Transactions of The Royal Society of Tropical Medicine and Hygiene

Background: The World Health Organization proposes that elimination of onchocerciasis transmission (EOT) be verified in 12 endemic countries by 2030. In sub-Saharan Africa (SSA), where most cases occur, Niger is the only country that has been verified to date. Despite decades of ivermectin mass drug administration (MDA), infection persists in West and Central Africa. Alternative treatment strategies (ATS) are necessary to accelerate progress towards EOT by 2030 and beyond. Methods: We used the EPIONCHO-IBM transmission model to project the number of years, from 2026, to reduce microfilarial (mf) prevalence below 1% across 1,634 implementation units (IUs) in 19 SSA countries. We fitted the model to geostatistically-derived mf prevalence in 1975, 2000 and 2018, and projected mf prevalence through to 2025. We classified IUs according to their baseline endemicity, intervention history programmatic performance, and current (2025) MDA frequency (annual or biannual). For those IUs that would not reach < 1% mf prevalence by 2030 if current strategies were continued, we simulated ATS (increasing treatment frequency, improving coverage, and adopting moxidectin MDA) from 2026 to 2040. Results: Of the 1,486 IUs currently under annual ivermectin MDA, 45% would require ATS. In those low-moderate endemicity IUs, biannual ivermectin would have a comparable impact to that of switching to annual moxidectin; in those with high endemicity, adopting biannual moxidectin would be more impactful. Of the 148 IUs currently receiving biannual ivermectin, 24% would benefit from ATS, switching to biannual moxidectin being the best option. Conclusion: This work brings into sharper focus which IU profiles are most likely to require ATS across SSA. In highly-endemic IUs with long intervention histories, biannual moxidectin MDA may be required under our modelling assumptions, with substantial uncertainty surrounding the permanent sterilising effect, of the two drugs under comparison, upon adult female worms. National programmes aiming to reach EOT will have options that need to be balanced against financial considerations. Implementation studies will also be important for translating these modelling projections into national policy decisions, particularly where different intervention strategies generate similar epidemiological benefits. Economic and epidemiological evaluations of repeated moxidectin MDA are needed to inform these decisions.

Background: Sickle cell anaemia (SCA) is characterised by chronic haemolysis, inflammation, platelet activation, and recurrent vaso-occlusive complications. Mean platelet volume (MPV) is a readily available platelet index, but evidence regarding its relationship with disease severity in paediatric SCA remains limited and inconsistent, particularly in African populations. Objective: To evaluate the relationship between MPV and disease severity among children with SCA in Kwara State, North-Central Nigeria. Methods: This hospital-based cross-sectional study included 51 clinically stable children with confirmed SCA consecutively recruited from the paediatric haematology clinic of Children Emergency Specialist Hospital, Ilorin. Complete blood count, including MPV, was performed using a Rayto RT-7600 automated haematology analyser. Disease severity was assessed using a composite clinical and laboratory scoring system based on a previously described method. Pearson's correlation, Spearman's rank correlation, simple linear regression, and the Kruskal-Wallis test were used as appropriate. Statistical significance was set at p < 0.05. Results: Of 51 participants, 14 (27.5%) had mild, 33 (64.7%) moderate, and 4 (7.8%) severe disease. Mean MPV was 9.34 +/- 0.76 fL (range, 8.0-11.2). Pearson's correlation showed a weak positive, non-significant linear relationship with severity score (r = 0.231, p = 0.103), whereas Spearman's analysis showed a weak positive monotonic association (rho = 0.286, p = 0.042). Regression explained 5.3% of severity-score variation (R2 = 0.053, p = 0.103). MPV did not differ significantly across severity categories (H = 2.163, p = 0.339). MPV correlated inversely with haemoglobin (r = -0.556, p < 0.001) and positively with platelet count (r = 0.307, p = 0.029). Conclusion: MPV showed a weak relationship with disease severity but inconsistent statistical evidence across analyses. The limited explained variance and absence of significant differences between severity categories do not support MPV as a standalone severity marker. Larger longitudinal studies are warranted. Keywords: Sickle cell anaemia; Mean platelet volume; Disease severity; Platelet indices; Paediatric haematology; Cross-sectional study; Nigeria.

Background: In malaria-endemic tropical regions, the overlapping coagulopathy in COVID-19 and malaria poses diagnostic and prognostic challenges, particularly with potential sex differences. This study evaluated sex-specific variations in platelet indices and fibrinolytic markers and assessed the utility of Platelet Distribution Width (PDW) and D-dimer in mild/asymptomatic cases. Methods: A case-control study was conducted with 220 participants (55 each in healthy controls, malaria-positive, COVID-19-positive, and COVID-19+malaria co-infected groups), aged 20-65 years, in Port Harcourt, Nigeria. Platelet indices were analysed using Sysmex XP-300 haematology analyser, while D-dimer and fibrinogen were measured by ELISA. Data were analysed using SAS 9.4 with ANOVA, Tukey's HSD, Pearson correlation, and sex-stratified comparisons. Results: PDW was significantly elevated in all infected groups compared to controls (malaria: 15.21 +/- 0.22 fL; COVID-19: 15.21 +/- 0.22 fL; co-infection: 15.61 +/- 0.21 fL vs. control: 13.26 +/- 0.17 fL; F=25.850, p < 0.001). D-dimer levels were highest in the co-infected group (553.42 +/- 59.74 ng/ml, F=2.816, p = 0.040). No significant changes were observed in other platelet indices or fibrinogen across groups. No significant correlation existed between platelet indices and the fibrinolytic markers. Males exhibited significantly higher D-dimer levels across all infected groups (p < 0.05) and higher fibrinogen in COVID-19 subjects (p = 0.036). Sex exerted a stronger influence on parameters than age. Conclusion: Males show heightened fibrinolytic activation in COVID-19 and malaria co-infection. PDW and D-dimer are promising, cost-effective biomarkers for screening mild infections in resource-limited tropical settings.

Background: Public health initiatives increasingly target multiple overlapping high-risk groups to maximize impact. However, a common challenge in modelling these initiatives is to capture these overlapping risk factors, leading to potential misallocation of resources and biased effectiveness estimates. Using China's tuberculosis (TB) control program as an example, this study explores different possible frameworks to account for population heterogeneity and risk overlap. Methods: We examined four risk allocation frameworks: (i) Direct Summation (DS), a simple additive benchmark; (ii) Probabilistic Union Deduplication (PUD), using inclusion-exclusion principles; (iii) Risk population combination (RPC), modeling interaction effects; and (iv) Agent-Based Framework (ABF), a granular microsimulation. To show how these frameworks could be used in epidemiological modelling, we embedded each within a deterministic transmission model of TB epidemiology in China, to simulate the impact of China's National Tuberculosis Strategic Plan (NTSP). We explored each framework when implemented in both static and dynamic versions. We compared them using methodological principles and indicators of intervention cost (screening volume) and benefits (cases/deaths averted). Results: Under the static version, the detection yield of active cases followed a consistent hierarchy: DS > PUD > RPC {approx} ABF. The DS method systematically overestimated yields by double-counting overlapping populations, while PUD corrected for overlap but ignored interaction. The RPC and ABF methods provided the most granular estimates by incorporating Risk population combinations. Additionally, comparing static versus dynamic versions revealed that for the same multi-risk screening framework, mortality reductions remained stable and incidence reductions varied significantly. Conclusion: This study presents potential screening frameworks for overlapping risk populations. The RPC method offers optimal balance of real-world plausibility and computational efficiency. We propose the dynamic RPC method as the preferred tool for routine analysis where multimorbidity and intersectional risks exist, providing a robust evidence base for optimizing resource allocation in heterogeneous populations.

