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Issue. Articles

4(15) // 2013

 

 

1. Editorial

 

The role of primary health care in the system of prevention of HIV sexual transmission in Ukraine

N.N. Nizova, K.. Talalayev, I.S. Mironyuk

The article emphasizes the need for active involvement of primary health care potential to treat sexually transmitted diseases, including infections among high-risk populations and people living with HIV/AIDS, to influence the spread of the HIV epidemic in Ukraine.

Keywords: primary health care, STIs, HIV/AIDS, high risk groups, Ukraine.

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2. Editorial

 

Current issues and practical approach to the enhancement of efficiency of the State tuberculosis control program in Ukraine

G.G. Kovaliova

The article presents current data on tuberculosis prevalence in Ukraine, aspects of efficiency of tuberculosis control, including MDR-TB and TB/HIV coinfection, providing of the state financing and how does current diagnostics and treatment match modern standards.

Keywords: tuberculosis incidence, tuberculosis epidemics, Ukraine, latent infection, case detection, multidrug-resistant tuberculosis, TB/HIV coinfection.

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3. Original research

 

Moxifloxacin use in the treatment of new cases of tuberculosis/HIV co-infection

S.O. Cherenko, G.M. Royenko, M.V. Pogrebna, Yu.O. Senko, N.A. Marchenko

Objective — to study the effectiveness of treatment regimen with ethambutol to moxifloxacin change for the treatment of patients with new cases of co-infection TB / HIV.
Materials and methods. Controlled, randomized, prospective study included 60 HIV infected patients with newly diagnosed smear positive pulmonary tuberculosis. The patients were divided by random numbers into two comparison groups including 30 persons. The study group underwent the improved treatment regimen that included moxifloxacin during the initial phase — 2HRZMfx 4HR, while the comparison group received standard 5-component 1-st Category regimen — 2HRSEZ 1HREZ 5HRE.
The patients in the comparison groups did not differ in form of the disease and severity of immunosuppres­sion — both groups had the same prevalence of destructive process (46.7 % and 50.0 % patients respectively), infiltrative form (60.0 % and 53.3 % patients respectively). The remaining patients had disseminated tuberculosis, p > 0.05. All patients had severe immunodeficiency with CD4 lymphocytes < 200 cells/ml. 25 patients of the study group and 28 patients in the control group had viral hepatitis B and/or C.
Results and discussion. Application of the advanced moxifloxacin-containing regimen of treatment resulted in significant improvement of treatment efficacy at the end of initial phase in comparison to the standard treatment for 1-st category: smear conversion — in 80.0 % against 50.0 % patients (p < 0.05), clinical improvement and resorption of infiltrative changes in the lung tissue — in 86.7 % vs. 56.7 patients (p < 0.05). The incidence of anti-TB and antiretroviral drugs adverse reactions was significantly lower — 26.7 % vs. 50.0 % (p < 0.05). Reduction in the incidence of adverse reactions was due to the administration of the smaller amount of drugs (streptomycin was excluded) and reducing the duration of the initial phase from 3 months to 2, when the most hepatotoxic drug with concomitant viral hepatitis (pyrazinamide) is applied, and also due to the smaller number of TB drugs in the continuation phase — from 3 to 2 drugs. ART was applied in 28 (93.3 %) patients versus 19 (63.3 %) patients in the control group (p < 0.05) due to good treatment efficacy of tuberculosis. Following the appointment of ART most patients in the control group (52.6 %) reported worsening of tuberculosis course, that manifested with aggravation of clinical symptoms and focal infiltrative changes in the lungs. 2 of them (10.5 %) died of tuberculosis and viral hepatitis. Patients receiving advanced treatment regimen developed IRS in significantly fewer cases — in 21.4 % (p < 0.05), and not a single one died of it.
Conclusions. The inclusion of moxifloxacin instead of ethambutol into the 1-st category regimen of treatment for patients with TB/HIV co-infection and severe immunodeficiency allows to increase the frequency of smear conversion at the end of the initial phase of treatment on 37.5 %, reduction the incidence of adverse reactions on 46.6 % from combination of anti-TB and antiretroviral therapy, apply ART for the greater number of patients with severe immunodeficiency after initial phase and reduce the frequency and severity of immune reconstitution syndrome.

