2026-03-30
Nkuba Nyerere, Damaris Felistus Mulwa
by Nkuba Nyerere, Damaris Felistus Mulwa Background Neglected Tropical Diseases (NTDs) affect 1.5 billion people worldwide with 39% of the global burden occurring in Africa. In Kenya, NTDs remain endemic despite control efforts, with co-endemicity of soil-transmitted helminths (STH), schistosomiasis (SCH), and lymphatic filariasis (LF) complicating intervention strategies. This study developed machine learning models to predict high-risk co-endemic areas using demographic and Water, Sanitation, and Hygiene (WASH) indicators. Methodology The study analyzed Kenya’s 2022 NTD co-endemicity data from the Expanded Special Project for Elimination of Neglected Tropical Diseases, incorporating WASH and population variables. Three machine learning algorithms, Random Forest, Gradient Boosting Machine, and Extreme Gradient Boosting (XGBoost) were trained to classify regions by STH prevalence levels and co-endemicity status. Model performance was evaluated using cross-validation, Receiver Operating Characteristic – Area under the Curve (AUC) and variable importance analysis. Results The RF model achieved the highest predictive performance (AUC = 0.70), followed by XGBoost (AUC = 0.66) and GBM (AUC = 0.62). Key predictors included improved sanitation access (mean importance score: 0.24), population density (0.21), and co-endemicity with LF/SCH (0.18). Spatial analysis identified Eastern and North-Eastern Kenya as persistent hotspots, correlating with low WASH coverage ( Conclusion Machine learning models effectively identified the high-risk NTD co-endemic areas in Kenya, with RF outperforming other models. These findings support targeted interventions integrating WASH improvements with mass drug administration in identified hotspots. We propose a real-time dashboard for dynamic risk mapping to optimize resource allocation; a strategy aligned with Kenya’s NTD Elimination Strategic Plan 2030.
DOI: 10.1371/journal.pntd.00141562026-03-27
Luke Gamble, Karlette A. Fernandes, Keiichiro Tazawa, Rubaiya Ahmad, Kamrul Islam, James Hood, Bernadette Abela, Balaji Chandrashekar, Frederic Lohr, Ryan M. Wallace, Tim Parkin, Andrew D. Gibson, Catherine Swedberg
by Luke Gamble, Karlette A. Fernandes, Keiichiro Tazawa, Rubaiya Ahmad, Kamrul Islam, James Hood, Bernadette Abela, Balaji Chandrashekar, Frederic Lohr, Ryan M. Wallace, Tim Parkin, Andrew D. Gibson, Catherine Swedberg Background Rabies causes over 60,000 deaths annually, primarily among children, with dog bites responsible for nearly all human cases. Although mass dog vaccination is effective in low-resource settings, structured campaigns have rarely been implemented in refugee camps, where unmanaged dog populations and limited access to post-exposure prophylaxis heighten rabies risk. This study aimed to demonstrate the possibility of delivering systematic mass dog vaccination within a short operational timeframe in a humanitarian setting and to assess community perceptions of rabies risk and prevention. Methodology/principal findings In May 2025, a four-day mass dog vaccination campaign was conducted across the Kutupalong-Balukhali refugee settlement in Cox’s Bazar, Bangladesh, with real-time data collection to guide operations. Post-vaccination dog sight surveys assessed operational coverage, while community surveys evaluated knowledge, attitudes and practices (KAP) regarding rabies. Of the 2,275 dogs encountered, 1,781 (78.3%) were vaccinated, with 86.4% classified as unowned community dogs. The overall proportion of marked dogs across all surveyed zones was 71.5% (95% CI: 66.8–75.9%). In the community survey, 34.6% of 1,311 adult respondents (gender-adjusted) had heard of rabies, and 41.2% correctly identified dog bites as the primary route of transmission. Regarding appropriate post-bite care, 25.9% knew to both wash the wound and seek medical care. Approximately 8.7% of households experienced a dog bite in the preceding year, corresponding to a minimum annual incidence of 13.3 bites per 1,000 persons, equating to over 15,000 bites per year. Conclusions/significance This study represents the first structured mass dog vaccination campaign in a refugee setting, demonstrating that rabies control can be effectively implemented even in complex humanitarian contexts. The campaign’s success offers a replicable model for integrating zoonotic disease prevention into emergency health responses, underscoring the critical need to safeguard displaced populations from preventable diseases.
