Plasmodium falciparum artemisinin-resistant K13 mutations confer a sexual-stage transmission advantage that can be overcome with atovaquone-proguanil

Containing the spread of artemisinin (ART)-resistant Plasmodium falciparum will be assisted by improved understanding of its human-to-mosquito transmission. We compared gametocyte dynamics among field isolates containing k13 mutations conferring ART resistance and K13 wild-type parasites. In Pailin, Cambodia, the male to female gametocyte ratio was higher among k13 mutant infections compared to K13 wild-type infections. We also investigated the effects of artesunate and atovaquone-proguanil on the transmissibility of an ART-resistant k13 mutant strain, Cam3.IIR539T, in a volunteer infection study. Gametocyte production was higher after a single dose of artesunate (2 mg/kg) in volunteers infected with ART-resistant compared to ART-sensitive parasites. Despite the presence of gametocytes in volunteers infected with ART-resistant parasites, there was no infection observed in Anopheles stephensi mosquitoes after atovaquone-proguanil treatment. We report transmission determinants of ART-resistant infections that could be advantageous over ART-sensitive infections. Moreover, we show additional benefits of treating ART-resistant infections with atovaquone-proguanil treatment.