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Issue. Articles

2(21) // 2015



1. Editorial


Modeling epidemics of multidrug-resistant M. tuberculosis of heterogeneous fitness (UKR)

T. Cohen, M. Murray

Mathematical models have recently been used to predict the future burden of multidrug-resistant tuberculosis (MDRTB). These models suggest the threat of multidrug resistance to TB control will depend on the relative «fitness» of MDR strains and imply that if the average fitness of MDR strains is considerably less than that of drug-sensitive strains, the emergence of resistance will not jeopardize the success of tuberculosis control efforts.
Multidrug resistance in M. tuberculosis is conferred by the sequential acquisition of a number of different single-locus mutations that have been shown to have heterogeneous phenotypic effects.
Here we model the impact of initial fitness estimates on the emergence of MDRTB assuming that the relative fitness of MDR strains is heterogeneous. We find that even when the average relative fitness of MDR strains is low and a well-functioning control program is in place, a small subpopulation of a relatively fit MDR strain may eventually outcompete both the drug-sensitive strains and the less fit MDR strains.
These results imply that current epidemiological measures and short-term trends in the burden of MDRTB do not provide evidence that MDRTB strains can be contained in the absence of specific efforts to limit transmission from those with MDR disease.

Keywords: Tuberculosis, fitness, MDR, strain.

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Original language: Ukrainian

2. Editorial


The problem of tuberculosis in Ukraine (UKR)

V.I. Petrenko, R.G. Proziuk

Was analyzed tuberculosis epidemical situation in Ukraine. Was found that there is a decrease in tuberculosis morbidity and mortality. Lowest indexes in Ukraine were registered in 1990 (32 cases and 8,1 cases per 100 thousand of population respectively). The morbidity of tuberculosis in Ukraine from 1990 till 2005 increased in 2,7 times (from 8,1 cases per 100 thousand of the population in 1990 to 25,3 in 2005). From 2006 there was reducing in morbidity and mortality. In 2013 the tuberculosis incidence was 67,9 per 100 thousand of the population, that is 19,3 % less than in 2005. The mortality rate was decreased in 44,1% (from 25,3 cases per 100 thousand of the population in 2005 to 14,1 in 2013).

Keywords: tuberculosis, morbidity, mortality.

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Original language: Ukrainian

3. Editorial


Actual questions of implementation substitution maintenance therapy in Ukraine (UKR)

M.V. Zelenska, .G. Eshenko, I.L. Demchenko

This article provides information on the most pressing issues for substitution therapy in Ukraine.

Keywords: risk groups, consumers opiate injection drug substitution maintenance therapy, pregnant, monitoring and evaluation of measures, laws and regulations, coordinating councils, the sites of substitution therapy.

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Original language: Ukrainian

4. Original research


Toxic effect of antituberculosis drugs on vital organs and research of pyridoxine protective actions during antituberculosis drugs intoxication (UKR)

L.V. Gaeva

Objective — to conduct morphological evaluation of the internal organs damage (lungs, liver, kidney, spleen) after experimental treatment of tuberculosis in guinea pigs by different doses of isoniazid and pyridoxine hydrochloride (vitamin B6) in order to identify the optimal combination of drugs that leads to less residual internal organs lesion.
Materials and methods. To reproduce experimental tuberculosis was used various kinds of animals: guinea pigs, rabbits, white mice, rats, dogs, monkeys, etc. For diagnostic purposes was used guinea pigs because they are highly sensitive to the human Mycobacterium tuberculosis and bovise type. Guinea pigs are the most convenient object for experimental study of the immunity and allergy issues during tuberculosis. By the type of manifestations dog’s reactions on TB infection similar to human response, so they are also important targets for research. Rats and mice are used as animal more resistant to tuberculosis. For the chemotherapy the most convenient animals are white mice, for which there is the possibility of using drugs in small amounts and for a short time experience.
Results and discussion. Based on the analysis, is traced such tendencies: firstly, an increase in dose of isoniazid increases the degree of damage of the liver tissue; secondly, the combined effect of isoniazid and vitamin B6 helps to reduce the overall index of liver damage; thirdly, the lowest level liver damage occurs in the case of chemotherapy only with isoniazid at a dose of 10 mg/kg and isoniazid 10 mg/kg  incombination of vitamin B6 50 mg/kg; Lastly, in the event of discontinuance of isoniazid and vitamin B6 at doses (10 and 5) mg/kg (32 and 50) mg/kg (100 and 5) mg/kg (100 and 50) mg/kg, respectively, had same level of liver tissue damage (9.8 v.o.), and thus the state of the liver tissue was not dependent on changes in the quantities of doses of drugs.
Conclusions.The examples are the results of histological studies signs of tubercular inflammation and non-specific changes in the organs of guinea pigs with experimental model of tuberculosis treatment by various ratios of doses of isoniazid in combination with pyridoxine hydrochloride. In the experiment model «INH — pyridoxine hydrochloride» 32 and 5 mg/kg, respectively, leads to reducing of specific and non-specific manifestations of inflammation in the lung, liver, kidney and spleen.

Keywords: tuberculosis, indices of infestation, isoniazid, vitamin B6, the optimal mathematical model.

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Original language: Ukrainian

5. Original research


Effects of Asp299Gly TLR-4 gene polymorphism on the condition of antiendotoxin immunity in patients with frequent and rare exacerbations of asthma (RUS)

Yu.A. Bisyuk, A.I. Kurchenko

Objective — to study the gene polymorphism Asp299Gly of TLR-4 and condition of anti-endotoxin immunity in patients with frequent and rare exacerbations of asthma in Crimea population.
Materials and methods. Asp299Gly polymorphism and condition of anti-endotoxin immunity were studied in 219 patients with rare and 112 with frequent exacerbations of asthma. The control group consisted of 285 healthy individuals.
Results and discussion. In the control group, the distribution of genotype frequency (AA — 242 (85 %), AG — 40 (14 %), GG — 3 (1 %)) did not significantly differ from asthma with frequent (AA — 87 (78 %), AG — 24 (21 %), GG — 1 (1 %), χ2 = 3.254, p = 0.197) and rare exacerbations (AA — 174 (80 %), AG — 42 (19 %), GG — 3 (1 %) χ2 = 2.565, p = 0,277). Analysis risk allele G revealed that the frequency of AG + GG genotype patients with frequent exacerbations (22 %) tends to increase (odds ratio = 1.617, p = 0.085) compared to controls (15 %). In patients with frequent exacerbations of asthma with AG + GG genotype compare to the AA levels of anti-ET-IgM and serum sCD14 did not significantly (p > 0.05) differ from controls.
Conclusions. Phenotypic differences of asthma in Crimea population with rare and frequent exacerba­tions may be associated with a tendency to predominance of AG + GG genotype TLR-4 polymorphism.

Keywords: bronchial asthma, endotoxin, Asp299Gly polymorphism of TLR-4.

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Original language: Russian

6. original research


Risk factors of hepatotoxic side reactions in patients with new cases co-infection tuberculosis/HIV in combination with viral hepatitis B and/or C (UKR)

S.O. Cherenko, L.Ya. Maniv

Objective — to determine the risk factors of hepatotoxicity during the intensive phase of TB chemothe­rapy in patients with new cases co-infection tuberculosis/HIV in combination with viral hepatitis B and/or C.
Materials and methods.The association between the functional state of the liver at the beginning of the treatment and the development of hepatotoxic reactions during the intensive phase of TB chemotherapy was studied in a prospective study that included 58 patients with with new cases of co-infection tubercu­losis/HIV in combination with viral hepatitis B and/or C. The biochemical blood tests defined the level alanine aminotransferase and aspartate aminotransferase (ALT/AST), bilirubin, γ-glutamiltranpeptidase (GPT), alkaline phosphatase (ALP), albumin was mesured out before and during the intensive phase of TB treatment (for 1 time per month and according to indications of symptoms hepatotoxic reactions).
Results and discussion. During the intensive phase of chemotherapy hepatotoxic reactions occurred in 27 (46.6 %) patients, including severe that led to the interruption of anti-TB treatment — in 16 (27.6 %) cases. High risk of hepatotoxic reactions occurs in patients with initially elevated ALT/AST more than 2 times or any simultaneous increase of ALT/AST and bilirubin, decreased blood levels of albumin, or ultrasound signs of liver damage. There was no significant association between the occurrences of hepatotoxic adverse reactions and increase the output level of GPT and ALP, beginning of ART, degree of immune deficiency.
Conclusions. Risk factors of hepatotoxicity of antituberculosis drugs in patients with new cases of co-infection tuberculosis/HIV in combination with viral hepatitis B and C are the baseline increasing of ALT/AST level more than 2 times the reference value, or any increasing of simultaneous ALT/AST and bilirubin; reduction of blood albumin, ultrasound signs of liver damage.

Keywords: new cases co-infection tuberculosis/HIV, viral hepatitis B and C, hepatotoxic side effects of anti-TB drugs.

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Original language: Ukrainian

7. Original research


Contents essential amino acids blood in patients with respiratory tuberculosis during the treatment (UKR)

I.O. Galan

Objective — to study the dynamics of the content of essential amino acids in the blood of patients with respiratory tuberculosis during treatment.
Materials and methods. Study groups includes 50 patients with first detected pulmonary tuberculosis (study group) and 30 healthy individuals (control group). Was determined the content of essential amino acids in blood before treatment in the first days of hospitalization and after 2 months of treatment.
Results and discussion. All patients of the main group with severe symptoms of intoxication and common specific process in the lungs before treatment was marked significant change in the amino acid spectrum and in the total number of amino acids which manifested in reducing of the content of total and individual amino acids amounts. During the treatment there was a statistically significant increase of some amino acids, namely lysine, arginine, histidine, isoleucine compared to a levels of concentration before treatment. But this concentration of lysine, arginine, isoleucine still not reached the normal levels. Due to the increase in concentration of certain amino acids total amount was equal to the indexes of amino acids among healthy individuals, despite the fact that among patients was imbalance of amino acid spectrum.
Conclusions. Application antimycobacterial therapy for two months has promoted content of some essential amino acids levels. But the full normalization of blood content of essential amino acids did not happen. Prospects of future research is to study the state of protein metabolism in patients with respiratory tuberculosis, the influence of its impact on the clinical course of tuberculosis and the duration of treatment and the development of new methods for correcting failures in order to improve the treatment of tuberculosis.

Keywords: essential amino acids blood, tuberculosis.

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Original language: Ukrainian

8. Original research


Effectiveness of treatment in patients with new cases of multidrug resistant tuberculosis that diagnosed molecular-genotypic or phenotypic methods (UKR)

S.. Cherenko, H.. Varytska

Objective — to examine and compare the dynamics of sputum conversion in patients with multidrug resistant tuberculosis (MDR TB), which is diagnosed molecular-genetic or phenotypic method to deter­mine the impact of diagnosis delay on the effectiveness of treatment.
Materials and methods. In a prospective study that included 68 patients with new cases of MDR TB, studied the frequency and dynamics of sputum conversion during the intensive phase of 8-month duration. Patients was divided in to 2 groups: the main (34 people), in which MDR TB diagnosed by molecular genetic method (GeneXpert) and a control group in which MDR TB diagnosed by phenotypic (in liquid or solid medium). Patients treated with individualized chemotherapy regimens, including 6 effective drugs according to drug sensitivity test.
Results and discussion. Diagnosis of MDR TB using phenotypic methods was delayed on averages (54.1 ± 3.7) days from the date of diagnosis of tuberculosis cases. At the end of the intensive phase of sputum conversion were in 33 (97.1 %) patients of the main group and in 26 (76.5 %) patients in the control group, which is 20.6 % higher and significant difference (p < 0.05). In the period up to 1 month sputum conversion was 2.8 times more frequently in patients of the main group, up to 2 months — in 2.5 times. After 2 months sputum conversion in the main group was 14.6 % of patients in the control group was 20.6 %.
Conclusions. Delay in diagnosis of new cases of multidrug-resistant tuberculosis reduce the effectiveness of treatment by 20.6 %.

