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What are enterovirulent E. coli (EEC)?
Enterovirulent Escherichia coli (E. coli) is composed of several serotypes (strains of related bacteria identified by their slightly different antigenic structures) of bacteria that have a strong propensity to cause infections, initially in the gastrointestinal tract ("entero" in Greek means intestine; virulent means deadly or disease-causing). Enterovirulent Escherichia coli (EEC) are members of the bacterial genus Escherichia, named after T. Escherich, who first isolated the bacteria in 1885. The majority of the genus Escherichia is composed of one species termed "coli" (Latin for colon); however, there are over 700 serotypes of this bacterial species. Many E. coli serotypes may cause infections other than in the intestine, but the focus of this article is on the enterovirulent groups (EEC groups), with symptoms of the disease primarily limited to the gastrointestinal tract.
Escherichia coli (E. coli) are gram-negative rod-shaped bacteria that can survive in aerobic and anaerobic environments (termed a facultative anaerobe), and may or may not produce flagella and pili (thin hair-like projections) depending on environmental needs.
E. coli strains are found worldwide and live in significant numbers in humans and other animals as part of the normal bacterial population found in their large intestines. The organisms have likely co-existed with humans for eons in the normal flora (bacterial populations usually found in healthy individuals) of human and other animal colons. However, among the 700 strains of E. coli, there are a few strains that cause disease. These E. coli strains are some of the most frequent causes of many common bacterial infections, including diarrhea, cholecystitis, bacteremia, cholangitis, urinary tract infection (UTI), traveler's diarrhea, and other clinical infections such as neonatal meningitis, pneumonia, abdominal abscesses, and hemolytic uremic syndrome (HUS).
A classic example of such an E. coli strain is E. coli 0157:H7. The name E. coli 0157:H7 seems complex; however, scientists use the numbers and letters to specifically designate small differences in E. coli strains. The 0157 is the "O" serotype antigen that identifies one of the over 700 strains and the "H" of H7 represents the antigen type on the bacterium's flagella. Some E. coli also possesses K antigens (protein/polysaccharide surface components) that have been used to identify certain strains. These designations (O, H, and K) may be used to identify strains causing specific diseases and have been utilized to identify outbreaks of disease.
A new EEC group? (E. coli 0104:H4)
As an update to this article, the addition of the newest EEC E. strain will be presented. It recently arose in Germany in early 2011 and has now been documented in 11 European countries; at least four people who traveled to Germany and returned to the US have been infected with this strain. In most people, the exposure to the infection source occurred while people were visiting Germany, most likely through contaminated food (salads).
The strain has been identified as E. coli 0104:H4 (also termed STEC 0104:H4). It is presented in this section because as stated in the previous paragraph, there are unfortunate overlaps in ECC-caused disease and this new strain seems to exhibit some of the worst overlap features of the ECC group members. For example, E. coli 0104:H4 is reported to contain about 93% of the genome of EHEC and produces the Shiga (Vero) toxin; however, it also seems to have the ability like EAEC strains to attach well to gastrointestinal cells.
The outbreak in Germany was the third largest ever reported for E. coli (about 4320 infected people) and the most lethal (at least 82 dead). In addition, most strains isolated are resistant to multiple antibiotics (aminoglycosides, macrolides, and Beta-lactams). The source of the infection may be contaminated bean sprouts grown organically and then shipped to many German restaurants. One major difference in E. coli 0104:H4 from other E. coli that cause hemolytic uremic syndrome or HUS (mainly E. coli 0157:H7) is that the organism is causing HUS in young adult females and other adults. Often, HUS caused by E. coli 0157:H7 is seen in children and the elderly, not relatively healthy adults. This outbreak had 850 people develop HUS. This new strain had three disease-causing (pathogenic) mechanisms; 1) Shiga toxin, 2) adherent fimbriae (pili), and 3) EXPEC (extra-intestinal pathogenic E. coli). E. coli 0104:H4 may constitute a new group as yet unnamed.
The CDC suggested the following guidelines for E. coli 0104:H4. It is not recommended to give antibiotics to individuals with suspected STEC infections until complete diagnostic testing can be performed and STEC infection is ruled out. Some studies have shown that administering antibiotics to people with STEC infections might increase their risk of developing HUS. However, clinical decision-making must be tailored to each affected individual. There may be indications for antibiotics in those with severe intestinal inflammation if perforation is of concern. Of note, isolates of STEC O104:H4 from patients in Germany have demonstrated resistance to multiple antibiotics.
