Amplicon deep sequencing (Amp-Seq) of malaria parasite genomes towards understanding forest transmission systems

疟疾寄生虫基因组的扩增子深度测序（Amp-Seq）有助于了解森林传播系统

• 批准号: 10187078
• 负责人: Neil Lobo
• 金额: $ 9.36万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-22 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10187078
• 关键词: Address; Anopheles Genus; Beds; Behavior; Behavioral; Cambodia; Culicidae; Future; Genotype; Haplotypes; Health care facility; Human; Infection; Insecticides; Intervention; Intervention Studies; Latin America; Location; Malaria; Maps; Measures; Migrant; Movement; Parasites; Parents; Pattern; Phase; Plasmodium; Population; Population Density; Prophylactic treatment; Province; Residual state; Risk; Risk Factors; Role; Seasons; Sleep; Source; Southeastern Asia; Structure; System; Time; Transportation; Travel; Work; base; cohort; deep sequencing; evidence base; forest; insight; malaria infection; malaria transmission; parasite genome; prevent; scale up; spreading factor; transmission process; vector; vector control; vector mosquito

ABSTRACT Forest malaria transmission is poorly understood, and is challenging malaria elimination efforts in Southeast Asia and Latin America. There is a lack of clarity on the source of parasites that initiate seasonal transmission, and how these infections propagate. Leveraging a larger parent study, this project seeks to advance the evidence base on the seasonal transmission of forest malaria in Mondulkiri Province, Cambodia using parasite genotyping and GPS tracking to map the transportation of parasite strains across a malaria season. Aim 1: To characterize baseline Plasmodium population structure in three risk-groups in Mondulkiri province, Cambodia. We will use Amplicon deep sequencing (Amp-Seq) to both baseline characterize and follow parasite haplotypes in groups of forest goers that have different travel patterns and behaviors: seasonal forest workers from local villages, permanent forest dwellers, and forest rangers. We hypothesize that each group will have different populations (density and diversity) of Pf and Pv haplotypes, with one of these groups primarily responsible for initiating seasonal forest malaria transmission. Aim 2: To map the movement of Plasmodium haplotypes in a radically cleared cohort of the primary three forest-risk groups and in nearby villages across a year in Mondulkiri province, Cambodia. We will identify new malaria infections and their parasite genotypes, the time of infection, and their locations. We hypothesize that each group of forest goer have specific risk factors that contribute to ongoing transmission, which may include their behaviors and sleeping conditions in the forest, intervention use, the locations they frequent and its corresponding abundance of Anopheles vectors, and their degree of mobility. Aim 3: To estimate the relative contribution of village forest workers, forest goers, and forest dwellers to malaria transmission in Mondulkiri province, Cambodia. We will investigate the movement of parasite genotypes across time and space along with risk factors and drivers of transmission. We hypothesize that contributions to transmission will be highest among a reservoir of local Anopheles mosquitos, followed by forest goers, with a smaller transmission reservoir among villagers. Results from this study will provide a basis for a future phase 3 intervention study that targets the sources that initiate forest malaria transmission, transport parasites to other locations, and substantially contribute to the reservoir of transmission in Mondulkiri Province, Cambodia.

抽象的 森林疟疾的传播知之甚少，并且在东南部挑战疟疾消除努力 亚洲和拉丁美洲。对启动季节性传播的寄生虫来源缺乏明确的清晰度， 以及这些感染如何传播。利用更大的父母研究，该项目旨在推进 证据基于柬埔寨Mondulkiri省森林疟疾的季节性传播 基因分型和GPS跟踪以绘制寄生虫菌株在疟疾季节的运输。 目的1：表征Mondulkiri三个风险组的基线疟原虫种群结构 柬埔寨省。我们将使用Amplicon Deep测序（AMP-SEQ）来表征和 在具有不同旅行模式和行为的森林群体中遵循寄生虫单倍型：季节性 来自当地村庄，永久森林居民和森林护林员的森林工人。我们假设每个 组将具有PF和PV单倍型的不同人群（密度和多样性），其中一个组之一 主要负责发起季节性森林疟疾传播。 目标2：绘制疟原虫单倍型在主要清除群体中的运动 在柬埔寨蒙杜尔基里省的一年中，三个森林风险群体和附近的村庄附近的村庄。我们将 鉴定新的疟疾感染及其寄生虫基因型，感染时间及其位置。我们 假设每组森林群体都有特定的风险因素，这些风险因素有助于持续传播， 其中可能包括他们的行为和森林中的睡眠条件，干预使用，他们的位置 频繁及其相应的Anopheles载体及其迁移程度。 目标3：估计乡村森林工人，森林居民和森林居民的相对贡献 在柬埔寨蒙杜尔基里省的疟疾传播。我们将研究寄生虫的运动 跨时间和空间的基因型以及传播的危险因素和驱动因素。我们假设这一点 在局部肛门蚊子的水库中，对传播的贡献最高，其次是 森林访客，村民的传输水库较小。 这项研究的结果将为未来的3阶段干预研究提供基础，该研究针对来源 启动森林疟疾传播，将寄生虫运送到其他地方，并为 柬埔寨Mondulkiri省的传播水库。