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: 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 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.

Abstract Preventable neonatal deaths remain a major public health problem in Zimbabwe, where near-universal antenatal and facility-delivery coverage coexist with a rising neonatal mortality rate. This study evaluated whether institutionalising three core "vital signs" of the community health system (a trained village health worker (VHW) workforce, functional community governance structures, and modified women's and men's participatory learning and action groups) reduces preventable neonatal deaths in Mashonaland West Province. An embedded QUAN (qual) mixed-methods design was used, with a two-arm, parallel-group cluster-randomised controlled trial as the dominant strand. Fifty-two ward-level clusters were randomised 1:1 to the institutionalised community health system package or to standard Ministry of Health and Child Care community services, and 984 pregnant women were enrolled between 1 September 2020 and 31 October 2021, with each mother-infant pair followed to 28 days after delivery, yielding 973 mother-infant pairs for intention-to-treat analysis. The primary outcome was neonatal death within 28 days of life, expressed per 1,000 live births. The primary analysis used a three-level mixed-effects log-binomial regression model with cluster and community-health-worker random intercepts, adjusted for pre-specified covariates. Supervised machine-learning classifiers with leave-one-cluster-out cross-validation, Cox proportional-hazards regression, and multilevel logistic models were fitted as supplementary analyses. An embedded longitudinal process evaluation used key informant interviews and focus group discussions, which were analysed thematically and integrated with the quantitative findings. The neonatal mortality rate was 44.8 per 1,000 live births in the intervention arm versus 110.1 per 1,000 in the control arm. The adjusted risk ratio for neonatal death was 0.43 (95% CI 0.26-0.70; p < 0.001), a 57% relative reduction, with a number needed to treat of 16 mother-infant pairs (95% CI 11-29). Low birthweight (<2,500 g), birth interval under two years, and low community women's literacy were the strongest risk factors, while trained VHWs, functional community governance, early antenatal care, and sustained participatory group attendance were independently protective. The women's and men's groups were protective in a dose-dependent manner, becoming significant at four or more cycles (about 14 meetings) (adjusted odds ratio 0.71; 95% CI 0.60-0.85; p = 0.001). A random forest classifier discriminated against neonatal deaths with a cross-validated area under the curve of 0.842 and a sensitivity of 0.912. Qualitative findings converged with the trial results, identifying male engagement, earlier care-seeking, danger-sign literacy, social-network activation, and community death audits as the behavioural and structural mechanisms of change. Institutionalising the community health system package (trained VHWs, functional governance, early antenatal engagement, and sustained participatory groups) was associated with a substantial reduction in preventable neonatal deaths. The findings suggest that in high-coverage, high-mortality settings, the binding constraint is structural rather than clinical, and that scaling functional community governance and workforce infrastructure in the most disadvantaged communities may accelerate progress toward neonatal survival targets. The principal limitations are a one-year follow-up period, the rarity of neonatal death, and concurrent national programming that only partially reached the control clusters. Trial registration: Pan African Clinical Trials Registry, PACTR202607591142118 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=PACTR202607591142118); registered retrospectively on 7 July 2026.

Background: HIV/HBV coinfection is associated with substantial liver-related morbidity and mortality, yet the impact of social vulnerability (SV) on clinical outcomes has not been systematically assessed. We evaluated associations of multidimensional SV with mortality, hepatic, virologic, and extrahepatic organ outcomes among adults with HIV/HBV. Methods: We conducted a retrospective cohort study using TriNetX data from 110 U.S. healthcare organizations (2010-2026). We propensity score matched adults with HIV/HBV with and without documented SV 1:1 (2,024 per group). SV was defined using a four-domain framework encompassing material, healthcare access and engagement, interpersonal, and psychosocial vulnerability. Results: Over 15,900 person-years, SV was associated with higher mortality (hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.72-2.47), liver composite events (HR, 1.37; 95% CI, 1.07-1.76), hepatic decompensation (HR, 1.94; 95% CI, 1.39-2.70), hepatic failure (HR, 2.39; 95% CI, 1.53-3.73), HBV viremia (HR, 1.69; 95% CI, 1.32-2.16), and HIV viremia (HR, 2.05; 95% CI, 1.71-2.46). SV was also associated with major adverse cardiovascular events (HR, 1.47), chronic kidney disease (HR, 1.49), and diabetes (HR, 1.25). Multidomain SV generally showed stronger associations than single-domain SV for most hepatic and virologic outcomes, with HR ranges of 1.76-2.62 versus 1.35-1.76 for single-domain SV. Healthcare access and engagement vulnerability was most consistently associated with mortality and hepatic outcomes. Conclusions: SV was associated with mortality, hepatic disease, impaired HIV/HBV control, extrahepatic organ morbidity, and acute care utilization in adults with HIV/HBV. SV assessment may improve risk stratification and identify actionable intervention targets during HIV/HBV care.

