PLOS Neglected Tropical Diseases

Introduction Cutaneous leishmaniasis (CL) is a neglected tropical disease associated with reduced health-related quality of life (HRQoL) that leads to permanent scars, anatomical damage and functional impairment. We aimed to translate, culturally adapt and validate the disease specific HRQoL measure the Cutaneous Leishmaniasis Impact Questionnaire (CLIQ) into Afan Oromo. Methods The English version of the CLIQ was translated into Afan Oromo, and culturally adapted by experts with feedback from individuals affected by CL. The finalized Afan Oromo version was then administered to adults with CL. Its psychometric properties were examined using internal reliability, inter rater reliability, construct validity, and responsiveness to change. In addition, the clinical importance difference (CID) and cut-off points for the total CLIQ score were determined. Results The Afan Oromo CLIQ demonstrated acceptable content validity, with I-CVI values ranging 0.83 to1.00. One hundred and forty-four individuals with confirmed CL with a mean age of 35.5 ({+/-}16.5) years were interviewed using the Afan-Oromo version of the CLIQ. The overall median CLIQ score was 40 (IQR=24). The median score for general impacts of CL (Cluster-1), and perceptions about health services and treatment (Cluster-2) were 32 and 9 respectively. The internal consistency (Cronbach alpha= 0.87) and inter-rater reliability (ICC=0.98) were excellent. The differences in median CLIQ scores between physicians determined CL severity classifications and between small and larger lesions were significant. The Afan Oromo CLIQ was responsive to change following treatment (P = 0.037). The CID was 9 and 7 units, using distribution and anchor methods, respectively. Conclusion The Afan Oromo CLIQ is a valid and reliable disease-specific instrument to assess HRQoL of CL affected individuals.

Purpose: This study estimated out-of-pocket (OOP) expenses associated Human African Trypano-somiasis (HAT) care, in the Democratic Republic of the Congo (DRC) and explored how they influ-enced care-seeking behavior and participation in HAT control, aiming to inform effective and finan-cially accessible elimination strategies. Methods: A sequential mixed-methods study was conducted using 16 semi-structured interviews and 6 focus group discussions, followed by a structured survey of 444 recently tested participants across 6 health zones. Medical and non-medical expenditures were collected by health structure type and screening strategy (active vs. passive). Catastrophic health expenditure (CHE) was defined as OOP costs, excluding food, exceeding 10% or 25% of annual household income. Results: Payments at health facilities, transport costs and long distances delayed care-seeking, par-ticularly in passive screening (PS). Active screening (AS) was associated with minimal OOP, 93% of visits were cost-free, with a median OOP of 0.76 USD among those incurring costs. PS generated higher expenses, only 12% of PS visits were cost-free, with a median OOP of 9.08 USD among those with expenditures. Among confirmed cases, median OOP was lower through active (9.84 USD) than PS (24.23 USD). Nearly 90% of confirmed cases sold assets or borrowed money to cover expenses. CHE was uncommon under average household income(<4%), however 36% of passively detected cases exceeded the 10% threshold under minimum-wage income assumptions. Conclusion: Despite free diagnosis and treatment, accessing HAT care in rural, low-resource foci in the DRC still imposes a substantial financial burden. Reaching elimination targets and ensuring eq-uitable access will require minimizing indirect costs and logistical barriers to screening and diagno-sis. As active screening declines, routine health systems assume greater surveillance responsibilities, reducing indirect costs and logistical these barriers will be critical to sustain coverage and maintain an effective and equitable HAT elimination strategy.

BackgroundLeptospirosis is a re-emerging zoonosis in French Guiana, with broad and sometimes misleading clinical spectrum. Neurological involvement, referred to as neuroleptospirosis, lacks a consensus definition. Therefore, it is likely underrecognized, raising concerns about missed diagnosis and potentially poor outcomes. This study aimed to characterize the epidemiology, clinical features and outcomes of neuroleptospirosis. Methodology/ Principal findingsA multicenter retrospective study was conducted across all public healthcare facilities of French Guiana (2015-2021). Neuroleptospirosis was defined by the combination of (i) neurological symptoms and (ii) objective evidence of neurological involvement based on cerebrospinal fluid (CSF) analysis and/or neuroimaging. Cases were compared with leptospirosis without neurological involvement. Among 146 consecutive hospital-managed cases of leptospirosis, 18 (12%) met criteria for neuroleptospirosis (incidence 0.88 cases/100,000 inhabitants/year; 95% CI 0.52-1.39). Among them, 78% (14/18) presented a meningeal syndrome, 22% (4/18) an encephalitic syndrome, and 17% (3/18) showed paresthesia. Lumbar puncture was performed in 28/146 (19%) patients, with pleocytosis observed in 18/28 (64%) patients; median CSF leukocyte count was 42 cells/mm3 (range 13-240/mm3), with lymphocytic predominance in 8/13 (62%), a slight protein level (median 0.51 g/l, range 0.32-0.88) and no hypoglycorachia. Brain MRI revealed abnormalities in 2/8 (25%) cases of neuroleptospirosis: one cerebral infarct and one pachymeningitis. Compared with patients without neurological involvement, factors associated with a diagnosis of neuroleptospirosis were an age <30 years (p=0.004, 95% CI 1.72-18), no leukocytosis (p=0.042, 95% CI 1.04-10.39) nor thrombocytopenia (p=0.012, 95% CI 1.39-14.32) during hospitalization. Neuroleptospirosis cases had milder disease: they less often progressed to sepsis (OR 0.28; 95% CI 0.10-0.79); none required intensive care admission nor died. Discussion/ConclusionsThis study provides new insights into the clinical spectrum and outcomes of neuroleptospirosis in French Guiana. Prospective studies incorporating a consensus definition, systematic CSF analysis and microbiological testing are warranted to further characterize the pathophysiology and optimize diagnostic strategies for neuroleptospirosis. Author summaryLeptospirosis is a re-emerging infection in French Guiana, with a broad range of clinical presentations. Yet, its neurological manifestations--referred to as neuroleptospirosis -- remain likely underrecognized, lacking a consensus definition. We conducted a multicenter retrospective study to describe the epidemiological, clinical features and outcomes of neuroleptospirosis. Then, we compared cases with non-neurological leptospirosis. We used a standardized definition of neuroleptospirosis, based on neurological symptoms associated with cerebrospinal fluid analysis and/or neuroimaging. Neuroleptospirosis accounted for one tenth of leptospirosis cases. Clinical presentation was largely dominated by meningitis (three quarters of cases). Laboratory parameters showed lower rates of leukocytosis and renal involvement. CSF profiles revealed moderate lymphocytic pleocytosis, closely mimicking viral infections. Strikingly, compared with non-neurological forms, neuroleptospirosis cases exhibited fewer severity markers and uniformly favorable outcomes, with lower sepsis, no deaths nor need for intensive care admission. Factors associated with a diagnosis of neuroleptospirosis were an age lower than 30, the absence of hyperleukocytosis and thrombocytopenia during hospitalization. Neuroleptospirosis accounted for a non-negligible proportion of leptospirosis cases in French Guiana, exhibiting CSF features mimicking viral meningitis, and carrying excellent outcomes. Increasing awareness and improving recognition of this presentation is essential to reduce underdiagnosis and refine patient management in endemic settings.

African Animal Trypanosomosis (AAT) is a disease affecting domestic animals, in particular cattle, in sub-Saharan Africa, resulting in billion-dollar losses annually. New drugs to combat and control AAT are urgently required, yet few treatment candidates are currently on the horizon. This can be attributed, in part, to the relative challenges associated with culturing the clinically relevant parasite species in a laboratory environment. Particularly, effective culture of bloodstream form Trypanosoma congolense, the trypanosome species responsible for a large proportion of AAT disease in cattle, requires the use of goat serum, whilst T. brucei is typically cultured in FBS-supplemented culture. This constrains in vitro studies on biology, especially comparative analyses between AAT-causing species. The differing serum supplementation requirements of these two trypanosome species point to metabolic distinctions, which may be important considerations in developing experimental systems to enable the identification and design of novel, pan-species therapies. In this study, untargeted LC-MS lipidomics analyses were conducted to determine the relative lipidomic profiles of T. congolense and T. brucei bloodstream form parasites. Employing a new media formulation that permits effective in vitro culture of both species, it was possible to establish that their global lipidomic profiles are distinct. Notably, T. congolense exhibits a relatively low abundance of ether phospholipids compared to T. brucei, whilst also possessing an enrichment of long-chain polyunsaturated fatty acids (PUFAs). These observations indicate that there are significant differences in the ways these parasites synthesise and remodel their lipid complement, highlighting an evolutionary divergence between the species that likely carries implications for host-pathogen interactions as well as trypanosome membrane biology. Furthermore, this study demonstrates that fine-tuning fatty acid supplementation may aid in optimising a universal medium suited for multiple species of AAT parasites. SummaryMultiple species of protozoan parasites can cause African Animal Trypanosomosis (AAT) in livestock and other animals. However, AAT research has largely centred on a single species, Trypanosoma brucei, partially due to the comparative difficulties in sustaining the other economically important parasite species - Trypanosoma congolense and Trypanosoma vivax - in laboratory culture. In this work, we aimed to determine whether distinctions in use of lipids between T. brucei and T. congolense explains their differing in vitro culture requirements. Using a newly designed media formulation, it was possible to culture mammalian-infective forms of both parasite species under identical conditions, enabling direct comparison of their lipidome - a complete inventory of the different fats and lipids the cells contain. We demonstrate that the T. congolense lipidome significantly differs from that of T. brucei, and that T. congolense shows a preference for longer, more unsaturated lipids. These differences are likely to underlie species-specific differences observed during host infections. Furthermore, our work demonstrates that understanding the lipid biology of protozoan parasites aids in optimisation of laboratory culturing conditions, thereby facilitating further research into these understudied pathogens, including the development of new therapies.

