Artemisinin resistance phenotypes and K13 inheritance in a <i>Plasmodium falciparum</i> cross and <i>Aotus</i> model

Abstract

Significance Artemisinin-based combination therapies (ACTs) are first-line antimalarial therapies used worldwide. The artemisinin drug (ART) component clears the bulk of infection rapidly, but small numbers of persistent parasites must be removed by the partner drug. Longer parasite clearance t 1/2 values have been associated with a Kelch-propeller mutation (K13 C580Y), raising concerns of increased ART resistance. We investigated effects of C580Y by using a Plasmodium falciparum cross and a monkey malaria model. Following three standard doses of ART, infections with or without the C580Y mutation cleared to microscopically undetectable levels, as in humans; however, frequent recrudescences occurred with both types of infection. These results emphasize the importance of effective partner drugs to kill the parasites that persist through the ART component of ACT.