{"title":"Coronary artery lesions in pediatric scrub typhus: A case series from Guangzhou, China.","authors":"Shiying Liu, Qing Wang, Yu Gong, Xufang Li, Fansen Zeng, Yi Xu","doi":"10.1371/journal.pntd.0014784","DOIUrl":"10.1371/journal.pntd.0014784","url":null,"abstract":"<p><strong>Background: </strong>Scrub typhus, caused by Orientia tsutsugamushi, is a mite-borne rickettsial infection endemic to the Asia-Pacific region. While its systemic complications are well documented, coronary artery lesions (CALs) associated with scrub typhus in children remain poorly characterized. This study aimed to describe the clinical features, diagnostic challenges, and treatment outcomes of pediatric scrub typhus complicated by CALs.</p><p><strong>Methodology/principal findings: </strong>We retrospectively analyzed seven pediatric patients (aged 11 months to 8 years) with scrub typhus and echocardiographically confirmed CALs, admitted to Guangzhou Women and Children's Medical Center, Guangzhou Medical University between 1January 2020 and 30 May 2026. Between 15 June 2025 and 1 July 2026, clinical data including epidemiological history, laboratory findings, imaging results, treatment regimens, and outcomes were collected from electronic medical records.</p><p><strong>Conclusions/significance: </strong>Among the seven cases, CAL manifestations included coronary artery aneurysm (n = 2), coronary artery dilatation (n = 2), and coronary artery intimal thickening (n = 3). All seven patients were initially suspected of having Kawasaki disease.Six patients received intravenous immunoglobulin (IVIG), but all failed to respond. Among these six, four met the diagnostic criteria for Kawasaki disease (KD) or incomplete KD. Ultimately, all seven patients-including the one who did not receive IVIG-defervesced within 1-3 days of initiating antimicrobial therapy directed at scrub typhus.At follow-up, five patients with available echocardiography showed normalization of coronary arteries within one week to three months. These findings suggest that O. tsutsugamushi infection can trigger CALs indistinguishable from KD and that pathogen-directed therapy, rather than IVIG alone, is critical for fever resolution in such cases. Clinicians should maintain a high index of suspicion for scrub typhus in pediatric patients presenting with CALs, particularly when IVIG response is suboptimal.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 10","pages":"e0014784"},"PeriodicalIF":3.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13667921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149129010","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":"Prevalence of Strongyloides stercoralis infection among African children: A systematic review and meta-analysis.","authors":"Tadesse Hailu, Arancha Amor, Getaneh Alemu, Hiwot Tadesse, Veeranoot Nissapatorn, Hesham M Al-Mekhlafi","doi":"10.1371/journal.pntd.0014759","DOIUrl":"10.1371/journal.pntd.0014759","url":null,"abstract":"<p><p>Strongyloides stercoralis is a neglected parasite that causes strongyloidiasis. However, the true prevalence of strongyloidiasis is underreported due to low-sensitivity diagnostic methods. This systematic review assessed the prevalence of S. stercoralis among African children and its variation by diagnostic methods, countries, and study settings. All studies published in African countries on S. stercoralis prevalence up to the year 2025 in the PubMed, Google Scholar, Scopus, and ScienceDirect databases were included. Identification, screening, checking the eligibility, and including the relevant studies were done following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Out of 651 articles screened, 27 studies involving 16,358 children were included in the systematic review. The pooled prevalence of S. stercoralis among African children was 14% using a random-effect model. The highest pooled prevalence of S. stercoralis was recorded at 27% in Côte d'Ivoire, followed by 26% in Ethiopia. A high prevalence (36%) of S. stercoralis was obtained by a combination of PCR, culture, and microscopic diagnostic methods. This review indicated that S. stercoralis prevalence in African children is considerable and likely underestimated due to low-sensitivity diagnostics. Therefore, further studies using sensitive diagnostic approaches are urgently needed to determine the true burden of strongyloidiasis.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 10","pages":"e0014759"},"PeriodicalIF":3.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13667923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128946","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}