Keywords: multidrug-resistant tuberculosis, bacteriological and molecular genetic diagnosis of tuberculosis.

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Original language: Ukrainian

9. Original research


Cytological structure of blood in patients with chemical resistant tuberculosis and its value for the evaluate of the intensity of endogenous intoxication (UKR)

I.L. Platonov, E.I. Pysarenko, K.D. Mazhak, .. Tkach, G.D. Shtybel, .V. Pavlenko, O.V. Omelyan, T.V. Turchyna, N.I. Kiromasova, L.G. Bozhko

Objective — to explore peculiarities of cytological structure of blood in patients with the first diagnosed (FDTB) and relapse (RTB) of drug resistant destructive pulmonary tuberculosis. To perform the calcula­tion of integrated leukocyte indexes and describe the intensity of endogenous intoxication (EI) in these patients.
Materials and methods. A determination of bloodhemogram and mathematical calculation of integ­ra­tedleukocyte indices in 84 patients with drug resistant destructive pulmonary tuberculosis was made. There were — 33 patients with FDTB and 51 — with RTB.
Results and discussion. The moderately expressed neutrophilic leukocytosis, with a shift formula to the left to stabnuclear neutrophils were in 77.2 % of patients with FDTB and in the 55.6 % of people with RTB.
The presence of lymphopenia was noted in 64.4 and 58.8 %. Lymphocytosis and aneozynofiliy was respectively in 4.0 and 5.9 % and 50,0 and 47.1 % of the patients.
Eosinophilia detected only in 12.5 % of patients with lung FDTB. We found that in the predominant majority of patients with FDTB indicators of erythrocytes (Er) in the 76.0 % and the hemoglobin (Hb) in the 44.0 % did not reach beyond confidence level of interval standards. In patients with RTB proportion of normal values of Er and Hb was respectively — 84.3 and 52.9 %. Presence of EI of mild to moderate severity condition were in the 96.0 % of patients with FDTB and in the 83.4 % of RTB, severe degree of EI in the stage of decompensation was respectively in 4.0 and 5.6 % of patients.
Conclusions. FDTB group according to hemogram and leukocyte indexes of endogenous intoxication showed heavier progress of specific process.

Keywords: hemogram of blood, indices of endogenous intoxication, drug resistant tuberculosis (FDTB, RTB).

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Original language: Ukrainian

10. Original research


Biochemical features of livers disfunction in treatmet of patients with destructive pulmonary tuberculosis (UKR)

V.I. Zozuliak, N.V. Zozuliak, I.I. Pylypenko

Objective — to explore peculiarities of biochemical analysis of liver among patients with destructive pulmonary tuberculosis.
Materials and methods. The study included 136 persons with destructive pulmonary tuberculosis using epidemiological, general clinical, laboratiry and biochemical methods. We use the Veltman’s testing, thymol test, activity of aspartataminotransferaze, alataminotransferaze, bilirubin, urea, creatinine. We examined the level of arginaze, cholinesteraze, ornithinkarbomaniltreansferaze,  sorbitoldehydrogenaze.
Results and discussion. In studied group of patients we finded the toxic damage of liver wich manifasted by typical clinical symptoms and abnormality of liver biochemical indexes. The early signs of toxic hepatitis are changes of no less than two biochemical indexes which indicate function of liver.
Conclusions. Infection tuberculosis process and longlasted anti-tuberculosis therapy lead to toxic hepatitis which complicates pathological process and reduces efectivety of treatment.

Keywords: tuberculosis, destruction, mycobacteriaexcretion, the biochemical indexes of livers function.

