The Lancet Global Health

BackgroundPreventive chemotherapy targeting school-aged children has substantially reduced schistosomiasis morbidity, however, a key strategic tension remains between sustaining morbidity control and pursuing transmission elimination, particularly in settings characterised by heterogeneous transmission dynamics and persistent adult infection reservoirs. We developed a health system-integrated transmission and economic evaluation framework to identify optimal age-targeting and district-level prioritisation, providing a basis for determining when elimination-focused approaches offer advantages over morbidity reduction alone. MethodsThe Thanzi la Onse individual-based model was used to evaluate alternative age-targeted mass drug administration (MDA) strategies for Schistosoma haematobium and Schistosoma mansoni across all 32 districts of Malawi from 2024-2050. Strategies included treatment of school-aged children (MDA-SAC), pre-school and school-aged children (MDA-PSAC+SAC), and community-wide treatment (all ages). Health outcomes included person-years with any infection (PY), disability-adjusted life years (DALYs), probability of elimination (defined as reaching <2% prevalence of infection in all ages). The cost-effectiveness was evaluated using incremental cost-effectiveness ratios (ICERs), net health benefit (NHB), and by quantifying the maximum costs available for implementation, using a cost-effectiveness threshld for Malawi of 88 USD per DALY averted. FindingsIn the absence of MDA, the majority of the infection burden over 2024-2050 would be concentrated in adults aged 15 years and older (219.6 million person-years [PY], 95% CI 215.4-223.4), compared with 72.8 million PY (95% CI 71.5-74.3) among school-aged children (SAC) and 25.5 million PY (95% CI 25.1- 26.2) among preschool-aged children. Annual MDA-SAC would avert approximately 18.0 million DALYs (95% CI 17.6-18.4) between 2025 and 2050 and would be highly cost-effective nationally (ICER 4.76 USD/DALY, 95% CI 4.47-4.95). Across districts, ICERs were highly variable; 25 of 32 districts were cost-effective in [&ge;]90% of runs and 29 of 32 in [&ge;]50% of runs. Expanding treatment to include preschool-aged children (MDA PSAC+SAC) would produce modest additional gains (additional 44,500 DALYs averted) but with substantially higher costs (national ICER 606 USD/DALY, 95% CI 472-695), being dominated in 22 districts and cost-effective only in the high-burden Likoma district. Community-wide MDA would achieve elimination for both species in all districts by 2030 and avert a further 98,000 DALYs; nationally it would be cost-saving relative to PSAC+SAC although outcomes were heterogeneous, with this strategy being cost-saving in 11 high-prevalence districts (2023 prevalence range 13.7 - 41.5%) but dominated (in >80% of model runs) in 16 others. Threshold analyses of maximum implementation costs indicated substantial cost margins in high-burden districts, with cost-effectiveness maintained up to approximately 25-38 USD per treatment. InterpretationThe choice of schistosomiasis strategies should depend on whether programmes prioritise short-term morbidity reduction or long-term elimination, as well as the local disease burden and the prevailing cost of service delivery. Integrating district-level transmission dynamics with opportunity-cost-based economic evaluation reveals when broader coverage is justified and provides a framework for designing fiscally grounded elimination pathways in heterogeneous endemic settings.

BackgroundReductions in United States (US) funding for tuberculosis (TB) and HIV programmes have raised concerns and challenges for TB care and management in South Africa and globally. We used mathematical modelling to illustrate the potential impact of unmitigated funding disruptions, estimating long-term effects on TB incidence and mortality over 2025-2035. MethodsStakeholder-informed scenarios were modelled, assuming both minimal and maximal disruptions to key TB and HIV services, including preventive therapy for people living with HIV (PLHIV), TB testing, TB treatment initiation, and antiretroviral therapy (ART) coverage. Results and discussionBetween 2025 and 2035, reduced ART coverage was projected to result in 235,000-1,000,000 additional HIV infections; and a 12-41% increase in TB episodes, and 21-72% rise in TB deaths among people living with HIV. Overall, 220,000-730,000 additional TB episodes and 67,000-225,000 TB deaths are anticipated, potentially reversing years of progress. Although mitigation efforts were not included in the model, early responses in South Africa have involved increased diagnostic testing and additional domestic funding. To maintain progress in TB and HIV control, rapid and sustained programmatic responses and funding are essential to prevent substantial setbacks and avert avoidable illness and death.