DOI: 10.1371/journal.pntd.00141432026-03-27
Kim Halpin, Raúl Gómez Román
by Kim Halpin, Raúl Gómez Román Hendra virus (HeV) emerged in Australia in 1994, causing a devastating outbreak among horses in Brisbane with spread to humans, resulting in one death. This nonsegmented, negative-stranded RNA virus belongs to the family Paramyxoviridae and represents the first zoonotic paramyxovirus isolated from bats. Flying foxes (genus Pteropus ) serve as the natural reservoir, with all four mainland Australian species carrying antibodies with no apparent disease. HeV initiates infection by binding ephrin-B2 receptors on vascular endothelial cells, driving characteristic pathology involving vasculitis, thrombosis, and neurological complications. Horses are amplifying hosts, shedding virus abundantly in respiratory secretions and posing transmission risks to humans during invasive procedures. To date, seven confirmed human infections have been documented, with a 57% fatality rate, presenting as severe respiratory disease or progressive encephalitis. Two genetic variants are now recognized: the original HeV genotype 1 and the emerging HeV genotype 2, identified in limited equine cases. Recent surveillance of bat roosts revealed substantial viral diversity, with peak shedding occurring during winter—coinciding with equine spillover peaks. Prevention integrates multiple strategies: the licensed equine vaccine Equivac which provides One Health protection for both horses and human contacts; biosecurity measures including proper PPE; and habitat restoration to reduce nutritional stress in bat populations. Emerging therapeutics include monoclonal antibodies, with m102.4 showing cross-protective activity against both HeV and the closely related Nipah virus. No licensed human vaccines currently exist, though candidates are in development. Future prevention strategies increasingly recognize the importance of Indigenous-led conservation approaches alongside biomedical interventions. This review will focus on the history of HeV, virus replication and diversity, epidemiology, clinical manifestations, diagnosis, treatment, prevention, as well as ecological and interdisciplinary countermeasures.
DOI: 10.1371/journal.pntd.00141382026-03-26
Emily Robb, Sarah Muise, Lana Watt, Rebecca Armstrong, Duncan Wells, Paul McCusker, John Harrington, Andreas Krasky, Paul M. Selzer, Nikki J. Marks, Aaron G. Maule
by Emily Robb, Sarah Muise, Lana Watt, Rebecca Armstrong, Duncan Wells, Paul McCusker, John Harrington, Andreas Krasky, Paul M. Selzer, Nikki J. Marks, Aaron G. Maule Fasciola hepatica causes fasciolosis, a parasitic disease that poses significant animal and human health challenges. Control relies on flukicides, most of which are adulticides, with only triclabendazole effective against the pathogenic migratory juvenile. Classical neurotransmitter pathways are widely targeted by anthelmintics yet remain underexplored for flukicide development. Here we explore the importance of serotonin (5-HT) signaling in juvenile fluke. In silico analyses confirmed all F. hepatica life stages express a complete 5-HT signaling pathway encompassing genes encoding proteins for 5-HT synthesis, transport, and reuptake, as well as five putative 5-HT G protein-coupled receptors (GPCRs). Homology and binding motif analyses supported the presence of two 5-HT 1 (Fh5HT 1A , Fh5HT 1B ) and three 5-HT 7 (Fh5HT 7A , -7B , -7C ) GPCRs. Immunocytochemistry and in situ hybridization revealed widespread neuronal expression of 5-HT, its synthetic enzyme tryptophan hydroxylase (FhTPH), and the GPCR Fh5HT 7C . 5-HT addition stimulated juvenile fluke motility; consistent with this observation, serotonin reuptake inhibition, which causes 5-HT persistence at synaptic junctions, also enhanced juvenile movement. Silencing of FhTPH, a key enzyme in 5-HT synthesis, blunted juvenile motility, a phenotype reversed by the addition of 5-HT. Silencing the fluke vesicular monoamine transporter (FhVMAT), which packages 5-HT into synaptic vesicles, reduced juvenile motility, whilst silencing the 5-HT reuptake transporter (FhSERT) which recycles synaptic 5-HT increased juvenile motility and growth, consistent with 5-HT accumulation enhancing effects. Whilst combinatorial silencing of Fh5HT 1 receptors reduced fluke motility, silencing Fh5HT 7 receptors led to a greater reduction in motility. Exogenous addition of 5-HT partially rescued motility deficits of juveniles with silenced Fh5HT 1 receptors, but 5-HT excitation was abolished in Fh5HT 7 -RNAi juveniles, exposing their importance to fluke motility. Notably, sustained 5-HT exposure promoted juvenile growth, but these effects were not blunted by receptor-RNAi. The findings emphasize a central role of serotonin signaling in both juvenile motility and growth, exposing novel aspects of receptor function and encouraging therapeutic exploitation for liver fluke control.
