Theme of lecture: Determination of tuberculosis as scientific and practical problem. Phthisiology history. Epidemiology of tuberculosis. Etiology, pathogenesis of tuberculosis.

Immunity at tuberculosis.

HISTORICAL REVIEW
Tuberculosis, as an illness, is known since ancient times. The principal clinical manifestations of tuberculosis are described still by Hippocrate, Gallen, Avizenna. The fact that tuberculosis is infectious disease was confirmed by Fracastoro in the 16th century. It was Morton who published the first monography "Phthisiology or a treatise on the phthisis" (R. Morton, 1689) and named a science of tuberculosis "phthisiology" (from the Greek word "phthisis" -which means exhaustio. In the 17th century the French anatomist Sylviy, describing the hurt lungs of patients who had died of phthisis, used the word "hump" (tuberculum). However, it was only in the 19th century in France that pathologists and therapeutists G. Bayle, and then R. Laennec proved the hump and caseous necrosis to be specific morphological substratum of tuberculosis. In 1865 the French physician B. Villemin experimentally proved the infectious nature of tuberculosis, though he could not reveal the pathogene. In 1882 the German bacteriologist Robert Koch (fig. 1) discovered the pathogene of tuberculosis, which was named bacillus of Koch (BK). He was also the first who obtained tuberculin with the hope to successful treatment of tuberculosis patients. These expectations of the scientist did not come true, nevertheless for the purpose of diagnostics tuberculine has been used for over 100 years. M.I. Pyrohov studied clinico-morphoiogical properties of tuberculosis of various localization and for the first time described typhoid form of miliar tuberculosis, histologic structure of tuberculous granuloma. Further study of pathomorphologyl alterations at lungs tuberculosis was proceeded by A.I. Abrykosov and A.I. Strukov.

In 1887 R. Philip in Edinburgh (Scotland) founded the world first antituberculosis dispansery. This new institution offered the patients not only medical but also social help, which later on laid the foundation of the organization of antituberculosis service also in this country. In 1882 in Rome C. Forlanini offered artificial pneumothorax for treating lung tuberculosis patients. In 1895 Wilhelm Kondrat Roentgen discovered X-rays, which have been widely used in medicine up to today. Actually, it's known well enough that X-rays were discovered by Ukrainian scientist Ivan Pulyuy (1845-1918) from Halichina 17 years earlier. However, he made his announcement about the discovery 7 days after Mr. Roentgen had made his one, thus the preference was given to Mr. Roentgen who received Nobel Prize. In 1909 the first free hospital for tuberculosis patients was opened in Moscow. An important achievement of the start of the 20th century was the creation by the French scientists Calmette and Guerin (1919) of the antituberculosis vaccine BCG (Bacilles Calmette, Guerin). Since 1935 mass vaccination began. At the same time in 1924 Abre in Brazile introduced the method of fluorographic observation of the population for active revealing lung tuberculosis patients. In 1944 the American bacteriologist from Odesa S. Waksman obtained streptomycin, for which he was awarded the Nobel Prize (1952). PASA, tibon, GINA preparations (the most effective of them -isoniazidum, synthesized in Fox's laboratory. GB, 1951) came into practice somewhat later, and since 1965 rifampicinum, the most effective antimycobacterial medicine has been used.

THE WORLD TUBERCULOSIS EPIDEMIOLOGICAL SITUATION

More than 6 billion people live on our planet now. More than 2 billion of them suffer from various diseases. Every fifth earthman lives in extreme need and poverty, which has become the main death reason in the world. Today tuberculosis is the most widely spread infectious disease which ranks first as to the deathrate among the people from infectious pathology. Moreover, new misfortunes are added. In 2001 A.D. there are 30-40 million carriers of the human immunodeficite virus in the world and 10 million AIDS patients, who increase the number of tuberculosis patients considerably. According to the data of the World Health Organization half of the globe population is infected with tuberculosis mycobacteria. In some countries infectiousness of the population with tuberculosis reaches 80-90 %. 1 his is also true about Ukraine. Every year each tuberculosis patient can infect 10-15 and more persons of which 5-10 % will catch the disease.