BackgroundTuberculosis (TB) and human immunodeficiency virus (HIV) are leading causes of infectious disease deaths, with disproportionate impact in low- and middle-income countries (LMICs). Despite well-established biological relationships between these diseases, there is limited information on how TB prevalence differs between people living with and without HIV. MethodsWe conducted a systematic review and meta-analysis of TB prevalence surveys conducted in LMICs and published during January 1st 1993-October 13th 2025 (PROSPERO CRD42024503853). We extracted bacteriologically-confirmed TB prevalence estimates stratified by participant HIV status. Surveys that offered HIV testing to all, sputum-collection-eligible, or TB-positive participants were included in the primary analysis. We applied Bayesian meta-regression to estimate pooled risk ratios (RR) of bacteriologically-confirmed TB prevalence among participants living with versus without HIV. Additionally, we estimated country-level and overall TB notification-to-prevalence (N:P) ratios by HIV status. FindingsOf 10,211 potentially relevant publications, 12 TB prevalence surveys--representing 264,530 participants within nine countries in Southern and Eastern Africa--were used in the primary analysis. Reported TB prevalence was higher among participants living with versus without HIV in 11/12 surveys, with an overall pooled RR of 3{middle dot}86 (95% credible interval: 2{middle dot}41-5{middle dot}53). N:P ratios were higher among participants living with HIV in all examined countries. The overall pooled N:P ratios were 1{middle dot}74 (0{middle dot}59-4{middle dot}56) and 0{middle dot}48 (0{middle dot}17-1{middle dot}20) among participants living with versus without HIV, respectively. InterpretationIn Southern and Eastern Africa, bacteriologically-confirmed TB prevalence is three- to six-times higher among people living with HIV. Comparison of prevalence and notification data suggest higher rates of TB diagnosis for people living with versus without HIV, but also indicates substantial delays in the detection of untreated TB cases for both populations. FundingWellcome Trust, UK National Institute for Health and Care Research, UK Foreign, Commonwealth and Development Office, NIH. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThere is limited systematic evidence on how the prevalence of TB disease differs between people living with HIV and without HIV. Multiple observational cohorts have described substantially elevated TB incidence among populations with HIV, but disease prevalence will also be affected by differences in mortality and treatment uptake rates. We searched PubMed from inception through January 21, 2026 using the search string ((HIV AND TB) OR HIV/TB) AND (prevalence AND (systematic review OR meta-analysis)) without any restrictions on language. We also reviewed investigators personal libraries. This search yielded 506 publications; however few of these included prevalence data. An analysis conducted in 2020 synthesized HIV status-stratified data from seven national TB prevalence surveys in Africa and found that HIV prevalence was lower among prevalent TB cases than among notified cases. This study did not include subnational surveys and did not distinguish between survey participants with self-reported or test-confirmed HIV status. Added value of this studyThis study synthesized TB prevalence data, stratified by participant HIV status, from national and subnational surveys conducted in LMICs and published between January 1st 1993 and October 13th, 2025. Collated data represented 681,402 survey participants across ten countries. All but one study were conducted in Southern and Eastern Africa. We limited our primary analysis to surveys that systematically tested participants for HIV and bacteriologically-confirmed TB. The prevalence of bacteriologically-confirmed TB was estimated to be three to six times higher than among people living with versus without HIV. Ratios of TB notifications to TB prevalence were higher for people living with HIV compared to people without HIV, suggesting higher rates of TB case detection (and likely shorter duration of disease) for people living with HIV and untreated TB than those without HIV. Implications of all available evidenceFew estimates of community-representative TB prevalence stratified by participant HIV status exist. These surveys have been concentrated in Southern and Eastern Africa, despite TB-HIV burden being distributed globally. Our findings highlight the elevated burden of TB among people living with HIV in these settings, as well as the limited data on the intersection of TB and HIV epidemiology in other world regions. Furthermore, our comparison of notification and prevalence data demonstrate substantial shortfalls in TB case detection, regardless of an individuals HIV status.

BackgroundDuring Nigerias largest recorded diphtheria outbreak, hospital capacity in Kano State was rapidly overwhelmed. Medecins Sans Frontieres introduced home-based care (HBC) for patients with mild disease to prioritise facility-based care for severe cases. We assessed whether HBC was non-inferior to facility-based treatment in terms of mortality, sequelae, and household transmission. MethodsWe conducted a retrospective matched cohort study. Mild diphtheria cases treated between January 2023 and May 2024 were matched 1:1 by treatment modality (HBC or diphtheria treatment centre [DTC]) on sex, age group, vaccination status, and residence. Conditional logistic regression estimated the association between treatment modality and mortality, with robustness assessed through propensity score weighting, sensitivity analyses, and E-value computation. FindingsOf 990 sampled patients, 678 (367 HBC, 311 DTC) were enrolled (68{middle dot}5%). After adjustment, treatment modality was not independently associated with mortality (HBC vs. DTC: aOR 0{middle dot}40, 95% CI 0{middle dot}13-1{middle dot}30), with similar estimates across sensitivity analyses (E-value 4{middle dot}40). Clinical complications were the strongest predictor of death (aOR 23{middle dot}1, 95% CI 1{middle dot}73-307). Vaccination was protective (aOR 0{middle dot}28, 95% CI 0{middle dot}08- 0{middle dot}94) and treatment delay of four or more days increased mortality (aOR 4{middle dot}15, 95% CI 1{middle dot}23-14{middle dot}0). HBC was not associated with increased household transmission or long-term sequelae. InterpretationVaccination and early treatment, rather than care setting, were the main determinants of survival. When supported by clinical triage and structured follow-up, decentralised care can be used to manage mild cases during diphtheria epidemics in settings with constrained hospital capacity. FundingMedecins Sans Frontieres, West and Central Africa. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and Google Scholar for articles published between January 1, 2000, and February 28, 2026, using combinations of the terms "diphtheria", "outbreak", "home-based care", "outpatient", "ambulatory", "community care", and "decentralised care". We found no published studies evaluating any form of decentralised or home-based clinical management for diphtheria. The existing literature on diphtheria case management is confined to facility-based settings: outbreak reports from multiple affected countries describe hospital-based treatment with diphtheria antitoxin (DAT) and antibiotics, and a systematic review pooled epidemiological and clinical data from historical outbreaks. Decentralised care models have been evaluated for other epidemic-prone diseases, including a measles epidemic in the Democratic Republic of the Congo (DRC) where decentralised management reduced mortality among children, and Ebola virus disease outbreaks in DRC where decentralised treatment centres were piloted to improve geographic access, though with limited outcome data. No study has assessed whether patients with diphtheria can be safely managed outside hospital settings. Added value of this studyNo prior evaluation of home-based care for diphtheria has been published. Using a retrospective matched cohort design with 678 patients during the largest diphtheria outbreak in Africa in decades, we found no evidence that home-based care increased mortality, long-term complications, or household transmission compared with facility-based care, and acceptability was high among patients in both groups. The study also provides one of the largest datasets on household transmission of diphtheria in an urban epidemic setting, finding no evidence that home-based care increased secondary transmission, and showing that vaccination status of the index case was the main factor influencing spread within the household. Implications of all the available evidenceProvided that triage is reliable, antibiotics are started promptly, and a functioning referral pathway exists, mild diphtheria can be managed safely at home during large epidemics. This approach preserves limited hospital and DAT resources for patients with moderate or severe disease, shortens treatment delays, and is acceptable to patients. Given ongoing outbreaks across West and Central Africa and persistent DAT supply constraints, decentralised care warrants inclusion in epidemic preparedness.