CDC guidelines to ensure as complete as possible detection and characterization of STEC infections include the following:
- All stools submitted for testing from patients with acute community-acquired diarrhea should be cultured for STEC O157:H7. These stools should be simultaneously assayed for non-O157 STEC with a test that detects the Shiga toxins or the genes encoding these toxins.
- Clinical laboratories should report and send E. coli O157:H7 isolates and Shiga toxin-positive samples to state or local public health laboratories as soon as possible for additional characterization.
- Specimens or enrichment broths in which Shiga toxin or STEC are detected, but from which O157:H7 STEC isolates are not recovered, should be forwarded as soon as possible to a state or local public health laboratory so that non-O157:H7 STEC can be isolated.
- It is often difficult to isolate STEC in stool by the time a patient presents with HUS. Immunomagnetic separation (IMS) has been shown to increase the recovery of STEC from HUS patients. For any patient with HUS without a culture-confirmed STEC infection, stool can be sent to a public health laboratory that performs IMS or to the CDC (through a state public health laboratory). In addition, serum can be sent to CDC (through a state public health laboratory) for serologic testing of common STEC serogroups.
The benefits of adhering to the recommended testing strategy include early diagnosis, improved patient outcomes, and detection of all STEC serotypes.
All patients with Shiga toxin-positive diarrheal illness or HUS should be reported to health departments, regardless of travel history to Germany.
How do enterovirulent E. coli groups cause disease?
In general, all EEC groups cause disease by disruption of the normal secretory mechanisms of the intestines which leads to diarrhea. As outlined previously, different groups use different methods that ultimately result in diarrhea; the type of diarrhea and the intensity of the disease are related to the mechanisms used by the bacteria.
- EHEC secrete Shiga toxins that can not only destroy intestinal cells but can be spread to other organ systems to cause additional disease. E. coli 0157:H7 is the major EHEC pathogen responsible and is considered to be one of the most virulent organisms in all of the EEC groups because of Shiga toxin production.
- EPEC group organisms also can produce a toxin closely related to Shigella toxin that has many of the same properties as Shiga toxin although the serotypes cause the disease (sometimes milder) mainly in children.
- The ETEC group does not produce Shiga toxins or their closely related toxins, but ETEC does produce two other exotoxins that stimulate the intestines to secrete fluid and mucus.
- EIEC organisms, these bacteria can penetrate the epithelial cells that line areas of the human intestines. EIEC organisms then cause many of the cells to lyse thus disrupting the fluid adsorption and secretion capacity of the intestines.
- Both EAEC and EAggEC groups of bacteria, by attaching to intestinal cells, cause irritation or inflammation of the intestinal cells. This physiologic and immunologic response also disrupts adsorption and secretion in the intestines.
What are the signs and symptoms of enterovirulent E. coli (EEC)?
The major symptom that all enterovirulent E. coli (EEC) produce in common is diarrhea; these organisms are the leading cause of bacterial gastroenteritis. However, the type of diarrhea (for example, bloody, chronic, or self-limiting) and the complications that may accompany the infections differ somewhat from each other. These symptoms have caused researchers and clinicians to arrange E. coli serotypes into groups according to their different symptoms and disease-causing (pathogenic) mechanisms. Depending on which research or clinical physician publications are read, there are 4 to 6 groups of E. coli that comprise all of the enterovirulent E. coli (EEC). Unfortunately, some investigators have more than one term for some members of the groups.
The following is a summary of the groups that are currently in the literature and the symptoms E. coli group members cause:
- EHEC (enterohemorrhagic E. coli): bloody diarrhea, hemorrhagic colitis, hemolytic uremic syndrome (HUS), and thrombotic thrombocytopenic purpura (TTP); additional terms for EHEC are VTEC and STEC which stand for Vero toxin-producing E. coli and Shiga toxin-producing E. coli, respectively. One serotype, E. coli 0157:H7, is responsible for the majority of the bloody diarrhea that occurs due to the production of Shiga toxins.
