Mycobacteriosis of the lungs (nontuberculous mycobacteria and their role in human disease). Respiratory infections caused by atypical mycobacteria Mycobacteria are

Mycobacterium
Lehmann and Neumann

The uniqueness and key role of mycolic acids in the structural organization and physiology of mycobacteria make them an excellent target for etiotropic therapy.

They reproduce by cell division. Widely distributed in soil. Saprophytic forms are involved in the mineralization of organic residues, some oxidize paraffins and other hydrocarbons. They can be used to combat oil pollution of the biosphere.

Pigmentation

According to the 1959 Runyon classification of non-tuberculous mycobacteria based on cultural differences, 4 groups of mycobacteria are distinguished by the production of pigment by colonies:

Photochromogenic (Group I) Mycobacteria that are unpigmented when grown in the dark but acquire a bright yellow or yellow-orange pigmentation after exposure or reincubation in the light.

• ex: M. kansasii, M. marinum, M.simiae, M. asiaticum

• ex: M. scrofulaceum, M. gordonae, M. xenopi, M. szulgai

• ex: M. tuberculosis, M. avium, M.intra-cellulare, M. bovis, M. ulcerans
• ex: M. chelonae

• ex: M. phlei, M. smegmatis, M. fortuitum

Pathogenic species

Pathogenic species cause diseases in humans (tuberculosis, leprosy, mycobacteriosis) and animals. A total of 74 species of such mycobacteria are known. They are widely distributed in soil, water and among humans.

Tuberculosis in humans is caused by : Mycobacterium tuberculosistypus(human kind) Mycobacterium bovis(bull look) and Mycobacterium africanum(intermediate type), in AIDS patients - also types Mycobacterium avium complex. These species are able to penetrate, live and multiply inside a person.

Members of the genus Mycobacteria

According to the old system, mycobacteria were classified, depending on their properties and growth rate on nutrient media. However, the newer nomenclature is based on cladistics.

slow growing

Mycobacterium tuberculosis complex (MTBC)

• Mycobacterium tuberculosis complex(MTBC) representatives of the complex are pathogenic for humans and animals, and cause the disease tuberculosis. The complex includes: M. tuberculosis, most dangerous to humans, as the causative agent of tuberculosis M. bovis M. bovis BCG M. Africanum M. canetti M. caprae M. microti M. pinnipedii

Mycobacterium avium-complex (MAC)

Mycobacterium avium complex (MAC)- part of a large group of non-tuberculous mycobacteria (NTMB), the species that make up this complex are pathogenic for humans and animals, more often cause disseminated processes of extrapulmonary localization and were previously one of the main causes of death in AIDS patients. The complex includes:

• M. avium M. avium paratuberculosis M. avium silvaticum M. avium "hominissuis" M.colombiense

Gordonae-branch

• M. asiaticum
• M. gordonae

Kansasii-branch

• M. gastri

Nonchromogenic/terrae-branch

• M. hiberniae
• M. nonchromogenicum
• M. terrae
• M. triviale

Mycobacteria that produce mycolactone

• M. ulcerans
• M. pseudoshottsii
• M. shottsii

Simiae-branch

• M. triplex
• M. genavense
• M. florentinum
• M. lentiflavum
• M. palustre
• M. kubicae
• M. parascrofulaceum
• M. heidelbergense
• M. interjectum
• M.simiae

Uncategorized

• M. branderi
• M.cookii
• M. celatum
• M. bohemicum
• M. haemophilum

fast growing

Сchelonae-branch

• M. abscessus
• M. chelonae
• M. bolletii

Fortuitum-branch

• M. fortuitum
• M. fortuitum subsp. acetamidolyticum
• M. boenickei
• M.peregrinum
• M.porcinum
• M. senegalense
• M. septicum
• M. neworleansense
• M. houstonense
• M. mucogenicum
• M. mageritense
• M. brisbanense
• M. cosmeticum

parafortuitum-branch

• M. parafortuitum
• M. austroafricanum
• M. diernhoferi
• M. hodleri
• M. neoaurum
• M. frederiksbergense

Vaccae-branch

• M. aurum
• M. vaccae

CF branch

• M. chitae
• M. fallax

Uncategorized

• M. confluentis
• M. flavescens
• M.madagascariense
• M. phlei
• M. smegmatis
  • M. goodii
  • M. wolinskyi
• M. thermoresistible
• M.gadium
• M. komossense
• M. obuense
• M. sphagni
• M. agri
• M. aichiense
• M. alvei
• M.arupense
• M. brumae
• M. canariasense
• M. chubuense
• M. conceptionense
• M. duvalii
• M. elephantis
• M. gilvum
• M. hassiacum
• M. holsaticum
• M. immunogenum
• M. massiliense
• M. moriokaense
• M. psychrotolerans
• M. pyrenivorans
• M. vanbaalenii

Atypical (non-tuberculous, non-leprosy) mycobacteria belong to the Mycobacteriaceae family and differ from M. tuberculosis in nutrient requirements, ability to form pigments, enzymatic activity, and sensitivity to anti-tuberculosis drugs. In addition, M. tuberculosis tends to spread from person to person, and infection with atypical mycobacteria occurs through contact with the environment.

Epidemiology

Atypical mycobacteria are ubiquitous and serve as saprophytic inhabitants of soil and water, pathogens of infections in pigs, birds and cattle, in addition, mycobacteria can be part of the normal microflora of the human pharynx.

