Yersiniosis: expanding traditional ideas about diagnosis, treatment and medical examination of patients

Type of infection and route of infection

The causative agent of the disease is intestinal bacteria Enterobacteriaceae from the genus Yersinia. They are gram-negative rods up to 0.9 microns in size, growing on regular and depleted nutrient media. The most favorable temperature for them is in the range from +4 to +8 degrees, at which they are able to survive for a long time and actively reproduce on various foods. The mechanism of transmission of yersioniasis infection is close to pseudotuberculosis.

Some strains of bacteria are resistant to pasteurization, but boiling kills any of them within a few seconds. They are also sensitive to the effects of disinfectants. The peak incidence is usually observed in November and spring. People of any age are susceptible to the disease; yersiniosis is often found in children. Women are more resistant to pathogens than men.

Pathogens enter the human body through the fecal-oral or alimentary route, through a transfusion of contaminated blood, or directly under the skin through injury or injection. Transmission of intestinal yersiniosis infection can occur through contaminated foods that have not undergone heat treatment - meat, vegetables and milk, as well as water from open sources.

Symptoms of yersiniosis

The incubation period of yersiniosis pathogens lasts 1-6 days. Symptoms of yersiniosis are nonspecific. The disease is characterized by polymorphism of clinical manifestations:

• begins acutely, with the appearance of chills, headaches, weakness and malaise;
• possible pain in muscles and joints, sore throat, loss of appetite and insomnia;
• body temperature is subfebrile, can sometimes rise to 38-40 degrees;
• symptoms of general intoxication of the body are combined with signs of gastrointestinal damage - abdominal pain, nausea, diarrhea, vomiting;
• the skin becomes dry and a scaly, dotted or small-spotted rash may appear on it;
• Relative tachycardia and hypotension may occur;
• During the course of the disease, symptoms are possible that indicate damage to various internal organs - dark urine, heaviness or pain in the right hypochondrium, etc.;
• icteric staining of the sclera and skin indicates an enlarged liver; headaches may intensify over time, and focal and meningeal symptoms of central nervous system damage may appear;
• damage to the genitourinary system is accompanied by pain during urination and a decrease in daily diuresis up to complete anuria;
• as the disease progresses, pain in the abdominal area intensifies, signs of peritoneal irritation appear;
• in the second week, signs of acute arthritis may appear with damage to large joints, swelling of the face and elements of urticaria, hyperemia and pain in the eyes.

Forms of yersiniosis disease and their complications

The clinical classification of yersiniosis has not yet been fully developed. Taking into account the leading syndrome, it is customary to distinguish 2 groups of clinical forms:

• localized (gastroenterocolitic):
• generalized (icteric, septic, exanthem and arthralgic).

The clinical picture of yersiniosis of the localized form is limited primarily to damage to the gastrointestinal tract; generalized forms are accompanied by damage to other organs and systems.

1. The gastroenterocolitic form of siniosis is the most common disease, accounting for almost 70% of all cases. The disease begins acutely, with an increase in temperature to 38-39 degrees, accompanied by headaches, anorexia, chills, malaise, abdominal pain and loose stools - up to 15 times a day. The duration of the disease is 2-14 days; severe forms are rare. It can occur in the form of enterocolitis, enteritis and gastroenterocolitis. In most cases, the syndrome of general intoxication is mild, abdominal pain is of low intensity, and the frequency of stools is 2-4 times per bowel movement.
2. The icteric form is a complication of yersiniosis and can develop simultaneously with the gastroenterocolitic form or 2-4 days after the onset of intestinal dysfunction. Signs of liver damage come to the fore, and toxic hepatitis develops. Patients complain of pain and a feeling of heaviness in the right hypochondrium, sometimes itching of the skin appears. The disease is accompanied by yellowness of the sclera and skin, the size of the liver increases, pain appears on palpation, discoloration of feces and darkening of urine are observed. Hypertransaminasemia and hyperbilirubinemia are determined.
3. The exanthema variety of the disease is manifested by exanthema and intoxication syndrome. With this form of yersiniosis, a rash appears on the skin on the 1st-6th day of illness; it can be dotted, large or small-spotted, with or without itching. After a few days, the rash usually disappears without a trace, and pityriasis-like peeling appears in its place.
4. The arthralgic form occurs with intoxication, fever and severe pain in the joints, which, however, do not change externally. Arthralgia can cause immobility and insomnia.
5. The septic type of the disease is quite rare and is the most dangerous, with mortality accounting for up to 30% of cases. It manifests itself as high fever with a daily range of up to 2 degrees, chills, enlarged liver and spleen. Damage to other organs is possible. The consequences of septic yersiniosis are endocarditis, nephritis with acute renal failure, pneumonia, hepatitis, meningitis, meningoencephalitis. Sometimes the result of a complication of yersiniosis is mocarditis - inflammation of the heart muscle. It is manifested by heart rhythm disturbances and tachycardia.
6. The secondary focal form can occur independently or as a complication of other forms. In the second case, primary and secondary signs of the disease can be separated by a long period of well-being. Secondary manifestations are signs of damage to individual organs, causing concomitant diseases - the liver, thyroid gland (autoimmune thyroiditis), joints (arthritis), meninges (meningitis).

Complications of yersiniosis most often occur in the second or third week of the disease. Among them: exanthema (erythema nodosum, urticaria), arthritis of the joints (usually large ones), Quincke's edema, myocarditis, urethritis, appendicitis and conjunctivitis.

If you experience similar symptoms, consult your doctor

. It is easier to prevent a disease than to deal with the consequences.

Yersiniosis and pseudotuberculosis

A single generally accepted clinical classification of yersiniosis still does not exist, although this is forced by the variety of forms and variants of the disease. Clinical classification of yersiniosis The incubation period for pseudotuberculosis varies from 3 to 18 days, for intestinal yersiniosis - within 1-6 days. Clinical manifestations of yersiniosis usually involve a combination of several syndromes. The degree of their severity varies in different forms and variants of the disease.

General toxic syndrome . It appears most often. At the onset of the disease, an increase in body temperature to 38-40 ° C, chills, headache, myalgia, general weakness, and loss of appetite are noted. The temperature reaction lasts for 7-10 days, and in the generalized form of the disease - much longer.

Dyspeptic syndrome (abdominal pain, nausea, diarrhea, vomiting). More often encountered in lesions caused by Y. enterocolitica, which, together with signs of toxicosis, forms the clinical basis of the gastrointestinal form.

Catarrhal syndrome. They occur most often with pseudotuberculosis (up to 80% of cases). Characterized by sore throat, hyperemia of the mucous membrane of the oropharynx, spotted enanthema on the mucous membranes.

Exanthematous syndrome. More often observed with pseudotuberculosis. It manifests itself as a maculopapular (small-spotted, large-spotted, ring-shaped) rash on various parts of the skin. The rash usually appears on the 2-6th day of illness. The most typical appearance of a scarlet fever rash of a pinpoint nature is on the face and neck in the form of a “hood”, and on the distal parts of the extremities in the form of “socks” and “gloves”. With intestinal yersiniosis, manifestations of exanthema are observed less frequently.

Arthralgic (arthropathic) syndrome. Pain in the joints of the hands, feet, knees, elbows, etc. is noted. Characteristic signs are swelling and limitation of movements in the joints. Along with pronounced manifestations of toxicosis and the development of hepatolienal syndrome, these signs of yersiniosis are more often found in generalized lesions.

Gastrointestinal form. They occur most frequently (more than 50% of cases) and are clinically similar in many ways to other acute intestinal infections, primarily salmonellosis and foodborne illnesses. Dyspeptic syndrome develops in more than half of the cases, while the severity and duration of diarrhea is more typical for intestinal yersiniosis. Intoxication usually occurs simultaneously, but in 1/3 of cases it can precede the development of dyspeptic syndrome.

In 10-20% of cases, moderate catarrhal symptoms from the upper respiratory tract are noted at the onset of the disease. In some cases, in the dynamics of yersiniosis, dysuric phenomena occur (15-17%), arthralgia at the height of the disease and a skin rash on the 2-6th day from the onset of the disease, burning in the palms and soles with their subsequent large-plate peeling. With pseudotuberculosis, as already mentioned above, the cardinal signs can be a kind of scarlet-like exanthema and a “crimson” tongue. The rash is more pronounced on the flexor surfaces of the extremities and in the natural folds of the skin. Elements of the rash disappear within a period of several hours to 3-4 days and leave behind fine-scaly or large-plate (on the palms and soles) peeling.

