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

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.

• Authors: Andrea L Conroy, Simon J Glover, Michael Hawkes, Laura K Erdman, Karl B Seydel, Terrie E Taylor, Malcolm E Molyneux, Kevin C Kain
• Journal: Critical care medicine (Crit Care Med) Vol. 40 Issue 3 Pg. 952-9 (Mar 2012) ISSN: 1530-0293 [Electronic] United States
• PMID: 22343839 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Angiopoietin-2
• Biomarkers

Topics

• Adult
• Aged
• Angiopoietin-2 (blood)
• Biomarkers (blood)
• Case-Control Studies
• Female
• Humans
• Malaria, Cerebral (blood, complications, mortality)
• Malawi
• Male
• Middle Aged
• Predictive Value of Tests
• Prognosis
• Retinal Diseases (blood, mortality, parasitology)
• Retrospective Studies
• Young Adult