Great Ape Reservoirs of Human Malaria
人类疟疾的类人猿储存库
基本信息
- 批准号:8520170
- 负责人:
- 金额:$ 62.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-09-20 至 2015-02-09
- 项目状态:已结题
- 来源:
- 关键词:AccountingAddressAfricaAfricanAreaBindingBiologicalBiological AssayBiologyBloodBlood specimenCenters for Disease Control and Prevention (U.S.)Central AfricaClinicalCollectionCommunicable DiseasesCross InfectionDNADataErythrocytesEventEvolutionFrequenciesFundingFutureGeographic LocationsGorilla gorillaHigh PrevalenceHumanIn VitroInfectionInstitutesKnowledgeLifeLigand BindingLightLocationMalariaMethodsMicroscopyMitochondriaMolecularMorbidity - disease rateNatural HistoryNon-Invasive Cancer DetectionNuclearPan GenusPan paniscusParasitesPathogenesisPathway interactionsPhenotypePhylogenetic AnalysisPlasmodiumPlasmodium falciparumPongidaePopulationPrevalenceProcessPropertyPublic HealthRecurrenceReportingSamplingShippingShipsSiteSourceSpecificityStagingSurveysTestingValidationVariantVeterinariansWorkbasedeep sequencingfollow-upgenome sequencinginsightmanmortalitynovelpandemic diseasescreeningsuccesstransmission process
项目摘要
DESCRIPTION (provided by applicant): Previous funding by an R03 application allowed us to develop novel methods that permit the amplification of Plasmodium sequences from fecal DNA. Screening ape samples from over 50 field sites throughout central Africa, we found that P. falciparum is of gorilla origin, and not of chimpanzee, bonobo or ancient human origin. We also found that chimpanzees and gorillas harbor at least nine Plasmodium species, including parasites that are near identical to P. vivax, P. ovale and P. malariae. Given the magnitude of this Plasmodium reservoir and the fact that gorilla P. falciparum has crossed the species to humans already once, the question arises whether additional cross-infections of ape Plasmodium parasites are occurring. This is of critical public health importance, not because such transmissions would be expected to contribute to current malaria morbidity and mortality, but because they would give an indication of the potential of ape malaria parasites to colonize humans should a reduction of P. falciparum transmission rates generate a new ecological niche. In this application, we will examine whether wild apes serve as a recurrent source of human malaria. We will continue to screen wild ape populations for Plasmodium infections, and test humans who live in close proximity to these apes for evidence of cross-species infection. Our hypothesis is that ape parasites have the potential to infect humans but fail to establish persistent infections because of the predominance of P. falciparum. Determining the types, locations and frequencies of ape Plasmodium cross-species infections will be critical to gauge the success of future P. falciparum eradication campaigns. 1. To determine the prevalence of P. vivax and other non-Laverania species in wild apes. We will determine the prevalence, host specificities and distribution of non-Laverania parasites in wild apes, and determine whether chimpanzees and/or gorillas represent a reservoir for human P. vivax in west central Africa. 2. To determine whether wild chimpanzees or gorillas serve as recurrent sources of human infection. We will use ultradeep (454) sequencing to screen humans who live in close proximity to wild apes for evidence of zoonotic Plasmodium infections. This approach will identify Laverania and non-Laverania parasites even if they infect humans at very low frequencies and in the context of multispecies infections. 3. To determine the natural history of ape Plasmodium infections. We will prospectively follow Plasmodium infected sanctuary apes to examine their clinical status, validate our non-invasive detection methods, and obtain blood samples for ape Plasmodium isolation and whole genome sequencing studies. 4. To determine the biological properties that distinguish human P. falciparum from related ape species. We will express ape Plasmodium erythrocyte binding ligands and test their ability to bind to human erythrocytes in order to investigate the molecular basis of Plasmodium host specificity and to assess which ape Plasmodium species have the capacity to cause a blood stage infection in humans.
描述(由申请人提供):之前 R03 申请的资助使我们能够开发新的方法,允许从粪便 DNA 中扩增疟原虫序列。通过对整个非洲中部 50 多个野外地点的猿类样本进行筛选,我们发现恶性疟原虫起源于大猩猩,而不是起源于黑猩猩、倭黑猩猩或古人类。我们还发现黑猩猩和大猩猩至少携带九种疟原虫,其中包括与间日疟原虫、卵形疟原虫和三日疟原虫几乎相同的寄生虫。考虑到疟原虫储存库的规模以及大猩猩恶性疟原虫已经与人类发生过一次的事实,出现了是否正在发生更多猿类疟原虫寄生虫交叉感染的问题。这对于公共卫生至关重要,不是因为这种传播预计会导致当前的疟疾发病率和死亡率,而是因为它们表明,如果恶性疟原虫传播率降低,产生新的生态位,猿疟原虫就有可能在人类中定殖。在此应用中,我们将研究野生猿是否是人类疟疾的反复来源。我们将继续对野生类人猿种群进行疟原虫感染筛查,并对生活在这些类人猿附近的人类进行测试,以寻找跨物种感染的证据。我们的假设是,猿类寄生虫有可能感染人类,但由于恶性疟原虫占主导地位,因此无法建立持续感染。确定猿类疟原虫跨物种感染的类型、地点和频率对于衡量未来恶性疟原虫根除运动的成功至关重要。 1. 确定间日疟原虫和其他非薰衣草属物种在野生猿中的流行情况。我们将确定野生猿中非拉维尼亚寄生虫的流行率、宿主特异性和分布,并确定黑猩猩和/或大猩猩是否是非洲中西部人类间日疟原虫的宿主。 2. 确定野生黑猩猩或大猩猩是否是人类反复感染的来源。我们将使用超深 (454) 测序来筛查生活在野生猿附近的人类,以寻找人畜共患疟原虫感染的证据。这种方法将识别紫菜属和非紫菜属寄生虫,即使它们以非常低的频率感染人类并且是在多物种感染的情况下。 3. 确定猿疟原虫感染的自然史。我们将前瞻性地追踪疟原虫感染的保护区猿类,检查它们的临床状况,验证我们的非侵入性检测方法,并获取血液样本用于猿类疟原虫分离和全基因组测序研究。 4. 确定区分人类恶性疟原虫与相关猿种的生物学特性。我们将表达猿类疟原虫红细胞结合配体并测试其与人类红细胞结合的能力,以研究疟原虫宿主特异性的分子基础并评估哪些猿类疟原虫物种有能力引起人类血液阶段感染。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Beatrice H Hahn其他文献
Beatrice H Hahn的其他文献
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10686018 - 财政年份:2019
- 资助金额:
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Optimizing glycan shield coverage, germline B cell receptor binding and epitope diversity of V2-apex targeted HIV-1 Env immunogens
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10021396 - 财政年份:2019
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Optimizing glycan shield coverage, germline B cell receptor binding and epitope diversity of V2-apex targeted HIV-1 Env immunogens
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10241429 - 财政年份:2019
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Optimizing glycan shield coverage, germline B cell receptor binding and epitope diversity of V2-apex targeted HIV-1 Env immunogens
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