Peruvian/Brazilian Amazon Center of Excellence in Malaria

描述(由申请人提供)：该疟疾研究英才中心的总体研究目标是组织一种全面的方法，以了解亚马逊疟疾的生物学特征，以实现区域控制和消灭恶性疟原虫和间日疟原虫的最终目标。我们主要关注间日疟原虫，因为它在该地区的影响更大。我们预计，吸取的经验教训将有助于实现全球根除疟疾这一大胆目标。行政、数据管理和共享实验室资源中心将支持一套综合和互动的5个项目，以研究疟疾流行病学、病媒生物学和生态学、诊断学、传播生物学和临床发病机制，以实现南美洲亚马逊地区疟疾控制、区域消除和根除的目标。将研究三个不同的流行病学地点，主要受间日疟原虫(约80%的病例)影响，但也受恶性疟原虫(约20%)病例的影响：巴西的阿克雷；秘鲁的伊基托斯；秘鲁的马德雷·迪奥/马尔多纳多港。来自圣保罗大学和秘鲁利马的Peruana Cayetano Heredia大学的研究人员将成为牵头的外国合作者，并将与牵头机构加州大学圣地亚哥分校、合作机构纽约卫生部沃兹沃斯中心、约翰·霍普金斯公共卫生学院和秘鲁利马的美国海军医学研究中心支队合作，以实现该中心的目标。 相关性：秘鲁/巴西疟疾研究英才中心将采取综合方法研究疟疾流行病学、病媒生物学和生态学、诊断学、传播生物学和临床发病机制，以支持南美洲亚马孙地区的疟疾控制、消除和根除工作。 项目1： 标题：秘鲁和巴西亚马逊地区的疟疾流行病学 项目负责人：费雷拉，M。 项目1说明(由申请人提供)：巴西和秘鲁这两个疟疾流行国家的机构正在与美国的一个领先研究小组合作，长期目标是提供可转化为亚马逊地区疟疾控制的有效公共卫生干预措施的科学证据。为了确定无症状寄生虫携带是否是该地区疟疾传播的主要因素，我们的目标是：(A)估计亚马逊农村地区无症状疟疾寄生虫携带的流行率、发病率和危险因素；(B)估计配子体携带配子体的流行率、发生率、平均持续时间和风险因素；(C)比较有症状和无症状的配子体携带者实验感染野生捕获的当地媒介的能力；(D)前瞻性地比较居住在同一社区的无症状寄生虫携带者和未感染的对照组随后临床疟疾的风险，并确定这些发作是由于持续的寄生虫谱系还是由于新的感染；以及(E)测试寄主内不同的寄生虫克隆的竞争是否有助于提高寄生虫的毒力、更大的疾病风险和增加配子体的产量。这些目标将通过以人口为基础的调查，使用统一的临床和实验室方案，在亚马逊的三个流行病多样化的环境中实现：(A)巴西疟疾流行的典型农业定居点；(B)秘鲁的城郊村庄最近暴露于疟疾流行的村庄；(C)秘鲁的金矿飞地，由于间日疟原虫导致疟疾暴发。实地的临床和流行病学分析将辅之以免疫学参数的测量、广泛的寄生虫基因分型和通过膜喂养试验对蚊子的实验感染，从而为亚马孙盆地无症状寄生虫携带对公共卫生的意义提供独特的多学科视角。至关重要的是，实地七年积极监测疟疾的基础设施和数据将为这项提议的病媒生物学和发病机制部分以及在亚马逊地区实施未来的疟疾疫苗试验奠定基础。 相关性：在提倡将根除疟疾作为全球疟疾控制战略的最终目标的时候，仍不清楚为什么在亚马逊盆地传播水平相对较低的地区疟疾如此难以控制。我们假设，无症状感染可能是该地区寄生虫的主要宿主，而传统的疟疾控制战略并没有解决这一问题。

DESCRIPTION (provided by applicant): The overall research aim of this Center of Excellence in Malaria Research is to organize a comprehensive approach to understanding the biological features of Amazonian malaria towards the ultimate goal of regional control and elimination of Plasmodium falciparum and P. vivax. We focus primarily on P. vivax due to its greater impact in the region. We anticipate that the lessons learned will contribute towards the audacious goal of global malaria eradication. An integrated and interactive set of 5 projects will be supported by Administrative, Data Management and Shared Laboratory Resource Cores to study malaria epidemiology, vector biology and ecology, diagnostics, transmission biology and clinical pathogenesis towards the goal of malaria control, regional elimination and eradication in the Amazon region of South America. Three epidemiological distinct sites primarily affected by P. vivax (~80% of cases) but also by P. falciparum (~20%) of cases will be studied: Acre, Brazil; Iquitos, Peru; and Madre de Dio/Puerto Maldonado, Peru. Investigators from University of Sao Paulo and the Universidad Peruana Cayetano Heredia in Lima, Peru will be the lead foreign collaborators, and will join forces with lead institution University of California San Diego, and collaborating institutions Wadsworth Center of the New York Health Department, Johns Hopkins School of Public Health, and the U.S. Naval Medical Research Center Detachment, Lima, Peru to carry out the aims of the Center. RELEVANCE: The Peru/Brazil Center of Excellence in Malaria Research will take an integrated approach to the study of malaria epidemiology, vector biology and ecology, diagnostics, transmission biology and clinical pathogenesis to underpin malaria control, elimination and eradication efforts in the Amazon region of South America. PROJECT 1: Title: Epidemiology of Malaria in the Peruvian and Brazilian Amazon Project Leader: Ferreira, M. PROJECT 1 DESCRIPTION (provided by applicant): Institutions based in two malaria-endemic countries, Brazil and Peru, are partnering with a leading research group in the USA with the long-term goal of providing scientific evidence that can be translated into effective public health interventions for malaria control in Amazonia. To determine whether asymptomatic parasite carriage is a major contributor to malaria transmission across the region, we aim: (a) to estimate the prevalence, incidence and risk factors for asymptomatic malaria parasite carriage in rural Amazonia; (b) to estimate the prevalence, incidence, average duration and risk factors for gametocyte carriage; (c) to compare the ability of symptomatic and asymptomatic carriers of gametocytes to experimentally infect wild-caught local vectors; (d) to compare prospectively the risk of subsequent clinical malaria among asymptomatic parasite carriers and non-infected controls living in the same communities and to determine whether these episodes are due to persistent parasite lineages or to new infections; and (e) to test whether intra-host competition of genetically distinct parasite clones contributes to increased parasite virulence, greater risk of disease, and increased gametocyte production. These aims will be achieved with population-based surveys, using uniformized clinical and laboratory protocols, in three epidemiologically diverse Amazonian settings: (a) a typical agricultural settlement with endemic malaria transmission in Brazil, (b) periurban villages in Peru that became recently exposed to epidemic malaria, and (c) gold-mining enclaves in Peru with explosive malaria outbreaks due to P. vivax. The field-based clinical and epidemiological analysis will be complemented with measurements of immunological parameters, extensive parasite genotyping and experimental infections of mosquitoes through membrane-feeding assays, providing a unique multidisciplinary perspective on the public health significance of asymptomatic parasite carriage in the Amazon Basin. Of crucial importance, the infrastructure and the data resulting from seven years of active malaria surveillance in the field sites will establish the bases for the vector biology and pathogenesis components of this proposal and for implementing future malaria vaccine trials in the Amazon region. RELEVANCE: At a time when eradication is advocated as the ultimate goal of malaria control strategies worldwide, it remains unclear why malaria proved so difficult to control in areas of relatively low levels of transmission across the Amazon Basin. We hypothesize that asymptomatic infections may represent a major reservoir of parasites in this region, which is not addressed by traditional malaria control strategies.