PLoS Neglected Tropical Diseases[JOURNAL]
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200 papers
Severe visceral leishmaniasis in Ethiopia: Outcomes, co-infections and mortality in a prospective real-world cohort.
Ayele E, Henten SV, Ayalew DG … +21 more , Atnafu S, Mereed AE, Yohannes H, Mekonnen T, Bogale T, Mossa A, Legese GL, Yasin J, Berens-Riha N, Pham TT, Boodman C, Mondelaers A, Adriaensen WJ, Abdellati S, Diro E, Mohammed R, Alves F, Asres MS, Pareyn M, Kassa M, Griensven JV
PLoS Negl Trop Dis · 2026 Jun · PMID 42247476 · Full text
BACKGROUND: Visceral leishmaniasis (VL) remains a major public health challenge in East Africa, particularly in Ethiopia. Clinical trials on VL often exclude patients with severe comorbidities or laboratory abnormalities...
BACKGROUND: Visceral leishmaniasis (VL) remains a major public health challenge in East Africa, particularly in Ethiopia. Clinical trials on VL often exclude patients with severe comorbidities or laboratory abnormalities, limiting the generalizability of evidence used to guide real-world management. We comprehensively characterised the clinical profile, treatment outcomes, and mortality of VL patients treated in a referral centre. METHODOLOGY AND PRINCIPAL FINDINGS: This prospective cohort study enrolled patients at the Leishmaniasis Research and Treatment Center (LRTC), University of Gondar (02/2023-06/2024). All VL cases fulfilling eligibility criteria underwent detailed clinical, laboratory, and radiological assessments. VL treatment followed WHO guidelines. Outcomes, adverse events, and supportive care measures were recorded during treatment and over a 12-month follow-up period. Patients meeting at least one exclusion criterion (e.g., comorbidities, clinical signs of severe VL) of standard phase III VL treatment trials were defined as trial-ineligible patients and compared with trial-eligible patients. A total of 314 VL patients, mostly young adult males (median age 22 years), were enrolled. Of these, 21 (6.7%) had HIV co-infection; 204 (65%) met ≥ 1 key exclusion criterion typically used in VL clinical trials. Trial-ineligible patients had high parasitemia, more concurrent infections, more pronounced clinical and laboratory abnormalities and a higher need of supportive care measures including systemic antibiotics and blood transfusion. Overall cure rate was 90.1%. Mortality after the first VL treatment course was 6.4%, ranging from 1.8% in trial-eligible patients to 8.8% in trial-ineligible patients. Leading causes of death included severe bacterial infections, acute liver failure and haemorrhagic complications. CONCLUSIONS: These findings underscore the severity and complexity of VL in routine care in our study population, and highlight the limitations of current trial populations to inform broader clinical practice. Strengthening supportive care and expanding research inclusivity designed to respond to the needs of this patient population are critical to achieve VL elimination targets.
A systematic mapping review of therapeutic clinical trials in dengue.
Huyen TB, McBride A, Thein TL … +14 more , Le KM, Luu T, Huy NQ, Harriss E, Kain MJW, Cattrall J, Naylor C, Chanh HQ, Vuong NL, Munblit D, Chia PY, Lam PK, Watson JA, Yacoub S
PLoS Negl Trop Dis · 2026 Jun · PMID 42247469 · Full text
BACKGROUND: Dengue is a growing public health threat with increasing case numbers globally. Despite the substantial burden, there are no licensed therapeutics for patients with dengue. To inform the design of large-scale...
BACKGROUND: Dengue is a growing public health threat with increasing case numbers globally. Despite the substantial burden, there are no licensed therapeutics for patients with dengue. To inform the design of large-scale practice-changing clinical trials and to assess the feasibility of an individual patient data platform for meta-analysis, we conducted a systematic mapping review of clinical trials evaluating dengue therapeutics. Our aims were to characterise published and registered dengue therapeutic trials, describe their endpoints, and assess study design quality and internal validity to inform feasibility of meta-analysis and future research. METHODS: We systematically searched Ovid MEDLINE, Ovid EMBASE, WHO ICTRP and ClinicalTrials.gov for prospective clinical trials evaluating therapeutics in patients with symptomatic dengue. Two independent reviewers screened records using Covidence. Data were extracted into a REDCap database, and risk of bias was assessed using the ROB-2 and ROBINS-I tools to describe trial design rigour. Descriptive analyses summarised the interventions, trial characteristics, study populations, and primary endpoints. This systematic review was pre-registered with PROSPERO (CRD42023469022). RESULTS & DISCUSSION: A total of 121 clinical studies were identified, comprising 72 published trials and 49 registered but unpublished studies. Interventions were categorised according to the authors' proposed mechanism of action: antiviral (n = 10), host-directed (HDT, n = 34), supportive (n = 31), or undefined (n = 46). Aside from the studies of supportive therapies (n = 31) and unpublished studies (n = 37) which were only reviewed for their primary outcomes, 53 publications remained for review of therapeutic efficacy. Methodological concerns were common - 24 of 53 published trials (45%) were classified as having high or critical risk of bias. Corticosteroids were the most frequently evaluated intervention, involving a total of 944 randomised patients. The primary endpoints used in both antiviral and HDT trials were highly heterogeneous, limiting comparability. The combination of methodological concerns and non-standardised endpoints precluded meta-analysis for any intervention. No single treatment had sufficient or consistent evidence to support recommendations for use in clinical practice. CONCLUSIONS: Our findings highlight a remarkably sparse evidence base for dengue therapeutics and a lack of standardised, clinically meaningful endpoints. These factors have hindered progress in evaluating candidate treatments and limited the potential for individual patient data meta-analyses. Large, high-quality trials - powered for harmonised and clinically relevant endpoints - are urgently needed to advance the development of effective therapies for dengue.