Some atypical mycobacteria have distinct ecological niches that help explain their transmission patterns. So, fish and other cold-blooded animals serve as a natural reservoir for M. marinum, and the infection develops after injuries that have occurred in the water. M. fortuitum and M. chelonae are ubiquitous members of the hospital microflora and therefore cause hospital outbreaks of wound infection or infection associated with venous catheters. M. ulcerans is isolated exclusively from jungle water and soil; it serves as the causative agent of chronic skin infections in the tropics. M. avium complex mycobacteria are found in abundance in water, soil, and aerosols from the acidic brown swamps of the southeastern United States. In rural areas of this region, about 70% of people carry asymptomatic infections caused by the M. avium complex by the time they enter adulthood.

In children, atypical mycobacteria rarely become the causative agents of infections (an exception is cervical lymphadenitis). Infections with atypical mycobacteria (especially M. avium complex) are the most common infections occurring in the terminal period.

Pathogenesis

Histologically, foci of infection caused by M. tuberculosis and atypical mycobacteria are often indistinguishable. The classic morphological manifestation in both cases is a granuloma with caseous necrosis. But for atypical mycobacteria, granulomas without caseous necrosis, poorly delimited (without palisade-like structures), irregularly shaped or creeping are more characteristic. Granulomas may be absent, then only chronic inflammatory changes are found. In AIDS patients with infection with atypical mycobacteria, the inflammatory response is usually mild, and the tissues have a large number of histiocytes filled with acid-fast bacilli.

Clinical manifestations

In children, the most common manifestation of atypical mycobacteria infections is lymphadenitis of the anterior cervical or submandibular lymph nodes; occasionally parotid, posterior cervical, axillary, and inguinal lymph nodes are involved. Lymphadenitis is mainly observed in children 1-5 years old who have a habit of putting objects contaminated with soil, dust or stagnant water into their mouths. The reason for going to the doctor is an increase (relatively fast or slow) of a lymph node or a group of closely located lymph nodes on one side; systemic manifestations are usually absent. The affected lymph nodes are larger than 1.5 cm, dense, painless, mobile, the skin is not hyperemic. Without treatment, the lymph nodes can sometimes return to their original size, but most often they suppurate after a few weeks. A fluctuation appears in the center of the lymph node, and the skin above it becomes hyperemic and thinner. Soon the lymph node opens and a skin fistula is formed that does not heal for months or even years - the picture at this stage resembles classic tuberculous lymphadenitis. The causative agent of approximately 80% of lymphadenitis in children caused by atypical mycobacteria is the M. avium complex. Most of the remaining cases are caused by M. scrofulaceum and M. kansasii. Rare pathogens include M. xenopi, M. malmoense, M. haemophilum, and M. szulgai.

Skin infections with atypical mycobacteria are rare. Usually, the infection develops following the ingestion of water contaminated with M. marinum into a skin wound (small abrasion on the elbow, knee or foot in swimmers; abrasions on the hands of a granuloma of aquarists). Within a few weeks, a single nodule appears at the site of injury - bathers' granuloma. Usually the nodule is painless, increases and after 3-5 weeks. turns into a plaque with an ulcerated or warty surface (a similar picture is observed with skin tuberculosis). Sometimes the picture resembles sporotrichosis: satellite nodules appear near the primary nodule, which are located along the superficial lymphatic vessels. Lymphadenopathy is usually absent. Although in most cases the infection is limited to the skin, penetration into deeper tissues can lead to tendovaginitis, bursitis, osteomyelitis, or arthritis.

M. ulcerans also causes skin infections in children living in the tropics (Africa, Australia, Asia, and South America). The infection occurs after the introduction of the pathogen into the skin and manifests itself as a painless hyperemic nodule (most often on the legs), in the center of which necrosis occurs, and then an ulcer. The disease is called Buruli ulcer, after the region in Uganda where most cases are reported. The ulcer is characterized by undermined margins, slow enlargement, and can lead to extensive soft tissue destruction and be complicated by secondary bacterial infection. Within 6-9 months. the ulcer may heal or continue to grow, accompanied by deformities and contractures.

M. fortuitum, M. chelonae, and M. abscessus rarely cause infections in children. The place of introduction of the pathogen is usually stab wounds or small abrasions. Clinical manifestations (localized phlegmon, painful nodules or abscess with a fistulous tract) usually occur after 4-6 weeks. A single case of mastitis caused by M. abscessus due to a nipple piercing has been described. M. haemophilum causes painful subcutaneous nodules in immunosuppressed patients (especially after kidney transplantation); these nodules often ulcerate and suppurate.

Among the causative agents of infections associated with venous catheters, the proportion of atypical mycobacteria is small, but it is increasing. Such infections are bacteremia or suppuration during catheter placement; the main role in them is played by M. fortuitum, M. chelonae and M. abscessus.

In adults, atypical mycobacteria most often affect the respiratory system, but this is not typical for children. However, in immunocompetent children, M. avium complex-induced acute pneumonias, prolonged coughing, or wheezing due to airway compression by enlarged paratracheal or parabronchial lymph nodes have been described. Isolated cases of progression of infection with granulomatous inflammation of the bronchi are also described. In older patients with cystic fibrosis, the causative agents of chronic infections can be mycobacteria of the M. avium complex and the M. fortuitum complex. In adults with chronic lung disease, infections are caused by M. kansasii, M. xenopi, and M. szulgai; in children, these pathogens are atypical. The disease begins gradually with subfebrile body temperature, cough, night sweats and general malaise. The formation of thin-walled caverns is characteristic, infiltration of the parenchyma around which is minimally expressed; sometimes the x-ray picture resembles tuberculosis.

