From Big Medical Encyclopedia

TULYaREMYYa — (tularaemia; Tulare the name of the area in California + Greek haima blood) — the acute infectious disease with a natural ochagovost which is characterized by fever and damage of lymph nodes.

In the Soviet Union classification of T is accepted., offered by G. P. Rudnev (1950). Distinguish the following a wedge, forms T.: bubonic; ulcer and bubonic; glazobubonny; anginous and bubonic; abdominal; pulmonary; generalized.

History. For the first time a disease-producing factor allocated in 1911 IAC-which and Chapin (G. W. McCoy, Ch. W. Chapin, 1912) from sick gophers in California (USA). They called it Bacterium tularense on the district Tu-lyare, in the territory to-rogo sick animals were for the first time revealed. Later, in 1921 when the disease was found also in people, Fransis (E. Francis) offered for it the name «tularemia». In various places of the USA this disease was known under the names «fever from a cervine fly», «rabbit disease» etc. In Japan T. in people it is for the first time found in 1924 and in detail studied by Okhara (N. of Ohara, 1925) who gave it the name «yato-bio» (a hare disease). Further T. it is revealed in the majority of the countries sowing. hemispheres.

In the USSR T. it was for the first time diagnosed in 1926 when S. V. Suvorov, A. A. Volferts and M. M. Voronkova allocated the activator T. from sick people at inspection of the center in the delta of Volga.

Geographical distribution. Natural centers of T. are in the basic in the temperate climatic zone sowing. hemispheres. To the south they in places meet in tropics (Mexico, Venezuela), and on S. — behind a polar circle (in the USSR to 73 °C. highway). In Europe T. it is found in France, Belgium, the Netherlands, Switzerland, Italy, Germany, GDR, Austria, Czechoslovakia, Hungary, Poland, Yugoslavia, Romania, Bulgaria, Greece, Norway, Sweden, Finland; in Asia — in Turkey, Iran, Mongolia, China and Japan; in America — in the USA, Canada, Mexico and Venezuela.

In the USSR the natural centers of T. are found from its western borders to east, including Chukotka, Kamchatka, Sakhalin and Primorsky Krai. Most having sat down. point of detection of T. — the Pyasina River on the Taimyr peninsula in Krasnoyarsk Krai (73 °C. highway), and the most southern — in Tajikistan (38 °C. highway) and Azerbaijani SSR (39 ° 0,5' NL). T. it is not registered only in the Kyrgyz SSR. Unsuccessful on T. territories are located on S.-Z., in the center, on Yu. and Yu.-V. The European part of the USSR, and also in a forest-steppe part of Western Siberia, in the foothills and nizkogor-yakh Altai, Kuznetsk Alatau and Tien Shan. In other areas the centers of T. are localized mainly in valleys of the rivers, and in Transcaucasia — in the foothills and mountainous areas.

During the premilitary period in the USSR incidence of people of T. considerably varied in various years. In the Great Patriotic War and in the first post-war years (1945 — 1949) as a result of increase in number of rodents (what was promoted by the bread which is not removed on fields or not threshed) incidence of T. considerably increased. In the next years, thanks to preventive actions, hl. obr. vaccination, incidence of people of T. considerably decreased and during the period from 1967 to 1976 averaged apprx. 125 cases a year. In the USA in the same years 161 cases of T are registered on average. in a year.

Etiology. The activator — Fran-cisella tularensis (McCoy et Chapin, 1912) Dorofe’ev. 1947. The type of F. tularensis is subdivided into 3 subspecies: holarctic subspecies of F. t. a holarcti-sa, widespread in Europe, Asia and North America, moderately pathogenic for domestic rabbits; the Central Asian subspecies of F. t. media-asiatica widespread on valleys of the rivers of Central Asia, moderately pathogenic for domestic rabbits; not Arctic, or American, F. t. nearctica widespread in North America, high-pathogenic for domestic rabbits. The holarctic subspecies are divided into biotypes (biovar): Japanese (

biovar japonica Rod.), extended on the Japanese islands; eritromitsinochuvstvitelny (biovar 1, or erysh widespread in Europe, Asia. To North America, sensitive to antibiotics of group of macroleads (see); eritromitsinoustoychivy (biovar 11, or eryR), the extended hl. obr. in Eastern Europe and Western Siberia. Not Arctic subspecies have high pathogenicity for the person — at a skin way of infection and in the absence of treatment a lethality apprx. 6%. Holarctic and Central Asian subspecies at this way of infection moderately pathogens — a lethality of 0,1% and below.

Diameter of the activator T. 0,3 — 0,5 microns; at cultivation on artificial mediums usually has the form of a small coccus, and in bodies of animals — a kokkobakte-riya; motionless, gram-negative, the dispute does not form, around cells the indistinct kapsulopodobny mucous cover having non-constant thickness comes to light; has a gladkokonturny cover, than differs from related gram-negative bacteria of the sorts Yersinia, Brucella, etc., having twisting («corrugated») contours. Bacteria of T. do not grow on a usual beef-extract agar or broth. They are cultivated on vitelline environments (the environment of IAC-which) or on agar with addition of cystine and other nutrients, especially blood. An optimum of growth at t ° 36 — 37 °, at plentiful crops of colony appear in a day, less often later. Bacteria of T. are facultative anaerobes (see), breed more often budding. The isolated colonies manage to be received at crops on Yemelyanova's circle (a blood fish and barmy agar with cystine and glucose) or on Fransis's circle (a blood beef-extract agar with glucose and cystine). In liquid mediums breed worse, than on dense. Aeration of the environment strengthens growth. Ability to ferment carbohydrates and alcohols at bacteria of T. it is limited, it is revealed during the use of special dense environments. Allocation among the activator T is unknown. any serotypes. Bacteria of T. contain shell (Vi) and somatic (0) antigenic complexes. Pathogenic and immuno-gene properties of bacteria of T. are connected with the shell antigenic complex: with its loss the microbe becomes avirulent and neimmuno-gene. Bacteria of T. find antigenic proximity to brucellas therefore are possible cross serol. reactions, but in low credits. Disease-producing properties are generally connected with toxicants like endotoxin. Activator T. patogenen for mammals of many videv and especially rodents and hares. Degree of pathogenicity is not identical to various animals. For hoofs, and also for ggtitsa and hematocryal the activator T. in most cases maloiatogenen. From a lab. animals to it white mice and Guinea pigs are highly sensitive. Domestic rabbits are highly sensitive only to not Arctic subspecies, white rats are insensitive to all subspecies.

