Genetic relatedness of Cambodian Plasmodium falciparum isolates is driven by geography and occupation

Background: elimination, but targeted interventions are needed to prevent resurgence. Identity-by-descent (IBD)-based methods offer insight into parasite relatedness and transmission dynamics. Methods: isolates collected from military personnel and farmers in Cambodia between 2014 and 2016. All isolates underwent whole genome sequencing. Relatedness was defined as the proportion of the genome shared IBD between isolates. We evaluated associations between relatedness and epidemiologic factors, including occupation, location, time, age, and sex. Infomap community detection was used to identify clusters of highly related parasites and their association with covariates. Results: Mean IBD sharing was high (40%), with greater relatedness among isolates from Oddar Meanchey than from Kratie province (p90% IBD) were associated with occupation, K13 mutation (C580Y vs. R539T), and PfCRT mutation (p=0.0025, 0.0001, and 0.0001, respectively). Isolates from mixed-occupation pairs had lower odds of high relatedness (>90% IBD) than pairs from farmers (pd=0.958). Conclusions: High overall IBD sharing may reflect a combination of recent elimination efforts and expansion of drug-resistant lineages. Substantial differences in relatedness between provinces underscore the role of geography in shaping relatedness patterns. Lower relatedness among mixed-occupation pairs compared to farmer pairs suggests potential occupation-specific transmission sources and supports tailoring interventions to local micro-epidemiologic factors.