Postnatal care (PNC) is essential for reducing preventable maternal and neonatal deaths, but its utilization remain low across sub-Saharan Africa. Intimate Partner Violence (IPV) may be an under-recognized barrier to PNC utilization, particularly in Tanzania, where direct evidence shows that IPV is linked to limited utilization of PNC. Therefore, this study assessed the association between IPV and PNC utilization within 42 days postpartum among women in Tanzania. This study conducted a secondary analysis of the 2022 Tanzania Demographic and Health Survey (TDHS), a nationally representative cross-sectional survey. The analysis included 2,674 women aged 15-49 years who had a live birth in the five years preceding the survey and were selected for the domestic violence module. IPV (any, physical, sexual, and emotional) was the primary exposure, and PNC utilization within 42 days postpartum was the outcome. Modified Poisson regression was used to estimate crude and adjusted prevalence ratios (cPR/aPR) with 95% confidence intervals (CI) because the prevalence of the outcome was common. The prevalence of PNC utilization within 42 days postpartum was 42.0%, and the overall prevalence of IPV was 33.6% (physical 26.1%, emotional 21.8% and sexual 7.3%). Women who experienced any IPV had 16% lower PNC utilization than those who did not (aPR=0.84; 95% CI: 0.74-0.96). Physical IPV (16%, aPR=0.84; 95% CI: 0.73-0.96) and sexual IPV (25%, aPR=0.75; 95% CI: 0.57-0.98) were significantly associated with lower PNC utilization, while emotional IPV was not. Maternal education, partners age, travel time to the nearest health facility, and media exposure were also other covariates associated with PNC utilization. Intimate partner violence is associated with low utilization of PNC within 42 days postpartum in Tanzania. Integrating IPV screening and survivor support into postnatal care services, alongside addressing structural barriers to access, may improve postpartum care coverage and maternal-neonatal outcomes.

Background Rural-urban disparities in SARS-CoV-2 infection epidemiology remain poorly quantified and understood in Zambia despite differences in healthcare access, services and preventive interventions. This study examined the geographical distribution and associated factors of SARS-CoV-2 cases across selected rural and urban districts of Zambia. Methods A convergent mixed-methods study comprised of quantitative survey and qualitative interviews was conducted in; Ndola (Urban), Kafue (Peri-urban) and Lufwanyama (Rural). The proximate determinant framework guided variable selection and interpretation. Quantitative combined (Hospital-surveillance data with community survey), while qualitative included In-depth interviews. Participants were sampled using multistage sampling technique. Quantitative data were analysed using STATA version 17, while qualitative data were analysed thematically. Findings were integrated through triangulation. Results A total of 528 participants were included, with a median age 31 years (15-71). Overall SARS-CoV-2 positivity was 12.6%, varying across rural (16.5%), peri-urban (14.9%), and urban (9.9%) settings, though residence was not associated with infection (P<0.132). Participants aged [&ge;]49 years had significantly higher odds of infection (aOR=8.78; 95% CI:1.15-66.99), whereas secondary education (aOR=0.37; 95% CI:0.16-0.86) and hospital-based testing (aOR=0.37; 95% CI:0.15-0.92) were associated with lower odds of infection. Vaccine uptake was highest in urban areas but was not independently associated with infection. Qualitative findings revealed marked rural-urban differences in perceived susceptibility, testing access, vaccine decision-making, and adherence to preventive measures, explaining several quantitative observations. Conclusion SARS-CoV-2 infection across rural and urban settings in Zambia was influenced by demographic, behavioral, and health-system factors rather than geographic residence alone. These findings highlight the need for context-specific prevention strategies, equitable access to testing, strengthened community surveillance, and targeted risk communication to improve preparedness and response for future respiratory disease outbreaks.

