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

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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.