Mycobacteria.
The composition of the genus Mycobacterium families Mycobacteriaceae included acid- and alcohol-resistant aerobic still gram-positive straight or curved rod-shaped bacteria. Sometimes they form filamentous or mycelial structures. It is characterized by a high content of lipids and waxes (up to 60%). Catalase- and arylsulfatase-positive, resistant to the action of lysozyme... They grow slowly or very slowly.
Mycobacteria are widespread in the environment - water, soil, plants and animals.
On the basis of pathogenicity, the actual pathogenic, causing 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 system, bones, joints, skin, urogenital and some other organs. The disease has been known since ancient times. The pulmonary form of tuberculosis is described by ancient authors (Arteyus of Cappadocia, Hippocrates, etc.) However, the ancient invaders did not consider it as an infection, Ibn Sina considered it a hereditary disease. Fracastoro was the first to point directly to its infectious nature, and Sylvius noted the connection of pulmonary tubercles with consumption. The variety of clinical manifestations of tuberculosis led to many erroneous ideas: de Laaeneck attributed the pulmonary tubercles to malignant neoplasms, Virchow did not associate caseous necrosis with the tuberculous process. The growth of cities, overcrowding of the population and a low sanitary standard of living led to the fact that in the 18-19 centuries. tuberculosis reaped a bountiful harvest among different strata 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 Koch's short message at a meeting of the Berlin Physiological Society on March 24, 1882 on the etiology of tuberculosis, in which he outlined the basic 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 the pathological process; unfavorable living and working conditions play a special role. Currently, an increase in the incidence is observed, 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, apparently due to the displacement of natural competitors as a result of the use of antimicrobial agents.
b) Of no less importance are the "aging" of the population around the world and the increase in the number of people with chronic diseases accompanied by impaired immunity.
v) a special role in infection Mycobacterium Tuberculosis the overcrowding of the population plays: in the Russian Federation - pre-trial detention centers, refugee camps, people "homeless".
Morphology and tinctorial properties.
Thin, straight or slightly curved rods measuring 1-10 * 0.2-0.6 microns, with slightly curved ends, contain granular formations in the cytoplasm. The morphology varies depending on the age of the culture and the cultivation conditions - in young cultures, the rods are longer, and in old ones, they tend to simple branching. Sometimes form coccoid structures and L-forms retaining infectiousness, as well as filterable forms.
Immobile, do not form spores, lack capsules, but they have a microcapsule separated from the cell wall by an osmophobic 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 the rods.
Gram-positive, aniline dyes are perceived poorly, according to Ziehl-Nielsen they are colored in bright red, according to Much-Weiss - in violet (iodophilicity).
Cultural properties. Aerobes, but capable of growing under facultative anaerobic conditions, 5-10% CO2 content contributes to faster growth. They multiply by division, the process is very slow, an average of 14-18 hours. Temperature optimum 37-38 ° C, pH 7.0-7.2
(grows in the range of 4.5 - 8.0).
For growth, it needs the presence of a protein substrate and glycerin, 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, Petraniani, Dose), synthetic and semi-synthetic liquid media (Soton's medium) are used. On liquid media, growth is observed on the 5-7th day in the form of a dry wrinkled film (R - shape), rising to the edges of the test tube, the medium remains transparent. In media containing detergent (Tween-80), they give uniform growth throughout the medium. On liquid media and during intracellular development, the characteristic cord factor ( trehalose-6,6-dimicolate), causing the convergence of bacterial cells in microcolonies, their growth in the form of serpentine braids and related to the virulence of the pathogen. On solid media, growth is noted on the 14-40th day in the form of a dry, wrinkled cream-colored plaque, colonies with a raised center, resembling cauliflower, are crumbly, poorly wetted with water and have a pleasant aroma. Cultures are poorly removed from the environment, and crackle when pierced. Under the influence of antibacterial drugs, they can disassociate 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 niacin (niacin), which is used for its differential diagnosis with other mycobacteria (niacin test), one of the conditions is the need for sowing 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 grayish, oily plaque formed by elongated branching rods.
Koch's wand It is quite resistant to various influences, it dies in milk after 15-20 minutes at a temperature of 60 degrees C, at a similar temperature in sputum it lasts up to an hour, when boiled it dies after 5 minutes. Direct sunlight kills Koch's bacillus after 45-55 minutes, diffused light - after 8-10 days. Keeps well 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 phagocytose 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 determined 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, primary affect. In dynamics, along the regional lymphatic pathways 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 is not characteristic and is a cellular response of HRT. Sensitization of the body is due to the action of a number of mycobacterial products, known as old Koch tuberculin, which exhibits local and systemic effects. To a certain extent, the formation of granulomas is facilitated by the formation of lactic acid, a low pH value, and a high concentration of CO2. In the center of each tubercle there is a section of curdled necrosis, where Koch's bacillus 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 there are lymphocytes, plasma cells and mononuclear cells, most often the primary focus is observed in the lungs (Gona focus). In granulomas, the reproduction of the pathogen usually slows down or stops altogether.
Quite characteristic latency period"- a condition in which the penetrated mycobacteria do not cause the development of inflammatory reactions and freely disseminate throughout the body.
In most cases, the primary lesions heal with complete
degradation of the contents, its 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 radiographically.
Primary tuberculosis is characterized by a high sensitivity of tissues to metabolites of mycobacteria, which contributes to their sensitization, with healing of affect, hypersensitivity 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, are possible; they are usually localized in the lungs, kidneys, genitals and bones.
b) With a weakening of the body's immunity, 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, which causes a variety of toxic-allergic reactions in the patient.
reactivation occurs 20-25 years after the initial infection. Usually it is provoked by stress, nutritional disorders 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 coughed up.
Clinically reactive tuberculosis is manifested by coughing, frequent hemoptysis, weight loss, profuse night sweats, and chronic low-grade fever.
v) In more rare cases, in debilitated adolescents and adults, as well as in patients with immunodeficiency, it is observed disseminated (miliary) tuberculosis, characterized by the formation of granulomas in various organs.
the development of generalized lesions often occurs after the breakthrough of the granuloma contents into the bloodstream.
