PLoS Neglected Tropical Diseases最新文献

{"title":"Comparing diagnostic methods for historical arbovirus outbreaks: Insights from 19th century \"dengue\" epidemics.","authors":"Timothee Bonifay, Mathieu Nacher, Clémence Bonnefoy, Benjamin Rossi, Edouard Hallet, Philippe Abboud, Guillaume Bellaud, Nathalie Dournon, Aurélia Henn, Adrien Lemaignen, Liem Binh Luong Nguyen, Diane Sanderink, Gaelle Walter, Alexandre Bleibtreu, Loïc Epelboin","doi":"10.1371/journal.pntd.0013551","DOIUrl":"10.1371/journal.pntd.0013551","url":null,"abstract":"<p><p>This study reexamines historical \"dengue\" epidemics of the 18th and 19th centuries, suggesting that chikungunya virus (CHIKV), rather than dengue virus (DENV), may have been responsible for many of these outbreaks. While \"dengue\" was identified as a tropical disease in the 19th century, its exact characteristics remain unclear, and some descriptions align more closely with CHIKV, known for its distinctive symptom of joint pain. Three approaches were used to investigate these historical epidemics: (A) Expert opinion provided a contextualized and comprehensive analysis but faced criticism for its subjective nature (B) Clinical Score Application allowed for greater objectivity and a more stringent diagnosis, although it was limited by the need for a complete description (C) Double Proofreading: Two expert groups independently reviewed the articles, which enhanced objectivity but also led to greater variability in the results. The study suggests that CHIKV was mainly responsible for the epidemics historically attributed to \"dengue\". It highlights the challenges of diagnosing diseases from historical records. It also raises the possibility that other alphaviruses, like mayaro virus, could be involved, but CHIKV remains the primary candidate. This study offers intriguing insights into pathogen identification in historical epidemics, emphasizing the importance of a combined approach for a more precise understanding of past diseases and their evolution.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013551"},"PeriodicalIF":3.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic-based identification of novel EV-derived protein antibodies biomarkers for melioidosis diagnosis.","authors":"Nini Luo, Jun Tan, Xuemiao Li, Yanshuang Wang, Ting Zhang, Chen Chen, Lin Liu, Xinyi Song, Hua Pei, Bo Wang, Qi Li, Shen Tian, Nan Zhang, Wei Cheng, Qianfeng Xia","doi":"10.1371/journal.pntd.0013543","DOIUrl":"10.1371/journal.pntd.0013543","url":null,"abstract":"<p><p>Melioidosis, caused by Burkholderia pseudomallei (Bp), is a life-threatening disease characterized by diverse clinical manifestations and limited diagnostic capabilities. Extracellular vesicles (EVs) have emerged as critical carriers of novel antibody targets for serodiagnosis. In this study, we established a Bp-infected BEAS-2B cell model (Bp/BEAS-2B) and isolated EV from both Bp and Bp/BEAS-2B cells to generate EV proteome, identifying potential antigenic biomarkers for melioidosis diagnosis. Bioinformatics analysis identified PPEP and POMCR proteins as candidate antigens, with BLF1 and omp A serving as positive controls. Using a self-developed IgM-ELISA, serum samples from 43 melioidosis patients and 47 healthy volunteers were analyzed to detect antibodies against these antigens. Anti-POMCR IgM demonstrated exceptional diagnostic performance, with an AUC of 0.9872 (95% CI: 0.9713-1.003), sensitivity of 93.02% and specificity of 97.92% at a cutoff value of OD450 = 0.118. Similarly, IgM against PPEP, BLF1, and omp A also showed high diagnostic accuracy, with AUC values of 0.969, 0.9621, and 0.976, respectively. The accuracy of anti-POMCR and anti-PPEP were 96.43% and 95.54%, respectively, equivalent to anti-omp A (93.75%) and anti-BLF1 (91.96%). Antibodies to EV-derived proteins effectively differentiated melioidosis patients from other bacterial infections and healthy volunteers, highlighting their clinical potential as diagnostic tools for melioidosis.