{"title":"Nationwide registry-based analysis of rabies exposures in Iran: Epidemiological patterns and post-exposure prophylaxis adherence.","authors":"Ebrahim Babaee, Arash Yousefzadeh Eshkoori, Babak Eshrati, Marzieh Nojomi, Mohammad Reza Shirzadi, Mehran Asadi-Aliabadi, Amirhesam Moosazadeh","doi":"10.1371/journal.pntd.0014751","DOIUrl":"https://doi.org/10.1371/journal.pntd.0014751","url":null,"abstract":"<p><strong>Background: </strong>Animal bites remain an important public health issue in Iran. Understanding their epidemiological patterns and examining how registry-recorded cases are managed in relation to the Iranian rabies protocol and World Health Organization recommendations can provide insight into clinical practice and documentation quality within the national bite registry. Such analyses help identify strengths and gaps in protocol adherence and data completeness.</p><p><strong>Methodology/principal findings: </strong>We conducted a secondary analysis of 507,404 animal bite cases recorded in the national rabies registry between March 2022 and September 2023. The unit of analysis was registry-recorded exposure visits. Data on demographics, exposure characteristics, and clinical management were examined to describe epidemiological patterns and assess documented adherence to recommended post-exposure prophylaxis (PEP) practices. Males accounted for 73.6% of cases. The largest age group among all patients was 31-40 years, comprising 19.8% of cases. Dogs were responsible for 76.2% of exposures and cats for 20.8%. Northern provinces such as North Khorasan (773 per 100,000) and Golestan (767 per 100,000) recorded the highest incidence. Wound irrigation was documented in 94.3% of patients, and 96.4% received the first vaccine dose within 48 hours. Overall, 68.1% received three vaccine doses and 24.2% four doses. Rabies immunoglobulin was administered to 95.6% of Category III exposures, though inappropriate use was also observed in Category I (6.1%) and II (4.7%). Deviations from vaccine regimens and misclassification of exposure categories were identified, and among bat-related exposures only 36.8% were classified as Category III, with 38.7% receiving immunoglobulin.</p><p><strong>Conclusions/significance: </strong>Among registry-recorded animal bite attendees, rapid initiation of PEP and frequent appropriate use of rabies immunoglobulin in severe exposures were documented. However, gaps in documentation, vaccine dosing accuracy, and exposure classification indicate areas for improvement. These findings reflect patterns within the national bite registry and should not be interpreted as a comprehensive evaluation of all surveillance system attributes. Strengthening provider training, reinforcing protocol adherence, and improving data quality within the registry could support national rabies control efforts and inform broader prevention strategies aligned with global elimination goals.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 9","pages":"e0014751"},"PeriodicalIF":3.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117221","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":"First use of rapid ICT screening for Toxoplasma in pregnant women in Ethiopia: A multicenter study in Bahir Dar, Ethiopia.","authors":"Yared Mulu Gelaw, Gizachew Worku Dagnew, Mulusew Alemneh Sinishaw, Toyiba Hiyaru, Getu Degu Alene, Jean-Pierre Gangneux, Florence Robert-Gangneux","doi":"10.1371/journal.pntd.0014616","DOIUrl":"https://doi.org/10.1371/journal.pntd.0014616","url":null,"abstract":"<p><strong>Background: </strong>Toxoplasma gondii primary infection during pregnancy can lead to congenital transmission and cause serious fetal and neonatal complications. Seroprevalence for toxoplasmosis is an indicator of the intensity of transmission and of the risk of infection during pregnancy, yet such data are limited in Ethiopia. This multi-center study utilizing the immunochromatographic test (Toxoplasma ICT IgG-IgM, LD Bio) aimed at determining the seroprevalence of toxoplasmosis among pregnant women and its associated risk factors in Bahir Dar, Ethiopia.