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）：四种疟原虫寄生虫在人类中引起疟疾，但恶性疟原虫几乎造成几乎所有人类疟疾死亡率，每年造成超过100万人的死亡率。然而，恶性疟原虫仅与其他三种引起人类疟疾的疟原虫物种远距离相关，而p. reichenowi是黑猩猩和大猩猩的寄生虫，在形态上几乎与恶性疟原虫无法区分。因此，通过分子系统发育研究证实了这种非常紧密的关系，因此，对恶性疟原虫遗传多样性研究旨在鉴定在免疫选择压力下识别恶性疟原虫基因的恶性疟原虫遗传多样性研究是非常强大的外部组。生物体之间的相似之处也非常感兴趣，以理解恶性疟原虫发病机理的特定方面。然而，尽管在20世纪初的几次野生黑猩猩的血液中观察到了P. reichenowi，但科学界只有一个单一的P. reichenowi分离株，只有少数几个孤立的冷冻管保留在CDC上。尽管可以使用一些有限的P. reichenowi基因组序列，并使用这些冷冻储备产生，但它主要由短片段组成，并被黑猩猩DNA污染。 P. Reichenowi基因组的工作已经停止，直到找到新的Reichenowi DNA来源。因此，迫切需要新的P. reichenowi分离株来完成雷基诺维基因组序列，以及比较遗传和发病机理研究。为了获得新的P. reichenowi分离株，我们需要鉴定出发生在其中发生的野生黑猩猩种群，但从未对野生黑猩猩的雷切诺维感染进行患病率研究。黑猩猩的受保护状况对此类研究可以获得的样本严格限制。该应用的目的是采用独特的，无创和伦理敏感的测定法，以确立野生黑猩猩社区中雷切诺维感染的流行。为了实现这一目标，我们开发了一种使用尿液样品检测疟原虫感染的新颖测定法。我们建议将此测定法应用于黑猩猩尿液和粪便样品的独特且预先存在的集合。我们的具体目的是：1。建立使用尿液样品检测过去疟原虫感染的敏感性。 2。建立野生黑猩猩种群中P. Reichenowi的患病率和分布。预计该项目将首次定义野生黑猩猩雷切诺维感染的流行和分布。还可以直接导致识别新的P. Reichenowi分离株，这些分离物将可以免费提供给疟疾研究社区。这样的分离株将是理解最重要的人类传染病杀手之一，恶性疟原虫的出色和独特资源。恶性疟原虫寄生虫每年杀死超过100万人。为了理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紧密相关的寄生虫是一种称为Reichenowi P. reichenowi的寄生虫，只有曾经被分离出来，并且仅被隔离一次，并且仅被隔离一次。该应用的目的是确定野生黑猩猩中雷希诺维感染的普遍性，并使用该信息获得新的P. reichenowi分离株，这些分离株可用于疟疾研究社区进行比较研究。