Yersiniosis: Infection due to Yersinia enterocolitica and Yersinia pseudotuberculosis

INTRODUCTION — The yersinioses are zoonotic infections of domestic and wild animals; humans are incidental hosts that do not contribute to the natural disease cycle. Three species are important human pathogens: Yersinia pestis, Yersinia enterocolitica, and Yersinia pseudotuberculosis [1].

Y. enterocolitica and Y. pseudotuberculosis cause yersiniosis, a diarrheal illness; this condition is discussed below.

Y. pestis causes plague; this condition is discussed separately. (See "Epidemiology, microbiology and pathogenesis of plague (Yersinia pestis infection)" and "Clinical manifestations, diagnosis, and treatment of plague (Yersinia pestis infection)".)

EPIDEMIOLOGY

Reservoirs of infection

●Y. enterocolitica – Y. enterocolitica strains have been isolated from a variety of vertebrate hosts, including domesticated animals as well as wildlife [2]. In pigs, the organism colonizes the tonsils and other oropharyngeal lymphoid tissues; from these sites, it can be shed into the gastrointestinal tract. Healthy pigs are frequently colonized with strains that cause human illness, such as serotype O:3 and serotype O:9.

Y. enterocolitica in swine herds may spread as pigs are transferred from one farm to another and then can persist on a farm for many years [3]. The organisms can contaminate retail pork products, including neck trimmings, tonsillar tissue, tongue, and tripe, and can be transferred to other cuts of meat during slaughter [4,5].

●Y. pseudotuberculosis – Y. pseudotuberculosis has been isolated from a variety of mammals and birds. It causes epizootic disease in northern Europe among European brown hares, in Australia among sheep, and in New Zealand among farmed deer [6-8].

Transmission — Transmission of yersiniosis is largely foodborne (including pork and other food sources) and occasionally waterborne. Uncommon modes of transmission include exposure to household pets [9], person-to-person fecal-oral transmission [10], and transfusion of blood products [11,12].

Updated information on outbreaks may be found on websites maintained by the United States Centers for Disease Control and Prevention and the US Food and Drug Administration.

●Y. enterocolitica

•Pork and other food sources – Consumption of raw or undercooked pork products is a major mode of transmission for Y. enterocolitica. Case-control studies of sporadic illnesses in Belgium and Norway have noted a strong association between consumption of undercooked or raw pork products and yersiniosis [13,14]. In a Swedish study, strains of Y. enterocolitica isolated from retail pork had the same PFGE profiles as patient isolates [15]. In Norway and New Zealand, sporadic yersiniosis has been associated with drinking untreated surface water [14,16].

Yersiniosis has been associated with preparation of chitterlings, a winter holiday dish comprised of pig intestines [17-20]. This was first described in 1989 during an investigation of bacteremia among bottle-fed African American infants in the United States; transmission was attributed to cross contamination of infant bottles or formula during chitterling preparation [18].

Outbreaks have been attributed to other food sources [21-25], including tofu packaged in untreated spring water [21], contamination of salad greens, and post-pasteurization contamination of milk [22-27].

•Blood transfusion – In rare cases, Y. enterocolitica septicemia has occurred following transfusion with packed red cells [11]. Yersinia organisms are ferrophilic and capable of multiplying slowly in stored units of red cells at cold temperatures prior to transfusion. In one study conducted between 1998 and 2000, the incidence of transfusion-associated Yersinia sepsis was 1 in 23.7 million red cell transfusions [28]. (See 'Microbiology' below and "Transfusion-transmitted bacterial infection", section on 'Reducing risk of bacteria in the product'.)

●Y. pseudotuberculosis – Data on transmission of Y. pseudotuberculosis are limited; outbreaks have been associated with consumption of contaminated lettuce, carrots, and milk [29-33].

Risk factors — Individuals at increased risk for yersiniosis include:

●Children <5 years of age, especially <12 months of age.

●Patients with derangements of iron metabolism (such as cirrhosis, hemochromatosis, aplastic anemia, thalassemia, sickle cell disease, and iron overload) — Yersinia organisms are ferrophilic, and patients who undergo transfusion can develop iron overload. However, in one series of patients with thalassemia, yersiniosis was observed even among individuals whose iron burden was not greatly elevated; the reasons for this observation are not fully understood [34]. (See 'Microbiology' below.)

