Molecular Epidemiology of Vivax Malaria in Ethiopia

描述(申请人提供)：埃塞俄比亚的疟疾间日疟是地理上分布最广的人类疟疾，造成巨大的痛苦和对经济生产力的重大负面影响。非洲黑人或非洲血统的人被认为可以免受间日疟原虫感染，因为他们的红细胞表面缺乏Duffy抗原的表达，使得间日疟原虫无法入侵红细胞。然而，最近的研究挑战了这一传统观点，提出了间日疟原虫的一些谱系可能已经进化为使用Duffy以外的受体来入侵红细胞的可能性。然而，达菲阴性个体间日疟感染的流行病学意义尚不清楚。此外，没有关于间日疟原虫在达菲阴性个体中的进化史和感染多样性的信息。在这项应用中，我们建议研究埃塞俄比亚间日疟流行区间日疟原虫的分子流行病学和群体遗传学。两个具体目标是：1)确定间日疟原虫在埃塞俄比亚流行地区达菲阴性和达菲阳性人群中无症状感染的流行率和由间日疟原虫引起的有症状疟疾的发生率，以及2)确定达菲阴性人群间日疟原虫分离株的进化历史和遗传多样性。通过确定Duffy阴性和阳性个体中无症状感染的流行率和有症状感染的发生率，我们将能够评估Duffy阴性患者对间日疟原虫感染的保护水平。这项研究的发现将对基于间日疟原虫Duffy结合蛋白的疫苗战略具有重要意义，并显著提高我们对间日疟原虫在非洲一个主要由达菲阴性人群居住的地区的分布和传播的理解。由于我们的研究地点有大量间日疟病例，包括许多重症和脑部病例以及大量达菲阴性个体，它们为研究间日疟在非洲的流行病学和传播提供了独特的机会。

DESCRIPTION (provided by applicant): Malaria in Ethiopia Vivax malaria is the most geographically widespread human malaria, causing tremendous suffering and major negative effects on economic productivity. African blacks or people with African ancestry are thought to be protected from Plasmodium vivax infection because their lack of Duffy antigen expression on the surface of the erythrocytes renders P. vivax unable to invade the erythrocytes. However, recent studies challenge this conventional wisdom, raising the possibility that that some lineages of P. vivax may have evolved to use receptors other than Duffy for erythrocyte invasion. However, the epidemiological significance of vivax infection in Duffy-negative individuals is unknown. Furthermore, there is no information on the evolutionary history and infection diversity of P. vivax in Duffy-negative individuals. In this application, we propose to examine the molecular epidemiology and population genetics of P. vivax in a vivax endemic area in Ethiopia. The two specific aims are: 1) to determine the prevalence of asymptomatic infections and the incidence of symptomatic malaria due to P. vivax in Duffy-negative and Duffy-positive individuals in vivax endemic Ethiopia, and 2) to determine the evolutionary history and genetic diversity of P. vivax isolates from Duffy-negative people. By determining the prevalence of asymptomatic infections and incidence of symptomatic infections in Duffy-negative and -positive individuals, we will be able to assess the level of protection from vivax infection conferred by Duffy negativity. The findings from this study will have important implications on the vivax Duffy binding protein-based vaccine strategy against vivax infections, and significantly improve our understanding of vivax malaria distribution and transmission in a region of Africa that inhabited predominantly by Duffy-negative people. As our study sites have a large number of vivax cases, including many severe and cerebral cases and a large number of Duffy-negative individuals, they offer a unique opportunity to study the epidemiology and transmission of P. vivax in Africa.