Antibodies and Risk of Clinical Malaria in an Area of Low Malaria Transmission in Western Kenya

Abstract

Children and adults are at risk for clinical malaria in areas of low malaria transmission. Antibody or antibody effector mechanism correlates of immunity in these areas, and their differences by age, are poorly characterized. To address this research gap, we evaluated the relationship of Plasmodium falciparum-specific antibody levels and merozoite opsonic phagocytosis to the risk of clinical malaria in a case-control study nested within a cohort of 5,753 individuals in a Kenyan highland area with low malaria transmission. Plasma samples were collected in 2007, and individuals evaluated over 10-year follow-up for risk of clinical malaria. Individuals who developed clinical malaria (cases) were matched by village and age to those who did not (controls). We evaluated total IgG, IgG1, IgG3, IgA, and IgM antibodies to Plasmodium falciparum antigens by cytometric bead assay, and opsonic phagocytosis (OP) by flow cytometry. Antibody and OP levels were compared to risk of clinical malaria in three age groups (< 5 years, 5-14 years and  15 years), adjusting for multiple markers of malaria exposure. Antibody and OP levels increased with age. In children < 5 years old, higher levels of total IgG and IgG1 to the P. falciparum antigen GLURP-R2 and total IgG and IgG3 to the P. falciparum antigen MSP-2 were associated with reduced risk of clinical malaria, but OP levels were not associated with risk of clinical malaria. Conversely, in children 5-14 years old and individuals ≥ 15 years old, higher antibody levels to multiple antigens as well as higher OP levels were associated with increased risk of clinical malaria. In this low transmission area, antibody and OP levels in individuals ≥ 5 years old may serve as markers of malaria risk that add to known risk markers in this area such as insecticide-treated net use, elevation and proximity to forest.