In approximately half of the patients, a slight enlargement of the liver and a reaction from the peripheral lymph nodes can be observed. Unlike salmonellosis, isolated gastric lesions (acute gastritis) are practically not observed with yersiniosis.

In mild cases of the disease, all clinical manifestations may disappear within 2-3 days; in severe cases, they last 2 weeks or more. The disease takes on a wave-like course with high body temperature and the development of signs of dehydration.

Variants of the gastrointestinal form, such as acute appendicitis, terminal ileitis, can unfold either as an independent process or following symptoms of diarrhea. According to clinical signs, they practically do not differ from acute surgical pathology of the abdominal cavity of another etiology. When they are identified in cases of yersiniosis, extra-abdominal symptoms are usually detected: arthralgia and myalgia, exanthema, injection of scleral vessels, peripheral lymphadenopathy, hyperemia of the soft palate, “crimson” tongue, enlarged liver. The disease ends with recovery in 3-4 weeks, but sometimes takes a long, relapsing course.

Generalized form. Differs in polysyndromic manifestations. Against the background of the development of a general toxic syndrome with high fever, severe arthralgia is often noted, limiting the movements of patients (up to 80% of cases), pain when swallowing and catarrhal changes in the upper respiratory tract, exanthema from the 2-3rd day of illness with damage to the palms and soles ( up to 90% of cases). Dyspeptic syndrome can manifest itself only at the beginning of the clinical process, but sometimes persists during the peak period: abdominal pain, more often in the right iliac region, observed in half of the patients, usually occurs after an increase in body temperature, in approximately 25% of cases nausea is possible , vomiting and unstable stool.

As the disease progresses, hepatolienal syndrome develops, high fever persists for a long time and other signs of intoxication intensify. The disease can take an undulating or recurrent course. The symptoms described above are characteristic of the mixed variant of the generalized form.

With prolonged bacteremia and multi-organ dissemination of pathogens, the generalized form of infection can clinically manifest itself as hepatitis, pyelonephritis, small-focal pneumonia, and occasionally serous meningitis and yersinia sepsis (less than 1% of cases). These conditions develop against the background of subsiding or persisting symptoms described above. Reactive yersinia hepatitis is characterized by a short (3-4 days) pre-icteric period, the development of jaundice at the height of intoxication, the short duration of jaundice and hepatomegaly, a favorable course in most cases with moderately altered bilirubin and aminotransferase levels, and a normal thymol test. In contrast to viral hepatitis, leukocytosis and an increase in ESR are noted in the blood. Transition to a chronic form is not observed with yersinia hepatitis. However, in rare cases, the development of severe hepatitis up to the formation of abscesses in the liver is observed (in children, diabetics, with anemia, cirrhosis).

Secondary focal form . It can develop after any of the forms described above; it is based on autoimmune reactions with bacterial reactive processes. In some patients, the initial stage of the disease may be subclinical, but usually this form develops 2-3 weeks from the onset of the disease and later. Common features of variants of this form also include an undulating course and frequent vegetative-vascular disorders.

The most common variant of the secondary focal form is arthritic (yersinia polyarthritis) with damage to large and small joints (hands, feet). Monoarthritis is less common (20-25% of cases). Joint lesions are mainly reactive in nature; Bacteria are rarely isolated from intraarticular fluid. Arthritis is asymmetrical, swelling in the joint area is noted more often than pronounced hyperemia of the skin. Arthritis is accompanied by intense pain even with the slightest movements. Leukocytosis and ESR increase, and eosinophilia is often detected. Joint lesions may be accompanied by the development of sacroiliitis and tendovaginitis. The duration of manifestations is from 1 week to 2 years (with a prolonged or chronic course), more often - 2-3 months. The prognosis is favorable.

10-20% of patients develop erythema nodosum. From several to 20 subcutaneous nodes or more are formed, large, painful, bright with typical localization on the legs, thighs, and buttocks. The disease lasts from several days to 2-3 weeks, the course is favorable.

Reiter's syndrome with yersiniosis is expressed in a simultaneous combination of lesions of the eyes (conjunctivitis, scleritis), urethra and joints. The duration of myocarditis manifestations can reach several months, but its course is benign, circulatory failure does not develop.

Chronic enterocolitis, as a variant of the secondary focal form of yersiniosis, often develops in the proximal intestine; its development is anamnestically preceded by symptoms of acute intestinal infections or a generalized form of yersiniosis. Manifestations of enterocolitis can be combined with arthritis, exanthema, catarrhal symptoms of the upper respiratory tract, low-grade fever, asthenia, autonomic-neurotic reactions, etc.

Isolated cervical lymphadenitis without previous diarrhea and other clinical signs of yersiniosis are described as rare variants of the disease. They occur with pain, redness of the skin, enlarged lymph nodes and normal or subfebrile body temperature. Rare manifestations of yersiniosis can also include pyodermitis, osteomyelitis, ulceration and skin infiltration.

Relapses and exacerbations Occur with a frequency of 8 to 55%, transition to subacute and chronic forms - in 3-10% of cases. Early relapses occur at the beginning of the 3rd week of the disease, so they often prefer to keep patients in the hospital until the 21st day from the onset of the disease. The causes of relapses have not been sufficiently studied; perhaps short courses of treatment and early discharge of patients play a certain role in their formation. In terms of their clinical manifestations, relapses practically repeat the initial symptoms of the disease, but in an erased version.

Complications are numerous and include: myocarditis, hepatitis, cholecystitis and cholangitis, pancreatitis, appendicitis, adhesive intestinal obstruction, intestinal perforation, peritonitis, focal glomerulonephritis, meningoencephalitis, etc. Taking into account modern pathogenetic data, in one of the latest clinical classifications of yersiniosis, many of these complications are presented as separate variants of generalized, secondary focal or gastrointestinal forms of the disease. The outcomes of yersiniosis are usually favorable, excluding the septic variant, which leads to death in up to 50% of patients. The duration of the disease most often does not exceed 1.5 months, but a protracted and recurrent course of the disease lasting up to 3-6 months or more is observed. Chronic diseases of the musculoskeletal system and gastrointestinal tract are described, etiologically associated with yersiniosis (usually pseudotuberculosis), which can be regarded as a residual phase of the process. The development of chronic collagenosis and autoimmune disorders is possible. There are studies confirming the participation of Yersinia in the development of various thyroid dysfunctions (diffuse toxic goiter, thyroiditis, etc.).

Features of the pseudotuberculosis clinic Clinical manifestations of pseudotuberculosis are characterized by a wide variety of forms and variants. More often the disease develops in a mixed variant of the generalized form. The incubation period varies from 3 to 18 days, most often 5-7 days. The onset of the disease is distinguished by general toxic symptoms, arthralgia, abdominal pain, sometimes dyspeptic symptoms, catarrhal symptoms of the upper respiratory tract, enlarged liver, and the occurrence in some cases of swelling of the face, hands, and feet. After 5-7 days, a peak period begins, lasting from several days to 1 month. During this period, an exanthema of a predominantly scarlet-like nature develops, localized in the face, neck and distal extremities, including the palms and soles. At the same time, abdominal, hepatitis, and arthralgic manifestations are observed. As a rule, manifestations of intoxication dominate over local signs of the disease. One type of rash is erythema nodosum, which often appears during relapses of the disease. With the development of arthritic syndrome, smoothness of the contours of the joints and hyperemia of the skin over them are rarely noted. The period of convalescence lasts up to 1 month or more. Therefore, the disease is divided into acute (up to 1 month), prolonged (1 to 3 months) and chronic (more than 3 months) pseudotuberculosis. The frequency of exacerbations and relapses can reach 20% (from 1 to 3 relapses).

Diagnosis of yersiniosis

Diagnosis of yersiniosis is carried out on the basis of the symptoms of the onset of the disease - fever, intoxication and signs of an acute form of gastroenterocolitis in combination with jaundice, exanthema and arthralgia. The most common are enteritis, terminal ileitis, enterocolitis and mesadenitis. Less common forms are sepsis, tonsillitis and secondary foci of infection.

