INDIANAPOLIS — Indiana University School of Medicine scientists have uncovered new evidence that changes in the gut bacteria of African children with severe malaria are linked to life-threatening complications. The latest findings, published in Nature Communications, may lead to treatments that can reduce harmful bacteria and improve outcomes for children affected by the deadly disease.
The mosquito-transmitted parasite known as Plasmodium causes malaria in humans. While some cases are mild, severe malaria can cause critical symptoms like high fevers, seizures and organ failure. According to the World Health Organization's latest World malaria report, there were about 263 million cases of malaria in 2023 and nearly 600,000 deaths. Most malaria-related fatalities occur in African children younger than 5 years old.
"Our previous research in mice and in a cohort of Malian children showed that gut microbiota can influence how the body’s immune system responds to Plasmodium, subsequently determining the outcome of infection," said Nathan Schmidt, PhD, professor of pediatrics at the IU School of Medicine and the study's lead author. "Our latest study builds on those observations by analyzing new cohorts of African children and identifying the specific bacteria associated with clinical complications."
The research team studied samples from large cohorts of children in Uganda and Malawi. They found that in cases of severe malaria, the children's gut microbiota — the collection of microorganisms such as bacteria, viruses and fungi that live in the digestive tract — underwent substantial changes with notable increases in bacteria belonging to the Enterobacteriaceae family, which contains known pathogenic bacteria. The bacteria were linked to severe complications, hospitalizations and higher mortality risk.
"An underappreciated but significant complication of severe malaria is the increased risk of hospital readmission and death in the ensuing 6 to 12 months after the initial illness," said Chandy C. John, MD, Distinguished Professor and Ryan White Professor of Pediatrics at the IU School of Medicine and co-author of the study. "The reasons for these risks are poorly understood, but our analysis identified an increased abundance of specific pathogenic bacteria, including E. coli, in the cohort of Ugandan children who were later readmitted to the hospital or died."
The next phase of this research is already underway through collaborations between researchers from the Herman B Wells Center for Pediatric Research and the Ryan White Center for Pediatric Infectious Diseases and Global Health, including Schmidt, John and Andrea Conroy, PhD. Their ongoing work will follow two large cohorts of Ugandan children with severe malaria to confirm whether an increased abundance of these disease-causing bacteria are directly associated with life-threatening outcomes.
"If our results are substantiated in future studies of African children, they could guide the pursuit of treatments that reduce harmful gut bacteria during severe malaria and ultimately decrease the risk of hospital readmission and death among affected children," said Conroy, associate professor of pediatrics at the IU School of Medicine and co-author of the study.
Additional study authors from IU include Olivia J. Bednarski, Sawyer B. Lehman, Jie Ren and Tuan M. Tran. Other authors include David Mzinza of Malawi University of Science and Technology; Caroline Kazinga, Ruth Namazzi and Robert O. Opoka of Makerere University; and Terrie E. Taylor and Karl B. Seydel of Kamuzu University of Health Sciences.
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. 13 in 2024 National Institutes of Health funding among all public medical schools in the country.
Writer: Jackie Maupin, jacmaup@iu.edu
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