Cerebral Malaria and Severe Malarial Anemia, but not Other Forms of Severe Malaria, Are Associated With Long-Term Cognitive Impairment

BACKGROUND: Cerebral malaria (CM) and severe malarial anemia (SMA) are associated with long-term cognitive impairment in children, but little is known about cognitive impairment in children with other forms of severe malaria. METHODS: In this prospective cohort study of 600 Ugandan children 6 months to 4 years of age with 1 or more of the 5 most common forms of severe malaria (CM, respiratory distress, malaria with multiple seizures, SMA, or prostration), overall cognitive ability, attention, and associative memory were evaluated 12 months after hospital discharge. Age-adjusted z-scores for each domain were calculated from the scores of community children (CC) with no acute illness. Groups were compared using linear regression adjusted for potential confounding factors. RESULTS: Children with CM or SMA had significantly lower overall cognition scores than CC (mean difference [95% CI]: CM -0.66 [-1.12, -0.21], P = .001, SMA -0.71 [-1.05, -0.37], P < .001), and a greater proportion of children with CM (5/47, 10.6%) or SMA (17/140, 12.1%) had cognitive impairment (z-score < -2) than CC (2/104, 1.9%, P = .003 and 0.018, respectively). Cognition scores did not differ significantly between children with respiratory distress, multiple seizures or prostration and CC. Attention and associative memory scores did not differ significantly between children with any form of severe malaria and CC. CONCLUSIONS: CM and SMA, but not other forms of severe malaria, are associated with long-term cognitive impairment in children <5 years of age.