Enterotoxigenic Escherichia coli (ETEC) vaccines: Priority activities to enable product development, licensure, and global access

Abstract

Diarrhoeal disease attributable to enterotoxigenic Escherichia coli (ETEC) causes substantial morbidity and mortality predominantly in paediatric populations in low- and middle-income countries. In addition to acute illness, there is an increasing appreciation of the long-term consequences of enteric infections, including ETEC, on childhood growth and development. Provision of potable water and sanitation and appropriate clinical care for acute illness are critical to reduce the ETEC burden. However, these interventions are not always practical and may not achieve equitable and sustainable coverage. Vaccination may be the most cost-effective and equitable means of primary prevention; however, additional data are needed to accelerate the investment and guide the decision-making process for ETEC vaccines. First, to understand and quantify the ETEC disease burden, additional data are needed on the association between ETEC infection and physical and cognitive stunting as well as delayed educational attainment. Furthermore, the role of inappropriate or inadequate antibiotic treatment of ETEC-attributable diarrhoea may contribute to the development of antimicrobial resistance (AMR) and needs further elucidation. An ETEC vaccine that mitigates acute diarrhoeal illness and minimizes the longer-term disease manifestations could have significant public health impact and be a cost-effective countermeasure. Herein we review the ETEC vaccine pipeline, led by candidates compatible with the general parameters of the Preferred Product Characteristics (PPC) recently developed by the World Health Organization. Additionally, we have developed an ETEC Vaccine Development Strategy to provide a framework to underpin priority activities for researchers, funders and vaccine manufacturers, with the goal of addressing globally unmet data needs in the areas of research, product development, and policy, as well as commercialization and delivery. The strategy also aims to guide prioritization and co-ordination of the priority activities needed to minimize the timeline to licensure and use of ETEC vaccines, especially in in low- and middle-income countries, where they are most urgently needed.

Evaluation of a simple, rapid and field-adapted diagnostic assay for enterotoxigenic E. coli and Shigella

“…In spite of the high impact of these enteric pathogens on child health [4,5,6] a simple, sensitive and specific diagnostic test for ETEC and Shigella is lacking. Standard culture methods for Shigella lack sensitivity and assays for ETEC are only available in well-equipped research laboratories and therefore, the estimates of the burden of these pathogens are not readily available from the LMICs [1,6,7]. Consequently, regional public health officials and policy makers lack a clear appreciation of the impact that ETEC and Shigella have on child and adult health in their countries.…”

Characterization of Enteric Disease in Children by Use of a Low-Cost Specimen Preservation Method

“…We applied stringent cutoffs to minimize the likelihood of false attribution and improve applicability for vaccine trials. Ongoing trials of current Shigella and ETEC vaccines will need validation in additional countries of endemicity ( 11 , 23 , 24 ), and this study suggests that Shigella and ETEC are endemic in the pediatric population in Cameroon. The findings from this study support the use of filter paper preservation of stool specimens for PCR confirmation and, therefore, a more accurate understanding of diarrheal disease burden in the pediatric population in Cameroon.…”

Confronting Challenges to Enterotoxigenic Escherichia coli Vaccine Development

“…ETVAX has also been studied (phase 2b) in Finnish travelers to Benin, West Africa where there was an appreciable attack rate of ETEC diarrhea, and ETEC featured prominently in (~75%) cases of severe diarrhea (>16 loose stools/24 hours). In vaccine responders the protective efficacy was~52%, and far fewer vaccine recipients required antimicrobial treatment to mitigate severe illness suggesting that the vaccine was generally effective (20,99).…”