Background Onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus and transmitted by Simulium blackflies, remains a public health challenge in sub-Saharan Africa. Following the transition from vector control to large-scale ivermectin distribution, microfilariae (mf) prevalence has declined substantially across Ghana. The World Health Organization targets onchocerciasis elimination, defined as sustained mf prevalence below 1%. This requires identifying areas of persistent or resurgent transmission to guide targeted mapping surveys and interventions. Methods A Bayesian spatiotemporal, multilevel, generalized additive model with a zero-inflated beta-binomial outcome was fitted to mf prevalence data from 1353 surveys across 671 villages and environmental and socio-economic predictors. Temporal prevalence trends for ecozones within operational transmission zones (OTZ) were modelled using a 2D spatial smooth to account for residual spatial autocorrelation. Temporal autocorrelation in prevalence was accounted for using a random effect for village nested within ecozone. Results Runoff probability and surface wetness were positively associated with prevalence, consistent with Simulium breeding in fast-flowing water. Despite high initial mf prevalence, by 2015 the median prevalence across all OTZs in Ghana was estimated to be between 0.43 and 1.97%. The probability that prevalence was <1% in 2015 ranged from 0.15 to 0.87. Assuming testing rates and mass drug administration have remained consistent (twice a year and >80% coverage), linear extrapolation predicted that the three OTZs have some probability of exceeding the elimination threshold by 2030, while two were predicted to have near-zero prevalence. The Tano-Ankobra OTZ, which includes both savanna and forest agro-ecological zones, was a persistent hotspot. Conclusions This first comprehensive spatio-temporal analysis of onchocerciasis in Ghana reflects the well-documented challenge of onchocerciasis control in forested riverine environments. Persistent transmission foci in eastern and southern Ghana, particularly in forest zones with sustained vector habitat, warrant targeted investigation and intensified intervention to meet WHO elimination thresholds.

Abstract Introduction Onchocerciasis is targeted for elimination with community-directed treatment with ivermectin (CDTI). Alternative strategies are needed in areas where transmission persists despite long-term CDTI and/or are co-endemic with loiasis. This study assessed the efficacy of 35-day treatment with 100mg doxycycline on Wolbachia density at 6 months and microfilaridermia and palpable nodules at 30 months post-treatment. Methods A treatment follow-up study was conducted in 20 high-transmission onchocerciasis communities in a co-endemic loiasis area of South-West Cameroon. Community-based directly observed treatment with 100mg doxycycline was administered to community members aged [&ge;]9 years. Wolbachia clearance at 6-months and treatment efficacy on microfilaridermia and palpable nodules were assessed at 30-months post treatment. Factors associated with reductions in microfilaridermia post treatment, including adherence to doxycycline treatment were assessed with mixed-effects logistic regression. Results Over 92% (2835/3080) of eligible participants took 35 days of 100mg doxycycline over 5 or 6 weeks. This regimen achieved a 62.8% microfilaridermia reduction and 99% palpable nodule reduction in the 720 participants included at follow-up. Wolbachia depletion was observed in 92% of skin samples at 6 months post treatment. The most important factor associated with microfilaridermia after 30 months was having missed at least 7 doxycycline consecutive doses (OR 3.11, 95%CI: 1.17-8.26). Incomplete treatment to a lesser extent was not associated with reduced efficacy at follow-up. Conclusion This large-scale community intervention shows that a 5-week treatment with 100mg doxycycline is feasible and has high curative efficacy against adult O. volvulus as measured by the dramatic reduction in the proportion of palpable nodules at 30-months post treatment. The high efficacy shows the tremendous potential of anti-Wolbachia drugs as part of the arsenal for onchocerciasis elimination and paves the way for the next generation of anti-Wolbachia drugs with shorter treatment courses, which will facilitate the implementation of alternative strategies to accelerate onchocerciasis elimination.

Wolbachia-mediated incompatible-insect technique (IIT) via wAlbB, wMel or wPip/wAlbA/wAlbB strains are promising approaches for suppressing wildtype Aedes mosquitoes and therefore Aedes-borne diseases. Yet, the effectiveness of this technique under climate change remains uncertain. Here, we evaluate the long-term robustness of male Wolbachia-infected mosquito releases to suppress wildtype Aedes aegypti and Ae. albopictus populations across future climate scenarios across diverse geographical regions. We compiled large publicly available datasets on Aedes abundance across Singapore, China, the European Union and the United States, historical and projected climatic conditions in these regions and conducted experiments to test the thermal stability of cytoplasmic incompatibility in Wolbachia-infected male Aedes aegypti and albopictus. A climatically-driven entomological model was developed and calibrated using a Bayesian approach to model observed Aedes population dynamics and infer area-specific climate-driven variation in mosquito life-history traits. We back-inferred historical mosquito abundance and projected mosquito abundance in future climate change scenarios incorporating experimental and locally inferred entomological parameters and then simulated the counterfactual implementation of IIT in these regions. We find that Aedes populations are projected to increase in most regions across all climate change scenarios from 2050-2100 even under high heat conditions in the absence of interventions. While we found that IIT can suppress wild-type populations effectively across all future scenarios and in high heat conditions, effectiveness was found to depend heavily on mosquito emigration rates, overflooding ratios, release intervals and release strategies Extensive robustness checks confirmed that the model reproduced historical temporal trends, captured the influence of individual parameters on outcome and was sensitive to changes in values of inferred parameters and implement policy. These findings demonstrate that IIT may be a robust vector control tool under future climate conditions.

