BACKGROUND:In 2022, South Africa had an estimated hepatitis B prevalence of 4·7-6·0%. In an effort to eliminate viral hepatitis as a public health threat, a targeted (ie, selective) hepatitis B birth-dose vaccination (HepB-BD) policy was introduced in 2023. Under this policy, only infants born to mothers with confirmed hepatitis B positivity are eligible for HepB-BD, which is given in addition to peripartum antiviral prophylaxis (PAP) for mothers from the second or third trimester of pregnancy. This policy differs from the WHO recommendation that all newborns should receive a HepB-BD vaccine (ie, a universal HepB-BD policy). We aimed to assess comparative costs and benefits of this and alternate policies in South Africa. METHODS:A validated model of transmission, disease progression, and mortality was used to simulate the ongoing hepatitis B epidemic in South Africa. We projected outcomes from the current South African policy (ie, selective PAP plus selective HepB-BD), a universal HepB-BD-only policy, and the WHO-endorsed selective PAP plus universal HepB-BD policy. Health and economic impacts were compared with a baseline of no HepB-BD coverage, over a 2025-100 time horizon. Costs were reported in consumer price index-adjusted 2024 ZAR and outcomes discounted at 3% per annum. FINDINGS:The current South African HepB-BD policy required fewer vaccinations per outcome averted, with the number needed to vaccinate per vertically acquired chronic hepatitis B infection averted found to be six (95% uncertainty interval 3-15), compared with 462 (223-1479) under a universal HepB-BD-only policy or 77 (38-240) under a selective PAP plus universal HepB-BD policy. Despite incurring the greatest programmatic costs, a selective PAP plus universal HepB-BD policy averted the greatest disease burden and was modelled to be the most cost-effective option at a willingness-to-pay threshold of 0·5 × per-capita gross domestic product (ZAR 57 281). INTERPRETATION:Our findings support implementation of a universal HepB-BD policy alongside South Africa's current hepatitis B viral transmission elimination efforts. FUNDING:Vaccine Impact Modelling Consortium.
Global health researchers, UN agencies, and donors have become expert at documenting the deterioration of population health during conflict, yet documentation has not stopped that deterioration. Drawing on 15 years of field research in Syria, Lebanon, Gaza, and Jordan, we argue that part of the failure of the global health architecture stems not principally from violations of international humanitarian law, but from its design as a technical enterprise detached from the political economy of power, financing, and governance. In practice, the system was structured to document harm rather than to hold anyone accountable for it. We distinguish humanitarian neutrality, understood as the operational duty to assist all civilians, from technical neutrality, which excludes political accountability in ways that protects institutional relationships and funding. We define a political economy of health approach, identify specific actors capable of changing the system, and acknowledge both the real, although uneven, effects of documentation and the structural constraints, namely sovereignty, donor dependence, and entrenched interests, that any reform should confront. Finally, we propose six concrete shifts to move global health from monitoring harm and misery towards enabling accountability.