Enteritis and enterocolitis are the most common, they manifest themselves in inflammation of the large and small intestines, accompanied by loose, foul-smelling stools up to 10-15 times a day, sometimes with mucus and blood. The duration of diarrhea, depending on the severity of the disease, ranges from 1 day to several months. In most cases, the temperature remains low-grade - about 37.5 degrees, sometimes it can rise to 39-40 degrees.

Almost all forms of the disease are accompanied by enlarged lymph nodes. Pathogens are able to concentrate in the lymph nodes with the formation of microabscesses - purulent inflammations. To confirm the diagnosis, tests for yersiniosis are performed.

Tests for yersiniosis

Diagnosis of yersiniosis is based on bacteriological and serological research methods. The culture technique is the same as for pseudotuberculosis. For the purpose of laboratory confirmation of the diagnosis, cultures of feces, cerebrospinal fluid and blood are performed on nutrient media. From a series of serological methods, agglutination reactions, latex agglutination, indirect hemagglutination with erythrocyte diagnostics and enzyme-linked immunosorbent assay are used.

In uncomplicated forms of the disease, laboratory data are not specific. The leukocyte level is normal or slightly increased. ESR in reactive arthritis can reach 100 mm/h, but antinuclear antibodies and rheumatoid factor are usually absent. Blood, lymph node tissue, cerebrospinal fluid, peritoneal fluid, and abscess contents are subjected to standard clinical microbiology techniques.

Differential diagnosis is carried out taking into account the clinical picture of the disease. Its primary goal is to exclude acute intestinal infections, various joint diseases, viral hepatitis, acute appendicitis and sepsis of other etiologies.

When X-ray studies of the intestinal area, a sharp narrowing of the affected part of the ileum is observed, the relief of the mucous membrane is often smoothed (the so-called “cord” symptom). At the following stages, it is possible to develop a granulomatous-ulcerative lesion in the ileum, which is morphologically indistinguishable from Crohn's disease.

The presence of yersiniosis is signaled by the accelerated positive dynamics of clinical signs and morphological changes in the terminal ileum during treatment with antibacterial drugs, while glucocorticoids and mesalazine are effective in Crohn's disease.

Difficulties may arise in the differential diagnosis of hepatitis of viral etiology and yersinia hepatitis. Yersiniosis hepatitis can manifest itself both as an independent variant and in a generalized form of yersiniosis. From the first stages of the disease, an increase in the blood bilirubin content and pronounced signs of intoxication are observed, while the activity of transaminases slightly increases.

Yersiniosis: expanding traditional ideas about diagnosis, treatment and medical examination of patients

Yersiniosis is widespread in the Russian Federation, and the consistently low level of officially registered incidence does not reflect the true state of the problem. Yersiniosis has now gone beyond the scope of a purely infectious pathology, becoming a therapeutic problem due to the “weak” laboratory base used in practical healthcare, problems in choosing treatment tactics and rehabilitation of patients. Clinicians are particularly concerned about the adverse consequences of yersiniosis, in particular, the chronicity of the infectious process and the formation of systemic autoimmune diseases as a result of the disease [1].

Although in recent years the clinical manifestations of the disease, including the chronic course, have been described in sufficient detail, and significant adjustments have been made to the understanding of the links of immunopathogenesis, practicing doctors know how difficult it is to make a diagnosis, and most importantly, to select treatment for patients that is adequate to the stage of the disease.

As our experience shows, patients with yersiniosis, due to the polymorphism of clinical manifestations of different periods of the disease, are often referred not to an infectious disease specialist, but to doctors of other specialties (gastroenterologists, rheumatologists, endocrinologists, hematologists, etc.), each of whom makes a diagnosis, in fact, being syndromic, and, as a result, prescribes only symptomatic treatment. This statement is based on data from long-term monitoring of yersiniosis survivors, according to which recurrent course among hospitalized patients is recorded extremely rarely (1.3%) and does not correspond to real data on the true frequency of relapses (from 15.8% to 44% in different years).

Apparently, such a rare hospitalization of these patients is associated with the lack of long-term outpatient follow-up of patients who have had yersiniosis, as a result of which, after discharge from the hospital, they fall out of the field of view of the infectious disease specialist, and developing relapses are mistakenly interpreted by other specialists. However, it is early diagnosis and timely treatment that is given the leading role in the prevention of post-yersinia immunopathological diseases, leading to a long-term decrease in performance and disability of patients.

Diagnostic drugs and test systems widely used in practical medicine have rather low sensitivity and efficiency [2, 3]. Long-term monitoring of the diagnosis of “yersiniosis” in patients hospitalized at ICH No. 2 in Moscow has shown that over the past ten years the number of erroneous diagnoses of “yersiniosis” has been steadily increasing, which leads to unnecessary antibiotic therapy and long-term disability of patients. Thus, at the prehospital stage, 57.6% (ranges from 50.9% to 66.3% in different years) of patients are mistakenly diagnosed with yersiniosis, and the patients do not receive adequate treatment in specialized departments of general clinical hospitals.

In the infectious diseases hospital, 42% of these patients had other infectious diseases as their final diagnosis (acute intestinal infections, ARVI, enteroviral diseases, infectious mononucleosis, hemorrhagic fever with renal syndrome, viral hepatitis, generalized chlamydia, leptospirosis, HIV, brucellosis, tularemia, etc. .) and 58% had non-infectious pathology. Of particular concern is yersiniosis, which is misdiagnosed at the prehospital stage in 5.7–15.2% of patients with acute surgical pathology requiring emergency surgical intervention [4, 5].

One cannot but agree with the opinion of V. A. Orlov et al. (1991) that “most diagnostic errors are due to an incorrect approach to the diagnostic process.” Apparently, only this can explain the fact that over the course of ten years, 2.9–9.1% of patients with suspected yersiniosis are eventually diagnosed with heart and vascular diseases, and 2.8–6.4% with intestinal tumors , lungs and pelvic organs, in 2.9–7.1% - Hodgkin lymphoma, lympho- and myeloid leukemia, in 2.8–6.1% - diseases of the endocrine system (toxic goiter, thyrotoxicosis, autoimmune thyroiditis), in 2 1–12.1% - inflammatory diseases of the genital organs.

In our opinion, one of the main reasons for diagnostic errors leading to both under- and overdiagnosis of yersiniosis is the low information content of insufficiently specific techniques and diagnostic tools, as well as non-compliance with existing recommendations for the diagnosis of yersiniosis. In the Russian Federation there are modern diagnostic drugs, methods and culture media for the indication and identification of Yersinia enterocolitica and antibodies to them, but the system of their use is not unified, and the assessment of specificity is imperfect.

Laboratory diagnosis of yersiniosis should include bacteriological, immunodiagnostic and serological methods. The main method is bacteriological - seeding the patient’s biological material (feces, urine, washings from the back of the throat, blood clot, sputum, bile, cerebrospinal fluid, surgical material, etc.), material from the external environment and from animals on nutrient media to detect Y growth enterocolitica followed by culture identification. At least four materials must be tested (for example, feces, urine, blood, pharyngeal wash). The optimal time for collecting material is the first 7–10 days of illness. It is extremely rare to obtain a culture of Y. enterocolitica from material from patients with prolonged course and secondary focal forms of yersiniosis.

The main disadvantages of the bacteriological method are the low frequency of obtaining culture growth - on average in the Russian Federation, Y. enterocolitica is isolated in 2-3% of samples, 0.81%, and retrospectiveness (the final result is on the 21-28th day of production) [2]. For more than ten years, in the bacteriological laboratory of the IKB No. 2 in Moscow, it was possible to isolate Y. enterocolitica in only 0.2% of the samples taken (only in the generalized form of yersiniosis), which is consistent with the data of the GSEN center in Moscow and is four times worse, than in the Russian Federation as a whole [2, 3].

