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Shiga toxin-producing Escherichia coli (STEC)

Shiga toxin-producing Escherichia coli, known as STEC, are pathogenic bacteria belonging to a specific group of diarrheagenic E. coli. They are Gram-negative, facultative anaerobic bacteria capable of tolerating numerous environmental stresses, including temperature variations (they can survive between 6°C and 45.5°C, with an optimal growth temperature of 36°C-40°C), pH (ranging from 4.4 to 9, with an optimal growth pH of 6-7), and nutrient availability.
Although these microorganisms have been known for decades, they were identified as causal agents of Haemolytic Uremic Syndrome (HUS) by Professor Mohammed Karmali and his team in 1983 (Karmali et al, 1983).
STEC derive their name from the ability to produce potent cytotoxins, Shiga toxins (Stx), which can produce two main antigenic variants (Stx1 and Stx2) and numerous subtypes:

  • Stx1, very similar to the toxin produced by Shigella dysenteriae, is divided into three subtypes: Stx1a, Stx1c, and Stx1d;
  • Stx2, which is divided into more than eleven subtypes, some of which are associated with a greater severity of STEC infection.

Some STEC strains express only one type of toxin, while others express a combination of subtypes of one or both types. The Stx toxins are encoded by the stx1 and stx2 genes located on lysogenic lambdoid bacteriophages, mobile genetic elements integrated into the bacterial chromosome.

STEC strains of serogroup O157 were the first to be identified as STEC and are commonly associated with human disease worldwide. However, it is well established that STEC strains belonging to different serogroups (classified as non-O157) also significantly contribute to the disease burden caused by these pathogens, including fatalities and chronic disabilities. In Europe, the most frequently detected non-O157 serogroups include O26, O111, O80, O145, and O103. Notably, the most severe human cases are associated with STEC strains producing Stx2, regardless of their serogroup.


Pathogenesis of STEC

After ingestion, STEC strains bypass the stomach environment using various acid resistance mechanisms and reach the intestine, localizing in the colon where they outcompete other microorganisms in the microbiota.
Many STEC strains use an adhesion mechanism to the intestinal mucosa that subverts enterocyte functionality, causing a histopathological lesion known as “attaching and effacing” (A/E), also present in other pathogenic E. coli strains (EPEC), characterized by three main events:

  • Initial adhesion of the bacterium to the host cell;
  • effacement of microvilli at the site of bacterial attachment;
  • formation of pedestal structures.

This mechanism is very similar in STEC and EPEC strains, which encode a key protein in the adhesion process to the enterocyte: intimin.
The A/E lesion, although very common in STEC strains, does not represent the only mechanism used by these microorganisms to colonize the intestine.
The Stx produced by STEC strains within the intestinal lumen undergoes retrograde transport through enterocytes toward the basal lamina vessels, reaching the bloodstream in its intact form.  Once in circulation, the toxin targets organs expressing its receptor (Gb3) on their surface, particularly endothelial cells in the renal glomerulus and the brain, leading to both localized and systemic damage.


Epidemiology of STEC

STEC strains are zoonotic agents (link to an Italian website) considered of priority importance in Europe according to Directive 2003/99/EC (Zoonosis Directive). The primary natural reservoir of STEC strains is the gastrointestinal tract of cattle and other domestic and wild ruminants, although these bacteria have been identified in a wide range of animal species. It is important to note that ruminants are generally asymptomatic carriers of STEC and do not develop clinical symptoms.
From animal reservoirs, transmission to humans can occur through various routes:

  • Consumption of contaminated food of animal origin (e.g., meat and meat products, milk, cheese, or other dairy products) that has not undergone adequate heat treatment (e.g., cooking, pasteurization). These are considered the main vehicles of STEC infection in humans. The consumption of water and vegetables, particularly leafy greens, accidentally contaminated with STEC can also play a significant role. Food handling, both at household level and throughout the production chain, if not properly controlled through the proper hygiene measures, may lead to via cross-contamination between food matrices and the processing environment. Food contamination may also occur through handling by individuals infected with STEC (food handlers);
  • Direct contact with infected animals or environment exposure (e.g., recreational areas in pastures where infected cattle graze). This transmission route is relevant in the context of recreational activities in farm schools, agritourism, and petting zoos;
  • Person-to-person transmission (fecal-oral transmission). This transmission route is particularly relevant in family settings with close interpersonal contacts and in community settings such as nurseries, schools, and recreational centres hosting children.


Clinical manifestations of STEC infections

Some subgroups of the population, particularly children under 5 years old and the elderly, are more susceptible to severe forms of STEC infections, such as Haemolytic Uremic Syndrome (HUS). In children, the infectious dose is low.

STEC infection typically manifests with clinical symptoms appearing after an incubation period of approximatly 3-4 days (range: 2-12 days). The clinical onset is characterized by severe abdominal pain, diarrhoea with multiple episodes (especially on the second and third day), and vomiting. The disease often present without fever. If present, the fever is usually mild and does not exceed 38°C. After one or two days, blood may appear in the stool as streaks or haemorrhagic diarrhoea. The prodromal abdominal symptoms associated with haemorrhagic colitis can mimic conditions such as acute abdomen, intussusception, appendicitis, or volvulus (Ricciuto, 2024).