Rarely, usually in patients with surgical or puncture wounds, atypical mycobacteria can cause bone and joint infections indistinguishable from those caused by M. tuberculosis and other bacteria. In patients with foot puncture wounds, M. fortuitum causes infections resembling those caused by Pseudomonas aeruginosa or Staphylococcus aureus.

Atypical mycobacteria, usually related to the M. avium complex, rarely cause disseminated infection without visible signs of immunodeficiency. Most children have mutations in the genes that code for IFN-y or IL-12 receptors, or the formation of IL-12. In the absence of IFN-γ receptors, a severe infection develops that is difficult to treat. Infections in children with IFN-γ receptor deficiency or mutations in the genes involved in the synthesis of IL-12 are milder and treatable with interferon and antimycobacterial agents. The incidence of multifocal osteomyelitis is highest in children with the IFN-y 818del4 receptor-1 mutation. There are numerous descriptions of relapses occurring years after treatment.

Disseminated infection with the M. avium complex, one of the most common opportunistic infections, especially in the late stages of AIDS, when the number of CD4-lymphocytes falls below 100/mm3. Disseminated infection appears to be preceded by colonization of the respiratory or gastrointestinal tract with M. avium complex. But the study of the secret of the respiratory tract or feces for this pathogen does not predict the possibility of dissemination. Disseminated infection is characterized by prolonged bacteremia with a high content of pathogens in the blood and the defeat of many organs, primarily the lymph nodes, liver, spleen, bone marrow and gastrointestinal tract. The thyroid and pancreas, adrenals, kidneys, muscles, and brain may also be involved. The most common symptoms of disseminated infection in AIDS caused by the M. avium complex are fever with chills, night sweats, anorexia, marked weight loss, weakness, generalized lymphadenopathy, and hepatosplenomegaly. Jaundice, elevated alkaline phosphatase, and neutropenia are also possible. X-ray studies usually show a marked increase in the lymph nodes of the roots of the lungs, mediastinum, mesentery and retroperitoneal lymph nodes. The average life expectancy in children with AIDS after sowing the M. avium complex from blood or tissues is 5-9 months.

Diagnosis of atypical mycobacteria

Differential diagnosis of lymphadenitis from atypical mycobacteria includes acute bacterial lymphadenitis, tuberculous lymphadenitis, felinosis (pathogen - Bartonella henselae), mononucleosis, toxoplasmosis, brucellosis, tularemia and malignant tumors, primarily lymphomas. Mantoux test with 5 tuberculin units is usually weakly positive (infiltrate with a diameter of 5-15 mm). The CDC developed skin test antigens that distinguish between mycobacteria belonging to different Runyon groups, but these antigens are no longer available. Infections with atypical mycobacteria can be difficult to distinguish from tuberculosis. But with lymphadenitis from atypical mycobacteria, the diameter of the infiltrate during the Mantoux test usually does not reach 15 mm, the anterior cervical lymph nodes are enlarged on the one hand, chest radiographs are normal, there is no contact with an adult patient with tuberculosis. With tuberculous lymphadenitis, as a rule, there is a bilateral increase in the posterior cervical lymph nodes, the diameter of the infiltrate during the Mantoux test exceeds 15 mm, pathology is detected on chest x-ray, and contact with an adult patient with tuberculosis can also be detected. The final diagnosis is made after removal of the affected lymph nodes and sowing.

Diagnosis of skin mycobacterial infections is based on the culture of a biopsy specimen from the lesion. Diagnosis of respiratory infections caused by atypical mycobacteria is difficult because many of the atypical mycobacteria, including the M. avium complex, can be cultured from oral and gastric secretions in healthy children. Definitive diagnosis requires invasive studies, such as bronchoscopy with biopsy of the bronchus or lung. Mycolic acids and other lipids contained in the cell wall of mycobacteria render them acid-resistant when stained by Ziehl-Nelsen or Kinjun. Mycobacteria can also be detected by staining with fluorescent dyes such as kakauramine and rhodamine. The sensitivity of staining of atypical mycobacteria in tissues is lower than when detecting M. tuberculosis.

The sensitivity of blood cultures in AIDS patients with disseminated infection with atypical mycobacteria reaches 90-95%. Blood cultures on special media using the radiometric method make it possible to detect the M. avium complex in almost all patients within a week. DNA probes are also available that can distinguish between atypical mycobacteria and M. tuberculosis. A quick method for the preliminary diagnosis of disseminated mycobacterial infection is the detection in the bone marrow and biopsy specimens of other tissues of histiocytes containing many acid-resistant rods.

Treatment of atypical mycobacteria

In infections with atypical mycobacteria, both conservative and surgical treatment is used, as well as their combination. It is best if it is possible to isolate the pathogen and determine its sensitivity, because the latter varies. M. kansasii, M. xenopi, M. ulcerans, and M. malmoense are usually sensitive to standard anti-tuberculosis drugs. M. fortuitum, M. chelonae, M. scrofulaceum and the M. avium complex are resistant to anti-tuberculosis drugs in most cases; their sensitivity to new antibacterial agents, such as fluoroquinolones and macrolides, is variable. To avoid the development of resistance, it is necessary to prescribe several antibacterial agents at the same time.

