Enteroaggregative Escherichia coli

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Enteroaggregative Escherichia coli
EAEC Prager etal.jpg
EAEC infecting human cells
SpecialtyInfectious disease
SymptomsDiarrhea, mucoid diarrhea, fever, nausea, tenesmus[1]
Causespathotype of Escherichia coli [1][2] (EAEC is transmitted through the fecal-oral route and primarily contaminated by food and water.[3])
Diagnostic methodPresence of EAEC-associated genes using PCR[4]
TreatmentAntibiotics (Cipro)[5][6]

Enteroaggregative Escherichia coli (EAEC or EAggEC) are a pathotype of Escherichia coli which cause acute and chronic diarrhea in both the developed and developing world.[2][1] They may also cause urinary tract infections.[1] EAEC are defined by their "stacked-brick" pattern of adhesion to the human laryngeal epithelial cell line HEp-2.[7] The pathogenesis of EAEC involves the aggregation of and adherence of the bacteria to the intestinal mucosa, where they elaborate enterotoxins and cytotoxins that damage host cells and induce inflammation that results in diarrhea.

EAEC is now recognized as an emerging enteric pathogen. In particular, EAEC are reported as the second most common cause of traveler's diarrhea, second only to Enterotoxigenic E. coli, and a common cause of diarrhea amongst pediatric populations.[8][9] It has also been associated with chronic infections in the latter, as well as in immunocompromised hosts, such as HIV-infected individuals.[10] Awareness of EAEC was increased by a serious outbreak in Germany during 2011, causing about 3000 cases and at least 50 fatalities. The pathogen responsible was found to be an EAEC O104:H4 strain which was lysogenized by a Shiga toxin encoding phage (typically associated with Shiga toxin-producing Escherichia coli, which often encode the adhesin intimin).[11][12][13] The putative cause of the outbreak were sprouted fenugreek seeds.[14]

Strains of EAEC are highly genetically heterogeneous, and the identification of virulence factors important for pathogenesis has proven difficult.[4] Many EAEC encode a transcriptional factor named aggR (aggregative regulator), part of the AraC family of transcription activators. AggR regulates many plasmid, as well chromosomally encoded, virulence factors, that include genes implicated in aggregative adherence fimbriae biogenesis and toxin production. Several toxins have been linked to EAEC virulence, including ShET1 (Shigella enterotoxin 1), Pet (plasmid‐encoded toxin), and EAST-1. However, further studies of these factors have failed to elucidate their role in pathogenesis.[15]

Classification

Diarrhea is still an important disease burden worldwide. It causes considerable childhood mortality in the developing world and is correlated with morbidity (or of relating to disease) and substation health care costs in industrialized countries. The cause of infectious diarrhea is diarrheagenic Escheriachia coli (DEC) group. Subgroups of diarrheagenic Escheriachia coli (DEC) are the following: enteroinvasive E. coli (EIEC), enteropathogenic E. coli (EPEC), enterotoxigenic E.coli (ETEC), Shiga toxin-producing E. coli (STEC) and Enteroaggregative E. coli (EAEC).[1]

E. coli is a bacterium that is found in the intestines, its mostly harmless, but some strains of bacteria can cause illness and infection,[16]

Signs and symptoms

Enteroaggregative Escheichia coli (EAEC) is a type of strain from E.coli. E.coli causes intestinal infections, some intestinal infections include diarrhea, fever and abdominal pain. Most severe cases can lead to bloody diarrhea, dehydration or even kidney failure. People with weakened immune systems, young children, older adults and pregnant women are at increased risks for developing these complications. Symptoms of intestinal infection usually begin between 8 and 52 hours after you have been infected with E.coli,[1] this is the incubation period.

