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.

Assessment of susceptibility of Plasmodium falciparum to chloroquine, quinine, mefloquine, sulfadoxine-pyrimethamine and artemisinin in southern Viet Nam.

Resistance to antimalarial chemotherapy is a major concern for malaria control in Viet Nam. In this study undertaken in 1998, 65 patients with uncomplicated Plasmodium falciparum malaria were monitored for 28 days after completion of a 5-day treatment course with artemisinin. Overall 36.9% (24/65) of patients had recurrent parasitaemia during the surveillance period. P. falciparum isolates were tested for sensitivity in vitro to chloroquine, mefloquine, quinine, sulfadoxine-pyrimethamine and results were compared to those from a similar study in 1995. Increased parasite sensitivity to sulfadoxine-pyrimethamine, chloroquine and quinine was demonstrated, with significantly lower mean EC50 and EC99 values in 1998 compared to 1995. Parasite sensitivity to mefloquine did not differ significantly in the 2 surveys. Isolates were also tested for sensitivity in vitro to artemisinin in the 1998 survey. The mean EC50 was 0.03 mumol/L and the EC99 was 0.94 mumol/L. Parasite sensitivity to artemisinin will need to be monitored in view of its increasing use in Viet Nam.