Plasmodium falciparum: mefloquine resistance produced in vitro

Camp and Smith strains of the human malaria parasite Plasmodium falciparum became resistant to mefloquine after continuous cultivation in the presence of the drug. The 50% inhibitory dose (ID(50)) values for mefloquine, as assessed by [(3)H]hypoxanthine incorporation, were found to have increased 4-fold, from 3 mug/l to 12 mug/l. The ID(50) values obtained by morphological examination of the cultures increased 10-fold. Resistance was stable in both strains either when grown in a drug-free medium or when kept frozen in liquid nitrogen. The mefloquine-resistant Camp strain remained sensitive to chloroquine and amodiaquine, and became slightly more resistant to quinine; there was increased sensitivity to pyrimethamine. The mefloquine-resistant Smith strain remained sensitive to amodiaquine and resistant to pyrimethamine; there was increased resistance to quinine, and an increase in sensitivity to chloroquine.