Rickyle Balea, Alberto A Amarilla, Jody Hobson-Peters, Joanne Macdonald, Andreas Suhrbier, Vasilli M Kasimov, Daniel Watterson, Nina M Pollak, David J McMillan
{"title":"Development and proof-of-concept evaluation for a low resource compatible Chikungunya virus diagnostic.","authors":"Rickyle Balea, Alberto A Amarilla, Jody Hobson-Peters, Joanne Macdonald, Andreas Suhrbier, Vasilli M Kasimov, Daniel Watterson, Nina M Pollak, David J McMillan","doi":"10.1371/journal.pntd.0012352","DOIUrl":"10.1371/journal.pntd.0012352","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) is a positive sense RNA Alphavirus that continues to pose major public health threats throughout the world. CHIKV is primarily transmitted via the Aedes genus mosquito; however, has also exhibited transmission routes via blood transfusion and vertical transmission (mother to child). With only one approved vaccine thus far and no approved medicines or specific therapeutics, early detection is crucial in mitigating potential CHIKV outbreaks. Here, we designed and evaluated a sensitive and specific CHIKV diagnostic using reverse transcription-recombinase aided amplification (RT-RAA) coupled lateral flow strip detection (LFD) targeting a highly conserved region of the CHIKV E1 gene. Our results demonstrate that using our simple sample preparation reagent (TNA-Cifer-E), we can inactivate live CHIKV in two minutes at room temperature, whilst also sustaining viable viral RNA. Our specificity analysis demonstrates the Iso-CHIKV-Dx does not detect any closely related Alphaviruses nor any of the common co-circulating Flaviviruses. Proof-of-concept evaluation using urine spiked with CHIKV exhibited that in CHIKV infected urine samples, our Iso-CHIKV-Dx can detect as low as 570 copies/µL of CHIKV RNA in 30 minutes under isothermal conditions. Contrary to conventional RT-qPCR, our Iso-CHIKV-Dx does not require expensive machinery, advanced instrumentation or extensively trained personnel. Further performance comparisons also show that our Iso-CHIKV-Dx is four times faster than conventional RNA isolation and RT-qPCR. As such, pre-clinical, proof-of-concept evaluation demonstrates that our Iso-CHIKV-Dx has the potential to act as a robust, point of care CHIKV diagnostic that could prove to be highly beneficial in place of, or in the absence of conventional diagnostic approaches such as RT-qPCR.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0012352"},"PeriodicalIF":3.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056204","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}
Kehinde F Paul-Odeniran, Paul O Odeniran, Cécile Häberli, Jennifer Keiser, Charles A Laughton
{"title":"Computational and experimental exploration of statin and statin-like compounds as potential treatment of schistosomiasis.","authors":"Kehinde F Paul-Odeniran, Paul O Odeniran, Cécile Häberli, Jennifer Keiser, Charles A Laughton","doi":"10.1371/journal.pntd.0013524","DOIUrl":"10.1371/journal.pntd.0013524","url":null,"abstract":"<p><p>Schistosomiasis remains a global health challenge, affecting over 240 million people each year. Current treatment options, including praziquantel, are limited by their inability to target immature schistosomula and growing concerns around drug resistance. Targeting 3- hydroxy 3-methylglutaryl coenzyme A reductase from Schistosoma mansoni (SmHMGR), a key enzyme in the parasite's mevalonate pathway, presents a promising therapeutic strategy. Although the antischistosomal potential of statins has been previously explored, this study introduces a novel integrated pipeline that combines homology modelling, large scale analogue screening of a 1013 compound chemical space, validated molecular docking, molecular dynamics simulations, and experimental validation to systematically identify SmHMGR inhibitors. Following computational prioritisation, experimental validation revealed modest activity of three commercially available statins (lovastatin, pravastatin, and pitavastatin) against schistosomula with up to 56.3% at 50 µM, but no significant time-dependent effects. Three novel analogues of pitavastatin exhibited enhanced schistosomicidal activity, revealing activities of up to 96% and 55% against schistosomula and adult worms at 50 µM, respectively. These findings highlight the potential of structural modifications to improve the efficacy of statin-based compounds against S. mansoni.