Human Reservoirs of Plasmodium vivax Transmission in the Peruvian Amazon

秘鲁亚马逊地区间日疟原虫传播的人类宿主

• 批准号: 7450837
• 负责人: Joseph M. Vinetz
• 金额: $ 60.29万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-15 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7450837
• 关键词: Address; Admixture; Anopheles Genus; Aotus primate; Biological Assay; Candidate Disease Gene; Capital; Characteristics; Cluster Analysis; Culicidae; Data; Development; Enzyme-Linked Immunosorbent Assay; Epidemiology; Future; Genetic Markers; Genetic Polymorphism; Genotype; Goals; Health; Home environment; Human; Immunity; Incidence; Individual; Infection; Intervention; Knowledge; Laboratories; Latin America; Malaria; Malaria Vaccines; Medical Surveillance; Membrane; Molecular; Monkeys; Morbidity - disease rate; Nomads; None or Not Applicable; Pan Genus; Pan troglodytes; Parasitemia; Parasites; Patients; Pattern; Peru; Plasmodium; Plasmodium vivax; Polymorphic Microsatellite Marker; Population; Population Biology; Prevalence; Prevention; Public Health; Relapse; Reproduction; Research Personnel; Risk; Risk Factors; Rural; Site; Source; Spatial Distribution; Statistical Models; Testing; Travel; Vaccines; Vivax Malaria; base; feeding; in vitro Assay; in vivo; insight; nonhuman primate; novel; programs; prospective; success; time use; transmission process; vaccine development

DESCRIPTION (provided by applicant): Plasmodium vivax malaria, a leading health problem throughout the Amazon basin on Latin America, is endemic in the Peruvian Amazon. The long-term goal of this project is to determine specific epidemiological characteristics of P. vivax transmission and human reservoirs of maintaining P. vivax transmission in the Peruvian Amazon region towards the rational deployment of a transmission-blocking vaccine. This project will test the hypothesis that reproduction of exogenous P. vivax into local populations is responsible for continuing transmission in rural villages surrounding Iquitos, Peru, the capital of the Peruvian Amazon. Alternative hypotheses are 1) that relapsing P. vivax malaria is the source for maintaining local transmission; or 2) there is simply continuous transmission of already locally established genotypes within local populations. Specific aim 1 is to determine circulating Plasmodium vivax genotypes at the individual village level through prospective, population-based surveillance of people with P. vivax parasitemia. Changes or stability of P. vivax genotypes will be assessed over space and time using recently validated genetic markers. Specific aim 2 is to determine transmission dynamics of P. vivax using geographic spatio- temporal analysis of circulating genotypes using spatial statistical modeling and cluster analysis. These analyses will distinguish whether circulating P. vivax genotypes are already established in villages (either continuously circulating or resulting from relapsing P. vivax from hypnozoites) or are newly introduced by infected inhabitants returning from travel away from the village. Specific aim 3 is to determine whether transmission-blocking immunity develops in the Peruvian Amazon population to potentially modify P. vivax transmission dynamics. Membrane feeding studies will be performed using local Anopheles darlingi mosquitoes and local P. vivax patients as sources of parasites, and by experimental infections of Anopheles mosquitoes from splenectomized non-human primates infected experimentally with P. vivax. In vitro assays (ELISA, IFA) will be used to determine the validity of the in vivo mosquito infection assay. These data will provide the basis for planning transmission-blocking interventions and elimination of human reservoirs of P. vivax, and provide a rational basis for determining strategies to implement and deploy new transmission- blocking vaccines as one approach towards the future elimination of P. vivax malaria from the Amazon basin.

描述（由申请人提供）：在拉丁美洲的整个亚马逊盆地的主要健康问题疟原虫是秘鲁亚马逊的特有。该项目的长期目标是确定在秘鲁亚马逊地区维持私人疟原虫传播的特定的流行病学特征和人类储层的特定特征，以合理地部署传播疫苗。该项目将检验以下假设：秘鲁亚马逊首都秘鲁，秘鲁伊基托斯周围的农村村庄繁殖外源性疟原虫造成当地人口的繁殖。替代假设是1）复发性疟原虫是维持局部传播的来源；或2）仅在局部人群中仅连续传播已经建立的基因型。具体目的1是通过对患有寄生虫假单胞菌寄生虫患者的前瞻性，基于人群的监视来确定各个村庄循环疟原虫基因型。使用最近经过验证的遗传标记，将在空间和时间上评估体内疟原虫基因型的变化或稳定性。具体目标2是使用空间统计建模和群集分析对循环基因型进行循环基因型的时间分析来确定疟原虫的传播动力学。这些分析将区分循环假子基因型是在村庄中已经建立的（无论是在催眠症中持续循环还是因复发性疟原虫而导致），还是由从村庄旅行的被感染居民新引入。具体目标3是确定秘鲁亚马逊种群中是否发展传播障碍，以可能修改疟原虫的传播动力学。膜进食研究将使用局部的蚊子蚊子和局部疟原虫患者作为寄生虫来源，并通过对脾脏切除的非人类突起的蚊子的实验感染，并通过实验性地感染了Vivax。体外测定（ELISA，IFA）将用于确定体内蚊子感染测定的有效性。这些数据将为策划传输障碍干预措施和消除Vivax的人类储层提供基础，并为确定实施和部署新的传输疫苗的策略提供了合理的基础，这是一种未来消除亚马逊盆地中消除Vivax疟疾的方法。