The Lancet Global Health

BackgroundCurrent efforts to reduce global tuberculosis incidence have proved insufficient, highlighting that urgent action is needed to address underlying modifiable risk factors such as undernutrition. We aimed to estimate the global impact of eliminating undernutrition on tuberculosis incidence among adults accounting for varying nutritional status by country, sex, and age, in addition to incorporating the continuous, non-linear relationship between body mass index (BMI) and tuberculosis risk. MethodsWe used a continuous risk framework to consider the population-level implications of BMI distributions for tuberculosis incidence for those aged [&ge;]15 years. We generated BMI distributions for each country, sex, and age group applying a bilinear model for the logarithmic relative risk of tuberculosis incidence at different BMI values. We assessed the impact of eliminating moderate/severe undernutrition (BMI<17kg/m2) or all undernutrition (BMI<18.5kg/m2) on tuberculosis incidence by constructing counterfactual BMI distributions that redistributed those with low BMI to higher BMI, proportional to the remaining density. FindingsWe estimated that eliminating moderate/severe undernutrition would avert 1.4 million (95%UI, 1.1-1.7) tuberculosis episodes globally, representing 16.8% (14.3-19.2) of global adult incidence, while eliminating all undernutrition would avert 2.3 million (1.8-2.7) episodes, a reduction of 26.5% (23.2-29.8). The largest proportional reductions in tuberculosis incidence could be achieved by eliminating undernutrition in the African, South-East Asian, and Eastern Mediterranean regions; females; and adolescent or elderly adults. InterpretationOver a quarter of global tuberculosis incidence in adults would be averted by eliminating undernutrition, approximately three times higher than current estimates. These findings highlight the urgent need to scale up population-level nutritional interventions, which may have myriad social and health benefits beyond tuberculosis, alongside research to determine optimal implementation strategies and impacts. FundingNo specific funding

Background: Observational studies typically use routinely collected (RC) data to investigate TB treatment outcomes, but these data may be error-prone. Using RC data together with validated data on a subsample, we explored the association of TB testing results with mortality and TB treatment outcomes in persons living with HIV (PLWH). Method: We used RC data from two large HIV observational cohorts to evaluate the association of TB test result (positive/negative/unknown) at treatment start with death and the composite unfavorable outcome (treatment failure, loss-to-follow-up [LTFU], recurrence, or death) within 1.5 years of TB treatment start. We designed and implemented an optimal multi-wave validation study on a subsample of PLWH. We fitted logistic regression models using RC data only and combining them with the chartvalidated data using a generalized raking approach, controlling for age, sex, body mass index (BMI), antiretroviral therapy, CD4 count, and region. Results: RC data were extracted from 22,587 PLWH; 1122 were selected for validation, with 842 validated. We observed large discrepancies between validated and unvalidated data. We found that PLWH who started TB treatment with negative test results had higher odds of death compared to those who started treatment with a positive test: adjusted odds ratio (aOR)=1.22 (95% confidence interval [CI]=[1.03-1.45]) and aOR=3.94 (95% CI=[1.73-9.00]), using RC data only and RC plus validated data, respectively. Results for the composite outcome were inconclusive. Conclusion: In PLWH treated for TB, bacteriological confirmation was associated with lower mortality. Data validation for observational research using RC clinical data care is needed.

BackgroundWhile a range of interventions exist for tuberculosis prevention, screening, diagnosis, and treatment, their potential population impact and cost-effectiveness are seldom directly compared, or evaluated between settings with different background TB epidemiology and structural drivers. MethodsWe calibrated a deterministic TB model to epidemiological indicators in Brazil, India, and South Africa. We implemented seven interventions across countries focusing on prevention, screening and diagnosis, and treatment of TB, as well as TB screening in prisons in Brazil and nutritional supplementation in India. We standardised scale-up (2025-2030), coverage (80% of target population), and strength of evidence for epidemiological impact using published efficacy data. We estimated epidemiological impact and incremental cost-effectiveness ratios (ICERs), expressed as costs per disability-adjusted life year (DALY) averted by 2050. ResultsOnly three interventions prevented >10% of incident TB episodes by 2050: vaccination (median 15-28% across countries), symptom-agnostic community-wide screening (32-38%) and screening in prisons (23%). The impact of other interventions was more limited, ranging from 0% (shortened drug-susceptible treatment) to 5% (nutritional supplementation). ICERs varied widely by intervention and setting. Shortened drug-resistant treatment was cost-saving across settings, with the next lowest ICERs for prison screening in Brazil (72 USD/DALY) and nutritional supplementation in India (167 USD/DALY). Within each country, both low-cost community-wide screening and TB vaccine campaigns had lower USD/DALY than TB preventive treatment. ConclusionInterventions with meaningful epidemiological impact can also be cost-effective, but need to target populations beyond clinic-diagnosed individuals or their households. Achieving such potential requires a priority shift in funding, policy and product development.