The preferred treatment for atypical lymphadenitis is complete excision of the affected lymph nodes. The lymph nodes are removed while they are still dense and their capsule is intact. The development of extensive breech necrosis with the transition to the surrounding tissues makes excision difficult, and also increases the likelihood of complications (damage to the facial nerve, recurrence of infection). Only part of the lymph nodes should not be removed, as in this case a long-term non-healing fistula may occur. Standard anti-tuberculosis drugs for lymphadenitis caused by atypical mycobacteria are ineffective, and complete excision of the lymph nodes makes them unnecessary. If TB cannot be ruled out, isoniazid, rifampicin, and pyrazinamide are given until culture results are available. If for one reason or another it is impossible to excise the affected lymph nodes, or their excision was incomplete, or a relapse or fistula occurred, drug treatment is recommended for 4-6 months. Although there are no published data from controlled studies, a number of observations and small studies indicate the success of medical treatment alone or its combination with removal of lymph nodes. Most reports have used clarithromycin or azithromycin with rifabutin or ethambutol.

Skin infections caused by mycobacteria usually heal on their own afterward. M. marinum is susceptible to rifampicin, amikacin, ethambutol, sulfonamides, trimethoprim/sulfamethoxazole, and tetracycline. The combination of these drugs is prescribed for 3-4 months. Glucocorticoid injections are contraindicated. Superficial infections caused by M. fortuitum and M. chelonae usually heal after open drainage. For deep infections, as well as for infections associated with venous catheters, it is necessary to remove the catheter and start parenteral administration of amikacin, cefoxitin, or clarithromycin. For respiratory infections, a combination of isoniazid, rifampicin, and pyrazinamide is given until susceptibility testing results are available.

For disseminated infection with the M. avium complex, patients with impaired IL-12 synthesis or IFN-γ receptor deficiency, a combination of clarithromycin or azithromycin with one or more of the following drugs is indicated: rifabutin, clofazimine, ethambutol and fluoroquinolones. Treatment continues for at least 12 months. It is important to determine the sensitivity of the pathogen in vitro. After the end of treatment, lifelong relapse prevention is recommended, for which daily clarithromycin is prescribed. The presence of specific genetic defects is an indication for the appointment of interferon.

In adult patients with AIDS, daily prophylactic administration of azithromycin or its combination with rifabutin reduces the incidence of infections caused by the M. avium complex by more than 50%.

Mycobacteria.

Into the genus Mycobacterium families Mycobacteriaceae included acid- and alcohol-resistant aerobic immobile gram-positive straight or curved rod-shaped bacteria. Sometimes they form filamentous or mycelial structures. Characterized by a high content of lipids and waxes (up to 60%). Catalase- and arylsulfatase-positive, resistant to the action of lysozyme. Grow slowly or very slowly.

Mycobacteria are widely distributed in the environment - water, soil, plants and animals.

On the basis of pathogenicity, they are actually distinguished pathogens that cause specific diseases ( 5 groups - M. Tuberculosis, M. leprae, M. bovis, M. Miccroti, M. Lepraemurium) and atypical mycobacteria.

Pathogenic mycobacteria.

Mycobacterium Tuberculosis (Koch's wand). The causative agent of human tuberculosis is a chronic infectious disease characterized by lesions of the respiratory organs, bones, joints, skin, urogenital and some other organs. The disease has been known since ancient times. The pulmonary form of tuberculosis was described by ancient authors (Artaeus of Cappadocia, Hippocrates, etc.). However, the ancients did not consider it as an infection, Ibn-Sina considered it to be a hereditary disease. The first to directly point out its infectious nature was Fracastoro, and Sylvius noted the connection of pulmonary tubercles with consumption. The variety of clinical manifestations of tuberculosis caused many erroneous ideas: de Laaenek attributed pulmonary tubercles to malignant neoplasms, Virchow did not associate caseous necrosis with the tuberculous process. The growth of cities, crowding of the population and a low sanitary standard of living led to the fact that in the 18-19 centuries. Tuberculosis gathered a rich harvest among different sections of the population: suffice it to recall Mozart, Chopin, Nekrasov, Chekhov, and others.

The infectious nature of the disease was proved by Wilmen (1865), and the most important stage in the study and improvement of measures to combat tuberculosis was a short report by Koch at a meeting of the Berlin Physiological Society on March 24, 1882 on the etiology of tuberculosis, in which he outlined the main postulates-criteria for assessing the pathogenicity of any microorganism.

Epidemiology. Storage tank Mycobacterium Tuberculosis - a sick person, the main route of infection is aerogenic, less often through the skin and mucous membranes. In rare cases, transplacental infection of the fetus is possible.

a) The penetration of mycobacteria does not always cause the development of a pathological process, a special role is played by unfavorable living and working conditions. Currently, there is an increase in the incidence, which is associated with an obvious decrease in the standard of living of the population and a concomitant imbalance in nutrition, on the one hand, and the “activity” of the pathogen is increasing, obviously due to the displacement of natural competitors as a result of the use of antimicrobial agents.

b) Equally important are the "aging" of the population around the world and the increase in the number of people with chronic diseases accompanied by impaired immunity.

in) a special role in infection Mycobacterium Tuberculosis the overcrowding of the population plays a role: in the Russian Federation - pre-trial detention centers, refugee camps, "homeless" people.

Morphology and tinctorial properties.

