natalini, R. DA - Apr DP - Nlm ET - 2010/05/14 KW - Chemotaxis/immunology Computer Simulation Granuloma/ immunology/microbiology Humans Immunity, Innate/immunology Macrophages, Alveolar/ immunology/microbiology Models, Immunological Mycobacterium tuberculosis/ immunology Tuberculosis/ immunology/microbiology LA - eng M1 - 2 N1 - Clarelli, Fabrizio Natalini, Roberto United States Mathematical biosciences and engineering : MBE Math Biosci Eng. 2010 Apr;7(2):277-300. doi: 10.3934/mbe.2010.7.277. PY - 2010 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1551-0018 (Electronic) 1547-1063 (Linking) SP - 277-300 ST - A pressure model of immune response to mycobacterium tuberculosis infection in several space dimensions T2 - Math Biosci Eng TI - A pressure model of immune response to mycobacterium tuberculosis infection in several space dimensions VL - 7 ID - 557 ER - TY - JOUR AB - BACKGROUND: Accurate assessment of the burden of drug-resistant TB requires systematic efforts to quantify its magnitude and trend. In approximately half the countries where resistance has been reported, estimates are based on surveys conducted in public sector facilities. However, in locations where a substantial fraction of TB cases seek care with private providers, these surveys may not accurately measure resistance in the entire population. METHODS: We describe a mathematical model to investigate biases associated with sampling only from public sector cases in India, where TB treatment is offered in both public and private sectors. We then propose and demonstrate a weighted estimator as an efficient method for including small numbers of cases from the private sector as a way to recover valid estimates of resistance in the population under study. RESULTS: We find that public sector surveys rarely provide valid estimates of drug-resistance among new and retreatment cases. Further, the magnitude and direction of the bias are sensitive to many parameters describing the health-seeking behaviours and treatment outcomes of tuberculosis patients, disallowing simple adjustments to recover accurate estimates. CONCLUSIONS: In locations where large numbers of tuberculosis patients are diagnosed and treated by private sector practitioners who are not typically included in drug resistance surveys, targeted surveys for assessing drug resistance are required to validly estimate resistance. AD - Division of Global Health Equity, Brigham and Women's Hospital, 641 Huntington Avenue, Boston 02115, USA. tcohen@hsph.harvard.edu AN - 20565947 AU - Cohen, T. AU - Hedt, B. L. AU - Pagano, M. C2 - 2898828 DO - 1471-2458-10-355 [pii] 10.1186/1471-2458-10-355 [doi] DP - Nlm ET - 2010/06/23 LA - eng N1 - Cohen, Ted Hedt, Bethany L Pagano, Marcello DP2 OD006663-01/OD/NIH HHS/United States R01 EB006195/EB/NIBIB NIH HHS/United States T32 1007358/PHS HHS/United States U54 GM088558-01/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural England BMC public health BMC Public Health. 2010 Jun 21;10:355. PY - 2010 RN - fulltext fulltext_1208 SN - 1471-2458 (Electronic) 1471-2458 (Linking) SP - 355 ST - Estimating the magnitude and direction of bias in tuberculosis drug resistance surveys conducted only in the public sector: a simulation study T2 - BMC Public Health TI - Estimating the magnitude and direction of bias in tuberculosis drug resistance surveys conducted only in the public sector: a simulation study UR - http://www.biomedcentral.com/1471-2458/10/355 VL - 10 ID - 701 ER - TY - JOUR AB - OBJECTIVE: To evaluate the cost-effectiveness of the tuberculin skin test (TST), the QuantiFERON-TB Gold test (QFT) and a combination of TST and QFT (TST+QFT) for diagnosing latent tuberculosis infection (LTBI) in France in a bacille Calmette-Guerin (BCG) vaccinated population. METHODS: A decision analysis model evaluated three strategies among simulated adults in close contact with tuberculosis (TB). We calculated direct lifetime medical costs, life expectancies and incremental cost-effectiveness ratios (ICERs). RESULTS: The discounted direct medical costs of care per patient of no testing, TST, QFT and TST+QFT were respectively euro417, euro476, euro443 and euro435, while discounted life expectancies were respectively 25.030, 25.071, 25.073 and 25.062 years. TST had higher costs and lower efficacy than QFT; TST+QFT was associated with an ICER of euro560 per year of life gained (YLG) compared to no testing, and QFT was associated with an ICER of euro730/YLG compared to TST+QFT. The only scenario where QFT was associated with an ICER of >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 - 2010/03/06 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 M1 - 4 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 - 722 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. C2 - 2865521 DA - May DO - 10.1371/journal.pcbi.1000778 [doi] DP - Nlm ET - 2010/05/14 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 M1 - 5 N1 - Fallahi-Sichani, Mohammad Schaller, Matthew A Kirschner, Denise E Kunkel, Steven L Linderman, Jennifer J HL 092844/HL/NHLBI NIH HHS/United States HL 092853/HL/NHLBI NIH HHS/United States LM 009027/LM/NLM NIH HHS/United States N01 AI50018/AI/NIAID NIH HHS/United States R01 HL089216-03/HL/NHLBI NIH HHS/United States R33 HL092844-03/HL/NHLBI NIH HHS/United States Research Support, N.I.H., Extramural United States PLoS computational biology PLoS Comput Biol. 2010 May 6;6(5):e1000778. 