Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Lancet Glob Health. 2024 Jun;12(6):e919-e928. doi: 10.1016/S2214-109X(24)00078-0. Epub 2024 Apr 20.
Information on the causes of deaths from diarrhoea in children younger than 5 years is needed to design improved preventive and therapeutic approaches. We aimed to conduct a systematic analysis of studies to report estimates of the causes of deaths from diarrhoea in children younger than 5 years at global and regional levels during 2000-21.
For this systematic review and Bayesian multinomial analysis, we included 12 pathogens with the highest attributable incidence in the Global Enteric Multicenter Study. We searched PubMed, Scopus, Embase, Web of Science, Global Health Index Medicus, Global Health OVID, IndMed, Health Information Platform for the Americas (PLISA), Africa-Wide Information, and Cochrane Collaboration for articles published between Jan 1, 2000, and Dec 31, 2020, using the search terms "child", "hospital", "diarrhea", "diarrhoea", "dysentery", "rotavirus", "Escherichia coli", "salmonella", "shigella", "campylobacter", "Vibrio cholerae", "cryptosporidium", "norovirus", "astrovirus", "sapovirus", and "adenovirus". To be included, studies had to have a patient population of children younger than 5 years who were hospitalised for diarrhoea (at least 90% of study participants), at least a 12-month duration, reported prevalence in diarrhoeal stools of at least two of the 12 pathogens, all patients with diarrhoea being included at the study site or a systematic sample, at least 100 patients with diarrhoea, laboratory tests done on rectal swabs or stool samples, and standard laboratory methods (ie, quantitative PCR [qPCR] or non-qPCR). Studies published in any language were included. Studies were excluded if they were limited to nosocomial, chronic, antibiotic-associated, or outbreak diarrhoea or to a specific population (eg, only children with HIV or AIDS). Each article was independently reviewed by two researchers; a third arbitrated in case of disagreement. If both reviewers identified an exclusion criterion, the study was excluded. Data sought were summary estimates. Data on causes from published studies were adjusted when necessary to account for the poor sensitivity of non-qPCR methods and for attributable fraction based on quantification of pathogens in children who are ill or non-ill. The causes of deaths from diarrhoea were modelled on the causes of hospitalisations for diarrhoea. We separately modelled studies reporting causes of diarrhoea in children who were hospitalised in low-income and middle-income countries (LMICs) and in high-income countries (HICs).
Of 74 282 papers identified in the initial database search, we included 138 studies (91 included data from LMICs and 47 included data from HICs) from 73 countries. We modelled estimates for 194 WHO member states (hereafter referred to as countries), including 42 HICs and 152 LMICs. We could attribute a cause to 1 003 448 (83·8%) of the estimated 1 197 044 global deaths from diarrhoea in children younger than 5 years in 2000 and 360 730 (81·3%) of the estimated 443 833 global deaths from diarrhoea in children younger than 5 years in 2021. The cause with the largest estimated global attribution was rotavirus; in LMICs, the proportion of deaths from diarrhoea due to rotavirus in children younger than 5 years appeared lower in 2021 (108 322 [24·4%] of 443 342, 95% uncertainty interval 21·6-29·5) than in 2000 (316 382 [26·5%] of 1 196 134, 25·7-28·5), but the 95% CIs overlapped. In 2000, the second largest estimated attribution was norovirus GII (95 817 [8·0%] of 1 196 134 in LMICs and 225 [24·7%] of 910 in HICs); in 2021, Shigella sp had the second largest estimated attribution in LMICs (36 082 [8·1%] of 443 342), but norovirus remained with the second largest estimated attribution in HICs (84 [17·1%] of 490).
Our results indicate progress in the reduction of deaths from diarrhoea caused by 12 pathogens in children younger than 5 years in the past two decades. There is a need to increase efforts for prevention, including with rotavirus vaccine, and treatment to eliminate further deaths.
Bill & Melinda Gates Foundation via Johns Hopkins University and the University of Virginia.
