Tuberculosis decline in populations affected by HIV: a retrospective study of 12 countries in the WHO African Region.

OBJECTIVE: To investigate which of the World Health Organization recommended methods for tuberculosis control have had the greatest effect on case incidence in 12 countries in the World Health Organization (WHO) African Region that carry high burdens of tuberculosis linked to human immunodeficiency virus (HIV) infection. METHODS: We obtained epidemiological surveillance, survey and treatment data on HIV and tuberculosis for the years 2003 to 2016. We used statistical models to examine the effects of antiretroviral therapy (ART) and isoniazid preventive therapy in reducing the incidence of tuberculosis among people living with HIV. We also investigated the role of tuberculosis case detection and treatment in preventing Mycobacterium tuberculosis transmission and consequently reducing tuberculosis incidence. FINDINGS: Between 2003 and 2016, ART provision was associated with the decline of tuberculosis in each country, and with differences in tuberculosis decline between countries. Inferring that ART was a cause of tuberculosis decline, ART prevented 1.88 million (95% confidence interval, CI: 1.65 to 2.11) tuberculosis cases in people living with HIV, or 15.7% (95% CI: 13.8 to 17.6) of the 11.96 million HIV-positive tuberculosis cases expected. Population coverage of isoniazid preventive therapy was too low (average 1.0% of persons eligible) to have a major effect on tuberculosis decline, and improvements in tuberculosis detection and treatment were either weakly associated or not significantly associated with tuberculosis decline. CONCLUSION: ART provision is associated with tuberculosis decline in these 12 countries. ART should remain central to tuberculosis control where rates of tuberculosis-HIV coinfection are high, but renewed efforts to treat tuberculosis are needed.

Epidemiological metrics and benchmarks for a transition in the HIV epidemic.

Peter Godfrey-Faussett and colleagues present six epidemiological metrics for tracking progress in reducing the public health threat of HIV.

CD4 Cell Count: Declining Value for Antiretroviral Therapy Eligibility.

Antiretroviral therapy (ART) policy for people living with human immunodeficiency virus (HIV) has historically been based on clinical indications, such as opportunistic infections and CD4 cell counts. Studies suggest that CD4 counts early in HIV infection do not predict relevant public health outcomes such as disease progression, mortality, and HIV transmission in people living with HIV. CD4 counts also vary widely within individuals and among populations, leading to imprecise measurements and arbitrary ART initiation. To capture the clinical and preventive benefits of treatment, the global HIV response now focuses on increasing HIV diagnosis and ART coverage. CD4 counts for ART initiation were necessary when medications were expensive and had severe side effects, and when the impact of early ART initiation was unclear. However, current evidence suggests that although CD4 counts may still play a role in guiding clinical care to start prophylaxis for opportunistic infections, CD4 counts should cease to be required for ART initiation.

Field evaluation of Standard Diagnostics' Bioline HIV/Syphilis Duo test among female sex workers in Johannesburg, South Africa.

BACKGROUND: Point-of-care tests provide immediate results with the opportunity for same-day interventions with improved public health outcomes. A dual HIV/syphilis test enables early treatment of both diseases. METHODS: We conducted a field evaluation of the Standard Diagnostics' SD Bioline HIV/Syphilis Duo test (SD Bioline) among female sex workers. SD Bioline was conducted on finger-prick blood according to manufacturer's instructions and compared with (i) Genscreen HIV1/2 (third generation) and Vironostika Ag/Ab (fourth generation) assays for HIV, and (ii) Treponema pallidum particle agglutination (TPPA) and rapid plasma reagin (RPR) assays for syphilis. A negative TPPA test was considered negative, a TPPA-confirmed RPR titre ≤1:4 as past infection and a TPPA-confirmed RPR titre ≥1:8 as active syphilis. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Of 263 women recruited, 14 (5.3%) declined an HIV test. Among the remaining 249 women, 187 (75.1%) were HIV positive, 51 (20.5%) had syphilis antibodies with seven (2.8%) active infections. For HIV, the sensitivity and specificity were 98.9% (95% CI 95.8% to 99.8%) and 100% (95% CI 92.7% to 100%). For syphilis, the sensitivity and specificity were 66.7% (95% CI 52.0% to 78.9%) and 98.0% (95% CI 94.5% to 99.3%). Sera with high TPPA titres were more likely to test positive. CONCLUSIONS: In field conditions, while the SD Bioline test has high sensitivity and specificity for HIV and high specificity for syphilis, the test has lower sensitivity for syphilis than reported from laboratory evaluations. As the dual test detects only two thirds of syphilis cases, it should only be used in areas with weak screening programmes.