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 - 758 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 DP - NLM ET - 2010/08/31 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 M1 - 4 N1 - Kowada, Akiko Deshpande, Gautam A Takahashi, Osamu Shimbo, Takuro Fukui, Tsuguya Comparative Study New Zealand Mol Diagn Ther. 2010 Aug 1;14(4):229-36. doi: 10.2165/11538610-000000000-00000. 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 - 828 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 - 2010/01/12 KW - Basic Reproduction Number China/epidemiology Computer Simulation Humans Models, Biological Mycobacterium tuberculosis/ growth & development Seasons Tuberculosis/ epidemiology/microbiology LA - eng M1 - 4 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 - 847 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 - 2010/06/04 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=20519613 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877424/pdf/tropmed-82-1131.pdf VL - 82 ID - 856 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. C2 - 3150786 DA - Aug 21 DO - S0022-5193(10)00241-9 [pii] 10.1016/j.jtbi.2010.05.012 [doi] DP - Nlm ET - 2010/06/01 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 M1 - 4 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 - 865 ER - TY - JOUR AU - OKUONGHAE, D. AU - AIHIE, V. U. DO - doi:10.1142/S0218339010003160 M1 - 01 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 - 899 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 - 2010/02/23 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 M1 - 3 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 - 920 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 M1 - 9 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 - 985 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. C2 - 2984151 DA - Nov 9 DO - 1005660107 [pii] 10.1073/pnas.1005660107 [doi] DP - Nlm ET - 2010/10/27 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 M1 - 45 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 - 612 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. C2 - 3101801 DA - Aug 15 DO - 10.1086/655129 [doi] DP - Nlm ET - 2010/07/08 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 M1 - 4 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 - 614 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 - 2010/05/11 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=20454620 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862741/pdf/pone.0010468.pdf VL - 5 ID - 1023 ER - TY - JOUR AU - Yang, H. M. AU - Raimundo, S. M. DO - doi:10.1186/1742-4682-7-41 ET - 8 November M1 - 41 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 - 1024 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. C2 - 2994743 DO - 10.1371/journal.pone.0014140 [doi] DP - Nlm ET - 2010/12/15 KW - Brazil/epidemiology Geography Humans Incidence Population Density Population Dynamics Population Surveillance/ methods Socioeconomic Factors Tuberculosis/epidemiology/ prevention & control/ transmission LA - eng M1 - 11 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 - 1029 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. C2 - 3186817 DP - Nlm ET - 2011/10/06 KW - Adult Humans Models, Theoretical Prevalence Smoking/ adverse effects/epidemiology/prevention & control Tuberculosis/ epidemiology/mortality LA - eng N1 - Basu, Sanjay Stuckler, David Bitton, Asaf Glantz, Stanton A R36-CI000607-01/CI/NCPDCID CDC HHS/United States T32-GM07205-32/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S. England BMJ (Clinical research ed.) BMJ. 2011 Oct 4;343:d5506. doi: 10.1136/bmj.d5506. 