Infections caused by mycobacteria (Mycobacterium tuberculosis, leprae, avium, etc.): diagnosis, treatment, prevention. Mycobacteria are pathogens Mycobacteria cause
Atypical mycobacterioses are a number of granulomatous diseases caused by mycobacteria. The name of the disease includes the term atypical, since the causative agent of the disease differs from the classical pathogenic mycobacteria that cause the development of skin tuberculosis.
Mycobacteria are anaerobic, immobile microorganisms that do not form spores. The most important characteristic of these bacilli is their acid resistance and high lipid content in their cell walls.
About five dozen different mycobacteria are known today. Among them are:
- Definitely pathogenic. These include M. tuberculosis, M. Bovis, M. Leprae, which also cause leprosy.
- Other types of mycobacteria are classified as conditionally pathogenic, they are called atypical.
Reasons for development
Mycobacteria are atypical.The cause of mycobacteriosis is infection with certain types of mycobacteria.
You can get infected with mycobacteria in different ways - contact, airborne, dust. Moreover, a person with atypical mycobacteriosis does not pose a particular danger to others. Basically, infection occurs through contact with the environment.
For example, the mycobacterium M. Avium can be present in fumes from bodies of water, so infection often occurs during bathing. Poultry is often the source of infection. Mycobacteria can also live in the soil.
Of course, the mere fact of contact with mycobacteria does not mean that the disease will necessarily develop. Persons with reduced immunity (local and general) are predisposed to mycobacteriosis. Often there are facts of infection with mycobacteria in patients with obstructive pulmonary disease, cystic fibrosis of lung tissue, bronchiectasis. Among the provoking factors include injuries, including,.
Clinical picture
The clinic of mycobacteriosis caused by atypical mycobacteria is characterized by a variety of symptoms. The manifestations of the disease depend on the type of mycobacteria, the route of their penetration, age, gender, etc.
Bather's granuloma or pool granuloma
The causative agent of this disease is Mycobacterium marinum - mycobacteria that live in sea water. Penetration of mycobacteria is carried out through damage to the skin (scratches, abrasions, etc.). Infection can occur when swimming in pools with sea water, cleaning aquariums in which marine life lives, cleaning marine fish.
The incubation period for this type of skin disease caused by mycobacteria is on average 2.5 weeks. At the site of penetration of mycobacteria on the skin, a knot with a warty or covered with small scales surface is formed. The node has a bluish-reddish color.
This disease is more common in men aged 10-40 years. The resulting knot does not cause pain, has a fairly dense texture and is cold to the touch. Of the subjective sensations, itching is sometimes noted, but, usually, patients are more worried due to the formation of a cosmetic defect.
If the node is located above the joint, it may lead to a restriction of its mobility. When pressing on the node, a slight soreness is sometimes noted.
As the disease develops, an ulcer may form at the site of the node, covered with purulent or hemorrhagic crusts. At the bottom of the ulcer are observed. In some cases, child nodes and fistulas form around the ulcer.
Bather's granuloma is a disease with a long course. In place of a healed ulcer, it forms.
In the sporotrichoid form of the disease, soft subcutaneous nodes are formed that look like swellings with a diameter of about 2 cm. The nodes are located linearly, along the direction of the lymphatic vessel at a distance from the primary ulcer. When swelling is located above the joints, the clinic of the disease resembles bursitis or inflammatory arthritis.
The disseminated form of bathers' granuloma is extremely rare. Usually, this type of disease is observed in people with reduced immune status - HIV patients taking immunosuppressants, etc. In this case, in addition to the primary focus located at the site of penetration of mycobacteria, the formation of numerous linear nodes is observed. Localization of nodes depends on the method of infection. In bathers, the legs are usually affected; in aquarists, the dominant hand is usually affected. In the disseminated form of the disease, there is an increase in lymph nodes located near the primary focus.
Buruli ulcer
The causative agent of the disease is Mycobacterium ulcerans. This type of mycobacteria enters the body through damage to the skin. The disease is more common in tropical countries, mainly in young people. Women get sick a little more often.
Since the natural habitat of the Ulcerans mycobacteria has not been established, it is difficult to say how infection occurs. It is believed that infection occurs with minor injuries - with pricks with a thorn, a cut on a leaf of a plant, etc.
The incubation period of this disease is 3 months, so not all patients remember the microtrauma, which has become the "entrance gate" for mycobacteria.
Clinically, the disease is manifested by the appearance of a dense node, which quickly degenerates into an ulcer that does not cause pain. Ulcers in this disease can be very large, spreading to the skin of almost the entire affected limb. Most often, ulcers are localized on the legs, since it is the skin of the legs that is most often injured during walks in nature or as a result.
With Buruli ulcer, usually there are no symptoms of general intoxication, the lymph nodes are not changed.
Other varieties of atypical mycobacteriosis
Atypical mycobacterioses caused by Mycobacterium, Mycobacterium abscessus and Mycobacterium chelonae are very common. These mycobacteria usually enter through skin lesions and cause wound infections.
There is a geographical principle of the spread of infection. So, in European countries, skin infections caused by mycobacteria of the fortuitum type are more common. On the American continent, cases of infection with mycobacteria of the chelonae type are more common.
These mycobacteria are common in the environment, they can be found in water, soil, dust, wild or domestic animals.
Mycobacteria are introduced through wounds on the skin, and half of the cases of infection occur in wounds after operations and injections.
The incubation period lasts about a month, but sometimes it takes a longer time - up to 2 years.
At the site of penetration of mycobacteria, a dark red nodule is first formed, which is transformed into a cold abscess without pronounced signs of inflammation. After the opening of the abscess, separation of serous fluid is observed. In persons with a low immune status, a disseminated form of the disease is possible with the formation of multiple abscesses and joint damage. This type of disease develops with the hematogenous spread of mycobacteria throughout the body.
Diagnostic methods
The basis for the diagnosis of microbacterioses is the inoculation on media for mycobacteria. For research, discharge from ulcerative surfaces or biopsy material is taken. Additionally, the material is sown to us in the usual environment, this makes it possible to exclude the presence of secondary infection with other bacterial infections.
Treatment
Minocycline is used to treat the disease. The mainstay of treatment for skin lesions caused by mycobacteria is antibiotic therapy. The drug of choice for the fight against mycobacteria is usually minocycline. It is possible to use other antibiotics, taking into account the sensitivity of mycobacteria.
In the event that mycobacteria show little sensitivity to conventional antibacterial agents, rifampicin is prescribed in combination with ethambutol. By the way, rifampicin is also successfully used in the treatment,.
In the treatment of Buruli ulcer, antibiotics are often ineffective. With a large area of damage, the affected tissues are excised and the implantation of one's own skin is performed.
In disseminated forms of skin diseases caused by mycobacteria, anti-tuberculosis drugs are used.
Patients, as a rule, are offered hospitalization at the initial stage of treatment, since in order to select the most effective drug, it is necessary to constantly monitor the course of the disease. The general course of treatment for skin infections caused by mycobacteria can last up to a year.
With long-term treatment of the disease with antibiotics, hepaprotectors should be prescribed to protect the liver and probiotics to prevent the development of dysbacteriosis.
In the process of treating diseases caused by mycobacteria, it is necessary to provide the patient with good nutrition. It is recommended to limit exposure to the sun.
Treatment with folk remedies
For the treatment of folk remedies for skin infections caused by mycobacteria, it is recommended to choose recipes aimed at overall strengthening of immunity
In diseases provoked by atypical mycobacteria, it is recommended to take aloe preparations with honey. Useful vitamin teas from rose hips, mint, raspberries, currants.
Prevention and prognosis
Prevention of the development of skin diseases caused by mycobacteria is to prevent damage to the skin. The prognosis for these diseases is favorable, however, these skin infections require long-term treatment.
Mycobacteria.
Into the genus Mycobacterium families Mycobacteriaceae included acid- and alcohol-resistant aerobic immobile gram-positive straight or curved rod-shaped bacteria. Sometimes they form filamentous or mycelial structures. Characterized by a high content of lipids and waxes (up to 60%). Catalase- and arylsulfatase-positive, resistant to the action of lysozyme. Grow slowly or very slowly.
Mycobacteria are widely distributed in the environment - water, soil, plants and animals.
On the basis of pathogenicity, they are actually distinguished pathogens that cause specific diseases ( 5 groups - M. Tuberculosis, M. leprae, M. bovis, M. Miccroti, M. Lepraemurium) and atypical mycobacteria.
Pathogenic mycobacteria.
Mycobacterium Tuberculosis (Koch's wand). The causative agent of human tuberculosis is a chronic infectious disease characterized by lesions of the respiratory organs, bones, joints, skin, urogenital and some other organs. The disease has been known since ancient times. The pulmonary form of tuberculosis was described by ancient authors (Artaeus of Cappadocia, Hippocrates, etc.). However, the ancients did not consider it as an infection, Ibn-Sina considered it to be a hereditary disease. The first to directly point out its infectious nature was Fracastoro, and Sylvius noted the connection of pulmonary tubercles with consumption. The variety of clinical manifestations of tuberculosis caused many erroneous ideas: de Laaenek attributed pulmonary tubercles to malignant neoplasms, Virchow did not associate caseous necrosis with the tuberculous process. The growth of cities, crowding of the population and a low sanitary standard of living led to the fact that in the 18-19 centuries. Tuberculosis gathered a rich harvest among different sections of the population: suffice it to recall Mozart, Chopin, Nekrasov, Chekhov, and others.
The infectious nature of the disease was proved by Wilmen (1865), and the most important stage in the study and improvement of measures to combat tuberculosis was Koch's short report at a meeting of the Berlin Physiological Society on March 24, 1882 on the etiology of tuberculosis, in which he outlined the main postulates-criteria for assessing the pathogenicity of any microorganism.
Epidemiology. Storage tank Mycobacterium Tuberculosis - a sick person, the main route of infection is aerogenic, less often through the skin and mucous membranes. In rare cases, transplacental infection of the fetus is possible.
A) The penetration of mycobacteria does not always cause the development of a pathological process, a special role is played by unfavorable living and working conditions. Currently, there is an increase in the incidence, which is associated with an obvious decrease in the standard of living of the population and a concomitant imbalance in nutrition, on the one hand, and the “activity” of the pathogen is increasing, apparently due to the displacement of natural competitors as a result of the use of antimicrobial agents.
b) Equally important are the "aging" of the population around the world and the increase in the number of people with chronic diseases accompanied by impaired immunity.
V) a special role in infection Mycobacterium Tuberculosis the overcrowding of the population plays a role: in the Russian Federation - pre-trial detention centers, refugee camps, "homeless" people.
Morphology and tinctorial properties.