Thin, straight or slightly curved sticks 1-10 * 0.2-0.6 µm in size, with slightly curved ends, contain granular formations in the cytoplasm. The morphology varies depending on the age of the culture and cultivation conditions - in young cultures, the sticks are longer, and in old cultures they are prone to simple branching. Sometimes they form coccoid structures and L-forms that remain infectious, and filterable forms.

They are immobile, do not form spores, lack capsules, but have a microcapsule separated from the cell wall by an osmiophobic zone. acid resistant, which is due to the high content of lipids and mycolic acid in the cell wall, and also form acid-stable granules, mainly consisting of metaphosphate ( fly grains), located freely or in the cytoplasm of rods.

Gram-positive, aniline dyes are poorly perceived, according to Ziehl-Nielsen they are painted in bright red color, according to Fly-Weiss - in violet (iodophilicity).

cultural properties. aerobes, but able to grow under facultative anaerobic conditions, 5-10% CO2 promotes faster growth. They reproduce by division, the process is very slow, on average in 14-18 hours. Temperature optimum 37-38 gr.С, pH 7.0-7.2

(grows within 4.5 -8.0).

For growth, it needs the presence of a protein substrate and glycerol, as well as carbon, chlorine, phosphorus, nitrogen, growth factors (biotin, nicotinic acid, riboflavin), ions (Mg, K, Na, Fe).

For cultivation, dense egg media (Levinstein-Jensen, Petragnani, Doce), synthetic and semi-synthetic liquid media (Soton's medium) are used. On liquid media, growth is observed on days 5-7 in the form of a dry wrinkled film (R - form) rising to the edges of the test tube, the medium remains transparent. In environments containing detergent (tween-80) they give uniform growth throughout the thickness of the medium. On liquid media and during intracellular development, the characteristic cord factor ( trehalose-6,6-dimycolate), which causes the convergence of bacterial cells in microcolonies, their growth in the form of serpentine braids and is related to the virulence of the pathogen. On dense media, growth is noted on days 14-40 in the form of a dry wrinkled cream-colored coating, colonies with a raised center, reminiscent of cauliflower, crumbly, poorly wetted with water and have a pleasant aroma. Cultures are poorly removed from the environment, and crack when pierced. Under the influence of antibacterial drugs, they can dissociate with the formation of soft moist S-colonies or grow in the form of smooth or pigmented colonies. Distinctive feature Mycobacterium Tuberculosis - the ability to synthesize a significant amount of nicotinic acid (niacin), which is used for its differential diagnosis with other mycobacteria (niacin test), one of the conditions is the need for seeding on Levinstein-Jensen medium, which does not contain malachite green) because the dye reacts with the reagents used). On media with bile, it forms a greyish, oily coating formed by elongated branching rods.

Koch wand quite resistant to various influences, in milk it dies after 15-20 minutes at a temperature of 60 ° C, at a similar temperature it persists in sputum for up to an hour, and when boiled it dies after 5 minutes. Direct sunlight kills Koch's wand after 45-55 minutes, scattered - after 8-10 days. It is well preserved when dried (up to several weeks). Conventional chemical disinfectants are relatively ineffective, 5% phenol solution kills Mycobacterium Tuberculosis only after 5-6 hours, the pathogen is also able to quickly develop resistance to many antibacterial agents.

Pathogenesis of lesions and clinical manifestations.

a) Most often, infection occurs through inhalation of an aerosol containing mycobacteria, or through the use of contaminated products (penetration through the skin and mucous membranes is possible). Inhaled mycobacteria phagocytize alveolar and pulmonary macrophages and transport them to regional lymph nodes, phagocytic reactions are incomplete and the pathogen survives in the cytoplasm of macrophages. The ability to reduce the activity of phagocytes is caused by sulfatides, which enhance the toxic effect of the cord-factor, and inhibit phagosomal-lysosomal fusion. The inflammatory response is usually not pronounced, which is largely mediated by the ability of the cord factor to inhibit the migration of polymorphonuclear phagocytes. At the site of penetration may develop primary effect. In dynamics, along the regional lymphatic tracts and nodes, a primary complex is formed, characterized by the development of granulomas in the form of tubercles (hence tubercle, or tuberculosis).

the formation of granulomas has no characteristic features and is a cellular reaction of DTH. The sensitization of the body is due to the action of a number of products of mycobacteria, known as the old Koch tuberculin, which exhibits a local and systemic effect. To a certain extent, the formation of granulomas is promoted by the formation of lactic acid, low pH, high concentration of CO2. In the center of each tubercle there is a site of cheesy necrosis, where Koch's stick is located. The site of necrosis is surrounded by epithelioid and giant cells of Pirogov-Langhans. The center is surrounded by epithelioid cells, and along the perimeter - lymphocytes, plasmocytes and mononuclear cells, most often the primary focus is observed in the lungs (Gon's focus). In granulomas, the reproduction of the pathogen usually slows down or stops altogether.

Quite characteristic period of latent microbiism"- a condition in which the penetrated mycobacteria do not cause the development of inflammatory reactions and freely disseminate throughout the body.

In most cases, primary lesions heal with complete

content degradation, calcification and fibrosis

parenchyma.

Clinical manifestations are usually absent or resemble a flu-like syndrome, sometimes the primary focus or enlarged bronchopulmonary lymph nodes can be detected radiologically.

