Enterohemorrhagic Escherichia Coli (EHEC)


Article Author:
Rawish Fatima


Article Editor:
Muhammad Aziz


Editors In Chief:
Venkat Minnaganti
John Brusch
Janak Koirala


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
6/12/2019 9:27:02 PM

Introduction

Escherichia coli is a gram-negative, rod-shaped bacteria belonging to the genus Escherichia that commonly resides in human colon. Shigatoxigenic along with verotoxigenic E. coli (STEC), (VTEC) are strains of E. coli that are known to produce Shiga toxin and Shiga-like toxin (verotoxin) respectively. The strains that cause ailments in humans are commonly known as enterohemorrhagic E. coli (EHEC). The terms mentioned above are often used interchangeably. EHEC serotype O157:H7 is a human pathogen found to be responsible for bloody diarrhea outbreaks and hemolytic uremic syndrome (HUS) worldwide. [1]

Etiology

The infections caused by E. coli O157:H7 range from asymptomatic to severe. Few individuals can develop potentially fatal complications like hemolytic uremic syndrome (HUS). Chronic renal pathology may persist at times among those that survive. Humans are known to acquire E. coli O157:H7 in multiple ways, for example, contaminated food and water and direct contact with infected animals and humans. Consumption of contaminated food like ground beef, dairy products, and fresh produce is responsible for the majority of the outbreaks. [2]

Cattle are considered as the principal reservoirs for E.coli O157:H7; contamination takes place through their use as food, their manure used as a fertilizer, and through water supplies contaminated by runoff from cattle farms. Although variation has been reported in fecal shedding of E. coli O157:H7 has been ranging from 0% to 80% among cattle population, a seasonal pattern has also been shown, with prevalence increasing during summer months. Elevated temperature in summers might be responsible for favoring bacterial proliferation and survival.

Epidemiology

The Centers for Disease Control and Prevention (CDC) estimated that foodborne E. coli O157:H7 is responsible for over 63,000 illnesses per year that leads to more than 2100 hospitalizations and deaths in the United States. The economic burden of illness due to this bacteria resulting from medical expenses and death and loss of productivity is estimated to be $405 million per year. [3],[4]

According to the 10 US sites of the Foodborne Diseases Active Surveillance Network (FoodNet) preliminary report of 2017, STEC was listed as one of the 9 pathogens commonly transmitted by food. As compared to the incidence 2014 through 2016 the incidence in 2017 was 28% higher. Fifty-seven cases of HUS were identified in 2016; the incidence was not significantly different from 2013 through 2015.

In Norway, HUS was labeled as the second most common cause of acute kidney infection (AKI) in children with an estimated average annual incidence of 0.5 cases per 100,000 children.

Pathophysiology

On entry, EHEC strains produce Shiga-like toxins (Stx) which mediate the dysregulation of membrane ion channels in the epithelial membrane of the intestine that leads to loss of ions and a massive amount of water. This toxin also acts as a cell transduction and immune modulator leading to proinflammatory and pro-apoptotic sequela. Endothelial lesions in the microvasculature of kidney and less frequently of other organs is found to be responsible for sequela of the hemolytic uremic syndrome. Kidney and gastrointestinal (GI) tract are the most commonly affected organs in HUS, but evidence of central nervous system (CNS), pancreatic, skeletal, and myocardial involvement has also been shown in the studies conducted. The mechanism of this microvascular injury is unknown, but evidence shows that verocytotoxin plays a role in mediating cell injury with a resultant change in the normal anti-coagulant profile of the endothelial cell to a procoagulant state. [5] 

After E. coli infection, several factors determine the progression of the disease to HUS like:

  1. Bacterial strain: Serotype O157:H7 is most often found to be responsible
  2. Age: The rate of progression to HUS is higher in young children. A study showed it to be 12.9% in children younger than 5 years of age, 6.8% in children between 5 to 10 years, 8% in children older than 10 years of age.
  3. Antibiotic: Treatment with antibiotic therapy for E. coli O157:H7 has shown to increase the risk of HUS
  4. Environmental and genetic factors

Histopathology

In the acute phase of HUS, specimens of kidney show microvascular injury characterized by deposition of microthrombi along with detached and swollen glomerular endothelial cells associated with infiltration of inflammatory cells. Similar changes have been described in other organs. This shows that HUS is a multisystem disease characterized by endothelial cell injury. [6]

Toxicokinetics

Enterohemorrhagic E. coli is not invasive, making bacteremia rare. It adheres to mammalian cells, secreting bacterial proteins into host cells through type III secretion system. Ribosome-inactivating Shiga-like toxins (Stx1 and Stx2) are secreted which are responsible for organ damage. Stx 2 has been found to be more often associated with severe disease. Shiga toxin consists of 2 subunits: A and B. Proteolysis further degrades subunit A into A1 and A2. In target organs, for example, the kidney, brain, and gut, subunit B attaches to glycolipid receptors on the cell surface. In humans, these receptors have been identified as Gb3 which are mainly expressed in kidney tubular cells, brain and gut epithelium. The cytotoxicity is further amplified in the kidney due to the interplay of tumor necrosis factor- alpha. After it binds to the cell surface, Shiga toxin is endocytosed and transported to the Golgi apparatus and endoplasmic reticulum in a retrograde direction from there it is then translocated to the cytosol where it inactivates ribosomes and causes cell death. [5],[7]