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013524"},"PeriodicalIF":3.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056067","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":"Paratyphoid fever and the genomics of Salmonella enterica serovar Paratyphi A in Taiwan.","authors":"Ying-Shu Liao, Yu-Ping Hong, Bo-Han Chen, You-Wun Wan, Ru-Hsiou Teng, Shiu-Yun Liang, Hsiao Lun Wei, Jui-Hsien Chang, Ming-Hao Yang, Chi-Sen Tsao, Chien-Shun Chiou","doi":"10.1371/journal.pntd.0013048","DOIUrl":"10.1371/journal.pntd.0013048","url":null,"abstract":"<p><strong>Background: </strong>Salmonella enterica serovar Paratyphi A (S. Paratyphi A) has emerged as a significant global health concern due to the progressive development of antimicrobial resistance and its broader geographic distribution. In Taiwan, paratyphoid fever was historically rare and predominantly associated with imported cases. Since 2022, however, a marked increase in domestically acquired infections has been observed, prompting investigations into their origin and likely route of introduction.</p><p><strong>Methods: </strong>We analyzed surveillance data on 223 patients with paratyphoid fever reported in Taiwan between January 2001 and December 2024. Whole-genome sequencing and antimicrobial susceptibility testing were performed on 88 S. Paratyphi A isolates obtained from both imported and domestically acquired infections from 2007 to 2024. Phylogenetic analysis and genotyping were conducted to assess genetic relatedness and to trace potential sources of introduction by comparing them with global isolates.</p><p><strong>Results: </strong>Although 55.2% of paratyphoid fever infections were imported, domestically acquired infections became predominant after 2022. Most isolates (76.1%) were resistant to nalidixic acid and nonsusceptible to ciprofloxacin due to gyrA mutations at codon 83 (S83F or S83Y). The majority of domestic isolates were classified as ST129 and paratype 2.4 and showed close genetic relatedness to strains from Indonesia. Of the 31 domestic isolates collected between 2022 and 2024, 30 clustered with Indonesian strains, and 28 exhibited nearly identical genomic profiles, which suggested a prolonged outbreak likely linked to a common external source, such as contaminated imported food.</p><p><strong>Conclusions: </strong>The genomic evidence suggests that the recent increase in domestically acquired S. Paratyphi A infections in Taiwan represents a prolonged outbreak rather than a sustained epidemiological shift. These infections were closely related to strains from Indonesia, suggesting a potential epidemiological link between the two countries in the transmission of paratyphoid fever. While 76.1% of isolates were nonsusceptible to ciprofloxacin due to gyrA mutations, susceptibility to traditional first-line agents remained high. The observed decline in case numbers in 2024 may indicate that the outbreak is subsiding. Genomic surveillance played a crucial role in tracing sources of infection and informing targeted public health responses.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013048"},"PeriodicalIF":3.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041794","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}
Juan Felipe Valdés-López, Yordi Sebastián Tamayo-Molina, Geysson J Fernandez, Lady Johana Hernández-Sarmiento, Paula A Velilla, Silvio Urcuqui-Inchima
{"title":"Early events in dengue virus infection inducing cytokine storm: The dynamic interplay of pattern-recognition receptors, inflammasome activation, and biphasic NF-κB and STAT1-dependent inflammatory responses in human mononuclear phagocytes.","authors":"Juan Felipe Valdés-López, Yordi Sebastián Tamayo-Molina, Geysson J Fernandez, Lady Johana Hernández-Sarmiento, Paula A Velilla, Silvio Urcuqui-Inchima","doi":"10.1371/journal.pntd.0013366","DOIUrl":"10.1371/journal.pntd.0013366","url":null,"abstract":"<p><p>A Cytokine storm is critical in severe dengue, significantly contributing to disrupted endothelial integrity, plasma leakage, and haemorrhage manifestations in affected patients. Various reports have demonstrated that mononuclear phagocytes, including monocytes, dendritic cells, and macrophages, are target