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

Rou Zhang, Rossarin Suwanarusk, Benoit Malleret, Brian M Cooke, Francois H Nosten, Yee Ling Lau, Ming Dao, Chwee Teck Lim, Laurent Renia, Kevin S W Tan, Bruce Russell

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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.
Original languageEnglish
Pages (from-to)100-104
Number of pages5
JournalThe Journal of Infectious Diseases
Issue number1
Publication statusPublished - 2016

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