Yersinia: intestinal and systemic infections

Yersiniosis is a zoonotic bacterial infection caused primarily by Yersinia enterocolitica and Yersinia pseudotuberculosis. The typical presentation includes acute gastroenteritis with right iliac pain and diarrhea, as well as mesenteric lymphadenitis mimicking appendicitis. Foodborne transmission is primarily associated with raw or undercooked pork and unpasteurized milk.[1]

Far Eastern scarlatina-like fever (Far East scarlatina-like fever) is a distinct clinical entity—a systemic lesion caused by Y. pseudotuberculosis, described primarily in Russia and Japan. This condition is associated with the YPM superantigen and often resembles Kawasaki disease, leading to diagnostic delays. [2]

Modern diagnostics rely on molecular panels without culture isolation and targeted stool culture on selective media. Treatment in most uncomplicated cases is symptomatic; in severe cases, antibacterial drugs are indicated, taking into account typical resistance to ampicillin and first-generation cephalosporins. [3]

Table 1. What is important to know about yersiniosis

Paragraph	Briefly
Pathogens	Y. enterocolitica, Y. pseudotuberculosis
Sources	Pork, unpasteurized milk, contaminated water
Key syndromes	Enteritis, mesenteric lymphadenitis, pseudoappendicitis
Special form	Far Eastern scarlatina-like fever in Y. pseudotuberculosis
Treatment	Mainly supportive; in severe cases - third-generation cephalosporins, fluoroquinolones, tetracyclines or trimethoprim sulfamethoxazole
[4]

Epidemiology

Yersiniosis is reported worldwide. Pigs are considered the key reservoir for Y. enterocolitica, and the most common bioserotype in human cases is 4O colon 3. The risk increases with the consumption of raw or undercooked pork and intestine-based dishes, as well as with the consumption of unpasteurized milk and unboiled water. [5]

Outbreaks of Y. pseudotuberculosis in Europe are typically limited to self-limited enteritis, while severe systemic outbreaks of the Far Eastern form have been reported in Russia and Japan. These differences are associated with strain characteristics, including the production of the YPM superantigen and additional secretion systems. [6]

In households where casings are traditionally prepared, the risk of infection among infants through contact with hands and kitchen surfaces is increased. Seasonality is more frequent during the colder months, consistent with the pathogen's ability to grow at low temperatures. [7]

Table 2. Routes of infection and risk factors

Factor	Explanation
Undercooked pork	The main route of transmission of Y. enterocolitica
Unpasteurized milk	Risk of sporadic outbreaks
Contact when cooking offal	Household transmission in families with infants
Seasonality	Cold months and low temperature storage
[8]

Structure of bacteria

Both species are Gram-negative rods of the Enterobacteriaceae family with an outer membrane and a set of virulence factors. The virulence plasmid encodes a type-3 secretion system, Ysc Yop, which injects effector proteins into host cells and disables key components of the innate immune system. Surface factors include invasin, Ail, and the adhesin YadA. [9]

Y. enterocolitica exhibits psychrotrophic growth at four degrees Celsius, motility at twenty-five degrees Celsius, and loss of motility at thirty-seven degrees Celsius. This explains the epidemiological significance of refrigeration storage and provides a competitive advantage in low-temperature food products. [10]

Table 3. Key determinants of virulence

Component	Role
Ysc Yop System	Injection of effectors, blockade of phagocytosis and inflammation
Invazin, Ail, YadA	Adhesion and penetration into the epithelium and Peyer's patches
Psychrotrophic growth	Survival and reproduction in food at low temperatures
[11]

Life cycle

The external environment for Y. enterocolitica and Y. pseudotuberculosis includes animal-based food substrates, water, and biofilms on food processing equipment. In humans, initial colonization occurs in the ileum, involving Peyer's patches and regional lymph nodes, which explains pain in the right iliac region and pseudoappendiceal syndrome. [12]

Regulation of virulence depends on temperature and population density: under intestinal conditions, the adhesion and secretion systems are activated, while in dense microcolonies their subtle negative regulation is observed, helping to avoid the immune response and save resources. [13]

Table 4. Life cycle stages and clinical implications

Stage	Where	Investigation
Growth at low temperatures	Products and refrigerators	Preserving food infectivity
Colonization of the terminal ileum	Intestines	Diarrhea, pain, lymphadenitis
Persistence in lymph nodes	Abdominal cavity	Pseudoappendicitis
[14]

Pathogenesis

After adhering to enterocytes and M cells, bacteria penetrate the submucosal plexus and lymphoid tissue. Yop effectors disrupt actin cytoskeleton assembly and inhibit phagocytosis, facilitating survival and dissemination. Urease and thermoregulatory expression factors complement the role of plasmid and chromosomal virulence genes. [15]

For the Far Eastern form of Y. pseudotuberculosis, the key mediator of systemic inflammation is the YPM superantigen, which causes massive T-cell activation, fever, rash, joint damage, and lymphadenopathy. The clinical presentation may resemble Kawasaki disease, which requires laboratory confirmation. [16]