Thin, straight or slightly curved sticks 1-10 * 0.2-0.6 µm in size, with slightly curved ends, contain granular formations in the cytoplasm. The morphology varies depending on the age of the culture and cultivation conditions - in young cultures, the sticks are longer, and in old cultures they are prone to simple branching. Sometimes they form coccoid structures And L-forms that remain infectious, and filterable forms.
They are immobile, do not form spores, lack capsules, but have a microcapsule separated from the cell wall by an osmiophobic zone. acid resistant, which is due to the high content of lipids and mycolic acid in the cell wall, and also form acid-stable granules, mainly consisting of metaphosphate ( fly grains), located freely or in the cytoplasm of rods.
Gram-positive, aniline dyes are poorly perceived, according to Ziehl-Nielsen they are painted in bright red color, according to Fly-Weiss - in violet (iodophilicity).
cultural properties. aerobes, but able to grow under facultative anaerobic conditions, 5-10% CO2 promotes faster growth. They reproduce by division, the process is very slow, on average in 14-18 hours. Temperature optimum 37-38 gr.С, pH 7.0-7.2
(grows within 4.5 -8.0).
For growth, it needs the presence of a protein substrate and glycerol, as well as carbon, chlorine, phosphorus, nitrogen, growth factors (biotin, nicotinic acid, riboflavin), ions (Mg, K, Na, Fe).
For cultivation, dense egg media (Levinstein-Jensen, Petragnani, Doce), synthetic and semi-synthetic liquid media (Soton's medium) are used. On liquid media, growth is observed on days 5-7 in the form of a dry wrinkled film (R - form) rising to the edges of the test tube, the medium remains transparent. In environments containing detergent (tween-80) they give uniform growth throughout the thickness of the medium. On liquid media and during intracellular development, the characteristic cord factor ( trehalose-6,6-dimycolate), which causes the convergence of bacterial cells in microcolonies, their growth in the form of serpentine braids and is related to the virulence of the pathogen. On dense media, growth is noted on days 14-40 in the form of a dry wrinkled cream-colored coating, colonies with a raised center, reminiscent of cauliflower, crumbly, poorly wetted with water and have a pleasant aroma. Cultures are poorly removed from the environment, and crack when pierced. Under the influence of antibacterial drugs, they can dissociate with the formation of soft moist S-colonies or grow in the form of smooth or pigmented colonies. Distinctive feature Mycobacterium Tuberculosis - the ability to synthesize a significant amount of nicotinic acid (niacin), which is used for its differential diagnosis with other mycobacteria (niacin test), one of the conditions is the need for seeding on Levinstein-Jensen medium, which does not contain malachite green) because the dye reacts with the reagents used). On media with bile, it forms a greyish, oily coating formed by elongated branching rods.
Koch wand quite resistant to various influences, in milk it dies after 15-20 minutes at a temperature of 60 ° C, at a similar temperature it persists in sputum for up to an hour, and when boiled it dies after 5 minutes. Direct sunlight kills Koch's wand after 45-55 minutes, scattered - after 8-10 days. It is well preserved when dried (up to several weeks). Conventional chemical disinfectants are relatively ineffective, 5% phenol solution kills Mycobacterium Tuberculosis only after 5-6 hours, the pathogen is also able to quickly develop resistance to many antibacterial agents.
Pathogenesis of lesions and clinical manifestations.
A) Most often, infection occurs through inhalation of an aerosol containing mycobacteria, or through the use of contaminated products (penetration through the skin and mucous membranes is possible). Inhaled mycobacteria phagocytize alveolar and pulmonary macrophages and transport them to regional lymph nodes, phagocytic reactions are incomplete and the pathogen survives in the cytoplasm of macrophages. The ability to reduce the activity of phagocytes is caused by sulfatides, which enhance the toxic effect of the cord-factor, and inhibit phagosomal-lysosomal fusion. The inflammatory response is usually not pronounced, which is largely mediated by the ability of the cord factor to inhibit the migration of polymorphonuclear phagocytes. At the site of penetration may develop primary effect. In dynamics, along the regional lymphatic tracts and nodes, a primary complex is formed, characterized by the development of granulomas in the form of tubercles (hence tubercle, or tuberculosis).
the formation of granulomas has no characteristic features and is a cellular reaction of DTH. The sensitization of the body is due to the action of a number of products of mycobacteria, known as the old Koch tuberculin, which exhibits a local and systemic effect. To a certain extent, the formation of granulomas is promoted by the formation of lactic acid, low pH, high concentration of CO2. In the center of each tubercle there is a site of cheesy necrosis, where Koch's stick is located. The site of necrosis is surrounded by epithelioid and giant cells of Pirogov-Langhans. The center is surrounded by epithelioid cells, and along the perimeter - lymphocytes, plasmocytes and mononuclear cells, most often the primary focus is observed in the lungs (Gon's focus). In granulomas, the reproduction of the pathogen usually slows down or stops altogether.
Quite characteristic period of latent microbiism"- a condition in which the penetrated mycobacteria do not cause the development of inflammatory reactions and freely disseminate throughout the body.
In most cases, primary lesions heal with complete
content degradation, calcification and fibrosis
parenchyma.
Clinical manifestations are usually absent or resemble a flu-like syndrome, sometimes the primary focus or enlarged bronchopulmonary lymph nodes can be detected radiographically.