Background On the Zanzibar islands, Tanzania, mass drug administration (MDA) with praziquantel against Schistosoma haematobium infections has been implemented regularly since the early 2000s. Elimination of schistosomiasis as a public health problem has been achieved in most areas, with the goal of interruption of transmission. The RESIST project investigates the extent to which MDA-driven selection for praziquantel resistance is occurring and contributing to persistent transmission hotspots. Methodology As part of RESIST, the efficacy of praziquantel treatment was assessed in two schools on Pemba between October 2024 and March 2025. Longitudinal parasitological surveys were conducted before and two weeks after school-based MDA with praziquantel (40 mg/kg). Up to six urine samples per study participant were collected on different days pre- and post-MDA and examined for S. haematobium eggs by urine filtration microscopy. In a per-protocol analysis, drug efficacy was categorised as adequate, inconclusive, or reduced, based on hypothesis testing. A generalized linear mixed model was used to assess the association between pre-MDA infection intensity and drug efficacy at the individual level. Principal findings Pre-MDA, S. haematobium prevalence was 14.3% (62/434) in School 1 and 37.8% (233/617) in School 2. Post-MDA prevalence was 0.5% (2/434) and 9.6% (59/617), respectively. Egg reduction rates were 99.8% (90% confidence interval (CI): 99.2-100%) in School 1 and 94.8% (90% CI: 88.6-98.6%) in School 2, which were classified as adequate and inconclusive, respectively. In School 2, drug efficacy at the individual level was negatively associated with pre-MDA infection intensity. Conclusion/significance The efficacy of praziquantel on Pemba remains higher than the 90% threshold for optimal drug efficacy set by the World Health Organization. While the inconclusive efficacy results for School 2 can at least partially be explained by the variation in the participants pre-MDA infection intensities, further investigations are warranted to account for the disparity in praziquantel efficacy on Pemba. Trial registration: ISRCTN, ISRCTN59331501. Registered 24 October 2024, https://www.isrctn.com/ISRCTN59331501.

In 2026, a Bundibugyo ebolavirus (BDBV) outbreak emerged in the Democratic Republic of the Congo (DRC), with 4,566 confirmed cases and 2,128 deaths reported as of 11 August, potentially becoming the largest Ebola outbreak on record globally. We developed a susceptible-exposed-infectious-deceased-recovered (SEIDR) model incorporating incorporating three categories of interventions, public self-protection, safe burial, and treatment and convalescence, to assess early transmission dynamics, the current epidemic trajectory, and cross-border spillover risk, and to inform the formulation of control strategies. Based on cumulative confirmed case data up to 31 July, sensitivity analyses across multiple candidate start dates identified 28 March as the optimal start date of sustained transmission, with 31 March to 3 April as the most likely onset window. As of 31 July, the basic reproduction number (R0) was 1.83 (95% CI: 1.81-1.84). When 58.12% of the susceptible population adopted protective behaviours, the transmission chain could be effectively interrupted. By integrating the non-dominated sorting genetic algorithm II (NSGA-II) with Pontryagin's minimum principle (PMP), we derived a time-varying optimal control strategy, with adjustments every two weeks, that could shorten the epidemic duration by approximately 7 months. Using International Migrant Stock data and Facebook IP-based mobility data with the Prophet forecasting model, we assessed spillover risk. Four countries were identified as very high risk at the end of July. Compared with the status quo scenario, the optimised control strategy could substantially reduce global importation risk. Enhanced entry screening and preparedness are warranted in neighbouring countries of the DRC in Africa, France in Europe, and Canada in North America.

Summary Background Persistent transmission from relapsing Plasmodium vivax infections threatens malaria elimination programs in the Asia-Pacific and Americas. Tools to identify people at risk of relapse are urgently required. We aimed to validate a panel of eight P. vivax serological biomarkers for predicting future relapses. Methods In this observational study, soldiers returning from malaria-endemic Papua to non-endemic East Java, Indonesia, were screened at enrolment using antibody measurement (Luminex) and trained random forest classification algorithms, then followed for 6 months. Active case detection was performed fortnightly by microscopy. Algorithms classified soldiers as recently infected (last nine months) and thus at risk of relapse, based on anti-vivax antibody measurements at enrolment. Findings Between December 2018 and July 2022, 592 soldiers were enrolled, with 553 completing follow-up; 119 experienced a P. vivax relapse. Of these, 102 were correctly classified as at risk of relapse at enrolment, corresponding to 86% sensitivity and 86% specificity, with an AUC of 0.92. Interpretation P. vivax serological biomarkers can identify people at risk of relapse with high sensitivity and specificity and could be used as a novel public health intervention, P. vivax serological testing and treatment (PvSeroTAT), to reduce relapse-driven transmission.

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

BackgroundMalaria caused by Plasmodium knowlesi and lymphatic filariasis caused by Brugia malayi are mosquito-borne infections with non-human primates as reservoirs. P. knowlesi has emerged as a significant cause of human malaria in Southeast Asia over the past two decades. Belitung district, Indonesia, was until recently assumed to have eliminated B. malayi until infections were detected in humans and long-tailed macaques. To investigate whether the local reservoir of B. malayi is also a reservoir for malaria we screened macaques from 4 areas in Belitung for malaria parasites. Methods and findingsBlood samples from 163 long-tailed macaques (Macaca fascicularis) that had been tested for B. malayi were examined by quantitative PCR assays specific for Plasmodium spp., P. knowlesi, P. inui, P. coatneyi and P. cynomolgi. A total of 130 macaques (79.8%) tested positive in the pan-Plasmodium qPCR assay. Plasmodium inui was most prevalent (41.7%), followed by P. knowlesi (38.7%), P. coatneyi (24.5%) and P. cynomolgi (13.5%). Multiple species infections, with 2-3 Plasmodium species were detected in 37% of macaques. Notably, 20 (91%) of 22 B. malayi-positive macaques were co-infected with at least one Plasmodium species. We sequenced the complete mitochondrion from 9 samples diagnosed by qPCR as mono-infections. Phylogenetic analysis confirmed 7 as P. knowlesi, and the other two as P. inui and P. coatneyi. Phylogenetic and pairwise analysis revealed that P. knowlesi isolates from Belitung were closely related to each other and to P. knowlesi from humans and monkeys from Thailand, Malaysia and Indonesia. ConclusionsMolecular evidence shows high prevalence of zoonotic malaria parasites in macaques from Belitung, emphasizing the risk of human transmission. Increased surveillance, improved diagnostics, and targeted interventions are needed to prevent zoonotic spillover of P. knowlesi as it has been observed for B. malayi in Belitung. Author summaryWe examined macaques for Plasmodium parasites in Belitung Island, Indonesia, a region classified as free of locally transmitted human malaria. Plasmodium knowlesi is a monkey parasite that commonly infects humans and has emerged as a concern in Southwest Asia over the last 20 years. In Belitung, macaques are infected with Brugia malayi, a filarial nematode, that causes lymphatic filariasis in humans. Blood samples from 163 macaques were screened for Plasmodium DNA and 80% carried malaria parasites. Plasmodium inui was most common, followed by P. knowlesi, P. coatneyi, and P. cynomolgi. Many macaques were infected with multiple parasites simultaneously, but no host was infected with all four Plasmodium species. Ninety one percent of B. malayi-positive macaques were co-infected with malaria parasites, including P. knowlesi, indicating multi-parasite infections that could potentially spread to humans. Analysis of the mitochondrial genome of 7 P. knowlesi isolates from Belitung showed that they were most similar to each other and both human and monkey samples from Malaysia, Thailand and Indonesia. The study highlights the need for enhanced malaria monitoring and prevention, given the complex epidemiology of co-infecting parasites and risk to humans and animals.