BackgroundEvidence to guide the choice of injectable antibiotics and supportive care for children with severe pneumonia is limited and may not reflect changes in epidemiology associated with vaccination and antimicrobial resistance. MethodsIn this pragmatic, open-label, factorial, randomized trial conducted in 16 hospitals in Kenya, children aged 2-59 months with World Health Organization-defined severe pneumonia were assigned to receive one of three injectable antibiotic regimens: benzylpenicillin plus gentamicin (standard care), ceftriaxone, or amoxicillin-clavulanic acid. Eligible children were also randomly assigned to receive nasogastric tube feeding or intravenous fluids. The primary outcome was death from any cause by day 5 after enrollment. ResultsA total of 4393 children underwent randomization to the antibiotic groups, and 1064 to the supportive care groups. By day 5, deaths occurred in 87/1463 children (6.0%) receiving benzylpenicillin plus gentamicin, 82/1458 (5.6%) receiving amoxicillin-clavulanic acid (adjusted risk ratio [aRR], 0.94; 97.5% confidence interval [CI], 0.67 to 1.31), and 81/1462 (5.5%) receiving ceftriaxone (aRR vs. benzylpenicillin plus gentamicin, 0.95; 97.5% CI, 0.68 to 1.33). Death by day 5 occurred in 30/531 children (5.7%) receiving nasogastric tube feeding and 35/532 (6.7%) receiving intravenous fluids (aRR, 1.13; 97.5% CI, 0.71 to 1.79). Secondary outcomes were similar across groups. ConclusionsAmong children hospitalized with severe pneumonia, outcomes with benzylpenicillin plus gentamicin were similar to those with ceftriaxone or amoxicillin-clavulanic acid, and nasogastric tube feeding was similar to intravenous fluids with respect to mortality and safety.

BackgroundTuberculosis (TB) remains a leading cause of morbidity and mortality among people living with HIV (PLHIV), who face a 12-fold higher risk of active TB reactivation than HIV-negative individuals. TB preventive therapy (TPT) is an effective intervention, yet TB/HIV co-infection persists at 40-45%, raising questions about the durability of a single course of TPT. This study assessed the time from TPT completion to TB diagnosis and predictors of early TB reactivation. MethodsWe conducted a retrospective case-only cohort study using routine data from Ugandas electronic medical record system, TB registers, and patient files at three TASO Centres of Excellence (Soroti, Mbale, Tororo). PLHIV on antiretroviral therapy (ART) diagnosed with TB after completing TPT between 2022-2024 were included. Participant characteristics and time to TB diagnosis were summarised descriptively; predictors of early TB were identified using logistic regression. ResultsAmong 670 participants, most were female (464, 69.3%) with mean age 51.6 years (SD 14.5). Newly diagnosed TB accounted for 638 (95.2%), including bacteriologically confirmed pulmonary TB (535, 79.9%), clinically diagnosed TB (123, 18.4%), and extrapulmonary TB (12, 1.8%). Overall, 548 (82.8%) participants were virally suppressed, with most on Dolutegravir-based regimens (641, 95.7%). Early TB occurred in 144 (21.5%), with average time to diagnosis 2.6 years. Multivariable analysis showed care at TASO Soroti was protective (aOR = 0.104, p < 0.001), while clinically diagnosed TB (aOR = 1.91, p = 0.007), shorter ART duration (<5 years: aOR = 3.07, p = 0.001; 5-10 years: aOR = 1.74, p = 0.018), and viral suppression (aOR = 1.87, p = 0.014) increased odds of early TB. ConclusionsTB can occur soon after TPT completion, with one in five PLHIV developing early disease particularly those with shorter ART duration despite viral suppression. Strengthening TB screening, continuous monitoring, and repeat TPT for high-risk groups may improve prevention.

