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

血吸虫病是一个主要的健康负担，感染了超过2.07亿人，超过2000万人患有严重疾病。有一种药物可用于大规模化疗，即吡喹酮(PZQ)。该项目(P2)的动机是缺乏关于顺序PZQ治疗对寄生虫种群遗传构成的影响的信息，特别是在南美洲，那里采用了独特的大规模治疗方案。此外，几乎没有关于用于制定控制措施的感兴趣基因的多态水平的信息。本项目的目的是确定PZQ治疗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以及生物标志物的选择、诊断或疫苗目的。P2有两个主要目标。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基因多态以及它们与治疗后耐药性发展的关系。方法将是对感染个体的亚群进行基因分型。由于在人类感染中不可能对成虫进行采样，我们将从粪便样本中收集卵子并孵化卵子。获得的毛滴虫将被保存。对于基因分型，来自一个感染个体的毛虫池将被提交给全基因组扩增，以便产生足够的DNA用于基因分型。基因分型将通过SNP分型或深度测序完成。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将通过使编码阵列中编码的蛋白质的基因的多态与观察到的不同组的反应谱相关联来与项目1相互作用。它还将提供能够将不同的抗原识别模式与寄生虫基因图谱进行比较的信息。项目3提供了用于基因分型的材料。与此同时，P2产生的数据，包括种群的多态和遗传构成，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 .