At cultivation on artificial mediums there is attenuation of bacteria and their transformation from a virulent S-form into an avirulent and not immunogene V-form. Vaccinal strains of bacteria represent an intermediate form of variability, and designate them as SB option. They have residual virulence for sensitive to T. animals, napr, white mice.

Bacteria of T. can long remain (without reproduction) in the environment, especially at a low temperature. So, at t ° 1 ° strains of holarctic subspecies remain in water up to 9 months, not Arctic subspecies — up to 4 — 6 months, and in ice at t ° — 5 ° respectively 10V2 and

8 months without decrease in virulence. Bacteria of T. remain at f 20 — 25 ° in water of 1 — 2 month, at t ° 8 — 10 ° in milk and cream not less than 1 week, and in the frozen milk — up to

3 months, in the frozen carcasses of sheep to 7kh! 2 — 9 months, in grain and straw at a temperature below 0 ° up to 6 months, and at 20 — 30 ° — up to 20 days. In the frozen corpses died from T. rodents of a bacterium St. 3 months remain; on skins of the animals who fell from T., at t ° 8 — 12 ° more than 1 month, and at f 32 — 33 ° — only during 1 week. They are unstable to high temperatures — boiling immediately kills them, heating to 60 ° leads to death in 20 min.; under the influence of direct sunshine of a bacterium perish in 20 — 30 min., on disseminated to light their viability remains up to 3 days. Bacteria of T. are unstable to usual desinfectants, collapse ultrasound, perish under the influence of ultraviolet rays and ionizing radiation.

Epidemiology. Owners of the activator T. from among vertebrate animals hl under natural conditions are. obr. rodents and hares, and in the USA also wild rabbits. In the USSR natural infectiousness activator T. it is established at wild vertebral 82 types, including at rodents of 45 types, hares of 3 types, insectivorous 7 types, predatory

10 types, hoofed 2 types, birds

of 11 types, amphibians of 2 types and fishes

of 2 types. All these animals on degree of a susceptibility and infectious sensitivity to T. can be divided into 3 groups. Despite a wide range of possible carriers, maintenance of the natural centers of T. it is provided only with the few small mammals, highly sensitive to this infection, i.e. capable to ache at the minimum infecting dose of the activator (animal I groups). This is a water vole, a muskrat, an ordinary vole, a house mouse, a hare, a hamster, a shrew common shrew, etc. Their T. proceeds as an acute septic disease; animals perish 5 — 12 days later after infection. Bodies, blood and excrements of patients or the fallen little wild beasts contain a huge number of tulyaremiyny bacteria, as causes paramount value of these animal species as source of a contagium.

Nek-ry small mammals, napr, a gopher, a squirrel, gray and black rats, a field mouse, the Far East types of meadow mouses, a hedgehog, a kutor, are susceptible, but are insensitive to T. (animal II groups). They catch only sporadic, usually survive, and their role as source of a contagium is limited owing to moderate planting to microbes of bodies and fabrics. After a disease at animals of this group strong immunity to T is developed.

Are even less susceptible and less sensitive to T. predators — a fox, a raccoon dog, a polecat, and from domestic animals — a cat and a dog (animal III groups). Even at infection with massive doses of the activator the disease at them can proceed asymptomatically, with formation of immunity, and they do not manage to be infected with small doses of the activator at all. These animals have no practical value as a source of the activator T.

In the territory of the natural centers (see. Natural ochagovost) T. sheep, pigs, cattle, reindeers, etc. can catch, but the disease at domestic animals proceeds easily, with small planting of bodies and fabrics bacteria. These animals do not support natural circulation of an infection. Activator T. it is allocated also from aquatic organisms of 14 types (e.g., mollusks, Crustacea, a caddis fly, a water scorpion, bloodsuckers), but their value as source of the activator T. it is insignificant.

Transfer of the activator T. among mammals it is most often carried out by blood-sicking arthropods, especially ixodic mites (see), mosquitoes (see Mosquitoes blood-sicking), to a lesser extent fleas (see) and gamazoidny mites (see). In ixodic mites activator T. it is capable to breed intensively and it is long to remain owing to what in the majority of the natural centers of T. mites play a role of the main keepers (tanks) of a contagium; transovarial transfer of the activator T. at mites is absent. In the territory of the USSR natural infectiousness the activator T. it is established at backboneless animal 75 types, including at ixodic mites of 21 look, gamazovy mites of 12 types, fleas

of 19 types, mosquitoes of 12 types, gadflies of 6 types, midges of 2 types and nek-ry other. At ixodic mites of nek-ry types (from the sorts Dermacentor, Ixodes, Rhipicephalus, Haemaphysalis and Hyalomma) the spontaneous carriage and ability to transfer of activators T are established. at a krovoso-saniye. Blood-sicking flies are only mechanical carriers of the activator T., nevertheless their role in distribution of T. can be essential, especially mosquitoes of the sorts Aedes, Culex and Anopheles and gadflies of the sorts Chrysops and Haematopota. Along with a transmissible way of transfer of the activator T., to-ry among wildings is the basic, plays an additional role alimentary, especially during the eating of corpses of the small animals who died from T., infection through skin and mucous membranes with the water contaminated by excrements of sick animals.

