[ORGANIZATION OF EPIDEMIOLOGICAL MONITORING OF TUBERCULOSIS IN THE CITY OF MOSCOW].

Ensuring effective epidemiological surveillance of tuberculosis is essential and one of the paramount tasks for any national tuberculosis control program. The article analyzes the organization of the tuberculosis epidemiological monitoring system at the level of the subject, based on the experience of implementing such a system in the city of Moscow in 1996-2020, defines its tasks and principles of its construction. The systems of epidemiological monitoring of tuberculosis, implemented taking into account the developed principles, provide an analysis of the epidemiological situation in the territory, the results of which can be successfully used for making managerial decisions, program-target planning and evaluating the effectiveness of the measures taken.

[Clinico-morphological characteristics of pulmonary mycobacteriosis].

According to the criteria of the American Thoracal Societypulmonary mycobacteriosis has been diagnosed at 40patients without clinically important immunosupression (MAC--35%, Mkansasii--25%, M. xenopi--20%, M. fortuitum--12.5% and M. chelonae--7.5%). 95% patients have had clinically important symptomatology with polymorphic radiologic development such as a deformation of a lung pattern and focal dissemination (75%), locus and infiltration (52.5%), cavities (42.5%), marked pneumosclerosis (60%) and bronchiectasis (17.5%). 75% patients have had some changes of the bronhial tree. As opposed to tuberculosis the morphology of mycobacteriosis is more homogeneous and includes inflammation with epithelioid giant-cell granuloma and fibrosis, pneumogenic and bronchogenic cavernous cavities, mycobacterial endobronchitis. The polymorphism of clinic-radiologic developments, a similarity of lung diseases morphology caused by nontuberculous mycobacteria makes difficulties to diagnose theirs.

[Legal aspects of compulsory hospitalization of incompliant patients with tuberculosis].

The main task of an antituberculosis service is to treat patients with tuberculosis and to follow up needy persons in order to prevent the spread of tuberculosis among the population. However, phthisiatricians are unable to solve some problems without assistance from the government as they are associated with social and behavioral causes--no or partial patient's motivation for treatment. Early therapy discontinuation in patients with tuberculosis, latent or obvious interruption of chemotherapy, patients' use of a partial dose of drugs give the vast majority of Russian phthisiatricians concern. These lower the efficiency of treatment, increase the likelihood of drug resistance in Mycobacterium tuberculosis, and contribute to the chronic pattern of the tuberculosis process, continuously replenishing the pool of untreatable patients with tuberculosis and bacterial discharge. An incompliant tuberculosis patient discharging bacteria may be compulsorily taken to a tuberculosis hospital by the court decision. This is in line with Article 10, the 18 June, 2001 Federal Law No. 77--"On Prevention of Tuberculosis Spread in the Russian Federation". This investigation was undertaken to enhance the effectiveness of involvement of incompliant bacteria-discharging patients with tuberculosis to compulsory examination and treatment. The mechanism of realization of Article 10 of the abovementioned Law was analyzed from the experience of an antituberculosis service of the Ryazan Region (178 writs). At present, it is impossible to fulfill this Article 10 in corpore due to there is an improper legal base that is in no subordinate legislation and actuate sentences for non-implementation of court decisions. Subordinate legislation regulating a compulsory hospitalization procedure by officers of justice should be elaborated. It is necessary to introduce amendments into the base to make patients with infectious tuberculosis who have not carried a court decision on compulsory hospitalization. Tuberculosis facilities should be used to set up social centers for the complex work and treatment of socially dysadapted patients with tuberculosis (including those who have been released from confinement institutions). For this, tuberculosis institutions should be staffed by social workers, psychologists, psychiatrists, lawyers, and narcology experts with the appropriate funds being allocated.

[Diagnosis of respiratory tuberculosis at multidisciplinary hospital].

Data on 104 patients with pneumonia treated at Moscow multidisciplinary hospitals for suspected respiratory tuberculosis (RT) show that general practitioners have lost tuberculosis-diagnosing skills and phthisiological alertness. This is suggested by frequent failures to collect medical historical data, neglect of risk factors for RT, poor orientation in the differential diagnosis of pneumonia and tuberculosis, violation of diagnostic standards of pulmonary tuberculosis, specifically a paucity of sputum microscopic studies and lateral lung X-ray studies. Upgrading the recognition quality of tuberculosis makes it necessary to observe the propedeutic rules for examining and studying a patient, to reveal important anamnestic and clinical data, and to follow instructions. At the same time, there is no need for new equipment and technologies, but it is critically important to increase the level of tuberculosis knowledge in physicians of all specialties and to create motivation for qualitative diagnostic work.

