The epidemiological situation of tuberculosis

in the world and the Republic of Uzbekistan;

Causes deterioration of the epidemiological situation of tuberculosis in the world are:

1. The absence or lack of implementation of National TB control programs, which is the result of underestimation of tuberculosis infection in relation to the achieved progress in recent decades the fight against tuberculosis.
2. Strengthening of processes of migration in the world, therefore the TB infection from developing countries is widely distributed in the economically developed countries.
3. The growth of HIV infection. WHO predicts AIDS by 2000, increasing from 2 million to 12-18 million, and total number of infected status Avita 30-40 million This 5-10 million children will be born infected with HIV. According to the WHO in the world in 1995, the number of infections of tuberculosis and HIV were about 5-6 million is particularly significant for this reason the developing countries, where already 30-50% of AIDS patients simultaneously suffering from tuberculosis.
4. The growth of drug-resistant and especially multidrug-resistant strains of the ILO, which is the result of irrational use of anti-TB drugs.

The same reasons are important in the deterioration of the epidemiological situation of Tuberculosis that the former Soviet Union, including Uzbekistan.However, in Eastern Europe and Central Asian countries have their own reasons for the rise of tuberculosis infection, due to nye ecological catastrophes and new economic conditions.

Among these reasons are particularly important for Uzbekistan following yuschie:

1.Inadequate staffing agencies TB, due to migration nnaya Russian-speaking population and the inadequate training of personnel Phthisiology České in Uzbekistan in the last 10 years.Staffing Phtisio iatricheskih institutions in 1996-97. the whole country has reached almost 54%, and in some areas-36-48%.

2. Lack of participation in TB treatment facilities total b telephone network.Work on identifying and ak5tivnomu tuberculosis prevention is impossible without the active participation of general health. Lack of alertness phthisiological therapists, lack of logistical support services Flury ograficheskoy caused inefficiency of preventive examinations for tuberculosis.

3.Reduced immune stratum in children associated with the low coverage of specific prevention.

This led to an increase in the incidence of tuberculosis among children. In 1997 20% of newly diagnosed TB patients were children. Zabol has grown among evaemost contact, the number of cases of tuberculosis family. (2001, 1584)

4. The break-established economic ties to new economic conditions led to a lack of availability of TB in institutions protivotuberk for useful drugs.Today the shortage of anti-TB drugs eliminated, thanks to the firm “Surkhan Ajanta” and the supply of drugs from foreign countries.
5. Insufficiently balanced diet of certain populations. This prospect is especially significant ichina in areas of environmental disasters (SSC), where the deterioration of the epidemiological situation of tuberculosis is especially true t.k.tuberkulez problem not only biomedical, but also social.
6. Unfavorable epidemiological situation of tuberculosis in zhivotnovods TVE.According to 1997 6% of cattle afflicted with tuberculosis, which affected the epidemiology of tuberculosis in humans.In cotton growing areas in 8-11%, in ivotnovodcheskih Well – at 16-21% of TB patients is determined by the type of bull Office.
7. The growth of immunodeficiency states of primary and secondary, as well as diseases involving immune system disorders. Among them is the t rue and pathology: diabetes mellitus, peptic ulcer and 12 duodenal ulcer, drug addiction.Equally znachenie5 for the epidemiology of tuberculosis have okoe wide application in medical practice of immunosuppressive drugs, radiotherapy, corticosteroids.

This decrease in preventive flyurograficheskih surveys and increased incidence of tuberculosis has increased the number of newly infected with TB. seeking treatment in primary care: PRT, SVP. In this regard, general practitioners should be sufficiently master the methods of diagnosis and differential diagnosis of pulmonary tuberculosis and other locations.

On the shortcomings of diagnosis of TB shows the dynamics of the key epidemiological indicators and the following facts: an analysis of cases of new-onset pulmonary tuberculosis showed that 9.4% of patients are detected with advanced tuberculosis, 14.3% were ill of the dead 1 year, 1 / 3 of new cases is determined destruction.