Widespread epizooty of T. are noted in populations of small mammals only with a high number of little wild beasts, and the higher them number, the more intensively can be an epizooty. Intensity of an epizooty is defined also by the fact that the activator T. circulates in the nature only in a virulent form, and a little considerable fluctuations of its virulence during different seasons of year are unknown and at different levels of an epizooty.

Various landscapes — biotopes (see) and biocenoses (see the Biocenosis) are not equivalent under the terms, T. Optimalnymi providing existence of the natural centers are the forest-steppe, the steppe and partly the broad-leaved woods, and also floodplains and deltas of the rivers, coasts of lakes and swamps, a zone of the tundra. In the territory of the USSR on set of biocenotic and epizootological features allocate 7 landscape types of the natural centers of T.: tundra — the main owner of the activator T. lemmings are; inundated and marsh — a water vole, a muskrat, sometimes a hare, an ordinary vole, etc.; forest — red and red voles, forest and yellow gorlaya mice, sometimes a hare; lugopolevy — an ordinary vole; steppe — a house mouse, an ordinary vole; predgorno it (is mountain) - ruchyevy — a water vole; tygai (valleys of the rivers in nek-ry districts of Central Asia) — a hare bark. In the centers of different types seasonality of an epizooty of T. and their scales are various that is connected with features of ecology of mass species of small mammals, highly sensitive to T., and also ways of transfer of a contagium. Typing of the centers allows to put differentially epizootological and epidemiological forecasts and to purposefully hold preventive events. In natural biocenoses the natural centers of T. find considerable firmness and can exist vaguely long time. Resistant inundated and marsh centers of T. are known for more than 50 years in the delta of Volga, across Don and its inflows, on average a current of the Urals River, in a number of places of Western Siberia, in Yakutia; almost as much years there are lugopolevy centers in Moscow, Ryazan, Tula and nek-ry other areas. Economic activity of the person if it significantly changes natural biocenoses, can exert a great influence on the natural centers of T. — weakening or suppressing them.

Rodents, in particular an ordinary vole, a water rat, a house mouse, partly a muskrat and a hamster, and also a hare are the main source of a contagium for the person. Cases when the cattle during the cutting of hulks on meat-processing plants was a source of a contagium are described. The sick person is not infectious for people around.

Infection of the person T. occurs in various ways: contact

ny (through skin, including the unimpaired, or mucous membrane of an eye) — at contact with patients or the fallen little wild beasts, at removal of skins from sick animals, cutting of their hulks, at contact with the objects of the environment contaminated by allocations of rodents; transmissible (through skin) — during attack of blood-sicking arthropods (mosquitoes, gadflies, midges, mokrets, perhaps ixodic mites); alimentary — at the use of water or foodstuff contaminated by allocations of rodents; aspiration — at inhalation with air of dust or the droplets of moisture contaminated by allocations of rodents.

Depending on a combination of various conditions of infection and ways of transfer of a contagium distinguish the following types of the epidemic centers of T.: transmissible, trade, water, agricultural, house (household), food, hunting and production. During the Great Patriotic War in a zone of military operations still the trench type of the center of T was observed. Diseases in the center of T. the transmissible type is resulted by transfers of activators blood-sicking arthropods and are characteristic for warm' the period of year. In the center of trade type of a disease are noted among the persons occupied with catching of water rats, muskrats and other small mammals and removal from them of skins, infection occurs in the contact way; season zabolevany it is various, but the spring and fall are more often. Water type of the center of T. arises at the use for drink or washing of the water taken from the uncomfortable well or an open reservoir after hit in them of rodents, sick T.; infection through water of wells occurs in the winter more often, through water of open reservoirs — is preferential in summertime. Epidemic center of T. agricultural type can arise during the thrashing of bread, a partition of straw, hay, grain, the vegetables contaminated by allocations of the rodents sick with T. Zarazheniye more often occurs in the vozdushnopylevy way, diseases arise preferential late fall, in the winter and in the spring. Centers of T. house (household) and food types are most often connected with penetration into housing of the person, into grocery stores, warehouses of the house mice and ordinary voles contaminating the allocations household goods, and also foodstuff and water; diseases in these cases are observed late fall and in the winter. Epidemic center of T. hunting type arises during the hunting for hares; infection occurs in the contact way (through skin) at removal of a skin, cutting of carcasses and an alimentary way at consumption of their meat which is thermally insufficiently processed; diseases are observed in the fall, in the winter and in the spring. Epidemic center of T. production type arises during the processing at the industrial enterprises of page - x. the raw materials (grain, sugar beet etc.) contaminated by allocations of little wild beasts, sick T., or a contact way at a face on meat-processing plants of the cattle infected with a tularemia. In the USSR in pre-war years flashes of T were the most widespread. trade, transmissible and agricultural types; during the Great Patriotic War and in the first post-war years — flashes of T. agricultural and household types (in army — trench type); since the 50th prevailing steel of flash of transmissible type. Such shift is considerably connected with timely harvesting, and also with holding preventive actions (hl. obr. vaccination of the population).

People get sick with T. almost exclusively in rural areas. In big cities of a condition for infection of T. practically are absent, except for the cases connected with delivery of the contaminated products or the infected animals. Diseases on suburbs of the cities located near the inundated and marsh centers of T are noted. (it is filled in the infected blood-sicking flies). Separate cases or epidemic flashes of this or that intensity can depend on the number of rodents and hares (sources of contagiums), on number of not immune persons and the nature of their work etc.

Within a year of a disease of people of T. are possible in any month, but their number depends on type of the natural center of T. Vospriimchivost to an infection at the person of nearly 100%. Generally the adult efficient population catches. The diseased by the nature of occupations can treat the most various groups of the population, but in some cases infection carries is expressed professional character.