Primary tuberculosis is characterized by high sensitivity of tissues to metabolites of mycobacteria, which contributes to their sensitization; when the affect heals, the increased sensitivity disappears and the severity of immune reactions increases. However, under these conditions, dissemination of the pathogen from the primary foci and the formation of foci-screenings is possible, usually they are localized in the lungs, kidneys, genitals and bones.
b) When the body's immunity is weakened, the foci are activated and progress with the development of a secondary process. A certain contribution to the pathogenesis is made by the sensitization of the body, causing a variety of toxic-allergic reactions in the patient.
reactivation occurs 20-25 years after the initial infection. Usually it is provoked by stress, malnutrition and a general weakening of the body. In the lungs, bronchi and small vessels, cavities are formed, from which necrotic curd masses containing significant amounts of the pathogen are actively expectorated.
Clinically, reactive tuberculosis is manifested by cough, frequent hemoptysis, weight loss, profuse night sweats, and chronic low-grade fever.
V) In more rare cases, in frail adolescents and adults, as well as in patients with immunodeficiencies, there is disseminated (miliary) tuberculosis, characterized by the formation of granulomas in various organs.
the development of generalized lesions often occurs after the breakthrough of the contents of the granuloma into the bloodstream.
General manifestations are similar to those in secondary tuberculosis, but they are often accompanied by lesions of the brain and its membranes, the prognosis of this form is the most unfavorable.
The variety of forms has led to the complexity of its classification.
Currently, the clinical classification distinguishes three main forms:
Tuberculosis intoxication in children and adolescents.
Tuberculosis of the respiratory organs, including the primary complex, damage to the internal lymph nodes, pleura, upper respiratory tract, focal, infiltrative, cavernous, fibrous-cavernous, cirrhotic pulmonary tuberculosis, tuberculoma, etc.
Tuberculosis of other organs and systems, including lesions of the meninges, eyes, joints and bones, intestines and peritoneum, skin and subcutaneous tissue. Organs of the urinary-genital system, etc.
Laboratory diagnostics.
Includes methods included in the mandatory diagnostic minimum and additional research methods.
A). In case of illness – microscopy of pathological material(sputum, fistula discharge, urine, bronchial lavage) in Ziehl-Nielsen-stained smears, red acid-fast bacilli can be detected. (In recent years, the Murahashi-Yoshida method has been introduced, which makes it possible to differentiate between dead and living bacteria).
with a low content of the pathogen, the Ulengut accumulation method is used - the material is mixed with an equal or double volume of NaCl and NaOH, shaken and incubated for 30 minutes at a temperature of 21 ° C. Then cell debris and extraneous bacteria are removed by centrifugation, the precipitate is neutralized with 30% acetic acid solution and smears are prepared, stained according to Ztl-Nelsen or Kinyon.
the flotation method is more effective - NaOH solution, distillate, xylene (benzene) are added to the material and shaken vigorously, the resulting foam floats up and captures mycobacteria, it is sucked off and smears are prepared.
A certain value in assessing the severity of the process, the effectiveness of treatment and the prognosis of the disease has a quantitative assessment of the population of mycobacteria by the Gaffky-Stinken method (counting bacteria on calibrated glasses in certain fields of view).
The most effective bacterioscopic method - fluorescence microscopy, because fluorochrome staining (for example, auramine-rhodamine) makes it possible to detect even a small amount of mycobacteria (stained in white-yellow color), as well as forms with altered cultural and tinctorial properties.
B) Isolation of the pathogen. Before inoculation, the test material can be treated according to Ulengut or Sumioshi (15-20% HCl or H2SO4 solution), the test samples are centrifuged, washed with saline and inoculated, carefully rubbing onto solid nutrient media (usually Levinstein-Jensen). for simplicity, samples can be treated with various antibiotics that inhibit the growth of contaminating flora.
The disadvantage of the method is the duration of obtaining the result - from 2 to 12 weeks.
The advantage is the possibility of obtaining a pure culture, which makes it possible to identify it, evaluate its virulent properties, and determine sensitivity to drugs.
Accelerated methods for isolating the pathogen (Price) have been developed, the material is placed on a glass slide, treated with H2SO4, washed with saline and added to a nutrient medium supplemented with citrated blood. The glass is taken out after 3-4 days and stained according to Ziehl-Nelsen.
- "Gold standard" - in the diagnosis of tuberculosis - biological test on guinea pigs infected subcutaneously or intraperitoneally 1 ml of material obtained from the patient. Animals develop a generalized infection leading to death in 1-2 months, however, the disease can be recognized earlier by tuberculin tests - after 3-4 weeks, and lymphadenitis already on 5-10 days. Their punctures contain a large number of bacteria. However, the emergence of resistant and modified mycobacteria has reduced the sensitivity of this assay. To increase it, intratesticular infection is used, or the immunity of the animal organism is suppressed by the introduction of glucocorticoids.
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 according to Boyden. ELISA.
D. Skin tests with tuberculin are of particular importance, as they allow large-scale screening surveys of the population. The method involves the introduction of small doses (usually 5 units)
PPD-L into skin notches (Pirquet reaction), subcutaneously (Koch reaction).
With a positive result, 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 that the person has been exposed to the antigen. Mycobacterium Tuberculosis or other bacteria that cross-react. A positive reaction cannot be considered 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 a process - in immunodeficient individuals).
E. PCR - diagnostics.
G. Additional laboratory methods– assessment of the immune status.
Bacterioscopy
(gram positive sticks
Phlegm, urine, pus, punctate, etc.
