Collaborative Research: Impacts of the African Origin of Plasmodium vivax on Contemporary Parasite Populations

了解间日疟原虫的进化起源和全球传播可以为了解当代寄生虫种群中耐药等位基因的起源和其他重要遗传差异提供关键的见解。不幸的是，我们所知道的关于非洲间日疟原虫的几乎所有信息都来自于猿类粪便，带有一些特定基因的扩增。由于分析的测序空间相对较小，这种方法提供了一个不完整且可能有偏见的种群结构和间日疟原虫进化起源的图片。该项目的目标是描述中非间日疟种群的特征，并追踪该种群通过非洲之角和进入东南亚的迁移。疟疾仍然是世界上大多数热带和亚热带地区的一项公共卫生挑战。间日疟原虫是引起疟疾的寄生虫中分布最广的一种，每年造成近1400万临床病例，近25亿人面临感染风险。间日疟疾在非洲之角、南美洲和东南亚高度流行。然而，历史上认为它不存在于非洲中部和南部，因为在非洲土著人群中几乎一致缺乏达菲抗原趋化因子受体（DARC），这是寄生虫入侵红细胞的主要受体。然而，在过去十年中，很明显，间日传播正在这些地区发生，并没有因缺乏DARC而完全受到抑制。这些发现对间日疟原虫的历史及其进化起源提出了许多问题。间日疟原虫是我们小组最近在中非地区darc阴性人群中发现的。这一发现为研究全球间日疟原虫的可能来源人群打开了一个意想不到的、前所未有的窗口。该项目的目标是：1)基于2013年刚果民主共和国人口健康调查（OHS）确定间日疟原虫感染的危险因素；2)中非地区间日疟原虫种群的遗传变异和人口统计学特征；3)重建间日疟原虫向东南亚的非洲外迁移；4)重建间日疟原虫种群耐药等位基因的进化。中非人类间日疟原虫感染的鉴定首次使人们能够完全重建其进化起源和随后的迁徙历史。

Understanding the evolutionary origins and global spread of Plasmodium vivax can provide critical insight into the origin of drug resistance alleles and other important genetic differences in contemporary parasite populations. Unfortunately, nearly everything we know about African P. vivax comes from ape feces, with amplification of a few specific genes. This approach provides an incomplete and likely biased picture of population structure and the evolutionary origins of vivax due to the relatively small sequencing space analyzed. The goal of this project is to characterize the P. vivax population in Central Africa and trace migration of this population through the Horn of Africa and into Southeast Asia. Malaria remains a public health challenge through most of the tropical and subtropical regions of the world. Plasmodium vivax is the most widespread of the species of malaria causing parasites, causing nearly 14 million clinical cases annually with nearly 2.5 billion people at risk of infection. Vivax malaria is highly prevalent In the Horn of Africa, South America and Southeast Asia. However, it was historically assumed to not exist in Central and Southern Africa due to the nearly uniform lack in Indigenous African populations of the Duffy antigen receptor for chemokines (DARC), a primary receptor for red blood cell invasion by the parasite. However, over the last decade it has become clear that vivax transmission Is occurring in these regions and is not completely inhibited by the lack of DARC. These findings have raised many questions about the history of P. vivax and its evolutionary origins. P. vivax was recently detected by our group in DARC-negative humans in Central Africa. This discovery opens an unexpected and unprecedented window into studying the likely source population for global P. vivax. The goals of this project are: 1) Identification of risk factors for P. vivax infection based on the 2013 Demographic Health Survey (OHS) in the Democratic Republic of Congo, 2) Characterization of genetic variation and demographic properties of the human P. vivax population in Central Africa, 3) Reconstruction of the out-of-Africa migration of P. vivax into Southeast Asia, and 4) Reconstruction of the evolution of drug resistance alleles in P. vivax populations. The identification of human P. vivax infection in Central Africa allows, for the first time, a complete reconstruction of its evolutionary origins and subsequent history of migration.