●Patients with other comorbid conditions (such as immunosuppression, malignancy, diabetes, or severe malnutrition).

Individuals with relevant exposure risks (consumption of uncooked or raw pork products, exposure to other food sources or untreated water, or blood transfusion) are also at risk for yersiniosis. (See 'Transmission' above.)

Disease incidence

●Geographic distribution – Yersiniosis has been reported frequently in northern Europe, particularly in Belgium, Norway, and the Netherlands; it is rarely observed in tropical countries [35]. The reasons for these geographic patterns are uncertain but may reflect the frequency of infection in food animal reservoirs.

In Europe, the annual incidence in 2016 was 1.8 cases per 100,000; the incidence was highest in Finland (7.4 per 100,000) and Lithuania (5.9 per 100,000) [36]. In Belgium, the incidence peaked in 1986 at 14.7 per 100,000; in 2016 it was 3.1 per 100,000 [35,37]. Reasons for declining incidence may include public education to reduce consumption of raw or undercooked pork products, changing dietary habits, and efforts by the meat industry to reduce contamination of carcasses during processing [38].

In the United States, the incidence of yersiniosis is lower than in Europe. The incidence of yersiniosis reported to the Foodborne Disease Active Surveillance program (FoodNet) of the United States Centers for Disease Control and Prevention (CDC) was higher in 2022 compared with 2016 to 2018 (2.0 versus 0.9 per 100,000) [39]. This increase likely reflects the greater frequency of testing with rapid culture-independent diagnostic tests (CIDTs) [40]. Almost all yersiniosis in the United States is due to Y. enterocolitica; between 1996 and 2007, only 1 percent of reported yersiniosis was due to Y. pseudotuberculosis [41]. Accounting for underdiagnosis and under-reporting, the actual number of Y. enterocolitica infections occurring annually in the United States is estimated to be 117,000 [42].

In New Zealand, high rates of Y. enterocolitica infection have been described since the 1990s; in 2019 the incidence was 24.1 per 100,000 [43].

●Incidence among children – The incidence of Yersinia infections is highest among young children, although the age distribution may be changing in the era of multipathogen syndromic diagnostic panels.

In Europe, in 2016, the incidence among children <5 years of age was 7.5 per 100,000 [36].

In the United States between 1996 and 2009, children <5 years of age comprised 47 percent of Yersinia infections reported to the CDC's FoodNet program [44]. Over this time, the overall incidence among children dropped from 9.2 to 1.9 per 100,000, and the most substantial decrease was among African American children <5 years of age, in whom the incidence dropped from 41.5 to 3.5 per 100,000 cases [44].

MICROBIOLOGY — Yersinia are facultative gram-negative anaerobic coccobacilli [45,46]. Y. pseudotuberculosis and Y. enterocolitica are bile tolerant and grow on MacConkey agar, they ferment glucose but not lactose, they are oxidase negative, and reduce nitrate to nitrite.

Y. pseudotuberculosis and Y. enterocolitica are readily differentiated by biochemical tests. Yersinia can also be biotyped (by a combination of phenotypic markers) and serotyped (using antisera produced against cell surface lipopolysaccharide antigens, known classically as the O antigens) [47,48]. For Y. enterocolitica, biotype and serotype are correlated; the most common are serotype O:9 biotype 2, serotype O:3 biotype 4, and serotype O:8 biotype 1B [49]. Both species can be further subtyped using molecular methods. Biotype and serotype are useful epidemiologic tools that can provide clues to the environmental source of an infection [2]. Detecting a cluster of infections of the same molecular subtype may indicate that the cases are linked to a common source.

Noteworthy microbiological features of Y. enterocolitica include:

●The organism is cryophilic; on suitable media, it is capable of multiplying at refrigerator temperatures (2 to 4°C), although its optimal growth temperature is 25 to 28°C. (See 'Organism identification' below.)

●Most strains lack efficient intrinsic iron uptake mechanisms; they depend on the iron binding strategies of other bacteria to capture the iron they need [50]. Clinical conditions associated with iron-overload such as chronic liver disease, hemochromatosis, and thalassemias have been associated with an increased risk of invasive yersiniosis [51]. (See 'Risk factors' above.)

