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• W3040221009 abstract "Objectives: Evaluate the relationship between endothelial activation, malaria complications, and long-term cognitive outcomes in severe malaria survivors. Design: Prospectively cohort study of children with cerebral malaria, severe malarial anemia, or community children. Setting: Mulago National Referral Hospital in Kampala, Uganda. Subjects: Children 18 months to 12 years old with severe malaria (cerebral malaria, n = 253 or severe malarial anemia, n = 211) or community children ( n = 206) were followed for 24 months. Interventions: None. Measurements and Main Results: Children underwent neurocognitive evaluation at enrollment (community children) or a week following hospital discharge (severe malaria) and 6, 12, and 24 months follow-up. Endothelial activation was assessed at admission on plasma samples (von Willebrand factor, angiopoietin-1 and angiopoietin-2, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-Selectin, and P-Selectin). False discovery rate was used to adjust for multiple comparisons. Severe malaria was associated with widespread endothelial activation compared with community children ( p < 0.0001 for all markers). Acute kidney injury was independently associated with changes in von Willebrand factor, soluble intercellular adhesion molecule-1, soluble E-Selectin, P-Selectin, and angiopoietin-2 ( p < 0.0001 for all). A log 10 increase in angiopoietin-2 was associated with lower cognitive z scores across age groups (children < 5, β –0.42, 95% CI, –0.69 to –0.15, p = 0.002; children ≥ 5, β –0.39, 95% CI, –0.67 to –0.11, p = 0.007) independent of disease severity (coma, number of seizures, acute kidney injury) and sociodemographic factors. Angiopoietin-2 was associated with hemolysis (lactate dehydrogenase, total bilirubin) and inflammation (tumor necrosis factor-α, interleukin-10). In children with cerebral malaria who had a lumbar puncture performed, angiopoietin-2 was associated with blood-brain barrier dysfunction, and markers of neuroinflammation and injury in the cerebrospinal fluid (tumor necrosis factor-α, kynurenic acid, tau). Conclusions: These data support angiopoietin-2 as a measure of disease severity and a risk factor for long-term cognitive injury in children with severe malaria." @default.
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• W3040221009 date "2020-06-30" @default.
• W3040221009 modified "2023-10-10" @default.
• W3040221009 title "Endothelial Activation, Acute Kidney Injury, and Cognitive Impairment in Pediatric Severe Malaria" @default.
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• W3040221009 doi "https://doi.org/10.1097/ccm.0000000000004469" @default.
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