Host Polymorphisms and Uncomplicated Malaria

描述（由申请人提供）：疟疾仍然是世界上最重要的传染病之一。通过对人类健康的影响，疟疾寄生虫对其宿主的遗传构成产生了实质性的影响。拟议的研究将检查在这种强烈的选择压力下产生的遗传变异，并评估这种变异对疟疾临床结果的影响。该项目的具体目标是：(1)在乌干达坎帕拉评估宿主遗传多态性对简单疟疾发病率的影响；(2)评估宿主遗传多态性对乌干达抗疟疾治疗反应的影响；(3)鉴定影响培养疟原虫发育的宿主多态性。为实现这些目标而设计的研究将利用分子技术来评估在乌干达进行的多项已完成和正在进行的抗疟疾药物疗效研究的受试者的多态性。他们还将使用培养的疟疾寄生虫来评估人类红细胞多态性的体外影响。这些研究结果将有助于了解疟疾的发病机制。此外，确定天然宿主对这种寄生虫的防御将有助于药物发现，并有助于药物和疫苗试验的设计。

DESCRIPTION (provided by applicant): Malaria remains one of most significant infectious diseases world-wide. Through its impact on human fitness, the malaria parasite has had a substantial influence upon the genetic constitution of its host. The proposed research will examine the genetic variability which has arisen under this intense selective pressure and assess the impact of this variability on clinical malaria outcomes. The specific aims of this project are: (1) to assess the impact of host genetic polymorphisms on the incidence of uncomplicated malaria In Kampala, Uganda; (2) to assess the impact of host genetic polymorphisms on the response to antimalarial therapy in Uganda; (3) to identify host polymorphisms that impact upon the development of cultured malaria parasites. The studies designed to achieve these aims will utilize molecular techniques to evaluate polymorphisms in subjects from multiple completed and ongoing studies of antimalarial drug efficacy conducted in Uganda. They will also use cultured malaria parasites to evaluate the in vitro impacts of polymorphisms in human erythrocytes. Findings from these studies will contribute to the understanding of malaria pathogenesis. Additionally, the identification of natural host defenses against this parasite will aid in drug discovery, and assist in the design of drug and vaccine trials. The applicant, Dr. Sunil Parikh, is an infectious disease specialist with a strong commitment to malaria research and international health. This project is intended to provide him with in-depth training in translational clinical malaria research, molecular genetics, epidemiology, and biostatistics. Mentoring will be provided by senior investigators with overlapping expertise in clinical research, molecular parasitology, and epidemiology. With the skills gained from this project, Dr. Parikh will be able to utilize modern molecular epidemiology techniques to investigate human genetic factors underlying susceptibility to malaria and he will be well equipped for a career in academic research.