BACKGROUND:Paediatric acute kidney injury (AKI) is a complication of severe malaria, but its long-term outcomes remain poorly defined in low-income and middle-income countries. We aimed to evaluate the long-term association between paediatric AKI and kidney outcomes and mortality following severe malaria. METHODS:We pooled data from two prospective cohorts of Ugandan children (ie, those aged 6 months-12 years) admitted to hospital with severe malaria between 2008 and 2017. Children with stored admission blood samples available for creatinine measurement were included in the analysis. Surviving participants were enrolled in a follow-up study conducted from 2020 to 2023, when kidney function and survival were assessed, using Cox regression with age as the timescale to model mortality risk. Logistic regression was used to estimate the odds of chronic kidney disease (CKD), defined as two or more consecutive low estimated glomerular filtration rates 90 days or more apart, and long-term major adverse kidney events, defined as CKD or death. Adjusted analyses included the following enrolment characteristics: age, sex, height-for-age Z score, study site, study cohort, severe malaria group (ie, cerebral malaria, severe malarial anaemia, respiratory distress, complicated seizures, or prostration), and HIV status. FINDINGS:At enrolment, the median age was 2·5 years (IQR 1·8-3·5), 622 (57·8%) of 1077 were male and 455 (42·2%) were female, with Kidney Disease: Improving Global Outcomes-defined AKI occurring in 431 (40·0%) children. Over a median of 6·5 years (3·7-8·8), 147 (13·6%) of children died, with nearly half of deaths (71 of 147) occurring after hospital discharge. Adjusted odds of long-term major adverse kidney events were higher among children with AKI (adjusted odds ratio [aOR] 3·14, 95% CI 2·23-4·43), driven by a higher mortality risk (adjusted hazard ratio [aHR] 3·36, 95% CI 2·22-5·10) that remained elevated beyond 2 years after the acute episode (aHR 4·53, 1·80-11·37). AKI survivors had higher odds of chronic kidney disease over follow-up (odds ratio 1·77, 1·07-2·93), although not significant after adjustment (aOR 1·47, 95% CI 0·84-2·56; p=0·18). INTERPRETATION:In this paediatric population, AKI was associated with excess long-term mortality, suggesting AKI is a sentinel event that marks sustained vulnerability to death and highlights limitations of acute-care models in malaria-endemic settings. FUNDING:The US National Institute of Neurological Disorders and Stroke, the Fogarty International Center, the US National Institutes of Allergy and Infectious Diseases, and a Ralph W and Grace M Showalter Young Investigator Award.
BACKGROUND:In low-income and middle-income countries, where typhoid fever remains a major public health problem, WHO recommends the use of typhoid conjugate vaccine (TCV). Here, we report vaccine effectiveness up to 8 years following a single dose of TCV in Nepal. METHODS:TyVOID was a prospective cohort study that extended the follow-up of children enrolled in a phase 3, double-blind, randomised controlled trial in Lalitpur, Nepal (TyVAC; Nov 20, 2017, to Oct 20, 2021). Children aged 9 months to 15 years were randomly assigned (1:1) to receive Vi-tetanus toxoid conjugate vaccine (Vi-TT) or a capsular group A meningococcal conjugate (MenA) vaccine. After unmasking and crossover vaccination, our study followed the trial participants until Oct 31, 2025. TyVAC participants who received Vi-TT were eligible for this study and categorised into either the 2017-18 cohort or 2020-21 cohort, depending on when they received the Vi-TT vaccine. The primary outcome, which was assessed in children who received both Vi-TT and MenA vaccines and with known TCV vaccination status during the government catch-up campaign in 2022, was the incidence of blood culture-confirmed typhoid identified through facility-based passive surveillance and medical record review. Adjusted incidence rate ratios (IRRs) were estimated using Poisson regression adjusted for age and sex. Vaccine effectiveness at 1-5 years and 4-8 years post-vaccination was estimated using a test-negative design among febrile children presenting to surveillance clinics, comparing odds of Vi-TT vaccination between culture-confirmed typhoid cases with negative controls. FINDINGS:16 131 TyVAC participants were enrolled at TyVOID baseline, of whom 14 850 provided information on Vi-CRM197 vaccination during the government catch-up campaign. After crossover and unmasking, the primary analysis population included 4941 participants vaccinated with Vi-TT in 2017-18 and 4856 participants vaccinated with Vi-TT in 2020-21. In 4856 participants in the 2020-21 Vi-TT cohort, 2402 (49·5%) were female, 2454 (50·5%) were male, and the median age at Vi-TT vaccination was 10·4 years (IQR 7·3-13·7). In 4941 participants in the 2017-18 Vi-TT cohort, 2482 (50·2%) were female, 2459 (49·8%) were male, and the median age at Vi-TT vaccination was 7·7 years (IQR 4·5-11·0). During a median follow-up of 3·7 years (3·7-3·8), the typhoid incidence rate was 111 per 100 000 person-years (95% CI 64-177) in the 2017-18 cohort and 46 per 100 000 person-years (18-94) in the 2020-21 cohort (adjusted IRR 2·41 [95% CI 1·00-5·80]; one-sided p=0·025). Vaccine effectiveness was 77% (95% CI 46-90; p=0·0006) in the 2020-21 Vi-TT cohort (1-5 years after vaccination), and 53% (8-76; p=0·027) in the 2017-18 Vi-TT cohort (4-8 years after vaccination). INTERPRETATION:A single Vi-TT dose confers strong protection in the first 4 years among Nepali children, with evidence of waning by 8 years. These findings support consideration of a booster dose to sustain protection in school-age children who remain at high risk of typhoid fever. FUNDING:Gates Foundation and Wellcome Trust.
