Tracking Origins and Spread of Sulfadoxine-ResistantPlasmodium falciparum dhpsAlleles in Thailand

Abstract

ABSTRACTThe emergence and spread of drug-resistantPlasmodium falciparumhave been a major impediment for the control of malaria worldwide. Earlier studies have shown that similar to chloroquine (CQ) resistance, high levels of pyrimethamine resistance inP. falciparumoriginated independently 4 to 5 times globally, including one origin at the Thailand-Cambodia border. In this study we describe the origins and spread of sulfadoxine-resistance-conferring dihydropteroate synthase (dhps) alleles in Thailand. Thedhpsmutations and flanking microsatellite loci were genotyped forP. falciparumisolates collected from 11 Thai provinces along the Burma, Cambodia, and Malaysia borders. Results indicated that resistantdhpsalleles were fixed in Thailand, predominantly being the SGEGA,AGEAA, and SGNGA triple mutants and theAGKAA double mutant (mutated codons are underlined). These alleles had different geographical distributions. The SGEGA alleles were found mostly at the Burma border, while the SGNGA alleles occurred mainly at the Cambodia border and nearby provinces. Microsatellite data suggested that there were two major genetic lineages of the triple mutants in Thailand, one common for SGEGA/SGNGA alleles and another one independent forAGEAA. Importantly, the newly reported SGNGA alleles possibly originated at the Thailand-Cambodia border. All parasites in the Yala province (Malaysia border) hadAGKAA alleles with almost identical flanking microsatellites haplotypes. They were also identical at putatively neutral loci on chromosomes 2 and 3, suggesting a clonal nature of the parasite population in Yala. In summary, this study suggests multiple and independent origins of resistantdhpsalleles in Thailand.