Immunodiagnostic methods make it possible to detect Y. enterocolitica antigens in clinical material up to the 10th day from the onset of the disease (enzyme-linked immunosorbent assay (ELISA), coagglutination reaction (ICA), immunofluorescence reaction (RIF), indirect immunofluorescence reaction (IRIF), agglutination and lysis reaction ( RAL)). According to manufacturers, the sensitivity of test systems reaches 104–105 m cells/ml, and the efficiency of testing coprofiltrate and serum in the first five days of illness is 83–85%. Promising methods are methods for indicating and identifying pathogenic Y. enterocolitica by a set of phenotypic characteristics associated with its pathogenicity determinants (API test systems (sensitivity 79%) and genetic methods for diagnosing and typing Yersinia (polymerase chain reaction (PCR), multiprimer PCR) .The advantages of PCR include the speed of analysis (up to 6 hours), information content, high sensitivity and specificity. However, in practical medicine, the specificity of this reaction turned out to be the most vulnerable. The immunoblotting method, which makes it possible to detect and identify proteins (antigens) of Yersinia using antisera, in RF is used unreasonably rarely.

To determine specific antibodies to Y. enterocolitica antigens, serological methods are used. The study must be carried out from the 2nd week of illness in paired sera with an interval of 10–14 days. A 2–4-fold dynamics of antibody titer in paired sera is desirable, which, however, is not always observed in practice. At the onset of the disease, the most informative reaction is ELISA with determination of IgA, IgM and IgG, ELISA; at 3–4 weeks - ELISA, ELISA, agglutination test (RA), RSC, A-BNM. For the qualitative determination of IgA and IgG class antibodies to the virulence factors of pathogenic strains of Y. enterocolitica, you can use the immunoblotting method, which is used for the differential and retrospective diagnosis of yersiniosis. In the chronic course of yersiniosis, ELISA with the determination of IgA and IgG and immunoblotting are informative.

Despite the large number of test systems offered and various companies guaranteeing a high frequency of detection of yersinia antigens or antibodies to them (up to 85%), in practical health care the indirect hemagglutination test (IRHA) and RA are more often used, which actually makes it possible to diagnose yersiniosis only in every fourth patient (25.3%): with the abdominal form - in 41.7% of patients, with the generalized form - in 21.1% of patients, with the secondary focal form - in 30.8% of patients. It is extremely rare that serological methods confirm the gastrointestinal form of yersiniosis (4.5%). There is no reliable relationship between the level of antibodies to Yersinia and the severity of yersiniosis.

Quite often (21.1% of cases), attending physicians interpret a single detection of specific antibodies to Y. enterocolitica in the blood of patients as laboratory confirmation of yersiniosis. However, in the majority of patients (54.1%), the titer does not exceed 1:200, which means it cannot be considered laboratory confirmation of the clinical diagnosis. The explanation for this lies in the intensive circulation of Yersinia in the environment and among the population. According to materials from the GSEN centers in the Russian Federation, when examining healthy individuals, specific antibodies to Y. enterocolitica are detected in 0.4–4.4% of samples [2]. However, the immune layer among the population is much higher - 18.2–19.6% [6, 7].

Antibody titers to Y. enterocolitica in the direct hemagglutination reaction (DHR) and RA above 1:200 are recorded only in 45.9% of patients. However, a one-time blood test using the mentioned methods, even with a high titer, cannot be unambiguously interpreted as yersiniosis. Thus, in our practice there was a patient with severe articular syndrome, during a dynamic blood test of which antibodies to Y. enterocolitica using the RA method were at a constant level of 1:102,400, which only indicated that she had suffered yersiniosis and was not an indication for prescribing antibacterial therapy.

Analyzing the general recommendations for laboratory diagnosis of yersiniosis and the current situation in practice, we can state that laboratory diagnosis of the disease remains at the level of the early 90s. The reasons lie not only in the use of insufficiently effective methods, but also in non-compliance with existing recommendations for diagnosing yersiniosis. Thus, in most cases, when making a diagnosis, practitioners rely on a single examination of material taken from the patient and the titer of antibodies to Y. enterocolitica. However, the serological criterion for the diagnosis of “yersiniosis” should be considered not so much the achievement of the “diagnostic” titer of specific antibodies, but rather its dynamics when studying paired sera with an interval of 10–14 days. To increase the efficiency of diagnosing yersiniosis, we recommend examining the blood serum of patients with yersiniosis using at least three methods (for example, RNGA, RSK and ELISA, etc.).

Pathogenesis of yersiniosis. The choice of management tactics and drug treatment for patients with yersiniosis directly depends on the pathogenesis of different stages of the disease. It is known that the nature of the interaction of Y. enterocolitica with the macroorganism depends on the set of pathogenicity factors of the strain, the dose of the infection, the route of administration and the immunological reactivity of the macroorganism. Taking into account the available experimental data, the pathogenesis of yersiniosis in humans can be presented as follows. Y. enterocolitica enters the human body orally, and the disease develops after a fairly short incubation period - from 15 hours to 6 days (on average 2-3 days). The bulk of Yersinia overcomes the protective barrier of the stomach. In the stomach and duodenum, catarrhal-erosive, less commonly, catarrhal-ulcerative gastroduodenitis develops. Then the development of the pathological process can go in two directions: either local inflammatory changes will occur in the intestine, or a generalized process will develop with lympho- and hematogenous dissemination of Y. enterocolitica.

If the disease is caused by serotypes of Y. enterocolitica, which have pronounced enterotoxigenicity and low invasiveness, then, as a rule, processes localized in the intestine develop, the manifestations of which will be damage to the gastrointestinal tract (catarrhal-desquamative, catarrhal-ulcerative enteritis and enterocolitis) and intoxication.

If Y. enterocolitica penetrates the mesenteric nodes, the abdominal form develops. The pathomorphology of yersinia lymphadenitis is a combination of infectious, inflammatory and immunological processes. In the appendix, the inflammatory process is often catarrhal in nature, but the development of a phlegmonous process with subsequent destruction of the appendix and the development of peritonitis is possible. Gastrointestinal and abdominal forms of yersiniosis can be either independent or one of the phases of the generalized form.

There are two known ways of generalization of the yersinia process - invasive and non-invasive. The invasive route of entry of Y. enterocolitica through the intestinal epithelium is the classic and best studied. If the infection is caused by a highly virulent strain of Y. enterocolitica, then a non-invasive route of penetration through the intestinal mucosa inside the phagocyte is possible.

During the period of convalescence, the body should be freed from yersinia and the impaired functions of organs and systems should be restored, resulting in clinical and laboratory recovery. However, such a favorable development of events is possible only with an adequate immune response and the absence of immunogenetic and epigenetic markers of an unfavorable outcome. Dispensary observation of convalescents for five years after acute yersiniosis showed that the outcomes of yersiniosis can be:

1) clinical and laboratory recovery (55.2%);

2) unfavorable outcomes (29.2%):

a) with the formation of a chronic course (57%);

b) with the formation of pathological conditions and diseases of an autoimmune nature (43%);

3) relatively unfavorable outcomes with a predominance of the infectious and inflammatory component (10.5%):

a) with exacerbation of chronic inflammatory diseases (35.5%);

b) with the formation of new diseases with a predominance of the infectious-inflammatory component (64.5%);

4) residual effects (short-term low-grade fever, periodic myalgia and arthralgia, neurological symptoms involving nerve plexuses and roots, autonomic reactions, asthenic and hypochondriacal syndromes, the phenomenon of interoception, etc.) (5.1%).

The best prognosis is for patients aged 19–25 years. Among them, 71% recover. At the same time, 45% of survivors aged 26–45 years develop pathological conditions of various origins that are included in the category of unfavorable outcomes of yersiniosis.

According to our data, doctors diagnose secondary focal forms of yersiniosis more often than they actually form. This is due to the absence of pathognomonic clinical manifestations of secondary focal forms of yersiniosis and their systemic nature. The group of patients with the so-called secondary focal form of yersiniosis is not homogeneous. This group often unreasonably includes both patients with a pathological process of yersiniosis etiology (for example, the chronic course of yersiniosis), and patients with a chronic course of post-yersiniosis infection, with emerging new acute processes of non-yersinia etiology and patients with autoimmune pathology. This state of affairs requires special attention and analysis of clinical and laboratory parameters from the practicing physician, since further treatment tactics, and therefore the outcome of the entire pathological process, depend on their understanding.

In patients with chronic yersiniosis, Y. enterocolitica continues to circulate in the body for a long time. According to our data, the chronic course of yersiniosis develops in 16.6% of patients and is more often observed in people over 25 years of age. The “shelter” of pathogens is the lymph nodes, small intestine and cells of the macrophage-monocyte series. Activation of foci of infection can clinically manifest itself in the form of urethritis, nephritis, enteritis, meningitis, etc. From the foci, Yersinia antigens enter the blood as part of immune complexes, causing reactive arthritis, damage to the kidneys, intestines, organs of vision, etc. Slowing the speed of blood flow in the tissues - targets creates favorable conditions for the deposition of Y. enterocolitica antigens. A criterion for the persistence of the pathogen can be considered long-term (more than 6 months) circulation of specific IgA to Yersinia lipopolysaccharide.