IntroductionTuberculosis (TB) is the leading cause of death due to infectious disease worldwide. Social protection interventions can benefit TB-affected households. We conducted a systematic review and meta-analysis to quantify the effectiveness of social protection on TB treatment and socioeconomic outcomes. MethodsWe identified articles published from January 2012 to July 2024 by searching PubMed (includes MEDLINE), Embase, and Web of Science. We included studies that described at least one social protection intervention and reported on either TB treatment or socioeconomic outcomes for people with TB or TB-affected households. Random-effects meta-analysis was used for our primary outcome of interest, TB treatment success (treatment completion or cure). We performed a meta-regression to evaluate the association of study characteristics with odds of TB treatment success. Risk of bias was assessed using the Newcastle Ottawa Scale and the Cochrane Risk of Bias tool. This review was registered prospectively in the PROSPERO database (registration number CRD42022382181). FindingsOur search generated 47,245 articles. Of the 50 which were eligible for inclusion, 36 reported TB treatment outcomes, 8 reported on socioeconomic, and two studies reported both TB treatment and socioeconomic outcomes. Random-effects meta-analysis of 24 articles found that people with TB who received social protection interventions during treatment had 2.23 times the odds of TB treatment success (95% CI 1.82, 2.74, I2 93.8%). ConclusionSocial protection interventions significantly improve odds of TB treatment success. Outcomes and definitions used in our study have the potential to guide further research and implementation of social protection for TB-affected populations. Summary BoxO_ST_ABSWhat is already known on this topicC_ST_ABSSeveral studies have found that social and financial interventions designed to mitigate socioeconomic risk and promote resiliency, termed social protection interventions, have the potential to improve treatment outcomes for tuberculosis (TB), including treatment completion and cure. Additionally, several studies have demonstrated that social protection interventions can improve socioeconomic outcomes among TB-affected households such as averting catastrophic costs and negative financial coping strategies. What this study addsThis is the first systematic review and meta-analysis that comprehensively evaluates the impact of TB specific and TB sensitive social protection interventions on both TB treatment and socioeconomic outcomes, thereby generating evidence on the ability of these interventions to curb the well-known cycle of TB disease and poverty. Through the use of an extensive list of search terms, expanded and systematic inclusion of outcomes of interest, and a focused definition of social protection interventions, our systematic review included the adequate number of high-quality studies needed to conduct a meta-analysis. Additionally, our systematic review evaluated implementation outcomes described in eligible studies which provides the basis for feasibility of these strategies in programmatic settings. How this study might affect research, practice or policyOur study provides evidence that social protection interventions, when used in conjunction with standard biomedical treatment, have the potential to significantly improve TB treatment outcomes. This study fills an essential gap in existing synthesized evidence of the impact of social protection interventions on TB, socioeconomic, and implementation outcomes. Our findings also highlight the need for standardized definitions of social protection, as well as uniform reporting procedures, to better help evaluate the impact of social protection interventions for TB-affected individuals and households. Addressing these gaps provides scientific basis for meeting the commitments articulated in the 2023 United Nations General Assembly high level meeting for TB which calls for social protection for all individuals with TB.

BackgroundGlobal investments to combat HIV, tuberculosis, and malaria (HTM) have delivered substantial health gains, and may have reduced the burden placed by these diseases on the routine health system. We estimated the reduction in primary health care (PHC) utilization resulting from the scale-up of HTM services over 2000-2023 in 108 low- and middle-income countries. MethodsFor each disease, we applied established mathematical models to quantify PHC utilization (outpatient visits and inpatient bed-days provided outside of HTM programs) by individuals with symptomatic HIV, tuberculosis, or malaria unable to access HTM-specific services. For each country, we estimated averted PHC utilization by comparing a scenario describing the actual scale-up of HTM services to a counterfactual scenario holding HTM service coverage constant at year 2000 levels. We applied published unit costs to estimate the averted costs resulting from reduced PHC utilization. FindingsOver 2000-2023, scale-up of HTM services averted an estimated 6{middle dot}9 (95% interval: 4{middle dot}4-10{middle dot}4) billion outpatient PHC visits and 3{middle dot}9 (2{middle dot}5-6{middle dot}1) billion inpatient bed-days, representing US$135 (70-248) billion in averted costs. These reductions were greatest in Sub-Saharan Africa and East Asia and Pacific regions. Across study countries, these reductions represented a median of 4{middle dot}4% of hospital bed capacity and 1{middle dot}6% of government health spending in 2023. These percentages were 22{middle dot}9% and 5{middle dot}1% respectively for low-income countries. InterpretationOver recent decades, sustained investments in HTM services in high-burden settings have averted substantial PHC utilization and associated costs. These benefits should be considered when assessing investment impact. FundingThe Global Fund.

BackgroundRecent shifts in the global health funding landscape--most notably the dismantling of the United States Agency for International Development (USAID) and possible reduced contributions to the Global Fund to Fight AIDS, TB and Malaria (Global Fund)-- threaten essential tuberculosis (TB) services in low- and middle-income countries (LMICs). We quantified the potential impact on the household economic burden of TB. MethodsWe used linked epidemiological and economic models, calibrated to 79 LMICs, to estimate future TB patient costs under four scenarios: continuation of 2024 funding levels (baseline), termination of USAID, termination of USAID plus announced reductions in Global Fund contributions, and full elimination of external funding for TB. Outcomes included total TB-attributable household costs and numbers of households experiencing catastrophic costs (disease-related costs >20% of annual income). FindingsUSAID termination was projected to produce US$7.5 (95% uncertainty interval: $6.1-8.9) billion in additional patient-incurred costs and 3.9 (3.1-4.6) million additional households experiencing catastrophic costs over 2025-2050. The worst-case scenario (elimination of all external funding) resulted in $79.7 ($60.0-99.2) billion in additional patient-incurred costs and 40.5 (30.9-50.7) million additional households experiencing catastrophic costs--a 32% increase over baseline. Impacts were greatest for poorer households, with over 50% of additional catastrophic costs occurring in the poorest 20% of households. InterpretationAbrupt reductions in international donor funding for TB may reverse recent progress toward financial risk protection and health equity in LMICs. Strategies to reduce the disruption caused by funding cuts and protect vulnerable populations are urgently needed. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSeveral prior studies have examined the potential impact of cuts in international health funding from the United States of America. We searched PubMed and medRxiv for studies quantifying the effects of reductions in international donor funding on the economic burden of tuberculosis, published between January 1 and August 7, 2025, using search terms related to funding ("funding", "donor", "aid", "assistance"), tuberculosis ("tuberculosis", "TB"), patients or households (patient*, household*), and economic burden (cost*, econ*). The identified studies described a range of potential health consequences that could result from funding cuts. To our knowledge, no studies have considered the impact of funding cuts on the household economic burden of disease. Added value of this studyOur modelling suggested that termination of United States Agency for International Development (USAID) funding could lead to US$7.5 (95% uncertainty interval: $6.1-8.9) billion in additional patient-incurred costs and 3.9 (3.1-4.6) million additional households experiencing catastrophic costs over 2025-2050. Further reductions in funding to the Global Fund to Fight AIDS, TB and Malaria (Global Fund) in line with current announcements from donor countries could lead to a further $21.2 ($16.6-25.6) billion in patient-incurred costs and 10.7 (8.4-13.0) million households experiencing catastrophic costs. If all external TB funding were terminated, a projected $72.2 ($53.9-90.4) billion in patient-incurred costs could accrue and 36.6 (27.7-46.1) million households could experience catastrophic costs, compared with the impact of the funding cuts to USAID alone. Implications of all the available evidenceDisruptions to TB services resulting from reductions in international donor funding could result in increased tuberculosis-associated morbidity and mortality, which in turn could result in increased economic burden on resource-constrained households in the worlds poorest countries. Strategies to reduce the disruption caused by funding cuts and protect vulnerable populations are urgently needed.