Bacterioscopy
Bacterioscopy
bioassay
Non-tuberculous mycobacteria are independent species, widely distributed in the environment as saprophytes, which in some cases can cause severe diseases - mycobacteriosis. They are also called environmental mycobacteria (environmental micabacteria), causative agents of mycobacteriosis, opportunistic and atypical mycobacteria. A significant difference between nontuberculous 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 characteristics: 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, staining them yellow. Growth rate from 7 to 20 days at 25, 37 and 40 °C, katadazopositive.
M. kansasii - yellow bacilli, live in water, soil, most often affect the lungs. These bacteria can be identified by their large size and cruciform arrangement. An important manifestation of M. kansasii infections is the development of disseminated disease. Skin and soft tissue lesions, development of tenosynovitis, osteomyelitis, lymphadenitis, pericarditis and infections of the urinary tract are also possible.
2nd group - slow-growing cattle-chromogenic (M. scrofulaceum, M. matmoense, M. gordonae, etc.). Microorganisms form yellow in the dark, and in the light orange or reddish colonies, usually S-form colonies, grow at 37 °C. This is the most numerous group of nontuberculous 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 causes 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 have been isolated from raw milk and other dairy products.
M. maimoense - microaerophiles, form grayish-white smooth shiny opaque domed round colonies.
Primary isolates grow very slowly at 22-37°C. Their exposure to light does not cause pigment production. If necessary, the exposure is continued up to 12 weeks. In humans, they cause chronic lung disease.
M. gordonae are the most common recognized saprophytes, scotochromogens of water-bearing 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 non-chromogenic mycobacteria (M. avium complex, M. gaslri M. terrae complex, etc.). They form colorless S- or SR- and R-forms of colonies, which may have light yellow or cream hues. They are isolated from sick animals, from water and soil.
M. avium - M. inlracellulare are combined into one M. avium complex, since their interspecific differentiation presents certain difficulties. Microorganisms grow at 25-45 °C, pathogenic for birds, less pathogenic for cattle, pigs, sheep, dogs and non-pathogenic for guinea pigs. Most often, these microorganisms cause lung damage in humans. Lesions of the skin, muscle tissue and bone skeleton, as well as disseminated forms of diseases are described. They are among the causative agents of opportunistic infections that complicate acquired immunodeficiency syndrome (AIDS). M. avium subsp. paratuberculosis is the causative agent of Jones' disease in cattle and possibly Crohn's disease (a chronic inflammatory disease of the gastrointestinal tract) in humans. The microbe is present in the meat, milk, and faeces of infected cows, and is also found in water and soil. Standard water treatment methods do not inactivate this microbe.
M. xenopi causes human lung lesions and disseminated forms of disease associated with AIDS. They are isolated from frogs of the genus Xenopus. 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. With bacterioscopy, they look like very thin sticks, tapering at one end and parallel to each other (and in the form of a palisade). Often isolated 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 - the etiological agent of mycobacterial cutaneous N (Buruli ulcer), grows only at 30-33 ° C, the growth of colonies is observed only after 7 weeks. Isolation of the pathogen also occurs when mice are infected in the pulp of the sole of the paw. This disease is common in Australia and Africa. The source of infection is a tropical environment and vaccination with BCG 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 composed of subspecies. They cause disseminated processes, skin and postoperative infections, lung diseases. The microbes of this complex are highly resistant to anti-tuberculosis drugs.
M smegmatis is a representative of the normal microflora, 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 the skin and soft tissues. The causative agents of tuberculosis must be differentiated from M. smegmatis in the study of urine.
Epidemiology of mycobacterioses
The causative agents of mycobacteriosis are widely distributed in nature. They can be found in soil, dust, peat, mud, rivers, reservoirs and swimming pools. They are found in ticks and fish, cause diseases in birds, wild and domestic animals, and are representatives of the normal microflora of the mucous membranes of the upper respiratory tract and genitourinary 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. Transmission of microorganisms from person to person is uncommon. These are conditionally pathogenic bacteria, therefore, a decrease in the resistance of the macroorganism and its genetic predisposition are of great importance in the occurrence of the disease. Granulomas form in the affected areas. In severe cases, phagocytosis is incomplete, bacteremia is pronounced, and macrophages filled with non-tuberculous mycobacteria and resembling leprosy cells are determined in the organs.
, , , , , , , ,
Symptoms of mycobacteriosis
The symptoms of mycobacteriosis are varied. The respiratory system is most often affected. Symptoms of pulmonary pathology are similar to those of tuberculosis. At the same time, cases of extrapulmonary localization of the process involving the skin and subcutaneous tissue, wound surfaces, lymph nodes, urinary organs, bones and joints, and meninges are not uncommon. Organ lesions can begin both acutely and latently, but almost always proceed severely,
It is also possible to develop a mixed infection (mixt-infection), 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. The material for the study is taken based on the pathogenesis and clinical manifestations of the disease. Initially, the issue of whether the isolated pure culture belongs to the causative agents of tuberculosis or non-tuberculous mycobacteria is resolved. Then a set of studies is used to determine the type of mycobacteria, the degree of virulence, as well as the Runyon group. Primary identification is based on characteristics such as growth rate, pigment formation capacity, colony morphology, and ability to grow at various temperatures. To identify these signs, no additional equipment and reagents are required, so they can be used in the basic laboratories of TB dispensaries. The 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. Of great importance for baking is the determination of sensitivity to antibiotics. 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-tuberculous mycobacteria, conducting multiple studies in dynamics.
