A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609

TitleA Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609
Publication TypeJournal Article
Year of Publication2016
AuthorsZhang, R, Suwanarusk, R, Malleret, B, Cooke, BM, Nosten, F, Lau, YL, Dao, M, Lim, CT, Renia, L, Tan, KS, Russell, B
JournalJ Infect Dis
Volume213
Issue1
Pagination100-4
Date Published01/2016
ISBN Number1537-6613 (Electronic)0022-1899 (Linking)
KeywordsKae609, Malaria, Plasmodium falciparum, Plasmodium vivax, red blood cell, spiroindolones
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.

URLhttp://jid.oxfordjournals.org/content/213/1/100.full.pdf