BackgroundHIV incidence in sub-Saharan Africa has declined substantially since 2000 according to epidemic estimates published by UNAIDS. These estimates, derived by fitting mathematical models to national surveillance data, guide HIV programmes and epidemic response strategies. We assessed whether the level and age distribution of HIV incidence from modelled estimates were consistent with empirical HIV incidence observations, and whether incidence levels and trends were systematically different between study types, populations, and age groups. MethodsWe conducted an updated systematic review of adult HIV incidence data from sub-Saharan Africa published July 2019-February 2024 by searching Scopus, PubMed, Embase, and OVID databases, and combined with earlier systematic review data. We matched empirical incidence measurements between 1990-2023 to UNAIDS HIV incidence estimates by study area, sex, age group, and year. We used Bayesian mixed-effect Poisson regression to estimate (1) incidence rate ratios (IRR) between empirical observations and matched modelled incidence estimates adjusted for sex, year and study type/population; and (2) time trends in age-specific incidence from population-based cohort studies and household surveys. Results3560 HIV empirical incidence measurements were included from 179 studies conducted in 21 countries, comprising 23,000 new infections and 3.1 million person-years. Incidence observations from nationally-representative household surveys (IRR 1.07 95%CI 0.68, 1.67) and population-representative study populations (IRR 0.98 95%CI 0.51, 1.89) were not significantly different from matched modelled estimates, and declined at the same rate as modelled estimates (annual aRR 0.99 95%CI 0.98, 1.01). Studies among pregnant women (IRR 2.60 95%CI 1.58, 4.28), control arms of clinical trials (IRR 3.01 95%CI 1.90, 4.77) and key populations (FSW IRR: 6.46 95%CI 4.18, 10.00; MSM 44.02 95%CI 27.35, 70.87) had significantly higher incidence than modelled total population incidence estimates. Across population cohorts in Eastern and Southern Africa, HIV incidence among adults aged 15-49 declined by 75-90% between 2010-2023, and declined 7% (95%CI 4-10%) faster per year among young adults 15-24 compared to age 25+ years. Modelled incidence declined similarly to cohort data, but did not reflect the aging of the epidemic. ConclusionObserved incidence in population-representative studies in sub-Saharan Africa has declined steeply. Mathematical models that infer incidence from cross-sectional HIV surveillance data estimated the same incidence level and decline over time as population-representative studies. Studies with non-representative inclusion criteria had significantly higher incidence, including those among pregnant women and most HIV prevention/vaccine efficacy trials. The age pattern of incidence in modelled estimates should be reconsidered to capture the aging of the epidemic indicated by cohort studies.

Background Childhood respiratory infectious deaths are partitioned across four Global Burden of Disease cause modules-26 etiological attributions within lower respiratory infections, tuberculosis, COVID-19, and whooping cough-never jointly reported. Whether the structure of this combined mortality spectrum has changed over time, and with what implications for intervention design, has not been quantified. We assembled and analyzed the integrated spectrum for children and adolescents aged 0-19 years, 1990-2023. Methods We integrated Global Burden of Disease Study 2023 (release v8352) estimates into a 29-node spectrum-26 lower respiratory infection etiologies plus tuberculosis, COVID-19, and pertussis-globally and across seven super-regions, with uncertainty propagated by summing bounds. We computed Shannon diversity, Herfindahl concentration, and effective cause counts; phenotyped pandemic-window collapse and rebound per cause; linked pathogen shares to WHO/UNICEF vaccine coverage; and mapped geographic concentration in sub-Saharan Africa and South Asia. Reporting follows GATHER. Results In 2023 the 29 causes jointly accounted for 965,330 deaths (95% uncertainty interval [UI] 680,096-1,342,437). Shannon diversity rose from 2.336 to 2.711 (+16.1%) between 1990 and 2023; the effective number of causes nearly doubled (5.57 to 9.94), inversely coupled to total deaths (Spearman rho = -0.997). Whooping cough ranked second (112,954 deaths; 95% UI 64,576-185,708; 11.7%) and showed the spectrum's only rebound above 100% (-57.4% collapse, +111.0% rebound). Tuberculosis ranked third (87,764; 57,779-124,912; 9.1%) with the highest concentration in sub-Saharan Africa and South Asia (87.1%). COVID-19 entered at rank five (52,899; 47,275-59,183; 5.5%). Nineteen of 29 causes exceeded the poverty-lock threshold (>80.59% of deaths in sub-Saharan Africa plus South Asia). Conclusions Childhood respiratory infectious mortality has become more diverse and more concentrated in poverty as it has declined. Single-pathogen interventions now address a shrinking share; the spectrum's structure argues for platform interventions-oxygen, antimicrobial access, referral-tailored jointly by age and geography, implying that pathogen-specific strategies alone cannot finish the remaining mortality agenda.

