The Lancet Global Health

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 Long-acting HIV pre-exposure prophylaxis (LAP) could transform HIV prevention in sub-Saharan Africa, but its public-health impact and value-for-money will depend on whether programmes can reach people at greatest risk. We quantified the potential impact and efficiency of targeted LAP deployment across sub-Saharan Africa. Methods We developed a deterministic, age-structured compartmental model of HIV among adults aged 15 years or older in African countries accounting for 98% of adults living with HIV in sub-Saharan Africa. Antiretroviral therapy (ART) was assumed to reach 95% coverage by 2030 in all countries. LAP was assumed to reduce HIV acquisition by 96%. In model analyses, LAP was allocated according to rules that specify the degree to which programmes can effectively allocate it to those at greatest risk of acquiring HIV, including using a person's district, sex and age-group, and other signals of risk. Findings Across 34 countries, allocating a fixed quantity of LAP by district, sex and age averted 2 - 21 times as many infections as uniform allocation; perfect identification of within-group risk, an upper bound, raised this to 5 - 32 times. Multipliers were largest in low-prevalence countries, where absolute impact was smallest; in higher burden settings, they were 2 - 6 and 5 - 11, respectively. If 3 million people used LAP from 2028 in the 11 countries currently receiving Global Fund-supported lenacapavir, uniform allocation would avert about 41,000 infections by 2050, targeting by district, sex and age about 601,000 (range 360,000 - 1,660,000), and perfect risk targeting about 972,000 (490,000 - 3,570,000). Discounted averted ART costs fully offset LAP costs by 2050 at a total cost of up to ~US$50 per person-year with perfect risk targeting, $30 with targeting by district, sex and age, and $2 with uniform allocation. Expansion to 15 million users by 2035 brought modelled adult incidence across sub-Saharan Africa below 0.1 per 1000 person-years in 2049, about a decade earlier than projected without LAP, under the assumption that ART coverage reaches 95% in every country by 2030. Interpretation Targeting determines both the impact and the net cost of LAP. Allocation by district, sex and age is feasible now and multiplies the infections averted by each person-year of LAP. LAP offsets its cost through averted treatment only when it is targeted and its fully loaded cost is near the low end of current estimates. Better identification of people at highest risk within demographic groups, and sustained use among them, could add substantially to impact. The same approach could guide the allocation of LAP in other settings where HIV risk is concentrated.

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.

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. Tuberculosis preventive treatment (TPT) with levofloxacin reduces tuberculosis disease incidence in multidrug-resistant or rifampicin-resistant (MDR/RR)-tuberculosis household contacts. However, with age, disease progression risk falls and the frequency of adverse events (AE) rises. Methods. To inform decision-makers, we evaluated the cost-effectiveness of expanding the use of MDR/RR-TPT by age, with and without tests of tuberculosis infection. We modelled MDR/RR-household contact management (HHCM) in 189 countries, incorporating age-dependent risks of disease progression, death and AEs. Incremental cost-effectiveness ratios were calculated as USD/disability-adjusted life year (DALY) averted, and as a fraction of per capita gross domestic product (GDP). Findings. Compared to baseline of MDR/RR-HHCM with TPT for those <15 years, adding TPT up to 45 years was cost-effective at a threshold of 30% GDP in 160/189 modelled countries including 17 of the 30 highest incidence countries. Of these 160 countries, the intervention was cost-saving in 46. Strategies targeting TPT to those testing positive for M. tuberculosis infection were dominated by those without testing. Globally, full use of MDR/RR-HHCM with TPT for all would avert 11,900 (10,400 to 13,800) episodes of tuberculosis, 9,960 (9,100 to 10,900) deaths, and 289,000 (262,000 to 321,000) DALYs, but would result in 71,000 (68,000 to 74,000) SAEs and cost $359 million (294 to 449). Interpretation. Expanding MDR/RR-TPT use to older ages without testing appears cost-effective in most settings, but may require substantial resources and result in large numbers of AEs. Funding. Unitaid

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.