BackgroundCystic echinococcosis (CE) is a neglected parasitic zoonosis that primarily affects marginalized populations in rural endemic regions. These populations have limited access to, and availability of, the appropriate infrastructure, resources, and skills required to treat this complex disease. This retrospective study reviewed and analyzed the clinical management of CE patients in Bhutan, based on hospital records from January 2020 to December 2024. MethodsHospital records of 120 patients with hepatic or pulmonary CE treated between January 2020 and December 2024 in the three hospitals caring for CE patients in Bhutan were retrospectively reviewed. Data on clinical presentation, diagnosis, treatment, and outcomes were extracted from hospital records using a standardized questionnaire. Data analysis was performed using R software (version 4.4.3). FindingsThe median age of the patients was 36 years (IQR: 21.75-53), with 60% being female. The liver was the most affected organ (70%), followed by the lungs (8%). US and CT were used in 83% for diagnostic and pre-surgical assessments. WHO-recommended CE cyst staging was performed in only 11% of cases. Pre-intervention complications were reported in 40% of patients. Treatment approaches included surgery (open or laparoscopic partial cystectomy, deroofing, and cyst drainage) combined with albendazole (ABZ) therapy (74%), PAIR in 4%, and ABZ alone in 8% of cases. Antibiotic use beyond standard perioperative prophylaxis was common (44% of cases). Post-treatment complications occurred in 23% of surgical cases, including one death; biliary leakage was the most frequent complication (55%), and more than one-third of surgical patients were discharged with drains in situ. 23% of the cohort were readmissions and 11% of the patients with hepatic CE were due to documented recurrence requiring repeat surgery. Long-term follow-up was absent, limiting the early detection and management of recurrence. Conclusion and recommendationsThe study findings show that the care for CE patients in Bhutan urgently requires implementation of US-based cyst staging and treatment allocation, the development of infrastructure and skills for the major treatment modalities recommended by WHO guidelines and long-term follow-up to improve patient outcomes, including recurrence, and to ensure quality control of CE care. Safe and proven practices, particularly in surgery, must be prioritized over diversification. Such strategies are feasible and cost-effective. Author SummaryCystic echinococcosis (CE) is a neglected parasitic disease that develops silently and can affect people for years before causing serious complications. It is common in rural, livestock-rearing regions, including Bhutan, where access and availability to appropriate care is limited. We reviewed hospital records of 120 patients treated for CE in Bhutan between 2020 and 2024 to understand current clinical practices and treatment outcomes. Most patients had large liver cysts and were diagnosed at a late stage, often only once complications had occurred. US-based cyst staging was very rarely performed, and cyst-staging was not used to inform treatment decisions. Surgery combined with anti-parasitic (albendazole) therapy was the most common treatment. Postoperative complications and disease recurrence were frequent, and most patients had no long-term follow-up to attend complications and recurrences timely. Considerable variation in surgical and medical management was observed. Developing and implementing WHO-guideline-based infrastructure, resources and training for CE patient care is urgently needed.

BackgroundLymphatic filariasis remains a public health concern in many endemic regions, where chronic disease persists despite substantial reductions in transmission. In Ghana, more than two decades of mass drug administration have significantly reduced disease prevalence and transmission; however, chronic manifestations and gaps in community understanding continue to be reported in parts of the north. This study assessed infection status, chronic morbidity burden, and community knowledge in a rural setting in northern Ghana approaching elimination. Methodology/Principal FindingsA community-based cross-sectional study was conducted in Birifor, northern Ghana, from October 2024 to January 2025. A total of 261 residents aged ten years and above were selected using random sampling. Data collection included structured questionnaires, clinical examination for chronic disease, and night blood microscopy for the detection of infection. No microfilariae were detected (0/261; 0%). However, chronic lymphoedema was identified in five individuals (1.9%), all aged over 40 years. Awareness of the disease was high (95.8%), yet only 39.5% of participants demonstrated good community knowledge and perceptions and self-reported preventive practices. Misconceptions regarding transmission, particularly beliefs that the disease is hereditary or caused by spiritual factors, were common. Participation in mass drug administration was high (93.1%). Despite this, chronic disease imposed a notable socioeconomic burden: all affected individuals reported loss of income, and 60% reported additional household income loss due to caregiving. Conclusions/SignificanceThese findings suggest that transmission in the study area is likely very low, although residual infection cannot be excluded; however, chronic disease and gaps in community knowledge persist. Strengthening morbidity management, improving community education, and providing support for affected households are essential. Sustained surveillance and integrated approaches will be critical to prevent resurgence and support long-term elimination efforts. Author SummaryLymphatic filariasis, also known as elephantiasis, is a mosquito-borne disease that can cause long-term swelling of the legs, arms, or genitals. Global efforts have greatly reduced its occurrence, especially through repeated mass drug administration to afflicted communities. However, many people continue to live with chronic swelling caused by past infections, which can affect their ability to work and participate fully in daily life. In this study, we examined the current situation of lymphatic filariasis in a rural community in northern Ghana that has received many years of treatment. We tested people for active infection, assessed signs of chronic disease, and explored what community members know and believe about the disease. We found no evidence of active infection, suggesting that transmission is now very low. However, some individuals were still living with chronic swelling and reported loss of income, while households also experienced financial strain due to caregiving. Although most people had heard of the disease, many did not fully understand how it is transmitted. Our findings show that reducing transmission alone is not enough. Continued education, community support, and access to care are needed to address the long-term impact of the disease and support ongoing elimination efforts.

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.