BackgroundMarked declines in pediatric HIV have been achieved across sub-Saharan Africa, yet progress among adolescents remains uneven and strongly patterned by place. Drawing on place-based perspectives in health geography, we conceptualize Eastern and Southern Africa (ESA) and West and Central Africa (WCA) not merely as epidemiological regions, but as dis-tinct assemblages of health systems, gender norms, and historical investment trajectories shaping HIV risk and care. Using UNICEF-harmonized indica-tors from 2000 to 2024, we examined how place structures progress toward the 2030 Sustainable Development Goal (SDG 3.3) target. MethodsWe pooled country-level estimates using inverse-variance random-effects meta-analysis (restricted maximum likelihood for{tau} 2 with Hartung-Knapp adjustment). HIV incidence and AIDS-related mortality were analysed on the log scale, and mother-to-child transmission (MTCT) on the logit scale. Outcomes were pooled by region, age group (0-14; 15-19), sex, and year. We quantified percentage change from 2010 to 2024, the achieved annualized rate of change (ARC), and the required ARC from 2024 to 2030 to achieve a 90% reduction from 2010 levels. Robustness was assessed using prespecified sensitivity analyses. FindingsBetween 2010 and 2024, child HIV incidence declined by 72% in ESA and 66% in WCA, while adolescent incidence declined by 54% and 62%, respectively. In 2024, MTCT remained above elimination thresholds in both regions (9.9% in ESA; 17.6% in WCA). Adolescent girls experienced substantially higher HIV incidence than boys, with pooled female-to-male incidence rate ratios of 4.13 (95% CI: 3.32-5.13) in ESA and 4.92 (4.04-5.99) in WCA. Despite progress, achieved declines among adolescents (ARC: -5.4%/year in ESA; -6.6%/year in WCA) fall well short of the acceleration required to meet 2030 targets. ConclusionHIV progress among children and adolescents in sub-Saharan Africa is deeply place-dependent. While ESA reflects the benefits of earlier and sustained health system investments, persistent structural and gendered vulnerabilities continue to constrain adolescent outcomes, particularly in WCA. Achieving SDG 3.3 will require place-responsive strategies that integrate gender-sensitive adolescent prevention, differentiated care, and strengthened PMTCT within the specific social, political, and health system contexts shaping risk and access. HighlightsO_LIHIV declines among children and adolescents show strong place-based patterning. C_LIO_LIChild HIV incidence declined faster in ESA than in WCA, 2010-2024. C_LIO_LIAdolescent girls had four- to five-fold higher HIV incidence than boys. C_LIO_LIMTCT remains above elimination thresholds, especially in West and Central Africa. C_LIO_LIMeeting 2030 targets requires accelerated, place-responsive strategies. C_LI

Background Lower respiratory infections (LRI) remain the leading infectious cause of death in children, and survival once ill is a direct tracer of health-system quality. Whether countries are converging toward the best survival performance achieved within their own region has never been tested at national level. We measured each country's distance to an empirical episode-fatality-ratio (EFR) frontier in 204 countries from 1990 to 2023. Methods For each country and year we computed EFR = LRI deaths/incident episodes using Global Burden of Disease (GBD) 2023 estimates for ages 0-19 years. Deaths span the full 1990-2023 series; episodes are observed for 1990, 2019 and 2023, with intermediate years linearly interpolated. The frontier was the 10th-percentile country EFR within each GBD super-region and year (sensitivity: 5th and 25th percentiles); the gap = EFR_country/EFR_frontier. We classified 33-year gap trajectories into catch-up phenotypes, ranked COVID-window (2019-2023) movers, cross-tabulated gap against avoidable deaths to build a priority list, and benchmarked upper respiratory infections (URI) at three time points as a near-zero-fatality contrast. Findings The median country's gap was 1.86 in 1990, 1.80 in 2019 and 1.86 in 2023; the share of countries more than twice their regional frontier was 44.6% in 1990 and 46.6% in 2023. Of 137 eligible countries, 67 narrowed and 69 widened their gap, with one unchanged. Nineteen countries achieved sustained catch-up, concentrated in North Africa and the Middle East (7) and Latin America (5), with China closing from 2.43 to 0.50, below its regional frontier; 28 countries regressed, led by Central Asia (Uzbekistan x3.5) and including the United States (x2.0). Over the COVID-19 window the median gap peaked at 2.00 in 2021 (+10.8% versus 2019, from unrounded medians) before returning to 1.86. Combining gap with avoidable deaths identifies two distinct policy problems: high-burden, moderate-gap giants (Nigeria 67,490 avoidable deaths, gap 2.4; India 54,109, gap 1.6) and extreme-gap outliers (Uzbekistan, gap 28.6). The Sub-Saharan Africa frontier fell further behind the High-income frontier (ratio 4.2 in 1990, 9.5 in 2023); the median Sub-Saharan African country sits 11.0 times the global 10th-percentile frontier but only 1.78 times its own regional frontier, so within-region benchmarking understates the region's true distance. URI gaps likewise did not converge (median 4.15 to 4.60). Interpretation Convergence toward the survival frontier is not the default national trajectory: over three decades the typical country made no net progress toward the best decile of its own region, and pandemic-era divergence was only partly reversed. National gap trajectories separate system-wide quality shortfalls from extreme outliers warranting audit, and expose a measurement trap in which regions whose frontiers stagnate appear closer to best practice than they are.