An intuitive sampling framework for setting-specific decision-making in soil-transmitted helminthiasis control programs.
Kazienga A, Levecke B, de Vlas SJ … +1 more , Coffeng LE
PLoS Negl Trop Dis · 2026 Jun · PMID 42247466 · Full text
BACKGROUND: We recently developed a general egg count framework to support cost-efficient survey design choices to inform soil-transmitted helminthiasis (STH) control programs. Yet, the interpretation and the application...
BACKGROUND: We recently developed a general egg count framework to support cost-efficient survey design choices to inform soil-transmitted helminthiasis (STH) control programs. Yet, the interpretation and the application was not always intuitive for program managers. METHODS: We first adapted the existing framework to make the interpretation of risks of incorrect decision making more intuitive and to allow for prior information. Then, we assessed the impact of the allowable risk of incorrect decision-making and prior information on the required sample size. Finally, we determined the most cost-efficient survey design to inform the decisions (i) to switch to an event-based deworming program, and (ii) to declare STH eliminated as a public health problem (EPHP). PRINCIPAL FINDINGS: The required sample sizes increased when the allowable risk of incorrect decision reduced and when the mean prior approached the program prevalence threshold. For the decisions to switch to event-based deworming and to declare EPHP, we found that duplicate Kato-Katz thick smears on a single stool sample was the most cost-efficient survey design, particularly when accounting for the added benefits of the free internal quality control. The required sample size for these survey designs varied between program targets and STH species. When aiming to have one sample size that fits all STHs, we recommend sampling 6 schools and 56 children per school for decisions on switching to event-based control programs and 11 schools (74 children per school) for the decision to declare EPHP. CONCLUSIONS/SIGNIFICANCE: We developed an intuitive sampling framework for setting-specific decision-making in STH control programs. We identified the most cost-efficient survey designs for critical program decisions, but these are based on subjective but reasonable choices regarding the risk of incorrect decision making. Reaching consensus within the STH community on acceptable levels of risk is crucial to further support evidence-based decision-making.
Development of a deep learning based framework for classification of Indian venomous snakes integrated with explainable artificial intelligence for primary and emergency care providers.
Manna IIA, Wagle U, Balaji B … +4 more , Lath V, Sampathila N, Upadya P S, Sirur FM
PLoS Negl Trop Dis · 2026 Jun · PMID 42247465 · Full text
BACKGROUND: Snakebite envenoming is a significant global health crisis that has been long neglected as a global health priority. It is a huge problem for rural communities of low and middle-income countries, India accoun...
BACKGROUND: Snakebite envenoming is a significant global health crisis that has been long neglected as a global health priority. It is a huge problem for rural communities of low and middle-income countries, India accounts for the largest proportion of snakebite deaths globally. Timely identification of venomous snakebite and its syndromic pattern is essential for effective administration of antivenom and supportive treatment. Expert identification of snake species and syndromes is not always available in peripheral healthcare settings. This leads to delays, unnecessary referrals, or improper treatment choices. Additionally, diverse snake species distribution and venom variations across regions pose challenges. AI-powered image classification methods can help overcome these barriers. We propose a clinically oriented deep learning pipeline for binary classification of venomous and non-venomous snake species of India using real-world imagery data. This pipeline would serve as a baseline step towards aiding snakebite management at peripheral healthcare setups with scarce resources. METHODS: The selected dataset consisted of 20 medically important Indian species. MobileViT-S, ConvNeXt-Tiny, EfficientNet-V2-S and ResNeXt-50 (32 × 4d) were trained under same conditions for comparison of results. Model interpretability was evaluated using Grad-CAM ++ to ensure that classification was not performed based on background but on features like head shape and stripes present on body. For reliable implementation we connected it to a web interface with human in loop expert verification. Experts can confirm or override predictions in real time. RESULTS: Among the evaluated architectures, ResNeXt-50 (32 × 4d) showed the most reliable and consistent performance in classifying venomous and non-venomous snakes. It achieved the highest test accuracy, sensitivity, specificity, and F1-score. The model also had strong discriminative ability, with a ROC-AUC of 0.9950 and PR-AUC of 0.9959. These results indicate dependable performance in safety-critical screening situations. Grad-CAM++ visualizations confirmed that predictions were based on anatomically relevant features, especially in the head and body contour areas. This supports model interpretability and reduces background bias. CONCLUSIONS: Although the dataset size and single-institution source limit how widely the results can be applied, the proposed framework shows that it's possible to create a clinically oriented, ready-to-use deep learning system for snakebite triage support. This system is intended as a scalable tool to help rural healthcare workers, emergency responders, and telemedicine platforms in areas where snakebites are common.
Xeno-monitoring the impact of Vector Control on trypanosome transmission in the Forecariah sleeping sickness focus (Guinea).
Camara AD, Boedouno P, Camara I … +10 more , Soumah A, Kébé M, Koivogui J, Rotureau B, Bart JM, Bucheton B, Delamou A, Belem AMG, Kagbadouno M, Camara M
PLoS Negl Trop Dis · 2026 Jun · PMID 42247457 · Full text
BACKGROUND: Forecariah is one of the most active foci of gambiense human African trypanosomiasis (gHAT) in Guinea. The study aimed to evaluate the impact of a vector control intervention carried out in this focus from 20...
