Chemotherapy and prevention of drug-resistant malaria.

Abstract

Drug-resistant falciparum and vivax malaria will continue to be an increasing problem. The incidence of drug-resistant malaria has been increasing at a rate that exceeds new drug development. Plasmodium falciparum has rapidly developed resistance to new synthetic antimalarials, including mefloquine and halofantrine. P. vivax malaria resistant to chloroquine and primaquine is now widespread in parts of Oceania; the optimal therapy for this infection is unknown. At present, a combination of qinghaosu derivatives and mefloquine appears to be the most active drug regimen against multidrug-resistant falciparum malaria from Southeast Asia. However, qinghaosu compounds are not yet licensed and widely available. The capacity of P. falciparum to rapidly develop drug resistance and the growing evidence that other plasmodia can evolve resistance suggests that within the next 10 years, we face the real prospect of untreatable malaria. Ultimately, control of malaria may require more creative approaches than additional inhibitory drugs. These might include: the identification of biochemical pathways unique to the parasite (such as drug efflux and heme polymerase), making it possible to design new classes of antimalarial agents that are selectively toxic to the parasite; methods to block parasite development in the mosquito vector; and multistage vaccines against both asexual and sexual stages in order to block both the pathophysiology and transmission of disease.