BackgroundTuberculosis services in many settings rely heavily on international donor funding. In 2025, the United States Agency for International Development (USAID) was dismantled, and other countries also announced cuts to overseas development assistance. We quantified potential epidemiological impacts attributable to these reductions in international donor funding. MethodsWe calibrated a deterministic tuberculosis model to epidemiological indicators in low- and middle-income countries. We projected three future scenarios assuming: a) levels of funding in 2024 continue through 2035, b) termination of USAID funding from 2025, and c) additional reductions in funding through The Global Fund in line with current donor announcements from 2025. We assumed a reduction in tuberculosis treatment initiation rates proportional to budget reductions for each scenario, estimating cumulative excess incident episodes of symptomatic tuberculosis and tuberculosis deaths. FindingsWe modelled 79 countries, representing 91% of global tuberculosis incidence and 90% of global tuberculosis mortality in 2023. Our modelling suggested that the termination of USAID funding may lead to 420 500 excess tuberculosis deaths by 2035. Further reductions in funding in line with current announcements by the United States, France, the United Kingdom, and Germany may lead to an additional 699 200, 63 100, 50 500, and 30 500 TB deaths, respectively. Impacts would be greatest in low-income countries. InterpretationWe estimate substantial potential impacts on tuberculosis morbidity and mortality due to reductions in international donor funding. Expanded support from domestic and international donors is essential to address immediate gaps in prevention, diagnosis, and treatment. FundingThis work was unfunded.

BackgroundAfter completion of TB treatment patients may remain at-risk of complications and mortality. We determined the survival and predictors of all-cause mortality after completing TB treatment among ART experienced patients. MethodsThis was a retrospective cohort analysis of all ART experienced patients who completed TB treatment at a specialist HIV clinic in Uganda, between 2009 and 2014. The patients were followed for five years after TB treatment. We determined mortality rate, probability of death, and predictors of all-cause mortality after TB treatment using Poisson methods, Kaplan-Meier methods, and Cox proportional hazard models, respectively. ResultsA total 1,287 patients completed TB treatment between 2009 and 2014, of which 1,111 were included in the analysis. At TB treatment completion, the median age was 36 years (IQR: 31-42), 563 (50.7%) were males, and median CD4 count was 235 cells/mL (IQR: 139-366). The person time at risk was 4410.60 person-years. The all-cause mortality rate was 15.42 per 1000 person-years (95% CI: 12.14-19.59). The probability of death at five years was 6.9% (95%CI: 5.5%-8.8%). In the multivariable analysis, CD4 count<200 cells/mL was a predictor of all-cause mortality (aHR=1.81, 95%CI:1.06 - 3.11, p=0.03) alongside TB history (aHR=2.12, 95%CI: 1.16 - 3.85, p=0.01). ConclusionSurvival post TB treatment in ART experienced PLHIV is reasonably good and most deaths occur within two years of TB treatment completion. Patients with low CD4 and those with history of treatment have an increased risk of mortality which underscores the need for TB prophylaxis, detailed assessment, and close monitoring after TB treatment. What is already known on this topicTuberculosis is the leading cause of death in PLHIV and patients who complete treatment remain at risk of mortality. However, it is not clear what the mortality rate is, when it occurs, and what factors are associated with mortality in exclusively ART experienced patients. What this study addsMost deaths occur within two years after treatment completion decreasing drastically by year five. Patients with low CD4 count after TB treatment have an 81% increased risk of death and those with a history of TB have a 200% increased risk of mortality. How this study might affect research, practice or policyThe study provides a detailed understanding of post-TB survival in ART experienced PLHIV and underscores the need for programs and clinics to re-define TB treatment success and consider the use of enhanced prophylaxis after TB treatment.

Tuberculosis (TB) killed more people globally than any other single pathogen over the past decade. Where surveillance is weak, estimating TB burden estimates uses modeling. In many African countries, increases in HIV prevalence and antiretroviral therapy (ART) have driven dynamic TB epidemics, complicating estimation of burden, trends, and potential intervention impact. We therefore developed a novel age-structured TB transmission model incorporating evolving demographic and HIV/ART effects, and calibrated to TB prevalence and notification data from 12 African countries. We used Bayesian methods to include uncertainty for all TB model parameters, and estimated age-specific annual risks of TB infection (ARTI) and proportion of TB incidence from recent (re)infection (PR). We found ARTI of up to 16.0%/year in adults, but a mean PR across countries of 34%. Rapid reduction of the unacceptably high burden of TB in high HIV prevalence settings will require interventions addressing progression as well as transmission.

