Sequestration and microvascular congestion are associated with coma in human cerebral malaria.
The pathogenesis of coma in severe Plasmodium falciparum malaria remains poorly understood. Obstruction of the brain microvasculature because of sequestration of parasitized red blood cells (pRBCs) represents one mechanism that could contribute to coma in cerebral malaria. Quantitative postmortem microscopy of brain sections from Vietnamese adults dying of malaria confirmed that sequestration in the cerebral microvasculature was significantly higher in patients with cerebral malaria (CM; n = 21) than in patients with non-CM (n = 23). Sequestration of pRBCs and CM was also significantly associated with increased microvascular congestion by infected and uninfected erythrocytes. Clinicopathological correlation showed that sequestration and congestion were significantly associated with deeper levels of premortem coma and shorter time to death. Microvascular congestion and sequestration were highly correlated as microscopic findings but were independent predictors of a clinical diagnosis of CM. Increased microvascular congestion accompanies coma in CM, associated with parasite sequestration in the cerebral microvasculature.
Nuffield Department of Clinical Laboratory Sciences, The John Radcliffe Hospital, University of Oxford, United Kingdom.
Mark J
MJ
Ponsford
Isabelle M
IM
Medana
Panote
P
Prapansilp
Tran Tinh
TT
Hien
Sue J
SJ
Lee
Arjen M
AM
Dondorp
Margaret M
MM
Esiri
Nicholas P J
NP
Day
Nicholas J
NJ
White
Gareth D H
GD
Turner
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D001921:Brain / Q000473:pathology; D003128:Coma / Q000473:pathology*; D004912:Erythrocytes / Q000469:parasitology*; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D006940:Hyperemia / Q000473:pathology*; D016779:Malaria, Cerebral / Q000150:complications / Q000473:pathology*; D016778:Malaria, Falciparum / Q000150:complications / Q000473:pathology*; D008297:Male; D008853:Microscopy; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D012720:Severity of Illness Index; D016019:Survival Analysis; D014744:Vietnam