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The aetiologies, mortality, and disability of non-traumatic coma in African children: a systematic review and
Stephen T J Ray1, Charlotte E Fuller2, Alex Boubour3
1Oxford 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.
Insights
Cerebral malaria and meningitis are leading causes of non-traumatic coma in African children, with static mortality rates over 50 years. Improved diagnostics and healthcare are crucial for better outcomes in pediatric coma.
Area of Science:
- Pediatric Neurology
- Infectious Diseases
- Global Health
Background:
- Non-traumatic coma is a critical condition in African children, necessitating a clear understanding of its causes and outcomes.
- Existing evidence on disease-specific outcomes for pediatric non-traumatic coma in Africa is limited.
Purpose of the Study:
- To systematically review and estimate the prevalence of causes and outcomes of non-traumatic coma in African children.
- To analyze disease-specific outcomes, including mortality and morbidity, for pediatric non-traumatic coma.
Main Methods:
- A systematic review of MEDLINE, Embase, and Scopus databases was conducted.
- Studies involving children (1 month to 16 years) with non-traumatic coma in Africa were included.
- Pooled estimates for prevalence, mortality, and morbidity were calculated using a DerSimonian-Laird random effects model.
Main Results:
- Cerebral malaria was the most prevalent cause (58%), followed by unknown encephalopathy (23%) and acute bacterial meningitis (10%).
- Pooled case-fatality rates were 17% for cerebral malaria, 37% for unknown encephalopathy, and 45% for acute bacterial meningitis.
- Mortality rates for cerebral malaria and meningitis remained static over five decades; post-discharge mortality was higher for non-malarial comas.
Conclusions:
- Cerebral malaria and meningitis are persistent major causes of non-traumatic coma with static outcomes in African children over 50 years.
- Enhanced diagnostics, investment, policy, awareness, and health services are vital for improving outcomes.
- Earlier referral to specialist centers is needed to improve diagnostic yield and treatment effectiveness.
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.
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