The Lancet Global Health

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.

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.

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.

Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection is associated with accelerated liver disease, but whether coinfection is associated with newly documented social determinants of health (SDoH) is unclear. We conducted a retrospective cohort study using TriNetX across 110 U.S. healthcare organizations (2010-2026). We propensity score matched adults with HIV/HBV to adults with HIV or HBV monoinfection. We organized newly documented SDoH indicators using a dynamic individual-level framework with four clinically recognized domains of social disadvantage: material vulnerability, healthcare access and engagement, interpersonal adversity, and psychosocial vulnerability. Matched cohorts included 10,071 HIV/HBV-HIV pairs and 9,659 HIV/HBV-HBV pairs (mean age, 47 years; 79% male; 66% non-White; median follow-up, 3.3 years). Over 178,900 person-years, HIV/HBV was associated with higher risk of the primary SDoH composite compared with HIV (11.5% vs 9.7%; incidence rate, 2.50 vs 1.97 per 100 person-years; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.15-1.37) and HBV (11.0% vs 6.4%; incidence rate, 2.39 vs 1.67; HR, 1.50; 95% CI, 1.35-1.67). HIV/HBV was also associated with higher material vulnerability and healthcare access and engagement composites in both comparisons, including housing instability, food insecurity, financial insecurity, insurance instability, and care disengagement/nonadherence (HR range, 1.22-3.33 vs HIV; 1.31-1.94 vs HBV). In the HBV comparison, HIV/HBV was additionally associated with interpersonal adversity, primary support stressors, and violence or victimization (HR range, 1.36-2.16). Findings were robust across sensitivity analyses. HIV/HBV was associated with more newly documented SDoH than monoinfection, supporting dynamic SDoH assessment.

Background: Neonatal mortality remains a significant public health challenge in Sub Saharan Africa (SSA). The continuum of maternal care (COC), spanning antenatal care (ANC), skilled birth attendance (SBA), and postnatal care (PNC) represents an integrated pathway to improving neonatal survival. Multi-country evidence on how adherence to this full continuum affects neonatal outcomes across SSA is limited. Objectives: This study aimed to: (1) construct a composite COC indicator and describe its sociodemographic distribution; (2) estimate its association with neonatal mortality; (3) conduct a counterfactual analysis; and (4) examine cross country heterogeneity in the COC effect on neonatal mortality. Methods: Pooled Demographic and Health Survey (DHS) data from 35 SSA countries (2010 to 2026) were analyzed (N = 867,984 live births). A binary CoC indicator (coc1 = 1 if mother received [&ge;]4 ANC visits, skilled birth attendance, and PNC within 48 hours) was constructed. Survey-weighted logistic regression adjusted for wealth, education, residence, parity, maternal age, child sex, child age, and country. Counterfactual predictive margins and a COC and country interaction model were estimated in Stata 18. Results: Only 13.47% of mothers met the full COC threshold. COC completion was higher among wealthier, urban, more educated, and lower-parity women. After adjustment, CoC receipt was associated with significantly lower odds of neonatal death (aOR = 0.638, 95% CI: 0.577 - 0.706, p < 0.001). Counterfactual analysis showed the predicted neonatal mortality probability would fall from 3.15% (no CoC) to 2.04% (full CoC), an absolute risk reduction of 1.11 percentage points. Cross-country interaction terms were largely non-significant; only Namibia reached significance (p = 0.036). Conclusion: Completion of the full continuum of maternal care is independently associated with reduced neonatal mortality across SSA. Equity focused policies should prioritize integrated service delivery for rural, poor, and less educated women.