BackgroundNepal has set a goal to eliminate lymphatic filariasis (LF) by 2030. As of 2024, Nepal has stopped the mass drug administration (MDA) in 56 of the 64 endemic districts and completed two rounds of MDA in six districts with persistent LF ([&ge;]2% antigen prevalence) using the three-drug regimen of Ivermectin, Diethylcarbamazine, and Albendazole (IDA), exceeding 65% coverage. We subsequently conducted an Epidemiological Monitoring Survey (EMS) to assess the impact of the MDA in reduction of LF infection prevalence below the transmission threshold and examine the factors associated with it. MethodsWe conducted a cross-sectional EMS nine months after MDA in 12 evaluation units (EUs) across six districts, with two sites per EU. We recruited a total of 7,343 individuals aged [&ge;]20 years, sampled using multi-stage sampling, ensuring at least 300 blood samples collected per site. We collected data on demographics and MDA participation. We performed the LF antigen testing for all participants, followed by night blood microfilariae testing in antigen-positive individuals. Statistical analyses included non-parametric tests, Chi-square and Fishers Exact tests, and multivariable logistic regression to assess outcomes after adjusting for potential confounders. ResultsNine of 12 evaluation units (EUs) recorded <1% microfilaremia, meeting the WHO threshold for passing EMS, while three EUs failed with [&ge;]1% prevalence in at least one site. Antigen and MF prevalence were 4.47% and 0.34%, respectively (ratio 13:1). Both Antigen and MF prevalences were significantly associated with female sex (AOR= 0.564, 95% CI: 0.441-0.721 and AOR = 0.326, 95% CI: 0.129-0.826 respectively) and participation in the most recent MDA round (AOR = 0.477; 95% CI: 0.385-0.591 and AOR = 0.089; 95% CI: 0.017-0.464 respectively). MDA uptake was influenced by age (<40 years, AOR = 0.72; 95% CI: 0.653- 0.793), sex (female, AOR = 1.438; 95% CI: 1.29-1.603), cross-border residence (AOR = 0.616; 95% CI: 0.558-0.681), and occupation (agriculture and housewife, AOR = 1.144; 95% CI: 1.008-1.298). MF prevalence was also associated with younger age (<40 years, AOR = 0.211; 95% CI: 0.071-0.626). ConclusionThe survey indicates progress toward LF elimination, with nine of twelve EUs achieving WHOs <1% microfilaremia threshold after two rounds of IDA-MDA. However, transmission persists in three sites, likely linked to poor MDA participation among specific subgroups-- particularly males, younger adults, and cross-border populations. Strengthening MDA coverage and compliance across all demographic and occupational groups, with special focus on border areas, is essential to achieve LF elimination in Nepal.

AbstractO_ST_ABSBackgroundC_ST_ABSLeptospirosis is a neglected tropical disease with substantial public health impact in Brazil, closely associated with socio-environmental vulnerabilities and climatic extremes. This study analyzed the epidemiological profile, spatiotemporal distribution, and climatic influences on leptospirosis incidence and lethality in Brazil from 2015 to 2024. MethodsAn ecological time-series study was conducted using secondary data from the Notifiable Diseases Information System (SINAN). Variables included geographic region, probable infection environment, occupational, and educational level (ISCED-2011). The spatiotemporal correlation between disease incidence and El Nino-Southern Oscillation (ENSO) anomalies was assessed using the Oceanic Nino Index (ONI) and Spearmans rank correlation coefficient. ResultsA total of 31,397 cases were notified, with an annual average of 3,140 cases. The South and North regions exhibited the highest incidence rates, while the Northeast and Southeast presented lethality rates above the national average (9.20%). A marked reduction in notifications occurred during the COVID-19 pandemic. Contaminations occurred predominantly in the domiciliary environment (64%). Rural workers (27.45%) and civil construction workers (18.63%) were the most affected occupational groups, with a higher incidence among illiterate and low-education populations. Climatic analysis revealed a positive spatial correlation between El Nino intensification and leptospirosis incidence in the South and Southeast, and a negative correlation in specific Northeastern states. ConclusionThe dynamics of leptospirosis in Brazil are complex and multifactorial, strongly influenced by macroclimatic variations and driven by deficits in basic sanitation and urbanization. Mitigating the disease burden requires sustained, region-specific public health strategies, targeted infrastructure improvements, and enhanced epidemiological surveillance to address underreporting. Author SummaryLeptospirosis is a life-threatening, neglected tropical disease that disproportionately affects vulnerable populations in Brazil. Despite its significant impact on public health, the way climatic events and socioeconomic factors interact to drive the disease remains complex and regionally distinct. In this comprehensive 10-year study (2015-2024), we analyzed over 31,000 cases across all Brazilian states. We discovered that the home environment is the primary site of infection, largely due to inadequate basic sanitation. The disease takes a severe toll on individuals with lower educational levels and those engaged in rural or civil construction work. Furthermore, we demonstrated that the El Nino climate phenomenon acts as a major spatiotemporal modulator for leptospirosis, triggering infection spikes in the flood-prone South and Southeast regions, while reducing cases during severe droughts in the Northeast. Our findings underscore that leptospirosis is not merely an infectious disease, but a direct symptom of socio-environmental vulnerability. These insights are crucial for public health policymakers to design localized, climate-informed early warning systems and to prioritize basic sanitation infrastructure where it is most urgently needed.