Awurabena Quayeba Dadzie, Solomon Akwasi Ananya, Jean Jacques Ngamaleu Tougoue, Ruth Dede Tuwor, Michael Nkrumah-Appau, Joseph Kwadwo Larbi Opare, Ernest Mensah, Kwame Amankwah Bimpeh, Leslie Tetteh Gberbie, Abigail Agbanyo, Irene Dzathor, Bernadette Agbavor, Richard Odame Phillips, Yaw Ampem Amoako
{"title":"Integrating neglected tropical diseases into primary healthcare services in Ghana: Results from an initial pilot.","authors":"Awurabena Quayeba Dadzie, Solomon Akwasi Ananya, Jean Jacques Ngamaleu Tougoue, Ruth Dede Tuwor, Michael Nkrumah-Appau, Joseph Kwadwo Larbi Opare, Ernest Mensah, Kwame Amankwah Bimpeh, Leslie Tetteh Gberbie, Abigail Agbanyo, Irene Dzathor, Bernadette Agbavor, Richard Odame Phillips, Yaw Ampem Amoako","doi":"10.1371/journal.pntd.0014792","DOIUrl":"10.1371/journal.pntd.0014792","url":null,"abstract":"<p><strong>Background: </strong>Neglected Tropical Diseases (NTDs) affect billions globally, including a significant burden in Ghana where at least two NTDs are endemic in every district. Integrating NTD services into primary health care (PHC) is critical for achieving Universal Health Coverage (UHC) and meeting the 2021-2030 NTD roadmap goals. This study piloted the integration of Ghana Health Service NTD indicators into the Community-based Health Planning and Services (CHPS) home visit register in Ghana to assess the feasibility of this approach for national scale-up.</p><p><strong>Methods: </strong>A pilot implementation study was conducted in three districts representing different ecological zones in Ghana: Kassena Nankana West (northern), Nkwanta South (middle), and Ga South (southern). Following stakeholder workshops, the existing Community Health Officers' (CHOs) home visit register was revised to include seven key NTD clinical indicators (blood in urine, skin lesions, visible deformities, eye complications, lymphoedema or swelling, suspected hydrocele and presence of a deep skin wound). A total of 64 Community Health Officers (CHOs) were trained to use the revised register during routine household visits over a three-month period (September to December 2023). Data on NTD cases identification, referrals, and referral compliance were collected and analyzed descriptively.</p><p><strong>Results: </strong>A total of 1,932 home visits were conducted across 34 health facilities resulting in 1,117 suspected cases (observations of NTD-related indicators) identified, 615 referrals made with 67% compliance and district level compliance ranging from 6.5% to 92.1%. CHOs successfully identified various NTD-related conditions, with distinct geographical patterns observed. Blood in urine was most frequently reported in Ga South, while lymphoedema and eye-related complications were more commonly reported in Kassena Nankana West. The varying patient compliance with the referrals suggests important contextual differences in linkage to care. Over 85% of trained health workers were actively implementing their new skills.</p><p><strong>Conclusion: </strong>Integrating NTD surveillance into the CHPS platform is feasible and yields valuable epidemiological data. However, the success of integration hinges not only on case detection but also on strengthening the linkage to care. The significant disparity in referral compliance highlights a critical health system bottleneck that must be addressed to ensure integrated services translate into improved health outcomes.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 10","pages":"e0014792"},"PeriodicalIF":3.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149129005","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}
Melissa N Asongha, Toussaint N Ngakia, Pascaline Akawung, Chrisvalin Lokissidingao, Dum-Buo Nnamdi, Barou O Zephanias, Fotsa Blondeau, Abdoulaye Djelamde, David A Lewis, Efuetacha Betehndoh, Francis N Nkemngo
{"title":"\"We don't know schistosomiasis can affect the female reproductive system and increase the risk of HIV\": A mixed-methods analysis reveals gaps in risk factor determinants and health consequences of female genital schistosomiasis in Southern Chad.","authors":"Melissa N Asongha, Toussaint N Ngakia, Pascaline Akawung, Chrisvalin Lokissidingao, Dum-Buo Nnamdi, Barou O Zephanias, Fotsa Blondeau, Abdoulaye Djelamde, David A Lewis, Efuetacha Betehndoh, Francis N Nkemngo","doi":"10.1371/journal.pntd.0014791","DOIUrl":"10.1371/journal.pntd.0014791","url":null,"abstract":"<p><strong>Background: </strong>Urogenital schistosomiasis caused by Schistosoma haematobium infection is a public health problem in Chad. Despite reports of urinary S. haematobium prevalence in endemic communities, research on the genital aspect of the disease, which disproportionately affects women, remains neglected especially given the contemporary geographical overlap with HIV/AIDS. This study was undertaken to establish baseline data on the awareness and perception of female genital schistosomiasis (FGS) among community inhabitants and healthcare professionals in southern Chad to inform effective policy decision-making.