1. Human Biology and Medicine
  2. Neuroscience
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Neurovascular sequestration in paediatric P.falciparum malaria is visible clinically in the retina

  1. Valentina Barrera  Is a corresponding author
  2. Ian JC MacCormick
  3. Gabriela Czanner
  4. Paul Stephenson Hiscott
  5. Valerie Ann White
  6. Alister G Craig
  7. Nicholas Alexander Venton Beare
  8. Lucy Hazel Culshaw
  9. Yalin Zheng
  10. Simon Charles Biddolph
  11. Danny A Milner
  12. Steve Kamiza
  13. Malcolm E Molyneux
  14. Terrie E Taylor
  15. Simon Peter Harding
  1. University of Liverpool, United Kingdom
  2. University of British Columbia, Canada
  3. Liverpool School of Tropical Medicine, United Kingdom
  4. Royal Liverpool University Hospital, United Kingdom
  5. American Society for Clinical Pathology, United States
  6. University of Malawi College of Medicine, Malawi
  7. Malawi-Liverpool-Wellcome Trust Research Programme, Malawi
Research Article
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Cite this article as: eLife 2018;7:e32208 doi: 10.7554/eLife.32208

Abstract

Retinal vessel changes and retinal whitening, distinctive features of malarial retinopathy, can be directly observed during routine eye examination in children with P.falciparum cerebral malaria. We investigated their clinical significance and underlying mechanisms through linked clinical, clinicopathological and image analysis studies. Orange vessels and severe foveal whitening (clinical examination, n=817, OR, 95% CI: 2.90, 1.96-4.30; 3.4, 1.8-6.3, both p<0.001), and arteriolar involvement by intravascular filling defects (angiographic image analysis, n=260, 2.81, 1.17-6.72, p<0.02) were strongly associated with death. Orange vessels had dense sequestration of late stage parasitised red cells (histopathology, n=29; sensitivity 0.97, specificity 0.89) involving 360° of the lumen circumference, with altered protein expression in blood-retinal barrier cells and marked loss/disruption of pericytes. Retinal whitening was topographically associated with tissue response to hypoxia. Severe neurovascular sequestration is visible at the bedside and is a marker of severe disease useful for diagnosis and management.

Article and author information

Author details

  1. Valentina Barrera

    Department of Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom
    For correspondence
    v.barrera@liverpool.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0515-5901
  2. Ian JC MacCormick

    Department of Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Gabriela Czanner

    Department of Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Paul Stephenson Hiscott

    Department of Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Valerie Ann White

    Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Alister G Craig

    Liverpool School of Tropical Medicine, Liverpool, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Nicholas Alexander Venton Beare

    Department of Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Lucy Hazel Culshaw

    Department of Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Yalin Zheng

    Department of Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Simon Charles Biddolph

    National Specialist Ophthalmic Pathology Service, Royal Liverpool University Hospital, Liverpool, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Danny A Milner

    Center for Global Health, American Society for Clinical Pathology, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Steve Kamiza

    Department of Histopathology, University of Malawi College of Medicine, Blantyre, Malawi
    Competing interests
    The authors declare that no competing interests exist.
  13. Malcolm E Molyneux

    Malawi-Liverpool-Wellcome Trust Research Programme, Blantyre, Malawi
    Competing interests
    The authors declare that no competing interests exist.
  14. Terrie E Taylor

    Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi
    Competing interests
    The authors declare that no competing interests exist.
  15. Simon Peter Harding

    Department of Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

Funding

Wellcome (#092668/Z/10/Z)

  • Simon Peter Harding

NIH Clinical Center (#5R01AI034969-11)

  • Terrie E Taylor

Wellcome (#074125)

  • Malcolm E Molyneux

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The core and specific studies all received approval from the Research Ethics Committee at the University of Malawi College of Medicine P. 11/07/593, Michigan State University and the Royal Liverpool and Broadgreen University Hospital Trust n. 3690; research was performed in accordance with the Declaration of Helsinki. Written consent for the clinical eye examination was sought in English or in the language of the parent/guardian who gave permission on the patient's behalf. If a patient died, additional informed written consent for autopsy was sought from the parent/guardian.

Reviewing Editor

  1. Sara Healy, National Institutes of Health

Publication history

  1. Received: September 28, 2017
  2. Accepted: March 24, 2018
  3. Accepted Manuscript published: March 26, 2018 (version 1)
  4. Version of Record published: April 13, 2018 (version 2)

Copyright

© 2018, Barrera et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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