Pathogeny. Activator T. gets into a human body through skin, mucous membranes of eyes, respiratory tracts, went. - kish. path. In a pathogeny of T. allocate several phases: implementation and primary adaptation of the activator, its lymphogenous distribution, priming regional and focal and general reactions of an organism, hematogenous metastasises generalization, secondary centers, reactive allergic changes, the return metamorphoses and recovery. The leading value in a pathogeny of T. the phase of lymphogenous distribution of the activator has. In the place of its implementation primary affect (see Affect primary) with regional primary lymphadenitis (bubo) quite often develops. The periadenitis is expressed moderately. The activator and its toxins get into blood that leads to bacteremia and generalization of process, innidiation and development of secondary tulyaremiyny buboes.

Pathological anatomy. Character morfol. manifestations at T. is defined by the place of penetration of the activator into an organism. At infection through skin and mucous membranes the bubonic form T develops., the cut is the main sign regional (in the place of implementation of the activator) lymphadenitis —

Fig. 1. Finger of the patient with a tularemia: an ulcer in the place of implementation of the activator.

bubo. On skin originally there is a papule (see) which is quickly suppurating and nekrotiziruyu-shchayasya with formation of ulcer defect (fig. 1). In day of an ulcer inflammatory infiltrate from segmentoyaderny leukocytes, lymphocytes, epithelial cells with possible formation of tulyaremiyny granulomas is found. Healing of ulcers happens due to growth of granulyatsionny fabric and the subsequent scarring.

All groups of regional lymph nodes are exposed to inflammatory changes (polyadenitis), to-rye, increasing to 3 — 4 cm in the diameter, form a tumorous conglomerate. In early terms of development of a disease in limf, the nodes containing a tulyare-miyny stick hypostasis of a stroma, a plethora of vessels of trabeculas and a staza in them are noted, widespread proliferation of mononuclear phagocytes, infiltration of fabric granular leucocytes, in to-rykh happens incomplete phagocytosis of the activator. Is later in regional limf, nodes visible focal necroses in the form of serovatozhelty focuses with a softening and fusion of fabric appear. At microscopic examination during this period in the thickness limf, nodes and under their capsule there are separate granulomas (or groups of granulomas) with the central necrosis surrounded with epithelial cells, shaft of lymphoid elements with impurity of granular leucocytes. Occasionally colossal cells like Langkhans meet. Formation of granulomas, as a rule, begins with emergence of the center of a necrosis, but their development as focal proliferation of mononuclear phagocytes without primary alteration is possible.

For differential diagnosis of a tulyaremiyny granuloma, edge on structure it is similar on tubercular (see Tuberculosis), existence in its structure of granular leucocytes and much the expressed disintegration and wrinkling of kernels at disintegration of cells of a granuloma matters. In cases of a long course of an infection and in the period of reconvalescence there are an encapsulation and substitution of granulomas connecting fabric. Inflammatory changes in the cellulose surrounding struck limf, nodes at T. it is not observed.

Ulcer and necrotic changes on site of implementation of a contagium and pronounced regional lymphadenitis make primary tulyaremiyny complex (an ulcer and bubonic form). In internals at the same time the dystrophic changes which are combined with hemodynamic disturbances are found; the acute hyperplasia of a spleen is noted.

At a glazobubonny form T. typical ulcer and necrotic changes with inflammatory hypostasis of fabrics arise in a conjunctiva of an eye, and buboes develop in parotid and perednesheyny limf, nodes. At this form development of meningitis is possible (see) — the firm meninx is strained, hypostasis and limfoleykotsitarny infiltration of a soft meninx, brain swelling are noted. In neurons of bark and subcrustal kernels there are dystrophic changes, reaction of a glia is poorly expressed.

For an anginous and bubonic form T. initial defeat of palatine tonsils (perhaps unilateral) as focal is characteristic or widespread it is purulent-nekroti-cheskoy quinsies with existence under a zone of a necrosis of an acute hyperplasia of the adenoid tissue expressed to leukocytic infiltration, staz and thrombosis of vessels, by formation of typical granulomas. Nodes are surprised submaxillary and verkhnesheyny limf.

At an abdominal form primary changes are localized in a stomach or in intestines (is more often in distal department of an ileal gut). There is an acute inflammatory process in a mucous membrane, a submucosa with possible transition to a serous cover, infection of a peritoneum and development of serofibrinous or purulent peritonitis (see). In a wall of a stomach or intestines massive inflammatory infiltration, staza, thrombosis of vessels with the subsequent development of focal necroses and formation of ulcers are observed, in day to-rykh it is possible to find granulomas. Nodes with formation of typical buboes are surprised perigastric and mezenterialny limf. Characteristic of an abdominal form T. considerable dystrophic changes in a liver with possible formation of the granulomas which are exposed to a necrosis are. But is more often and in bigger number the granulomas merging in conglomerates form in a spleen, edges macroscopically looks bulked up and plethoric. Formation of granulomas is possible as well in periportal limf, nodes, a pancreas.

Primary affect at a pulmonary form is shown or development of a catarral laryngotracheobronchitis, to-ry quickly passes in gnoynonekrotichesky, or the center of a seroznofibrinozny inflammation of pulmonary fabric with existence in composition of exudate of the breaking-up leukocytes and pnev-motsit. In that and other case typical defeat intrathoracic (bronkhopulmonalny, bifurcation, paratracheal, mediastinal) limf, nodes is observed. Inflammatory changes in lungs quickly progress with formation of the centers of a necrosis, various size of heart attacks (fig. 2) and quite often are complicated by serofibrinous pleurisy (see) and a pericardis (see).