 

Dynamics of main epidemiological indicators

TB in Uzbekistan

Parameters	Years
	1988-1990	1998	2001		2002		2003
Morbidity	48.4 – 45.1	58.0	72.4 RU	149 RSC	79.1 RU	182.8 RSC	77.2 RU	154.8 RSC
Soreness	193,8-200,4	204.0	251.5	452.2	266.3	487.9
mortality	5,3-5,4	11.1.	12.5	34.6.	12.3.	39.6	11.5.	34.2.
Complete with NOSTA vr.kadrami			0.6		0.6

 

The most affected regions, the Aral Sea region, Bukhara, Syr-Darya, Samarkand. Thus, at a meeting of staff of the Ministry of Health of Uzbekistan in 1998, the situation in the RAC rated as an epidemic: oleznennost b-302, disease-109, 2 deaths, 34, 6.

Out of this situation can be carried out in two main directions: increasing living standards and improve TB control.The first purpose is served by the economic reforms that are found on Prospect Government of Uzbekistan, as well as the “Law of tuberculosis”, which was approved by the Oliy Majlis of Uzbekistan May 11, 2001Already self-government bodies of citizens (Mahalla), material aid to TB patients. However, for successful TB control alone is not enough social transformation. Need to improve methods for tuberculosis, which is aimed at “N ATIONAL tuberculosis program,” but unfortunately not yet approved by the Government of Uzbekistan.

The Programme improved TB control requires the participation of general practitioners who must perform the following tasks:

1.Early and timely detection of TB patients.

2. Formation of groups at risk for tuberculosis, activities of Prof. ilaktike and early detection of tuberculosis among them.

3.Providing full coverage of children of specific prophylaxis.

4. Early diagnosis of tuberculosis in persons who have applied for medical omoschyu n and with clinical manifestations of tuberculosis.

5.Analysis of key epidemiological indicators of tuberculosis, the TB program planning based on analysis of epidemiological screening studio and the full execution of them.

6. Conduct the public health education on TB.
7. Close collaboration with the TB dispensary, full of svedomlennost of tuberculosis and outbreaks of tuberculosis infection.
8. Participation in the analysis of late diagnosed cases of tuberculosis.

What instructional materials should be guided by GPs to conduct control activities?

Until 1993, the basic document for TB control was the order № 591 from 23/XI-1993 year, compiled by order of the USSR Ministry № 527 from Mr. 5/VI-1998

However, the new economic conditions to ensure the implementation of this order could not, in connection with which the Research Institute of tuberculosis and pulmonology Ministry of Health of Uzbekistan was developed by the order № 552 of 24/XI-1995 g for 14 pilot districts.

Decision of the staff of the Ministry of Health of the Republic of Uzbekistan dated March 15, 1999 on the basis of the work carried out in pilot areas rasprastranen order throughout the territory of Uzbekistan.

In accordance with this order, the main goal of TB control in Uzbekistan camp is to prevent transmission.To achieve this prick azom the following measures:

1.Timely detection of cases of pulmonary tuberculosis, especially bakteriovydelit firs.

2. Increased immune stratum of the population to tuberculosis infection in n omoschyu BCG vaccination and revaccination.
3. Prevention of infection and incidence of tuberculosis in persons who tries odyaschihsya in contact with smear-by chemoprophylaxis.
4. The use of intensive chemotherapy regimens of patients with pulmonary tuberculosis, resulting in the short term to permanent cessation of bacteria.

Putting into practice the TB service order number 552 does not mean cancellation of order number 591, but only complements it and makes a correction in the following sections.

 

Timely identification of patients with pulmonary tuberculosis.

The main methods of detection of tuberculosis in children remains a Mantoux test in adults, and microscopic examination flyurograficheskoe sputum at the Office.

In view of the impossibility of continuous enrollment tuberculin because of the high economic costs, divided into 3 groups of children subject to compulsory inspection:

I-group at risk of tuberculosis: the children with COPD, acute respiratory infections often ill, with recurrent pneumonia, bronchitis, chronic pnemoniey, diabetes mellitus. additionally receiving corticosteroids children under 7 years old and older than 7 years, with an intoxication of unknown etiology.