Introduction: Control of tuberculosis (TB) in children remains a major challenge globally. There is growing recognition that children with severe acute malnutrition (SAM) are a high-risk population for TB, but the global burden of TB in this group has never been comprehensively quantified. Methods: We conducted a systematic review and meta-analysis to estimate the prevalence of TB among children with SAM. Following PRISMA guidelines, we searched PubMed/MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, and WHO Global Index Medicus from database inception to June 15, 2026. We included studies reporting TB among systematically sampled cohorts of children <15 years with SAM as defined by the World Health Organization. Methodological study quality was assessed with adapted versions of the Newcastle-Ottawa Scale or the Joanna Briggs Institute critical appraisal checklist. Pooled TB prevalence was calculated using a random-effects model with predefined stratification of studies by geographic region, national TB incidence, and study quality. We also conducted subgroup analyses by age, sex, HIV status, SAM type, and TB exposure. Results: We included 73 studies comprising 33,869 children with SAM across 15 countries, predominantly from sub-Saharan Africa and South Asia, and predominantly reporting on hospitalized children. The pooled TB prevalence was 13% (95% CI: 11-16%), but there was substantial heterogeneity (I2=98%). Studies conducted in Southern Africa had the highest pooled TB prevalence (36%, 95% CI: 19-56%) compared to other regions (p<0.01). Pooled TB prevalence was higher in those with history of TB household exposure compared to those without (74% vs. 17%, p=0.01). Conclusions: Approximately one in eight children hospitalized with SAM have TB, greatest among children with history of TB exposure and those in Southern Africa. These findings highlight opportunities for improved early TB diagnosis and routine, integrated TB screening within hospital-based SAM care pathways.

Background In people living with Human Immunodeficiency Virus (PLWH), tuberculosis (TB) is the leading cause of death and is often associated with substantial morbidity. Better identifying PLWH with severe forms of TB could help target early interventions to reduce mortality and severe morbidity. Existing TB severity assessment tools may be sub-optimal for assessing disease severity in PLWH, since they incompletely integrate key determinants of disease severity. We aimed to develop a consensus-based TB severity score tailored to PLWH. Methods We developed a multifactorial TB severity score (TBSS) for PLWH using a modified Delphi process with a multidisciplinary group of international TB experts as the second part of a RAND/UCLA Appropriateness Method, following a previously published systematic review. Results Eight of 15 invited experts (53%) participated in both Delphi rounds. Of 62 candidate factors, 15 reflecting TB-related characteristics, host-related characteristics as well as characteristics related to both TB and host were rated as having high appropriateness for inclusion in the final TBSS. The total score ranges from 0 (no severity) to 61 (highest severity). Conclusion This study represents a first step towards the development of a multidimensional TB severity assessment tool for PLWH. However, its clinical usefulness, feasibility, and added value compared with existing severity scores remain to be demonstrated through validation studies before routine implementation can be considered. Key words: tuberculosis, HIV, severity.

Introduction: School feeding programs (SFPs) can contribute to address undernutrition in low- and middle-income country settings while can simultaneously improve education outcomes and deliver social and economic benefits. However, evidence on their comprehensive value for money (VfM) remains limited. This study models the multi-sectoral impacts of SFPs across education, health, social protection, and the local agricultural economy in five sub-Saharan African countries, providing benefit-cost ratio (BCR) and VfM estimates to inform policy decisions. Methods: The analysis used secondary data from national reports, program budgets, and national household surveys. SFP impacts on education were assessed through changes in years of schooling and linked to lifetime income gains. Health impacts were quantified as averted anemia cases, converted into disability-adjusted life years (DALYs) and monetized using gross domestic product (GDP) per capita. Social protection benefits were measured as the in-kind value of school meals relative to household food expenditures, while local economic impacts were assessed through monetary transfers to smallholder farmers (SHFs) from local food procurement. BCRs were calculated considering education and health impacts, with additional VfM and expanded BCR estimates considering broader benefits and transfers. Results: Across countries, SFPs were associated with a cumulative gain of 0.6 to 2.3 years of schooling per beneficiary. Moreover, reductions in anemia cases are expected to avert between 4 to 51 DALYs per 1,000 beneficiaries. The BCR for education and health ranged between 3 and 31. Meals provided covered up to 28% of annual household food expenditures for low-income families. Local food procurement generated economic transfers between USD 7 and USD 15 per beneficiary per year to SHFs. Conclusion: SFPs demonstrate high VfM, offering significant educational, health, and economic benefits. Policymakers in sub-Saharan Africa should prioritize the expansion and scaling of SFPs to enhance educational attainment, improve health, and foster economic resilience, contributing to sustainable development.