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013543"},"PeriodicalIF":3.4,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying hotspots of S. haematobium infection following praziquantel treatment during multiple annual mass drug administration campaigns in Zimbabwe.","authors":"Takafira Mduluza, Grace Zdesenko, Paradzayi Tagwireyi, Caitlin M Jones, Francisca Mutapi","doi":"10.1371/journal.pntd.0013546","DOIUrl":"https://doi.org/10.1371/journal.pntd.0013546","url":null,"abstract":"<p><p>Urogenital schistosomiasis is contracted from the Schistosoma haematobium parasite and is treated with the drug praziquantel (PZQ). Despite MDA interventions, persistent hotspots (PHS) of S. haematobium infection have been identified in multiple schistosome endemic African countries but have yet to be characterised in Zimbabwe. This study assessed long-term infection persistence and variability in praziquantel (PZQ) efficacy among school-aged children (6-15 years) in 29 districts of Zimbabwe, using data from MDAs conducted between 2012 and 2017. Metrics included infection prevalence, mean egg count, and treatment efficacy indicators. Two hotspot definitions were applied: (i) prevalence-based persistent hotspots (PPHS), identified by limited reduction or rebound in prevalence; and (ii) efficacy-based persistent hotspots (EPHS), defined by cure rates below 70%. Statistical comparisons between hotspot and non-hotspot (\"responder\") districts used regression models, Fisher's exact test and Mann-Whitney U tests. Analyses revealed four PPHS and six EPHS. PPHS districts exhibited significantly higher baseline prevalence and infection intensity compared with responders (P = 0.043), a pattern not observed for EPHS. Greater distance from freshwater sources was associated with EPHS occurrence (P = 0.016), although this appeared to be an indirect effect of initially high infection intensities. Lower treatment frequency correlated with increased hotspot occurrence, but the relationship was not statistically significant for either hotspot category. Other investigated factors including treatment coverage, timing of drug administration and ecological suitability for intermediate host snails showed no significant association with hotspot status. The elevated initial prevalence and infection intensity in PPHS suggest these indicators could be used for early hotspot identification, enabling targeted adjustments in intervention strategies. The findings underscore the limitations of relying solely on preventive chemotherapy in high-transmission settings. Integrating complementary measures such as water, sanitation and hygiene (WASH) interventions and snail control may improve outcomes, particularly in hotspot areas. In conclusion, the persistence of S. haematobium hotspots in Zimbabwe highlights the need for adaptive, integrated control approaches aligned with the WHO's 2030 roadmap. Monitoring baseline epidemiological indicators could facilitate earlier detection of persistent transmission foci, guiding more effective and sustainable schistosomiasis control.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013546"},"PeriodicalIF":3.4,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multifaceted molecular approach to surveillance of leishmaniasis: Identification of sand fly species, Leishmania parasites, and blood meal sources using high-resolution melting analysis.","authors":"Liora Studentsky, Fouad Akad, Debora Diaz, Irina Ben Avi, Shirly Lea Elbaz, Tamar Grossman, Maya Davidovich-Cohen, Oscar David Kirstein, Laor Orshan, Gad Baneth","doi":"10.1371/journal.pntd.0013412","DOIUrl":"10.1371/journal.pntd.0013412","url":null,"abstract":"<p><p>Leishmaniasis is a significant public health concern in large parts of the world including Israel, with limited diagnostic tools available for effective surveillance and control. Traditional methods for sand fly species identification, Leishmania detection, and blood meal analysis are time-consuming and prone to errors. To address these challenges, this study aimed to develop PCR-high resolution melt (HRM) assays to accurately determine sand fly species, Leishmania infection and blood meal sources in sand flies. Field-collected sand flies from all regions of Israel were used for the validation of three PCR-HRM assays. These included 254 sand fly males and females identified morphologically for species verification; 1,120 unfed females for Leishmania detection, and 538 engorged females for blood meal identification. PCR products were subjected to HRM curve analysis, and results were compared to nucleotide sequencing and sand fly morphology. Eleven sand fly species, 25 different host species blood meals and four Leishmania