Epidemiology, causes and pathogenesis of tularemia

Causes of tularemia

The cause of tularemia is Francisella tularensis, genus Francisella. Brucellaceae family. Gram-negative polymorphic (mostly coccoid) non-motile rod that does not form spores or capsules. Facultative anaerobe. The pathogen is demanding of cultivation conditions, grows on nutrient media with the addition of cysteine or egg yolk, defibrinated rabbit blood, tissue extracts (liver, spleen, brain) and other growth stimulants. Of laboratory animals, white mice and guinea pigs have increased susceptibility to tularemia.

The microorganism contains somatic (O) and membrane (Vi) antigens, which are associated with the virulence and immunogenic properties of the pathogen. The main pathogenicity factor is endotoxin.

F. tularensis is resistant in the environment, especially at low temperatures and high humidity (survives at -300 °C, survives in ice for up to 10 months, in frozen meat - up to 3 months). The pathogen is less resistant to drying (in the skins of rodents killed by tularemia it survives for up to 1.5 months, at a temperature of 30 °C - up to 1 week); remains viable in river water at a temperature of 10 °C for up to 9 months, in soil - up to 2.5 months, in milk - up to 8 days, on grain and straw at -5 °C - up to 192 days, at a temperature of 20-30 °C - up to 3 weeks. At the same time, F. tularensis is very sensitive to insolation, ultraviolet radiation, ionizing radiation, high temperatures and disinfectants (under the influence of solutions of lysol, chloramine, bleach, and corrosive sublimate they die in 3-5 minutes).

For complete disinfection, the corpses of infected animals are kept in a disinfectant solution for at least 24 hours, after which they are burned.

The pathogen is sensitive to chloramphenicol, rifampicin, streptomycin and other aminoglycosides, and tetracycline antibiotics.

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Pathogenesis of tularemia

F. tularensis penetrates the human body through the skin (even if not externally damaged) and the mucous membranes of the eyes, respiratory tract, tonsils and gastrointestinal tract. When infected through the skin or by airborne route, fifty viable microorganisms are enough for the development of the disease, and in case of alimentary infection - more than 10 ⁸ microbial cells.

At the entry point of the infection, the pathogen multiplies with the development of a necrotic-inflammatory reaction and primary affect (a skin ulcer that goes through the stages of a papule, vesicle and pustule; on the tonsils - necrotic angina, in the lungs - focal necrotic pneumonia, on the conjunctiva - conjunctivitis). Then the pathogen penetrates into the regional lymph nodes, causing the development of specific lymphadenitis - primary bubo. Partial death of bacteria occurs here, accompanied by the release of endotoxin (LPS complex), which intensifies the local inflammatory process and causes the development of intoxication when it enters the blood.

In some cases, the pathogen overcomes the lymphatic barrier and spreads hematogenously (generalization of the process), causing damage to other groups of lymph nodes not associated with the site of introduction of the microorganism (secondary buboes) and internal organs (liver, spleen, lungs). The death of the pathogen circulating in the blood and the release of endotoxin aggravate intoxication. Specific sensitization and allergization of the body play a significant role in the pathogenesis of the disease.

Relapses are possible, associated with long-term intracellular persistence of the pathogen in a latent state in specific foci and macrophages, with incomplete phagocytosis, and the formation of F. tularensisprotein that helps suppress TNF-os and IL-1 and ensure long-term survival of the microorganism.

Tularemia is characterized by a granulomatous type of inflammation as a result of incomplete phagocytosis. Granulomas are formed in the lymph nodes and internal organs (usually in the liver and spleen) from epithelial cells, polymorphonuclear leukocytes and lymphocytes. In appearance and cellular composition, tularemia granulomas resemble those in tuberculosis. They are subject to necrosis and suppuration with subsequent replacement by connective tissue. Abscesses may form in places where granulomas accumulate. In acute forms of tularemia, necrotic changes predominate, while in subacute forms, signs of reactive inflammation predominate.

The granulomatous process is most clearly expressed in regional lymph nodes, where primary lymphadenitis (bubo) develops. When it suppurates and opens, a long-term non-healing ulcer is formed on the skin. In secondary buboes, suppuration usually does not occur.

In aerosol infection, the most pronounced changes in the form of foci of alveolar necrosis, infiltration and formation of granulomas are observed in the tracheobronchial lymph nodes and pulmonary parenchyma. Dystrophic changes are noted in the heart and kidneys, and in the intestines - damage to Peyer's patches and mesenteric lymph nodes.

Epidemiology of tularemia

Tularemia is a classic natural focal disease, an obligate zoonosis. The source of the infectious agent is about 150 animal species, including 105 mammal species, 25 bird species, several fish species, frogs, and other aquatic organisms. The main reservoir and source of infection is rodents (mice, rabbits, hares, water rats, muskrats, hamsters, etc.). The excretions and carcasses of dead animals contain a large number of pathogens that seed environmental objects, including water objects, and persist in them for a long time. Between rodents, infection is transmitted by the alimentary route. Among domestic animals, the reservoir of infection can be sheep, pigs, cattle, horses, but people most often become infected in natural foci through direct and indirect contact with rodents. A sick person cannot be a source of infection for others.

Carriers of infection that support the existence of the pathogen in natural foci are blood-sucking insects (ixodid and gamasid ticks, mosquitoes, horseflies).

The pathogen can penetrate the human body through microtraumas of the skin and intact mucous membranes of the tonsils, oropharynx, gastrointestinal tract, respiratory tract, and eyes.

There are four mechanisms of pathogen transmission:

• contact - through contact with infected rodents (cutting carcasses, removing skins) and water (bathing, washing, rinsing clothes);
• alimentary - when consuming infected, thermally unprocessed food and water;
• aerosol - when inhaling infected dust through the mouth and nose during winnowing and threshing of grain, stacking hay and straw:
• transmissible (main) - when bitten by infected blood-sucking insects or crushed.

The pulmonary form of tularemia occurs with aerosol infection, angina-bubonic and abdominal - with alimentary infection, ulcerative-bubonic and oculo-bubonic - with transmission and contact infection.

Human susceptibility to tularemia is high (reaches 100%). Summer-autumn seasonality is noted. Human infection occurs mainly in rural areas, but in recent years, city dwellers have predominated among those infected (up to 2/3), which is associated with the desire of city dwellers to relax in nature, as well as with the use of thermally unprocessed agricultural products.

People who have recovered from the disease acquire persistent, long-lasting, but not absolute immunity.

Natural foci of tularemia exist on all continents of the Northern Hemisphere, in Western and Eastern Europe, Asia, and North America. Recently, the incidence of tularemia has ranged from fifty to several hundred people per year. An increase in the number of cases is noted in years of increased rodent numbers.

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