Basim I. Asmar
The genus Yersinia is a member of the Enterobacteriaceae family that includes eleven species. Y enterocolitica is most important as a cause of foodborne illness. Yersinia enterocolitica is a small pleomorphic gram-negative, non-spore-forming coccobacillus. Isolation of the organism from specimens likely to have mixed flora, such as stools, can be enhanced by incubation in broth at lower temperatures prior to streaking on solid media. Therefore, the microbiology laboratory should be alerted to look for this organism when indicated. The organism has been classified into 6 biotypes and into more than 60 serotypes. The serotypes most often associated with human disease are 0:3, 0:5, 0:8, 0:9, 0:13, and 0:27. Human illness can occur after consumption of Y enterocolitica-contaminated food, animal waste, and unchlorinated water.1,2This organism may survive and grow during refrigerated storage.
EPIDEMIOLOGY AND PATHOPHYSIOLOGY
Yersinia enterocolitica has been isolated from humans worldwide, but most commonly in cooler climates. The organism has a large animal reservoir, including cattle, sheep, swine, dogs, cats, horses, rodents, and lagomorphs. Streams, lakes, and drinking water have all been contaminated. The most common mode of transmission is ingestion of contaminated food, milk, or water.3Person-to-person transmission has not been conclusively proven but probably occurs. Seasonal isolation rates of Yersinia indicate that it is more prevalent as a cause of enteritis in winter months in the United States.4,5 Because pigs are often infected, persons who eat or handle pork are at risk of getting infected. Diarrheal illness in infants caused by Y enterocolitica 0:3 in the United States is associated with household preparation of raw pork intestines (chitterlings).6 African American infants have the highest incidence of infection in the United States.7
The frequency of isolation of Y enterocolitica from stools of patients with diarrhea is reported to be 1% to 3% in a number of studies.
Yersinia enterocolitica is an invasive organism and causes disease by tissue destruction. Pathogenic properties include chromosomally mediated effects such as invasion attachment to host cells, iron complexing and uptake, and enterotoxin production. Plasmid-mediated mechanisms include production of outer membrane antigens, calcium dependency for growth, and autoagglutination. Invasion and penetration of the mucosa occurs in the ileum, followed by multiplication in Peyer patches.
Drainage into the mesenteric lymph nodes can lead to systemic infection or mesenteric adenitis. The enterotoxin produced by Y enterocolitica appears to play a minor role in causing disease because diarrheal illness can occur in the absence of enterotoxin production. In addition, the toxin appears to be produced only at temperatures lower than 30°C. The plasmid-mediated outer membrane antigens are associated with bacterial resistance to opsonization and neutro-phil phagocytosis.
One unique property of Y enterocolitica is its inability to chelate iron. Bacteria produce and release iron-binding chelators known as siderophores that extract iron from transferrin. Yersinia enterocolitica does not produce siderophores but has receptors for them and can utilize siderophores produced by other bacteria including the gastrointestinal flora (eg, deferoxamine produced by Streptomyces pilosus). Iron overload substantially increases the pathogenicity of the organism, perhaps through attenuation of the bactericidal activity of the serum. However, to establish extraintestinal infection, an exogenous siderophore (eg, a chelating agent such as defer-oxamine) or excess iron is required. It is for this reason that Y enterocolitica bacteremia and other systemic infections are more often seen in patients with iron overload and those receiving chelation therapy including patients with thalassemia major with hemosiderosis and some patients with sickle-cell disease.10,11
CLINICAL MANIFESTATIONS
The most common clinical presentation is acute enteritis illness resulting in diarrhea (98%), fever (88%), abdominal pain (65%), and vomiting (38%). The mean duration of diarrhea is 2 weeks (range 1–28 days). Blood and mucus are found in the stool in 25% to 50% of the children. This clinical presentation is seen most frequently in children younger than age 5 years.7,9 Most enteric infections are benign and self-limited; however, intra-abdominal complications occur in a small percentage of patients and include diffuse ulceration, intestinal perforation, peritonitis, intussusception, toxic megacolon, and mesenteric vein thrombosis. In older children and adolescents, Y enterocolitica infection is more likely to present with pseudoappendicitis syndrome (mesenteric adenitis).13 Guarding and rebound tenderness are common; leukocytosis is frequently present. Appendectomy is often performed on these patients; however, at laparotomy the appendix is normal or slightly inflamed with mesenteric adenitis and terminal ileitis. The organism can be cultured from the ileum as well as the mesenteric nodes.
