Genetic surveillance ofPlasmodium falciparumreveals rapid population changes following first-line treatment policy revisions in the Greater Mekong Subregion

Background Genetic surveillance of Plasmodium falciparum (Pf) is an important tool for tracking antimalarial resistant strains, informing decision-making by National Malaria Control Programmes (NMCPs). Here, we present an analysis of 5,754 samples collected by the GenRe-Mekong project, in collaboration with NMCPs in the Greater Mekong Subregion (GMS), powered by new user-friendly visualization tools developed to translate genomic data into accessible actionable information. Methods Samples collected from patients presenting at public health facilities between 2017 and 2022 were genotyped using the SpotMalaria platform. Output data included genotypes for markers of antimalarial resistance, and genetic barcodes for analysis of relatedness. We developed the grcMalaria R package, which allows users to specify sample selection criteria, and produce geographical maps of prevalence, diversity and relatedness. It also identifies circulating parasite clusters, characterizing their drug resistance profile and mapping their spread. Results Since 2020, a rapid reduction in Pf incidence was observed, alongside a decline of the KEL1/PLA1 lineage resistant to dihydroartemisinin-piperaquine (DHA-PPQ), previously dominant in the eastern GMS. The frequency of plasmepsin2/3 amplifications, associated with piperaquine resistance, dropped from 62% in 2017-2019 to 2% in the first half of 2022. This coincided with a switch in frontline therapy, away from DHA-PPQ, in Cambodia, Thailand, and Vietnam. Artemisinin resistance levels remained high, with a regional prevalence of 89% in 2022. No evidence of emerging mefloquine resistance was found. Conclusion Routine genetic surveillance of Pf can reveal changes in parasite populations in response to public health interventions, especially when its results are translated into intuitive graphical visualizations, providing actionable information for NMCPs.