ETEC is an underrecognized but extremely important cause of diarrhea in the developing world where there is inadequate clean water and poor sanitation. It is the most frequent bacterial cause of diarrhea in children and adults living in these areas and also the most common cause of traveler's diarrhea. ETEC diarrhea is most frequently seen in children, suggesting that a protective immune response occurs with age. The pathogenesis of ETEC-induced diarrhea is similar to that of cholera and includes the production of enterotoxins and colonization factors. The clinical symptoms of ETEC infection can range from mild diarrhea to a severe cholera-like syndrome. The effective treatment of ETEC diarrhea by rehydration is similar to treatment for cholera, but antibiotics are not used routinely for treatment except in traveler's diarrhea. The frequency and characterization of ETEC on a worldwide scale are inadequate because of the difficulty in recognizing the organisms; no simple diagnostic tests are presently available. Protection strategies, as for other enteric infections, include improvements in hygiene and development of effective vaccines. Increases in antimicrobial resistance will dictate the drugs used for the treatment of traveler's diarrhea. Efforts need to be made to improve our understanding of the worldwide importance of ETEC.

https://cmr.asm.org/content/cmr/18/3/465.full.pdf

Enterotoxigenic escherichia coli in developing countries: epidemiology, microbiology, clinical features, treatment, and prevention

Acute, infectious diarrhea among children in developing countries.

Cholera continues to occur globally, particularly in sub-Saharan Africa and Asia. Oral cholera vaccines have been developed and have now been used for several years, primarily in traveller populations. The licensure in the European Union of a killed whole cell cholera vaccine combined with the recombinant B subunit of cholera toxin (rCTB-WC) has stimulated interest in protection against cholera. Because of the similarity between cholera toxin and the heat-labile toxin of Escherichia coli, a cause of travellers' diarrhoea, it has been proposed that the rCTB-WC vaccine may be used against travellers' diarrhoea. An analysis of trials of this vaccine against cholera (serotype O1) shows that for 4-6 months it will protect 61-86% of people living in cholera-endemic regions; lower levels of protection continue for 3 years. Protection wanes rapidly in young children. Because the risk of cholera for most travellers is extremely low, vaccination should be considered only for those working in relief or refugee settings or for those who will be travelling in cholera-epidemic areas and who will be unable to obtain prompt medical care. The vaccine can be expected to prevent 7% or less of cases of travellers' diarrhoea and should not be used for this purpose.

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(06)70494-7.pdf

Oral cholera vaccines: use in clinical practice

Diarrhea is the second leading cause of death in children younger than 5 years. Enterotoxigenic Escherichia coli (ETEC) strains are the most common bacterial cause of diarrhea in young children living in endemic countries and children and adults traveling to these areas. Pathogenesis of ETEC diarrhea has been well studied, and the key virulence factors are bacterial colonization factor antigens and enterotoxins produced by ETEC strains. Colonization factor antigens mediate bacteria attachment to host small intestinal epithelial cells and subsequent colonization, whereas enterotoxins including heat-labile and heat-stable toxins disrupt fluid homeostasis in host epithelial cells, which leads to fluid and electrolyte hypersecretion and diarrhea. Vaccines stimulating host anti-adhesin immunity to block ETEC attachment and colonization and also antitoxin immunity to neutralize enterotoxicity are considered optimal for prevention of ETEC diarrhea. Vaccines under development have been designed to stimulate local...

Progress and hurdles in the development of vaccines against enterotoxigenic Escherichia coli in humans

Diarrhea is a leading cause of mortality in children under 5 years along with its long-term impact on growth and cognitive development. Despite advances in the understanding of diarrheal disorders and management strategies, globally nearly 750,000 children die annually as a consequence of diarrhea. We conducted a systematic review of the efficacy and effectiveness studies. We used a standardized abstraction and grading format and performed meta-analyses for all outcomes. The estimated effect of cholera, shigella, Enterotoxigenic Escherichia coli (ETEC) and rotavirus vaccines was determined by applying the standard Child Health Epidemiology Reference Group (CHERG) rules. A total of 24 papers were selected and analyzed for all the four vaccines. Based on the evidence, we propose a 74% mortality reduction in rotavirus specific mortality, 52% reduction in cholera incidence due to their respective vaccines. We did not find sufficient evidence and a suitable outcome to project mortality reductions for cholera, ETEC and shigella in children under 5 years. Vaccines for rotavirus and cholera have the potential to reduce diarrhea morbidity and mortality burden. But there is no substantial evidence of efficacy for ETEC and shigella vaccines, although several promising vaccine concepts are moving from the development and testing pipeline towards efficacy and Phase 3 trials.

/pdf/vaccines-for-the-prevention-of-diarrhea-due-to-cholera-4hjs7efdan.pdf

Vaccines for the prevention of diarrhea due to cholera, shigella, ETEC and rotavirus

Safety and immunogenicity of an oral, inactivated enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Bangladeshi adults and children.

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Safety and immunogenicity of an oral, inactivated enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Bangladeshi adults and children.