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Original language: Ukrainian

11. Original research


Rehabilitation of patients with chronic obstructive pulmonary disease and concomitant spine pathology (UKR)

.P. Gumeniuk

Objective — to assess the impact of traumatic elements arising from the pathology of the spine, the course of chronic obstructive pulmonary disease and to investigate the potential rehabilitation of patients with COPD and concomitant diseases of the spine.
Materials and methods. Was studied 137 patients with chronic obstructive pulmonary disease with concomitant pathology of the spine. Among patients 67 people were male and 70 — women. The average age of patients was (50.6 ± 10.3) years. The main group consisted of 73 people, average age was (49.3 ± 3.7) years. The control group was 64 people, average age of this group was (49.7 ± 4.2) years. Was made a functional capacity survey of the respiratory system using spirography, evaluation of lung and bronchial microcirculation was performed by measuring the temperature of exhaled air and lateral rheogram of lungs determine the level of blood oxygen saturation. Conducted X-ray and MRI of the spine, somatography.
Results and discussion. Was established that complex therapy aimed on treatment of secondary traumatic elements with concomitant spine pathology in patients with COPD, improves the functional state of the bronchi, as evidenced by the dynamics spirographic parameters: vital capacity increased from (64.9 ± 3.4) to (70.8 ± 3.1) % (p < 0.05); FEV1 from (62.8 ± 4.9) to (70.3 ± 4.2) % (p < 0.05), air temperatu­re, which exhaled also increases, genral to decreases from (2.0 ± 0.3) to at (1.61 ± 0.2) (p < 0.001), oxygen saturation increases from (95.5 ± 0.3) to (97.3 ± 0.3) % (p < 0.001).
Conclusions. Using the methods of prevention, treatment and rehabilitation of comorbid disease, which includes chronic obstructive pulmonary disease and comorbidity spine leads to overcoming of the consequences pharmacoresistance, complications and improves progress of the main disease and comor­bidities. This issue requires further study and incorporation into a comprehensive rehabilitation therapy of internal diseases.

Keywords: chronic obstructive pulmonary disease, traumatic elements, rehabilitation.

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Original language: Ukrainian

12. Original research


Risk factors of severe infiltrative pulmonary tuberculosis development in contemporary epidemiologic conditions (RUS)

L.D. Todoriko, .V. Lsnic, S. Ghinda, O. Caraiani

Objective — to explore the role of risk factors of severe infiltrative pulmonary tuberculosis.
Materials and methods. We conducted analysis of social, epidemiological and medical risk factors in patients with pulmonary tuberculosis with different severity degrees of the main process.
Results and discussion. We calculated relative risk (RR) for each factor that leads to development of severe pulmonary tuberculosis. We revealed that important risk factors are: unemployment — RR = 1.424 (95 % CI 1.078—1.882), incomplete education — RR = 1.565 (95 % CI 1.239—1.979), lonely man civil status — RR = 1,752 (95 % CI 1,396—2,201), low standard of living — RR = 1.531 (95 % CI 1.187—1.975) migration — RR = 1.603 (95 % CI 1.28—2.007), tuberculosis contact — RR = 1.341 (95 % CI 1.055—1.704), chronic consumption of alcohol — RR = 1,962 (95 % CI 1.574—2.446) and related diseases — RR = 1.851 (95 % CI 1.38—2.481). Neutral factors are male — RR = 1.044 (95 % CI 0.726—1.264) and living in rural areas — RR = 1.0778 (95 % CI 0.841—1.382). Evaluation of «case management» found that detection of «new case» through a passive way, according to the strategy of DOTS, was significant risk factor — RR = 1.664 (95 % CI 0.991—2.729). In turn of late detection and diagnosis of pulmonary tuberculosis in new cases promoted the development of severe forms is confirmed by a high relative risk — RR = 1.491 (95 % CI 1.019—2.179).
Conclusions. Comparative analysis of risk factors role in the development of infiltrative pulmonary tuberculosis with different degrees of severity showed that unemployment, lonely man civil status, poor living conditions, migration, chronic alcohol consumption, tuberculosis contact and comorbidities are significant for the development of severe forms of disease.

Keywords: tuberculosis, risk factors.