History and Physical

EHEC clinically manifests as bloody diarrhea (visibly bloody stool specimen) without fever and a usually a white blood cell count above 10,000/microL at times associated with abdominal pain. The incubation period between exposure to EHEC and onset of symptoms is typically 3 to 4 days. [8],[3],[7]

HUS is a major complication of EHEC infection. It is a clinical triad of anemia secondary to hemolysis, impaired renal function, and thrombocytopenia mainly affecting young children. HUS following bloody diarrhea secondary to EHEC is called D+ HUS or typical HUS; whereas, HUS caused by other causes is referred to as D- HUS or atypical HUS.

Evaluation

Patients suspected of infection from EHEC are tested for Shiga toxin or EHEC by doing stool culture. Blood test and a urine test is also conducted in patients presenting with HUS which can show low red blood cell and platelets count and assess renal functions respectively. [9]

Treatment / Management

Supportive treatment is provided to those having EHEC diarrhea.[5]

Electrolytes and water deficiency should be replaced, especially in patients with D+ HUS. The current advancements in dialysis and intensive care have reduced mortality, mainly in young children. The best option for children is peritoneal dialysis. Bilateral nephrectomy is life-saving and can control the spread of microvascular lesions when the kidneys are the main site of the disease involvement especially in cases of therapy-resistant malignant hypertension. Because the prognosis is often severe, immediate supportive treatment may improve the outcome. Other supportive treatments available for patients with HUS are mainly dependent on their symptoms and mainly include: 

  • Red blood cell transfusions
  • Platelet transfusions
  • Plasma exchange

In general, the prevention of foodborne diseases must be based on good hygienic practices and control of the contamination of foods by biological and chemical hazards. This can be achieved most effectively through the application of food safety assurance programmes. Vaccines for EHEC are under study but have not been approved by FDA yet.

Differential Diagnosis

In all patients with HUS symptoms, Shiga toxin/STEC should be tested along with ADAMTS13 activity as clinical presentation, and the organ involvement in hemolytic uremic syndrome and thrombotic thrombocytopenic purpura can overlap. In patients of unusual age or in whom diarrhea is absent anomalous or atypical E. coli, HUS is a possible diagnosis. [5]

Prognosis

Diagnosing EHEC infection early and starting prompt fluid replacement has shown to improve long-term outcomes by reducing damage to the kidney. Advancement in dialysis therapy and improved care of the critically ill children have resulted in a significant reduction in acute mortality of HUS to such an extent that chronic complications in long-term survivors are becoming more apparent. [10]

Complications

Often, EHEC associated with bloody diarrhea can resolve without any long-term consequences. The prognosis is severe mainly in patients developing HUS. After being treated for HUS, some children can never recover renal functions and thus require long-term replacement therapies for renal functions whereas those who recover renal functions are at risk of late development of renal disease. Some children may have residual extrarenal problems including neurological defects, insulin dependent diabetes mellitus, pancreatic insufficiency or gastrointestinal complications. HUS is thus a disease with substantial mortality and multisystem morbidity. This shows that importance should be given to extra-renal manifestations in the acute phase and renal functions should be monitored in long-term follow-up of HUS patients. [11]

Deterrence and Patient Education

Taking measures like usage of drinkable water for food preparation, observing improved hygienic conditions during the slaughter of animals, use of appropriate measures of food processing, cooking food properly, educating/teaching food handlers and farm workers about the principles of food hygiene, and its application can significantly reduce the incidence of EHEC infections.

Pearls and Other Issues

EHEC is a foodborne disease that can be reduced by practicing good hygiene and controlling the contamination of food. It is a human pathogen found to be responsible for bloody diarrhea outbreaks and hemolytic uremic syndrome (HUS) worldwide. There is no specific treatment, but studies are being conducted. Supportive measurements are the mainstay of treatment.

Enhancing Healthcare Team Outcomes

The management of EHEC is multidisciplinary. For most patients, supportive treatment will suffice. Electrolytes and water deficiency should be replaced, especially in patients with D+ HUS. The current advancements in dialysis and intensive care have reduced mortality, mainly in young children. The best option for children is peritoneal dialysis. Bilateral nephrectomy is life-saving and can control the spread of microvascular lesions when the kidneys are the main site of the disease involvement especially in cases of therapy-resistant malignant hypertension. Because the prognosis is often severe, immediate supportive treatment may improve the outcome. Other supportive treatments available for patients with HUS are mainly dependent on their symptoms and may include plasma exchange and blood transfusions.

In general, the primary care provider and nurse practitioner should educate the patient on the prevention of foodborne diseases.  This can be achieved most effectively through the application of food safety assurance programmes. Vaccines for EHEC are under study but have not been approved by FDA yet.[12]


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Enterohemorrhagic Escherichia Coli (EHEC) - Questions

Take a quiz of the questions on this article.

