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„Approved” on methodical conference department of infectious diseases and epidemiology „____” ____________ 200 р. Protocol № _____ Chief of Dept. __________ V.D.Moskaliuk METHODOLOGICAL INSTRUCTIONS to a fifth year student of the Faculty of Medicine on independent preparation for practical training Topic: YERSINIOSIS. PSEUDOTUBERCULOSIS. Subject: Major: Educational degree and qualification degree: Year of study: Hours: Prepared by assistant professor Infectious Diseases Medicine Specialist 5 2 Sydorchuk A.S. Topic: Yersiniosis 1. Lesson duration: 2 hours 2. Aims of the lesson: 3.1. Students are to know: • etiology of yersiniosis, types of pathogens, their principal properties; • epidemiology of yersiniosis; • pathogenesis of yersiniosis and morphology of organs afflicted by Yersinia; • symptoms and development of typical and atypical yersiniosis; • clinical characteristic of yersiniosis; • complications of yersiniosis; • diagnosis of yersiniosis; • laboratory methods of examination at yersiniosis; • differential diagnosis of yersiniosis including distinguishing between similar diseases; • treatment of yersiniosis with taking into account of course severity; • prophylactic and antiepidemic measures at yersiniosis. 3.2. Students are to be able: • to question a patient in order for obtaining of information on disease history and epidemiologic anamnesis; • to perform clinical examination of a patient; • to formulate and to substantiate the diagnosis of yersiniosis; • to prepare a plan of additional patient examination; • to evaluate results of laboratory examination; • to determinate a course severity; • to make differential diagnosis to distinguish between similar diseases (cholera, food borne diseases, salmonellosis, typhoid fever etc); • to prescribe adequate pathogen and etiotropic treatment; • to prepare a plan and organize prophylactic and antiepidemic measures. 3.3. Students are to acquire the following skills: • to conduct clinical examination of a yersiniosis patient and other acute intestinal diseases; • to formulate and substantiate a clinical diagnosis; • to prepare a plan of paraclinic patient examination; • to take samples of material (stool, vomitory masses, suspicious food-stuffs, water after irrigation of the stomach) for bacterioscopy and other quick analysis methods and bacteriological examination for revealing of causative agents; and to take samples of material (blood) for PCR (polimerase chain reaction) and other quick analysis methods (ELISA) and serological examination for revealing of the agent or antibodies against their; • to evaluate results of paraclinic patient examination; • to organize hospitalization and treatment of a yersiniosis patient ; • to provide emergency aid at severe yersiniosis; • to plan and organize prophylactic measures against yersiniosis; • to plan and organize antiepidemic measures to localize and liquidate a yersiniosis source. 4. Advice to students. Y. Enterocolitica are Gram-negative rods or coccibacilli that is often isolated from clinical specimens such as wounds, faeces, sputum, and mesenteric lymph nodes. They have been isolated from animals such as pigs, birds, cats, and dogs, and have been in environmental and food sources, such as ponds, lakes, meats, ice cream, and milk. Most isolates have been found not to be pathogenic. They can survive and grow at temperatures down to 0°C and up to 60°C. The disease caused by Y. enterocolitica is often referred to as yersiniosis. The cells adhere and colonies the lining of the intestinal tract. In some cases they can spread to the liver, spleen and bloodstream. It is believe that they produce a toxin that is responsible for the illness. The diversity of the pseudotuberculosis clinical manifestations, the involvement of different organs and systems in the pathologic process are the basis for the suggestions of numerous classifications of this disease. The least cumbersome classification, though it does not lack drawbacks, is the classification by N. U. Zalmower, which is based on the syndrome principle with the following clinical forms: 1. A scarlatiniform characterized by the general intoxication symptoms, fine-dot rash, fever; 2. An arthralgic form resulting in the joints affection, it takes a course of arthralgia, less often - arthritis; 3. An abdominal form with the primary affection of different parts of the alimentary tract, sometimes in the initial period; 4. A generalized form with the affection of different organs and systems when it is impossible to pick out any main syndrome; 5. An icteric form, in which the affection of the liver with a jaundice syndrome is the primary symptom. The clinical manifestations of pseudotuberculosis are characterized by a great polymorphism with the prevalence of the general intoxication, which makes an early diagnostics extremely difficult. As well as other acute diseases pseudotuberculosis has a certain cyclic recurrence. The development of