Artemisinin-resistant Plasmodium falciparum Cambodian clinical isolates infect diverse vectors of Southeast Asia and Africa

Artemisinin-resistant Plasmodium falciparum parasites are rapidly spreading in Southeast Asia, yet very little is known about their transmission. This knowledge gap, and the possibility of their future spread to sub-Saharan Africa, endangers global efforts to control malaria. Studies on the population genetic structure of Plasmodium falciparum isolates from Cambodia revealed drug-resistant parasites that fell into highly structured groups, as distinct from each other as from African parasite isolates. The discovery of Kelch13-propeller polymorphism, a new marker for artemisinin resistance, helped to further resolve these parasite populations. To investigate the transmission dynamics of these parasites, we performed membrane feeding assays with Cambodian clinical isolates from several distinct parasite populations recently shown to be artemisinin resistant in patients and in vitro, to infect native and non-native mosquito vectors. We found that that six artemisinin-resistant and three artemisinin-sensitive isolates successfully infected two Southeast Asian vectors, Anopheles dirus and An. minimus, as well as the major African vector, An. coluzzii, and also produced human-infective sporozoites. We have also collected an extremely diverse set of anophelines, more than 25 species, from six sites in Cambodia and have seen P.f. infections in more than 5 local species. The ability of artemisinin-resistant parasites to infect highly diverse Anopheles species may explain their rapid and extensive spread in Southeast Asia and further challenge regional efforts to contain and eliminate them.