Take Quiz
An afebrile child presents with a complaint of abdominal pain and bloody diarrhea. Which bacterial infection should be ruled out?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 4-year-old child presents with weakness, lethargy, and bruises on the body. The parents mention episodes of bloody diarrhea few weeks before the current symptoms. For what should the child be immediately tested to help diagnose his condition?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What differential should be ruled out in patients suspected to be suffering from hemolytic uremic syndrome?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Involvement of microvasculature of which organ is mainly responsible for the sequela of hemolytic uremic syndrome?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What measures can be taken to prevent the spread of enterohemorrhagic Escherichia coli (EHEC)?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A school-age child presents with symptoms of bloody diarrhea for two days. Besides doing his stool, blood, and urine examination which step can improve his long-term disease outcome?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A middle-aged man who tested positive for enterohemorrhagic Escherichia coli (EHEC) strain O104:H4 develops hemolytic uremic syndrome (HUS). He did not seek medical attention for episodes of bloody diarrhea preceding the current symptoms. Family history is not positive for HUS. Which of the factors might have played a role in the progression of his disease to HUS?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 5-year-old boy tested positive for Shiga toxin on stool culture after presenting with bloody diarrhea and abdominal pain. During his admission, he develops anemia, thrombocytopenia, worsening kidney functions, and hypertension. His kidney functions continue to worsen, and he further develops therapy resistant malignant hypertension. Which of the following is the most appropriate life-saving management for the child?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Enterohemorrhagic Escherichia Coli (EHEC) - References

References

Preliminary Incidence and Trends of Infections with Pathogens Transmitted Commonly Through Food - Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2006-2017., Marder Mph EP,Griffin PM,Cieslak PR,Dunn J,Hurd S,Jervis R,Lathrop S,Muse A,Ryan P,Smith K,Tobin-D'Angelo M,Vugia DJ,Holt KG,Wolpert BJ,Tauxe R,Geissler AL,, MMWR. Morbidity and mortality weekly report, 2018 Mar 23     [PubMed]
The prevalence of Escherichia coli O157:H7 fecal shedding in feedlot pens is affected by the water-to-cattle ratio: A randomized controlled trial., Beauvais W,Gart EV,Bean M,Blanco A,Wilsey J,McWhinney K,Bryan L,Krath M,Yang CY,Manriquez Alvarez D,Paudyal S,Bryan K,Stewart S,Cook PW,Lahodny G Jr.,Baumgarten K,Gautam R,Nightingale K,Lawhon SD,Pinedo P,Ivanek R,, PloS one, 2018     [PubMed]
Shiga toxins and the pathophysiology of hemolytic uremic syndrome in humans and animals., Mayer CL,Leibowitz CS,Kurosawa S,Stearns-Kurosawa DJ,, Toxins, 2012 Nov 8     [PubMed]
Clinical features, therapeutic interventions and long-term aspects of hemolytic-uremic syndrome in Norwegian children: a nationwide retrospective study from 1999-2008., Jenssen GR,Vold L,Hovland E,Bangstad HJ,Nygård K,Bjerre A,, BMC infectious diseases, 2016 Jun 13     [PubMed]
Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations., Salvadori M,Bertoni E,, World journal of nephrology, 2013 Aug 6     [PubMed]
Diarrheagenic Escherichia coli., Gomes TA,Elias WP,Scaletsky IC,Guth BE,Rodrigues JF,Piazza RM,Ferreira LC,Martinez MB,, Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology], 2016 Dec     [PubMed]
Wasey A,Salen P, Escherichia Coli (E Coli 0157 H7) null. 2018 Jan     [PubMed]
Bystrom PV,Beck RJ,Prahlow JA, Hemolytic uremic syndrome caused by E. coli O157 infection. Forensic science, medicine, and pathology. 2017 Jun     [PubMed]
Cheong HI,Jo SK,Yoon SS,Cho H,Kim JS,Kim YO,Koo JR,Park Y,Park YS,Shin JI,Yoo KH,Oh D, Clinical Practice Guidelines for the Management of Atypical Hemolytic Uremic Syndrome in Korea. Journal of Korean medical science. 2016 Oct     [PubMed]
Grisaru S, Management of hemolytic-uremic syndrome in children. International journal of nephrology and renovascular disease. 2014     [PubMed]
Rahal EA,Kazzi N,Nassar FJ,Matar GM, Escherichia coli O157:H7-Clinical aspects and novel treatment approaches. Frontiers in cellular and infection microbiology. 2012     [PubMed]
Saeedi P,Yazdanparast M,Behzadi E,Salmanian AH,Mousavi SL,Nazarian S,Amani J, A review on strategies for decreasing E. coli O157:H7 risk in animals. Microbial pathogenesis. 2017 Feb;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Infectious Disease. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Infectious Disease, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Infectious Disease, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Infectious Disease. When it is time for the Infectious Disease board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Infectious Disease.