- ETEC (enterotoxigenic E. coli): traveler's diarrhea, watery diarrhea with nausea, abdominal cramping, and fever, caused by several serotypes of E. coli (0169:H47, 0148:H28, and several others) that produce two toxins that cause the gastrointestinal tract to secrete fluid (secretory exotoxins)
- EPEC (enteropathogenic E. coli): childhood diarrhea, caused by E. coli bacteria (many different serotypes) that can attach to gastrointestinal tissues, especially in infants, and produces watery or bloody diarrhea in infants by producing a toxin similar to that produced by the bacterium named Shigella dysenteriae.
- EIEC (enteroinvasive E. coli): Shigella-like dysentery with blood and mucus, due to E. coli that invade epithelial cells of people of all ages, also producing vomiting, fever, and chills. These serotypes are closely related to Shigella spp. (a few children develop HUS)
- EAEC (enteroadherent E. coli): childhood watery diarrhea, some cases of traveler's diarrhea in adults, and some urinary tract infections. This group is composed of E. coli strains (for example, 0119 or 055) that can adhere to human cells (gastrointestinal and other cell types). About one-half of this group can cause mild diarrhea, usually in children, while other E. coli serotypes that can adhere, do not cause any disease. Like EAggEC, these enteroadherent E. coli do not produce any Shiga toxins or secretory-causing exotoxins.
- EAggEC (enteroaggregative E. coli): persistent diarrhea in developing countries especially in children that usually lasts more than 14 days. The diarrhea is watery, mucus-containing, and in about one-third of individuals, bloody. Those with EAggEC usually have only a low fever (less than 101 F or 38.3 C) and almost no vomiting. These E. coli serotypes (for example, 042 and 044) do not produce any Shiga toxins or secretory exotoxins that cause secretions but cause intestinal inflammation that is linked to the abnormally high intestinal secretion that leads to watery diarrhea. These strains are unique because they "aggregate" (form small masses comprised of cultured tissue cells and bacteria) human gastrointestinal cells by attaching via fimbriae (pili).
As one can surmise, there are unfortunate overlaps in disease syndromes and that is one reason that authors disagree on the actual number of groups (EPEC, EAEC, and EAggEC or EACE and EAggEC are often lumped together). It seems unlikely that the group names will remain stable in the future (see next section).
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When should one seek medical care for enterovirulent E. coli infection?
Many people (the large majority) do not need to seek medical care as most of the infections are self-limiting unless the affected individual is immunocompromised or is an undernourished child in a developing country. Because several patients are children; their progress in self-limiting the disease needs to be carefully watched as they can, in some instances, rapidly deteriorate. This is the situation for all the EEC groups. Most infected individuals, unless diagnosed, will not even know they are infected with EEC since many bacterial and viral diseases have similar symptoms of nausea, low-grade fever, and diarrhea.
Many healthcare professionals suggest that affected individuals should seek medical care if they experience the following:
- Signs of dehydration (for example, decreased urination, dry mucous membranes), especially in children under 5 years of age and the elderly
- Sustained fever over 101 F (37.7 C)
- Presence of blood in the stool
- Known ingestion of E. coli 0157:H7 or contaminated food or fluid or close personal contact with individuals known to have any E. coli infection caused by an EEC group bacteria
- Any complication of an E. coli EEC group infection (see complication section below)
How are enterovirulent E. coli infections diagnosed?
The diagnosis is usually made by an accurate history, physical exam, and analysis of a fecal sample from the patient. A presumptive diagnosis is often made if the patient's history indicates an association with persons, foods, or fluids known to contain E. coli 0157:H7 or other EEC group bacteria; such a presumptive diagnosis is often made during outbreaks of the disease. However, in patients who require hospitalization, a definitive diagnosis is usually sought.
A definitive diagnosis is often made by culture of E. coli strains from fecal specimens on selective media (sorbitol-MacConkey agar) when colonies react with antiserum directed against specific "O" antigen strains. The selective medium and antiserum help distinguish E. coli serovars from other similar pathogens such as Listeria, Salmonella, and Shigella. Other tests include PCR (polymerase chain reaction) and immunofluorescence tests to help identify the E. coli serovar.
The CDC has recommended (2009) that all patients being evaluated for community-acquired diarrhea have their stool samples analyzed by immunologic test systems that detect all types of Shiga toxins as this test will likely detect almost all bacteria that produce Shiga toxins, especially E. coli 0157:H7 strains. The CDC suggests that this test is even better than bacterial culture techniques, but recommends that both culture and immunologic tests should be done at the same time. This is suggested since E. coli that produces Shiga or Shiga-like toxins usually have the potential to be very damaging to the infected person(s).
