Severe Malaria in Kids Linked to Certain Cognitive, Academic Deficits Years Later

Cerebral malaria and severe malarial anemia were linked to long-term cognitive and academic deficits in survivors of severe childhood malaria, according to a descriptive analysis in Uganda.

In participants who were tested 4 to 15 years after their severe malaria episode, those with a history of cerebral malaria or severe malarial anemia had lower z scores in overall cognition versus unaffected community children, with adjusted mean differences of -0.41 (95% CI -0.74 to -0.09) and -0.31 (95% CI -0.61 to -0.01), respectively, reported Chandy John, MD, of Indiana University School of Medicine in Indianapolis, and colleagues in JAMA.

These participants also had lower z scores in math, with adjusted mean differences of -0.46 (95% CI -0.78 to -0.14) and -0.32 (95% CI -0.61 to -0.03), respectively.

The study was recently presented at the European Society of Clinical Microbiology and Infectious Diseases congress in Munich.

There were no significant differences in attention or reading scores. Children who had other forms of severe malaria — respiratory distress, complicated seizures, or prostration — had no significant differences in cognitive or academic scores compared with community children who didn’t have malaria.

“These data suggest that children with cerebral malaria and severe malarial anemia, but not other forms of severe malaria, experience declines in cognition and academic achievement that persist into later childhood and adolescence,” John and colleagues wrote. “The results support the urgent need for additional interventions to prevent severe malaria and to help prevent cognitive declines among children who develop severe malaria.”

Despite decades of dogma that severe malaria survivors make full and uneventful recoveries, Sesh Sundararaman, MD, PhD, and Audrey Odom John, MD, PhD, both of the Children’s Hospital of Philadelphia, noted in an accompanying editorial that “it is now recognized that the consequences of malaria extend well beyond hospital discharge.”

Prior studies in children with cerebral malaria or severe malarial anemia have shown cognitive impairments 1 to 2 years after infection. “This new evidence suggests that this impairment may unfortunately persist for many years after an episode of severe malaria,” Sundararaman and Odom John observed.

Better understanding of the pathophysiology behind malaria’s effects on cognition could help drive development of adjunctive preventive therapies, they added. Clinical and biological factors linked with lower post-malarial cognition, such as hyperuricemia and elevated plasma angiopoietin-2 levels, could offer potential therapeutic targets.

The Malarial Impact on Neurobehavioral Development (MIND) study assessed the long-term neurocognitive and academic outcomes of participants who’d previously enrolled in two prospective studies of severe malaria in Uganda. Those participants were traced and enrolled in MIND between 2020 and 2023, along with a control group of community children who didn’t develop malaria.

This analysis included 889 participants with a mean age of 11.1 years; 44.2% were girls. They were tested 4 to 15 years after initial study enrollment, with a mean testing time of 8.4 years later.

There were no significant differences between those with cerebral malaria and those with severe malarial anemia in any of the cognitive or academic outcomes.

In children with either condition, 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, with adjusted mean differences of -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 (adjusted mean difference -0.42, 95% CI -0.79 to -0.05) and math (adjusted mean difference -0.39, 95% CI -0.74 to -0.04).

Study limitations included variable lengths of follow-up, the loss of patients to follow-up over time, and the evaluation of participants only in a single country.