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Simon J. Glover, Simon P. Harding, Paul Pensulo, Alice Muiruri, Ashley Mpakiza, Malcolm E. Molyneux, Terrie E. Taylor, Nicholas A. Beare; Marked And Continuous Leaking, A Retinal Sign Associated With Fatality In Cerebral Malaria. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4402.
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To study the integrity of the retinal circulation in children with malarial coma. The retina and its microvasculature are components of the central nervous system that can be observed directly and sequentially during an episode of cerebral malaria (CM). Sequestration - the adherence of parasitized red blood cells to blood vessel walls - is thought to be a central phenomenon in CM.
During five malaria high-transmission seasons (January to June, 2006-2010) we performed fundus fluorescein angiograms within 6 hours of admission on children with a clinical diagnosis of CM admitted to a pediatric research ward in Blantyre, Malawi. The procedure was subject to the informed consent of parents in their own language. Angiography was repeated if a child remained unconscious for 24 hours.
We studied 157 patients. 12 patients developed fluorescein leakage with the dye collecting in densely hyperfluorescent lesions. These ranged in size from ¼ disc area to more than 10 disc areas. This appearance has not previously been reported in cerebral malaria; we have termed it marked and continuous leaking (MCL). All of the 12 patients with MCL of fluorescein died, most within 6 hours. Of 145 patients without MCL, 17 died (11.7%), (p< 0.001). In areas affected by MCL there were ophthalmoscopically visible collections of retinal fluid, with a variable hemorrhagic component, causing marked thickening and elevation of the affected areas. In 2 patients with MCL who had angiograms at 24 hours after admission, similar leakage was still evident. In cases with MCL in whom further ophthalmoscopy was possible prior to death, the size and extent of the retinal thickening increased.
In some children with fatal CM, fluorescein angiography demonstrates zones of extensive breakdown of the blood retina barrier not previously identified. The pattern of leakage seen in MCL is strongly associated with fatal outcome. The finding warrants further study to shed light on the fatal processes in CM and to explore potential therapeutic pathways.
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