</p><p><strong>Methods: </strong>A cross-sectional study was conducted at two tertiary hospitals. Pregnant women below 20 weeks of gestation were included during the first antenatal care consultation. Participants were selected using systematic random sampling. A blood sample was collected for Toxoplasma serology, and socio-demographic and clinical data were collected through a questionnaire. Serology was performed using a rapid immunochromatographic test (ICT Toxo IgG/IgM, LD Bio). The test detects any Toxoplasma antibody (recent or chronic infection), but not separately reported. Data were analysed using SPSS version 23. Individual data were compared between Toxoplasma-seropositive and seronegative women to determine risk factors for infection. Bivariable and multivariable binary logistic regression were performed to identify factors associated with seropositivity.</p><p><strong>Results: </strong>Overall, 1010 women were included in the study at their first antenatal care visit (13.89 ± 4.26 weeks of gestation). Their mean age was 26.8 ± 4.67 years, 85.2% resided in urban areas, and the median monthly income was 5000 Ethiopian Birr. The seroprevalence was 75.8%. Seroprevalence increased with age and parity (p < 0.001), but did not differ according to socio-economic parameters, including educational level, monthly income, occupation, residence, or any hygienic factors. Multivariable analysis showed that age (AOR = 1.09), Parity (AOR = 1.33), eating undercooked meat (AOR = 1.29), and consumption of raw milk (AOR = 1.82) were significantly associated with the seropositivity of T. plasma gondii among pregnant women.</p><p><strong>Conclusion: </strong>The burden of toxoplasmosis among pregnant women was high in Bahir Dar. Therefore, efforts should be made to increase women's awareness of risk factors, particularly the habit of consuming raw meat and raw milk. The ease of use of the Toxoplasma ICT test allows serologic screening of pregnant women at antenatal care facilities.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 9","pages":"e0014616"},"PeriodicalIF":3.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117246","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}
Redeemer Joy Duboh, Dickson Kweku Delali, Emmanuel Manu
{"title":"Understanding influences on health-seeking behaviours among persons cured of leprosy in the Godokpe community, Volta Region of Ghana: A qualitative descriptive study.","authors":"Redeemer Joy Duboh, Dickson Kweku Delali, Emmanuel Manu","doi":"10.1371/journal.pntd.0014753","DOIUrl":"https://doi.org/10.1371/journal.pntd.0014753","url":null,"abstract":"<p><strong>Background: </strong>Leprosy, a curable neglected tropical disease, continues to affect vulnerable populations in low-resource settings despite global control efforts. In Ghana, although leprosy has been eliminated as a public health problem, new cases continue to be detected, and persons cured of leprosy (PCLs) continue to face long-term stigma, disability, and barriers to healthcare in segregated communities. This qualitative descriptive study aimed to understand the knowledge of leprosy, sources of healthcare, and challenges shaping health-seeking behaviours among PCLs in Godokpe, Ho Municipality, Volta Region, Ghana.</p><p><strong>Methodology: </strong>This qualitative descriptive study explored the knowledge, healthcare sources, and challenges shaping health-seeking behaviours among PCLs. Purposive sampling recruited 20 participants to reach saturation. Semi-structured, face-to-face, in-depth interviews lasting 20-30 minutes were conducted in Godokpe, audio-recorded, transcribed verbatim, and analysed using reflexive thematic analysis in Atlas.ti version 7.5.0, following COREQ guidelines.