SRSP
Pathogenic and conditionally pathogenic microbacteria: causative agents of tuberculosis, leprosy, actinomycosis. Condidiasis of the oral cavity. The manifestation of pathological processes in the maxillofacial region. Spirochetoses: syphilis, relapsing fever, leptospirosis, chlamydiliosis, microplasmomas. Odontogenic infections.
Group: 211 A
Faculty: Dentistry
Completed by: Vladimir Sukhanov
Checked by: Daulbaeva S.F.
1. Sources of pathogen
2. Classification of Mycobacterium tuberculosis
3. The causative agent of tuberculosis
Sources of the pathogen.
Tuberculosis is a chronic disease, often a latent infection that spreads relatively slowly. This is due to the slow reproduction of the pathogen (the rate of division of Mycobacterium tuberculosis Mitchison determines 18 hours, Frobisher - 24 hours) and the duration of the incubation period (from weeks to several years). An infection not detected in a timely manner often develops for years, and all this time the animal remains dangerous for surrounding healthy animals. The source of the pathogen can be not only different types of animals, but also a person. With tuberculosis of animals, multiple localization of lesions is possible: lungs, liver, udder, genitals, gastrointestinal tract. In other cases, only the lungs may be affected, but the release of mycobacteria occurs both through the respiratory tract and with feces, since sputum containing the pathogen is often swallowed and enters the gastrointestinal tract. One of the features of bovine tuberculosis is that when infected at a young age, the disease manifests itself only at the first, second and third calving.
Mycobacteria are resistant to environmental factors and can survive in soil, water, manure and other objects for months and years.
Many species of domestic and wild animals, game animals and birds (more than 55 species of mammals, more than 25 species of birds), as well as humans are susceptible to tuberculosis.
The process of spreading tuberculosis among animals is commonly called an epizootic process. It is a chain of successive infections from one animal to another. This is possible only if, firstly, there is a source of the pathogen, i.e. an infected animal secondly, transmission factors, i.e. objects of the external environment that can ensure the transfer of the pathogen; thirdly, the presence of susceptible livestock. The absence of one of the links makes the transmission of tuberculosis impossible.
The epizootic process is a complex phenomenon. Depending on the conditions of keeping, feeding, exploitation of animals, human economic activity, it is either suppressed. Or activated.
Infection is the result of the interaction of a living pathogen and the animal organism. The introduction of Mycobacterium tuberculosis into the body of an animal, their reproduction in it, moving to another living organism is a way of existence of the pathogen, i.e. it has been preserved in nature as a species.
Tuberculosis takes a long time, for several months and years. For him, as well as for other infectious diseases, a cyclical course is characteristic, i.e. successive change of periods of development: incubation, beginning, peak and attenuation. In the incubation period of the disease, the pathogen is usually not released into the external environment. In the initial period, as a rule, the release of the pathogen is noted. The peak period of the disease is characterized by the maximum release of the pathogen and the high risk of sick animals.
The main source of the causative agent of tuberculosis in cattle are sick animals of the same species. Other animals infected with bovine tuberculosis and having contact with healthy animals also play a certain role in the spread of the disease.
Classification of mycobacterium tuberculosis.
The classification of mycobacteria is based on both morphological and biological features. Types of mycobacteria differ from each other both in their effect on the human or animal body, and in their ability to use certain nutrients, form a pigment, and grow at different temperatures. When distinguishing between different species, particular importance is attached to the appearance of the colonies, which can be colorless or colored, transparent or dense, smooth or rough, have slow growth, etc.
The identification of mycobacteria presents great difficulties. Cases of isolation from pathological material of non-tuberculous (atypical) mycobacteria, which are independent species, have become more frequent. The genus of mycobacteria includes more than 30 species. Pathogenic species include M.bovis, M.tuberculosis, M.avium, M.africanum, M.paratuberculosis, M.leprae.
Potentially pathogenic species for humans include M.konsasii, M.marinum, M.scrofulaceum, M.xeponi, M.ulcerans, M.fortuitum, M.chelonei. The remaining 16 species are non-pathogenic to humans.
Some types of atypical mycobacteria cause pathomorphological changes in the lymph nodes in pigs, indistinguishable from changes caused by Mycobacterium tuberculosis, in other animals - their sensitization to tuberculin. Each type of mycobacteria is most dangerous for the animal species in which it has acquired pathogenic properties.
M.bovis give primary growth in the form of small smooth colonies on the 30-45-60th day. With passages, growth is observed on the 14-21st day. The colonies have no pigment, are white or grayish in color. A thin film is formed on a liquid medium. The temperature optimum is 37 - 38 C, at a temperature of 22 and 45 C - they do not grow. Pathogenic for cattle, pigs, sheep, goats, camels, buffaloes, deer, deer, dogs, cats and other animal species, as well as humans.
M.tuberculosis form the primary growth when sowing pathological material on the 21-45-60th day. Transplanted cultures grow faster - on the 10-14-21st day. Growth on solid egg medium containing glycerin is usually luxuriant; cultures are cream-colored and grow in the form of rough R-colonies, but can be smooth, merging with each other (S-variant). On a liquid nutrient medium, mycobacteria of the human type of tuberculosis form a wrinkled rough film, and sometimes even a crumbly growth near the bottom. The temperature optimum is 37-38 C, at 22 and 45 C they do not grow. In a Ziehl-Neelsen-stained smear, they are morphologically presented as polymorphic, thin, alcohol-, acid-resistant sticks, often curved. Pathogenic for humans, monkeys, guinea pigs, mice, dogs, cats, parrots. In cattle, as a rule, they cause sensitization of the body to tuberculin for mammals and only occasionally cause limited changes, mainly in the lymph nodes, regional sites of penetration of mycobacteria.
