Elevated uric acid levels may contribute to severe malaria outcomes in children

Elevated uric acid levels may contribute to severe malaria outcomes in children

Indiana University School of Medicine researchers and their collaborators in Uganda at Makerere University School of Medicine have uncovered a significant association between elevated uric acid levels and life-threatening outcomes in children with severe malaria.

Published inNatural medicineThe study identified hyperuricemia - high levels of uric acid - as a potential contributor to increased mortality and long-term neurodevelopmental challenges in children with severe malaria. These findings open the door to future research that could improve treatment strategies for children affected by severe malaria, a disease caused by mosquito-borne parasites and a leading cause of death in African children.

“Our results show that hyperuricemia is strongly associated with in-hospital and post-discharge death and with long-term cognitive impairment in children with severe malaria,” said Medicine, who co-led the study. “We also demonstrated multiple mechanisms by which hyperuricemia may lead to these outcomes, suggesting that hyperuricemia is not only associated with poor outcomes but also contributes to them.”

Researchers analyzed data from two independent groups of children with severe malaria in Uganda and found that 25% had hyperuricemia. This condition is caused by excess uric acid, a harmful body waste substance in the blood. The primary drivers of hyperuricemia in the study participants were broken infected red blood cells and kidney injury, reducing the body's ability to get rid of the extra uric acid.

In the study, hyperuricemia in children with severe malaria was associated with four negative outcomes: serious health complications such as coma and anemia, a higher risk of death during hospitalization, a higher risk of death after hospital discharge, and long-term cognitive impairment in survivors.

The study also found that children with hyperuricemia had more harmful gut bacteria, which can cross the injured intestinal lining and cause sepsis. Together, these findings highlight a need for clinical trials to test the effectiveness of uric acid medications as an additional treatment for severe malaria.

Additional studies are needed to determine whether lowering uric acid in children with severe malaria can reduce in-hospital deaths, post-discharge deaths, and long-term cognitive impairment. We hope these studies will provide new insights and potentially lead to improved treatments that save lives. “

Andrea Conroy, PhD, associate professor of pediatrics, IU School of Medicine and study co-leader

This research builds on the team's recent discovery of partial resistance to primary malaria treatment in African children with severe malaria. Both studies underscore the importance of prioritizing new strategies to combat malaria, which affected 263 million people and caused nearly 600,000 deaths worldwide in 2023.

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