The aetiologies, mortality, and disability of non-traumatic coma in African children: a systematic review and meta-analysis

Stephen T. Ray, Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; The Brain Infection and Inflammation Group, University of Liverpool, Liverpool, UK; Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi; Department of Paediatric Infectious Disease and Immunology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Wilson Lab, Weil Institute for Neurosciences, University of San Francisco, San Francisco, CA, USA. Electronic address: stephen.ray@paediatrics.ox.ac.uk.
Charlotte E. Fuller, The Brain Infection and Inflammation Group, University of Liverpool, Liverpool, UK; Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi; Department of Paediatric Immunology, Allergy and Infectious Diseases, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, UK.
Alex Boubour, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi.
Taty Tshimangani, Hôpital Pédiatrique de Kalembe Lembe, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of the Congo.
Edith Kafoteka, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi.
Alice Muiruri-Liomba, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi.
Albert Malenga, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi.
Andrew Tebulo, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi.
Paul Pensulo, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi.
Monfort B. Gushu, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi.
Maryke Nielsen, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi.
Madiha Raees, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Elisabeth Stockdale, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi.
Josephine Langton, Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi.
Gretchen L. Birbeck, Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Neurology, University of Rochester, Rochester, NY, USA.
Naomi Waithira, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Nakhon Pathom, Thailand.
Laura J. Bonnett, Department of Health Data Science, University of Liverpool, Liverpool, UK.
Marc Yr Henrion, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, UK.
Ericka L. Fink, Division of Critical Care Medicine, Department of Anaesthesiology and Critical Care, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, PA, USA.
Douglas G. Postels, Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Division of Neurology, George Washington University and Children's National Health System, Washington, DC, USA.
Nicole O'Brien, Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Hôpital Pédiatrique de Kalembe Lembe, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of the Congo; Department of Pediatrics, Division of Critical Care Medicine, Nationwide Children's Hospital and Ohio State University, Columbus, OH, USA.
Anne-Laure Page, Epicentre, Paris, France.
Emmanuel Baron, Epicentre, Paris, France.
Stephen B. Gordon, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, UK.
Elizabeth Molyneux, Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi.
Arjen Dondorp, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Nakhon Pathom, Thailand.
Elizabeth C. George, Medical Research Council Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK.
Kathryn Maitland, Department of Infectious Disease and Institute of Global Health and Innovation, Faculty of Medicine, Imperial College, London, UK; Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
Benedict D. Michael, The Brain Infection and Inflammation Group, University of Liverpool, Liverpool, UK; National Institute for Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK; Walton Centre NHS Foundation Trust, Liverpool, UK.
Tom Solomon, The Brain Infection and Inflammation Group, University of Liverpool, Liverpool, UK; National Institute for Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK; Walton Centre NHS Foundation Trust, Liverpool, UK; The Pandemic Institute, University of Liverpool, Liverpool, UK.
Yamikani Chimalizeni, Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi; School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
David G. Lalloo, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, UK.

Document Type

Journal Article

Publication Date

4-22-2025

Journal

The Lancet. Global health

DOI

10.1016/S2214-109X(25)00055-5

Abstract

BACKGROUND: Non-traumatic coma in African children is a common life-threatening presentation often leading to hospital attendance. We aimed to estimate the distribution of non-traumatic coma causes and outcomes, including disease-specific outcomes, for which evidence is scarce. METHODS: We systematically reviewed MEDLINE, Embase, and Scopus databases from inception to Feb 6, 2024. We included studies recruiting children (aged 1 month to 16 years) with non-traumatic coma (Blantyre Coma Scale score ≤2, ie deep coma or comparable alternative) from any African country. Disease-specific studies were included if outcomes were reported. Primary data were requested where required. We used a DerSimonian-Laird random effects model to calculate pooled estimates for prevalence of causes, mortality, and morbidity (in-hospital and post-discharge), including analysis of mortality by temporality. This study was registered with PROSPERO (CRD4202014193). FINDINGS: We screened 16 666 articles. 138 studies were eligible for analysis, reporting causes, outcome data, or both from 35 027 children with non-traumatic coma in 30 African countries. 114 (89%) of 128 studies were determined to be high quality. Among the causes, cerebral malaria had highest pooled prevalence at 58% (95% CI 48-69), encephalopathy of unknown cause was associated with 23% (9-36) of cases, and acute bacterial meningitis was the cause of 10% (8-12) of cases, with all other causes representing lower proportions of cases. Pooled overall case-fatality rates were 17% (16-19) for cerebral malaria, 37% (20-55) for unknown encephalopathy, and 45% (34-55) for acute bacterial meningitis. By meta-regression, there was no significant difference in cerebral malaria (p=0·98), acute bacterial meningitis (p=0·99), or all-cause coma (p=0·081) mortality by year of study. There was no substantial difference in deaths associated with cerebral malaria in-hospital compared with post-discharge (17% [16-19] vs (18% [16-20]). Mortality was higher post-discharge than in-hospital in most non-malarial comas, including acute bacterial meningitis (39% [26-52]) vs 53% [38-69]). Disability associated with cerebral malaria was 11% (9-12). Pooled disability outcomes associated with other non-malarial diseases were largely absent. INTERPRETATION: The prevalence and outcomes of cerebral malaria and meningitis associated with non-traumatic coma were strikingly static across five decades. Enhanced molecular and radiological diagnostics, investment, policy making, community awareness, and health service provision are all required to facilitate earlier referral to specialist centres, to drive a step-change in diagnostic yield and treatment options to improve these outcomes. FUNDING: Wellcome Trust. TRANSLATIONS: For the Chichewa, French and Portuguese translations of the abstract see Supplementary Materials section.

Department

Neurology

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