In 2013, the FDA approved a new test that can detect and differentiate between eleven pathogens (bacterial and viral) that include Escherichia coli O157, enterotoxigenic E coli LT/ST, Salmonella, Shigella, and Shiga-like toxin-producing E coli stx 1/stx 2) by detecting their nucleic acids. These types of tests will help healthcare professionals identify and differentiate the many causes of gastroenteritis.
How are enterovirulent E. coli infections treated?
Initial treatment methods are similar for all of the EEC groups; hydration is the main treatment, both oral and IV (intravenous) hydration. However, additional treatment measures may be needed. If the patient is infected with EHEC, antibiotics are not used unless the patient is septic. Studies have shown that antibiotics in the EHEC group (especially with E. coli 0157:H7) induce bacteria that produce Shiga toxin to increase toxin release and make the disease and complications worse. In addition, investigators suggest that other toxin-producing E. coli serovars in other groups (EPEC, ETEC, and EIEC) may not be helped by antibiotics since on some rare occasions; they can develop complications similar to those of EHEC.
Although some cases of traveler's diarrhea have been treated with antibiotics (for example, sulfamethoxazole and trimethoprim [Septra]), in general, antibiotics may reduce symptoms by only about 24/48 hours. EAEC and EAggEC frequently are self-limiting and many of the serovars are resistant to one or more antibiotics. If the decision to use antibiotics in any EEC infection is made, investigators suggest the E. coli serovar causing the infection to be tested to determine antibiotic susceptibilities.
How is self-care at home done for enterovirulent E. coli?
The majority of enterovirulent E. coli (EEC) infections are self-limited; they require no treatment except to keep the person well hydrated (oral hydration). This is especially the case for children and the elderly, who may quickly dehydrate during home care. If the person is unable to stay well hydrated at home, medical care should be sought. Most healthcare professionals warn people not to treat patients at home with any "left-over" antibiotics or over-the-counter drugs such as diphenoxylate and atropine (Lomotil), because such treatment may make the symptoms worse and cause complications (see complications section).
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What are the prognoses (outcomes) of enterovirulentE. coli infections?
Although individuals are frequently uncomfortable with EEC infections, most individuals that live in industrialized countries that get these infections have few if any serious complications. However, people that are immunocompromised and children in developing countries often have complications. Some countries report a death rate in children as high as 50%, with dehydration playing a central role in these deaths due to EEC bacteria. People infected with strains that are highly virulent like E. coli 0104:H4 are at risk for complications and a less favorable prognosis.
People with EHEC group infections (E. coli 0157:H7 is the major serotype) usually (about 90%) have a self-limited disease and the outcome is excellent. However, the prognosis declines, depending on the development of complication(s). Good hydration decreases the chances of complications and improves the outcome. Individuals who develop hemorrhagic diarrhea and are treated promptly have better outcomes with reduced hospitalization. Complications such as HUS and TTP have a wide range of prognoses from good to poor, depending on the overall health of the individual and how quickly the complications are diagnosed and treated. For example, some individuals can recover completely, but others may require IV fluids, plasma exchange, plasma infusion, or dialysis and may have end-organ failure (usually kidney failure) and neurologic problems. A few (about 10%) of TTP patients will die.
Although infrequent, even relatively healthy children and adults have died from EEC infections due to dehydration.
What are the complications associated with enterovirulent E. coli (EEC)?
All of the EEC groups may have complications associated with infection. However, some groups have far fewer and potentially less serious complications than other groups. All of the groups, however, have one potentially serious complication; dehydration. If left untreated, dehydration can lead to multiple organ damage and death. Severe dehydration happens infrequently in developed countries, but in developing countries, the death rate can reach 50% in children (ETEC). In general, in developed countries, ETEC, EAEC, and EAggEC group infections have few complications develop.
A relatively frequent complication of EHEC, EPEC, and EIEC is blood in the stool. Some individuals will have only a small amount of blood but others may have large amounts and may require a blood transfusion (severe hemorrhagic diarrhea).
However, about 10% of all persons infected with EHEC (usually E. coli 0157:H7) develop some complications. Occasionally, the complication(s) may lead to disability or death.
