MOLECULAR-GENETICS OF DRUG-RESISTANCE IN PLASMODIUM-FALCIPARUM MALARIA

Resistance to dihydrofolate reductase inhibitors and resistance to chloroquine have been mapped to single genetic loci in Plasmodium falciparum. Specific point mutations in the dihydrofolate reductase gene confer different degrees of resistance to two dihydrofolate inhibitors, cycloguanil and pyrimethamine, depending on the positions of the mutations and the residues involved. The chloroquine resistance locus has been mapped to a 400 kilobase (kb) segment of chromosome 7 in a P. falciparum cross. Identification and characterization of genes within this segment should lead to an understanding of the rapid drug efflux mechanism responsible for chloroquine resistance*.