It is estimated that ETEC causes about 220 million diarrhoea episodes globally, with about 75 million episodes in children under 5 years of age, resulting in between 18 700 deaths (Institute for Health Metrics and Evaluation (IHME) estimates), and 42 000 deaths (maternal child epidemiology (MCEE) estimates) in children younger than 5 years.  While diarrhoeal mortality rates for ETEC are declining due to improvements in economic development and availability of safe water and sanitation, these reductions have not been paralleled by significant declines in diarrhoea-associated morbidity, which continues to impact negatively on infant and child health in many low- and middle-income countries (LMICs).

ETEC may be the first enteric illness encountered infants in LMICs, and full protection is needed to cover peak incidence and mortality through the first 24 months of life. The widespread use of antibiotics contributes to the increased spread of anti-microbial resistant (AMR) strains of ETEC and other bacteria. Prevention and treatment options to address diarrhoeal illness from ETEC are available; however, their implementation and sustainability is not always practical in low-resource settings. Consequently, the need to develop vaccines with equitable access, remains a public health priority for the WHO, and been identified as priority by IVB’s Product Development for Vaccines Advisory Committee.

WHO has developed a draft Preferred Product Characteristics (PPC) to promote the development of a safe, effective and affordable ETEC vaccine that reduces mortality and morbidity due to moderate-to-severe diarrhoeal disease in infants and children under 5 years of age in low-middle income countries (LMICs).

Updated April 30, 2022

To better inform the Full Vaccine Value Assessment for enteric vaccines, including ETEC and Shigella, a Burden of Enteric Disease Working Group (BoED WG) has been established to better understand the approach to calculate mortality burden of enteric infections. The BoED WG assessed the sources of data used to estimate mortality, reviewed modelling methodologies, analysed underlying outputs and assumptions, and published a set of recommendations for studies to be included in future assessment of morbidity estimates(3). Further results will be published by the end of 2021. Workstreams related to morbidity assessment and quantification will conclude before end of 2023.

Drug resistant Enterobacteriaceae which include E. Coli have been identified as critical pathogens for which there is a priority to develop antimicrobials(4). WHO is evaluating the role of ETEC vaccines on antibiotic use, health and economic burden due to an infection with a resistant pathogen, and impact on equity and social justice.

1) Khalil IA, Troeger C, Blacker BF, et al. Morbidity and mortality due to shigella and enterotoxigenic Escherichia coli diarrhoea: the Global Burden of Disease Study 1990–2016. The Lancet Infectious Diseases 2018; 18: 1229–40.

2) Lanata CF, Fischer-Walker CL, Olascoaga AC, Torres CX, Aryee MJ, Black RE. Global Causes of Diarrheal Disease Mortality in Children <5 Years of Age: A Systematic Review. PLoS One 2013; 8. DOI:10.1371/journal.pone.0072788.

3) Butkeviciute E, Prudden HJ, Jit M, Smith PG, Kang G, Riddle MS, Lopman BA, Pitzer VE, Lanata CF, Platts-Mills JA, Breiman RF. Global diarrhoea-associated mortality estimates and models in children: Recommendations for dataset and study selection. Vaccine. 2021 Jun 13.

4) Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, Pulcini C, Kahlmeter G, Kluytmans J, Carmeli Y, Ouellette M, Outterson K, Patel J, Cavaleri M, Cox EM, Houchens CR, Grayson ML, Hansen P, Singh N, Theuretzbacher U, Magrini N; WHO Pathogens Priority List Working Group. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018 Mar;18(3):318-327. doi: 10.1016/S1473-3099(17)30753-3. Epub 2017 Dec 21. PMID: 29276051.