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Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite-infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite's sodium efflux pump (adenosine triphosphate 4). We also show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically impaired Plasmodium vivax- and Plasmodium falciparum-infected RBCs.

Original publication

DOI

10.1093/infdis/jiv358

Type

Journal article

Journal

J Infect Dis

Publication Date

01/01/2016

Volume

213

Pages

100 - 104

Keywords

KAE609, Plasmodium falciparum, Plasmodium vivax, malaria, red blood cell, spiroindolones, Antimalarials, Erythrocytes, Humans, Indoles, Malaria, Falciparum, Plasmodium falciparum, Plasmodium vivax, Spiro Compounds