Case fatality risk of diarrhoeal pathogens: a systematic review and meta-analysis.
Ernest O Asare, Dianna Hergott, Jessica Seiler, Brooks Morgan, Helena Archer, Alison B Wiyeh, Boya Guo, Matt Driver, Birgitte Giersing, Mateusz Hasso-Agopsowicz, Jairam Lingappa, Benjamin A Lopman, Virginia E Pitzer
Author Information
Ernest O Asare: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, CT, USA. ORCID
Dianna Hergott: Department of Epidemiology, University of Washington, Seattle, WA, USA.
Jessica Seiler: Department of Epidemiology, University of Washington, Seattle, WA, USA.
Brooks Morgan: Department of Epidemiology, University of Washington, Seattle, WA, USA.
Helena Archer: Department of Epidemiology, University of Washington, Seattle, WA, USA.
Alison B Wiyeh: Department of Epidemiology, University of Washington, Seattle, WA, USA.
Boya Guo: Department of Epidemiology, University of Washington, Seattle, WA, USA.
Matt Driver: Department of Epidemiology, University of Washington, Seattle, WA, USA.
Birgitte Giersing: Vaccine Product Delivery Research, Immunization, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland.
Mateusz Hasso-Agopsowicz: Vaccine Product Delivery Research, Immunization, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland.
Jairam Lingappa: Departments of Global Health, Medicine, and Pediatrics, University of Washington, Seattle, WA, USA.
Benjamin A Lopman: Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Virginia E Pitzer: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, CT, USA.
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.
