Impact of intensive control on malaria population genomics in Eastern Myanmar.

The malaria elimination program in Kayin State (Myanmar) utilizes malaria posts for rapid detection and treatment together with mass drug administration (MDA) in high transmission villages, and has reduced transmission by 97%. We examined the impact of control on parasite genomic parameters, using 2270 genome sequenced Plasmodium falciparum infections from 283 malaria posts, sampled over 58-months (2015 - 2020). Parasites were genetically depauperate: 1726 single-genotype infections comprised 166 unique genomes (≥90% IBD), while nine families (≥45% IBD) accounted for 62.5% of parasites sampled. Parasite effective population size decreased over the study period, but there was minimal change in artemisinin resistance alleles until 2020, when just one predominant genotype (carrying kelch13-R561H) remained. We observed sustained localized transmission of unique parasite genotypes revealing transmission chains: this resulted in positive correlations in parasite relatedness for ≤20 km. MDA resulted in parasite founder effects, providing genomic evidence for the efficacy of this control tool. These results reveal changes in population structure driven by control, and rapid shifts in allele frequency in a parasite population close to elimination.