Primary tuberculosis is characterized by high sensitivity of tissues to metabolites of mycobacteria, which contributes to their sensitization; when the affect heals, the increased sensitivity disappears and the severity of immune reactions increases. However, under these conditions, dissemination of the pathogen from the primary foci and the formation of foci-screenings is possible, usually they are localized in the lungs, kidneys, genitals and bones.

b) When the body's immunity is weakened, the foci are activated and progress with the development of a secondary process. A certain contribution to the pathogenesis is made by the sensitization of the body, causing a variety of toxic-allergic reactions in the patient.

reactivation occurs 20-25 years after the initial infection. Usually it is provoked by stress, malnutrition and a general weakening of the body. In the lungs, bronchi and small vessels, cavities are formed, from which necrotic curd masses containing significant amounts of the pathogen are actively expectorated.

Clinically, reactive tuberculosis is manifested by cough, frequent hemoptysis, weight loss, profuse night sweats, and chronic low-grade fever.

in) In more rare cases, in frail adolescents and adults, as well as in patients with immunodeficiencies, there is disseminated (miliary) tuberculosis, characterized by the formation of granulomas in various organs.

the development of generalized lesions often occurs after the breakthrough of the contents of the granuloma into the bloodstream.

General manifestations are similar to those in secondary tuberculosis, but they are often accompanied by lesions of the brain and its membranes, the prognosis of this form is the most unfavorable.

The variety of forms has led to the complexity of its classification.

Currently, the clinical classification distinguishes three main forms:

Tuberculosis intoxication in children and adolescents.

Tuberculosis of the respiratory organs, including the primary complex, damage to the internal lymph nodes, pleura, upper respiratory tract, focal, infiltrative, cavernous, fibrous-cavernous, cirrhotic pulmonary tuberculosis, tuberculoma, etc.

Tuberculosis of other organs and systems, including lesions of the meninges, eyes, joints and bones, intestines and peritoneum, skin and subcutaneous tissue. Organs of the urinary-genital system, etc.

Laboratory diagnostics.

Includes methods included in the mandatory diagnostic minimum and additional research methods.

BUT). In case of illness – microscopy of pathological material(sputum, fistula discharge, urine, bronchial lavage) smears stained according to Ziehl-Neelsen can reveal red acid-fast bacilli. (In recent years, the Murahashi-Yoshida method has been introduced, which makes it possible to differentiate between dead and living bacteria).

with a low content of the pathogen, the Ulengut accumulation method is used - the material is mixed with an equal or double volume of NaCl and NaOH, shaken and incubated for 30 minutes at a temperature of 21 ° C. Then cell debris and extraneous bacteria are removed by centrifugation, the precipitate is neutralized with 30% acetic acid solution and smears are prepared, stained according to Ztl-Nelsen or Kinyon.

the flotation method is more effective - NaOH solution, distillate, xylene (benzene) are added to the material and shaken vigorously, the resulting foam floats up and captures mycobacteria, it is sucked off and smears are prepared.

A certain value in assessing the severity of the process, the effectiveness of treatment and the prognosis of the disease has a quantitative assessment of the population of mycobacteria by the Gaffky-Stinken method (counting bacteria on calibrated glasses in certain fields of view).

The most effective bacterioscopic method - fluorescence microscopy, because fluorochrome staining (for example, auramine-rhodamine) makes it possible to detect even a small amount of mycobacteria (stained in white-yellow color), as well as forms with altered cultural and tinctorial properties.

B) Isolation of the pathogen. Before inoculation, the test material can be treated with Ulengut or Sumioshi (15-20% HCl or H2SO4 solution), the test samples are centrifuged, washed with saline and inoculated, carefully rubbing onto solid nutrient media (usually Levinstein-Jensen). for simplicity, samples can be treated with various antibiotics that inhibit the growth of contaminating flora.

The disadvantage of the method is the duration of obtaining the result - from 2 to 12 weeks.

The advantage is the possibility of obtaining a pure culture, which makes it possible to identify it, evaluate its virulent properties, and determine sensitivity to drugs.

Accelerated methods for isolating the pathogen (Price) have been developed, the material is placed on a glass slide, treated with H2SO4, washed with saline and added to a nutrient medium supplemented with citrated blood. The glass is taken out after 3-4 days and stained according to Ziehl-Nelsen.

- "Gold standard" - in the diagnosis of tuberculosis - biological test on guinea pigs infected subcutaneously or intraperitoneally 1 ml of material obtained from the patient. Animals develop a generalized infection leading to death in 1-2 months, however, the disease can be recognized earlier by tuberculin tests - after 3-4 weeks, and lymphadenitis already on 5-10 days. Their punctures contain a large number of bacteria. However, the emergence of resistant and modified mycobacteria has reduced the sensitivity of this assay. To increase it, intratesticular infection is used, or the immunity of the animal organism is suppressed by the introduction of glucocorticoids.

Atypical mycobacterioses are a number of granulomatous diseases caused by mycobacteria. The name of the disease includes the term atypical, since the causative agent of the disease differs from the classical pathogenic mycobacteria that cause the development of skin tuberculosis.

Mycobacteria are anaerobic, immobile microorganisms that do not form spores. The most important characteristic of these bacilli is their acid resistance and high lipid content in their cell walls.

About five dozen different mycobacteria are known today. Among them are:

• Definitely pathogenic. These include M. tuberculosis, M. Bovis, M. Leprae, which also cause leprosy.
• Other types of mycobacteria are classified as conditionally pathogenic, they are called atypical.

