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Issue. Articles

3(30) // 2017



1. advanced article


Prospects of Harm reduction strategy in combating the spread of HIV in Ukraine (UKR)

V. V. Korolenko

O. O. Bogomolets National Medical University, Kyiv, Ukraine

The concept of harm reduction is a strategy of the state policy, which includes a set of measures against harmful behavioral patterns (excessive alcohol consumption, smoking, poor nutrition, lack of physical activity, dependence on psychoactive substances, other variants of deviant behavior) through the introduction of mechanisms and instruments for stimulating consumption as Less harmful products and services. Spent the world practice counteract the dangerous consequences of drug use and paid sex services is one of the important measures to counter the spread of HIV/AIDS. Use of a harm reduction strategy to prevent the development of the TB epidemic is actual for Ukrainian practice to reduce the harm of tobacco, which is based on the thesis of less harmful nicotine itself, compared to other components of tobacco smoke, which has long been its use in the manufacture of nicotine­containing products. These organizational decisions are very efficient and allow practically implement European principle Health in all policies.
Implementation of harm reduction approach in the Ukrainian healthcare primarily needs urgent development and regulatory approval of the appropriate concept of a unified conceptual apparatus in accordance with international law and with the current global challenges and further involvement of harm reduction principles to solve practical health issues.

Keywords: epidemiology, public health, harm reduction, HIV, IDU, patient organizations.

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Original language: Ukrainian

2. advanced article


Introduction Bedakvilina in Ukraine: a new hope for patients with resistant forms of tuberculosis (UKR)

N.. Lytvynenko1, .V. Pavlova2, K.. Hamazyna2, E. Vaitek3, A.I. Barbova1

1 S «National Institute of Phthisiology and Pulmonology named by F.G. Yanovsky NAMS of Ukraine», Kyiv, Ukraine
2 Representation of PATH in Ukraine, Kyiv, Ukraine
3 The United States Agency for International Development (USAID), Kyiv, Ukraine

The article reviews information about the situation and effectiveness of treatment of multidrug-resistant tuberculosis in Ukraine and the world and describes ways to improve it through the use of new antituberculosis drugs, in particular, Bedakvilina. The pilot project for the implementation of Bedakville is for the first time in Ukraine to implement the Challenge TB project, which is being implemented in Ukraine by the PATH, in cooperation with KNCV (the Royal Dutch Tuberculosis Control Alliance) with the support of USAID. For the third year, Challenge TB has been helping Ukraine to overcome the multidrug-resistant tuberculosis epidemic. The introduction of a new drug will be carried out within the framework of the project, subject to mandatory use of modern methods of early diagnosis of extended resistance of Mycobacterium tuberculosis and modern principles of treatment of chemically resistant tuberculosis. The article describes algorithms for step-by-step introduction of new drugs: modern early diagnosis of extended resistance; Treatment of patients with the use of Bedakville on the basis of modern principles of the formation of regimens of anti mycobacterial therapy at the inpatient and outpatient stages of treatment, which also includes the principles for the selection of patients for the treatment of Bedakville. Challenge TB will begin a pilot project using Bedakville with a treatment of 200 patients with advanced TB tuberculosis at the clinic of the SI «National Institute of Phthisiology and Pulmonology named by F. Yanovskogo NAMS of Ukraine». In the future, these patients will be treated out-patient in the community using modern principles of the patient-centered approach.
Experience in the use of new drugs will help to work out a comprehensive algorithm for their correct use and conduct training for specialists from the regions in order to prevent errors in managing patients and prevent the formation of resistance to new antituberculous drugs. Experience in applying algorithms developed and worked out within the framework of the project will be transferred to the state for a further optimal introduction of new drugs on the territory of Ukraine.

Keywords: Bedakvilin, new drugs, multidrug-resistant tuberculosis.

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Original language: Ukrainian

3. Original researches


State immunity in the comprehensive treatment of tuberculosis (unspecified location, rifampicin-resistant of lungs, chemoresistant military and multi-resistant nervous system) in combined with HIV (UKR)

V. I. Petrenko1, O. V. Panasiuk1—4, G. V. Padysh1, O. B. Holub4, Ya. V. Lopatina4, L. S. Nychyporenko3

1 O.O. Bogomolets National Medical University, Kyiv, Ukraine
2 Kyiv Medical University UAFM, Kyiv, Ukraine
3 L.V. Gromashevsky Research Institute of Epidemiology and Infectious Diseases, NAMS of Ukraine, Kyiv, Ukraine
4 Kyiv Area City Center for Prevention and Control of AIDSth, Kyiv, Ukraine

Objective — to analyze the state of immunity during antimycobacterial therapy (AMBT) against the background of antiretroviral therapy (ART) in HIV-positive patients with newly diagnosed TB (TB) of unspecified localization (VDTB NUL), rifampicin-resistant TB (Rif TB) lung, chemoresistant TB HRTB) military and multiresistant TB (MRTB) of the nervous system.
Materials and methods. A clinical trial was conducted on 80 adult TB/HIV co-infected patients who were screened and treated in accordance with national standards. The patients are divided into 4 groups (20 persons), depending on the type and clinical form of TB and the chemoresistance of Mycobacterium tuberculosis: I group — patients with VDTB NUL; II group — RifTB of the lungs; III group — HRTB miliary and IV group — MRTB of the nervous system.
Results and discussion. In patients of each group, the prevalence of men (≥ 60 %) and persons aged 30—39 (≥ 55 %) and patients with deep (from 2 to 99 CD4 cells/mm3) and expressed (from 100 up to 199 CD4 cells/mm3) immunodeficiency (≥ 75 % of cases).
Patients in the , , and V groups significantly increase the level of CD4 cells/mm3 during B at the end of its intensive phase (F) and at the end of the continuing phase (PF) on the background of ART in the range of (118.5 ± 6, 8), (93.6 ± 8.0), (80.0 ± 8.5) and (60.8 ± 9.8) CD4 cells/mm3 at the beginning of the AMBT to (285.8 ± 5.1) (191.0 ± 6.8), (155.4 ± 6.1) and (184.0 ± 7.3) CD4 cells/mm3, p < 0.05 (IF) and up to (336.8 ± 5.4), (301.0 ± 5.0), (335.8 ± 5.6) and (281.0 ± 5.2) CD4 cells/mm3, p < 0.05 (IF-PF).
Conclusions. The significant increase in the level of CD4 cells in HIV-positive TB patients (VDTB NUL, Rif TB lungs, HRTB military and MRTB of the nervous system) during AMBT at the end of its intensive phase and at the end of the continuing phase against the ART background has been demonstrated.

Keywords: tuberculosis, specified, unspecified, chemoresistant, complex treatment, the condition of immunity, the combination with HIV.

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Original language: Ukrainian

4. Original researches


Treatment outcomes of multidrug-resistant tuberculosis in Kyiv blast (UKR)

O. Aibana1, M. Bachmaha2, V. Krasiuk3, N. Rybak4, V. Shurypa6,
A. Mamotenko3, M. Dolynska3, T. Flanigan4, V. Petrenko3, M. Murray5

1 The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USA
2 Brown University School of Public Health, Providence, RI, USA
3 .. Bogomolets National Medical University, Kyiv, Ukraine
4 Warren Alpert Medical School at Brown University, Providence, RI, USA
5 Harvard Medical School, Boston, MA, USA
6 Kyiv Oblast TB Hospital

Background. Ukraine is among ten countries with the highest burden of multidrug- resistant TB (MDR-TB) worldwide. Treatment success rates for MDR-TB in Ukraine remain below global success rates as reported by the World Health Organization. Few studies have evaluated predictors of poor MDR-TB outcomes in Ukraine.
Methods. We conducted a retrospective analysis of patients initiated on MDR-TB treatment in the Kyiv Oblast of Ukraine between January 01, 2012 and March 31st, 2015. We defined good treatment outcomes as cure or completion and categorized poor outcomes among those who died, failed treatment or defaulted. We used logistic regression analyses to identify baseline patient characteristics associated with poor MDR-TB treatment outcomes.
Results. Among 360 patients, 65 (18.1 %) achieved treatment cure or completion while 131 (36.4 %) died, 115 (31.9 %) defaulted, and 37 (10.3 %) failed treatment. In the multivariate analysis, the strongest baseline predictors of poor outcomes were HIV infection without anti-retroviral therapy (ART) initiation (aOR 10.07; 95 % CI 1.20—84.45; p 0.03) and presence of extensively-drug resistant TB (aOR 9.19; 95 % CI 1.17–72.06; p 0.03). HIV-positive patients initiated on ART were not at increased risk of poor outcomes (aOR 1.43; 95 % CI 0.58—3.54; p 0.44). There was no statistically significant difference in risk of poor outcomes among patients who received baseline molecular testing with Gene Xpert compared to those who were not tested (aOR 1.31; 95 % CI 0.63—2.73).
Conclusions. Rigorous compliance with national guidelines recommending prompt initiation of ART among HIV/TB co-infected patients and use of drug susceptibility testing results to construct treatment regimens can have a major impact on improving MDR-TB treatment outcomes in Ukraine.

