Plasmodium falciparum artemisinin-resistant K13 mutations confer a sexual-stage transmission advantage that can be overcome with atovaquone-proguanil
Pava, Z.; Mok, S.; Collins, K. A.; Rebelo, M.; Watts, R. E.; Robinson, G. J.; Wang, C. Y. T.; Mitchell, H.; Lynch, S.; Gower, J.; Webb, L.; McEwan, S.; Odedra, A.; Barber, B.; Marquart, L.; Dixon, M. W. A.; Moehrle, J. J.; Fidock, D. A.; McCarthy, J. S.
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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.
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