BACKGROUND Estimates of the relative contribution of different pathogens to all-cause diarrhoea mortality are needed to inform global diarrhoea burden models and prioritize interventions. We aimed to investigate and estimate heterogeneity in the case fatality risk (CFR) of different diarrhoeal pathogens. METHODS We conducted a systematic review and meta-analysis of studies that reported cases and deaths for 15 enteric pathogens published between 1990 and 2019. The primary outcome was the pathogen-specific CFR stratified by age group, country-specific under-5 mortality rate, setting, study year and rotavirus vaccine introduction status. We developed fixed-effects and multilevel mixed-effects logistic regression models to estimate the pooled CFR overall and for each pathogen, controlling for potential predictors of heterogeneity. RESULTS A total of 416 studies met review criteria and were included in the analysis. The overall crude CFR for all pathogens was 0.65%, but there was considerable heterogeneity between and within studies. The overall CFR estimated from a random-effects model was 0.04% (95% CI: 0.026%-0.062%), whereas the pathogen-specific CFR estimates ranged from 0% to 2.7%. When pathogens were included as predictors of the CFR in the overall model, the highest and lowest odds ratios were found for enteropathogenic Escherichia coli (EPEC) [odds ratio (OR) = 3.0, 95% CI: 1.28-7.07] and rotavirus (OR = 0.23, 95% CI: 0.13-0.39), respectively. CONCLUSION We provide comprehensive estimates of the CFR across different diarrhoeal pathogens and highlight pathogens for which more studies are needed. The results motivate the need for diarrhoeal interventions and could help prioritize pathogens for vaccine development.

中文翻译：

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腹泻病原体的病死率风险：系统评价和荟萃分析。

背景 需要估计不同病原体对全因腹泻死亡率的相对贡献，以便为全球腹泻负担模型和优先干预措施提供信息。我们的目的是调查和估计不同腹泻病原体的病死风险 (CFR) 的异质性。方法 我们对 1990 年至 2019 年间发表的 15 种肠道病原体病例和死亡报告的研究进行了系统回顾和荟萃分析。主要结果是按年龄组分层的病原体特异性病死率、国家特定 5 岁以下儿童死亡率、设置、研究年份和轮状病毒疫苗引进情况。我们开发了固定效应和多级混合效应逻辑回归模型来估计总体和每种病原体的合并病死率，控制异质性的潜在预测因子。结果 共有 416 项研究符合审查标准并被纳入分析。所有病原体的总体粗 CFR 为 0.65%，但研究之间和研究内部存在相当大的异质性。从随机效应模型估计的总体 CFR 为 0.04%（95% CI：0.026%-0.062%），而病原体特异性 CFR 估计范围为 0% 至 2.7%。当病原体作为整体模型中 CFR 的预测因子时，肠致病性大肠杆菌 (EPEC) [优势比 (OR) = 3.0, 95% CI: 1.28-7.07] 和轮状病毒 (OR = 0.23，95% CI：0.13-0.39）。结论 我们对不同腹泻病原体的 CFR 进行了综合估计，并强调了需要更多研究的病原体。