BACKGROUND: Forecariah is one of the most active foci of gambiense human African trypanosomiasis (gHAT) in Guinea. The study aimed to evaluate the impact of a vector control intervention carried out in this focus from 2018 to 2021. To achieve this, thousands of deltamethrin-impregnated blue tiny targets were deployed annually. METHODOLOGY AND PRINCIPAL FINDINGS: Thirty-one sentinel traps were used to assess the following entomological and parasitological parameters: (i) the apparent density (AD) of tsetse flies, monitored twice per year; (ii) the tsetse fly infection rates, evaluated once per year; and (iii) the trypanosome species, determined by molecular approaches before and after three years of vector control. Prior to the VC campaign, significantly higher densities of Glossina palpalis gambiensis were observed in the mangroves (AD = 17.2 F/T/D) than in mainland areas (AD = 6.2 F/T/D). Just 18 months after the start of the VC campaign, the maximum reduction in AD was reached (mean AD = 1.1 F/T/D; p < 0.001; 92% reduction) and was maintained throughout the campaign. Prior to VC, 18 out of 31 (58%) sentinel traps presented at least one infected fly observed by microscopy, whereas only two out of 31 (6%; p = 0.002) traps were positive after three years of VC. Molecular analysis of the tsetse midgut revealed positivity for T. brucei sl DNA in 45.2% of the traps prior to the VC baseline. T. congolense and T. vivax were observed in 6.5% of traps. Although one T. b. gambiense infection, which is responsible for human disease, was detected three years after the introduction of vector control, a significant decrease in T. brucei sl PCR positivity was observed (45.2% versus 22.6%; p = 0.05), whereas a slight increase was observed for T. vivax (6.5% versus 16.1%), while T. congolense trap positivity (6.5%) remained stable. CONCLUSION: In Forecariah, the prevalence of the disease was reduced by 76% during the study period. Hence, these results further emphasize that implementing vector control alongside medical control is an effective way of reducing the transmission of parasites to humans.
Emergence of Marburg virus disease in Ethiopia: Implications for public health preparedness and its impact on Ethiopia's health system.
Biadgilign S, Fransua M, Eshetu A … +1 more , Bedru A
PLoS Negl Trop Dis · 2026 Jun · PMID 42247433 · Full text
BACKGROUND: Marburg virus disease (MVD) is a rare but highly lethal viral hemorrhagic fever (VHF) caused by Marburg virus (MARV) and Ravn virus (RAVV). While MVD has historically been limited to specific areas of sub-Sah...
BACKGROUND: Marburg virus disease (MVD) is a rare but highly lethal viral hemorrhagic fever (VHF) caused by Marburg virus (MARV) and Ravn virus (RAVV). While MVD has historically been limited to specific areas of sub-Saharan Africa, recent outbreaks in previously unaffected countries indicate an expanding ecological and epidemiological risk. In November 2025, Ethiopia confirmed its first-ever MVD outbreak, constituting a significant national and regional public health emergency. METHODS: This narrative review synthesizes publicly available epidemiological data, government situation reports, and official communications from the Ethiopian Ministry of Health (MoH), Ethiopian Public Health Institute (EPHI), Africa Centres for Disease Control and Prevention (Africa CDC), and the World Health Organization (WHO). RESULTS: The outbreak was initially detected in Jinka town, South Ethiopia Region, an area bordering Kenya and South Sudan. As of 25 January 2026, more than 3,800 diagnostic tests were conducted, leading to a total of 19 cases comprising 14 confirmed (including nine deaths) and five probable (all deaths) and five recoveries from MVD in the country's South Ethiopia and Sidama regions, which were reported. A total of 857 contacts listed for monitoring all had completed their 21-day follow-up as of 25 January 2026. Ethiopia's response included rapid notification, laboratory confirmation, activation of incident management systems, deployment of mobile high-biosafety laboratories, establishment of isolation and treatment centers, and issuance of national clinical management guidelines. International partners provided technical, financial, and logistical support. However, the outbreak exposed ongoing challenges, including health system fragility, workforce shortages, misinformation, funding limitations, and heightened cross-border transmission risk. CONCLUSION: The emergence of MVD in Ethiopia represents a pivotal moment for national and regional health security. Sustained containment will require strengthened surveillance, community engagement, cross-border collaboration, and integrated One Health approaches. Long-term investment in resilient health systems and coordinated regional preparedness is essential to prevent future spillover events and protect vulnerable populations.
Plant-based therapeutics for leishmaniasis: A systematic review emphasizing human studies and clinical trial evidence.
Anning AS, Osmani V, Klug SJ … +1 more , Obiri-Yeboah D
PLoS Negl Trop Dis · 2026 Jun · PMID 42247419 · Full text
BACKGROUND: Leishmaniasis is a parasitic disease caused by Leishmania species and transmitted through sand fly bites, affecting some of the most vulnerable populations globally. Current treatments are limited by high tox...
BACKGROUND: Leishmaniasis is a parasitic disease caused by Leishmania species and transmitted through sand fly bites, affecting some of the most vulnerable populations globally. Current treatments are limited by high toxicity, poor tolerability, and resistance. Plant-based therapies offer a promising alternative, but human evidence has not been comprehensively reviewed. This review summarizes current evidence on the efficacy and safety of plant-based treatments for leishmaniasis in humans. METHODOLOGY/FINDINGS: We conducted a systematic review including studies that evaluated the efficacy and safety of plant-based treatments for leishmaniasis in humans. This review was registered with PROSPERO (ID: CRD42024567764). We searched PubMed, Scopus, and Web of Science from inception to May 28, 2024. Risk of bias was assessed using the Cochrane RoB 2 tool. We summarized the main study results qualitatively and quantitatively (where possible) by estimating risk ratios with 95% confidence intervals for treatment outcomes using the meta package in R. Ten studies met the inclusion criteria, nine from Iran and one from Sudan, all focused on cutaneous leishmaniasis (CL). Most used topical creams derived from medicinal plants, either alone or with conventional treatments. In studies combining herbal and standard treatments, four of six studies showed better outcomes in the intervention group. In studies using only the plant-based treatments compared to a standard treatment group, two of four showed better outcomes in the intervention group. Quantitative analysis of eight studies indicated significant healing improvements in the intervention group in three studies, specifically those using Juniperus excelsa, Nigella sativa, and poly-herbal formulations consisting of the pure extract mixture of Althaea (A.) rosa, A. officinalis, and members of the families Leguminosae, Faliaceae, Malvaceae, and Lythraceae (named Z-HE). Mild side effects such as itching and burning were reported with some herbal treatments, while conventional therapies caused more severe reactions in some cases. The risk of bias was mostly high in the studies. CONCLUSIONS: This review highlights the potential of certain plant-based compounds as adjunct or alternative therapies for CL. Despite promising results with Plantago ovata, Juniperus excelsa, and Z-HE poly-herbal extracts, current evidence is limited by methodological weaknesses. Larger, rigorously designed trials with broader representation are needed to confirm efficacy and safety and support policy integration in endemic regions.