Among the diseases that are of an autoimmune nature and are the outcome of yersiniosis, seronegative spondyloarthropathy (usually reactive arthritis and Reiter's syndrome), rheumatoid arthritis, autoimmune thyroiditis and Crohn's disease predominate.

Treatment of patients with yersiniosis and pseudotuberculosis should be comprehensive, pathogenetically substantiated and carried out taking into account the clinical form and severity of the disease (

), (

). The most important task is to relieve symptoms of the acute period and prevent adverse outcomes of the disease. Hospitalization of patients with yersiniosis is carried out according to clinical and epidemiological indications. For mild and uncomplicated moderate cases, treatment at home is allowed. According to epidemiological indications, patients belonging to the decreed group (military personnel, workers of water utilities, catering departments, etc.) are hospitalized.

For dietary nutrition, tables No. 4, 2 and 13 are used. Antibacterial therapy is prescribed for 10–14 days (for the gastrointestinal form it can be limited to seven days) to all patients, regardless of the form of the disease, as early as possible (preferably before the third day of illness) [8] .

The choice of drug depends on the antibiotic sensitivity of Yersinia strains circulating in a given area (determined twice a year). Currently, preference is given to fluoroquinolones and third-generation cephalosporins [9, 10].

The main direction of pathogenetic therapy for the gastrointestinal form of yersinia infection is oral (parenteral) rehydration and detoxification with polyionic solutions.

The treatment tactics for patients with the abdominal form are agreed with the surgeon. The surgeon decides whether surgical intervention is necessary. Before and after surgery, etiotropic and pathogenetic treatment is carried out in full.

In the generalized form, etiotropic drugs, in most cases, are prescribed parenterally. In generalized forms with symptoms of pyelonephritis, pefloxacin has proven itself well - 0.8 g/day. Levomycetin succinate is used for the development of meningitis of yersinia etiology (7–100 mg/kg per day). In severe cases of the generalized form, several courses of parenteral antibiotic therapy are carried out. Start with gentamicin - for 2-3 days at 2.4-3.2 mg/kg per day, then 0.8-1.2 mg/kg per day. In the absence of a therapeutic effect or drug intolerance, streptomycin sulfate is used at a dose of 1 g/day. If hepatitis develops, you should avoid prescribing medications that have a hepatotropic effect. For patients with a septic form of the disease, it is advisable to administer two or three antibiotics of different groups (fluoroquinolones, aminoglycosides, cephalosporins) intravenously. If antibacterial therapy is ineffective, L. A. Galkina, L. V. Feklisova (2000) recommend using polyvalent yersinia bacteriophage (50.0–60.0 ml 3 times a day, No. 5–7) as monoetiotherapy or in combination with antibiotics [eleven].

In addition to etiotropic treatment, pathogenetic therapy is indicated (detoxification, restorative, desensitizing drugs, stimulants). In complex therapy, agents for the treatment of dysbiotic disorders must be used.

Most patients with severe asthenic, vegetative and neurotic manifestations require taking nootropic drugs, tranquilizers, bromides, peony infusion, motherwort tincture, valerian root decoction, etc. The selection of therapy in such cases is coordinated with a neuropsychiatrist and a vegetarian.

Treatment of patients with a secondary focal form of yersiniosis is carried out according to an individual scheme for each patient. Antibacterial drugs have no independent significance, but should be prescribed when clinical and laboratory signs of intensification of the infectious process appear and there is no history of taking antibiotics. Treatment of patients is coordinated with a rheumatologist, gastroenterologist, endocrinologist, psychoneurologist and other specialists (as indicated). Immunocorrectors should be prescribed to patients strictly according to indications in the absence of laboratory signs of an autoimmune process based on the results of a study of the immune status and autoantibodies in the patient’s blood.

Dispensary observation of convalescents. There is still no consensus on the duration and tactics of dispensary observation of convalescents of yersiniosis and pseudotuberculosis. In accordance with the orders and guidelines of the Ministry of Health (Order No. 408 of 1989; Appendix 6 to the Order of the Ministry of Health of the Russian Federation of September 17, 1993 No. 220 “Regulations on the office (department) of infectious diseases”, etc.), monitoring of convalescents of yersinia infection is carried out in depending on the nosology and severity of the disease for 1–6 months after discharge from the hospital (for mild forms - one month, for moderate forms - three months, for severe forms - six months).

Some researchers recommend using the following indicators to predict unfavorable outcomes of yersiniosis: unfavorable premorbid background (chronic diseases, grade 3-4 dysbiosis, burdened allergic history, etc.), long-lasting decrease in albumin, alpha proteins, urea-ammonia ratio, dysproteinemia, increased concentration blood ammonia, fibrinogen, neutrophilia, monocytosis, lymphocytosis, eosinophilia, low activity of the complement system, decreased levels of T- and B-lymphocytes in the period of convalescence and nonspecific resistance factors, high levels of circulating immune complexes (CIC), the presence of HLA B7, B18 and B27 , O (I) blood group.

However, dynamic observation of patients who have had yersiniosis and the use of modern methods of statistical processing of clinical and laboratory parameters allow us to express the opinion that the clinical manifestations of yersiniosis and pseudotuberculosis, their severity and duration are not objective criteria for prognosis, and therefore cannot be used for prognosis course and outcome of the disease. The immunoprognostic testing algorithm we created (

) patients in the acute period of the disease and the developed set of criteria for assessing immunograms for yersiniosis enable doctors to predict an unfavorable course and outcome already in the first 2–4 weeks from the onset of the disease [12, 13].

In our opinion, if the patient does not have criteria for adverse outcomes of yersiniosis infection, dispensary observation of convalescents is recommended for one year after discharge from the hospital. If there are indicators of possible adverse outcomes of yersiniosis, dispensary observation should be carried out for five years after discharge from the hospital - the first year every 2-3 months, then once every six months in the absence of complaints and deviations in health. In the presence of clinical and laboratory problems - more often, as necessary. According to indications, patients should undergo clinical, laboratory and instrumental examination by a rheumatologist, endocrinologist, cardiologist, ophthalmologist, dermatologist, etc.

The tactics of medical examination of patients with yersiniosis are not regulated at all by orders of the Ministry of Health of the Russian Federation. Based on our own results of long-term observation of patients with yersiniosis, we recommend the following tactics for their clinical examination. After discharge from the hospital, the duration of clinical observation for survivors of yersiniosis and pseudotuberculosis in the absence of genetic and immunological prognostic criteria for adverse outcomes should be one year, and if they are present, at least three years. To monitor the completeness of recovery, it is recommended to use the following scheme: during the first year after the acute period, patients must be examined comprehensively (clinical, laboratory, immunological methods) every 2–3 months, then once every six months in the absence of complaints and deviations in health. In the presence of clinical and laboratory problems - more often, as necessary. According to indications, during clinical examination, patients should be consulted with other specialists (rheumatologist, gastroenterologist, endocrinologist, cardiologist, ophthalmologist, dermatologist, gynecologist and gynecologist-endocrinologist) with the necessary laboratory and instrumental studies.