Programmatic Implications of Acute and Early HIV Infection.

Human immunodeficiency virus (HIV) infection includes acute, early, chronic, and late stages. Acute HIV infection lasts approximately 3 weeks and early HIV infection, which includes acute HIV infection, lasts approximately 7 weeks. Many testing and blood screening algorithms detect HIV antibodies about 3 weeks after HIV infection. Incidence estimates are based on results of modeling, cohort studies, surveillance, and/or assays. Viral load is the key modifiable risk factor for HIV transmission and peaks during acute and early HIV infection. Empirical evidence characterizing the impact of acute and early HIV infection on the spread of the HIV epidemic are limited. Time trends of HIV prevalence collected from concentrated and generalized epidemics suggest that acute and early HIV infection may have a limited role in population HIV transmission. Collectively, these data suggest that acute and early HIV infection is relatively short and does not currently require fundamentally different programmatic approaches to manage the HIV/AIDS epidemic in most settings. Research and surveillance will inform which epidemic contexts and phases may require tailored strategies for these stages of HIV infection.

Epidemiological Trends for HIV in Southern Africa: Implications for Reaching the Elimination Targets.

Southern Africa is the region worst affected by HIV in the world and accounts for one third of the global burden of HIV. Achieving the UNAIDS 90-90-90 target by 2020 and ending the AIDS epidemic by 2030 depend on success in this region. We review epidemiological trends in each country in southern Africa with respect to the prevalence, incidence, mortality, coverage of anti-retroviral therapy (ART) and TB notification rates, to better understand progress in controlling HIV and TB and to determine what needs to be done to reach the UNAIDS targets. Significant progress has been made in controlling HIV. In all countries in the region, the prevalence of HIV in people not on ART, the incidence of HIV, AIDS-related mortality and, in most countries, TB notification rates, are falling. In some countries, the risk of infection began to fall before biomedical interventions such as ART became widely available as a result of effective prevention measures or people's awareness of, and response to, the epidemic but the reasons for these declines remain uncertain. Some countries have achieved better levels of ART coverage than others, but all are in a position to reach the 2020 and 2030 targets if they accelerate the roll-out of ART and of targeted prevention efforts. Achieving the HIV treatment targets will further reduce the incidence of HIV-related TB, but efforts to control TB in HIV-negative people must be improved and strengthened.

The temporal dynamics of relapse and reinfection tuberculosis after successful treatment: a retrospective cohort study.

BACKGROUND: There is increasing evidence from tuberculosis high-burden settings that exogenous reinfection contributes considerably to recurrent disease. However, large longitudinal studies of endogenous reactivation (relapse) and reinfection tuberculosis are lacking. We hypothesize a relationship between relapse vs reinfection and the time between treatment completion and recurrent disease. METHODS: Population-based retrospective cohort study on all smear-positive tuberculosis cases successfully treated between 1996 and 2008 in a suburban setting in Cape Town, South Africa. Inverse gaussian distributions were fitted to observed annual rates of relapse and reinfection, distinguished by DNA fingerprinting of Mycobacterium tuberculosis strains recultured from diagnostic samples. RESULTS: Paired DNA fingerprint data were available for 130 (64%) of 203 recurrent smear-positive tuberculosis cases in the 13-year study period. Reinfection accounted for 66 (51%) of 130 recurrent cases overall, 9 (20%) of 44 recurrent cases within the first year, and 57 (66%) of 86 thereafter (P < .001). The relapse rate peaked at 3.93% (95% confidence interval [CI], 2.35%-5.96%) per annum 0.35 (95% CI, .15-.45) years after treatment completion. The reinfection tuberculosis rate peaked at 1.58% (95% CI, .94%-2.46%) per annum 1.20 (95% CI, .55-1.70) years after completion. CONCLUSIONS: To our knowledge, this is the first study of sufficient size and duration using DNA fingerprinting to investigate tuberculosis relapse and reinfection over a lengthy period. Relapse occurred early after treatment completion, whereas reinfection dominated after 1 year and accounted for at least half of recurrent disease. This temporal relationship may explain the high variability in reinfection observed across smaller studies. We speculate that follow-up time in antituberculosis drug trials should take reinfection into account.