●Many virulent strains are relatively calcium dependent, and require calcium-supplemented medium to grow at 37°C.

Certain subtypes of Y. enterocolitica are virulent for humans [52]. The most important human pathogens are serogroups O:3, O:5,27, O:8, and O:9 though other serogroups may occasionally cause infection. Isolation of non-virulent types from a non-sterile body site is likely to be an incidental finding. Rapid tests can determine whether an isolate is likely to be pathogenic. (See 'Organism identification' below.)

CLINICAL MANIFESTATIONS — Major clinical manifestations include acute yersiniosis (eg, acute febrile enterocolitis) and pseudoappendicitis syndrome. A variety of complications (both gastrointestinal and extraintestinal) and post-infectious sequelae have also been described, as outlined in the following sections [53].

Acute yersiniosis — The typical incubation period for acute yersiniosis is 4 to 6 days (range 1 to 14 days) [18,21,54].

Enterocolitis

●General signs and symptoms – Clinical manifestations include fever, abdominal pain, and diarrhea; nausea and vomiting may also occur [55].

The onset of Yersinia enterocolitis can be more subacute than other diarrheal pathogens [13,56]. In a Norwegian study including 67 cases of sporadic yersiniosis, an average of more than a week elapsed before patients sought medical care and almost two weeks elapsed before a stool culture was obtained [56].

The median duration of diarrhea for yersiniosis can be longer than for other causes of acute enterocolitis. In four case series, the duration ranged from 12 to 22 days (table 1) [13,56-59]. Prolonged illnesses were observed in each case series, and some patients reported persistent diarrhea or abdominal pain up to a year following acute illness.

In some circumstances, localization of abdominal pain to the right lower quadrant may be a diagnostic clue for yersiniosis. (See 'Pseudoappendicitis' below.)

Following Yersinia enterocolitis, stool shedding of organisms may persist after resolution of diarrhea. Among 67 patients with yersiniosis in Norway, shedding was observed among 47 percent of cases and lasted a median of 40 days (range 17 to 116 days) after illness onset [56].

●Manifestations in children – Among children <5 years, the most prominent clinical manifestations are fever, diarrhea, and vomiting; abdominal pain is observed relatively infrequently [60]. In more severe infections, leukocytosis is often observed [17].

Bloody diarrhea is observed more frequently among children than adults. In case series of mainly pediatric patients, 20 to 60 percent reported bloody diarrhea (table 1) [18,21,22]. In contrast, in a series of 29 adults with yersiniosis, bloody diarrhea was noted in only 7 percent of cases [59].

The above features may be clinical clues for distinguishing from infection with Shiga toxin producing Escherichia coli (STEC), such as E. coli O157:H7, which may present with bloody stools, pronounced abdominal pain, and minimal fever. (See "Shiga toxin-producing Escherichia coli: Clinical manifestations, diagnosis, and treatment".)

Pharyngitis — Pharyngitis may also be a presenting symptom in patients with acute yersiniosis. In some case series, sore throat was reported by up to 20 percent of patients (table 1) [13,22,56,61]. In one outbreak, Y. enterocolitica was isolated from throat cultures in 14 patients, illustrating the propensity for involvement of lymphoid tissue, such as the tonsils (in humans as well as pigs) [61]. This symptom can be a helpful diagnostic clue since other causes of acute bacterial diarrhea are not associated with pharyngitis. (See 'Reservoirs of infection' above.)

In Eastern Siberia and Japan, a scarlet-fever like syndrome associated with Y. pseudotuberculosis has been described; this is characterized by fever, systemic illness, arthralgias, and a presence of a morbilliform or confluently erythematous rash that subsequently desquamates [62].

Bacteremia and sepsis — Yersinia septicemia can occur in the setting of acute infection, particularly among infants and individuals with impaired immunity or iron-overload states [63,64]. In addition, transient bacteremia may be more common than previously recognized, even among otherwise healthy individuals [11]. In one report of 55 cases associated with blood transfusion, rapid onset septic shock was described with an overall fatality of 50 percent [12]. (See 'Risk factors' above.)

Pseudoappendicitis — Acute yersiniosis may be confused with acute appendicitis; overlapping symptoms may include right lower quadrant abdominal pain, fever, vomiting, leukocytosis, and diarrhea.

