Identifying parasite reservoirs in areas approaching elimination

 描述(申请人提供)：血吸虫病导致肝纤维化、贫血，损害儿童生长发育，影响全球2亿人。虽然许多人仍然无法获得基本治疗，但由于我们不完全了解的原因，血吸虫病在一些地区仍然存在，这些地区已经实施了积极的疾病控制措施。例如，在西南部的中国，尽管实施了多年的疾病控制计划，包括治疗、健康教育、卫生条件改善和钉螺控制，但血吸虫病已经重新出现并持续存在。我们的目标是利用基因组学的最新进展，并利用先前对血吸虫病重新出现的纵向研究，以解决我们认为对理解血吸虫病持续存在至关重要的两个问题：1)连续感染的个人是否有持续的、未治愈的感染或偶发感染；2)偶发感染是否是以前观察到的当地寄生虫种群的后代？为了回答这些问题，我们将优化最近开发的一种高通量简化表示方法-限制位点相关DNA测序(RADSeq)，以在高分辨率下评估日本血吸虫基因组多样性。寄生虫将从2007年至2010年收集的日本血吸虫毛虫档案中获得，并作为该项目的一部分进行预期感染调查，从而能够在七年期间分析蠕虫多样性和相关性。将使用现有的微卫星基因分型方法和RADSeq对日本血吸虫毛虫进行分析。使用微卫星和RADSeq的并行分析将使我们能够比较粗略和对基因组多样性进行高分辨率测量，并评估未来项目的最佳抽样策略。我们的研究综合了基因组学和血吸虫病控制前沿的专业知识，以推进阻断血吸虫病和其他人类蠕虫病传播的努力为广泛目标。

 DESCRIPTION (provided by applicant): Schistosomiasis causes liver fibrosis, anemia, impairs child growth and development, and affects 200 million people globally. While many people still lack access to basic treatment, schistosomiasis persists in some areas where aggressive disease control measures have been implemented for reasons we do not fully understand. In southwest China, for example, schistosomiasis has reemerged and persists despite multi-year disease control programs including treatment, health education, sanitation improvements and snail control. We aim to harness recent advances in genomics and leverage a prior longitudinal study of schistosomiasis reemergence in order to address two questions we view as essential to understanding the persistence of schistosomiasis: 1) do individuals with consecutive infections have persistent, uncured infections or incident infections and 2) are incident infections the progeny of local parasite populations observed previously? To answer these questions, we will optimize a recently developed high-throughput reduced representation method, restriction-site- associated DNA sequencing (RADSeq), to assess Schistosoma japonicum genomic diversity at high- resolution. Parasites will be obtained from an archive of S. japonicum miracidia collected from 2007 to 2010 and prospective infection surveys conducted as part of this project, allowing analysis of helminth diversity and relatedness over a seven year period. S. japonicum miracidia will be analyzed using existing microsatellite genotyping methods and RADSeq. The parallel analysis using both microsatellites and RADSeq will allow us to compare statistical power and efficiency of coarse-vs. high-resolution measures of genomic diversity and evaluate optimal sampling strategies for future projects. Our research synthesizes expertise at the forefront of genomics and schistosomiasis control, with the broad goal of advancing efforts to interrupt the transmission of schistosomiasis and other human helminthiases.