A basis for rapid clearance of circulating ring-stage malaria parasites by the spiroindolone KAE609

Recent clinical trials revealed a surprisingly rapid clearance of red blood cells infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite-infected red blood cells exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite s Na+ efflux pump (ATP4). We further show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically-impaired Plasmodium vivax and P. falciparum infected red blood cells.