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:Oral pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) provision via online pharmacies (henceforth online PrEP and PEP) offers promise in increasing biomedical HIV prevention coverage. In this study, we aimed to estimate the cost-effectiveness of online PrEP and PEP scale-up in western Kenya. METHODS:We adapted a network-based model, EMOD-HIV, to simulate online PrEP and PEP implementation from 2026 to 2036; costs and use of online PrEP and PEP and client characteristics were informed by the ePrEP Kenya pilot study, which evaluated online PrEP and PEP provision in Nairobi and Mombasa, Kenya. Other parameters were obtained from surveillance data and published literature. Eligible clients were aged 15-49 years reporting condomless sex with non-marital partners. We assumed online PrEP and PEP provision was implemented through public-private partnership, with the Kenya Ministry of Health providing PrEP and PEP drugs and service delivery costs paid by the online pharmacy (and charged to clients). We estimated HIV infections, HIV-related deaths, and disability-adjusted life-years (DALYs) averted compared with the baseline scenario of background oral PrEP only. We calculated incremental cost-effectiveness ratios (ICERs) assessing only costs incurred by the Kenya Ministry of Health over 35 years and used a supply-side threshold of US$500 per DALY averted. We calculated 95% uncertainty intervals (UIs) across 100 parameter sets. FINDINGS:Online PrEP and PEP was projected to reach population coverage of 0·7% (95% UI 0·7-0·8) for PEP and 0·3% (0·2-0·3) for PrEP and avert 13·9% (10·1-17·1) of HIV infections over 10 years. HIV-related deaths were reduced by 4·3% (95% UI 2·0-6·9) over the 35-year time horizon. The intervention was cost-effective from the Kenya Ministry of Health perspective (ICER $212 [95% UI 15-1409] per DALY averted). In a scenario assuming only online PEP availability (to isolate the effect of PEP), 11·6% (95% UI 8·6-15·2) of HIV infections were averted (ICER $210 [95% UI 41-3798] per DALY averted). The intervention remained cost-effective when varying PrEP and PEP effectiveness and assuming HIV testing and treatment disruptions. INTERPRETATION:Online PrEP and PEP can avert substantial HIV infections, even with low population coverage. PEP was responsible for most intervention health benefits, likely due to high observed demand for PEP compared with PrEP in the pilot study. Leveraging private retailers can be efficient for scaling up HIV prevention in an era of shrinking donor funding. FUNDING:Gates Foundation.
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.
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.
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: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.