[Cardiac damage in sarcoidosis: clinical features and impact of steroid therapy].

Twenty-seven sarcoidosis patients with signs of cardiac damage were examined to study the clinical features of cardiac sarcoidosis and the impact of systemic glucocorticosteroid (GCS) therapy on its course. ECG and echoECG changes were observed in 21 (78%) and 17 (63%) patients, respectively; abnormal perfusion was seen in 25 (93%) patients at single-photon emission myocardial computed tomography using 99mTc-MIBI. Three clusters (clinical types) of patients were identified, which differed in the pattern and degree of cardiac disorders. The use of systemic GCSs in 13 of 20 patients resulted in myocardial perfusion recovery and clinical improvement, the degree and duration of which depended on what cluster it belonged to. Seven GCS-untreated patients had progressive perfusion disorders with subsequent or synchronous clinical deterioration (p < 0.05). The degree and duration of the positive effect of a GCS differed depending on the clinical type of cardiac damage.

[A social backing program and motivation provision in patients with tuberculosis].

The purpose of the study was to obtain information on tuberculosis patients' needs, perception, and expectations from health care as a whole and social backing in order to improve the implementation of a program for enhancing tuberculosis patients' motivation for recovery and treatment. Anonymous voluntary questioning using the standard questionnaire was carried out among new tuberculosis cases registered to be treated in 4 subjects of the Russian Federation (the Oryol, Vladimir, and Belgorod Regions, and the Republic of Mariy-El). Eighty-seven patients who had stopped being treated before the appointed time and 1302 patients who were receiving chemotherapy at the time of questioning were interviewed using the questionnaire. The main reasons for treatment discontinuance in those who stopped treatment before the appointed time were the necessity of earning their living (30%), alcohol consumption (30%), inadequate health education of the patients who considered themselves to be healthy (25%). Most patients (67%) preferred rewards as social backing, products/hot food (41%), and fare (32%). Among the proposed social backing schemes, the most popular ones were those that envisaged small daily rewards (23%) or a large final bonus (21%). The majority (67%) of patients preferred outpatient treatment. Thus, patients with tuberculosis face a great deal of problems that affect their motivation for treatment. To satisfy some of these problems is not the direct duties of an antituberculosis service due to the fact that the manning table lacks appropriate posts and an item of expenses. Therefore additional funds should be allocated from the budgets of a subject of the Russian Federation and/or municipal entities for adequate organization of social backing of patients with tuberculosis to enhance the efficiency of their treatment. Collaboration of antituberculosis services of the Russian Federation's subjects with social organizations and an addiction service along the availability of psychological and legal consultations to patients is the most optimum variant of social backing organization to improve the patients' motivation for treatment.

[Significance of determination of gamma-interferon in the diagnosis of tuberculous exudative pleurisy].

The pleural fluid concentration of gamma-interferon (gamma-IFN) was studied in 44 patients with exudative pleurisy. The tuberculous nature of exudative pleurisy was established in 25 patients on the basis of X-ray study, a follow-up, microbiological study of pleural exudate specimens, and morphological studies of biopsy specimens obtained at video-assisted thoracoscopy or surgery. The the pleural exudate concentrations of gamma-IFN were over 300 pg/ml (mean 1019 +/- 161 pg/ml) in 19 out of 21 patients with exudative pleuritis in a phase of active inflammation. The patients with the fibrous outcome of pleurisy of tuberculous etiology and those with exudative pleurisy of non-tuberculous etiology, including that in malignancies and papapneumonic pleurisy, were observed to have lower concentrations of gamma-IFN (mean 118 +/- 16 pg/ml). With the discriminating level of above 300 pg/ml, the sensitivity and specificity of the test were 90.5 and 100%, respectively.

Social support and incentives programme for patients with tuberculosis: experience from the Russian Federation.

SETTING: Tuberculosis (TB) services including social support and incentive programmes in four Russian regions (Orel, Vladimir, Belgorod Oblasts and Republic of Mari-El). OBJECTIVES: To determine reasons for TB treatment default among non-adherent patients and to describe patient views of social support programmes and the organisation of treatment. METHODS: Standard anonymous questionnaires were administered to new pulmonary TB patients registered for treatment. RESULTS: A total of 87 non-adherent patients and 1302 adherent patients were interviewed. The leading reasons for treatment default given by non-adherent patients were the need to earn money (30%), alcohol use (30%) and not perceiving themselves as being sick (25%). Monetary incentives were preferred by the majority of patients (67%), followed by food/hot meals (41%) and transportation reimbursement (32%). Overall, among the proposed social support programmes, those that offered small daily incentives (23%) or a big final bonus (21%) were the most popular. The majority of patients (67%) preferred out-patient treatment. CONCLUSION: Collaboration between TB services and social organisations and substance abuse services as well as availability of psychological testing/counselling for patients are social support modalities for improving adherence suggested by study findings. Social support should be combined with a patient-centred approach to TB treatment.

Risk factors associated with default among new pulmonary TB patients and social support in six Russian regions.

SETTING: Tuberculosis (TB) services in six Russian regions in which social support programmes for TB patients were implemented. OBJECTIVE: To identify risk factors for default and to evaluate possible impact of social support. METHODS: Retrospective study of new pulmonary smear-positive and smear-negative TB patients registered during the second and third quarters of the 2003. Data were analysed in a case-control study including default patients as cases and successfully treated patients as controls, using multivariate logistic regression modelling. RESULTS: A total of 1805 cases of pulmonary TB were enrolled. Default rates in the regions were 2.3-6.3%. On multivariate analysis, risk factors independently associated with default outcome included: unemployment (OR 4.44; 95%CI 2.23-8.86), alcohol abuse (OR 1.99; 95%CI 1.04-3.81), and homelessness (OR 3.49; 95%CI 1.25-9.77). Social support reduced the default outcome (OR 0.13; 95%CI 0.06-0.28), controlling for age, sex, region, residence and acid-fast bacilli (AFB) smear of sputum. CONCLUSION: Unemployment, alcohol abuse and homelessness were associated with increased default outcome among new TB patients, while social support for TB patients reduced default. Further prospective randomised studies are necessary to evaluate the impact and to determine the most cost-effective social support for improving treatment outcomes of TB in patients in Russia, especially among populations at risk of default.

[Early treatment discontinuation in tuberculosis hospital].

By analyzing the data on patients (n = 17295) who were discharged from 5 regional tuberculosis hospitals of Central Russia, the authors defined and assessed the major factors showing a steady-state strong correlation with early treatment termination through a patient's fault. Descriptive and univariate analyses and multifactor modeling were made to determine interfering factors and systematic errors (logistic regression modeling). For inpatient treatment at a tuberculosis hospital, a logistic regression model was used to develop a predictive decision rule that would determine the probability of treatment discontinuation, the quality control of the predictive rule on the basis of the bootstrap method. The rule makes it possible to form high and very high discontinuation risk groups in order to organize target measures to enhance the efficiency of tuberculosis control.

[The effectiveness and safety of sparfloxacine in combined therapy for tuberculosis].

The effectiveness and safety of the difluoroquinolone sparflo (sparfloxacine) used in combined therapy for drug-sensitive and drug-resistant pulmonary tuberculosis were studied. Clinical trials were carried out in 60 patients with severe pulmonary tuberculosis. The more effective combinations of sparfo and other antituberculous drugs were determined. Data on the satisfactory tolerability of sparfo used in various combinations of first- and second-line agents are presented.

[Sarcoidosis as a biological and medical problem].

The paper considers the basic biological, medical, and organizational problems that investigators and practitioners of different specialties come up against in recognizing sarcoidosis. Particular emphasis should be placed on the etiology and pathogenesis of sarcoidosis, the selection of management policy. Russia's currently established situation associated with the duration of a follow-up of patients with sarcoidosis is analyzed and the priorities of researches and organizational-and-practical work are proposed.

[Criteria for prediction of recurrent sarcoidosis].

