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. ? ? ?
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