the cycle's periods with a certain time limitation, which is accompanied by different morphologic, immunologic, and clinical changes, results in a characteristic picture of the disease. There are following periods in pseudotuberculosis: an initial period, a high point, a period of acute courses and relapses, convalescence. Evaluating the descriptions of the clinic given in the literature and observing the patients, it is necessary to note that in each certain case these periods can be manifested in different ways depending on the reactivity of the macroorganism, virulence of the pathogen, the time when the treatment began, the quantity of the daily and course doses of the medications and other factors. All the periods of the disease can be observed in the typical cases in half the patients (especially, in case of the pathogenic therapy and short courses of some antibiotics). In other cases some of them cannot be observed or they can be slightly manifested. There can be only some symptoms of the initial period without a temperature rise in the deleted forms of the disease. Judging by the epidemiological history, the incubation period in this infection most often lasts 7-10 days with the fluctuations from 3 to 18 days. In this period the disease does not usually have any clinical manifestations, the people consider themselves to be practically healthy and continue working. The initial period is the time when the first symptoms of the disease develop till the highest possible development of the clinical picture with the symptoms of the local affection. In most patients the disease has an acute course with a rapid temperature rise, which is accompanied by chills. The prodromal phenomena in the form of malaise, slight chills, the development of uncertain pains in the abdomen, which developed 1-2 days before the onset of the disease, were described only in some cases. This period is clinically characterized by expressed polymorphism and absence of specific symptoms typical of only this disease. The temperature rise is accompanied by a headache of different intensity with its primary location in the forehead and temple areas, pain in the muscles, joints, waist, general asthenia, weakness, and lack of appetite. In a number of cases the sick people complain of the pain in the throat at swallowing. In some cases patients complain of pain in the stomach, diarrhea 2-3 times a day, nausea and single or recurrent vomiting. There is brief fainting in some patients in the first hours of the disease together with general asthenia. An early toxicosis resulting in a lethal outcome can develop in rare cases, especially, in children during 2-4 days. While examining the patients it is possible to observe hyperemia of face and neck, some puffiness of the face, hyperemia of the conjunctiva and an injection of the sclera vessels, there is a pale nose-lip triangle in some patients. There is often herpetic rash on the lips and the nose wings, expressed hyperemia of the throat, which is of different intensity, less often – an enanthema on the soft palate, angina. During the first days of the disease the tongue has a grayish-white patch, which begins to clear and becomes raspberry with expressed papilla on the third day. There are symptoms of acute catarrh of the upper respiratory tract such as a running nose, cough, pains in the throat at swallowing in most patients in the initial period of the disease. Similar symptoms of the disease sometimes result in diagnosing catarrh of the upper respiratory tract and difficulties in deciphering the outbreak. When the massive diseases appeared during the first outbreak of the FESF in the Far East, all the cases were diagnosed as grippe and only the development of rash in the patients caused alarm in doctors and made them turn to the infectionists. The symptoms of the local affection of the alimentary tract and locomotor system, which were manifested by the increasing pain in the abdomen and joints, develop in a quarter of the patients at the end of the initial period. Such diversity of symptoms testifies about the involvement of different organs and systems in the pathological process even on the first days of pseudotuberculosis infection, which is often the reason for a false diagnostics in this period. The most parts of such patients are treated at home, the smaller part is sent to a hospital with the diagnoses: acute respiratory disease, polyarthritis, gastroenteritis, catarrhal angina, scarlatina, and others. These diagnoses often remain the final ones as a doctor examines a patient for a second time only in the period of convalescence and does not pay attention to some important symptoms of the disease (rash, “raspberry” tongue, pain in the ileocecal area, etc.) Rash is one of the most striking symptoms of this period. It develops on the 1-4th day of the disease, sometimes on the 5-6th day. According to its character it is often fine-spotted on the hyperemic background or normal skin. During the first outbreak