</p><p><strong>Results: </strong>This study revealed four central themes. Knowledge of Leprosy showed predominant supernatural attributions, including bewitchment, ancestral curses, and contaminated food, alongside rare bacterial recognition, with signs such as skin lesions, ulcers, nodules, limb deformities, loss of sensation, and body pain. Social Treatment and Stigma reflected two distinct patterns: ongoing, unevenly resolved interpersonal avoidance by family and community, contrasted with a documented shift toward equal treatment of PCLs at health facilities over time. Health-Seeking Behaviour reflected a pluralistic pattern, drawing on biomedical facilities such as the Ho Polyclinic and Ho Teaching Hospital, herbal remedies, self-medication, and spiritual or church-based healing based on perceived severity. Challenges Influencing Health-Seeking encompassed logistical barriers such as distance, transport costs, drug unavailability, and informal charging for nominally free medication; physical limitations such as mobility impairment, painful or wounded legs, and visual loss; and socioeconomic constraints such as unemployment, financial hardship, low allowances, donor dependence, and the prioritisation of food over healthcare.</p><p><strong>Conclusion: </strong>This study revealed persistent supernatural attributions of leprosy, an uneven trajectory of stigma reduction, pluralistic health-seeking, and layered barriers, including a documented gap between free-care entitlements and informal charging in practice, among PCLs in Godokpe. Addressing these gaps requires verification of fee-exemption entitlements at the facility level alongside sustained family- and community-level engagement, advancing Sustainable Development Goal (SDG) 1 on poverty reduction, SDG 3 on good health and well-being, and SDG 10 on reduced inequalities.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 9","pages":"e0014753"},"PeriodicalIF":3.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117238","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}
Robert Machang'u, Jacob N Kagesyeko, Majani Edward, Wisdom Owoicho Ameh, Lucy Chuwa, Gabriel Upunda, Jovin R Tibenderana
{"title":"Epidemiological profile of leprosy cases at Nazareti Leprosy Center, Tanzania: A retrospective analysis (2000-2024).","authors":"Robert Machang'u, Jacob N Kagesyeko, Majani Edward, Wisdom Owoicho Ameh, Lucy Chuwa, Gabriel Upunda, Jovin R Tibenderana","doi":"10.1371/journal.pntd.0014761","DOIUrl":"https://doi.org/10.1371/journal.pntd.0014761","url":null,"abstract":"<p><strong>Introduction: </strong>Leprosy, also commonly known as Hansen's Disease (HD) remains a neglected tropical disease and a public health concern in disease endemic regions of the world. However, significant progress in disease reduction has been achieved in recent years through multidrug therapy programs, implemented by the World Health Organization (WHO). This study assessed the trend and epidemiological profile of HD cases diagnosed at Nazareti Leprosy Center (NLC), Ifakara, Tanzania, over a 25-year period.</p><p><strong>Methods: </strong>A retrospective cross-sectional study was conducted using routinely collected clinical records of newly diagnosed HD cases registered at NLC between 2000 and 2024. Data on demographic characteristics, clinical classification of HD, operational categories (paucibacillary and multibacillary), and disability grades of patients at presentation were collected. Poisson regression estimated annual incidence trends as incidence rate ratios (IRRs), while logistic regression assessed changes in leprosy characteristics as odds ratios (ORs), both reported with 95% confidence intervals (CIs).</p><p><strong>Results: </strong>A total of 801 HD cases were recorded, of which males accounted for 67.4% of cases, with the highest proportion occurring among individuals aged 50 + years (33.2%). Multibacillary disease predominated (62.7%), while grade 1 disability (G1D), at diagnosis was more common (52.7%) than G2D. Overall, case notifications increased significantly over time, with an average annual rise of 4.0% (IRR = 1.04; 95% CI: 1.03-1.07; p < 0.001). Significant increases were observed among male individuals aged ≥50 years. Multibacillary HD cases and G1D disability also increased. In contrast, childhood cases (0-14 years) declined significantly during the study period.</p><p><strong>Conclusions: </strong>Leprosy epidemiology in rural Tanzania shows evolving patterns characterized by increasing case detection, a rising burden of multibacillary disease, and disability at diagnosis, versus a decline in childhood cases over time. Intensifying early case detection, community awareness, treatment and surveillance are essential to eliminate HD as a public health concern.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 9","pages":"e0014761"},"PeriodicalIF":3.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117290","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}
