Neurovascular sequestration in paediatric P.falciparum malaria is visible clinically in the retina
- University of Liverpool, United Kingdom
- University of British Columbia, Canada
- Liverpool School of Tropical Medicine, United Kingdom
- Royal Liverpool University Hospital, United Kingdom
- American Society for Clinical Pathology, United States
- University of Malawi College of Medicine, Malawi
- Malawi-Liverpool-Wellcome Trust Research Programme, Malawi
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
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.
Reviewing Editor
- Sara Healy, National Institutes of Health
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.
Version history
- Received: September 28, 2017
- Accepted: March 24, 2018
- Accepted Manuscript published: March 26, 2018 (version 1)
- 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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Neurovascular sequestration in paediatric P.falciparum malaria is visible clinically in the retina
eLife 7:e32208.
https://doi.org/10.7554/eLife.32208
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