General manifestations are similar to those in secondary tuberculosis, but lesions of the brain and its membranes are often added to them, the prognosis of this form is the most unfavorable.
The variety of forms led to the complexity of its classification.
Currently, clinical classification distinguishes three main forms:
Tuberculous intoxication in children and adolescents.
Respiratory tuberculosis, including primary complex, damage to internal lymph nodes, pleura, upper respiratory tract, focal, infiltrative, cavernous, fibro-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 system, etc.
Laboratory diagnostics.
Includes methods included in the mandatory diagnostic minimum and additional research methods.
A). In case of illness - microscopy of pathological material(sputum, discharge from fistulas, urine, washings from the bronchi) in smears stained according to Ziehl-Nielsen, red acid-resistant sticks can be detected (In recent years, the Murahashi-Yoshida method was introduced, which allows to differentiate between dead and live bacteria).
with an insignificant 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 detritus and extraneous bacteria are removed by centrifugation, the precipitate is neutralized with a 30% solution of acetic acid and smears are prepared, stained according to Ztlu-Nelsen or Quignon.
the flotation method is more effective - a solution of NaOH, distillate, xylene (benzene) is introduced into the material and vigorously shaken, the resulting foam floats and captures mycobacteria, it is sucked off and smears are prepared.
The quantitative assessment of the population of mycobacteria by the Gaffki-Stinken method (counting bacteria on calibrated glasses in certain fields of view) has a certain value in assessing the severity of the process, the effectiveness of treatment and the prognosis of the disease.
The most effective bacterioscopic method is fluorescence microscopy since staining with a fluorochrome (for example, auramine-rhodamine) makes it possible to detect even a small amount of mycobacteria (stained white-yellow), as well as forms with altered cultural and tinctorial properties.
B) Isolation of the pathogen. Before inoculation, the studied material can be treated according to Ulengut or Sumioshi (15-20% HCl or H2SO4 solution), the test samples are centrifuged, washed with saline and inoculated, carefully rubbed 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 this method is the duration of the result - from 2 to 12 weeks.
The advantage is the possibility of obtaining a pure culture, which allows it to be identified, to evaluate its virulent properties, and to determine the sensitivity to drugs.
Accelerated methods of isolating the pathogen (Price) have been developed, the material is placed on a glass slide, treated with H2SO4, washed with saline and introduced into a nutrient medium supplemented with citrated blood. The glass is taken out after 3-4 days and stained according to Tsil-Nelsen.
- "Gold standard" - in the diagnosis of tuberculosis - biological assay on guinea pigs infected subcutaneously or intraperitoneally 1 ml of material obtained from the patient. In animals, a generalized infection develops, leading to death in 1-2 months, however, the disease can be recognized earlier by setting tests with tuberculin - after 3-4 weeks, and lymphadenitis already on 5-10 days. Their points contain a large number of bacteria. However, the appearance of resistant and altered mycobacteria reduced the sensitivity of this sample. To increase it, intra-testicular infection is used, or the immunity of the animal body is suppressed by the administration of glucocorticoids.
G. Serological studies. A large number of different reactions have been proposed that detect the antigen of mycobacteria and antibodies to them, for example, RSK, RA. RPGA for Boyden. ELISA.
E. Skin tests with tuberculin are of particular importance, as they allow large-scale screening surveys of the population. The method includes the introduction of small doses (usually 5 units)
PPD-L into skin incisions (Pirquet's reaction), subcutaneously (Koch's reaction).
If the result is positive, after 48 hours (in the elderly, after 72 hours), a papule with a diameter of 10 mm with hyperemic edges is formed at the injection site. In most countries, the Mantoux test is the most common, because the results of the Pirquet reaction often cause difficulties in their interpretation.
A positive Mantoux test indicates a person's contact with the antigen. Mycobacterium Tuberculosis or other bacteria that cross-react. A positive reaction cannot be seen as a sign of an active process.
With a papule of 5-10 mm, the result is doubtful and the test must be repeated with the introduction of 10 units.
At smaller sizes - a negative result. (Does not always indicate the absence of the process - in immunodeficient individuals).
E. PCR - diagnostics.
G. Additional laboratory methods- assessment of the immune status.
Bacterioscopy
(gram-positive sticks
Sputum, urine, pus, punctate, etc.
Bacterioscopy
Bacterioscopy
Bioassay
Mycobacterium Lehmann & Neumann, 1896
| Taxonomy on Wikisource |
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Mycobacteria (Mycobacteriaceae) is a family of actinomycetes. The only genus - Mycobacterium... Some members of the genus Mycobacterium(ex. M. tuberculosis, M. leprae) pathogens for mammals (see tuberculosis, mycobacteriosis, leprosy).
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 multiply by cell division. Widely distributed in soil. Saprophytic forms are involved in the mineralization of organic residues; some oxidize paraffins and other hydrocarbons. Can be used to combat oil pollution of the biosphere. ...
Pigmentation
According to Runyon's classification of non-tuberculous mycobacteria based on cultural differences from G., 4 groups of mycobacteria are distinguished by the production of pigment by colonies:
Photochromogenic (Group I) mycobacteria that are not pigmented when grown in the dark, but acquire a bright yellow or yellow-orange pigmentation after incubation or incubation 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. In total, 74 species of such mycobacteria are known. They are widespread in soil, water, and among humans.
Tuberculosis in humans causes Mycobacterium tuberculosis typus (human species), Mycobacterium bovis(bovine) and Mycobacterium africanum(intermediate view). These species are able to penetrate, live and reproduce inside humans.
Representatives of the genus of mycobacteria
In the old system, mycobacteria were classified according to 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 tuberculosis. The complex includes: M. tuberculosis, the most dangerous for 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), 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
Mycolactone-producing mycobacteria
- 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
- M. szulgai
- M. lepraemurium
- M. lepromatosis, another (less common) cause of leprosy
- M. africanum
- M. botniense
- M. chimaera
- M. conspicuum
- M. doricum
- M. farcinogenes
- M. heckeshornense
- M. intracellulare
- M. lacus
- M. marinum
- M. monacense
- M. montefiorense
- M. murale
- M. nebraskense
- M. saskatchewanense
- M. shimoidei
- M. tusciae
With an average growth time
- M. intermedium
Fast growing
Сhelonae-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. thermoresistibile
- 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
- M. pulveris
Uncategorized
- M. arosiense
- M. aubagnense
- M. caprae
- M. chlorophenolicum
- M. fluoroanthenivorans
- M. kumamotonense
- M. novocastrense
- M. parmense
- M. phocaicum
- M. poriferae
- M. rhodesiae
- M. seoulense
- M. tokaiense
Literature
- Biological encyclopedic dictionary. M., Soviet Encyclopedia, 1989
Atypical (non-tuberculosis, non-tuberculous) mycobacteria belong to the Mycobacteriaceae family and differ from M. tuberculosis in terms of nutrient requirements, ability to form pigments, enzymatic activity and sensitivity to anti-tuberculosis drugs. In addition, M. tuberculosis usually spreads 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 how they are transmitted. Thus, 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 representatives of hospital microflora, therefore they cause hospital outbreaks of wound infection or infection associated with venous catheters. M. ulcerans is isolated exclusively from the water and soil of the jungle; it is the causative agent of chronic skin infections in the tropics. The M. avium mycobacterium is found in abundance in water, soil, and aerosols from the acidic brown water of swamps in the southeastern United States. In rural areas of this region, asymptomatic infections caused by the M. avium complex are transmitted by about 70% of people by the time they enter adulthood.
In children, atypical mycobacteria rarely become infectious agents (with the exception of cervical lymphadenitis). Infections with atypical mycobacteria (especially with the M. avium complex) are the most common infections that occur in the terminal period.
Pathogenesis
Histologically, the 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), irregular 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 reaction is usually mild, and the tissues contain a large number of histiocytes filled with acid-fast rods.
Clinical manifestations
In children, the most common manifestation of atypical mycobacterial infections is lymphadenitis of the anterior cervical or submandibular lymph nodes; occasionally, the 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 in 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 spaced 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 may return to their original size in some cases, but most often they fester after a few weeks. Fluctuation appears in the center of the lymph node, and the skin above it becomes hyperemic and becomes thinner. Soon the lymph node is opened and a skin fistula is formed, which 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 of atypical mycobacteria are rare. Usually, the infection develops after getting into the skin wound (small abrasion on the elbow, knee or foot in swimmers; abrasions on the hands of aquarists' granulomas) of water contaminated with M. marinum. Within a few weeks, a single nodule develops at the site of the injury - a bather's granuloma. Usually the nodule is painless, and increases 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: satellites 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 destruction of soft tissue and be complicated by a secondary bacterial infection. Within 6-9 months. the ulcer can heal or continue to grow, which is 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 puncture wounds or minor abrasions. Clinical manifestations (localized phlegmon, painful nodules, or abscess with fistulous tract) usually occur after 4-6 weeks. Described a single case of mastitis caused by M. abscessus, caused by piercing of the nipple of the mammary gland. M. haemophilum causes painful subcutaneous nodules in immunosuppressed patients (especially after kidney transplantation); these nodules often ulcerate and fester.
Among the causative agents of infections associated with venous catheters, the proportion of atypical mycobacteria is small, but it is growing. Such infections are bacteremia or suppuration during catheter insertion; 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. Nevertheless, in children with normal immunity, acute pneumonia caused by the M. avium complex, prolonged cough or wheezing due to compression of the airways by enlarged paratracheal or parabronchial lymph nodes have been described. Also described are isolated cases of progression of infection with granulomatous inflammation of the bronchi. 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 diseases, 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. Characterized by the formation of thin-walled cavities, the infiltration of the parenchyma around which is expressed minimally; sometimes the radiological picture resembles tuberculosis.
Rarely, usually in patients with surgery or puncture wounds, atypical mycobacteria can cause infections of the bones and joints indistinguishable from those caused by M. tuberculosis and other bacteria. In patients with puncture wounds to the feet, M. fortuitum causes infections similar to those caused by Pseudomonas aeruginosa or Staphylococcus aureus.
Atypical mycobacteria, usually belonging to the M. avium complex, occasionally cause disseminated infection without visible signs of immunodeficiency. Most children have gene mutations that code for IFN-y or IL-12 receptors, or the formation of IL-12. In the absence of receptors for IFN-y, a severe infection develops that is difficult to treat. Infections in children with a deficiency of IFN-y receptors or gene mutations that are involved in the synthesis of IL-12 are easier and can be treated with interferon and antimycobacterial agents. The frequency 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 M. avium complex, one of the most frequent opportunistic infections, especially in the late stages of AIDS, when the number of CD4 lymphocytes falls below 100 / mm3. Disseminated infection, most likely, is preceded by colonization of the respiratory tract or gastrointestinal tract by the M. avium complex. But the study of the secretion of the respiratory tract or feces for this pathogen does not predict the possibility of dissemination. For disseminated infection, long-term bacteremia with a high content of pathogens in the blood and damage to many organs, primarily the lymph nodes, liver, spleen, bone marrow and gastrointestinal tract, are typical. The thyroid, pancreas, adrenal glands, 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, loss of appetite, severe weight loss, weakness, generalized lymphadenopathy, and hepatosplenomegaly. Jaundice, increased alkaline phosphatase activity, and neutropenia are also possible. Radiation studies usually show a pronounced 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 (causative agent - Bartonella henselae), mononucleosis, toxoplasmosis, brucellosis, tularemia and malignant tumors, primarily lymphomas. Mantoux test with 5 tuberculin units is usually weakly positive (infiltration with a diameter of 5-15 mm). The CDC has created skin test antigens to distinguish between mycobacteria belonging to different Runyon groups, but these antigens are no longer being released. 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 increase on one side, chest radiographs are normal, there is no contact with an adult patient with tuberculosis. With tuberculous lymphadenitis, as a rule, there is a bilateral enlargement of the posterior cervical lymph nodes, the diameter of the infiltrate during the Mantoux test exceeds 15 mm, the chest X-ray reveals pathology, and it is also possible to identify contact with an adult patient with tuberculosis. The final diagnosis is made after removal of the affected lymph nodes and culture.