species were discerned and each presented a specific HRM pattern. Of the 1,658 analyzed females, 16 (1%) were positive for Leishmania, and the species identified were: Leishmania major, L. tropica, L. infantum and L. donovani. Blood meal source was identified in 520 (96.7%) engorged females. Blood from four animal species (domestic cat, rock hyrax, European hare, cow) accounted for 53% of the sand fly blood meals and the remaining 47% came from 21 other animal species. The sand fly species distribution showed that L. major and L. donovani vectors were mostly prevalent in arid southern Israel while L. tropica and L. infantum vectors were abundant in central and northern Israel. These results present the current knowledge of the different Leishmania species life cycles, vectors, and host species present in Israel and substantiate the utility of the assays developed herein which combine the advantages of PCR and the discriminatory power of HRM.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013412"},"PeriodicalIF":3.4,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing the implementation of case-area targeted interventions during cholera outbreaks with context-specific delivery mechanisms.","authors":"Jessica Dunoyer, Ruwan Ratnayake, Sandy Moore, Gregory Bulit, Samuel Beaulieu, Christophe Valingot, Pierre-Yves Oger, Bertrand Sudre, Daniele Lantagne, Nicola Desmond","doi":"10.1371/journal.pntd.0013534","DOIUrl":"10.1371/journal.pntd.0013534","url":null,"abstract":"<p><p>Cholera, a severe fecal-oral disease, disproportionately affects the poorest communities who lack access to safe water and sanitation. Individuals living in the same household, or within a few hundred meters, of a patient are at increased risk of infection. Thus, during cholera outbreaks, targeted response strategies, such as case-area targeted interventions (CATIs), provide health (e.g., vaccination and antibiotic prophylaxis) and water, sanitation, and hygiene services for affected households and at-risk neighbors living in a defined ring. Previous research on CATIs has focused on impact and effectiveness, and less on implementation processes. As cholera outbreaks occur in diverse settings with differentiated challenges, we investigated how CATI and CATI-like mechanisms can be best used and adapted. Drawing on 43 peer-reviewed articles and gray literature sources retrieved through a narrative review, and 15 key informant interviews conducted using a snowball sampling approach, we identified 27 CATI or CATI-like experiences across 15 countries in Africa, Asia, the Caribbean, and Middle East between 2004 and 2024. Four delivery mechanisms were identified: CATI, pre-CATI, case-cluster, and health-facility-based interventions (HBI). Challenges to implementation included: delays in response; difficulty accessing populations; resource shortages to initiate, maintain, or scale up response; overwhelmed response capacity; limited skills and knowledge; low uptake and acceptance; weak coordination; poor reporting and monitoring; and sustainability concerns. Implementers adapted delivery to overcome challenges, particularly in outbreaks with high case-loads and in insecure and hard-to-reach contexts by ensuring readiness and early activation, strengthening local actors' capacity, optimizing resources, adjusting ring sizes, and prioritizing cases. Based on these results, we developed a practitioner-centered framework to optimize programmatic implementation through context-specific delivery mechanism and ultimately decrease cholera incidence.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013534"},"PeriodicalIF":3.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammatory cytokine profile and Jarisch-Herxheimer reaction in Leptospirosis patients: A prospective case-series study in New Caledonia.","authors":"Julie Cagliero, Anne Loarec, Julien Lebon, François Baur, Patrick Lefevre, Emilie Follenfant, Cyrille Goarant, Damaris Ukeiwe, Julien Colot, Sylvie Tardieu, Catherine Werts, Cécile Cazorla","doi":"10.1371/journal.pntd.0013189","DOIUrl":"10.1371/journal.pntd.0013189","url":null,"abstract":"<p><strong>Background: </strong>Leptospirosis is a neglected zoonosis. This spirochetal disease is common in tropical countries where rainfall and poor sanitation facilitate skin contact with environmental Leptospira shed in animal urine. Antibiotics are effective against spirochetes, although a harmful Jarisch-Herxheimer (JHR) reaction can occur within hours of treatment, with the onset of chills, fever and/or hypotension. However, the awareness and incidence of JHR in leptospirosis are poorly understood.