PLoS Neglected Tropical Diseases最新文献

Background: Schistosomiasis remains an important public health challenge in Egypt despite decades of control programs. Intestinal involvement is relatively common but usually presents with diffuse mucosal disease, ulcerations, or multiple polyps. A solitary bleeding rectal polyp as the sole manifestation is exceedingly rare and can be mistaken for inflammatory bowel disease or colorectal neoplasia. This report aims to highlight this diagnostic challenge within the Egyptian context.

Case presentation: A 28-year-old Egyptian male from a rural area presented with a 3-month history of intermittent lower abdominal pain and rectal bleeding. Physical examination was unremarkable except for mild lower abdominal tenderness and blood on digital rectal exam. Laboratory tests, including inflammatory markers, were normal; notably, stool microscopy was repeatedly negative for schistosome ova, despite the presence of RBCs and WBCs. Colonoscopy identified a solitary, pedunculated, and ulcerated rectal polyp (1.5 × 3.0 cm) at 20 cm from the anal verge, which was completely resected. Histopathological examination confirmed the diagnosis by demonstrating viable Schistosoma mansoni ova within eosinophilic granulomas and, critically, an adult worm residing in the submucosal vasculature, confirming active infection.The patient achieved full clinical recovery after praziquantel therapy, and this case underscores the importance of integrating parasitological, endoscopic, and histopathological perspectives when managing atypical colorectal lesions in endemic regions.

Conclusion: This case is a striking example of intestinal schistosomiasis masquerading as a sporadic colorectal neoplasm. In endemic regions like Egypt, schistosomiasis must be considered in the differential diagnosis of solitary rectal polyps, even with negative stool examinations. The definitive diagnosis hinges on histopathological analysis, which is indispensable for guiding correct management and avoiding unnecessary interventions. This report reinforces the ongoing, evolving challenge of schistosomiasis in Egypt post-control programs.

Introduction: Limited financial and human resources and infrastructure can affect the implementation of Good Clinical Practice (GCP), which can have a detrimental impact on data quality and the robustness and application of clinical trial outcomes. Monitoring frameworks are designed to ensure good data quality and help to guide adaptations of trial procedures over time. However, these frameworks tend to be based on datacentric approaches, which often neglect vital aspects of trials, such as social responsibility, capacity strengthening, and contextual influence. Therefore, this study analyses barriers and facilitators of the implementation of GCP in resource-limited settings to inform the establishment of adapted frameworks for trial management and monitoring.

Methods: In this multi-method analysis of the freeBILy trial, conducted in Madagascar from 2019-2022, a random subset of trial participants (n = 500) and informed consents (n = 500) was analyzed for protocol deviations through descriptive statistics and trend analysis. Framework analysis of focus group discussions and individual semi-structures interviews provided a sociological viewpoint of the study context. Findings were subsequently triangulated, merging the viewpoints on the influences towards GCP in resource-limited settings.

Results: A decreasing trend in incorrect database entries was found (z = -6.968, Mann-Kendall Test, p < 0.001) over the course of the study, with an overall rate of 1.8% incorrect data entries. Triangulation showed three key areas of GCP implementation in resource-limited settings, which extend previous frameworks: a) Context adaptation towards infra-, team- and social structures as promoting factors, b) External influences, such as external threats, study personnel attitudes and perception towards the trial require recurrent assessment, and c) Promote GCP-compliant data collection subject to regular documentation and training cycles to facilitate capacity strenghtning and data ownership.

Conclusion: This study shows the limitations of datacentric clinical trial management to assess GCP performances in the frame of clinical trials in resource-limited settings. We highlight the importance of well-trained and integrated study staff, as well as thorough preparation, budgeting and context appropriate monitoring. This achieves high quality, patient centered and compliant research, implemented through alternative frameworks for monitoring and evaluation.