cells of DENV infection. They contribute to viral spread into tissues and promote robust inflammatory responses and immunopathology. However, it remains unclear whether the early events of DENV infection play a role in triggering cytokine storms in infected mononuclear phagocytes. To address this knowledge gap, we conducted a comprehensive analysis of the transcriptomic profile of in vitro DENV-2-infected human monocyte-derived macrophages (MDMs) based on the kinetics of viral replication through a standard growth curve. To verify the accuracy of our approach, we used RT-qPCR, ELISA, and transcriptomic data from in vitro DENV-2-infected monocyte-derived dendritic cells (MDDCs) and monocytes obtained from acute dengue patients. RNA-Seq analysis revealed dynamic changes in the transcriptional profile of DENV-2-infected MDMs throughout the viral growth curve. Two waves of differentially expressed genes were observed: the first occurred during the eclipse period of viral replication (3 to 5.5 h.p.i) and was associated with the induction of NF-kB-dependent pro-inflammatory factors, while the second wave at 24 h.p.i coincided with peaks of DENV-2 replication and induction of both NF-kB- and STAT1-dependent pro-inflammatory responses. Additionally, DENV-2 infection promoted the dynamic activation of Toll-like receptors, RIG-like receptors, inflammasomes, and inflammatory pathways, triggering innate pro-inflammatory and antiviral responses. A robust multi-type IFN-dependent antiviral response was also observed at the late stage of infection. A similar transcriptomic profile was found in DENV-2-infected MDDCs and monocyte subsets from acute dengue patients, further confirming the reliability of our in vitro model of DENV-infected MDMs. Together, results suggest that recognizing viral PAMPs during the eclipse period of DENV-2 infection promotes a robust NF-kB-dependent pro-inflammatory response in MDMs. In addition, at later stages of infection, recognizing structural DENV-PAMPs and/or viral replication intermediates induces both NF-kB- and STAT1-dependent pro-inflammatory responses, leading to a cytokine storm. These findings highlight the critical role of monocytes, macrophages, and dendritic cells in detecting DENV infection and triggering a cytokine storm in vitro and in vivo. This suggests that these cell populations could be potential targets for future immunotherapies to modulate the inflammatory response to DENV infection.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013366"},"PeriodicalIF":3.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042081","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}
Davi Alvarenga Lima, Héllida Marina Costa-Silva, Karen Stephanie Sebe Albergaria, Juliana Martins Ribeiro, Daniela de Melo Resende, Bruno Alves Santarossa, Daniel Barbosa Liarte, Simone Guedes Calderano, Silvane Maria Fonseca Murta
{"title":"Glycosomal ABC transporter 3 (GAT3) deletion enhances the oxidative stress responses and reduces the infectivity of Trypanosoma cruzi.","authors":"Davi Alvarenga Lima, Héllida Marina Costa-Silva, Karen Stephanie Sebe Albergaria, Juliana Martins Ribeiro, Daniela de Melo Resende, Bruno Alves Santarossa, Daniel Barbosa Liarte, Simone Guedes Calderano, Silvane Maria Fonseca Murta","doi":"10.1371/journal.pntd.0013479","DOIUrl":"10.1371/journal.pntd.0013479","url":null,"abstract":"<p><p>Glycosomes, peroxisome-like organelles in Trypanosoma cruzi, contain enzymes involved in various metabolic processes, including glycolysis. Glycosomal ABC transporters (GATs) play a vital role in maintaining metabolic homeostasis by facilitating metabolite exchange between glycosomes and the cytoplasm. GAT3 is a member of the GAT family, which also includes GAT1 and GAT2. GAT3 transcript levels are downregulated in benznidazole-resistant T. cruzi populations; however, its specific functions remain unknown. Therefore, in this study, we generated GAT3 single-knockout and null mutant lines of the T. cruzi Dm28c strain using the CRISPR/Cas9 system to investigate GAT3 roles in parasite biology. RT-qPCR revealed increased GAT2 transcript levels in the GAT3 null mutant line, without any changes in GAT1 levels. Our findings suggest that GAT3 is not essential for T. cruzi survival, as null mutant parasites showed no growth difference compared to