Every year 7-10 million people fall ill with tuberculosis all over the world, including 4-4,5 mln. - with bacterial secretion and about 3 mln. adults die of it (of these 97 % - in the developing countries) and approximately 300 thousand children. The total number of tuberculosis patients reaches 50-60 mln. Nowadays tuberculosis is the most menacing illness forthe whole mankind. It kills more patients worldwide than all the infectious and parasitic illnesses taken together. Present tuberculosis epidemic has acquired the global scales. In many parts of the world tuberculosis epidemic is beyond the control. The highest tuberculosis statistics of sickness is noted in African and Asian regions, in the countries of the Pacific Ocean coast. Tuberculosis epidemic situation got worse in the countries of Europe too, especially in the countries of the former Socialist community. In 1998 the lowest tuberculosis index was registered in the highly developed countries, such as Malta (4,2), Sweden (5), Norway (5,5), Iceland (6,2), Italy (8,4 per 100000 of the population), the highest- in Romania (114,6), in the former Soviet Union, as in Kyrgystan (127,8), Kazakhstan (126,4), Georgia (124,4), Turkmenistan (86,1 per 100.000 of the population).

Ukraine 68,4%
68,0% 51,0% 82,5% 59,0% 34,6%

76,0%
56,1%

52,9%

57,8% 93,7%

66,3%

53,1% 54,7% 56,3 %

59,5% 81,4% 90,5%

80,2% 67,3%

66,1% 49,2% 106,9%

59,9%

77,4%
63,9%

TUBERCULOSIS MICROBIOLOGY

The causative agent of tuberculosis belongs to Mycobactrium species, Actinomycetales order, Schizomycetes class. Representatives of Mycobacterium species also cause leprosy, many of them are saprophytes found in smegma, cerumen, sputum from bronchiectasis. They are also acid-fast microbes vegetating on mucosal surface, batter, milk, plants, in water, soil, etc. By contagiousness for man and animals Mycobacterium species are divided into two groups: the first group is pathogenic tuberculosis bacteria proper subdivided into three types: M.tuberculosis causing tuberculosis in man, M.bovis causing bovine tuberculosis, and M.africanum; the second group is atypical Mycobacterium species with saprophytes (nonpathogenic for man and animals) and opportunistic pathogens.

The chemical composition of Tb

Is well studied: they consist of 80% water and 2-3 % lime. Solid residue consists of 50 % protein, mostly tubercular proteins, 8-40 % lipids, and about the same percentage of polysaccharides. Tubercular proteins have been suggested to be complete antigens able to cause anaphylaxis in animals.Mycobacteria resistance is provided by fat content; polysaccharide fraction plays a role in immunogenesis. Tubercular proteins and lipid fractions are responsible for the toxicity of Mycobacteria,which they retain even after having been killed. High fat content gives Mycobacteria the following properties: 1. Fastness to acids, alkalis, and alcohol (mostly due to mycolic acid content). 2. Resistance to basic disinfectants. 3. Pathogenicity. Exotoxins have not been detected in Mycobacteria, but the cells themselves are toxic, loading to partial or entire leucocyte disintegration. The antigen composition of Mycobacteria is complicated and not well understood. Different strains have different antigens. Commonly present antigens in all Mycobacteria are polysaccharides, which are also responsible for bacterial resistance to heating and proteolytic enzymes.

Tb immunogenicity is determined by the antigenic complex of Mycobacteria cell wall as well as thermolabile ribosomes fraction. Pathogenicity is the capability of Mycobacteria species to cause diseases. The basic factor of pathogenicity is toxic glycolipid cord factor, which is toxic to tissues and protects Mycobacteria from phagocytosis. Because of this, Mycobacteria propagate even in phagocytes, leading to their death. Acid-fast saprophytes are not characteristic of the cord factor. Virulence is the degree of pathogenicity and capability of Mycobacteria to grow and develop in the host, causing specific organic changes. Mycobacterium strain is said to be virulent if 0.1-0.01 mg of it causes clinical symptoms of tuberculosis and death of a 250-300 g guinea pig in 2 months. If the animal dies in 5-6 months, the strain is said to be weakly virulent. Virulence is not a constant property of Mycobacteria: it decreases with culture ageing, growth on nutrient media, and due to antituberculosis treatment. Passage on animals or disease exacerbation leads to virulence increase.

