Shiga toxin-producing Escherichia coli remains a critical public health challenge globally, linked to severe pediatric complications like hemolytic uremic syndrome.
Pathogen Biology and Shiga Toxin Mechanics
Numerous supportive public health measures have led people to erroneously believe that epidemics of many bacterial infectious diseases are no longer a serious health risk. However, Shiga-toxin-producing Escherichia coli (STEC) still poses a threat to public health. Shiga toxin (Stx) is prototypically synthesized by the bacterium Shigella dysenteriae serotype 1, with genetically and structurally related toxin variants produced by certain serotypes of E. coli, including enterohaemorrhagic strains of E. coli (EHEC). The pathogen Shiga toxin producing Escherichia coli (STEC), also known as verotoxigenic, verocytotoxigenic, verotoxin-producing, verocytotoxin-producing E. coli (VTEC) or Enterohemorrhagic E. coli (EHEC), is a subset of pathogenic bacterium E. coli. It carries genes that can produce the Shiga toxins, stx1 with four subtypes (a, c, d and e), and stx2, with 15 subtypes (a to o) recently described. These toxins particularly affect small blood vessels, such as those found in the digestive tract and the kidneys. The outcome of infection is dependent on several factors, including the stx subtype. Although all STEC strains are potentially pathogenic in humans and capable of causing diarrhoea, serious illness with bloody diarrhoea and haemolytic-uremic syndrome (HUS) is more often associated with STEC that carry stx2 genes − in particular the stx2a or stx2d subtypes. This highlights the importance of subtyping the Shiga toxin genes in clinical cases. In Europe, five serogroups (O157, O26, O111, O103 and O145) are associated with the majority of severe cases in humans. Although a recent pathogenicity assessment of STEC affirms that serogroup is not a marker of pathogenicity, data can be useful for identifying STEC and to observe the circulation of the different STEC serogroups in food and human cases.
Escherichia coli O157:H7 and other Shiga toxin (Stx)-producing E. coli (STEC) strains cause diarrhea, hemorrhagic colitis, and the hemolytic uremic syndrome. The mechanisms underlying the adherence of STEC to epithelial cells are only partly understood. The ability to adhere to epithelial cells is an important virulence trait, because adherence presumably enables enteric pathogens to deliver toxins efficiently to host organs, overcome peristaltic clearance, and gain access to host-derived nutrients. Intimin is the best-characterized E. coli O157:H7 adherence molecule. Encoded by eae, intimin mediates the attaching and effacing lesion caused by enteropathogenic E. coli (EPEC) and many STEC serotypes and is an important component of pathogenicity. Two cosmids from an E. coli O157:H7 DNA library contain an adherence-conferring chromosomal gene encoding a protein similar to iron-regulated gene A (IrgA) of Vibrio cholerae. This product is termed the IrgA homologue adhesin (Iha), which is encoded by iha. Iha is 67 kDa in E. coli O157:H7 and 78 kDa in laboratory E. coli and is structurally unlike other known adhesins. DNA adjacent to iha contains tellurite resistance loci and is conserved in structure in distantly related pathogenic E. coli, but it is absent from nontoxigenic E. coli O55:H7, sorbitol-fermenting Stx-producing E. coli O157:H−, and laboratory E. coli, a region termed the tellurite resistance- and adherence-conferring island. Iha is a novel bacterial adherence-conferring protein contained within an E. coli chromosomal island of conserved structure that pathogenic E. coli O157:H7 has only recently acquired.
Clinical Outcomes and Pediatric Complications
Shiga toxin–producing Escherichia coli (STEC) bacteria are responsible for a spectrum of disease, ranging from simple to bloody diarrhea, and pose increased risk for severe complications, including hemolytic uremic syndrome (HUS) in children <5 years of age and the elderly. Bacillary dysentery due to infection by Stx-producing bacteria, characterized by acute infectious diarrhea, primarily affects children aged <5 years. Endemic bacillary dysentery occurs globally, including in portions of Africa, Southeast Asia, and the Indian subcontinent, with an estimated 2–7 per 1000 children per year requiring clinical care and 164,300 deaths per year attributable to shigellosis. By contrast, STEC-associated illnesses in young children are more prevalent in developed countries, in which residents consume higher levels of beef and beef products.
STEC infection causes gastroenteritis, accompanied by stomach cramps, abdominal pain, vomiting, and diarrhoea, which is often bloody. The incubation period is from three to eight days after exposure. The infective dose of STEC is low.
Surveillance Data and Regional Distribution in France
Although STEC infections represent a global burden that is difficult to characterize, in part because of differences in diagnostic capacity and disease surveillance systems, an estimated 2.8 million STEC infections and 3,890 STEC-HUS cases occur annually worldwide. Estimated notification rates of STEC infection in Europe during 2017–2021 ranged from 1.6 to 2.4 cases/100,000 population. In France, STEC surveillance is conducted through voluntary clinical and microbiologic surveillance of HUS in children <15 years of age. Annual incidence rates for pediatric STEC-HUS in France remain relatively high, and in recent years have been close to estimated notification rates for all STEC infections in Europe. Since 1996, annual incidence rates have ranged from 0.6 to 1.5 cases/100,000 population (73 to 168 cases reported annually), and incidence has exceeded 4 cases/100,000 population in children <3 years of age. The primary serogroups identified in cases are O26, O80, and O157; an increase of serogroups O26 and O80 in the 2010s coincided with a decrease in O157.
Transmission Routes and Animal Reservoirs
Major outbreaks of diarrheal diseases caused by EHEC may be due to the ingestion of foods such as uncooked meat, unpasteurized milk, water contaminated with these bacteria, and by the contamination of foods used in the preparation of fast-food. Perhaps the largest outbreak of hemorrhagic colitis was caused by an O157 infection in and around Sakai City, Japan, in 1996, which resulted in approximately 1000 hospitalizations among 7000 infected cases. Many non-O157 STEC serotypes have been increasingly reported, and a massive outbreak caused by the hybrid STEC/enteroaggregative E. coli (EAEC) O104:H4 strain occurred in northern Germany from May to June 2011. More recently, 439 outbreaks and 5 deaths caused by EHEC-contaminated romaine lettuce were reported in multiple states of the United States in 2018.
Ruminants are the primary reservoir, excreting STEC in their feces, thereby potentially contaminating food and their environment and posing a risk for STEC contamination in humans. Although STEC pose a substantial outbreak potential, most infections are sporadic; only 3% of cases are linked to recognized outbreaks.
Diagnostic Challenges and Microbiota Interactions
Shiga toxin-producing Escherichia coli (STEC) infection is notifiable in the EU, and the European case definition is publicly available. Diagnostics and surveillance rely on identifying these distinct serogroups and subtyping the Shiga toxin genes in clinical cases, as the overall outcome of infection is dependent on several factors including the specific stx subtype.
