Molecular tools to monitor eradication of Schistosoma haematobium transmission

监测埃及血吸虫传播根除的分子工具

• 批准号: 7357760
• 负责人: CHARLES Harding KING
• 金额: $ 21.32万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-15 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7357760
• 关键词: Address; Africa; Anemia; Area; Biological Assay; Body Water; Cells; Clinical Data; Communities; DNA; Databases; Detection; Development; Disease; Ecosystem; Effectiveness; Environment; Exploratory/Developmental Grant; Goals; Habitats; Health; Human; Infection; International; Kenya; Knowledge; Laboratories; Lead; Malnutrition; Mediating; Medical Surveillance; Methods; Middle East; Molds; Molecular; Molecular Medicine; Monitor; Morbidity - disease rate; Nucleic Acids; Parasite Control; Parasites; Performance; Performance Status 4; Persons; Polymerase Chain Reaction; Population; Prevention program; Program Sustainability; Public Health; Quality Control; Research; Research Project Grants; Residual state; Risk; Sampling; Schistosoma; Schistosoma haematobium; Schistosomiasis; Snails; System; Techniques; Testing; Thinking; Translational Research; Trematode Infections; Uncertainty; United States National Institutes of Health; Work; base; design; implementation research; improved; new technology; next generation; novel; programs; sensor; tool; transmission process; treatment program

DESCRIPTION (provided by applicant): Current large-scale schistosomiasis treatment programs are a first step to reducing the global burden of Schistosoma-related disease, yet such programs may not significantly alter parasite transmission in high-risk areas. Consequently, the sustainability of these programs' initial benefits remains in doubt, as recurring low-level reinfection can be associated with persistent morbidity such as anemia, undernutrition, and diminished performance. Novel molecular tools for rapid, sensitive transmission monitoring are needed to obtain more informative surveillance of schistosome propagation over extended areas. In accord with the R21 program's developmental focus, this project will create and validate new technologies that can significantly advance knowledge of the environmental features of schistosome transmission, and will materially contribute to health-related implementation research for improved schistosomiasis control. The overall aim of the proposed study is to test the capacity of new S. haematobium DNA-detection molecular tools to efficiently monitor schistosomiasis transmission in multi-community campaigns. The parasite is widely prevalent in Africa and the Middle East, with 120 million persons currently infected. Effective 'xenomonitoring' snail sampling strategies can provide highly sensitive systems for monitoring transmission potential following implementation of parasite control campaigns. The present study's Loop-mediated Isothermal Amplification is a scalable approach can be adapted to provide low-tech DNA detection systems that regional and international control programs will be able use as a means to document their effectiveness and confirm attainment of schistosomiasis eradication. The Specific Aims of the study are: 1. To validate the established 525 bp Sh110/SmSl PCR technique as a species-specific means to identify snails infected with S. haematobium in ecosystems where related schistosome species are sympatric. 2. To develop a low-tech detection of prepatent snail infection by adapting the Loop-Mediated Isothermal Amplification (LAMP) assay for amplifying the inter-repeat 525 bp Sh110/SmSL sequence of S. haematobium. 3. To validate the LAMP assay by examining laboratory infected snails and field snails collected from S. haematobium-endemic areas in Kenya. 4. To establish the LAMP as a working assay in a pilot field laboratory in Kenya and in a central reference laboratory for backup and quality control. 5. To evaluate S. haematobium-LAMP performance in an existing control setting in Kenya. Human schistosomiasis is a parasitic trematode infection that imposes a major health burden on the developing world and new strategies are needed for tracking its uneven transmission through the environment. This proposal develops new DNA detection systems to monitor parasite transmission (through local infested water bodies) among infected intermediate host snails. This tool will provide a highly useful method of directing schistosomiasis control programs, and could lead to much more effective targeted strategies for eradication of parasite transmission.

描述（由申请人提供）：当前的大规模血吸虫病治疗计划是减轻全球血吸虫相关疾病负担的第一步，但此类计划可能不会显着改变高风险地区的寄生虫传播。因此，这些计划最初效益的可持续性仍然存在疑问，因为反复出现的低水平再感染可能与贫血、营养不良和表现下降等持续发病有关。需要用于快速、灵敏的传播监测的新型分子工具，以获得对大范围血吸虫传播的更多信息监测。根据R21计划的发展重点，该项目将创建和验证新技术，这些技术可以显着增进对血吸虫传播环境特征的了解，并将为改善血吸虫病控制的健康相关实施研究做出重大贡献。拟议研究的总体目标是测试新的埃及沙门氏菌 DNA 检测分子工具在多社区活动中有效监测血吸虫病传播的能力。这种寄生虫在非洲和中东广泛流行，目前有 1.2 亿人感染。有效的“异种监测”蜗牛采样策略可以提供高度敏感的系统，用于监测实施寄生虫控制活动后的传播潜力。本研究的环介导等温扩增是一种可扩展的方法，可用于提供低技术 DNA 检测系统，区域和国际控制计划将能够使用该系统作为记录其有效性并确认血吸虫病根除目标的手段。该研究的具体目标是： 1. 验证已建立的 525 bp Sh110/SmSl PCR 技术作为一种物种特异性手段，可在相关血吸虫物种同域的生态系统中识别感染 S. haematobium 的蜗牛。 2. 通过采用环介导等温扩增 (LAMP) 测定来扩增埃及蜗牛的重复 525 bp Sh110/SmSL 序列，开发一种低技术检测潜伏期蜗牛感染的方法。 3. 通过检查从肯尼亚沙门氏菌流行区收集的实验室感染蜗牛和田螺来验证 LAMP 测定。 4. 将 LAMP 建立为肯尼亚试点现场实验室和中央参考实验室的工作测定方法，用于备份和质量控制。 5. 评估肯尼亚沙门氏菌-LAMP 在肯尼亚现有对照环境中的性能。人类血吸虫病是一种寄生吸虫感染，给发展中国家带来了重大的健康负担，需要新的策略来追踪其在环境中的不均匀传播。该提案开发了新的 DNA 检测系统，以监测受感染的中间宿主蜗牛中的寄生虫传播（通过当地受感染的水体）。该工具将提供一种非常有用的方法来指导血吸虫病控制计划，并可能导致更有效的有针对性的根除寄生虫传播的策略。