Analysis of resistance to pyrimethamine/sulphadoxine of isolates of Plasmodium falciparum from Eastern Thailand

Abstract

The in vitro susceptibility of five field isolates of Plasmodium falciparum from the region of the Thai-Kampuchean border to pyrimethamine, sulphadoxine, and their combination, was determined using a microtitre test system and media deficient in p-aminobenzoic acid and folic acid. Two-fold serial dilutions of pyrimethamine ranging from concentrations of 8·0 to 0·125 μM and sulphadoxine ranging from 800 to 50 μM were evaluated for antimalarial activity. Viability was based on the maturation of the ring stages to normally-appearing schizonts. Tested singly the parasites had an average ID 90 of 3·82 μM for pyrimethamine and > 800 μM for sulphadoxine. Analysis of the drugs interaction showed maximum potentiation at approximately 0·8 μM of pyrimethamine and 80 μM of sulphadoxine. These results suggest that resistance to Fansidar is due to the resistance to both components. Although there was a potentiating effect it was probably not sufficient enough for the drugs to be effective in vivo. This may, in part, explain the reduction in clinical cures with the sulphadoxine-pyrimethamine combination in eastern Thailand. © 1986.