April 19, 2026
3 min read
Key takeaways:
- Despite recent advances, malaria still kills more than 600,000 people per year globally.
- A new study shows that severe malaria in childhood can lead to lasting cognitive impairment.
MUNICH — Children who survive severe malaria can experience cognitive impairment for many years after the infection, according to new study findings.
The study, conducted in Uganda, reassessed around 900 children 4 to 15 years after their bouts with severe malaria and found they had diminished overall cognitive and math scores.
Study findings demonstrating severe childhood malaria’s long-term negative impact on cognition come amid important gains in malaria control, including the development of the first two malaria vaccines. Image: Gavi, the Vaccine Alliance
That far exceeds previous findings by the same research team that showed severe malaria in childhood can impact cognition for 1 or 2 years, according to Chandy C. John, MD, MS, Ryan White Professor of Pediatrics at the Indiana University School of Medicine, who presented findings from the new analysis at ESCMID Global. The full study was published at the same time in JAMA.
According to WHO, malaria still infects more than 280 million people every year, killing more than 600,000 — mostly children in Africa.
The discovery of its long-lasting impact on cognition is timely, coming as foreign aid cuts by the United States and other countries threaten to blight recent gains made against the mosquito-borne disease, including the development and licensure of the world’s first two malaria vaccines and the distribution of improved insecticide-treated bed nets.
“The findings … are a poignant reminder that the burden of malaria extends far beyond the acute infection and reinforce the importance of continued investment in malaria elimination,” Children’s Hospital of Philadelphia physicians Sesh A. Sundararaman, MD, PhD, and Audrey R. Odom John, MD, PhD, wrote in a JAMA editorial.
John and colleagues were able to track down 958 of the 1,247 children enrolled in two previous studies of severe malaria conducted from 2008 to 2018 in Uganda — “an incredible feat, given that some participants had originally been enrolled 15 years prior,” Sundararaman and Odom John wrote.
The researchers enrolled 939 of the 958 former study participants into a new cohort and assessed the cognitive development and academic achievement of the 889 participants aged younger than 18 years.
They did this by measuring the age-adjusted z scores for cognitive ability, attention, and academic achievement in math and reading of participants who survived severe malarial anemia (n = 249), cerebral malaria (n = 184) and other forms of severe malaria (n = 239) and comparing those scores with a control group of children who did not have malaria (n = 217).
The episodes of severe malaria in the main cohort occurred 4 to 15 years before the new study — a mean of 8.4 years earlier.
According to John and colleagues, the adjusted mean difference in z scores for overall cognition among participants who had cerebral malaria or severe malarial anemia were –0.41 and –0.31, respectively, compared with the control group, which is equal to a reduction of 4 to 7 IQ points, John said. For math, the differences were –0.46 and –0.32, respectively, compared with controls, but the researchers did not see any significant deficits in attention and reading scores.
Scores for participants who had other attributes of severe malaria — including respiratory distress, complicated seizures and prostration — did not differ significantly from the control group, which lined up with earlier studies, John said during his presentation.
Several factors were associated with worse reductions in z scores for cognitive ability among participants in those two groups, including acute kidney injury (–0.44), hyperuricemia (–0.45) and elevated plasma angiopoietin-2 levels (–0.33). Their scores for math (–0.39) and reading (–0.42) were also lower if they had acute kidney injury.
John said the identification of those factors “[gives] us some hope that we can target children for early intervention.”
It will take additional studies to determine if they are causing cognitive impairment in children with severe malaria “or simply markers of more severe malaria disease,” Sundararaman and Odom John wrote.
“Manipulation of endothelial angiopoietin signaling has become an attractive therapeutic target for cancer and other conditions, with multiple monoclonal antibodies and
small molecule inhibitors in development,” they wrote. “If elevations of angiopoietin-2 levels reflect a pathogenic role in severe malaria, adjunctive therapies at the time of acute infection might prove to be of benefit.
“Cognitive impairment has also been observed in pediatric and neonatal sepsis, and future studies should examine whether these effects occur through a common mechanism. Studies such as these will be critical in providing more comprehensive care for patients with severe malaria, with a focus on both decreasing mortality as well as improving long-term quality of life.”
Sources/Disclosures
Source:
John C, et al. Abstract J0002. Presented at: ESCMID Global; April 17-21, 2026; Munich.
References:
Disclosures:
Chandy and the other authors of the study report no relevant financial disclosures. Odom John reports holding a patent for malaria biomarkers. Sundararaman reports receiving grants from the NIH, Pediatric Infectious Diseases Society, St. Jude Children’s Research Hospital and Thrasher Research Foundation outside the submitted work.
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