</p><p><strong>Methods: </strong>A mixed-methods cross-sectional design was employed for data collection in communities within the Guelo district from June to July 2025. Structured questionnaires were applied to capture quantitative data, while qualitative information was obtained through eleven focus group discussions (FGDs) and fifteen key informant interviews (KIIs). Quantitative and qualitative data were analyzed using statistical tools and NVIVO software, respectively, and outcomes were organized according to thematic categories.</p><p><strong>Results: </strong>A marked disparity characterized by sufficient knowledge about the urinary form of schistosomiasis [93.8% (CI: 91.5 - 96.2), 514/548] and minimal knowledge of FGS [3.1% (CI: 2.3 - 4.9), 17/548] was documented among the population. Moderate [63.2% (CI: 59.4 - 71.7), 325/514] and low [17.7% (CI: 11.3 - 21.8), 3/17] levels of awareness were respectively identified as predictors of urinary schistosomiasis and FGS, consistent with the perception that FGS is neither a risk factor for HIV nor cervical cancer. Additionally, verbal reports among informed community members and healthcare professionals revealed a shared belief that FGS is sexually transmitted and typically treated with antibiotics/antifungal medications. This belief was associated [χ2 = 13.7 (CI: 10.1 - 15. 6), p = 0.002] with negative consequences on hospital-treatment-seeking habits that arise from fear of identity-related stigma, particularly in cases involving recurrent genital symptoms.</p><p><strong>Conclusion: </strong>This study highlights the need for integrating FGS education and awareness initiatives within praziquantel delivery campaigns and sexual/reproductive preventive services at primary health care facilities in rural Chad. Furthermore, it underscores the urgency of providing comprehensive training for local healthcare professionals on the diagnosis and clinical management of FGS and the improvement of water, sanitation and hygiene (WaSH) services to minimize contact with freshwater bodies.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 10","pages":"e0014791"},"PeriodicalIF":3.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117027","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":"Early-warning surveillance of West Nile and Usutu viruses in wetland and larval habitat waters and in mosquito excreta using digital PCR.","authors":"Julien Mocq, Julie Raymond, Karine Bolloré, Anaïs Fossot, Rachel Beaubaton, Alexandre Lepeule, Cécile Gruet, Franz Durandet, Jeanne Hanin, Guillaume Lacour, Albin Fontaine, Olivier Courot, Antoine Mignotte, Yannick Simonin","doi":"10.1371/journal.pntd.0014799","DOIUrl":"10.1371/journal.pntd.0014799","url":null,"abstract":"<p><p>West Nile virus (WNV) and Usutu virus (USUV) are mainly avian mosquito-borne pathogens, increasingly cause human and equine disease in temperate regions. Mostly asymptomatic, current surveillance in France is reactive, based on clinical and veterinary reports, delaying signals for vector control and preventative interventions. We implemented in Southern France, in 2024 and 2025, a proactive surveillance methodology combining molecular xenomonitoring of mosquito excreta and environmental water detection of viral RNA in wetlands and mosquito larval habitat, through a multiplex reverse transcription digital PCR workflow. The analytics process was characterised through the limits of blank, detection, and quantification. Low-level positives were confirmed by Sanger sequencing. WNV and USUV RNA repeated detections revealed previously unrecognized, cryptic circulations up to 19 weeks before the first WNV human cases and equine alert. Environmental surveillance represents a paradigm shift for early detection of emerging Culex-borne arboviruses and a key enabler of proactive and effective One Health responses.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 10","pages":"e0014799"},"PeriodicalIF":3.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117134","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":"Correction: The psychosocial impacts of skin-neglected tropical diseases (SNTDs) as perceived by the affected persons: A systematic review.","authors":"Dasha L Alderton, Caroline Ackley, Mei L Trueba","doi":"10.1371/journal.pntd.0014781","DOIUrl":"10.1371/journal.pntd.0014781","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.pntd.0012391.].</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 10","pages":"e0014781"},"PeriodicalIF":3.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117019","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}
Natacha Ferreira de Oliveira, Adrielly Viveiros Torres, Marcelo Larami Santoro
