Microscopic and Submicroscopic Asymptomatic Plasmodium falciparum Infections in Ghanaian Children and Protection against Febrile Malaria

Naturally acquired immunity to malaria is thought to be nonsterile and sustained by persistence of low-level parasitemia. This study assessed the association between baseline microscopic and submicroscopic asymptomatic infections and antimalarial antibody levels and whether these parasitemia modify protective associations between antibody levels and malaria in Ghanaian children. Healthy children ( = 973, aged 0.5 to 12 years) were recruited into a 50-week longitudinal malaria cohort study from January 2016 to January 2017. Baseline asymptomatic parasitemia were determined by microscopy (microscopic parasitemia) and PCR (submicroscopic parasitemia), and antibody levels against crude schizont antigens were measured by enzyme-limited immunosorbent assay (ELISA). Antibody levels, parasite diversity, and risk of malaria in the ensuing transmission season were compared among children who had baseline asymptomatic microscopic or submicroscopic or no infections. Of the 99 asymptomatic baseline infections, 46 (46.5%) were microscopic and 53 (53.5%), submicroscopic. Cox regression analysis adjusting for age group, sex and community found a strong association between both baseline microscopic (hazard ratio [HR] = 0.36, 95% confidence interval [95% CI] = 0.21 to 0.63;