Keywords: new cases of TB / HIV co-infection, co-infection TB/HIV treatment, moxifloxacin, immune reconstitution syndrome.

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4. Original research

 

Analysis of the drug resistance in the hernivtsi region and study of imidazole derivatives activity against Mycobacterium tuberculosis

L.D. Todoriko, I.V. remenchuk

Objective — to carry out a retrospective analysis of the drug resistance of Mycobacterium tuberculosis in patients with newly diagnosed pulmonary tuberculosis in the Chernivtsi region and analyze the activity of the newly synthesized heterocyclic compounds against Mycobacterium tuberculosis.
Materials and methods. A retrospective analysis of Mycobacterium tuberculosis drug resistance in patients with newly diagnosed pulmonary tuberculosis registered in 2008—2012 in the Chernivtci region was conducted. The study included 22 new synthesized heterocyclic compounds with the subsequent establishment of their activity against M. tuberculosis.
Results and discussion. A retrospective study of the prevalence of drug resistant tuberculosis in the Chernivtsi region over the 2008 to 2012 period showed high level of drug resistance. Analysis of the efficiency and the effect of heterocyclic compounds on MTB showed that studied compounds (, V, V, V, VII) were 4 times more active in the medium with the concentration of 0.05 µg/ml than isoniazid. Sinthetized compounds are practically nontoxic (the 4th class of toxicity — slightly toxic substance), and in case of a peroral administration to mice the lethal dose (LD50) was defined to be 1500 mg/kg (1001 < < LD50 < 3000 mg/kg).
Conclusions. The increase in multidrug resistance from 4.7 % to 35.3 % among patients with newly diagnosed pulmonary tuberculosis in the Chernivtsi region during 2008—2012 was revealed. The highest percentage of resistance among the poli-drug resistant strains had ethambutol + streptomycin (65.3 %), among monoresistant — streptomycin (44.5 %), what is typical of the Chernivtsi region. Study on the newly synthetized (on the basis of the isoniazid molecule) heterocyclic compounds (, V, V, V, VII) with the concentration in the nutrient medium of 0.05 µg/ml showed its 4 times higher activity in comparosin to the well-known isoniazid used as a test-object.

Keywords: Mycobacterium tuberculosis, multidrug-resistant pulmonary tuberculosis, heterocyclic compounds, imidazole derivatives, isoniazid.

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5. Original research

 

Efficacy and safety of linezolid in complex treatment of patients with multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis

N.I. Kibizova, S.O. Cherenko, N.A. Litvinenko, M.V. Pogrebna, Yu.O. Senko, O.A. Reva, V.V. Davydenko, O.P. Chbotar

