PLoS Neglected Tropical Diseases最新文献

{"title":"Exploration of tongue dorsum sampling to support clinical diagnosis of leprosy patients in the Comoros: A cross-sectional study.","authors":"Lena Krausser, Maren Van Nieuwenhove, Nissad Attoumani, Silahi H Grillone, Magalie Van Dyck-Lippens, Leen Rigouts, Abdallah Baco, Wirdane Abdou, Aboubacar Mzembaba, Epco Hasker, Younoussa Assoumani, Bouke C de Jong, Sofie M Braet","doi":"10.1371/journal.pntd.0013541","DOIUrl":"10.1371/journal.pntd.0013541","url":null,"abstract":"<p><strong>Background: </strong>The accuracy of the WHO-endorsed clinical leprosy diagnosis depends on the expertise of health care workers. For molecular confirmation of clinically diagnosed patients, skin biopsies have the highest sensitivity to detect Mycobacterium leprae. As less invasive tongue swabs showed promising results for qPCR-based M. tuberculosis detection, this study investigated the presence of M. leprae on the tongue dorsum of clinically diagnosed leprosy patients.</p><p><strong>Methods and findings: </strong>During the activities of the (BE-)PEOPLE study, 499 clinically diagnosed, consenting patients from the Comoros were recruited. Samples collected included skin biopsies from active lesions, nasal swabs, tongue swabs, and, in some cases, tongue scrapes. M. leprae DNA was quantified with the RLEP qPCR assay and human mitochondrial DNA was quantified as sample adequacy control (SAC). On 18.1% (90/498) of tongue swabs and 13.2% (12/91) of tongue scrapes M. leprae DNA was detected. In only six patients tongue scrapes outperformed the tongue swab based on the number of bacilli/sample. Except for two paucibacillary (PB) patients, all 100/102 positive tongue samples were from multibacillary (MB) patients. Only patients with a RLEP-positive skin biopsy and positive bacteriological index (BI) yielded M. leprae DNA on the tongue scrape. The skin biopsy samples had a sensitivity of 92.5% (248/268) for MB and 74.3% (130/175) for paucibacillary (PB) patients. Nasal swabs were positive for 60.2% (162/269) of MB but only 2.2% (5/229) of PB patients.</p><p><strong>Conclusion: </strong>This is the first study to identify M. leprae bacilli on the tongue dorsum of clinically diagnosed leprosy patients by RLEP qPCR. Due to low positivity rates, tongue sampling has limited added value over skin biopsies and nasal swabs for the microbiological confirmation of leprosy. However, the mouth in general and the tongue specifically remain interesting sampling sites to gain further insights on the distribution of M. leprae bacilli in the body and potential transmission modes.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013541"},"PeriodicalIF":3.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082316","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":"Roles of tick-cofeeding hedgehogs in the natural transmission of spotted fever group Rickettsia.","authors":"Haiming Yi, Weilin Huang, Changqiang Zhu, Yixin Ge, Xijing Yang, Sunjie Yang, Chuchu Ye, Junhu Wang, Qiong Chen, Yingqing Mao, Hongming Wang, Lele Ai, Wei Guo, Chao Chen, Weilong Tan, Yuexi Li, Yong Qi","doi":"10.1371/journal.pntd.0013224","DOIUrl":"10.1371/journal.pntd.0013224","url":null,"abstract":"<p><p>Tick-borne spotted fever group Rickettsia (SFGR) poses a significant threat to public health worldwide. The cofeeding behavior of ticks attaching host animals, such as hedgehogs, has been identified as a potential mechanism for transmitting SFGR between infected and uninfected ticks, potentially increasing the prevalence of SFGR. However, the overall positive rate of SFGR in free-living ticks remains relatively low, suggesting that the role of tick-cofeeding in amplifying SFGR prevalence may not be as substantial as previously believed. To explore the impact of tick-cofeeding hedgehogs on the natural transmission of SFGR, to clarify the underlying hypotheses, and to provide robust data to support targeted prevention and control strategies for spotted fever, this study developed a transmission model using tick-cofeeding hedgehogs that simulates the natural transmission process. Both Rickettsia-infected and uninfected tick populations were established and used for cofeeding on mice or hedgehogs. Among formerly uninfected nymphs that cofed on mice, 75.61% acquired Rickettsia after engorgement, but this infection rate dropped sharply to 9.68% after molting. In contrast, formerly uninfected adults that cofed on hedgehogs showed a 100% infection rate after engorgement. However, the infection rates declined significantly in their offspring, with only 11.12% of normal-hatching eggs and 3.12% of larvae testing positive. Additionally, we observed mortality in infected engorged adults and their eggs. Our results demonstrate that while tick-cofeeding on hedgehogs can lead to a high positive rate of Rickettsia in ticks, the infections acquired through cofeeding fail to sustain this high positivity rate due to several mechanisms. Firstly, rickettsiae obtained through cofeeding or blood meals do not consistently