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

Background: Vaccination with rVSV-ZEBOV is highly effective against Zaire ebolavirus, but protection against Bundibugyo ebolavirus (BDBV) is unknown. We used a stochastic network model of the 2026 Democratic Republic of the Congo BDBV outbreak to evaluate the potential impact of a partially cross-protective vaccine under operationally realistic conditions. Methods: We developed a susceptible-exposed-infectious-recovered model on a two-layer household-community contact network calibrated to public data through July 5, 2026. The model incorporated stochastic detection, isolation, first- and second-degree contact tracing, reactive ring vaccination, and community vaccination. Base-case vaccine efficacy was 45% and included post-exposure protection against disease and mortality, with time to protection modelled as a continuous sigmoidal function. Sensitivity analyses varied vaccine efficacy, timing, case detection, and contact tracing. Findings: Increasing case detection from 30% to 70% and contact tracing from 30% to 80% reduced deaths by 59.8% (IQR 54.6-65.0) compared with base operations without vaccination. Adding reactive ring vaccination reduced deaths by 65.5% (IQR 59.1-71.2) versus base, but by 13.6% (IQR -3.2 to 27.9) versus enhanced operations alone. Community vaccination at 20-80% coverage reduced deaths by 47.1-91.0%. With 50% community coverage, mortality reduction declined from 86% at outbreak declaration to 58% with a 14-day delay. Ring vaccination impact was sensitive to immune-onset timing, with incremental mortality benefit declining from 23% to 10% as the assumed immune-onset midpoint increased from 5 to 14 days. Interpretation: Strengthening case finding and contact tracing is central to mortality reduction in BDBV outbreak response. If rVSV-ZEBOV provides clinically meaningful cross-protection against BDBV, reactive ring vaccination could provide a measurable but modest incremental benefit when operations are already strong. Larger mortality reductions require vaccination that reaches susceptible individuals before exposure, which is more consistent with rapid community vaccination in affected areas.

Introduction: Household contacts (HHCs) of pulmonary TB patients remain at high risk for TB infection and disease progression, yet many remain asymptomatic and are missed by symptom-screening pathways. While India expanded its TB preventative guidelines to include all HHCs in 2021, chest X-ray (CXR) screening continues to be used selectively, representing a missed opportunity in early case detection. Methods: The analysis uses programmatic data from Project JEET 2.0 (Joint Effort for Elimination of Tuberculosis), implemented by the William J. Clinton Foundation in India, between October 2021 and March 2024. Eligible HHCs (>=5 years) were offered CXR screening as part of TB preventive therapy (TPT) evaluation. Descriptive and multivariable analyses examined predictors of CXR uptake and TB yield. A two-stage logistic regression model estimated potential TB yield under universal CXR coverage. Model performance was evaluated using the area under the curve (AUC), and bootstrap simulations generated counterfactual estimates of missed TB cases. Results: Among 1,034,621 HHCs, 1.02% individuals were found positive for TB, which includes 7,786 HHCs who were on TB treatment already, while an additional 2,812 were identified during pre-TPT evaluation. Among eligible HHCs (n = 1,026,835), 70% were screened with CXR, of which 2.4% had suggestive TB findings. Of these, 79% went for further TB assessment. Symptomatic HHCs were more likely to be CXR screened (84% vs 69%) and assessed for TB, yet two-thirds of all detected TB cases were asymptomatic. It is estimated that universal CXR coverage and TB testing for suggestive cases can increase TB detection by at least 87%. Conclusion: The study provides a scalable approach to expand CXR coverage through public-private partnerships, enabling early TB detection among HHCs, especially among asymptomatic contacts. Future implementations will benefit from integrating AI-enabled reading, along with systematic follow up for those with suggestive findings.

