Volume 13 Supplement 1

Challenges in malaria research: Core science and innovation

Open Access

Therapeutic disruption of Plasmodium vivax infected red cell deformability

  • Rou Zhang1,
  • Wenn-Chyau Lee2,
  • Benoit Malleret1, 3,
  • Rossarin Suwanarusk3,
  • Ming Dao6,
  • Cindy Chu4, 5,
  • Chwee Teck Lim7,
  • Laurent Renia3,
  • Francois Nosten4, 5 and
  • Bruce Russell1
Malaria Journal201413(Suppl 1):O25

https://doi.org/10.1186/1475-2875-13-S1-O25

Published: 22 September 2014

Background

Chloroquine (CQ) and artesunate (AS) are widely used as blood schizontocides in P. vivax treatment. Recent clinical observations show late stage parasites are cleared more rapidly than expected post treatment. As the high deformability of P. vivax facilitates its escaping from the splenic clearance, we hypothesize that CQ and AS directly affect the P. vivax infected red blood cells (iRBCs) rigidity. As a consequence, parasites are rapidly cleared from the blood circulation.

Materials and methods

P. vivax isolates from Thailand were pulse incubated with AS, CQ and a spiroindolone (NITD609). Morphological changes and rosetting frequency were assessed by sub vital staining. The micropipette aspiration technique was the used to quantify the cell membrane shear modulus. Microfluidics were used to study the in vitro iRBCs behaviour after drug treatment.

Results

While CQ and AS did not directly affect iRBC shear modulus, it significantly enhanced rosetting frequency and consequently the rigidity of rosetted iRBCs (the attachment of a single red cell results in a significant increase in shear modulus of the iRBC). NITD609 directly affected the iRBC rigidity. A microfluidic model of the spleen shows that P. vivax iRBCs with a higher rigidity are removed from flow. This study also show that normocytes that rosette with P. vivax iRBCs; form strong attachments (~500pN) that withstand a range of physiological shear stresses.

Conclusions

In addition to providing new and important baseline biomechanical data on P. vivax rosettes; this ex vivo study also provides a possible explanation for the clinically observed disappearance of P. vivax parasites soon after treatment.

Authors’ Affiliations

(1)
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore
(2)
Department of Parasitology, Faculty of Medicine, University of Malaya
(3)
Singapore Immunology Network (SIgN), A*STAR
(4)
Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford
(5)
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University
(6)
Department of Materials Science and Engineering, Massachusetts Institute of Technology
(7)
Department of Biomedical Engineering Faculty of Engineering, National University of Singapore

Copyright

© Zhang et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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