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

Zhang R 1 , Suwanarusk R 2 , Malleret B 3 , Cooke BM 4 , Nosten F 5 , Lau YL 6 Show all authors , Dao M 7 , Lim CT 8 , Renia L 2 , Tan KS 1 , Russell B 1

Affiliations 

  • 1 Department of Microbiology, Yong Loo Lin School of Medicine
  • 2 Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Biopolis
  • 3 Department of Microbiology, Yong Loo Lin School of Medicine Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Biopolis
  • 4 Department of Microbiology, Monash University, Melbourne, Victoria, Australia
  • 5 Shoklo Malaria Research Unit, Mae Sot, Tak Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom
  • 6 Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur
  • 7 Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge
  • 8 Biomedical Engineering, National University of Singapore
J Infect Dis, 2016 Jan 1;213(1):100-4.
PMID: 26136472 DOI: 10.1093/infdis/jiv358

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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