INDIANAPOLIS — Severe childhood malaria is linked to long-term cognitive impairment, according to a new study from Indiana University School of Medicine researchers and their collaborators at Makerere University in Uganda.
The findings, recently published in JAMA, suggest children who survive cases of cerebral malaria and severe malarial anemia experience cognitive and academic impairment that persists into adolescence. The correlation highlights an urgent need for the development of better prevention strategies and more effective therapies to minimize the lasting effects of one of the world’s most dangerous diseases.
The World Health Organization reported 282 million malaria cases in 2024, with children under 5 accounting for about 75% of 610,000 global deaths.
"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," said Chandy John, MD, the Ryan White Professor of Pediatrics at the IU School of Medicine, who co-led the study. "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."
Malaria is caused by mosquito-transmitted parasites, with symptoms ranging from mild to life-threatening. Severe cases can cause complications to blood cell production resulting in malarial anemia, and serious neurological issues leading to coma, which defines cerebral malaria.
In the Malarial Impact on Neurobehavioral Development (MIND) study, children from two prior cohort studies of severe malaria were followed up four and 15 years after their initial episode, and their scores in cognition and academic achievement were compared to those of children in the community who did not have severe malaria. They found that children who survived cerebral malaria and severe malarial anemia experienced cognitive impairment, with cognition scores the equivalent of 3 to 7 IQ points below their community peers.
Specific clinical factors in children with cerebral malaria or severe malarial anemia, such as the presence of acute kidney injury and elevated levels of uric acid, which is necessary for some body functions but can be toxic when present in too high levels, were found to be associated with worse long-term cognitive outcomes.
The group’s future work will focus on determining if cerebral malaria and severe malarial anemia are causing the cognitive impairment, and how to prevent it.
"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. That’s what we’re doing in our current study, SMART Brain."
SMART Brain, short for Severe Malaria and Risk to The Brain, will allow the scientists to use models of the brain to explore further the link between specific processes that occur in severe malaria and brain injury.
"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."
IU School of Medicine’s Kagan Mellencamp, Jie Ren, Andrea Conroy, Dibyadyuti Datta, Christian Kautzman and Michael Goings are co-authors on the study. Additional authors include Paul Bangirana, Jacqueline Nakitende, Ruth Namazzi and Richard Idro from Makerere University, Robert Opoka from Aga Khan University and Bjarne Robberstad from University of Bergen.
This research was supported by funding from the National Institutes of Health.
About the Indiana University School of Medicine
The IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability. According to the Blue Ridge Institute for Medical Research, the IU School of Medicine ranks No. 15 in 2025 National Institutes of Health funding among all public medical schools in the country.
Writer: Jackie Maupin, jacmaup@iu.edu
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