Cambodia strives to eliminate all species of human malaria by 2025, requiring that foci among forest-exposed populations in remote settings be addressed. This study explores malaria risk factors amongst forest-exposed groups in Mondulkiri and Kampong Speu Provinces, Cambodia as part of a multi-stage study on novel bite prevention tools (Project BITE). A serial cross-sectional survey explored the demographics, housing structure openness, mosquito bite prevention habits, and gaps in protection amongst three target groups: forest goers who work in the forest, forest dwellers who live in the forest, and forest rangers who patrol forested regions. Malaria prevalence data was collected at three time points using rapid diagnostic tests (RDTs) for febrile individuals and qPCR for all participants. Infection locations and travel patterns of P. falciparum-infected individuals were analyzed for clustering and the potential movement of infections. 2,935 participants were enrolled between October 2022 and February 2023, consisting of 1,093 (37%) forest goers and 1,787 (61%) forest dwellers across both provinces, and 55 (5%) forest rangers in Mondulkiri province. Most worked outdoors as farmers, day laborers, and forest collectors, and reported going to the forest five to seven days a week. For housing, 29% and 39% of participants reported living in partially open primary and secondary structures, respectively. The main methods of mosquito bite protection used were insecticide-treated nets, wearing long sleeves, and burning mosquito coils, with gaps in protection during the daytime and outside at night. All febrile individuals had negative RDT test results. For qPCR, 24 P. falciparum infections (<1%) were detected among forest goers and dwellers, clustered in Pu Trom and Pu Nhav villages in Mondulkiri Province, and Banteay Roka and Banteay Roka Kirisenchey (M) villages in Kampong Speu Province. P. vivax cases were detected (216 cases, 5%) across all enrolled villages. Only two infections were found in forest rangers. Malaria elimination strategies for forest-exposed populations in Cambodia should focus on vector intervention strategies that offer protection during the day and outside at night, and the use of drug-based strategies to clear subpatent infections, targeting forest goers and dwellers in villages where cases are detected.
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