Background: Despite several trials on the hematological outcomes of intravenous (IV) iron in pregnancy, only few have examined its effect on birth outcomes. We estimated the causal effect of IV-iron on moderate or severe anaemia and birth outcomes. Methods: Women presenting to routine antenatal care in Pakistan with haemoglobin <10 g/dL were eligible for treatment. We used target trial emulation (TTE) methodology to estimate the effect of IV-iron treatment within 14 days of anaemia identification, compared to no treatment, on anaemia status at follow-up. A modified TTE analysis examined birth outcomes at delivery for singleton pregnancies, including birthweight, size-for-gestational-age, and mortality. We conducted a separate TTE for each of five gestational-age periods and pooled the results of each TTE. Results: We screened 3115 pregnancies of which 1715 were eligible for IV-iron; 1043 participants were treated during pregnancy. Those who received IV-iron had half the risk of moderate or severe anaemia in pregnancy compared with no treatment (pooled relative risk (RR) 0.40; 95% confidence interval (CI): 0.27, 0.59). The pooled effect of IV-iron on stillbirth suggested an 83% risk reduction (95% CI 55-94%), and trends were similar for perinatal and neonatal mortality. Conclusion: IV-iron treatment improved haematological status in pregnant women and was associated with a large reduction in stillbirth. Given limited data from randomised trials regarding fetal death and treatment earlier in pregnancy, this study contributes important information to the potential benefit of IV-iron in contexts where anaemia and its sequelae are a major public health problem.

Background: Case fatality reflects the quality and timeliness of clinical care for leptospirosis, yet no study has examined it at a national level in the Dominican Republic (DR), where leptospirosis is endemic. We describe the case fatality rate (CFR) of leptospirosis in the DR between 2012 and 2026 and identify associations with mortality. Methods: We conducted an analytical cross-sectional study, using national surveillance records merged with a discharge-condition extract via a composite key. We calculated CFR with Wilson 95% confidence intervals among 5,412 valid cases (suspected, probable, or confirmed) reported from January 2012 through June 2026. We compared proportions with Pearson's chi-square test, assessed annual trend with ordinary least squares linear regression, and fitted multivariable logistic regression models to account for confounding. Results: Overall CFR was 8.5% (460/5,412), with no significant annual trend (p=0.372). CFR was higher in men than women (p < 0.001) and increased significantly with age (p < 0.001). Male gender (OR: 1.79; 95%CI: 1.18-2.73) and pre-existing comorbidity (OR: 1.76; 95% CI: 1.21- 2.57) were independent predictors of death. Clinical complications were the strongest predictor in the adjusted model (OR: 3.16; 95%CI: 2.17-4.61), attenuating the gender effect. CFR varied widely by province (2.43-22.22%) and correlated negatively with incidence at the province level (p = 0.066). Conclusions: Leptospirosis case fatality is concentrated among men, people with comorbidity, and those who develop clinical complications. These national, long-term findings can help prioritize clinical and surveillance resources as extreme weather events are expected to intensify across the Caribbean.

