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

说明）： 血吸虫病是一个重大的健康负担，感染了2.07亿多人，2000多万人患有 严重的疾病。有一种药物可用于大规模化疗，吡喹酮（PZQ）。项目（P2） 是由于缺乏关于序贯PZQ治疗对遗传组成的影响的信息， 寄生虫种群，特别是在南美洲，那里采用了一种独特的大规模治疗方案。 此外，实际上没有关于存在于用于本发明的目的基因中的多态性水平的信息。 制定控制措施。本项目的目的是确定PZQ处理的影响 对曼氏血吸虫种群动态及适应潜力的影响。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 疫苗用途。P2有两个主要目标。在aim1中，我们将研究寄生虫的遗传多样性 人口以及它们与本提案其他项目中研究的许多变量的关系。在目标2中， 将评估存在的或选择的多态性，以及它们如何与耐药性的发展相关， 治疗这种方法将是对感染个体的亚群体进行基因分型。作为成年人的样本 蠕虫不可能感染人类，我们将从粪便样本中收集虫卵并孵化虫卵。 将保存获得的毛蚴。对于来自一个感染个体的毛蚴的基因分型池， 进行全基因组扩增，以产生足够的DNA用于基因分型。分型 将通过SNP分型或通过深度测序来完成。制作的资料会上载至 SchistoDB基因组数据库，供研究界广泛使用。P2将通过以下方式与项目1交互： 使编码阵列中编码的蛋白质的基因中的多态性与反应相关 观察到不同组的特征。它还将提供信息，使比较 不同的抗原识别模式与寄生虫基因谱。项目3提供了将使用的材料 基因分型在P2产生的同一时间数据中，多态性和遗传组成都是由P2产生的。 人口，将告知传播的数学模型。 相关性（见说明）： 我们提出的分子群体遗传学方法将为传播和 控制寄生虫，补充从使用鸡蛋的传统流行病学调查中收集的信息 计数，并可用于参数化数学模型。这些模型将提供对控制的洞察力 在巴西和其他血吸虫病流行的国家。

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.