DOI: 10.1371/journal.pntd.00140972026-03-26
Andie I. Lun, Barbara de Barros, Stephen L. Walker
by Andie I. Lun, Barbara de Barros, Stephen L. Walker Background Leprosy is a chronic infectious disease caused by Mycobacterium leprae ( M. lepra e ) and Mycobacterium lepromatosis ( M. lepromatosis ), primarily affecting the skin and peripheral nervous system. Leprosy is complicated by immune-mediated reactions which are risk factors for nerve damage and disability. Systemic corticosteroids are the mainstay of therapy; however, prolonged use in chronic or recurrent reactions carries significant risks but the evidence on the short- and long-term adverse effects of corticosteroids in leprosy is limited. We conducted a systematic review to evaluate corticosteroid-associated adverse effects in leprosy affected individuals. Methodology Eight electronic databases were searched (including PubMed, Embase and LILACS) without language or year restriction for studies reporting adverse effects associated with systemic corticosteroid use in individuals with leprosy. Eligible studies included randomised controlled trials, observational studies, case series and case reports. Data variability was assessed using Stata software. Main findings A total of 111 studies were included; of which 22 were randomised controlled trials. Due to heterogeneity, findings were synthesised narratively. The most frequently reported adverse effects were metabolic complications, with approximately one-third of individuals developing corticosteroid-induced lipodystrophy. Infections were the second most common adverse effect (15.5%), followed by gastritis (12.6%). Infections accounted for three-quarters of corticosteroid-associated mortality, predominantly due to tuberculosis, with 88.2% of corticosteroid-associated mortalities occurring in individuals with erythema nodosum leprosum (ENL). There was an association between ENL and the development of cataract and osteoporosis, with 69.7% of cataract cases and 84.4% of osteoporosis cases occurring among individuals with ENL. Conclusion This systematic review illustrates the range and severity of adverse effects affecting individuals with leprosy who received systemic corticosteroids. Although this review is limited by study heterogeneity, publication bias, and the scarcity of long-term data, it highlights the need for corticosteroid stewardship, structured pharmacovigilance and further research for safer therapeutic alternatives to corticosteroids for leprosy reactions.
DOI: 10.1371/journal.pntd.00141522026-03-23
Shui Yu, Zhepeng Sun, Yiqi Wang, Peipei Zhang, Hongxing Sun, Ziqi Meng, Chufan Yang, Yu Shen, Zhanhao Guo, Wei Li
by Shui Yu, Zhepeng Sun, Yiqi Wang, Peipei Zhang, Hongxing Sun, Ziqi Meng, Chufan Yang, Yu Shen, Zhanhao Guo, Wei Li Giardia duodenalis is an important extracellular protozoan parasite of the gut responsible for waterborne diarrhea in human and nonhuman animals worldwide. Giardia trophozoites express and secrete excretory-secretory proteins (ESPs) affecting structural, cellular, and soluble components of the host small intestinal milieu, of which tenascins are present in high abundance . Giardia -induced intestinal epithelial cell (IEC) apoptosis is known as an important aspect of pathogenesis of giardiasis, while the underlying molecular mechanisms remain largely unclear. Here we used in vitro models of IECs to explore the regulatory mechanism of Giardia -induced apoptosis. We initially confirmed the occurrence of apoptosis and the activation of epidermal growth factor receptor (EGFR) when IECs were exposed to Giardia trophozoites, and EGFR activation involved Giardia -induced IEC apoptosis. The recombinant Tenascin15, Tenascin30, and Tenascin33 were then studied for their potential to activate EGFR/signal transducer and activator of transcription 3 (STAT3)-dependent IEC apoptosis. All the three recombinant proteins were demonstrated to be effective in triggering IEC apoptosis and EGFR/STAT3 activation. Strikingly, IEC apoptosis induced by rTenascin15 and rTenascin30 were found to be dependent on the activation and nuclear translocation of EGFR and STAT3, while this is not the case for rTenascin33. Collectively, our study identified tenascins as potential virulence factors related to Giardia -induced IEC apoptosis, and demonstrated that EGFR-STAT3 axis played a critical regulatory role in the process, advancing our understanding of the pathogenesis of Giardia infection.