BACKGROUND:Hypoxaemic lower respiratory infections (LRIs) are a leading cause of childhood mortality, with the highest burden in low-income and middle-income countries (LMICs). Hypoxaemia-low peripheral capillary oxyhaemoglobin saturation (SpO2)-is a marker of severity, and WHO recommends hospitalisation and oxygen administration for patients with SpO2 <90%. We aimed to update estimates from a 2015 systematic review and meta-analysis examining the association between hypoxaemia and mortality among children with LRIs in LMICs by incorporating studies published over the subsequent decade and evaluating mortality risk across multiple SpO2 thresholds. METHODS:We conducted a systematic review with meta-analysis by searching PubMed, Embase, LILACS, Global Index Medicus, Web of Science, and Scopus for peer-reviewed studies published between Jan 1, 2015, and June 18, 2025, with combined terms related to pneumonia, children, mortality, and LMICs. We also included selected earlier studies through citation checking. Eligible studies reported associations between hypoxaemia and mortality in children younger than 5 years with LRIs in LMICs. We excluded case reports and case series with fewer than five deaths, studies focused exclusively on the neonatal period, and those limited to children with specific comorbidities or to postoperative patients, for consistency with the original review. Two reviewers independently screened studies, extracted data, and assessed quality. Eligible studies were combined with those from the original review and analysed using random-effects models to estimate odds ratios (ORs) by hypoxaemia threshold subgroup. The protocol was registered on PROSPERO (CRD42023433946). FINDINGS:We identified 7734 records; 26 new studies met inclusion criteria and were combined with 18 from the original review. The 44 studies were published between 1993 and 2024 and were primarily from Africa (25 [57%] of 44) or Asia (19 [43%]); some studies spanned multiple locations. Data from 33 studies including 155 633 participants were included in the primary meta-analysis. Hypoxaemia of any threshold was associated with higher odds of LRI mortality (OR 4·36 [95% CI 3·52-5·39]) compared with no hypoxaemia. For SpO2 <90% versus 90-100%, OR for death was 4·75 (95% CI 3·42-6·58). For SpO2 90-94% versus 95-100%, mortality risk was more than twice as high (OR 2·27 [95% CI 1·22-4·25]). Heterogeneity was substantial (I2 64-85% across analyses), and eight (24%) of 33 studies in the primary meta-analysis had a high overall risk of bias; however, a sensitivity analysis restricted to studies with low or moderate risk of bias yielded similar results. INTERPRETATION:SpO2 <90% strongly predicts mortality in children with LRIs in LMICs. Children with SpO2 90-94% also have elevated risk, suggesting that paediatric LRI and pneumonia treatment algorithms should consider management at this hypoxaemia threshold. FUNDING:None.