IntroductionHIV testing for children of women living with HIV (WLHIV) is an efficient method of diagnosing HIV in children. We analyzed pooled data from 13 Population-based HIV Impact Assessments (PHIA) conducted from 2015 through 2019 to determine the gap in diagnosing HIV in children of WLHIV. MethodsIn each PHIA, children younger than 15 years in a subset of households were sampled for HIV testing. Mother-reported responses on childs status were linked to maternal interviews and biomarker data. Analysis was restricted to children whose mothers were alive, older than 15 years and aware of their HIV-positive status prior to the survey. We calculated weighted proportions of children who were never previously tested and proportion of children living with HIV (CLHIV) with no evidence of antiretroviral treatment (ART) use (categorized as newly diagnosed). Survey weights were pooled across all PHIAs to account for survey design and nonresponse. ResultsOf 4,234 WLHIV, 3,436 were aware of their HIV status and had at least one child (n=6,173) for whom responses were obtained. Of the 6,173 children, 43.5% (n=2,371) were reported as never been tested. Overall, 5,500 children provided blood for HIV testing during the survey. Newly diagnosed test positivity was 1.7% (90/5,191); 2.9% (61/2,120) among those with reported unknown HIV status and 0.9% (29/3,071) among those with reported HIV negative status. Among children with reported HIV positive status, 94.5% were confirmed by survey testing and of these, 91% had antiretrovirals (ARVs) detected. ConclusionsOver 40% of children of WLHIV who were aware of their HIV positive status had never been tested for HIV. HIV positivity ranged between 0.9% to 2.9% while 9.0% of children known to be HIV positive were not on ART. The study calls for renewed efforts to enhance testing of children and treatment linkage for those diagnosed with HIV.

BackgroundInsecticides remain the cornerstone of mosquito vector control for malaria, dengue, and other mosquito-borne diseases, yet global patterns of deployment and their socioeconomic and environmental drivers are poorly characterized. Understanding where and why insecticides are used is essential for better targeting control efforts and ensuring they are effective, equitable, and efficient. MethodsWe analyzed annual country-level insecticide-use data from 122 countries (1990-2019), reported as standard spray coverage for insecticide-treated nets (ITNs), residual spraying (RS), spatial spraying (SS), and larviciding (LA). Generalized linear mixed models and hurdle models quantified associations between deployment and disease incidence, human development index (HDI), human population density, temperature, and precipitation. Models were evaluated using repeated cross-validation and applied to generate downscaled predictions of insecticide use at subnational administrative region level 2 (ADM2) globally. FindingsInsecticide deployment increased with malaria and dengue incidence, but this response was substantially stronger in higher-HDI countries, indicating that deployment depends on socioeconomic capacity as well as disease burden that leads to weaker scaling in lower-resource settings. Intervention types exhibited distinct patterns; ITN use tracked malaria burden, whereas infrastructure-intensive approaches (e.g., RS and SS) were concentrated in higher-HDI settings and increased with Aedes-borne disease incidence. Downscaled ADM2-level maps uncovered substantial within-country heterogeneity that is obscured at the national scale, highlighting regions where predicted deployment remains low relative to disease risk across sub-Saharan Africa, South Asia, and parts of Latin America. InterpretationGlobal insecticide deployment reflects not only epidemiological need but also economic and logistical capacity, creating mismatches between risk and control. High-resolution mapping can support more equitable allocation of interventions, guide insecticide resistance stewardship, and improve strategic planning as climate and urbanization reshape mosquito-borne disease risk.

Despite substantial progress in preventing mother-to-child transmission (PMTCT) of HIV in Zambia, HIV infection among children whose mothers test HIV-negative represents an understudied phenomenon that may reflect non-vertical transmission pathways. This cross-sectional secondary analysis of the 2024 Zambia Demographic and Health Survey (ZDHS) examined the prevalence and correlates of HIV among children aged 2-14 years whose mothers tested HIV-negative. Children with valid HIV blood test results were linked to their co-resident mothers HIV test results using household-level identifiers. HIV prevalence with 95% confidence intervals was estimated by age group, sex, residence, province, and wealth quintile. Bivariate associations were assessed using chi-square tests and odds ratios. Among 13,960 children of HIV-negative mothers, 69 (0.49%; 95% CI: 0.39%-0.63%; weighted: 0.58%) tested HIV-positive. Prevalence varied substantially by province (p < 0.001), with Copperbelt Province exhibiting the highest burden at 2.97%. Urban children had significantly higher prevalence than rural children (1.10% vs. 0.26%; OR = 3.68, 95% CI: 2.25-6.03, p < 0.001). A paradoxical wealth gradient was observed, with children in richer households showing higher prevalence than those in the poorest households (OR = 4.93, 95% CI: 2.19-11.10, p < 0.001). Maternal education was marginally associated with child HIV status (p = 0.04). Neither child sex (p = 0.10) nor age group (p = 0.29) was significantly associated with HIV positivity. A substantial proportion of HIV-positive children in Zambia have HIV-negative mothers, highlighting important gaps in the current PMTCT-focused paradigm and calling for expanded prevention strategies that address transmission risks beyond vertical transmission.