DOI: 10.1371/journal.pntd.00141532026-03-23
Yongxin Huang, Wenli Liang, Mingyao Huang, Yingying Deng, Zhenyi Huang, Changhan Ai, Weiqing Tan, Lingxiao Jiang
by Yongxin Huang, Wenli Liang, Mingyao Huang, Yingying Deng, Zhenyi Huang, Changhan Ai, Weiqing Tan, Lingxiao Jiang Background Salmonella spp. infections can manifest in various clinical symptoms, from asymptomatic carriage to gastroenteritis, and even severe sepsis. Given the rapid progression of the disease and its potential to cause severe outcomes or trigger cluster outbreaks, making the detection of Salmonella spp. critically important. Although broth enrichment culture is considered the gold standard, it is time-consuming and involves multiple steps, making it difficult to meet urgent diagnostic needs. Hence, prompt and precise detection of Salmonella spp. is crucial not only for early diagnosis and effective treatment, but also for preventing transmission, controlling outbreaks, and screening asymptomatic Salmonella carrier. Methods This study developed a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated (Cas) -SE assay that integrated the advantages of the recombinase polymerase amplification (RPA) and CRISPR/Cas13a system for detecting Salmonella spp. The clinical performance of CRISPR/Cas13a-SE assay was evaluated by a cohort of 94 inpatients with diarrhea and three prospective studies. Results The CRISPR/Cas13a-SE assay can be completed within 60 minutes, and its limit of detection was 100 fg/μL. Compared to the broth enrichment culture, the CRISPR/Cas13a-SE assay demonstrated a sensitivity of 87.5% and a specificity of 98.8% in a cohort of 94 inpatients with diarrhea. In our prospective studies involved three distinct cohorts: 1,662 food handlers, 211 outpatients with diarrhea, and 154 inpatients with Gram-negative bacteremia. Compared with broth enrichment culture, CRISPR/Cas13a-SE assay had a high concordance rate of 98.79% (1,642/1,662), 99.52% (210/211), and 100.00% (154/154) respectively. Conclusions We demonstrated that the CRISPR/Cas13a-SE system showed excellent detection performance for infectious diarrhea caused by Salmonella spp. The combined use of CRISPR/Cas13a-SE with the blood culture method enhances the rapid diagnosis of invasive salmonellosis, which is crucial for early target-based therapy. Additionally, screening of asymptomatic Salmonella carrier will be benefit for disease prevention and control.