establish infections in all recipient ticks, resulting in a significant decline in positive rates as ticks progress to subsequent developmental stages. Secondly, adult ticks infected via cofeeding tend to reduce the infection rate in their offspring through various mechanisms, including tick mortality caused by rickettsiae, egg hatching failure, and a low transovarial transmission rate. Additionally, in natural settings, infections from other pathogens may similarly contribute to tick mortality and reduced egg hatching. This study elucidates why rickettsiae maintain a low prevalence in nature and evaluates the actual effects of tick-cofeeding on pathogen distribution among ticks. While tick-cofeeding on host animals have been considered important amplifiers of SFGR prevalence, our findings indicate that their impact is not as significant as previously assumed.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013224"},"PeriodicalIF":3.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071059","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":"Fixed-dose ivermectin for Mass Drug Administration: Is it time to leave the dose pole behind? Insights from an Individual Participant Data Meta-Analysis.","authors":"Adriana Echazu, Daniela Bonanno, Pedro Emanuel Fleitas, Julie Jacobson, Gabriela Matamoros, Charles Mwandawiro, Wendemagegn Enbiale, Áuria de Jesus, Alan Brooks, Alejandro Javier Krolewiecki","doi":"10.1371/journal.pntd.0013059","DOIUrl":"10.1371/journal.pntd.0013059","url":null,"abstract":"<p><strong>Background: </strong>Ivermectin (IVM) is widely used in mass drug administration (MDA) programs for the control of neglected tropical diseases (NTDs). Current regimens rely on weight- or height-based dosing, which lead to operative challenges. This study evaluates an age-based fixed-dose regimen for IVM.</p><p><strong>Methodology: </strong>This is an individual participant data (IPD) meta-analysis including anthropometric data from over 700,000 individuals, across 53 NTD-endemic countries. Fixed-dose regimens were developed based on weight distribution by age. The proportion of individuals achieving the target range dose (200-400 µg/kg) was assessed and compared to traditional dosing regimens.</p><p><strong>Principal findings: </strong>Fixed-doses of 3 mg for pre-school children (PSAC), 9 mg for school-aged children (SAC), and 18 mg for women of reproductive age (WRA) resulted in a higher proportion of participants receiving the target dose compared to weight- and height-based regimens (79.9% vs. 32.7% and 37.3%, respectively, p < 0.001). Underdosed individuals were fewer with fixed-dose (8.7%) compared to weight-based (32.6%) and height-based (46.3%) regimens. Although doses above the target range increased slightly, most remained within 600 µg/kg.</p><p><strong>Conclusions: </strong>An age-based fixed-dose regimen for IVM could improve treatment coverage and simplify MDA activities. Simplified logistics could lead to cost savings in drug distribution and administration, improving the overall efficiency of MDA programs. These findings support the inclusion of currently excluded PSAC in IVM-based MDA interventions. More broadly, this paper provides evidence for considering the potential policy and programmatic implications of fixed-dose IVM. This Individual Participant Data Meta-analysis (IPD-MA) is registered in PROSPERO (CRD42024521610).</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013059"},"PeriodicalIF":3.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071025","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":"Exploring the status of brucellosis in pregnant women presented with febrile illness at different healthcare facilities of Vehari and Lodhran zones of Pakistan.","authors":"Syed Muhammad Tauseef Shafqat, Mian Muhammad Awais, Ulas Acaroz, Masood Akhtar, Abdul Sammad Ali Khan Shirwany, Imran Rasool, Naseer Ali Shah","doi":"10.1371/journal.pntd.0013525","DOIUrl":"10.1371/journal.pntd.0013525","url":null,"abstract":"<p><strong>Background: </strong>Brucellosis is an important zoonotic disease which causes stillbirth and abortion in pregnant women. It remains undiagnosed due to nonspecific symptoms like febrility, a very common ailment sign. Accordingly, this study was conducted to determine the seroprevalence and risk-determinants of brucellosis among pregnant women presented with febrile condition to healthcare facilities of Vehari and Lodhran regions of southern Punjab-Pakistan.</p><p><strong>Methods: </strong>For this cross-sectional study, a total of 250 pregnant women with febrile condition were approached. Of these, 200 willing women were included in this study. Blood samples of participants were analyzed for sero-detection of brucellosis using serum agglutination test (SAT) and commercially available indirect-ELISA kits (sensitivity and specificity>95%) followed by detection of Brucella (B.) species using PCR. Univariate and multivariate analyses were employed to determine the risk factors associated with brucellosis.