M.avium differ from the bovine and human species in colony morphology. They are soft, slimy, grayish-white, occasionally slightly yellow-pigmented, sometimes, when sown from pathological material, they grow in the form of “cakes” or “bagels” rising above the surface of the medium. Growth appears by the end of the 15-20-30th day, sometimes later, with resowing by 7-10 days. In subcultures, they are presented in the form of a smooth, wet coating. Cultures grow better at 43-45 C. Morphologically, M. avium in culture smears looks like thin acid-resistant rods, longer and more polymorphic in smears-prints from the organs of infected chickens and rabbits. Pathogenic mainly for birds, rabbits, white mice, can cause pathological changes in organs in pigs and other animals.
M. africanum causes tuberculosis in humans in tropical Africa. The systematic position as a separate species is still being discussed.
M. microti causes natural tuberculosis in field mice.
M. paratuberculosis in smears from pathological material are arranged in groups, nests and palisades, rarely - in pairs, three, four, and even less often - singly. It is extremely difficult to grow on artificial nutrient media and only with the obligatory addition of the so-called growth factor to them. The optimum growth temperature is 38 C. Primary growth appears in 30-60 days, sometimes later, in the form of tiny colonies, gradually acquiring a white-cream color and increasing. Pathogenic for cattle, goats, camels, sheep, reindeer.
M.konsasii - sticks are moderately long to long, expanding and have a noticeable transverse striation. On egg media, they form smooth or rough colonies after 7 days or after sowing. Optimum growth temperature is 37 C. Refers to photochromogenic mycobacteria. Pathogenic for humans. Causes chronic lung disease in humans similar to tuberculosis.
M.simiae are photochromogenic, niacin-negative, catalase- and peroxidase-positive. Pathogenic mainly for monkeys.
M. marinum causes skin granulomas in humans due to abrasions from swimming in the pool. Cultures are photochromogenic.
M.scrofulaceum - grow on egg media at 25-37 C in the form of smooth yellow or orange colonies. Growth appears 7 days after sowing when grown in a thermostat at 37 C. Slightly pathogenic for animals, localized lesions of the liver and spleen are rarely detected in rats, hamsters and chickens; in guinea pigs infected subcutaneously, abscesses appear at the site of inoculation and regional lymph nodes increase.
M.intracellularae - sticks from short to long. On egg media, 7 days after inoculation, they form smooth, unpigmented colonies at a temperature of 37 ° C. As they age, the colonies may turn yellow. Cause pathoanatomical changes in the lymph nodes of pigs. pathogenic for chickens.
M.xeponi - long filamentous sticks. Grow at a temperature of 40-45 C. Young cultures give unpigmented rough colonies; later a yellow pigment appears. isolated from toad. Potentially pathogenic to humans.
M. gastri - moderately long and thin sticks. On egg media, they form smooth and rough colonies 7 days or more after sowing. They grow at a temperature of 25-40 C. They are isolated from soils, waters, and the human stomach.
M.terrae - moderately long thin sticks. They grow on egg media for 7 days or more after sowing in the form of smooth or rough colonies of white or dark yellow color at a temperature of 37 C. They are isolated from the soil.
M. triviale - on egg media grow in the form of rough R-colonies.
M.fortuitum - sticks from 1-3 microns long, coccoid, thickened, sometimes with thread-like branches. On egg media, growth is noted 2-4 days after sowing, colonies can be smooth, hemispherical in shape. Guinea pigs, rabbits and mice rarely cause generalized infection even at high doses of infection.
causative agents of tuberculosis.
The true mycobacteria of tuberculosis are M.bovis, M.tuberculosis, M.avium, the latter only as the causative agent of avian tuberculosis; if M. avium is isolated from pigs and cattle, then we are talking about atypical mycobacteria.
M.bovis is the main causative agent of bovine tuberculosis. However, it is also pathogenic for other domestic and wild ruminants, humans and primates, carnivores, as well as parrots, and possibly some other birds of prey.
M.bovis - slightly curved or straight, short or moderately long, thin rods with rounded ends (0.3 - 0.6 microns in width, 1.5 - 4 microns in length). Grains (Fly grains) are sometimes found inside the sticks, usually located at the ends of mycobacteria. Both the size and the number of granules in them depend on the age of the culture and the conditions of its growth (Drabkina, 1963). However, polymorphism of mycobacteria is noted not only in culture, but also in pathological material, where, along with coccus-like forms, longer forms can also be present. In the pathological material, Mycobacterium tuberculosis of the bovine species are located in parallel or at an angle, or in groups.
Mycobacterium tuberculosis are immobile, do not form spores, do not have flagella. The optimum growth temperature for M. bovis is 37-38 C. The addition of glycerol to egg media slows down the growth of mycobacteria or does not appear at all. When sowing pathological material on the Levenshtein-Jensen medium, round, small, moist, almost transparent colonies of ivory color (dysgonic growth) grow. M.bovis culture is microaerophilic. Therefore, sowing in liquid or semi-liquid media gives growth in the depth of the medium. When reseeded, the culture adapts to aerobic growth.