BackgroundUntreated pulmonary tuberculosis (TB) causes ongoing lung damage, which may persist after treatment. Conventional approaches for assessing TB health effects may not fully capture these mechanisms. We evaluated how TB-associated lung damage and post-TB sequalae affect the lifetime health consequences of TB in high HIV prevalence settings. MethodsWe developed a microsimulation model representing dynamic changes in lung function for individuals evaluated for TB in routine clinical settings. We parameterized the model with data for Uganda, Kenya, and South Africa, and estimated lifetime health outcomes under prompt, delayed, and no TB treatment scenarios. We compared results to earlier modelling approaches that omit progressive lung damage and post-TB sequelae. FindingsWe estimated 4.6 (95% uncertainty interval 3.4-5.8), 7.2 (5.1-9.6), and 18.0 (15.1-20.0) year reductions in life expectancy due to TB under prompt, delayed, and no treatment scenarios, respectively. Disability-adjusted life years (DALYs) from TB were estimated as 8.3 (6.2-10.6), 12.6 (9.0-17.0), and 27.8 (24.1-30.6) under prompt, delayed, and no treatment scenarios, respectively. Post-TB DALYs represented 9-53% of total DALYs. Modelling approaches that omit progressive lung damage and post-TB sequelae underestimated lifetime health losses of TB by 48-57%, and underestimated the benefits of prompt treatment by 45-64%. InterpretationDelayed initiation of TB treatment causes greater lung damage and higher mortality risks during and after the disease episode. In settings with co-prevalent TB and HIV, accounting for these factors substantially increased estimates of the lifetime disease burden and life expectancy loss caused by TB. FundingNIH. Research in context Evidence before this studyResearch on long-term sequalae among tuberculosis (TB) survivors has focused on describing the prevalence and nature of these post-TB sequalae, and quantifying their contribution to the overall burden of TB disease. There is limited evidence describing how improvements in TB diagnosis and prompt treatment initiation could affect the overall health losses associated with TB, inclusive of post-TB sequelae. We searched PubMed from database inception until July 19, 2024, with no language restrictions for studies reporting how TB diagnosis and treatment affect post-TB sequelae and lifetime health losses, using the search terms "(tuberculosis OR TB) AND (post-TB OR post-tuberculosis) AND (diagnos*) AND (treat*) AND (model*)". We retrieved 21 publications based on this search. Of these, one study reported a mathematical modeling approach for estimating lifetime health outcomes and costs by considering the delay in diagnosis, post-TB sequelae, and treatment discontinuation among TB patients in Brazil, but did not simulate changes in lung function during the TB episode. Added value of this studyTo our knowledge, this is the first study to investigate the effects of timeliness of TB diagnosis on progressive lung damage and lifetime health outcomes for individuals with TB. To do so, we constructed a mathematical model simulating changes in lung function before, during, and after TB treatment, and simulated multiple counterfactual scenarios for a cohort of individuals presenting to primary health services with undiagnosed TB disease in Uganda, Kenya, and South Africa. We compared the results of this analysis to the estimates produced by earlier modelling approaches that do not represent TB-associated lung damage or post-TB sequelae. Implications of all the available evidenceThe results of this analysis showed that post-TB sequelae represent a substantial share of the overall health losses associated with TB, and that better post-TB lung function (resulting from a shorter duration of untreated TB disease) is a major contributor to the overall health benefits of prompt TB diagnosis and treatment. These results are not accurately captured by earlier modelling approaches that did not consider TB-associated lung damage or post-TB sequelae. The findings of this analysis contribute to the evidence base describing how TB interventions can influence lung function dynamics during and after TB disease, and the resulting changes in disability and mortality due to TB.

BackgroundCharacterising disparities in HIV infection across populations by gender, age, and HIV risk is key information to guide intervention priorities. We compared 9 models representing 15 different settings across Africa to assess how indicators measuring HIV acquisitions, transmissions, or potential long-term infections influence estimates of the contribution of different populations to new infections, including key populations (KPs, including female sex workers (FSW), their clients, men who have sex with men). MethodsWe evaluated four indicators: I1) acquisition indicator measuring the annual fraction of all new infections acquired by a specific population, I2) direct transmission indicator measuring the annual fraction of all new infections directly transmitted by a specific population, I3) 1-year and I4) 10-year transmission population-attributable fractions (tPAFs). tPAFs measure the fraction of new infections averted if transmission involving a specific population was blocked over a specific time period. We compared estimates of the four indicators across 7 populations and 15 settings and assessed if the contribution of specific populations is ranked differently across indicators for 10 settings. FindingsIndicators identified distinct priority populations as the largest contributors: The acquisition indicator (I1) identified women aged 25+ years outside KPs as contributing the most to acquired infections in 8/10 settings in 2020, but to direct transmissions (I2) in only two settings. In 6/10 settings, the 10-year tPAFs (I4) identified non-KP men aged 25+ years and clients of FSW as the largest contributors to HIV transmission. Notably, non-KP women aged 15-24 years acquired (I1) more infections in 2020 (median of 1{middle dot}7-fold across models) than they directly transmitted (I2), while non-KP men aged 25+ years and clients of FSWs transmitted more infections than they acquired in all but one model (median: 1{middle dot}4 and 1{middle dot}6-fold, respectively). Estimates of the 10-year tPAFs accounting for transmission in the long-term were substantially larger than the direct transmission indicator for all populations, especially for FSW (median: 2{middle dot}0-fold). InterpretationIndicators that reflect HIV acquisitions and transmissions over the short and long term can be utilised to capture the complexity of HIV epidemics across different populations and timeframes. The added nuance would improve the effectiveness of the HIV prevention response across all populations at risk. FundingNIH, MRC. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSMeasures of the distribution of HIV acquisition across population groups are commonly used for assessing the contribution of populations to new HIV infections and prevention priorities. However, alternative indicators documented in the literature reflect transmissions or potential long-term effects. It is unclear how the choice of indicator affects the identification of populations that require additional prevention and treatment efforts to accelerate progress towards ending AIDS. We searched PubMed on March 08, 2025, with the terms (HIV) AND (Africa*) AND (acqui*) AND (transm*) AND (model*), with no language or publication date restriction, and identified no meta-assessment or mathematical model comparison studying differences in estimates of the fraction of all infections acquired and transmitted by a population when using different epidemiological indicators. Added value of this studyUsing estimates from 9 models representing 15 different epidemic settings across Africa, we studied indicators of HIV epidemic contribution for 7 populations, including female sex workers, their clients, men who have sex with men, and non-key populations stratified by gender and age. We measured four commonly reported indicators of HIV contribution. One focused on acquired infections and the other three focused on transmissions. We found that estimates from these different indicators can differ greatly for the same model and population, to the extent that they identify different populations for prioritising interventions to accelerate HIV incidence declines. The acquisition-focused indicator (i.e. fraction of all infections acquired by a given population), the most used and communicated by UNAIDS, substantially underestimates the large contribution of men, and particularly male clients of female sex workers, to ongoing HIV transmission. Implications of all the available evidenceThe choice of indicators measuring a populations contribution to the HIV epidemic should be carefully considered and precisely defined. Modelling teams working in partnership with government, implementers, funders, and community members should systematically report both acquisition- and (long-term) transmission-focused indicators, instead of only measuring acquisitions in the short term as currently done. Multiple indicators will more comprehensively capture the potential impact of prevention efforts addressing acquisition and transmission risks of different vulnerable populations.