the Cas9-expressing controls. Moreover, the GAT3 single-knockout line exhibited increased resistance to benznidazole, whereas the null mutant line exhibited benznidazole susceptibility similar to the control. Furthermore, both GAT3 single-knockout and null mutant lines showed increased tolerance to hydrogen peroxide-induced oxidative stress. In vitro infection assay of L929 murine fibroblasts revealed that the GAT3 null parasites exhibited a significantly lower infection rate and fewer intracellular amastigotes than the controls. Overall, GAT3 is crucial for T. cruzi infectivity and the regulation of oxidative stress responses, playing key roles in the metabolic regulation and pathogenicity of this parasite.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013479"},"PeriodicalIF":3.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042038","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}
Xiaofeng Xu, Xiaohong Su, Weipeng Li, Li Xu, Dongcheng Li, Kai Dai, Junyu Liu, Jia Liu, Fuhua Peng, Ying Jiang
{"title":"Clinical features and mortality risk factors in non-HIV elderly patients with cryptococcal meningitis: A retrospective cohort study from 2013 to 2022.","authors":"Xiaofeng Xu, Xiaohong Su, Weipeng Li, Li Xu, Dongcheng Li, Kai Dai, Junyu Liu, Jia Liu, Fuhua Peng, Ying Jiang","doi":"10.1371/journal.pntd.0013521","DOIUrl":"10.1371/journal.pntd.0013521","url":null,"abstract":"<p><strong>Background: </strong>Cryptococcal meningitis (CM) is a life-threatening fungal infection with increasing incidence among non-HIV (human immunodeficiency virus) elderly populations. However, data on CM in non-HIV elderly patients are limited. This study aimed to analyze the clinical features, outcomes, and prognostic factors in non-HIV elderly CM patients using the largest dataset to date.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using data from 667 non-HIV CM patients treated between 2013 and 2022. Patients were categorized into elderly (≥60 years) and non-elderly groups. Clinical features, laboratory findings, and neuroimaging results were analyzed. Least Absolute Shrinkage and Selection Operator regression identified prognostic factors, and multivariate logistic regression was used to construct a nomogram for predicting mortality. The model's discrimination, calibration, and decision curve analysis (DCA) were evaluated.</p><p><strong>Results: </strong>Elderly patients accounted for 23.5% of the study population, exhibited distinct clinical characteristics, and had a significantly higher one-year all-cause mortality rate (31.2% [95% confidence interval (CI) 23.61-38.71] vs. 13.8% [95% CI 10.77-16.81], P < 0.001). Four prognostic factors for elderly patients were identified, and a predictive nomogram was developed. The predictive model achieved an area under the curve (AUC) of 0.81 (95% CI 0.71-0.91), and the AUC was 0.79 (95% CI 0.70-0.87) in the internal validation. The model was well-calibrated, and DCA indicated a net benefit.</p><p><strong>Conclusion: </strong>Non-HIV elderly CM patients present distinct clinical characteristics and have a higher mortality risk. The predictive model may facilitate the early identification of high-risk patients and guide timely interventions.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013521"},"PeriodicalIF":3.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042121","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}
Henri Claude Moungui, Paul Tonkoung Iyawa, Hugues Nana-Djeunga, Jose Antonio Ruiz-Postigo, Carme Carrion
{"title":"Usability and quality evaluation of the World Health Organization SkinNTDs app among frontline health workers in Cameroon: A mixed methods study.","authors":"Henri Claude Moungui, Paul Tonkoung Iyawa, Hugues Nana-Djeunga, Jose Antonio Ruiz-Postigo, Carme Carrion","doi":"10.1371/journal.pntd.0013461","DOIUrl":"10.1371/journal.pntd.0013461","url":null,"abstract":"<p><strong>Background: </strong>Originally adapted from a paper-based guide for skin-related neglected tropical diseases (NTDs), version 3.0.0 of the World Health Organization (WHO) SkinNTDs app aims to strengthen disease surveillance and frontline health worker capacity in NTD-endemic settings. Evidence on its usability in routine care remains limited.</p><p><strong>Objective: </strong>To assess the usability and perceived quality of the SkinNTDs app in a real-life setting.