Elevated Levels of the Endothelial Molecules ICAM-1, VEGF-A, and VEGFR2 in Microscopic Asymptomatic Malaria

Background: In malaria, clinical disease has been associated with increased levels of endothelial activation due to the sequestration of infected erythrocytes. However, the levels and impact of endothelial activation and pro-Angiogenic molecules such as vascular endothelial growth factor (VEGF)-A and its receptor vascular endothelial growth factor receptor 2 (VEGFR2) in asymptomatic malaria have not been well characterized. Methods: Blood samples were obtained from community children for malaria diagnosis using microscopy and polymerase chain reaction. A multiplex immunoassay was used to determine the levels of intracellular adhesion molecule (ICAM)-1, vascular endothelial growth factor (VEGF)-A, and VEGFR2 in the plasma of children with microscopic or submicroscopic asymptomatic parasitemia and compared with levels in uninfected controls. Results: Levels of ICAM-1, VEGF-A, and VEGFR2 were significantly increased in children with microscopic asymptomatic parasitemia compared with uninfected controls. Also, levels of VEGF-A were found to be inversely associated with age. Additionally, a receiver operating characteristic analysis revealed that plasma levels of ICAM-1 (area under the curve [AUC], 0.72) showed a moderate potential in discriminating between children with microscopic malaria from uninfected controls when compared with VEGF-A (AUC, 0.67) and VEGFR2 (AUC, 0.69). Conclusions: These data imply that endothelial activation and pro-Angiogenic growth factors could be one of the early host responders during microscopic asymptomatic malaria and may play a significant role in disease pathogenesis.