BackgroundIvermectin, a widely used endectocide with activity against Anopheles (An) mosquitoes, has emerged as a promising complementary tool for malaria vector control. However, currently approved oral formulations provide only short-lived plasma concentrations at mosquitocidal levels, thereby limiting their operational impact. To overcome this limitation, a long-acting injectable formulation based on ivermectin and BEPO technology (mdc-STM-001) was selected through laboratory screening using mosquito colonies. This formulation demonstrated mosquitocidal efficacy meeting WHO criteria, with a hazard ratio (HR) >4 maintained for at least two months. The present study aims to further characterize the efficacy of ivermectin under robust field conditions and to expand susceptibility assessments to wild Anopheles populations representing different species and vectorial status. Ivermectin was tested in cattle at two doses under field conditions using experimental huts and tent traps. Plasma drug levels were also monitored to characterize the pharmacokinetic profile of ivermectin. MethodsThirty-six calves were involved in the study and allocated to three groups (n = 12 per group). The mdc-STM-1.0 group received a single subcutaneous injection of the long-acting ivermectin formulation mdc-STM-001 at a dose of 1.0 mg/kg; the mdc-STM-1.5 group received the same formulation at 1.5 mg/kg and the third group served as controls. Using a three-arm design, cattle from each treatment group were simultaneously exposed to mosquitoes in experimental huts and tent traps, following a Greco-Latin Square rotation to minimize positional confounding factors. Pharmacokinetic data were collected to assess ivermectin release from the subcutaneous depot. Correlations between plasma ivermectin concentrations and mosquito mortality were explored, and survival analysis including Kaplan-Meier and cox proportional hazards models were performed to assess the effect of treatment on mosquito survival. ResultsThe mdc-STM-001 formulation was well tolerated and produced sustained, dose-dependent plasma ivermectin concentrations, with detectable levels maintained for more than 90 days after a single administration. Both doses induced strong mosquitocidal activity against wild Anopheles, with hazard ratios reaching 8.03 and 16.47 for the 1.0 and 1.5 mg/kg doses, respectively. An. funestus and An. rufipes were the most susceptible species (LC50: 5.1-6.9 ng/mL) exhibiting prolonged LC50 coverage (>75 days), whereas An. coustani was less susceptible (LC50: 12.4-19.2 ng/mL) resulting in a shorter duration of effective coverage (17-41 days). ConclusionsTaken together, our results revealed the potential of the mdc-STM-001 long-acting ivermectin formulation as an effective endectocide against residual malaria transmission by primary and secondary vectors and establish evidence basis to support its progression to early-phase clinical trials in humans.

Background: Human Tungiasis is a neglected tropical skin disease caused by the sand flea Tunga penetrans, associated with pain, inflammation, secondary bacterial infections, and significant morbidity. Despite its health impact on school children, it remained understudied in Kamushoko Parish, Bubaare Sub-County, Mbarara District, Uganda. Objectives: To determine the prevalence and identify associated factors of human Tungiasis among primary school children in Kamushoko Parish, Bubaare Sub-County, Mbarara District. Methods: A school-based cross-sectional descriptive study was conducted among 415 primary school children (P1-P7) at Katooma II and Komuyaga Primary Schools in March 2026. A census sampling approach enrolled all eligible pupils. Data were collected through structured face-to-face questionnaires and clinical examination of exposed areas. Tungiasis diagnosis was based on clinical identification of characteristic lesions with microscopic confirmation of extracted specimens. Bivariate and multivariate logistic regression analyses identified independently associated factors. Results: Of 415 children examined, 22 had active Tungiasis lesions, yielding an overall prevalence of 5.3% (95% CI: 3.53%-7.90%). Katooma II Primary School recorded a slightly higher prevalence (6.29%) than Komuyaga Primary School (4.78%), though the difference was not statistically significant (p = 0.499). Male children had higher odds of infection than females (7.1% vs. 3.7%). Children aged 9-10 years had the highest prevalence (7.7%). In the multivariate logistic regression, walking barefoot at school was the only independently significant predictor of infection (aOR = 0.18 for home vs. school; 95% CI: 0.04-0.78, p = 0.022). Conclusion: The prevalence of Tungiasis among primary school children in Kamushoko Parish was 5.3%, confirming ongoing transmission in the community. Walking barefoot at school was the only independent predictor of infection, highlighting the school environment as a critical intervention site. School-based strategies including grounds improvement, routine classroom cleaning, enforcing no-barefoot policies, and health education are recommended.