The study based on history data, including age, educational level, social status, smoking, occupational risk factors, and a history of allergy and comorbidity, and on radiation diagnostic and fibroscopic findings could yield criteria for predicting potential recurrent sarcoidosis at the early stages of diagnosis of the pathological process.

[Respiratory mechanics in patients with stage III pulmonary sarcoidosis and idiopathic fibrosing alveolitis: similarities and differences].

Impaired function of the lung was studied in 28 patients with Stage 111 pulmonary sarcoidosis and 17 patients with idiopathic fibrosing alveolitis (IFA). The study involved spirography, body plethysmography, and esophageal probing of respiratory mechanics. In patients with Stage III pulmonary sarcoidosis, the mechanics of respiration has the following similarities: restrictive ventilation disorder is revealed in IFA; the functional syndrome with a predominance of restriction is also detectable in some patients with Stage III sarcoidosis; significant differences are found in patients with IFA and Stage III pulmonary sarcoidosis: there is no marked impaired patency of peripheral bronchi in IFA; and all the functional changes found suggest that there is an increase in lung tissue rigidity and a decrease in the capacity of the lung to straighten; in Stage III sarcoidosis, of great importance is a marked impairment of patency of peripherally located bronchi, which is associated with the increase of this or that degree of lung compliance and in the retraction index.

[Free radical processes in the phagocytes of the lung in the diagnosis of granulomatous diseases].

The functional activity of pulmonary phagocytes (alveolar macrophages and macrophages isolated from biopsy specimens) was studied in patients with active sarcoidosis and active tuberculosis, by examining the level of free radical processes in them by luminol-enhanced chemiluminescence (CL). The CL parameters of alveolar macrophages were found to significantly differ in their baseline and peak CL-induced levels and the time of emergence of the peak CL-induced level. The CL level of macrophages isolated from the biopsy specimens does not play a prominent role in the differential diagnosis between these groups of diseases. The time of emergence of the peak of CL-induced alveolar macrophages in response to Mycobacterium BCG strain stimulation is of the most informative value in the differential diagnosis of active tuberculosis and active sarcoidosis. A relationship was found between the clinical and laboratory manifestations and the parameters of free radical processes of pulmonary phagocytes in a granulomatous inflammatory process (in case of sarcoidosis). The CL alveolar macrophage parameters that characterize the activity of the process were related to the magnitude of patients' complaints, the levels of haptoglobin and neutrophils in blood samples. The CL parameters of macrophages isolated from the biopsy specimens correlated with the levels of haptoglobin and gamma-globulin.

[The cytokine profile in granulomatous lung diseases].

Twenty-five patients with new-onset pulmonary tuberculosis, 52 patients with active sarcoidosis, and 5 healthy donors were examined. Cytokines (IL-2, IL-4, IL-6, TNF-alpha, and gamma-1FN were determined by enzyme immunoassay in the serum and cultured mononuclear supernatant from peripheral blood. IL-2, TNF-alpha, and gamma-IFN) were found in the sera of all the examinees. There were significant differences in the presence of IL-4 that was more commonly detected in sarcoidosis than in tuberculosis (96.2% versus 68%; p = 0.001) and in healthy individuals (40%; p = 0.0001) and in the presence of IL-6 (84.6% in patients with sarcoidosis; 20% in healthy individuals; p = 0.0015; 12% in patients with tuberculosis; p < 0.0001). Supernatant studies showed that IL-4 was absent in 25% of patients with sarcoidosis, nor gamma-IFN in 21.7% of patients with tuberculosis and in 12.5% of patients with sarcoidosis. In tuberculosis, the mean levels of IL-2, IL-4, IL-6, TNF-alpha, and gamma-IFN were greater than those in the control group; but these differences were not statistically significant primarily due to the fact that there was a great scatter of readings. In sarcoidosis, the serum levels of IL-4 (40.9 +/- 38.5 pg/ml) and IL-6 (19.0 +/- 2.7 pg/ml) were significantly higher than those in healthy individuals (p = 0.01 and p = 0.026, respectively) and in patients with tuberculosis (p = 0.0005 and p < 0.0001). The supernatant from patients with tuberculosis showed no significant differences in the content of cytokines than that from donors. In patients with sarcoidosis, the increase in the level of TNF-alpha (757.8 +/- 142.8 pg/ml) was statistically significant, as compared with the controls (p = 0.036) and patients with tuberculosis (p = 0.018), so as that of gamma-IFN (272.9 +/- 58.0 pg/ml), as compared with patients with tuberculosis (p = 0.046). Thus, the serum levels of IL-6 and IL-4 and the capacity of monocytes and macrophages for synthesizing TNF-alpha and gamma-IFN may be used as an auxiliary criterion for the nosological diagnosis of sarcoidosis and tuberculosis.

