Genetic Diversity of Plasmodium falciparum and Severe Malaria in Africa

描述（由申请人提供）：疟疾继续对全球健康产生重大影响，每年有1-3百万人死亡，其中绝大多数发生在撒哈拉以南非洲的儿童中，原因是严重的疟疾（即，严重疟疾贫血和脑型疟疾）。脑型疟疾的临床综合征，迄今为止只能通过尸检确诊，可能是人类宿主、感染性寄生虫和传播的环境动力学之间复杂相互作用的结果。恶性疟原虫粘附于人类宿主的内皮从而将自身从循环中隔离的独特能力已被清楚地证明是必要的，但不足以解释死亡率。阐明寄生虫遗传多样性在脑型疟疾病理学中的作用可能会导致强大的药物靶点，扩大疫苗制剂的范围，并确定以前未知的发病机制。最近可用的非常强大的恶性疟原虫基因组全屏幕的遗传多态性，利用少量的寄生虫DNA允许非常详细的研究问题的变量在脑疾病中看到的病理损伤。该提案的长期目标是：1）充分界定恶性疟原虫遗传多样性的概念，因为它有助于严重的疾病; 2）为研究人员提供基因组学研究和流行病学方法的额外必要补充技能，以发展成为疟疾的独立研究人员。

DESCRIPTION (provided by applicant): Malaria continues to have a major impact on global health with rates of 1-3 million deaths annually, the vast majority of which occur in children in sub-Saharan Africa as a result of severe malaria (i.e., severe malaria anemia and cerebral malaria). The clinical syndrome of cerebral malaria, thus far definitively diagnosed only by autopsy, probably results from the complex interactions of the human host, the infecting parasite, and the environmental dynamics of transmission. The unique ability of Plasmodium falciparum to adhere to the endothelium of the human host and thus sequester itself from the circulation has clearly been shown to be necessary but not sufficient to account for mortality. Elucidation of the role of parasite genetic diversity in the pathology of cerebral malaria could lead to powerful drug targets, expand the spectrum of vaccine formulations, and define previously unknown mechanisms of pathogenesis. The recent availability of extremely powerful Plasmodium falciparum genome wide screens for genetic polymorphisms which utilize small amounts of parasite DNA allow for very detailed study of questions the variable pathologic lesions seen in cerebral disease. The long term goal of this proposal is 1) to fully define the concept of Plasmodium falciparum genetic diversity as it contributes to severe disease and 2) to provide the investigator with the additional necessary complementary skills of genomics research and epidemiological methods to develop into an independent investigator in malaria.