为了设计改进的预防和治疗方法，我们需要了解导致 5 岁以下儿童腹泻死亡的原因。我们旨在对研究进行系统分析，以报告 2000-21 年全球和区域范围内 5 岁以下儿童腹泻死亡原因的估计数。
对于这项系统评价和贝叶斯多项式分析，我们纳入了全球肠道多中心研究中发病率最高的 12 种病原体。我们使用“child”、“hospital”、“diarrhea”、“diarrhoea”、“dysentery”、“rotavirus”、“Escherichia coli”、“salmonella”、“shigella”、“campylobacter”、“Vibrio cholerae”、“cryptosporidium”、“norovirus”、“astrovirus”、“sapovirus”和“adenovirus”等搜索词，在 PubMed、Scopus、Embase、Web of Science、全球健康索引医学、全球健康 OVID、IndMed、美洲卫生信息平台（PLISA）、非洲信息网和 Cochrane 协作网中检索了 2000 年 1 月 1 日至 2020 年 12 月 31 日期间发表的文章，以获取关于儿童腹泻住院的文章。为了纳入研究，研究必须有一个患者人群，即年龄小于 5 岁的因腹泻住院的儿童（至少 90%的研究参与者），至少有 12 个月的持续时间，报告腹泻粪便中至少两种 12 种病原体的流行率，所有腹泻患者都在研究地点或系统抽样中纳入，至少有 100 名腹泻患者，直肠拭子或粪便样本进行实验室检测，以及标准实验室方法（即定量 PCR [qPCR]或非 qPCR）。纳入了任何语言发表的研究。如果研究仅限于院内、慢性、抗生素相关或暴发腹泻，或仅限于特定人群（例如，仅患有 HIV 或 AIDS 的儿童），则排除研究。每个文章都由两名研究人员独立审查；如果意见不一致，第三名仲裁。如果两名评审员都确定了排除标准，则排除该研究。研究人员寻求的是总结估计数。对于已发表的研究，在必要时调整了病因数据，以考虑到非 qPCR 方法的敏感性较差以及基于对患病或非患病儿童病原体定量的归因分数。腹泻住院的病因模型是基于腹泻住院的病因模型。我们分别对报告了在中低收入国家（LMICs）和高收入国家（HICs）住院的儿童腹泻病因的研究进行了建模。
在初始数据库搜索中，共发现了 74282 篇论文，我们纳入了来自 73 个国家的 138 项研究（91 项研究的数据来自 LMICs，47 项研究的数据来自 HICs）。我们对 194 个世界卫生组织成员国（以下简称国家）进行了建模估计，包括 42 个 HICs 和 152 个 LMICs。我们可以归因于 1197044 名全球 5 岁以下儿童腹泻死亡的 19436073 名（83.8%），归因于 443833 名全球 5 岁以下儿童腹泻死亡的 3607360 名（81.3%）。在全球范围内，估计归因最大的病因是轮状病毒；在 LMICs 中，2021 年 5 岁以下儿童因轮状病毒导致腹泻的死亡比例似乎低于 2000 年（443342 例中的 108322 例[24.4%]，95%置信区间 21.6-29.5），但 95%CI 重叠。2000 年，第二大估计归因是诺如病毒 GII（LMICs 中的 1196134 例中的 95817 例[8.0%]，HICs 中的 225 例[24.7%]）；2021 年，志贺氏菌属在 LMICs 中的第二大估计归因（36082 例[8.1%]，443342 例），但诺如病毒在 HICs 中的第二大估计归因仍保持不变（490 例中的 84 例[17.1%]）。
我们的结果表明，在过去二十年中，在降低 12 种病原体导致的 5 岁以下儿童腹泻死亡方面取得了进展。需要加强预防工作，包括使用轮状病毒疫苗，并进行治疗以消除进一步的死亡。
比尔及梅琳达·盖茨基金会通过约翰霍普金斯大学和弗吉尼亚大学提供。
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