Atypical Mycobacterium Species. E.N. Runyon divided these into four groups based on their growth rate and pigment formation: - the Ist'group (photochromogeneous bacteria) produce lemon-yellow pigment on exposure to light; it takes 2-3 weeks for a colony to grow. The representatives are M.kansasii, M.marinum; - the 2nd' group (scotochromogeneous bacteria) produce yellow-orange pigments in the dark or on exposure to light. The representatives are M.aquae, M.serofulaeeum; - the 3rd' group (nonphotochromogeneous bacteria) produce weak or no pigment; it lakes 5 10 days for a colony to grow. The representatives are M.avium, M.intracellulare, M.xenopi, M.haemophilum; - the 4th group (rapidly growing bacteria) forms a colony in 25 days. These are predominantly saprophytes (M.phlei, M.smegmatis, M.fortuitum).

There are three types of mycobacteriosis singled out by the type of Mycobacterium and the host's immune status: 1.Generalized infection with macroscopic signs similar to I hose of tuberculosis, but different from it microscopically. There is a diffuse interstitial alteration in the lungs without granuloma or caverna formation. The clinical signs are fever, dissemination in the middle and lower segments of both lungs, the patients are anemic and neutropenic. Other symptoms include diarrhea and abdominal pain. The diagnosis is proved by the causative agent culture from sputum, feces or by means of biopsy. Mycobacteriosis is difficult to treat. Effective preparations include cycloserin, ethambutol, kanamycin, rifampicin, and sometimes streptomycin. 2. Localized infection is characterized by micro- and macroscopic local alteration in the host. 3. Infection without visible signs. The causative agent is harbored in the lymph nodes.

Pathogenesis
MBT pathways in the body limentary (8%) rogenic (92%) 10000-100 000 MBT Bronchial tree (ciliary epithelium) Nonspecific inflammation (toxins) Noncompleted phagocytosis MBT lymphocytes and phagocytes Lymphocytes absorbed MBT Intrathoracic lymph nodes Tuberculosis granuloma With the lowered immune resistance breeding MBT Blood (bacylemiya) Lymph (limfemiya) MBT accumulate in the RES, lymph nodes, liver, spleen, bone marrow, lungs Intrauterine

contact (in skin, mucous)

Phases of primary infection

Phase immunomorphological responses (macrophages make phagocytosis MBT , highlighting factors chemotaxis and activation of immune reorganization of the organism nonspecific epithelioid granuloma

Phase bacteremia and hematogenous dissemination (lasts 4-6 hours, MBT penetrate the submucosa, the lymph and blood vessels and spread throughout the body. At this time there is elimination of the MBT in the tissues of various organs.

Phase clinical and pathomorpholog ical manifestations of the disease hyperener gy

Phase completion of tuberculosis and residual change or transformation in chronic forms exudativedestructive processes with formation of cavities

productively-caseous and exudative-necrotic anenergy impressions productively-cheesy caseous tissues without or with little degradation

Tuberculosis granuloma normenergy

Secondary infection
exogenous superinfection
MBT enters the body, nonspecific inflammation, phagocytosis is not finished (formed superantyhen) endogenous reactivation

macrophage dies, the MBT enters the tissue, it takes another macrophage B-lymphocyte plasmatic cell Ig M Ig G -h (activation B) -k (kill B) Carries information in the thymus Part of the MBT go out another

Some MBT excreted in the urine, sputum

lymphocyte

-s (inhibits the immune )

- lymphocyte

In the body finished memory of infection. This information carries T - memory that

ends up in the RES system and there are over ten years.