In this group of children screened with the Mantoux test 2me and 7 years in addition carried out flyurografiya. Responsibility for the investigation of the group assigned to the n ediatra general medical network and the SES.

II-group children from contact with the smear, a contingent of Group IV dispensaries sulfur.In this group are mandatory Mantoux test with 2 TE and flyurograficheskoe survey. Responsibility for the investigation of the group assigned to Phtisio pediatrician.

III-Group – VI Group dispensary, children with allergic symptoms of infectious energy.This group is mandatory statement of the Mantoux test with 2 TE and x e technologically survey.Responsibility for the investigation of the group assigned to Phtisio pediatrician.

To ensure the timely detection of active pulmonary TB in adolescents and adults, the basic method remains flyurograficheskoe survey in 4 groups of adolescents and adults.

People most at risk of tuberculosis: a person with an atypical course of respiratory disease, pneumonia, pleurisy had undergone suffering from COPD, diabetes, gastric ulcer disease, pneumoconiosis, the business of long-term principles corticosteroids, radiation therapy, immunosuppressants, and cytotoxic agents, postpartum women, drug addicts, alcoholics, , the mentally ill and those with young hyperergic results of the Mantoux test.In this group, for organizing and conducting a survey flyurograficheskogo near agaetsya responsibility to GPs.

This group consists of individuals located on the dispensary at clinics and health care facilities in general hospitals with respiratory diseases. In the presence of cough, sputum from these individuals is investigated by the Office BACT erioskopicheskim method.

2 – Group – binding force.

This is a large group of people working in professions where the work is contraindicated in patients with active tuberculosis, and large residual changes moved Nogo tuberculosis.For ensuring flyurograficheskogo examination in this group of T medical officer of the Chamber of SES. GPs control the regularity and completeness of coverage flyurograficheskim survey of people in this group.Issues of access to the work of those that did not pass inspection, health officer decides.

 

Group 3 patients with smear-contacts (IV group accounting protivotuberku useful to clinic) flyurograficheski examined twice a year (spring and fall).Flyurograficheskoe examination of this group, Kaka, and the last four group will ensure ivaet district TB doctor.

Group 4-VII group accounting tuberculosis dispensary, a person with great residual changes myocardial tuberculosis and a high risk of recurrence that Tuberculosis.This group also examined twice a year (spring and fall).

2. Increased immune stratum of the population to TB infection by vaccination and revaccination with BCG.

In accordance with the plans of immunization of Uzbekistan, adopted Tym in November 1997, BCG vaccination is carried out in a maternity hospital for 3-5 days of life.Responsibility for the usefulness of vaccination coverage rests with the chapters. physician maternity home.

Vaccination is carried out dry thermostable vaccine, which is inserted into / skin method and diluted immediately before use. In the presence of contraindications to vaccination is carried out a delayed vaccination before the age of 1 year. At the same time up to 6 months of vaccination is carried out after removing the contra at a later date, along with the removal of contra-make sure you have a negative reaction to tuberculin. Delayed vaccination is carried out with BCG-M.

Revaccination is carried out 2-fold at 6-7 and 14-15, in the absence of contraindications and negative tuberculin sensitivity, confirmed by the Mantoux test with 2 TE.

Responsibility for the conduct of revaccination is vested in the pediatric general hospitals.

Found that in children without skin grafting characters infection in 3 times and the detection of TB is 6 times higher than similar rates in patients with cutaneous vaccination marks.

In patients with tuberculosis in children 35 – 40% of patients with tuberculous meningitis de Tay -80-85% noted the lack of postvaktsinnyh scars.Quality of vaccination and revaccination reduces the incidence of TB in children is 23 times, and prevents the development of severe tuberculosis. To avoid introducing into the body of living tuberculosis bacteria, scientists around the world working to develop chemical algebraically vaccine.

 

3.Prevention of infection and incidence of tuberculosis among persons who were in contact with yaschihsya smear with chemoprophylaxis.