Reasons for development

The cause of mycobacteriosis is infection with certain types of mycobacteria.

You can get infected with mycobacteria in different ways - contact, airborne, dust. Moreover, a person with atypical mycobacteriosis does not pose a particular danger to others. Basically, infection occurs through contact with the environment.

For example, the mycobacterium M. Avium can be present in fumes from bodies of water, so infection often occurs during bathing. Poultry is often the source of infection. Mycobacteria can also live in the soil.

Of course, the mere fact of contact with mycobacteria does not mean that the disease will necessarily develop. Persons with reduced immunity (local and general) are predisposed to mycobacteriosis. Often there are facts of infection with mycobacteria in patients with obstructive pulmonary disease, cystic fibrosis of lung tissue, bronchiectasis. Among the provoking factors include injuries, including,.

Clinical picture

The clinic of mycobacteriosis caused by atypical mycobacteria is characterized by a variety of symptoms. The manifestations of the disease depend on the type of mycobacteria, the route of their penetration, age, gender, etc.

Bather's granuloma or pool granuloma

The causative agent of this disease is Mycobacterium marinum - mycobacteria that live in sea water. Penetration of mycobacteria is carried out through damage to the skin (scratches, abrasions, etc.). Infection can occur when swimming in pools with sea water, cleaning aquariums in which marine life lives, cleaning marine fish.

The incubation period for this type of skin disease caused by mycobacteria is on average 2.5 weeks. At the site of penetration of mycobacteria on the skin, a knot with a warty or covered with small scales surface is formed. The node has a bluish-reddish color.

This disease is more common in men aged 10-40 years. The resulting knot does not cause pain, has a fairly dense texture and is cold to the touch. Of the subjective sensations, itching is sometimes noted, but, usually, patients are more worried due to the formation of a cosmetic defect.

If the node is located above the joint, it may lead to a restriction of its mobility. When pressing on the node, a slight soreness is sometimes noted.

As the disease develops, an ulcer may form at the site of the node, covered with purulent or hemorrhagic crusts. At the bottom of the ulcer are observed. In some cases, child nodes and fistulas form around the ulcer.

Bather's granuloma is a disease with a long course. In place of a healed ulcer, it forms.

In the sporotrichoid form of the disease, soft subcutaneous nodes are formed, which look like swellings with a diameter of about 2 cm. The nodes are located linearly, along the location of the lymphatic vessel at a distance from the primary ulcer. When swelling is located above the joints, the clinic of the disease resembles bursitis or inflammatory arthritis.

The disseminated form of bathers' granuloma is extremely rare. Usually, this type of disease is observed in people with reduced immune status - HIV patients taking immunosuppressants, etc. In this case, in addition to the primary focus located at the site of penetration of mycobacteria, the formation of numerous linear nodes is observed. Localization of nodes depends on the method of infection. In bathers, the legs are usually affected; in aquarists, the dominant hand is usually affected. In the disseminated form of the disease, there is an increase in lymph nodes located near the primary focus.

Buruli ulcer

The causative agent of the disease is Mycobacterium ulcerans. This type of mycobacteria enters the body through damage to the skin. The disease is more common in tropical countries, mainly in young people. Women get sick a little more often.

Since the natural habitat of the Ulcerans mycobacteria has not been established, it is difficult to say how infection occurs. It is believed that infection occurs with minor injuries - with pricks with a thorn, a cut on a leaf of a plant, etc.

The incubation period of this disease is 3 months, so not all patients remember the microtrauma, which has become the "entrance gate" for mycobacteria.

Clinically, the disease is manifested by the appearance of a dense node, which quickly degenerates into an ulcer that does not cause pain. Ulcers in this disease can be very large, spreading to the skin of almost the entire affected limb. Most often, ulcers are localized on the legs, since it is the skin of the legs that is most often injured during walks in nature or as a result.

With Buruli ulcer, usually there are no symptoms of general intoxication, the lymph nodes are not changed.

Other varieties of atypical mycobacteriosis

Atypical mycobacterioses caused by Mycobacterium, Mycobacterium abscessus and Mycobacterium chelonae are very common. These mycobacteria usually enter through skin lesions and cause wound infections.

There is a geographical principle of the spread of infection. So, in European countries, skin infections caused by mycobacteria of the fortuitum type are more common. On the American continent, cases of infection with mycobacteria of the chelonae type are more common.

These mycobacteria are common in the environment, they can be found in water, soil, dust, wild or domestic animals.

Mycobacteria are introduced through wounds on the skin, and half of the cases of infection occur in wounds after operations and injections.

The incubation period lasts about a month, but sometimes it takes a longer time - up to 2 years.

At the site of penetration of mycobacteria, a dark red nodule is first formed, which is transformed into a cold abscess without pronounced signs of inflammation. After the opening of the abscess, separation of serous fluid is observed. In persons with a low immune status, a disseminated form of the disease is possible with the formation of multiple abscesses and joint damage. This type of disease develops with the hematogenous spread of mycobacteria throughout the body.

Diagnostic methods

The basis for the diagnosis of microbacterioses is the inoculation on media for mycobacteria. For research, discharge from ulcerative surfaces or biopsy material is taken. Additionally, the material is sown to us in the usual environment, this makes it possible to exclude the presence of secondary infection with other bacterial infections.

Treatment

The mainstay of treatment for skin lesions caused by mycobacteria is antibiotic therapy. The drug of choice for the fight against mycobacteria is usually minocycline. It is possible to use other antibiotics, taking into account the sensitivity of mycobacteria.