For patients who undergo surgery, operative findings include inflammation around the appendix, terminal ileum, and mesenteric lymph nodes; the appendix itself is generally normal. Yersinia can be cultured from the appendix and involved lymph nodes [65].

One outbreak of yersiniosis among children was identified because of an unusually high number of cases of suspected appendicitis; approximately 42 percent of identified cases underwent surgery [66]. In other outbreaks, the rates of surgical intervention have ranged from 0 to 14 percent (table 1) [18,21,22].

In regions where the incidence of yersiniosis is high, an appreciable fraction of appendectomies occurs in the setting of yersiniosis [67-69]. In one study including 2861 patients in Belgium who underwent appendectomy for clinically suspected appendicitis, pathogenic Y. enterocolitica was cultured from the appendix in 3.6 percent of cases; among 73 patients with a positive appendix culture, gross examination demonstrated mesenteric adenitis and/or terminal ileitis (rather than frank appendicitis) in 75 percent of cases [68].

Complications — Gastrointestinal complications of acute yersiniosis are rare; they include [54,70-76]:

●Diffuse ulcerating ileitis and colitis

●Intestinal perforation

●Peritonitis

●Intussusception

●Paralytic ileus

●Toxic megacolon

●Necrotic small bowel

●Cholangitis

●Mesenteric vein thrombosis

Extraintestinal complications of acute yersiniosis are also rare; they include [54,70-76]:

●Abscess of the liver, spleen, kidney or lung

●Pharyngeal abscess

●Empyema

●Endocarditis

●Mycotic aneurysm

●Meningitis

●Ophthalmitis

●Osteomyelitis

●Septic arthritis

●Suppurative lymphadenitis

●Skin manifestations (carbuncle, granuloma, vesiculobullous lesions, pustules, wound infection)

Myocarditis, glomerulonephritis, and liver failure have all been reported following yersiniosis; these are extremely rare.

Post-infectious sequelae — The most common post-infectious sequelae are erythema nodosum and reactive arthritis; these are particularly common in northern Europe, especially among those with the HLA-B27 tissue type [77].

Erythema nodosum has been observed to occur following acute Yersinia infection in up to 30 percent of patients in Finland, particularly among young women; it is less frequently recognized elsewhere [78]. It typically occurs within one month after acute infection and is self-limited. (See "Erythema nodosum".)

Reactive arthropathy has been described in up to 30 percent of adults affected in an outbreak of Y. pseudotuberculosis infections in Finland; most patients had HLA-B27 tissue type [79]. Reactive arthritis typically affects the large weight-bearing joints and begins several weeks after the onset of acute infection. Symptoms can be self-limited (lasting three to five months) or can persist with a relapsing pattern [53]. In a ten-year follow-up study of Finnish patients with reactive arthritis, 52 percent reported mild peripheral joint symptoms, 36 percent reported chronic low back pain, and 36 percent had radiographic evidence of sacroiliitis [80]. (See "Reactive arthritis".)

Ocular involvement including conjunctivitis and uveitis has also been described [81].

The time course of these complications mirrors the humoral immune response to bacterial infections. The pathogenesis of reactive arthropathy reflects "molecular mimicry" (eg, the antigenic similarity of Yersinia antigens to antigens in the joints of susceptible individuals). The immune response to Yersinia antigens can cross-react against host antigens. Some studies have identified Yersinia-like antigens in synovial fluid, although it is unlikely that these reflect microbial growth in joints [82,83].

Yersinia also shares an antigen with thyroid tissue that resembles the thyrotropin (TSH) binding site. Therefore, individuals with Graves' disease may have antibodies that cross react with Yersinia [84]. However, there is no evidence that yersiniosis actually triggers thyroiditis [2].

DIAGNOSIS

Clinical approach

●Clinical suspicion – Yersiniosis should be suspected in the setting of relevant clinical manifestations (fever, abdominal pain, and diarrhea, with or without nausea and vomiting). These manifestations may occur in the presence or absence of relevant epidemiologic exposure (such as consumption of raw or undercooked pork or exposure to food or water implicated in an outbreak).

