About 40% of the world population is exposed to malaria, which results in the death of over 2 million people per year in Africa, Latin America, Southern Asia and Oceania. The most severe type of malaria in humans is caused by the protozoan parasite Plasmodium falciparum. Chemotherapy is still one of the main control strategies for this parasite. Many of the antimalarials act by inhibiting the enzyme dihydrofolate reductase (DHFR), resulting in protozoan death. However, the development of drug resistance is reducing the efficiency of antifolates as antimalarials. This phenomenon has been linked to the occurrence of mutations in the dihydrofolate reductase of the parasite. This article includes a preliminary review of some of the features of falciparum malaria, followed by a more extensive review of the dihydrofolate reductase of P. falciparum and the mutations related to antifolate resistance.
malaria; Plasmodium falciparum; dihydrofolate reductase; antifolate resistance