Order № 552 provided for prophylaxis of tuberculosis with chemotherapy in 3 groups of people:

1. Contacts with massive smear – are controlled by chemical ioprofilaktiku two chemotherapeutic agents (isoniazid + ethambutol).
2. Contact with patients with pulmonary tuberculosis with collapse and poor bakteriovydel eniem and without bacterial-controlled chemoprophylaxis get him one drug (isoniazid).Providing for chemoprevention in the two coarse ppah responsible SES and TB dispensary.
3. Contacts of patients with pulmonary tuberculosis without decay with poor bakteriovydelen and eat – get a by intermittent chemotherapy.For providing chemoprophylaxis in this group is also responsible TB dispensary and SES.

Along with these groups of individuals subject to chemoprophylaxis after a full clinical and radiographic examination and exclusion of children with active tuberculosis, “Veera pulp” Tuberculin test.If you have hyperergic reactions himioprof ilaktika carried out by two agents, in other cases, one anti-TB drugs.

GPs should be aware of the persons to be chemoprophylaxis and complete coverage of chemoprophylaxis on their contact site.

Along with active participation in early detection of tuberculosis GPs should know the basic epidemiological parameters of tuberculosis, and to be able to analyze them based on their analysis of planning control activities in the service area.

Volume of the reservoir of TB infection characterized by parameters: infection, the risk of infection and disease.

Infection is determined by the number of individuals reacting positively to tuberculin as a percentage of the number of patients. Indicators of infection tubercle ezom in Uzbekistan.

 

In countries where vaccination and revaccination newborns, the definition of rate of infection is very difficult because of the appearance of a positive tuberculin sensitivity caused postvaccinal allergies.

The risk of infection is established by means of repeated tuberculin tests, the number of persons with tuberculin reactions superelevation – direct method of determining the risk of infection. The risk of infection can be determined by the number of Zab olevshih tuberculous meningitis at the age of 0-4 years.

The incidence of TB is estimated by the number of newly registered patients in the current year for every 100 thousand population. Incidence of Dr. AET more detailed view of the structure of TB patients, when studied in isolation: the incidence of pulmonary or extrapulmonary tuberculosis incidence dependence or destructive forms of bacteria.High incidence of fibro-cavernous tuberculosis indicating a large reservoir of infection among the population, poorly delivered early work on identifying eniyu tuberculosis.

The incidence in children under 1 year of life characterized by risk of primary infection.

Tuberculosis Morbidity-size contingent of patients with active pulmonary tuberculosis at the end of the year to 100 thousand people.

Mortality – the number of deaths from tuberculosis during the year to 100 thousand people.

Cumulative incidence, morbidity and mortality provides a picture of the prevalence of tuberculosis, the TB status of the various sections of the work and assess the rules determining the epidemic process in the whole country and for individual regions of her.

Sanitary tuberculosis prevention, aimed at ozdorovleie foci of tuberculosis infection is of concern to institutions of TB services.

GPs should be aware of category centers on the degree of epidemiological risk, and to have information about the structure and number of foci of tuberculosis in the service area.

The main objective of GPs in health prevention is health education that illuminates the issues of prevention, early detection of tuberculosis and its diagnosis.

The alternative adopted in the Republic of Uzbekistan methods of TB control is DOTS, which is being tested in pilot areas in Uzbekistan: Kungrad sky regions of the republic and Muinak RSC, the Fergana region, the Syr-Darya region.Planned introduction of DOTS in Urgut district of Samarkand region. DOTS-Directly Observed Treat ment translated to English means “short-course chemotherapy under direct observation of health worker ‘, the strategy of treatment and diagnosis of tuberculosis in the WHO introduced more than 70 countries worldwide.

The basic five elements of DOTS

-Direct (Direct) Your efforts to detect infectious pulmonary tuberculosis by sputum smear microscopy.