BackgroundTo promote sustainability and strengthen national ownership of Advanced HIV Disease (AHD) services, a transition was implemented across 22 health facilities in Central Malawi. This transition involved shifting responsibility for key AHD program elements, including clinical service delivery, diagnostics, provider mentorship, and reporting systems, from implementing partner-led implementation to full Ministry of Health (MoH) leadership. This evaluation assessed the impact of this transition on diagnostic coverage, TB preventive therapy (TPT) uptake, and 12-month survival outcomes. MethodsA retrospective cohort study was conducted involving all children and adults enrolled in AHD care during the pre-MoH transition (January 2020-December 2021) and post-MoH transition (January 2023-December 2024) periods. Eligibility followed national AHD criteria: CD4 count <200 cells/mm3, WHO stage 3 or 4 illness, or age <5 years. AHD clients data were abstracted from clinical records and linked across routine facility registers to assess diagnostic and treatment indicators. Kaplan-Meier survival curves, Cox proportional hazards, and Fine and Gray competing risk models were used to evaluate 6 and 12-month mortality and retention as primary outcomes. ResultsA total of 1,044 AHD clients were included (553 pre-transition; 491 post-transition) in the evaluation. Median age increased post-transition (35.9 to 38.5 years, p<0.001). CD4 testing declined (80.7% to 46.0%, p<0.001) testing uptake, while WHO staging and TB diagnostic coverage improved. TB diagnoses decreased (44.5% to 31.2%, p=0.002). TPT uptake dropped from 46.4% to 31.6% (p<0.001). Twelve-month mortality significantly declined from 9.4% to 5.5% (adjusted hazard ratio [aHR]=0.59, 95% CI: 0.37-0.94, p=0.026). Retention in care remained stable (HR=0.86, 95% CI: 0.62- 1.20, p=0.384). ConclusionsTransitioning AHD services to MoH leadership sustained key program outcomes and significantly reduced mortality. Continued mentorship and government ownership were key drivers of success. However, declines in CD4 testing and TPT coverage highlight the need for strengthened diagnostics and preventive care integration. These findings support scaling nationally-led AHD models in high-burden HIV settings.

BackgroundNovel HIV prevention interventions such as long-acting pre-exposure prophylaxis (PrEP) could substantially reduce HIV transmission in Africa. However, efficient implementation in high-prevalence settings where incidence has declined requires an understanding of the contemporary dynamics driving new infections. MethodsWe identified incident HIV cases from a longitudinal, population-based cohort in Uganda. We individually matched cases to HIV-negative controls; traced and enrolled reported sexual partners; and enrolled female sex workers (FSWs) from reported venues. Conditional logistic regression, transmission modeling, and phylogenetics were used to characterize transmission networks. FindingsFrom 2021-2024, 38,899 HIV tests among 22,255 people identified 187 people with incident infections (47.6% male); 164 (88%) were enrolled and matched to 164 HIV-negative controls. Overall, 593 non-sex-worker partners (371 enrolled,62.6%), 146 FSW partners (21 enrolled,14.4%), and 28 venues (208 FSWs enrolled) were reported. Incident infection was most strongly predicted by partnership with a FSW (odds ratio:15.5; 95%CI:3.7-64.8), identified in 43.0% of male cases versus 6.3% of controls. Men with FSW partners had larger sexual networks than men without (median:6 vs 2 partners), and 91.2% of men with FSW partners also had non-sex-worker partners. Transmission modeling attributed 34.4% (95%CI:31.5-36.8%) of all male infections and 80.0% (95%CI:73.2-84.4%) of infections among male clients to sex with FSWs. Oral PrEP use among HIV-negative partners of incident cases was low (8.9% in women; 2.1% in men). InterpretationMen with FSW partners accounted for a substantial share of incident HIV infections and had markedly higher odds of infection than men without such partnerships. Together with the high potential for onward transmission within male client networks, these findings suggest that inclusion of male clients in long-acting HIV prevention strategies could be highly efficient and impactful. FundingNational Institutes of Health, United States; Gates Foundation; National Health and Medical Research Council, Australia

BackgroundThe WHO End TB strategy targets 80% and 90% reductions in TB incidence and mortality, respectively, between 2015 and 2030. ObjectiveWe assess which epidemiologic factors, including existing and new interventions, are most critical to reducing future TB in South Africa. MethodsWe adapted an existing mathematical model of TB and HIV in South Africa. Prior distributions were specified to represent uncertainty ranges for 27 model parameters that are highly uncertain and potentially important in driving future TB dynamics. Latin Hypercube Sampling was used to sample 1000 parameter combinations from these distributions, and the model was projected to 2040 for each. Partial rank correlation coefficients (PRCCs) were calculated to assess correlation between each parameter and average adult TB incidence and mortality rates over 2025-2040. ResultsAdult TB incidence and mortality rates in South Africa are projected to decline by 46% (95% CI: 17-69%) and 54% (95% CI: 21-84%) respectively by 2030, relative to 2015. The parameters most strongly associated with future TB incidence are the increase in microbiological testing in symptomatic individuals due to near-point-of-care/tongue swab (NPOC/TS) testing (PRCC=-0.67), reductions in social contact rates post-COVID (PRCC=-0.61), the probability of sputum testing in symptomatic individuals in the absence of NPOC/TS testing (PRCC=-0.39), and the efficacy of TB preventive therapy (PRCC=-0.35). TB mortality predictors are similar. ConclusionsIncreasing testing among people with TB symptoms, including through new NPOC/TS technologies, is likely to have the largest impact on progress towards End TB goals in South Africa, though attainment by 2030 is unlikely.