{"title":"Rutin (quercetin-3-rutinoside) administered orally after experimental Bothrops jararaca envenomation prevents hemostatic, inflammatory and hemorrhagic disturbances.","authors":"Natacha Ferreira de Oliveira, Adrielly Viveiros Torres, Marcelo Larami Santoro","doi":"10.1371/journal.pntd.0014786","DOIUrl":"10.1371/journal.pntd.0014786","url":null,"abstract":"<p><p>Bites caused by Bothrops snakes represent a major public health problem in South America and are associated with severe systemic and local clinical manifestations. Bothrops venom induces marked hemostatic and inflammatory disturbances that may result in hemorrhage, thrombocytopenia, tissue necrosis, and kidney injury. The recommended treatment for snakebite envenomation is intravenous administration of anti-Bothrops antivenom (SAB); however, this therapy has limited efficacy against venom-induced local tissue injury mediated by the release of inflammatory mediators. In this context, adjunct pharmacological strategies capable of delaying or attenuating envenomation effects before antivenom administration may be clinically valuable, particularly in remote settings. Rutin and its derivative, rutin succinate, are flavonoids with anti-inflammatory, antioxidant, and vasoprotective properties, and have been previously shown to mitigate venom-induced damage when administered parenterally prior to Bothrops jararaca (Bj) envenomation. Herein, we evaluated the efficacy of orally administered rutin, formulated for rapid gastrointestinal absorption (nano-rutin), used alone or in combination with SAB, in a murine model of Bj snakebite envenomation. Mice received nano-rutin by gavage 10 min after venom injection and were subsequently treated with or without SAB after 1 hour. Envenomed mice developed thrombocytopenia, leukocytosis, fibrinogen consumption, elevated levels of IL-6 and cell-free DNA (cfDNA), reduced DNAse activity, hypoalbuminemia, and marked local hemorrhage and dermonecrosis. Oral nano-rutin restored most evaluated systemic parameters, and significantly reduced local hemorrhage and dermonecrosis, even in the absence of SAB. These findings support nano-rutin as an effective complementary therapy to antivenom, particularly for mitigating local tissue damage induced by Bothrops venoms.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 10","pages":"e0014786"},"PeriodicalIF":3.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117243","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}
Lam Anh Nguyet, Nguyen To Anh, Du Tuan Quy, Nguyen Thi Thu Hong, Ngo Ngoc Quang Minh, Phung Nguyen The Nguyen, Pham Van Quang, Do Duong Kim Han, Nguyen Thi Han Ny, Le Nguyen Truc Nhu, Truong Hoang Chau Truc, Cao Thu Thuy, Nhung Ngoc Hoang, Tran Ba Thien, Le Kim Thanh, Nguyen Thanh Hung, Truong Huu Khanh, Cao Minh Hiep, Nghiem My Ngoc, Nguyen Thanh Dung, Le Nguyen Thanh Nhan, Nguyen Van Vinh Chau, Ha Manh Tuan, H Rogier van Doorn, Marc Choisy, Tran Tan Thanh, Le Van Tan
{"title":"Virological and epidemiological investigations of a severe hand foot and mouth disease outbreak, Vietnam, 2023.","authors":"Lam Anh Nguyet, Nguyen To Anh, Du Tuan Quy, Nguyen Thi Thu Hong, Ngo Ngoc Quang Minh, Phung Nguyen The Nguyen, Pham Van Quang, Do Duong Kim Han, Nguyen Thi Han Ny, Le Nguyen Truc Nhu, Truong Hoang Chau Truc, Cao Thu Thuy, Nhung Ngoc Hoang, Tran Ba Thien, Le Kim Thanh, Nguyen Thanh Hung, Truong Huu Khanh, Cao Minh Hiep, Nghiem My Ngoc, Nguyen Thanh Dung, Le Nguyen Thanh Nhan, Nguyen Van Vinh Chau, Ha Manh Tuan, H Rogier van Doorn, Marc Choisy, Tran Tan Thanh, Le Van Tan","doi":"10.1371/journal.pntd.0014789","DOIUrl":"10.1371/journal.pntd.0014789","url":null,"abstract":"<p><p>We report on the virological and epidemiological features of a severe hand foot and mouth disease outbreak in Vietnam in 2023. Enterovirus A71 (EV-A71) subgenogroup B5, first emerging around November 2022, and imported into Vietnam through a single introduction, was the primary cause. Convalescent plasma collected from patients infected with subgenogroups B5 in 2014 and 2023 could neutralize both contemporary viruses with comparable titers, suggesting no evidence of immune evasion. However, at one and six months before the start of the outbreak, only 6.7% of 0- < 3 year-old children in Ho Chi Minh City, an epicenter of the outbreak, had neutralizing antibodies against EV-A71. Seroprevalence increased as the outbreak progressed, coinciding with a drop in EV-A71 infected patients residing in Ho Chi Minh City, suggesting that serosurveillance could be a useful tool to assess the risk of pathogen emergence. Our collective findings have provided novel insights into the epidemiological factors driving EV-A71 emergence, and therefore would inform outbreak preparedness and response, and in particular the development of serosurveillance-based approach to assess the risk of pathogen emergence. EV-A71 infection represents an ongoing public health threat, currently affecting countries in the Asia-Pacific region, but with a high potential to become a global problem, and therefore should be closely monitored.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 10","pages":"e0014789"},"PeriodicalIF":3.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117224","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":"Novel inhibitors against Cryptosporidium parvum through blocking its energy metabolism.","authors":"Chang Xu, Yaru Ji, Qiang Sha, Kun Li","doi":"10.1371/journal.pntd.0014742","DOIUrl":"10.1371/journal.pntd.0014742","url":null,"abstract":"<p><p>Through systematic structural optimization and modification of anti-Cryptosporidium parvum compound NSC158011 (N-1-naphthalenyl-2-(phenylthiol) ethane thioamide), we constructed a virtual compound library comprising 1,440 derivatives, and 29 derivatives were selected via molecular docking for chemical synthesis. Among them, eight derivatives exhibited significant inhibitory effects on LDH compared with NSC158011. In vitro examination found that two derivatives could markedly reduce the number of C. parvum in cells while exhibiting reduced toxicity. In vivo studies in model animals (IFN-γ knockout mouse) and native animals (calves) further validated the derivatives' potent anti-parasitic effects and their ability to alleviate intestinal villus atrophy caused by parasitic infections. Further investigations revealed that compound treatment was associated with upregulated expression of intestinal tight junction proteins (ZO-1, Occludin, Claudin-1) and downregulated the expression level of inflammatory protein Caspase-1. Analysis of the gut microbiota and metabolomics in calves indicated that treatment significantly restored the abundance of beneficial flora and regulated key metabolites, including isocitric acid and ornithine. The two derivatives identified in this study represent promising lead compounds for further development as anti-cryptosporidiosis agents, with potential relevance to livestock production and public health.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 10","pages":"e0014742"},"PeriodicalIF":3.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117135","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":"Winning the endgame against sleeping sickness: Efficacy profiling of acoziborole against African trypanosomes with the focus on Trypanosoma brucei rhodesiense.","authors":"Monica Cal, Sonja Keller, Romina Rocchetti, Stéphanie Braillard, Jean-Robert Ioset, Pascal Mäser, Marcel Kaiser","doi":"10.1371/journal.pntd.0014762","DOIUrl":"10.1371/journal.pntd.0014762","url":null,"abstract":"<p><p>Human African trypanosomiasis (HAT) is caused by two subspecies of Trypanosoma brucei, T. b. gambiense and T. b. rhodesiense, with the former accounting for over 95% of all cases. HAT is an elusive disease, which is fatal unless treated, with a focal prevalence in the rural areas of tropical Africa where the tsetse fly vectors are endemic. At the same time, HAT is one of the very few infectious diseases where global elimination seems possible. The incidence is at a historic low, and new orally bioavailable drugs have been developed that will expand the coverage of treatment in endemic regions. In particular, acoziborole has passed the clinical development as a single-dose oral cure of T. b. gambiense infection. However, to win the endgame against HAT, acoziborole also needs to be extended to T. b. rhodesiense. In order to strengthen the preclinical dossier of acoziborole, we conducted an in-depth evaluation of acoziborole against the bloodstream forms of all three T. brucei subspecies with a focus on T. b. rhodesiense. Acoziborole had consistent and high activity against different T. b. rhodesiense strains, including a multidrug-resistant field isolate, with IC50 values around 600 nM. Acoziborole is faster acting than fexinidazole, and it exhibits irreversible cidality against T. b. rhodesiense at concentrations of ≥4.3 μM (1.6 μg/ml) after 15 h of incubation. At very short exposure times (≤8 h), T. b. gambiense appeared to be more sensitive than T. b. rhodesiense. However, given the extremely long elimination half-life of acoziborole in the human body, this difference will be irrelevant for its trypanocidal action in patients. We therefore conclude that acoziborole is expected to be as effective against r-HAT as against g-HAT in patient populations.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 10","pages":"e0014762"},"PeriodicalIF":3.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117304","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}