Diagnosis of mycobacterial skin infections is based on sowing a biopsy specimen from the lesion. Diagnosis of respiratory tract infections caused by atypical mycobacteria is difficult, since many of the atypical mycobacteria, including the M. avium complex, can be sown from the secretions of the oral cavity and stomach in healthy children. Definitive diagnosis requires invasive examinations such as bronchoscopy with bronchial or lung biopsy. Mycolic acids and other lipids contained in the cell wall of mycobacteria give them acid resistance when stained according to Tsilu-Nelsen or Kinyun. Mycobacteria can also be detected by staining with fluorescent dyes such as auramin and rhodamine. The sensitivity of staining atypical mycobacteria in tissues is lower than when M. tuberculosis is detected.
The sensitivity of blood cultures in AIDS patients with disseminated infection with atypical mycobacteria reaches 90-95%. Sowing blood on special media in which the radiometric method is used makes it possible to detect the M. avium complex in almost all patients within a week. DNA probes are also produced, with the help of which it is possible to distinguish between atypical mycobacteria and M. tuberculosis. A quick method for preliminary diagnosis of disseminated mycobacterial infection is the detection in the bone marrow and biopsies of other tissues of histiocytes containing many acid-resistant rods.
Treatment of atypical mycobacteria
For infections with atypical mycobacteria, both conservative and surgical treatment, as well as their combination, is used. 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-TB 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 inconsistent. 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 the capsule is intact. The development of extensive breech necrosis with the transition to the surrounding tissues complicates excision, and also increases the likelihood of complications (damage to the facial nerve, recurrence of infection). You should not remove only part of the lymph nodes, 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 obtained. 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 successful use of drug treatment alone or its combination with removal of lymph nodes. According to most reports, clarithromycin or azithromycin was used with rifabutin or ethambutol.
Skin infections caused by mycobacteria usually heal on their own. M. marinum is sensitive 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 begin parenteral administration of amikacin, cefoxitin or clarithromycin. For respiratory infections, a combination of isoniazid, rifampicin, and pyrazinamide is prescribed until the sensitivity test is obtained.
In case of disseminated infection with the M. avium complex, patients with impaired IL-12 synthesis or deficiency of IFN-y receptors are shown a combination of clarithromycin or azithromycin with one or more of the following drugs: rifabutin, clofazimine, ethambutol and fluoroquinolones. Treatment continues for at least 12 months. Determining the sensitivity of the pathogen in vitro is important. After the end of treatment, life-long prevention of relapse is recommended, for which a daily intake of clarithromycin is prescribed. The presence of specific genetic defects is an indication for the appointment of interferon.
In adult AIDS patients, daily prophylactic intake of azithromycin or its combination with rifabutin reduces the incidence of infections caused by the M. avium complex by more than 50%.
The article was prepared and edited by: surgeon
Non-tuberculous mycobacteria are independent species, widespread in the environment, like saprophytes, which in some cases can cause severe diseases - mycobacteriosis. They are also called environmental micabacteria, mycobacteriosis pathogens, opportunistic and atypical mycobacteria. A significant difference between non-tuberculosis mycobacteria and mycobacterium tuberculosis complex is that they are practically not transmitted from person to person.
Non-tuberculous mycobacteria are divided into 4 groups according to a limited number of traits: growth rate, pigment formation, colony morphology and biochemical properties.
1st group - slow-growing photochromogenic (M. kansasii and others). The main sign of representatives of this group is the appearance of pigment in the light. They form colonies from S to RS-forms, contain carotene crystals, which color them yellow. Growth rate from 7 to 20 days at 25, 37 and 40 ° C, catadase positive.
M. kansasii - yellow bacilli, live in water, soil, most often infect the lungs. These bacteria can be identified by their large size and cruciform arrangement. An important manifestation of infections caused by M. kansasii is the development of disseminated disease. There are also possible lesions of the skin and soft tissues, the development of tenosynovitis, osteomyelitis, lymphadenitis, pericarditis and infections of the urinary tract.
2nd group - slow-growing cathochromogenic (M. scrofulaceum, M. matmoense, M. gordonae, etc.). Microorganisms form II in the dark yellow, and in the light orange or reddish colonies, usually S-shaped colonies, grow at 37 ° C. This is the largest group of non-tuberculous mycobacteria. They are isolated from polluted water bodies and soil and have a slight pathogenicity for humans and animals.
M. scrofulaceum (from the English scrofula - scrofula) is one of the main reasons for the development of cervical lymphadenitis in children under 5 years of age. In the presence of severe concomitant diseases, they can cause damage to the lungs, bones and soft tissues. In addition to water and soil, microbes are isolated from raw milk and other dairy products.
M. maimoense - microaerophiles, form grayish-white smooth shiny opaque dome-shaped round colonies.
Primary isolates grow very slowly at 22-37 ° C. Exposure to light does not cause pigment production. If necessary, exposure is continued up to 12 weeks. In humans, they cause chronic lung disease.
M. gordonae are the most widespread recognized saprophytes, cathochromogens of water-flowing water, cause mycobacteriosis extremely rarely. In addition to water (known as M. aquae), they are often isolated from soil, gastric lavage, bronchial secretions, or other material from patients, but in most cases they are non-pathogenic to humans. At the same time, there are reports of cases of meningitis, peritonitis and skin lesions caused by this type of mycobacteria.
3rd group - slow-growing nonchromogenic mycobacteria (M. avium complex, M. gaslri M. terrae complex, etc.). They form colorless S- or SR- and R-forms of colonies, which can have light yellow and cream shades. They are excreted from sick animals, from water and soil.
M. avium - M. inlracellulare are combined into one M. avium complex as their interspecific differentiation presents certain difficulties. Microorganisms grow at 25-45 ° C, pathogenic for birds, less pathogenic for cattle, pigs, sheep, dogs and not pathogenic for guinea pigs. Most often, these microorganisms cause lung damage in a person. Described lesions of the skin, muscle tissue and bone skeleton, as well as disseminated forms of diseases. They are among the causative agents of opportunistic infections that complicate the acquired immunodeficiency syndrome (AIDS). M. avium paratuberculosis subspecies is the causative agent of Jones disease in cattle and possibly Crohn's disease (chronic inflammatory disease of the gastrointestinal tract) in humans. The microbe is present in the meat, milk and feces of infected cows, and is also found in water and soil. Standard water treatment methods do not inactivate this microbe.