Background: People living with HIV (PLHIV) in sub-Saharan Africa exhibit high rates of pneumococcal carriage compared to HIV-uninfected adults, despite antiretroviral therapy. We established a novel controlled human infection model of experimental pneumococcal carriage in people living with HIV to understand carriage dynamics in this at-risk population. Methods: Seventy-five virally suppressed and clinically stable PLHIV and 75 HIV-uninfected controls were inoculated with escalating doses of pneumococcus serotype 6B. Carriage acquisition and density were determined by microbiological culture of nasal wash samples collected before and up to 14 days after inoculation. Adverse events were identified by active and passive surveillance. Participant-reported acceptability was established using a Likert scale. Findings: No serious adverse events occurred. Mild adverse events were similar between groups (19% [14/75] in PLHIV, 13% [10/75] in HIV-uninfected; p=0.505). More than 90% of participants reported acceptability with all study procedures. Experimental carriage occurred in 21% (16/75) of PLHIV compared with 36% (27/75) of HIV-uninfected participants (adjusted odds ratio 0.39 [95% CI 0.16-0.91]). Among PLHIV without detectable cotrimoxazole, 28% (8/29) acquired experimental carriage. Carriage clearance rates were lower in PLHIV (hazard ratio 0.44 [95% CI 0.14-1.42]). Interpretation: In carefully selected PLHIV with effective viral suppression and clinical stability experimental pneumococcal carriage acquisition did not exceed that in HIV-uninfected adults, even after accounting for antibiotic use, natural pneumococcal co-colonisation, and sociodemographic differences. These findings suggest that high carriage prevalence in PLHIV in sub-Saharan Africa may be driven more by prolonged carriage duration than increased susceptibility to acquisition. This model provides a platform to investigate mechanisms underlying carriage susceptibility and impaired clearance in PLHIV and to evaluate interventions aimed at reducing the carriage burden in sub-Saharan Africa. Funding: Wellcome Trust

BackgroundNigeria has experienced its largest recorded diphtheria outbreak since late 2022, centred on Kano State, where facility-based surveillance documented over 18,000 confirmed cases. The true community burden remains unknown. We conducted a population-based household survey to estimate community attack rates, mortality, vaccination coverage, and determinants of infection and death. MethodsWe performed a retrospective household survey (September-October 2024) using spatially randomised cluster sampling (65 clusters, ~15 households each; recall period January 2023 to interview). Survey-weighted analyses, multivariable logistic regression, and sensitivity analyses were used. FindingsWe enrolled 7,998 individuals from 1,068 households. The community attack rate was 1{middle dot}1% (95% CI 0{middle dot}7-1{middle dot}4), 4{middle dot}2 times (2{middle dot}7-5{middle dot}3) higher than facility-based estimates. The case fatality ratio was 8{middle dot}8% (1{middle dot}9-15{middle dot}6) overall and 21{middle dot}3% among children under five; two thirds of deaths occurred at home. Delayed care-seeking of four or more days was associated with markedly higher mortality (risk ratio 32{middle dot}6, 95% CI 2{middle dot}4-450{middle dot}0). Vaccination was strongly protective against death (vaccine effectiveness 57%, 95% CI 34-72%; E-value 4{middle dot}07). Among campaign-eligible children, routine EPI coverage was 58{middle dot}1% and campaign coverage was 52{middle dot}4%; 41{middle dot}9% (95% CI 39{middle dot}0-44{middle dot}9) of eligible children had no evidence of vaccination from either source. InterpretationCommunity diphtheria burden substantially exceeded facility surveillance estimates, with most deaths occurring outside the health system. Delayed care-seeking and low vaccination coverage were the main drivers of mortality, highlighting the need for improved community surveillance, decentralised care, and better-targeted vaccination.

ObjectiveTo evaluate the impact of equity-focused community-engagement initiatives on the uptake of five routine childhood vaccinations. DesignQuasi-experimental study within a synthetic control analysis framework. SettingPrimary care in England between April 2019 and March 2025. Childhood vaccination data were obtained from the Cover of Vaccination Evaluated Rapidly (COVER) programme. InterventionThe Health Equity Liverpool Project (HELP) is a community-engagement vaccination initiative implemented between October 2023 and June 2024 across nine sites in central and north Liverpool. Activities were co-developed with local partners and delivered in neighbourhoods with persistently low childhood vaccine coverage. Intervention practices were defined as those located within 1 km of HELP delivery sites (n=19). A weighted combination of non-intervention practices across England (n=5826) was used to construct a synthetic control group. Main outcomesQuarterly counts of vaccinated children following intervention implementation for first doses of the measles, mumps and rubella vaccine (MMR1 at 24 months and at 5 years), second dose of MMR (MMR2 at 5 years), pneumococcal conjugate vaccine (PCV at 24 months), the 6-in-1 vaccine, covering diphtheria, tetanus, pertussis, polio, haemophilus influenzae type b, and hepatitis B (at 12 months), and the rotavirus vaccine (at 12 months). ResultsFollowing HELP, rotavirus vaccine uptake increased by 10.03% (95% CI 0.37% to 24.63%), corresponding to 120 (95% CI 4 to 295) additional infants vaccinated in the intervention group compared to the synthetic control. Similarly, 6-in-1 vaccine uptake rose by 11.56% (95% CI 2.37% to 25.56% [~]143 95% CI 29 to 317 additional children vaccinated. No statistically significant changes were observed for MMR1, MMR2, or PCV. Improvements were short-lived, with uptakes returning to pre-intervention levels after approximately nine months. ConclusionsCommunity-engagement vaccination interventions may produce a modest short-term improvement in uptake of selected early life vaccines but show limited evidence of benefit for MMR uptake. Our findings suggest that such approaches are unlikely to have a sustained impact without long-term investment, integration into existing immunisation systems and addressing the wider social determinants of health. What is already known on this topic?O_LIChildhood vaccination rates in England have declined over the last decade and inequalities in uptake are persistent andwidening. C_LIO_LIChildren in socioeconomically deprived areas are less likely to receive routine vaccinations, reflecting both structural barriers and vaccine hesitancy driven by misinformation and lack of trust. C_LIO_LIInnovative community engagement interventions are recommended to address these inequalities, yet evidence of their effectiveness remains limited. C_LI What this study adds?O_LIOur study shows that hyperlocal community engagement interventions can increase uptake of early-life infant vaccines (rotavirus and 6-in-1) by around 10-12% but provides limited evidence of similar improvements for the MMR vaccine. C_LIO_LIThe observed improvements in infant vaccines were transient, returning to baseline levels after approximately nine months, suggesting that one-off initiatives may not produce sustained public health gains without tackling wider social determinants of health. C_LI

