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Angiopoietin-2 levels are associated with retinopathy and predict mortality in Malawian children with cerebral malaria

Conroy, Andrea L., Glover, Simon J., Hawkes, Michael, Erdman, Laura K., Seydel, Karl B., Taylor, Terrie E., Molyneux, Malcolm E and Kain, Kevin C. (2012) 'Angiopoietin-2 levels are associated with retinopathy and predict mortality in Malawian children with cerebral malaria'. Critical Care Medicine, Vol 40, Issue 3, pp. 952-959.

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Abstract

Objective: To investigate the relationship among the angiopoietin–Tie-2 system, retinopathy, and mortality in children with cerebral malaria.

Design: A case–control study of retinopathy-positive vs. retinopathy-negative children with clinically defined cerebral malaria.

Setting: Queen Elizabeth Central Hospital in Blantyre, Malawi.

Subjects: One hundred fifty-five children presenting with severe malaria and meeting a strict definition of clinical cerebral malaria (Blantyre Coma Score <=2, Plasmodium falciparum parasitemia, no other identifiable cause for coma) were included in the study.

Interventions: None.

Measurements and Main Results: Clinical and laboratory parameters were recorded at admission and funduscopic examinations were performed. Admission levels of angiopoietin-1, angiopoietin-2, and a soluble version of their cognate receptor were measured by enzyme-linked immunosorbent assay. We show that angiopoietin-1 levels are decreased and angiopoietin-2 and soluble Tie-2 levels are increased in children with cerebral malaria who had retinopathy compared with those who did not. Angiopoietin-2 and soluble Tie-2 were independent predictors of retinopathy (adjusted odds ratio [95% CI], angiopoietin-2, 4.3 [1.3–14.6], p = .019; soluble Tie-2, 9.7 [2.1–45.8], p = .004). Angiopoietin-2 and soluble Tie-2 were positively correlated with the number of hemorrhages, the severity or retinal whitening, and the extent of capillary whitening observed on funduscopic examination (p < .05 after adjustment for multiple comparisons). Angiopoietin-2 and soluble Tie-2 levels were elevated in children with cerebral malaria who subsequently died and angiopoetin-2 was an independent predictor of death (adjusted odds ratio: 3.9 [1.2–12.7], p = .024). When combined with clinical parameters, angiopoetin-2 improved prediction of mortality using logistic regression models and classification trees.

Conclusions: These results provide insights into mechanisms of endothelial activation in cerebral malaria and indicate that the angiopoietin–Tie-2 axis is associated with retinopathy and mortality in pediatric cerebral malaria.

Item Type: Article
Subjects: QS Anatomy > Histology > QS 532.5.E7 Epithelium
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WL Nervous System > WL 20 Research (General)
WS Pediatrics > Diseases of Children and Adolescents > By System > WS 340 Nervous system
WW Ophthalmology > Eye Structures and their Diseases > WW 270 Retina
Faculty: Department: Groups (2002 - 2012) > Clinical Group
Digital Object Identifer (DOI): https://doi.org/10.1097/CCM.0b013e3182373157
Depositing User: Lynn Roberts-Maloney
Date Deposited: 15 Dec 2014 11:35
Last Modified: 06 Feb 2018 13:08
URI: https://archive.lstmed.ac.uk/id/eprint/4671

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