[Immunophenotyping of epithelioid-cell granulomas in sarcoidosis].

The specimens of biopsy of the lung and lymph nodes from 24 patients with sarcoidosis were immunophenotyped. The monoclonal antibody panel for immunophenotyping the monocyte-macrophage cells included HLA-DR, CD64, CD163; CD7, CD3, CD4, CD8, HLA-DR, and CD20 were used to assess lymphocytic populations. In sarcoidosis, the majority of cell elements of a granuloma are in a state of activation, as evidenced by HLA-DR expression on the epithelioid, giant cells, T lymphocytes (which was observed in more than in 90% of cases), the extent of this expression decreasing as fibrosis develops. There is a statistically significant correlation between the presence of individual lymphocytic subpopulations and monocyte-macrophage cells in the granuloma. No clear relationship of the phenotype of a granuloma to the clinical form (stage) of sarcoidosis suggests that is based on the common self-sustaining process of formation, functioning, and involution of granulomas, which has no direct agreements in the X-ray and laboratory manifestations of the disease.

[The composition and drug sensitivity of a mycobacterial population in patients with suspected tuberculosis].

By using the diagnostic material (175 sputum samples and 103 bronchoalveolar lavage fluid samples) taken from 39 patients with suspected tuberculous infection during a 2.5-month follow-up, the authors traced the time course of changes in the composition and drug sensitivity of a mycobacterial population to rifampicin. Along with the traditional microbiological studies, the latest molecular biological studies, a TB-BIOCHIP test system (enzyme immunoassay) in particular, were employed to detect the bacterial and L-transformed forms of the causative agent. A molecular biological assay was first developed to detect the drug sensitivity of L-forms of Mycobacterium tuberculosis.

An approach to estimating tuberculosis incidence and case detection rate from routine notification data.

OBJECTIVE: To estimate tuberculosis (TB) incidence and case detection rate (CDR) using routine TB surveillance data only. METHODS: A mathematical model of the case detection process, representing competition between disease progression and case finding, is proposed. The model describes disease progression as a two-stage process (bacillary and non-bacillary TB), and so relates the proportion of bacillary TB cases on detection to the effectiveness of detection. Thus, given the annual numbers of newly detected TB cases stratified by bacillary status, the model estimates detection rates, incidence and CDR. Routine notification data from eight provinces in Russia, 2000-2011, were used for the study. RESULTS: Subnational level estimates of incidence and CDR were obtained. Incidence estimates varied by two-fold among the provinces; corrected CDR estimates varied by 1.5 times. The trend in the incidence estimates was similar to that in the World Health Organization estimates for the whole of Russia. The change in the trend in WHO CDR estimates in 2008-2009 was not supported by our estimates. CONCLUSION: The general approach that uses multistage models of disease progression and accordingly stratified notification data can be applied in various settings for the routine estimation of incidence and CDR.

[Comparative characteristics of granulomatous inflammation in sarcoidosis and tuberculosis]. / Sravnitel'naia kharakteristika granulematoznogo vospaleniia pri sarkoidoze i tuberkuleze.

Comparisons are given of clinical manifestations and pathomorphological changes in lymph nodes and lungs of 76 patients with sarcoidosis and 48 patients with tuberculosis. Two types of tissue reactions were shown: with minimal and marked fibrosis. The former type is characterized by high density of granulomatosis and low density of fibrosis, large granulomas which contained many giant cells. The latter type is characterized by advanced fibrosis, small granulomas with rare giant cells. For clinically marked sarcoidosis, tissue reaction with predominant granulomatosis is typical, for patients with scare symptoms--tissue reaction with evident fibrosis. In the absence of caseous necrosis, differential diagnosis between tuberculosis and sarcoidosis with prevalent granulomatosis is impossible by morphological picture and morphometric evidence.