Новосибирский НИИ туберкулеза Минздрава России (ННИИТ) имеет богатую историю научных достижений в самых разнообразных областях фтизиатрии, в том числе в исследовании эпидемиологических закономерностей распространения инфекции, в хирургии легочного и внелегочного туберкулеза, разработки новых методов фармакотерапии и фундаментальных исследованиях патогенеза туберкулезной инфекции. В настоящей статье рассмотрены четыре перспективных направления исследований, которые ННИИТ инициировал недавно и уже получил первые результаты: исследование распространения латентной туберкулезной инфекции (ЛТИ) у взрослого населения и ее роли в эпидемическом процессе; изучение малоизученных штаммов M. tuberculosis, таких как B0/W148; исследование механизмов локальной иммуносупрессии в зоне туберкулезного очага, в том числе потенциальной роли мезенхимальных стволовых клеток (МСК), аккумулирующихся в туберкулезных воспалительных инфильтратах; разработка новых лекарственных форм противотуберкулезных препаратов, представленных в виде наноаэрозолей для ингаляционного введения.

The article describes changes in the main tuberculosis epidemiological indicators in Siberian and Far Eastern Federal Districts over the last decade. The rate of changes was analyzed for 21 regions within two districts, total number and structure of those followed up by phthisiologists in 2007-2016 were compared. TB situation has not significantly improved since the drug resistance and HIV infection become more and more frequent, providing an indirect impact on the epidemiological indicators. It is very difficult to treat such categories of patients and these difficulties do not allow enhancing treatment efficiency and cause an abrupt growth of the costs per one patient, both financial and organizational ones.

Goal of the study: to compare two surgical tactics for the treatment of bilateral pulmonary tuberculosis.

Materials and methods: 189 patients with tuberculous lesions in both lungs underwent lung resections: 91 patients had it done simultaneously on both lungs from the unilateral intercostal-mediastinal access by video-assisted thoracoscopy; 98 patients had resections of the left and right lung done one after another, time period between resections made 20.8 ± 9.4 days on the average.

Results. When comparing two tactics – simultaneous bilateral lung resection from a unilateral access and bilateral consecutive resections the following results were obtained respectively: 100 and 96.9% of patients had sputum conversion (p = 0.09, χ2); 100 and 93.8% of patients had healing of lung cavities (p = 0.11, χ2 ). During simultaneous surgery, the risk of intra-operative blood loss exceeding 300 ml was much lower (OR = 9.94; 95% CI 8.60-11.28) as well as the risk of postoperative complications (OR = 2.11; 95% CI 1.89-2.33). 

Prostate tuberculosis is difficult to be diagnosed, especially if lesions are limited only by this organ. The article analyses the experience of differential diagnostics of prostate tuberculosis based on the data of examination of 84 patients. 45 of them were diagnosed with prostate tuberculosis, and 39 patients were diagnosed with chronic bacterial prostatitis. Pathognomonic diagnostics criteria of prostate tuberculosis were the following: detection of tuberculous mycobacteria in the prostatic fluid or ejaculate, signs of granulomatous prostatitis with areas of cavernous necrosis in prostate biopsy samples, and prostate cavities visualized by X-ray or ultrasound examinations. Should the above criteria be absent, the disease can be diagnosed based on the combination of indirect signs: symptoms of prostate inflammation with active tuberculosis of the other localization; large prostate calcification, extensive hyperechoic area of the prostate, spermatocystic lesions, leucospermia and hemospermia, failure of the adequate non-specific anti-bacterial therapy.

Annual statistic forms were analyzed by means of an open cross-sectional single-step cohort study in order to assess the impact of the available infection control on the changes in tuberculosis incidence among medical personnel of TB medical units in Siberian and Far Eastern Federal Districts. A significant negative correlation was found out between the changes in TB incidence in the region and the year when this infection control was introduced, such as time period of a patient's transfer to the relevant ward or out-patient treatment when the result of smear microscopy was received, splitting up flows of patients depending on the microscopy result from treatment – diagnostic rooms, and availability of visual aids on the infection control for patients and personnel. It was demonstrated that the early introduction of administrative measures provided the most significant impact on the reduction TB incidence among the medical workers of TB units.

The article describes three cases of deep venous thrombosis in those suffering from fibrous cavernous pulmonary tuberculosis. The causes of thrombotic complications were analyzed. In all cases the patients had a central venous catheter installed. The state of thrombotic readiness associated with genetic causes as well was confirmed in two patients. Under follow-up by thrombodynamics testing, it was found out that the effective dose of low-molecular heparin was above the estimated dose prescribed according to the instructions. One case had a lethal outcome. Certain actions to be taken by anesthesiologists and emergency physicians are offered in order to minimize the risk of thrombotic complications in pulmonary tuberculosis patients in need of surgery and (or) a venous catheter.

The pool of TB infection in Siberian and Far Eastern Federal Districts is still full of complicated cases: among those being followed up by TB dispensaries, there are many patients suffering from fibrous cavernous TB as well as any clinical forms of tuberculosis with multiple drug resistance.

The situation can be improved through activated use of surgical treatment (along with the other interventions), first of all among those mentioned above. There is significant international and Russian experience of managing tuberculosis patients using surgery as a part of comprehensive treatment.

Surgical services of special medical units in the regions of Siberian and Far Eastern Federal Districts possess certain potential to increase the number surgeries for such complicated cases. 

Goal of the study: to define the informativeness of diaskintest as a screening method in urogenital tuberculosis patients.

Materials and methods. A simple, open cohort study was conducted enrolling 130 patients: Group 1 included active cases of urogenital tuberculosis – 58 persons; Group 2 included those suffering from chronic urogenital disorders confirmed to have no urogenital tuberculosis – 72 persons.

Results. 63.8% of patients from Group 1 had a positive result of diaskintest, as well as 62.5% of patients from Group 2. Sensitivity to diaskintest in adult cases of active urogenital tuberculosis made 63.8%. The high rate of positive results of diaskintest in those suffering from chronic urogenital disorders proved the low specificity of the test – 37.5%. 

In 2015 the implementation of Edicts no. 951 by the Russian Ministry of Health On Guidelines on Improvement of Respiratory Tuberculosis Treatment and Diagnostics was started.

Goal of the study: to analyze the characteristics of tuberculosis patients referred to treatment to Novosibirsk Tuberculosis Research Institute (NTRI) in 2014-2016 from the areas supervised by the Institute; to evaluate the clinical assessment of comprehensive chemotherapy efficiency after the introduction of the updated treatment regimens and express methods of microbiological diagnostics.

Materials and methods: a prospective cohort study was conducted using the data of 481 patients referred for treatment to NTRI from the areas supervised by it, i.e. Siberian and Far Eastern Federal Districts.

Results. Among the patients referred for treatment to NTRI in 2014-2016, new tuberculosis cases with multiple/extensive drug resistance (64.3-80.5%) and pulmonary destructions (67.9-82.7%) were very frequent. Among the patients already receiving treatment and referred to NTRI, the part of those with progressing course of the disease reduced from 35.0% in 2014 down to 9.7% in 2016 as well as the part of those with concurrent bronchial tuberculosis reduced from 41.3% in 2014 down to 27.9% in 2016.

After introduction of the provisions of the Edict to NTRI, treatment efficiency of new patients improved assessed as per the cessation of bacillary excretion (by sputum smear microscopy: in 2016 – 91.7%, in 2014 – 75%; by culture: in 2016 – 90.9%, in 2014 г. – 77.3%). 

Goal of the study: analysis of drug resistance of certain species of non-tuberculous mycobacteria through testing by minimum inhibitory concentrations on the fluid nutritional media.

Materials and method: drug resistance of non-tuberculous mycobacteria was tested by the method of minimum inhibitory concentrations on the fluid nutritional media. 51 strains of non-tuberculous mycobacteria from the species of M. intracellulare, M. avium, M. kansasii, M. gordonae, M. fortuitum, M. abscessus were tested. The minimum inhibitory concentration of the drug for slow-growing non-tuberculous mycobacteria was defined using the panel of 13 drugs (SLOWMYCO) and for the fast-growing mycobacteria – the panel of 15 drugs RAPMYCO Sensititre (Trek Diagnostic System, Thermo Scientific, USA) was used. It was proved that the majority of tested fast growing mycobacteria were resistant to ceftriaxone, cefepime, cefoxitin but susceptible to amikacin; and slow growing non-tuberculous mycobacteria were susceptible to clarithromycin, linezolid and amikacin. 

Goal of the study: to define the effect of various doses of laser radiation with 662 nm wave on the growth of M. tuberculosis in vitro.

Materials and methods. Samples of mycobacterial suspension of M. tuberculosis H37Rv were processed by monopositional light radiation (λ = 662 nm) in six dosing regimens varying in power and duration of the exposure to the light. All samples of mycobacterial suspension of M. tuberculosis were inoculated on the solid nutritional media of Lowenstein-Jensen in triplets for each dose of the exposure to light. Cultures were incubated under 37°С for 90 days with weekly inspection of samples.

Results. Continuous irradiation by diffused laser with 662 nm wave provides the most expressed bacteriostatic and bactericidal effects against M. tuberculosis H37Rv under the density of the energy dose of 234.5 and 703.5 of J/sq.cm. Such a dose was obtained through 5 and 15-minute exposure respectively. 

Goal of the study: to enhance the efficiency of the comprehensive treatment of destructive pulmonary tuberculosis in HIV patients using bronchial valve block.

Materials and methods. A study was conducted enrolling two groups of tuberculosis patients with destructive drug resistant pulmonary forms and concurrent HIV infection having comparable clinical and laboratory characteristics. Treatment of the patients in the main group (n = 68) included valve bronchial block. Patients from the comparison group (n = 57) received the same treatment but without valve bronchial block.

Results of the study. Adding valve bronchial block to the treatment of tuberculosis is a positive factor confidently promoting sputum conversion (OR = 4.13; 95% CI 3.50-4.75) and healing of cavities (OR = 3.89; 95% CI 3.30-4.48). When using valve bronchial block the healing of cavities made 55.9%, while in the comparison group it made only 24.6%; (p = 0.0004, χ2 ). Sputum conversion was achieved in 75.0%, and in the comparison group, this rate was 42.1% (p = 0.0002, χ2 ). The above rates varied respectively the degree of immunosuppression in the patients.