Yersinia Species

Epidemiology

Yersiniosis due to infection with Y. enterocolitica is a zoonotic gastrointestinal disease in humans. Y. enterocolitica can be isolated from a variety of domestic and wild animals (e.g., pigs, cattle, sheep, goat, rabbits, dogs, cats, wild boars, small rodents). Pigs are considered to be the main reservoir of human pathogenic strains. People who eat or handle pork are at risk for illness, and pork intestines (i.e., chitterlings) are a documented source of infection. Eating food prepared from raw products or treated sausage and contact with domestic animals are the main risk factors for sporadic yersiniosis in children. Human infections are more common in cooler climates and tend to occur in winter months.

Milk and other dairy products, even if pasteurized, can sometimes be the source of outbreaks because organisms proliferate at refrigerator temperatures, and low levels of contamination can lead to substantial risk. Refrigerator stored blood is a source of transfusion-acquired illness. Contaminated water can also be a source of infection. Familial and nosocomial spread of Y. enterocolitica suggest that person-to-person transmission occurs.

Most reported cases have been from Canada, Europe, and the US. Higher risk groups in the US include young African American and Asian children, diabetics and individuals with chronic liver disease, malnutrition, or iron-overload states. The higher rates among African American children were considered attributable to cross-contamination within the home during preparation of chitterlings (pig intestines). These high incidence rates in African American children observed in the late 1990s have declined dramatically following preventive health campaigns focusing on avoidance of cross-contamination in the kitchen. Nevertheless, in 2019, the Foodborne Disease Active Surveillance Network (FoodNet) of the US Centers for Disease Control and Prevention (CDC) reported 1.4 cases per 100,000 population, which evidences an increase of 153% in incidence from 2016 to 2018. ^, Almost all cases of yersiniosis are due to Y. enterocolitica . In 2015, FoodNet reported the highest incidence rates of yersiniosis among children under 5 years (0.74 per 100,000).

In the European Union, according to the 2018 epidemiological report of the European Center for Disease Prevention and Control, yersiniosis ranked fourth among reported bacterial zoonoses, reporting ~6800 confirmed yersiniosis cases in 29 European countries; the great majority of which (99%) were due to Y. enterocolitica . The overall notification rate was 1.6 cases per 100,000 individuals, throughout 2014–2018. Most cases were reported from Germany with an incidence of 2.3 cases per 100,000 individuals; however, the highest rates were reported from Finland, the Czech Republic, Denmark and Lithuania with 9.6, 5.9, 4.9 and 4.9 cases per 100,000, respectively. The highest rate was detected in 0 to 4-year-old children: 7.4 per 100,000 population for males and 6.4 per 100,000 for females.

High rates of Y. enterocolitica infection have been reported in New Zealand since 2010 with an incidence of 24.6 per 100,000 population in 2018.

Clinical Manifestations

Laboratory Findings and Diagnosis

Fecal leukocytes are common in patients with colitis. Y. enterocolitica can be isolated from stool and sometimes from mesenteric lymph nodes or peritoneal fluid specimens from children who have undergone appendectomy. Y. enterocolitica grows on all commonly used enteric media. Cold enrichment in phosphate-buffered saline or other selective enrichment media are useful for recovery of Y. enterocolitica. Cefsulodin–irgasan–novobiocin (CIN) agar, which is selective for the growth of Yersinia, is preferred for isolation from fecal samples. Growth of pathogenic Yersinia can require up to 4 weeks of incubation.

Yersinia organisms are coccobacillary and exhibit bipolar staining in blood agar. Stored samples or cultures grown on more restrictive media show morphologic variation with Gram stain. Avirulent strains are pyrazinamidase positive and fail to autoagglutinate; virulent strains stain with crystal violet and Congo red binding assays.

Y. enterocolitica species are divided into six biotypes (i.e., 1A, 1B, and 2–5), which include several serotypes. Most human pathogenic Y. enterocolitica strains are biotype 4, serotype O:3. Serotypes most commonly associated with disease in North America are different from those identified in Europe. Serologic responses can be used as evidence of infection when culture results are negative and a compatible syndrome is identified.

Titer determinations are available through commercial laboratories for the most common serotypes, but results should be interpreted with caution. Children younger than 1 year of age are less likely to develop a serologic response than older children. Cross-reactions with Brucella abortus, Morganella morganii, Salmonella species , Bartonella henselae, Chlamydophila pneumoniae, Rickettsia rickettsii, and Borrelia burgdorferi and persistence of titers for several years after Y. enterocolitica infection limit the usefulness of serodiagnosis. Using antibodies raised against the recombinant attachment-invasion locus (Ail) protein, detected by indirect enzyme immunoassay and Western blot immunoassay, can aid in identifying pathogenic Y. enterocolitica strains.