of the disease in some patients it is fine-spotted, and in combination with angina, the enlargement of the submandibular lymph nodes, “raspberry” tongue, the development of peeling typical of scarlatina in the later period gave a ground to first diagnose “scarlatina” in all patients. Later during the development of other pseudotuberculosis outbreaks and the exposure of the sporadic cases of this disease it was found out that the rash can be spotty (looking like German measles and measles) and confluent erythematous. The spreading of the rash can be different, if it is spread all over the body, it is mainly located on the symmetrical parts. The rash is not often found on the face and neck. There is often hyperemia and swelling of the skin on the hands and feet – the symptoms of “gloves” and “socks”. The petechial-hemorrhagic elements are mainly localized in the natural folds of the skin and on each side of the chest. The development of hemorrhages in the form of stripes and changes on the side surfaces of the shoulders and in the area of the armpit line. There are endothelial symptoms of plait, pinch with hemorrhages in the patients with a severe form. The development of rash can be accompanied by the deterioration of the patients' condition, pulse acceleration, hypotonia, and even a collapse condition. There is scaly laminar peeling on the skin of the chest, abdomen, and lobes of the ear and then on the dorsal surface of the hands, feet, and palms during the 2-3rd week of the disease. The duration of the initial period is 1-5 days. The highest point of the pseudotuberculosis infection is manifested by the maximum development of fever and other symptoms of intoxication and expressed signs of the local affection. The highest point of the disease, especially, the first days are characterized by considerable intoxication, which is manifested by the affection of the central nervous system – general asthenia, hypotonia, dizziness, intense headache, tactile hyperesthesia, photophobia, vomiting, insomnia, increased excitability or suppression. In a severe course there are manifestations of meningoencephalitis with the symptoms characteristic of it: a headache, nausea, vomiting, drowsiness, suppression, consciousness disorders, signs of irritation of the meninges and the substance of the brain. There are such meningeal symptoms as rigidity of the neck muscles, Kernig, and Brudzinsky symptoms, in the cerebrospinal liquid the cytosis is more than 400 cells, the increased protein contents. Besides the mentioned symptoms there are characteristic disorders of the vegetative nervous system function. In some patients the affection of the nervous system is similar to the intercostal and nape neuralgia or lumbosacral radiculitis. The changes of the locomotor system are observed almost in all patients. There is often arthralgia, sometimes with very intense pain in the sacrum, waist, joints and less often – acute polyarthritis, which is characterized by swelling of the tissues around the joints with skin hyperemia. The radiocarpal, interphalangeal, knee and ankle joints are most often affected in pseudotuberculosis, less often – shoulder and hip joints. Acute polyarthritis is often confused with the attacks of acute rheumatism in case of the poor knowledge of the pseudotuberculosis clinic. The pain syndrome depends on the severity of the disease and can be weak or strong, hindering free movement. The joints are swollen, painful, and hot. Most patients complain of myalgia in the acute period of the disease. It prevails in the muscles of the neck, abdomen, and extremities. In some cases myalgia of the abdomen muscles is sharply expressed, which simulates “acute abdomen”. In such cases it is necessary to pay attention even to slight manifestations of other symptoms of the disease. The submaxillary, neck, and axillary lymph nodes can be enlarged in the acute period of the disease. They are slightly painful, elastic, not united with one another and the surrounding tissue. The changes of the cardiovascular system at the highest point of the disease are manifested by hypotonia; dullness of the heart sounds, and in some patients there is a systolic murmur at the apex and extrasystole. In spite of the fact that in a considerable number of patients the subjective symptoms of the heart affection (pain, heartbeat, arrhythmia, and others) are extremely rare, the electrocardiograms show changes, some of them are considerable. The decrease of P and T waves voltage is the most frequent of them, less often - the deformation as a result of the toxic-infectious influences on the cardiac muscle. There were sometimes symptoms of its diffusive affection. The respiratory organs also get involved in the pathological process in pseudotuberculosis. Pain in the throat, hyperemia of the fauces mucous membrane, spotted enanthema on the mucous membrane of the soft palate, rhinitis, cough, dry rale in the lungs testify of their affection. There is dulling of the percussion