Accelerating vaccine research and development for skin neglected tropical diseases: A case for leishmaniasis, leprosy, and Buruli ulcer.
Wang H, Novais FO, Gómez MA … +6 more , Muhi S, de Oliveira CI, Pham TT, Vermaak S, VALIDATE Network Skin NTDs Working Group, Reljic R
PLoS Negl Trop Dis · 2026 Jun · PMID 42247386 · Full text
Neglected tropical diseases (NTDs), particularly those with prominent cutaneous manifestations such as leishmaniasis, leprosy, and Buruli ulcer, represent a substantial global health burden, affecting hundreds of million...
Neglected tropical diseases (NTDs), particularly those with prominent cutaneous manifestations such as leishmaniasis, leprosy, and Buruli ulcer, represent a substantial global health burden, affecting hundreds of millions of people and perpetuating cycles of poverty and disability. Despite the current availability of treatment strategies, vaccines remain the most sustainable and cost-effective intervention that can reduce reliance on chemotherapeutics. However, vaccine research and development (R&D) for these diseases face considerable challenges that cannot be overcome without a strategic shift in response by national and international health programmes and organisations, research funders, and the pharmaceutical industry. This paper draws on collective insights from the VALIDATE Network workshop on "Vaccines for Skin Neglected Tropical Diseases-Progress and Challenges" (Bogotá, Colombia, 5-8 May 2025). We advocate for a multisectoral shift across three critical pillars: i) an increase in funding for NTD vaccine R&D, ii) integration of NTD vaccine R&D into the preparedness and response policies by international agencies and local governments, and iii) fostering patient and public engagement and advocacy for NTD vaccine R&D and implementation. Coordinated efforts across these three pillars will unlock the transformative potential of vaccines and substantially reduce the health, societal, and economic burdens from these diseases.
Genomic and phylogenetic characterization of severe fever with thrombocytopenia syndrome virus in companion animals in Korea, 2023-2024.
Lee DY, Lee HJ, Choi HY … +2 more , Park JS, Lee DH
PLoS Negl Trop Dis · 2026 Jun · PMID 42241469 · Full text
BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne Phlebovirus with high fatality rates in humans and expanding geographic distribution in East Asia. Companion animals, including dogs a...
BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne Phlebovirus with high fatality rates in humans and expanding geographic distribution in East Asia. Companion animals, including dogs and cats, are increasingly recognized as susceptible hosts that may contribute to viral maintenance and spillover. However, genomic information on SFTSV strains circulating in companion animals in Korea remains limited. METHODOLOGY/PRINCIPAL FINDINGS: Between April 2023 and June 2024, 63 SFTSV-positive clinical specimens from dogs and cats were collected across the Republic of Korea. Whole-genome sequencing using a multiplex tiling RT-PCR and next-generation sequencing approach yielded 39 complete viral genomes. Phylogenetic analysis revealed that most viruses clustered within genotype B, including 10 viruses classified as the highly virulent B2 subtype. Five reassortant viruses (12.8%) were identified, comprising four intra-genotypic (B1/B2/B2) and one inter-genotypic (B2/C/B2) reassortants. Multiple amino acid substitutions linked to increased human case fatality, such as RdRp-T1433A (94.9%) and Gn-Q341P (97.4%), were prevalent among companion animal viruses. In addition, mutations within neutralizing antibody epitopes (Y83F, K113R, G218S, P222A, F225L, V323I, and S340N) were detected, several of which significantly reduced antibody binding affinity in silico (G218S, P222A, F225L, and S340N). CONCLUSIONS/SIGNIFICANCE: This study provides nationwide genomic characterization of SFTSV in companion animals in Korea. The detection of highly virulent subtypes, frequent reassortment, and epitope-altering mutations highlights the evolutionary potential of SFTSV in non-human hosts. The close genetic relationship between animal- and human-derived viruses underscores the risk of cross-species transmission. These findings emphasize the need for integrated One Health surveillance systems linking veterinary and human health sectors to enable early detection, risk assessment, and mitigation of emerging SFTSV threats.
Estimating the distributional impact of improving access to snake antivenom in urban and rural Lao People's Democratic Republic: An extended cost-effectiveness analysis.
Patikorn C, Khuharatanachai T, Cho JY … +5 more , Taychakhoonavudh S, Mayxay M, Senbounsou K, Blessmann J, Chaiyakunapruk N
PLoS Negl Trop Dis · 2026 Jun · PMID 42241467 · Full text
INTRODUCTION: Snakebite is a significant public health issue in the Lao People's Democratic Republic (PDR), with victims often seeking traditional healers due to inadequate antivenom supply and high out-of-pocket (OOP) e...