Precision targeting is essential for maximising impact and cost-effectiveness of interventions at this stage of the HIV response in Malawi. We aimed to measure gaps in access to and use of condoms, HIV testing, pre-exposure prophylaxis (PrEP) and voluntary medical male circumcision among HIV-negative individuals at public health facilities and social venues (bars, rest houses and liquor stores) in Blantyre, Malawi. We analysed cross-sectional data from 2,227 HIV-negative patients at government clinics and 1,634 patrons at social venues recruited in the Clinic vs Venue (CLOVE) study between January and March 2022. We estimated gaps in access to and use of condoms, HIV testing, PrEP and circumcision. Estimates were stratified by risk group, defined as reporting transactional sex, having multiple sex partners in the past 4 weeks, being female aged 15 to 24, or being male aged 30 and above. Access and use were based on self-reports. Overall, 30% of clinic and 60% of venue participants reported higher risk. Among men, we found a gap between access to condoms and condom use at last sex (76.7% vs 29.8% among clinic men; 75.4% vs 36.7% among venue men). Among women, the gap between access and use of condoms was 65.9% vs 18.0% at clinics and 79.9% vs 46.0% in the venues. Approximately 80-85% of participants reported knowing where to get an HIV test in Blantyre but less than half reported testing in the past 6 months. Use of PrEP was low (~2%). Comparable proportions of men who paid for sex and those with multiple partners (~77%) reported being circumcised, but this was lower among those aged 30 years or older (~57%). Despite expanded HIV prevention services in Blantyre, gaps remain in the uptake of prevention services among people reachable at public health facilities and social venues. Use of PrEP was particularly low across all groups. Condom and testing use remained suboptimal despite high reported access. Targeted efforts are needed to address barriers to uptake, particularly for PrEP among high-risk venue-based populations.

Background: A central concern in global health priority-setting is whether the supply of scientific knowledge aligns with health needs and demands. This alignment is usually assessed by comparing research effort with disease burden, overlooking other type of "social demand" of disease, in particular whether diseases are socially visible and generate public attention. We develop an analytical framework that treats public attention and epidemiological burden as complementary dimensions of health demand and examines their alignment with knowledge supply. Methods: We combine data on publications indexed in OpenAlex, disability-adjusted life years from the Global Burden of Disease, and Wikipedia pageviews for 2016 to 2023, as indicators of research effort, disease burden, and public attention, respectively. We map 19 disease groups and 138 specific diseases across these three dimensions. Ternary plots are used to position diseases according to their relative balance across dimensions and to identify diseases that are over- or under-represented in research effort relative to epidemiological burden and public attention. We compare Global North-South patterns using German, Persian, Swahili, and Vietnamese language areas to assess how these relationships vary across territories. Results: The three dimensions show limited alignment. At the disease group level, cardiovascular diseases account for the largest share of disease burden, mental disorders attract the largest share of public attention, and neoplasms concentrate the largest share of research effort. Public attention and disease burden are weakly correlated at both group and specific disease levels, indicating that Wikipedia pageviews and DALYs capture distinct dimensions of health demand. Ternary plots reveal different forms of misalignment, with some diseases showing plots dominated by burden, others by research effort, and others by public attention. Territorial analyses add a further layer by showing that diseases follow disparate patterns of supply-demand (mis)alignment across different linguistic territories. Conclusions: Public attention provides a complementary dimension for mapping global health needs and demands. Our approach identifies where scientific knowledge supply fails to match epidemiological and/or public attention, supporting more nuanced global health analysis that may be useful for priority-setting.

