Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria

Abstract

Malaria has devastating consequences: it strikes over 250 million people worldwide and kills approximately 1 million people each year, many of whom are children under 5 years of age. Malaria can be prevented by interventions focused on breaking the cycle of transmission, either by eliminating the mosquito (through the use of insecticides) or preventing bites (through the use of insecticide-treated bed nets). It can also be treated through the use of antimalarial drugs. Drug resistance, however, remains the biggest threat to current drug efficacy. The former mainstays of antimalarial chemotherapy, chloroquine and sulfadoxine–pyrimethamine, have been rendered ineffective for the treatment of Plasmodium falciparum malaria by the emergence and spread of drug-resistant parasites. Almost all malaria-endemic regions have switched to artemisinin (ART)-based combination therapies (ACTs) for the first-line treatment of P. falciparum malaria. ACTs combine an ART semisynthetic derivative, which has a short half-life, with a longer-lasting partner drug. This results in sustained antimalarial pressure after the plasma concentrations of the ART derivatives have fallen below therapeutic levels ACTs are discussed in terms of their modes of action and pharmacokinetic properties and the proposed mechanisms of resistance to them. We summarize several therapeutic strategies that might decrease the emergence of drug resistance and present a perspective on the current ACT-based efforts to reduce the burden of malaria.