TUBERCULOSIS PATHOLOGY.
The main morphological element of tubercular inflammation is a tubercle, often called a tubercular granuloma. A distinctive feature of a tubercular granuloma is central cheesy or caseous necrosis -dense amorphous cell detritus consisting of dead phagocytes. The zone of caseous necrosis is surrounded by several layers of epithelioid cells, macrophages, lymph and plasma cells. Great multinuclear Pirogov-Langhans' cells can be found among epithelioid cells. The cells around the zone of caseous necrosis form granulation tissue. These cells may be dystrophic and destroyed. Specific inflammation involves parenchyma cells, lymphatics, and blood vessels of the affected organ. In the course of pulmonary tuberculosis specific inflammation also involves the bronchi. Tuberculosis is said to be a granulomatous disease due to its immunological and pathological features of specific inflammation. The function of the affected parenchyma cells is significantly compromised due to their dystrophy and destruction. The draining function of lymphatics is decreased as lymph enters the intercellular space due to the damaged endothelium of the lymphatic vessels. Thrombosis of small blood vessels leads to microcirculation compromise: blood vessels are damaged due to the fixation of circulating immune complexes to their basal layer as can be seen under the electronic microscope. There are almost no blood vessels in the tubercular granuloma: nutrients are supplied to granuloma cells by diffusion from the extracellular fluid.

Tuberculosis granuloma

The character of cell reaction determines the cell content of a granuloma and necrosis prevalence. Epithelioid, macrophage, and multinuclear giant cells are prevalent in productive cell reaction. The outer cell layer has fibroblasts synthesizing collagen. There is little or no necrosis at the center of such a granuloma. Larger necrosis is seen in exudation cell reaction: necrosis takes from 30 % to 50 % of the granuloma. Macrophages and lymph cells are prevalent in the cellular layer but a limited number of epithelioid and giant cells can also be seen in such a granuloma as well. Alteration cell reaction features prevalent necrosis and a weak or absent cellular layer of the granuloma. Prevalent exudation tissue reaction signifies tubercular Inflammation progression. Serum and fibrin infiltrate the tissues surrounding granulomas. The latter gradually merge into tubercular focus, a pathologic formation up to 1 cm in diameter. Foci progress as inflammation spreads; the latter can be serous, fibrinous or suppurative from the start. Then appear new tubercular granulomas with prevalent central necrosis surrounded by a layer of few epithelioid and giant cells being the signs of specific inflammation. The progressive merging of tubercular foci results in the formation of tubercular infiltrates with caseous necrosis foci, followed by the infiltration of caseous masses with polynuclear leucocytes. Caseous masses melt under the influence of proteolytic enzymes from leucocytes leaving disintegration cavities, which later may transform into caverns. A sharp decline of cell-mediated immunity leads to the fast progress of pathological process resulting in necrotic granuloma formation. Quite soon large foci of caseous necrosis are formed in the affected organ.

The absence of specific granulation tissue in the localized foci is a pathology and a clinical sign of recuperation from tuberculosis with the formation of residual posttuberculous changes. These changes can take different forms, for instance a scar, an encapsulated or calcified fibrotic focus, or an area of focal or diffusive pneumofibrosis. In some cases tubercular inflammation ends with the formation of "sanitized" disintegration cavities. Residual posttuberculous changes contain metabolically inactive Tb between fibrotic fibers. The changes are the reservoir of endogenous tubercular infection; they support antituberculous immunity and might cause tuberculosis relapse. Tubercular inflammation involution with the complete dissolution of pathological foci, no residual changes completed with Mycobacteria elimination from the host happen very rarely. Such an outcome is possible with uncomplicated primary tuberculosis and the fast renewal of immunity damaged at the beginning of the disease. Infection with Tb may also lead to unspecific changes in tissues. Even caused by Tb, these changes do not have any specific tubercular features. For this reason these are called paraspecific. Para-specific tissue reactions may develop in the cardiovascular system and parenchymatous organs. Timely diagnosed and adequately treated, these paraspecific changes heal rather, quickly and without residual changes. Two consecutive periods of the primary and secondary tuberculosis also have a peculiar pathology.