●Diagnostic evaluation – Patients with enterocolitis should have stool sent for culture. If available, stool may also be sent for rapid molecular panel testing; such panels may facilitate diagnosis of yersiniosis but are not able to assess antimicrobial susceptibility. If Yersinia is identified via molecular testing, reflex culture and susceptibility testing should be performed. (See 'Organism identification' below.)

Patients with fever should have blood cultures obtained. Patients with pharyngitis should have a throat culture obtained. In infants with yersiniosis, cerebrospinal fluid should be examined in infants [85].

For patients who undergo surgery in the setting of suspected appendicitis, specimens of appendix or mesenteric lymph nodes obtained operatively should be cultured.

For clinical circumstances in which abscess material, pleural fluid, or other focal suppurative samples are obtained, these should be cultured as well.

Organism identification — The diagnosis of Yersinia infection is usually established by culture of the organism from stool or blood; it may also be established by culture from the throat, appendix, mesenteric lymph nodes, or other sterile sites [2]. Specimens that test positive via culture-independent techniques should be set up for reflex culture and susceptibility testing [86].

●Culture – Most laboratories do not screen for Yersinia species routinely on stool culture. Yersinia species grow poorly on the agars commonly used for the isolation of stool pathogens [48]. The organisms do grow well on MacConkey agar; however, at routine incubation temperatures, they form small colorless lactose-negative colonies, which are easily overlooked by the inexperienced eye unless the plates are examined for them specifically [48].

The most widely studied selective growth medium is cefsulodin-irgasin-novobiocin (CIN) agar, which inhibits the growth of competing flora and produces a characteristic colony morphology (figure 1) [87]. If Yersinia culture is requested, the laboratory usually will use CIN media or reincubate the original MacConkey agar culture. CHROMagar Yersinia has been reported to be more selective for pathogenic strains of Y. enterocolitica, but Y. pseudotuberculosis does not grow on it at all [88].

The optimal growth temperature for Yersinia species is 25 to 28°C; this condition also inhibits growth of other organisms, even on non-selective MacConkey agar. At this temperature, Yersinia species can be isolated within 24 to 48 hours. (See 'Microbiology' above.)

●Culture-independent tests – Evaluating the performance of culture-independent tests for detection of Y. enterocolitica is challenging given the rarity of infection. Two multiplex platforms showed sensitivity of 48 to 100 percent and specificity of 99.6 to 100 percent [89].

Specimens that test positive by culture-independent tools should be set up for reflex culture to secure the diagnosis, obtain antimicrobial susceptibility, and to strengthen public health surveillance [86,90].

Multiplex panels do not usually include Y. pseudotuberculosis targets.

DIFFERENTIAL DIAGNOSIS

●Other causes of diarrhea – The differential diagnosis for Yersinia infection includes infection with Salmonella, Campylobacter, Shigella, enteroinvasive E. coli, E. histolytica, or Clostridioides difficile, as well as noninfectious inflammatory bowel disease. (See "Approach to the adult with acute diarrhea in resource-abundant settings" and "Approach to the adult with acute diarrhea in resource-limited settings" and "Diagnostic approach to diarrhea in children in resource-abundant settings" and "Approach to the child with acute diarrhea in resource-limited settings".)

●Pseudoappendicitis – Campylobacter infection may also present with pseudoappendicitis. The differential diagnosis of appendicitis is discussed separately. (See "Campylobacter infection: Clinical manifestations, diagnosis, and treatment", section on 'Pseudoappendicitis' and "Acute appendicitis in adults: Clinical manifestations and differential diagnosis".)

TREATMENT

Antibiotic susceptibility — The Y. enterocolitica serotype most commonly associated with clinical illness (O:3) usually produces chromosomally-mediated beta-lactamases and thus is resistant to penicillin, ampicillin, and most first generation cephalosporins [2,91]. In addition, Yersinia is usually resistant to macrolides.

Clinical strains are usually susceptible to other beta-lactam agents including cephalosporins (second, third, or fourth generation), fluoroquinolones, aminoglycosides, tetracyclines, trimethoprim-sulfamethoxazole, and chloramphenicol [92]. In one series, strains were uniformly susceptible to piperacillin, imipenem, ceftazidime, cefepime, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole [93].

Quinolone resistance, including resistance to nalidixic acid and reduced susceptibility to ciprofloxacin, has been reported in Spain [94,95]. As person-to-person transmission of Y. enterocolitica is rare, this is likely attributable to use of antimicrobials in agriculture.