Purpose Despite the high documented prevalence of hunger and poor mental health in adolescent girls and young women (AGYW) in South Africa, this relationship remains understudied, with existing studies limited by their cross-sectional designs. This longitudinal study aimed to identify the association of hunger trajectories with anxiety and depressive symptoms, and hope in AGYW. Methods We used secondary data from the HIV Prevention Trials Network (HPTN) -068 conducted in rural Agincourt, South Africa. Complete data from 1779 AGYW collected at baseline (2011/12) and three annual follow-up visits were used. Hunger trajectories, measured using the Household Hunger Scale, were estimated via Group-Based Trajectory Modelling. Self-reported incident anxiety and depressive symptoms and hope were assessed based on AGYWs last two follow-up visits. Covariate adjusted modified Poisson regression models estimated the association between hunger trajectories and incident anxiety symptoms, incident depressive symptoms, and hope. Results Moderate-severe hunger was prevalent in 11.0%, 10.8%, and 6.0% of the households at baseline, follow-up 1, and 2, respectively. Incident anxiety symptoms were reported by 4.5%, incident depressive symptoms by 20.0% and hopelessness by 52.8% of the AGYW. Two hunger trajectories were identified- no hunger (82%) and marginal hunger (18%). Hunger trajectories were not associated with incident anxiety symptoms [RR:1.09, 95% CI: 0.55, 2.18], incident depressive symptoms [RR: 0.97; 95% CI: 0.72, 1.33] nor hope [RR: 1.00; 95% CI: 0.81, 1.23] in AGYW. Conclusion Better understanding of the factors that promote resiliency and mental health of AGYW in this setting is warranted to inform the design of interventions.

Background: Snakebite envenoming is a major cause of preventable death and disability in the Brazilian Amazon, where long distances, sparse roads, and dependence on river transport delay access to antivenom. We developed location-allocation models to identify community health centers that could strategically expand access to antivenom in Amazonas State, Brazil. Methodology/Principal Findings: We conducted an ecological geospatial study using a 2025 WorldPop population surface, locations of existing and candidate health facilities, and a multimodal road-and-river transportation network derived from OpenStreetMap and HydroSHEDS. Population demand was represented by 7,065 populated centroids, including 1,586 within Indigenous territories. We applied a maximize-coverage algorithm with a six-hour travel-time threshold. Two models were developed: one for Amazonas excluding Manaus and one for populations living in Indigenous territories. Both models began with 77 facilities already providing antivenom and progressively added candidate community health centers until coverage gains plateaued. The plateau occurred at 110 facilities, corresponding to 33 additional centers. In the model excluding Manaus, this configuration covered 1,118,831 people, or 75.11% of the target population; 87.61% of those covered could reach care within three hours. In Indigenous territories, coverage increased from 50.55% to 69.50%, reaching 50,434 people, of whom 81.39% were within three hours of care. Validation used 3,595 snakebite notifications from the 30 highest-burden municipalities in the Brazilian Notifiable Diseases Information System during 2023-2025. The median proportion reaching care within six hours was 40.81% in observed data and 72.17% in model estimates. Conclusions/Significance: Strategically equipping 33 additional existing community health centers could substantially expand timely access to antivenom, particularly in rural and Indigenous areas. Location-allocation modeling that incorporates river transportation can support evidence-based decentralization of time-sensitive health services in geographically complex settings.

Background: Sexual and reproductive health (SRH) is essential for youth development, particularly in Sub-Saharan Africa where youth represent a significant proportion of the population. Despite global efforts to promote Sexual and Reproductive Health rights, many disadvantaged youths face barriers to accessing comprehensive information and services. Youth-friendly sexual and reproductive health (YFSRH) services are central to improving youth health outcomes. Despite national standards in Ethiopia, implementation challenges persist. Healthcare workers (HCWs) are key actors in promoting and delivering YFSRH services Method: A concurrent mixed-methods design was employed among youth (18-24 years) and health care workers in Guraghe Zone, Southern Ethiopia. Quantitative data were collected using self-administered questionnaires, while qualitative data were gathered through key informant interviews. Quantitative data were analyzed using SPSS version 29, and qualitative data were analyzed thematically. Result: Although youths showed strong interest in Sexual and Reproductive Health information, help-seeking was often delayed due to discomfort, secrecy, social pressure, and limited foresight. Utilization of youth-friendly Sexual and Reproductive Health services was constrained by distance, inconvenient service hours, limited privacy and confidentiality, perceived judgmental provider attitudes, and financial barriers, reducing trust and repeat use. Conclusion: Improving youth Sexual and Reproductive Health requires integrated actions across education, families, and health services. Strengthening multi-channel Sexual and Reproductive Health education with life skills and psychosocial support, alongside decentralized, affordable, confidential, and non-judgmental youth-friendly services, is essential.

