Abstract:
Background. Subclinical inflammation and cognitive deficits have been separately associated with asymptomatic Plasmodium
falciparum infections in schoolchildren. However, whether parasite-induced inflammation is associated with worse cognition has
not been addressed. We conducted a cross-sectional pilot study to better assess the effect of asymptomatic P. falciparum parasitemia
and inflammation on cognition in Kenyan schoolchildren.
Methods. We enrolled 240 children aged 7–14 years residing in high malaria transmission in Western Kenya. Children per-
formed five fluid cognition tests from a culturally adapted NIH toolbox and provided blood samples for blood smears and laboratory
testing. Parasite densities and plasma concentrations of 14 cytokines were determined by quantitative PCR and multiplex immuno-
assay, respectively. Linear regression models were used to determine the effects of parasitemia and plasma cytokine concentrations
on each of the cognitive scores as well as a composite cognitive score while controlling for age, gender, maternal education, and an
interaction between age and P. falciparum infection status.
Results. Plasma concentrations of TNF, IL-6, IL-8, and IL-10 negatively correlated with the composite score and at least one of
the individual cognitive tests. Parasite density in parasitemic children negatively correlated with the composite score and measures
of cognitive flexibility and attention. In the adjusted model, parasite density and TNF, but not P. falciparum infection status, inde-
pendently predicted lower cognitive composite scores. By mediation analysis, TNF significantly mediated ~29% of the negative effect
of parasitemia on cognition.
Conclusions. Among schoolchildren with PCR-confirmed asymptomatic P. falciparum infections, the negative effect of para-
sitemia on cognition could be mediated, in part, by subclinical inflammation. Additional studies are needed to validate our findings
in settings of lower malaria transmission and address potential confounders that could affect both inflammation and cognitive
performance.