DOI: 10.1371/journal.pntd.00141502026-03-23
Barbara de Barros, Saba Lambert, Vivianne Lopes Antonio Dias, Diana N.J. Lockwood, Stephen L. Walker
by Barbara de Barros, Saba Lambert, Vivianne Lopes Antonio Dias, Diana N.J. Lockwood, Stephen L. Walker Background Erythema nodosum leprosum (ENL) is a severe immunological complication of leprosy, characterised by painful nodules, fever, arthralgia, oedema, and systemic symptoms. Temporal classifications—acute, recurrent, and chronic—are inconsistently applied, complicating data comparisons. Standardised and agreed definitions are essential to ensure consistency in diagnosis, research, and clinical management. Objective To examine how temporal classifications of ENL are used in modern literature and compare them to descriptions from the pre-corticosteroid era. Methods We conducted a semi-systematic review of historical and contemporary literature. Historical texts published before 1940, prior to the introduction of sulfone antibiotics and corticosteroids, were purposively selected to capture descriptions of the natural history of ENL. For modern studies, we systematically searched PubMed, EMBASE, LILACS, SciELO, Scopus, African Index Medicus, Cochrane, and ClinicalTrials.gov from May 2024 to March 2025. The systematic review identified 572 articles after de-duplication, and 41 met inclusion criteria for providing definitions of ENL subtypes. Results Five historical treatises were selected. Their clinical observations of nodular skin lesions with systemic symptoms—ranging in duration from weeks to months or even years—align with contemporary understandings of ENL. 41 studies included, at least one of the three temporal classifications (acute, recurrent, or chronic). The six-month criterion distinguishing acute and chronic ENL is used in all current definitions. However, definitions for recurrent and chronic ENL frequently overlapped, both referring to prolonged or multiple episodes after initial treatment, underscoring a lack of conceptual clarity. Conclusion The absence of standardised ENL terminology impedes data comparison, meta-analysis, and clinical guideline development. A Delphi consensus process and longitudinal observational studies are recommended to refine, standardise agreed ENL classifications.
DOI: 10.1371/journal.pntd.00141002026-03-23
Gulnara Minbaeva, Nelya Akhunbaeva, Kalis Nogoibaeva, Vera Toygombaeva, Kenesh Dzhusupov, Paul R. Torgerson
by Gulnara Minbaeva, Nelya Akhunbaeva, Kalis Nogoibaeva, Vera Toygombaeva, Kenesh Dzhusupov, Paul R. Torgerson The purpose of this study is to assess some aspects of the burden of cystic and alveolar echinococcosis in the Kyrgyz Republic. From 2015-2020 a total of 5568 cases of primary cystic echinococcosis (CE) were reported and a further 1008 recurrent cases. Over the same time period 880 primary cases of primary alveolar echinococcosis (AE) were reported and a further 343 recurrent cases. The estimated DALYs for CE was 7849, that is 1308 per annum or 19.5 per 100,000 per annum. For AE was there were 3809 DALYs, that is 634 per annum or 9.5 per 100,000 per annum. The proportion of fatal cases of AE was 3.6 times higher than from CE. The total economic damage in terms of purchasing power equivalent (PPE) from CE amounted to more than 10,5 million international US dollars. For AE it amounted to more than 5.1 million international US dollars. Most of the financial burden falls on the patients themselves and amounts to 68.4%, i.e., 1223 PPE dollars per case out of total spending 1615 PPE dollars per case. To reduce the social and economic burden of echinococcosis, it is necessary to timely identify the disease, prevent the development of complications and multiple lesions, and promote preventive chemotherapy where appropriate. A deep understanding of the etiology, epidemiology, clinical manifestations, and tactics of early diagnosis of various forms of echinococcosis is also important for timely detection, effective control, and, most importantly, the organization of preventive measures to combat this disease.