</p><p><strong>Methods: </strong>This prospective observational study enrolled 81 patients diagnosed with leptospirosis from four hospitals in New Caledonia between 2021 and 2024. To evaluate the patients' inflammatory status and identify risk factors for JHR, we collected data on clinical, socioeconomic, and biological factors (including blood cytokine levels) at admission and during the hours following treatment with different regimens of β-lactam antibiotics.</p><p><strong>Main results: </strong>The majority of the cohort were middle-aged men, most of them Melanesian farmers. They exhibited high levels of C-reactive protein (CRP), neutrophilia, thrombocytopenia, and elevated biochemical markers indicative of liver and kidney dysfunction, which are typical of leptospirosis. Unexpectedly, pro-inflammatory cytokine levels were low or undetectable upon admission, while high levels of the anti-inflammatory cytokine IL-10 were measured. After antibiotherapy, increased levels of the pro-inflammatory cytokines TNF and IL-6, as well as IL-10 were observed. Strikingly, there was no increase in IL-1ß, the main player in the \"cytokine storm\". JHR, identified with a new clinical score, occurred in 48% (possibly 61%) of patients and was associated with higher cytokine levels, as expected.</p><p><strong>Conclusion/significance: </strong>This study confirms the stealth nature of leptospires, which induce a potent anti-inflammatory response rather than inflammation. It calls into question both the cytokine storm hypothesis, which is often cited in leptospirosis and the use of immunosuppressive drugs. The high incidence of JHR in New Caledonia suggests that the systematic use of ß-lactams as a first-line treatment should be reevaluated.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013189"},"PeriodicalIF":3.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Etiological spectrum and diagnostic features of lymphadenopathy in People Living with HIV in French Guiana: A 17-years multicenter retrospective case series.","authors":"Morgane Bourne-Watrin, Ugo Françoise, Sophie Alexandra Baron, Antoine A Adenis, Dufens Pierre Louis, Loïc Epelboin, Mathieu Nacher, Félix Djossou, Kinan Drak Alsibai, Pierre Couppié","doi":"10.1371/journal.pntd.0013558","DOIUrl":"10.1371/journal.pntd.0013558","url":null,"abstract":"<p><strong>Introduction: </strong>Lymph node enlargement can be present at any stage of the HIV infection, reactive to HIV itself, another infection, or a malignant source. The aim of our study was to describe the causes of lymphadenopathy in the people living with HIV (PLHIV) of French Guiana, a French territory in the Amazon region.</p><p><strong>Methods: </strong>A retrospective multicenter case series was conducted between January 2005 and December 2021. Inclusion population consisted of PLHIV who underwent a fine needle aspiration or a biopsy of a lymph node that was analyzed at the Department of Pathology of Cayenne hospital.</p><p><strong>Results: </strong>We included 152 adults, with a median age of 43 [35-51] years and median CD4 count of 185/mm3 [60-344]. The main causes of lymphadenopathy were: histoplasmosis (25%, CI95%: 18-33), followed by tuberculosis (24%, CI95%: 18-32), HIV-reactive lymphadenitis (21%, CI95%: 15-29) and lymphoproliferative disorder (11%, CI95%: 7-18). Multiple causes were present in 6% of cases. Opportunistic infections represented 53% (CI95%: 44-61) of cases. The main characteristics associated with opportunistic disease (infectious or neoplastic) were lymph node > 5 cm, CD4 count < 200/mm3, hepatomegaly or splenomegaly and the presence of extra-ganglionic symptoms.</p><p><strong>Conclusion: </strong>For the last 17 years, opportunistic infections represented 53% of the causes of lymphadenopathy among PLHIV. Histoplasmosis, already recognized as the first AIDS-defining condition and first cause of AIDS-related deaths in French Guiana, is also the first cause of lymphadenopathy in PLHIV, ahead of tuberculosis and reactive lymphadenopathy. The CD4 count and the size of the lymph nodes appear to be the most important factors in the diagnostic process and should lead to a quick lymph node analysis in these patients.