Abstract
The enterotoxigenic Escherichia coli (ETEC) are a diverse and genetically plastic pathologic variant (pathovar) of E. coli defined by their production of heat-labile (LT) and heat-stable (ST) enterotoxins. These pathogens, which came to recognition more than four decades ago in patients presenting with severe cholera-like diarrhea, are now known to cause hundreds of millions of cases of symptomatic infection annually. Children in low-middle income regions of the world lacking access to clean water and basic sanitation are disproportionately affected by ETEC. In addition to acute diarrheal morbidity, these pathogens remain a significant cause of mortality in children under the age of five years and have also been linked repeatedly to sequelae of childhood malnutrition and growth stunting. Vaccines that could prevent ETEC infections therefore remain a high priority. Despite several decades of effort, a licensed vaccine that protects against the breadth of these pathogens remains an aspirational goal, and the underlying genetic plasticity of E. coli has posed a fundamental challenge to development of a vaccine that can encompass the complete antigenic spectrum of ETEC. Nevertheless, novel strategies that include toxoids, a more complete understanding of ETEC molecular pathogenesis, structural details of target immunogens, and the discovery of more highly conserved antigens essential for virulence should accelerate progress and make a broadly protective vaccine feasible.
Highlights
Reviewed by: Jaime Torres, Central University of Venezuela, Venezuela Yun-Chi Chen, Morgan State University, United States
Despite several decades of effort, a licensed vaccine that protects against the breadth of these pathogens remains an aspirational goal, and the underlying genetic plasticity of E. coli has posed a fundamental challenge to development of a vaccine that can encompass the complete antigenic spectrum of enterotoxigenic Escherichia coli (ETEC)
ETEC are responsible for hundreds of millions of cases of diarrheal illness [1], disproportionately affecting young children under the age of five who have yet to become immune through prior exposure [2]
Summary
Enterotoxigenic E. coli (ETEC) are ubiquitous pathogens in areas of the world where clean water and sanitation remain limited. While ETEC are more prevalent among young children in LMICs, they are not limited to any particular age group and can be found globally These pathogens are a major cause of diarrheal morbidity in older children and adults of LMICs [7], and perennially the most common etiology of diarrhea in travelers to LMICs. These pathogens are a major cause of diarrheal morbidity in older children and adults of LMICs [7], and perennially the most common etiology of diarrhea in travelers to LMICs Both sporadic cases [8] as well as multiple large scale outbreaks [9,10,11,12,13,14,15,16] are welldocumented in the United States and other industrialized regions demonstrating that even where clean water and sanitation are widely available these organisms can be problematic. Heterogeneity of disease burden estimates [1, 4, 17,18,19], can significantly confound cost-effectiveness estimates fundamental to setting vaccine development priorities, ETEC vaccines remain high priority targets of advisory groups including the World Health Organization (WHO) Product Development Vaccines Advisory Committee (PDVAC) [20]
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