</p><p><strong>Results: </strong>Overall seropositivity rate of brucellosis by SAT in study population was 18% whereas ELISA revealed the seroprevalence rate of 12% (n = 24/200). PCR findings showed the presence of B. abortus and B. melitensis in seropositive participants. Analysis revealed that nutritional status (P = 0.037, OR=0.2431), educational status (P = 0.049, OR=0.2168), contact with Brucella-susceptible animals (P = 0.009, OR=10.5142), abortion history (P = 0.012, OR=8.7308), raw milk's consumption (P = 0.002, OR=37.1499) and lack of disease awareness (P < 0.001, OR=0.0340) were significantly associated risk factors with brucellosis. Data regarding clinical manifestations revealed the highest frequency (87.50%) of fatigue with general weakness and the lowest one of night sweats (20.83%) in seropositive women.</p><p><strong>Conclusions: </strong>Brucellosis is prevalent in febrile pregnant women of study area. It is suggested to devise disease control/prevention measures which may include but not limited to enhancing awareness about disease-dynamics, improving disease diagnostic facilities and immunization of susceptible animals from where disease originate.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013525"},"PeriodicalIF":3.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071027","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":"Disability and quality of life assessment using WHODAS-12 items 2.0 and EQ-5D-5L in a rural area endemic for loiasis in the Republic of Congo: A population-based cross-sectional study (the MorLo project).","authors":"Marlhand C Hemilembolo, Jérémy T Campillo, Valentin Dupasquier, Elodie Lebredonchel, Samuel Beneteau, Ludovic G Rancé, Glorifié Madoulou Moulabou, Ange Clauvel Niama, Richard R Bileckot, Sébastien D S Pion, Michel Boussinesq, François Missamou, Cédric B Chesnais","doi":"10.1371/journal.pntd.0013491","DOIUrl":"10.1371/journal.pntd.0013491","url":null,"abstract":"<p><strong>Background: </strong>Loa loa filariasis, a parasitic infection endemic to Central Africa, is a common cause of medical consultation in this region.</p><p><strong>Methods: </strong>To evaluate the quality of life (QoL) of individuals living in loiasis-endemic areas, we enrolled 991 subjects (one-third being microfilaremic) from the general population of a rural area in the Republic of Congo. QoL and disability were assessed using WHODAS 2.0 12-items and EQ-5D-5L questionnaires. We collected data on the number of eye worm (Ew) and Calabar swelling episodes experienced throughout their lives, as well as individual L. loa microfilarial densities and information on infections with soil-transmitted helminthiasis.</p><p><strong>Principal findings: </strong>Individuals with a history of Ew had a nearly doubled risk of experiencing at least moderate disability (score >25/100) (adjusted Odds-Ratio = 1.77 (95%CI [1.05-2.99], p = 0.033), compared to those without such a history. Those with more than 10 episodes of Ew during their lifetime had a 28% increase in overall disability as measured by WHODAS. No other variable related to loiasis (Calabar swelling frequency, L. loa microfilarial density and positivity to L. loa antibody rapid test) was associated with the various scores. Additionally, infection with Trichuris trichiura was associated with worse anxiety score (adjusted incidence risk ratio = 1.22 (95% CI [1.06-1.39], p = 0.004)).</p><p><strong>Conclusions: </strong>The impact of loiasis on daily QoL appears to be primarily due to adult worms rather than microfilarial density. Indeed, our findings strongly suggest that the number of Ew episodes, likely reflecting the cumulative burden of adult worms, is the main correlate of worse QoL scores. These episodes seem to affect multiple dimensions of functioning, with notable impact on mobility, pain, anxiety, and daily activities. In contrast, microfilariae would primarily induce organ dysfunction. Further studies are needed to better understand the respective clinical impacts of adult worms and L. loa microfilariae.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013491"},"PeriodicalIF":3.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071016","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":"Chikungunya virus in Thailand (2020-2023): Epidemiology, clinical features, and genomic insights.","authors":"Sarawut Khongwichit, Watchaporn Chuchaona, Sumeth Korkong, Lakkhana Wongsrisang, Thanunrat Thongmee, Yong Poovorawan","doi":"10.1371/journal.pntd.0013548","DOIUrl":"10.1371/journal.pntd.0013548","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) caused significant outbreaks in Thailand during 2008-2009 and 2018-2020. Despite the COVID-19 pandemic, CHIKV continued to circulate; however, data on its epidemiological, clinical, and genetic characteristics during and after this period remains limited. This study investigated CHIKV infections in Thailand from March 2020 to December 2023. Serum samples (n = 1,264) were collected from patients with suspected CHIKV infection at 14 hospitals across five