Epidemiology, causes and pathogenesis of tularemia

Causes of tularemia

The cause of tularemia is Francisella tularensis, the genus Francisella. Family Brucellaceae. Gram-negative polymorphic (mainly coccoid) immobilized rod, not forming spores and capsules. Facultative anaerobic. The causative agent is demanding for cultivation conditions, grows on nutrient media with the addition of cysteine or egg yolk, rabbit defibrinated blood, tissue extracts (liver, spleen, brain) and other growth stimulants. From laboratory animals, the increased susceptibility to tularemia is due to white mice and guinea pigs.

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

F. Tularensis is stable in the environment, especially at low temperatures and high humidity (survives at -300 ° C., stored in ice up to 10 months, in frozen meat - up to 3 months). The causative agent is less resistant to drying (in the skins of rodents that have died from tularemia it persists up to 1.5 months, at 30 ° C - up to 1 week); remains viable in river water at a temperature of 10 ° C to 9 months, in the 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 irradiation, ionizing radiation, high temperature and disinfectants (under the action of solutions of lysol, chloramine, bleach, and mercuric chloride dies in 3-5 minutes).

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

The causative agent is sensitive to chloramphenicol, rifampicin, streptomycin and other aminoglycosides, antibiotics of the tetracycline group.

[1], [2], [3], [4], [5]

Pathogenesis of tularemia

F. Tularensis penetrates the human body through the skin (even externally undamaged) and the mucous membranes of the eyes, respiratory tract, tonsils and gastrointestinal tract. When infected through the skin or by aerogenic means, fifty viable microorganisms are sufficient for the development of the disease, and for alimentary infection - more than 10 ⁸ microbial cells.

At the entry gate of the infection, the pathogen multiplies with the development of a necrotic inflammatory reaction and primary affect (skin ulcer, passing papules, vesicles and pustules, tonsils on necrotic tonsillitis, in the lungs - focal necrotic pneumonia, conjunctivitis in conjunctiva). Then the pathogen penetrates into the regional lymph nodes, causing the development of a specific lymphadenitis - the primary bubo. There is a partial death of bacteria, accompanied by the release of endotoxin (LPS complex), which intensifies the local inflammatory process and causes the development of intoxication when entering the blood.

In some cases, the causative agent overcomes the lymphatic barrier and spreads hematogenously (generalization of the process), causing damage to other groups of lymph nodes that are not related to the place 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 exacerbate intoxication. An essential role in the pathogenesis of the disease is played by specific sensitization and allergization of the body.

Relapses associated with long-term intracellular persistence of the pathogen in the latent state in specific foci and macrophages are possible, with incomplete phagocytosis, the formation of F. Tularensis protein, which suppresses TNF-α and IL-1 and prolonged preservation of the microorganism.

Tularemia is characterized by granulomatous type of inflammation as a result of incomplete phagocytosis. Granulomas are formed in 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 of tuberculosis. They are prone to necrosis and suppuration, followed by replacement with connective tissue. In the places of accumulation of granules, the formation of abscesses is possible. In acute forms of tularemia, necrotic changes predominate, while in subacute forms - signs of reactive inflammation.

The most pronounced granulomatous process is expressed in regional lymph nodes, where primary lymphadenitis (bubon) develops. With its suppuration and autopsy, a long, non-healing ulcer forms on the skin. In secondary buboes, suppuration does not usually occur.

In aerosolized 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. In the heart and kidneys, dystrophic changes are noted, in the intestine - the defeat of Peyer's plaques 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 species of animals, including 105 mammal species, 25 bird species, several species of fish, frogs, and other hydrobionts. The main reservoir and source of infection are rodents (mice, rabbits, rabbits, water rats, muskrats, hamsters, etc.). Isolations and corpses of dead animals contain a large number of pathogens that infect environmental objects, including water, and persist in them for a long time. Between the rodents transmission of the infection is carried out alimentary way. Among domestic animals, the reservoir of infection may be sheep, pigs, cattle, horses, but people are most often infected in natural foci by direct and indirect contact with rodents. A sick person can not be a source of infection for others.

The carriers of the infection, which support the existence of the pathogen in natural foci, are blood-sucking insects (iksodovye and gamasovye mites, mosquitoes, horseflies).

In the human body, the pathogen can penetrate through the microtraumas of the skin and the undamaged mucous membrane of the tonsils, oropharynx, gastrointestinal tract, respiratory tract, eyes.

There are four mechanisms of transmission of the pathogen:

• contact - in contact with infected rodents (cutting carcasses, removing skins) and water (bathing, washing, rinsing);
• alimentary - with the use of infected, thermally unprocessed products and water;
• aerosol - by inhaling the infected dust through the mouth and nose during the withering and threshing of the grain, hay and straw baling:
• transmissive (basic) - with the bite of infected blood-sucking insects or their crushing.

The pulmonary form of tularemia occurs with aerosol infection, anginal-bubonic and abdominal - with alimentary, ulcerative-bubonic and glaucobular - in case of transmissible and contact infection.

People's susceptibility to tularemia is high (reaches 100%). They note the summer-autumn seasonality. Human infection occurs predominantly in rural areas, but in recent years, urban dwellers (up to 2/3) are the most affected, due to the desire of urban residents to relax in nature, as well as the use of thermally unprocessed agricultural products.

Persons who have suffered a disease acquire a persistent, prolonged, but not absolute, immunity.

Natural foci of tularemia exist on all continents of the Northern Hemisphere, in Western and Eastern Europe, in Asia, and in North America. Recently, the incidence of tularemia ranges from fifty to several hundred people a year. The increase in the number of cases is observed in the years of increased numbers of rodents.

[6], [7], [8], [9], [10]