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

血吸虫病是一项重大卫生负担，感染人数超过2.07亿，2000多万人患有严重疾病。有一种药物可用于大规模化疗，吡喹酮（PZQ）。该项目（P2）的动机是缺乏关于序贯PZQ处理对寄生虫种群遗传组成的影响的信息，特别是在南美洲，那里采用了一种独特的大规模处理模式。此外，几乎没有关于基因中存在的多态性水平的信息，以制定控制措施。本项目目的是确定PZQ处理对曼氏血吸虫种群动态和适应潜力的影响。P2产生的信息将用于血吸虫病传播的建模和生物标志物的选择、诊断或疫苗目的。P2计划有两个主要目的。在目标1中，我们将研究寄生虫种群的遗传多样性，以及它们与本提案其他项目中研究的许多变量之间的关系。在目标2中，我们将评估存在或选择的多态性以及它们与治疗后耐药性发展的关系。该方法将是对受感染个体进行基因分型。由于在人类感染中不可能取样成虫，我们将从粪便样本中收集卵并孵化卵。获得的Miracidia将被保存。为了进行基因分型，将来自一个感染者的miracidia池提交给全基因组扩增，以产生足够的DNA进行基因分型。基因分型将通过SNP分型或深度测序来完成。所产生的信息将被上传到SchistoDB基因组数据库，供研究界广泛使用。P2将与项目1相互作用，使编码阵列中编码的蛋白质的基因多态性与在不同组中观察到的反应谱相关。它还将提供能够将不同抗原识别模式与寄生虫遗传谱进行比较的信息。项目3提供用于基因分型的材料。同时，P2产生的数据，包括群体的多态性和基因组成，将为传播的数学模型提供信息。

Schistosomiasis is a major health burden, infecting over 207 million people and over 20 million suffering from 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 genetic 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 objective of this project is to determine the impact of PZQ treatment on Schistosoma mansoni population dynamics and adaptive 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 infrapopulations 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 information 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 information 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 time data generated by P2, both polymorphism and genetic makeup of the population, will inform the mathematical models of transmission .