provinces in central, eastern, and northeastern Thailand. Samples were tested by RT-qPCR and IgM fluorescence immunoassay. CHIKV infection was confirmed in 50.5% (638/1,264) of cases. Infections occurred across all age groups, with the highest prevalence among individuals aged ≥56 years. Clinical symptoms significantly associated with infection included myalgia, arthralgia, rash, and conjunctivitis. Rash was more frequently in individuals aged ≤15 years and was significantly associated with lower viral loads. Arthralgia was more common among older adults and was linked to later illness onset. Myalgia was least frequently reported in younger patients. Thirty-eight complete coding sequences of our Thai CHIKV strains were analyzed in phylogenetic and time-scaled trees alongside 186 global strains and 109 ECSA-IOL strains from GenBank, respectively. Genome analysis revealed that CHIKV strains circulating in Thailand during 2020-2023 belonged to the East/Central/South African-Indian Ocean lineage (ECSA-IOL). These strains did not evolve from earlier ECSA-IOL variants that carried the E1-A226V mutation, which was previously detected in Thailand. Instead, all isolates carried E1-K211E and E2-V264A, along with E1-226A, likely introduced from the Indian subcontinent around 2016-2017. This introduction triggered a major outbreak between late 2018 and 2020, followed by sustained transmission. The 2020-2023 Thai strains exhibited high genetic similarity to those from neighboring countries, with multiple nonsynonymous mutations suggesting ongoing viral adaptation. Understanding CHIKV epidemiology, clinical features, and evolution supports improved surveillance, diagnostics, and public health interventions.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013548"},"PeriodicalIF":3.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071035","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":"Unexplained subcutaneous swelling: Keep echinococcosis in mind! Report of two primary extrahepatic subcutaneous echinococcosis cases and literature review.","authors":"Louis Bohard, Eléonore Brumpt, Noémie Tissot, Marie Lacoste, Olivia Chapuis, Sophie Felix, Jenny Knapp, Carole Hartmann-Gouvenot, Yannick Jeffredo, Frederic Grenouillet, Damien Montange, Anne-Pauline Bellanger, Catherine Chirouze, Solange Bresson-Hadni","doi":"10.1371/journal.pntd.0013511","DOIUrl":"10.1371/journal.pntd.0013511","url":null,"abstract":"<p><p>Alveolar and cystic echinococcoses (AE and CE) are parasitic zoonoses, mainly affecting the liver. Primary extrahepatic localizations remain rare and are difficult to diagnose. We report two cases of primary subcutaneous echinococcosis and the largest literature review on the subject. The first case is an alveolar echinococcosis located in the forehead region and the second a cystic echinococcosis in the abdominal wall. To our knowledge, a primary AE location in the face has never been described before. Pre-surgical diagnosis was not made in these two cases. However, it is essential to apply specific measures, depending on the type of echinococcosis (AE or CE), to prevent parasitic dissemination and recurrence. In view of the cases presented here, prolonged albendazole can be a second-line alternative to a surgical strategy. Echinococcosis should be kept in mind for differential diagnosis of soft tissue lesions in any part of the body.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013511"},"PeriodicalIF":3.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071070","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":"Whole genome sequencing of Yersinia pestis isolates from Central Asian natural plague foci revealed the role of adaptation to different hosts and environmental conditions in shaping specific genotypes.","authors":"Aigul A Abdirassilova, Duman T Yessimseit, Altynai K Kassenova, Beck Z Abdeliyev, Zauresh B Zhumadilova, Gulnara Zh Tokmurziyeva, Galina G Kovaleva, Ziyat Zh Abdel, Tatiyana V Meka-Mechenko, Saule K Umarova, Elmira Zh Begimbayeva, Sanzhar D Agzam, Vladimir L Motin, Oleg N Reva, Altyn K Rysbekova","doi":"10.1371/journal.pntd.0013533","DOIUrl":"10.1371/journal.pntd.0013533","url":null,"abstract":"<p><p>The genetic diversity and biovar classification of Yersinia isolates from Central Asia were investigated using whole-genome sequencing. In total, 98 isolates from natural plague foci were sequenced using the MiSeq platform. Computational pipelines were developed for accurate assembly of Y. pestis replicons, including small cryptic plasmids, and for identifying genetic polymorphisms. A panel of 99 diagnostic polymorphisms was established, enabling the distinction of dominant Medievalis isolates derived from desert and upland regions. Evidence of convergent evolution was observed in polymorphic allele distributions across genetically distinct Y. pestis biovars, Y. pseudotuberculosis, and other Y. pestis strains, likely driven by adaptation to similar environmental conditions. Genetic polymorphisms in the napA, araC, ssuA, and rhaS genes, along with transposon and CRISPR-Cas insertion patterns, were confirmed as suitable tools for identifying Y. pestis biovars, although their homoplasy suggests limited utility for phylogenetic inference. Notably, a novel cryptic plasmid, pCKF, previously associated with the strain of the population 2.MED0 from the Central-Caucasus high-altitude autonomous plague focus, was detected in a genetically distinct isolate of 2.MED1 population from the Ural-Embi region, indicating potential plasmid transfer across the 2.MED lineage. These findings emphasize the need for ongoing genomic surveillance to monitor the spread of virulence-associated genetic elements and to improve our understanding of Y. pestis evolution and ecology.