</p><p><strong>Methods: </strong>This mixed methods evaluation was conducted between April and September 2024 among frontline health workers in five regions of Cameroon. Data included online questionnaires, based on the user version of the Mobile Application Rating Scale (uMARS), completed by 180 participants, and focus group discussions with 214 participants. Analyses were performed using jamovi 2.6.13 for quantitative analyses, and NVivo 12 Plus for qualitative analyses.</p><p><strong>Results: </strong>Participants reported limited dermatology experience (46.1% untrained or unexperienced), and nearly half were trained to use the app (66.1%). The app received moderate overall quality (mean = 3.61/5), with functionality and information scoring highest (both 3.69) and engagement lowest (3.50). Perceived impact was strong (3.88), and users were highly willing to recommend the app (3.96) but reluctant to pay (1.82). Prior app training to use the app was identified as the strongest predictor of higher quality ratings. Qualitative feedback highlighted critical needs: offline functionality (essential in low-connectivity areas), multilingual support, inclusion of darker skin tone images, and data-saving features. Digital barriers (e.g., data storage) and contextual adaptation were emphasized for effective implementation, alongside formal training integration.</p><p><strong>Conclusion: </strong>The app is a promising diagnostic support and educational tool, particularly when user training is provided. However, enhancements in engagement, cultural relevance (e.g., diverse imagery and local languages), offline utility, and reduced technical demands are critical for wider adoption. Scaling up adoption may be enhanced by integrating training modules into health system programs government endorsement, and addressing digital access barriers.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013461"},"PeriodicalIF":3.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034412","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}
Natalia Ortiz, Juan Diego Pinotti, Verónica Andreo, Raúl Enrique González-Ittig, Cristina Noemí Gardenal
{"title":"Orthohantavirus rodent hosts and genotypes in Southern South America: A narrative review.","authors":"Natalia Ortiz, Juan Diego Pinotti, Verónica Andreo, Raúl Enrique González-Ittig, Cristina Noemí Gardenal","doi":"10.1371/journal.pntd.0013489","DOIUrl":"10.1371/journal.pntd.0013489","url":null,"abstract":"<p><p>Orthohantaviruses, family Hantaviridae, are zoonotic agents that pose a significant public health threat, particularly in South America, where they cause severe respiratory illnesses in humans. Despite their importance, knowledge gaps remain regarding the distributions of both the viruses and their rodent hosts in Southern South America, a region characterized by a great complexity of viral genotypes and reservoirs. This review provides an updated overview of orthohantavirus hosts and their associated viral genotypes in Argentina, Chile, Paraguay, and Uruguay. Through an extensive literature review, we identified 14 rodent species that serve as reservoir hosts for 15 distinct orthohantavirus genotypes. These rodent hosts inhabit a variety of ecosystems, from forests and arid zones to grasslands and wetlands, and even modified or anthropized habitats, demonstrating a wide geographic and ecological range. Our findings highlight the diversity of orthohantaviruses in this region, reflecting their complex evolutionary histories. Maintaining an up-to-date knowledge base on this topic is essential for effective decision-making in public health.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013489"},"PeriodicalIF":3.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030929","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}
Richard Olumide Daodu, Ebenezer Awotoro, Jens-Uwe Ulrich, Denise Kühnert