Objectives: Estimate fertility rate ratios (FRR) of HIV-positive relative to HIV-negative women in sub-Saharan Africa (SSA) by age group, CD4 stage, ART status, and country. Design: Analysis of nationally representative household surveys with HIV serological testing. Methods: We analysed current pregnancy and births in the past three years by HIV status from 72 nationally-representative household surveys in SSA between 2003 and 2017. Spectrum 2018 estimates for the distribution by CD4 stage and ART status were used to infer fertility of women on ART from changes in fertility of all HIV-positive women as ART coverage increased. We allowed regional differences in the age pattern of relative fertility and estimated country-specific random effects. Results: The ratio of fertility in untreated HIV-positive women with CD4 [&ge;]500 to HIV-negative women was 1.6 to 1.8 for age 15-19, relatively similar to 10% times lower for age 20-29, and 15-50% lower above age 30. Among age 15-19, each 15-point increase in percent sexually active reduced relative excess fertility by 24%. Fertility decreased with lower untreated CD4 count stages, consistent with previous estimates. Women on ART >6 months had fertility closer to that of HIV-negative women for ages 15-29, but still 25-40% lower above age 30. There was substantial variation across countries. Conclusions: Fertility differences for HIV-positive women compared to HIV-negative women are smaller than previous estimates, but vary substantially across countries. Recent data suggest fertility of women on ART is greater than that of untreated HIV-positive women, but remains lower than HIV-negative women. This conclusion should be reviewed as new evidence becomes available.

Background: In 2019, WHO recommended three consecutive reactive serological test results for HIV diagnosis to reduce false-positive diagnoses. Malawi changed from a two-test to a three-test strategy in 2022 as HIV test positivity declined. We assessed diagnostic performance, implementation fidelity, and costs. Methods: We analysed national HIV testing data from Nov 1, 2022, to Oct 31, 2025. Using observed three-test classifications as the reference standard, we reconstructed classifications under the two-test strategy. We estimated positive predictive value (PPV), implementation fidelity, potential false-positive diagnoses prevented, incremental costs, and time to offset testing costs through avoided antiretroviral therapy expenditure. Results: Among 9,885,599 encounters eligible for implementation-fidelity analysis, 99.98% followed a valid three-test pathway. The diagnostic-performance analysis included 9,862,908 encounters, of which 171,351 (1.7%) were classified HIV-positive and 9,138 (0.09%) were inconclusive. Under the two-test strategy, 1,209 inconclusive encounters with a T1+/T2+/T3- sequence would have been classified as HIV-positive. Retesting and reference-laboratory data indicated that 82.5% of these would subsequently be classified as HIV-negative, corresponding to 997 false-positive diagnoses prevented (10.3 per 100 000 three-test non-positive encounters; 95% CI 9.7-10.9). Retesting within 1-2 weeks was associated with the highest odds of potential false-positive classification (adjusted OR 39.37, 95% CrI 30.63-50.61). The incremental cost was US$471 per false-positive diagnosis averted and was offset within 7.30 years. Conclusions: Malawi's transition to a three-test HIV testing strategy prevented false-positive diagnoses and unnecessary antiretroviral therapy at modest cost, supporting broader adoption of WHO guidance in similar settings. Funding: Gates Foundation.

Background Nontuberculous mycobacteria (NTM) are clinically important pathogens but often weakly positioned within health systems, with unclear institutional ownership, variable notification arrangements, and limited surveillance visibility. Methods We conducted a multilingual online survey among programme-facing national and subnational mycobacterial stakeholders from November to December 2025. Using an adaptive hierarchical recruitment strategy, we targeted 217 countries and jurisdictions. One response per programme was requested. We assessed institutionalisation, notification, agenda maturity, thematic discussion priorities, and barriers to action. We also derived relative policy momentum from three urgency domains (diagnostics, clinical management, and surveillance) using within-WHO region hierarchical clustering. Findings were used to develop a heuristic roadmap for staged NTM governance and system visibility. Results We received 193 programme-level responses, including from subnational jurisdictions, representing 171 of 217 targeted countries (78.8% jurisdictional coverage). NTM institutionalisation status was heterogeneous: 34% reported NTM integration within the NTP, while 37% expressed intents to institutionalise within the NTP in nearest future. Mandatory notification was reported by 21% of programme units, voluntary notification by 10%, and notification under consideration by 24%. NTM appeared to enter policy discussions along a gradient, with clinical management and diagnostics attracting earlier attention than surveillance, training needs, and financing. Globally, pulmonary NTM was discussed more frequently than extrapulmonary disease. Across WHO regions, policy momentum clustering separated programmes into higher and lower profiles, with surveillance consistently being the weakest domain. Financing and lack of epidemiological data were identified as the most actionable barriers. There was broad support for TB-NTM surveillance integration. Conclusions NTM governance is heterogeneous and frequently weakly anchored globally. The findings do not support a single universal institutional model; rather, existing mycobacterial platforms may provide pragmatic starting points for improving programme visibility, coordination, and reporting. The proposed heuristic roadmap outlines staged governance options according to burden, capacity, and institutional context.