Keywords: Multidrug-resistant, tuberculosis, risk factors, treatment outcomes.

List of references:
1.    World Health Organization. Global tuberculosis report 2016. http://www.who.int/tb/publications/global_report/en/. Accessed 20 Oct 2016.
2.    World Health Organization. Tuberculosis country profiles. http://www.who.int/tb/country/data/profiles/en/. Accessed 20 Oct 2016.
3.    Farley JE, Ram M, Pan W, Waldman S, Cassell GH, Chaisson RE, et al. Outcomes of multi-drug resistant tuberculosis (MDR-TB) among a cohort of South African patients with high HIV prevalence. PLoS One. 2011;6(7):e20436.
4.    Brust JC, Gandhi NR, Carrara H, Osburn G, Padayatchi N. High treatment failure and default rates for patients with multidrug-resistant tuberculosis in KwaZulu-Natal, South Africa, 2000—2003. Int J Tuberc Lung Dis. 2010;14(4):413-9.
5.    Kliiman K, Altraja A. Predictors of poor treatment outcome in multi- and extensively drug-resistant pulmonary TB. Eur Respir J. 2009;33(5):1085-94.
6.    Kurbatova EV, Taylor A, Gammino VM, Bayona J, Becerra M, Danilovitz M, et al. Predictors of poor outcomes among patients treated for multidrug-resistant tuberculosis at DOTS-plus projects. Tuberculosis (Edinb). 2012;92(5):397-403.
7.    Johnston JC, Shahidi NC, Sadatsafavi M, Fitzgerald JM. Treatment outcomes of multidrug-resistant tuberculosis: a systematic review and meta-analysis. PLoS One. 2009;4(9):e6914.
8.    Shin SS, Pasechnikov AD, Gelmanova IY, Peremitin GG, Strelis AK, Mishustin S, et al. Treatment outcomes in an integrated civilian and prison MDR-TB treatment program in Russia. Int J Tuberc Lung Dis. 2006;10(4):402-8.
9.    Franke MF, Appleton SC, Bayona J, Arteaga F, Palacios E, Llaro K, et al. Risk factors and mortality associated with default from multidrug-resistant tuberculosis treatment. Clin Infect Dis. 2008;46(12):1844-51.
10.    Miller AC, Gelmanova IY, Keshavjee S, Atwood S, Yanova G, Mishustin S, et al. Alcohol use and the management of multidrug-resistant tuberculosis in Tomsk, Russian Federation. Int J Tuberc Lung Dis. 2012;16(7):891-6.
11.    Satti H, McLaughlin MM, Hedt-Gauthier B, Atwood SS, Omotayo DB, Ntlamelle L, et al. Outcomes of multidrug-resistant tuberculosis treatment with early initiation of antiretroviral therapy for HIV co-infected patients in Lesotho. PLoS One. 2012;7(10):e46943.
12.    Palacios E, Franke M, Muñoz M, Hurtado R, Dallman R, Chalco K, et al. HIV-positive patients treated for multidrug-resistant tuberculosis: clinical outcomes in the HAART era. Int J Tuberc Lung Dis. 2012;16(3):348-54.
13.    Orenstein EW, Basu S, Shah NS, Andrews JR, Friedland GH, Moll AP, et al. Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis. Lancet Infect Dis. 2009;9(3):153-61.
14.    Ministry of Health of Ukraine, Unified Clinical Protocol for Primary, Secondary (Specialized) and Tertiary (Highly Specia­lized) Medical Care for Adults with Tuberculosis. 04 September 2014. http://moz.gov.ua/docfiles/dn_20140904_0620_dod.pdf. Accessed 23 Nov 2014.
15.    World Health Organization. Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. 2014. Available at: http://apps.who.int/iris/bitstream/10665/130918/1/9789241548809_eng.pdf?ua=1&ua=1. Accessed 15 Nov 2015.
16.    Khaliaukin A, Kumar AM, Skrahina A, Hurevich H, Rusovich V, Gadoev J, et al. Poor treatment outcomes among multidrug-resistant tuberculosis patients in Gomel Region, Republic of Belarus. Public Health Action. 2014;4Suppl 2:24-8.
17.    Dolgusev O, Obevzenco N, Padalco O, Pankrushev S, Ramsay A, Van den Bergh R, et al. Pattern of primary tuberculosis drug resistance and associated treatment outcomes in Transnistria, Moldova. Public Health Action. 2014;4 Suppl 2:64-6.
18.    Kuksa L, Riekstina V, Leimane V, Ozere I, Skenders G, Van den Bergh R, et al. Multi- and extensively drug-resistant tuberculosis in Latvia: trends, characteristics and treatment outcomes. Public Health Action. 2014;4 Suppl 2:47-53.
19.    Keshavjee S, Gelmanova IY, Farmer PE, Mishustin SP, Strelis AK, Andreev YG, et al. Treatment of extensively drug-resistant tuberculosis in Tomsk, Russia: a retrospective cohort study. Lancet. 2008;372(9647):1403-9.
20.    Lytvynenko N, Cherenko S, Feschenko Y, Pogrebna M, Senko Y, Barbova A, et al. Management of multi- and extensively drug-resistant tuberculosis in Ukraine: how well are we doing? Public Health Action. 2014;4 Suppl 2:67-72.
21.    Gandhi NR, Andrews JR, Brust JC, Montreuil R, Weissman D, Heo M, et al. Risk factors for mortality among MDR- and XDR-TB patients in a high HIV prevalence setting. Int J Tuberc Lung Dis. 2012;16(1):90-7.
22.    Daniels JF, Khogali M, Mohr E, Cox V, Moyo S, Edginton M, et al. Time to ART initiation among patients treated for rifampicin-resistant tuberculosis in Khayelitsha, South Africa: impact on mortality and treatment success. PLoS One. 2015;10(11): 0142873.
23.    Velásquez GE, Becerra MC, Gelmanova IY, Pasechnikov AD, Yedilbayev A, Shin SS, et al. Improving outcomes for multidrug-resistant tuberculosis: aggressive regimens prevent treatment failure and death. Clin Infect Dis. 2014;59(1):9-15.
24.    Mitnick CD, Franke MF, Rich ML, Alcantara Viru FA, Appleton SC, Atwood SS, et al. Aggressive regimens for multidrug-resistant tuberculosis decrease all-cause mortality. PLoS One. 2013;8: e58664.
25.    Franke MF, Appleton SC, Mitnick CD, Furin JJ, Bayona J, Chalco K, et al. Aggressive regimens for multidrug-resistant tuberculosis reduce recurrence. Clin Infect Dis. 2013;56(6):770-6.
26.    Padayatchi N, Naidu N, Yende-Zuma N, O’Donnell MR, Naidoo K, Augustine S, et al. Implementation and operational research: clinical impact of the Xpert MTB/RIF assay in patients With multidrug-resistant tuberculosis. J Acquir Immune Defic Syndr. 2016;73(1):e1-7.
27.    Ciobanu A, Domente L, Soltan V, Bivol S, Severin L, Plesca V, et al. Do incentives improve tuberculosis treatment outcomes in the Republic of Moldova? Public Health Action. 2014;4 Suppl 2:59-63.
28.    Gelmanova IY, Taran DV, Mishustin SP, Golubkov AA, Solovyova AV, Keshavjee S. ‘Sputnik’: a programmatic approach to improve tuberculosis treatment adherence and outcome among defaulters. Int J Tuberc Lung Dis. 2011;15(10):1373-9.
29.    Toczek A, Cox H, du Cros P, Cooke G, Ford N. Strategies for reducing treatment default in drug-resistant tuberculosis: a systematic review and meta-analysis. Int J Tuberc Lung Dis. 2013;17(3):299-307.

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Original language: Ukrainian

5. Original researches


Ways to optimize radiation therapy of lung cancer patients (RUS)

O. Y. Stoliarova

National Cancer Institute, Kyiv, Ukraine

Objective — to evaluate the effectiveness of radiotherapy in different variants of LC course, to identify risk factors for negative results of treatment, to determine its complications, to develop ways to optimize radiotherapy in such patients and to identify prognostic criteria.
Materials and methods. 1071 patient with LC at the age of 24 to 86 (average age — 59 years old), of which 82.8 % of men and 17.2 % of women, were under supervision. Any patient wasnt operated on for LC previously, and 73.1 % of the patients received combined chemo radiotherapy. Lesion of upper lung lobes was found in 27.0 % of cases, lower ones — 15.3 %, upper bottom localization on the left — in 18.7 %, middle upper — 25.0 %, middle bottom — 1.4 %, middle lobe — 3.7 %. Central form of LC was determined in 78.7 % of the patients and peripheral form in 21.3 %. Small cell lung histology variant of the disease was detected in 17.6 % of the cases and non-small — in 82.5 %. IA disease stage was defined in 0.3 % of the patients, IB — 0.6 %, IIA — 1.1 %, IIB — 3.3 %, IIIA — 35.1 %, IIIB — 23.7 %, IV — 36.0 %.
Results and discussion. The ratio of the quantity of one, two and three RT sessions with LC was 68:  56: 1, and the highest radiotherapy power was directed to the tumor process in the lungs directly, less on distant metastases in the organs, even less — on lymph nodes with metastases. Risk factors for ineffective use of radiotherapy with LC included paracancerous exudative pleurisy, tumor invasion into the trachea, esophagus and thoracic wall, a number of metastases in distant organs, development of metastasis in a brain, adrenal glands, pancreas, and scapula. Integral nature of the complications of treatment was detected in 2 % of LC patients, was associated with combined radical primary tumor radiotherapy and palliative RT for distant metastases was determined by the irradiation power (development of myelosuppression, radia­tion esophagitis, tubulointerstitial nephritis).
Conclusions. Radical radiation therapy with LC was optimal for a primary tumor with high doses of concomitantly used podophyllotoxins, antimetabolites, and anthracycline antibiotics.

