Asymptomatic carriage of Plasmodium falciparum in children living a hyperendemic area occurs independently of IgG responses but is associated with induction of IL-10

BackgroundAsymptomatic carriage of infected red blood cells (iRBCs) can be prevalent in communities regardless of transmission patterns and can occur with infection of different Plasmodium species. Clinical immunity dampens the inflammatory responses leading to disease symptoms in malaria. The aim of this study was to define the immunological correlates of asymptomatic carriage of P. falciparum in a highly exposed population. Methods142 asymptomatic Plasmodium-infected individuals greater than 2 years of age without fever (body temperature <37.5{degrees}C) were followed weekly for 10 weeks before being treated with artemisinin-based combination treatment (ACT). Plasma levels of 38 cytokines were measured at baseline by Luminex and the quantity and growth inhibitory activities of circulating parasite-reactive antibodies measured. The Plasmodium antigen tested included P. falciparum merozoite extract (ME) and schizont extract (SE), and the recombinant proteins Erythrocyte binding antigen 175 (EBA-175) and merozoite surface protein 1 (MSP-119). ResultsMedian levels of IgG against P. falciparum EBA-175 and MSP-119 at baseline were significantly higher in those older than 20 years of age compared with the younger age group and appeared to correlate with better parasite control. Amongst all participants there were no discernible changes in IgG levels over time. Parasite density was higher in the younger age group and associated with IL-10, TNF- and MCP-1 levels. A balanced IL-10:TNF- ratio was associated with asymptomatic malaria regardless of age, and balanced ratios of IL-10/TNF- and IL-10/IFN-{gamma} were the only significant correlate of maintenance of asymptomatic malaria over the course of the study in individuals 20 years of age and younger. ConclusionThe above findings indicate that asymptomatic carriage of P. falciparum in children living in a hyperendemic area occurs independently of IgG but is associated with a balanced inflammatory cytokine ratio.