Abstract Background: In resource-rich regions, such as the U.S. and Europe, the incidence of Kaposi sarcoma (KS) amongst persons living with HIV (PWH) has dramatically declined with the advent of combination antiretroviral therapy (ART). In contrast, in low- and middle-income countries (LMICs), much less is known, particularly since the World Health Organization's recommendation in late 2015 to use ART in all PWH. We take advantage of the coincident electronic clinical data capture at HIV care facilities to estimate the incidence of KS among PWH in care with ready access to ART, piloting a data validation approach to address errors in these routine clinic data. Methods: We evaluated PWH enrolled from January 2010 to December 2019 in 13 HIV care clinics in 8 countries participating in the East Africa (EA-IeDEA) and Caribbean, Central and South America (CCASAnet) regions of the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium. Selected measurements were validated via chart review on a subset of PWH, and we estimated KS incidence in both unvalidated and validated data via generalized raking techniques. Results: A total of 235,474 PWH from EA-IeDEA and 19,683 from CCASAnet gave rise to 719 and 103 incident cases of KS, respectively. A total of 824 eligible records were validated. ART use was substantially lower in EA-IeDEA than CCASAnet in 2010 but equalized by 2019. From 2010 to 2019, KS incidence decreased on average 21% per year (incidence rate ratio [IRR] 0.79; 95% CI 0.75-0.82) in EA-IeDEA but only 6% (IRR=0.94; 95% CI 0.83-1.06) in CCASAnet. Conclusions: Among PWH attending HIV care facilities in East Africa, we observed a trend suggesting a reduction in KS incidence that paralleled increased Treat All era ART use in these clinics. In the Caribbean, Central and South America, there was hardly a change in the incidence, despite high-frequency ART use in the region as well.

Tuberculosis (TB) is increasingly recognised as a spectrum of infection and disease, yet the prevalence of viable, asymptomatic Mycobacterium tuberculosis (M.tb) infection remains uncertain. Subclinical Tuberculosis (scTB), defined as microbiologically confirmed M.tb infection in the absence of recognised symptoms, is under detected by symptom, sputum and imaging-based approaches. We conducted postmortem examinations of 94 adults who died from non-infectious causes, none of whom were clinically suspected of TB or reported TB related symptoms prior to death. Lung and extrapulmonary tissues were cultured for M.tb. Viable M.tb was confirmed in six individuals, corresponding to a prevalence of 6.4% (95% CI: 2.4 to 13.4%). These findings provide direct tissue-based evidence that viable, asymptomatic M.tb infection can persist beyond the reach of conventional clinical detection. Our data suggest that a biologically active reservoir of infection may exist undetected within high-burden settings, with implications for surveillance strategies aimed at TB elimination.