Literature

1. Shestakova I.V., Yushchuk N.D., Andreev I.V., Shepeleva G.K., Popova T.I. On the issue of the formation of immunopathology in patients with yersiniosis // Ter. archive. 2005; 11:7–10.
2. Opochinsky E. F., Mokhov Yu. V., Lukina Z. A., Yasinsky A. A. Analysis of the activities of the centers of the State Sanitary and Epidemiological Supervision of the Russian Federation for laboratory diagnosis of yersiniosis. In the book: Infections caused by Yersinia (yersiniosis, pseudotuberculosis), and other current infections. St. Petersburg, 2000: 42–43.
3. Filatov N. N., Salova N. Ya., Golovanova V. P., Shesteperova T. I. Current state of laboratory diagnosis of yersiniosis in Moscow. In the book: Infections caused by Yersinia (yersiniosis, pseudotuberculosis), and other current infections. St. Petersburg, 2000: 59–60.
4. Shestakova I.V., Yushchuk N.D., Popova T.I. Yersiniosis: diagnostic errors // Doctor. 2007; No. 7: 71–74.
5. Yushchuk N.D., Shestakova I.V. Problems of laboratory diagnosis of yersiniosis and ways to solve them // ZhMEI. 2007; No. 3: 61–66.
6. Ghukasyan G. B., Khachatryan T. S., Aleksanyan Yu. T., Khanjyan G. Zh. Epidemiological patterns of yersiniosis in Armenia. In the book: Infections caused by Yersinia (yersiniosis, pseudotuberculosis), and other current infections. St. Petersburg, 2000: 13.
7. Belaya Yu. A. Yersinia in “healthy” people. Results of long-term prospective studies. In the book: Infections caused by Yersinia (yersiniosis, pseudotuberculosis), and other current infections. St. Petersburg, 2000: 5.
8. Karetkina G. N. Yersiniosis. In the book: Yushchuk N. D., Vengerov Yu. Ya. (ed.) Lectures on infectious diseases. M.: VUNMC; 1999: 339–354.
9. Luchshev V.I., Andreevskaya S.G., Mikhailova L.M. et al. Treatment of patients with yersiniosis with fluoroquinolone drugs // Epidem. and infectious Diseases. 1997; 3:41–44.
10. Dmitrovsky A. M., Karabekov A. Zh., Merker V. A. et al. Clinical aspects of yersiniosis in Almaty. In the book: Infections caused by Yersinia (yersiniosis, pseudotuberculosis), and other current infections. St. Petersburg, 2000: 17–18.
11. Galkina L. A., Feklisova L. V. Results of the use of polyvalent yersiniosis bacteriophage in the treatment of yersiniosis in children. In the book: Infections caused by Yersinia (yersiniosis, pseudotuberculosis), and other current infections. St. Petersburg, 2000: 11.
12. Shestakova I.V., Yushchuk N.D., Balmasova I.P. Clinical and prognostic criteria for various forms and variants of the course of yersinia infection // Ter. archive. 2009, vol. 81,11: 24–32.
13. Shestakova I.V., Yushchuk N.D. Chronic yersiniosis as a therapeutic problem // Ter. archive. 2010, vol. 82, 3: 71–77.

I. V. Shestakova , Doctor of Medical Sciences, Associate Professor N. D. Yushchuk , Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Medical Sciences MGMSU , Moscow

Contact information for authors for correspondence

Treatment of yersiniosis

How to treat yersiniosis is determined for each patient by the doctor individually. Treatment of yersiniosis is prescribed depending on the form of the disease and its clinical picture. Uncomplicated forms of intestinal yersiniosis require treatment with etiotropic drugs and detoxification therapy for 7-10 days, depending on the severity of the patient’s condition, orally or parenterally.

Yersiniosis is also treated with antibiotics. The septic form of yersiniosis, secondary foci of infection and intestinal forms of the disease against a background of weakened immunity are treated with 2-3 types of antibacterial agents for 12-14 days, with detoxification therapy and the prescription of drugs that promote rehydration. If necessary, probiotics and multienzyme preparations can be used.

A comprehensive study to identify the causative agent of yersinia (Yersinia enterocolitica) and pseudotuberculosis (Yersinia pseudotuberculosis), including serological tests and polymerase chain reaction (PCR).

Synonyms Russian

Tests for yersiniosis and pseudotuberculosis.

English synonyms

Laboratory Diagnostics of Yersiniosis, Enteropathogenic Yersiniae Lab Panel.

What biomaterial can be used for research?

Venous blood, feces.

How to properly prepare for research?

• The study is recommended to be carried out before starting antibiotics and other antibacterial chemotherapy drugs.
• Avoid taking laxatives, administering rectal suppositories, oils, limit (in consultation with your doctor) taking medications that affect intestinal motility (belladonna, pilocarpine, etc.) and drugs that affect the color of stool (iron, bismuth, barium sulfate), within 72 hours before stool collection.
• Do not smoke for 30 minutes before the test.

General information about the study

Yersinia are gram-negative, facultative anaerobic rods belonging to the family Enterobacteriaceae. There are 11 known species of Yersinia, three of which are causative agents of human diseases: Yersinia pestis is the causative agent of plague, Yersinia enterocolitica (Y. enterocolitica) and Yersinia pseudotuberculosis (Y. pseudotuberculosis) are intestinal pathogens. Although Y. enterocolitica and Y. pseudotuberculosis are different species, they have many similarities, especially in terms of clinical presentation and diagnosis.

The main “reservoir” of Yersinia is wild and domestic animals (pigs, rodents, sheep, goats, cows, dogs, cats and birds). It is believed that humans do not participate in the natural life cycle of these pathogens either as an intermediate or definitive host and that their infection is thus accidental. As a rule, infection with intestinal Yersinia occurs through the fecal-oral route through consumption of contaminated food (dairy products, raw or undercooked meat, especially pork). Both Y. enterocolitica and Y. pseudotuberculosis remain viable at low temperatures. Cases of transmission of infection from person to person or through transfusion of infected blood have been described, but are very rare.

It should be noted that not all intestinal Yersinia are pathogens. Thus, serotypes Y. enterocolitica O:3, O:8, O:9 and O:5,27 and Y. pseudotuberculosis O:1 and O:2 lead to the development of the disease in humans. Only the indicated serotypes are truly entropathogenic Yersinia.

A feature of enteropathogenic Yersinia is their affinity for lymphatic tissue. Penetrating through the intestinal mucosa, these microorganisms enter the mesenteric lymph nodes. The developing inflammatory response is accompanied by abdominal pain and diarrhea, as well as mesenteric lymphadenitis. In immunocompetent individuals, infection with enteropathogenic Yersinia is more often limited to gastroenteritis and regional lymphadenitis. If the causative agent of the disease is Y. enterocolitica, they speak of yersiniosis, if Y. pseudotuberculosis, they speak of pseudotuberculosis. Yersiniosis is more common than pseudotuberculosis. Both with yersiniosis and pseudotuberculosis, immunopathological phenomena in the form of reactive arthritis and erythema nodosum can be observed. In persons with immunodeficiency, as well as young children, severe forms of yersiniosis and pseudotuberculosis with bacterial dissemination and sepsis may be observed.

Diagnosis of yersiniosis and pseudotuberculosis is quite difficult. Although bacteriological culture of stool (blood or other biological materials) is considered the “gold standard” for diagnosis, it is difficult to implement. This is due to the fact that enteropathogenic Yersinia is difficult to distinguish from other intestinal microorganisms that normally predominate in the intestinal flora. After identifying the growth of Yersinia, additional biochemical tests are carried out to determine their enteropathogenicity. In addition, the bacteriological culture method is characterized by rather low sensitivity (103-106 CFU per gram of biomaterial sample is required to obtain a result). Taking these features into account, the diagnosis of yersiniosis and pseudotuberculosis is complex and includes the following additional tests:

• Polymerase chain reaction (PCR) is one of the molecular diagnostic methods, during which the genetic material (DNA) of a microorganism is determined in a sample of biomaterial (in feces). The main advantages of PCR are the speed of obtaining results, high sensitivity and specificity. This comprehensive study includes PCR analysis for Y. pseudotuberculosis.
• Serological tests. Antibodies to enteropathogenic Yersinia can usually be detected in the first 2-4 weeks of illness (IgM antibodies). It should be noted that due to a certain antigenic similarity of Yersinia to bacteria of other genera (Salmonella, Morganella, Brucella), serological tests may give false positive results. Another disadvantage of serological tests is that antibodies to Yersinia (IgG antibodies) persist for several years after infection, which can interfere with interpretation of the result. It should be remembered that the result of serological tests depends on the immune status of the body.

The accuracy of PCR and serological tests is less affected by antibacterial drugs than the bacteriological method. However, the most accurate test result will be obtained by analyzing the biomaterial obtained before the start of treatment.

Gastroenteritis that occurs when infected with enteropathogenic Yersinia is difficult to distinguish from salmonellosis, campylobacteriosis and other intestinal infections. For this reason, additional laboratory tests are often required.

What is the research used for?

• For the diagnosis of yersiniosis and pseudotuberculosis.

When is the study scheduled?