Extra-couple HIV transmission in sub-Saharan Africa: a mathematical modelling study of survey data.

BACKGROUND: The proportion of heterosexual HIV transmission in sub-Saharan Africa that occurs within cohabiting partnerships, compared with that in single people or extra-couple relationships, is widely debated. We estimated the proportional contribution of different routes of transmission to new HIV infections. As plans to use antiretroviral drugs as a strategy for population-level prevention progress, understanding the importance of different transmission routes is crucial to target intervention efforts. METHODS: We built a mechanistic model of HIV transmission with data from Demographic and Health Surveys (DHS) for 2003-2011, of 27,201 cohabiting couples (men aged 15-59 years and women aged 15-49 years) from 18 sub-Saharan African countries with information about relationship duration, age at sexual debut, and HIV serostatus. We combined this model with estimates of HIV survival times and country-specific estimates of HIV prevalence and coverage of antiretroviral therapy (ART). We then estimated the proportion of recorded infections in surveyed cohabiting couples that occurred before couple formation, between couple members, and because of extra-couple intercourse. FINDINGS: In surveyed couples, we estimated that extra-couple transmission accounted for 27-61% of all HIV infections in men and 21-51% of all those in women, with ranges showing intercountry variation. We estimated that in 2011, extra-couple transmission accounted for 32-65% of new incident HIV infections in men in cohabiting couples, and 10-47% of new infections in women in such couples. Our findings suggest that transmission within couples occurs largely from men to women; however, the latter sex have a very high-risk period before couple formation. INTERPRETATION: Because of the large contribution of extra-couple transmission to new HIV infections, interventions for HIV prevention should target the general sexually active population and not only serodiscordant couples. FUNDING: US National Institutes of Health, US National Science Foundation, and J S McDonnell Foundation.

Modeling the implementation of universal coverage for HIV treatment as prevention and its impact on the HIV epidemic.

The Joint United Nations Programme on HIV/AIDS (UNAIDS) recently updated its global targets for antiretroviral therapy (ART) coverage for HIV-positive persons under which 90 % of HIV-positive people are tested, 90 % of those are on ART, and 90 % of those achieve viral suppression. Treatment policy is moving toward treating all HIV-infected persons regardless of CD4 cell count-otherwise known as treatment as prevention-in order to realize the full therapeutic and preventive benefits of ART. Mathematical models have played an important role in guiding the development of these policies by projecting long-term health impacts and cost-effectiveness. To guide future policy, new mathematical models must consider the barriers patients face in receiving and taking ART. Here, we describe the HIV care cascade and ART delivery supply chain to examine how mathematical modeling can provide insight into cost-effective strategies for scaling-up ART coverage in sub-Saharan Africa and help achieve universal ART coverage.

Longitudinal evolution of the HIV effective reproduction number following sequential expansion of treatment as prevention and pre-exposure prophylaxis in British Columbia, Canada: a population-level programme evaluation.