Background Respiratory infections remain the leading infectious cause of death among children and adolescents, yet the share of these deaths that could be averted with currently feasible care is not routinely quantified. Existing amenable-mortality frameworks rely on cause lists and population-level mortality benchmarks and do not exploit information on how many episodes occur. We propose an episode-fatality-ratio (EFR) frontier approach and apply it to lower respiratory infections (LRI), whooping cough (pertussis) and upper respiratory infections (URI) in 204 countries, 1990-2023. Methods For each cause, country and year we computed EFR = deaths/incident episodes using Global Burden of Disease (GBD) 2023 estimates for ages 0-19 years. The frontier was defined as the 10th-percentile country EFR within each GBD super-region, cause and year; avoidable deaths = max(0, deaths - episodes x frontier EFR). Primary estimates are deterministic; 95% uncertainty intervals (UIs) come from 2,000 Monte Carlo draws. Sensitivity analyses varied the frontier percentile, applied an aspirational global frontier, constructed pertussis counterfactuals, and recomputed all estimates within the single under-5 age band. Results In 2023, 333,803 childhood deaths from lower respiratory infections (95% UI 289,123-417,460; 46.9% of LRI deaths) were avoidable. Summing the three causes deterministically gives 391,034 avoidable deaths (46.5% of 840,444); the combined figure is a deterministic sum, and a UI is available for the LRI component only. The pertussis (43,958; 39.0%) and URI (13,273; 81.0%) estimates are secondary: their deterministic point values fall below their own Monte Carlo intervals and the underlying death estimates carry very wide uncertainty (global pertussis UI 12,545-321,874). Avoidable deaths fell from 1,050,468 (44.9%) in 1990, but between 2019 and 2023 the avoidable share for LRI+URI barely moved (48.7% to 47.7%) while absolute avoidable deaths fell 14.5%, a pattern consistent with stalled convergence to the frontier. Sub-Saharan Africa plus South Asia held 73.1% of avoidable deaths in 2023 versus 41.8% in 1990; ten countries accounted for 59.1%. Conclusion Nearly half of childhood respiratory-infection deaths remain avoidable relative to within-region best practice, and the residual burden is increasingly concentrated in low-income settings. In the pertussis counterfactual, most countries kept pace with their regional frontier, so further gains require advancing the frontier itself through quality-of-care improvements.

Background Tuberculosis remains the leading infectious cause of death worldwide. In the WHO African region, declining incidence has coincided with antiretroviral therapy (ART) scale-up, though whether this reflects reduced progression to disease or reduced transmission is unclear. We evaluated how ART and symptom status influence within-household Mycobacterium tuberculosis complex (MTBC) transmission risk. Methods We conducted a case-contact household study in rural South Africa, enrolling index adults with bacteriologically-confirmed pulmonary tuberculosis. MTBC immunoreactivity was measured in all child household contacts (aged 2-14 years) as a proxy measure of within-household transmission. We assessed the influence of index person ART status and symptom status, and explored effect-measure modification of the association between index person HIV status and transmission risk by sex. Results Among 755 child contacts of 296 index persons, effective ART was not associated with within-household MTBC transmission risk (risk ratio [RR], 1.07; 95% CI, 0.66-1.74). Among PLHIV engaged in ART care, WHO TB four-symptom screen (WHO4SS) status was not associated with transmission risk (RR, 0.80; 95% CI, 0.43-1.47), although absence of reported cough reduced risk (RR, 0.61; 95% CI, 0.38-0.96). A pronounced interaction between sex and HIV status was observed: HIV-negative women had the highest within-household MTBC transmission risk (30.5% vs. 14.3% in women with HIV) whereas risks were similar between HIV-positive and HIV-negative men. Conclusions We found no evidence that effective ART or WHO4SS status influenced within-household MTBC transmission risk, though confidence intervals were wide. Absence of reported cough was associated with lower risk, and transmission risk was highest among child contacts of HIV-negative women. These findings suggest reported cough is a useful marker of transmission risk and that routine tuberculosis screening within ART care may reduce transmission from PLHIV; intensified efforts are nonetheless needed to achieve earlier tuberculosis detection in HIV-negative individuals.

