Artemisinin Action and Resistance in Plasmodium falciparum

Abstract

The worldwide use of artemisinin-based combination therapies (ACTs) has contributed in recent years to a substantial reduction in deaths resulting from Plasmodium falciparum malaria. Resistance to artemisinins, however, has emerged in Southeast Asia. Clinically, resistance is defined as a slower rate of parasite clearance in patients treated with an artemisinin derivative or an ACT. These slow clearance rates associate with enhanced survival rates of ring-stage parasites briefly exposed in vitro to dihydroartemisinin. We describe recent progress made in defining the molecular basis of artemisinin resistance, which has identified a primary role for the P. falciparum K13 protein. Using K13 mutations as molecular markers, epidemiological studies are now tracking the emergence and spread of artemisinin resistance. Mechanistic studies suggest potential ways to overcome resistance.

Keywords: Kelch13; artemisinin resistance; malaria.; proteasome; ubiquitination; unfolded protein response.