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: Global HIV programmes are transitioning virally suppressed children and adolescents with HIV (CAWH) from prior regimens to dolutegravir-based antiretroviral therapy (ART). However, the supporting evidence largely stems from randomised trials in viraemic CAWH. The effect of transition for virally suppressed CAWH is unknown. Methods: We used observational, de-identified data from 724 clinics in KwaZulu-Natal, South Africa. We sequentially emulated three distinct target trials to estimate the effect of transitioning to dolutegravir-based ART in three paediatric populations: i) ages 8-17 years taking efavirenz-based ART, ii) 8-17 years taking ritonavir-boosted lopinavir (LPV/r)-based ART, and iii) 0-7 years taking LPV/r-based ART, all with a last viral load <1,000 copies/mL. The risk difference (RD) of death or viraemia >1,000 copies/mL through 12 and 24 months was estimated using an inverse probability weighting approach. Findings: From January 2020 to August 2024, 37,145 CAWH contributed 454,081 person-trials. In CAWH initially taking efavirenz, the standardised 12-month risk of death or viraemia was 11.9% with continued efavirenz and 6.7% with transition to dolutegravir (RD -5.2 [95% CI -5.8 to -4.6]). In older CAWH initially taking LPV/r, these risks were 17.8% and 9.5%, respectively (RD -8.3 [-10.0 to -6.8]). In younger children, the respective risks were 15.8% and 6.7% (RD -9.0% [-12.7 to -5.4]). Where available, 24-month endpoints showed slightly greater RDs. Interpretation: This large-scale, causal analysis highlights improvements in viral suppression and strongly supports ongoing transition to dolutegravir-based ART for virally suppressed CAWH. Funding: Gates Foundation, National Institute for Health and Care Research, Swiss National Science Foundation

Background Cardiovascular disease remains the leading cause of death worldwide, yet progress in reducing its burden has not been shared equally across regions. Sub-Saharan Africa has previously been identified as the only world region where age-standardized cardiovascular mortality failed to decline, but long-term, disease-specific trends in Western Sub-Saharan Africa (WSSA) remain poorly characterized. Methods We conducted an ecological trend analysis using Global Burden of Disease (GBD) 2023 data to evaluate age-standardized mortality and disability-adjusted life years (DALYs) for stroke and ischemic heart disease (IHD) in WSSA and globally from 1990 to 2023. Linear and segmented regression assessed long-term trends and breakpoints, risk factor attribution examined six major cardiovascular risk factors, and Pearson correlation evaluated associations between the Socio-demographic Index (SDI) and mortality. Results Global stroke and IHD mortality declined by 51.7% and 38.2%, respectively, between 1990 and 2023. In WSSA, stroke mortality declined by only 21.8%, while IHD mortality increased by 3.3%. Segmented regression identified a breakpoint in IHD mortality around 2007, after which the trend reversed from declining to increasing. High systolic blood pressure was the leading attributable risk factor for both diseases, while obesity, ambient air pollution, and elevated fasting glucose showed the largest relative increases. SDI rose 69.5% in WSSA but correlated strongly only with stroke mortality (r = 0.87), not IHD (r = 0.21). Conclusions WSSA is falling behind global cardiovascular progress, with IHD mortality reversing course despite substantial socioeconomic development. Targeted investment in hypertension control, cardiometabolic risk reduction, and cardiovascular care capacity is urgently needed to prevent this divergence from deepening.

Background: COVID-19 movement restrictions reduced social contact worldwide, curbing viral spread but with unequal economic consequences where social safety nets are limited. Little evidence exists on how these impacts varied by occupation, wealth and age in resource-constrained settings. This paper examined pre-pandemic contact and lockdown-related change. Methods: The paper documents analysis of a population-representative survey (N=8,499) in Manicaland, Zimbabwe, during April-May 2021, capturing typical weekday contacts before and during the first COVID-19 lockdown. Negative binomial regression models assessed pre-lockdown contact counts by socio-economic characteristics, overall and by place (home, school, work, transport, entertainment); linear regression assessed predictors of lockdown declines. Results: Pre-COVID-19, respondents reported a median of 12 daily contacts (interquartile range [IQR] 4-47), with higher counts among manual labourers (incidence rate ratio [IRR] 2.21, 95% confidence interval [CI] 2.00, 2.44), retail and public sector workers (IRR 2.33, 95%CI 2.09, 2.60) and students (IRR 2.59, 95%CI 2.38, 2.82), males, wealthier respondents, under-30s, and urban and agricultural estate residents. Counts were highest in schools. During lockdown, contacts fell across all subgroups to a median of 8 (IQR 4-28). Declines were greatest among those with most pre-COVID-19 contacts: urban (mean -17.5, 95%CI -19.53, -15.37) and agricultural estate residents (-18.1, 95%CI -19.99, -16.13), students and teachers (-17.7, 95%CI -19.82, -15.59), males and 30-44 year olds. Drops were greatest in schools and on transport. Conclusion: Reductions in contact under blanket lockdown varied markedly between subgroups and places in Manicaland, Zimbabwe. Selectively targeting high-contact groups might have achieved similar transmission reductions while limiting economic damage, holding lessons for similar settings.