Fadwa M Arafa, Mohamed Hagar, Ahmed Zakaria, Eman Sheta, Nehal N Hezema
{"title":"Unravelling the synergistic potential of Olibanum extract and Bacillus clausii in combating intestinal cryptosporidiosis in immunosuppressed mice.","authors":"Fadwa M Arafa, Mohamed Hagar, Ahmed Zakaria, Eman Sheta, Nehal N Hezema","doi":"10.1371/journal.pntd.0014734","DOIUrl":"https://doi.org/10.1371/journal.pntd.0014734","url":null,"abstract":"<p><p>Given the grave risk posed by intestinal cryptosporidiosis to vulnerable populations, the current research focused on a new therapeutic avenue. Olibanum (OL) extract and probiotic Bacillus clausii (B. clausii) and their combination were evaluated against Cryptosporidium in vivo in immunosuppressed mice via parasitological, ultrastructural, biochemical, and histopathological analysis. Liquid chromatography-mass spectrometry (LC-MS) analysis of OL revealed the predominance of incensole isomers in its chemical composition. Regarding oocyst count in stool, the highest percentage of oocyst reduction was achieved after combined therapy (98.4%) on the 19th day post-infection, followed by B. clausii-treated group (87.6%), then the OL-treated group (87%). Similar ultrastructural alterations were noticed by scanning electron microscopy (SEM) following treatment by both OL and B. clausii, ranging from shrunken oocysts to severely deformed ones with extensive pits or protrusions. Nonetheless, their combination resulted in complete distortion of the oocysts, leading to their rupture. Biochemically, both OL and B. clausii treatment, either alone or in combination, provoked a decrease in the serum MDA levels, together with a corresponding rise in the mean levels of GSH. Concerning the histopathological findings, the best results were achieved following the combined OL and B. clausii treatment, which has restored villus architecture and remarkably ameliorated detrimental intestinal inflammation and goblet cell count. Finally, immunohistochemical analysis of the lymphocytic population of the intestinal villi revealed a statistically significant rise in the CD4+ /CD8+ ratio after treatment with either OL, B. clausii or their combination, which signals their proficient use for this therapeutic endeavour.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 9","pages":"e0014734"},"PeriodicalIF":3.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149116799","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}
Barbara de Barros, Farha Sultana, Neeta Maximus, Vivek V Pai, Anju Wakade, Bhagyashree Bhame, Bishwanath Acharya, Abdulnaser Hamza, Alemtsehay Getachew, Medhi Denisa Alinda, M Yulianto Listiawan, Shimelis N Doni, Deanna A Hagge, Indra Napit, Mahesh Shah, Joydeepa Darlong, Peter Nicholls, Bernd Genser, Saba M Lambert, Diana N J Lockwood, Stephen L Walker
{"title":"Methotrexate and Prednisolone compared to placebo and prednisolone in the treatment of severe Erythema Nodosum Leprosum: An international multicentre, double-blind randomised controlled clinical trial-MaPs in ENL.","authors":"Barbara de Barros, Farha Sultana, Neeta Maximus, Vivek V Pai, Anju Wakade, Bhagyashree Bhame, Bishwanath Acharya, Abdulnaser Hamza, Alemtsehay Getachew, Medhi Denisa Alinda, M Yulianto Listiawan, Shimelis N Doni, Deanna A Hagge, Indra Napit, Mahesh Shah, Joydeepa Darlong, Peter Nicholls, Bernd Genser, Saba M Lambert, Diana N J Lockwood, Stephen L Walker","doi":"10.1371/journal.pntd.0014739","DOIUrl":"10.1371/journal.pntd.0014739","url":null,"abstract":"<p><strong>Background: </strong>Erythema nodosum leprosum (ENL) is a severe inflammatory complication of leprosy that often requires prolonged corticosteroid therapy which is associated with adverse effects. Methotrexate is an affordable immunomodulatory agent with limited evidence for its use in ENL treatment. We evaluated whether weekly oral methotrexate in addition to prednisolone reduces the need for additional prednisolone in adults with severe ENL.