M. xenopi causes lung damage in humans and disseminated forms of disease associated with AIDS. They are isolated from frogs of the genus Xenopus. The bacteria form small, non-pigmented colonies with a smooth shiny surface, which subsequently turn bright yellow. Thermophiles do not grow at 22 ° C and grow well at 37 and 45 ° C. During bacterioscopy, they look like very thin sticks, tapering at one end and located parallel to each other (and in the form of a palisade). Often excreted from cold and hot tap water, including drinking water stored in hospital tanks (nosocomial outbreaks). Unlike other opportunistic mycobacteria, they are sensitive to the action of most anti-tuberculosis drugs.
M. ukerans is an etiological agent of mycobacterial cutaneous N (Buruli ulcer), grows only at 30-33 ° C, Colony growth is noted only after 7 weeks. Isolation of the pathogen also occurs when mice are infected into the pulp of the sole of the paws. The disease is common in Australia and Africa. The source of infection is a tropical environment and BCG vaccination with a vaccine against this mycobacteriosis.
4th group - fast-growing mycobacteria (M. fortuitum complex, M. phlei, M. xmegmatis, etc.). Their growth is noted in the form of R- or S-forms of colonies within 1-2 to 7 days. They are found in water, soil, sewage and are representatives of the normal microflora of the human body. Bacteria of this group are rarely isolated from pathological material from patients, but some of them are of clinical importance.
The M. fortuitum complex includes M. fortuitum and M. chcionae, which are sub-species. They cause disseminated processes, skin and postoperative infections, and lung diseases. The microbes of this complex are highly resistant to anti-tuberculosis drugs.
M smegmatis is a representative of normal microflora; it is isolated from smegma in men. Grows well at 45 ° C. As a causative agent of human diseases, it ranks second among the fast-growing mycobacteria after the M. fortuitum complex. Affects skin and soft tissues. The causative agents of tuberculosis must be differentiated from M. smegmatis in the study of urine.
Epidemiology of mycobacteriosis
The causative agents of mycobacteriosis are widespread in nature. They can be found in soil, dust, peat, mud, river water, ponds and swimming pools. They are found in ticks and fish, cause diseases in birds, wild and domestic animals, are representatives of the normal microflora of the mucous membranes of the upper respiratory tract and the urinary tract in humans. Infection with non-tuberculous mycobacteria occurs from the environment aerogenically, by contact with damage to the skin, as well as by food and water. Human-to-human transmission of microorganisms is uncommon. These are conditionally pathogenic bacteria, therefore, a decrease in the resistance of a macroorganism and its genetic predisposition are of great importance in the onset of the disease. Granulomas form in the affected areas. In severe cases, phagocytosis is incomplete, bacteremia is expressed, and macrophages filled with non-tuberculous mycobacteria and resembling leprosy cells are determined in the organs.
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Symptoms of mycobacteriosis
The symptoms of mycobacteriosis are varied. The respiratory system is most often affected. The symptomatology of pulmonary pathology is similar to that of tuberculosis. At the same time, there are frequent cases of extrapulmonary localization of the process involving the skin and subcutaneous tissue, wound surfaces, lymph nodes, urogenital organs, bones and joints, as well as the meninges. Organ lesions can begin both acutely and latently, but are almost always difficult,
The development of a mixed infection (mixt infection) is also possible; in some cases, they can be the cause of the development of a secondary endogenous infection.
Microbiological diagnosis of mycobacteriosis
The main method for diagnosing mycobacteriosis is bacteriological. Material for research is taken based on the pathogenesis and clinical manifestations of the disease. Initially, the question of whether the isolated pure culture belongs to the causative agents of tuberculosis or non-tuberculosis mycobacteria is solved. Then a set of studies is used to establish the type of mycobacteria, the degree of virulence, as well as the Runyon group. Primary identification is based on traits such as growth rate, ability to form pigments, colony morphology, and ability to grow at different temperatures. To identify these signs, additional equipment and reagents are not required, so they can be used in basic laboratories of anti-tuberculosis dispensaries. Final identification (reference identification) using complex biochemical studies is carried out in specialized moratoriums of scientific institutions. In most cases, preference is given to their identification by biochemical facts, such as modern molecular genetic methods are laborious, have many preparatory stages, require special equipment, and are expensive. Determination of antibiotic sensitivity is of great importance for the liver. Of decisive importance for the diagnosis of mycobacteriosis is the criterion of the simultaneity of the appearance of clinical, radiological, laboratory data and the isolation of a pure culture of non-tuberculosis mycobacteria, conducting multiple studies in dynamics.
The genus Mycobacterium (family Mycobacteriaceae, order Actinomycetales) includes more than 100 species that are widespread in nature. Most of them are saprophytes and opportunistic. In humans, tuberculosis is caused (Mycobacterium tuberculosis - in 92% of cases, Mycobacterium bovis - 5%, Mycobacterium africanus - 3%) and leprosy (Mycobacterium leprae).
Mycobacterium tuberculosis.
Mycobacterium tuberculosis, the main causative agent of tuberculosis in humans, was discovered in 1882 by R. Koch.
Tuberculosis (tuberculosis, phthisis) is a chronic infectious disease. Depending on the localization of the pathological process, tuberculosis of the respiratory organs and extrapulmonary forms (tuberculosis of the skin, bones and joints, kidneys, etc.) are isolated. The localization of the process to a certain extent depends on the ways of penetration of mycobacteria into the human body and the type of pathogen.
Morphology, physiology. Mycobacterium tuberculosis - gram-positive straight or slightly curved rods 1-4 x 0.3-0.4 microns. The high lipid content (40%) gives the cells of mycobacterium tuberculosis a number of characteristic properties: resistance to acids, alkalis and alcohol, difficult perception of aniline dyes (the Ziehl-Nielsen method is used to stain tubercle bacilli, according to this method they are painted pink). There can be no other acid-fast microorganisms in the sputum, therefore, their detection is an indication of possible tuberculosis. In crops, there are granular forms, branching, the grains of the Fly are spherical, acid-yielding, easily stained according to Gram (+). Transition to filterable and L-forms is possible. Immobile, do not form spores and capsules.
