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Crit Care Med. 2012 Mar;40(3):952-9. doi: 10.1097/CCM.0b013e3182373157.

Angiopoietin-2 levels are associated with retinopathy and predict mortality in Malawian children with cerebral malaria: a retrospective case-control study*.

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  • 1Sandra A Rotman Laboratories, McLaughlin-Rotman Centre for Global Health, University Health Network-Toronto General Hospital, University of Toronto, Toronto, Canada.

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.

Comment in

PMID:
22343839
[PubMed - indexed for MEDLINE]
PMCID:
PMC3284252
Free PMC Article

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