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 - 649 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. C2 - 3005502 DA - Jan DO - 84/1/30 [pii] 10.4269/ajtmh.2011.10-0472 [doi] DP - Nlm ET - 2011/01/08 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 LA - eng M1 - 1 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 VL - 84 ID - 552 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 - 2010/08/21 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 M1 - 6 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 - 2011 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 - 660 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 - 2011/05/25 KW - Adolescent Adult Child Cluster Analysis Female Humans Male Molecular Epidemiology Odds Ratio Risk Factors Sampling Studies Tuberculosis/ epidemiology LA - eng M1 - 2 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 - 672 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=21592987 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096792/pdf/jir162.pdf VL - 203 ID - 678 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 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 - 2011/05/07 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 M1 - 8 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 - 750 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. C2 - 3191742 DO - 10.1155/2011/398476 [doi] DP - Nlm ET - 2011/10/19 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 - 751 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 - 2012/01/31 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 M1 - 10 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 - 2011 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 - 755 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. C2 - 3127549 DA - Mar 15 DO - jimmunol.1003299 [pii] 10.4049/jimmunol.1003299 [doi] DP - Nlm ET - 2011/02/16 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 M1 - 6 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 - 757 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 - 2011/08/13 KW - Homeostasis Iron/ metabolism Models, Biological Mycobacterium tuberculosis/ metabolism LA - eng M1 - 10 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 - 778 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 - 2011/02/22 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 M1 - 3 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 - 787 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 - 2011/05/25 KW - Animals Antitubercular Agents/pharmacokinetics/pharmacology/ therapeutic use Mice Models, Theoretical Rifampin/pharmacokinetics/pharmacology/ therapeutic use Tuberculosis, Pulmonary/ drug therapy LA - eng M1 - 1 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 - 788 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. C2 - 3208139 DA - Nov 21 DO - S0022-5193(11)00435-8 [pii] 10.1016/j.jtbi.2011.08.032 [doi] DP - Nlm ET - 2011/09/13 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 - 796 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. C2 - 3219798 DA - Sep 30 DO - 10.1002/sim.4287 [doi] DP - Nlm ET - 2011/07/01 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 LA - eng M1 - 22 N1 - Izu, Alane Cohen, Ted Mitnick, Carole Murray, Megan De Gruttola, Victor 2 T32 AI 7358-21/AI/NIAID NIH HHS/United States 5 T35 ES 7293-9/ES/NIEHS NIH HHS/United States R01 51164/PHS HHS/United States R01 AI051164-10/AI/NIAID NIH HHS/United States T32 AI007358-21/AI/NIAID NIH HHS/United States U19AI076217/AI/NIAID NIH HHS/United States U54 GM088558-02/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural England Statistics in medicine Nihms321244 Stat Med. 2011 Sep 30;30(22):2708-20. doi: 10.1002/sim.4287. Epub 2011 Jun 30. 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 VL - 30 ID - 812 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] DP - Nlm ET - 2011/02/24 LA - Eng N1 - Jia, Zhongwei Cheng, Shiming Jia, Xiaowei Journal of evidence-based medicine J Evid Based Med. 2011 Feb 5. doi: 10.1111/j.1756-5391.2011.01116.x. 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 - 815 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 - 2012/01/26 LA - eng M1 - 11 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 - 2011 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 - 818 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 - 2011/08/16 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 M1 - 10 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 - 827 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 - 2011/03/29 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 M1 - 2 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 - 829 ER - TY - JOUR AU - LI, XUE-ZHI AU - BHATTACHARYA, SOUVIK AU - YANG, JUN-YUAN AU - MARTCHEVA, MAIA DO - doi:10.1142/S0218339011003889 M1 - 02 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 - 837 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] DP - Nlm ET - 2012/01/04 LA - Eng N1 - Liao, Chung-Min Cheng, Yi-Hsien Lin, Yi-Jun Hsieh, Nan-Hung Huang, Tang-Luen Chio, Chia-Pin Chen, Szu-Chieh Ling, Min-Pei Risk analysis : an official publication of the Society for Risk Analysis Risk Anal. 2011 Dec 28. doi: 10.1111/j.1539-6924.2011.01750.x. PY - 2011 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 - 838 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 - 2011/07/12 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 M1 - 8 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 - 577 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=21562129 http://ajrccm.atsjournals.org/content/184/5/590.long VL - 184 ID - 844 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 KW - Tuberculosis Vaccination Treatment Lyapunov function Global stability M1 - 1–2 M3 - doi: 10.1016/j.mcm.2011.03.033 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/S0895717711001932 http://ac.els-cdn.com/S0895717711001932/1-s2.0-S0895717711001932-main.pdf?