For the reproduction of mycobacterium tuberculosis in laboratory conditions, complex nutrient media containing eggs, glycerin, potatoes, and vitamins are used. Stimulates the growth of mycobacteria aspartic acid, ammonium salts, albumin, glucose, tween-80. The most commonly used medium is Lowenstein-Jensen (egg medium with the addition of potato flour, glycerin and salt) and Soton's synthetic medium (contains asparagine, glycerin, iron citrate, potassium phosphate). Mycobacterium tuberculosis multiplies slowly. The generation period is long - under optimal conditions, cell division occurs once every 14-15 hours, while most bacteria of other genera divide in 20-30 minutes. The first signs of growth can be detected 8-10 days after sowing. Then (after 3-4 weeks) on dense media, wrinkled, dry colonies with uneven edges (resembling cauliflower) appear. In liquid media, a delicate film initially forms on the surface, which thickens and falls to the bottom. At the same time, the medium remains transparent.
They are obligate aerobes (settle in the tops of the lungs with increased aeration). Bacteriostats (malachite or brilliant green) or penicillin are added to the media to suppress the growth of the accompanying microflora.
Signs that are used to differentiate Mycobacterium tuberculosis from some other mycobacteria found in the test materials:
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mycobacterium species |
growth time during isolation, days. |
loss of catalase activity after heating for 30 min at 68 ° C |
presence of enzymes |
recovery of nitrates |
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nicotine amidase |
niacinase |
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Designations: + - the presence of a feature, - - the absence of a feature, ± - the feature is unstable.
Antigens. Mycobacterial cells contain compounds whose protein, polysaccharide and lipid components determine antigenic properties. Antibodies are formed on tuberculin proteids, as well as on polysaccharides, phosphatides, cord factor. The specificity of antibodies to polysaccharides, phosphatides is determined in RSK, RNGA, gel precipitation. The antigenic composition of M. tuberculosis, M. bovis, M. leprae, and other mycobacteria (including many saprophytic species) is similar. Tuberculin protein (tuberculin) has pronounced allergenic properties.
Resistance. Getting into the environment, mycobacterium tuberculosis retains its viability for a long time. So, in dried sputum or dust, microorganisms survive for several weeks, in wet sputum - 1.5 months, on objects surrounding the patient (linen, books) - more than 3 months, in water - more than a year; in soil - up to 6 months. These microorganisms persist for a long time in dairy products.
Mycobacterium tuberculosis is more resistant to the action of disinfectants than other bacteria - higher concentrations and a longer exposure time are required to destroy them (phenol 5% - up to 6 hours). When boiled, they die instantly, are sensitive to direct sunlight.
Ecology, distribution and epidemiology. 12 million people are sick with tuberculosis in the world, another 3 million get sick annually. Under natural conditions, M. tuberculosis causes tuberculosis in humans, apes. Among laboratory animals, guinea pigs are highly sensitive, and rabbits are less sensitive. Rabbits are highly sensitive to M. bovis, the causative agent of tuberculosis in cattle, pigs and humans, and guinea pigs are less sensitive. M. africanus causes tuberculosis in humans in tropical Africa.
The source of infection in tuberculosis is people and animals with active tuberculosis, with the presence of inflammatory and destructive changes, secreting mycobacteria (mainly pulmonary forms). A sick person can infect 18 to 40 people. A single contact is not enough for infection (the main condition is prolonged contact). For infection, the degree of susceptibility also matters.
A sick person can excrete from 7 to 10 billion mycobacterium tuberculosis per day. The most common airborne route of infection, in which the pathogen enters the body through the upper respiratory tract, sometimes through the mucous membranes of the digestive tract (alimentary route) or through damaged skin.
Pathogenicity. Mycobacteria do not synthesize exo- and endotoxin. Tissue damage is caused by a number of substances in the microbial cell. Thus, the pathogenicity of tuberculosis pathogens is associated with the direct or immunologically mediated damaging effect of lipids ( wax D, muramine dipeptide, phthionic acids, sulfatides ), which manifests itself when they are destroyed. Their action is expressed in the development of specific granulomas and tissue damage. The toxic effect is exerted by glycolipid (trehalosodimicolate), the so-called cord factor ... It destroys the mitochondria of the cells of the infected organism, disrupts the respiratory function, inhibits the migration of leukocytes to the affected focus. Mycobacterium tuberculosis in cultures with a cord factor form twisting strands.
Pathogenesis of tuberculosis. Tuberculosis is a chronic granulomatous infection that can affect any tissue, according to the frequency in children: lungs, lymph nodes, bones, joints, meninges; in adults: lungs, intestines, kidneys.
Primary tuberculosis (child type) - the infection can last for several weeks. In the zone of penetration and reproduction of mycobacteria, an inflammatory focus occurs (the primary effect is an infectious granuloma), there is sensitization and a specific inflammatory process in the regional lymph nodes (in case of damage to the lungs - chest, pharyngeal lymphoid clusters, tonsils) - the so-called primary tuberculosis complex is formed (as a rule the lower lobe of the right lung is affected). Since a state of sensitization develops, reproduction in a sensitized organ leads to specific changes in the tissue: microorganisms are absorbed by macrophages → a barrier (phagosome) is formed around them → lymphocytes attack these cells (lining up along the periphery of the focus) → specific tubercles (tuberculum - tubercle) are formed - small (diameter 1-3 mm), granular, white or grayish-yellow. Bacteria are located inside, then the limiting belt (giant or epithelioid) cells, then lymphoid cells, then fibroid tissue. Tubercles can merge into conglomerates → vascular compression → circulatory disorders → necrosis in the center of the conglomerate in the form of dry cheese-like crumbs (caseous necrosis). The vessel wall may become necrotic → bleeding.
