Children who survive severe malaria may face long-term cognitive impairment and decreased academic achievement for years after infection, according to a study published late last week in JAMA.

In the analysis, researchers assessed neurocognitive and academic outcomes among nearly 900 children in Uganda who had experienced severe malaria (672 children) in early childhood and 217 uninfected controls. Participants were evaluated for an average of about eight years, and up to 15 years, after their initial illness. The mean age of the participants was 11 years. 

The findings show that children with a history of cerebral malaria or severe malarial anemia, two of the most severe forms of malaria, had lower scores in overall cognition and math than children who had not had malaria. Attention and reading scores did not differ significantly between the two groups, and cognitive and academic scores were not significantly different between children with other forms of severe malaria and children in the control group.

Cerebral malaria, severe malarial anemia

Cerebral malaria and severe malarial anemia are the most common forms of malaria. Previous research has shown that both cerebral malaria and severe malarial anemia are associated with cognitive impairment up to two years after initial illness. 

“Cerebral malaria and severe malarial anemia, which affect more than a million children every year, are not only causes of death in children, but also associated with very long-term costs in terms of a child’s thinking and their academic achievement,” senior author Chandy John, MD, of Indiana University, said in a university news release. “These costs, particularly in the area of math skills, can affect their ability to do well in school, to go to college and to get a good job.”

In the current study, the researchers also identified that, among children with cerebral malaria or severe malarial anemia, other factors, such as acute kidney injury, elevated angiopoietin-2 (a marker of vascular dysfunction), and neurologic deficits at or after infection, were associated with long-term cognitive impairment years later. 

Cerebral malaria and severe malarial anemia, which affect more than a million children every year, are not only causes of death in children, but also associated with very long-term costs in terms of a child’s thinking and their academic achievement.

This finding suggests that some biological processes linked to severe illness may be connected to the thinking and learning problems that can develop after infection. “Cohort studies can show an association, but they can’t prove that these illnesses caused the impairment,” John said. “Instead, we can look at potential pathways in the body and the brain and see how they relate to cognition.”

Need for prevention strategies, early detection

Malaria is a major global health threat, with an estimated 263 million cases and nearly 600,000 deaths reported in 2023—most of them in African and among children younger than five years. 

Advances in treatment have reduced mortality, but emerging signs of resistance to antimalarial drugs are raising new concerns about the impact of severe cases. At the same time, a growing body of evidence suggests that surviving severe malaria may come with lasting consequences, including cognitive and academic impairment.

The authors say more research is needed to explain how disease processes in cerebral malaria and severe malarial anemia relate to long-term cognitive impairment and that the findings highlight the importance of prevention strategies, early detection, and cognitive rehabilitation for survivors. 

“If we can identify pathways that lead to brain injury, then we can come up with interventions that may prevent brain injury, and test these in clinical trials,” John said. “That could potentially protect the brain and improve cognitive and academic outcomes for hundreds of thousands of children in countries with malaria.”