BackgroundSchistosomiasis causes substantial chronic morbidity in sub-Saharan Africa, yet case definitions, clinical management guidance, and health worker training for schistosomiasis-related morbidity remain limited. MethodologyWe conducted a qualitative needs assessment for schistosomiasis morbidity management. Workshops were held over one day in each of Pakwach, Buliisa, and Mayuge Districts in Uganda in October 2024. 105 government health workers participated including clinicians, nurses, laboratory technicians, sonographers, and district health managers from health facilities at different levels of care. The workshops comprised six structured sessions: presentations on schistosomiasis burden in Uganda and the SchistoTrack cohort, a clinical case report by an expert clinician, an interactive session on patient case studies from the SchistoTrack cohort, mapping of patient pathways, anonymous participation and feedback, and demonstrations of schistosomiasis diagnosis. Workshop discussions were documented through notes taken in English and analysed using qualitative thematic analysis as per Braun and Clarke. FindingsHealth workers demonstrated substantial gaps in understanding schistosomiasis case definitions, particularly in distinguishing current infection from chronic morbidity and in grading disease severity. Patient pathways for schistosomiasis morbidity management were fragmented and inconsistent, with weak triage, unclear referral and feedback mechanisms, and limited follow-up across facility levels. Health facilities lacked essential capacity and resources, including routine access to praziquantel outside mass drug administration, diagnostic reagents, functional ultrasound equipment, trained sonographers, and standardized training and reference tools. Collectively, these gaps contributed to inconsistent clinical decision-making and under-recognition of severe schistosomiasis-related morbidity. ConclusionsIntegrating case management into routine health services through standardized case definitions, clearer patient pathways, and targeted practical training for health workers is essential to complement preventive chemotherapy and reduce preventable morbidity. The engagement framework and patient case studies used here can support needs-based assessments in other endemic settings to inform the development of context-appropriate clinical guidance and training programmes. Author summarySchistosomiasis is a disease common in sub-Saharan Africa that can cause serious, lifelong health problems, even after the infection itself has been treated. While mass drug administration programmes have reduced infections, we found that health facilities are often not equipped to recognize or manage the chronic illness that remains after mass drug administration. In this study, we worked with government health workers in three rural districts of Uganda to understand their experiences, challenges, and training needs related to schistosomiasis morbidity. Through interactive workshops, we learned that many health workers struggle to distinguish between current infection and long-term organ damage, especially liver disease. Patient care pathways were often unclear, referrals were poorly coordinated, and essential tools, such as diagnostic supplies, ultrasound access, and routine availability of treatment, were frequently missing. These gaps make it difficult to identify severe cases early and provide consistent care. We show that strengthening routine health services through clearer case definitions, better training, and more coordinated patient pathways is essential to reduce preventable suffering from schistosomiasis. Our approach offers a practical way to support health systems in other endemic settings facing similar challenges.

BackgroundScrub typhus is a major yet neglected vector-borne disease in Thailand, where it has been nationally notifiable for over two decades. However, long-term changes in its epidemiology, including reporting rates, transmission intensity, disease severity, and seasonal patterns, have not been comprehensively characterised at the national level. MethodologyWe analysed 22 years of national surveillance data for scrub typhus in Thailand (2003-2024) using a latent process model that jointly fits reported cases with published nationwide seroprevalence data and antibody kinetics to estimate reporting rates and underlying transmission dynamics across all 77 provinces of Thailand. FindingsOver the 22-year study period, 143096 cases and 119 deaths were reported nationally. Estimated reporting proportion broadly mirrored transmission intensity, being higher in high-burden regions and lower elsewhere. A synchronous decline in detection was observed across all regions during the COVID-19 pandemic, followed by rapid rebound by 2024. After accounting for these reporting dynamics, the force of infection was highest in the northern provinces but also substantial in the northeast and south, with upward trends in some provinces. Susceptibility among older adults aged 65 and above increased progressively over the study period, reversing the pattern observed two decades earlier. Case-fatality in the 25-35-year reference group was low and declined from 0.14% (95% Credible Interval [CrI]: 0.06-0.29%) to 0.06% (95% CrI: 0.02-0.12%), but relative case-fatality remained consistently highest among adults above 65 across all periods. Three geographically distinct seasonal patterns were identified, all stable over time. ConclusionOver two decades, scrub typhus transmission in Thailand has been shown to extend well beyond its traditionally recognised northern focus, with substantial burden in previously underappreciated regions, while the demographic profile of those most affected has shifted progressively toward older adults. These findings support the need for regionally tailored surveillance, age-targeted clinical preparedness, and sustained investment in understanding the ecological drivers of transmission. Key messagesScrub typhus is a common but neglected cause of fever in Thailand, where it has been reported through the national surveillance system for over two decades. However, trends in reported cases can be misleading because they reflect not only true changes in transmission but also variation in diagnosis and reporting over time and across regions. We developed a model that combines surveillance data with seroprevalence surveys and antibody kinetics to separate true changes in transmission from variation in reporting, allowing us to estimate how transmission intensity, disease severity, and seasonal patterns have evolved from 2003 to 2024 across all 77 provinces. We found that substantial transmission occurs not only in the well-studied northern provinces but also in the northeast and south, where the disease has received less attention. Susceptibility has progressively shifted toward older adults, who also face the highest case-fatality, while three distinct seasonal patterns vary by region but have remained stable over time. These findings suggest that scrub typhus control in Thailand requires a shift from a predominantly northern focus toward regionally tailored strategies that account for local transmission timing, an ageing at-risk population, and the ecological drivers that sustain transmission in each setting.