The primary tuberculosis always involves lymphatics. Local or total caseous necrosis of lymph nodes is the most important feature of the primary tuberculosis, as is the presence of large perifocal inflammation. In the lung the primary affection is chiefly localized in such well-ventilated areas as the middle and lower lung lobes. Characteristic of the primary tuberculosis bacteriemia leads to blood-borne metastatic infection foci in the lungs and other organs. Generalized paraspecific reactions happen quite often. Residual posttuberculous changes undergo slow formation after the primary tuberculosis: they gradually dissolve, undergo scarring or calcifying, and sometimes ossifying. The secondary tuberculosis develops from residual changes after the primary tuberculosis. The secondary tuberculosis happens due to weak antituberculous immunity. In these cases different organs are affected with a focus, an infiltrate or a cavern. The mode of Tb transmission is bronchogenic. The secondary tuberculosis mostly affects the superior and posterior segments of lungs. There is no calcification or ossification seen in the residual changes after the secondary tuberculosis.

 Allergy (from Greek allos - other, ergon - action) is the host's increased sensitivity to different substances caused by the changed reactivity. Allergy at tuberculosis is a nonspecific component of the specific immune reaction. It is observed in sensitized hosts only. Allergy basics: sensitized Tlymphocyte interaction with antigen release several cytokines (IL-2, gamma-interferon) activating and involving macrophages into the reaction. Immune memory is sensitized T-lymphocytes ability to respond with accelerated reaction to the repeated encounter with antigen (Tb). The first contact of a T-lymphocytes population with Tb sensitizes the former; this sensitization is transmitted genetically to other T-lymphocytes. Thus, immune response will develop faster with the second encounter with Tb. Immune memory is short-term and its agents are not clear. Immune tolerance is a state of nonresponsiveness to antigens, which cause immune reaction under usual conditions. The tolerance at tuberculosis is not well studied. It can be experimentally proved: intrauterine seeding of a fetus with tuberculin or killed Tb depresses the immunity to this antigen in future. Thus, population vaccination after birth does not create immunity. The antigen activates T-suppressors responsible for the depression of the immunity to the same antigen.

Defense Mechanisms of the Respiratory Tract (K.F. Chemushenko, 2003)

Non -immune Immune

Physical

Humoral

Nonspecific

Specific

humoral

cell

humoral

cell

cough ciliate apparatus mucus

- lysocyme lactoferrin (-antitrypsin, surfactant, enzymes)

natural antibodies - phagocytosis lysozyme complement - enzymes

- slg A - phagocytosis Ig A, M, Gopsonins cytokines

CLINICAL CLASSIFICATION OF TUBERCULOSIS

Tuberculosis is found under five paragraphs in the International Statistical Classification of Diseases and Related Conditions (10-th edition): A 15. Respiratory organs tuberculosis confirmed by bacteriology or histology. A 16. Respiratory organs tuberculosis unconfirmed by bacteriology or histology. A 17. Tuberculosis of the nervous system. A 18. Tuberculosis of other organs. A I 9. Miliary tuberculosis. In Ukraine a new tuberculosis classification was introduced by the order of the Ministry of Public Health of Ukraine No. 499 of November 28, 2003. This classification takes into account: 1) the type of tuberculosis; 2) the clinical form of tuberculosis; 3) tuberculosis characteristics; 4) complications of the disease; 5) clinical and dispensary follow-up of the patient; 6) effectiveness of the tuberculous patient treatment; 7) outcome of the disease. This classification is adapted to the international tuberculosis classification.

I. The type of tuberculosis.

1. Primary tuberculosis, or PTB (the date of diagnosis). The date of diagnosis is to be recorded after the type of tuberculosis. Primary tuberculosis is diagnosed when the patient had never had any treatment for tuberculosis or had taken antituberculous medication for less than one month. 2. Relapse of tuberculosis, or RTB (the date of diagnosis). Tuberculosis relapse is the activation of tuberculosis in individuals, who had had tuberculosis before, completed a course of anti-tubercular medication and were considered recovered. Relapse may be TB+, TB-, HIST+, HIST-, and one diagnosed by clinical and radiological examination. 3. Chronic tuberculosis, or CTB (the date of diagnosis). Chronic tuberculosis is diagnosed in: 1) patients without clinical and radiological stabilization or in cases of clinical and radiological deterioration (i.e. caverns retain with TB+ and TB-) during not less than 2 year follow-up; 2) patients after the first and second courses of antimycobacterial therapy, in 2 years after the beginning of treatment, registered ineffective treatment (treatment failure, a break in treatment, or being treated for more than 2 years). Chronic tuberculosis is tuberculosis in the patients of the 1st, 2"d, and 3rd category and with ineffective repeated treatment in the patient of the 2nd category, diagnosed in 2 years after the beginning of antimycobacterial therapy.