Clinical approach

Nonsevere enterocolitis

Indications – For patients with mild enterocolitis in the absence of risk for severe illness, antibiotic therapy is not warranted, given lack of benefit. Maintenance of proper hydration and correction of electrolyte abnormalities should be the focus of therapy.

For patients with nonsevere enterocolitis who are neonates, or who have underlying immunosuppression or derangement of iron metabolism, we favor treatment with oral antibiotic therapy. (See 'Risk factors' above.)

●Rationale – No clinical data have demonstrated benefit to antimicrobial therapy for treatment of yersiniosis. In two trials of antimicrobial therapy for yersiniosis (one among 34 children in Canada with Y. enterocolitica infection treated with trimethoprim-sulfamethoxazole, and another among 136 children in Japan with Y. pseudotuberculosis infection treated with ampicillin), treatment was not associated with clinical benefit in either group [96,97].

Similarly, in a retrospective case series among 67 adults in Norway with Y. enterocolitica enterocolitis (67 case-patients and 132 controls), the duration of illness was comparable between the groups (18 versus 21 days) [56].

In addition, no clinical data have demonstrated any association between early antimicrobial therapy and the frequency or severity of chronic sequelae for infection due to Y. enterocolitica or Y. pseudotuberculosis [98,99].

Antimicrobial treatment has been associated with a reduction in stool shedding [56,96,97]; however, this is not an indication for treatment since person-to-person transmission of Yersinia infection is rare [56].

●Antibiotic selection and duration – For treatment of adults with nonsevere enterocolitis, when indicated, we use a fluoroquinolone (such as ciprofloxacin 500 mg orally twice daily or levofloxacin 500 mg orally once daily). Alternative agents include doxycycline or trimethoprim-sulfamethoxazole [54].

For treatment of children with nonsevere enterocolitis, when indicated, we use trimethoprim-sulfamethoxazole (TMP 8 mg/kg per day and SMX 40 mg/kg per day in two divided doses).

Antibiotic therapy should be tailored to susceptibility data when available. The usual treatment duration is five days.

Severe illness

●Indications – For patients with bacteremia, sepsis, or severe illness (grossly bloody stools and high fever, other manifestations of extraintestinal infection), we favor treatment with intravenous antibiotic therapy [54].

●Antibiotic selection and duration – We use a third-generation cephalosporin such as ceftriaxone (adults: 2 g IV once daily; children: 100 mg/kg per day in one or two divided doses, to a maximum dose of 4 g per day), combined with gentamicin (adults: 5 mg/kg per day in one to three divided doses). An alternative to ceftriaxone is ciprofloxacin (adults: 400 mg IV twice daily), if susceptible. In children, the benefit of ciprofloxacin should be weighed against risk of side effects [100].

Antibiotic therapy should be tailored to susceptibility data as soon as it is available.

We administer treatment in patients with severe illness for at least three weeks; a longer duration may be appropriate for patients with compromised immunity or focal extraintestinal infection. Once clinically improved, the patient can be switched to oral treatment to complete therapy [63,70].

●Rationale – Clinical data for treatment of Yersinia bacteremia or sepsis are limited. In a retrospective case series of 43 patients with Y. enterocolitica septicemia, third generation cephalosporins (with or without other antibiotics) were effective in 85 percent of cases; fluoroquinolones (alone or in combination), cured all of 15 infections [63]. Agents that were ineffective when used as monotherapy included ampicillin, amoxicillin, first-generation cephalosporins, and amoxicillin-clavulanate. The duration of therapy varied from two to six weeks, with a median of 22 days (intravenous followed by oral therapy).

OUTCOMES — Mortality from yersiniosis is relatively low. In one study including 458 patients in Norway, only two fatalities occurred during the acute phase of illness [101]. Similarly, among 1373 cases of yersiniosis in the United States between 1996 and 2007, 18 deaths (1.2 percent) were reported [41]. Of the cases identified, 30 percent were hospitalized and 3 percent had documented bacteremia.

PREVENTION — Measures to prevent Yersinia infection include:

●Food and animal safety – Basic tenets of food safety are important for prevention of yersiniosis [102]. These include safe food preparation and hand washing after exposure to pigs or raw pork products and avoiding cross-contamination, as well as avoiding consumption of raw or undercooked pork [103]. Important industrial interventions include careful hygiene at slaughter, as well as milk pasteurization and careful hygiene in dairy plants.