INTRODUCTION: Snakebite is a significant public health issue in the Lao People's Democratic Republic (PDR), with victims often seeking traditional healers due to inadequate antivenom supply and high out-of-pocket (OOP) expenses, contributing to inequities between urban and rural populations. METHODS: An extended cost-effectiveness analysis (ECEA) was conducted to evaluate the distributional impact of improving access to antivenom in urban and rural Lao PDR, where all victims with systemic envenoming clinically indicated for antivenom receive antivenom at conventional hospitals, on disease burdens (deaths and disability-adjusted life years [DALYs]) and economic burden (%household OOP expenditure per monthly income). Sensitivity analyses were performed. RESULTS: Rural areas had higher mortality (3.14 vs. 0.35, +2.79 per 100,000 population), DALYs lost (78.97 vs. 8.86, +70.11 per 100,000 population), and household OOP expenses (39% vs. 38%, +1% of household monthly income) than urban areas. Full access to antivenom reduced health inequities in mortality (from +2.79 to +1.22 per 100,000 population) and DALYs (from +70.11 to +32.14 per 100,000 population) but increased inequities in household OOP expenses (from +1% to +39% of household monthly income). These differences had considerable uncertainties. Sensitivity analyses showed that free snakebite treatment and transportation costs with one caregiver reduced household OOP expenses in both areas (5% rural, 6% urban). CONCLUSIONS: While improving access to snake antivenom mitigates health inequities in disease burden, it exacerbates financial inequities between urban and rural areas. Policies targeting equitable access to care and financial protection are critical to achieving health equity for snakebites in the Lao PDR.
Epidemiological insights and genetic diversity of the Duffy binding protein of Plasmodium vivax in Duffy-negative Cameroonians.
Dieng CC, Ning RT, Kipayko C … +10 more , Schroeder RE, Mdluli-Berndt N, Ayukenchengamba B, Nematchoua Weyou Z, Sona TD, Reward AE, Zhou G, Sumbele Ngole Ule I, Kimbi HK, Lo E
PLoS Negl Trop Dis · 2026 Jun · PMID 42241439 · Full text
BACKGROUND: Malaria remains a major public health concern in sub-Saharan Africa. Plasmodium vivax (P. vivax), historically considered rare due to the predominance of Duffy-negative individuals, is increasingly reported i...
BACKGROUND: Malaria remains a major public health concern in sub-Saharan Africa. Plasmodium vivax (P. vivax), historically considered rare due to the predominance of Duffy-negative individuals, is increasingly reported in Central and West Africa. The ability of P. vivax to infect Duffy-negative populations challenges long-standing assumptions regarding parasite invasion biology and highlight surveillance gaps across Africa. METHODOLOGY/PRINCIPAL FINDINGS: This study investigated P. vivax prevalence and genetic diversity across three ecological zones in Cameroon. A total of 1,373 samples were screened by microscopy, rapid diagnostic tests (RDTs), and qPCR; and all participants were genotyped for Duffy antigen status. PvDBP1 region II was successfully sequenced from 75 P. vivax isolates. P. vivax prevalence was 10.8% among hospital patients (86/793) and 5.5% in community participants (32/580), and all confirmed infections occurred in Duffy-negative individuals. Hospital infections exhibited significantly higher parasitemia than asymptomatic cases. PvLDH-based RDTs failed to detect over 85% of qPCR-confirmed infections. Genetic analysis of PvDBP1 identified eight nonsynonymous mutations, with I379L (74.1%) and E225K (61.3%) as the most common variants, suggesting possible adaptive evolution. Phylogenetic analysis clustered Cameroonian P. vivaxisolates with those from Botswana, distinct from East African and Asian lineages, indicating regional adaptation and potential gene flow within Central-Southern Africa. CONCLUSION/SIGNIFICANCE: This study provides the first integrated epidemiological and PvDBP1 genetic characterization of P. vivax infections in Duffy-negative Central Africans, revealing widespread subclinical infections and poor diagnostic performance of current PvLDH-based RDTs. The observed genetic signatures of adaptation highlight the urgent need to prioritize P. vivax within national malaria programs and investigate alternative invasion pathways beyond PvDBP1 to guide improved diagnostic and vaccine strategies.
Prevalence of multiple human intestinal parasites across diverse environments in Madagascar.
Wu SM, Gupta SS, Ravelomanantsoa MA … +12 more , Andry S, Viana DF, Zamborain-Mason J, Uzomah UA, Randriamady HJ, Howard C, Friedman G, Castonguay A, Hazen J, Milner DA, Rice BL, Golden CD
PLoS Negl Trop Dis · 2026 Jun · PMID 42241434 · Full text
BACKGROUND: Intestinal parasitic infections affect more than 1·5 billion people globally, leading to severe health consequences such as malnutrition, anemia, diarrhea, and impaired cognitive development. METHODOLOGY/PRIN...
BACKGROUND: Intestinal parasitic infections affect more than 1·5 billion people globally, leading to severe health consequences such as malnutrition, anemia, diarrhea, and impaired cognitive development. METHODOLOGY/PRINCIPAL FINDINGS: Samples were collected from 3,872 individuals (all ages and both sexes) across 31 rural communities in Madagascar between 2013 and 2017, representing diverse ecological and socioeconomic regions. Intestinal parasite prevalence was assessed by fecal microscopy. Bayesian multilevel logistic regression models were used to estimate overall and regional prevalences while accounting for demographic and spatial variability. Parasite prevalence varied widely across Madagascar, with the highest rates observed for Ascaris lumbricoides (22·0%) and Trichuris trichiura (15·3%), followed by Hymenolepis nana (up to 10·5%), hookworm (up to 8·1%), Strongyloides (0·5%), and Schistosoma mansoni (0·5%). Infection burden was greatest in the northeast and southeast-especially among school-aged children aged 5-19. Sex differences were minor, except for higher hookworm prevalence in males. CONCLUSIONS/SIGNIFICANCE: This study provides the most comprehensive assessment to date of intestinal parasite prevalence across Madagascar, revealing that A. lumbricoides and T. trichiura infections were highly endemic in the humid eastern regions, while H. nana was most common in dry regions. The findings highlight substantial geographic heterogeneity and underscore the need for regionally targeted, multi-sectoral interventions, including improved sanitation and deworming.