• If yersiniosis or pseudotuberculosis is suspected: fever, nausea, abdominal pain (pain may be localized in the right groin area), diarrhea, as well as erythema nodosum or reactive arthritis;
• in some cases, if acute appendicitis is suspected.

What do the results mean?

Reference values

For each indicator included in the complex:

• [07-115] Yersinia pseudotuberculosis, Yersinia enterocolitica, IgM, semi-quantitative
• [07-116] Yersinia pseudotuberculosis, Yersinia enterocolitica, IgG, semi-quantitative
• [09-101] Yersinia pseudotuberculosis, DNA [real-time PCR]

What can influence the result?

• Time elapsed since infection;
• state of the body's immune system;
• use of antibacterial drugs (aminoglycosides, co-trimoxazole, cephalosporins, tetracyclines, fluoroquinolones).

Prevention of yersiniosis

Specific prevention of yersiniosis has not yet been developed. All preventive measures are based on the epidemiological characteristics of the infection. They come down to the fight against rodents as the main carriers of infectious diseases. In vegetable stores, warehouses and stores, rodents are periodically exterminated. In order to timely identify individuals with yersiniosis among domestic animals and birds, scheduled and extraordinary veterinary examinations are periodically carried out on farms. Dairy plants establish control over the processing of dairy products.

When storing fruits and vegetables, attention is paid to the quality of preventive measures for disinfection and deratization of vegetable stores when a new crop arrives. Current disinfection and deratization is carried out in winter and autumn. Places for storing any products that are not subject to heat treatment are subject to careful control; catering establishments monitor compliance with the technological and sanitary regime during storage and preparation of food. In the event of a separate disease or outbreak, the food enterprise from which the product that caused the infection came is identified.

In medical institutions, the prevention of yersiniosis is based on compliance with the anti-epidemic and sanitary regime adopted for intestinal infections. Along with sanitary measures, timely identification of relatives and medical personnel infected while caring for sick people is important.

This article is posted for educational purposes only and does not constitute scientific material or professional medical advice.

Yersiniosis in children: relevance of the problem, clinical case

Incidence of yersiniosis in the Russian Federation during 2010–2015. consistently high with uneven distribution across individual territories. Higher incidence rates from 50 to 150 or more per 100,000 children are recorded in the northern regions of Russia. Indicators in the south of Russia are much lower - from 6 to 10 per 100,000 children [1].

The causative agent of the disease, Yersinia enterocolitica, persists in the environment for a long time (up to several months), which determines its epidemic significance.

The main source of infection is animals, people with yersiniosis and bacteria-shedding agents, which is confirmed by the growth of infected individuals during the complication of the epidemic situation and the possibility of nosocomial infection with yersiniosis.

Under natural conditions, the causative agents of yersiniosis exist as parasites of rodents and are released into the external environment with feces and urine. The most contaminated by Yersinia are long-term stored vegetables, in which the detection of the pathogen can be 10–20% or more [2].

Clinical diagnosis of yersiniosis is difficult due to the polymorphism of symptoms, which can be mistaken for various diseases of an infectious and non-infectious nature. The following clinical forms of yersiniosis are distinguished: gastroenterocolitic, icteric, arthralgic, eczematous, meningeal, catarrhal, mixed and septic.

The clinical picture of yersiniosis is characterized by an acute onset, toxicosis, an increase in body temperature to 39–40 °C, symptoms of damage to the gastrointestinal tract (nausea, vomiting, cramping or constant abdominal pain, loose stools). From the first day of the disease, patients may experience muscle and joint pain, injection of blood vessels in the sclera and conjunctiva, catarrhal phenomena in the oropharynx, exanthema, etc. With the development of the icteric form of yersiniosis, symptoms of liver damage come to the fore: pain in the right hypochondrium, an increase in the size of the liver and its pain on palpation, icterus of the skin and sclera, darkening of urine, discolored feces [3, 4]. The general clinical picture of the icteric form of yersiniosis bears little resemblance to viral hepatitis, but among the diagnostic errors of yersiniosis occurring with jaundice, this form of the disease is most often interpreted as viral hepatitis.

It should be noted that with the icteric form of yersiniosis and viral hepatitis, there are many common symptoms: icterus of the skin and sclera, enlargement of the liver and its pain, change in color of the skin and stool. At the same time, there are differences in the clinical picture of these diseases that are crucial for the diagnosis of yersiniosis even at the stages of anamnestic and clinical examination.

We observed three children aged 4 to 10 years who were admitted to the clinic with a referral diagnosis of viral hepatitis. In all cases, the leading clinical signs were toxicosis and jaundice.

Here is one of our observations.

Andrey K., 10 years old. A child from unfavorable living conditions. Got acutely ill. Body temperature increased to 38 °C, headache, weakness, nausea appeared, and appetite worsened. The next day, the patient’s health remained poor, the temperature remained at 38–38.5 °C, icterus of the skin and sclera, and dark urine appeared. Hospitalized on the second day of illness with a diagnosis of viral hepatitis.

When examined in the emergency department, the patient’s condition was serious, temperature 38 °C. Pronounced icterus of the skin and sclera. Pulse 90 per minute, rhythmic, satisfactory filling and tension, blood pressure 90/60 mm Hg. Art. Heart sounds are muffled and clear. Above the lungs, the percussion tone is clear, vesicular breathing. The abdomen is soft, not swollen, painless on palpation. The lower edge of the liver is palpated 6 cm below the costal arch, its surface is smooth, elastic, palpation is painless. The spleen was not palpable. The feces are colored, the urine is saturated. From the epidemic history it turned out that the patient had no contact with patients with jaundice, and had not received any injections over the past 6 months. All family members are healthy.

Blood test on admission: erythrocytes - 3.5 × 1012/l, hemoglobin - 122 g/l, leukocytes - 5.9 × 109/l, eosinophils - 2%, band leukocytes - 3%, segmented leukocytes - 46%, lymphocytes - 43%, monocytes - 2%, ESR - 6 mm/hour. Total blood bilirubin is 68 µmol/l with a predominance of the direct fraction. Alanine aminotransferase level (ALT > 31 µmol/l). Prothrombin index - 70%.

Despite the ongoing detoxification and antibacterial therapy (Cefotaxime in a daily dose of 2 g), followed by its replacement with amikacin in a daily dose of 10 mg/kg body weight, febrile fever persisted. Jaundice increased, and by the 11th day of the disease, total blood bilirubin increased to 129 µmol/l, direct - 97 µmol/l, indirect 32 µmol/l, fermentemia remained: ALT - 24.8 µmol/l, cholesterol - 5.14 µmol/l, alkaline phosphatase - 0.60 µmol/l. In the general blood test, with a normal number of leukocytes, neutrophilia with a band shift and ESR up to 60 mm/hour appeared. The liver increased to 8 cm below the edge of the costal arch and became more dense. The urine remained dark, the feces became discolored. Changing antibacterial therapy to Levomycetin sodium succinate at the rate of 50 mg/kg body weight (daily dose) made it possible to achieve relief of fever during the first 3 days of using this drug to low-grade levels and its normalization on the 10th day of treatment with Levomycetin (21st day of illness ). At the same time, there was a decrease in the icterus of the skin and sclera. By the 22nd day of the disease, total bilirubin was 47 µmol/l, ALT - 16.5 µmol/l, cholesterol - 1.7 µmol/l, alkaline phosphatase - 0.60 µmol/l. By the 30th day of the disease, the levels of total bilirubin and its fractions were completely normalized. The ALT level decreased to 2.38 µmol/l, the hemogram values ​​were normal. The size of the liver has decreased. Complete normalization of ALT was achieved on the 37th day of the disease.

An additional blood examination for markers of viral hepatitis, blood culture, determination of antibody titer in paired blood sera using RNGA with yersinia antigen, examination for leptospirosis, pseudotuberculosis gave a negative result. Enzyme immunoassay blood test for yersiniosis is positive (IgM). On the 17th day of the disease, Yersinia enterocolitica serovar 03, biotype 4 was isolated from the patient’s blood. On the 19th day of the disease, this pathogen was isolated from the feces. On the 24th day of the disease, the antibody titer in the indirect hemagglutination reaction (IRHA) was 1:50, followed by a 3-fold increase in the antibody titer to the yersinia antigen. The isolated pathogen turned out to be sensitive to Levomycetin.

