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

Author:

Verschuuren Tess DORCID,Wasakul VaranyaORCID,Thuy-Nhien Nguyen,Booth Ethan,Quang Huynh Hong,Thang Ngo Duc,Chindavongsa Keobouphaphone,Sovannaroth Siv,Banouvong Virasak,Sengsavath Viengphone,Mayxay Mayfong,Tuyen Nguyen Thi Kim,Phuong Vo Ngoc Lam,Trung Pham Duc,Gonçalves Sónia,Chen Soun,Phalivong Sonexay,Xayvanghang Saiamphone,Mahaphontrakoon Supaporn,Pearson Richard D,Newton Paul N,Maude Richard J,Ashley Elizabeth A,Ariani Cristina V,Simpson Victoria J,Day Nicholas P,Dondorp Arjen M,Miotto OlivoORCID

Abstract

ABSTRACTBackgroundGenetic surveillance ofPlasmodium 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.MethodsSamples 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.ResultsSince 2020, a rapid reduction inPfincidence was observed, alongside a decline of the KEL1/PLA1 lineage resistant to dihydroartemisinin-piperaquine (DHA-PPQ), previously dominant in the eastern GMS. The frequency ofplasmepsin2/3amplifications, 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.ConclusionRoutine genetic surveillance ofPfcan 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.

Publisher

Cold Spring Harbor Laboratory

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