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Original language: Russian

13. Original research


The incidence of tuberculosis health workers of Vinnytsya region (UKR)

O.P. Litvinuk, S.V. Zaykov, .. Zakharchenko, T.I. Klimenko

Objective — to analyze the incidence of tuberculosis (TB) health workers of antituberculous establishments and General health network of Vinnytsya region in 2007—2012.
Materials and methods. The analysis of incidence rates of tuberculosis (TB) health workers Vinnytsya region 2007—2012 according to official indicators of TB services in the region over a six-year period.
Results and discussion. From 2007 to 2012 years, the incidence of TB health workers of General health network and TB institutions increased from 50.5 to 51.5 to 100 thousand medical workers on the background of reduction of morbidity among the population of Vinnytsya region (60.0 to 55.3 per 100 thousand population). Therefore, the problem of incidence on TB medical personnel remains a very important issue and requires further study. The poor quality of treatment and follow up shows and a large number of relapses 14.3 % of all TB cases among health care workers. Among infected health care workers 21.8 % worked in tuberculosis dispensary. The gender structure are females in 75.0 % of TB cases, which is associated with a high incidence of nursing staff. The main part of TB cases of health care workers occurs among the inhabitants of the cities. In the age structure of TB most cases was among the young and middle age people. The highest risks of TB disease are health professionals with experience of up to 3 years.
Conclusions. On the background reducing of the incidence of TB among the population of Ukraine in Vinnytsya region in the period 2007—2012 remained increase incidence rate among health care workers of antitubercular establishments and General health network. The highest incidence rate was among nursing staff. During the 2007—2012 period a fifth part of cases among TB medical workers in worked in TB facilities. Structure of the patients was mainly females who live in the cities and whose experience was less than three years.

Keywords: tuberculosis, health workers, morbidity, Vinnitsya region, Ukraine.

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Original language: Ukrainian

14. Clinical case


The pleural effusion syndrome a manifestation of tuberculous spondylitis (UKR)

I.D. Duzhiy, G.P. Piddubna, L.A. Bondarenko, I.Ya. Gresko, A.V. Yurchenko

Objective — to introduce pulmonologist and phtisiology experts clinical features of tuberculosis pleurisy caused by primarily resistant forms of Mycobacterium tuberculosis, which can be complicated by tuberculosis spondylitis, and diagnosis may be delayed for the last few months, followed by a failure of treatment.
Materials and methods. Under the authors supervision in 2013, there were 97 patients with tuberculous pleuritis, and 9 (9.27 %) patients with tuberculous spondylitis.
Results and discussion. Among patients with tuberculous spondylitis 6 persons for 4—6 months before had tuberculosis pleuritis. Specific treatment was carried out only in two patients, but in both cases was unsatisfactory. One patient from this group had tuberculous spondylitis after treatment. After 3 months of treatment appeared sputum, where multiresistant MBT were found and diagnosed infiltrative tuberculosis of right lung.
Conclusions. Patient’s pleuritis caused by primary resistant MBT, and was treated for 3 months by first-line drugs, which led to a prolongation of the process: pleuritis — spondylitis — pulmonary tuberculosis.

Keywords: tuberculous pleurisy, tuberculous spondylitis, diagnostics.

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Original language: Ukrainian

15. point of view


Osteoarticular tuberculosis as part of the tuberculosis problem (UKR)

G.G. Golka, O.G. Fadeev, D.A. Istomin, V.V. Vesnin

Objective — to improve the efficiency of diagnostic osteoarticular tuberculosis.
Was analyzed actual state of the problem in diagnostic and treatment of the patients with osteoarticular tuberculosis in our country. Revealed difficulties and the reasons of untimely diagnostic.
Was found that difficulty in diagnosis of early forms of the osteoarticular tuberculosis is not caused because of the latent nature of the specific process and asymptomatic manifestations but due to incorrect interpretation: of clinical and radiographic signs, laboratory studies information, pathomorphism of the disease
The authors suggest ways to figure out the existing issues.

Keywords: diagnostic of osteoarticular tuberculosis, radiological investigation methods, improvement of diagnostic.

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Original language: Ukrainian