BACKGROUND: Treatment as prevention and pre-exposure prophylaxis (PrEP) are key strategies in the control of HIV/AIDS. We aimed to characterise the longitudinal effects of antiretroviral therapy (ART), followed by treatment as prevention and the addition of PrEP, on the HIV effective reproduction number (Re) in British Columbia, Canada. METHODS: This population-level programme evaluation used data from the Drug Treatment Program of the British Columbia Centre for Excellence in HIV/AIDS (Vancouver, British Columbia, Canada). We also used estimates of HIV incidence and prevalence from the Public Health Agency of Canada, data on the number of new HIV diagnoses per year from the British Columbia Centre for Disease Control, and mortality data from the British Columbia Vital Statistics Agency. Data were obtained from 1985 until 2022, depending on the database source. Outcomes were the annual HIV prevalence, HIV incidence, number of new HIV diagnoses, number of people living with HIV on ART, HIV/AIDS-related and all-cause mortality rates, the HIV incidence-to-all-cause-mortality ratio, and Re. We calculated the modified effective reproduction number (Rme) using two thresholds of viral suppression and compared these values with Re. FINDINGS: We found a 95% decline in HIV/AIDS-related mortality and a 91% decrease in HIV incidence over the study period. The Re progressively declined from 1996 to 2022; however, from 1996 to 2017, Rme remained stable (>1) when calculated for people living with HIV with unsuppressed viraemia, suggesting that treatment as prevention reduces HIV incidence by decreasing the pool of individuals who are potentially able to transmit the virus. From 2018 to 2022, a decline in the estimated Re and Rme (<1) was observed regardless of whether we considered all people living with HIV or only those who were virologically unsuppressed. This finding suggests that PrEP decreases HIV incidence by reducing the number of susceptible individuals in the community, independently of viral suppression. INTERPRETATION: Our results show the synergy between generalised treatment as prevention and targeted PrEP in terms of decreasing HIV incidence. These findings support the incorporation of longitudinal monitoring of Re at a programmatic level to identify opportunities for the optimisation of treatment-as-prevention and PrEP programmes. FUNDING: British Columbia Ministry of Health, Health Canada, Public Health Agency of Canada, Vancouver Coastal Health, Vancouver General Hospital Foundation, Genome British Columbia, and the Canadian Institutes of Health Research.

Antiretroviral therapy for tuberculosis control in nine African countries.

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.

HIV treatment as prevention: debate and commentary--will early infection compromise treatment-as-prevention strategies?

Universal HIV testing and immediate antiretroviral therapy for infected individuals has been proposed as a way of reducing the transmission of HIV and thereby bringing the HIV epidemic under control. It is unclear whether transmission during early HIV infection--before individuals are likely to have been diagnosed with HIV and started on antiretroviral therapy--will compromise the effectiveness of treatment as prevention. This article presents two opposing viewpoints by Powers, Miller, and Cohen, and Williams and Dye, followed by a commentary by Fraser.

Antiretroviral therapy for prevention of tuberculosis in adults with HIV: a systematic review and meta-analysis.

BACKGROUND: Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa. In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV worldwide. Antiretroviral therapy has substantial potential to prevent HIV-associated tuberculosis. We conducted a systematic review of studies that analysed the impact of antiretroviral therapy on the incidence of tuberculosis in adults with HIV infection. METHODS AND FINDINGS: PubMed, Embase, African Index Medicus, LILACS, and clinical trial registries were systematically searched. Randomised controlled trials, prospective cohort studies, and retrospective cohort studies were included if they compared tuberculosis incidence by antiretroviral therapy status in HIV-infected adults for a median of over 6 mo in developing countries. For the meta-analyses there were four categories based on CD4 counts at antiretroviral therapy initiation: (1) less than 200 cells/µl, (2) 200 to 350 cells/µl, (3) greater than 350 cells/µl, and (4) any CD4 count. Eleven studies met the inclusion criteria. Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis in all baseline CD4 count categories: (1) less than 200 cells/µl (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.07 to 0.36), (2) 200 to 350 cells/µl (HR 0.34, 95% CI 0.19 to 0.60), (3) greater than 350 cells/µl (HR 0.43, 95% CI 0.30 to 0.63), and (4) any CD4 count (HR 0.35, 95% CI 0.28 to 0.44). There was no evidence of hazard ratio modification with respect to baseline CD4 count category (p = 0.20). CONCLUSIONS: Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis across all CD4 count strata. Earlier initiation of antiretroviral therapy may be a key component of global and national strategies to control the HIV-associated tuberculosis syndemic. REVIEW REGISTRATION: International Prospective Register of Systematic Reviews CRD42011001209 Please see later in the article for the Editors' Summary.

