New prospects for the treatment of malaria

This update focuses on drugs for both uncomplicated and severe falciparum malaria. Chloroquine, long the mainstay of therapy, is no longer reliable because of widespread resistance, but is still attractive because of its very low cost. The following strategies for the future use of 4-aminoquinolines in uncomplicated malaria are discussed: the use of other existing 4-aminoquinolines such as amodiaquine, drug-induced reversal of chloroquine resistance, and the development of new 4-aminoquinolines with activity against resistant isolates. Pyrim- ethamine-sulfadoxine is now the drug of first-choice in much of Africa, but resistance to this antifolate combination is expected to become clinically apparent within the next five years. Research into the utility of novel antifolate combinations is described. Mefloquine and halofantrine are drugs which are extensively used in Southeast Asia, but are too expensive for general use in most African countries. The possible roles for artemisinine derivatives (alone and in combination with either mefloquine or benflumitol), pyronaridine and atovaquone-proguanil are described. The absolute importance of drug cost as a determinant of its utility in poorer countries is emphasised.