BackgroundNeonatal disorders such as post-infectious hydrocephalus exhibit a higher incidence in Africa, where the intricate relationships between genetic ancestry, environmental exposures, and other risk factors likely contribute to the increased incidence. MethodsTo start to characterize the common genetic architecture of Ugandan infants, we analyzed genome sequencing data from 1,030 Ugandan infants recruited from studies targeting neonatal sepsis and hydrocephalus. We employed genetic admixture analysis and integrated geospatial data to examine the relationships between genetic backgrounds and disease prevalence within this cohort. ResultsOur results identified four distinct genetic admixture groups, each correlating strongly with specific geographic distributions across Uganda. Notably, a predominance of one admixture group, most common in northern Uganda, was overrepresented in the participants with post-infectious hydrocephalus. ConclusionThis study underscores the importance of genetic factors in disease manifestation at the population level, and a role for such precision public health approaches in complex neonatal disorders in African populations.

Low- and middle-income countries face critical shortages of healthcare workers (HCWs) and funding for human resources for health (HRH), while patients often receive less care time than expected. Understanding how the existing workforce capacity is used is therefore essential for improving health system performance in resource-constrained settings. We examined HCW time-use patterns in Malawi using data from a time-and-motion study conducted between January and May 2024, which recorded activities across multiple cadres, days, and representative health facilities in the healthcare system. Across cadres, median daily working time, including breaks, was 7.35 hours (IQR 4.40-8.35), approximately 1.65 hours below the typical contracted schedule. HCWs spent most time on direct patient care: 2.82 hours per day (IQR 1.89-3.97), accounting for 48% of total working time (IQR 30%-67%). Administrative tasks accounted for 0.30 hours (IQR 0.00-1.23; 5.21%, IQR 0%-18%) and break time remained consistent with the contracted expectations at 1.25 hours (IQR 0.00-2.12; 18%, IQR 0%-28%). Unallocated time, defined as time neither work-related nor recorded as breaks, was 0.72 hours (IQR 0.02-1.92; 12%, IQR 0%-29%), mainly attributed to the absence of patients based on available information. Median patient load was 21 per staff member per day in outpatient care (IQR 12-35), 12 in inpatient care (IQR 7-18), and 14 in emergency care (IQR 10-23), with median time per patient of 3 (IQR 1.0-6.5), 6 (IQR 2.5-14), and 10 (IQR 5-20) minutes, respectively. These measures, particularly time per patient, vary by cadre, facility type, facility ownership, region, and service area. The findings present a first system-wide picture of HCW time use in a low-income setting and can inform health systems planning. The gap between contracted and actual working time and unallocated time suggests scope to improve workforce utilisation, while high patient loads highlight the need for sustained HRH investment and workforce expansion. Key MessagesO_LIIn low- and middle-income countries with persistent health workforce and human resources for health (HRH) funding constraints, it is essential to understand how healthcare worker (HCW) time is utilised in practice to identify opportunities to improve service delivery and overall health system performance. C_LIO_LIBased on a time-and-motion study in Malawi health system, we observed that HCWs worked a median of 7.35 hours per day (including breaks), below the typical contracted schedule. Although most working time was devoted to direct patient care, the patient-facing time was limited relative to high patient loads, with short service time per patient, particularly in outpatient settings. The time-use patterns also varied across HCW cadres, facility types, regions, facility ownership, and service areas. C_LIO_LIWorkforce planning should address both utilisation and capacity: reducing avoidable unallocated time may improve efficiency, but high patient loads and short service time per patient indicate that sustained HRH investment and workforce expansion remain essential. C_LI