The resulting tuberculosis can:
● persist for a long time (not accompanied by clinical manifestations);
● in case of a benign course of the disease, the primary focus may dissolve, the affected area can scar (the function of the organ is not impaired) or calcified (foci of Gon are formed, which persist for life without clinical manifestations). However, this process does not end with the complete release of the organim from the pathogen. In the lymph nodes and other organs, tuberculosis bacteria persist for many years, sometimes throughout life. Such people, on the one hand, are immune, but on the other, they remain infected.
● Softening and infiltration of the primary focus may occur → this may be accompanied by a breakthrough of the focus into nearby tissues → can lead to rupture of the bronchus → necrotic tissue slips into the bronchial lumen → a spoon-shaped cavity (caverna) is formed.
If this process takes place in the intestines or on the surface of the skin, a tuberculous ulcer forms.
Chronic tuberculosis (adult type) occurs as a result of reinfection (usually endogenous). The activation of the primary complex develops as a result of reduced body resistance, which is facilitated by unfavorable living and working conditions (poor nutrition, low insolation and aeration, low mobility), diabetes mellitus, silicosis, pneumoconiosis, physical and mental trauma, other infectious diseases, and genetic predisposition. Women are more likely to become chronic. Activation of the primary tuberculosis complex leads to the generalization of the infectious process.
Generalization forms:
● Most often pulmonary (upper and posterior part of the upper lobe) with the formation of cavities, in the walls of the cavities Staphylococcus and Streptococcus can multiply → debilitating fever; if the walls of blood vessels are eroded → hemoptysis. Scars are formed. Sometimes there are complications: tuberculous pneumonia (with a sudden spill of exudate from the focus) and pleurisy (if the damaged areas of the lungs are close to the pleura). Therefore, any pleurisy should be considered as a tuberculous process until proven otherwise.
● The infection can be spread by hematogenous and lymphogenous.
● The bacteria can spread to nearby tissues.
● Can move naturally (from the kidneys to the ureters).
● May spread to the skin.
● Tuberculous sepsis may develop (material loaded with microorganisms from tubercles enters a large vessel).
Dissemination of pathogens leads to the formation of tuberculous foci in various organs, prone to decay. Severe intoxication causes severe clinical manifestations of the disease. Generalization leads to damage to the organs of the genitourinary system, bones and joints, meninges, eyes.
Clinic depends on the localization of the lesion, common is prolonged malaise, rapid fatigue, weakness, sweating, weight loss, in the evenings - subfibril temperature. If the lungs are affected - cough, with destruction of the pulmonary vessels - blood in the sputum.
Immunity. Mycobacterium tuberculosis infection does not always lead to the development of the disease. Susceptibility depends on the state of the macroorganism. It increases significantly when a person is in unfavorable conditions that reduce general resistance (exhausting work, inadequate and malnutrition, poor housing conditions, etc.). Contributes to the development of the tuberculous process and a number of endogenous factors: diabetes mellitus; diseases that are treated with corticosteroids; mental illness, accompanied by depression, and other diseases that reduce the body's resistance. The significance of antibodies formed in the body in the formation of resistance to tuberculosis infection is still unclear. It is believed that antibodies to mycobacterium tuberculosis are "witnesses" of immunity and do not have an inhibitory effect on the pathogen.
Cellular immunity is of great importance. Indicators of its changes are adequate to the course of the disease (by the reaction of lymphocyte blast transformation, the cytotoxic effect of lymphocytes on target cells containing mycobacterial antigens, the severity of the reaction of inhibition of the migration of macrophages). After contact with antigens of mycobacteria, T-lymphocytes synthesize mediators of cellular immunity, which enhance the phagocytic activity of macrophages. With suppression of the function of T-lymphocytes (thymectomy, administration of anti-lymphocyte sera, other immunosuppressants), the tuberculosis process was rapid and difficult.
Microbacteria of tuberculosis are destroyed intracellularly in macrophages. Phagocytosis is one of the mechanisms leading to the release of the body from Mycobacterium tuberculosis, but it is often incomplete.
Another important mechanism contributing to the limitation of the multiplication of mycobacteria, their fixation in the foci, is the formation of infectious granulomas with the participation of T-lymphocytes, macrophages and other cells. This is the manifestation of the protective role of HRT.
Immunity in tuberculosis was previously called non-sterile. But it is not only the preservation of living bacteria that maintain an increased resistance to superinfection that matters, but also the phenomenon of “immunological memory”. With tuberculosis, the HRT reaction develops.
Laboratory diagnostics tuberculosis is carried out by bacterioscopic, bacteriological and biological methods. Allergy tests are sometimes used.
Bacteriological method ... Mycobacterium tuberculosis is detected in the test material by microscopy of smears stained according to Ziehl-Nielsen and using luminescent dyes (most often auramine). You can use centrifugation, homogenization, flotation of the material (homogenization of daily sputum → addition of xylene (or toluene) to the homogenate → xylene floats, entraining mycobacteria → this film is collected on glass → xylene evaporates → smear is obtained → staining, microscopy). Bacterioscopy is considered as an indicative method. Accelerated methods are used for the detection of mycobacteria in crops, for example, according to the Price (microcolony) method. Microcolonies also make it possible to see the presence of the cord factor (the main virulence factor), due to which the bacteria that formed it fold into braids, chains, and bundles.
Bacteriological method is the main one in the laboratory diagnosis of tuberculosis. The isolated cultures are identified (differentiated from other types of mycobacteria), the sensitivity to antimicrobial drugs is determined. This method can be used to monitor the effectiveness of treatment.
Serological methods are not used for diagnostics, since there is no correlation between the content of antibodies and the severity of the process. Can be used in research projects.
Biological method It is used in cases where the pathogen is difficult to isolate from the test material (most often in the diagnosis of renal tuberculosis from urine) and to determine virulence. Material from the patient is contaminated with laboratory animals (guinea pigs susceptible to M. tuberculosis, rabbits susceptible to M. bovis). The observation is carried out for 1-2 months before the death of the animal. From the 5-10th day, you can examine the punctate of the lymph node.
Allergic tests. To carry out these tests, it is used tuberculin- preparation from M. tuberculosis. This substance was first obtained by R. Koch in 1890 from boiled bacteria ("old tuberculin"). Tuberculin, purified from impurities and standardized in ED, is now used (PPD - purified protein derivative). This is the filtrate of bacteria killed by heating, washed with alcohol or ether, freeze-dried. From an immunological point of view, hapten reacts with immunoglobulins fixed on T-lymphocytes.
