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

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.