In dengue endemic, resource-limited settings, accurate and timely diagnosis is critical for effective clinical management and outbreak control, especially where multiple arboviruses co-circulate and overlap in clinical presentations. However, most dengue diagnosis in such settings rely on approaches with limited sensitivity such as clinical assessment, or easily deployable methods such as ELISA or rapid diagnostic tests (RDTs). Molecular diagnostics with superior diagnostic performance are rarely implemented beyond reference laboratories due to perceived logistical and operational barriers. This study provides real-world evidence comparing the performance of clinical, serological and molecular approaches for dengue diagnosis in a decentralized setting. We prospectively enrolled 271 patients with acute febrile illness at Santa Gema Hospital in Yurimaguas, Peru, during a dengue outbreak in 2023-2024. Patients underwent clinical evaluation (WHO 2009 dengue classification), and laboratory testing including NS1/ IgM RDTs and ELISAs, a triplex RT-PCR for ZIKV/DENV/CHIKV (ZDC-PCR), a newly developed multiplex RT-PCR for ZIKV/YFV/DENV/CHIKV (ZYDC-PCR), and a serotype-specific dengue RT-PCR used as reference. Diagnostic performance was assessed using sensitivity, specificity, ROC-AUC analysis, and logistic regression models. A subset of 131 samples underwent inter-laboratory comparison of the ZYDC-PCR between the regional (Yurimaguas) and central (Lima) laboratories. Of the 271 dengue-suspected cases, 88 (32.6%) were confirmed by the reference PCR. The ZYDC-PCR had a strong agreement with the reference (sensitivity 86.0%, Cohen's kappa 0.893) and consistent performance across the central and regional laboratory. NS1-based tests showed high specificity (≥96%) but moderate sensitivity (~72%). ROC analysis confirmed the accuracy of PCR (AUC = 0.97), outperforming RDTs, ELISAs (AUC = 0.85 - 0.89) and clinical assessment (AUC = 0.65). Our study demonstrates the added value and feasibility of implementing a multiplex PCR at a regional hospital to significantly improve diagnostic accuracy, enabling earlier detection of disease presence or absence, critical for clinical management and outbreak response.

Knowledge about Chagas disease (CD) among health professionals is essential to control this public health problem. The objective was to evaluate the knowledge about CD among these professionals. A descriptive cross-sectional study was conducted between April and September 2023, in the city of Irecê, Bahia State, Brazil. Data were collected using a standardized questionnaire and analyzed descriptively. Of the 257 participants, 226 (87.9%) claimed to know the etiological agent, although only 173 (76.5%) recognized it as a protozoan. Regarding the modes of transmission, all workers recognized the vector-borne route, but only 102 (39.7%) identified the vertical route. The majority of workers identified the heart as the affected organ (n = 255; 99.2%). The most identified signs/symptoms in the acute phase were fever (n = 196; 76.6%) and edema (n = 218; 85.2%); in chronic cases, it was recognized that they can be asymptomatic, but the majority recognized that electrocardiographic changes and congestive heart failure may be present. Regarding etiological treatment, 175 (72.0%) acknowledged its existence, but 122 (65.9%) could not state the recommended medication; and for 189 (73.5%), CD is incurable. Regarding the vector insect, 210 (82.0%) reported knowing it. Concerning the service to which located triatomine bugs should be sent, 165 (65.7%) identified the Zoonoses Control Center, and that the precaution to be taken when handling triatomine bugs was to protect their hands; for 234 (91.8%) of the participants, the procedure in case of a triatomine bite in humans was to perform serological tests, and 243 (94.6%) had never had access to information about CD. The health workers' knowledge about CD was incipient and differed among occupational categories. For accurate surveillance of CD, training should be offered to health professionals, covering everything from signs/symptoms to the investigation of household and entomological contacts.

Background: Mpox remains a public health emergency of international concern, especially in regions beyond its usual endemic areas in Africa. Assessing healthcare workers good knowledge and positive attitudes is essential for effective prevention and control efforts. This systematic review and meta-analysis aim to determine the pooled good knowledge and positive attitudes toward mpox among healthcare workers in Sub-Saharan Africa after the 2022 outbreak.

