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) mutat ions associated with sulphonamide resistance and the dihydrofolate reductas e (DHFR) mutations associated with resistance to pyrimethamine and cyclogua nil in samples from Plasmodium falciparum-infected Vietnamese patients. Of the 40 samples analysed, 39 had DHFR mutations associated with high level r esistance to pyrimethamine, whereas only three had mutations at position 16 4, which is linked to cross resistance to both DHFR inhibitors. The DHPS, 4 37Gly variant associated with very mild resistance to sulphadoxine was foun d in 38 out of the 40 samples. Of seven samples resistant to Fansidar in vi vo, only two were fully explained by the currently documented DHPS mutation s. The treatment failure could be due to a high level of pyrimethamine resi stance caused by the detected mutations. Most patients, however, were cured with a single dose of Fansidar in spite of the high number of resistance m utations found. (C) 1999 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved.