Microscopic and sub-microscopic asymptomatic Plasmodium falciparum infections in Ghanaian children and protection against febrile malaria

Naturally acquired immunity to Plasmodium falciparum malaria is thought to be non-sterile and sustained by persistence of low level parasitaemia. This study assessed the association between baseline microscopic and submicroscopic asymptomatic P. falciparum infections and anti-malarial antibody levels and whether these parasitaemia modify protective associations between antibody levels and malaria in Ghanaian children. Healthy children (N=973, aged 0.5-12 years) were recruited into a 50-week longitudinal malaria cohort study from January 2016 to January 2017. Baseline asymptomatic parasitaemia were determined by microscopy (microscopic parasitaemia) and polymerase chain reaction (submicroscopic parasitaemia) and antibody levels against crude schizont antigens measured by 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 P. falciparum 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%CI=(0.21, 0.63), p<0.001] and submicroscopic [HR=0.22, 95%CI=(0.11, 0.44), p<0.001] asymptomatic parasitaemia and a reduced risk of febrile malaria compared to those who were uninfected at baseline. Baseline asymptomatic submicroscopic parasitaemia had a significant effect on associations between anti-schizont antibodies and protection against febrile malaria (likelihood ratio test p<0.001). The study found both baseline P. falciparum asymptomatic microscopic and more strongly submicroscopic infections to be associated with protection against febrile malaria in the ensuing transmission season. This could have important implications for malaria sero-epidemiological studies and vaccine trials.