Methods: We searched major databases for relevant studies published up to June 25, 2025. Studies reporting knowledge and/or attitudes toward mpox were included. Study quality was assessed using a standardized appraisal tool, and heterogeneity was assessed using the I2 statistic. Data were extracted using a standardized protocol, and a random-effects model was used to calculate pooled prevalence estimates with 95% confidence intervals.

Results: The meta-analysis included sixteen and eight studies in knowledge and attitude analyses, respectively, to estimate the pooled prevalence. The pooled prevalence of good knowledge and positive attitudes toward monkeypox was 45.3% (95% CI: 36.8, 53.9) and 53.8% (95% CI: 43.0, 64.7), respectively. Significant heterogeneity was observed across studies; however, both statistical tests (Egger's test, p = 0.14; Begg's test, p = 0.19) indicated no significant publication bias.

Conclusion: The good knowledge and positive attitudes of healthcare workers toward mpox were low and unsatisfactory in sub-Saharan Africa. The review result underscores the need for targeted interventions to improve healthcare providers' understanding of mpox transmission, prevention, and management. Targeted educational programs and training are needed to improve the preparedness of healthcare workers for mpox outbreaks and other emerging diseases.

Cases of melioidosis have been recorded for many years in Vietnam though it is still not a nationally reportable disease in Vietnam. More research is needed to understand the disease ecology and public health impacts of melioidosis in the country. To this aim, broadening the knowledge base of strains and epidemiology of infections in relation to genotypes present in the soil reservoir can tell us about the propensity of Burkholderia pseudomallei genotypes to transmit from soil to humans. Thirty-five clinical B. pseudomallei isolates, ten from soil, one from swine, and one from a bear were collected by the Institute of Microbiology and Biotechnology, Vietnam National University and sequenced at the National Institute of Hygiene and Epidemiology in Hanoi. The clinical strains were isolated from melioidosis patients from Ha Tinh in each month of 2020 (except July). There were 15 STs identified and four of the clinical isolates were new sequence types (ST) as determined by traditional seven marker multi-locus sequence typing (MLST) analysis. Twenty of the thirty-five (57%) clinical strains isolated in this study were ST 41, with ST 41 isolates obtained throughout the year and across Ha Tinh province with core genome (cg) MLST identifying finer scale differences. ST 41 was recovered from one soil sample approximately 1 year after the clinical isolates. cgMLST analysis and whole genome SNP analysis revealed nucleotide differences among strains in Ha Tinh historically contextualizing them in Vietnam and globally. As melioidosis moves towards a reportable disease in Vietnam, molecular epidemiological methods can connect human, veterinary, and environmental genotypes of concern.

Breast milk confers infants with immunity to a multitude of pathogens reflective of prior maternal infections and vaccinations. However, in outbreak situations where infants may be vulnerable to lethal infections due to gaps in the maternal immune repertoire, a case can be made for supplementing breast milk with one or more pathogen-specific monoclonal antibodies (mAbs) with known prophylactic or therapeutic activity. As oral delivery of recombinant IgG and IgA mAbs to infants has proven challenging, we investigated the use of mRNA-lipid nanoparticle (LNP) technology to stimulate pathogen-specific mAbs in milk. mRNA encoding the Vibrio cholerae O1 specific mAb, ZAC-3, as a human IgG1 or dimeric IgA2, was encapsulated in lipid nanoparticles (LNP) and administered parenterally to lactating and non-lactating female mice. A single intravenous administration of mRNA-LNPs resulted in high and sustained expression of functional ZAC-3 IgG1 in the blood and breast milk of lactating dams. ZAC-3 IgA2 levels were lower and more transient. ZAC-3 IgG1 (but not IgA2) was also detected in the serum of suckling pups at levels proportional to those in the mothers, demonstrating successful transfer of functional antibodies to newborns. Levels of ZAC-3 IgG1 and IgA2 were not sufficient to limit intestinal colonization of V. cholerae O1 when pups were separated from dams following intragastric challenge; however, a significant reduction in bacterial burden was observed when challenged pups remained with dams for continuous breastfeeding. Our findings highlight the potential of mRNA-based mAb platforms in the maternal-newborn context, while acknowledging the need for optimized antibody isotypes, dosing, and tissue-specific delivery to improve mucosal immunity.

