Reduced inflammation and increased endothelial activation in children with asymptomatic Plasmodium falciparum parasitemia in a low transmission area

Abstract

Abstract Few studies investigate asymptomatic parasitemia (AP) and researching the mechanism by which these children remain healthy can provide novel information to understand the pathogenesis of Plasmodium falciparum malaria. We hypothesized children with AP to have higher levels of pro-inflammatory cytokines, angiogenic growth factors, and markers of endothelial activation compared to children without parasitemia. Healthy children were recruited from the community as part of a study on cognitive and neurological deficits in children with central nervous system malaria in Kampala, Uganda. Plasma was prepared from blood samples acquired at enrollment and tested using magnetic bead assay. Nested PCR was performed to detect P. falciparum DNA. Of the 211 community children (CC) samples tested, 73 CC had AP and 138 CC without parasitemia. CC with AP had lower levels of pro-inflammatory cytokines and chemokines IFN-γ (p<0.0001), IL-1β (p=0.0001), IL-8 (p=0.0015), MIP-1α (p=0.01), IL-12p70 (p=0.0002), and RANTES (p=0.0001), and higher levels of TNF-α (p=0.05), MIP-1β (p=0.04), and IP-10 (p=0.01) when compared to CC without parasitemia. CC with AP had lower levels of angiogenic growth factors G-CSF (p<0.0001) and FGF-basic (p<0.0001), and higher levels of markers of endothelial activation ICAM-1 (p=0.0007), VCAM-1 (p<0.0001), and VWF (p=0.0006). In this area of low malaria transmission, children with parasitemia have suppression of these pro-inflammatory cytokines, chemokines and angiogenic factors, but an increase in endothelial activation. Endothelial activation may be an early uniform response to P. falciparum, but symptoms may be controlled by ability to suppress the inflammatory response.