BackgroundLeishmaniasis is endemic in southern Europe with high risks of outbreaks and geographical spread. However, the risk factors for human leishmaniasis are understudied in this region. MethodologyTo evaluate these risk factors, we tested associations between leishmaniasis incidence and an array of variables related to socioeconomics, immunocompetence, climate, land use, biodiversity, and ecology (i.e., the pathogen and its vectors and reservoirs). FindingsSocioeconomic factors, such as demography, occupation, and housing conditions, were strongly associated with leishmaniasis incidence in endemic regions. The specific factors and the magnitude of their impacts varied among the five countries studied. Human immunosuppressive condition was highly correlated with leishmaniasis risk in Spain and Italy. Climate likely delineated leishmaniasis-free regions from endemic regions in France. Our results suggest that climate change alone may not drive the spread of leishmaniasis within this century. Pathogen hazard and reservoir abundance affected leishmaniasis risk more than vector hazard in countries where data were available. Biodiversity was weakly, negatively related to leishmaniasis. SignificanceOur results highlight the importance of socioeconomic risk factors and immunosuppression for human leishmaniasis, suggesting potential implications for disease control and prevention policies. Surveillance of Leishmania spp. in humans, vectors, and reservoirs; assessment of reservoir abundance; and data accessibility are crucial for disease prevention and preparedness. Because of possible biodiversity regulation, efforts to understand and control leishmaniasis could benefit from a One Health approach that involves epidemiologists, social scientists, and ecologists, among others. Author summaryLeishmaniasis is a common disease in tropical and subtropical regions, but it also occurs in southern Europe. While some infectious disease experts are concerned that climate change might lead to the emergence of new diseases in new areas, the main factors shaping leishmaniasis in Europe are not well understood. This study considered a wide array of potential risk factors in a variety of categories, ranging from climate and nature to how people live and work. We found that the risk for leishmaniasis is mostly related to occupation, housing type, age, and sex, though the exact risk factors change from country to country. People with weakened immune systems face high risk, and infected animals pose a major threats, but climate change alone may not drive the spread of leishmaniasis as much as once feared. Interestingly, a healthy variety of wildlife may help keeping the disease in check. To limit the impacts of leishmaniasis, we need to protect the most vulnerable populations, such as people living with weakened immune systems, working in high-risk sectors, residing in single-dwelling buildings, or experiencing or facing homelessness. We need to monitor the parasite in people and animals and share those surveillance data openly. Ultimately, we need a "One Health" approach where doctors, social workers, and scientists work together to keep our ecosystems healthy and our communities safe.

Knowledge, attitudes, and practices (KAP) studies help identify priority groups for control interventions. They include multiple factors, such as threat perception--encompassing perceived susceptibility and severity of a health risk--and sociodemographic data, which have been shown to be associated with individual prevention and control measures for mosquito-borne diseases. However, their application to tick-borne diseases (TBDs) remains largely unstudied in limited-resource settings. Ehrlichia canis, transmitted by Rhipicephalus sanguineus s.l. ticks, is highly prevalent in Iquitos, Peru, a city in the Peruvian Amazon. We analyzed data from a questionnaire completed by 285 dog owners in Iquitos to assess whether the perceived threat from ticks and TBDs is linked to preventive measures for homes and dogs. Secondary aims included examining the associations between TBD awareness and preventive/control measures, as well as identifying sociodemographic factors linked to these measures and threat perception. We used simple and multiple regression models to evaluate the associations of interest. We found that 31.6% of participants (n = 90) were unaware that TBDs could occur in humans. This group tended to be older, with lower education levels and lower income. Only a small portion of the included participants reported using preventive/control measures. After adjusting for sociodemographic factors, TBD awareness was associated with a higher likelihood of home spraying. Furthermore, those who perceived TBDs as moderate diseases were marginally more likely to apply spray acaricide to their dogs, while those who perceived these diseases as severe to very severe were more likely to administer oral acaricides to their dogs. These findings highlight variability in the link between threat perception and preventive measures. Results suggest TBD awareness campaigns may benefit from focusing on older individuals with lower education and income, while educational efforts promoting effective prevention measures like acaricidal pills should target all dog owners. Author summaryIn Iquitos, Peru, the high prevalence of Rhipicephalus sanguineus s.l. infestation in dogs and homes and the high prevalence of Ehrlichia canis infection in dogs, highlight the need for urgent tick prevention and control. Understanding the influence of awareness, attitudes (including perceived threat) and sociodemographic factors on practices is key to designing effective interventions and identifying target groups. We analyzed data from 285 dog owners to assess if perceived threat (susceptibility and severity) from ticks and tick-borne diseases (TBDs) was linked to self-reported preventive measures for homes and dogs. We also examined TBD awareness and sociodemographic factors potentially associated with preventive practices. Among participants, 31.6% were unaware that TBDs could affect humans, with this group tending to be older and have lower education and income levels. Perceived susceptibility to tick bites and TBDs was not linked to preventive measures, while perceiving TBDs as moderate to severe increased the likelihood of using spray and oral acaricides on dogs. However, usage remained low even among those with high perceived severity. These findings reveal varied associations between threat perception and preventive practices, as they may be influenced by factors such as perceived benefits, barriers, and self-efficacy. Educational efforts should target older adults, and those with lower education and income, while campaigns promoting effective measures like acaricidal pills should address all dog owners.

Leishmaniases remain a significant global public health threat, with Leishmania amazonensis and Leishmania infantum representing the etiological agents of the cutaneous and visceral forms in the Americas, respectively. Building on our previous identification of Phospholipase A1 (PLA1) in Leishmania braziliensis, this study provides a comprehensive molecular, immunological, and biochemical characterization of PLA1 in L. amazonensis and L. infantum promastigotes. We analyzed PLA1 activity and expression, purified the recombinant enzyme from L. amazonensis, and validated protein expression using a specific anti-PLA1 serum. The major contribution of this research is the first description of the subcellular localization of a PLA1 within the Leishmania genus. Moreover, our results reveal an unprecedented association between PLA1 and lipid droplets within the parasites. This discovery is of particular interest as it provides the first evidence linking this enzyme to lipid storage organelles in Leishmania. Given that PLA1 is an established virulence factor in other trypanosomatids, these findings suggest a specialized role for the enzyme in parasite lipid metabolism and potentially in its pathogenic mechanisms, opening new perspectives for understanding Leishmania biology.