In response to immune pressure and nutritional deficiencies, bacteria switch behavior, which affects the duration of symptoms and the risk of complications, including reactive arthritis in susceptible individuals with the HLA B twenty-seven antigen. [17]

Table 5. "Mechanism-manifestation"

Mechanism	Cellular target	Clinical effect
Yop injection	Macrophages, epithelium	Inhibition of phagocytosis, persistence
Superantigen YPM	T cells	Systemic inflammatory reaction, rash
Psychrotrophy	Food substrates	Long-term storage in the refrigerator
[18]

Symptoms

In young children, fever, abdominal pain, and diarrhea, which may be bloody, are the predominant symptoms. Adolescents and adults often experience lower right abdominal pain and fever with less severe diarrhea, mimicking acute appendicitis. Pharyngitis, erythema nodosum, and arthralgia are also possible. [19]

Following gastroenteritis, some patients develop reactive arthritis, more often in those with the HLA B27 antigen, as well as erythema nodosum. These manifestations typically regress within a few months but can become chronic. [20]

Table 6. Frequent manifestations by age

Group	Predominant symptoms
Young children	Fever, diarrhea, abdominal pain
Teenagers and adults	Pain in the lower right abdomen, fever, pseudoappendicitis
Post-infectious	Erythema nodosum, reactive arthritis
[21]

Stages

The incubation period is approximately four to seven days. This is followed by an acute gastrointestinal stage lasting one to three weeks. Some patients develop pain in the right iliac region due to mesenteric lymphadenitis. With timely supportive therapy, most acute forms are self-limiting. [22]

The late stage includes post-infectious immune manifestations—arthritis, erythema nodosum, and, less commonly, iridocyclitis. These complications are not prevented by antibacterial therapy and require symptomatic management. [23]

Table 7. Staging and clinical emphases

Stage	Duration	Tactics
Incubation	A few days	Observation
Acute	One to three weeks	Rehydration, electrolyte correction
Post-infectious	Weeks and months	Treatment of arthritis and skin manifestations
[24]

Forms

The intestinal form is the most common: enteritis with mesenteric lymphadenitis and pseudoappendiceal syndrome. Extraintestinal forms include bacteremia in weakened patients, organ abscesses, and, extremely rarely, transfusion-associated sepsis. The Far Eastern systemic form of Y. pseudotuberculosis is considered separately. [25]

Transfusion-related cases develop rapidly, with a high mortality rate, requiring immediate recognition and etiotropic therapy. The risk is associated with the ability of the pathogen to multiply in red blood cell components at refrigerated temperatures. [26]

Table 8. Main clinical forms

Form	Key Features
Intestinal	Diarrhea, pain, fever
Pseudoappendicitis	Pain in the lower right side, lymphadenitis, normal appendix
Far Eastern	Rash, desquamation, arthralgia, high fever
Transfusion	Rapid post-transfusion sepsis
[27]

Complications and consequences

In immunocompromised patients, bacteremia, liver and spleen abscesses, and septic shock are possible. After a severe acute episode, recovery can take weeks, requiring gradual rehabilitation and monitoring of comorbidities. [28]

Postinfectious immune complications include reactive arthritis and erythema nodosum. Antibiotics do not prevent these events, so the emphasis is on early diagnosis and symptomatic treatment, including nonsteroidal anti-inflammatory drugs and physical therapy when indicated. [29]

Table 9. Frequent complications

Complication	Clinical significance
Reactive arthritis	Joint pain, limited mobility
Erythema nodosum	Painful nodules on the skin of the shins
Bacteremia and abscesses	Rarely, in weakened patients
Transfusion sepsis	High mortality without immediate treatment
[30]

Diagnostics

The first line of confirmation is a laboratory stool test. Molecular panels without culture isolation are widely used in routine practice, having significantly increased the detection of Yersinia, although they are more often targeted at Y. enterocolitica. If the result is positive and epidemiologically significant, culture isolation is recommended for verification and typing. [31]

The culture requires a selective CIN medium with incubation at 25 degrees Celsius and a characteristic "bull's eye" colony. Cold enrichment at 4 degrees Celsius is possible to increase yield at low bacterial concentrations. [32]

Visualization helps differentiate from appendicitis: ultrasound and computed tomography reveal enlarged mesenteric nodes with an intact appendix, sometimes with thickening of the terminal ileum. This approach reduces the number of unnecessary appendectomies. [33]

Serology is of limited use in the acute phase, but can be used when systemic forms of Y. pseudotuberculosis are suspected. Genomic typing is increasingly being used in epidemiological investigations to establish source links. [34]

Table 10. Diagnostic tools

Method	What does it give?	When to prescribe
Panels without culture selection	Rapid detection of Y. enterocolitica DNA	For acute gastroenteritis
Culture on CIN	Confirmation and typing	In severe cases and in foci
Ultrasound and computed tomography	Differentiation from appendicitis	For pain in the right lower abdomen
Serology	Confirmation of Y. pseudotuberculosis	For systemic forms and outbreaks
[35]

Differential diagnosis

Yersiniosis should be distinguished from appendicitis, campylobacteriosis, salmonellosis, shigellosis, and inflammatory bowel disease. Key clues to yersiniosis include pain in the lower right abdomen with a normal appendix, mesenteric lymphadenitis, and a positive culture on selective media. [36]