_tid=6e401a810ebafd6a2b564ba57d5e7e04&acdnat=1345012593_1c343b0c8216062a71c1fa8ef9a99469 VL - 54 ID - 846 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 M1 - 9 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 - 860 ER - TY - JOUR AU - Mellor, Georgina R. AU - Currie, Christine S. M. AU - Corbett, Elizabeth L. C1 - 2000499 DO - 10.1145/2000494.2000499 M1 - 4 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 - 584 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. C2 - 3163428 DA - Oct 7 DO - rsif.2011.0160 [pii] 10.1098/rsif.2011.0160 [doi] DP - Nlm ET - 2011/04/22 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 M1 - 63 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 - 587 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 - 2011/07/16 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 - 887 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 - 2010/10/13 KW - Basic Reproduction Number Computer Simulation Humans Models, Biological Nigeria/epidemiology Tuberculosis/ diagnosis/ epidemiology/therapy Uncertainty LA - eng M1 - 1 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 - 2011 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 - 900 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 M1 - 1 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.abstract http://mdm.sagepub.com/content/31/1/53 VL - 31 ID - 902 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 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 M1 - 1 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 - 593 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. C2 - 3159079 DA - Apr 15 DO - 201004-0620OC [pii] 10.1164/rccm.201004-0620OC ET - 2010/12/15 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 LA - eng M1 - 8 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 - 2011 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=21148723 http://ajrccm.atsjournals.org/content/183/8/1103.long http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159079/pdf/AJRCCM18381103.pdf VL - 183 ID - 596 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. C2 - 3111980 DA - Jul 7 DO - S0022-5193(11)00201-3 [pii] 10.1016/j.jtbi.2011.04.011 [doi] DP - Nlm ET - 2011/04/26 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 LA - eng M1 - 1 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 VL - 280 ID - 952 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. C2 - 3209814 DA - Dec 15 DO - jir658 [pii] 10.1093/infdis/jir658 [doi] DP - Nlm ET - 2011/10/25 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 LA - eng M1 - 12 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 VL - 204 ID - 605 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. C2 - 3039588 DO - 10.1186/1471-2458-11-55 ET - 2011/01/29 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/21269503 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039588/pdf/1471-2458-11-55.pdf VL - 11 ID - 606 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 - 2011/06/02 KW - Disease Transmission, Infectious Endemic Diseases Humans Models, Statistical Prevalence South Africa/epidemiology Tuberculosis/diagnosis/drug therapy/ epidemiology/ transmission LA - eng M1 - 12 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 - 607 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. C2 - 3210757 DA - Nov DO - 10.1371/journal.pmed.1001120 [doi] PMEDICINE-D-11-00805 [pii] DP - Nlm ET - 2011/11/17 KW - Clinical Laboratory Techniques/ economics/methods Cohort Studies Cost-Benefit Analysis Humans India South Africa Tuberculosis, Pulmonary/ diagnosis/economics Uganda LA - eng M1 - 11 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 - 608 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 - 2011/03/29 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 M1 - 1 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 - 1013 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. C2 - 3386166 DA - Jun DO - 10.1371/journal.pcbi.1002573 [doi] PCOMPBIOL-D-11-01614 [pii] DP - Nlm ET - 2012/07/05 LA - eng M1 - 6 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 - 615 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 M1 - 1 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.aspx http://graphics.tx.ovid.com/ovftpdfs/FPDDNCDCLFEDDD00/fs047/ovft/live/gv024/00126334/00126334-201205010-00016.pdf VL - 60 ID - 540 