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: 10376334
• 负责人: Neil Lobo
• 金额: $ 7.95万
• 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 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10376334
• 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.

摘要 人们对森林疟疾的传播知之甚少，并正在挑战东南部消除疟疾的努力 亚洲和拉丁美洲。目前尚不清楚引发季节性传播的寄生虫的来源， 以及这些感染是如何传播的。利用更大的家长研究，该项目寻求推动 柬埔寨蒙多基里省森林疟疾利用寄生虫季节性传播的证据 基因分型和GPS跟踪，以绘制跨越疟疾季节的寄生虫菌株的传播情况。 目的1：描述蒙多基里三个危险人群的基础疟原虫种群结构 柬埔寨的一个省。我们将使用扩增片段深度测序(Amp-Seq)来鉴定基线和 在有不同旅行模式和行为的森林游人群体中跟踪寄生虫单倍型：季节性 来自当地村庄的森林工人、永久森林居民和护林员。我们假设每个人 组将具有不同的群体(密度和多样性)的Pf和PV单倍型，其中一个组 主要负责发起季节性森林疟疾传播。 目的2：绘制疟原虫单倍型在基本清除的原虫队列中的运动图谱 柬埔寨蒙多基里省的三个森林风险团体和附近村庄的一年时间里。我们会 确定新的疟疾感染及其寄生虫基因类型、感染时间和位置。我们 假设每一组去森林的人都有导致持续传播的特定风险因素， 可能包括它们在森林中的行为和睡眠条件，干预使用，它们的位置 频繁及其对应的丰富的按蚊媒介，以及它们的流动程度。 目标3：估计乡村森林工人、森林守护者和森林居民的相对贡献 柬埔寨蒙多基里省的疟疾传播。我们将调查寄生虫的移动 跨越时间和空间的基因类型以及传播的风险因素和驱动因素。我们假设 对传播的贡献将在当地按蚊的宿主中最高，其次是 去森林的人，在村民中有一个较小的输电水库。 这项研究的结果将为未来的第三阶段干预研究提供基础，该研究针对的是 启动森林疟疾传播，将寄生虫传播到其他地点，并大大促进 柬埔寨蒙多基里省的传播水库。