Molecular epidemiology of Plasmodium reichenowi

赖氏疟原虫的分子流行病学

• 批准号: 7547060
• 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 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7547060
• 关键词: African; 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; Knowledge; Lead; Malaria; Molecular; Molecular Epidemiology; Natural History; Organism; Pan Genus; 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）：四种疟原虫寄生虫会引起人类疟疾，但恶性疟原虫几乎造成了所有人类疟疾死亡，每年导致超过 100 万人死亡。然而，恶性疟原虫与引起人类疟疾的其他三种疟原虫物种只有远亲关系，而黑猩猩和大猩猩的寄生虫赖切诺维疟原虫在形态上与恶性疟原虫几乎没有区别。这种非常密切的关系已被分子系统发育研究所证实，因此 P. reichenowi 序列对于恶性疟原虫遗传多样性研究来说是非常强大的外群，旨在识别免疫选择压力下的恶性疟原虫基因。生物体之间的相似性对于了解恶性疟原虫发病机制的具体方面也非常有意义。然而，尽管在 20 世纪初曾多次在野生黑猩猩的血液中观察到 P. reichenowi，但科学界仅获得了单一 P. reichenowi 分离物，并且仅保留了该分离物的少数冷冻试管。在疾病预防控制中心。尽管利用这些冷冻原种生成了一些有限的 P. reichenowi 基因组序列，但它主要由短片段组成，并且受到黑猩猩 DNA 的严重污染。在找到 P. reichenowi DNA 的新来源之前，对 P. reichenowi 基因组的研究已经停止。因此，迫切需要新的 P. reichenowi 分离株来完成 P. reichenowi 基因组序列，以及用于比较遗传和发病机制研究。为了获得新的 P. reichenowi 分离株，我们需要鉴定发生 P. reichenowi 感染的野生黑猩猩种群，但尚未对野生黑猩猩中 P. reichenowi 感染的流行情况进行研究。黑猩猩的受保护地位对此类研究可以获得的样本有严格的限制。本申请的目的是采用独特、非侵入性且伦理敏感的检测方法来确定野生黑猩猩群落中 P. reichenowi 感染的流行情况。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。我们建议将该测定应用于独特且预先存在的黑猩猩尿液和粪便样本收集。我们的具体目标是： 1. 建立使用尿液样本检测过去疟原虫感染的敏感性。 2. 确定 P. reichenowi 在野生黑猩猩种群中的流行情况和分布。该项目预计将首次确定野生黑猩猩中 P. reichenowi 感染的流行和分布。预计还将直接导致新的 P. reichenowi 分离株的鉴定，并将其免费提供给疟疾研究界。这些分离株将成为了解最重要的人类传染病杀手之一恶性疟原虫的进化和发病机制的杰出而独特的资源。恶性疟原虫寄生虫每年导致超过 100 万人死亡。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，但与恶性疟原虫最密切相关的寄生虫，一种名为 P. reichenowi 的黑猩猩寄生虫，仅被分离出一次，而且数量有限。该分离物仍然存在。本应用的目的是确定野生黑猩猩中赖氏疟原虫感染的流行情况，并利用该信息获得新的赖氏疟原虫分离株，将其提供给疟疾研究界进行比较研究。