sound over the pulmonary fields and moist rale in the limited areas in some patients who suffer a severe course of the disease. The x-ray investigations usually demonstrate the intensification of the bronchial-vascular picture, the opacity of the roots, less often - infiltration of the lung tissue. In a mild case of the disease the affection of the alimentary tract is manifested by complaints of a poor appetite, nausea, less often - vomiting diarrhea. The stool is fluid or watery 3-5 times a day with admixture of mucous. The pain at the abdomen is observed in a half of the patients and is often revealed only at palpation. The tongue is furred, it becomes raspberry when it gets cleaned. The changes of the alimentary tract are strongly expressed and prevail over the rest ones in a more severe course. In this case a pseudotuberculosis abdominal form is diagnosed. It is characterized with a pain in the epigastric area of the abdomen, umbilical or right iliac area, less often -in the right hypochondrium and left iliac area. The abdominal syndrome is clinically revealed primarily in the form of the symptoms of mesenteric lymphadenitis, terminal ileitis, acute appendicitis. Mesenteric adenitis of the pseudotuberculosis etiology without any other manifestations is quite often observed in the countries of Western Europe. The affection of the mesentery lymph nodes can occur in different periods of the infectious process, more often in the initial period and at the high point of the disease. In this case there is pain in the right iliac and paraumbilical area, the palpation demonstrates an enlarged, painful and “grumbling” cecum and mesenteric lymph nodes. Such patients come to hospital with various diagnoses: “acute appendicitis”, “acute cholecystitis”, etc. These patients can come to both infectious and surgical hospitals, and only the carefully collected history of the disease and the clinical investigation data allow diagnosing pseudotuberculosis. The intensity of pain in the ileocecal area can be different. In some patients that is revealed only at palpation, in others there are constant aches, in some patients they are so intense that the patients groan and take a forced position with their knees pulled to the abdomen. The patients cannot remain in the same position for a long time. The pain subsides and ceases troubling the patients on the 2-3th day from the time of their appearance. However, in 3-4 days they recommence and become more intense, The local manifestations of mesadenitis are usually accompanied by general symptoms. They are temperature increase, sometimes up to 39 °C, chills, which intensify with the development of pain in the abdomen, diarrhea - 2-3 stools a day without admixture of mucous or blood, nausea, and vomiting in almost half of the patients. Besides the patients complain of headaches, pains in the joints of the upper and lower extremities, body muscles, general asthenia, and sore throat. The skin of the face, neck, chest is often hyperemic in the patients with mesenteric lymphadenitis. In certain cases there is fine-spotted rash, which rise above the skin in the area of the chest, abdomen, groin folds, axillary region, forearms and thighs, the rash gets pale at pressing. There is muscles tension and other symptoms of the peritoneum irritation, which are very similar to the picture of the “acute abdomen” in case of a severe course of the disease. However, in contrast to acute appendicitis in the mesadenitis patients the pain in the abdomen does not increase when the abdominal press is strained. This new symptom was observed in all the cases of pseudotuberculosis mesadenitis. The clinic of acute appendicitis in pseudotuberculosis has its peculiarities connected with the fact that besides the affection of the vermicular process the patients have the manifestations of the main disease. As a rule, the patients, in whom the appendicular syndrome develops during treatment in the infectious hospitals or who arrived with the diagnosis “pseudotuberculosis” and have an expressed appendicular syndrome are not operated on, and the disease has a favorable outcome after the conservatory treatment. It is natural that such patients should be carefully observed by both an infectious doctor and a surgeon in order not to miss authentic appendicitis, whose pathogen can be pseudotuberculosis along with other microbes. It is known that the pseudotuberculosis microbe is isolated in about 7 % cases during the bacteriological investigation of the processes ablated during the appendectomy. The surgical aspects of pseudotuberculosis are of a great practical interest and need to be thoroughly studied. Regional ileitis in the abdominal form of pseudotuberculosis is more often observed in the relapse and remission period of the disease. In this case the pains in the abdomen develop on the background of the seeming convalescence, they are accompanied by a recurring rise of the body temperature up to 38-39 °C and chills. The pain is usually