Objective — to study of the efficacy and safety of linezolid in a dose of 1.2 and 0.6 g per day in patients with MDR TB and XDR TB.
Materials and methods. The controlled study presents data on the analysis of the efficacy and tolerabi­lity of individualized treatment regimens that included linezolid in 46 patients with MDR-TB and 37 with XDR-TB. The comparison group, which is formed according to the method of selecting a pair of cases and drug resistance profile, was administered the same individualized treatment regimens without linezolid. Each group contained the same number of patients with various cases of MDR/XDR-TB: new cases in 15 (18.1 %) patients, discontinued treatment — 6 (7.2 %),  failure of the first course — 11 (13.2 %), retreatment failure — 16 (19.3 %), relapse — 19 (22.9 %), chronic cases —16 (19.3 %) patients. Linezolid was used at a dose of 0.6 g 2 times or once per day for 3—8 months, depending on the severity of tuberculosis. Dose was reduced to 0.6 g after smear conversion.
Results and discussion. Smear conversion and clinical symptoms improvement in the study group was achieved in 80 patients (96.4 %), including 36 (97.3 %) of patients with XDR-TB and 44 (95.6 %) patients with MDR-TB, p > 0.05. Smear conversion in the control group was reached in 71.1 % and 43.2 % of cases respectively, that significantly differed from treatment results in the study group. Adverse reactions of complex treatment was observed in 41 ( 49.4 %) patients of the study group and in 31 (37.4 %) patients of the control group, including serious ones, which required discontinuation of the drug, —in 18.1 % and 10.8 % of patients respectively, p > 0.05. Adverse reactions of linezolid were recorded in 16,9 % patients and manifested with hematologic disorders, maculopapularexanthem, peripheral polyneuropathy and diarrhea.
Conclusions. The inclusion of linezolid in individualized treatment regimens during initial phase enables to achieve the same treatment results in patients with XDR and MDR-TB. The scheme of linezolid in a dose of 1.2 g at the start of the treatment and 0,6 g after smear conversion achieves good tolerability with a low incidence of adverse reactions — 16.9 %, including serious ones — in 10.8 % of patients. Linezolid is more likely to cause hematologic adverse reactions (10.8 %) — anemia and/or leukopenia and/or plateletpenia. Blood count indices return to normal after discontinuation of drug.

Keywords: linezolid, multidrug-resistant tuberculosis, extensively drug-resistant tuberculosis.

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6. Original research

 

Rational choice of individualized chemotherapy regimens for multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis patients

N.A. Lytvynenko, S.O. Cherenko, M.V. Pogrebna, Yu.O. Senko, V.V. Davydenko, O.A. Reva, G.I. Barbova, G.M. Roenko, S.P. Vasylenko

Objective — to determine the optimal individualized chemotherapy regimens for patients with MDR-TB and extensively drug-resistant (XDR) TB in composition, the number of anti-TB drugs for the initial phase of chemotherapy (IP).
Materials and methods. Randomized, controlled, prospective study provides the results of treatment of 140 MDR-TB patients and 60 XDR-TB patients. New cases of MDR-TB or patients treated with the I line anti-TB drugs in the past were divided into 2 groups. The first group (40 patients) was administered at least 4 MTB susceptible anti-TB drugs and in addition to this 1—3 anti-TB drugs with low activity and MTB non-susceptible. The second group (49 patients) was administered at least 4 MTB susceptible anti-TB drugs. MDR-TB patients who previously recieved treatment including I and II line anti-TB drugs were divided into 2 groups: the third group (29 patients) was administered at least 4 MTB susceptible anti-TB drugs and in addition to this 1—3 anti-TB drugs with low activity and MTB non-susceptible; the fourth group (22 patients) was administered at least 4 MTB susceptible anti-TB drugs. XDR-TB patients were divided into 3 groups: The fifth group (34 patients) was administered 5—6 MTB susceptible anti-TB drugs and in addition to this 1—3 MTB non-susceptible anti-TB drugs, VI (16 patients) — 4 MTB susceptible anti-TB drugs and in addition to this 3—4 MTB non-susceptible anti-TB drugs, the seventh group (10 patients) was administered only 5—6 MTB susceptible anti-TB drugs.
Results and discussion. Sputum conversion in MDR-TB patients ranged from 92.5 % to 75.9 % and was independent of the supplemental assignment of MTB resistant anti-TB drugs. Supplementation of 1—3 MTB resistant to anti-TB drugs for XDR-TB patients increased the effectiveness of treatment: in group V in comparison to the VI and VII groups, sputum conversion were obtained in 52.9 % of patients to 37.5 % and 40.0 % of patients, respectively (p > 0.05). The cost-effectiveness of treatment in the V and VII group were 1030.82 UAN and 1338.57 UAN respectively.
Conclusions. MDR-TB patients treatment regimen as adequate when includes at least 4 MTB suscep­tible anti-TB drugs. XDR-TB patients should be prescribed 6—7 anti-TB drugs, 5 of them must be MTB susceptible. Failing to provide such adequate chemotherapy regimen one should prescribe regimen inclu­ding 3—4 MTB susceptible anti-TB drugs and 1—3 MTB resistant to anti-TB drugs.

