Yersinia

Keywords

• abdominal pain

• appendicitis

• bacteremia

• blood products

• chitterlings

• diarrhea

• enterocolitis

• food-borne infection

• iron overload

• mesenteric lymphadenitis

• pharyngitis

• pig

• pork

• water-borne infection

Etiology

Yersinia enterocolitica is a large, gram-negative coccobacillus that exhibits little or no bipolarity when stained with methylene blue and carbolfuchsin. It ferments glucose and sucrose but not lactose, is oxidase negative, and reduces nitrate to nitrite. These facultative anaerobes grow well on common culture media and are motile at 22°C (71.6°F) but not 37°C (98.6°F). Optimal growth temperature is 25-28°C (77-82.4°F); however, the organism can grow at refrigerator temperature. Y. enterocolitica includes pathogenic and nonpathogenic members. It has 6 different biotypes (1A, 1B, and 2-5). Y. enterocolitica relies on other bacteria for iron uptake, and conditions associated with iron overload increase risk of infection.

Epidemiology

Y. enterocolitica is transmitted to humans through food, water, animal contact, and contaminated blood products. Transmission can occur from mother to newborn. Y. enterocolitica appears to have a global distribution but is seldom a cause of tropical diarrhea. In 2014, incidence of culture-confirmed Y. enterocolitica infection in the United States was 0.28 per 100,000 population (52% decrease from incidence in 1996–1998). Infection may be more common in Northern Europe. Most infections occur among children <5 yr old (incidence: 1.6-1.9 per 100,000 population), with the majority among children <1 yr old. It is estimated that Y. enterocolitica accounts for 5% of illnesses secondary to major bacterial enteric pathogens in children <5 yr old in the United States. Cases are more common in colder months and among males.

Natural reservoirs of Y. enterocolitica include pigs, rodents, rabbits, sheep, cattle, horses, dogs, and cats, with pigs being the major animal reservoir. Direct or indirect contact with animals, including pets, other domesticated animals, and wild animals, may be responsible for <1% of cases of enteric illnesses caused by Y. enterocolitica . Culture and molecular techniques have found the organism in a variety of foods and beverages, including vegetable juice, pasteurized milk, carrots, and water. Consumption of contaminated water or food, particularly undercooked pork, is the most common form of transmission to humans. A source of sporadic Y. enterocolitica infections is chitterlings (pig intestines, “chitlins”), a traditional dish in the southeastern United States as well as Latin America, often in celebration of winter holidays. The infection is often seen in young infants in the household due to contamination of bottle and food preparation when chitterlings are prepared. In one study, 71% of human isolates were indistinguishable from the strains isolated from pigs. Y. enterocolitica is an occupational threat to butchers.

In part because of its capacity to multiply at refrigerator temperatures, Y. enterocolitica can be transmitted by intravenous injection of contaminated fluids, including blood products.

Patients with conditions leading to iron overload are at higher risk of developing Yersinia infections.

Pathogenesis

The Yersinia organisms most often enter by the alimentary tract and cause mucosal ulcerations in the ileum. Necrotic lesions of Peyer patches and mesenteric lymphadenitis occur. If septicemia develops, suppurative lesions can be found in infected organs. Infection can trigger reactive arthritis and erythema nodosum , particularly in HLA-B27–positive individuals.

Virulence traits of pathogenic biotypes(1B and 2-5) are encoded by chromosomal genes and a highly conserved 70 kb virulence plasmid (pYV/pCD). The chromosomal genes control the production of heat-stable enterotoxins, and the plasmid allows penetration through the intestinal wall. Adherence, invasion, and toxin production are the essential mechanisms of pathogenesis. The bacteria mainly invade the intestinal epithelium in the Peyer patches of the ileum. After invasion, plasmid-encoded type III secretion of 3 antiphagocytic proteins protects Yersinia against the immunologic response of local macrophages. From Peyer patches, bacteria can disseminate to cause local or systemic disease. Motility appears to be required for Y. enterocolitica pathogenesis. Serogroups that predominate in human illness are O:3, O:8, O:9, and O:5,27. Yersinia does not produce siderophores and uses analogous siderophores from other bacteria or host-chelated iron stores to thrive, placing patients with iron overload, as in hemochromatosis, thalassemia, and sickle cell disease, at higher risk for infection.