After the prodromal phase, in most cases, the disease is usually self-limiting, with spontaneous resolution of symptoms within approximately one week. However, in about 10-15% of cases, particularly with Stx2-producing STEC strains, the disease progresses to severe forms with systemic involvement (haemorrhagic colitis, HUS). HUS is a syndrome characterized by haemolytic anemia, thrombocytopenia, acute renal failure, and potential involvement of other organs.

Other clinical signs may include pallor, asthenia, anorexia, generalized edema, weight gain, neurological symptoms such as altered consciousness, lethargy, seizures, haematuria, proteinuria, and jaundice. At this stage, laboratory tests (complete blood count, renal function, urine examination, LDH) are crucial. Laboratory findings typically include anemia, thrombocytopenia, and elevated LDH levels. The most frequent clinical presentation is acute renal failure (80% of cases), due to which patients should be referred to a specialized nephrology unit as they often require dialysis and transfusions. In a minority of cases (2-5%), cardiomyopathy may occur (Ricciuto, 2024).


Diagnosis of STEC Infections

Timely diagnostic suspicion of STEC infection based on clinical symptoms is essential, particularly in children under five years old (high-risk patients for HUS), to ensure proper clinical monitoring and management of potential systemic complications.

In children under 5 years with severe abdominal pain, diarrhea, and blood in the stool, STEC infection should always be suspected, and stool samples should be sent to the laboratory for diagnostic confirmation. Not all laboratories are equipped to perform diagnostic tests for STEC. Therefore, it is necessary to verify in advance the availability of STEC tests and refer to laboratories that conduct investigations based on molecular methods (PCR, Real-Time PCR), usually the laboratories of large regional hospital facilities.

STEC infection should always be suspected in children under five years old presenting with severe abdominal pain, diarrhoea, and blood in the stools. Faecal samples should be sent to a laboratory for diagnostic confirmation. Not all laboratories are equipped to perform STEC diagnostic tests. Therefore, it is necessary to verify in advance the availability of STEC tests and refer to laboratories that conduct investigations based on molecular methods (PCR, Real-Time PCR), usually major hospital laboratories.

Laboratory diagnosis of STEC infection is based on the detection of the stx1 and stx2 genes in faecal samples using molecular methods (PCR, Real-Time PCR). These methods have become increasingly available in hospital laboratories and are currently considered the "gold standard" due to their accuracy and timeliness (results available within hours). Other diagnostic tests, such as stool cultures or immunochromatographic methods, which were more commonly used in the past, are considered less reliable and may yield false negatives.

Faecal samples for STEC testing should be collected as early as possible after symptom onset (diarrhoea) and sent promptly to a laboratory equipped for molecular diagnostics for immediate examination. If this is not possible, they can be kept refrigerated (+4°C) for a few days or alternatively frozen at -20°C for later examination. However, this latter possibility may negatively impact the execution of diagnostic tests and should be avoided where possible.
For HUS cases, direct detection of faecal Stx via Vero cell cytotoxicity assay and indirect serological tests for anti-LPS antibodies against common STEC serogroups (O157, O26, O111, O80, O145, O103) are available exclusively at the Italian National Institute of Health (ISS).


Surveillance of STEC Infections in Italy and Europe

In Italy, reporting STEC infections and HUS cases is mandatory under the Ministerial Decree of March 7, 2022, "Revisione del sistema di segnalazione delle malattie infettive (Revision of the Infectious Disease Notification System) (PREMAL)”. General practitioners, paediatricians, and hospital health departments must report STEC infections and HUS cases to the local health authority (ASL), which validates and transmits the notification to the national PREMAL system.

Data on the incidence of STEC infections and HUS in Italy are annually transmitted to the European Centre for Disease Prevention and Control (ECDC) and are accessible via the Surveillance ATLAS of infectious diseases platform. This data flow primarily consists of paediatric HUS cases collected by Italian Registry of Hemolytic Uremic Syndrome coordinated by the Istituto Superiore di Sanità. The HUS registry is based on voluntary reporting of cases by paediatric nephrology centres that regularly participate in the surveillance of this disease. Quarterly updates of the registry's data are published on the "EpiCentro" website, where additional information on clinical management and a list of participating paediatric nephrology centres are available.

Some Italian regions (Lombardy and Apulia) have implemented surveillance initiatives for haemorrhagic gastroenteritis (HGE) in children, aiming for early identification of STEC infections. These initiatives use molecular screening for STEC on faecal or rectal swab samples from children with HGE.


Epidemiological investigation of cases of STEC infection

STEC infections have a high epidemic potential. Outbreak sizes vary, with most outbreaks involving a few cases within families, daycare centres, and preschools, where person-to-person transmission is common.

Community-wide outbreaks can affect hundreds of individuals over large geographic areas, typically resulting from the distribution of STEC-contaminated food products.

Prompt notification of STEC cases to the ASL is crucial, along with immediate collection of exposure data from patients to facilitate epidemiological investigations and targeted environmental and food sampling. HUS is considered a sentinel event that may indicate additional STEC cases among close contacts (e.g., family, daycare centers) or in the broader community.

Outbreak investigations aim to identify and remove sources of contamination to protect public health, preventing other people from being exposed to the same source of infection and developing illness. This activity, starting from the reporting of cases by paediatricians and family doctors, primarily involves the prevention departments of local health authorities (public health and hygiene services, food hygiene and nutrition services, veterinary services). This requires a collaborative multidisciplinary and multisectoral approach, capable of integrating knowledge and expertise across a wide and diverse range of events.


Further Informations

Elenco Argomenti