The incubation period is the time between catching an infection and symptoms appearing.[17]

Bloody diarrhea has only been observed in children, and only rarely.[1] On the other hand, the STEC-EAEC hybrid strain identified in the 2011 Germany outbreak caused bloody diarrhea.[18]

Transmission

The trasmission of Enteroaggregative Escherichia coli can be:

  • Contaminated water – Human and animal feces may pollute ground and surface water, and water used or irrigate crops. Although public water systems use chlorine and other chemicals to kill such organisms like E. coli, some outbreaks have been linked to contaminated water supplies.[19]
  • Contaminated food – most common way to get a E.coli infection is by eating contaminated food such as ground beef, unpasteurized milk and fresh produce.[19]
  • Improper food handling – by consuming raw food, or not cooking the food properly, especially meats and poultry. It can also be transmitted by not cleaning your cooking utensils properly, causing cross contamination.[20]

Pathogenesis

EAEC is transmitted through the fecal-oral route and primarily contaminated by food and water.[3] EAEC has been associated with many symptoms such as diarrhea in some individuals and intestinal colonization in others.[5] Because many strains of EAEC have been identified, it is difficult to identify the mechanism of its pathogenesis. Most candidate virulence genes are not always connected with disease.[4]

The model of EAEC pathogenesis comprises three stages: Stage 1 is the attachment of the intestinal mucosa by aggregative adherence fimbriae and other adhering projections, Stage 2 an increase in mucus that covers EAEC on its surface of enterocytes is found; Stage 3 evocation of an inflammatory response, mucosal toxicity, and intestinal secretion as well as a release of toxins exist.[21][4]

Stage one: Aggregative adherence factors (AAF) are responsible for the adhesion to the intestinal mucosa. AAF are made up of three fimbriae encoded by the pAA plasmid; aag aafA agg-3. aggA is in charge of aggregative phenotype and human erythrocyte haemagglutination of EAEC. aafA allows EAEC to adhere to the intestinal mucosa. agg-3 serves as an adhesion. MAP, three-membrane associated proteins, are essential in the EAEC adherence to haemagglutination of animal cells.[4]

Stage two: After AAF factors in stage 1, adherence to the mucosa is characterized by the presence a biofilm. The production of biofilm is regulated by AggR and demands several genes. The loss of biofilm production and diffuse adherence pattern was reported in EAEC at a pH of 4.0. Many studies reveal that EAEC are capable of surviving in the mucus layer. This evidence can support why malnourished children who are infected with EAEC and live in poor conditions develop mucoid stools and prolonged diarrhea.[4]

Stage three: Cytotoxic effects are found in the release of toxins in EAEC as well as an elicitation of the inflammatory response, mucosal toxicity, and intestinal secretion. EAEC toxins are destructive to the intestinal villi and enterocytes. There are three toxins found in EAEC; plasmid encoded toxin (Pet), heat-stable toxin (EAST1), and Shigella enterotoxin 1 (ShET1).[4]

Diagnosis

Diagnosis of infectious diarrhea and identification of antimicrobial resistance is performed using a stool culture with subsequent antibiotic sensitivity testing. It requires a minimum of 2 days and maximum of several weeks to culture gastrointestinal pathogens. The sensitivity (true positive) and specificity (true negative) rates for stool culture vary by pathogen, although a number of human pathogens can not be cultured.[23][24][25]

Current point of care molecular diagnostic tests can identify EAEC and antimicrobial resistance in the identified strains much faster than culture and sensitivity testing; Microarray-based platforms can identify EAEC and AMR genes in two hours or less with high sensitivity and specificity, but the size of the test panel is limited. [26][27][28]

Prevention

Proven prevention methods for E. coli transmission include handwashing and improved sanitation and drinking water, as transmission occurs through fecal contamination of food and water supplies. Additionally, thoroughly cooking meat and avoiding consumption of raw, unpasteurized beverages, such as juices and milk are other proven methods for preventing E. coli. Lastly, avoid cross-contamination of utensils and work spaces when preparing food.[29]

Treatment

Chemical structure of ciprofloxacin

Fluoroquinolone, especially ciprofloxacin, may be effective for Enteroaggregative E.coli (EAEC) infections, with a reductions in duration of diarrhea.[5][30]