moderate, it is of attacklike character. In 2-3 days from pain development it becomes less intensive, in some cases it ceases troubling a patient. However, on the 3-4th day they increase and become very intense. In some patients pseudotuberculosis begins with the symptoms of regional ileitis. In such cases the pseudotuberculosis symptoms are poorly expressed. This results in the diagnostic mistakes. In case of regional ileitis the pain in the stomach is often accompanied by nausea. In half of the patients there is vomiting, sometimes repeated. The affection of the terminal part of the ileum can be accompanied by watery stool up to 3 times a day without an admixture of mucous and blood. The abdomen is sometimes bloated. The right iliac area is the most painful, there is also muscle tension of the front wall of the abdomen. The similarity of the clinical picture of regional ileitis to that of acute appendicitis is a characteristic feature. In many cases it is extremely difficult to diagnose the case before a surgery. The patients with the pseudotuberculosis abdominal form often have gastroenteritis. Its development can be observed in all periods of the disease. Gastroenteritis usually has a rapid development. The disease starts with pain in the abdomen, nausea, vomiting, it is usually accompanied by the abdomen inflation, watery or pasty stool up to 2-3 times a day, general asthenia, chills, headache and other pseudotuberculosis manifestations. Sometimes gastroenteritis takes a chronic course. In these cases patients complain of the periodic pain in the abdomen, which disturb them, general asthenia, headache, general malaise. The stool in such patients is unstable. There is an expressed asthenia right after the meals. The pains in the abdomen can resemble attacks and do not have a distinct localization. The symptoms of the general intoxication are often expressed. The affection of the alimentary system is not only limited by the pathologic changes of the gastrointestinal tract. The liver affection of any degree is often observed in almost half of the patients, actually it is acute parenchymatous hepatitis; its expressiveness depends on the severity of the disease. The affection of the liver is manifested by the enlargement of its size, icteric color of the skin and scleras, the bilirubin increase in the blood; it sometimes resembles the clinic of viral hepatitis. The thorough comparison of the clinical symptoms with the biochemical investigations shows the involvement of the pancreatic gland in the pathologic process. The patients complain of pain in the abdomen, which resembles attacks and is localized in the epigastric area, in the right and left hypochondrium. In some cases it irradiates in waist or back. The patients complain of nausea, vomiting, and general asthenia. There can be watery stool. The amylase level of blood and urine as well as the lipase activity in blood can confirm the diagnosis. Some authors pay much attention to elastase. In 1986 V. A. Ivanis noted that the elastase level depended on the severity of the disease and its indexes normalized in the period of convalescence. The generalized form of the disease is characterized by the combination of a high temperature, exanthema, and severe intoxication with all the main syndromes of the disease: terminal ileitis, parenchymatous hepatitis, acute polyarthritis, meningeal symptoms and a long relapsing character. Diagnosis. There are no reliable diagnostic tests on pseudotuberculosis among the nonspecific laboratory signs. In particular the blood clinical analysis is not informative. The changes of the morphological blood contents do not take place in all the patients and are of a moderate character. The specific laboratory diagnostics of pseudotuberculosis is very important in its diagnosing. It is of primary importance in the mild and unexpressed forms of the disease, especially, occurring in the form of separate sporadic cases. The main material for the bacteriologic investigation is excrement and in lesser degree – washouts from the fauces, urine and the appendicular processes, which are ablated during the surgery. The pseudotuberculosis patients excrete bacteria with mucous from the fauces, excrement, urine. The duration of their excreting with mucous and urine is not long. The pseudotuberculosis pathogen is found in excrement during all the disease and in the period of relapses. In separate cases it can be excreted with excrement for about 75 days. The serologic investigations began to be done after the discovery of the Far East scarlatiniform fever. In the beginning the agglutination reaction with alive cultures as an antigen was used, later a reaction of indirect hemagglutination as well as the reaction of the bacterial lysis, method of fluorescent antibodies and others. In spite of the fact that the pseudotuberculosis diagnostics is improving every year, it does not satisfy the practical doctors so far. The percentage of the bacteriologic confirmation of the