Recurrent treatment: Effect on rural and urban S. mansoni population structure

描述（由申请人提供）：当地曼氏血吸虫种群中存在的生物异质性很难研究，但这种多样性和当地寄生虫种群动态是疾病的重要风险因素;它们可能有助于药物设计，并可能影响控制策略。控制程序为S. mansoni中心每2-3年重复一轮化疗，以降低感染强度，从而降低发病率。由于这些人群迅速恢复，流行率受到的影响要小得多，传播也没有中断。周期性收缩和再扩张种群对寄生虫生物学的影响在很大程度上是未知的，这是由于缺乏区分蠕虫亚群的工具和方法。我们已经确定了7个多态性微卫星标记，表现得像单拷贝位点，是种特异性的，并产生可解释的模式从寄生虫卵分离的DNA。此外，为了优化采样，我们开发了从粪便中分离寄生虫卵DNA的方法，以及利用合并样本而不是离散基因型的等位基因频率的统计方法。为了了解反复化疗如何改变S。mansoni种群结构，这一建议将直接决定S.通过从受感染个体的粪便中分离出虫卵DNA并对其进行基因分型，这些等位基因频率将与每年化疗前后寄生虫的区域和微地理分布相关。借助我们开发的工具，该项目将：1）确定微地理学如何与亚群分布和基因流动相关，2）确定广泛的化疗如何改变群体结构，3）确定化疗后持续存在的群体如何与治疗前群体相关，4）测量迁移或常住人口增加对恢复易感群体的贡献，5）评估当地寄生虫传播与向城市疫源地迁移的贡献。6）比较治疗前后城市疫源地与农村人群。将使用种群间固定指数（Fsr）并通过估计有效种群大小（Ne）和移民率（m）来比较种群结构。混合种群分析也将用于分析移徙。

DESCRIPTION (provided by applicant): The biologic heterogeneity that exists within local Schistosoma mansoni populations is difficult to study, yet this diversity and local parasite population dynamics are important risk factors for disease; they may assist drug design and may affect control strategies. Control programs for S. mansoni center on repeated rounds of chemotherapy every 2-3 years to reduce infection intensities and thereby reduce morbidity. Prevalence is much less affected and transmission is not interrupted, since these populations rapidly recover. The resultant effect of periodic contracting and re-expanding populations on schistosome biology is not known in large part due to the lack of tools and methodologies for differentiating subpopulations of worms. We have identified 7 polymorphic microsatellite markers that behave like single-copy loci, are species-specific, and produce interpretable patterns for DNA isolated from parasite eggs. Further, to optimize sampling, we have developed methods to isolate parasite egg DNA from stool and statistical methods that utilize allele frequencies from pooled samples rather than discrete genotypes. In order to understand how repeated chemotherapy changes S. mansoni population structure, this proposal will directly determine the allele frequency distribution of S. mansoni by isolating and genotyping egg DNA from the stool of infected individuals. These allele frequencies will then be related to the regional and microgeographic distribution of the parasite before and after yearly chemotherapy. With the tools we have developed, this project will: 1) Determine how microgeography relates to subpopulation distribution and gene flow, 2) Determine how widespread chemotherapy changes population structure, 3) Determine how populations that persist after chemotherapy are related to pre-treatment populations, 4) Measure the contribution of migration or increase in the resident population to recovery of schistosome populations, 5) Assess the contribution of local parasite transmission versus immigration to urban foci, 6) Compare urban foci to rural populations before and after therapy. Population structure will be compared using the between populations fixation index (Fsr) and by estimation of both effective population size (Ne) and the immigration rate (m). Mixed stock analysis will also be used to analyze migration.