BackgroundGlobally, Mycobacterium tuberculosis (Mtb) is the leading cause of death due to a single pathogen, with most tuberculosis cases occurring in low- and middle-income countries. A growing proportion of tuberculosis cases in high-income countries occur among foreign-born individuals, often resulting from a Mtb infection acquired before migration. As a result, tuberculosis trends in many high-income countries are increasingly influenced by tuberculosis epidemiology in and migration patterns from other countries. Our objective was to estimate how the future risks of tuberculosis in high-income countries will change depending on the success or failure of efforts to combat tuberculosis in high-burden settings. MethodsWe defined scenarios representing different levels of optimism regarding tuberculosis control in high-burden settings. The most optimistic scenario assumed high-burden countries would achieve tuberculosis elimination targets proposed by the WHO. The most pessimistic assumed major increases in tuberculosis following sharp reductions in international health aid. A base-case scenario assumed continuation of pre-2025 trends. We used calibrated mathematical models to predict how these scenarios would change Mtb infection prevalence among future migrants and thereby affect tuberculosis incidence and deaths in high-income countries. We considered 49 high-burden countries (as defined by the WHO), and projected tuberculosis outcomes in 60 high-income countries until 2050. FindingsOver 2025-2050, we project there will be 2,266,000 (95% credible interval (CI): 1,938,000-2,744,000) tuberculosis cases in high-income countries if pre-2025 trends continue, with 57% (95%CI: 50-65) of these cases occurring among foreign-born individuals (up from 39% in 2024), for an average incidence rate of 6.5 (95%CI: 5.3-8.3) per 100,000 in 2050. Under the most optimistic scenario we estimated that there would be 785,000 (95%CI: 647,000-950,000) fewer tuberculosis cases and 63,000 (95%CI: 52,000-78,000) fewer tuberculosis deaths in high-income countries over 2025-2050, with an incidence of 2.3 (95%CI: 1.8-3.0) per 100,000 in 2050. Under the most pessimistic scenario, we estimated there would be 1,168,000 (95%CI: 983,000-1,324,000) additional tuberculosis cases and 95,000 (95%CI: 83,000-106,000) additional tuberculosis deaths in high-income countries over 2025-2050, with incidence of 11.5 (95%CI: 9.5-14.0) per 100,000 in 2050. The United States, United Kingdom, Germany, France, and Italy were projected to be the most affected high-income countries. InterpretationFor high-income countries, the future risks of tuberculosis incidence and mortality could vary by as much as 5-times depending on the success or failure of tuberculosis control in high-burden settings, fundamentally shaping the strategies required to prevent, detect and treat tuberculosis in these settings.

BackgroundLong-acting injectable HIV pre-exposure prophylaxis (PrEP), including Lenacapavir, has the potential to accelerate HIV incidence declines in eastern and southern Africa (ESA). However, high product and delivery costs and constrained budgets necessitate efficient prioritization strategies to maximize impact and achieve cost-effectiveness. MethodsWe used district-level HIV incidence estimates published by UNAIDS to estimate the direct health and economic impact of prioritizing Lenacapavir delivery according to geography, age, and sex across 837 districts in 11 high-burden ESA countries. Infections and disability-adjusted life years (DALY) averted, number needed to treat (NNT), cost per DALY averted, and price thresholds to achieve cost-effectiveness were estimated across geographic prioritization scenarios. Cost-effectiveness was assessed against a $500 per DALY averted threshold, assuming $5,000 discounted lifetime HIV treatment costs and 10 DALYs per HIV infection. Sensitivity analyses varied Lenacapavir costs (commodities + delivery) per person per year (pppy) ($125 versus $55), DALYs per HIV infection (7.5), and the risk differentiation among those who uptake long-acting PrEP. ResultsHIV incidence varied substantially across ESA, with 50% of new infections in districts containing less than 20% of at-risk adults. Lenacapavir cost-effectiveness varied accordingly, with high-incidence districts exhibiting substantially lower NNT and higher price thresholds for cost-effective delivery. In high-incidence districts, [>5/1,000 person-years (py)], of South Africa, Mozambique, Lesotho, and eSwatini, Lenacapavir would be cost-effective at $50-100 pppy. In South Africa, at annual cost $55 pppy, Lenacapavir was cost-effective in all 52 districts when provided to women aged 15-24 years with incidence exceeding twice the district average and could reach approximately 18-20% of new infections while covering 4% of the full HIV-negative adult population aged 15-49 years. Geographically optimized prioritization in South Africa with minimal age and risk-group stratification achieved efficiency comparable to country-level prioritization to high-risk groups and key populations ([~]20% incidence reduction with 3-5% coverage). Impact and cost-effectiveness were sensitive to assumptions about risk heterogeneity. ConclusionsLenacapavir impact and cost-effectiveness varies substantially across geographic settings, driven primarily by variation in HIV incidence. Simple incidence-based models can identify where universal provision to certain demographic groups is both impactful and cost-effective, particularly in high-incidence districts and age groups.