diagnosis remains low, and the reaction of indirect agglutination, which is used everywhere, is not enough sensitive and specific. The reaction of coagglutination and immune ferment analysis, which make it possible to discover both the antigen and antibodies to it during the first 3-5 days from the disease onset, is considered to be promising. Treatment. It is impossible to agree with the recommendations of some author about the possibility of treating the pseudotuberculosis patients at home. In spite of some positive results the possibility of sudden acute forms development and relapses obliges to treat the patients only in hospital and to follow thoroughly the regimen and an according nursing. The patients do not need a special diet. The nutrition is typical of the patients with an acute fever. The food should be easily assimilating and high-calorie, containing a sufficient amount of vitamins. A daily food allowance should contain 3200-3500 big calories. The patients with the predominant liver affection, are prescribed diet №5 containing a sufficient amount of carbohydrates and a limitation of fat, especially, refractory. The treatment depends on the clinical form, the period and gravity of disease. Among etiotropic agents there are used Levomycetin, Metacyclin, Tetracyclin, Streptomycin, Gentamicin, Ampicillin in moderate therapeutic doses during not less than 7 days and more. At severe current of disease, the septic form the best results can be gained if simultaneously use 23 antibiotics and one of them infuse into vein: course of treatment prolongs up to 10-14 days, and through 6-7 days it is replaced by preparations with the account of antibioticosensitivity of allocated yersinias. Cefazolin (Kefzol), Cefotaxim (Claforan) are effective. As alternative preparation may be Bactrim (Biseptol). Less effective are Nitrofuranes and Sulfanilamid preparations. With the purpose of desintoxication and rehydratation of the organism 5 % solution of a glucose, a seralbum, Reopolyglycin, Trisol, Quartasol are indicated. Widely there are used vitamins, antihistamine preparations and agents stimulating regenerative processes – Diprazin, Suprastin, Tavegil, Methyluracil (Methacil), Pentoxyl, Apylac, Natrii nucleinic, Thymalin etc. At gastroenterocolitic form Enterosorbents (activated microspherical coals, Sillard P, Enterosgel, Smecta), replaceable fermental therapy (Festal, Pancreatin, Pancurmen, Pancitrat), diet № 4 are indicated. Colibacterin, Bificol and other biological preparations are indicated in case of development of dysbacteriosis. At acute tonsillitis gargles should be indicated. Development of arthritis, myocarditis, Reiter syndrome is the indication to use Indomethacin, Ibufrofen, Diclofenac-Natrii (Ortophen) and other not steroid preparations. All the patients are prescribed vitamin therapy in the form of complex B, vitamins A, C, PP and others. The therapeutic tactics should be strictly individual in case of every patient who is to be constantly looked after. Only an individual approach and a complex of the treatment measures can bring invariable success and allow achieving good results. Prophylaxis. In spite of the achieved success in the pseudotuberculosis study, the problems of the specific prophylaxis have not been worked out so far. A complex of nonspecific measures directed at the source and transmission factors is widely used in the medicine to prevent the pseudotuberculosis spreading. Complications The major complication is the unnecessary performance of appendectomies. Other complications can include bacteraemia (entrance of organisms into the blood stream), in which case the possibility of a disseminating disease may occur. Long term complaints can include persistent joint problems, ankylosing spondylitis, rheumatoid arthritis, insulin-dependent diabetes, nephritis, long standing thyroid disease and neurological disease. Susceptible individuals Complications can occur in the very young, the debilitated, the very old and persons undergoing immunosuppressive therapy. Associated foods Pathogenic strains of Y. enterocolitica have been isolated from a wide range of food products including pigs and pork, goats, raw milk, cream, meat and meat products, oysters, vegetables, fish and poultry. They have also been isolated from environment sources such as lakes, streams, well water, and soil. Y. enterocolitica can be isolated and presumptively identified using standard cultural techniques in 36 to 48 hours. Confirmation that a strain is pathogenic would require further testing consisting of biochemical and serological tests. Outbreaks Y. enterocolitica can cause both sporadic infections and disease outbreaks. In most sporadic infections the cause of the infection is often difficult to investigate, although it is thought that pork products are the likely source. Case reporting is essential. Pseudotuberculosis is an acute infectious disease characterized by the polymorphism of the clinical manifestations, affection of the alimentary tract, locomotor system, liver and other organs, general intoxication, exanthema and frequently prolonged course with relapses. The pseudotuberculosis microbe is a polymorph bacillus, which does not form spores and often has an ovoid form. It is Gram-negative, well painted by all aniline dyes. The question of a capsule in the pseudotuberculosis bacteria is still under discussion. The pseudotuberculosis bacteria grows at a temperature of 4-30 °C are actively mobile, have flagellum, whose length is 3-5 times bigger than the length of the body of the bacterial cell. At a temperature higher than 30 °C the flagellum atrophy and the mobility of the bacteria ceases. The pseudotuberculosis microbe is a facultative anaerobe, it is quite undemanding to the nutrition, and that is why it grows well on the common dense nutrient media, it can grow on the media without peptone. This characteristic of the pathogen was used to distinguish the pseudotuberculosis bacteria from the plague pathogen. The bacteria contain H-antigen and 0-antigen, which determine their variability. The Hantigen is thermolabile and is destroyed at boiling, it is synthesized at a temperature of 2-30 °C best of all. Animals are a reservoir of the infection under the natural conditions. The pseudotuberculosis microbe was isolated from the organs and excrement of many kinds of the mammals, birds, reptiles, fish and arthropoda. Such a diverse and spontaneous infection of many kinds of animals by the pseudotuberculosis microbe gives a ground to think that none of them are a specific biological host of this pathogen and it testifies that in case its ubicvator spreading in nature all kinds of animals get involved in the general process of the microbe circulation and serve as a short-term or prolonged reservoir of the pathogen depending on the species susceptibility to it. Rodents are the most frequent reservoir of the pseudotuberculosis microbe. It is explained by the fact that on the one hand, rodents are distinguished by a high susceptibility and sensitivity to the pseudotuberculosis microbe and on the other hand, they are considerably widespread on the Earth and the speed of their replication is high. The infection of humans can occur at a direct contact with domestic and wild animals, birds while skinning them and processing the carcasses. A possible mechanism of the infection of humans is using the food and water contaminated by the discharge of rodents and birds carriers of the pseudotuberculosis microbe. Besides this there is a number of convincing investigations confirming that soil is a reservoir of the pseudotuberculosis pathogens. The authors think that the pseudotuberculosis microbe cannot exist in the soil for a long time without reproduction as it cannot form spores. It has saprophytic and parasitic characteristics and correspondingly has two natural biospheres of existing - the warm-blooded animals and environment. The pseudotuberculosis pathogen was isolated during the bacteriologic investigation of the soil from the fields where vegetables and edible roots, as well as wash-outs from them (beet-roots, carrots, cabbages, onions, potatoes). The epidemiological examination of many outbreaks of the disease made it possible to ascertain that among all the food staffs vegetables, edible roots, dry food, some dry products, which are eaten without any thermal processing, are of the most importance in the pathogen transmission. The importance of vegetables and edible roots as a factor of the pathogen transmission was proved by the isolation of the pseudotuberculosis microbe from them during the outbreaks, the microbes were identical by their serologic variant to the cultures isolated from the sick people who had eaten that food. Such outbreaks most often occur when dishes from fresh cabbage are used as food at the public feeding places. Besides vegetables and edible roots, the second important factor in the pseudotuberculosis pathogen transmission is dairy products. Such dairy products as cottage cheese, sour cream are the most important. It is necessary to note that the pasteurization of milk (at a temperature of 65 °C for 30 minutes) does not destroy the pathogen. Water can also be a factor of the pseudotuberculosis microbe transmission under the favorable conditions. The diversity of the pseudotuberculosis clinical manifestations, the involvement of different organs and systems in the pathologic process are the basis for the suggestions of numerous classifications of this disease. The least cumbersome classification, though it does not lack drawbacks, is the classification by N. U. Zalmower, which is based on the syndrome principle with the following clinical forms: 6. A scarlatiniform characterized by the general intoxication symptoms, fine-dot rash, fever; 7. An arthralgic form resulting in the joints affection, it takes a course of arthralgia, less often - arthritis; 8. An abdominal form with the primary affection of different parts of the alimentary