There is an ongoing Oropouche Fever (OF) outbreak in Brazil since 2024. There are dengue and chikungunya prediction models available, but none to help discriminate dengue, chikungunya, and OF. ObjectiveThis study aims to develop and validate clinical prediction models for dengue, chikungunya, OF. MethodsThis study uses surveillance data from Espirito Santo state / Brazil, from 2023-2025. Epidemiological investigations and biological samples were used to conclude cases as either (a) clinical-epidemiologically confirmed, (b) laboratory confirmed, or (c) "discarded". The predictors were all data related to signs, symptoms, and comorbidities available in the notification forms. The analysis was performed using random forest regression models, one for each outcome, in development and validation datasets. ResultsA total of 465,280 observations were analyzed, 261,691 dengue cases (56.6%), 18,676 chikungunya cases (4.0%), 12,174 OF cases (2.6%), and 179,115 discarded cases (38.6%). All three models had good discrimination and moderate to good calibration after scaling prediction. The models retained from 26 to 16 predictors each. Leukopenia and vomiting were the most discriminatory predictors for dengue, arthritis, arthralgia, and rash were the most discriminatory for chikungunya, and epidemiological features were the most relevant for OF. The dengue, chikungunya, and OF models had ROC AUC of 0.726, 0.851, and 0.896 in the validation set, respectively. ConclusionThis research identified predictors most discriminative between dengue, chikungunya, and OF. We developed and validated predictive models, one for each condition, with moderate to very good performance available at https://pedrobrasil.shinyapps.io/INDWELL/. One may use them in diagnostic work-up and arbovirus surveillance. LAY SUMMARYO_LIDengue fever was by far the most common confirmed infection in the surveillance system (56.6%), followed by chikungunya cases (4.0%), oropouche cases (2.6%), zika cases (0.2%), with different seasonality. C_LIO_LIAlthough suspected dengue cases were more laboratory tested, laboratory confirmation was more frequent among oropouche fever cases. It was possible to develop and validate models for dengue, chikungunya, and oropouche diagnostic investigation, and their performance was from moderate to very good, with suggested decision limits to aid the users. All attempts to develop Zika models returned models with unacceptable performance. C_LIO_LIWe developed an instrument to predict the three conditions with the same predictors and made it available for users at https://pedrobrasil.shinyapps.io/INDWELL/. C_LI

Human African Trypanosomiasis (HAT) is a two-stage infection caused by Trypanosoma brucei ssp. In stage I the trypanosomes are in blood, lymph and tissue interstitial space and the infection progresses to stage II when the parasites enter the central nervous system (CNS), resulting in behavioural aberrations that proceed to coma and death. Here, we use a bioluminescent murine model of HAT to examine parasite localisation and the changes in host brain gene expression, metabolism and function, and behaviour that occur over the course of the infection. The murine HAT model reproduces the decrease in brain tryptophan seen in clinical samples, and we report for the first time an unprecedented 1.8-fold decrease in global brain glucose metabolism in stage II infection. These metabolic changes are accompanied by an 18-fold decrease in brain insulin transcripts without changes in pathways regulating the cellular responses to insulin. By contrast, genes involved in fatty acid and lipid metabolism are upregulated in the brain during stage II infection. Moreover, we show that transcriptional programmes regulating mitochondrial metabolism dynamically adapts across the time course of HAT infection, ultimately leading to a transcriptional programme that diverts host brain metabolism away from glycolysis during stage II infection. Overall, our data demonstrate a reprogramming of brain energy metabolism during stage II HAT infection that favours the utilization of fatty acids and lipids to meet the energy demands of the brain, with a reduced reliance on glucose metabolism. Despite the profound neurometabolic changes observed, host anxiety-like behaviour is unchanged and episodic learning and memory is not impaired, suggesting that brain metabolic reprogramming enables the utilisation of adipose reserves to maintain core brain functions. These finding may explain the progressive onset of neurological symptoms in HAT patients and inform the development therapeutic interventions to alleviate them. Author SummaryHuman African Trypanosomiasis is classically characterised as being a two-stage infection, stage I where the extracellular Trypanosoma brucei multiply in the blood, lymph and peripheral tissues, and stage II where parasite cross the blood-brain barrier (BBB) causing neurological symptoms and eventually death. Using a murine model of HAT we show that in stage II the key brain metabolite tryptophan is depleted and cerebral glucose utilisation is decreased, accompanied by extensive metabolic transcriptome reprogramming of the cerebral tissue during stage II infection. Despite this we see no significant change in mouse anxiety-like behaviour or learning and memory. Our data are consistent with the brain switching from glucose as the primary energy source, instead utilising the products of lipolysis to maintain essential brain functions. This new understanding of the neurometabolic changes that occur in stage II HAT may help to develop new treatments for the neurological symptoms that affect patients at this stage of the disease.