DOI: 10.1371/journal.pntd.00140742026-03-23
Pierre Gontao, Christopher G. Laine, Gaelle Kamdjo Guela, Charles Olivier Gomsu Dada, Hortense Abiba, Charles Félix Bilong Bilong, Wilfred Mbacham, Daniel G. Garcia-Gonzalez, Sonia Vection, John D. Gillece, Jeffrey T. Foster, Abel Wade, Angela M. Arenas-Gamboa
by Pierre Gontao, Christopher G. Laine, Gaelle Kamdjo Guela, Charles Olivier Gomsu Dada, Hortense Abiba, Charles Félix Bilong Bilong, Wilfred Mbacham, Daniel G. Garcia-Gonzalez, Sonia Vection, John D. Gillece, Jeffrey T. Foster, Abel Wade, Angela M. Arenas-Gamboa Brucellosis, a neglected zoonotic disease, is endemic in many sub-Saharan African countries, including Cameroon. Recent studies have shown that Brucella abortus infects multiple livestock species throughout Cameroon. While the presence and risk to humans have been identified at farms and abattoirs, the bacterium has never been detected in milk intended for human consumption. In Cameroon, milk is commonly sold at open-air markets for human consumption without regulation. This study investigates the presence of Brucella spp. in milk sold at these markets in three regions: the Far North, North, and West. Cow milk samples and surveys were collected from 380 merchants in each region, totaling 1,140 samples and surveys. Each sample underwent iELISA, culture, real-time PCR, and next-generation sequencing (NGS). Surveys assessed the knowledge, attitudes, and practices (KAP) of milk merchants. Results indicate that B. abortus is not only endemic in livestock but present in milk sold for human consumption. Culture results show a countrywide positivity of 1.3% (1.1% Far North, 1.1% North, 1.8% West). Real-time PCR results indicate a 4.0% positivity rate (2.4% Far North, 5.5% North, 4.0% West). iELISA indicates 21% of the milk samples contained anti- Brucella antibodies, with significant regional variations (38.4% Far North, 15.5% North, 8.9% West). Finally, NGS revealed that the bacterial isolates from milk are epidemiologically linked to those obtained from animals across the region. KAP analysis shows that only 26.4% of merchants boil and 91.2% mix the milk from multiple cattle before sale. All surveyed merchants selling culture-positive milk engaged in risky behaviors, resulting in the sale of contaminated milk to approximately 720 people each week. This study highlights the risk of human brucellosis extending beyond farms and abattoirs to the general public. Future research should investigate milk consumers’ habits and prevalence to better understand brucellosis risk in Cameroon.
DOI: 10.1371/journal.pntd.00140512026-03-20
David H. Duncan, Lucinda E. Harrison, Abbey Potter, Craig Brockway, Kimberly L. Miller, Stephen L. Doggett, Rebecca Feldman, Peter J. Neville, Andrew F. van den Hurk, Cassie C. Jansen, Michaela Hobby, Vicki Burns, Andrew Vickers, Nina Kurucz, Nick Golding, Freya M. Shearer
by David H. Duncan, Lucinda E. Harrison, Abbey Potter, Craig Brockway, Kimberly L. Miller, Stephen L. Doggett, Rebecca Feldman, Peter J. Neville, Andrew F. van den Hurk, Cassie C. Jansen, Michaela Hobby, Vicki Burns, Andrew Vickers, Nina Kurucz, Nick Golding, Freya M. Shearer In the austral summer of 2021–2022, Australia experienced an unprecedented Japanese encephalitis virus (JEV) outbreak, with detections over 3000 km south of previous occurrences. Given the limited knowledge of JEV transmission ecology in Australia, we developed geospatial models of transmission risk to support the public health response. We created time-varying habitat suitability models for suspected mosquito vectors and ardeid hosts using month-scaled occurrence and covariate data from 2000–2023. Ardeid host presence-absence data were obtained from eBird and BirdLife Australia, with habitat suitability estimated using gradient-boosted regression tree models. A national dataset of Culex occurrences was compiled from mosquito surveillance records, literature, and biodiversity databases. Penalised logistic regression was used to model mosquito vector habitat suitability. Vector and host habitat predictions for the outbreak peak in February 2022 were rescaled using JEV infection locations in the public domain to create a combined habitat suitability surface. Our models aligned with detected JEV infections at the continental scale, highlighting transmission suitability across tropical northern Australia and major inland drainage basins in the East. Unlike existing models, we predicted lower suitability along the eastern seaboard, suggesting a delimiting effect of the Great Dividing Range. Our approach provides the most comprehensive and temporally dynamic models for JEV hosts and vectors in Australia, with a significantly larger vector dataset than previous studies. The novel method of rescaling host and vector outputs into a combined surface offers new insights into JEV transmission risk. Favourable conditions were repeated in 2023 with few detected infections, emphasising that JEV ecology in Australia remains poorly understood. This study’s results can support improvements in arbovirus surveillance systems, promoting earlier detection of circulating viruses. Increased focus on vector ecology and distributions is crucial for better understanding JEV transmission in Australia.
DOI: 10.1371/journal.pntd.0014127