For most people treatments include, rest and the intake of fluids. For patients with profuse diarrhea or vomit should be rehydrated by drinking much water or by drinking rehydration solutions such as Rehydralyte or Pedialyte.[31]

History

Theodor Escherich

In 1885, the German-Austrian pediatrician Theodor Escherich discovered this organism in the feces of healthy individuals. He called it Bacterium coli commune because it is found in the colon. Early classifications of prokaryotes placed these in a handful of genera based on their shape and motility.[32][33][34]

Bacterium coli was the type species of the now invalid genus Bacterium when it was revealed that the former type species ("Bacterium triloculare") was missing.[35] Following a revision of Bacterium, it was reclassified as Bacillus coli by Migula in 1895[36] and later reclassified in the newly created genus Escherichia, named after its original discoverer, by Aldo Castellani and Albert John Chalmers.[37]

In 1996, the world's worst to date outbreak of E. coli food poisoning occurred in Wishaw, Scotland, killing 21 people.[38][39] This death toll was exceeded in 2011, when the 2011 Germany E. coli O104:H4 outbreak, linked to organic fenugreek sprouts, killed 53 people.[40]

Enteroaggregative Escheichia coli (EAEC) was first found in 1987, in a child in Lima, Peru.[7]

Since 1987, Enteroaggregative Escheichia coli (EAEC) has been recognized as agents of diarrhea in industrialized and developing countries, Enteroaggregative Escheichia coli is most commonly found in developing countries due to less developed industrial base and low human development compared to other countries (India, Jamaica and Mexico are the most commonly risked countries).[41][42]

Epidemiology

2011 outbreak
Number of cases reported to the WHO as of 21 July 2011[11]
Country Non-HUS cases HUS cases Deaths
 Austria 4 1 0
 Canada 1 0 0
 Czech Republic 1 0 0
 Denmark 16 10 0
 France 4 9 0
 Germany 2947 818 51
 Greece 1 0 0
 Luxembourg 1 1 0
 Netherlands 7 4 0
 Norway 1 0 0
 Poland 1 2 0
 Spain 1 1 0
 Sweden 35 18 1
 Switzerland 5 0 0
 United Kingdom 3 4 0
 United States 2 4 1
Total 2987 855 53

Escherichia coli O104:H4 is an enteroaggregative Escherichia coli strain of the bacterium Escherichia coli, and the cause of the 2011 Escherichia coli O104:H4 outbreak.[43]

Analysis of genomic sequences obtained by BGI Shenzhen shows that the O104:H4 outbreak strain is an enteroaggregative E. coli (EAEC or EAggEC) type that has acquired Shiga toxin genes, presumably by horizontal gene transfer.[44][45][46]

Cases began as early as 1 May 2011 with a man in Aachen reporting bloody diarrhea.[11]

Cases then rapidly increased, with over 100 cases of EHEC gastroenteritis and/or HUS were being reported each day by 16 May.[11]

The outbreak centered on the five northern German states of Hamburg, Schleswig-Holstein, Bremen, Lower Saxony, and Mecklenburg-Western Pomerania.[11]

Cases would eventually be reported in all 16 German states; however most cases outside of the northern states were linked to travel in northern Germany.[47]

Additionally, a small number of cases were reported from other countries, although most of those ill had previously travelled to Germany. The most substantial outbreak outside of Germany was in Bordeaux, France where 15 cases of EHEC gastroenteritis were associated with the same strain of E. coli which caused the outbreak in Germany. The French cases had not previously travelled to Germany, suggesting they acquired the bacteria from contaminated sprouts grown in France.[11]

Cases of EHEC HUS and gastroenteritis peaked on 21 and 22 May respectively.[47]

Cases then slowly decreased over the following month, with cases reported throughout the month of June and ending during July 2011. German authorities deemed the outbreak over in early July 2011.[11]

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