Several molecular techniques have been developed to identify Y. enterocolitica DNA in clinical, food, and environmental samples. The detection rate of pathogenic Y. enterocolitica in clinical specimens is higher using polymerase chain reaction (PCR) than culture, but results must be interpreted with caution when the sample is from a nonsterile site. The use of multi-pathogen gastrointestinal diagnostic panels for fecal specimens has expanded. In 2018, 68% of yersiniosis cases reported to FoodNet were diagnosed using such culture-independent panels; of those, approximately one-third were culture positive for Yersinia , one-third were culture negative, and in one-third the culture was not done.

Treatment and Prevention

The benefit of antibiotics for management of immunocompetent people with Yersinia enterocolitis has not been established conclusively. Infected patients with abdominal pain and mesenteric adenitis are usually treated. Patients who are immunocompromised and patients with extraintestinal dissemination should be treated with antibiotics. Y. enterocolitica usually is susceptible in vitro to trimethoprim-sulfamethoxazole, chloramphenicol, fluoroquinolones, aminoglycosides, tetracycline, piperacillin, and extended-spectrum cephalosporins and resistant to most penicillins and first-generation cephalosporins.

If septicemia develops during desferrioxamine treatment in patients with iron overload states, chelation should be stopped temporarily. Antibiotic therapy has no beneficial effect on postinfectious syndromes.

Outbreaks of illness due to Y. enterocolitica are often foodborne and should receive prompt and thorough investigation. Recall of suspected contaminated items can abort an outbreak. Careful attention to appropriate cooking practices in handling of pig products, especially intestines, should decrease the risk associated with these food products. Consumption of uncooked meats should be avoided, and meat should not be refrigerated for prolonged periods before consumption because Y. enterocolitica growth can be enhanced at refrigerator temperatures. No vaccine against Y. enterocolitica is available, although several candidates are under evaluation.

Epidemiology

Y. pseudotuberculosis is distributed worldwide in animals, including rodents, birds (e.g., turkey, duck, geese, pigeons, canaries), rabbits, deer, and farm animals. Infection can follow exposure to well and mountain water. The organism was originally described as causing tuberculosis-like lesions in guinea pigs. Household pets often are the source of infection for children. Y. pseudotuberculosis also can be transmitted through food products, and outbreaks have been linked to pasteurized milk, and contaminated root vegetables with a long cold storage such as lettuce, and carrots. ^,

As with Y. enterocolitica, infections in humans cluster in colder months. Human infections are most common among children between 5 and 15 years of age, with a threefold male predominance. Y. pseudotuberculosis infection has primarily been reported in the Northern hemisphere in Europe, North America, Russia, and Japan, but infection occurs at low incidences on all continents. Disease may arise sporadically or in the form of outbreaks; albeit most cases are sporadic. In Europe, among 6800 cases of yersiniosis reported in 2018, only 74 were due to Y. pseudotuberculosis. From 1996 through 2007, the average annual incidence of Y. pseudotuberculosis infection in the US was 0.04 cases per 1 million people. Compared with Y. enterocolitica, Y. pseudotuberculosis infects older individuals, who are more likely to require hospitalization for invasive infection. Patients with iron overload are at increased risk for infection, although this seems to be a less common risk factor than for Y. enterocolitica infections .

Clinical Manifestations

Y. pseudotuberculosis causes acute gastroenteritis and mesenteric lymphadenitis, often accompanied by fever and abdominal pain. The most common clinical syndrome is pseudoappendicitis, which is characterized by abdominal pain, right lower quadrant tenderness, fever, and leukocytosis. Less commonly, Y. pseudotuberculosis can mimic Kawasaki disease and has been implicated as a possible cause. Yersinia has also been associated with intussusception, mainly in children. Septicemia or extraintestinal spread of Y. pseudotuberculosis is uncommon and primarily has been reported in patients with underlying conditions such as cirrhosis, malignancy, diabetes, aplastic anemia, thalassemia, iron overload, and human immunodeficiency virus (HIV) infection.

Y. pseudotuberculosis infection may cause severe systemic inflammatory symptoms. This disease variant is called Far East scarlet-like fever (FESLF) and has been reported sporadically as well as in outbreaks in Russia and Japan. Some studies suggest that the ability of Far Eastern strains to produce superantigen toxin Y. pseudotuberculosis- derived mitogen A (YPMa) may be key to FESLF pathogenesis.

Acute renal failure with interstitial nephritis is a complication in up to 14% of patients with Y. pseudotuberculosis , although prognosis is usually good. ^, Y. pseudotuberculosis infection occasionally leads to postinfectious sequelae such as reactive arthritis and erythema nodosum. Reactive arthritis and severe clinical outcome have been particularly associated with Y. pseudotuberculosis serotype O:3.