ANTIMALARIAL CHEMOTHERAPY IN THE AGE OF DRUG-RESISTANCE

The incidence of drug-resistant malaria continues to increase worldwide at a rate that exceeds new drug development. Plasmodium falciparum has rapidly developed resistance to new synthetic antimalarials, including mefloquine and halofantrine, forcing a tenuous reliance on age-old drugs such as quinine and qinghaosu (artemisinin). At present, a combination of qinghaosu derivatives and mefloquine appear to be the most active drug regimen against multi-drug-resistant P. falciparum malaria from Southeast Asia. However, qinghaosu compounds are neither licensed nor are they widely available. In addition, Plasmodium vivax resistance to chloroquine and primaquine is now widespread in parts of Oceania; the optimal alternative therapy for this infection is unknown. Fortunately, new insights have recently been gained into the mechanism of chloroquine action and chloroquine resistance that may aid in the design of new classes of anti-malaria agents.