Background: Child acute malnutrition remains persistently above emergency thresholds in Chad's Sahelian drylands, with a predictable, but rarely recognized, dry season peak linked to declining pasture and livestock productivity, reduced milk availability and heightened exposure to zoonotic infections. Humanitarian responses remain largely reactive and treatment-focused, with limited evidence on preventive strategies that address drivers embedded in local livelihood systems. We evaluated the effectiveness and return on investment (ROI) of an integrated livestock management intervention designed to prevent the dry-season peak of child acute malnutrition in pastoral and agro-pastoral communities in Chad. Methods: We conducted a cluster-randomised controlled trial in Kanem and Barh-El-Gazel provinces, Chad. Seventy-six villages were randomised (1:1) to intervention or control. Eligible households had at least one child aged 6-59 months and access to milking livestock during the dry season. The intervention (December 2024-June 2025) combined livestock feed supplementation to sustain milk production near households during the dry season, household-level zoonotic risk mitigation, and nutrition counselling. Primary outcomes were the prevalence of global acute malnutrition (GAM) and severe acute malnutrition (SAM) at the dry-season peak (May 2025), assessed in a prespecified random subsample of 52 clusters. All 76 clusters were assessed post-peak (July 2025). Analyses followed an intention-to-treat approach using mixed-effects models. A societal ROI analysis was conducted over six months with projections to 24 months. Findings: At the dry-season peak, 821 children 6-59 months from 521 households were assessed across 52 villages. GAM prevalence was 22.2% in intervention villages versus 47.4% in controls (adjusted OR 0.29 [95% CI 0.18-0.49]; p<0.001), and SAM prevalence was 4.4% versus 19.4% (adjusted OR 0.17 [0.08-0.37]; p<0.001). Intervention households had higher daily milk availability (+588 mL per household; p<0.001), and children consumed more milk (+102 mL per day; p=0.008). Odds of self-reported diarrhoeal disease and acute respiratory infection were substantially lower among children in intervention villages (aOR 0.21 [0.10-0.44] and 0.22 [0.11-0.46], respectively). Post-peak, women's dietary diversity increased (aOR 3.68 [1.90-7.13]), alongside reduced workload, lower household food insecurity and distress livestock sales, improved livestock condition, and a benefit-cost ratio of 5.40 at six months, rising to 16.40 at 24 months. Interpretation: Protecting livestock productivity and sustaining children's access to milk while reducing zoonotic exposure during the pastoral lean season effectively prevents seasonal peaks of child acute malnutrition. This integrated anticipatory action and One Health livelihood-based approach offers a scalable, dignifying, high-return lifesaving preventive model for pastoral and agro-pastoral humanitarian settings.

BackgroundTuberculosis (TB) continues to cause substantial morbidity and mortality, with adults and adolescents carrying the largest burden of disease. Multiple promising novel vaccine candidates are in clinical trials, and their eventual impact will depend on effective implementation strategies. Information on TB vaccine preparedness efforts that could inform coordination remains fragmented. MethodsWe developed the first living and interactive online repository (https://tbvaxrepository.org/) collating completed, ongoing, and planned adult and adolescent TB vaccine preparedness initiatives. Data were obtained through a prior scoping review, direct stakeholder engagement, international conferences, and open calls via social media and partner networks between March 2023-November 2024. Projects were categorized using the World Health Organizations (WHO) framework for TB vaccine preparedness across three thematic areas: availability, accessibility, and acceptability. FindingsBy December 2024, the repository included 90 projects from 119 countries. Most projects focused on health- (47%) and economic modelling (21%), demand and acceptability studies (19%) or implementation feasibility (14%). Most of the projects were situated in India (n=36), South Africa (n=34), China (n=19), Indonesia, (n=17), Kenya (n=17), Brazil (n=14), and Pakistan (n=14). Few initiatives targeted key populations such as people living with HIV, pregnant or lactating individuals, or socially marginalized and occupational high-risk groups. Research on communication strategies for facilitating uptake as part of rollout were absent. ConclusionsThe repository reveals both progress and gaps in global TB vaccine preparedness across WHOs three thematic areas, with particular attention to geographic coverage, and the inclusion of key populations. As novel vaccines for adults and adolescents approach potential licensure, coordinated and inclusive preparedness efforts will be critical to ensure equitable and effective rollout. This repository offers a transparent platform to strengthen collaboration, reduce duplication, and guide strategic planning in a historically underfunded field.

Background: Several large multisite studies have been conducted to describe etiology-specific burden of diarrhea among children in low-resource settings. Here, we combined data across studies to describe geographic and temporal trends in incidence and attributable fractions (AFs) of etiology-specific moderate-to-severe diarrhea (MSD), and to evaluate etiology-specific case fatality ratios (CFRs). Methods: We harmonized case definitions and analytic methods across the Global Enteric Multicenter Study (GEMS), Malnutrition and Enteric Disease (MAL-ED), Vaccine Impact on Diarrhea in Africa (VIDA), AntiBiotics for Children with severe Diarrhea (ABCD), and Enterics for Global Health (EFGH) studies. Cases were 6-35-month-olds with acute MSD. Incidence estimates for GEMS, VIDA, and EFGH were adjusted for enrollment, healthcare seeking, and diagnostic testing. AFs were calculated as the proportion of MSD cases attributed to each etiology, and CFRs were estimated within 14 and 90 days of an MSD episode. Findings: Pre-rotavirus vaccine introduction, rotavirus had the highest incidence and was the leading etiology among 6-11-month-olds, accounting for approximately 22-28% of MSD; the proportion of diarrhea due to rotavirus declined following vaccine introduction, with average AF 10-11% in Africa and Asia. Shigella incidence was highest among 12-23-month-olds and was the dominant etiology among 12-23 and 24-35-month-olds, causing approximately one-third to one-half of MSD. Overall, 90-day mortality declined substantially over time, from 2.21% in GEMS to 0.30% in EFGH. Bacterial (2.52%) and protozoal pathogens (3.55%) had higher average CFRs than viral pathogens (1.42%). Conclusion: Harmonized analysis of five multisite studies reveals consistent evidence that rotavirus and Shigella are the dominant causes of MSD in children under three years in low-resource settings, with burden shifting toward Shigella following rotavirus vaccine introduction.