CD163⁺ monocytes and soluble CD163 as prognostic indicators in severe fever with thrombocytopenia syndrome: An integrative analysis.
Wang J, Song H, Zhang Y … +9 more , Cheng Z, Huang L, Jia B, Zhu G, Hu L, Xue J, Li J, Wu W, Xia Q
PLoS Negl Trop Dis · 2026 Jun · PMID 42234715 · Full text
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) carries high short-term mortality and lacks approved antiviral therapy, highlighting the need for admission risk tools grounded in upstream host immune patho...
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) carries high short-term mortality and lacks approved antiviral therapy, highlighting the need for admission risk tools grounded in upstream host immune pathobiology. METHODS: Public single-cell RNA sequencing (scRNA-seq) data (GSE175499) from 15 SFTS patients (4 non-survivors, 11 survivors) and 4 healthy controls were reanalyzed to map cell-cell communication and identify monocyte subsets and pathways. Findings were validated by bulk RNA sequencing and flow cytometry. A multicenter clinical cohort (n = 150, 132 survivors and 18 non-survivors) measured admission sCD163 using enzyme-linked immunosorbent assay (ELISA) and assessed 30-day mortality using area under the curve (AUC), Kaplan-Meier, and Cox models. RESULTS: Single-cell analysis identified expansion of CD163 ⁺ intermediate monocytes in SFTS, along with antiviral and complement activation programs in non-survivors. Communication analysis prioritized thrombospondin (THBS) signaling with the dominant sender shifting from CD163 ⁺ intermediate (survivors) to CD163 ⁺ classical monocytes (non-survivors). Flow cytometry confirmed increased CD163 ⁺ monocytes in SFTS. At admission, sCD163 independently predicted 30-day mortality (optimal threshold = 1.17 µg/mL, AUC 0.80). A two-marker model combining sCD163 with blood urea nitrogen (BUN) improved discrimination (AUC 0.87), yielded stepwise separation across three risk tiers (Score 0, 1, and 2) and replicated externally (AUC 0.73 and 0.83). Elevated sCD163 was consistently associated with higher mortality across sex and age subgroups. However, further subgroup analyses within the three-tier risk score were limited by small sample sizes and should be considered exploratory. CONCLUSIONS: We identified and orthogonally validated CD163 ⁺ monocyte programs linked to outcomes, establishing admission serum sCD163 as a biomarker. An admission two-marker score (sCD163 and BUN) provides a simple three-tier admission score that rapidly stratifies 30-day mortality risk and guides intensified monitoring and timely supportive care.
A snapshot of selected neglected tropical disease research using the World Health Organization International Clinical Trials Registry Platform database, 1999-2023.
Peploe R, Jauncey H, Sakai Y … +7 more , Karam G, Ross AL, Charnaud SC, Dahal P, Solomon AW, Guerin PJ, Naylor C
PLoS Negl Trop Dis · 2026 Jun · PMID 42234695 · Full text
BACKGROUND: Knowledge of clinical study methodology and location can inform researchers, clinicians, funders, and policymakers of the gaps which exist in a disease's evidence landscape, thereby conferring guidance for ap...
BACKGROUND: Knowledge of clinical study methodology and location can inform researchers, clinicians, funders, and policymakers of the gaps which exist in a disease's evidence landscape, thereby conferring guidance for appropriate resource allocation. This study summarises registered studies for selected neglected tropical diseases (NTDs) and identifies evidence gaps. METHODOLOGY: The International Clinical Trials Registry Platform (ICTRP) was searched in September 2023 to extract 315 clinical study registrations submitted between January 1999 and September 2023 on Chagas disease, schistosomiasis, soil-transmitted helminthiases, and visceral leishmaniasis. Data were standardised before a descriptive analysis was performed on study location, inclusion age range, study design, phase, and population access to studies. RESULTS: Registered studies were partially aligned to the geographical distribution of disease burden; countries in which the highest number of studies were registered often face great burden, though there were several endemic countries with few or no studies. The number of registered studies increased over time in the period covered by the review, with 51-62% of studies across the 4 diseases conducted in 2014-23 period, as opposed to 42%-49% in the preceding 15 years. Only 12-17% of studies were multi-country studies across the 4 NTDs. 14% of Chagas disease studies included children under the age of 16 years (much lower than other NTDs) and only 2 studies (2%) exclusively studied under 16s. CONCLUSIONS: These findings highlight areas of research for these diseases which have been neglected between 1999-2023, indicating need for further research to fill these gaps and aid progress towards the World Health Organization's roadmaps to elimination of NTDs by 2030.
Knowledge, attitude, and prevention practices of cutaneous leishmaniasis in highly-endemic rural areas of Kandahar province, Afghanistan: A large cross-sectional community-based study.
Rahimi BA, Resha S, Khaksar M … +6 more , Saeed KMI, Osmani H, Daqiq AB, Rahmani H, Saleem H, Taylor WR
PLoS Negl Trop Dis · 2026 Jun · PMID 42234692 · Full text
BACKGROUND: Cutaneous leishmaniasis (CL) is highly endemic in Kandahar province of Afghanistan, but data on the population's knowledge of CL and measures they adopt to prevent it are unknown. The main objectives of the s...