II. Clinical forms of tuberculosis.

A15-A16 Pulmonary tuberculosis (PTB) (with a facultative indication of the form of the disease): A15-A16 Primary Tubercular Complex A15-A16 Disseminated Pulmonary Tuberculosis A15-A16 Focal Pulmonary Tuberculosis A15-A16 Infiltrative Pulmonary Tuberculosis A15-A16 Caseation Pneumonia A15-A16 Pulmonary Tuberculoma A15-A16 Fibrocavernous Pulmonary Tuberculosis A15-A16 Cirrhotic Pulmonary Tuberculosis A15-A16 Pulmonary Tuberculosis Associated with Occupational Dust Disease (Coniotuberculosis) A15-A18 Extrapulmonary tuberculosis (EPTB) (with an indication of localization): A15-A16 Extrapulmonary Tuberculosis of the Bronchi, Trachea, Larynx, and Upper Respiratory Tract A15-A16 Intrathoracic Lymph Node Tuberculosis A15-A16 Tuberculous Pleuritis (including empyema) A17 Neurotuberculosis and Meningeal Tuberculosis A18.0 Tuberculosis of Bones and Joints A18.1 Genitourinary Tuberculosis A18.2 Peripheral Lymph Node Tuberculosis A18.3 Tuberculosis of the Bowels, Peritoneum, and Mesenteric Lymph Nodes A18.4 Tuberculosis of Skin and Subcutaneous Fat A18.5 Eye Tuberculosis A18.6 Ear Tuberculosis A18.7 Adrenal Tuberculosis A18.8 Tuberculosis of Other Organs A19 Miliary Tuberculosis A18 Tuberculosis of Unknown Primary Site

III. Characteristics of Tuberculosis.

The chief parameters characterizing tuberculosis are localization, distribution, destruction (as a stage of the disease) and the 11roof of bacterioexcretion. 1. Localization. Tuberculosis is localized according to the affected pulmonary segment or lobe; in other organs it is localized according to the anatomical location of the disease. Most often tuberculosis affects the 2nd (posterior) segment corresponding to the lateral subclavicular area, then the 1st (apical) and the 4th (upper) segments of the lower lobe. 2. Destruction is the destroying of tissue by tuberculosis followed by cavity formation; is detected during X-ray examination. In the diagnosis, (DESTR+) means the presence of destruction, and (DESTR-) means the absence of destruction. The phase of infection may also be included in the diagnosis: infiltration, destruction (DESTR+), seeding; resolving, consolidation, scarring, calcification. In filtration, destruction (DESTR+), and seeding characterize the activity of tubercular alteration. Resolving, consolidation, scarring, calcification are considered good signs and reflect the stabilization of tuberculosis. In case of incomplete phase it is also recorded in the diagnosis as "incomplete resolving" or "incomplete consolidation".

Etiologic verification
3. Etiologic verification of diagnosis is the basis for contemporary clinical phthisiology. There are only two reliable methods of tuberculosis verification: bacteriological and histological. The paragraph Verification Method should include the full range of respective data. For example, in case of Tb finding the diagnosis should read (TB+) followed by explanation: (M+) - positive swab bacterioscopy, meaning that acid-fast bacilli (AFB) were found in 2-3 sputum swabs during 3 consecutive days, stained after Ziehl-Neelsen; (M-) - negative swab bacterioscopy. Bacterioscopy is always completed with bacteriology, the culture of sputum on nutrient media of Levenstein-Yensen for 3 consecutive days. This information is reflected in the diagnosis as: (KO) - no culture performed; (K-) - negative culture for Tb; (K+) - positive culture for Tb. Thus, (TB+) is possible with (M-), but always with (K+).

