Amino acid mutations in Plasmodium vivax DHFR and DHPS from several geographical regions and susceptibility to antifolate drugs.
The increasing use of sulfadoxine-pyrimethamine (SP) for the treatment of chloroquine-resistant Plasmodium falciparum has resulted in increased reports of SP resistance of P. falciparum worldwide. Selection of SP-resistant Plasmodium vivax in areas where P. falciparum and P. vivax co-exist is not entirely clear. We examined the prevalence and extent of point mutations in pvdhfr and pvdhps in 70 P. vivax isolates from China, East Timor, Papua New Guinea (PNG), Philippines, Vanuatu, and Vietnam. Mutations in seven codon positions were found in pvdhfr, with the majority of isolates having double mutations (S58R/S117N). The greatest range of mutations was observed in the PNG and Vanuatu isolates, ranging from single to quadruple mutations (F57L/S58R/T61M/S117T). Single mutations in pvdhps were observed only in parasites with mutations in corresponding pvdhfr. Parasites with the S58R/S117N dhfr allelic type showed an MIC level for pyrimethamine and cycloguanil comparable to that previously reported, but were susceptible to WR99210.
Auliff
Alyson
A
Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Qld, Australia. alyson.auliff@defence.gov.au
Wilson
Danny W
DW
Russell
Bruce
B
Gao
Qi
Q
Chen
Nanhua
N
Anh
Le Ngoc
le N
Maguire
Jason
J
Bell
David
D
O'Neil
Michael T
MT
Cheng
Qin
Q
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001210:Asia, Southeastern; D002681:China; D004094:Dihydropteroate Synthase / Q000737:chemistry / Q000235:genetics*; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D006801:Humans; D008542:Melanesia; D008969:Molecular Sequence Data; D010966:Plasmodium vivax / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D017354:Point Mutation; D002727:Proguanil; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000235:genetics*; D014227:Triazines / Q000494:pharmacology
D000962:Antimalarials; D004338:Drug Combinations; D005493:Folic Acid Antagonists; D014227:Triazines; C026009:cycloguanil; C001205:fanasil, pyrimethamine drug combination; C006201:BRL 6231; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D002727:Proguanil; D011739:Pyrimethamine