Ray Stephen T J, Fuller Charlotte E, Boubour Alex, Tshimangani Taty, Kafoteka Edith, Muiruri-Liomba Alice, Malenga Albert, Tebulo Andrew, Pensulo Paul, Gushu Monfort B, Nielsen Maryke, Raees Madiha, Stockdale Elisabeth, Langton Josephine, Birbeck Gretchen L, Waithira Naomi, Bonnett Laura J, Henrion Marc Yr, Fink Ericka L, Postels Douglas G, O'Brien Nicole, Page Anne-Laure, Baron Emmanuel, Gordon Stephen B, Molyneux Elizabeth, Dondorp Arjen, George Elizabeth C, Maitland Kathryn, Michael Benedict D, Solomon Tom, Chimalizeni Yamikani, Lalloo David G, Moxon Christopher A, Taylor Terrie, Mallewa Macpherson, Idro Richard, Seydel Karl, Griffiths Michael J
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.
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.
Lancet Glob Health. 2025 Jun;13(6):e1043-e1056. doi: 10.1016/S2214-109X(25)00055-5. Epub 2025 Apr 22.
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.
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).
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.
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.
Wellcome Trust.
For the Chichewa, French and Portuguese translations of the abstract see Supplementary Materials section.
非洲儿童的非创伤性昏迷是一种常见的危及生命的症状，常常导致患儿就医。我们旨在评估非创伤性昏迷的病因分布及其后果，包括特定疾病的后果，目前这方面的证据很少。
我们系统检索了MEDLINE、Embase和Scopus数据库，检索时间从建库至2024年2月6日。我们纳入了招募来自任何非洲国家的非创伤性昏迷儿童（年龄1个月至16岁，布兰太尔昏迷量表评分≤2，即深度昏迷或类似情况）的研究。如果报告了特定疾病的研究结果，则纳入此类研究。必要时索取原始数据。我们使用DerSimonian-Laird随机效应模型来计算病因患病率、死亡率和发病率（住院期间和出院后）的合并估计值，包括按时间顺序分析死亡率。本研究已在国际前瞻性系统评价注册库（PROSPERO）注册（注册号：CRD4202014193）。
我们筛选了16666篇文章。138项研究符合分析条件，报告了30个非洲国家35027例非创伤性昏迷儿童的病因、结局数据或两者。128项研究中的114项（89%）被判定为高质量研究。在病因方面，脑型疟疾的合并患病率最高，为58%（95%CI 48-69），不明原因脑病占病例的23%（9-36），急性细菌性脑膜炎占病例的10%（8-12），其他所有病因所占病例比例较低。脑型疟疾的合并总体病死率为17%（16-19），不明原因脑病为37%（20-55），急性细菌性脑膜炎为45%（34-55）。通过Meta回归分析，按研究年份，脑型疟疾（p=0.98）、急性细菌性脑膜炎（p=0.99）或全因昏迷（p=0.081）的死亡率无显著差异。与脑型疟疾相关的死亡在住院期间和出院后没有实质性差异（17%[16-19]对18%[16-20]）。在大多数非疟疾性昏迷中，包括急性细菌性脑膜炎，出院后的死亡率高于住院期间（39%[26-52]对53%[38-69]）。与脑型疟疾相关的残疾率为11%（9-12）。与其他非疟疾性疾病相关的合并残疾结局基本没有报道。
在过去五十年中，与非创伤性昏迷相关的脑型疟疾和脑膜炎的患病率及后果惊人地稳定。需要加强分子和放射学诊断、投资、政策制定、社区意识以及卫生服务提供，以促进更早转诊至专科中心，推动诊断率和治疗选择的重大改变，从而改善这些结局。
惠康信托基金会。
摘要的奇切瓦语、法语和葡萄牙语翻译见补充材料部分。