BACKGROUND:Afghanistan has made remarkable progress in addressing its high maternal and neonatal mortality rates between 2001 and 2021. Recent restrictions banning midwifery and nursing education for women risk reversing these gains. Using scenario-based modelling, this study examined the potential long-term impact of the ban on service coverage and mortality. METHODS:In this modelling study, we developed four scenarios reflecting slow versus fast attrition among women nurses and midwives and the possibility of male substitution and simulated projected changes in care seeking for six services accessed by women and children. Projections were from 2022 to 2035. Baseline data were collected from the 2023 Human Resources for Health Situational Assessment. We used a mathematical model that estimated care seeking as a function of health worker density and the proportion of women providers, accounting for varying levels of gender sensitivity to male substitution for each service as assessed by provincial-level Afghan health workers through a subjective expert elicitation exercise. Mortality outcomes were estimated using the Lives Saved Tool. FINDINGS:Our model projected decline in women's workforce entry, resulting in reduced service utilisation. We projected relative reductions in women's care seeking for maternal and reproductive health to 50-55% of current levels under the best-case scenarios to as low as 33-35% of current levels under the worst-case scenarios. These reductions translate into significant increases in the maternal mortality ratio, ranging from 29% under the best scenario to 41% under the worst scenario. Child health services would also suffer, but with greater substitutability of male providers to a lesser degree, with projected declines in care seeking to 76-80% under the best-case scenario and to 56-59% under the worst-case scenario. The resulting increase in child mortality rates could range between 10% and 16% and in neonatal mortality rates between 12% and 17%. INTERPRETATION:These findings represent scenario-based projections rather than forecasts and are highly dependent on assumptions regarding workforce attrition and substitution. Nonetheless, they show that the ban on women's medical education in Afghanistan will severely restrict women not only from providing health care but from accessing it as well. The policy threatens to reverse hard-won gains in maternal and child survival, with women's health and life chances disproportionately affected. Sustained advocacy and interventions are therefore urgently needed. FUNDING:The Global Financing Facility Trust Fund.
Over 1 billion people across low-income and middle-income countries live in urban informal settlements, where these residents face severe health disparities. In this Viewpoint, we argue that the absence of legal recognition in informal settlements is a foundational cause of the causes of ill health, as the absence of recognition contributes to unsafe housing and inadequate access to water, sanitation, and other life-sustaining basic services. Despite the importance of legal recognition, few public health researchers have explored how legal barriers influence health outcomes in these communities. Based on the evidence identified through a systematic search, we argue that previous research focused on how tenure or titling can improve living conditions but overlooked other legal interventions that might better enhance health equity by expanding basic service access. We propose an innovative research agenda aimed at characterising the global landscape and underlying mechanisms of a wider spectrum of legal interventions—beyond tenure or titling alone—that could improve health in informal settlements.
BACKGROUND:Peripheral arterial disease is a growing public health concern. We aimed to provide updated estimates of peripheral arterial disease prevalence and case numbers at the global, regional, and national levels in 2023, and synthesise evidence on factors associated with peripheral arterial disease. METHODS:In this systematic review and modelling analysis, we searched PubMed, Embase, MEDLINE, CINAHL, Global Health, AMED, and ProQuest Dissertations and Theses Global for articles and grey literature published between April 30, 2019, and Dec 9, 2024, reporting peripheral arterial disease prevalence in the general population. This search was supplemented by eligible studies identified through relevant systematic reviews and manual reference screening. Studies were eligible if peripheral arterial disease was defined as an ankle-brachial index (ABI) lower than or equal to 0·90. Studies using hospital-based or clinical samples and studies conducted exclusively in populations with specific characteristics (eg, diabetes) were excluded. Two reviewers independently screened records for eligibility, extracted study-level data, and assessed the study quality using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies. An age-sex splitting procedure was applied to disaggregate prevalence data. A multilevel multivariable mixed-effects meta-regression approach was used to examine the associations between age and peripheral arterial disease prevalence, stratified by sex and income level (high-income countries [HICs] and low-income and middle-income countries [LMICs]). Pooled odds ratios (ORs) for factors associated with peripheral arterial disease were estimated through a random-effects meta-analysis. Peripheral arterial disease prevalence at regional and national levels was derived using an associated factor-based distribution model. The study protocol was registered in PROSPERO (CRD420261290434). FINDINGS:Of 