Background: Age is an important determinant of tuberculosis (TB) risk, but population-level age patterns in TB prevalence have not been systematically quantified across settings. We conducted a systematic review of surveys conducted in low- and middle-income countries to quantify trends in TB prevalence across age groups. Methods: We collated age-stratified TB prevalence data for individuals aged 15+ years, from population-based surveys reported between 1993 and 2025. We analyzed data using Bayesian meta-regression models, estimating trends in bacteriologically confirmed pulmonary TB prevalence across age groups. We extended models to understand how age trends varied with alternative outcome definitions and data subsets, and examined correlations between TB age trends and sociodemographic determinants. We also estimated age-stratified notification-to-prevalence ratios as a measure of diagnostic delays for untreated TB. Findings: We included 82 unique surveys reporting age-stratified TB prevalence, spanning 30 countries and 4.6 million participants. These data demonstrated a pattern of increasing bacteriologically confirmed TB prevalence with older age, with each 10-year increase associated with a 30% (95% credible interval: 22, 38) increase in prevalence. TB prevalence for the oldest age group (75+: 796 per 100,000 [522, 1178]) was 6.4 (4.0, 10.4) times higher than the youngest (15-19: 127 per 100,000 [79, 186]), and positive age gradients were estimated for all countries (interquartile range: 23-40% increase per 10-year increase in age). Age gradients were lower in Africa compared to other regions, and for smear-positive compared to bacteriologically confirmed TB. Countries with HIV prevalence [&ge;]5% had flatter age gradients above 40 years of age. Age gradients declined slowly over the study period. Notification-to-prevalence ratios demonstrated a negative age gradient, declining by 10% (7, 14) per 10-year increase in age. Interpretation: The prevalence of untreated TB disease increases substantially throughout adulthood, and lower notification-to-prevalence ratios suggest poorer case detection among older individuals.

Since its inception in 2003, the United States President's Emergency Plan for AIDS Relief (PEPFAR) has played a central role in HIV/AIDS prevention and treatment across Sub-Saharan Africa. Following the January 2025 suspension of United States foreign aid, which includes PEPFAR funding, countries across Sub-Saharan Africa demonstrated varying governmental responses to the resulting HIV funding disruptions. This study evaluates whether national characteristics were associated with a country's ability to respond to this funding crisis. Countries in Sub-Saharan Africa receiving PEPFAR funding were classified into one of three response categories: Level 1 (minimal or no governmental response), Level 2 (government response without sufficient plans or resources to fully offset funding losses), or Level 3 (high governmental response with strategies to maintain HIV/AIDS prevention and treatment services). Response categories were compared with national Human Development Index (HDI), GDP per capita, HIV prevalence, total population living with HIV, annual HIV mortality, and historical PEPFAR funding. Univariable proportional-odds ordinal logistic regression was used to identify factors associated with response level. Five countries (17.2%) were classified as Level 1, 10 (34.5%) as Level 2, and 14 (48.3%) as Level 3. Higher HDI was significantly associated with stronger governmental response (OR = 4.05; 95% CI, 1.49-11.04; Holm-adjusted p = 0.0376). GDP per capita (OR = 2.35; 95% CI, 1.00-5.51; unadjusted p = 0.0489) and HIV prevalence (OR = 3.53; 95% CI, 1.03-12.11; unadjusted p = 0.0452) demonstrated positive associations before adjustment for multiple comparisons, but neither remained significant after Holm correction (adjusted p = 0.2261 for both). Historical PEPFAR funding, total population living with HIV, and annual HIV mortality were not significantly associated with response level after adjustment. Countries with higher levels of human development demonstrated stronger governmental responses to the 2025 PEPFAR funding disruptions. Several countries with minimal documented responses were also affected by active conflict or political instability, potentially compounding their vulnerability to treatment interruptions. These findings suggest that broader national development may play an important role in governmental responses to funding disruptions and highlight the need to strengthen resilient health systems, diversify HIV financing, and prioritize support for countries at greatest risk of future funding shocks.

