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J Infect Dis. 2015 Jun 15;211(12):1977-86. doi: 10.1093/infdis/jiu592. Epub 2014 Oct 28.

Severity of retinopathy parallels the degree of parasite sequestration in the eyes and brains of malawian children with fatal cerebral malaria.

Author information

1
Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool.
2
Liverpool School of Tropical Medicine.
3
Department of Pathology and Laboratory Medicine Department of Ophthalmology and Visual Science, University of British Columbia and Vancouver General Hospital, Canada.
4
Anatomic and Clinical Pathology, Brigham and Women's Hospital Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts.
5
Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool St. Paul's Eye Unit, Royal Liverpool University Hospital, United Kingdom.
6
Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool Malawi-Liverpool-Wellcome Trust Clinical Research Programme.
7
Department of Histopathology.
8
Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing Blantyre Malaria Project, College of Medicine, University of Malawi, Blantyre.
9
Liverpool School of Tropical Medicine Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts.

Abstract

BACKGROUND:

Malarial retinopathy (MR) has diagnostic and prognostic value in children with Plasmodium falciparum cerebral malaria (CM). A clinicopathological correlation between observed retinal changes during life and the degree of sequestration of parasitized red blood cells was investigated in ocular and cerebral vessels at autopsy.

METHODS:

In 18 Malawian children who died from clinically defined CM, we studied the intensity of sequestration and the maturity of sequestered parasites in the retina, in nonretinal ocular tissues, and in the brain.

RESULTS:

Five children with clinically defined CM during life had other causes of death identified at autopsy, no MR, and scanty intracerebral sequestration. Thirteen children had MR and died from CM. MR severity correlated with percentage of microvessels parasitized in the retina, brain, and nonretinal tissues with some neuroectodermal components (all P < .01). In moderate/severe MR cases (n = 8), vascular congestion was more intense (ρ = 0.841; P < .001), sequestered parasites were more mature, and the quantity of extraerythrocytic hemozoin was higher, compared with mild MR cases (n = 5).

CONCLUSIONS:

These data provide a histopathological basis for the known correlation between degrees of retinopathy and cerebral dysfunction in CM. In addition to being a valuable tool for clinical diagnosis, retinal observations give important information about neurovascular pathophysiology in pediatric CM.

KEYWORDS:

Plasmodium falciparum malaria; cerebral malaria; clinicopathological correlation; histopathology; malarial retinopathy; microvascular congestion; neurovasculature; parasite sequestration; pediatric coma; vascular pathology

PMID:
25351204
PMCID:
PMC4442623
DOI:
10.1093/infdis/jiu592
[Indexed for MEDLINE]
Free PMC Article

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