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013533"},"PeriodicalIF":3.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056168","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":"Molecular docking to homology models of human and Trypanosoma brucei ERK8 that identified ortholog-specific inhibitors.","authors":"Matthew Merski, Zachary B Mackey","doi":"10.1371/journal.pntd.0013487","DOIUrl":"10.1371/journal.pntd.0013487","url":null,"abstract":"<p><p>Human African Trypanosomiasis (HAT), also known as sleeping sickness, is a lethal disease caused by two vector-borne parasites: Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. The limited number of antitrypanosomal therapies for treating these deadly parasites suffer from toxicity, poor efficacy, and unspecified targets; thus, more and better medicines are needed. We used in silico methods to predict features of the bioactive compound AZ960 that make it an ortholog-specific inhibitor for the extracellular-signal regulated kinase 8 of T. brucei (TbERK8). Our homology models showed that the TbERK8 ATP binding pocket was smaller and more hydrophobic than that of human ERK8 (HsERK8). Molecular docking studies predicted six FDA-approved compounds that would be orthologue-specific inhibitors of HsERK8 or TbERK8. Experimental testing of these compounds identified prednisolone as an HsERK8-specific inhibitor. Sildenafil inhibited TbERK8, as predicted by our binding model. Its impact on TbERK8 activity supports our hypothesis that designing compounds that can exploit differences in the orthologs as buildable scaffolds and expand the repertoire of ortholog-specific antitrypanosomal agents.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013487"},"PeriodicalIF":3.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056185","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":"Cryptosporidium parvum protease INS6 plays an important role in parasite proliferation and pathogenicity.","authors":"Wei He, Zuwei Yang, Jing Wang, Fuxian Yang, Na Li, Rui Xu, Songrong Zeng, Lihua Xiao, Yaoyu Feng, Yaqiong Guo","doi":"10.1371/journal.pntd.0013532","DOIUrl":"10.1371/journal.pntd.0013532","url":null,"abstract":"<p><strong>Background: </strong>Cryptosporidium parvum is a common protozoan pathogen responsible for moderate to severe diarrhea in humans and animals. Parasite invasion and egress cause damage to intestinal epithelial cells, which is mediated by a variety of secretory proteins from several unique organelles, such as micronemes. Previous spatial proteomic analysis has identified insulinase-like protease 6 (INS6) as a putative microneme protein in C. parvum. However, the functional contribution of INS6 to Cryptosporidium pathogenicity remains poorly characterized. In this study, we used genetic manipulation techniques to investigate the expression and biological functions of INS6 in C. parvum.</p><p><strong>Methodology/principal findings: </strong>The INS6 gene was tagged and deleted in C. parvum using CRISPR/Cas9 technology. The expression of INS6 was determined by immunofluorescence analysis, ultrastructure-expansion microscopy, and immunoelectron microscopy. Endogenous labelling showed low levels of INS6 expression, which is found in C. parvum micronemes and is absent during the male gamont stage. The effect of INS6 deletion on parasite growth and pathogenicity was assessed in vitro using HCT-8 cultures and in vivo by infection of interferon-γ knockout mice. Deletion of the INS6 gene impaired C. parvum proliferation in vitro and significantly reduced the parasite burden in infected mice. In addition, mice infected with the Δins6 strain showed a significant reduction in the intestinal villus-to-crypt ratio, attenuated body weight loss and increased survival rates, compared to those infected with the INS6-3HA strain.</p><p><strong>Conclusions/significance: </strong>These results indicate that INS6 protein is involved in C. parvum proliferation and plays a critical role in modulating the pathogenicity of this zoonotic parasite. Deletion of this gene affects the invasion efficiency and pathogenicity of the parasite.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013532"},"PeriodicalIF":3.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056087","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}