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的遗传差异提供重要的见解。不幸的是，我们所知道的关于非洲间日疟原虫的几乎所有东西都来自猿类粪便，带有几个特定基因的扩增。由于所分析的测序空间相对较小，这种方法提供了关于间日疟原虫种群结构和进化起源的不完整和可能有偏见的图景。该项目的目标是描述中非间日疟原虫种群的特征，并追踪这一种群通过非洲之角进入东南亚的迁徙情况。疟疾仍然是世界大部分热带和亚热带地区的公共卫生挑战。间日疟原虫是引起疟疾的寄生虫中分布最广泛的物种，每年造成近1400万临床病例，近25亿人面临感染风险。间日疟在非洲之角、南美洲和东南亚高度流行。然而，由于非洲土著人口几乎一致缺乏Duffy抗原趋化因子受体(DARC)，历史上认为这种寄生虫在中部和南部不存在，DARC是寄生虫入侵红细胞的主要受体。然而，在过去的十年里，已经很明显，间日疟正在这些地区发生传播，并且不会因为缺乏DARC而完全被抑制。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。我们小组最近在中非DARC阴性的人类中发现了间日疟原虫。这一发现为研究全球间日疟原虫可能的来源群体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)根据刚果民主共和国2013年人口健康调查(OHS)确定间日疟原虫感染的风险因素；2)描述中部非洲间日疟原虫种群的遗传变异和人口特征；3)重建间日疟原虫走出非洲迁移到东南亚的情况；4)重建间日疟原虫种群中耐药等位基因的进化。在中部非洲发现人间日疟原虫感染，首次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.