Chemotherapy of malaria: a battle against all odds?

The most important treatment of malaria to date is chemotherapy using a number of different natural and synthetic drugs. Antifolates, such as pyrimethamine, inhibit the parasite's dihydrofolatereductase, whereas the aminoquinolines, such as chloroquine, have the digestive vacuole as their major site of action. The use of these drugs in chemotherapy of malaria infections is strongly hampered by widespread resistance and in this review current knowledge on the molecular mechanisms of resistance is discussed. Finally, new antimalarial drugs and treatment strategies are considered which may offer new possibilities for the treatment of malaria resistant to the drugs currently in use.