Septicemia with Y enterocolitica is the major complication of enteric infection in the very young and in those with iron overload syndromes. One report indicated that 28% of children younger than age 3 months with Y enterocolitica enteritis developed sepsis.7
Conditions that seem to predispose to septicemia with this organism include liver disease; hemochromatosis; diabetes mellitus; malnutrition; immunosuppressive therapy; iron overdose; iron overload states such as transfusion-dependent blood dyscrasias (sickle-cell diseases, β-thalassemia, aplastic anemia); and chelation therapy.
Adults with Yersinia infection are more susceptible to 2 manifestations that are presumed to be immunologically mediated: arthritis and erythema nodosum.14 Reactive arthritis is more common in individuals who are HLA B27 positive. The illness lasts 1 to 4 months, but can persist for more than a year.
Other occasional manifestations of infection with Y enterocolitica include exudative pharyngitis (with or without gastrointestinal manifestations), pneumonia, lung abscess, endocarditis, urinary tract infection, cutaneous abscess, and conjunctivitis. The atypical presentations are associated with serotypes other than 0:3, 0:8, and 0:9.
DIAGNOSIS
Diagnosis of Y enterocolitica infection should be made by isolating the organism from appropriate clinical specimens such as stools and sometimes from mesenteric lymph nodes or peritoneal fluid specimens. When infection with Y enterocolitica is suspected, the laboratory should be instructed to culture specifically for this organism. Although Y enterocolitica can grow on commonly used enteric media, growth is slow and can be overlooked by concomitant growth of multiple isolates of normal flora. The use of selective media such as agar containing cefsulodin, irgasan, and novobiocin (CIN) is more effective than routine enteric media for recovery of the organism from stools.
When the organism cannot be cultured, but Yersinia is suspected, serologic testing may be of benefit. Tube agglutination test is the standard assay; however, enzyme-linked immunoassays (ELISA) and radioimmunoassays have also been developed. Agglutinin titers rise 1 week after onset of symptoms and reach a peak in the second week of illness. The usefulness of serologic testing, however, is limited by cross-reactions between Y enterocolitica and Brucella abortus, Rickettsia, Salmonella sp, and Morganella morganii. Children younger than age 1 year are also less likely to develop serologic response than are older children. An agglutinin titer greater than 1:128, in the appropriate clinical setting, is considered presumptive evidence of infection.
TREATMENT
In vitro testing indicates that Y enterocolitica is susceptible to trimethoprim-sulfamethoxazole, aminoglycosides, chloramphenicol, tetracycline, third-generation cephalosporins, and the quinolones. Strains are often resistant to penicillins, ampicillin, first-generation cephalosporins, and most second-generation cephalosporins.15 Despite the in vitro testing, the effectiveness of antibiotics in the treatment of uncomplicated gastroenteritis or mesenteric adenitis (pseudoappendicitis syndrome) has not been established.
Immunocompromised patients with enterocolitis, patients with septicemia, and those with focal extraintestinal infections should be treated with antimicrobial therapy. Although there are no controlled clinical comparisons of antimicrobials in the treatment of severe Y enterocolitica infections in human beings, doxycycline and gentamicin were promising in a mouse model. Trimethoprim-sulfamethoxazole (or doxycycline in older patients) can be used for focal disease. Third-generation cephalosporins, often in combination with an aminoglycoside, were shown to have a successful outcome in the treatment of patients with extraintestinal infection such as septicemia. Selection of appropriate antimicrobial treatment should ultimately be guided by the clinical response of the patient and antimicrobial susceptibility results. Treatment of septicemia in patients with iron overload should include temporary discontinuation of desferrioxamine chelation therapy. Recent data indicate that the third-generation cephalosporin cefotaxime is effective in the treatment of Y enterocolitica bacteremia in children.7 Antibiotic treatment has no effect in patients with postinfectious syndromes.
PREVENTION
Attention to appropriate handling and cooking of pig products, especially intestines, should decrease the risk of infection associated with these food items. Consumption of uncooked meat should be avoided. Refrigeration of cooked meat for prolonged periods of time before consumption should be avoided because Y enterocolitica grows at refrigerator temperature.
Patients and at-risk individuals should be instructed about appropriate hygiene methods and signs and symptoms of infection. Careful hand-washing and enteric precautions are required for a prolonged period following infection. In one Canadian report, the duration of excretion of Y enterocolitica in the stool ranged from 14 to 97 days (mean 42 days). Spread of the organism occurred in 27 of 57 families studied.9