Yersinia Enterocolitica 

Yersinia enterocolitica is a pleomorphic gram-negative bacillus that belongs to the family Enterobacteriaceae. As a human pathogen, Y enterocolitica is most frequently associated with acute diarrhea, terminal ileitis, mesenteric lymphadenitis, and pseudoappendicitis.^[1] The bacterium was first reported in 1934 by Mclver and Picke.^[2] Schleifstein and Coleman provided the first recognized description of 5 human isolates of Y enterocolitica in 1939.^[3]

In several countries, Y enterocolitica has eclipsed Shigella species and approaches Salmonella species and Campylobacter species as the predominant cause of acute bacterial gastroenteritis. Y enterocolitica most commonly affects young individuals, but whether this represents an increased susceptibility or a greater likelihood of developing symptomatic illness is unclear. Most cases of Y enterocolitica infection are sporadic, but reports have documented large outbreaks centered on a single contaminated source.

Human yersiniosis is attributed to contaminated pork, milk, water, and tofu consumption, as well as blood transfusion. Infected individuals may shed Y enterocolitica in stools for 90 days after the symptom resolution, suggesting that early detection of Y enterocolitica from diarrheal stool samples is critical in preventing its transmission and an eventual outbreak.^{[4, 5]}

Y enterocolitica is non–lactose-fermenting, glucose–fermenting, and oxidase-negative. Most, but not all, Y enterocolitica isolates reduce nitrates. The presence of bile salts in the medium prevents the organism's ability to ferment lactose. Colonies of Y enterocolitica do not produce hydrogen sulfide in triple sugar iron medium, but the organism is urease-positive. Y enterocolitica is a facultative anaerobe that is motile at 25°C and nonmotile at 37°C.

Upon initial isolation on enteric media, Y enterocolitica resembles other common Enterobacteriaceae. Using duplicate sets of enteric media followed by incubation at both 25°C and 37°C for 48 hours increases the yield from stool cultures. Cefsulodin-irgasan-novobiocin (CIN) agar is a highly selective medium for this organism. It requires 18-20 hours of incubation at 25°C to create unique colony morphology, representing 0.5- to 1-mm colonies with a red "bull's-eye" and a clear border. Use of this media allows differentiation between Y enterocolitica and Y enterocolitica– like isolates.

Y enterocolitica is classified according to various distinct biochemical and serologic reactions. Based on biochemical characteristics, 6 biotypes of Y enterocolitica have been described. Biotypes 2, 3, and 4 are most common in humans. The serotyping is based on O and H antigens. More than 60 serotypes of Y enterocolitica have been described. The serotypes most clearly pathogenic to humans include serotypes O:3, O:5,27, O:8, O:9, and O:13. H-antigen typing can be valuable supplement to O-antigen typing and biochemical characterization in epidemiological investigations. Accurate identification of pathogenic strains requires consideration of both the biotype and the serotype because some strains can contain multiple cross-reacting O antigens.

As with other members of the genus Yersinia, Y enterocolitica is an invasive organism that appears to cause disease by tissue destruction. Researchers have elucidated several potential pathogenic properties, including chromosomally mediated effects (eg, attachment to tissue culture, production of enterotoxin) and plasmid-mediated mechanisms (eg, production of Vw antigens, calcium dependency for growth, autoagglutination). Invasion of human epithelial cells and penetration of the mucosa occurs in the ileum, followed by multiplication in Peyer patches. A 103-kd protein, known as invasin and determined by the inv gene, mediates bacterial invasion. The best defined pathway is through the action of invasin.^[6]

As a foodborne pathogen, Y enterocolitica can efficiently colonize and induce disease in the small intestine. Following ingestion, the bacteria colonize the lumen and invade the epithelial lining of the small intestine, resulting in the colonization of the underlying lymphoid tissues known as Peyer patches. A direct lymphatic link between the Peyer patches and mesenteric lymph nodes may result in bacterial dissemination to these sites, resulting in mesenteric lymphadenitis. Dissemination to extraintestinal sites, such as the spleen, is hypothesized to occur via two main mechanisms: (1) colonization of the Peyer's patches, which can then be used as a staging ground for spread into the blood and/or lymph, ultimately resulting in the appearance of bacteria in other tissues and (2) bypass of the Peyer patches and straight to systemic colonization. Furthermore, the possibilities of additional avenues for dissemination have yet to be excluded.

Y enterocolitica colonization of the intestinal lymphoid tissues requires transmigration of the bacteria from the intestinal lumen across an epithelial tissue barrier. Specifically, antigen-sampling intestinal epithelial cells known as M cells are thought to be critical for this transmigratory process. The epithelium overlying the Peyer patches has a high concentration of M cells; however, these cells have recently been identified throughout the non–Peyer patch areas of the small intestine.

