Association of asymptomatic Plasmodium falciparum infections and its treatment with short-term cognitive performance in school-aged children: a prospective cohort study in western Kenya.

OBJECTIVES: We examined how asymptomatic Plasmodium falciparum (Pf) infections and their treatment affect short-term cognitive trajectories among schoolchildren living in western Kenya and explored whether subclinical inflammation may contribute to this relationship. METHODS: In this prospective cohort study, 254 children aged 7-9 years underwent neurocognitive assessment and Pf detection by microscopy at baseline, 4, and 8 weeks. Microscopy-positive cases were treated. Haemoglobin, parasitaemia by quantitative PCR (PfqPCR), molecular force of Pf infection, and 21 plasma cytokines were measured longitudinally. Adjusted generalized linear mixed models were used to evaluate the associations between parasitaemia, treatment, and longitudinal changes in cognition. RESULTS: In pre-specified adjusted analyses, PfqPCR-detectable parasitaemia correlated with a decline in a composite cognitive score over time (adjusted β for interaction: -0.11, 95% CI -0.19--0.031), while treatment of microscopy-detectable infections correlated with improvement (0.082, 95% CI 0.0027-0.17). Higher levels of the inflammatory cytokine CXCL11/ITAC were associated with lower cognitive performance (adjusted β: -0.30, 95% CI -0.60--0.022), which was validated in an independent cross-sectional cohort (-0.18, 95% CI -0.34--0.019). CONCLUSIONS: Asymptomatic Pf parasitaemia may negatively influence short-term cognition in young schoolchildren living in an area of intense malaria transmission. Low-level inflammation may play a role in this effect.