Tracking origins and spread of sulfadoxine-resistant Plasmodium falciparum dhps alleles in Thailand.
The emergence and spread of drug-resistant Plasmodium falciparum have 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 in P. falciparum originated 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. The dhps mutations and flanking microsatellite loci were genotyped for P. falciparum isolates collected from 11 Thai provinces along the Burma, Cambodia, and Malaysia borders. Results indicated that resistant dhps alleles were fixed in Thailand, predominantly being the SGEGA, AGEAA, and SGNGA triple mutants and the AGKAA 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 for AGEAA. Importantly, the newly reported SGNGA alleles possibly originated at the Thailand-Cambodia border. All parasites in the Yala province (Malaysia border) had AGKAA 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 resistant dhps alleles in Thailand.
Alam
Md Tauqeer
MT
Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Vinayak
Sumiti
S
Congpuong
Kanungnit
K
Wongsrichanalai
Chansuda
C
Satimai
Wichai
W
Slutsker
Laurence
L
Escalante
Ananias A
AA
Barnwell
John W
JW
Udhayakumar
Venkatachalam
V
D000483:Alleles; D000962:Antimalarials / Q000494:pharmacology*; D004094:Dihydropteroate Synthase / Q000145:classification / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005838:Genotype; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000145:classification / Q000235:genetics*; D013413:Sulfadoxine; D013785:Thailand
D000962:Antimalarials; D015800:Protozoan Proteins; D013413:Sulfadoxine; D004094:Dihydropteroate Synthase