</p><p><strong>Methods and findings: </strong>We performed an international, multicentre, double-blind, randomised, placebo-controlled trial conducted at five leprosy referral centres in Ethiopia, India, Indonesia, and Nepal. Adults aged 18-60 years with severe ENL were randomised to receive oral methotrexate (15mg, increased to 20mg in participants weighing ≥ 60 kg) for 48 weeks and prednisolone, or matching placebo and prednisolone. All participants received an identical 20-week prednisolone regimen, starting at 40mg daily, and were followed for 60 weeks. The primary outcome was time to first ENL flare requiring additional prednisolone, assessed over 24 and 48 weeks. Between January 2023 and June 2024, 231 individuals were screened and 137 were randomised (68 methotrexate and prednisolone; 69 placebo and prednisolone). By 24 weeks, 85/137 (62.0%) participants experienced an ENL flare requiring additional prednisolone; the adjusted hazard ratio (HR) for methotrexate versus placebo was 0.98 (95% CI 0.62-1.54). By 48 weeks, 102/137 (74.5%) experienced an ENL flare; adjusted HR 0.95 (95% CI 0.62-1.43). Secondary outcomes were similar: methotrexate did not reduce ENL severity at first flare, flare frequency, or severity of subsequent flares. Health-related quality of life improved substantially in both groups with no evidence of a differential treatment effect. Methotrexate was generally well tolerated. The trial was registered at ClinicalTrials.gov (NCT03775460).</p><p><strong>Conclusions: </strong>Oral methotrexate added to prednisolone did not reduce the requirement for additional prednisolone or delay ENL flares compared to placebo and prednisolone, and our study does not support the use of methotrexate for severe ENL.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT03775460 registered on 29th November 2018.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 9","pages":"e0014739"},"PeriodicalIF":3.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117297","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}
Abigail Agbanyo, Yaw Ampem Amoako, Charles Opondo, Michael Ntiamoah Oppong, Adwoa Asante-Poku, Jacob Novignon, Joseph Tuffour, Ishaque Saim Mintah, Ruth Dede Tuwor, Dzifa Kofi Ahiatrogah, Richard Adjei Akuffo, Miriam Gborglah, Iris Mosweu, Catherine Pitt, Elizabeth Allen, Stephen L Walker, Dorothy Yeboah-Manu, Michael Marks, Richard Odame Phillips
{"title":"High-dose rifampicin and clarithromycin for 4 weeks versus standard-dose rifampicin and clarithromycin for 8 weeks to treat Buruli ulcer: An open-label, individually randomized, controlled trial in Ghana.","authors":"Abigail Agbanyo, Yaw Ampem Amoako, Charles Opondo, Michael Ntiamoah Oppong, Adwoa Asante-Poku, Jacob Novignon, Joseph Tuffour, Ishaque Saim Mintah, Ruth Dede Tuwor, Dzifa Kofi Ahiatrogah, Richard Adjei Akuffo, Miriam Gborglah, Iris Mosweu, Catherine Pitt, Elizabeth Allen, Stephen L Walker, Dorothy Yeboah-Manu, Michael Marks, Richard Odame Phillips","doi":"10.1371/journal.pntd.0014783","DOIUrl":"10.1371/journal.pntd.0014783","url":null,"abstract":"<p><strong>Background: </strong>The current 8-week regimen of rifampicin and clarithromycin for Buruli ulcer (BU) is suboptimal. High-dose rifampicin could shorten treatment and improve outcomes. We evaluated whether a 4-week high-dose regimen could improve time to clearance of viable Mycobacterium ulcerans.</p><p><strong>Methodology: </strong>In this open-label, individually randomised trial conducted in Ghana, participants with PCR-confirmed BU were assigned (1:1) to either high-dose oral rifampicin (20mg/kg) with clarithromycin (15mg/kg) for 4 weeks (HR) or standard-dose rifampicin (10mg/kg) with clarithromycin (15mg/kg) for 8 weeks (SR). All wounds were dressed with DACC-coated dressings. The primary outcome was time to clearance of viable M. ulcerans assessed by 16S rRNA qPCR up to week 20.