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 - 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 - 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 - 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 - 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 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 - 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 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 - 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 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 - 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 - 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 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 - 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 - 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 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 - 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 - 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 - 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 - 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 - 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 - 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 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 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 - 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 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 - 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 - 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 - 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 - 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 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: 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 - 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 - 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 - 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 - 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 - 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 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 - 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 - 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 - 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 - 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 - 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 - 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 - OBJECTIVE: To investigate the factors influencing the performance and cost-efficacy of periodic rounds of active case finding (ACF) for TB. METHODS: A mathematical model of TB dynamics and periodic ACF (PACF) in the HIV era, simplified by assuming constant prevalence of latent TB infection, is analyzed for features that control intervention outcome, measured as cases averted and cases found. Explanatory variables include baseline TB incidence, interval between PACF rounds, and different routine and PACF case-detection rates among HIV-infected and uninfected TB cases. FINDINGS: PACF can be cost-saving over a 10 year time frame if the cost-per-round is lower than a threshold proportional to initial incidence and cost-per-case-treated. More cases are averted at higher baseline incidence rates, when more potent PACF strategies are used, intervals between PACF rounds are shorter, and when the ratio of HIV-negative to positive TB cases detected is higher. More costly approaches, e.g. radiographic screening, can be as cost-effective as less costly alternatives if PACF case-detection is higher and/or implementation less frequent. CONCLUSION: Periodic ACF can both improve control and save medium-term health care costs in high TB burden settings. Greater costs of highly effective PACF at frequent (e.g. yearly) intervals may be offset by higher numbers of cases averted in populations with high baseline TB incidence, higher prevalence of HIV-uninfected cases, higher costs per-case-treated, and more effective routine case-detection. Less intensive approaches may still be cost-neutral or cost-saving in populations lacking one or more of these key determinants. AD - London School of Hygiene and Tropical Medicine, London, United Kingdom. peter.dodd@lshtm.ac.uk AN - 22216182 AU - Dodd, P. J. AU - White, R. G. AU - Corbett, E. L. C2 - 3245256 DO - 10.1371/journal.pone.0029130 [doi] PONE-D-11-12349 [pii] DP - Nlm ET - 2012/01/05 KW - HIV Infections/complications Health Care Costs Humans Incidence Models, Theoretical Prevalence Tuberculosis/complications/ diagnosis/epidemiology LA - eng M1 - 12 N1 - Dodd, Peter J White, Richard G Corbett, Elizabeth L 091769/Wellcome Trust/United Kingdom G0802414/Medical Research Council/United Kingdom Research Support, Non-U.S. Gov't United States PloS one PLoS One. 2011;6(12):e29130. Epub 2011 Dec 22. PY - 2011 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e29130 ST - Periodic active case finding for TB: when to look? T2 - PLoS One TI - Periodic active case finding for TB: when to look? UR - http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0029130&representation=PDF VL - 6 ID - 561 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 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 -