Molecular epidemiology of Plasmodium falciparum antifolate resistance in Vietnam: genotyping for resistance variants of dihydropteroate synthase and dihydrofolate reductase.
Using PCR techniques, we analysed the dihydropteroate synthase (DHPS) mutations associated with sulphonamide resistance and the dihydrofolate reductase (DHFR) mutations associated with resistance to pyrimethamine and cycloguanil in samples from Plasmodium falciparum-infected Vietnamese patients. Of the 40 samples analysed, 39 had DHFR mutations associated with high level resistance to pyrimethamine, whereas only three had mutations at position 164, which is linked to cross resistance to both DHFR inhibitors. The DHPS, 437Gly variant associated with very mild resistance to sulphadoxine was found in 38 out of the 40 samples. Of seven samples resistant to Fansidar in vivo, only two were fully explained by the currently documented DHPS mutations. The treatment failure could be due to a high level of pyrimethamine resistance caused by the detected mutations. Most patients, however, were cured with a single dose of Fansidar in spite of the high number of resistance mutations found.
Masimirembwa
C M
CM
Department of Pharmaceutical Biosciences, Uppsala University, Sweden.
Phuong-dung
N
N
Phuc
B Q
BQ
Duc-Dao
L
L
Sy
N D
ND
Sköld
O
O
Swedberg
G
G
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D004094:Dihydropteroate Synthase / Q000235:genetics*; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D017720:Molecular Epidemiology; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D016133:Polymerase Chain Reaction; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D014744:Vietnam
D017931:DNA Primers; D005493:Folic Acid Antagonists; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase