TULAREMIA

Tularemia is an acute infectious disease of a septicemic character that is manifested by intoxication, fever and the affection of the lymph nodes; it belongs to the zoonosis group with natural foci.

Historic reference

In 1910 the american bacteriologist named Mc Coy who studied plague in the shot of ground squirrels in California discovered in them anatomic pathologic changes similar to plague, but the plague pathogen was not isolated. In 1911 having used a special dense medium cultivated by himself Mc Coy together with Chapin isolated the pathogen of this disease from ground squirrels in the clean medium. After the name of the district Tulare, the word "tule" means "large cane" in aztec, the pathogen was named "Bacterium tularense1' in 1912. During the work Chapin had a feverish disease for 28 days, it was not accompanied by an enlargement of the lymph nodes, after the recovery he discovered complement bound antigens and agglutinins to B. tularense in his own blood serum.

In 1912 Vail observed a patient with conjunctivitis and an enlargement of the regional lymph nodes. Wherry and Lamb isolated the B. tularense culture from an eye of the pathologic material taken from this patient for the first time in the medical practice. Some time later they reported on the isolation of the same microbe from two hares that had been found dead. In 1919 and 1920 having examined seven patients (one of them died on the 28th day of his disease) Francis isolated the B. tularense from the blood and pus taken from them. In 1921 this gave him a ground to suggest the name "tularemia" for the disease, it became part of the international nomenclature.

Etiology

The tularemia bacteria have very small dimensions, they have an ability to pass the bacterial filter of Zeits. In case of cultivation on the small coccus, and in the animals organs it can be more often found in the form of coccobacteria. In the cultures on the nutrient medium tularemia bacteria are polymorphic, it is especially expressed in the American variety. The microbe is immobile, it does not make spores, it has a small capsule. It is characteristic of the bacteria to produce mucous in the cultures, it can be easily detected during the preparation of smears on the glass. The tularemia bacteria can be tinctured with all kinds of stains, which are usually used in the laboratory practice. The tularemia bacteria are preserved in water as well as in other objects of the environment comparatively long under the condition of a low temperature and increased humidity. The microbe is not very sensitive to low

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temperatures, it survives "in the frost of 30 °Ñ; it can be preserved in the frozen meat up to 93 days. The tularemia bacteria are not stable to the temperature increase. The higher the temperature is the quicker the microbes die. Thus,the pathogen remains in the animal skins at a temperature of 8-12 °Ñ for more than a month, and at a temperature of 32-33 °Ñ - only during a week. The microbe dies at a temperature of 60 °Ñ in 20 minutes, and boiling kills them momentarily. The tularemia bacteria die under the influence of the sun rays in 20-30 minutes, their vital capacity remains in the diffused light up to 3 days. The tularemia bacteria are not stable to common disinfectants and are destroyed by an ultrasound.

Epidemiology

Tularemia is epidemically defined as zoonosis which has natural foci mainly supported by wild rodents and blood sucking insects. The adherence of the people who live in the rural areas to this disease is one of the main peculiarities of the tularemia epidemiology, it is connected with the natural foci of this infection and the absence of the conditions for spreading among the home rodents in the big cities. The cases of the people infection in the cities are infrequent and connected with bringing infected food or animals from the rural areas. More often the city-dwellers get infected when they go to the country where there are natural foci.

The main sources of the tularemia infection for humans are rodents, especially, common field voles, water-rats, house mice, sometimes muskrats and hamsters as well as hares. The infection of humans occurs either as a result of the contact with sick or dead rodents and hares or the bites of the infected blood-sucking arthropoda or due to water, food, straw and other substrata contaminated by the discharge of the animals sick with tularemia. A typical feather of the tularemia microbe is its ability to penetrate the organism of the humans and animals through small scratches on the skin, unaffected mucous membranes of the eye, throat, pharynx, the respiratory tract, and in case of a considerable dose the infection may penetrate through the unaffected skin. One of the typical epidemiological peculiarities of tularemia is almost 100 % susceptibility of the humans to it irrespective of age and also the fact that the sick people are not contagious for the healthy ones.

The mentioned above peculiarities of the tularemia infection, e. i. a great adaptation of the pathogen in nature, its possible ability to be transmitted by the animals or different objects of the environment (water, food etc) and a high susceptibility of the human to this infection resulted in the tularemia outbreaks, which involved great numbers of people under certain conditions. The tularemia outbreaks often reminded the epidemics of grippe or malaria in their character, and earlier they were diagnosed like this. Many materials on the tularemia epidemiology confirm this.

The concrete ways (mechanisms) of the tularemia infection of the humans are the following: contagious, alimentary, aspirational, transmissional. The infection

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often occurs by means of a contact with sick animals, a contact with the objects contaminated by them (hay, straw, corn, etc), swimming in the reservoirs. The diseases belonging to this group are mainly typical of hunters-producers and in some cases of the members of their families who helped them to skin the shot animals. Besides this, there have been described some sporadic cases and even separate outbreaks occurring as a result of hunting hares. Not only did the hunters fell ill, but also the housewives who were infected while cutting carcasses.

The aspirational way of infection often occurred during the belated agricultural work while inhaling the dust rising into the air from the infected straw, corn and other substrates during their machinery or manual processing, cleaning, transportation, etc. In some cases the infection was accompanied by a contagious way.

The alimentary way of infection occurs while using the water and food containing the tularemia pathogen. The water way of the microbe transmission is due to the fact that it is considerably stable in water, especially, at a low temperature. The reservoir infection is due to the sick with the infection water rats that live on their banks. The infection of the humans usually occurs in the summer, the morbidity increase is connected with hay mowing and other field work during which the population widely uses the water from the open reservoirs for drinking and washing.

The disease of the alimentary type is often connected with house mice penetrating the human's house or food stores, warehouses and other facilities and contaminating the food with their discharge. Bread, milk, cookies, crackers can be among such kinds of food.

The transmission outbreaks depend on the infection transmission by mosquitoes and gadflies, less often - by ixodes ticks. The insects are infected while sucking the blood of the sick animals but there are indications that the gadflies can be infected by the carcasses of the water rats as well as the water infected with tularemia. The infection of the humans at the transmission outbreaks occurs exclusively in the warm season and, as a rule, not far from the reservoirs, on the flood lands, during hay mowing and haymaking.

Pathogenesis

The tularemia pathogen can be brought into the human organism by different ways: through the skin, mucous membrane of the eye, respiratory tract, the gastroenteric tract and by a combined way. The localization of the infection gate undoubtedly influence the tularemia clinical manifestations. But it would be a mistake to consider this fact to be the only one and a decisive one. The ways of the human infection combined with immunobiologic reactions of the microorganism and the pathologic peculiarities of the pathogen determine the development of one or another clinical form of tularemia, one or another clinical course of the disease.

The tularemia pathogen is not known to have ability for an independent movement. That is why it is clear that from the entrance gate where its primary

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adaptation may take place, the following movement of the infect can be only in the direction of the liquid substrate. As a rule,it actually takes place with the lymph flow and very seldom with the blood flow. The tularemia pathogen often gets into blood some time later, this causes bacteremia and may result in the generalized process. Hence in the pathogenesis of the tularemia infection in the humans the phase of the lymphatic mole precedes the pathogen penetration into blood. It is by the phases of the lymphatic mole and corresponding reactions of the microorganism that the formation and presence of the tularemia local clinical manifestations, that are so important for the diagnostics, are determined. Among such clinically expressed symptoms tularemia lymphadenitis, which is more often called a bubo, is sure to take the first place. Pathogenically a sum of the reactive local changes in response to the influence of the tularemia bacteria is the basis for the development of such buboes. They remain in the lymph node during the lymph filtration and due to phagocytosis. The tularemia bacilli brought with the lymph flow reproduce in the lymph node and partly dying influence the node and the surrounding tissues by the secreted endotoxins, it results in adenitis and later periadenitis, e. i. the tularemia bubo development. Pathogenically the buboes can be divided into primary and secondary. The primary ones are often connected with the location of the entrance gate and are divided into the buboes of the first, second degree, etc. In contrast to the primary tularemia buboes the secondary ones do not have a territorial connection with the localization of the infection gate. Pathogenically they develop as a result of the hematogenic metastases. According to the terms of the development they are delayed and less expressed clinically. The secondary buboes do not usually produce any puriform softening. It is clear that it is not only the reproduction of the tularemia microbes that takes place in the foci of their concentration, but also their death with the excretion of endotoxins,which stipulate the symptoms of the general intoxication. Thus every clinical form of tularemia has the symptoms of the general intoxication though the intensity and character of the local changes are different and retain their diagnostic value. Hence, the general intoxication of the patient's organism with specific endotoxins is the basis of the general manifestations of the disease. The tularemia pathogen penetrates the organism through the mucous membranes of the eyes, respiratory tract, gastroenteric tract and the localization of the entrance gate influences the development one or another clinical form of tularemia. However theoretically the ways of the tularemia pathogen movement remain the same - the lymphatic and then the hematogenic one. The bacteremia breaks of the tularemia bacilli followed by metastases in the lungs, liver, spleen, marrow is the basis of the specific pathomorphologic changes and the development of the multiple foci, which is the basis for the possible development of the tularemia process as a septic one. In some patients such metastases stipulate the presence of such specific complications of the secondary character as. for example, secondary tularemia pneumonia, tularemia meningitis, etc. In the most

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severe cases with the increasing symptoms of intoxication the lethal outcomes are possible (severe secondary tularemia sepsis).

The mentioned subsequent phases of the tularemia pathogenesis cannot be considered to be obligatory in each separate case of the disease. On the contrary, the infectious process can be stopped at the first stages, it is of the practical importance for solving the problems of the rational treatment. Bacteremia is not a constant phenomenon and in some cases the localization of the tularemia infection can be limited by a lymph node, because the lymphatic barrier cannot be always broken.

Anatomic pathology

The anatomic pathologic changes in human tularemia have not been studied very well partly because of the low mortality. The formation of the tularemia granulomas in the form of whitish or whitish-yellow nodes is very typical. The granulomas are characterized by a zonal structure: there are epithelioid cells in the center, then ~ lymphoid plasmatic and neutrophilic erythrocytes then fibroblasts and often eosinophils. The central necrotic disintegration is crumb-like, acidophilic with a great number of chromatin clods in the fresher granulomas. The granulomas gradually enrich themselves with fibroblasts, argyrophil and collagenic fibrae that result in the granulomas scarring. There are no capillaries in the granulomas and they desolate soon. There are focal hemorrhages on the periphery of the granulomas. The granulomas in tularemia are similar to those in tuberculosis.

On the spot of the primary affect on the skin develops a papule, which quickly suppurates and ulcerates. The bottom of the ulcer,which is often brown, is a dry necrosis. The healing occurs by replacing the defect with cicatrizing connective tissue. The confluent areas of necrosis and granulomas occur in the regional lymph nodes. These nodes usually suppurate and open through the skin. Periadenitis often develops. Hyperplasia of the lymphoid tissue and reticuloendothelium is first observed in the nodes through a microscope, then the granulomas and the areas of necrosis, which are followed by suppuration. In the secondary (not regional) lymph nodes there are less expressed necrotic and granulomatous changes, which are not accompanied by suppuration. In the generalized form the spleen increases 2-3 times, in the chronic forms -insignificantly. The pulp is cherry-red and can be scraped off.

There is multiple small foci of necrosis in the tissue of the organ. The hystologic changes are identical to those in the secondary buboes.

In abdominal tularemia a granulation inflammatory process with focal necrosis and possible ulceration of the mucous membrane develops in the stomach and intestines. There are granules and necrosis foci in the perigastrial and mesenteric lymph nodes. There is stagnant plethora, dull swelling and adiposity of parenchyma in the liver. The necrotic and granulematous foci are not so widely spread as in the spleen. There is parenchymatous and fatty degeneration of the

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convoluted tubules epithelium in the kidneys. There are frequent lymphoid infiltrates in stroma. The granulomas and necrotic changes are not constant.

Catarrhal laryngotracheobronchitis often develops in the primary pulmonic forms. The inflammatory changes of the lungs are macrofocal and can be similar to croupous pneumonia but tularemia pneumonia develops as serous or serous-fibrinous with a conversion to necrotic one. The abscess formation is usually observed. Pneumonia is usually complicated by serous-fibrinous or purulent pleuritis, later by similar pericarditis. There are changes typical of tularemia (necrosis, granulomas, suppuration) in the peribronchial and mediastinal lymph nodes.

In the anginous-glandular form one tonsil is affected. The process can only be limited by plethora and hyperplasia. However, more often focal necrosis develops in the beginning, then it is followed by extended necrosis and ulceration with purulent melting or diphtheritic patches. The transformation of the submaxillary, superior cervical lymph nodes into buboes occurs simultaneously.

The eye disease can be in the form of the primary eye-glandular form and in the form of the secondary affections. At first there develop papules mainly in the lower eyelid mucous membrane, they suppurate and ulcerate with the discharge of purulent exudate. The eyelids are sharply swollen. The cornea is not often affected. The buboes typical of tularemia are localized in the parotid lymph nodes but the superior cervical lymph nodes also be affected.

Clinical manifestations

The incubation period in tularemia often lasts from 3 to 7 days. The cases of the incubation period in humans within the limits of the first 24 hours are practically very rare exceptions, and the cases of the incubation period exceeding two weeks are very doubtful.

There are three periods in the clinical course of the disease: 1) primary, 2) high point of the disease, 3) period of convalescence. It is extremely important to pay special attention to the first period for the sake of both clinical and epidemiological diagnostics.

The onset is always acute without prodromal phenomena, which are accompanied by chills or expressed shivering and abrupt temperature increase up to 39 °Ñ and higher. Most patients name not only the day but also the hour of the disease onset without any difficulties. The patients complain of a headache, malaise, various muscle aches, which are often in the sural and waist areas. Besides this there is dizziness and appetite worsening, which develops into complete anorexia. The sleeping disorders as well as increased sweating,especially at night,are quite typical. In more severe cases there is vomiting, nose bleeding and later there can develop the conscious darkening and delirium. The headaches are the most persistent and prolonged. The hyperemia of the face and sometimes of the fauces is objectively observed. On the part of the upper respiratory tract there are usually no catarrhal symptoms, rhinitis and sneezing are very rare. Conjunctivitis and watery eyes are the most clearly expressed in the primary eye affection.

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As the primary period of tularemia does not have any pathognomonic symptoms, the epidemiological anamnesis, which should be distinctly reliable and exhaustive, is of great importance. The total duration of the primary period is 2-3 days. Later the clinical symptoms of the disease develop in different ways depending on the development of tularemia in one or another clinical form.

The forms of tularemia which are distinguished according to the clinic-pathogenic and epidemiological data are as follows. The bubonic, ulcer-bubonic, eye-bubonic forms develop when the infection penetrates through the skin and eye mucous membrane. In the anginous-bubonic and abdominal forms the infection penetrates through the mouth. In the pulmonic (bronchial and pneumonic variants) the infection penetrates through the respiratory tract. Besides there is a generalized or primary septic form (it is observed in any way of infection, especially, in weakened people).

The bubonic form of tularemia is characterized by the development of the inflammatory process in the regional lymphatic node (Fig. 14). A bubo (lymphadenitis) is an obligatory and fundamental symptom of the disease here. There are primary and secondary buboes. The primary buboes develop in a lymphogenous way and are connected with the area of the pathogen penetration. The secondary buboes develop as a result of the hematogenic spreading and are not connected with the localization of the entrance gate. The size of the tularemia buboes varies from the size of a small nut to a chicken egg and larger. It is usually not a separate regional node that gets involved in the process, but several nodes in a particular area. The buboes are dense, slightly painful, there is no expressed periadenitis. There can be several main variants of the tularemia bubo outcome: complete dissolving, suppuration, ulceration with the following scarring and sclerotization. If there is no suppuration, the reverse development or dissolving is slow and undulating with changing of improvement and an acute condition. The process lasts up to 2 and more months. The softening of the bubo begins in 2-3 weeks from the disease onset, but sometimes even later. The suppurating softening develops approximately in half of the cases. At first there is no distinct reaction on the part of the surrounding cellular and skin but soon there develops swelling and skin reddening gradually increasing in intensity and extensity and, finally, there is a breakage with buboes draining. The puss of the tularemia buboes is thick, white, without any smell, it looks like cream or sour cream. There are often primary inflammatory changes at the area of the infection entrance gate in case of a cutaneous way of infection. These changes of the primary character are the basis for diagnosing the cutaneous-bubonic or ulcer-bubonic forms. A cutaneous ulcer develops during the first days of the patient's feverish condition. The inflammatory process often affects all the skin depth but sometimes is limited by the superficial layers in the form of erosion. At first a spot develops, it often remains unnoticed, then it quickly turns into a papule. A vesicle soon develops on the top of the papule, it first has transparent serous and then serous-

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purulent contents. The Vesicle bursts, out and turns into an ulcer. The form of the ulcer is round or oval with a size of a dime. The redness and swelling on the ulcer circumference are insignificant. The redness quickly loses its brightness, and the ulcer becomes pink and later it has a cyanotic-reddish tint. The ulcer discharge is serous-purulent, purulent and very seldom it is of a sanies character. The tenderness at touching is insignificant, that is why the patients cannot often name the time of its development. The ulcer course is dull with a slow healing during 15-45 days.

Many authors describe the allergic eruption in the form of roseola, petechia, papules, erytematous-papuleous eruption, etc. In case of tularemia, more often in the second period of the disease, it has a diverse localization, sometimes symmetrical. There is usually peeling, sometimes scaly and less often macrolaminar after the disappearance of such eruption.

The bubonic form of tularemia with the primary affection on the part of the sight organ - eye-bubonic form develops if the pathogen penetrates the eye mucous membrane. In this case there is expressed conjunctivitis, sometimes the presence of papules and ulcers besides regional (parotid, front cervical, submaxillary) lymphadenitis on the part of an eye. The eyelids are swollen and dense, the patients complain of their tenderness at moving, the amount of the mucopurulent discharge is moderate. On the eyelid mucous membrane there are inflammatory small foci in the form of the cone, they are yellowish and have a whitish top with the size of a pin's head. There is a considerable number of separate groups of yellow dots on the lower eyelid on the background of a big number of scattered formations, a smaller number of them is observed on the upper eyelid.

There are inflammatory small foci with a bunch of the superficial widened vessels on the sclera conjunctivas, the foci are almost always located near the limbus. No changes on the part of the cornea or other refracting media of the eye have been found. In a number of cases the eye-bubonic form is accompanied by dacryocystitis. The lachrymal sack phlegmons have been described. Almost all the patients have an affection of the parotid and submaxillary lymph nodes, in some patients their increase is observed on the 3-10th day of the disease. The clinical course of the eye tularemia affection is within the limits of 20 days to 3 months. The eye affection may be secondary, in this case the eye changes as well as the eyelid skin ones take a course similar to that of metastatic granulomatosis and is observed in different clinical forms of tularemia.

The anginous-bubonic form of tularemia is first accompanied by the development of angina with characteristic local changes on the part of the tonsils: hyperemia, hyperplasia, grayish-whitish patch, which is often on one side. There are local pains and swallowing difficulties. The degree and quality of the local affections in the anginous-bubonic form as well as the dynamics of the process are diverse. According to the clinical peculiarities there are three types of tularemia angina: catarrhal patch-diphtheritic and infiltrative-ulcerative.

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There is hyperemia of the fauces, pain at swallowing, high temperature, enlargement of the cervical lymph nodes - the formation of buboes in the catarrhal variant of tularemia angina. The fauces hyperemia remains up to 8-10 days, the buboes - up to 1 month and longer. A white patch firmly sticking to the mucous membrane develops on the tonsils and airfoils in the second form. There is hyperemia with a cyanotic tint in the circumference of the grayish-greenish covers. The covers usually remain for a long time and begin to tear away only two weeks later. A massive, quite dense infiltrate, which has no inclination to abscess forming and which goes up till the hard palate, develops from the very beginning in case of infiltrative-ulcer variety. Its reverse development lasts 2-3 weeks and in some cases ulcers develop in the area of the infiltrate.

Expressed catarrhal pharyngitis, cyanosis of the mucous membrane with a crimson tint that looks like venous congestion are observed in all cases. The congestion phenomena in the fauces remain for a long time, even after the end of the ulcerative-necrotic processes. The insignificant subjective feelings during a severe ulcerative-necrotic destructive process in the fauces are typical of tularemia angina. In some cases the enlargement and tenderness of the cervical lymph nodes coincide with the changes in the throat, sometimes buboes are formed only by the moment of the angina disappearance. A bubo remains for 2-8 months, less often shorter. Tularemia angina is characterized by a strict localization in most cases the changes are limited by one tonsil irrespective of the severity of the changes.

The abdominal form of tularemia has not been studied well so far, so it is supposed to occur more often than it is diagnosed. Severe pains in the stomach are typical of the abdominal form. The process is characterized by a deep localization of the affected, mainly mesenteric lymph nodes, in contrary to other variants of the bubonic form with the peripheral buboes localization. This variant cannot be united with the generalized form as in this case the affection of the lymph nodes of a certain (abdominal) area prevails. Epidemiological^ it is most often observed at the outbreaks, which are characterized by the massive doses of infection that penetrate through the throat (water outbreaks).

The disease is manifested by a general feverish condition with a high temperature, chills, in some patients - sickness and vomiting, less often - delirium. The spasmlike pains in the abdomen of different duration and intensity, meteorism, and sometimes constipation are also typical. In some patients the abdomen pains can be so intense that resemble the picture Q( the "acute abdomen" and can result in the surgery. The clinical phenomena in the abdominal variant of the bubonic form depend on the inflammatory changes (hyperemia, swelling, etc.) in the mesenteric nodes that causes the irritation of the peritoneum followed by acute pains, sickness, vomiting, etc. The cases of the tularemia abdominal form, which are accompanied by suppuration of the mesenteric lymph nodes and peritonitis, have been described. There are cases, which where diagnosed posthumous.

The difficulties of the clinical diagnosing of the tularemia abdominal form are connected with the peculiarities of the clinical manifestations, and perhaps a relatively bad knowledge of the doctors.

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In case of the distinct data of the anginous-bubonic form, in which the infection occurs through the mouth, the possibility of the affection of the intestines and the mesenteric lymph nodes, especially, in the people who suffer from deferred acidity or achylia, can't be excluded. That is why it is necessary to thoroughly investigate the abdomen even ii there are certain symptoms of the anginous-bubonic form.

The pulmonary (thoracal) form of tularemia occurs in case of the aspiration way of infection and is characterized by the development of the primary inflammatory process in the lungs. Epidemiologically this pneumonia is connected with certain conditions of infection. Thus, during threshing when the stacks are infected with the discharge of the mouse-like rodents, the infection is airborne and several people fall ill. The airborne infection in the laboratories is less frequent,with separate cases.

In case of the primary pulmonary form the inflammatory process develops in the lungs from the very beginning. There can be two main variants in this case: bronchial, when the process occupies only the large respiratory tracts, and bronchial pneumonic when the deeper parts are affected - bronchioles, alveoles. The clinical picture is diverse and depends on the localization of the intensity process and the combination of the inflammatory changes. Only tracheitis, bronchitis and their combinations are possible, this confirms their aspirational way of infection. Hence in some cases the pulmonary tissue does not get involved in the pathological process. But the process is localized in the chest and spreads on the mediastinal lymph nodes, that is why these forms of tularemia are named thoracal.

The bronchial pneumonic variant, or tularemia pneumonia, is characterized by a dull and exhausting course, it lasts up to a month, less often 2 months and longer. Anatomically these are small foci, which have a tendency to confluence and cause lobar pneumonia.

Besides the dry rale (as in the first variant) it is possible to auscultatory hear the moist and often crepitant fine bubbling rale. In some patients they remain for a long time and are heard even in the period of convalescence. During the X-ray examination besides the darkening of the pulmonary tissue it is possible to notice the inflammatory phenomena in the lymph nodes of the mediastinum and the lungs roots, they are limited only by one area confirming in this way the local manifestations of the disease.

Pneumonia has a severe course but it does not have a cyclic course, it has a tendency to relapses and the formation of different specific complications: bronchiectasia, abscesses, the lungs gangrene, dry and moist pleuritis. Necrosis in the affected parts of the lung can result in the cavity formation - tularemia caverns. Sometimes the changes in the lung tissue have a dull prolonged character with clinically expressed intoxication. The patient with tularemia pneumonia is not contagious for the surrounding people.

It is necessary to distinguish this primary tularemia form from the secondary one, which can join any other clinical form as a complication. It develops in a

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metastatic way later and deteriorates the course of the disease. The terms of the end of such pneumonia are quite various - from 2 weeks to 2 months and longer.

In case of the generalized form of tularemia the fundamental sign is the development of the general symptoms of the disease without previous local symptoms, which are absent in the future, as a rule. It is the only form of tularemia, which does not have a primary and a regional reaction. Clinically the generalized form is distinguished by more severe manifestations of intoxication, sometimes even fainting and delirium.

The headaches are intense and persistent, adynamia and muscle aches are very expressed. The fever lasts about 3 and more weeks, and the temperature curve is often oscillatory. A rash similar to exudative polymorph erythema often develops during the second half of the disease. The rash on the upper and lower extremities is usually symmetric, pink-red, later has a crimson-coppery tint and at the end it has a cyanotic shimmer in the form of the tularemia "gloves", "gaiters", "socks". The rash remains for 8-12 days, there is peeling and prolonged pigmentation after the rash disappears.

In the generalized form of tularemia the capacity to work is recovered especially slow, the relapses are not excluded.

Diagnosis

There are several methods of the tularemia pathogen isolation in the laboratory. These are direct bacterioscopia, bacteriology with the microbes identification and a biological method. However the immunologic methods are more often used to diagnose the disease in people than the bacteriological ones. It depends on the fact that the tularemia pathogen belongs to the first group of microorganisms, that is why its isolation and identification can be done only in the specially equipped laboratories.of the departments for the especially dangerous infections.

The agglutination reaction is the most popular method of the serologic diagnostics. The reaction is considered positive when serum is diluted 1:100 and higher and becomes positive from the second week of the disease.

The compliment binding reaction (CBR), hemagglutination reaction, precipitation reaction and others can also be used.

An intracutaneous allergic reaction on the injection of allergen -tularin, 1 mL of which contains 100 million microbic bodies killed by heating at a temperature of 70 °Ñ during an hour, is highly specific. The test is quite specific (it is necessary to take into account the possibility of inoculative or anamnestic reaction) and usually allows to diagnose the disease from the fifth day after its onset.

Differential diagnosis

The tularemia diagnosis in case of the sporadic morbidity is difficult because of the polymorphism of the clinical symptoms and various localization of the process. The diagnostic mistakes are often made at the initial period. First of all

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it is necessary to take into account the epidemiological data for the clinical diagnostics: patient's occupation, rural living conditions, a rapid reproduction and intensive death of rodents. Plague should be put in the first place because tularemia is still known under the name "plague-like disease".

Commonplace lymphadenitis of the strepto- and staphylococci etiology is characterized by an intense tenderness,early suppuration,frequent lymphangitis and local edemas. There are often inflammatory processes at the area of the infection entrance gate.

Tuberculosis lymphadenitis is distinguished by a gradual development of the disease, subfebrile temperature, density and absence of tenderness. They are often located in the form of a chain, characterized by a comparatively rare change of the skin over it and are considerably smaller than in tularemia.

The anginous-bubo form of tularemia can imitate different forms of angina, mainly Symanovsky-Vincent angina and diphtheria of the fauces.

The distinguishing of the eye-bubonic form of tularemia from adenoviral conjunctivitis and eye diphtheria is based on the serous-allergic reactions and bacteriologic investigation for diphtheria.

The differential diagnosis of tularemia from pneumonia of a different etiology is the most difficult.

In the generalized and the abdominal form there is sometimes a typhus-like condition of the patients that gives one a ground to suppose typhoid fever and spotted fever.

Treatment

The patients are treated in the infectious hospital. Antibiotics are the main in complex therapy. Streptomycin is the most effective: 0.5 gm 2 times per day in a muscle. At pulmonary and generalized forms daily dose of streptomycin enlarges till 2 gm. Course of treatment lasts all period of fever and the next 5 days with normal body temperature. Streptomycini sulfas has bactericidal effect, after its introduction Yarish-Hercscheimer reaction may be observed. Therefore in serious cases antibiotic therapy is combined with prednisolon or its analogues.

Tetracyclin, doxycyclin, levomycetin, kanamycin, gentamicin, rendering bacteriostatic action are less effective. At pulmonary and generalized forms daily dose of the specified antibiotics is enlarged in 1.5 times. Preparations of tetracyclin are expedient for combining with aminoglycosides.

At lingering course and relapses of tularemia combined treatment is provided with antibiotics and inactivated vaccine which infuse parenteraly in a single dose 1.5 - 15 million microbic bodies with interval 5-6 days. Course of treatment consists of 6 - 12 infusions.

As desintoxication therapy it is expedient to use reopoliglycin, standard saline solutions with glucose. Vitamin preparations are widely used as desensitizing agents. At pyesis of buboes they should be opened and a bandage with unguenti of streptomicin should be used.

Tularemia 331

At anginous-bubonic form of tularemia the inhalation of chlorophilyptus are recomended. At procces of eyes 20-30 % a solution of sulfacyl-natrii is indicated. The treatment is complex, the antibacterial therapy plays the main role in it. Streptomycin, tetracycline, Chloromycetin are the most effective medicines. A day's dose of streptomycin 1-2 gm, tetracycline - 1.5-2 gm, Chloromycetin - 2 gm. At the highest point of the disease detoxication therapy is prescribed (intravenous injection of the salt solutions, haemodesum, polyglucinum, 5 % solution of glucose, ascorbic acid). The detoxication therapy is done by taking enterodesum and other preparations of this group. Calcium gluconate, diphenylhydramine, pi polphen, diazolinum are used to decrease the allergic manifestations.

In case of relapses and acute forms it is necessary to prescribe antibiotics courses, but it is necessary to remember about dysbacteriosis.

Compresses, ointment bandages and wanning treatment are used at the area of buboes at the stage of dissolving. If the buboes suppurate, they are widely opened and treated as a purulent wound together with treating the main disease. In case of the timely and valuable treatment the prognosis is usually favorable. The lethality is up to 0.5 % and occurs in the complicated pulmonary and abdominal forms of tularemia. The ability to work is recovered slowly.

Prophylaxis

The prophylaxis includes the control over the natural foci, the interruption of the mechanism of the disease transmission, as well as the vaccination of the population in the epidemic foci. The planning and the fulfillment of this work in the tularemia foci are done by the sanitary-antiepidemic service with the participation of the medical workers of the medical institutions who perform the rounds in the houses and the vaccination of the population.

Control questions:

1. Tularemia etiology.

2. Epidemiology of tularemia.

3. Pathogenesis and pathomorphology of tularemia.

4. Classification of clinical forms of tularemia.

5. Clinical manifestations of different tularemia forms.

6. Laboratory diagnosis of tularemia.

7. Differential diagnosis of tularemia.

8. Treatment of patients with tularemia.

9. Preventive measures against tularemia.

332 Infectious diseases

Date: 2014-12-21; view: 1148