{"title":"CLASV: Rapid Lassa virus lineage assignment with random forest.","authors":"Richard Olumide Daodu, Ebenezer Awotoro, Jens-Uwe Ulrich, Denise Kühnert","doi":"10.1371/journal.pntd.0013512","DOIUrl":"10.1371/journal.pntd.0013512","url":null,"abstract":"<p><p>Lassa fever, caused by the Lassa virus (LASV), is a deadly disease characterized by hemorrhages. Annually, it affects approximately 300,000 people in West Africa and causes about 5,000 deaths. It currently has no approved vaccine and is categorized as a top-priority disease. Apart from its endemicity to West Africa, there have been exported cases in almost all continents, including several European countries. Distinct Lassa virus lineages circulate in specific regions, and have been reported to show varying immunological behaviors and may contribute to differing disease outcomes. It is therefore important to rapidly identify which lineage caused an outbreak or an exported case. We present CLASV, a machine learning-based lineage assignment tool built using a Random Forest classifier. CLASV processes raw nucleotide sequences and assigns them to the dominant circulating lineages (II, III, and IV/V) rapidly and accurately. CLASV is implemented in Python for ease of integration into existing workflows and is freely available for public use.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0013512"},"PeriodicalIF":3.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030948","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}
Jonathan Rigby, Catherine N Wilson, Allan Zuza, Yohane Diness, Charity Mkwanda, Katalina Tonthola, Oscar Kanjerwa, Chifundo Salifu, Oliver Pearse, Chisomo Msefula, Blanca M Perez-Sepulveda, Jay C D Hinton, Satheesh Nair, Nicola Elviss, Mathew A Beale, Patrick Musicha, Nicholas A Feasey
{"title":"Diversity of Salmonella enterica isolates from urban river and sewage water in Blantyre, Malawi.","authors":"Jonathan Rigby, Catherine N Wilson, Allan Zuza, Yohane Diness, Charity Mkwanda, Katalina Tonthola, Oscar Kanjerwa, Chifundo Salifu, Oliver Pearse, Chisomo Msefula, Blanca M Perez-Sepulveda, Jay C D Hinton, Satheesh Nair, Nicola Elviss, Mathew A Beale, Patrick Musicha, Nicholas A Feasey","doi":"10.1371/journal.pntd.0012413","DOIUrl":"10.1371/journal.pntd.0012413","url":null,"abstract":"<p><strong>Background: </strong>Salmonella enterica encompasses over 2,600 serovars, including several commonly associated with severe infection in humans. Salmonella is a major cause of sepsis in Africa; however, diagnosis requires clinical microbiology facilities. Environmental surveillance has the potential to play a role in Salmonella surveillance.</p><p><strong>Methods: </strong>We undertook water-based environmental surveillance in Blantyre, Malawi, from 2018-2020, taking samples from rivers (87.9%), a sewage plant (8.85%) and other water sources (3.24%), isolating and storing 1,042 non-typhoidal Salmonella (NTS) isolates in this period. Of these, 341 NTS isolates were whole genome sequenced, genome quality was checked, duplicate genomes from any given sample were removed and core genome phylogeny was reconstructed. AMRFinder, PathogenWatch and SISTR were used to further investigate serovar, sequence type and antimicrobial resistance determinants.</p><p><strong>Results: </strong>After quality checks, and removal of duplicate genomes, 270 NTS genomes remained for further analysis. Multiple Salmonella serovars associated with human infection were detected, of which S. Typhimurium (55/270 isolates) was the most common, including 44 of Sequence Type (ST) 313, a serovar commonly associated with severe invasive disease (iNTS). Six lineage 2 ST313 genomes possessed AMR genes predicting multidrug resistance (MDR), while 29 lineage 3 isolates contained no AMR predictive genes. PCR based detection of staG has been proposed as a diagnostic marker of S. Typhi; however, all eight genomes that contained staG identified as Salmonella enterica serovar Orion, raising concerns about the specificity of this marker as a monoplex for environmental surveillance of S. Typhi.</p><p><strong>Discussion: </strong>The study identified diverse Salmonella serovars in the environment, including those reported to cause invasive disease, emphasizing the complex but potentially valuable contribution of implementing environmental surveillance for Salmonella in high burden areas lacking diagnostic microbiology capacity.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"19 9","pages":"e0012413"},"PeriodicalIF":3.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12431665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030955","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}