BACKGROUND: Cutaneous leishmaniasis (CL) is highly endemic in Kandahar province of Afghanistan, but data on the population's knowledge of CL and measures they adopt to prevent it are unknown. The main objectives of the study were to study the knowledge, attitude, and prevention practices of CL, and their associated factors, in two highly-endemic rural districts, Daman and Arghandab, in Kandahar province. METHODS: This community-based cross-sectional analytical study took place over seven months, from September 2024-March 2025, in adults. Data were analysed by descriptive statistics, the Chi-square test, and multivariate logistic regression. RESULTS: A total of 2,118 adults were recruited with a mean age of 35.8 years; 60.3% were males, 56.1% farmers, 91.5% illiterate, and 91.4% from poor families. Among the study participants, 24.1%, 41.5%, and 17.9% had good CL knowledge, a positive attitude towards CL, and good preventive practices towards CL. Independent factors associated with: (i) poor CL knowledge were being not single (adjusted odds ratio [AOR] 1.2), being a farmer (AOR 1.1) and coming from a poor family (AOR 1.3), (ii) a negative attitude towards CL were being aged >40 years (AOR 1.3) female (AOR 1.5), a resident in Arghandab district (AOR 1.2), and literate (AOR 1.1), and (iii) poor preventive practices against CL were being resident of Daman district (AOR 1.6), single (AOR 1.5), and illiterate (AOR 2.5). CONCLUSIONS: The majority of Daman and Arghandab residents had poor CL knowledge, a negative attitude, and poor prevention practices. Our results underscore the need for the Afghan Ministry of Public Health and international donor agencies, such as WHO and UNICEF, to plan and implement strategies to create/increase awareness of CL and measures to prevent and control it in Kandahar Province and beyond.
Landmark-based morphometrics with fewer landmarks: Some examples for medical entomology.
Dujardin JP, Sriwichai P, Samung Y … +3 more , Ruangsittichai J, Sumruayphol S, Dujardin S
PLoS Negl Trop Dis · 2026 Jun · PMID 42228751 · Full text
Geometric morphometrics based on two-dimensional landmarks is a powerful tool for distinguishing morphologically similar or cryptic taxa, an important asset in the fight against medically and veterinary important arthrop...
Geometric morphometrics based on two-dimensional landmarks is a powerful tool for distinguishing morphologically similar or cryptic taxa, an important asset in the fight against medically and veterinary important arthropods. While it is commonly assumed that increasing the number of landmarks should improve discriminatory power by capturing more shape information, our findings challenge this assumption. In terms of shape discrimination (thus excluding size variation), we demonstrate that small subsets of landmarks can equal or even outperform full sets of landmarks. Fifteen examples of comparisons between closely related species were considered.These examples are drawn from published data covering six insect families: Culicidae, Glossinidae, Muscidae, Psychodidae, Reduviidae and Tabanidae. To assess the relevance of smaller subsets of landmarks, we compared the accuracy scores of unsupervised classification using full sets of landmarks (10-22 points) with those obtained using smaller subsets. To eliminate the potential influence of chance on reclassification scores, we validated our results by accounting for correct reclassification due to chance alone. The strategy for selecting relevant landmark subsets employed two different approaches. The first relied on each landmark's contribution to the total distance between shapes, thus establishing a hierarchy among them. The second, more comprehensive approach compared the reclassification scores of large random samples of landmarks, from the smallest subsets (3 landmarks) to the full set. From a public health perspective, the value of our approach lies in simplifying the tasks required for entomological surveillance: it could accelerate morphometric identification for large surveillance datasets, improve standardization among users, and reduce noise introduced by problematic landmarks. These gains are particularly relevant for distinguishing medically important but morphologically similar taxa, or when molecular tools are unavailable or too resource-intensive. The statistical procedures have been integrated into the XYOM online software, providing accessible tools for efficient landmark selection and improved morphometric analysis.
Geographical disparities and programmatic determinants of hydrocele surgery and lymphoedema management coverage for lymphatic filariasis in the Democratic Republic of the Congo, 2018-2024: A national analysis of routine programme data.
Makenga Bof JC, Muteba D
PLoS Negl Trop Dis · 2026 Jun · PMID 42228748 · Full text
BACKGROUND: Lymphatic filariasis (LF) is a significant neglected tropical disease in the Democratic Republic of the Congo (DRC). Although progress has been made toward interrupting transmission through mass drug administ...
BACKGROUND: Lymphatic filariasis (LF) is a significant neglected tropical disease in the Democratic Republic of the Congo (DRC). Although progress has been made toward interrupting transmission through mass drug administration, LF-related morbidities-particularly hydrocele, lymphoedema, and recurrent acute dermatolymphangioadenitis-continue to cause substantial disability, comorbid infections, and reduced quality of life. National evidence on the burden of LF morbidities and factors associated with access to morbidity management remains limited. METHODS: We conducted a national retrospective analysis of routinely collected programmatic data from the National Neglected Tropical Diseases Control Programme in the DRC between 2018 and 2024. Data included estimates and management of LF-related hydrocele and lymphoedema across endemic provinces. Descriptive analyses assessed morbidity burden, geographic distribution, and temporal trends. Care cascade analyses were performed to quantify attrition across key stages of morbidity management. Multivariable linear regression models at provincial level were used to identify programmatic and health-system factors associated with hydrocele surgery coverage and lymphoedema management coverage. RESULTS: A total of 8,471 hydrocele cases and 5,310 lymphoedema cases were identified nationwide. During the study period, 2,013 hydrocele surgeries (23.8%) were performed, while 877 lymphoedema patients (16.5%) received the essential package of care. Marked geographic disparities were observed, with several high-burden provinces exhibiting particularly low coverage. Care cascade analyses revealed substantial attrition between case identification and receipt of care for both conditions. In multivariable analyses, hydrocele surgery coverage was positively associated with external partner support and availability of trained surgical personnel, while higher caseloads, post-Transmission Assessment Survey (post-TAS) surveillance phase, and geographic inaccessibility were associated with lower coverage. Lymphoedema management coverage was strongly associated with community-based care activities, health worker training, and availability of basic hygiene supplies. CONCLUSIONS: LF-related morbidities remain a substantial and unevenly addressed public health burden in the DRC, including in provinces that have achieved or are approaching interruption of transmission. Strengthening and scaling up morbidity management and disability prevention services-particularly for lymphoedema and hydrocele-are essential to improve patient quality of life and to meet World Health Organization requirements for elimination of lymphatic filariasis as a public health problem.