Each positive culture (K+) should include sensitivity testing for first line antibiotics like isoniazid (H), rifampicin (R), streptomycin (S), ethambutol (E), and pyrazinamide (Z). Sensitivity testing for second line antibiotics is performed along with testing for first line drug therapy to avoid repeated 1.5-2 month long culture in case of multiple and multi-resistant Tb. Drug resistance should be recorded as follows: (ResistO) - no testing performed for drug-resistant Tb; (Resist-) - first line therapy-resistant Tb not found; (Resist +) (R, H, S) - rifampicin, isoniazid, streptomycin-resistant Tb found. Drug resistance for second line antibiotics should be recorded as follows: (ResistIIO) - no testing performed for second line drug-resistant Tb; (Resist II-) - second line therapy resistance of Tb was not found; (Resist +) (K, Cf) - kanamycin and ciprofloxacin-resistant Tb found. In the absence of bacterioexcretion (TB-) culture results should be recorded as follows: (MO) - no swab taken; (M-) - the swab of 1-2 specimens out of 3 was negative; (KO) - no culture made; (K-) - Tb not found in the culture; culture for Tb is negative. Histological examination should be conducted with or without bacteriology and should be presented as follows: (HISTO) - no histology examination done; (HIST-) - tuberculosis is unconfirmed with histology; (HIST+) - tuberculosis is confirmed with histology.

IV. Complications of tuberculosis.

Complications are an addition to the basic diagnosis. Classification includes the most frequently observed complications. Tuberculosis complication is pathological processes related to tuberculosis proper or other diseases. For example, if tuberculosis is complicated with pulmonary hemorrhage, followed by middle lobe atelectasis resulting in pneumonia, then pulmonary hemorrhage is the complication of the 1st degree, atelectasis - of the 2nd, and pneumonia - of the 3rd degree. Complications should be listed along with the data of their diagnosis. Complications of pulmonary tuberculosis: hemoptysis, pulmonary hemorrhage, spontaneous pneumothorax, pulmonary failure, cor pulmonale, atelectasis, amyloidosis, etc. Complications of extrapulmonary tuberculosis: bronchial stenosis, pleural empyema, fistula (bronchial, thoracic), kidney failure, adrenal crisis, infertility, adhesion, ankylosis, amyloidosis, rtc. V. Follow-up: clinical and dispensary categories of patients. After recording complications, if any, the physician should record the patient's category of treatment. There are the following categories and groups of tuberculous patients: 1 (Cat 1), 2 (Cat 2), 3 (Cat 3), 4 (Cat 4), 5 (Cat 5); group 5.1; group 5.2; group 5.3; group 5.4; group 5.5. When wording the diagnosis, one should also include the cipher of the cohort (1, 2, 3, 4) and note the year, to which the cohort belongs, e.g. Coh4 (2001), Cohl (2000), Coh3 (2002). With such a cohort cipher patients are followed up in dispensaries.

VI. Treatment effectiveness. I. Effective treatment 1.1. Recovery. 1.2. Ceased bacterioexcretion. 2. Completed treatment. 3. Ineffective treatment (treatment failure). 4. Interrupted treatment. 5. Continuing treatment. 6. Transferred. 7. Lethal outcome. "Effective treatment" and "Completed treatment" are united in the category "Successful treatment". VII. Tuberculosis outcome. Tuberculosis outcome is residual changes after the clinical recovery from tuberculosis and postoperative changes related to tuberculosis. Residual changes are classified as great and small. A patient with residual changes is among those with the higher risk of tuberculosis relapse or a new disease. These residual changes are the signs of inactive tuberculosis. Residual changes after the clinical recovery from pulmonary tuberculosis: fibrotic, fibronodular, bullae and dystrophy, calcifications in the lungs and lymph nodes, pleuropneumosclerosis, cirrhosis, postoperative changes (followed by the record of the date and type of operation), etc. Residual changes after the clinical recovery from extrapulmonary tuberculosis: scarring in different organs and its outcome, calcifications, postoperative changes (followed by the record of the date and type of operation), etc.

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