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 - 625 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 M1 - 8 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.aspx http://graphics.tx.ovid.com/ovftpdfs/FPDDNCDCLFEDDD00/fs047/ovft/live/gv024/00002030/00002030-201205150-00010.pdf VL - 26 ID - 541 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. C2 - 3257304 DA - Jan DO - 10.1371/journal.ppat.1002487 [doi] PPATHOGENS-D-11-01392 [pii] DP - Nlm ET - 2012/01/19 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 LA - eng M1 - 1 N1 - Ankomah, Peter Levin, Bruce R GM 091875/GM/NIGMS NIH HHS/United States R01 GM091875/GM/NIGMS NIH HHS/United States Evaluation Studies Research Support, N.I.H., Extramural United States PLoS pathogens PLoS Pathog. 2012 Jan;8(1):e1002487. Epub 2012 Jan 12. 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 VL - 8 ID - 627 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. C2 - 3583706 DO - 10.1186/1471-2458-12-1091 DP - NLM ET - 2012/12/20 J2 - BMC public health LA - eng N1 - Ben-Haim, Yakov Dacso, Clifford C Zetola, Nicola M England BMC Public Health. 2012 Dec 19;12:1091. doi: 10.1186/1471-2458-12-1091. 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 - 1304 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 - 2012/03/03 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 - 674 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 KW - The discrete epidemic model Age structure The reproduction number Persistence Tuberculosis M1 - 3–4 M3 - doi: 10.1016/j.mcm.2011.08.017 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/S0895717711004973 http://ac.els-cdn.com/S0895717711004973/1-s2.0-S0895717711004973-main.pdf?_tid=b65602f0816ab609a42cfd7d29e713ae&acdnat=1345012081_5cbd0b42f5c3d8599432f3d0cf273413 VL - 55 ID - 686 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/22873611 http://www.tandfonline.com/doi/pdf/10.1080/17513758.2012.677483 VL - 6 ID - 687 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. C2 - 3529460 DO - 10.1155/2012/790482 DP - NLM ET - 2013/02/01 J2 - Computational and mathematical methods in medicine LA - eng N1 - Carvalho, Rafael V Kleijn, Jetty Meijer, Annemarie H Verbeek, Fons J United States Comput Math Methods Med. 2012;2012:790482. doi: 10.1155/2012/790482. Epub 2012 Dec 9. PY - 2012 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 - 1282 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 DP - NLM ET - 2012/03/15 J2 - Statistics in medicine LA - eng M1 - 27 N1 - Chen, Michael P Shang, Nong Winston, Carla A Becerra, Jose E England Stat Med. 2012 Nov 30;31(27):3278-84. doi: 10.1002/sim.5343. Epub 2012 Mar 13. 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 - 1403 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 - 2012/05/31 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 - 733 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. C2 - 3401708 DA - May DO - IndianJMedRes_2012_135_5_737_97762 [pii] DP - Nlm ET - 2012/07/10 LA - eng M1 - 5 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 - 740 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. C2 - 3293131 DO - 10.1136/bmjopen-2011-000630 DP - NLM ET - 2012/03/03 J2 - BMJ open LA - eng M1 - 2 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 - 753 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. C2 - 3350683 DA - Jun 22 DO - rspb.2011.2712 [pii] 10.1098/rspb.2011.2712 [doi] DP - Nlm ET - 2012/02/24 LA - eng M1 - 1737 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 - 784 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. C2 - 3309013 DO - 10.1371/journal.pone.0033893 [doi] PONE-D-11-23961 [pii] DP - Nlm ET - 2012/03/27 LA - eng M1 - 3 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 - 797 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] 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=22496801 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319591/pdf/pone.0034411.pdf VL - 7 ID - 803 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 DP - NLM ET - 2012/01/12 J2 - Epidemiology and infection KW - Humans Incidence Models, Statistical Tuberculosis/ epidemiology/prevention & control United States/epidemiology LA - eng M1 - 10 N1 - Hill, A N Becerra, J E Castro, K G England Epidemiol Infect. 2012 Oct;140(10):1862-72. doi: 10.1017/S095026881100286X. Epub 2012 Jan 11. 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 - 1410 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. C2 - 3260212 DO - 10.1371/journal.pone.0030194 DP - NLM ET - 2012/01/25 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 LA - eng M1 - 1 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 VL - 7 ID - 808 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/22137190 http://ac.els-cdn.com/S0954611111003453/1-s2.0-S0954611111003453-main.pdf?