Point mutations and pyrimethamine resistance in Plasmodium falciparum

Pyrimethamine was first introduced as a prophylactic antimalarial in 1952, with the advantages of low toxicity and freedom from side-effects. As early as the mid-1950s, parasite resistance to this compound had been reported from several areas, and it has since become widespread on all continents where malaria is found. Although it is still used for the suppression of infection, predominantly in conjunction with sulphone or sulphonamide drugs, even these combinations are now useless in many areas. Pyrimethamine resistance is less important globally than resistance to the major curative drug chloroquine, but it has long tantalized molecular parasitologists because pyrimethamine belongs to the only class of antimalarials for which the target molecule is unambiguously known.