12 733 records identified, 157 articles from 37 countries met the inclusion criteria, encompassing more than 9·7 million participants. In 2023, the global prevalence of peripheral arterial disease among individuals aged 25 years and older was 6·58% (95% CI 4·83-9·02), equivalent to 316·54 million (232·34-433·78) affected individuals. Peripheral arterial disease prevalence increased consistently with age, ranging from 4·31% (2·82-6·81) among those aged 25-29 years to 22·09% (15·50-30·26) among those aged 90-99 years, with a similar pattern in both sexes. Prevalence was slightly higher in women (6·79% [5·14-9·05]) than in men (6·37% [4·52-9·00]), and was higher in HICs (7·52% [5·57-10·45]) than in LMICs (6·33% [4·63-8·63]). Despite the lower prevalence in LMICs, these countries accounted for over three-quarters of the global peripheral arterial disease cases (239·35 million [175·11-326·50]). Four associated factors were incorporated into the distribution model, namely current smoking (OR 2·85 [95% CI 2·13-3·80]), diabetes (1·81 [1·63-2·00]), hypertension (1·64 [1·48-1·81]), and hypercholesterolaemia (1·34 [1·17-1·53]). Across WHO regions, prevalence was the highest in the European region (8·09% [5·99-11·14]) and the lowest in the African region (5·18% [3·78-7·07]). The largest number of cases was in the Western Pacific region (91·91 million [67·45-125·34]), whereas the smallest was in the African region (25·40 million [18·57-34·70]). Approximately 60% of global cases (189·67 million) were concentrated in just ten countries. INTERPRETATION:Peripheral arterial disease is a substantial and growing global public health challenge, particularly in LMICs. Reducing its long-term health consequences will require standardised population-based studies in under-represented regions, early detection through ABI-based and risk-based case-finding, improved access to diagnosis and vascular care, and integration of peripheral arterial disease into broader cardiovascular prevention and health-system planning. FUNDING:None.
BACKGROUND:Infectious diseases remain the leading cause of death among children younger than 5 years due to disparities in access and acceptance of essential interventions. The Community Mobilisation and Community Incentivisation (CoMIC) trial was designed to evaluate a customised community mobilisation and incentivisation strategy for improving coverage of evidence-based interventions for child health in Pakistan. This unplanned follow-up study was designed to assess the health effects, adherence to behaviour change, and sustainability of this strategy 3 years after the completion of the trial. METHODS:A cross-sectional follow-up study was conducted 3 years after the completion of the CoMIC trial. CoMIC was a three-group, cluster-randomised, controlled trial in rural areas of the Tando Muhammad Khan district in Pakistan. Clusters were randomly assigned (1:1:1) to either community mobilisation and incentivisation, community mobilisation, or the control group. Community mobilisation included formation of village committees who conducted awareness activities, whereas clusters in the community mobilisation and incentivisation group were provided with a novel conditional, collective, community-based incentive (C3I) in addition to community mobilisation. C3I, chosen by the village committees, were conditioned on serial incremental targets for collective improvement in coverage at cluster level of three primary outcomes: proportion of fully immunised children, use of oral rehydration solution, and sanitation index. For this follow-up study 3 years after the cessation of original trial activities, survey data were collected between Sept 4 and Nov 24, 2023 on all outcomes from the mothers or caregivers of children younger than 5 years in selected households. Analyses followed the intention-to-treat approach (ie, all eligible participants were analysed according to the original cluster randomisation irrespective of intervention uptake or participation status). Additional survey and observational data were collected from the village committees to assess the usage and sustainability of the incentive. The trial is registered at ClinicalTrials.gov, NCT03594279, and is completed. FINDINGS:Between Sept 4 and Nov 24, 2023, a total of 5658 children younger than 5 years from 3906 households in 48 clusters (villages) were included in the follow-up survey. 451 (88%) of the 514 water and sanitation facilities constructed as incentives in the trial and 221 (56%) of the 397 village committees remained functional 3 years after they were created as a part of community mobilisation and incentivisation group. Multivariable analysis indicated a higher proportion of fully immmunised children (adjusted risk ratio [RR] 1·20 [95% CI 1·00-1·43]) and a better sanitation index (mean difference 1·12 [95% CI 0·81-1·43]) in the community mobilisation and incentivisation group compared with the control group. There was no evidence of a difference in oral rehydration solution use (adjusted RR 0·99 [95% CI 0·75-1·31]) in the community mobilisation and incentivisation group compared with the control group. An improved sanitation index and increased use of oral rehydration solution was also observed in the community mobilisation group compared with the control group, despite no such differences being observed in the initial trial. INTERPRETATION:Findings from this 3-year follow-up of CoMIC suggest that behaviour changes can be sustained after the intervention if there is an active community engagement strategy with conditional benefits that appeal to the community. FUNDING:Bill & Melinda Gates Foundation.
BACKGROUND:People with HIV have poor access to care for other chronic conditions despite the increasing disease burden and associated mortality. We evaluated the impact of integrated HIV and hypertension care on blood pressure control, electronic prescribing of antihypertensive medicines, and HIV viral suppression in Botswana. METHODS:We conducted a 24-month, pair-matched, cluster-randomised, type 2 hybrid effectiveness-implementation trial at 14 HIV clinics among adults aged 20-75 years with HIV and hypertension. HIV clinics were eligible if they had the Patient Integrated Medical Record System (PIMS), the national electronic health record (EHR) platform for HIV care in Botswana. Clinics were pair-matched by catchment population size, antiretroviral therapy access, age structure, and geographical location before one clinic from each pair was randomly allocated to the intervention or standard-of-care group. The main implementation strategy in the intervention group included HIV health-care provider training, ongoing coaching, engagement of community treatment partners, and the use of the EHR to support diagnosis, management, and electronic prescribing during routine HIV clinic visits. The coprimary outcomes, at 12 months, were (1) the proportion of participants taking antihypertensive medicines with blood pressure controlled within the targets (systolic and diastolic blood pressure <140 mm Hg and <90 mm Hg, respectively; or <130 mm Hg and <80 mm Hg for those with diabetes or chronic kidney disease), and (2) the proportion of clinic encounters with documented antihypertensive prescriptions in the EHR (ie, prescriptions for antihypertensive medicines generated electronically using the PIMS). The trial was registered at ClinicalTrials.gov (NCT05414526) and is complete. FINDINGS:Between Jan 13, 2023, and Sept 10, 2025, 4654 participants were enrolled (2327 per group). At 12 months, blood pressure control among participants receiving antihypertensive medication was attained in 719 (67·1%) of 1072 participants in the intervention group versus 593 (51·5%) of 1152 in the standard-of-care group (risk ratio [RR] 1·29, 95% CI 1·10-1·51; p=0·0013 unadjusted). The prescription for antihypertensive medicines was issued electronically to 428 (39·9%) of the 1072 eligible encounters in the intervention group compared with 124 (10·8%) of the 1152 in the standard-of-care group (RR 5·95, 2·18-16·2; p=0·0005 unadjusted). At 12 months, serious adverse events were infrequent and did not differ significantly between the intervention and standard-of-care groups (22 [0·9%] of 2127 vs 20 [0·9%] of 2188; p=0·69), and viral suppression rates also did not differ significantly between the two groups (1759 [98·6%] of 1784 vs 1821 [99·0%] of 1839; p=0·39). INTERPRETATION:Integrating hypertension care into HIV care programmes is an effective way to achieve blood pressure control and to increase the prescription of antihypertensive medicines electronically among people with HIV without compromising HIV outcomes. FUNDING:The National Heart, Lung, and Blood Institute of the US National Institutes of Health.
