TY - JOUR
T1 - Neurovascular sequestration in paediatric P.falciparum malaria is visible clinically in the retina
AU - Barrera, Valentina
AU - MacCormick, Ian James Callum
AU - Czanner, Gabriela
AU - Hiscott, Paul Stephenson
AU - White, Valerie Ann
AU - Craig, Alister
AU - Beare, Nicholas Alexander Venton
AU - Culshaw, Lucy Hazel
AU - Zheng, Yalin
AU - Biddolph, Simon Charles
AU - Milner, Danny Arnold
AU - Kamiza, Steve
AU - Molyneux, Malcolm Edward
AU - Taylor, Terrie Ellen
AU - Harding, Simon Peter
PY - 2018/3/26
Y1 - 2018/3/26
N2 - Retinal vessel changes and retinal whitening, distinctive features of malarial retinopathy, can be directly observed during routine eye examination in children with 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. [Abstract copyright: © 2018, Barrera et al.]
AB - Retinal vessel changes and retinal whitening, distinctive features of malarial retinopathy, can be directly observed during routine eye examination in children with 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. [Abstract copyright: © 2018, Barrera et al.]
U2 - 10.7554/elife.32208
DO - 10.7554/elife.32208
M3 - Article
SN - 2050-084X
VL - 7
SP - 32208
JO - eLife
JF - eLife
M1 - e32208
ER -
