Severe Childhood Malaria linked to Neurocognitive and Academic Sequelae: JAMA

Participants were recruited from among a total of 1247 children and young individuals younger than 18 years of age who had been recruited to participate in two separate Ugandan cohorts. Of those, the investigators managed to locate 958 children (77%), out of whom 939 (75%) agreed to participate in the current follow-up research. Participants were assigned different groups according to their previous experiences of being sick with the disease: the first group included 184 children who had recovered from cerebral malaria, another 249 children who had contracted severe malarial anemia, and the third one comprised of 239 cases of various kinds of severe malaria.

To provide a contrast, the unaffected community group included 217 children who had not experienced any serious diseases before. The average age of the participants at the moment of testing was 11.1 years; almost equal numbers of females and males took part in the study.

Key findings:

• Children with cerebral malaria and severe malarial anemia also exhibited significant differences in cognitive performance relative to their counterparts.
• In particular, cognitive scores in children with cerebral malaria were observed to be -0.41 lower on average than those of children without cerebral malaria (95% CI, -0.74 to -0.09), while children with severe malarial anemia demonstrated -0.31 differences (95% CI, -0.61 to -0.01).
• The influence of previous malarial conditions on mathematics achievement scores revealed deficits of -0.46 in cognitive skills and -0.32 in mathematics abilities.
• It is noteworthy that attention and reading abilities did not exhibit statistically significant differences between cases and control subjects.
• Cognitive z score deficiencies several years after children's suffering from cerebral malaria or severe malarial anemia were associated with three variables: acute kidney injury, hyperuricemia, and increased plasma levels of angiopoietin-2.
• Specifically, acute kidney injury at the moment of the malarial episode correlated with -0.44 decrease in cognitive ability scores, while hyperuricemia correlated with -0.45.
• As regards other indicators of academic success, apart from general cognitive functions, acute kidney injury was the only variable associated with low reading scores (-0.42) and mathematics achievement (-0.39).

The research reveals that the effects of childhood malaria are not temporary obstacles but are developmental problems. Cerebral malaria and severe malarial anemia affect the cognitive development of those who have suffered from the disease. They suffer from reduced intelligence levels and poor academic results between 4 to 15 years post-index infection. Although some skills like reading and attention are unaffected, the deficiency in mathematics and basic cognitive skills demonstrates impaired brain health.

Reference:

Bangirana P, Mellencamp KA, Ren J, et al. Long-Term Cognitive Ability and Academic Achievement After Childhood Severe Malaria. JAMA. Published online April 18, 2026. doi:10.1001/jama.2026.0704