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Children with retinopathy-negative cerebral malaria: a pathophysiologic puzzle.

ABSTRACT: BACKGROUND:Cerebral malaria, defined as otherwise unexplained coma in a patient with circulating parasitemia, is a common disease in the developing world. The clinical diagnosis lacks specificity and children with other underlying causes of coma might be misdiagnosed as having cerebral malaria. The presence of malarial retinopathy can be used to differentiate children whose comas are caused by Plasmodium falciparum and its attendant pathophysiologies from those with other reasons for their abnormal mental status. Children with cerebral malaria who lack malarial retinopathy have not previously been described. METHODS:All patients admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi, during a 12-month period with a clinical diagnosis of cerebral malaria were evaluated for the presence of malarial retinopathy. Thirty-two patients lacked retinopathy findings. Clinical, laboratory, and radiologic information data were collected. RESULTS:Thirty-two cases of retinopathy-negative cerebral malaria are presented. CONCLUSIONS:Children with retinopathy-negative cerebral malaria share a common clinical phenotype with lower rates of mortality compared with those who have malarial retinopathy. There are at least 4 possible pathophysiologic explanations for this common condition.

SUBMITTER: Postels DG

PROVIDER: S-EPMC3196647 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Children with retinopathy-negative cerebral malaria: a pathophysiologic puzzle.

Postels Douglas G DG Birbeck Gretchen L GL

The Pediatric infectious disease journal 20111101 11

<h4>Background</h4>Cerebral malaria, defined as otherwise unexplained coma in a patient with circulating parasitemia, is a common disease in the developing world. The clinical diagnosis lacks specificity and children with other underlying causes of coma might be misdiagnosed as having cerebral malaria. The presence of malarial retinopathy can be used to differentiate children whose comas are caused by Plasmodium falciparum and its attendant pathophysiologies from those with other reasons for the ...[more]

PMID: 21694660

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Project description: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.

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Children with retinopathy-negative cerebral malaria: a pathophysiologic puzzle.

Publications

Children with retinopathy-negative cerebral malaria: a pathophysiologic puzzle.

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