M.tuberculosis is the main causative agent of human tuberculosis, but it is also pathogenic for primates, dogs, parrots and some animals that come into contact with humans. Slightly pathogenic for rabbits, cats, goats, cattle and poultry.
M.tuberculosis - straight or slightly curved thin sticks, sometimes very short or long, and sometimes branching forms. Thus, tuberculosis bacteria are characterized by polymorphism. Mycobacteria polymorphism is especially often described in antibiotic therapy. Young individuals of mycobacteria are longer, and more mature ones are shorter, coccal forms appear. Old cultures sometimes have branched forms of mycobacteria. Mycobacteria contain granules, the number of which varies and depends on many factors.
M.tuberculosis grows faster on artificial nutrient media than M.bovis. addition of glycerin to culture media improves and accelerates the growth of M.tuberculosis. Mycobacterium tuberculosis of the human species on dense egg media grow in the form of dry, crumbly, opaque colonies of irregular shape, sometimes resembling cauliflower. On bovine serum, glycerine potatoes and 5% glycerine whey, they grow slowly, luxuriantly, with thick folded edges (eugonic growth). Usually the colonies are ivory in color, but with aging they become cream or even yellow in color. They are poorly suspended in water. M.tuberculosis culture is highly aerobic; sowing in a liquid or semi-liquid nutrient medium gives growth on the surface of the medium. The optimal growth temperature is 37 C, but it grows, although much worse, at 30-34 C (pH 6.4 - 7.0). At room temperature and elevated temperature (45 C), like M. bovis, growth does not.
M.avium is the main causative agent of tuberculosis in domestic and wild birds. It is also pathogenic for pigs, to a lesser extent for cattle. In humans, it can cause tuberculosis, often with a severe course (Blagodarny, 1980).
Microorganisms. At the ends of the sticks, inclusions in the form of beads and granules are usually visible. Chains of bacteria are often formed, sometimes branched. A characteristic property of mycobacteria is acid, alcohol and alkali resistance (see Acid-resistant bacteria), associated with the accumulation of wax-like substances in the cell and the special structure of the cell membrane. Mycobacteria are cultivated on enriched dense media with the addition of eggs, milk, potatoes and on liquid synthetic media with the addition of albumin. Mycobacteria include the causative agents of tuberculosis,.
According to Bergi (D. Bergey, 1957), pathogenic representatives of mycobacteria include seven species: M. tuberculosis hominis, M. tub. bovis, M. tub. avium, M. microti, M. para tuberculosis, M. leprae hominis, M. lep. murium. Recently, the 8th species, M. ulcerans, has been included in the pathogenic group of mycobacteria. Mycobacteria of this species grow at t° not higher than 33°, isolated from ulcerative lesions of the human lower extremities, in the experiment cause skin lesions in mice and rats. A special potentially pathogenic group is made up of mycobacteria isolated from skin lesions of humans, cattle, from cold-blooded animals - fish, snakes, etc., from the soil. The main representatives of the group - M. fortuitum, M. marinum, M. thamnopheos, M. platypoecilus - grow at t° 10-20-25°; for pigs, rabbits, mice are not pathogenic.
True saprophytes are morphologically and tinctorially similar to pathogenic mycobacteria, but they are more polymorphic, relatively acid-resistant, weakly alkali- and alcohol-resistant. They grow rapidly on ordinary and special media at t° 10-20°. The main representatives of saprophytes: M. phlei (Timothy grass stick) - grows at t ° 28-52 ° in the form of a soft coating of grayish or yellow color, which forms folds during aging; M. smegmatis - polymorphic, relatively short sticks, grow 2-4 days on all media at t ° 28-45 ° in the form of a juicy, oily cream coating, sometimes dry. Both species are not pathogenic for experimental animals.
A special heterogeneous group consists of the so-called atypical, or abnormal, unclassified mycobacteria. Their nature and significance in human pathology have not been precisely elucidated. They are isolated relatively rarely from material from people with tuberculosis or clinically similar diseases (“mycobacteriosis” of the lungs, pleura, lymph nodes, joints, etc.). It is temporarily accepted to divide "anonymous" mycobacteria into 4 groups: 1) photochromogenic mycobacteria (Kansas type); cultures of them, usually pigmentless when grown in the dark, even with a short exposure to light, acquire a lemon-yellow color; 2) scotochromogenic mycobacteria - cultures of orange color when growing in the dark; 3) non-photochromogenic, non-pigmented mycobacteria - grayish, pale yellow, do not produce pigment when exposed to light; 4) rapidly growing at room temperature. On dense media, atypical mycobacteria form a smooth, finely folded, often oily coating; on liquid media, they grow on the bottom in the form of flakes, and on the surface of the medium in the form of a thin oily film. Cells of atypical mycobacteria are polymorphic, grow on different nutrient substrates at t° 20-37-38°, they do not form "tangles". Most strains are not pathogenic and not virulent for guinea pigs and rabbits, some, especially photochromogenic ones, are virulent in significant doses for white mice when administered intravenously (0.5-1 mg) and for golden hamsters when administered intraperitoneally (1-10 mg). Acid-resistant; stained red according to Ziehl-Nelsen. They have a pronounced catalase activity, mostly initially resistant to such anti-tuberculosis drugs (see), as tubazid, sodium paraaminosalicylate. Tuberculin reactions in humans and experimental animals with "mycobacterioses" are unstable.
Mycobacterium tuberculosis - see Tuberculosis.