At a generalized form T. formation of buboes is not observed, there are no also typical damages of skin and mucous membranes. However on skin hemorrhagic rashes are possible. The changes found in internals are characteristic of a septicaemia (see Sepsis). Macroscopically in a pulp of the spleen increased in sizes and 1sheyushchey weight to 300 — 400 g the centers of a necrosis (fig. 3) in places merging to small fields of grayish-yellow color are visible. Microscopically are found a diffusion hyperplasia of cells mono-nuklearov, plazmokletochny infiltration, nekrotiziruyushchiyesya granulomas. Liver a little uve-

Fig. 2. Macrodrug of a lung at a tularemia (a frontal section): the centers of a necrosis of white color are visible.

Fig. 3. Macrodrug of a spleen at a tularemia (on a section): the multiple roundish centers of a necrosis are visible (it is shown in white color).

mask in sizes, its parenchyma on a section dim. Krupnokapelny obesity of hepatocytes, swelling of star-shaped retikuloendoteliotsit, perikapillyarny hypostasis, melkoochagovy hemorrhages are microscopically noted. On the course of portal paths the forming and nekrotizirovanny granulomas come to light. Characteristic of a generalized form T. widespread defeats of small vessels in the form of destructive vasculites and focal hemorrhages in lungs, a liver, kidneys are, went. - kish. path, closed glands. In parenchymatous bodies and hemadens dystrophic and necrobiotic changes come to light. At a long current of a generalized form T. in internals on site of granulematozny reaction and focal necroses zones of a sclerosis form. This form T. can be complicated by the serofibrinous pneumonia (see) which is quite often gaining hemorrhagic character.

For gistol. and bacterial. researches during the opening of the dead take pieces of fabric limf, nodes, spleens, a liver, lungs, digestive tract, make crops from bodies on special environments, infect with suspension from bodies white mice or Guinea pigs.

Immunity. As a result of the postponed T. the immunity (see) protecting from reinfection (see), as a rule, it forms remains many years, and in some cases and for life. Antibodies are found in such people in blood (see). There is also considerable sensitization (allergization) of an organism to antigens of the activator. A high-intense acquired immunity to T. it is reached by introduction of a live vaccine (see below the section Prevention). Duration of postvaccinal immunity at the majority of vaccinated 5 years, up to 15 years more rare. Inoculative immunity as well as postinfectious, protects from a disease at any natural ways of infection. At vaccinated allergic reorganization of an organism, in blood — accumulation of antibodies, but in smaller quantity, than at had is found. Immunol. reactions, especially skin allergy test (see. Skin tests), use for assessment of development and fading of immunity.

Clinical picture. At all variety a wedge, forms T. a number of its manifestations is characteristic of all forms of infectious process. The incubation interval lasts of several hours to 3 weeks on average

3 — 7 days. The disease begins sharply, suddenly, without prodrome. Chilling is typical. Temperature quickly increases to 38 — 40 °. Fever is more often than remittiruyushchy type lasting from 5 days up to

2 months and more, 2 — 3 weeks are more often. The sharp headache, weakness, dizziness, pains in muscles of legs, backs, waists, anorexia, sometimes vomiting, stupefaction and nonsense are characteristic. The sleep is interrupted. Perspiration is expressed. The person is hyperemic and pastozno, vessels of scleras are injected, conjunctivas are hyperemic. On a mucous membrane of an oral cavity dot hemorrhages. Language is laid over. There can be enanthesis with the subsequent peeling and pigmentation. The liver increases and probed from the 2nd day of a disease, a spleen — with 6 — the 9th day.

For a bubonic form T., except the listed signs, buboes (lymphadenitis) are characteristic. Their localization is various and depends on ways of infection. At trade flashes of T. axillary buboes prevail, at alimentary flashes — cervical and submaxillary. Buboes happen single and multiple, unilateral and bilateral. They are moderately painful, with accurate contours, the size of their from 1 to 5 cm. Their outcomes are various: a rassasyvaniye, suppuration with

release of dense slivkoobrazny pus both further scarring and sclerotization. Buboes resolve slowly.

Primary inflammatory changes can arise on site implementations of the activator; more often it is observed at a transmissible way of infection and is characteristic of an ulcer and bubonic form T. On skin the spot, then a papule, a vesicle, a pustule and an ulcer is formed, edges cicatrizes slowly. At generalization of process emergence of rash is possible, is more often than allergic genesis. After its fading on this place the peeling of skin is noted.

At a glazobubonny form, along with regional lymphadenitis, sharp conjunctivitis is observed, it is frequent with papules and sores, follicles of yellow color,

2 in size — 4 millimeters. It is difficult for patient to open eyes because of puffiness a century.

For an anginous and bubonic form T. at an alimentary way of infection local changes in almonds in the form of their hyperplasia with the advent of plaques of grayish-white color are typical, is more often on one party. Patients complain of a pharyngalgia, difficulty during the swallowing. Palatal handles and a uvula are edematous and hyperemic, plaques have an appearance of islands in the beginning, and then merge and remind a picture of diphtheria of a pharynx (see Diphtheria). In the subsequent necrotic process with formation of the deep, slowly beginning to live ruts ulcers develops. Lymphadenitis (tonsillar, submaxillary and cervical) develops along with quinsy.

At an abdominal form into the forefront defeat limf, nodes of intestines acts. Severe pains in a stomach are typical, to-rye sometimes are mistakenly regarded as a syndrome of an acute abdomen (see). High temperature with small remissions. The liver and a spleen are increased. Patients can have a nausea, vomiting, a meteorism, a delay of a chair, and sometimes a diarrhea.

Pulmonary form T. proceeds by pneumonic or bronkhitiche-sky option. At pneumonic option the disease begins sharply with a fever and high temperature. Fever more often alternating with plentiful potakhm. Patients complain of a stethalgia, cough, to-ry can be dry less often with mucopurulent, and sometimes a bloody phlegm. Physics of l the ny phenomena scanty also appear late. It is connected with the fact that inflammatory process begins in a root of a lung, in and around bronchial tubes, extending to the periphery. At rentgenol. a research for the 7th day of a disease find increase radical, paratracheal and mediastinal limf, nodes. Against the background of the strengthened pulmonary drawing inflammatory changes of pulmonary fabric of the focal, segmented, lobar or disseminated character come to light. The disease proceeds hard and is long, up to 2 months and more, with bent to a recurrence and development of abscesses, bronchiectasias, pleurisy, etc. Nek-rotization in affected areas of a lung can lead to education polost (tulyaremiyny cavities) of various size.