BackgroundPreventive chemotherapy targeting school-aged children has substantially reduced schistosomiasis morbidity, however, a key strategic tension remains between sustaining morbidity control and pursuing transmission elimination, particularly in settings characterised by heterogeneous transmission dynamics and persistent adult infection reservoirs. We developed a health system-integrated transmission and economic evaluation framework to identify optimal age-targeting and district-level prioritisation, providing a basis for determining when elimination-focused approaches offer advantages over morbidity reduction alone. MethodsThe Thanzi la Onse individual-based model was used to evaluate alternative age-targeted mass drug administration (MDA) strategies for Schistosoma haematobium and Schistosoma mansoni across all 32 districts of Malawi from 2024-2050. Strategies included treatment of school-aged children (MDA-SAC), pre-school and school-aged children (MDA-PSAC+SAC), and community-wide treatment (all ages). Health outcomes included person-years with any infection (PY), disability-adjusted life years (DALYs), probability of elimination (defined as reaching <2% prevalence of infection in all ages). The cost-effectiveness was evaluated using incremental cost-effectiveness ratios (ICERs), net health benefit (NHB), and by quantifying the maximum costs available for implementation, using a cost-effectiveness threshld for Malawi of 88 USD per DALY averted. FindingsIn the absence of MDA, the majority of the infection burden over 2024-2050 would be concentrated in adults aged 15 years and older (219.6 million person-years [PY], 95% CI 215.4-223.4), compared with 72.8 million PY (95% CI 71.5-74.3) among school-aged children (SAC) and 25.5 million PY (95% CI 25.1- 26.2) among preschool-aged children. Annual MDA-SAC would avert approximately 18.0 million DALYs (95% CI 17.6-18.4) between 2025 and 2050 and would be highly cost-effective nationally (ICER 4.76 USD/DALY, 95% CI 4.47-4.95). Across districts, ICERs were highly variable; 25 of 32 districts were cost-effective in [&ge;]90% of runs and 29 of 32 in [&ge;]50% of runs. Expanding treatment to include preschool-aged children (MDA PSAC+SAC) would produce modest additional gains (additional 44,500 DALYs averted) but with substantially higher costs (national ICER 606 USD/DALY, 95% CI 472-695), being dominated in 22 districts and cost-effective only in the high-burden Likoma district. Community-wide MDA would achieve elimination for both species in all districts by 2030 and avert a further 98,000 DALYs; nationally it would be cost-saving relative to PSAC+SAC although outcomes were heterogeneous, with this strategy being cost-saving in 11 high-prevalence districts (2023 prevalence range 13.7 - 41.5%) but dominated (in >80% of model runs) in 16 others. Threshold analyses of maximum implementation costs indicated substantial cost margins in high-burden districts, with cost-effectiveness maintained up to approximately 25-38 USD per treatment. InterpretationThe choice of schistosomiasis strategies should depend on whether programmes prioritise short-term morbidity reduction or long-term elimination, as well as the local disease burden and the prevailing cost of service delivery. Integrating district-level transmission dynamics with opportunity-cost-based economic evaluation reveals when broader coverage is justified and provides a framework for designing fiscally grounded elimination pathways in heterogeneous endemic settings.

BackgroundWe aimed to determine antiretroviral therapy (ART) initiation timing and outcomes in people living with HIV (PLHIV) receiving tuberculosis treatment in KwaZulu-Natal, South Africa. MethodsWe performed a retrospective cohort analysis of routinely collected de-identified data from 62 clinics including PLHIV not already receiving ART aged [&ge;]16 years, starting tuberculosis treatment between October 2016-November 2019. Multivariable Poisson regression models with robust standard errors evaluated associations between timing of ART initiation (after starting tuberculosis treatment) and successful tuberculosis treatment, and 6-month HIV viral load (VL) <50 copies/mL. ResultsAmong 5,548 PLHIV with tuberculosis, 29.8% initiated ART within 15 days ("early"), 36.2% in 16-56 days, 8.7% in 57-210 days, with 25.3% not initiating ART by 7 months. Proportions with successful tuberculosis treatment were similar comparing 16-56 and 57-210 days to early initiation, with a lower likelihood of successful tuberculosis outcome with no ART within 7 months (adjusted risk ratio [aRR] 0.81 [0.77-0.86], p<0.001). In those with a known VL 6 months post-ART initiation (n=2,658), initiation within 57-210 days had a lower likelihood of viral suppression (aRR 0.90 [0.82-0.99], p<0.03). ConclusionAlthough <30% of PLHIV with tuberculosis initiated ART early, this was associated with better tuberculosis outcomes and VL suppression.

IntroductionChildren experience elevated risks of developing and dying from tuberculosis (TB). We estimated the additional pediatric TB cases and deaths that could occur over 2025-2034 if programmes supported by United States bilateral health aid and the Global Fund to Fight AIDS, Tuberculosis, and Malaria (Global Fund) are discontinued. MethodsWe collated data on funding sources for TB and HIV programs in low- and middle-income countries and constructed scenarios representing reductions in health aid from 2025. Using calibrated transmission-dynamic models for 130 countries, we projected the discontinuation of TB and HIV treatment services under several funding reduction scenarios, and how this would affect pediatric TB exposure and treatment access. We projected pediatric TB incidence and mortality over 2025-2034 to calculate the impact of funding reductions. ResultsCompared to maintenance of pre-2025 service levels, withdrawal of services currently supported by US bilateral health aid was projected to result in an additional 2.5 million (95% uncertainty interval: 1.8-3.3) pediatric TB cases and 340,000 (240,000-460,000) deaths over 2025-2034. Withdrawal of US support to the Global Fund and reduction in non-US contributions was projected to result in an additional million 8.9 (6.9-11.5) pediatric TB cases and 1.5 million (1.1-2.0) deaths, more than double the number expected with continued service levels. Impacts were greatest in Sub-Saharan Africa and South-East Asia. Restoration of services in 2026 led to a substantially smaller number of additional deaths. FindingsWithout actions to restore discontinued services, cuts to health aid for TB and HIV programs could result in large numbers of childhood TB deaths over the next decade.