The causative agent of tuberculosis is microbiology. Pathogenic mycobacteria - F. K. Cherkes Mycobacterium tuberculosis microbiology
![The causative agent of tuberculosis is microbiology. Pathogenic mycobacteria - F. K. Cherkes Mycobacterium tuberculosis microbiology](https://i2.wp.com/img-lib.med-tutorial.ru/2239746527/b00005354.jpg)
Pathogen
Mycobacterium tuberculosis - acid-, alcohol- and alkali-resistant microorganisms. They are motionless, do not form spores and capsules, do not have flagella. The typical shape is slender or slightly curved sticks with rounded edges. In the electron microscope, all types of mycobacteria look like rods with rounded edges. However, there are often curved and oval shapes. Cell sizes can vary significantly depending on the age of the culture: length from 1.5 to 4 µm, width from 0.2 to 0.5 µm. The phylogenetic proximity of Mycobacterium tuberculosis with radiant fungi-actinomycetes has been established: the slow development of mycobacteria on elective nutrient media, the method of reproduction, polymorphism and the ability, under certain conditions, to sometimes form filamentous branched forms with bulb-shaped swellings at the ends. This was the reason for replacing the name of Koch's bacillus with Mycobacterium tuberculosis (Mus. tuberculosis).
Mycobacteria are characterized by a high lipid content (from 30.6 to 38.9%), as a result, they are difficult to stain with aniline dyes, but they perceive the dye well after treatment with carbolic fuchsin when heated. With this method, Mycobacterium tuberculosis retains dyes well and does not discolor when exposed to diluted acids, alkalis and alcohol, which distinguishes it from other microbes. This is the basis of the Ziehl-Neelsen staining method for mycobacteria.
Mycobacteria stain positively for Gram with difficulty and acquire a blue-violet color.
For the rapid detection of mycobacteria in various objects, there is a luminescent method, which is based on their ability to stain with luminescent dyes (rhodamine-auramine) and give a golden yellow color under the influence of ultraviolet radiation. The method has high sensitivity, gives a color image of the pathogen. The study is carried out at medium magnification, which makes it possible to view a larger field than with immersion microscopy at high magnification.
Thanks to electron microscopy, a three-layer cell wall, a microcapsule, a cytoplasmic membrane, etc. were revealed in mycobacteria. The composition of the cytoplasmic membrane includes lipoprotein complexes, various enzyme systems, in particular, those responsible for redox processes. The cytoplasm of mycobacteria is represented by granules, vacuoles and cavities, the number of which may increase after exposure to chemical agents.
In microcultures developing in liquid nutrient media, mycobacteria of human and bovine species form braids, plaits, whorls, clusters. Microcultures are easily detected by conventional microscopy of smears stained by the Ziehl-Neelsen method. In preparations prepared from primary inoculations, when examined under phase contrast, homogeneous granular elements are usually distinguished, among which there are spherical light-refracting structures.
In cultures isolated from cattle, spherical formations of the correct shape, of the same size, as well as separately lying filamentous structures, are more often found.
cultivation
Mycobacterium tuberculosis reproduces under strictly aerobic conditions on special elective nutrient media containing compounds of carbon, nitrogen, hydrogen and oxygen, as well as magnesium, potassium, sulfur and phosphorus. Iron salts and some other elements have a stimulating effect on the growth of tuberculous mycobacteria. A necessary condition for the implementation of biochemical processes in mycobacteria is the creation of an optimal temperature: 37-38°C for the human, 38-39°C for the bovine and 39-41°C for the avian species. It should be noted that Mycobacterium tuberculosis is characterized by a slow metabolism: the growth of cultures manifests itself after 15-30 days or more, at the beginning in the form of almost imperceptible microcolonies, from which visually observable macrocolonies are then formed. In 1887, Nocard and Roux discovered glycerinophilicity in Mycobacterium tuberculosis. Glycerin proved to be the best source of carbon: adding it to meat broth and agar causes abundant growth of cultures.
When choosing a medium, its purpose should be taken into account: for reseeding and preserving subcultures, it is better to use simple glycerin-containing media (MPGB, glycerin potatoes). For the primary isolation of cultures, only dense egg media of Petragnani, Gelberg, and others have justified themselves. To study the biochemical properties of mycobacteria and for other purposes, it is advisable to use protein-free synthetic media of Soton, Model.
The causative agents of tuberculosis, especially the avian species, a number of atypical and saprophytic mycobacteria, when growing in liquid nutrient media, form both superficial and bottom growth with the presence of a bumpy, wrinkled film of a crumbly consistency, which has a yellowish-brown, cream or brown color.
On dense media, mycobacteria form confluent, bumpy colonies, which may have a smooth, shiny or rough surface, as well as a continuous wrinkled coating of white, or white with a yellowish tinge, or another color.
There are methods of accelerated cultivation (microcultivation) of mycobacteria proposed by a number of researchers (Price, 1941; E. A. Shkolnikova, 1948; N. M. Kolychev, 1970, etc.).
Price method. The smear on the glass is dried, then incubated for 5 minutes in a 5% sterile aqueous solution of sulfuric acid. The acid is washed off with sterile distilled water. The smear is placed in a liquid nutrient medium, in which the growth of mycobacteria appears on the glasses in 2-6 days in the form of microcultures, after they are stained by Ziehl-Neelsen under microscopy.
Biochemical properties
Mycobacterium tuberculosis contains various enzymes. The enzymes esterase and lipase break down fats; dehydrase - organic acids, including amino acids; urease - urea, perigalose - carbohydrates, catalase - hydrogen peroxide; proteolytic enzymes (protease) - protein. Mycobacteria ferment alcohol, glycerol and numerous carbohydrates, lecithin, phosphatides. In young cultures of mycobacterium tuberculosis, reducing properties are strongly pronounced, which, in particular, is manifested in their ability to restore tellurite.
Toxin formation. Mycobacterium tuberculosis contains endotoxins - tuberculins (R. Koch, 1890), which exhibit a toxic effect only in a diseased organism. Fatty acids (butyric, palmitic, tuberculostearic, oleic) contribute to the breakdown of cellular elements, cheesy degeneration of tissues, block lipase and proteases produced by mycobacteria. Virulent mycobacteria contain polysaccharide components, a cord factor that increases their virulence, in addition, the cord factor destroys the mitochondria of cells of an infected macroorganism, disrupting the processes of respiration and phosphorylation.
Antigenic structure
Mycobacterium tuberculosis contains a polysaccharide-protein-lipoid complex called the complete antigen. When administered parenterally in animals, the formation of antibodies is observed, which are detected in serological reactions - RA, RP, RSK, etc.
Tuberculins are also antigens. Separately, none of the fractions of Mycobacterium tuberculosis (tuberculoproteins, tuberculolipids, tuberculopolysaccharides) causes immunological changes in the body. The formation of antibodies causes only a polysaccharide-lipoid complex, that is, a complete antigen.
Among atypical mycobacteria, common and group antigens are distinguished. For their identification, serological tests are used, more often the method of diffusion precipitation in agar according to Ouchterlony.
Sustainability
Mycobacterium tuberculosis are resistant to chemical and physical influences, especially to drying. In dried sputum, pieces of affected tissue, dust, Mycobacteria remain viable from 2 to 7 months or more; in running water - more than a year, in soil - up to 3 years. Low temperatures do not affect the viability of mycobacteria.
Mycobacteria are very sensitive to direct sunlight, on hot days they die in sputum in 1.5-2 hours. Ultraviolet radiation is especially detrimental to them. The high sensitivity of mycobacteria to heat is of great importance in sanitary and preventive terms. In a humid environment, they die at 60°C within 1 hour, at 65°C - after 15 minutes, at 70-80°C - after 5-10 minutes. In fresh milk, the causative agent of tuberculosis persists for 9-10 days, and in sour milk it dies under the influence of lactic acid; in oil - weeks, and in some cheeses - even months. Mycobacterium tuberculosis is significantly more resistant to chemical disinfectants than other non-spore-forming bacteria; 5% phenol solution and 10% Lysol solution destroy the pathogen after 24 hours, 4% formalin - after 3 hours.
As disinfectant solutions for tuberculosis, the most effective are: 3% alkaline solution of formaldehyde with a 3-hour exposure; 2% (by formaldehyde) metaphor solution, solutions of bleach, neutral calcium hypochlorite and suspensions containing at least 5% active chlorine at an exposure of 3 hours; 1% solution of glutaraldehyde, 8% emulsion of phenosmoline at the rate of 1 l/m2 and at an exposure of 3 hours, etc.
Pathogenicity and pathogenesis
Pathogenicity. The bovine species of mycobacteria causes disease in cows, sheep, goats, pigs, horses, cats, dogs, deer, deer, etc. Of the laboratory animals, rabbits and guinea pigs are the most susceptible, which develop generalized tuberculosis.
The avian species of mycobacteria causes tuberculosis in chickens, turkeys, guinea fowls, pheasants, peacocks, pigeons, ducks, etc. Under natural conditions, it is possible to infect domestic animals (horses, pigs, goats, sheep, sometimes cattle) and even humans.
Of laboratory animals, rabbits are most susceptible, guinea pigs are less susceptible. The incubation period lasts from several weeks to several years. The persistence of L-forms, which have the ability to revert to typical mycobacteria, has been proven. The presence of L-forms is considered as the cause of recurrence of tuberculosis in healthy herds (V. S. Fedoseev, A. N. Baigazanov, 1987).
Pathogenesis. The causative agent of tuberculosis, having entered the body by aerogenic, alimentary and other routes, penetrates into the intercellular cracks of the mucous membrane, where they are absorbed by mobile polymorphonuclear leukocytes (phagocytes) and carried throughout the body with a current of lymph or blood. The reproduction of Mycobacterium tuberculosis and the interaction of macrophages with them occurs mainly in tissues with selective localization of the tuberculosis process (lymph nodes, lungs, liver, etc.). In the future, in the places of vital activity of the pathogen, a protective focus is formed - a tubercle.
Tuberculous changes in tissues are an inflammatory reaction, which includes the processes of alteration (necrosis of part of the tissue elements), exudation (exit from plasma vessels with formed elements) and proliferation (formation of a connective capsule). Tuberculosis is based on phagocytes. The tubercle initially has a grayish color and a rounded shape; its size is from a pinhead to a lentil grain.
Then the nodule is surrounded by a connective tissue capsule. The tissue inside the encapsulated nodule, due to the lack of influx of nutrients and under the influence of pathogen toxins, dies and turns into a dry, crumbly mass resembling cottage cheese (caseosis).
The process of formation of the primary tuberculous focus is called the primary complex. The outcome of the primary tuberculous process may be different. With a high natural resistance of the organism and minimal doses of the pathogen, the healing of the primary tuberculosis complex can occur with the simultaneous destruction of the mycobacteria contained in it. But most often, encapsulated primary foci calcify and, together with tuberculous mycobacteria inside them, remain in the body for a long time, even throughout life.
In an organism with reduced resistance, the process of encapsulation of the pathogen in the primary focus is poorly expressed. Due to insufficient regeneration of the connective tissue, the walls of the tuberculous nodule melt, while mycobacteria enter healthy tissue, which leads to the formation of many small nodules that can merge with each other, forming large tuberculous foci.
Mycobacteria from tuberculous foci can enter the bloodstream, which leads to a generalization of the process and the development of tuberculous foci of various sizes in different organs. At this stage of the disease, an unfavorable outcome of tuberculosis infection is noted - exhaustion and death.
It should be noted that in recent years, a latent course of tuberculosis infection has been quite often observed, in which the pathogen remains in the macroorganism for a long time, but there are no specific tuberculous changes in the internal organs and tissues.
Tuberculosis (tuberculosis; from Latin tuberculum - tubercle) is an infectious disease caused by mycobacteria, characterized by damage to various organs and systems (lungs, digestive tract, skin, bones, genitourinary system, etc.). It is caused by three types of mycobacteria: M. tuberculosis, M. bovis, M. africanum. All three species differ in morphological, cultural, biochemical and pathogenic properties. In addition to them, this genus includes nontuberculous or opportunistic mycobacteria (M. avium, M. cansasi), which can sometimes cause diseases in humans and animals. The causative agent was discovered by R. Koch (1882).
Taxonomy. The causative agent belongs to the Firmicutes division, the Mycobacteriaceae family, the Mycobacterium genus.
Morphology and tinctorial properties. Cultivation. M. tuberculosis - long (1-3.5 microns), thin (0.2-0.4 microns), slightly curved rods, gram-positive, immobile, do not form spores and capsules, stained according to Ziehl.Nielsen. On liquid media, after 2-3 weeks they give growth in the form of a wrinkled film, and on a dense medium they form a warty plaque. The optimal medium for cultivation is an egg medium with the addition of glycerol (Levenshtein-Jensen medium). The optimal biological model is the guinea pig. During microcultivation on glass slides in a liquid medium, microcolonies are formed after 3 days, where virulent mycobacteria are arranged in the form of “braids” or “bundles”. This phenomenon is called the cord factor. M. bovis - short thick sticks with grains. The optimal biological model is rabbits. M. africanum - thin long sticks. Grow on simple nutrient media. The temperature optimum is 40.42ºС. Low pathogenic for humans. Virulent strains of M. tuberculosis produce R-colonies on solid media.
Enzymatic activity. Tuberculous mycobacteria give a positive result in the niacin test, reduce nitrates, decompose urea, nicotinamide, pyrazinamide.
Antigenic structure. The antigenic structure of mycobacteria is quite complex. Antigens are associated with the cell wall, ribosomes, cytoplasm, have a protein and lipopolysaccharide nature, participate in the reactions of DTH and HNT, and have protective activity.
resistance. Mycobacteria are resistant to the environment: they remain in dust for 10 days, on books, toys - up to 3 months, in water - up to 5 months, oil - up to 10 months, cheese - up to 8 months, sputum - up to 10 months. When boiled, they die after 5 minutes. For disinfection, activated solutions of chloramine and bleach are used.
Epidemiology, pathogenesis and clinical picture. Tuberculosis is ubiquitous and is a social problem; population infection, morbidity and mortality are quite high, especially in underdeveloped countries. Human susceptibility to tuberculosis is universal. Morbidity is influenced by social conditions of life of the population. The source of infection is a sick person; ways of transmission of infection - mainly airborne, rarely contact-household. Only patients with an open form of tuberculosis pose an epidemic danger when the pathogen is released into the environment. When infected (incubation period 3.8 weeks), a primary tuberculous complex (inflammatory or inflammatory-necrotic reaction) is formed at the site of the introduction of the pathogen, which can spread and give the disease various forms - from mild to severe septic, with damage to various organs and systems. Tuberculosis most often affects the lungs. Tuberculosis infection is characterized by the reaction of HRT, which is detected by intradermal administration of tuberculin (Mantoux reaction). For this test, a PPD-protein purified preparation from Mycobacterium tuberculosis is used. A non-sensitized organism does not react to the drug, but if live mycobacteria are present in the body (in a patient or vaccinated), then after 48 hours a local inflammatory reaction develops.
Tuberculosis immunity fragile and is preserved only in the presence of mycobacteria in the body.
Microbiological diagnostics. For laboratory confirmation of the diagnosis of tuberculosis, sputum, bronchial washings, urine, cerebrospinal fluid, etc. are usually examined. Bacterioscopy of smears stained according to Ziehl.Nielsen is effective only at a high concentration of mycobacteria in the test material. For "enrichment" of the studied material, various methods are used, in particular, centrifugation. The bacteriological method, sowing on liquid and solid nutrient media are more effective, but require 3-4 weeks. As an accelerated diagnostic method, microculturing on glasses in Shkolnikov's medium is used. Sometimes a biological method is used - infection of a guinea pig.
Treatment. Isoniazid, rifampicin, ethambutol, prothionamide, pyrazinamide, cycloserine, streptomycin, kanamycin, florimycin, thioacetazone (tibon), para-aminosalicylic acid (PASA) are prescribed.
Prevention. Carrying out a complex of sanitary-hygienic and anti-epidemic measures (sanitary condition of enterprises, children's institutions, schools, etc., identifying patients, registering families, medical examination, epidemiological surveillance, etc.). Specific prophylaxis is carried out by introducing a live vaccine - BCG (Bac. Calmette.Guerin), obtained by Calmette and Guerin during attenuation of mycobacteria on a special medium. Vaccinate newborns (5-7th day of life) intradermally with subsequent revaccination at 7, 12 and 17 years. Before revaccination, a Mantoux test is performed. With a positive reaction, revaccination is not carried out.
The textbook consists of seven parts. Part one - "General Microbiology" - contains information about the morphology and physiology of bacteria. Part two is devoted to the genetics of bacteria. The third part - "Microflora of the biosphere" - considers the microflora of the environment, its role in the cycle of substances in nature, as well as the human microflora and its significance. Part four - "The Doctrine of Infection" - is devoted to the pathogenic properties of microorganisms, their role in the infectious process, and also contains information about antibiotics and their mechanisms of action. Part five - "The Doctrine of Immunity" - contains modern ideas about immunity. The sixth part - "Viruses and the diseases they cause" - provides information about the main biological properties of viruses and the diseases they cause. Part seven - "Private Medical Microbiology" - contains information about the morphology, physiology, pathogenic properties of pathogens of many infectious diseases, as well as modern methods of their diagnosis, specific prevention and therapy.
The textbook is intended for students, graduate students and teachers of higher medical educational institutions, universities, microbiologists of all specialties and practitioners.
5th edition, revised and enlarged
Book:
Tuberculosis (lat. . tuberculum- tubercle) - an infectious disease of humans and animals with a tendency to a chronic course, characterized by the formation of specific inflammatory changes, often in the form of small tubercles, with predominant localization in the lungs and lymph nodes. Tuberculosis is ubiquitous. In the incidence of tuberculosis and its spread, social and living conditions are of decisive importance, since both innate resistance and acquired immunity to it are determined by these conditions.
The causative agent of tuberculosis Mycobacterium tuberculosis- was discovered in 1882 by R. Koch. It belongs to the genus Mycobacterium families Mycobacteriaceae. Mycobacteria are widely distributed in nature: they are found in soil, water, in the body of warm-blooded and cold-blooded animals. Morphologically characterized by the ability to form filamentous and branching forms, especially in old cultures. In addition, they differ from other microorganisms in their higher resistance to acids, alkalis and alcohol, which is associated with the peculiarities of the chemical composition of their cells.
M. tuberculosis has the form of thin, slender, short or long, straight or curved sticks, 1.0 - 4.0 microns long and 0.3 - 0.6 microns in diameter; motionless; spores, do not form capsules, gram-positive; have great polymorphism. In old cultures, filamentous, branching forms are observed, often granular forms (Fly grains), both in the form of free-lying grains and in the form of grains contained intracellularly. In the body of patients under the influence of chemotherapy drugs, ultrasmall forms are often formed that can pass through finely porous bacterial filters (“filterable forms”). M. tuberculosis- aerobe, the optimum temperature for growth is 37 °C, the optimum pH is in the range of 6.4 - 7.0. The content of G + C in DNA is 62 - 70 mol % (for the genus). Growth at 37°C is stimulated by incubation in air containing 5–10% CO2 and the addition of 0.5% glycerol to the medium. Mycobacterium tuberculosis is capable of synthesizing niacin; catalase activity is relatively weak and is lost at 68 °C. Many biological properties of mycobacteria are explained by the high content of lipids, which make up up to 40% of the dry residue of cells. Three lipid fractions were found: phosphatidic (ether-soluble), fatty (ether- and acetone-soluble), and waxy (ether- and chloroform-soluble). Lipids contain various acid-resistant fatty acids, including tuberculostearic, phthioid, mycolic, and others. The high lipid content determines the following properties of tubercle bacilli.
1. Resistant to acids, alkalis and alcohol.
2. Difficult dyeing. For their staining, intensive methods are used. For example, according to the Ziehl-Nielsen method, they are stained with a concentrated solution of carbolic fuchsin when heated. Having perceived the color, tuberculous bacteria, unlike other cells, do not discolor with alcohol, acid, or alkali, therefore, when stained with methylene blue in a smear, all bacteria, cellular elements and mucus are stained blue, and tubercle bacilli retain their original red color (see color incl., Fig. 107.1). This method allows them to be differentiated from some non-pathogenic mycobacteria, for example M. smegmatis contained on the mucous membrane of the urethra, but discolored by alcohol. At the same time, it must be borne in mind that there are also acid-suppressing (“blue” when stained according to Ziehl-Nielsen) forms of tuberculosis bacteria (including rod-shaped, filamentous and granular).
3. Relatively high resistance to drying and exposure to sunlight. Scattered sunlight kills them only after 8-10 days. In sputum, when boiled, death occurs in 5-7 minutes. In dried sputum, viability persists for many weeks.
4. Resistance to the action of conventional disinfectants: 5% phenol solution, when added in equal volume to sputum, causes the death of tubercle bacilli after 6 hours, but 0.05% benzylchlorophenol solution kills after 15 minutes.
5. High hydrophobicity, which is reflected in cultural properties: on glycerin broth, growth is in the form of a yellowish film, which gradually thickens, becomes brittle and acquires a bumpy-wrinkled appearance, while the broth remains transparent. On glycerol agar, after 7-10 days, a dry scaly coating develops, gradually turning into coarse warty formations (see color inc., fig. 107.2 and see fig. 107.3). On alkaline albuminate (or on glass placed in citrate lysed blood), the growth of tuberculous bacteria containing surface glycolipid - cord factor, serpentine: multiplying cells are located, forming a structure resembling a snake, tourniquet, rope or female braid.
6. The pathogenicity of tuberculosis bacteria is also associated with a high content of lipids. Phthioid, mycolic and other fatty acids contained in lipids have a peculiar toxic effect on tissue cells. For example, the phosphatide fraction, the most active of all lipids, has the ability to cause a specific tissue reaction in a normal body with the formation of epithelioid cells, the fatty fraction - tuberculoid tissue. These properties of these lipid fractions are associated with the presence of phthioic acid in their composition. The wax fraction containing mycolic acid causes reactions with the formation of numerous giant cells. Thus, with lipids consisting of neutral fats, waxes, sterols, phosphatides, sulfatides and containing such fatty acids as phthioid, mycolic, tuberculostearic, palmitic, etc., the pathogenic properties of tubercle bacillus and those biological reactions that tissues respond to their introduction are associated. The main factor of pathogenicity is toxic glycolipid (cord factor), which is located on the surface and in the thickness of the cell wall. According to its chemical nature, it is a polymer consisting of one molecule of trehalose disaccharide and mycolic and mycolic high molecular weight fatty acids associated with it in equivalent ratios, trehalose-6,6 "-dimycolate (C 186 H 366 O 117). ondria of macrophages.Being absorbed by phagocytes, they multiply in them and cause their death.The cord factor has two characteristic properties indicating its important role as the main factor of pathogenicity.
1. With intraperitoneal infection of white mice, it causes their death (after several repeated injections of 0.005 mg) after 1–2 weeks. after the first injection with symptoms of widespread pulmonary hyperemia. No other fraction of tubercle bacillus has a similar effect.
2. It inhibits the migration of leukocytes from a person with tuberculosis (in vivo and in vitro).
M. tuberculosis, devoid of the cord factor, are non-pathogenic or slightly pathogenic for humans and guinea pigs. The unusual chemical composition of tuberculous cells is also associated with their ability to cause a delayed-type hypersensitivity reaction characteristic of tuberculosis, detected using a tuberculin test.
Apart from M. tuberculosis, human diseases can cause M. bovis- the causative agent of bovine tuberculosis, and M. avium is the causative agent of avian tuberculosis.
M. bovis- short and moderately long thick sticks. M. avium they are distinguished by high polymorphism (short and long sticks, sometimes filaments), the optimum temperature for their growth is 42–43 °C.
Main difference M. bovis from M. tuberculosis lies in their high pathogenicity for rabbits and other mammals. With intravenous infection M. bovis in doses of 0.1 and 0.01 mg of culture, rabbits die from generalized tuberculosis in 3-6 weeks. rabbit infestation M. tuberculosis even at a dose of 0.1 mg does not cause their death, they develop local benign, non-progressive foci in the lungs. With intravenous infection of rabbits M. avium animals die in 1.5 - 2 weeks. from septicemia.
Genus Mycobacterium includes more than 40 species. As it turned out, many of them are often isolated in different countries of the world from people, warm-blooded and cold-blooded animals suffering from diseases of the lungs, skin, soft tissues and lymph nodes. These diseases are called mycobacteriosis. There are three types of mycobacteriosis, depending on the type of mycobacteria and the immune status of the body.
I. Generalized infections with the development of pathological changes visible to the naked eye, outwardly resembling tuberculosis, but histologically somewhat different from them.
II. Localized infections, characterized by the presence of macro- and microscopic lesions detected in certain areas of the body.
III. Infections that occur without the development of visible lesions; the pathogen is found in the lymph nodes intracellularly or extracellularly.
By pathogenic properties, the genus Mycobacterium subdivided into two groups: 1) pathogenic and opportunistic (potentially pathogenic) and 2) saprophytes. For their accelerated preliminary differentiation, first of all, three features are taken into account: a) the rate and conditions of growth; b) the ability to pigment formation; c) the ability to synthesize nicotinic acid (niacin).
According to the growth rate Mycobacterium are divided into three groups:
1. Fast growing - large visible colonies appear before the 7th day of incubation (18 species).
2. Slow growing - large visible colonies appear after 7 or more days of incubation (20 species).
3. Mycobacteria that require special conditions for growth or do not grow on artificial nutrient media. This group includes two types: M. leprae And M. lepraemurium.
Differentiation of mycobacteria species among fast-growing and slow-growing ones is carried out taking into account a number of their biochemical characteristics: reduction of nitrates, tellurite; the presence of catalase, urease, nicotine- and pyrazinamidase, the ability to synthesize niacin; as well as pigmentation (see table. 46).
According to the ability to pigment formation, mycobacteria are also divided into 3 groups:
1. Photochromogenic - form a lemon-yellow pigment when grown in the light.
2. Scotochromogenic - form an orange-yellow pigment when incubated in the dark.
3. Non-photochromogenic - do not form a pigment (regardless of the presence of light), sometimes cultures have a light yellowish color.
Pathogenic and potentially pathogenic include 24 species.
1. Slow growing:
3. Not growing extracellularly or requiring special conditions for growth:
The most common causative agents of tuberculosis and mycobacteriosis include:
M. tuberculosis M. bovis M. ulcerans
All of them are slow growing, non-photochromogenic (except M. kansasii) mycobacteria. The main differences between them are shown in Table. 49.
In Russia, the main role in the etiology and epidemiology of tuberculosis is played by M. tuberculosis, for the share M. bovis accounts for 2–3% (in the world, this pathogen accounted for 4–20%) of diseases. However, in African countries, the USA and a number of other countries, mycobacterioses caused by other species account for up to 30% of all diseases classified as tuberculosis.
Table 49
Differential characters of some slow-growing species of the genus Mycobacterium
Note. (+) - sign is positive; V - variable sign; (–) – sign is negative; f - photochromogenic.
For the cultivation of tuberculosis bacteria, various nutrient media have been proposed: glycerin, potato with bile, egg, semi-synthetic and synthetic. The Levenshtein-Jensen egg medium is considered the best. In addition, a special semi-liquid medium was proposed for the isolation of L-forms M. tuberculosis. The efficiency of obtaining cultures of mycobacteria depends on the strict observance of a number of conditions: acidic pH, optimum temperature, high quality of the nutrient medium, sufficient provision of O 2 , appropriate seed dose, especially considering the possible presence of altered forms of the pathogen.
Antigenic structure M. tuberculosis. Antigenically, this species is homogeneous (no serovars have been identified), it is very similar to M. bovis And M. microti, but differs significantly from other species. However, the microbial cell has a complex and mosaic set of antigens that can cause the formation of antipolysaccharide, antiphosphatide, antiprotein and other antibodies in the human and animal body, which differ in their specificity. Live and killed bacteria are capable of inducing the development of delayed-type hypersensitivity. Neither proteins nor any of the lipid fractions of mycobacteria possess this property.
For intraspecific differentiation M. tuberculosis a classification system was developed based on phage typing of strains using a set of ten mycobacteriophages: 4 main and 6 auxiliary.
Pathogenicity for laboratory animals. most susceptible to M. tuberculosis Guinea pigs. With any method of infection, a tubercle bacillus causes a generalized form of tuberculosis in them, from which the mumps dies after 4-6 weeks. With subcutaneous infection after 1.5 - 2 weeks. an infiltrate is formed at the injection site, turning into an ulcer, which does not heal until the death of the animal. Regional lymph nodes increase, become dense and undergo caseous decay. Numerous tubercles are formed in the liver, spleen, lungs and other organs, in which, during bacterioscopy, M. tuberculosis.
Epidemiology. The source of infection is a person with tuberculosis, less often animals. From a sick person, the pathogen is excreted mainly with sputum, as well as with urine, feces and pus. Tuberculosis bacillus enters the body most often through the respiratory tract - by airborne droplets and, especially often, by airborne dust. However, the entrance gate can be any mucous membranes and any damaged area of the skin. Infection M. bovis from cattle occurs mainly through the alimentary route through infected milk and dairy products. tuberculosis caused by M. bovis, is observed most often in children, since milk is the main food for them. However, infection M. bovis from sick animals and possibly aerogenic way.
Features of pathogenesis. Depending on the two main ways of infection, the primary tuberculous focus is localized either in the lungs or in the mesenteric lymph nodes. However, some experts believe that at first there is a lymphohematogenous spread of the pathogen in both cases of infection, and then it selectively affects the lungs or other organs and tissues. When it enters through the respiratory tract (or in another way) into the alveoli and bronchial glands, tubercle bacilli cause the formation of a primary affect in the form of a bronchopneumonic focus, from which they penetrate through the lymphatic vessels into the regional lymph node, causing specific inflammation. All this together: bronchopneumonic focus + lymphangitis + lymphadenitis - and forms a primary tuberculosis complex (primary focus of tuberculosis). Tuberculosis bacillus, due to the presence of various fatty acids and other antigens in its cells, causes a certain biological reaction in the tissues, which leads to the formation of a specific granuloma - a tubercle. In the center of it, giant Pirogov-Langgans cells with many nuclei are usually located. Tuberculosis bacilli are found in them. The center of the tubercle is surrounded by epithelioid cells, which make up the main mass of the tubercle. On the periphery of it are located lymphoid cells. The fate of the primary focus may be different. In cases where the overall resistance of the child is reduced for a number of reasons, the focus may increase and undergo cheesy (caseous) decay as a result of the action of toxic products of the tubercle bacillus and the absence of blood vessels in the tubercles. Such caseous pneumonia can cause severe primary pulmonary consumption, and if the pathogen enters the blood, it can cause generalized tuberculosis, leading the child to death. In most cases, in the presence of a sufficiently high natural resistance of the organism, the primary focus is surrounded by a connective tissue capsule after some time, shrinks and becomes impregnated with calcium salts (calcified), which is considered as the completion of the body's protective reaction to the introduction of a tubercle bacillus and means the formation of an already acquired non-sterile (infectious) immunity to tuberculosis, since mycobacteria can remain viable in the primary focus for many years.
In the case of infection by the alimentary route, tubercle bacilli enter the intestine, are captured by phagocytes of the mucous membrane and are carried along the lymphatic pathways to the regional intestinal lymph nodes, causing their characteristic lesions. According to some experts, tubercle bacilli in this case through ductus thoracicus and the right side of the heart can also enter the lungs and cause pulmonary tuberculosis.
Tuberculosis bacillus can affect almost any organ and any tissue with the development of the corresponding clinic of the disease.
The clinic of pulmonary tuberculosis is characterized by alternating periods of recovery that occur after effective chemotherapy, and frequent relapses, the cause of which is the persistence of tubercle bacilli in the body, especially in the form of L-forms, and a change in the patient's immune status. L-forms of mycobacteria are not very virulent, but, returning to their original form, they restore virulence and are able to cause exacerbations of the process again and again.
Features of immunity. The human body has a high natural resistance to the causative agent of tuberculosis. It is the reason that in most cases, primary infection does not lead to the development of the disease, but to the formation of a focus, its delimitation and calcification. Natural resistance is largely determined by the social conditions of life, therefore, in children who are in difficult living conditions, it can be easily undermined, and then the primary infection will lead to the development of a severe tuberculosis process. The deterioration of the living conditions of adults can also lead to a weakening of both natural resistance and acquired immunity. Between 1991 and 1996, the incidence rate of tuberculosis in Russia rose from 30.6 to 42.2, and the death rate increased from 7.9 to 15.0 per 100,000 population.
Acquired post-infectious immunity in tuberculosis has a number of features. Although patients and recovered patients have antibodies to various antigens of tubercle bacillus, they do not play a decisive role in the formation of acquired immunity. To understand its nature in tuberculosis, the following observations by R. Koch were very important. He showed that if tubercle bacilli are injected into a healthy guinea pig, a delimited infiltrate is formed at the site of infection after 10-14 days, and then an ulcer that stubbornly does not heal until the death of the pig. At the same time, the pathogen spreads along the lymphatic tract, which leads to a generalized process and the death of the animal. If you introduce live tubercle bacilli to a guinea pig infected with tuberculosis a week before, then the reaction develops faster: inflammation appears after 2 to 3 days, leads to necrosis, and the resulting ulcer heals quickly. In this case, the process is limited to the site of a new infection and the pathogen does not spread from it. The Koch phenomenon indicates that an organism infected with a tubercle bacillus responds to re-infection in a completely different way than a healthy one, since it has developed an increased sensitivity (sensitization) to the pathogen, due to which it has acquired the ability to quickly bind a new dose of the pathogen and remove it from the body. Sensitization manifests itself as delayed-type hypersensitivity, it is mediated by the T-lymphocyte system. T-lymphocytes, using their receptors and with the participation of class I MHC proteins, recognize cells infected with tubercle bacilli, attack and destroy them. Specific antimicrobial antibodies, binding to various microbial antigens, form circulating immune complexes (CIC) and help to remove antigens from the body. However, interacting with microbial cells, antibodies to the cord factor and other virulence factors can have a toxic effect on mycobacteria; antibodies to polysaccharide antigens - enhance phagocytosis, activate the complement system, etc.
Allergic restructuring of the body plays an important role in the pathogenesis of tuberculosis. The disease in adults already infected with tubercle bacillus, in most cases, proceeds in a relatively benign form of a local process in the lungs, and not in the form of a generalized process, as in children with primary infection. The appearance of a delayed-action hypersensitivity reaction to a tubercle bacillus indicates the formation of acquired post-infectious (and post-vaccination) immunity to it. This type of delayed-type hypersensitivity was first identified by R. Koch using a tuberculin test.
Tuberculin test and its significance. R. Koch obtained his tuberculin preparation in the following way. He sterilized with flowing steam at 100 °C for 30 min a 5-6-week culture of tubercle bacillus in glycerin broth, and then evaporated it at a temperature of 70 °C to 1/10 of the volume and filtered. Persons infected with tubercle bacillus respond to the introduction of small doses of tuberculin with a characteristic reaction: a small induration appears at the site of intradermal injection not earlier than after 6-8 hours, the maximum development of the reaction occurs within 24-48 hours, a well-demarcated papule with a diameter of at least 0.5 cm with a hemorrhagic or necrotic center is formed. Tuberculin allergic reaction is very specific. Such sensitization can only be caused by whole live or killed tubercle bacilli, it is detected by tuberculin, but it does not in itself cause such sensitization. A positive tuberculin test specifically indicates infection of the body with a tubercle bacillus and, consequently, the presence of acquired immunity to it. The tuberculin test was of great diagnostic value for detecting primary infection with tuberculosis in children at a time when there was no mandatory mass vaccination against tuberculosis, but not in adults, since in most cases they are infected with tubercle bacillus. The tuberculin test is now widely used to monitor the effectiveness of anti-tuberculosis vaccination. Due to the fact that the old Kochovsky tuberculin contains various foreign substances and is difficult to standardize, since 1934, a highly purified tuberculin preparation obtained by F. Seibert - PPD-S (purified protein derivative-Seibert) has been used for tuberculin samples since 1934. The international standard unit of tuberculin is 0.000028 mg dry powder. 0.0001 mg PPDS is used to determine tuberculin sensitivity. In our country, the old Koch tuberculin (ATK - Koch alt-tuberculin) is produced, containing 10,000 TU (tuberculin units) per 1 ml (it is used for skin test and graduated skin test according to Pirke), and a purified PPD preparation containing either 5 TU in 0.1 ml or 100 TU in 0.1 ml. A purified PPD preparation containing 5 IU/0.1 ml is used for the intradermal Mantoux test to select individuals for revaccination. Persons who react negatively to intradermal administration of 5 TU PPD are subject to revaccination. In addition, sensitin preparations are available to detect hypersensitivity to other pathogenic mycobacteria.
Laboratory diagnostics. All methods are used to diagnose tuberculosis: bacterioscopic, bacteriological, serological, biological, allergic tests, PCR. When bacterioscopic examination of the source material (sputum, urine, pus, cerebrospinal fluid, feces), it must be taken into account that the content of mycobacteria in it may be insignificant, their excretion is episodic and it may contain altered variants of the pathogen, including L-forms. Therefore, to increase the probability of detecting Mycobacterium tuberculosis, methods of concentrating them by centrifugation or flotation are used, as well as phase-contrast (to detect L-forms) and luminescent microscopy (auramine, auramine-rhodamine, acridine orange, etc. are used as fluorochromes).
The biological method - infection of guinea pigs - is one of the most sensitive. It is believed that the infectious dose of the pathogen for them is several cells. Guinea pigs can also be used to detect L-forms of tuberculous bacteria, but in this case it is necessary to make several successive infections, since L-forms have less virulence and cause a benign form of tuberculosis in pigs, which, in case of reversion of L-forms to its original state, can turn into a generalized process.
The significance of the tuberculin test has been discussed above.
From among the serological reactions for the diagnosis of tuberculosis, RSK, RPHA, precipitation reactions, enzyme immunoassay methods (including pinpoint), radioimmunoassay, immunoblotting, aggregate-hemagglutination reaction (to detect CEC), etc. have been proposed. The use of various antigens makes it possible to detect the presence of certain antibodies. To improve serological methods for diagnosing tuberculosis, it is important to obtain monoclonal antibodies to various antigens of mycobacteria. This will make it possible to identify those specific epitopes of tuberculosis bacteria and, accordingly, those antibodies to them, the detection of which is of the greatest diagnostic value, and will also make it possible to create commercial test systems for the immunodiagnosis of tuberculosis.
Among all the methods of microbiological diagnosis of tuberculosis, bacteriological still remains decisive. It is necessary not only for the diagnosis of the disease, but also for monitoring the effectiveness of chemotherapy, timely assessment of the sensitivity of mycobacteria to antibiotics and chemotherapy drugs, the diagnosis of relapses of tuberculosis, the degree of purification of the patient's body from the pathogen and the identification of its altered variants, especially L-forms. Before sowing, the test material must be treated with a weak solution of sulfuric acid (6–12%) to eliminate the accompanying microflora. The isolation of pure cultures of mycobacteria is carried out taking into account the rate of their growth, pigment formation and niacin synthesis. Differentiation between individual species of mycobacteria is carried out on the basis of their biological properties, as indicated above. The question of the virulence of mycobacteria is solved with the help of biological samples and based on the detection of the cord factor. For this purpose, cytochemical reactions have been proposed. They are based on the fact that virulent mycobacteria (containing the cord factor) firmly bind dyes - neutral red or Nile blue - and, when alkali is added, retain the color of the dye, while the solution and non-virulent mycobacteria change their color.
For faster isolation of the causative agent of tuberculosis, a microculture method has been proposed. Its essence is that the test material is applied to a glass slide, treated with sulfuric acid, washed, the glass is placed in lysed citrate blood and incubated at a temperature of 37 °C. Already after 3 - 4 days. the growth of mycobacteria on the glass manifests itself in the form of microcolonies, which reach their maximum development by the 7-10th day, and mycobacteria are well detected by microscopy. At the same time, virulent mycobacteria form serpentine colonies, while non-virulent ones grow in the form of amorphous clusters.
Tuberculosis is a dangerous disease from which no person is insured, regardless of gender, age, social class. Mycobacterium tuberculosis, or Koch's bacillus, is the causative agent of a dangerous infectious disease in humans and animals. Infection first occurs in childhood. Before the appearance of favorable conditions for the development and reproduction of a pathogenic microbe, it does not show activity. Tuberculosis can affect any tissues and organs when immune defenses are weakened. In Latin, the name of the causative agent of tuberculosis is Mycobacterium tuberculosis. The microbe is resistant to adverse environmental factors and has a high virulence.
Koch wand under magnification
Despite the fact that more than a hundred years have passed since the discovery of the causative agent of tuberculosis, the incidence and mortality from this disease remains high. The danger of Mycobacterium tuberculosis lies in its virulence and pathogenicity. This means that the pathogen has a high ability to infect the body and the potential property, under favorable conditions, to provoke an infectious process.
The tuberculosis microbe should not be confused with the Koch-Wicks bacillus, which causes acute conjunctivitis.
MBT (mycobacterium tuberculosis) refers to gram-positive bacteria of the family Mycobacteriaceae of the genus mycobacterium, which are pathogenic to humans and animals. This bacterium is not a virus, but a microorganism that has some of the properties of fungi. Characteristic features of the pathogen:
- The disease is caused by three types of mycobacteria - intermediate, bovine and human.
- More than 90% of pathogens affect the respiratory system. Extrapulmonary localization of the rest - the gastrointestinal tract, the musculoskeletal system, the genitourinary system.
- Mycobacteria in the body are in the barrier-phagocytic system of macrophages.
- Bacteria are characterized by a complex metabolic pattern, which ensures their resistance and cell variability for survival.
- When sowing mycobacteria on a nutrient medium, the pathogen absorbs oxygen. Like fungi, it forms a colony with a rough, milky-pink surface.
The disease caused by Koch's wand is treatable if the patient seeks medical help in a timely manner. With a weakening of the host's immunity and the presence of serious concomitant diseases, Mycobacterium bacillus Koch initially infects macrophages, binds to cell membranes, and is phagocytosed inside, using macrophage organelles for its vital activity.
The history of the discovery of Mycobacterium tuberculosis
Hippocrates was the first physician to draw attention to a serious disease of the lungs and respiratory organs. He gave the name to the disease - phthisis. Until the 19th century, tuberculosis was called consumption. The disease gave high mortality among the population of different countries. Consumption struck young people, and those infected often did not live to old age.
For many years, doctors and scientists have tried to identify the cause of infection with consumption. Only in 1882, the famous German microbiologist Heinrich Hermann Robert Koch discovered the causative agent of tuberculosis using Leeuwenhoek's microscope. For his serious work, Koch received the Nobel Prize (1905), and mycobacteria were given the name of Koch's bacillus. He conducted many experiments to discover the causative agent of tuberculosis, and only the 271st experiment became a breakthrough in the field of medicine and microbiology. An oblong, rod-shaped bacterium, Mycobacterium tuberculosis, was studied in detail by Koch, for which the MD applied a phased experiment:
- Removal of tuberculosis bacteria from an infected organism.
- Sowing material on a nutrient medium to grow a pure colony.
- Experimental infection of a laboratory mouse to obtain a clinical picture.
In the nineteenth century, every seventh inhabitant died of consumption in Germany. For a long time, Robert Koch took tissue sections of deceased patients for experiments, stained the experimental material with chemical dyes, and studied it under a microscope. The result of the 271st experiment finally lived up to expectations - the bacterium was bred. Animal blood serum was used as a nutrient medium, and experimental guinea pigs were infected with the bacillus.
Hippocrates, nicknamed the "Father of Medicine"
The causative agent of tuberculosis was discovered by Koch in 1882, but research and study of the bacillus continues to find effective methods to combat the disease. As a result of the high resistance of the bacillus to adverse environmental factors, mycobacterium is able to adapt to medicines and neutralize the beneficial effects of medicines. Back in 1882, Koch discovered the cause of tuberculosis. The results of his own work include the identification of pathogens of anthrax, cholera.
The causative agent of tuberculosis: a taxonomy
According to taxonomic studies, Mycobacterium tuberculosis is classified as a prokaryote, since there are no highly organized organelles in the cytoplasm - a type of actinobacteria. The cells of the Koch rod are resistant (resistant) to alcohol, acid, alkaline staining, which for a long time made it difficult to identify the bacterium that causes tuberculosis. The taxonomy of the pathogen is determined by the following characteristics:
- Due to the similarity of bacteria with fungi, the tuberculosis pathogen belongs to the genus of mycobacteria - Mycobacterium.
- Previously, the genus Mycobacterium was conditionally divided into types and subgenera, but according to recent taxonomic studies, mycobacteria were divided into 3 groups.
- Groups of the genus Mycobacterium are classified according to the rate of growth of bacteria - Koch's bacillus belongs to the first group, capable of producing colonies after 7 days.
- The first group combines slowly growing bacteria: Mycobacterium tuberculosis types grow on dense nutrient media for more than one week.
- Koch's stick is a prokaryote (not a eukaryote), since it is a living microorganism whose cells do not contain a nucleus and membrane organelles.
- Mycobacterium tuberculosis species are human, bovine and intermediate. Human infection in 95% of cases occurs from sick people.
The Hippocratic school left many scientific works that have been used in the Mediterranean for over 1000 years.
Medical statistics show that tuberculosis infection from animals occurs in 5% of cases, another 5% of the total number of registered diseases occurs when infected through food: milk, meat, cheese, cottage cheese, that is, through the alimentary route. The taxonomic description of Koch's bacillus defines the causative agent of tuberculosis as a microorganism belonging to mesophylls and aerophiles. Cells need oxygen to breathe and live and reproduce best at moderate temperatures.
Appearance and internal structure
What does a Koch wand look like? This is an oblong straight or curved bacterium, characterized by small size. Tuberculosis pathogens do not exceed ten micrometers in length, and reach 0.5 micrometers in diameter. Mycobacterium has an oblong shape with a dense multilayered shell, which ensures high survival of the microorganism in adverse environmental conditions. In the characteristics of Mycobacterium tuberculosis, several features are distinguished by structure:
- A prokaryotic bacterium without a nucleus and highly developed organelles, the internal composition of which includes 90% water, as well as proteins, mineral salts, carbohydrates, and fats.
- In the internal structure of a bacterial cell, a wall of 3-4 layers, bacterial cytoplasm, nuclear substance, cytoplasmic membrane are determined.
- Morphological properties of the causative agent of tuberculosis: the formation of filamentous forms, polymorphism, acid resistance, the formation of variable L-forms.
- In morphology, the ability to retain color in an alkaline, acidic, alcoholic environment is distinguished due to the content of waxes, fats, mycolic acid.
Heinrich Hermann Robert Koch
Mycobacterium tuberculosis agent can be confused with saprophytic atypical mycobacteria - paratuberculous bacilli, which are found in sewage, tap water, some foodstuffs, on human skin, in feces, urine, saliva, sputum. The microbiology of the causative agent of tuberculosis includes complex and diverse diagnostics to eliminate errors in recognizing the nature of the pathogen. Unlike a strain of Mycobacterium tuberculosis, paratuberculous bacilli do not cause typical changes in the body of a host - a person or an animal.
To detect Mycobacterium tuberculosis, common methods of staining the test material are used according to the Ziehl-Neelsen method, according to Gram, according to the method of Fly, Schiengler, Fly-Weiss. When stained in bacteria, bright red and purple granules are revealed, which makes it possible to visualize the structure of the complex shell of microorganisms.
Features of life
Mycobacterium tuberculosis shows high resistance to negative external influences, they are reliably protected from mechanical damage by a dense, durable cell membrane, which ensures the integrity and safety of the intracellular apparatus. Due to the multilayer structure of the shell, the life cycle of mycobacteria is characterized by a high duration.
Features of the vital activity of the causative agent of tuberculosis and its properties:
- It tolerates harmful external influences of a chemical and mechanical nature.
- In a dark, humid environment with a constant temperature of 23°C, bacteria can survive up to seven years.
- MTB reproduces by simple cell division, the cycle of which is from 14 to 18 hours.
- Mycobacterium tuberculosis antigens include proteins, lipids, phosphatides, polysaccharides. Common and specific antigens of pathogens have been identified.
- For the cultivation of Mycobacterium tuberculosis, a dense nutrient medium with good air access is ideal.
- Koch's wand needs oxygen for active life, but under certain conditions it can develop as an aerobe or anaerobe.
- Cell reproduction begins with the indentation of the membrane into the cytoplasm to form the intercellular septum and form a daughter cell.
- An important property of Mycobacterium tuberculosis is the possibility of alternative reproduction by complex budding or branching.
On the left - the destruction of the lungs under the influence of tuberculosis; on the right - the normal state of the organs
Absorbed by macrophages, mycobacteria remain viable for a long time, can cause tuberculosis after several years of being in a latent state without manifestation of activity and characteristic symptoms. Detection of Mycobacterium tuberculosis is carried out by the method of flotation, luminescent study, which increases the frequency of bacilli detection in sputum, gastric lavage, feces, exudate, cerebrospinal fluid. The automatic system for cultivating mycobacteria significantly reduces the time required for breeding bacilli on nutrient media.
As a result of the high contagiousness of tuberculosis, the increase in mortality among the population, children of preschool and school age are conducting a primary study - the Mantoux reaction. A test with tuberculin is performed with dead Koch sticks, after which the reaction of the body is determined. With redness, swelling, inflammation of the injection site, additional laboratory tests are prescribed. Is it possible to sow dead Koch sticks? Obviously, cells that have lost the ability to live will not be able to develop and multiply.
Routes of entry into the human body
Infection of a healthy body with Koch's tubercle bacillus occurs in several ways. With strong immune protection, contact with a carrier does not always provoke the development of the disease. Every person has Koch's wand, but the bacteria are in an asymptomatic state. Koch sticks are transmitted as follows:
- The most common route of infection with Mycobacterium tuberculosis is airborne transmission (sneezing, coughing, runny nose).
- The alimentary type of infection (through products) with Koch's tubercle bacillus is 5% of all infections.
- Mycobacterium tuberculosis can be found in foods of animal origin - cheese, cottage cheese, milk, meat.
- Transmission of the strain through animals is another way that healthy people can become infected with Koch's bacillus.
- Tuberculosis in veterinary practice occurs in cats, dogs, and is diagnosed in cattle.
The world pays great attention to the treatment of animals, because people's health depends on it.
Koch's wand is a pathogen with a high level of pathogenicity and virulence, it is capable of infecting any group of people. But there is a category of persons belonging to the risk group, as well as a number of factors that can provoke infection:
- Babies. Newborns have a weak, unformed immune defense. The causative agent of tuberculosis can be transmitted with mother's milk during lactation if a woman is infected with Koch's bacillus.
- People living in unsanitary conditions: residents of homeless shelters, prisoners in prisons, persons without a fixed place of residence.
- Patients with oncological diseases, HIV-infected patients, people whose families already have tuberculosis are easily infected with Koch's wand.
- Provocative factors of infection with tuberculosis: hereditary predisposition, decreased immunity, mental and nervous disorders, bad habits (alcoholism, drug addiction), poor nutrition.
- With a decrease in the quality of life, tuberculosis bacteria from a latent form can move to active life, therefore, sanitation, balanced nutrition, and strengthening of immunity are important in the prevention of the disease.
According to medical statistics, most often infection with Koch's wand is observed in patients aged 18 to 26 years - a young working-age population. But anyone can get infected, so it is important to pay attention to the prevention of the disease.
Map showing TB death rates among HIV-infected people worldwide
Where and how long does Koch's wand live
Scientific studies have proven the high resistance of Mycobacterium tuberculosis in the external environment. Due to the three-layer wall, bacteria survive in almost any adverse conditions. Treatment of patients is complicated by drug resistance of Mycobacterium tuberculosis. Cells "get used" and adapt to drugs. In an anaerobic latent state, Koch's wand sleeps for months and years, always ready to "wake up" under favorable conditions. Stability in the external environment changes under the influence of various factors:
- Dried state - causative agents of tuberculosis live up to three years, while maintaining vital activity.
- Outside the body, Koch's wand lives up to seven years within a warm, dark room and optimal humidity.
- The causative agent of tuberculosis is resistant to the influence of high and low environmental temperatures.
- In manure, viability lasts up to 15 years, in soil - up to six months, in water - up to five months.
- Koch's wand can live indoors for years; if microbes enter a house or apartment, it remains in books and on things for up to three months.
- If the pathogen is found in cheese, butter, viability lasts up to a year, in milk - a couple of weeks.
Under unfavorable conditions, mycobacterium tuberculosis survives, passing into a latent state and forming L-forms. Boiling, freezing, chlorine treatment are used to disinfect Koch's sticks. Despite the fact that the causative agent of tuberculosis is resistant to external influences, a couple of minutes in sunlight is enough for the bacteria to die. The life time of Koch's sticks is reduced in adverse conditions: lack of oxygen, nutritional environment, optimal humidity. If infection is suspected in a patient, sputum should be collected for laboratory testing. The patient's medical history, description of the clinical picture, symptoms, and tests performed are stored on the outpatient card.
Map of countries with a high incidence rate (number of infected per 100,000 population)
What kills mycobacterium tuberculosis
The variability and complex nature of the metabolism and morphology of Koch's bacillus requires differential diagnosis to obtain accurate information about the patient's infection. To kill Koch's wand, patients are prescribed therapy and taking a wide range of medications. In the premises in which TB patients live, disinfection and sanitization are carried out. What is Koch's wand afraid of:
- Boiling - mycobacterium dies in 15-20 minutes; when heating the liquid to 60-70°C - in 40-60 minutes.
- Under the influence of dry heat, the causative agent of tuberculosis dies in an hour, increased acidity kills Koch's bacillus in half an hour.
- Mycobacterium tuberculosis is most sensitive to ultraviolet light - when exposed to direct sunlight, they die in a couple of minutes.
- At home and on an outpatient basis, Koch's wand can be killed with chlorine-containing solutions or hydrogen peroxide in five hours.
- Ultraviolet irradiation lamps (UVI) create unfavorable conditions under which Koch's wand dies completely.
Since Mycobacterium tuberculosis is very resistant, the pathogen tolerates low and high temperatures, drying, and dehydration well. Koch's wand can die from drugs, but with the same success it can develop L-forms with drug chemotherapy or an increase in the patient's immunity. At what temperature Koch's wand dies, scientific studies of the bacillus have established - at least sixty degrees Celsius in a liquid medium.
Drug resistance of Mycobacterium tuberculosis is multiple - MDR. Medical experts note that the number of TB patients with MDR is increasing every year. The causative agent "gets used" to anti-tuberculosis drugs of different groups and types, including the most powerful drugs Isoniazid and Rifampicin.
Sudanese with tuberculosis
germ danger
The pathogenic pathogen enters the body mainly with reduced immunity by airborne droplets. Initially, the bacillus multiplies slowly outside the cells, after which it begins to attack macrophages, penetrates the lymphatic system, and begins to affect tissues. The danger of the microbe is as follows:
- Koch's stick causes damage to the tissues of various organs with good blood microcirculation;
- tubercles are formed on the affected tissues, which grow rapidly, provoking an inflammatory process;
- the immune response of the body comes in a few weeks from the moment of infection and the activity of the pathogen;
- MBT in humans cause a disease of an open or closed form;
- the number of Mycobacterium tuberculosis in the body is not of fundamental importance - immunity plays a decisive role;
- high danger is the virulence of mycobacteria, due to factors of high pathogenicity of microorganisms;
- the survival of Koch's bacillus is caused by the constant change in the DNA genome.
In adults, in 90% of cases, the cause is reinfection, which occurs as a result of primary, not completely cured tuberculosis. The causative agent of the disease in children is Koch's bacillus, which infects the body with poor-quality anti-tuberculosis vaccination or through direct contact with a sick person - a relative, a family member.
Koch's wand has a pronounced harmful effect as a result of a high degree of pathogenicity. The causative agent of tuberculosis belongs to the category of the most dangerous infectious agents that can cause the death of a patient. The main reason for the danger of the pathogen is the latent course of the incubation period and the rapid progression of the infection provoked by mycobacterium.
The picture clearly demonstrates the main mode of transmission of the disease.
How is the causative agent of tuberculosis detected?
If infection with Koch's bacillus is suspected, differential diagnosis is carried out. After the incubation period, the first symptoms of the disease appear, and the signs are completely similar to a respiratory viral infection, and at this stage the Mantoux test shows a negative result. Nevertheless, the causative agent of tuberculosis is Koch's wand. Bacteria can be detected in several ways:
- Sputum analysis for Mycobacterium tuberculosis. Laboratory diagnostics of three portions of the material is carried out, the children are taken with gastric lavage. A sputum examination for MBT content is performed when a patient contacts a doctor with complaints and suspicion of pulmonary localization of the focus of infection.
- If the affected area is not concentrated in the lungs, any liquid medium obtained from the body can be the material for diagnosis. Assign a blood test for Mycobacterium tuberculosis, fluid sampling from the pleura, a urine test for Mycobacterium tuberculosis. With the defeat of the genital organs, women do a menstrual blood test.
- Material for laboratory analysis are particles of infected tissues obtained during surgical biopsy, bone marrow puncture, liquid media of the articular and abdominal cavities, exudate, cerebrospinal fluid, purulent compartments, feces. The study of Koch's bacillus in a smear allows you to confirm or exclude damage to the genitourinary system.
The sputum collection algorithm for the detection of Mycobacterium tuberculosis consists of several steps: referral for biomaterial collection, preparation of a spittoon with labeling with patient data, thorough oral hygiene, and spitting of sputum. Only specialists can check for the presence of Koch's bacillus in the material taken for analysis.
Health worker giving a sputum collection container to a person
Modern medicine has several methods by which it is possible to accurately establish or disprove the presence of a colony of microbes in the human body.
Methods for diagnosing tuberculosis:
- Direct bacterioscopic examination. Identification of the pathogen is possible in the presence of a large number of pathogens in the test material - at least ten thousand microbes per millimeter. The time for obtaining the result when performing diagnostics by microscopy is one hour.
- PCR analysis. If several tens of microbes are present in the material during the polymerase chain reaction, the Koch stick test gives a positive result with 100% certainty. The PCR method eliminates the presence of cross-reactions, allows you to identify cell DNA.
- Cultural way of research. It consists in sowing biological material on a nutrient medium to obtain a pure culture. Mucus after taking sputum is sown, growing a pure culture takes up to three months. The culture method works when hundreds of microbes are present.
- X-ray examination, Mantoux or Pirquet test. An x-ray taken in three projections gives a detailed visualization of the patient's lungs. The allergic method (Mantoux reaction) is based on the injection of tuberculin into the human body. The response is evaluated after 72 hours. If the Mantoux test is "normal" - what does it mean? The size of the papule and the area of redness according to the table corresponds to the normal value.
- Serological diagnosis. The indirect hemagglutination test (RIHA) uses human erythrocytes loaded with Mycobacterium tuberculosis extract or tuberculin as an antigen. Serological diagnostics using RIGA, enzyme immunoassay, radioimmunoassay and immunoblotting provides reliable research results.
When a patient is infected with Koch's wand, the following data can be obtained:
- increased ESR;
- determination of DNA in blood serum;
- an increased number of leukocytes with a change in the shape of the cells.
For the purpose of early diagnosis of tuberculosis infection, antibodies of Mycobacterium tuberculosis are detected. The in vitro Mycobacterium tuberculosis assay is a test using the A60 antigen. The diagnostic method makes it possible to detect antibodies to Mycobacterium tuberculosis in the blood as an alternative test during a comprehensive examination of the patient.
Clinical trials after the in vitro test showed the high effectiveness of the method - 86-90%. Total antibodies to Mycobacterium tuberculosis IgM + IgG + IgA help determine the stage of the disease. The antibody test can be used instead of Mantoux when the test is negative during the incubation period of the disease. The material of the study is venous blood, the time for obtaining the result is from five to seven days.
The results of a highly sensitive enzyme immunoassay can be interpreted as follows:
- acute form of infection;
- previous infection;
- chronic course of the disease;
- pulmonary or extrapulmonary localization of tuberculosis.
The result is assessed by the presence or absence of IgM, IgG, IgA antibodies. However, a negative test may indicate an early stage of the disease, so re-diagnosis is required after a few weeks.
Tuberculosis: features of the disease
Mycobacterium tuberculosis can persist in the human body and infect other people. The disease caused by Koch's wand poses a serious danger to humans, since the outcome of infection can be fatal. As a result of dangerous factors of pathogenicity of Mycobacterium tuberculosis, the rate of damage to tissues around the source of infection increases.
The most common symptom of the pulmonary form is a cough with pain syndrome.