Keywords: multidrug-resistant tuberculosis, extensively drug-resistant tuberculosis, chemotherapy regimen, sputum conversion.

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7. Original research

 

Main risk factors for relapse of tuberculosis in Poltava region

A.H. Yareshko, M.H. Boiko, M.V. Kulish, V.H. Bondarenko, A.K. Vorodiukhina

Objective — to identify the main risk factors for relapse of tuberculosis in Poltava region.
Materials and methods. The study conducted analysis of case histories and hospital records of 54 pa­tients with newly diagnosed pulmonary tuberculosis, who was later diagnosed a relapse of tuberculosis.
Results and discussion. The main risk factors for relapce of tuberculosis in the Poltava region are health neglect, alcohol abuse, insufficient duration of treatment in a hospital on the first admission, inadequate treatment regimen, early transfer of patients in the inactive follow-up group, presence of comorbidities.
Conclusions. The results emphasize the special place of relapses of tuberculosis in epidemic situation in the Poltava region. Most of these patients are smear positive and show low effectiveness of treatment, thus becoming the main source of chronic destructive drug-resistant tuberculosis cases and spread of Mycobacterium tuberculosis.

Keywords: tuberculosis, relapse, risk factors.

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8. Original research

 

Analysis of the efficacy of etiotropic treatment of mild course community acquried pneumonia in the therapeutic department of municipal hospital

I.M. Butvin

Objective — to examine the features of etiotropic therapy in patients of different clinical groups with mild course community acquired pneumonia (NP) in the therapeutic department of municipal hospital.
Materials and methods. The retrospective study of 84 NP case histories was conducted. The study included analysis on the disease anamnesis, previous antibiotic use, clinical manifestations of the disease, the presence of comorbidity, the duration of etiotropic treatment and variability and compatibility with current treatment protocol of care for patients with NP.
Results and discussion. Studied patients belonged to the II and III clinical groups of NP mainly with present comorbidity. Accordng to the analyzed medical records patients were prescribed one to three antibiotics. Combination of etiotropic drugs and duration of therapy in most patients with NP correspon­ded the guidelines. Some patients were registered to have inadequate combination of antibiotics and delayed treatment efficiency control.
Conclusions. The treatment of the mild course NP in therapeutic department demonstrated that etiological treatment was prescribed timely and its duration was sufficient. Use of inadequate combinations of drugs and delayed control treatment efficiency control should be adjusted in future clinical practice.

Keywords: community acquired pneumonia, clinical group, antibacterial treatment.

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9. Original research

 

Bone metabolism disorders in menopausal women with COPD

N.P. Masik

Objective – to evaluate the bone metabolism disorders in COPD menopausal women.
Materials and methods. The comprehensive clinical study of 253 women with COPD was performed, 142 patients were in the menopausal period. Parameters of bone metabolism as serum calcium, phosphorus, alkaline phosphatase, osteocalcin, parathyroid hormone were estimated. Parameters of bone mineral density were determined by ultrasound.
Results and discussion. The most marked disturbances of bone metabolism determined in menopausal women were manifested by hypercalcemia, hypophosphatemia and suppression of PTH synthesis. These processes occurred due to decrease of concentrations of alkaline phosphatase, serum osteocalcin in patients of both groups, indicating inhibition of bone formation in COPD women. Osteopenia was diagnosed in 65.35 % of menopausal women and 58.52 % in young adults, osteoporosis — in 18.81 % and 18.52 % respectively.
Conclusions. Severity of bone tissue impairment was determined by summation of hormonal disorders of menopausal women and systemic inflammation in COPD.

Keywords: chronic obstructive pulmonary disease (COPD), menopause, systemic inflammation, bone metabolism, osteopenia, osteoporosis.