Clinical Manifestations

Disease occurs most often as enterocolitis with diarrhea, fever, and abdominal pain. Acute enteritis is more common among younger children, and mesenteric lymphadenitis that can mimic appendicitis may be found in older children and adolescents. Incubation period is usually 4-6 days after exposure (range 1-14 days). Stools may be watery or contain leukocytes and, less often, frank blood and mucus. Duration of diarrhea is often longer for Y. enterocolitica than for other causes of acute gastroenteritis, ranging from 12-22 days in several studies. Fever is common. Notably, prominent pharyngitis may be seen in 20% of patients at presentation, which may help distinguish it from other causes of gastroenteritis. Y. enterocolitica is excreted in stool for 1-4 wk. Family contacts of a patient are often found to be asymptomatically colonized with Y. enterocolitica. Y. enterocolitica septicemia is less common and is most often found in very young children (<3 mo old) and immunocompromised persons. Systemic infection can be associated with splenic and hepatic abscesses, osteomyelitis, septic arthritis, meningitis, endocarditis, and mycotic aneurysms. Exudative pharyngitis, pneumonia, empyema, lung abscess, and acute respiratory distress syndrome occur infrequently.

Reactive complications include erythema nodosum, reactive arthritis, and rarely uveitis. These manifestations may be more common in select populations (northern Europeans), in association with HLA-B27, and in females.

Diagnosis

Diagnosis is made typically through isolation of the organism, usually from the stool. Y. enterocolitica is easily cultured from normally sterile sites but requires special procedures for isolation from stool, where other bacteria can outgrow it. Yersinia should be cultured on selective agar (CIN, cefsulodin-irgasan-novobiocin) at 25-28°C to increase yield. If O:3 serogroup is suspected, MacConkey agar should be used at 25-28°C. Multiplex polymerase chain reaction (PCR) testing is also available. Many laboratories do not routinely perform the tests required to detect Y. enterocolitica ; procedures targeted to this organism must be specifically requested. A history indicating contact with environmental sources of Yersinia and detection of fecal leukocytes are helpful indicators of a need to test for Y. enterocolitica. The isolation of a Yersinia from stool should be followed by tests to confirm that the isolate is a pathogen. Serodiagnosis is not readily available, and utility is limited by cross-reactivity.

Treatment

Enterocolitis in an immunocompetent patient is a self-limiting disease, and no benefit from antibiotic therapy is established. Patients with systemic infection and very young children (in whom septicemia is common) should be treated. Yersinia organisms are typically susceptible to trimethoprim-sulfamethoxazole (TMP-SMX), aminoglycosides, third-generation cephalosporins, and quinolones, although strains resistant to quinolones have been reported. Y. enterocolitica produces β-lactamases, which are responsible for resistance to penicillins and first-generation cephalosporins. TMP-SMX is the recommended empirical treatment in children for enterocolitis (generally a 5-day course), because it has activity against most strains and is well tolerated. In severe infections such as bacteremia, third-generation cephalosporins, with or without aminoglycosides, are effective, and usually a 3 wk course of therapy is administered, with possible transition to oral therapy. Patients on deferoxamine should discontinue iron chelation therapy during treatment for Y. enterocolitica, especially if they have complicated gastrointestinal (GI) infection or extraintestinal infection.

Complications

Reactive arthritis, erythema nodosum, erythema multiforme, hemolytic anemia, thrombocytopenia, and systemic dissemination of bacteria have been reported in association with Y. enterocolitica infection. Septicemia is more common in younger children, and reactive arthritis is more common in older patients. Arthritis appears to be mediated by immune complexes, which form as a result of antigenic mimicry, and viable organisms are not present in involved joints.

Prevention

Prevention centers on reducing contact with environmental sources of Yersinia. Families should be warned of the high risk of chitterling preparation, especially with young infants and children in the household. Breaking or sterilization of the chain from animal reservoirs to humans holds the greatest potential to reduce infections, and the techniques applied must be tailored to the reservoirs in each geographic area. There is no licensed vaccine.