Koch's stick quickly adapts to drugs, which complicates the treatment of the disease. It is impossible to know everything about tuberculosis, but it is necessary to familiarize yourself with the important points:
- In the process of life, Mycobacterium tuberculosis can release toxic substances into the body that adversely affect cellular immunity.
- After entering the body of the carrier, the bacterium remains in a latent state and passes to the active phase when favorable conditions are created.
- Koch's wand provokes the disease in two forms - open and closed. In the first case, the patient can infect others, in the second case, he cannot.
- Varieties of tuberculosis include pulmonary and extrapulmonary form of the disease - damage to tissues and organs with good blood microcirculation.
- According to the degree of damage, focal, latent, fibrous, disseminated, caseous form of tuberculosis and rare varieties are distinguished.
- Symptoms and treatment for infection with Koch's wand depend on the localization of the pathology: lungs, spinal nerves, meninges, skin, digestive system, bones, eyes, kidneys, genitourinary system.
People with strong immunity can live their whole lives with Koch's wand and not get sick with tuberculosis. If mycobacteria move from a latent form to an active phase, infection occurs before the body has time to give an immune response to infection. The clinical picture of tuberculosis is determined by the symptoms of the disease. After differential diagnosis, patients are prescribed treatment.
Sometimes x-rays can save a person's life.
According to WHO, every year about three million people die from tuberculosis in the world, and about ten million are infected. That is, almost a third of patients do not survive. Therefore, it is important to know the signs and symptoms of Koch's bacillus infection in order to recognize tuberculosis in a timely manner:
- Initial symptoms include fatigue, weakness, and malaise.
- The onset of the disease is accompanied by symptoms such as lack of appetite, severe weight loss, irritability, and poor sleep.
- When the respiratory organs are affected, the patient has a dry paroxysmal cough, which can intensify at night and in the morning.
- The development of pulmonary tuberculosis is an inflammatory process, which is characterized by an increase in the base body temperature to 37.5-38°C for a long time.
- The patient's face becomes pale, the eyes acquire an unhealthy luster, and increased sweating is characteristic.
Tuberculous inflammation is characterized by symptoms of severe cough caused by lung damage. With the progression of the disease, expectoration of sputum with blood occurs. If Mycobacterium tuberculosis affects other organs and tissues, the symptoms may be supplemented by the following signs:
- With pulmonary tuberculosis, there is pain in the chest, radiating to the shoulder blades, hypochondrium, wheezing, runny nose, swollen lymph nodes are characteristic.
- Infection of the genitourinary system in various forms of the disease (acute, chronic) is accompanied by painful urination, abdominal pain.
- Tuberculosis of the joints and bones causes the destruction of cartilage tissue, pain in the spine, damage to the intervertebral discs, and immobilization.
- When the Mycobacterium tuberculosis of the digestive system is infected, the patient develops constipation, blood is formed in the feces, and the temperature rises.
- If the tuberculosis pathogen affects the skin, nodules of a dense structure appear under the skin. When combed, they secrete a curdled infiltrate.
- Damage to the central nervous system is accompanied by severe headaches, mental disorders, impaired hearing, vision, coordination.
Cough with bloody sputum indicates the need for emergency care for the patient
In most cases of infection with Mycobacterium tuberculosis, infection of the lungs occurs. The disease is asymptomatic for a long time, and is detected only during routine medical examinations, X-rays and fluorography. The danger of tuberculosis lies in the complications that the disease causes: removal of the lung, meningitis, death.
Treatment
After testing for tuberculosis, patients are prescribed a course of treatment. The sooner an effective therapy is chosen, the easier it is to cure a Koch's bacillus infection. As a result of the high drug resistance of mycobacteria in medical practice, treatment regimens with anti-tuberculosis drugs are constantly being improved.
Medical
Includes chemotherapy using multicomponent antibacterial regimens. You can destroy a dangerous bacterium with the following drugs:
- Isoniazid, Streptomycin, PAS;
- Isoniazid and Ftivazid, Streptomycin and Kanamycin, Rifabutin and Rifampicin, Pyrazinamide and Ethionamide;
- four pairs of antibiotics plus one last-generation drug of the series Cycloserine, Capreomycin, Ciprofloxacin.
The patient is prescribed enhanced therapy for two to six months or prolonged treatment for two to four years.
supportive
Therapy is carried out using medications that strengthen the body of a sick person. These include drugs of the probiotic group (restoration of the normal microflora of the digestive organs) Linex, Befiform. With maintenance therapy, appoint:
- hepatoprotectors to strengthen liver cells Karsil, Essentiale, Silimar;
- immunostimulants to restore the immune system Galavit, Imudon;
- antipyretic drugs Paracetamol, Ibuprofen;
- NSAIDs - Ketanov, Naproxen;
- glucocorticoids and vitamin complexes.
Surgical
Removal of foci of primary tuberculosis is possible surgically. Surgery is performed in several ways:
- collapse therapy with fixation of the lung for fusion of caverns;
- speleotomy to remove large tuberculous caverns;
- removal of part or all of the lung;
- valvular bronchoblocking to restore breathing in patients with tuberculosis.
Surgical treatment is used in extreme cases, when conservative therapy is ineffective. In addition, patients are prescribed vitamin therapy, physiotherapy, physiotherapy exercises.
Treatment is complex and time consuming
Mycobacterium tuberculosis should not be confused with atypical mycobacteria when choosing treatment. The main principles of therapy are as follows:
- prescribe drugs, the sensitivity of the strain to which is proven;
- apply the maximum dosage;
- continue therapy for at least six months;
- if there is no effect, extend the treatment for another few months.
Forecast
An infectious disease caused by Mycobacterium tuberculosis is amenable to conservative treatment if the patient seeks medical help in a timely manner. After a thorough diagnosis, the pathogen is determined in the body, after which the doctor can choose the most effective treatment regimen. Since the bacillus can adapt to drugs, it is possible to change the treatment regimen to include additional components.
The prognosis for recovery from tuberculosis infection is positive if the disease is diagnosed in the early stages of infection. The lethal outcome of the course of the disease is possible with untimely access to a doctor, ineffective treatment, incomplete therapy. If the treatment has given a positive effect, patients may refuse further therapy, but after a few weeks or months, a relapse of primary tuberculosis is possible. Elderly patients are more difficult to recover from Koch's bacillus infection, since the body is not able to produce enough antibodies.
Prevention
Mycobacterium tuberculosis is characterized by high resistance, virulence and pathogenicity. The disease is ubiquitous, highly contagious, and often causes death, so the main method of prevention is vaccination of newborns and Mantoux test for children of preschool and school age.
Performing a Mantoux test
BCG vaccination protects children from tuberculosis. They do it in the hospital. Preventive measures include the following:
- periodic fluorography;
- increasing the immune defense of the body;
- compliance with the rules of personal hygiene;
- eating healthy wholesome food;
- refusal of bad habits, physical education;
- taking vitamins, timely rest.
The causative agents of tuberculosis are Koch's sticks. Mycobacteria, once in the body, enter the active phase of life in one case out of ten. This means that each person can protect himself from the disease if he adheres to preventive measures. Immunity in tuberculosis plays an important role. Restoring the protective properties of the body allows you to quickly localize the focus of infection and destroy the Koch sticks.
Individual cases
Mycobacterium tuberculosis belongs to the Mycobacteriaceae family and causes infection in humans and animals. It should not be confused with another pathogen - the Koch-Wicks stick, which provokes catarrhal conjunctivitis of an epidemiological nature. The disease is common in countries with a humid hot climate. The Koch-Wicks wand is not identical to Mycobacterium tuberculosis.
When diagnosing the presence of Koch's bacillus in different environments, atypical mycobacteria that do not cause tuberculosis can be detected. Infection occurs mainly through contact with the environment. Atypical mycobacteria cause skin infections, cervical lymphadenitis. The lesions of tuberculous bacteria and atypical mycobacteria do not differ even under a microscope, but microorganisms have different enzymatic activity, resistance, and cultivation speed on nutrient media.
Koch's wand is able to form L-forms of mycobacterium tuberculosis as a result of deep morphological and functional cellular changes. L-forms are bacteria that are completely or partially devoid of a cell wall, but have not lost the ability to develop. When normal bacterial cells develop unbalanced, for example under the action of antibacterial drugs, stable and unstable L-forms are formed. The danger of modified forms is the absence of a cell membrane, due to which mycobacteria can pass through the histohematogenous barrier and quickly spread throughout the body, causing allergic changes.
Mycobacterium tuberculosis is currently the most studied. More than a hundred morphological reactions have been described, thousands of experiments have been carried out aimed at studying the strain of Koch's bacillus and searching for drugs against tuberculosis. The disease is treatable. Mycobacterium tuberculosis can be destroyed, so at the first sign of infection with the Koch stick, you should consult a doctor.
Skin tuberculosis
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