 

Pathogenesis of tuberculosis

 

Modes of transmission

– Aerogenic

– Nutritional

– Contact

– Prenatal

Local protection:

1. Mucociliary clearance
2. When primary infection – Office and meet with polinuklearami phagocytes and undergo phagocytosis

 

Phagocytosis consists of 3 phases:

n                   Phase I – contact, when the macrophages with receptors on the cell membrane is fixed by the Office.

n                   Phase II – Office entry into macrophages, there is an invagination of the wall macrophages and the ILO, as it were enveloped on all sides formed vacuoles, which enters the macrophage, forming phagosomes.

n                   Phase III – digestion, when present in macrophage phagosomes fuse with the lysozyme-containing MBT. Released in fagozosomah enzymes have a destructive effect on the Office and destroy them.

 

Activation of macrophages: the macrophages phagocytized Office and digesting their hard, isolated fragments of the extracellular space destroyed Office, proteolytic enzymes, and mediators (including interleukin-1), which are in contact with T lymphocytes in particular T-helper cells. Activates T-helper cells and selection of mediators – lymphokines, including interleukin 2 – interferon and other lymphokines. Under the influence of mediators of macrophages rush to the location of the ILO, as the great migration inhibition factor, eye-catching B-lymphocytes, increases the enzymatic activity of macrophages under the influence of factor activation of macrophages. This factor is identified with interleukin-2. Activated macrophages secrete and skin-reactive factor, which causes inflammation, increased vascular permeability. With this factor associated with the appearance PCHZT and positive tuberculin reaction.

 

n                   In the process of liquefaction cheesy masses Office an opportunity for a rapid extracellular multiplication.During this period, due to the large bacterial population is the process of increasing suppressor cells (T suppressor), which leads to the oppression PCHZT, reducing the number of T-helper cells, lymphopenia and anergy, deter the progression of tuberculosis.

n                   With a relatively small bacterial population in PCHZT and more efficient phagocytosis observed another tissue reaction – the formation of tuberculous granuloma and the formation of tuberculous lesions.

n                   Acquired immunity supports a population of T lymphocytes sensitized with tuberculous antigen.The role of anti-antibody-producing B-lymphocytes, as well as circulating immune complexes remains unexplored.

n                   The interaction between macrophages and T B-lymphocytes.

n                   The immune response in the form of complex reactions that lead to sensitivity or resistance to disease development.

n                   Production of lymphokines, cytotoxins T and B lymphocytes and macrophages.

n                   Isolation of HLA / W glycoproteins.

 

n                   Reversal of persistent forms of mycobacteria in the Office of breeding going on in pockets of endogenous reactivation of tuberculosis and other residual changes.The mechanism of endogenous reactivation and the development of tuberculosis at the present level have been studied enough.

n                   At the heart of reactivation is a progressive proliferation of the bacterial population and increase the number of mycobacteria.However, to date it remains unknown what facilitates reversion of the causative agent of tuberculosis, was in the persistent state.

n                   Established that the reactivation of tuberculosis and the development of different clinical forms of secondary tuberculosis is more common in persons with residual changes in the presence of factors that weaken the immune system.

 

The role of immunity in the pathogenesis of tuberculosis.

Immunity (lat – liberation, freedom from something) – immunity to infectious and noninfectious agents possess the antigenic properties.

Types of immunity:

• Congenital (from an absolute resistance to any microorganism to a relative immunity, which can be overcome as a result of various influences)
• Acquired (occurs after vaccination and revaccination)

One of the main features of acquired immunity – his strict specificity: it is produced only to a particular microorganism (antigen), who got or introduced into the body.

1. a) active – can occur as a result of vaccination and revaccination, and after the disease or latent infection, is set from 1-2 to 4-8 weeks. after vaccination and revaccination, and onset of the disease, remains a relatively long time – years or decades
2. b) passive – there is a fetus, the placenta has received antibodies from the mother and newborn remain so for some time immune to certain infections, such as measles. Passively acquired immunity can be created artificially – by introducing into the body of antibodies derived from what had been ill – an infectious disease or vaccinated humans or animals.

One critical factor is the lack of innate immune receptors for viruses, the Office on the cell surface, resulting in viruses, the Office can not adsorb to the cells and thus penetrate into them.