</p><p><strong>Findings: </strong>Between 26th November 2021 and 31st July 2024, 42 participants were randomised (HR:23, SR:19), which was short of the target (n = 112). The mean time to clearance was 4.9 weeks (SE 1.4) in the HR arm versus 7.0 weeks (SE 1.9) in the SR arm, with an adjusted mean difference of -0.5 weeks (95%CI -5.0 to 4.1, p = 0.835). No recurrences occurred in either arm. Paradoxical reactions were observed in 0/21 participants in the HR arm vs. 5/15 in the SR arm (adjusted OR 0.19, 95%CI 0.00-1.35, p = 0.102). Secondary infection rates were similar between groups.</p><p><strong>Conclusion: </strong>High‑dose rifampicin combination for 4 weeks was well tolerated in this population. A nominally lower proportion of paradoxical reactions was observed in the high-dose rifampicin arm compared with standard therapy. The trial did not find evidence of significantly shorter time to microbiological clearance or healing compared with standard therapy. Larger trials are needed to determine efficacy and safety.</p><p><strong>Trial registration: </strong>Pan African Clinical Trials Repository, trial registration number: PACTR202011867644311 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=14534).</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 9","pages":"e0014783"},"PeriodicalIF":3.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082567","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}
Ana Paula Menezes, Camila Gachet-Castro, Suzanne McGill, Richard Burchmore, Ariel Silber, Maria Carolina Elias, Júlia P C da Cunha
{"title":"Nuclear proteome analysis suggests spatial and temporal compartmentalization of metabolic enzymes during Trypanosoma cruzi cell cycle.","authors":"Ana Paula Menezes, Camila Gachet-Castro, Suzanne McGill, Richard Burchmore, Ariel Silber, Maria Carolina Elias, Júlia P C da Cunha","doi":"10.1371/journal.pntd.0013299","DOIUrl":"10.1371/journal.pntd.0013299","url":null,"abstract":"<p><p>Trypanosoma cruzi, the etiological agent of Chagas Disease (CD), represents a significant public health concern and serves as a valuable model for investigating the cell cycle in early-diverging eukaryotes. Its unique cellular features,including the absence of chromosome condensation and the coordination of nuclear division with specialized organelles, provide insights into non-canonical regulatory mechanisms, and underscore the pivotal role of the nucleus in maintaining genomic integrity and regulating fundamental processes such as DNA replication and gene expression. To investigate nuclear dynamics throughout the cell cycle, we synchronized T. cruzi epimastigotes at the G1/S transition using hydroxyurea (HU), followed their progression through S and G2/M phases, and quantitatively analyzed isolated nuclear proteins by LC-MS/MS. We identified 2,937 nuclear-enriched proteins, revealing distinct, phase-specific expression patterns. The G1/S phase was marked by increased levels of metabolic enzymes including those related to energy and nucleotide/nucleoside metabolisms. The S phase showed elevated abundance of canonical and variant histones, consistent with chromatin remodeling and DNA replication. The G2/M phase was enriched in proteins involved in protein synthesis and microtubule dynamics, essential for mitosis. Notably, metabolic enzymes represented approximately 6% of the proteins identified in the purified nuclear fraction, consistent with previously published proteomic analyses of T. cruzi nuclear-enriched fractions. Hexokinase, citrate synthase, and pyruvate kinase activities were detected in extracts from this fraction, while immunofluorescence supported the association of hexokinase and citrate synthase with the nuclear region. These results suggest that metabolic enzymes and/or their metabolites may modulate nuclear processes in T. cruzi, potentially influencing the epigenome and gene expression regulation, as proposed in other eukaryotic models. Altogether, our findings reveal dynamic remodeling of the nuclear proteome during the T. cruzi cell cycle and point to a previously underappreciated role for metabolic enzymes likely regulating nuclear functions in a cell cycle-dependent manner.