Long-Term Cognitive Ability and Academic Achievement after Childhood Severe Malaria

Importance: Cerebral malaria and severe malarial anemia are associated with cognitive impairment and decreased academic achievement 1 to 2 years after the initial episode. The extent to which impairment persists into later childhood and adolescence is unknown. Objective: To determine whether severe malaria in children is associated with long-term cognitive impairment or decreased academic achievement. Design, Setting, and Participants: Assessment of Ugandan children enrolled in 2 prior cohort studies of severe malaria; 1247 children completed the prior studies (2008-2018), of whom 958 were traceable (77%), and 939 (75%) enrolled in the present study (2020-2023). Data from 889 individuals younger than 18 years were analyzed. Exposures: Cerebral malaria (n = 184), severe malarial anemia (n = 249), other forms of severe malaria (respiratory distress, complicated seizures, or prostration, n = 239), and unaffected community children (n = 217). Main Outcomes and Measures: Descriptive analysis including age-adjusted z scores of overall cognitive ability, attention, and academic achievement (math, reading). Results: Participants (mean age, 11.1 [SD, 3.4] years; 44.2% female) were tested 4 to 15 years (mean, 8.4 [SD, 2.7] years) after their severe malaria episode. Compared with community children, children with a history of cerebral malaria or severe malarial anemia had lower scores in overall cognition (adjusted mean difference, -0.41 [Bonferroni-corrected 95% CI, -0.74 to -0.09] and -0.31 [95% CI, -0.61 to -0.01], respectively) and math (-0.46 [95% CI, -0.78 to -0.14] and -0.32 [95% CI, -0.61 to -0.03], respectively), while attention and reading scores did not differ significantly. Cognitive and academic scores were not significantly different between children with other forms of severe malaria and community children. In children with cerebral malaria or severe malarial anemia, acute kidney injury, hyperuricemia, and elevated plasma angiopoietin-2 levels at the time of the severe malaria episode were associated with worse z scores in overall cognitive ability (-0.44 [95% CI, -0.80 to -0.08], -0.45 [95% CI, -0.88 to -0.02], and -0.33 [95% CI, -0.63 to -0.03], respectively). In children with cerebral malaria or severe malarial anemia, acute kidney injury was additionally associated with lower z scores in reading (95% CI, -0.42 [95% CI, -0.79 to -0.05]) and math (95% CI, -0.39 [-0.74 to -0.04]). Conclusions and Relevance: Among survivors of a severe childhood malaria episode, cerebral malaria and severe malarial anemia in childhood are associated with cognitive impairment and decreased academic achievement in some metrics 4 to 15 years after the index episode.