Background: Plasmodium falciparum erythrocyte membrane protein 1(PfEMP1) is a family of variant surface antigens\n(VSA) that mediate the adhesion of parasite infected erythrocytes to capillary endothelial cells within host tissues. Opinion\nis divided over the role of PfEMP1 in the widespread endothelial activation associated with severe malaria. In a previous\nstudy we found evidence for differential associations between defined VSA subsets and specific syndromes of severe\nmalaria: group A-like PfEMP1 expression and the ââ?¬Å?rosettingââ?¬Â phenotype were associated with impaired consciousness and\nrespiratory distress, respectively. This study explores the involvement of widespread endothelial activation in these associations.\nMethods: We used plasma angiopoietin-2 as a marker of widespread endothelial activation. Using logistic regression analysis,\nwe explored the relationships between plasma angiopoietin-2 levels, parasite VSA expression and the two syndromes of\nsevere malaria, impaired consciousness and respiratory distress.\nResults: Plasma angiopoietin-2 was associated with both syndromes. The rosetting phenotype did not show an independent\nassociation with respiratory distress when adjusted for angiopoietin-2, consistent with a single pathogenic mechanism\ninvolving widespread endothelial activation. In contrast, group A-like PfEMP1 expression and angiopoietin-2 maintained\nindependent associations with impaired consciousness when adjusted for each other.\nConclusion: The results are consistent with multiple pathogenic mechanisms leading to severe malaria and heterogeneity\nin the pathophysiology of impaired consciousness. The observed association between group A-like PfEMP1 and impaired\nconsciousness does not appear to involve widespread endothelial activation
Loading....