The most important factors of innate immunity are complement, a complex system of serum proteins, as well as free antibodies involved in many defense reactions.

Defense response

n                   Inflammation

n                   Phagocytosis

Phagocytosis of cells carry two systems: macrophages (granulocytes), and macrophages – motile cells (monocytes are the blood and lymph macrophages, and belong to the system of mononuclear phagocytes), and mononuclear cells, fixed in the liver, spleen, lymph nodes.

STAGE Phagocytosis

n                   phagocyte adherence to the microorganism

n                   its absorption

n                   enzymatic digestion in special structures phagocyte – fagolizosomah

Macrophages perform a more complex function than macrophages, but they can digest bacteria fungi, protozoa altered own body cells, including and the cells of malignant tumors. Macrophages are also involved in the formation of antibodies.

Types and properties of lymphocytes

T-lymphocytes (thimic-dependent)

 

n                   T cells that recognize antigens.

n                   T-helper cells that help B lymphocytes produce antibodies

n                   T-suppressors – suppressing the immune response

n                   T-killer cells – cytotoxic properties have engaged in the destruction of genetically foreign cells

B cells (bone marrow) – plasma cells that are producers of specific immunoglobulins – antibodies.

 

Along skorotkozhivuschimi plasma

cells produtsirtsyuschimi antibodies are long-lived

B cells, providing an immunological memory.

n                   Humoral immunity (aniteloobrazovanie)

n                   Cell-mediated immunity (delayed-type sensitivity povyschennaya – PCHZT)

n                   Tolerance.

n                   Immunological memory.

n                   Allergy.

 

HUMORAL ANTI
IMMUNITY

After the vaccine antibody titers increased progressively, reaching a maximum at a time when most pronounced is the resistance of vaccinated animals to subsequent infection (M. Auerbach, 1970).

 

In the event of experimental chemotherapy of tuberculosis when he was over pretty much prolonged, there is a growing synthesis of antibodies (IA Ilyina, 1972)

Main issues:

n                   What do the antibodies in resistance to TB infection?

n                   Helpful or harmful is the synthesis of?

n                   Do they opsoniruyuschimi properties with respect to the Office and how do they work on phagocytosis?

n                   Can they direct toxic effect on the Office, kill them with a complement or inhibit their proliferation?

 

CELLULAR ANTI-
IMMUNITY

The reaction of cellular immunity is in the interaction of T lymphocytes with antigen and subsequent mobilization (usually by means of mediators) of other subpopulations of T – lymphocytes and macrophages that perform effector functions

Office break and grow only intracellularly in macrophages. Thus, phagocytosis is the primary mechanism of destruction by the Office.

Cellular immunity is central to resistance to tuberculosis, and that the effector cells of cellular immunity is likely to exert their regulative effect on the course of tuberculosis infection, enhancing the phagocytic activity of macrophages

 

 

IMMUNOLOGICAL TOLERANCE

n                   This suppression of the ability to develop cellular and (or) humoral immunity – specific areactivity by prior exposure to the antigen.

n                   Tolerance may play a role in the pathogenesis of tuberculosis, for example, a negative value of tolerance can occur at re-vaccination of children with depressed immunocompetent system, when the BCG vaccine has not stimulating the immune system, and tolerogenny effect.

n                   Tolerance may also exert its negative effect of chronic massive infection.

n                   Even more important may have in the pathogenesis of tuberculosis infection immunological rejection when, due to various reasons hyperfunction antibody inhibits cell-mediated immunity and, thus, reduces the likely protective potential of the body.

 

IMMUNOLOGICAL MEMORY

n                   Immunological memory in tuberculosis develops in the same basic laws as the introduction of any antigen, allowing for the persistence in the body caused by a live agent.

n                   Immunological memory remain special cellular elements (T and B memory cells), and the presence of antigen (in whatever form) for the maintenance of immunological memory is not necessary.

n                   For example, after BCG vaccination in experiment and clinic increased resistance to tuberculosis and tuberculin skin sensitivity continues much longer than the time when the body discovered Mycobacterium BCG.