The Bronkhitichesky option differs in easier current. The trachea, large and average bronchial tubes are surprised. Temperature is subfebril-ny, the condition of patients significantly is not broken. Retrosternal pains, dry cough, scattered dry rattles in lungs are typical. Process in 8 — 12 days comes to an end with recovery.

The generalized form is characterized by development of the general symptoms of a disease. Toxicosis is more expressed, sometimes with a loss of consciousness and nonsense, an adynamia, a severe headache, muscular pains. Fever of wavy type lasts to 3 weeks. On skin of a rash, quite often symmetric on the lower and upper extremities or on a face, a neck, a breast. Rash of rose-red color, then becomes bagrovomedny and in the subsequent gets a cyanotic shade. Rash of 8 — 12 days keeps. Then there is a peeling (scaly, small, macrolaminar) reminding a peeling at scarlet fever. The increased liver and spleen are palpated. Patients recover slowly, palindromias are possible.

Complications are observed rather seldom. It is secondary pneumonia, meningitis, an encephalomeningitis, vegetative neurosises. After a pulmonary form T. the residual phenomena of pneumonia can be found radiological in

3 — 4 months and later.

The diagnosis is made on the basis epidemiol. the anamnesis (e.g., contact with animals — possible sources of activators T.), wedge, pictures of a disease, results of a skin allergy test and data lab. researches.

The skin allergy test is carried out by intradermal or cutaneous (scarifying) administration of tulyaremiyny antigen — tularin. The drug is administered of 0,1 ml strictly vnutrikozhno in the palmar surface of the left forearm, on border of upper and its average third. At positive reaction on site of an injection in 12 — 24 hours there is a redness and small puffiness disappearing in the next days. Sometimes local allergic reaction is followed by formation of an iustulka or a short-term limfangiit with insignificant increase regional limf, nodes and even small short-term temperature increase. Nakozhno tularin is entered, doing two parallel notches (scarifications) through the drop of drug applied on skin of an outer surface of the left shoulder (in its average third). Positive reaction in the form of puffiness and redness of skin around notches usually appears in 48 — 72 hours and then gradually dies away. Allergic reaction becomes positive with 3 — the 5th day of a disease and can keep many years, and sometimes for life.

The l and about r and t about r N and I d and and of N of wasps of t and to and is based on results serol. and bacterial. researches, and also blood test. From serol. researches apply agglutination tests (see) and gem.agglyutination (see), to-rye are strictly specific and in a combination are quite reliable to consider only for T. Sleduyet's diagnosis possible cross serol. reaction with brucellas in low cultivations of serum. The agglutination test is put in the volume way according to the practical standard. She is positive in a caption 1: 100 and above with

2 — also reaches the 3rd week from an onset of the illness on 4 — the 6th week of a caption 1: 400 — 1: 800, 1 is more rare: 1600 and above then the caption begins to decrease.

For reaction of passive (indirect) hemagglutination (RPGA) the tulyaremiyny antigenic erythrocyte diagnosticum is usually used. Hemagglutinins are found at the end of the 1st or on the 2nd week from the beginning of a disease, and in a month the gemagglyutinatsionny caption can reach 1: 10 000 — 1: 40 000 and above then gradually decreases. For differentiation of the antibodies appearing in blood after vaccination from the antibodies appearing at T., trace increase of agglyutinatsionny and ge-magglyutinatsionny credits of blood serum; at T. antiserum capacities нарастают^ at vaccination they remain at the previous level, and sometimes even decrease. For diagnosis of T. apply also reaction of binding complement (see), reaction immunoflyuorestsepts and and

(see) — an indirect method and about the peon about - phagocytal reaction (see Opsonins).

In the first 10 — 12 days of a disease it is possible to mark out culture of bacteria of T. from the patient for what contents of a skin ulcer or a bubo, and also blood of the patient enter subcutaneously or viutribryushinno to a Guinea pig or a white mouse. In the presence of a tulyaremiyny infection the animal perishes and from his bodies mark out culture of the activator. Crops on mediums and a bacterioscopy of the material taken from the patient usually happen unsuccessful. For a lab. animals lethal dose of the activator T. at hypodermic introduction makes only several bacteria. After infection death of animals occurs in

5 — 10 days, seldom later. During the opening find a sharp hyperemia of vessels of hypodermic cellulose, increase and a nekrotization regional limf, nodes, increase and consolidation of a spleen and liver, at pigs find multiple necrotic small knots in these bodies etc. Release of pure growth on mediums works well from a spleen, a liver, blood, regional limf, a node etc. For crops the curtailed vitelline environment of IAC-which is most practical.

At a blood analysis of the patient T. the moderate leukopenia, toxic granularity of neutrophils and lymphocytes, increase in number of monocytes by 3 — 4 times are defined. In cases of heavy disease eosinophils disappear, the leukocytosis, the accelerated ROE is noted. In urine a moderate albuminuria, a cylindruria and a hamaturia.

At the beginning of a disease of T. it is necessary to differentiate with plague (see), a typhoid (see), paratyphus (see), a sapropyra (see the Sapropyra epidemic), pneumonia, in the subsequent — with a malignant anthrax (see), diphtheria (see), Vincent's quinsy (see Quinsy), purulent or tubercular lymphadenites (see), a brucellosis (see), etc. It is especially important to distinguish T. from a bubonic form of plague in the territory of the natural centers of these infections. At plague toxicosis, a condition of the patient heavy is more expressed, morbidity in the place of formation of a bubo is more expressed, there are no accurate contours of a bubo.