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013558"},"PeriodicalIF":3.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody responses to Japanese encephalitis virus and dengue virus serotype 2 in children from an orthoflavivirus endemic region after IMOJEV vaccination.","authors":"Fatima Ericka S Vista, Leslie Michelle M Dalmacio, Pauline R Solis, Cecilia Nelia C Maramba-Lazarte, Diane M Lang, Alan L Rothman, Sheriah Laine M de Paz-Silava","doi":"10.1371/journal.pntd.0013550","DOIUrl":"10.1371/journal.pntd.0013550","url":null,"abstract":"<p><strong>Background: </strong>Japanese encephalitis virus (JEV) is a mosquito-borne pathogen that causes severe neurologic disease. Its endemicity in Asia has prompted its inclusion in nationwide immunization programs. However, the Philippines, which is also endemic for related viruses like dengue (DENV), has not yet adopted this practice. Vaccine hesitancy is a major challenge, exacerbated by concerns over cross-reactive antibodies that may enhance viral infection. This study aimed to determine whether IMOJEV vaccination would induce cross-neutralizing or enhancing antibodies against DENV.</p><p><strong>Methodology/principal findings: </strong>Pre- and one-month post-vaccination samples from IMOJEV-vaccinated Filipino children (9-24 months old) were analyzed. A reporter virus particle (RVP)-based neutralization assay against JEV showed neutralization in 28/29 subjects post-vaccination. Presence of DENV2-reactive antibodies was measured via DENV2 VLP ELISA, which revealed increased DENV2 binding reactivity post-vaccination. Pre-vaccination DENV2 binding reactivity also had no significant correlation with the JEV vaccine response. RVP-based neutralization and enhancement assays against DENV2 showed that there was no significant change in neutralizing or enhancing antibody activity against DENV2 after JEV vaccination.</p><p><strong>Conclusions/significance: </strong>This study shows that IMOJEV vaccination elicited a JEV neutralizing response in 97% of vaccinees and that the magnitude of JEV neutralizing titers post-vaccination was not associated with pre-existing binding antibodies to DENV2. Further, while live JEV vaccination increases DENV2-binding antibodies, this cross-reactivity does not lead to DENV2 enhancement. These findings contribute to a better understanding of the orthoflavivirus antibody response following immunization and the influence of pre-existing heterologous orthoflavivirus antibodies. This could guide vaccination strategies, especially in orthoflavivirus-endemic regions.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013550"},"PeriodicalIF":3.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endemicity, disability and neglect: Leprosy in Colombia 2007-2020.","authors":"Carlos Arango-Úsuga, Jesús Ochoa, Doracelly Hincapié-Palacio, Alba León","doi":"10.1371/journal.pntd.0013514","DOIUrl":"10.1371/journal.pntd.0013514","url":null,"abstract":"<p><strong>Background: </strong>Disability due to leprosy in Colombia is a neglected public health problem. This work aims to describe the magnitude of leprosy in Colombia, the spatiotemporal distribution of the disability and explore the potential relationship between individual and treatment delay characteristics with degrees of disability.</p><p><strong>Methods: </strong>Official leprosy data in Colombia between 2007 and 2020 were analyzed. The distribution of the grade 2 disability (G2D) rate was estimated. A Poisson spatiotemporal model was constructed to form clusters of municipalities with risk of G2D. A multinomial logistic regression model was used to quantify the relationships between patient characteristics and disability grades 1 (G1D) and 2 (G2D).</p><p><strong>Results: </strong>During the fourteen-year period, 5240 leprosy cases were registered (median age: 51 years, IQR: 35-63), of which 63.8% (n = 3341) were men. The proportion of multibacillary forms was 65.9% (n = 3453), 47.1% (n = 2468) for grade 0 disability (G0D), 18.4% (n = 966) for G1D and 9.7% (n = 507) for G2D. Three clusters and 10 municipalities were detected for the municipal rate of G2D. The national rate of G2D ranged between 0.03/100,000 inhabitants in 2010 and 0.05/100,000 inhabitants in 2020. The prevalence ratio of G1D and G2D was significant in individuals aged 60 years or older, men, from the subsidized or uninsured health system, who had relapses, multibacillary type and in whom the delay between the onset of symptoms and treatment was 7-12 years.