While a causal link between urogenital schistosomiasis (Schistosoma haematobium) and anaemia is well established, quantitative associations between infection intensity and haemoglobin levels across endemic communities, at fine spatial scales, remain insufficiently characterized. As part of the broader Hybridisation in Urogenital Schistosomiasis (HUGS) investigation, we studied the micro-epidemiology of anaemia within two study communities in southern Malawi where S. haematobium remains endemic. Urine samples were examined by microscopy to quantify S. haematobium infection intensity, categorised as low (0-9 eggs/10 mL), moderate (10-49 eggs/10 mL), and heavy ([&ge;]50 eggs/10 mL). Individual haemoglobin concentrations were measured using a HemoCue photometer in 1,149 participants from Samama village (Mangochi District) and 977 participants from Mthawira village (Nsanje District). Linear geostatistical models incorporating individual-level characteristics and spatial covariates were used to estimate anaemia prevalence at fine geographical scales. Moderate anaemia (Hb 80-109 g/L) was most prevalent among children aged 6-12 years (45.30% in Samama and 39.54% in Mthawira), while severe anaemia was more frequent among adults aged [&ge;]19 years in both villages. Increasing S. haematobium infection intensity was associated with lower haemoglobin levels, with individuals harbouring heavy infections being at greater risk of moderate-to-severe anaemia. Spatial modelling revealed longer-range spatial correlation in Nsanje ({phi} = 66.7 km) than in Mangochi ({phi} = 25.5 km), indicating more spatially persistent risk in Nsanje and more localised heterogeneity in Mangochi. Predicted anaemia prevalence among female children aged 6-12 years with moderate infection intensity ranged from 25-65% in Mangochi and 64-76% in Nsanje. At the micro-epidemiological level, S. haematobium infection intensity was associated with the severity of anaemia, with substantial spatial heterogeneity within and between villages. Identification of high-risk clusters supports targeted interventions, including stepped-up preventive chemotherapy, improved water and sanitation, and iron supplementation.

Background Viral load suppression (VLS) remains suboptimal among adolescents and youth living with HIV (AYLWH) in Malawi. Depressive symptoms may affect treatment adherence and HIV outcomes, but evidence is limited. We assessed the association between depressive symptoms and VLS among AYLWH using Malawi Population-based HIV Impact Assessment (MPHIA) 2020-2021 data. Methods We conducted a cross-sectional secondary analysis of AYLWH aged 15-24 years. VLS was defined as HIV RNA less than 200 copies/mL and depressive symptoms as a Patient Health Questionnaire-2 score of 3 or higher. Survey-weighted logistic regression assessed associations with VLS, adjusting for sex, education, residence, household wealth, alcohol use, Teen Club participation, and awareness of HIV-positive status. Findings Among 201 participants, viral-load results were available for 200; 137 (68.5%) achieved VLS. Six (3.0%) participants had depressive symptoms. Depressive symptoms were not associated with VLS in univariable analysis (OR 0.8, 95% CI 0.1-4.6; p=0.80) or multivariable analysis (aOR 0.3, 95% CI 0.1-2.4; p=0.28). Urban residence (aOR 0.2, 95% CI 0.1-0.5; p=0.0020) and unawareness of HIV-positive status (aOR 0.1, 95% CI 0.02-0.1; p<0.001) were associated with lower odds of VLS. Interpretation Depressive symptoms were not significantly associated with VLS, although their low prevalence and PHQ-2 limitations reduced precision. The findings highlight the importance of strengthening HIV-status awareness and addressing context-specific barriers to care among AYLWH. Funding This secondary analysis received no specific funding.