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.