Treatment. Effective antibacterial drugs are streptomycin, tetracycline and levomycetinum, erythromycin, Oleandomycinum. Also aminoglycosides (Neomycinum, Kanamycinum) are shown. In cases of a long current carry out the combined treatment by antibiotics and a vaccine (see Vaccinotherapy). The inactivated vaccine is applied, edges it is entered in various ways (nakozhno, subcutaneously, intramusculary or intravenously) in doses from 1 to 15 million microbic bodies on a bucketed injection from 3 to 6 days; course of treatment of 6 — 10 injections.

In the presence of skin ulcers and buboes before development of suppuration compresses, salve dressings, thermal procedures are shown locally. With the advent of fluctuation make a wide section of buboes, empty them from pus and necrotic masses. Carry out pathogenetic therapy with use of disintoxication means — enter Haemodesum, Polyglucinum, isotonic solution of sodium chloride with glucose, etc. (see Dezintopsikatsionnaya therapy). According to indications administer the drugs improving action of the heart (Cordiaminum, camphor, caffeine, strychnine). In cases of allergic manifestations carry out ginosensibiliziruyushchy therapy by antihistaminic drugs (Pipolphenum, Suprastinum, Dimedrol, Prednisolonum in small doses).

Forecast favorable. Lethal outcomes are observed seldom, generally at pulmonary and abdominal forms T.

Prevention. In the natural centers of T. carry out fight against rodents and ixodic ticks. Apply the grain or vegetable baits poisoned with phosphide of zinc or other toxic chemical to destruction of a water vole. Grain baits with the same poisons use for extermination of small mouse-like rodents. On fields the basis of fight against rodents is made by agrotechnical actions, in particular timely harvesting, autumn plowing of fields, destruction of weeds etc. Sistekhmati-chesky trade and hunting for hares, a water rat, hamsters and other carriers of the activator T. rarefies population of animals and prevents emergence among them a widespread epizooty of T.

For the purpose of prevention of T. exercise control for a dignity. a condition of sources of water supply, shops, warehouses and dwellings, do not allow penetration of rodents into them; carry out vaccination by a tulyare-miyny vaccine of the people who are put risk of infection etc. In planning of preventive actions in the center of T. the annual forecasts of an epizootological situation made a dignity are of great importance. - epid. service on the basis of the censuring of small mammals — the main sources of the activator T. and data their micro-biol. researches. Much attention is paid a dignity. - a gleam, work among the population on prevention of a tularemia.

At emergence in the center of T. diseases among people vaccinate not vaccinated population, will organize catching and delivery in laboratory of rodents for detection of an epizooty among them; in premises, in warehouses, catering establishments, etc. carry out deratization (see). At transmissible flash of T. establish a temporary ban on visit of places where presumably there was infection of people, carry out destruction of blood-sicking flies — carriers of a contagium by processing of vegetation by insecticides (see Dezinsitsiruyushchy means), apply individual means of protection from attack of insects — repellents

(see), protective clothes (see Clothes special), Pavlovsky's grids (see. Protecting screens) etc. At infection of people on trade, in the course of preparation of skins of rodents (a water rat, a muskrat, etc.) strengthen supervision of observance a dignity. rules (use of rubber gloves, points, the gauze bandage protecting a neck, a mouth and a nose at removal of skins; washing of hands with soap before food, etc.). The prepared skins disinfect, standing them in the dry and warm room within 2 months, or process in a disinfection chamber chloropicrin. At water flash of T. immediately stop use of water from the infected water source, wells chlorinate. At agricultural flash of T., napr, during winter thrashing, it is necessary to observe measures of personal hygiene — to work in the gauze bandage protecting from dust of companies and a nose in mittens, before food to wash hands with soap. Disinfecting of grain and straw in cold season is reached by keeping them within 6 months; during the drying on an elevator grain is maintained at t ° 70 ° within 1 hour. At revenues to production of raw materials from unsuccessful on T. areas wash it previously (e.g., beet at the sugar plants), adding to water for washing lime chloride from such calculation that the content of active chlorine in the used water made not less than 1 mg on 1 l.

Specific prevention (vaccination) is an easy and highly effective way of the prevention of a disease of T. The live tulyare-miyny vaccine was received for the first time

by N. A. Gaysky and B. Ya. Elbert that was large achievement of the Soviet scientists. The live dry cutaneous vaccine is released in ampoules lyophilized (dried up in vacuum), suitable for long-term storage (see Immunization). Before the use the vaccine is parted with the solvent attached to it. In enzootichny on T. regions of an inoculation carry out as a planned action. The inoculation is done on a shoulder of the left hand, scarifying skin (by notches an ospoprivivatelny feather) and rubbing a vaccine. Apply also needleless injektor that considerably simplifies an inoculation. Local reaction in the form of a hyperemia and infiltration of skin develops in the first days after an inoculation and disappears in 3 — 4 weeks. By this time at vaccinated immunity develops. The general reactions of an organism to an inoculation in the form of fervescence and regional lymphadenitis are observed seldom and quickly take place. The revaccination is carried out in 5 years.

Vaccination against T is allowed simultaneous, or associated. and brucellosis, T. and plagues, and also T. and nek-ry other infections. The condition of immunity at at -

twisted is determined by allergic reaction for what use cutaneous tulyarinovy test (see above the section Diagnosis). Systematic timely vaccination of the population in the centers of T. in combination with other preventive actions gave notable effect, incidence sharply decreased, only sporadic cases or diseases of small groups

of people are observed.

Features of epidemiology and prevention of a tularemia in troops

are connected with specific conditions of their placement, catering services, water supply, educational fight - howl activity of staff.

The infection in troops can arise at dislocation of bodies in the territory where cases of T are celebrated. among animals.