Furthermore, Y enterocolitica and the related pathogen Yersinia pseudotuberculosis produce at least 3 invasion proteins, invasin, Ail, and YadA, which could potentially promote adherence to and invasion of M cells. Invasin, the principle invasion factor of Y enterocolitica and Y pseudotuberculosis, binds to ß₁ -chain integrin receptors with high affinity, promoting internalization. These receptors are found at high levels on the luminal side of M cells but not on the luminal side of enterocytes.^[7]

Drainage into the mesenteric lymph nodes can lead to systemic infection or mesenteric adenitis. The enterotoxin produced by Y enterocolitica is similar to the enterotoxin produced by the heat-stable Escherichia coli; however, it likely plays a minor role in causing disease, as diarrheal syndromes have been observed in the absence of enterotoxin production. In addition, the toxin does not appear to be produced at temperatures higher than 30°C. The plasmid-mediated outer membrane antigens are associated with bacterial resistance to opsonization and neutrophil phagocytosis.

One unique property of Y enterocolitica is its inability to chelate iron, which is an essential growth factor for most bacteria and is obtained through the production of chelators known as siderophores. Y enterocolitica does not produce siderophores but can utilize siderophores produced by other bacteria (eg, desferrioxamine E produced by Streptomyces pilosus). Iron overload substantially increases the pathogenicity of Y enterocolitica, perhaps through attenuation of the bactericidal activity of the serum. Researchers observe differences in the iron requirements between different serotypes of the organism. This may explain, in part, the varying degrees of virulence of certain serotypes.

After an incubation period of 4-7 days, infection may result in mucosal ulceration (usually in terminal ileum and rarely in ascending colon), necrotic lesions in Peyer patches, and mesenteric lymph node enlargement. In severe cases, bowel necrosis may occur as a result of mesenteric vessel thrombosis.^[8] Focal abscesses may occur. In persons with HLA-B27, reactive arthritis is not uncommon, possibly because of the molecular similarity between HLA-B27 antigen and Yersinia antigens.^[9] The pathogenesis of Yersinia -associated erythema nodosum is unknown.

Frequency

United States

Yersiniosis is rare in the absence of a breakdown in food-processing techniques. The Centers of Disease Control and Prevention (CDC) estimates that about 17,000 cases of yersiniosis (including both Y enterocolitica and Y pseudotuberculosis infections) occur annually in the United States.^[10]

The Foodborne Diseases Active Surveillance Network (FoodNet) of CDC's Emerging Infections Program, which collects surveillance data from 10 US states, identified a total of 17,883 laboratory-confirmed cases of infection in 2007. The number of cases and incidence per 100,000 population were reported as follows: Salmonella (6,790; 14.92), Campylobacter (5,818; 12.79), Shigella (2,848; 6.26), Cryptosporidium (1,216; 2.67), STEC O157 (545; 1.20), STEC non-O157 (260; 0.57), Yersinia (163; 0.36), Listeria (122; 0.27), Vibrio (108; 0.24), and Cyclospora (13; 0.03). The report found that the incidence of Yersinia infections did not change significantly compared with data collected from 2004-2006.^[11]

International

Y enterocolitica has been isolated in patients in many countries worldwide, but the infection appears to occur predominantly in cooler climates. It is much more common in northern Europe, Scandinavia, and Japan. Most isolates reported from Canada and Europe are O:3 and O:9 serotypes.^[12] The O:3 serotype is common in Japan. Isolation of Y enterocolitica in developing countries is uncommon.

Mortality/Morbidity

• Most patients with Y enterocolitica infection are symptomatic; however, asymptomatic carriage may occur. Death is uncommon, but Y enterocolitica bacteremia carries a case fatality rate of 34-50%.
• Y enterocolitica has emerged as a significant cause of transfusion-associated bacteremia and mortality (64%), with 27 cases reported between 1975 (when this condition was first documented^[13] ) and 1997.^[14]
• A national registry-based study of 52,121 patients in Denmark reported estimates for the risk of developing severe, hospitalization-requiring complications and long-term sequelae up to 1 year after infection with 5 common bacterial gastrointestinal pathogens. Of the 3922 cases of Y enterocolitica infection reported, 368 required hospitalization.^[15]
• Various manifestations of Y enterocolitica infection have been reported, including enterocolitis, pseudoappendicitis, mesenteric adenitis, reactive arthritis, erythema nodosum, septicemia, pharyngitis, dermatitis, myocarditis, and glomerulonephritis.
• Iron is an essential growth factor for the organism, and iron overload (eg, chronic hemolysis, hereditary hemochromatosis) is associated with an increased risk of systemic disease. Deferoxamine therapy also increases susceptibility to Y enterocolitica disease.

Race

Y enterocolitica infection has no racial predilection.

Sex

Y enterocolitica infection has no racial predilection, although erythema nodosum appears to be more common in females.

Age

Reports document symptomatic Y enterocolitica infection most commonly in younger age groups. A sample collection from 1988-1991 showed that 77.6% of infections occurred in children aged 12 months and younger, making Y enterocolitica the second most common cause of bacterial gastrointestinal infection in children.^[16] Clinical manifestations of Y enterocolitica infection exhibit some age-dependent predilections, with reactive arthritis and erythema nodosum being more common in older patients. Older patients with more debility are more likely to develop bacteremia than are younger healthier patients.