●Transfusion safety – Measures for prevention of transfusion-associated infection include testing packed red blood cells for presence of bacterial endotoxin and limiting the shelf-life of packed red cells. (See "Transfusion-transmitted bacterial infection".)

SUMMARY AND RECOMMENDATIONS

●Epidemiology

•Transmission – Transmission of yersiniosis is largely foodborne (including consumption of raw or undercooked pork, as well as other food sources) and occasionally waterborne. Uncommon modes of transmission include household pet exposure, person-to-person transmission, and blood transfusion. (See 'Transmission' above.)

•Risk factors – Factors conferring increased risk for yersiniosis include age <5 years of age, derangements of iron metabolism, and other comorbid conditions including immunosuppression. (See 'Risk factors' above.)

●Clinical manifestations – Major clinical manifestations include enterocolitis and pseudoappendicitis. A variety of complications and post-infectious sequelae have also been described.

•Acute yersiniosis – The typical incubation period is 4 to 6 days (range 1 to 14 days). Clinical manifestations include fever, abdominal pain, and diarrhea; nausea and vomiting may also occur. Bloody diarrhea is observed more frequently among children. Pharyngitis may be a presenting symptom. Bacteremia and sepsis can occur, particularly among infants and individuals with impaired immunity or iron-overload states. (See 'Acute yersiniosis' above.)

•Pseudoappendicitis – Acute yersiniosis may be confused with acute appendicitis; overlapping symptoms may include right lower quadrant abdominal pain, fever, vomiting, leukocytosis, and diarrhea. (See 'Pseudoappendicitis' above.)

•Post-infectious sequelae – Post-infectious sequelae include erythema nodosum and reactive arthritis. (See 'Post-infectious sequelae' above.)

●Diagnosis

•Clinical suspicion – Yersiniosis should be suspected in the setting of relevant clinical manifestations (fever, abdominal pain, and diarrhea, with or without nausea and vomiting); these may occur in the presence or absence of relevant epidemiologic exposure (such as consumption of raw or undercooked pork or exposure to food or water implicated in an outbreak). (See 'Clinical approach' above.)

•Diagnostic evaluation – Stool should be sent for culture; if available, stool may also be sent for rapid molecular panel testing. Patients with fever should have blood cultures obtained. Patients with pharyngitis should have throat culture obtained. For patients who undergo surgery in the setting of suspected appendicitis, operative specimens should be cultured. (See 'Clinical approach' above.)

•Organism identification – The diagnosis of Yersinia infection is usually established by culture of the organism from stool or blood; it may also be established by culture from other sterile sites. Specimens that test positive by culture-independent tools should be set up for reflex culture to confirm the diagnosis and obtain antimicrobial susceptibility data. (See 'Organism identification' above.)

●Treatment of enterocolitis (See 'Nonsevere enterocolitis' above.)

•Indications

-For patients with mild enterocolitis in the absence of risk for severe illness, we suggest not treating with antibiotic therapy (Grade 2C), given lack of demonstrated benefit.

-For patients with nonsevere enterocolitis who are neonates, or have underlying immunosuppression or derangement of iron metabolism, we suggest treatment with oral antibiotic therapy (Grade 2C).

•Antibiotic selection and duration – For adults we treat with a fluoroquinolone (ciprofloxacin or levofloxacin); alternative agents include trimethoprim-sulfamethoxazole or doxycycline. For children we treat with trimethoprim-sulfamethoxazole.

The usual treatment duration is five days.

●Treatment of severe illness (See 'Severe illness' above.)

•Indications – For patients with bacteremia, sepsis, or severe illness (grossly bloody stools and high fever, other manifestations of extraintestinal infection), we suggest treatment with intravenous antibiotic therapy (Grade 2C).

•Antibiotic selection and duration – We favor treatment with ceftriaxone in combination with gentamicin; ciprofloxacin is an alternative agent to ceftriaxone.

We treat for at least three weeks; a longer duration may be appropriate for patients with compromised immunity or focal extraintestinal infection. Once clinically improved, treatment may be completed with oral therapy.