HIV treatment as prevention: systematic comparison of mathematical models of the potential impact of antiretroviral therapy on HIV incidence in South Africa.

BACKGROUND: Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART. METHODS AND FINDINGS: Twelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/µl and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results. CONCLUSIONS: Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. There was broad agreement regarding the short-term epidemiologic impact of ambitious treatment scale-up, but more variation in longer term projections and in the efficiency with which treatment can reduce new infections. Differences between model predictions could not be explained by differences in model structure or parameterization that were hypothesized to affect intervention impact.

Update on treatment as prevention of HIV illness, death, and transmission: sub-Saharan Africa HIV financing and progress towards the 95-95-95 target.

PURPOSE OF REVIEW: After over 40 years, the HIV pandemic is amongst the deadliest in history - 100% fatal without treatment, HIV has infected over 84 million people, and has caused over 40 million deaths. Global HIV spending between 2000 and 2015 totaled over a half trillion dollars. Delays in harnessing scientific advances, including 'test and treat' and treatment as prevention of illness, death, and transmission (TasP) provide a cautionary tale applicable to other pandemics. Resource allocation has also been problematic with many highest burden countries spending less than 50% on care and treatment. RECENT FINDINGS: Between 2002 and 2021, over $94 billion was budgeted for HIV in 40 sub-Saharan African countries, with 19 countries over $1 billion. In 2021, 8.1 million (32%) People Living with HIV (PLHIV) are still not on treatment; viral suppression data, the most important programme success indicator, is unavailable for 50% of countries. Of 19 countries with at least one billion dollars budgeted, seven have below 80% ART coverage, leaving 3.5 million (29%) of PLHIV off treatment and vulnerable to illness, death, and transmitting the virus to partners and children. SUMMARY: With additional funding and improved efficiency, achieving the 95-95-95 target to diagnose 95% of all HIV-positive individuals, provide antiretroviral therapy (ART) for 95% of those diagnosed and achieve viral suppression for 95% of those treated by 2030 is feasible and the humane pathway towards ending the HIV pandemic.

The HIV-associated tuberculosis epidemic--when will we act?

Despite policies, strategies, and guidelines, the epidemic of HIV-associated tuberculosis continues to rage, particularly in southern Africa. We focus our attention on the regions with the greatest burden of disease, especially sub-Saharan Africa, and concentrate on prevention of tuberculosis in people with HIV infection, a challenge that has been greatly neglected. We argue for a much more aggressive approach to early diagnosis and treatment of HIV infection in affected communities, and propose urgent assessment of frequent testing for HIV and early start of antiretroviral treatment (ART). This approach should result in short-term and long-term declines in tuberculosis incidence through individual immune reconstitution and reduced HIV transmission. Implementation of the 3Is policy (intensified tuberculosis case finding, infection control, and isoniazid preventive therapy) for prevention of HIV-associated tuberculosis, combined with earlier start of ART, will reduce the burden of tuberculosis in people with HIV infection and provide a safe clinical environment for delivery of ART. Some progress is being made in provision of HIV care to HIV-infected patients with tuberculosis, but too few receive co-trimoxazole prophylaxis and ART. We make practical recommendations about how to improve this situation. Early HIV diagnosis and treatment, the 3Is, and a comprehensive package of HIV care, in association with directly observed therapy, short-course (DOTS) for tuberculosis, form the basis of prevention and control of HIV-associated tuberculosis. This call to action recommends that both HIV and tuberculosis programmes exhort implementation of strategies that are known to be effective, and test innovative strategies that could work. The continuing HIV-associated tuberculosis epidemic needs bold but responsible action, without which the future will simply mirror the past.

