Identifying parasite reservoirs in areas approaching elimination

 描述（由申请人提供）：血吸虫病导致肝纤维化，贫血，损害儿童生长和发育，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，原因我们并不完全了解。例如，在中国西南部，尽管开展了多年的疾病控制计划，包括治疗、健康教育、卫生改善和控制蜗牛，血吸虫病仍然死灰复燃。我们的目标是利用基因组学的最新进展，并利用先前的纵向研究血吸虫病的重新出现，以解决两个问题，我们认为是必不可少的理解血吸虫病的持续性：1）连续感染的个人有持续的，未治愈的感染或事件感染和2）事件感染的后代，当地的寄生虫种群观察到以前？为了回答这些问题，我们将优化最近开发的高通量简化表示方法，限制性位点相关DNA测序（RADSeq），以评估日本血吸虫基因组多样性的高分辨率。寄生虫将从S.日本毛蚴收集2007年至2010年和前瞻性感染调查作为该项目的一部分进行，允许蠕虫的多样性和相关性的分析超过七年的时间。S.将使用现有的微卫星基因分型方法和RADSeq分析日本毛蚴。使用微卫星和RADSeq的并行分析将使我们能够比较基因组多样性的粗与高分辨率测量的统计功效和效率，并为未来的项目评估最佳采样策略。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，其广泛目标是推进阻断血吸虫病和其他人类蠕虫病传播的努力。

 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.