Public genomic repositories can support antimicrobial resistance (AMR) surveillance, but unequal sampling can bias interpretation. We characterised AMR determinants, multicountry genomic cluster overlap and surveillance gaps across Africa using an NCBI Pathogen Detection snapshot retrieved on 24 August 2026 for 55 African Union member states. Records were validated and deduplicated by BioSample, and complete AMRFinderPlus calls were summarised across five United Nations M49 subregions and eight overlapping regional economic communities (RECs). Country-pair cluster overlap was assessed using the Jaccard index, while project-based and composition-standardised sensitivity analyses evaluated repository bias. The dataset contained 86,829 unique BioSamples from 51 states; South Africa, Malawi and Kenya contributed 55.8%. Complete extended-spectrum {beta}-lactamase calls were detected in 21,513 isolates and carbapenemase calls in 4,642. blaCTX-M-15 dominated the ESBL profile, while NDM and OXA types predominated. Seventy clusters contained carbapenemase-positive isolates from at least two countries. A shared REC covered all participating countries in 38 clusters, while 32 crossed REC boundaries. Normalised country-pair overlap was low, with a maximum Jaccard index of 9.5%. Project balancing reduced the Northern African carbapenemase estimate from 32.3% to 17.9% and the Eastern African ESBL estimate from 36.9% to 12.5%. Public repositories identify determinants and clusters for investigation but do not estimate prevalence or transmission. AMR surveillance should combine national confirmation, regional institution-led investigation where countries share an REC, and continent-wide coordination through Africa CDC for cross-REC signals, supported by representative One Health sampling, standardised metadata and sustained African sequencing capacity.

All primary healthcare centers owned by the Ugandan government in the Western Region of Uganda were submitted to a questionnaire concerning current availability of POCT from the Essential diagnostic List 2 part 1a and 1b, and the African laboratory inventory done by African Society of Laboratory Medicine and AfricaCDC. The data from the questionnaire was then linked to open source geodata provided by TomTom, and population data to calculate and visualize the accessibility of captured POCT. Findings: Availability of POCT Malaria is almost 100%, HIV 68-90%, and >30% for a majority of the POCT in the EDL-2 panel. 90% of the population in Western Region live within 1 hour by car from most of the essential POCT. Figures in the complementary web-based application visualize the accessibility of POCT for Western Uganda. Diagnostic deserts are visualized. Interpretation: Access to POCT at primary health care facilities in western Uganda has expanded substantially over the past decades. The geo-mapping tool presented here could inform policy decisions on strengthening diagnostic capacity at the national, regional, and provincial level. Funding: Swedish Research Council and Infravis All supplementary materials and a preprint of this submission are available on our OSF repository https://osf.io/j7puk/.