EHEC strains (and sometimes, EIEC group organisms) may produce the serious problems listed below:
- Hemorrhagic (bloody) diarrhea: This complication can prolong the disease by about a week, and cause severe abdominal pain. The individual may also develop dehydration, anemia and may need a blood transfusion.
- Hemolytic-uremic syndrome (HUS): This condition also prolongs the disease as it usually becomes apparent about 7 to 10 days after the onset of symptoms. Children under 10 years of age are the most likely to get this complication; HUS is the most common cause of kidney failure in children. The toxin produced by EHEC bacteria (mainly E. coli 0157:H7) enters the blood, causing blood cells to be damaged and small clots to form. The toxin can also lodge in the kidneys and eventually destroy kidney tissue; sometimes the damage is severe enough to cause kidney failure.
- Thrombotic thrombocytopenic purpura (TTP): This complication is a variation of HUS that usually occurs in the elderly. The same mechanisms as those for HUS are responsible for TTP. However, the elderly develop more clotting problems and use up more platelets resulting in easy or "spontaneous" bruising over the body. The elderly experience more fever and neurologic changes, in addition to kidney damage. Until the 1980s, TTP was considered a fatal disease. However, treatment with plasma exchange and infusion techniques has reduced the mortality rate (deaths) of TTP to about 10%.
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How are enterovirulent E. coli (EEC) infections prevented?
Almost every person who gets infected with EEC has touched and eventually ingested either foods or fluids contaminated with EEC bacteria. Numerous outbreaks occur worldwide each year due to food or fluid source contamination with these organisms; some of the most serious problems are often related to contaminated meat products by the EHEC group. However, the potential sources of EEC group infections are vast. Fortunately, some guidelines can help reduce the chance of getting EEC infections.
The following guidelines on preventing EHEC, especially E. coli 0157:H7, are recommended by the CDC, but they apply to all EEC groups:
- Wash hands thoroughly after using the bathroom or changing diapers and before preparing or eating food. Wash hands after contact with animals or their environments (at farms, petting zoos, fairs, and even your pets in your yard).
- Cook meats thoroughly. Ground beef and meat that has been needle-tenderized should be cooked to a temperature of at least 160 F (70 C). It's best to use a thermometer, as meat color is not a very reliable indicator of "doneness."
- Avoid raw milk, unpasteurized dairy products, and unpasteurized juices (like fresh apple cider).
- Avoid swallowing water when swimming or playing in lakes, ponds, streams, swimming pools, and backyard "kiddie" pools.
- Prevent cross-contamination in food preparation areas by thoroughly washing hands, counters, cutting boards, and utensils after they touch raw meat. (This recommendation is especially important for anyone who prepares and serves food to others.)
One of the major sources of numerous outbreaks is hamburger meat contaminated with E. coli 0157:H7; such infections have been termed "hamburger disease". Many authors recommend that hamburgers ordered in a restaurant should be "medium or well done," with no pink hamburger meat visible in the middle of the burger. Any "pink" hamburger meat should be cooked until brown to reduce the chance that viable E. coli is still present.
In addition, any food or liquid involved in a recall due to possible E. coli contamination should be disposed of immediately. On August 8, 2010, about I million pounds of beef in California was recalled due to possible E. coli 0157:H7 contamination. In 2010, the FDA recalled several productions of beef, including material put into dry pet foods due to this organism. Other FDA recalls due to EEC in 2010 included spinach and romaine lettuce.
There is controversy about the use of antibiotics to prevent EEC, some physicians suggest the use of rifaximin (Xifaxan); other physicians do not. Data to support such use of the antibiotic is not available. There are no commercially available anti-EEC vaccines available in the US, although vaccine research is ongoing.
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CDC.gov. CDC Health Advisory: Notice to Health Care Providers — Shiga Toxin-producing E. coli O104 (STEC O104:H4) Infections in U.S. Travelers Returning from Germany. June 3, 2011.
FDA.gov. BBB - Escherichia coli O157:H7 (EHEC).
Itskowitz , M., Bacterial Diarrhea, N. Engl. J. Med., 2010; 362:558-559, 2010
Sodha SV, Griffin PM, Hughes JM. Foodborne Disease. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa: Elsevier Churchill Livingstone, Chapter 99, 2009
MedscapeReference.com. Bacterial Gastroenteritis.
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