VP1-141 is a determinant of a Vero cell-adapted Coxsackievirus A10 for vaccine development.
Chen CH, Fang CY, Shen YS … +3 more , Wang JR, Wu SC, Liu CC
PLoS Negl Trop Dis · 2026 Jun · PMID 42228746 · Full text
Coxsackievirus A10 (CVA10) infection primarily causes hand, foot, and mouth diseases (HFMD) in children. As CVA10 is one of the most widespread enteroviruses, the development of a CVA10 vaccine is essential. It could als...
Coxsackievirus A10 (CVA10) infection primarily causes hand, foot, and mouth diseases (HFMD) in children. As CVA10 is one of the most widespread enteroviruses, the development of a CVA10 vaccine is essential. It could also be used to create a multivalent vaccine for preventing HFMD alongside other enteroviruses. Most clinical isolates of CVA10 are difficult to propagate in Vero cells, while only a few pre-screened CVA10 clones could. In this study, we have successfully isolated a highly Vero cell-adapted CVA10 strain (CVA10-V) from the parental CVA10. After propagation of CVA10-V in Vero cells, the purified full-particle (F-particle) of CVA10-V could induce strong immunogenicity in mice model, while the empty-particle of CVA10-V did not. The CVA10-V F-particle were mixed with EV-A71 bulk for immunization and a good neutralization response to each virus were observed. In this study, a RD-propagated CVA10 strain (CVA10-R) was not unable to infect Vero cells. Five amino acid variations of P1 protein (470, 664, 705, 792, and 804) were noted between the CVA10-V and CVA10-R. Infectious clones with single-site mutation representing these five locations were constructed to investigate the effects of these variations on Vero infectivity. Substitution of D from E at position VP1-141 (P1-705) was found to be the critical determinant for CVA10-V infection of Vero cells. Variation at this position was found to affect CVA10's ability to attach to Vero cells. Our study pinpoints the critical sites of viral P1 protein that render the Vero-adaptation and this Vero-adapted CVA10-V strain would be beneficial for multivalent HFMD vaccine development using the Vero cell culture system.
Correction: Association of avian biodiversity and West Nile Virus circulation in Culex mosquitoes in Emilia-Romagna, Italy.
PLOS Neglected Tropical Diseases Staff
PLoS Negl Trop Dis · 2026 Jun · PMID 42228640 · Full text
[This corrects the article DOI: 10.1371/journal.pntd.0014076.].
[This corrects the article DOI: 10.1371/journal.pntd.0014076.].
The cost-effectiveness of Wolbachia-based biocontrol interventions for dengue: A scoping review of the available evidence.
Turner HC, Hung TM, Brady OJ … +3 more , Velayudhan R, Dorigatti I, Clapham HE
PLoS Negl Trop Dis · 2026 Jun · PMID 42224379 · Full text
BACKGROUND: Dengue incidence has increased sharply worldwide, placing nearly half of the global population at risk. In response, various innovative technologies and interventions, including biocontrol strategies that dep...
BACKGROUND: Dengue incidence has increased sharply worldwide, placing nearly half of the global population at risk. In response, various innovative technologies and interventions, including biocontrol strategies that deploy Wolbachia-infected mosquitoes, are being explored. These can be used to either replace the existing mosquito population with one that is less likely to transmit infection or to suppress the existing mosquito population. We conducted a scoping review of economic evaluations of Wolbachia-based interventions for dengue control, aimed at summarising assumptions and results of existing studies. METHODOLOGY/PRINCIPAL FINDINGS: A scoping review of the published literature was conducted on the 29th of April 2024 using the MEDLINE (via OVID), Embase Classic+Embase (via OVID), Global Health - OVID, PubMed, and Econ Lit electronic databases. No date or language restrictions were applied to the searches. We identified nine studies that reported the results of economic evaluations of Wolbachia-based interventions for dengue control. The majority (eight out of nine studies) investigated Wolbachia replacement-based programmes. Overall, the results were supportive for the use of replacement-based programmes in large urban settings, with the intervention likely to generate cost savings from a societal perspective. CONCLUSIONS/SIGNIFICANCE.: The available economic evaluations consistently suggest that Wolbachia-based replacement interventions can be cost-effective for dengue control when targeted to densely populated urban areas, and several studies indicate that they can generate substantial long‑term cost savings from a societal perspective. Further research is needed to understand how heterogeneity in epidemiological effectiveness influences long-term projected cost‑effectiveness and to investigate the combination of Wolbachia-based interventions with other dengue control/prevention measures (such as vaccination). To support more robust and comparable analyses, we provide recommendations for future studies in this area, emphasising the importance of reporting results disaggregated by cost and outcome components, and making important underlying assumptions related to the intervention more explicit.
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