Chapter 195 Yersinia
The genus Yersinia is a member of the family Enterobacteriaceae and comprises >14 named species, 3 of which are established as human pathogens. Yersinia enterocolitica is by far the most common Yersinia species causing human disease and produces fever, abdominal pain that can mimic appendicitis, and diarrhea. Yersinia pseudotuberculosis is most often associated with mesenteric lymphadenitis. Yersinia pestis is the agent of plague and most commonly causes an acute febrile lymphadenitis (bubonic plague) and less commonly occurs as septicemic, pneumonic, or meningeal plague. Untreated and delayed treated plague has significant mortality. Other Yersinia organisms are uncommon causes of infections of humans, and their identification is often an indicator of immunodeficiency. Yersinia is enzootic and can colonize pets. Infection of humans most often results from contact with infected animals or their tissues; ingestion of contaminated water, milk, or meat; or, for Y. pestis, the bite of infected fleas. Association with human disease is less clear for Y. frederiksenii, Y. intermedia, Y. kristensenii, Y. aldovae, Y. bercovieri, Y. mollaretii, Y. rohdei, and Y. ruckeri. Some Yersinia isolates replicate at low temperatures (1-4°C) or survive at high temperatures (50-60°C). Thus, common food preparation and storage and common pasteurization methods might not limit the number of bacteria. Most are sensitive to oxidizing agents.
195.1 Yersinia enterocolitica
Etiology
Y. enterocolitica is a large, gram-negative coccobacillus that exhibits little or no bipolarity when stained with methylene blue and carbol fuchsin. These facultative anaerobes grow well on common culture media and are motile at 22°C but not at 37°C. Y. enterocolitica includes pathogenic and nonpathogenic members.
Epidemiology
This agent 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. There is approximately 1 culture- confirmed Y. enterocolitica infection per 100,000 population/yr in the USA, and infection may be more common in Northern Europe. Cases are more common in colder months and among younger persons and boys. Most infections in children are among those <7 yr of age, with the majority among children <1 yr of age.
Natural reservoirs of Y. enterocolitica include pigs, rodents, rabbits, sheep, cattle, horses, dogs, and cats, with pigs being the major animal reservoir. Contact with feral animals or a colonized pet is a common source of human infections. Culture and molecular techniques have found the organism in a variety of foods, including vegetable juice, pasteurized milk, and carrots and in water. A source of sporadic Y. enterocolitica infections is pig offal (chitterlings). 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 is transmitted at times by intravenous injection of contaminated fluids, including blood products.
Y. enterocolitica infections have increased, and Y. pseudotuberculosis infections have declined, leading to the suggestion that the former organism is replacing the latter in an ecologic niche. In part, the mass production of animals, development of meat factories based on chains of cold storage, and international trade of meat products and animals are believed to be the reasons for the increasing prevalence of yersiniosis in humans. There is evidence that under farm conditions pigs can be raised free of Y. enterocolitica.
Pathogenesis
The 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.
Adherence, invasion, and toxin production are established as essential mechanisms of pathogenesis. Bacterial components, some associated with the bacterial type III secretion apparatus, can actively suppress immunologic capacities, suggesting that immunosuppression can contribute to pathogenesis. 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. Virulence traits are both chromosomal and plasmid encoded. Possibly because pathogenic strains require iron, patients with iron overload as in hemochromatosis, thalassemia, and sickle cell disease are at high 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. Stools may be watery or contain leukocytes and, less commonly, frank blood and mucus. 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 of age) and immunocompromised persons. Systemic infection is associated with splenic and hepatic abscesses, osteomyelitis, meningitis, endocarditis, and mycotic aneurysms. Exudative pharyngitis, pneumonia, empyema, lung abscess, and acute respiratory distress syndrome uncommonly occur. Y. enterocolitica infection in immunocompromised persons can manifest with physical and CT findings suggesting colon cancer with liver metastases.
Reactive complications include erythema nodosum, arthritis, and the uveitis rash syndrome. These manifestations may be more common in selected populations (northern Europeans), in association with HLA-B27, and in girls. Y. enterocolitica has been associated with Kawasaki disease.
Diagnosis
Y. enterocolitica is easily cultured from normally sterile sites but requires special procedures for isolation from stool, where other bacteria can outgrow it. Cold enrichment, where a sample is held in buffered saline, can result in preferential growth of Yersinia, but the procedure takes weeks. Polymerase chain reaction (PCR) and DNA microarray are more sensitive than culture with DNA microarray more sensitive and accurate than multiplex PCR. Many laboratories do not routinely perform the procedures 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 possible but not readily available.
Differential Diagnosis
The clinical presentation is similar to other forms of bacterial enterocolitis. The most common considerations include Shigella, Salmonella, Campylobacter, Clostridium difficile, enteroinvasive Escherichia coli, Y. pseudotuberculosis, and occasionally Vibrio diarrheal disease (Chapter 332). Amebiasis, appendicitis, Crohn disease, ulcerative colitis, diverticulitis, and pseudomembranous colitis should also be considered.
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. Many Yersinia organisms are susceptible to trimethoprim-sulfamethoxazole (TMP-SMX), aminoglycosides, 3rd-generation cephalosporins, and quinolones. TMP-SMX is the recommended empirical treatment in children, because it has activity against most strains and is well tolerated. In severe infections such as bacteremia, 3rd-generation cephalosporins with or without aminoglycosides are effective. Y. enterocolitica produces β-lactamases, which are responsible for resistance to penicillins and 1st-generation cephalosporins. Patients on deferoxamine should discontinue iron chelation therapy during treatment for Y. enterocolitica, especially if they have complicated gastrointestinal 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, and viable organisms are not present in involved joints.
Prevention
Prevention centers on reducing contact with environmental sources of Yersinia. 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.
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