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

Abstract

AbstractBackgroundMalaria immuno-epidemiological data suggest that two key immunological processes, including anti-parasite and anti-disease immunity, may be implicated in the maintenance of asymptomatic infections. However, in highly exposed persons where the duration of chronic malaria infection could range from a few weeks to several years, the host immunological factors that determine the persistence of asymptomatic parasitemia remain poorly understood. This study therefore aimed to define the association between antibody or cytokine responses with asymptomatic malarial parasitemia amongst highly exposed individuals in Cameroon.MethodsAn initial cross-sectional study was carried out (week 1) and individuals were classified as having asymptomatic Plasmodium parasitemia with no fever (AS), symptomatic Plasmodium parasitemia with an axillary temperature ≥37.5°C (SY) and non-infected (NI) (no Plasmodium parasitemhia and a normal body temperature). Asymptomatic individuals were followed for 10 weeks before being treated with artemisinin-based combination treatment (ACT) and a final sample taken at week 16, 5 weeks after treatment. Those who continued to carry Plasmodium parasites with no measureable fever were defined as having chronic asymptomatic malaria. Antibody levels to P. falciparum schizont extract (SE), merozoite extract (ME), erythrocyte binding antigen-175 (EBA-175) and merozoite surface protein-1 (MSP-1) were quantified by ELISA. The growth inhibitory activities of circulating anti-parasite antibodies were quantified using the 3D7 laboratory strain of P. falciparum and a Sybr Green-I based parasite growth inhibition assay. Plasma levels of 38 cytokines were measured by Luminex technology.ResultsAmongst infected individuals, parasitemia significantly decreased with increased age although this decrease in parasitemia with age was only observed until age 20. Individuals older than 20 years of age had low parasitemia and this remained constant between the ages of 20 and 80. Although there was no difference in the magnitude of the antibody response between AS, SY and NI groups to any of the antigens tested, median levels of antibody against P. falciparum crude extracts and recombinant proteins EBA-175 and MSP-1 were significantly higher in those older than 20 years of age compared with the younger age group as might be expected from lower parasite levels. Parasite densities and P. falciparum clones fluctuated widely over the 10-week follow-up period in individuals with persistent asymptomatic parasitemia but collectively there was no change in the antibody levels over time within this group. Similar to antibody levels, many levels of the cytokines measured were stable over time. However, IL-10 levels decreased after treatment indicating that this cytokine was associated with parasite carriage in asymptomatic individuals. The ratio of IL-10 to pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and lymphotoxin-α (LT-α) ratios were higher in the symptomatic group compared to the asymptomatic individuals but only in the younger (<20 years old) age group.ConclusionTaken together, the above findings indicate that asymptomatic carriage of Plasmodium falciparum in children living in a hyperendemic area occurs independently of antibody responses, but is associated with induction of IL-10.