The Mantoux test is carried out by intradermal injection of tuberculin. Accounting for results in 48-72 hours. A positive result is a local inflammatory reaction in the form of edema, infiltration (induration) and redness - papula. A positive result indicates sensitization (or the presence of mycobacteria in the body). Sensitization can be caused by infection (the reaction is positive 6-15 weeks after infection), illness, immunization (in those vaccinated with a live vaccine).
A tuberculin test is put in order to select for revaccination, as well as to assess the course of the tuberculous process. The Mantoux turn is also important: positive(after a negative test, positive) - infection, negative(after a positive test, negative) - the death of mycobacteria.
Prevention and Treatment. For specific prophylaxis, a live vaccine is used BCG- BCG (Bacille de Calmette et de Guerin). The BCG strain was obtained by A. Calmette and M. Gérin by long-term passaging of tubercle bacilli (M. bovis) on a potato-glycerin medium with the addition of bile. They made 230 passages over 13 years and obtained a culture with reduced virulence. In our country, all newborns are currently vaccinated against tuberculosis on the 5-7th day of life by the intradermal method (the outer surface of the upper third of the shoulder), after 4-6 weeks an infiltrate is formed - pustula (small scar). Mycobacteria take root and are found in the body from 3 to 11 months. Vaccination protects against infection with wild street strains during the most vulnerable period. Revaccination is carried out to persons with a negative tuberculin test with an interval of 5-7 years up to 30 years of age (in grades 1, 5-6, 10 of school). In this way, an infectious immunity is created, in which a HRT reaction occurs.
For the treatment of tuberculosis, antibiotics, chemotherapy drugs, to which pathogens are sensitive, are used. These are drugs of the first row: tubazid, ftivazid, isoniazid, dihydrostreptomycin, PASK and the second row: ethionamide, cycloserine, kanamycin, rifampicin, viomycin. All anti-tuberculosis drugs act bacteriostatically, resistance to any drug quickly develops (cross), therefore, for treatment, combined therapy is carried out simultaneously with several drugs with different mechanisms of action, with frequent changes in the complex of drugs.
The complex of therapeutic measures uses desensitizing therapy, as well as stimulation of the body's natural defense mechanisms.
Mycobacterium leprosy.
The causative agent of leprosy (leprosy) - Mycobacterium leprae was described by G. Hansen in 1874. Lepra is a chronic infectious disease that occurs only in humans. The disease is characterized by generalization of the process, damage to the skin, mucous membranes, peripheral nerves and internal organs.
Morphology, physiology. Mycobacterium leprosy - straight or slightly curved rods from 1 to 7 microns in length, 0.2-0.5 microns in diameter. In the affected tissues, microorganisms are located inside the cells, forming dense globular clusters - leprosy balls, in which the bacteria closely adjoin each other with their lateral surfaces (“cigarette sticks”). Acid-resistant, dyed red by the Ziehl-Nielsen method.
Mycobacterium leprosy is not cultivated on artificial nutrient media. In 1960, an experimental model was created with the infection of white mice in the pads of the paws, and in 1971 - of armadillos, in which typical granulomas (leprosy) form at the injection site of mycobacterium leprosy, and with intravenous infection, a generalized process develops with the reproduction of mycobacteria in the affected tissues.
Antigens. Two antigens were isolated from the leproma extract: a thermostable polysaccharide (group for mycobacteria) and a thermolabile protein, highly specific for leprosy rods.
Ecology and distribution. The natural reservoir and source of the causative agent of leprosy is a sick person. Infection occurs with prolonged and close contact with the patient.
The properties of the pathogen and its relation to the effects of various environmental factors have been insufficiently studied.
Pathogenicity of the pathogen and the pathogenesis of leprosy. The incubation period of leprosy is on average 3-5 years, but lengthening up to 20-30 years is possible. The disease progresses slowly over many years. There are several clinical forms, of which the most severe and epidemically dangerous is lepromatous: on the face, forearms, and legs, multiple infiltrates-lepromas are formed, which contain a huge number of pathogens. In the future, lepromas disintegrate, slowly healing ulcers are formed. The skin, mucous membranes, lymph nodes, nerve trunks, and internal organs are affected. Another form - tuberculoid - is clinically easier and less dangerous to others. With this form, the skin is affected, and the nerve trunks and internal organs are less common. Rashes on the skin in the form of small papules are accompanied by anesthesia. There are few pathogens in the lesions.
Immunity. During the development of the disease, sharp changes in immunocompetent cells, mainly the T-system, occur - the number and activity of T-lymphocytes decreases and, as a result, the ability to respond to antigens of mycobacterium leprosy is lost. Mitsuda's reaction to the introduction of lepromin into the skin in patients with lepromatous form, occurring against the background of deep suppression of cellular immunity, is negative. In healthy individuals and in patients with tuberculoid leprosy, it is positive. This indicator, therefore, reflects the severity of the T-lymphocyte lesion and is used as a prognostic one, characterizing the effect of treatment. Humoral immunity is not impaired. In the blood of patients, antibodies to mycobacterium leprosy are found in high titers, but they, apparently, do not play a protective role.
Laboratory diagnostics. The bacterioscopic method, examining scrapings from the affected areas of the skin, mucous membranes, reveals characteristically located mycobacterium leprosy of a typical form. The smears are stained according to Ziehl-Nielsen. There are currently no other methods of laboratory diagnostics.
Prevention and Treatment. There is no specific prevention of leprosy. A complex of preventive measures is carried out by anti-leprosy institutions. Patients with leprosy are treated in leper colony until clinical recovery, and then on an outpatient basis.
In our country, leprosy is rarely recorded. Isolated cases occur only in some areas. According to the WHO, there are more than 10 million patients with leprosy in the world.
Leprosy is treated with sulfone drugs (diacetylsulfone, selusulfone, etc.). They also use desensitizing agents, drugs used to treat tuberculosis, as well as biostimulants. Methods of immunotherapy are being developed.
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