The Far Eastern form should be differentiated from Kawasaki disease and toxic-allergic syndromes. The epidemiological history, rash with subsequent desquamation, arthralgia, and laboratory markers of inflammation are crucial. [37]

Table 11. How yersiniosis is similar and how it is different

State	General	Differences in favor of yersiniosis
Acute appendicitis	Pain in the lower right abdomen	Clusters of nodes, unchanged appendix
Campylobacteriosis	Diarrhea, fever	Pseudoappendicitis, lymphadenitis
Kawasaki disease	Fever, rash	Epidemiological anamnesis, YPM association
[38]

Treatment

Most uncomplicated intestinal forms in immunocompetent patients are treated symptomatically: rehydration, electrolytes, a gentle diet, and avoiding antidiarrheal medications if bloody stools occur. Antibacterial therapy is indicated for severe or protracted cases, bacteremia, and in newborns and immunocompromised patients. [39]

Antibiotic selection takes into account intrinsic resistance to ampicillin and first-generation cephalosporins. The most commonly used are ceftriaxone, ciprofloxacin or levofloxacin, doxycycline, trimethoprim, and sulfamethoxazole. These classes are generally active against Y. enterocolitica. Doses are adjusted based on age and weight, following national guidelines. [40]

For the systemic form of Y. pseudotuberculosis, treatment is also based on active third-generation beta-lactams, fluoroquinolones, or tetracyclines with early onset and adjustment of duration based on clinical dynamics. Transfusion-associated sepsis requires immediate administration of bactericidal drugs and intensive care. [41]

Antibiotics do not prevent reactive arthritis and other post-infectious immune complications. Nonsteroidal anti-inflammatory drugs, topical measures, and short courses of glucocorticosteroids are used for these conditions as indicated under specialist supervision. [42]

Table 12. Examples of therapeutic tactics

Situation	Approach	Comment
Mild gastroenteritis	Rehydration, observation	Antibiotics are not required
Severe course or risk group	Ceftriaxone or a fluoroquinolone, or doxycycline, or trimethoprim sulfamethoxazole	Consider contraindications and interactions
Bacteremia, abscesses	Parenteral therapy with bactericidal drugs	Adjust for sensitivity
Transfusion sepsis	Immediate etiotropic therapy and support	High mortality rate with delay
[43]

Prevention

Key measures include thoroughly cooking pork to a safe internal temperature, using a thermometer to check for doneness, avoiding unpasteurized milk, and maintaining kitchen hygiene. When preparing offal, separate cutting surfaces and thorough hand washing are required. [44]

Food processing and catering companies must monitor refrigeration conditions and the sanitary condition of equipment containing biofilms. Quality and monitoring standards are important for blood services, given the risk of Y. enterocolitica proliferation in red blood cell components at low temperatures. [45]

Table 13. Prevention at home and at work

Level	Measure
House	Finish cooking pork, do not drink unpasteurized milk, wash hands and surfaces
Retail	Cold chains, equipment sanitization
Blood service	Compliance with quality and storage protocols
[46]

Forecast

Most immunocompetent patients have a favorable prognosis, with full recovery within one to three weeks. Severe outcomes are rare and are typical in immunocompromised individuals, neonates, and transfusion-associated cases. [47]

Postinfectious manifestations, such as reactive arthritis, may persist for months but usually regress. Early recognition, appropriate diagnostic workup, and supportive therapy influence prognosis. [48]

Table 14. Factors of favorable and unfavorable prognosis

Factor	Meaning
Immune status	Determines the risk of invasive forms
Timeliness of diagnosis	Reduces interventions and complications
Source of infection	Kitchen and supply chain control
[49]

Frequently Asked Questions - FAQ

Should every episode of yersiniosis be treated with antibiotics?
No. In mild cases, rehydration and symptomatic therapy are sufficient. Antibiotics are indicated for severe or protracted cases, in newborns, immunocompromised individuals, and for extraintestinal forms. [50]

What drugs are typically active against Y. enterocolitica?
Aminoglycosides, third-generation cephalosporins, fluoroquinolones, tetracyclines, and trimethoprim-sulfamethoxazole are typically active. Resistance to ampicillin and first-generation cephalosporins is often observed. [51]

Why is this bacteria dangerous when stored in the refrigerator?
Y. enterocolitica grows at four degrees Celsius, so low temperatures do not guarantee inactivation. A reliable measure is sufficient heat treatment. [52]

How can it be differentiated from appendicitis?
Visualization and clinical examination are helpful: enlarged mesenteric nodes, thickened terminal ileum, and an unchanged appendix in yersiniosis. The doctor makes a decision based on all the data. [53]

What is Far Eastern yersiniosis?
It is a systemic disease caused by Y. pseudotuberculosis, characterized by fever, rash, arthralgia, and possible desquamation. It occurs primarily in Russia and Japan and can resemble Kawasaki disease. [54]

Do antibiotics prevent reactive arthritis?
No. Antibiotics do not prevent post-infectious immune complications. Treatment for these conditions is determined separately based on symptoms. [55]