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

合作研究：非洲起源的间日疟原虫对当代寄生虫种群的影响

• 批准号: 9899345
• 负责人: Jonathan J Juliano
• 金额: $ 47.01万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-20 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9899345
• 关键词: Africa; African; Antigen Receptors; Central Africa; Clinical; Data; Democratic Republic of the Congo; Demographic and Health Surveys; Drug resistance; Erythrocytes; Evolution; Feces; Genes; Genetic; Genetic Variation; Genome; Goals; Horns; Human; Indigenous; Infection; Malaria; Maps; Parasites; Plasmodium vivax; Pongidae; Population; Property; Public Health; Recording of previous events; Research; Risk Factors; Source; South America; Southeastern Asia; Southern Africa; Structure; Time; Vivax Malaria; base; chemokine receptor; infection risk; insight; migration; parasite invasion; population migration; receptor; reconstruction; resistance allele; transmission process

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.

了解间日疟原虫的进化起源和全球传播，可以提供关键的洞察耐药等位基因的起源和其他重要的遗传差异，在当代寄生虫种群。不幸的是，我们对非洲间日疟原虫的了解几乎都来自猿类的粪便，其中有一些特定的基因被扩增了。这种方法提供了一个不完整的和可能有偏见的图片人口结构和间日疟原虫的进化起源，由于相对较小的测序空间分析。该项目的目标是描述中非间日疟原虫种群的特征，并追踪该种群通过非洲之角进入东南亚的迁移。疟疾仍然是世界上大多数热带和亚热带地区的公共卫生挑战。间日疟原虫是最广泛的疟疾寄生虫，每年造成近1400万例临床病例，近25亿人面临感染风险。间日疟在非洲之角、南美洲和东南亚非常流行。然而，历史上认为它不存在于中部和南部非洲，因为在非洲土著人群中几乎统一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，在过去的十年中，间日疟传播在这些地区发生，并且没有完全被DARC的缺乏所抑制，这一点已经变得很清楚。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。我们的研究小组最近在中非的DARC阴性人群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种群打开了一扇意想不到的、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）鉴定间日疟原虫感染的风险因素，2）表征中非人类间日疟原虫种群的遗传变异和人口统计学特性，3）重建间日疟原虫从非洲迁移到东南亚的过程，（4）重建间日疟原虫群体耐药等位基因的进化。在中非发现人类间日疟原虫感染，首次使人们能够完全重建其进化起源和随后的迁徙历史。