Comparison of two active case-finding strategies for community-based diagnosis of symptomatic smear-positive tuberculosis and control of infectious tuberculosis in Harare, Zimbabwe (DETECTB): a cluster-randomised trial.

BACKGROUND: Control of tuberculosis in settings with high HIV prevalence is a pressing public health priority. We tested two active case-finding strategies to target long periods of infectiousness before diagnosis, which is typical of HIV-negative tuberculosis and is a key driver of transmission. METHODS: Clusters of neighbourhoods in the high-density residential suburbs of Harare, Zimbabwe, were randomised to receive six rounds of active case finding at 6-monthly intervals by either mobile van or door-to-door visits. Randomisation was done by selection of discs of two colours from an opaque bag, with one disc to represent every cluster, and one colour allocated to each intervention group before selection began. In both groups, adult (≥16 years) residents volunteering chronic cough (≥2 weeks) had two sputum specimens collected for fluorescence microscopy. Community health workers and cluster residents were not masked to intervention allocation, but investigators and laboratory staff were masked to allocation until final analysis. The primary outcome was the cumulative yield of smear-positive tuberculosis per 1000 adult residents, compared between intervention groups; analysis was by intention to treat. The secondary outcome was change in prevalence of culture-positive tuberculosis from before intervention to before round six of intervention in 12% of randomly selected households from the two intervention groups combined; analysis was based on participants who provided sputum in the two prevalence surveys. This trial is registered, number ISRCTN84352452. FINDINGS: 46 study clusters were identified and randomly allocated equally between intervention groups, with 55 741 adults in the mobile van group and 54,691 in the door-to-door group at baseline. HIV prevalence was 21% (1916/9060) and in the 6 months before intervention the smear-positive case notification rate was 2·8 per 1000 adults per year. The trial was completed as planned with no adverse events. The mobile van detected 255 smear-positive patients from 5466 participants submitting sputum compared with 137 of 4711 participants identified through door-to-door visits (adjusted risk ratio 1·48, 95% CI 1·11-1·96, p=0·0087). The overall prevalence of culture-positive tuberculosis declined from 6·5 per 1000 adults (95% CI 5·1-8·3) to 3·7 per 1000 adults (2·6-5·0; adjusted risk ratio 0·59, 95% CI 0·40-0·89, p=0·0112). INTERPRETATION: Wide implementation of active case finding, particularly with a mobile van approach, could have rapid effects on tuberculosis transmission and disease. FUNDING: Wellcome Trust.

Lives saved by tuberculosis control and prospects for achieving the 2015 global target for reducing tuberculosis mortality.

OBJECTIVE: To assess whether the global target of halving tuberculosis (TB) mortality between 1990 and 2015 can be achieved and to conduct the first global assessment of the lives saved by the DOTS/Stop TB Strategy of the World Health Organization (WHO). METHODS: Mortality from TB since 1990 was estimated for 213 countries using established methods endorsed by WHO. Mortality trends were estimated separately for people with and without human immunodeficiency virus (HIV) infection in accordance with the International classification of diseases. Lives saved by the DOTS/Stop TB Strategy were estimated with respect to the performance of TB control in 1995, the year that DOTS was introduced. FINDINGS: TB mortality among HIV-negative (HIV-) people fell from 30 to 20 per 100,000 population (36%) between 1990 and 2009 and could be halved by 2015. The overall decline (when including HIV-positive [HIV+] people, who comprise 12% of all TB cases) was 19%. Between 1995 and 2009, 49 million TB patients were treated under the DOTS/Stop TB Strategy. This saved 4.6-6.3 million lives, including those of 0.23-0.28 million children and 1.4-1.7 million women of childbearing age. A further 1 million lives could be saved annually by 2015. CONCLUSION: Improvements in TB care and control since 1995 have greatly reduced TB mortality, saved millions of lives and brought within reach the global target of halving TB deaths by 2015 relative to 1990. Intensified efforts to reduce deaths among HIV+ TB cases are needed, especially in sub-Saharan Africa.