Background Accelerated efforts to eliminate lymphatic filariasis (LF) as a public health problem have been supported by the introduction of the triple-drug regimen of ivermectin, diethylcarbamazine and albendazole (IDA) in endemic settings. In Sao Tome and Principe, nationwide mass drug administration (MDA) with diethylcarbamazine and albendazole was implemented in 2018, followed by IDA in 2019 and 2020. This study assesses progress towards elimination using post-MDA impact assessment surveys conducted after cessation of treatment. Methods Cross-sectional surveys were conducted among adults aged 20 years and older in 2022 and again between December 2024 and January 2025. Circulating filarial antigen (CFA) was detected using the filarial test strip (FTS). Individuals who tested positive were examined for microfilaremia using nocturnal calibrated thick blood smear microscopy. Additionally, programme data on MDA coverage and morbidity were obtained from national surveillance records. Results Three rounds of nationwide MDA achieved high epidemiological coverage (86.4% in 2018, 74.2% in 2019 and 80.0% in 2020). The impact assessment surveys conducted in 2022 evaluated 14 132 adults, with 21 individuals (0.15%) testing positive for CFA, while the follow-up survey conducted between December 2024 and January 2025 assessed 14 653 adults and detected seven positive cases (0.05%). No microfilariae were detected among the 28 antigen-positive individuals examined using nocturnal calibrated thick blood smears. National morbidity records documented 190 cases of lymphoedema and nine cases of hydrocoele. Conclusions Infection indicators remain well below WHO decision thresholds, suggesting that LF transmission is unlikely to be sustained. Sao Tome and Principe appears to be close to eliminating LF as a public health problem. However, strengthening morbidity management services will be essential to support the preparation of the national elimination dossier.

The persistence of Plasmodium vivax is driven by the hidden reservoirs of infection, presenting a key obstacle to elimination. Antibodies persist after asexual infections are cleared from peripheral blood and therefore can indicate current and recent past infections. Here, we present a machine learning algorithm that classifies recent P. vivax infections using serological markers to identify likely hypnozoite carriers. Using serological measurements from year-long observational cohort studies conducted in three low-transmission settings (including negative controls, N=2,635), we selected optimal subsets of markers by balancing sero-diagnostic performance against assay complexity and scalability. We initially trained a random forest classifier and then subsequently we compared several machine learning classifiers. Tree-based methods consistently performed best, although differences were marginal. An online R Shiny application (PvSeroApp) was developed to automate data processing, quality control, and serostatus classification. This algorithm underpins the P. vivax serological testing and treatment (PvSeroTAT) strategy, enabling targeted anti-hypnozoite therapy and strengthening elimination efforts.

The 17th Ebola outbreak in the Democratic Republic of the Congo, announced on 15 May 2026, was attributed to Bundibugyo ebolavirus (BDBV). Although case isolation is the main control strategy, its effectiveness is compromised when patients escape isolation facilities before recovery. Between 14 May and 17 June 2026, 175 individuals reportedly left isolation facilities without formal discharge across Ituri Province. We assessed how this "isolation leakage" affects community transmission. We refined the SEIHFR framework to distinguish undetected community infections, detected but not-yet-isolated cases, isolated individuals, leakage, funeral-associated transmission, and removals. Using Bayesian inference, we fitted the model to daily Ituri surveillance data, escapee counts, and isolation census records. We estimated the leakage rate, reporting and detection probabilities, and the transmission rate, while fixing other parameters based on the BDBV literature. The model reproduced confirmed cases, deaths, discharges, and escapees. We estimated R_0=3.67 (95% HDI: 2.0-5.7), a leakage rate of {rho} {approx} 0.034 day^-1 (0.022-0.051), and high contact-tracing-driven detection (p_d {approx} 0.91-0.99). Leakage increased the detection-dependent reproduction number [R](p_d) from approximately 3.2 to above 5. Eliminating leakage reduced cumulative infections by about one-third, from 1,120 to 764, while the minimum detection level required for control increased from p_d [&ge;] 0.73 without leakage to p_d [&ge;] 0.87 at the fitted leakage rate. Shortening time to isolation prevented the most infections (73.4%; 59-84), followed by reducing leakage (29.7%; 14-52) and re-isolating escapees (12.6%; 6-24). Delaying leakage reduction until week 4 reduced its benefit from about 27% to below 2%. Isolation leakage represents a major transmission pathway that has until now gone largely unmeasured. While rapid initiation of isolation is highly beneficial, it cannot compensate for permeable isolation; therefore, early, community-driven efforts to control leakage, embedded within a multilayered response, are critical.