Introduction. By the end of 2023, many low-income countries had not reached 50% COVID-19 vaccine coverage, while most high-income countries had exceeded 80%. It remains unclear whether receiving vaccine deliveries translated into faster population coverage. We examined cross-national inequalities in the timing of the vaccine rollout and whether deliveries through the COVID-19 Vaccines Global Access (COVAX) facility were associated with subsequent national uptake. Methods. We conducted an observational study of 218 countries and territories using country-level data up to December 2023. We used generalized additive mixed models to identify country-level correlates of coverage at an early and a later stage of the pandemic, survival analysis to compare the time to 50% coverage between COVAX Advance Market Commitment (AMC) and non-AMC countries, and an event study to estimate the association between the timing of the first COVAX delivery and subsequent monthly coverage in AMC countries. Results. AMC-supported countries reached 50% coverage substantially more slowly than non-AMC countries. The hazard of reaching the threshold was 0.17 times that of non-AMC countries at month 1 (95% CI 0.07 to 0.41) and 0.53 times at month 18 (95% CI 0.33 to 0.85). One year after rollout began, 65.9% of AMC countries (95% CI 56.7 to 76.6) had not reached 50% coverage, compared with 21.1% of non-AMC countries (95% CI 15.1 to 29.5). The timing of COVAX deliveries was not significantly associated with subsequent national uptake in any post-delivery month. In the early stage of rollout, higher maternal mortality was associated with lower coverage, while a larger urban population was associated with higher coverage. By the end of the observation period, larger household size was associated with lower coverage, while higher health expenditure and a larger urban population were associated with higher coverage. Conclusion. Receiving COVAX deliveries was not, on its own, associated with faster coverage. Coverage differences were more consistently associated with country-level structural and health-system characteristics, while we found no significant association with the timing of the first COVAX delivery. Achieving vaccine equality likely requires strengthening the capacity of health systems to convert deliveries into administered doses, and preparedness efforts should invest in last-mile delivery capacity ahead of future emergencies.

Background In adults, cold-attributable mortality exceeds heat-attributable mortality roughly 17-fold. Child-specific evidence has begun to emerge only recently - a nationwide Brazilian case-crossover study located the minimum mortality temperature (MMT) for under-five deaths, and a 56-country survey-based analysis linked monthly temperature anomalies to under-five mortality - but no multi-country, climate-zone-resolved estimate of the childhood respiratory-infection MMT exists, and whether temperature variability is independently associated with childhood respiratory mortality at the global scale is unknown. We quantified both. Methods We combined Global Burden of Disease 2023 mortality estimates, lower respiratory infection (LRI) deaths at ages 0-19 years and asthma deaths at ages 0-24 years, 171 countries, 1990-2023 - with 0.5 deg monthly land temperature and diurnal temperature range (DTR) fields from C-LSAT/C-LDTR (1901-2023). Four exposure dimensions (annual mean, DTR, seasonal amplitude, interannual variability) entered two-way fixed-effects models with Driscoll-Kraay standard errors. A quadratic term in mean temperature located the MMT, with percentile confidence intervals from a 300-replication country-cluster bootstrap. Future-exposure leads, country-level detrending, and permutation tests assessed contemporaneous causality, applied to both the linear coefficients and the quadratic term generating the MMT; national pneumococcal conjugate vaccine (PCV3) coverage and ambient PM2.5 exposure series were added as time-varying mechanistic covariates. Results The childhood LRI MMT was 17.1 C (95% CI 14.7-19.8), the 36th percentile of the annual-temperature distribution; zone estimates were 24.7 C in tropical and 15.8 C in subtropical countries, with weak temperate and no subarctic identification. The quadratic term underpinning the MMT, however, failed both falsification checks - future temperatures reproduced the U-shape and country-level detrending erased it - so these MMT values describe a trend-level geographic pattern of the annual construct rather than a contemporaneous dose-response. Interannual temperature variability was positively associated with LRI (+0.278, 95% CI 0.102-0.454; p = 0.002) and asthma mortality (+0.836, 95% CI 0.447-1.226; p = 2.6 x 10^-5) per 1 C, but future-exposure models returned nearly identical significant coefficients and detrending erased significance, supporting only a trend-level association; adjustment for national PCV3 coverage and PM2.5 exposure left these estimates essentially unchanged. Annual mean temperature was likewise inversely associated with both outcomes at the trend level; DTR and seasonal amplitude showed no independent within-country effects. Conclusions This study provides the first multi-country, climate-zone-resolved geography of the optimal temperature for childhood respiratory survival, spanning 171 countries; because the underlying quadratic association is trend-level, the estimates are directional. The observed variability-mortality associations are trend-level signals rather than contemporaneous causal evidence; daily-scale, child-specific designs are required to determine whether short-term thermal variability affects paediatric respiratory mortality.