This paper examines the establishment and lessons learned from the LeDoxy Trial, a multinational, double-blind, randomized, placebo-controlled study that evaluated doxycycline (200 mg/d and 100 mg/d) over six weeks for the treatment of filarial lymphedema in Tanzania's Lindi and Pwani regions. Conducted from 2018 to 2021 across four sites, the trial enrolled 420 participants aged 14-65 years, addressing a critical gap in lymphatic filariasis (LF) research in geographically remote and historically under-researched areas. The trial faced significant challenges, including limited pre-existing research infrastructure, community research fatigue, and disruptions from the COVID-19 pandemic, which delayed regulatory approvals and supply chains. To overcome these, the TAKeOFF Consortium with Tanzania's National Institute for Medical Research (NIMR) as local sponsor led a 12-month site preparation effort, upgrading Lindi's laboratory from a 2-star to a 4-star rating through infrastructure enhancements (e.g., centrifuges, freezers) and staff training in Good Clinical Laboratory Practice (GCLP). Community health workers (CHWs) leveraging established community-directed approaches from NTD control programs played a pivotal role, achieving a 92% retention rate through targeted recruitment, door-to-door engagement, and follow-up support, including the distribution of hygiene kits. The trial trained 93 healthcare professionals in LF management and clinical research, fostering a research culture despite initial resistance. Additional strategies included remote monitoring to adapt to travel restrictions and stakeholder collaboration to address cultural misconceptions, such as stigma around LF. These efforts not only ensured trial success but also created foundational capacity that has begun to support post-trial research activities, with ongoing evaluation needed to assess long-term sustainability. This paper provides comprehensive, integrated documentation of the infrastructure development process from laboratory accreditation and regulatory navigation to community engagement and sustainability planning, offering actionable guidance for conducting high-quality NTD trials in resource-limited settings. The lessons emphasizing local sponsorship, adaptive protocols, and community trust demonstrate how strategic investments in research infrastructure, local capacity-building, and stakeholder engagement can strengthen clinical research ecosystems in LMICs, advancing health systems, local ownership, and global health equity. This paper focuses exclusively on the operational and implementation aspects of establishing the trial infrastructure.

Background: Despite over two decades of Community-Directed Treatment with Ivermectin (CDTI), onchocerciasis transmission persists in localized pockets in Ghana, particularly in the Kwanware-Ottou community within the Wenchi Health District. This study trialled a scalable approach to identifying context-specific barriers and solutions for improving CDTI effectiveness.

Methodology/principal findings: A mixed-methods approach was employed, including Geographical Information System mapping, community consultation, census and treatment coverage evaluation, and qualitative assessments. These informed the participatory development of an Action Plan, which was implemented and evaluated across three sub-districts. Key challenges identified and addressed included poor data quality, high population mobility, remote settlements with accessibility issues, limited awareness, and inadequate number and deployment of community drug distributors. As a result, therapeutic coverage increased from 70.8% to 88.2. Seven out of eight communities with pre-intervention coverage below the recommended 65% threshold not only achieved but exceeded this target. Ultimately, all communities met the coverage goal. The intervention also improved data accuracy and quality, community engagement, and adherence to directly observed treatment, while addressing systemic gaps in CDTI delivery.

Conclusions/significance: This study demonstrates that a coordinated, locally adapted stimulus package can significantly enhance CDTI performance in areas of persistent onchocerciasis transmission. The approach presents a scalable model for similar endemic settings and aligns with the World Health Organization's 2021-2030 Roadmap for the elimination of Neglected Tropical Diseases.