Electroencephalogram Features Distinguish Cases of Cerebral Malaria Among Malawian Children With Fever and Coma

Alexander Andrews, Division of Neurology, The George Washington University/Children's National Hospital, Washington D.C., USA.
Dana B. Harrar, Division of Neurology, The George Washington University/Children's National Hospital, Washington D.C., USA.
Tesfaye Zelleke, Division of Neurology, The George Washington University/Children's National Hospital, Washington D.C., USA.
Jiahui Zhang, Division of Statistics, University of Washington, Seattle, Washington, USA.
Bo Zhang, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
John Barber, Division of Biostatistics and Study Methodology, Children's National Research Institute, Washington D.C., USA.
Rohini Dasan, The George Washington University, School of Medicine and Health Sciences, Washington D.C., USA.
Nathaniel Amoah, The George Washington University, School of Medicine and Health Sciences, Washington D.C., USA.
Olivia Findorff, University of Virginia, Charlottesville, Virginia, USA.
Sean Krieger, College of Osteophatic Medicine, Michigan State University, East Lansing, Michigan, USA.
Emmalee Barrett, The George Washington University, School of Medicine and Health Sciences, Washington D.C., USA.
Nicole O'Brien, Blantyre Malaria Project, Kamuzu University of Health Sciences/University of Malawi College of Medicine, Blantyre, Malawi.
Charlotte E. Fuller, Blantyre Malaria Project, Kamuzu University of Health Sciences/University of Malawi College of Medicine, Blantyre, Malawi.
Christopher A. Moxon, Blantyre Malaria Project, Kamuzu University of Health Sciences/University of Malawi College of Medicine, Blantyre, Malawi.
Terrie E. Taylor, College of Osteophatic Medicine, Michigan State University, East Lansing, Michigan, USA.
Michael J. Griffiths, Centre for Child and Adolescent Health Research, Western Sydney (Baludarri) Precinct, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Stephen T. Ray, Blantyre Malaria Project, Kamuzu University of Health Sciences/University of Malawi College of Medicine, Blantyre, Malawi.
Douglas G. Postels, Division of Neurology, The George Washington University/Children's National Hospital, Washington D.C., USA.

Document Type

Journal Article

Publication Date

7-30-2025

Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

DOI

10.1093/cid/ciaf316

Keywords

central nervous systems infection; cerebral malaria; coma; electroencephalography

Abstract

BACKGROUND: In febrile comatose patients living in malaria-endemic areas, overlapping symptoms and limited laboratory capacity make it difficult to distinguish parasitic, bacterial, and viral central nervous system infections. We evaluated electroencephalography (EEG) as a biomarker to differentiate the microbiologic etiology of pediatric febrile coma at a major referral center in Malawi. METHODS: This was a retrospective case-control study comparing EEG recordings of Malawian children with cerebral malaria to those with febrile coma of nonmalarial cause (bacterial meningitis, viral encephalitis, or unknown cause). Participants were admitted to Queen Elizabeth Central Hospital (Blantyre, Malawi) between 2013 and 2021. Inclusion criteria were fever, coma (Blantyre Coma Score ≤2), and coma etiology (malarial or nonmalarial) defined by laboratory testing. Four supervised machine learning algorithms were used to train a balanced ensemble classifier, SuperLearner, generating test characteristics of the diagnostic ability of EEG features. RESULTS: Two hundred three children with cerebral malaria and 87 children with nonmalarial coma were included. Univariate analysis of qualitative (visual) EEG interpretations revealed higher voltage, slower background frequency, more sleep elements, less variability, more abnormal organization, and less continuity in cerebral malaria. Quantitative waveform analysis showed greater power in cerebral malaria. Both quantitative and qualitative EEG interpretation distinguished coma etiology (area under the receiver operating characteristic curve [AUROC] = 0.85 and 0.86, respectively). Combining qualitative and quantitative interpretation methods, the test characteristic improved (AUROC = 0.90). CONCLUSIONS: EEG features distinguish malarial from nonmalarial coma in febrile Malawian children. This technology may aid in distinguishing the microbiologic etiology of febrile coma in malaria-endemic areas.

Department

Pediatrics

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