Background Childhood respiratory mortality in China has fallen by over 90% in three decades alongside sustained national warming, yet national long-run evidence on temperature and child respiratory mortality is lacking. Methods We linked Global Burden of Disease (GBD) 2021 mortality estimates for China - lower respiratory infections (LRI), ages 0-19, and asthma, ages 0-24, 1990-2021 - with C-LSAT 0.5 deg gridded temperature data (1990-2019), aggregated nationally and to five climate zones. Four annual indicators (mean temperature, diurnal temperature range, seasonal amplitude, interannual variability) entered regressions of log mortality rates with Newey-West standard errors. A bootstrapped (500 resamples) quadratic model probed the minimum mortality temperature (MMT), with PM2.5-adjusted analyses and future-exposure, permutation, and detrended falsification tests. Results LRI deaths fell by 96.3% (330,194 in 1990 to 12,098 in 2021; 95% uncertainty interval 9,669-14,891) and asthma deaths by 94.9% (3,287 to 167), while mean temperature rose 0.364 deg C per decade and diurnal temperature range narrowed 0.092 deg C per decade. Baseline coefficients were large (mean temperature -1.696, SE 0.174; diurnal temperature range +2.408, SE 0.336; seasonal amplitude -0.162, SE 0.082; interannual variability +2.924, SE 1.514, per 1 deg C in log rate), but the future-exposure test failed and detrending nullified every coefficient: the associations are trend-level, and short-cycle causal effects are not identifiable. Nor was the national MMT identifiable - observed temperature support spans only 6.66-8.13 deg C, and the nominal turning point of 35.84 deg C is an extrapolation artifact (quadratic term p = 0.963). Within the observed range, warming and declining mortality moved in the same direction. Conclusions The 96% decline in childhood respiratory mortality cannot be attributed to warming. China sits on the low-temperature side of the optimum, and the marginal direction of future warming requires stronger designs to establish. The falsification framework offers a discipline for climate-health inference in China.

Background Computerised cognitive testing may address the global challenge in identifying cognitive changes in people living with HIV scalably and affordably. We assessed a computerised battery (CB) of cognitive tests, in a prospective cohort (CONNECT) of people with HIV in a low-income peri-urban area of Cape Town, South Africa during a national programmatic switch from efavirenz- to dolutegravir-based antiretroviral therapy (ART). Methods We recruited 170 people with HIV and 91 people without HIV (controls) (140[82%] and 41[45%] followed up). The CB and gold-standard pen&paper cognitive testing (P&P) were performed at both timepoints. Technology familiarity/use questionnaire data were also collected. We compared performance in detecting lower group-level cognitive performance associated with efavirenz treatment. Furthermore, the CB was compared to P&P in classifying individuals with low cognitive performance, correlation of global test scores and domain-level scores between batteries, and practice effects between timepoints. Exploratory principal component analysis was also performed. Results People with HIV on efavirenz at baseline had lower performance on the computerised battery than controls, {Delta}T=2.6, p=0.0047. This difference was lost after switching to dolutegravir-based ART at follow-up. CB and P&P global T were moderately correlated (R2=0.203, p<0.001), and the CB performed moderately in classification of low cognitive performance against the gold standard (AUC 0.70, sensitivity 0.52, specificity 0.76, PPV 0.40, and NPV 0.84). Selecting the first three principal components improved both classification of low cognitive performance (AUC 0.77) and correlation strength with P&P global T (R2=0.3, p<0.001). The CB did not show practice effects. Most participants owned a mobile phone (95%, 85.9% of these smartphones). Performance was better in smartphone owners ({Delta}T=1.8) and computer owners (23%, {Delta}T=1.8). Conclusions Delivering computerised cognitive testing was feasible in this low-income southern African setting. The CB showed reasonable construct validity (detecting known lower cognitive performance associated with efavirenz-ART) and may detect broad cognitive characteristics such as processing speed and accuracy. However, correlation of CB results with gold standard P&P testing was low-moderate and may limit its applicability as a diagnostic tool. This might be improved by including a wider range of cognitive domains tested in the CB, or data driven analysis. Brief CBs may fulfil an initial screening role, followed by more detailed clinical assessment.