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- Title
A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609.
- Authors
Rou Zhang; Suwanarusk, Rossarin; Malleret, Benoit; Cooke, Brian M.; Nosten, Francois; Yee-Ling Lau; Ming Dao; Chwee Teck Lim; Renia, Laurent; Wei Tan, Kevin Shyong; Russell, Bruce; Zhang, Rou; Lau, Yee-Ling; Dao, Ming; Lim, Chwee Teck; Tan, Kevin Shyong Wei
- Abstract
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.
- Subjects
PLASMODIUM vivax; ANTIMALARIALS; MALARIA prevention; PLASMODIUM falciparum; OSMOTIC pressure
- Publication
Journal of Infectious Diseases, 2016, Vol 213, Issue 1, p100
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiv358