The article describes the most pertinent techniques for morphologic diagnosis of tuberculosis incorporating the related problems encountered by practicing pathologists including frequently meet co-infection with HIV, increase of non-tuberculous mycobacterioses and detection of mycobacteria possessing atypical properties presented by coccus and branching forms. The detection of causative agents located extracellular is discussed as well as their potential ability to form biofilms.

Retrospective cohort study was conduced in order to investigate the efficiency of surgical treatment in pulmonary tuberculosis patients residing in the region with high prevalence of the disease. Two groups of patients were enrolled comparable regarding the course of the disease, presence of surgery indications, living in Altai Republic, who had been examined by TB surgeon (totally 185 persons). 110 patients enrolled into the first group included and 75 patients were enrolled in the control one. While analyzing the results it was found out that surgery allowed achieving sputum conversion in 90.7% of patients in the main group, and among those who refused surgical treatment conversion rate made 66.1% Destructive changes were eliminated in 90.8% in the main group while in the control group cavity healing was achieved only in 56.3% of patients (p = 0.0001, χ2 ).

Goal: to study the structure, profile of primary drug resistance and viability of mycobacteria in tuberculosis patients with concurrent HIV infection.

Materials and methods. Structure, profile of primary drug resistance and viability of mycobacteria were studied in 67 pulmonary tuberculosis patients with concurrent HIV infection.

Results. It has been found out that new drug resistance tuberculosis in those suffering from HIV infection is characterized by severe structure of drug resistance with obvious predominance of multiple (73.1%) and extensive (16.4%) primary drug resistance combined with resistance to main and reserve TB drugs in the majority of cases. Nearly total primary drug resistance to isoniazid, streptomycin and rifampicin has been observed as well as severe burden of TB strains resistant to reserve drugs among which special attention is to be paid to resistance to ofloxacin, detected in the each 4th patient. The above features of drug resistance in tuberculosis patients with concurrent HIV infection create significant difficulties for compilation of the proper regimen of TB drugs for chemotherapy as per regimens IV and V thus inevitably deteriorating treatment efficiency and significantly increasing mortality of such patients. 

404 sarcoidosis and 404 tuberculosis patients were examined in order to detect correlations between clinical manifestations, psychological adaptation and accentuation of personality traits and granulomatous lesions of respiratory organs in case of sarcoidosis and tuberculosis. All patients had subjective and objective examinations and answered the following questionnaires: Schmieschek questionnaire to identify accentuation of personality traits, clinical questionnaire to detect and evaluate neurotic disorders, Taylor Manifest Anxiety Scale to detect the level of anxiety. It has been found out that sarcoidosis patients are characterized both by asymptomatic course of the disease as well as diverse clinical manifestations: pain syndrome, nodal fever, intoxication with expressed general fatigue, respiratory insufficiency. It is combined with stuck, pedant, cycloid, exalted, emotive accentuations of personality traits, with psychological maladaptation as per the scores of autonomic imbalance, neurotic depression, asthenia, with average high level of anxiety. The following is typical of tuberculosis patients: syndrome of bronchial tree lesions and respiratory insufficiency; distymny, demonstrative, excitable, exalted, anxiety-hypochondriac accentuations of personality traits, with psychological maladaptation as per the scores of autonomic imbalance, obsessive-phobic disorders and hysteria; average high level of anxiety. The strong correlation has been found between the degree of symptoms expression, level of anxiety and psychological maladaptation and the type of patient's accentuation of personality traits.

Goal of the study: to identify profile of mutations of tuberculous mycobacteria responsible for resistance to anti-tuberculosis drugs in HIV positive and HIV negative tuberculosis patients without prior history of treatment.

Materials and methods. 165 strains of tuberculous mycobacteria from HIV positive patients and 166 strains of tuberculous mycobacteria from HIV negative patients were studied in Sverdlovsk Region (TB Dispensary, Yekaterinburg). Mutations in genes were identified using microchips of TB-BIOCHIP® and TB-BIOCHIP®-2 in compliance with the manufacturer's guidelines (OOO Biochip-IMB, Moscow).

Results. It was observed that 85/165 (51.52%) strains isolated from HIV positive tuberculosis patients and 58/166 (34.94%) strains isolated from tuberculosis patients not associated with HIV possessed MDR genotype (p < 0.01). The majority of MDR strains had mutations in the 531th codon of rpoB (Ser→Leu) and 315th codon of katG (Ser→Thr) (64/85, 75.29% and 38/58, 65.52% respective the groups), resulting in the high level of resistance to rifampicin and isoniazid. Each group also had approximately equal ratio (11/165, 6.67% and 12/166, 7.23% respective the groups) of strains with genomic mutations defining the resistance to isoniazid, rifampicin and fluoruquinolones. No confident difference was found in mutation patterns of genome of tuberculous mycobacteria isolated from HIV positive and HIV negative tuberculosis patients. 

Primorsky Kray has one of the highest tuberculosis incidence in Russia and one of the highest HIV incidence among the regions of the Far Eastern Federal District. Understanding of interfacing mechanisms of two epidemics is necessary for planning tuberculosis control activities in the regions with high speed of increase and high prevalence of HIV infection. Applying this integrated approach allows detecting presence of such correlations when they are manifested on the population level during epidemic development. This interfaced epidemiological analysis of tuberculosis and HIV incidences resulted in concluding that current epidemic of tuberculosis is assessed as emergency and HIV epidemic as unstable. It has been proved that dissemination of HIV infection promotes tuberculosis epidemic in Primorsky Kray and mechanism of formation of tuberculosis and HIV incidences is interdependent.

Goal of the study: to justify the need for annual fluorography screening of the population.

Materials and methods. Nosologic structure of chest pathologies detected by fluorography screening in 2007-2015 has been studied. The changes in the estimated number of undetected active tuberculosis cases have been calculated, provided that there was no 100% coverage by preventive fluorography screening. The obtained data were compared with the rates in the Russian Federation.

Results. Nosologic structure of chest pathologies has been analyzed. It has been found out that respiratory tuberculosis patients made 4.8-10.8% out of those screened in 2007-2015, non-specific pulmonary diseases made – 16.6-36.2%, cancer cases made – 4.9-7.0% and other disorders made – 49.3-72.0%. Due to annual fluorography screening conducted in Voronezh Region from 2007 to 2015 the hidden reservoir of tuberculous infection significantly reduced and thus the number of detected patients decreased every year. In 2007-2015 the number of detected tuberculosis cases decreased by 2.2 fold in Voronezh Region, and by 1.4 fold in the Russian Federation. Tuberculosis incidence in Voronezh Region decreased from 69.3 (2007) down to 31.4 (2015) per 100,000 population (reduction by 54.69%), in the Russian Federation from 83.3 down to 57.7 (by 30.73%) respectively.

Role of nitric oxide in the pathogenesis of pulmonary tuberculosis has been studied in 77 patients with new infiltrate pulmonary tuberculosis and 34 patients with fibrous cavernous pulmonary tuberculosis. The level of cumulative and endogenous nitrite depended on the clinical form of tuberculosis: in infiltrate pulmonary tuberculosis patients it was within the limits of reference ranges, and in fibrous cavernous pulmonary tuberculosis patients it was significantly lower. Results of statistical analysis point out at the significant homogeneity (monofunctionality) of the set of rates, defining the level of NO metabolites in blood serum in infiltrate pulmonary tuberculosis, namely: impact of adenosine deaminase, levels of α1-protease inhibitor, ceruleoplasmin and age. On the contrary in case of fibrous cavernous pulmonary tuberculosis the diverse (multi-functional) complexes were detected including clinical blood rates providing influence on the reduction of NO level in blood. Nitric oxide in the patients with both clinical forms of tuberculosis correlated with classical markers of system inflammatory response, thus nitric oxide can be regarded as an integral component of inflammatory response with potential evaluation of prognosis of specific lesions during follow-up of changes.

The efficiency of using co-trimoxazole for treatment of mice infected with tuberculous mycobacteria with extensive drug resistance and supposed sensitivity to co-trimoxazole have been investigated.

The study of 78 clinical cultures of tuberculous mycobacteria has demonstrated that drug resistance to first line drugs (cases with multiple drug resistance – MDR) can be accompanied by the expansion of polymorphism in the part of drug susceptibility to co-trimoxazole, thus this drug can be used as an additional drug in the treatment of M/XDR tuberculosis patients. Using co-trimoxazole as an additional drug to isoniazid in the model of generalized tuberculosis in mice infected with Beijing strain with XDR reduced the bacterial load of the lungs by 10 times.

Detail evaluation of drug susceptibility/resistance of tuberculous mycobacteria to the additional drug of co-trimoxazole and investigation of the interaction of this drug with other agents included into treatment regimens IV and V can form the basis for improvement of treatment regimens for M/XDR tuberculosis patients with specification of doses and frequency of drug in-takes for each specific case. 

Despite the positive trends in the tuberculosis epidemic situation in general, changes in the extrapulmonary tuberculosis incidence are still unstable.

Materials and methods. The incidence structure of certain forms of tuberculosis has been analyzed depending on the concurrent HIV infection including analysis of the incidence structure of extrapulmonary tuberculosis with concurrent tuberculosis of other localizations as per the data of Novosibirsk Regional TB Dispensary for 2015.

Results. 95 patients were diagnosed with isolated extrapulmonary tuberculosis. In general the equal numbers of bone and joint tuberculosis and central nervous system tuberculosis were registered – 31.6% of each. However those suffering from central nervous system tuberculosis without compromised immunity made only 4.1%, while among the HIV infected this rate made 60.9%; those suffering from bone and joint tuberculosis prevailed more than twice among the HIV negative. Tuberculosis of peripheral lymph nodes was diagnosed in 14.7%, urogenital tuberculosis all together – in 13.9%. Significant differences in extrapulmonary tuberculosis classification between World Health Organisation and RF have been found out. Concurrent forms of tuberculosis were detected in 97 patients, of them 57.7% were HIV positive. Tuberculosis of respiratory organs and central nervous system, tuberculosis of respiratory organs and bones and joints prevailed among concurrent forms.

Conclusion: It is necessary to review the structure of reports on extrapulmonary tuberculosis in order to provide true statistic data.