Evidence of Endothelial Activation in Asymptomatic Plasmodium falciparum Parasitemia and Effect of Blood Group on Levels of von Willebrand Factor in Malaria.

BACKGROUND Endothelial activation may contribute to development of severe disease from Plasmodium falciparum infection, but optimal markers of endothelial activation in severe malaria, the extent of endothelial activation in asymptomatic infection, and the effect of blood group O on endothelial activation have not been defined. METHODS Serum levels of 3 markers of endothelial activation-von Willebrand factor (VWF), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1)-were assessed in Ugandan children with cerebral malaria (CM) (n = 86), children with uncomplicated malaria (UM) (n = 81), and community children (CC) (n = 90). RESULTS Serum VWF, sICAM-1, and sVCAM-1 levels were all elevated in asymptomatic community children with microscopy-confirmed parasitemia when compared with children without parasitemia by microscopy or polymerase chain reaction (all, P ≤ .05). Levels of VWF, sICAM-1, and sVCAM-1 were higher in children with UM than in CC (all, P < 0.001), but only VWF levels effectively distinguished CM from UM (P < 0.001), a finding confirmed by receiver operating characteristic analyses (area under the curve = 0.67; 95% confidence interval, .58-.75). Von Willebrand factor levels were lower in children with blood group O versus non-O blood groups across the disease spectrum, but VWF levels remained higher in CM versus UM, even after controlling for blood group. CONCLUSIONS Endothelial activation, as assessed by serum levels of VWF, sICAM-1, and sVCAM-1, occurs even in subclinical P. falciparum parasitemia. Von Willebrand factor levels increase with greater malaria disease severity. Blood group O is associated with lower VWF levels, but presence of blood group O alone does not explain the higher VWF levels seen in children with CM.