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Study finds link between kidney injury, neurocognitive impairment in children with malaria

2019 05 Conroy Child Lab

The CHILD lab team cuts a ribbon at the lab opening in July 2018. From left, Ronald Wasswa, CHILD lab manager; Chandy John, MD; Cordelia (front, daughter of Priscilla Amenya, IU administrative assistant and D43 grant coordinator); Ivan Mufumba, lab technologist; and Andrea Conroy, PhD, with her daughter, Maya.

More than 200 million children around the world are at risk of failing to meet their developmental potential, and the risk is highest for children in sub-Saharan Africa.

In that part of the world, severe malaria is a leading cause of acquired neurodisability—leaving many children with developmental delay even years after recovery. Scientists don’t fully understand how malaria impacts the developing brain in children, but led by Indiana University School of Medicine researchers is the first to link malaria-related acute kidney injury (AKI) to long-term neurocognitive impairment.

Led by Chandy John, MD, Ryan White Professor of Pediatrics in the Department of Pediatrics, IU researchers partnered with the Makerere University College of Health Sciences and the Mulago National Referral Hospital in Kampala, Uganda, to conduct a large clinical study evaluating the long-term impact of AKI on children with severe malaria. They found that AKI is not only a common complication of severe malaria, but is linked to long-term adverse health outcomes.

The project followed hundreds of Ugandan children with severe malaria between the ages of 18 months to 12 years. It confirmed an earlier study from John’s team that suggested AKI is a more common complication of severe malaria than previously believed—occurring in about one-third of children with severe malaria. Their data provides novel evidence that AKI during severe malaria is associated with neurological deficits in children—such as developmental delay in speech and motor skills—which are persistent for up to two years.

Importantly, the study also found that children with severe malaria and AKI were at a higher risk for prolonged hospitalization, mortality, and chronic kidney disease. Because chronic kidney disease affects about one-fifth of the Ugandan population, the study provides some insight on how severe malaria during childhood may contribute to the widespread burden of chronic kidney disease in adults.

“These results highlight AKI as a clinically important and underappreciated complication in children with severe malaria,” said Andrea Conroy, PhD, first author on the paper and a pioneer in describing the risk of AKI in children with severe malaria. “It suggests that prevention, earlier identification and improved clinical management of AKI might enhance survival and long-term wellbeing of children with severe malaria.”

John and Conroy said that they intend to further investigate the development of AKI in instances of severe malaria. By investigating the mechanisms that lead to AKI in some children with severe malaria—or the mechanisms that prevent AKI in others—scientists may begin to develop improved therapies that could lead to positive long-term health outcomes for people in sub-Saharan Africa.


The above reference project is titled Malarial Impact on Neurobehavioral Development, project number R01 NS055349-11, and is funded by the National Institute of Neurological Disorders and Stroke. The study was published on May 21, 2019 by BMC Medicine.

Chandy John, MD, is the Ryan White Professor of Pediatrics and chief of the Department of Pediatrics Division of Infectious Disease. He is the director of the Ryan White Center for Pediatric Infectious Disease and Global Health at IU School of Medicine.

Additional IU researchers who contributed to this include Andrea Conroy, PhD, assistant research professor of pediatrics and director of the Child Lab in Kampala, Uganda; and Dibyadyuti Datta, PhD, assistant research professor of pediatrics.

Contributing authors of this collaborative study represent the Makerere University College of Health Sciences, the University of Minnesota, and the University of Alberta.