</p><p><strong>Conclusion: </strong>In the context of leprosy elimination in Colombia, the prevalence of disability is high and heterogeneous in time and space. It is recommended to coordinate the necessary actions to \"revitalize\" the active epidemiological surveillance in the prioritized municipalities and strengthen the program including improving early detection, treatment and individual follow-up of patients with disabilities.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013514"},"PeriodicalIF":3.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population pharmacokinetic-pharmacodynamic analysis of benznidazole monotherapy and combination therapy with fosravuconazole in chronic Chagas disease (BENDITA).","authors":"Frauke Assmus, Cintia Cruz, James A Watson, Nicholas J White, Ayorinde Adehin, Richard M Hoglund, Bethania Blum de Oliveira, Fabiana Barreira, Ivan Scandale, Joel Tarning","doi":"10.1371/journal.pntd.0013522","DOIUrl":"10.1371/journal.pntd.0013522","url":null,"abstract":"<p><strong>Introduction: </strong>The currently recommended 8-week daily benznidazole regimen for Chagas disease is poorly tolerated. While shorter benznidazole monotherapy and combination regimens have been explored, the pharmacokinetic/pharmacodynamic (PK/PD) relationship remains poorly understood.</p><p><strong>Objectives: </strong>i) To describe the population pharmacokinetics of benznidazole and assess drug-drug interactions with fosravuconazole in patients with chronic Chagas disease, ii) to explore the relationship between benznidazole exposure and anti-trypanosomal treatment effects.</p><p><strong>Methods: </strong>This was a secondary analysis based on data from the previously published BENDITA study (NCT03378661), a dose evaluation trial in adults with chronic indeterminate Chagas disease (n = 210). Patients were randomized to placebo, the standard benznidazole dose (300 mg/day for 8 weeks), or lower total dose regimens (300 mg/day for 4 or 2 weeks; 150 mg/day for 4 weeks alone or combined with fosravuconazole 300 mg/week; 300 mg/week for 8 weeks plus fosravuconazole 300 mg/week). Benznidazole pharmacokinetics were evaluated using nonlinear mixed-effects modeling. The relationship between individual benznidazole exposure and the pharmacodynamic (PD) endpoint was explored using beta binomial regression. The PD endpoint (qPCR positivity) was defined as the proportion of qPCR-positive blood samples collected post-treatment over 12 months of follow-up, capturing the frequency of detectable parasitemia per patient.</p><p><strong>Results: </strong>Benznidazole pharmacokinetics were well described by a transit-absorption model with one-compartment disposition. Bioavailability was 13% lower in men than in women, and coadministration of fosravuconazole increased benznidazole clearance by 18% (both effects considered not clinically relevant). In the placebo arm, nearly all patients (97%) remained qPCR positive, with most showing qPCR positivity above 40%. Among patients receiving benznidazole, post-treatment qPCR positivity was substantially lower. In the 2-week arm, three patients had multiple positive qPCR samples (up to 43% PCR positivity). In contrast, individual qPCR positivity in the 4-8-week arms did not exceed 20% (i.e., one or no positive samples), with one non-adherent exception. The PK/PD analysis did not identify a significant pharmacokinetic driver of treatment response. While the study was not powered for between-arm comparisons, the findings suggest that lower total dose regimens (4 weeks daily or 8 weeks weekly) may provide efficacy comparable to the standard 8-week regimen.</p><p><strong>Conclusion: </strong>This study supports prior findings that the standard 8-week benznidazole regimen is excessive. Future trials using qPCR in factorial randomized designs should evaluate both treatment duration and dosing to optimize tolerability while maintaining efficacy.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013522"},"PeriodicalIF":3.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}