Neurovascular sequestration in paediatric P. falciparum malaria is visible clinically in the retina

oleh: Valentina Barrera, Ian James Callum MacCormick, Gabriela Czanner, Paul Stephenson Hiscott, Valerie Ann White, Alister Gordon Craig, Nicholas Alexander Venton Beare, Lucy Hazel Culshaw, Yalin Zheng, Simon Charles Biddolph, Danny Arnold Milner, Steve Kamiza, Malcolm Edward Molyneux, Terrie Ellen Taylor, Simon Peter Harding

Format: Article
Diterbitkan: eLife Sciences Publications Ltd 2018-03-01

Deskripsi

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.