Final clinical diagnosis: yersiniosis, icteric form.

The peculiarity of this clinical observation is the high activity of hepatocellular enzymes, which is considered not typical for yersinia hepatitis.

A complex of anamnestic, clinical and laboratory data obtained during the examination of the patient allowed us to assume yersiniosis with a greater degree of certainty. Specific examination methods only confirmed the established diagnosis.

Analyzing the given clinical example, a convincing and simple argument can be made to reject viral hepatitis.

As we have seen, the patient noticed jaundice of the skin and darkening of the urine on the day when the body temperature rose to its maximum, but his health remained poor. With viral hepatitis, in the vast majority of cases, with the appearance of jaundice, the well-being and condition of the patients improve noticeably: the temperature normalizes (if it was elevated), appetite appears, weakness decreases, i.e., many symptoms of the pre-icteric period weaken or disappear completely. Only in the most severe course of viral hepatitis the appearance of jaundice is not accompanied by an improvement in the well-being of patients; on the contrary, the symptoms of intoxication may increase, but against the background of normal or, less often, low-grade fever.

Recognition of the icteric form of yersiniosis with a severe course of the disease can be simple or, on the contrary, not easy, and at the stage of outpatient examination, impossible. The diagnosis is simple during an outbreak of yersiniosis and very difficult in sporadic cases of infection, as in our example.

Differentiation of yersiniosis from typhoparatyphoid diseases, leptospirosis, viral hepatitis, pseudotuberculosis, etc. in an infectious diseases hospital is not difficult and is based on studying the dynamics of the main manifestations of infection, differences in hematological changes and, most importantly, on the isolation of the pathogen and the results of a serological examination . It should be remembered that negative results of serological testing for yersiniosis do not exclude the diagnosis. To increase the reliability of the diagnosis, it is necessary to use bacteriological and serological methods.

The bacteriological method makes it possible to determine the pathogen in sick people, animals, and also on environmental objects. The materials for the study are: swabs from the nasopharynx, blood, joint fluid, cerebrospinal fluid, surgical material, feces, urine. It is advisable to conduct a bacteriological study before starting antibacterial therapy, in the first week of the disease, three times. The results of this study are obtained in 2–3 weeks.

For early diagnosis, immunological methods for identifying pathogen antigens are used: enzyme immunoassay, indirect immunofluorescence reaction, latex agglutination reaction, etc. The materials for these studies are saliva, blood, coprofiltrates, animal organs, swabs from environmental objects. It is better to conduct research in the first 10 days of the disease, using at least 2 types of materials from patients.

For serological diagnostics in order to identify specific antibodies, the agglutination reaction (diagnostic titer 1:160) and RNGA are used. Available for most infectious disease hospital laboratories is the determination of antibodies to Yersinia enterocolitica 03 and 09 by the RNGA method. A titer of 1:400 is considered diagnostic. Studies are carried out from the 5th–7th day of illness in paired blood sera taken at an interval of 10–14 days. In recent years, genetic diagnostics—polymerase chain reaction—have become more frequently used [5].

The drugs of choice for the treatment of yersiniosis are antibacterial drugs: III generation cephalosporins, II–III generation aminoglycosides, doxycycline (from 8 years of age), chloramphenicol (Levomycetin), carbapenems (for generalized forms of yersiniosis). The duration of treatment is 10–14 days or more according to indications. Pathogenetic therapy includes detoxification, antihistamines, immunocorrection for severe forms using immunoglobulins for intravenous administration. According to indications, sorbents, enzymes, antispasmodics, hepatoprotectors, antipyretics, etc. are prescribed [3, 5, 6].

Literature

1. Karbysheva N.V., Bobrovsky E.A. Activity of natural foci and morbidity in yersinia infection // Journal of Infectology. 2016. T. 8 (2). P. 52.
2. Ogoshkova N.V., Kashuba T.G., Drozdova O.O., Lyubimtseva N.N. Clinical and epidemiological characteristics of yersiniosis / Current issues of infectious pathology and vaccine prevention. Materials of the XII Congress of Children's Infectious Diseases of Russia. M., 2013. P. 52.
3. Yushchuk N. D., Vengerov Yu. Ya. Kryazheva S. S. Infectious human diseases M.: OJSC Publishing House "Medicine", 2009. P. 78–79.
4. Serova Yu. S., Kuimova I. V., Vasyunin A. V., Krasnova E. I. Frequency and severity of articular syndrome in pseudotuberculosis in children / Current issues of infectious pathology and vaccine prevention. Materials of the XII Congress of Children's Infectious Diseases of Russia. M., 2013. pp. 60–61.
5. Children's infections / Ed. L. N. Mazankova. M.: MEDpress, 2009. pp. 76–81.
6. Kharchenko G. A., Oganesyan Yu. V., Maruseva I. A. Infectious diseases in children: diagnostic and treatment protocols. Textbook allowance. Rostov-on-Don: Phoenix, 2007. pp. 48–49.

G. A. Kharchenko1, Doctor of Medical Sciences, Professor O. G. Kimirilova, Candidate of Medical Sciences

Federal State Budgetary Educational Institution of Higher Astana State Medical University, Ministry of Health of the Russian Federation, Astrakhan

1 Contact information

Antibodies to the causative agent of yersiniosis IgG, Yersinia enterocolitica Ig G, quantity.

Antibodies to the causative agent of yersiniosis Ig G, Yersinia enterocolitica, Ig G, quantity.

— identification of antibodies that are produced by the immune system in response to infection with the causative agent of yersiniosis.
Yersinia enterocolitica
is the causative agent of yersiniosis. These are gram-negative rod-shaped bacteria.

The route of transmission is fecal-oral, that is, through contaminated food and water that contain bacteria.

The reservoir of infection is animals (pigs, rats, mice and other rodents, domestic animals and birds).

Yersiniosis

- an acute bacterial infectious disease that mainly affects the gastrointestinal tract. This disease has nothing to do with tuberculosis (the original name is associated with the external resemblance to tuberculosis granulomas identified in the tissues of sick animals).

The duration of the incubation period is 1–2 days. The minimum period is 15 hours, the maximum is 4 days.

Clinical picture of yersiniosis

The main clinical symptoms of the disease: acute onset, fever up to 38–40 ºС, fever, abdominal pain, mainly in the right iliac region, nausea, vomiting, loose stools without pathological impurities, pain in muscles and joints, enlargement of the liver, spleen and peripheral lymph nodes, joint pain, in many patients - a rash, often small-spotted, facial flushing, swelling and redness of the hands and feet. Lymphadenitis and polyadenitis, arthralgia, arthritis and polyarthritis are common manifestations.

Antibodies to Yersinia enterocolitica

The detection of specific antibodies to the pathogen can be observed by the end of the first week of the disease with a rapid increase in their concentration over 2 weeks and, subsequently, a decrease after 2–6 months. The study of antibodies should be carried out dynamically - in paired sera taken at the onset of the disease and then after 7-10 days. A 4-fold (or more) increase in Ig M antibody titer is considered a diagnostically reliable serological indicator. In the absence of pronounced dynamics of titers or the need to evaluate single results, the epidemiological situation and timing of the disease should be taken into account, and it is permissible to use a minimum conditional diagnostic titer of 1:100– 1:200.

Indications:

• examination of patients with clinical signs of acute intestinal infection;
• to confirm a clinical diagnosis upon receipt of a negative result of a bacteriological examination;
• for the purpose of retrospective confirmation of diagnosis;
• in case of late presentation of the patient, prescription of antibacterial therapy.

Preparation
It is recommended to donate blood in the morning, between 8 and 11 am. Blood is drawn on an empty stomach, after 4–6 hours of fasting. It is allowed to drink water without gas and sugar. On the eve of the examination, food overload should be avoided.

Interpretation of results

Units: U/ml

The result is given in the form of “negative” or “positive”. In the latter case, the antibody titer is indicated - the last dilution of the serum that gives a positive result.

An increase in antibodies by 4 or more times in 7–10 days is considered diagnostically reliable.

Positively:

• current or past infection. It is recommended to examine the patient at least twice - at the onset of the disease and with an interval of 7-10 days. A 4-fold or more increase in antibody titers is considered diagnostically reliable.

Negative:

• absence of infection;
• low concentration or absence of antibodies in the early period of infection.