Human leptospirosis is a disease of public health importance in Thailand, but the animal species involved in the transmission cycle have not been fully uncovered. This study investigated Leptospira infection in dogs and terrestrial micromammals in rural Nan Province, Thailand, and the pathogen diversity. Sera from 95 seemingly healthy dogs and kidney samples from 399 micromammals were analyzed using real-time PCR for Leptospira detection, followed by conventional PCR and sequencing of infecting Leptospira. We investigated environmental factors associated with Leptospira infection in micromammals, using data collected during trapping. Real-time PCR revealed ongoing infection in 8.4% (8/95) of dogs and 10.0% (40/399) of terrestrial micromammals, with 12 infected species including Bandicota indica, Berylmys berdmorei, Berylmys bowersi, Mus cervicolor, Mus cookii, and Hylomys suillus. In this qPCR-positive micromammals, three pathogenic Leptospira species were identified: L. interrogans, L. weilii, and L. borgpetersenii. This represents the first confirmed detection of L. weilii in rodents in Thailand. Infected micromammals were found in agricultural and forest habitats but not in human settlements. Our study demonstrates potential complex leptospirosis epidemiology in rural Thailand, with multiple species serving as pathogenic Leptospira reservoirs across diverse habitats, and some shared pathogen diversity with human leptospirosis cases in Thailand. Free-roaming dogs may serve as bridge hosts, transmitting zoonotic Leptospira from micromammals to humans by visiting both animal habitats and human settlements. These findings emphasize the need for integrated One Health surveillance approaches to control leptospirosis in rural communities.

Background: Skin-related neglected tropical diseases (skin NTDs) continue to affect people living in remote communities of endemic countries, particularly in regions with limited access to dermatological care. This operational research evaluated the impact of the eSkinHealth app, a digital health tool designed to enhance case management of skin NTDs and other skin diseases in Cote d'Ivoire. The eSkinHealth app functions as a portable electronic medical record and a platform for teledermatology, connecting frontline healthcare workers to remote specialists. Methodology/Principal Findings: The study was conducted across sixteen primary health centers (PHCs) in the Sinfra and Bouafle districts, regions endemic for skin NTDs. Using a before-and-after implementation design, baseline data were collected from paper registries and compared with data captured through the app. The primary objective was to assess changes in skin disease detection and diagnosis, while also evaluating usability, acceptability, and feasibility of the tool among healthcare workers. A total of 1,766 patients were included in the analysis (mean age 22.8 years; 55% male). During the intervention period, skin NTD registrations increased significantly from 30 to 91 cases (p < 0.01). Buruli ulcer cases rose from 6 to 14 (p = 0.05), scabies from 24 to 70 (p = 0.13), and other NTDs such as leprosy, lymphatic filariasis, and yaws were newly detected and documented. In contrast, registrations of non-NTD skin diseases decreased from 662 to 472 cases (p < 0.01); however, the proportion of non-NTD cases which received diagnostic confirmation increased markedly, from 0% at baseline to 94% during the intervention period (p < 0.01). Qualitative interviews with nurses and community health workers highlighted improvements in diagnostic accuracy, patient engagement, and confidence in daily practice, while also noting persistent challenges such as stigma, transportation barriers, technical difficulties, and patient concerns about privacy. Conclusions/Significance: The integration of the eSkinHealth app into routine PHC services proved effective in enhancing diagnostic capacity for skin NTDs in resource-limited settings. However, capturing other skin diseases proved more difficult given their high prevalence. While the app demonstrated clear benefits in improving diagnostic rates and healthcare worker confidence, persistent challenges such as technical issues and patient concerns about privacy need to be addressed for future scalability. As with many digital tools, further refinement will be an ongoing process, and the lessons learnt from this study may provide valuable guidance for similar initiatives in comparable settings.

In 2025 Guinea was validated as achieving elimination as a public health problem for the highly pathogenic, vector-borne infection, gambiense human African trypanosomiasis (gHAT) after reaching several years of low-level case reporting. gHAT cases in Guinea have overall seen a large decrease between 2000 and 2024, however there have been notable fluctuations. Transmission modelling was used to assess these trends in observed cases for the foci Boffa East, Boffa West, Dubreka, and Forecariah and evaluate transmission changes. This study quantifies the impact of interruptions due to Ebola and the introduction of new interventions (particularly the rapid diagnostic tests in the passive health system and vector control) in each focus. The model suggests that transmission of gHAT has fallen 97% (83-100%) between 2000 and 2024, with disease burden measured in disability-adjusted life years (DALYs) reduced by 94% (63-100%). We estimated that Ebola interruptions caused an additional 1,147 gHAT DALYs due to the suspension of gHAT activities, however passive screening improvements and the introduction of vector control likely averted 1,719 and 9,038 DALYs respectively. This study quantifies the impact of Ebola related interruptions on gHAT transmission and disease burden and highlights the success of medical and vector control interventions in Guinea.

Social stigma surrounding chronic skin Ulcer leads patients to hide their wounds or delay seeking medical care. The aim of this study was to explore the types and causes of chronic skin ulcers among patients seen in the dermatology departments of two university hospitals in Burkina Faso. This was a cross-sectional, retrospective study covering an 11-year period, from 2013 to 2023. A review of consultation records allowed for the collection of sociodemographic and clinical data from 104 patients who were seen for chronic skin ulcers over the 11-year period, averaging 9 patients per year. The patients were primarily adults (n=60) and older adults (n=21). Leg ulcers were the condition observed in most patients (n=59). Eight cases of Buruli ulcer (7.69%) were identified among the 104 patients. Five of the eight cases, or 62.50%, were aged between 0 and 19 years. Half of the eight patients resided in Ouagadougou. These results highlight low utilization of dermatology services for chronic skin ulcers. Furthermore, indigenous cases of Buruli ulcer have been identified in Burkina Faso. Consequently, our findings call for the implementation of strategies focused on addressing social perceptions of these ulcers and on the screening and management of this disease.