BACKGROUND: Nontuberculous mycobacteria (NTM) are environmental organisms increasingly causing chronic respiratory infection. Although NTM pulmonary infection is rising globally, most studies are single-country. This study evaluated temporal trends in pulmonary NTM incidence across Queensland (Australia), Phnom Penh (Cambodia), Japan, Thailand, and the United States (US), and described regional species distribution. METHODS: Laboratory and insurance claims data were used. Incident infections were defined using region-specific criteria. For Queensland, Japan, and Thailand, data and denominators covered entire regions. US estimates included Medicare beneficiaries aged [&ge;]65 years, and Cambodian incidence was estimated from Phnom Penh data and standardised nationally. Incidence rates per 100,000 population and incidence rate ratios (IRRs) were calculated overall and by sex. Age-stratified analyses and species distributions were summarised where data were available. RESULTS: Pulmonary NTM incidence increased in all regions and was highest in Japan (47.20-57.40 per 100,000) and lowest in Phnom Penh (0.23-0.38). Queensland showed the largest increase over 24 years (IRR 7.06, p<0.0001). Female predominance occurred in high-income regions, whereas Thailand showed ~1.5-fold male predominance and Phnom Penh showed no sex predominance. Incidence was higher among individuals aged [&ge;]60 years. Mycobacterium avium complex predominated in Japan and Queensland, and M. abscessus in Thailand and Phnom Penh. CONCLUSIONS: Pulmonary NTM incidence increased in all regions, varying by demographic patterns and species distribution. Differences largely reflect under-ascertainment related to diagnostic capacity and tuberculosis-focused health systems rather than true infection burden. Strengthened surveillance and diagnostic capacity are needed to define the global burden of NTM pulmonary infection.

Reducing inequality in health-service coverage is central to universal health coverage, but the evidence base on how to design successful equity-oriented policies is inadequate to inform decision makers and tends to rely on case studies. Further, conventional measures of inequality capture a single timepoint, one service at a time; this obscures how inequity evolves as coverage increases. We reframe equity as a trajectory and ask how it evolves as total coverage rises, comparing systematically across countries and health areas. Using 132 Demographic and Health Surveys from 22 low- and middle-income countries (1990-2023), we estimated coverage at the subnational (admin1) level by wealth quintile for six representative maternal and child health indicators. For each country-indicator pair, we fit a natural cubic spline of the wealthiest-poorest gap against total regional coverage, extracted features describing each curve, and grouped them using hierarchical clustering. This yielded three archetypes: large rollout gaps (mean peak ~58%), modest but persistent inequality (~30%), and minimal inequality that sometimes reversed to favor the poor (~17%). Most trajectories traced an inverted U pattern, widening early, then closing only near 100% regional coverage. How a service is delivered, more than where, drove its path: institutional delivery was the most inequitable (15 of 20 countries with large gaps), whereas one-touch and campaign-delivered services such as bed nets and vaccines rarely produced large gaps and were sometimes pro-poor. Despite this, some countries achieved equity across nearly all services, indicating that proactive governance may be able to overcome structural challenges to achieve equitable outcomes. For policy, these archetypes let programs anticipate which groups will be left behind and when, replace assumed scenarios with empirical ones in impact models, and target investment early to ensure that new services achieve more equitable coverage.

Abstract Dengue, malaria, and yellow fever remain major mosquito-borne public health threats in tropical and subtropical regions. Yet most global spatial studies have focused on single diseases or on potential transmission suitability rather than empirically observed shared burden. We therefore sought to identify robust global co-hotspots of these three diseases across 142 countries from 1990 to 2023, treating mosquito-borne diseases as an integrated public health problem. Using annual country-level incidence data from the Global Burden of Disease study and demographic, health-system, and climate covariates, we compared a fully Bayesian shared-component model, a neural network model with spatial-lag features, and a two-stage hybrid model. Shared scores were standardised for cross-model comparison and externally validated against an independent mortality anchor. Overall, 29 countries were classified as consensus hotspots, all in sub-Saharan Africa, while seven countries formed a moderate-agreement watch list at the margins of the main hotspot belt, suggesting potential transition zones of shared burden. By shifting the analytical focus from potential suitability to the empirical identification of realised burden and shared control vulnerability, this study provides actionable global evidence on where mosquito-borne disease prevention and control may be most structurally constrained. The findings may support more integrated prioritisation of vector control, surveillance, and health-system preparedness across countries.