Molecular epidemiology of Plasmodium reichenowi

赖氏疟原虫的分子流行病学

• 批准号: 7386188
• 负责人: Julian Charles Rayner
• 金额: $ 7.25万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7386188
• 关键词: African; American Type Culture Collection; Biological Assay; Biology; Blinded; Blood; Centers for Disease Control and Prevention (U.S.); Cessation of life; Collaborations; Collection; Communicable Diseases; Communities; Comparative Study; DNA; Data; Drug resistance; Evolution; Feasibility Studies; Freezing; Genes; Genetic; Genetic Materials; Genetic Variation; Genome; Goals; Gorilla gorilla; Health; Housing; Human; Immune; Infection; Invasive; Knowledge; Lead; Malaria; Molecular; Molecular Epidemiology; Natural History; Organism; Pan Genus; Pan troglodytes; Parasites; Pathogenesis; Pathogenicity; Phylogenetic Analysis; Plasmodium; Plasmodium falciparum; Population; Prevalence; Prevalence Study; Primates; Protocols documentation; Reagent; Recording of previous events; Research; Resources; Sampling; Screening procedure; Source; Specificity; Time; Tube; Urine; Virulence; Work; comparative; genome sequencing; innovation; interest; killings; mortality; novel; pressure

DESCRIPTION (provided by applicant): Four species of Plasmodium parasites cause malaria in humans, but Plasmodium falciparum is responsible for almost all human malaria mortality, killing more than 1 million people each year. However P. falciparum is only distantly related to the other three Plasmodium species that cause malaria in humans, whereas P. reichenowi, a parasite of chimpanzees and gorillas, is morphologically almost indistinguishable from P. falciparum. This remarkably close relationship has been confirmed by molecular phylogenetic studies and P. reichenowi sequences are therefore very powerful outgroups for P. falciparum genetic diversity studies aimed at identifying P. falciparum genes under immune selection pressure. The parallels between the organisms are also of great interest in understanding specific aspects of P. falciparum pathogenesis. However, although P. reichenowi was observed in the blood of wild chimpanzees on several occasions in the early 20th century, only a single P. reichenowi isolate has ever been obtained by the scientific community, and only a handful of frozen tubes of that isolate remain at CDC. Although some limited P. reichenowi genome sequence is available, generated using these frozen stocks, it consists largely of short fragments and is heavily contaminated with chimpanzee DNA. Work on the P. reichenowi genome has ceased until new sources of P. reichenowi DNA can be found. New P. reichenowi isolates are therefore urgently needed to complete the P. reichenowi genome sequence, as well as for comparative genetic and pathogenesis studies. In order to obtain new P. reichenowi isolates we need to identify wild chimpanzee populations in which P. reichenowi infections occur, but no prevalence study of P. reichenowi infection in wild chimpanzees has ever been carried out. The protected status of chimpanzees places strict limits on the samples that can be obtained for such studies. The objective of this application is to employ a unique, non-invasive and ethically sensitive assay to establish the prevalence of P. reichenowi infection in wild chimpanzee communities. To achieve this objective we have developed a novel assay that uses urine samples to detect Plasmodium infection. We propose to apply this assay to a unique and pre-existing collection of chimpanzee urine and fecal samples. Our specific aims are: 1. Establish the sensitivity of using urine samples to detect past Plasmodium infections. 2. Establish the prevalence and distribution of P. reichenowi in wild chimpanzee populations. This project is expected to define for the first time the prevalence and distribution of P. reichenowi infection in wild chimpanzees. It is also expected to lead directly to the identification of new P. reichenowi isolates that would be made freely available to the malaria research community. Such isolates would be an outstanding and unique resource for understanding of the evolution and pathogenesis of one of the most important human infectious disease killers, Plasmodium falciparum. Plasmodium falciparum parasites kill more than 1 million people each year. In order to understand P. falciparum virulence and pathogenicity we need to compare it with closely related parasite species, but the parasite most closely related to P. falciparum, a chimpanzee parasite called P. reichenowi, has only ever been isolated once and only limited stocks of that isolate remain. The objective of this application is to establish the prevalence of P. reichenowi infection in wild chimpanzees and to use that information to obtain new P. reichenowi isolates that would be made available to the malaria research community for comparative studies.

描述（由申请人提供）：四种疟原虫寄生虫引起人类疟疾，但恶性疟原虫是几乎所有人类疟疾死亡的原因，每年造成100多万人死亡。然而，恶性疟原虫与其他三种引起人类疟疾的疟原虫物种只有远亲关系，而黑猩猩和大猩猩的寄生虫赖氏疟原虫在形态上几乎无法与恶性疟原虫区分。这种非常密切的关系已被分子系统发育研究所证实，因此，赖氏疟原虫序列是恶性疟原虫遗传多样性研究的非常强大的外群，目的是在免疫选择压力下鉴定恶性疟原虫基因。这些生物体之间的相似性对于理解恶性疟原虫发病机制的特定方面也具有极大的意义。然而，尽管在世纪早期曾多次在野生黑猩猩的血液中观察到雷氏疟原虫，但科学界只获得过一种雷氏疟原虫分离株，CDC也只保存了少量该分离株的冷冻试管。虽然一些有限的P. reichenowi基因组序列是可用的，使用这些冷冻的股票，它主要由短片段组成，并严重污染了黑猩猩的DNA。在发现新的赖氏疟原虫DNA来源之前，赖氏疟原虫基因组的研究已经停止，因此迫切需要新的赖氏疟原虫分离株来完成赖氏疟原虫基因组序列，以及进行比较遗传学和致病性研究。为了获得新的赖氏疟原虫分离株，我们需要鉴定发生赖氏疟原虫感染的野生黑猩猩种群，但尚未进行过野生黑猩猩中赖氏疟原虫感染的流行率研究。黑猩猩的受保护地位严格限制了此类研究所能获得的样本。本申请的目的是采用一种独特的、非侵入性的和伦理上敏感的测定方法来确定野生黑猩猩群落中赖氏疟原虫感染的流行率。为了实现这一目标，我们开发了一种新的检测方法，使用尿液样本来检测疟原虫感染。我们建议将此检测应用于黑猩猩尿液和粪便样本的独特和预先存在的收集。我们的具体目标是：1.建立使用尿液样本检测既往疟原虫感染的灵敏度。2.建立野生黑猩猩种群中赖氏疟原虫的流行率和分布。该项目有望首次确定野生黑猩猩中赖氏疟原虫感染的流行和分布。预计还将直接导致鉴定新的赖氏疟原虫分离株，并免费提供给疟疾研究界。这些分离株将是了解人类最重要的传染病杀手之一恶性疟原虫的进化和发病机制的杰出和独特的资源。恶性疟原虫每年杀死100多万人。为了了解恶性疟原虫的毒力和致病性，我们需要将其与密切相关的寄生虫物种进行比较，但是与恶性疟原虫最密切相关的寄生虫，一种称为P.reichenowi的黑猩猩寄生虫，只分离过一次，并且只有有限的分离物存在。本申请的目的是确定赖氏疟原虫感染在野生黑猩猩中的流行率，并利用该信息获得新的赖氏疟原虫分离株，供疟疾研究界进行比较研究。