title: Severity of retinopathy parallels the degree of parasite sequestration in the eyes and brains of malawian children with fatal cerebral malaria.
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.
authors.affiliation: Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool.
authors.forename: Valentina
authors.initials: V
authors.lastname: Barrera
authors.affiliation: Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool.
authors.forename: Paul Stephenson
authors.initials: PS
authors.lastname: Hiscott
authors.affiliation: Liverpool School of Tropical Medicine.
authors.forename: Alister Gordon
authors.initials: AG
authors.lastname: Craig
authors.affiliation: Department of Pathology and Laboratory Medicine Department of Ophthalmology and Visual Science, University of British Columbia and Vancouver General Hospital, Canada.
authors.forename: Valerie Ann
authors.initials: VA
authors.lastname: White
authors.affiliation: Anatomic and Clinical Pathology, Brigham and Women's Hospital Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Danny Arnold
authors.initials: DA
authors.lastname: Milner
authors.affiliation: 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.
authors.forename: Nicholas Alexander Venton
authors.initials: NA
authors.lastname: Beare
authors.affiliation: Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool Malawi-Liverpool-Wellcome Trust Clinical Research Programme.
authors.forename: Ian James Callum
authors.initials: IJ
authors.lastname: MacCormick
authors.affiliation: Department of Histopathology.
authors.forename: Steve
authors.initials: S
authors.lastname: Kamiza
authors.affiliation: Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing Blantyre Malaria Project, College of Medicine, University of Malawi, Blantyre.
authors.forename: Terrie Ellen
authors.initials: TE
authors.lastname: Taylor
authors.affiliation: Liverpool School of Tropical Medicine Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Malcolm Edward
authors.initials: ME
authors.lastname: Molyneux
authors.affiliation: Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool.
authors.forename: Simon Peter
authors.initials: SP
authors.lastname: Harding
mesh_terms: D001921:Brain / Q000469:parasitology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005128:Eye Diseases / Q000469:parasitology* / Q000473:pathology*; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016779:Malaria, Cerebral / Q000150:complications / Q000473:pathology*; D016778:Malaria, Falciparum / Q000473:pathology*; D008295:Malawi; D008297:Male; D059208:Parasite Load; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D012160:Retina / Q000469:parasitology* / Q000473:pathology*
keywords: Plasmodium falciparum malaria; cerebral malaria; clinicopathological correlation; histopathology; malarial retinopathy; microvascular congestion; neurovasculature; parasite sequestration; pediatric coma; vascular pathology