Keywords: lungs, cancer, radiation therapy, optimization.

List of references:
1.    Ceniceros L, Aristu J, Castanon E, Rolfo C, Legaspi J, Olarte A et al. Stereotactic body radiotherapy (SBRT) for the treatment of inoperable stage I non-small cell lung cancer patients. Clin Transl Oncol. 2015;55(8):213-9. doi: 10.1186/s13014-015-0417-5.
2.    Chen X, Kong X, Zhang Z, Chen W, Chen J, Li H et al. Alpha‑2-macroglobulin as a radioprotective agent: a review. Chin J Cancer Res. 2014;26 (5):611-21. doi: 10.3978/j.issn.1000-9604.2014.09.04.
3.    Datta NR, Samiei M, Bodis S. Radiotherapy infrastructure and human resources in Europe - ​present status and its implications for 2020. Eur J Cancer. 2014;50(15):2735-43. doi: 10.1089/tmj.2014.0154.
4.    Fan X, Jia C, Yang J, Li G, Mao H, Jin Q, Zhao J. A microfluidic chip integrated with a high-density PDMS-based microfiltration membrane for rapid isolation and detection of circulating tumor cells. Biosens Bioelectron. 2015;71(15):380-6. doi: 10.1016/j.bios.2015.04.080.
5.    Farr KP, Muller DS, Khalil AA, Kramer S, Morsing A, Grau C. Loss of lung function after chemo-radiotherapy for NSCLC measured by perfusion SPECT/CT: Correlation with radiation dose and clinical morbidity. Acta Oncol. 2015;23(7):1-5. doi: 10.3109/0284186X.2015.1061695.
6.    Grdalska-Lampart M, Karczmarek-Borowska B, Radziszewska AU. Lung cancer in Podkarpackie region in the years 2002-2011. Pneumonol Alergol Pol. 2015;83 (2):109-19. doi: 10.5603/PiAP.2015.0018.
7.    Khalil AA, Hoffmann L, Moeller DS, Farr KP, Knap MM. New dose constraint reduces radiation-induced fatal pneumonitis in locally advanced non-small cell lung cancer patients treated with intensity-modulated radiotherapy. Acta Oncol. 2015;22(7):1-7. doi: 10.3109/0284186X.2015.1061216.
8.    Kong FM, Wang S. Nondosimetric risk factors for radiation-induced lung toxicity. Semin Radiat Oncol. 2015;25(2): 100-9. doi: 10.1016/j.semradonc.2014.12.003.
9.    Larson SM, Carrasquillo JA, Cheung NK, Press OW. Radioimmunotherapy of human tumours. Nat Rev Cancer. 2015;15 (6):347-60. doi: 10.1038/nrc3925.
10.    Lian C, Li H, Denoeux T, Chen H, Robinson C, Vera P, Ruan S. MO-AB-BRA‑10: Cancer therapy outcome prediction based on dempster-shafer theory and pet imaging. Med Phys. 2015;42(6):3549. doi: 10.1109/TBME.2017.2688453.
11.    Neal JW, Gainor JF, Shaw AT. Developing biomarker-specific nd points in lung cancer clinical trials. Nat Rev Clin Oncol. 2015;12(3):135-46. doi: 10.1038/nrclinonc.2014.222.
12.    Oh JH, Craft JM, Townsend R. A bioinformatics approach for biomarker identification in radiation-induced lung inflammation from limited proteomics data. J Proteome Res. 2011;10(3):1406-15. doi: 10.1021/pr101226q.
13.    Pabinger I, Thaler J, Ay C. Biomarkers for prediction of venous thromboembolism in cancer. Blood. 2013;122(12):2011-8. doi: 10.1182/blood‑2013-04-460147.
14.    Page BR, Hudson AD, Brown DW, Shulman AC, Abdel-Wahab M, Fisher BJ, Patel S. Cobalt, linac, or other: what is the best solution for radiation therapy in developing countries? Int J Radiat Oncol Biol Phys. 2014;89(3):476-80. doi: 10.1016/j.ijrobp.2013.12.022.
15.    Pollock S, O’Brien R, Makhija K, Hegi-Johnson F, Ludbrook J, Rezo A et al. Audiovisual biofeedback breathing guidance for lung cancer patients receiving radiotherapy: a multi-institutional phase II randomised clinical trial. BMC Cancer. 2015;18(15):526-36. doi: 10.1186/s12885-015-1483-7.
16.    Ricardi U, Badellino S, Filippi AR. Stereotactic radiotherapy for early stage non-small cell lung cancer. Radiat Oncol J. 2015;33(2):57-65. doi: 10.3857/roj.2015.33.2.57.
17.    Safi S, Rauch G, Op den Winkel J, Kunz J, Schneider T, Bischof M  et al. Sublobar resection, radiofrequency ablation or radiotherapy in stage i non-small cell lung cancer. Respiration. 2015;89(6):550-7. doi: 10.1159/000381555.
18.    Shen B, Zhao K, Ma S, Yuan D, Bai Y. Topotecan-loaded mesoporous silica nanoparticles for reversing multi-drug resistance by synergetic chemoradiotherapy. Chem Asian J. 2015;10(2):344-8. doi: 10.1002/asia.201403117.
19.    Wallerek S, Sorensen JB. Biomarkers for efficacy of adjuvant chemotherapy following complete resection in NSCLC stages I—$ 5IIA. Eur Respir Rev. 2015;24(136):340-55. doi: 10.1183/16000617.00005814.
20.    Xie D, Marks R, Zhang M, Jiang G, Jatoi A, Garces YI et al. Nomograms predict overall survival for patients with small-cell lung cancer incorporating pretreatment peripheral blood markers. J Thorac Oncol. 2015;10(8):1213-20. doi: 10.1097/JTO.0000000000000585.
21.    Zhang H, Xia H, Zhang L, Zhang B, Yue D, Wang C. Clinical significance of preoperative neutrophil-lymphocyte vs platelet-lymphocyte ratio in primary operable patients with non-small cell lung cancer. Am J Surg. 2015;11(1):150-60. doi: 10.1016/j.amjsurg.2015.03.022.

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Original language: Russian

6. Original researches


Some questions of the epidemic of family tuberculosis (UKR)

I. D. Duzhiy, L. A. Bondarenko, V. O. Oleshchenko

Sumy State University, Sumy, Ukraine

Objective — tuberculosis continues to be an insurmountable problem. In the context of the reform of the anti-TB service, the future of the problem is unclear, which determines its relevance.
Materials and methods. The authors studied the frequency of «family» tuberculosis in the two study groups: the first in 2006—2010, the second in 2011—2015. In the first group, the family tuberculosis was found in 64 (2.4 %) persons, in the second — in 42 (1.3 %).
Results and discussion. Among patients with newly diagnosed pulmo­nary processes in the first group «family» forms of tuberculosis accounted for 2.4 %, and the second — 1.5 %. The source of «family» tuberculosis was infiltrative tuberculosis among patients of the first group in 41 (63.1 %) persons, and among patients of the second group — in 16 (38.1 %), disseminated tuberculosis in patients of the first group was the cause of «family» tuberculosis in 20 (31.5 %) persons, tuberculous pleurisy in both study groups cases caused the «family» tuberculosis 7 (6.6 %) times, leading to 8 different forms of the disease.
Conclusions. In the early period of study (the first group) an infiltrative form of «family» tuberculosis was revealed in 60.9 % of the subjects, while in the second group — 54.8 %; the disseminated form of «family» tuberculosis in the first group was discovered in 12.5 %, in the second — 19.0 %. To establish the tendency in the development of «family» tuberculosis, it is necessary to «expand» the study groups.

Keywords: family tuberculosis, sources of family tuberculosis.

List of references:
1.    Bialyk IB. The efficacy and tolerance of the intensive anti-tuberculosis treatment at multidrug-resistant destructive pulmonary tuberculosis patients with simultaneous and equable during the day administration of antituberculous drugs. Tuberculosis, lung diseases, HIV infection. 2014;3(18):11-15 (in Ukr).
2.    Duzhyy ID. Khirurhiya tuberkulozu lehen ta plevry. K: Zdorovya. Sumy VAT «SOD»; Vydavnytstvo «Kozatskyy val»;2003:360 (in Ukr).
3.    Lytvynenko NA, Feshchenko Yu I, Pogrebna MV t al. Efficacy of treatment MDR and XDR tuberculosis: the main reasons for poor results. Tuberculosis, lung diseases, HIV infection. 2016;2(25):22-29 (in Ukr).
4.    Litvinuk OP, Zaykov SV, Zakharchenko OO, Klimenko TI. The incidence of tuberculosis health workers of Vinnytsya region. Tuberculosis, lung diseases, HIV infection. 2015;2(21):101-105 (in Ukr).
5.    Nakaz Ministerstva okhorony zdorov»ya Ukrayiny vid 4 veresnya 2014 roku N 620 «Pro zatverdzhennya ta vprovadzhennya medyko-tekhnolohichnykh dokumentiv zi standartyzatsiyi medych­noyi dopomohy pry tuberkulozi» (in Ukr).
6.    Petrenko VI, Panasyuk OV, Radysh GV t al. Comparative results of treatment of patients with TB (unspecified localization, ryfampicinresistant of lungs, multiresistant of lungs, milliar and multiresistant of nervous system) combined with HIV infection. Tuberculosis, lung diseases, HIV infection. 2017;1(28):21-26 (in Ukr).
7.    Petrenko VI, Proziuk RG. The problem of tuberculosis in Ukraine. Tuberculosis, lung diseases, HIV infection. 2015;2(21):16-29 (in Ukr).
8.    Pylypchuk NS, Podlesnkh HA, PylypchukVN. Oshybky v dyahnostyke zabolevanyy lehkykh. K.: Zdorovya, 1993:247 (in Rus).
9.    Suprun U. Kontseptsiya zahalnoderzhavnoyi tsilovoyi sotsialnoyi prohramy protydiyi zakhvoryu­vannyu na tuberkuloz na 2017-2021 roky. Tuberkuloz, lehenevi khvoroby, VIL-infektsiyi. 2017;1:5-11 (in Ukr).
10.    Feshchenko Yu I, Melnyk VM, Turchenko LV, Lirnyk SV. Tuberculosis: organization of diagnosis, treatment, prevention and control of mortality. .: Zdorovya, 2010:448 (in Ukr).
11.    Khomenko AG, Chukanov VI, Mishin VYu. Detection, diagnosis and chemotherapy of tuberculosis of respiratory organs in modern epidemiological conditions. Methodical manual for doctors. Moscow, 2000:36 (in Rus).

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7. Original researches


Damage of liver function in newly diagnosed patients with multidrug-resistant pulmonary tuberculosis (UKR)

L.A. Hryshchuk1, O.M. Okusok2

1 I.Ya. Horbachevsky Ternopil State Medical University, Ministry of Healthcare of Ukraine, Ternopil, Ukraine
2 Ternopil Regional Tuberculosis Hospital, Ternopil, Ukraine

Objective — to study determined markers characteristic of liver function disorders, in particular, of cytolytic and cholestatic syndromes, in patients with newly diagnosed multidrug-resistant pulmonary tuberculosis, before and after their discharge from the hospital.
Materials and methods. 55 patients first time diagnosed with multidrug-resistant pulmonary tuberculosis were examined prior to the start of the treatment and upon discharge from the hospital after treatment with anti-tuberculosis drugs. A group of 27 practically healthy people served as a control group. The study group was divided into two subgroups: (27 people), patients with moderately expressed intoxication syndrome at the time of hospital admission, and B (28 people),  patients with fully expressed intoxication syndrome at the time of hospital admission.
Results and discussion. Study of the functional state of the liver in patients with newly diagnosed multidrug-resistant pulmonary tuberculosis demonstrated increased levels of biochemical markers such as lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyltranspeptidase before the treatment has started. Prior to discharge from the hospital subsequent to sustained treatment with second-line anti-tuberculosis drugs, the levels of all measured markers, such as transaminases, total and direct bilirubin, lactate dehydrogenase, alkaline phosphatase and gamma-glutamyltranspeptidase, have significantly increased.
Conclusions. Patients with newly detected multi-resistant pulmonary tuberculosis suffered from significant disruption of the liver function coupled with severe intoxication syndrome. A significant increase in cytolysis and cholestasis markers was observed in these patients even before the treatment commenced. Following an intensive phase of the treatment, the increase in these marker levels continued.

Keywords: multidrug-resistant pulmonary tuberculosis, functional disorders of the liver, biochemical markers.

List of references:  
1.    «Analiz prohalyn u likuvanni tuberkul’ozu» final’nyy zvit proektu GRANT-03-OR [Elektronnyy resurs]. - Rezhym dostupu: http://pdf.usaid.gov/pdf_docs/PA00MHB8.pdf (in Ukr).
2.    Balasanyants GS, Sukhanov DS. Pobochnyye deystviya protivotuberkuleznykh preparatov i metody ikh ustraneniya. Sankt-Peterburg: Taktik-Studio, 2011:88 (in Rus).
3.    Volf SB. Adverse reactions to tuberculosis chemotherapy.
J Grodno State Medical University. 2016;3:141-146 (in Rus).
4.    Galan IO, Pavlenko EN, Potaychuk VI, Zdoryk IF. Influence of antituberculosis therapy on some indices of protein metabolism and hepatobilliary system in patients with newly diagnosed lung tuberculosis. Ukr Pulmonol J. 2008;3:70-72 (in Ukr).
5.    Zozuliak VI, Zozuliak NV, Pylypenko II. Biochemical features of liver’s difunction in treatment of patients with destructive pulmonary tuberculosis. Tuberculosis, pulmonary diseases, HIV-infection. 2015;2(21):85-89 (in Ukr).
6.    Koroliova  MV. Pharmaco-epidemiological, clinical and laboratory characteristics of drug-induced liver injury in tuberculosis / J Infectiol. 2015;7(4):44-50 (in Rus).
7.    Okusok OM, Hryshchuk LA. Impact of toxic hepatitis on treatment efficiency of drug-resistant pulmonary tuberculosis. Inf Dis. 2016;4:77-81. Doi 10.11603 / 1681-2727.2016.4.7220 (in Ukr).
8.    Perelik zakhvoryuvan’ pechinky, yikh symptomy ta diahnostyka [Elektronnyy resurs]. Rezhym dostupu: http://medprice.com.ua/ukr/articles/perelik-zahvoryuvan-pechinki-yih-simptomi-ta-diagnostika-4708.html (in Ukr).
9.    Petrenko VI, Proziuk RG. The problem of tuberculosis in Ukraine. Tuberculosis, pulmonary diseases, HIV infection. 2015;2(21):16-29 (in Ukr).
10.    Lyashenko OO, Poteyko PI, Lebid LV et al. A method for diagnosing the possible course of pulmonary tuberculosis. Patent number: 96483. Published: Feb 10, 2015. [Electronic resource]. Mode of access: http://uapatents.com/7-96483-sposib-diagnostiki-mozhlivogo-perebigu tuberkulozu-legeniv.html (in Ukr).
11.    Raznatovs’ka OM. Otsinka biokhimichnykh pokaznykiv ta aktyvnosti zapal’noho protsesu u khvorykh na khimiorezystentnyy tuberkul’oz lehen’. Ukrayinskyy zhurnal klinichnoyi ta laboratornoyi medytsyny. 2011;6(1):181-184 (in Ukr).
12.    Todoriko LD, Petrenko VI, Grishin MM. Resistance of Mycobacterium tuberculosis: myths and reality. Tuberculosis, pulmonary diseases, HIV infection. 2014;1(16):60-67 (in Ukr).
13.    Tuberkul’oz v Ukrayini: analitychno-statystychnyy dovidnyk./ MOZ Ukrayiny. DU «Ukrayins’kyy tsentr kontrolyu za sotsial’no-nebezpechnymy khvorobamy MOZ Ukrayiny».Kyyiv: Blank-Pres, 2015. [Elektronnyy resurs]. Rezhym dostupu: http://www.slideshare.net/Ukraine_CDC/2014-52881494 (in Ukr).
14.    Unifikovanyy klinichnyy protokol pervynnoyi, vtorynnoyi (spetsializovanoyi) ta tretynnoyi (vysokospetsializovanoyi) medychnoyi dopomohy doroslym. Tuberkul’oz. [Nakaz MOZ Ukrayiny vid 04.09.2014 r. 620].K.: Ministerstvo okhorony zdorov’ya, 2014:128 (in Ukr).
15.    Feshchenko YuI, Lytvynenko NA, Pogrebna MV et al. Efficacy of treatment MDR and XDR tuberculosis: the main reasons for poor results. Tuberculosis, pulmonary diseases, HIV-infection. 2016;2(25):22-29 (in Ukr).
16.    Feshchenko YuI, Cherenko SO, Matveeva OV et al. Adverse reaktions of anti-tuberkulosis drugs in treatment of patients with tuberculosis. Tuberculosis, pulmonary diseases, HIV-infection. 2014;4(19):13-20.
7.    Baghaei P, Tabarsi P, Chitsaz E et al. Incidence, clinical and epidemiological risk factors, and outcome of drug-induced hepatitis due to antituberculous agents in new tuberculosis cases. Am J Ther. 2010;17(1):17-22.
18.    Keshavjee S, Gelmanova IY, Shin SS et al. Hepatotoxicity during treatment for multidrug-resistant tuberculosis: occur­rence, management and outcome. Int J Tuberc Lung Dis. 2012;16(5):596-603. Doi: 10.5588/ijtld.11.0591.
19.    Lee SS, Lee CM, Kim TH et al. Frequency and risk factors of drug-induced liver injury during treatment of multidrug-resistant tuberculosis. Int J Tuberc Lung Dis.2016;20(6):800-805. Doi: 10.5588/ijtld.15.0668.
20.    Hsu HL, Bai KJ, Chiang YC et al. Hepatitis associated with prothionamide for treatment of multidrug-resistant tuberculosis.  J Formos Med Assoc. 2010;109(12):923-927. Doi: 10.1016/S0929-6646(10)60141-6.

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8. Original researches


Etiological structure and trends of dynamics of pulmonary syndrome dissemination among patients with physio-pulmonological profile (UKR)

N. S. Opanasenko, M. I. Kalenichenko, . V. Tereshkovich, V. I. Borisova, R. S. Demus, O. K. Oremska

SI «National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky of NAMS of Ukraine», Kyiv, Ukraine

Objective — to examine the dynamics trends and the etiological structure of the pulmonary dissemina­tion syndrome (SLD) in patients with phthisiopulmonologic profile who were on examination and treatment at the National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky of the National Academy of Medical Sciences of Ukraine (NIFP NAMS) from 2006 to 2015 years.
Materials and methods. For 10 years, 1140 patients with SLD were treated at NIFP NAMN, which amounted to (2.1 ± 0.1) % of the total number of patients.
Results and discussion. In the structure of the etiological factors that caused SLD, sarcoidosis of the lungs (group I) was most often found — 524 (46.0 ± 1.5) % of cases. SLD was predominantly found in patients of working age: 46.6 % from 40 to 59 years and 31.0 % from 19 to 39 years.
Conclusions. The fastest increase in the number of patients with SLD was observed in 2015, when the absolute indices increased by 30.9 %, which can be explained both by a general increase in the number of patients with this pathology and by the educational work carried out at the NIFP NAMN in the form of conferences, Publication of monographs, methodical recommendations, and scientific works.

Keywords: pulmonary dissemination, morbidity structure, morbidity dynamics.

List of references:  
1.    Havrysiuk VK et al. Idiopathic pulmonary fibrosis: clinical picture, diagnosis, treatment. Ukr Pulmonol J. 2012;3:55-59. (in Rus.).
2.    Havrysiuk VK et al. Essays on clinical pulmonology. K: Veles;2016:336. (in Rus.).
3.    Havrysiuk VK. Rare interstitial lung diseases. K.: Veles; 2012:148. (in Rus.).
4.    Ilkovych MM. Disseminated lung diseases. K.: HEOTAR-Medya; 2011:480. (in Rus.).
5.    Feshchenko YuI, Melnyk VM, Ilnytskyi IH. Diseases of the respiratory system. Kyiv-Lviv; 2008:495. (in Ukr.).
6.    Feshchenko YuI et al. Idiopathic interstitial pneumonia: clinic, diagnosis, treatment (draft national agreement). Ukr Pulmonol J. 2008;3(Dodatok):38-46. (in Ukr.).
7.    An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med. 2015;192:e3–e19.
8.    Navaratnam V et al. The rising incidence of idiopathic pulmonary fibrosis in the UK. Thorax. 2011;66(6):462-467.

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9. Original researches


Comparative analysis of efficiency of isoniazidmonoresistant tuberculosis treated with different drug regimens (RUS)

O.. Hovardvska1, O. S. Shevchenko1, T. V. Sencheva2, T. F. Kovaleva2

1 Kharkiv National Medical University, Kharkiv, Ukraine
2 Region Tuberculosis Dispensary N 1, Kharkiv, Ukraine

Objective — to compare results of patients with isoniazid­monoresistant TB treated by short (only I line anti-tuberculosis drugs) and long (I and II line drugs) regimens.
Materials and methods. Retrospective analysis of 91 history cases of patients with pulmonary TB with isoniazid­monoresistance or isoniazid&streptomicyn­polyresistance of MBT was done. All of them were registered in Kharkiv region and treated by 1 or 2 categories. 1 group (46 patients) — received tuberculosis treatment by short or individual regimen using only I line drugs. 2 group (45 patients) –treated by the long regimen including II line drugs (fluoroquinolones and aminoglycosides).
Results and discussion. In the end of antituberculosis chemotherapy, 65.9 % patients from 1 group and 77.7 % from 2 group got effective treatment (results «reccured» and «finished treatment»). During treatment 2.3 % (1 patient) and 5.7 % (2 patients) died, «treatment failure» got 27.3 and 5.7 %, in 1 and 2 group respectively. Result «interrupted treatment» was fixed at 6.8 % in 1 group and at 14.2 % in 2 group. Duration of treatment course was (8.16 ± 2.86) months in 1 group and (10.86 ± 3.15) months in 2 group, that was longer for 2.7 months. The frequency of sides­effects was 8.69 and 26.6 % in 1 and 2 group respectively.
Conclusions. Including of II line drugs in the treatment regimen of isoniazid­monoresistant TB allows raising the results of effective treatment to 11.8 %. So we can recommend long regimens with using of II line drugs in individual way for patients with isoniazid­monoresistant TB, depending on the type of case, the level of bacteria excretion, the presence and volume of destruction in pulmonary tissue, necessity of hospitalisation, the adherence to treatment and the risk of side­effects, because this treatment is longer for 2.7 months then short regimen and is supported by the higher risk of side­effects, death, interruption of treatment.

Keywords: tuberculosis, isoniazidmonoresistant TB, treatment outcomes, individual drug regimen.

List of references:  
1.    Nakaz MOZ Ukrainy N 1091 vid 21.12.2012 r. «Pro zatverdzhennia ta vprovadzhennia medyko-tekhnolohichnykh dokumentiv zi standartyzatsii medychnoi dopomohy pry tuberkulozi».
2.    Nakaz MOZ Ukrainy N 600 vid 22.10.2008 h. «Pro zatverdzhennia standartu nadannia medychnoi dopomohy khvorym na khimiorezystentnyi tuberkuloz».
3.    Nakaz MOZ Ukrainy N 620 vid 04.09.2014 r. «Unifikovanyi klinichnyi protokol pervynnoi, vtorynnoi (spetsializovanoi) ta tretynnoi (vysokospetsializovanoi) medychnoi dopomohy doroslym».
4.    Nizova NM ta in. Tuberkuloz v Ukrayini [Tekst]: analityko-statystychnyy dovidnyk. Kyiv: Blank-Pres, 2015:142.
5.    Petrenko VI. Do mizhnarodnoho dnya borotby z tuberkulozom: Okhopyty try milyony: vyavyty, likuvaty, vylikuvaty tuberkuloz" Tuberkuloz, lehenevi khvoroby, VIL-infektsiya. 2014;1:5-7.
6.    Feshchenko YuI, Melnyk VM, Turchenko LV. A fight with tubrculosis in Ukraine: view to a problem. Ukr Pulmonol J. 2016;3:5-10.
7.    Shevchenko S, Hovardvska OA. Drug resistant tuberculosis: the dynamic of epidemiological indicators in groups of patients with new and reccured cases. Tuberkuloz, lehenevi khvoroby, VIL-infektsiya. 2016;4:98-102.
8.    Guidelines for the programmatic management of drug-resistant tuberculosis: emergency update 2008. Geneva: World Health Organization; 2008:77.
9.    WHO Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. Geneva: World Health Organization; 2014:100.

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Original language: Russian

10. Original researches


The mechanism of oxygen exchange in living nature and its disturbance in multidrug-resistant tuberculosis patients (UKR)

S. I. Kornaha, I. T. Pyatnochka, N. V. Thork

I.Ya. Horbachevsky Ternopil State Medical University, Ministry of Healthcare of Ukraine, Ternopil, Ukraine

Objective — to investigate the oxygen saturation in first diagnosed multidrug-resistant infiltrative and disseminated lung tuberculosis patients.
Materials and methods. A comparative analysis of blood oxygen saturation was carried out in patients with first diagnosed sensitive infiltrative (46 patients) and multidrug-resistant (45) and, respectively, in patients with disseminated sensitive (44) and multidrug-resistant (45) lung tuberculosis. Patients were representative of the age, sex, and prevalence of a specific process. The control group consisted of 37 healthy persons correlative with patients of age. Determination of saturation of arterial blood with oxygen was carried out in the lying position of patients using the poloxamer «Yutasoksi 201». The digital material was statistically processed with the deduction of the probability indicator.
Results and discussion. The comparative analysis of clinical data and oxygen saturation in patients with first diagnosed sensitive and multidrug¬resistant infiltrative and disseminated pulmonary tuberculosis showed significant negative changes in multidrug resistance. In particular, a greater frequency of destruction, catarrhal phenomena in the lungs, pathological changes in the peripheral blood and a violation of the function of external respiration and a significant decrease in oxygen saturation of the blood were noted. All this is a consequence of a much heavier course of the disease and a lower immunological status due to the aggressiveness of Mycobacterium multidrug-resistant tuberculosis.
Conclusions. In recent years there have been negative changes in the clinical course in patients with first diagnosed infiltrative and disseminated, primarily multidrug-resistant lung tuberculosis. They often observed widespread destructive processes in the lungs, which led to a pronounced clinical picture of the disease, significant disturbances in the function of external respiration, and a significant decrease in blood oxygen saturation. This requires the use of complex adequate pathogenetic-means aimed at increasing blood oxygen saturation and, as a result, improving the effectiveness of treatment.

Keywords: multidrug-resistant, infiltrative, disseminated tuberculosis, oxygen saturation of blood.

List of references:  
1.    Gavrysiuk VK. Respiratory failure: mechanisms of development,evaluation methods, oxygen therapy (Ukr). Ukr pulmonol J [Ukrainian Pulmonology Journal] (Ukr). 2016;4;56-58.
2.    Opimakh SG. Evaluation  of oxygen gas exchange in chronic obstructive pulmonary disease patients (Ukr). Astma ta alergiya [Asthma and allergy] (Ukr). 2013;4;34-39.
3.    Pyatnochka IT, Kornaha SI, Thork NV. Blood oxygen saturation at different forms of lung tuberculosis depending on the various factors (Ukr). Visnyk naukovych doslidzhen'. 2013;1;12-14.
4.    WHO manual on pulseoximetry. World Health Organization; 2009:23.
5.    Safonov VA. Dyhanie - etoxhyzn' (Rus.). M. Znaniye; 1982:64.
6.    Fizicheskaya kul'tura, zdravoochraneniye I obrazovaniye. Materialy X mezhdunarodnoyi nauchno-prakticheskoiy konferenzcii, posvyashchonnoyi pamyati VS Pirusscogo. Tomsk, 17 noyabrya 2016. Podred. prof. VGShil'ko. Tomsk; 2016:376.
7.    Frayt V, Frayt O, Frayt YU. Legeneve krovopostachannya, gipertenziya i tuberkul'oz.  Drogobich: Vidrodzhennya; 2001:291.
8.    Global initiative for chronic obstructive lung disease revised 2011[Text] / GOLD executive committee, GOLD-science committee; 2011:90.
9.    Ocenaczynnościpłuc w chorobachukładuoddechowego / Red. Janusz Kowalski, Antoni Koziorowski, Leszek Radwan, Mał­go­rzata Bartosiewicz et al. Warszawa: Borgis;2004:392.

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11. Original researches


Dynamics of immunity changes in patients with multi-resistant pulmonary tuberculosis during the intensive phase of treatment (UKR)

I. L. Platonova1, M. I. Sakhelashvili2, . A. Tkach1, N. E. Lapovec’1, G. D. Shtybel2, O. V. Omelyan3, R. M. Tupychak3, M. K. Novosad3, A. J. Szczsny3

1 SI «Lviv Research Institute of Epidemiology and Hygiene Ministry of Health of Ukraine», Lviv, Ukraine
2 Lviv National Medical Universitynamed after Danyl Galitsky, Lviv, Ukraine
3 PU «Lviv Regional pulmonologyclinicaldiagnostic and treatment center», Lviv, Ukraine

Objective — ​to study the dynamics of the immune system changes in patients with the first­ever diag­nosed multidrug­-resistant pulmonary tuberculosis (MRFDTB) during an intensive phase of treatment.
Materials and methods. The study of changes in the system of phagocytic, T-­cell, specific anti-TB and humoral immunity during the intensive phase of chemotherapy (before treatment, 3.5—4 months, 8 months of chemotherapy) was performed in 28 patients with MRFDTB of lung.
Results and discussion. Chemotherapy of the intensive phase of treatment contributed to the normalization of the indicators of specific anti-TB and humoral immunity links in 35.7 %, T-cell — in 14.2 %. Disturbances in the system of specific protection at the level of baseline values observed in one-third of patients. In 28.6 % of people, together with T-cell immunodeficiency, an increase in the proliferative activity of T-lymphocytes sensitized to tuberculin, anti-inflammatory IgA (25.0 %), IgM (17.9 %), and 16.7 % — an increase in the level of circulating immune complexes, in 28.5 % of patients reducing the oxygen-dependent metabolism of granulocytic leukocytes.
Conclusions. A comparative analysis of the results of immunological studies obtained in patients with MRFDTB during an intensive phase of treatment can be a control of the activity of the process and the evaluation of the effectiveness of treatment.

Keywords: multi drug resistant tuberculosis, changes in immune system, chemotherapy.

List of references:
1.    Lytvynenko NA. Faktory ryzyku shchodo vynyknennya rozshyrenoyi ta prerozshyrenoyi rezystentnosti MBT sered patsiyentiv z mul'tyrezystentnym tuberkul'ozom. Suchasni med. tekhnol. 2014;2:36-42.
2.    Mel'nyk VM, Novozhylova IO, Matusevych VH. Khimiorezys tentnyy tuberkul'oz: stan problemy v Ukrayini. Ukr med chas. 2013;6:26-28.
3.    Mordyk AV, Batishcheva TL, Bryukhanova NS, Puzyreva LV. Vliyaniye immunologicheskikh narusheniy na iskhod vpervyye vyyavlennogo infil'trativnogo tuberkuleza u sotsial'no sokhrannykh patsiyentov. Infektsiya i immunitet. 2014;4(4):353-358.
4.    Petrenko VI, Dolynska MH. Ob’iednuimosia, shchob poklasty krai tuberkulozu!. Tuberkuloz, lehenevi khvoroby, VIL-infektsiia. 2016;1:5-6.
5.    Tuberkuloz v Ukraini: analitychno-statystychnyi dovidnyk. Tuberkuloz, lehenevi khvoroby, MOZ Ukrainy, DU «Ukrainskyi tsentr kontroliu za sotsialno-nebezpechnymy khvorobamy MOZ Ukrainy», Derzhavnyi zaklad «Tsentr medychnoi statystyky MOZ Ukrainy»; uklad. Nizova NM, Pavlova OV, Shcherbinska AM ta in. K.: Blank-Pres; 2015:116
6.    Feshchenko YuI, Melnyk VM, Zaikov SV ta in. Osoblyvosti suchasnoi sytuatsii z tuberkulozu v Ukraini. Ukr pulmonol. zhurn. 2016;1:5-9.
7.    Feshchenko YuI, Melnyk VM, Matusevych VH, Novozhylova IO. Naukovi pidkhody do vyrishennia problem tuberkulozu. Ukr pulmonol zhurn. 2013;2:5-14
8.    Feshchenko YuI, Melnyk VM, Matusevych VH ta in. Orhanizatsiini pidkhody do vyiavlennia i likuvannia khvorykh na tuberkuloz iz rezystentnistiu do antymikobakterialnykh preparativ (metodychnyi posibnyk). Orhanizatsiini pidkhody do vyyavlennia i likuvannia khvorykh. [Elektronnyi resurs]. Rezhym dostupu: http://ifp.pulm/ftp1/metoddoc/posibnyk_2_2013.
9.    Chernushenko YeF, Panasyukova AR. Immunologicheskiye me -khanizmy progressirovaniya tuberkuleza. Ekolohichni problemy u ftyziatrii i pulmonolohii: mater. nauk.-prakt.konf. K;2004:222-225.
10.    Aleman M, Garcia A, Saab M, et al. Mycobacterium tuberculosis - ​inducet activation accelerates apoptosis in peripheral blood neutrophils from patients with active tuberculosis. Am J Respir Cell Mol Biol. 2002;27:583-592.
11.    Anibarro L, et al. Tretment completion in latent tuberculosis infectionat specialist tuberculosis unitsin Spain. Int J Tuber Lung Dis. 2010;14(6):701-707.
12.    Ciobanu S, Lesnic E, Todoriko L, Haidarli I, Tudos. Predictive exogenous conditions for tuberculosis treatment default. Tuberkuloz, lehenevi khvoroby, VIL-infektsiia. 2015;3(22):35-38.
13.    Flynn JL, Chan J. Immune evasion by Mycobacterium tuberculosis: living with the Enemy. Curr Opin Immunol Cell Mol Biol. 2003;15:450-455.
14.    Lunnroth K, et. al. Tuberculosis control andelimination 2010-50: cure, careandsocial development. Lancet. 2010;375:1814-1829.
15.    Wahab F, et al. Risk factors for multi-drug resistant tuberculosis in patients at tertiary care hospital, Peshawar. J Coll  Physicians Surg Pak. 2009;19(3):162-164.
16.    World Health Organization. Global tuberculosis report 2015. Geneva: WNO, 2015.

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Regulatory management for preventive regimen by dental care for persons living with HIV/AIDS (UKR)

V.I. Shatylo1, J.Ya. Halinskyi2, V.M. Kosenko1

1 MHEI «Zhytomyr Nursing Institute» of Zhytomyr Regional Council, Zhytomyr, Ukraine
2 Zhytomyr Regional Center for HIV/AIDS Prevention of Zhytomyr Regional Counci, Zhytomyr, Ukraine

Objective — the research of the progress of preventive and protective measures taken for the purpose of therapeutic dental care for persons living with HIV/AIDS in Zhytomyr Regional Center for HIV/AIDS Prevention.
Materials and methods. The group of patients seeking dental care in Zhytomyr Regional Center for HIV/AIDS Prevention has been researched; medical records of the healthcare institution have been reviewed and analyzed. Bibliosemantic, system analysis, logic generalization and statistical data processing methods were used.
Results and discussion. The study revealed a negative trend of changes in results representing number of HIV/AIDS-infected patients in Zhytomyr Region. The results of work of the dental surgery in Zhytomyr Regional Center for HIV/AIDS Prevention have been analyzed. Much attention has been given to disinfection, pre-sterilization and sterilization of infected instruments, devices and equipment.
Conclusions. Under the conditions of rapidly rising rates of HIV infection among the population of Zhytomyr Region each patient during dental care is considered as HIV-infected.
Compliance with the sanitary and anti¬epidemic regime is one of the most important matters during dental care.
In order to improve dental care of the HIV-infected it is necessary to provide the phased replacement of worn-out dental equipment, especially equipment, devices and instruments used for disinfection, pre-sterilization and sterilization.
It is necessary to use disposable dental instruments during dental invasive surgeries to the maximum possible extent.
The main safety factors for dental practitioners are advanced professional skills and safe contact with biological material that can contain HIV. Training and further professional development of dentists and dental nurses is actual and very significant.

Keywords: HIV-infected, dental care, sanitary and anti-epidemic regime.

List of references:
1.    Borysenko AV, Antonenko MIu, Lynovytsk LVa ta in. Stomatolohichni zakhvoriuvannia: terapevtychna stomatolohiia: pidruchnyk. Za red. AV Borysenka. ​K. VSV «Medytsyna», 2017:664.
2.    Borovskyi E.V., Mashkylleison A.I. Zabolevanyia slyzystoi obolochky polosty rta y hub. ​M.; MEDpress, 2001:320.
3.    Danylevskyi NF, Borysenko AV, Antonenko MIu y dr. Terapevtycheskaia stomatolohyia. Zabolevanyia parodonta. ​K. Medytsyna, 2013;4:632.
4.    Nakaz N 148 vid 17.03.2015 «Pro zatverdzhennia Poriadku pidtverdzhennia zviazku zarazhennia VIL-infektsiieiu z vykonanniam pratsivnykom svoikh profesiinykh oboviazkiv». [Elektronnyi resurs]. ​Rezhym dostupu: http://search.ligazakon.ua/l_doc2.nsf/link1/RE 26822.html. (data zvernennia 21.10.2016).
5.    Nakaz N 236 vid 4.04.2012 «Pro orhanizatsiiu kontroliu ta profilaktyky pisliaoperatsiinykh hniino-zapalnykh infektsii, sprychynenykh mikroorhanizmamy, rezystentnymy do dii antymikrobnykh preparativ».  [Elektronnyi resurs]. Rezhym dostupu: http://search.ligazakon.ua/l_doc2.nsf/link1/RE 21224.html. (data zvernennia 27.09.2016).
6.    Nakaz N 325 vid 8.06.2015 «Pro zatverdzhennia Derzhavnykh sanitarno-protyepidemichnykh pravyl i norm shchodo povodzhennia z medychnymy vidkhodamy». [Elektronnyi resurs]. ​Rezhym dostupu: http://search.ligazakon.ua/l_doc2.nsf/link1/RE 27404.html. (data zvernennia5.10.2016).
7.    Nakaz N 410 vid 22.05.2013 «Pro zatverdzhennia form oblikovoi dokumentatsii ta zvitnosti stosovno reiestratsii vypadkiv kontaktu osib z kroviu chy biolohichnymy materialamy liudyny, zabrudnenymy nymy instrumentariiem, obladnanniam chy predmetamy, provedennia postkontaktnoi profilaktyky VIL-infektsii ta instruktsii shchodo yikh zapovnennia». [Elektronnyi resurs]. Rezhym dostupu: http://search.ligazakon.ua/l_doc2.nsf/link1/RE 23434.html. — (data zvernennia 10.10.2016).
8.    Nakaz N 552 vid 11.08.2014 «Pro zatverdzhennia Derzhavnykh sanitarnykh norm ta pravyl «Dezinfektsiia, peredsterylizatsiine ochyshchennia ta sterylizatsiia medychnykh vyrobiv v zakladakh okhorony zdorovia». [Elektronnyi resurs]. ​Rezhym dostupu: http://www.infectioncontrol.org.ua/wp content/docs/Nakaz.552_11.08.2014_sanpin_ster.pdf. (data zvernennia 18.09.2016).
9.    Nakaz N 955 vid 5.11.2013 «Poriadok provedennia ekstreno postkontaktnoii profilaktyky VIL-infektsii u pratsivnykiv pry vykonanni profesiinykh oboviazkiv». [Elektronnyi resurs].-Rezhym dostupu: http://search.ligazakon.ua/l_doc2.nsf/link1/RE 24512.html. (data zvernennia 14.09.2016).
10.    Nikolishyn AK, Zhdan VM, Borysenko AV ta in. Terapevtychna stomatolohiia. Zakhvoriuvannia slyzovoi obolonky porozhnyny rota. ​Vinnytsia, Nova Knyha, 2012:680.

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Gender characteristics of multidrug-resistant pulmonary tuberculosis (UKR)

I.A. Ovcharenko, O.S. Shevchenko

Kharkiv National Medical University, Kharkiv, Ukraine

Objective — to investigate of gender characteristics of the course of the first diagnosed multidrug-resistant pulmonary tuberculosis.
Materials and methods. The medical history of 141 patients with newly diagnosed pulmonary tuberculosis was analyzed. There were 99 men, 42 women.
Results and discussion. In both groups were mainly people of working age, but women were younger than men. Men were more likely to have HIV/TB in combination with other pathologies, and women were more likely to be isolated by HIV/TB. In men, diabetes and hepatitis C and/or B were more often diagnosed, and in women, the pathology of the cardiovascular and reproductive systems. Men were three times more likely than women to have at least one bad habit. They also often complained of coughing, and women — for a cough in combination with authentication. In men, more often than women, there were common processes that occupied one or both of the lungs, whereas, in women, processes predominated within one lobe of the lung. The disintegration of lung tissue and bacterial excretion were observed in men more often. In addition, the massiveness of bacterial excretion was also greater in men. The best results of treatment were demonstrated by women.
Conclusions. Differences between groups established during the study indicate the need for further research on gender-related factors that may affect the tuberculosis process.

Keywords: gender, multidrug-resistant tuberculosis, treatment effectiveness, destruction, bacterial excretion.

List of references:
1.    WHO report on the global fight against TB by 2016. http://www.who.int/tb/publications/global_report/gtbr2016_executive_summary_ru.pdf? ua=1
2.    Koretskaya NM, Narkevich , Narkevich N. Gender features of newly diagnosed infiltrative pulmonary tuberculosis. Pul’monologiya;1:77-80.
3.    Order of Ukrainian Ministry of Health N 600 of 22.10.2008 “On approval of the standard of care for patients with chemoresistant tuberculosis”. Ukrainian Ministry of Health. Kyiv, 2008:105.
4.    Order of Ukrainian Ministry of Health N 1091 of 21.12.2012 «On approval and introduction of medical and technological documents for standardization of care in tuberculosis». Ukrainian Ministry of Health. Kyiv, 2012:172.
5.    Order of Ukrainian Ministry of Health 620 of 14.09.2008 «On approval of the standard of care for patients with himiorezystentnyy tuberculosis». Ukrainian Ministry of Health. Kyiv, 2014;105.
6.    Petrenko VI To the World TB day: « Reach the 3 million: find, treat, cure TB»// Tuberculosis, Lung diseases, HIV-infectin. Kyiv;2014:5-7.
7.    Tuberculosis and Gender aspects. http://www.euro.who.int/__data/assets/pdf_file/0005/69017/fs05R_TBgender.pdf.
8.    Feshchenko YuI, Melnyk VM, Matusevych VH, Novozhylova IO, YukhymetsVO, LynnykMI. Basic principles of medical care for patients with tuberculosis (guidance on organizational and technical work). Kyiv;2012:156.
9.    What is a gender-sensitive approach? The German Initiative BACKUP / German Society for International Cooperation (GIZ). GmbH. Bonn. Germany; 2013:7.
10.    World Health Organization. WHO Treatment guidelines for drug-resistant tuberculosis — ​2016 update / [Text]. ​WHO: Geneva;2016:60.

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14. Reviews


Immunopathogenesis of resistant tuberculosis from the positions of the today (UKR)

L. D. Todoriko

HSEI Ukraine «Bukovinian State Medical University», Chernivtsi, Ukraine

The review of the literature presents current views on the evolution of immunopathogenesis of drug-resistant tuberculosis (LUTB), analyzes the results of studies on the fundamental issues of the formation and regulation of the immune response and, in particular, T-cell resistance in resistant tuberculosis infection. It has been confirmed that the main factor of the antituberculous immune response is the clearly determined interaction of the key links in the reactions of specific and nonspecific immunity and their cytokine regulation. It is shown that the evolution of immunopathogenesis of drug-resistant tuberculosis is based on the hypothesis of double recognition of the infectious antigen with the determining role of T-cell immunity responses (T cells are responsible for induction and suppression of protective immunity, delayed type hypersensitivity, cytolysis and AT production) and anti-inflammatory cytokines, cell adhesion molecules and transforming growth factors that depend on the activity of the major histocompatibility complex, determinism Genetic component.

Keywords: immunopathogenesis, cellular immunity, tuberculosis, chemoresistance, cytokines, apoptosis.

List of references:
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2.    Antonenko PB, Kresyuk VY, Bazhora YuI et al. The genotyping of micobacterium tuberculosis at six loci. Ukr Pulmon J. 2010;3:15-18.
3.    Varchenko Yu A. Influence of interferon on the dynamics of closure of decomposition cavities in patients with infiltrative first-time diagnosed pulmonary tuberculosis. Tuberculosis, pulmonary diseases, HIV infection. 2013;1:26-29.
4.    Bazhora YuM et al. Molekulyarno-geneticheskiye mekhanizmy tuberkuleznoy infektsi. Odessa: Odesskiy gosudarstvennyy meduniversitet; 2005:259.
5.    Dzyublyk YO. Antibiotic resistance of respiratory pathogens: a review of the results of the SOAR study and the prospects for microbiological monito­ring in Ukraine. Ukr Pulmon J. 2010;3:33-35.
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8.    Liadova IV, Gergert VA. Reaction of T-cell immunity in tuberculosis: experimental and clinical studies. Tub Lung Dis. 2009;11:9-18.
9.    Melnik VM, Prikhodko AM, Arefeva LV. History of the emergence and development of chemo-resistant tuberculosis. Ukr Pulmon J. 2012;2:59-61.
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11.    Todoriko LD, Petrenko VI, Grishin MM. Resistance of Mycobacterium tuberculosis — ​myths and realities. Tub Pulmonary Dis HIV infection. 2014;1:60-67.
12.    Urazova OI, Novitsky VV, Strelis AK et al. Apoptosis of blood lymphocytes in patients with pulmonary tuberculosis. Proceedings of the All-Russian Scientific and Practical Conference with International Participation: Questions of the pathogenesis of typical pathological processes. Novosibirsk, 2009:392-396.
13.    Feshchenko YuI, Gumenyuk MI, Denisov OS. Antibiotic resistance of microorganisms: the state of the problem and the ways of its solution. Ukr Chemotherapeutic J. 2011;1-2:4-10.
14.    Todoriko LD. Features of evolution of immunopathogenesis of drug-resistant tuberculosis. Clin Immunol Allergol Infectol. 2014;3:16-20.
15.    Feshchenko YuI, Melnik VM, Turchinov LV. A look at the problem of fighting tuberculosis in Ukraine. Ukr Pulmon J. 2016;3:5-10.
16.    Chernousova LN, Andreevskaya SN, Smirnova TG et al. Properties of strains of M. tuberculosis cluster W. Probl Tub Lung Dis. 2008;10:45-49.
17 Filinyuk OV. Faktory riska, assotsiirovannyye s mnozhestvenno lekarstvenno-ustoychivym tuberkulezom / Avtoreferat dissertatsii dok. med. nauk (14.01.16. ftiziatriya). Novosibirsk, 2011:36.
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20.    Becq J, Gutierrez M, Rosas-Magallanes V et al. Contribution of horizontally acquired genomic islands to the evolution of the tubercle bacilli. J Mol Biol Evol. 2007;24:1861-1871.
21.    Caws M, Thwaites G, Dunstan S et al. The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis. PLoS Pathog. 2008;4:450-457.
22.    Crane M, Iser D, Lewin SR. Human immunodeficiency virus infection and the liver. World J Hepatol. 2012;4(3):91-98.
23.    Ejele OA. A comparative study of CD 4 positive lymphocyte count and the ESR of HIV sero-positivc patients at University of Port Harcourt Teaching Hospital. Pmjumu Pioneer Med. J Umuahia. 2012;2(1):13-21.
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29.    Miller TI. Metabolic abnormalities and viral replication are associated with biomarkers of vascular dysfunction in HIV-infected children. HIV Med. 2012;5:264-275.
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31.    Moreland NJ, Charlier C, Dingley AJ et al. Making sense of a missense nutation: characterization of MutT2, a Nudix hydrolase from Mycobacterium tuberculosis, and the G58R mutant encoded in W-Beijing strains of M. Tuberculosis. Biochemistry. 2009;8:699-708.
32.    Moreland NJ, Charlier C, Dingley AJ et al. Phylogeny of Mycobacterium tuberculosis Beijing Strains Constructed from Polymorphisms in Genes Involved in DNA Replication. Recombination and Repair. PLoS One. 2011;6(1): [ ]. : http:. www.plosone.org/article/info%3Adoi%2F10.1371 %2 Fjournal. pone.0016020.
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15. Epidemic situation


Tuberculosis morbidity of medical workers (UKR)

I. D. Duzhiy, L.A. Bondarenko, G. P. Oleshchenko, V. O. Oleshchenko

Sumy State University, Sumy, Ukraine

Objective — to investigate in the dynamics incidence of tuberculosis of medical workers of the Sumy region in 2011—2015 years.
Materials and methods. We analyzed the incidence of TB of health workers of general medical network and antituberculous institutions of the region in 2011—2015 years.
Results and discussion. During 2011—2015 in Sumy region 43 health care worker contracted tuberculosis. Of these, 7 (16.3 %) workers of TB facilities, 36 (83.7 %) — medical workers of a general network. The incidence of health workers of general medical network decreased by 2.7 times, and the incidence of health workers of antituberculous institutions has increased by 10.1 times. Among employees of general medical network and TB facilities more often were ill with TB middle medical workers (44.4 and 42.9 % respectively) and paramedical workers (27.8 and 28.6 % respectively). More often there were infiltrative forms of pulmonary tuberculosis — 41.7 % among medical workers of general network and 57.1 % among workers of TB facilities. The second of frequency was focal tuberculosis — 30.6 and 28.6 % respectively.
Conclusions. The morbidity of middle medical workers and paramedical workers in PTC is higher than that of general medical institutions, which can be explained by their close contact with bacillary patients.

Keywords: tuberculosis, health workers, morbidity.

List of references:
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3.    Litvinuk OP, Zaykov SV, Zakharchenko OO, Klimenko TI. The incidence of tuberculosis health workers of Vinnytsya region (Ukr). Tuberkuloz, legenevi xvoroby, VIL-infekciya (Ukr). 2015;2:101-105.
4.    Pustovyy YuG, Dolynska MG, Voloshyna VV, Gritsova NA. Risk factors for tuberculosis: prevalence among patients with new cases (Ukr). Ukrayinskyj pulmonologichnyj zhurnal (Ukr). 2009;1:22-24.
5.    Skrahina AM, Hurevich HL, Kalechits AM, Klimuk DA, Dziusmikeyeva MI, Bobrukevich AL, i dr. The prevention of the incidence of tuberculosis among medical profession (Rus). Klinicheskaya infektologiya i parazitologiya (Blr). 2015;3:28-39.
6.    Tuberkuloz v Ukrayini: Analitychno-statystychnyj dovidnyk (Ukr). Kyiv; 2016:235.
7.    Tuberkuloz v Ukrayini: Analitychno-statystychnyj dovidnyk za 2001-2012 roky (Ukr). Kyiv; 2013:122.
8.    Feshhenko YuI, Melnyk VM, Opanasenko MS. Reorganizaciya, restrukturyzaciya ta reformuvannya protytuberkul`oznoyi sluzhby v Ukrayini (Ukr). Kyiv: Vydavnycztvo Lira-K; 2015:172.
9.    Feshhenko Yu I. Tuberkuloz v Ukrayini yak medyko-socialna i politychna problema (Ukr). Zhurnal Akademiyi medychnyh nauk Ukrayiny (Ukr);11(1):17.
10.    Cole E, Cook C. Characterization of infectious aerosols in health care facilities: an aid to effective engineering controls and preventive strategies. Am J Infect Control. 1998;26(4):453-464.
11.    World Health Organization (WHO). Global tuberculosis report 2015 (WHO/HTM/TB/2015.22). Geneva: WHO; 2015. Available from: http://www.who.int/tb/publications/global_report/en/.

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Original language: Ukrainian