_tid=f0fb9cfc-6b2f-11e2-85ca-00000aacb35e&acdnat=1359586622_4d20eeb6452ae11ec466e6aa649b2371 VL - 106 ID - 811 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 - 2012/06/08 LA - eng M1 - 3 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 - 831 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 - 2012/07/13 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 - 832 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 DP - NLM ET - 2012/07/24 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 M1 - 10 N1 - Liao, Chung-Min Lin, Yi-Jun Canada Int J Infect Dis. 2012 Oct;16(10):e739-47. doi: 10.1016/j.ijid.2012.06.001. Epub 2012 Jul 19. 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 - 1376 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. C2 - 3471051 DA - Oct 1 DO - 10.2471/blt.11.101436 DP - NLM ET - 2012/10/31 J2 - Bulletin of the World Health Organization LA - eng M1 - 10 N1 - Lin, Hsien-Ho Dowdy, David Dye, Christopher Murray, Megan Cohen, Ted Research Support, Non-U.S. Gov't Switzerland Bull World Health Organ. 2012 Oct 1;90(10):739-747A. doi: 10.2471/BLT.11.101436. Epub 2012 Jul 16. 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 - 1329 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 - 2011/10/05 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 - 2012 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 - 855 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. C2 - 3264596 DO - 10.1371/journal.pone.0030457 ET - 2012/02/01 J2 - PloS one LA - eng M1 - 1 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/22291958 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3264596/pdf/pone.0030457.pdf VL - 7 ID - 580 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 DP - NLM ET - 2012/03/30 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 M1 - 4 N1 - Malvankar-Mehta, Monali S Xie, Bin Netherlands Health Care Manag Sci. 2012 Dec;15(4):327-38. doi: 10.1007/s10729-012-9194-y. Epub 2012 Mar 29. 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 - 1402 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. C2 - 3377630 DO - 10.1371/journal.pone.0039187 DP - NLM ET - 2012/06/23 J2 - PloS one LA - eng M1 - 6 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 VL - 7 ID - 581 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 - 2012/06/22 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 - 861 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. C2 - 3502465 DO - 10.1371/journal.pmed.1001347 DP - NLM ET - 2012/11/28 J2 - PLoS medicine LA - eng M1 - 11 N1 - Menzies, Nicolas A Cohen, Ted Lin, Hsien-Ho Murray, Megan Salomon, Joshua A R25 CA092203/CA/NCI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States PLoS Med. 2012;9(11):e1001347. doi: 10.1371/journal.pmed.1001347. Epub 2012 Nov 20. 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 VL - 9 ID - 1316 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] 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/22693561 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365041/pdf/pone.0036966.pdf VL - 7 ID - 585 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. C2 - 3405656 DO - 10.1155/2012/124861 DP - NLM ET - 2012/08/01 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 N1 - Oei, Welling Nishiura, Hiroshi U54 GM088558/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Comput Math Methods Med. 2012;2012:124861. doi: 10.1155/2012/124861. Epub 2012 Jul 17. 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 - 1371 ER - TY - BILL 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 - 901 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 - 2012/06/14 LA - eng M1 - 8 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 - 905 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] 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/22558301 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340407/pdf/pone.0036001.pdf VL - 7 ID - 591 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. C2 - 3494236 DP - NLM ET - 2013/01/11 J2 - Iranian journal of public health LA - eng M1 - 10 N1 - Rafei, A Pasha, E Jamshidi Orak, R Iran Iran J Public Health. 2012;41(10):87-96. Epub 2012 Oct 1. PY - 2012 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 - 1297 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. C2 - 3509125 DO - 10.1371/journal.pone.0049492 DP - NLM ET - 2012/12/05 J2 - PloS one LA - eng M1 - 11 N1 - Ramkissoon, Santosh Mwambi, Henry G Matthews, Alan P Research Support, Non-U.S. Gov't United States PLoS One. 2012;7(11):e49492. doi: 10.1371/journal.pone.0049492. Epub 2012 Nov 28. 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 - 1310 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. C2 - 3486525 DA - Nov DO - 10.1128/aac.05988-11 DP - NLM ET - 2012/07/11 J2 - Antimicrobial agents and chemotherapy LA - eng M1 - 11 N1 - Sahota, Tarjinder Della Pasqua, Oscar United States Antimicrob Agents Chemother. 