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 9","pages":"e0013299"},"PeriodicalIF":3.6,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149076423","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":"Pre-extensively and extensively drug-resistant tuberculosis prevalence among multidrug-resistant tuberculosis cases in Ethiopia: A systematic review and meta-analysis.","authors":"Muluneh Assefa, Mitkie Tigabie, Abebaw Setegn, Yenesew Mihret Wondmagegn, Azanaw Amare, Getu Girmay, Sirak Biset, Wesam Taher Almagharbeh","doi":"10.1371/journal.pntd.0014744","DOIUrl":"10.1371/journal.pntd.0014744","url":null,"abstract":"<p><strong>Background: </strong>The burden of pre-extensively drug-resistant tuberculosis (Pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) cases in Ethiopia has become one of the most challenging problems for monitoring the treatment of patients with multidrug-resistant tuberculosis (MDR-TB). This study aimed to provide a valuable evidence synthesis on the pooled prevalence of Pre-XDR and XDR-TB among MDR-TB patients in Ethiopia.</p><p><strong>Methodology: </strong>This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Extracted data from relevant articles were analyzed using STATA version 17.0. The pooled estimate of the effect size was computed using a restricted maximum likelihood random-effects model, considering a 95% confidence interval, and a forest plot was used to visualize the proportion of Pre-XDR and XDR-TB. Because the Pre-XDR and XDR-TB cases are rare, the Freeman-Tukey double arcsine transformation was applied to estimate the pooled proportions. The I2 statistic and Galbraith plot confirmed heterogeneity. A univariate meta-regression, sensitivity, and subgroup analyses were conducted to identify the source of heterogeneity. Egger's test and funnel plot were used to check publication bias.</p><p><strong>Results: </strong>Eight studies comprising 1,518 MDR-TB patients, with 656 new and 862 previously treated cases, were included. Among those, 52 Pre-XDR and 13 XDR-TB cases were identified. According to the Freeman-Tukey transformation, the overall pooled prevalence of Pre-XDR-TB was 3% (95% CI: 2%-5%, I2 = 43.69%) and XDR-TB was 1% (95% CI: 0%-4%, I2 = 54.07%). In the subgroup analysis, the prevalence of Pre-XDR-TB across studies from multiple regions of Ethiopia was 7% (95% CI: 3%-13%), and in Addis Ababa, it was 3% (95% CI: 2%-4%). Single studies in the Amhara, Tigray, and Oromia regions reported Pre-XDR-TB prevalence of 6%, 5%, and 3%, respectively. The pooled prevalence of XDR-TB in Addis Ababa was 1% (95% CI: 0%-2%). A single study conducted in Oromia reported a relatively higher prevalence of XDR-TB; 10% (95% CI: 3%-26%). Regarding the study year, the XDR-TB prevalence was 3% (95% CI: 0%-11%) in 2005-2018 and 1% (95% CI: 0%-2%) in 2019-2024. A statistically significant publication bias was observed in XDR-TB prevalence (p = 0.024).</p><p><strong>Conclusion: </strong>There is a significant prevalence of Pre-XDR and XDR-TB cases among MDR-TB patients in Ethiopia. It highlights the need for strengthened surveillance in all regions and expanded drug susceptibility testing of local strains for better management of MDR-TB patients.</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 9","pages":"e0014744"},"PeriodicalIF":3.6,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149076400","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: Implementation of syndromic surveillance systems in two rural villages in Senegal.","authors":"","doi":"10.1371/journal.pntd.0014748","DOIUrl":"10.1371/journal.pntd.0014748","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.pntd.0005212.].</p>","PeriodicalId":49000,"journal":{"name":"PLoS Neglected Tropical Diseases","volume":"20 9","pages":"e0014748"},"PeriodicalIF":3.6,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149076433","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}