In the event that mycobacteria show little sensitivity to conventional antibacterial agents, rifampicin is prescribed in combination with ethambutol. By the way, rifampicin is also successfully used in the treatment,.

In the treatment of Buruli ulcer, antibiotics are often ineffective. With a large area of ​​damage, the affected tissues are excised and the implantation of one's own skin is performed.

In disseminated forms of skin diseases caused by mycobacteria, anti-tuberculosis drugs are used.

Patients, as a rule, are offered hospitalization at the initial stage of treatment, since in order to select the most effective drug, it is necessary to constantly monitor the course of the disease. The general course of treatment for skin infections caused by mycobacteria can last up to a year.

With long-term treatment of the disease with antibiotics, hepaprotectors should be prescribed to protect the liver and probiotics to prevent the development of dysbacteriosis.

In the process of treating diseases caused by mycobacteria, it is necessary to provide the patient with good nutrition. It is recommended to limit exposure to the sun.

Treatment with folk remedies

For the treatment of folk remedies for skin infections caused by mycobacteria, it is recommended to choose recipes aimed at overall strengthening of immunity.

In diseases provoked by atypical mycobacteria, it is recommended to take aloe preparations with honey. Useful vitamin teas from rose hips, mint, raspberries, currants.

Prevention and prognosis

Prevention of the development of skin diseases caused by mycobacteria is to prevent damage to the skin. The prognosis for these diseases is favorable, however, these skin infections require long-term treatment.

• Mycobacterium tuberculosis(Koch's wand) - causative agent human tuberculosis
• Mycobacterium leprae(Hansen stick) - causative agent leprosy (leprosy)[A30.-]
• Mycobacterium bovis- pathogen bovine tuberculosis and, less frequently human
• Mycobacterium avium- the causative agent of various mycobacterioses, tuberculosis in HIV-infected people, lung infections[A31.0], mycobacterial gastritis and etc.
• Mycobacterium intracellulare and Mycobacterium kansasii- pathogens lung infections[A31.0] and other mycobacterioses
• Mycobacterium ulcerans- pathogen Buruli ulcers[A31.1]
• Mycobacterium marinum- pathogen skin infections[A31.1]

Mycobacterial infections in gastroenterology

Tuberculosis of the intestine

• anus and rectum † (K93.0*)
• intestines (large) (small) † (K93.0*)
• retroperitoneal (lymph nodes)

Note. In ICD-10, a cross † marks the main underlying disease codes that must be used. An asterisk * marks optional additional codes related to the manifestation of the disease in a separate organ or area of ​​the body, which is an independent clinical problem.

Tuberculosis of the intestine is a chronic infectious disease caused by mycobacteria. Mycobacterium tuberculosis. Usually it is a secondary process that occurs against the background of pulmonary tuberculosis. It is manifested by the formation of specific granulomas in various parts of the intestine, more often in the ileocecal region.

Tuberculous ileotiflitis (tuberculosis of the caecum) is a tuberculous lesion of the ileocecal region.

Although the defeat of the stomach in tuberculosis is quite rare, in recent years there has been a significant increase in the incidence and mortality from this disease, which is due to a number of reasons:

• a sharp increase in population migration;
• insufficient level of anti-tuberculosis measures;
• an increase in cases of tuberculosis caused by drug-resistant mycobacteria.

The defeat of the stomach is more often observed in secondary tuberculosis, which is due to the ingestion of sputum containing mycobacteria by the patient. In addition, damage to the gastric mucosa may be due to the spread of infection through the lymphatic vessels from the affected mesenteric lymph nodes.

There are such forms of tuberculous lesions of the stomach:

• ulcerative
• hypertrophic (tumor-like)
• fibrosclerotic
• ulcerative hypertrophic (mixed)

Recognition of gastrointestinal tuberculosis is a rather difficult task. The diagnosis is verified mainly on the basis of the results of bacteriological or histological examination. In addition to taking an anamnesis aimed at identifying the relationship between the disease and tuberculosis infection, it is necessary to use all the currently existing diagnostic methods: examination, percussion, palpation of the patient, detection of Mycobacterium tuberculosis in the contents of the stomach and intestines, tuberculin diagnosis, polymerase chain reaction to identify a specific pathogen, detection in blood antigens of mycobacteria and antibodies by immunological methods (enzymatic immunoassay), radiological, instrumental methods, histological and bacteriological studies of biopsy material, sonography (Frolova-Romanyuk E.Yu.).

Gastritis and duodenitis caused by mycobacteria in perspective classifications

In the section Infectious gastritis (infectious gastritis) there is a subsection Bacterial gastritis (bacterial), where, among other types of bacterial gastritis, there is:

• Mycobacterial gastritis (mycobacterial gastritis)
• Tuberculous gastritis (tuberculous gastritis)
• Non-tuberculous mycobacterial gastritis (non-tuberculous mycobacterial gastritis)
• Mycobacterium avium-intracellulare gastritis (gastritis caused by infection Mycobacterium avium)
• Gastritis due to other specified non-tuberculous mycobacteria

• Mycobacterial duodenitis (mycobacterial)
• Non-tuberculous mycobacterial duodenitis (non-tuberculous mycobacterial)
• Tuberculous duodenitis (tuberculosis duodenum)

Mycobacteria in modern* taxonomy of bacteria