Impact of PZQ on Parasite Population Dynamics, Adaptive Potential, &Transmission

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instmctions): Schistosomiasis is a major health burden, infecting over 207 million people and over 20 million suffering form severe disease. There is one drug available for mass chemotherapy, praziquantel (PZQ). This Project (P2) is motivated by the lack of information on the effect of sequential PZQ treatment on the genefic makeup of the parasite population, especially in South America where a distinct schema of mass treatment is employed. Furthermore, there is virtually no information on the level of polymorphism existing in genes of interest for the development of control measures. The objecfive of this project is to determine the impact of PZQ treatment on Schistosoma mansoni population dynamics and adaptafive potenfial. The information generated by P2 will be used in modeling of schistosomiasis transmission and in the selection of biomarkers, diagnosfic or vaccine purposes. P2 has two main aims. In aim 1 we will study the genetic diversity of the parasite populations and how they relate to the many variables studied in other projects of this proposal. In aim 2 we will evaluate polymorphisms present or selected and how they relate to the development of resistance after treatment. The approach will be to genotype infrapopulafions of infected individuals. As sampling the adult worm is not a possibility in human infections, we will collect eggs from fecal samples and hatch the eggs. Miracidia obtained will be preserved. For genotyping pools of miracidia from one infected individual will be submitted to whole genome amplification, in order to generate sufficient DNA for genotyping. Genotyping will be accomplished by SNP typing or by deep sequencing. The informafion produced will be uploaded into SchistoDB genome database for wide use of the research community. P2 will interact with Project 1 by enabling the correlation of polymorphisms in genes coding the proteins coded in the arrays with the reaction profile observed with the different groups. It will also provide informafion that will enable the comparison of distinct antigen recognition patterns with parasite genetic profiles. Project 3 provides the material to be used for genotyping. At the same fime data generated by P2, both polymorphism and genetic makeup of the populafion, will inform the mathematical models of transmission . RELEVANCE (See instmctions): The molecular populafion genefic approach we propose will provide additional insights into transmission and control of parasites that complement informafion gleaned from traditional epidemiological surveys using egg counts, and can be used to parameterize mathematical models. The models will provide insight into control of schistosomiasis in Brazil and other endemic countries.