tract, sometimes in the initial period; 9. A generalized form with the affection of different organs and systems when it is impossible to pick out any main syndrome; 10. An icteric form, in which the affection of the liver with a jaundice syndrome is the primary symptom. The clinical manifestations of pseudotuberculosis are characterized by a great polymorphism with the prevalence of the general intoxication, which makes an early diagnostics extremely difficult. As well as other acute diseases pseudotuberculosis has a certain cyclic recurrence. The development of the cycle's periods with a certain time limitation, which is accompanied by different morphologic, immunologic and clinical changes, results in a characteristic picture of the disease. There are following periods in pseudotuberculosis: an initial period, a high point, a period of acute courses and relapses, convalescence. In a mild case of the disease the affection of the alimentary tract is manifested by complaints of a poor appetite, nausea, less often - vomiting diarrhea. The stool is fluid or watery 3-5 times a day with admixture of mucous. The pain at the abdomen is observed in a half of the patients and is often revealed only at palpation. The tongue is furred, it becomes raspberry when it gets cleaned. The local manifestations of mesadenitis are usually accompanied by general symptoms. They are temperature increase, sometimes up to 39 °C, chills, which intensify with the development of pain in the abdomen, diarrhea - 2-3 stools a day without admixture of mucous or blood, nausea, and vomiting in almost half of the patients. Besides the patients complain of headaches, pains in the joints of the upper and lower extremities, body muscles, general asthenia, and sore throat. The skin of the face, neck, chest is often hyperemic in the patients with mesenteric lymphadenitis. In certain cases there is fine-spotted rash, which rise above the skin in the area of the chest, abdomen, groin folds, axillary region, forearms and thighs, the rash gets pale at pressing. The treatment depends on the clinical form, the period and gravity of disease. Among etiotropic agents there are used Levomycetin, Metacyclin, Tetracyclin, Streptomycin, Gentamicin, Ampicillin in moderate therapeutic doses during not less than 7 days and more. At severe current of disease, the septic form the best results can be gained if simultaneously use 23 antibiotics and one of them infuse into vein: course of treatment prolongs up to 10-14 days, and through 6-7 days it is replaced by preparations with the account of antibioticosensitivity of allocated yersinias. Cefazolin (Kefzol), Cefotaxim (Claforan) are effective. As alternative preparation may be Bactrim (Biseptol). Less effective are Nitrofuranes and Sulfanilamid preparations. With the purpose of desintoxication and rehydratation of the organism 5 % solution of a glucose, a seralbum, Reopolyglycin, Trisol, Quartasol are indicated. Widely there are used vitamins, antihistamine preparations and agents stimulating regenerative processes – Diprazin, Suprastin, Tavegil, Methyluracil (Methacil), Pentoxyl, Apylac, Natrii nucleinic, Thymalin etc. At gastroenterocolitic form Enterosorbents (activated microspherical coals, Sillard P, Enterosgel, Smecta), replaceable fermental therapy (Festal, Pancreatin, Pancurmen, Pancitrat), diet № 4 are indicated. Colibacterin, Bificol and other biological preparations are indicated in case of development of dysbacteriosis. At acute tonsillitis gargles should be indicated. Development of arthritis, myocarditis, Reiter syndrome is the indication to use Indomethacin, Ibufrofen, Diclofenac-Natrii (Ortophen) and other not steroid preparations. 5. Test questions. 1. What kind of an agent of yersiniosis? 2. What is yersiniosis pathogenesis? 3. How is yersiniosis spread (transmitted)? 4. What are the symptoms of yersiniosis? 5. Describe clinical forms of yersiniosis and pseudotuberculosis. 6. How is yersiniosis diagnosed? 7. What medications are used to treat yersiniosis? 8. What can be done to prevent yersiniosis? 9. Describe complications of yersiniosis and pseudotuberculosis. 10. Make a differential diagnostics between similar diseases (acute apendicitis, scarlet fever etc). 11. Prophylactic measures of diseases, caused by pathogenic yersinia. 12. Treatment schemes of intestinal yersiniosis. 6. References: A. Basic. 1. Nikitin E., Andreychyn M. Infectious Diseases. – Ternopil: Ukrmedknyga, 2004. – P. 67-77. 2. A practical approach to infections disease / Richard E Reese M.D. /Boston. Toronto 1986. 3. The Mark Manual of diagnosis and therapy. Robert Berkow. 1987. 4. Understanding infectious disease / P.D. Ellner, H.C. Neu. – 1992. B. Additional. 1. Gorbach Sherwood L. and oth. Infectious Diseases. – Philadelphia: Saunders Co., 1992. – 2048 pp., ill. 2. Hoerich Paul D. Infectious Diseases: a modern treatise of infectious processes /Ed. By Paul D. Hoeprich. – Third Edition. – Philadelphia: Harper&Row, Published, 1983. – 1464 pp., ill.