Mechanisms of Antimalarial Drug Resistance

Resistance is the inevitable consequence of chemotherapy. The past decade has seen for the first time in generations, a decline in deaths and morbidity from malaria, largely on account of the use of highly effective antimalarials and the widespread coverage of bed nets and other transmission preventative measures. However over the same period the malaria parasite has assembled even more counter measures than ever before to overcome chemotherapy with some parts of the World reporting clinical failures to artemisinin and artemisinin based combination therapy (ACTs), the cornerstone of current control and elimination strategies. With mortality still at ca. 0.5 million per year, mainly in African children under the age of 5 years old, and the emergence of multi-drug resistant parasites resistant to all known antimalarial drug classes, the need for the development of new drugs which circumvent current parasite resistance mechanisms remains an urgent priority. However, a comprehensive knowledge of drug resistance mechanisms is required to support the development of such strategies. Here we review the latest genetic, biochemical and physiological data that underpin current theories of resistance mechanisms to existing antimalarial drugs.