From all sources of a contagium the greatest value in distribution of T. in troops mouse-like rodents have (a field and house mouse, an ordinary vole, etc.). Danger of infection of staff increases with development of an epizooty (see) among the bred mouse-like rodents who with the onset of cold weather usually in a large number get into rooms and field constructions in search of a forage and heat. Therefore T., at a cut a source of a contagium are mouse-like rodents, constitutes the greatest danger to staff of troops at their dislocation in the open field, on sites with an unharvested harvest, especially with grain and cereal. Population sick rodents and pollution by their allocations territories, dwellings, food warehouses and water sources create real danger of infection of staff that visually is confirmed by materials of the Great Patriotic War of 1941 — 1945. Rodents got into blindages, dugouts and other field constructions. Big density of people in military constructions, abundance in them of the straw used for warming of overlappings and as a laying, availability to rodents in these conditions of stocks of food of staff, and it is frequent and waters promoted infection of staff of troops. E.g., in 1943 in separate connections of the Southern front of 80% from all sick T. the persons staying in blindages and entrenchments made. Group diseases of T. the water type was resulted by the uses for drink and domestic needs of water from the water sources contaminated by allocations and corpses of the fallen rodents.

In system of actions for prevention of T. in troops the leading place is taken by measures for destruction of rodents as main tank of a contagium. For early detection of an epizooty among rodents, their case, and also cases of diseases among local population the military-medical service will organize and carries out a dignity. - epid. investigation (see. Medical investigation) and sanitary and epidemiologic observation (see) in the studied territory. Density of settling by rodents of the territory, existence of a case among them is specified, the lab is made selective. a research of rodents on T. At data acquisition of investigation about identification of districts of enzooty measures for the prevention of a drift of an infection in troops are taken: protection from rodents of water sources, foodstuff, food warehouses, dining rooms, bases and other places of storage of products. Tents, blindages, and also all places of storage violevy conditions of products and fodder are dug round flutes 40 cm wide and 50 — 60 cm of Rodents in depth, got to these flutes, destroyed. Surround with ice slopes warehouses, blindages and other field constructions in the winter. Carry out also systematic deratization (see) in places of possible accumulation of rodents. Prohibit to use not decontaminated water, especially from open water sources. For protection against blood-sicking arthropods — carriers of the activator of a tularemia widely apply various repellents and other means of protection from attack of insects and mites. Indications for carrying out preventive inoculations are: cases of diseases among local population, establishment of the fact of an epizooty with allocation of the activator T., obtaining information on enzooty of T. in the territory of the forthcoming dislocation or the forthcoming fighting of troops, cases of diseases in troops of the opponent in a strip of fighting. The staff is imparted once live tulya-remiyny vaccine. In case of emergence regarding patients, suspicious on T., they are immediately isolated. After specification of the diagnosis of patients hospitalize in inf. hospital (inf. department of garrison hospital), carry out to parts epidemiological obsaestivation (see). Bibliography: Bobrova A. S. To pathological anatomy of pi of histology of a tularemia of the person, Arkh. patol., t. 11, century 5, page 61, 1949; Burgasov P. N. Vaccinal prevention of a tularemia, Voyen. - medical zhurn., No. 7, page 50, 1950; D. A. Heads, etc. Chumopodobny diseases (tularemia?) on the Urals River in Orenburg and Ural lips. in the spring of 1928, Vestn. mikr., epid. and parazitol., t. 7, century 3, page 301, 1928; Yemelyanova O. S. Microbiology of a tularemia, M., 1951; Mno

the gotomny guide to pathological anatomy, under the editorship of A. I. Strukov, t. 9, page 324, M., 1964; Hammers B.

To pathological anatomy of a pulmonary form of a tularemia at the person, the Clip, medical, t. 21, No. 6, page 35, 1943; II and to about l and e Sunday to and y G. P., Frolov V. I. and Morozov V. I. The current state of prevention of a tularemia to the USSR and further tasks, Zhurn. mikr., epid. and immun., No. 10, page 104, 1978; About l with at f-e in N. G. Taksonomiya, microbiology and laboratory diagnosis of the activator of a tularemia, M., 1975; About l with at f e in N. G., and Dunayev T. N. Natural ochagovost, epidemiology and prevention of a tularemia, M., 1970; Olsufyev N. G. and Meshcheryakova I. C. Further studying of intraspecific taxonomy of the activator of a tularemia, Zhurn. mikr., epid. and immun., No. 10, page 16, 1981; Experience of the Soviet medicine in the Great Patriotic War of 1941 — 1945, t. 32, page 10, etc., M., 1955; Anti-epidemic

protection of troops, under the editorship of A. I. Burnazyan, page 18, 28, M., 1944; Rudnev G. P * Antropozoonoza, M., 1970; The Management

on a zoonosis, under the editorship of V. I. Pokrovsky, page 225, JI., 1983; Tulyaremiyny infek

tion, iod of an edition of JI. M. Hatenevera, M., 1943; Tularemia, under the editorship of N. G. Olsufyev and G. P. Rudnev, M., 1960; Baskervil-1 e A., H a m b 1 e t o n P. D o w-s e t t A. B. The pathology of untreated and antibiotic-treated experimental tularaemia in monkeys, Brit. J. exp. Path., v. 59, p. 615,1978; Francis E. Tularaemia Francis 1921, The occurrence of tularemia in nature as a disease of man, Publ., Hlth Rep. (Wash.), v. 36, p. 1731, 1921; McCoy G. W. a. Chapin C. W, Further observations on the plague-like disease of rodents with a preliminary note on the causative agent, Bacterium tularense, J. infect. Dis., v. 10, p. 61, 1912.

Yu. F. Shcherbak; V. I. Agafonov (soldier.),

A.S. Zinovyev (stalemate. An.), N. G. Olsufyev (epid., etiol., lab. diagnosis, profit.).