2012 Nov;56(11):5442-9. doi: 10.1128/AAC.05988-11. Epub 2012 Jul 9. 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 - 1380 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. C2 - 3387814 DA - May 23 DO - 4/135/135ra67 [pii] 10.1126/scitranslmed.3003815 [doi] DP - Nlm ET - 2012/05/25 LA - eng M1 - 135 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/4/135/135ra67 http://stm.sciencemag.org/content/4/135/135ra67.short VL - 4 ID - 601 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. C2 - 3315507 DO - 10.1371/journal.pone.0034109 [doi] PONE-D-12-01538 [pii] DP - Nlm ET - 2012/04/06 LA - eng M1 - 3 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 - 990 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 - 2012/02/22 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 - 992 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. C2 - 3507963 DO - 10.1371/journal.pmed.1001348 DP - NLM ET - 2012/12/05 J2 - PLoS medicine LA - eng M1 - 11 N1 - Winetsky, Daniel E Negoescu, Diana M DeMarchis, Emilia H Almukhamedova, Olga Dooronbekova, Aizhan Pulatov, Dilshod Vezhnina, Natalia Owens, Douglas K Goldhaber-Fiebert, Jeremy D K01 AG037593/AG/NIA NIH HHS/United States K01 AG037593-01A1/AG/NIA NIH HHS/United States R01DA015612/DA/NIDA 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 Med. 2012;9(11):e1001348. doi: 10.1371/journal.pmed.1001348. Epub 2012 Nov 27. 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 VL - 9 ID - 1312 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. C2 - 3557254 DO - 10.1371/journal.pone.0055017 DP - NLM ET - 2013/02/06 J2 - PloS one LA - eng M1 - 1 N1 - Agliari, Elena Asti, Lorenzo Barra, Adriano Scrivo, Rossana Valesini, Guido Wallis, Robert S United States PLoS One. 2013;8(1):e55017. doi: 10.1371/journal.pone.0055017. Epub 2013 Jan 28. 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 - 1280 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 DP - NLM ET - 2013/02/21 J2 - American journal of epidemiology LA - eng M1 - 6 N1 - Andrews, Jason R Morrow, Carl Wood, Robin United States Am J Epidemiol. 2013 Mar 15;177(6):556-61. doi: 10.1093/aje/kws331. Epub 2013 Feb 18. 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 - 1278 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. C2 - 3553722 DA - Feb DO - 10.1128/aac.01876-12 DP - NLM ET - 2012/11/28 J2 - Antimicrobial agents and chemotherapy LA - eng M1 - 2 N1 - Chigutsa, Emmanuel Patel, Kashyap Denti, Paolo Visser, Marianne Maartens, Gary Kirkpatrick, Carl M J McIlleron, Helen Karlsson, Mats O Research Support, Non-U.S. Gov't United States Antimicrob Agents Chemother. 2013 Feb;57(2):789-95. doi: 10.1128/AAC.01876-12. Epub 2012 Nov 26. PY - 2013 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 - 1317 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 DP - NLM ET - 2012/12/25 J2 - American journal of respiratory and critical care medicine LA - eng M1 - 5 N1 - Dowdy, David W Basu, Sanjay Andrews, Jason R United States Am J Respir Crit Care Med. 2013 Mar 1;187(5):543-51. doi: 10.1164/rccm.201207-1217OC. Epub 2012 Dec 21. PY - 2013 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 - 1303 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 DP - NLM ET - 2012/12/19 J2 - Mathematical biosciences LA - eng M1 - 2 N1 - Hohmann, N Voss-Bohme, A United States Math Biosci. 2013 Feb;241(2):225-37. doi: 10.1016/j.mbs.2012.11.008. Epub 2012 Dec 13. PY - 2013 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 - 1306 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 - 2013/01/30 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 - 1284 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 DP - NLM ET - 2012/11/14 J2 - Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases LA - eng N1 - Magombedze, Gesham Mulder, Nicola Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Netherlands Infect Genet Evol. 2013 Jan;13:267-83. doi: 10.1016/j.meegid.2012.09.017. Epub 2012 Nov 10. PY - 2013 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 - 1321 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 DP - NLM ET - 2013/02/05 J2 - South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde LA - eng M1 - 2 N1 - Schnippel, K Meyer-Rath, G Long, L Stevens, W S Sanne, I Rosen, S U2RTW007373/PHS HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't South Africa S Afr Med J. 2013 Jan 14;103(2):101-6. doi: 10.7196/samj.6182. 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 - 1281 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 ET - 2013/03/15 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease LA - eng M1 - 4 N1 - Sun, D Dorman, S Shah, M Manabe, Y C Moodley, V M Nicol, M P Dowdy, D W France Int J Tuberc Lung Dis. 2013 Apr;17(4):552-8. doi: 10.5588/ijtld.12.0627. 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 - 1422 ER -