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10. Original research

 

Child and adolescent morbidity in the sites of tuberculosis infection in the Lviv region and its association with the epidemic situation

I.S. Vivhar

Objective — to examine the epidemiological situation on tuberculosis over the 2006 to 2010 period and its impact on the child and adolescent morbidity in the sites of tuberculosis infection in the Lviv region.
Materials and methods. Data n epidemiological monitoring of tuberculosis in children and adolescents in the Lviv region were analyzed. The study assessed the incidence of tuberculosis in children and adolescents aged 0 to 17 years, from the sites of tuberculosis infection in 2006—2010.
Results and discussion. The main cause of tuberculosis among children and adolescents is socio-economic instability in the country. Over the 2008 to 2010 period a decrease in the coverage of preventive examination among children to 59.5 % in 2010 in Lviv region and 71.4 % in Ukraine was observed. Unfavorable factors to be considered are the presence of secondary and extrapulmonary forms of disease, tuberculous meningoencephalitis in the morbidity structure, increasing of the number of cavitary and smear positive cases, the emergence of drug-resistant cases.
Conclusions. The difficult economic and environmental situation, high latent infection rate among children and adolescents, presence of a large number of smear positive cases among adult population does not allow to predict a significant improvement of the epidemiological situation on tuberculosis in children and adolescents.

Keywords: pulmonary tuberculosis, children, adolescents, epidemiological situation.

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11. Lectures

 

Lungs immune system Lecture 2. The immunological aspect

B.V. Noreyko, S.B. Noreyko

The lecture is aimed to familiarize doctors with the multifunctional features of lungs immune system. Various alveolar membrane immune functions in case of lung pathology are being discussed. The alveolar macrophages as the major components of cell element of immunity in broncho-pulmonary system are thoroughly estimated. The role of the endoperoxides, leykotriens and prostaglandins formed in the process of surfactant affliction is being considered. The oxygen explosion that emerges due to oxygen and surfactant phospholipids is regarded by authors as the effect of fulminate form of «membrane» immune answer of the alveolar tunic, which differs greatly from the well-known respond of «immediate type» that is realized by immunoglobulin E and aeroantigens.

Keywords: lungs immune system, lung pathology, alveolar macrophages, surfactant.

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12. Reviews

 

HIV infection and mucosal immunity

A.G. Dyachenko, S.L. Grabovyi, P.A. Dyachenko

Recently the pathogenesis of HIV infections is of high interest, especially mucosal immunity. The gastrointestinal tract is a major site of HIV replication, which results in massive depletion of lamina propria CD4+ T cells during acute infection. Highly active antiretroviral therapy usually leads to incomplete suppression of viral replication and substantially delayed and only partial restoration of gastrointestinal CD4+ T cells. The gastrointestinal pathology associated with HIV infection comprises significant enteropathy with increased levels of inflammation and decreased levels of mucosal impairment and regeneration. Assessment of gut mucosal immune system has provided novel directions for therapeutic interventions that modify the consequences of acute HIV infection.

Keywords: human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV), depletion of CD4+ T cells, bacterial translocation, immune activation.

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13. Reviews

 

Characteristics of M. tuberculosis of the Beijing family

O.K. Asmolov, M.M. Chesnocova, O.A. Baburina, O.K. Lobanov

The review presents the basic properties of Mycobacterium tuberculosis of Beijing family, spread in the different geographic regions. The main negative characteristics of the strains of this family are their high virulence, transmissibility and potency for the rapid drug resistance development, which is of great importance in the conditions of the TB epidemic.

Keywords: Mycobacterium tuberculosis, Beijing family, drug resistance.

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14. EPIDEMIC SITUATION

 

The dynamics and peculiarities of epidemiological indices of HIV-associated tuberculosis in children in Ukraine for the period 20062011

O.I. Belogortseva, Ya.I. Dotsenko, O.V. Stopolianskyi, O.E. Sivachenko, M.A. Sadlovska, I.E. Shechter

The study of the dynamics of epidemiological indicators of HIV infection and HIV-associated tuberculosis in Ukraine during 2006—2011 years is presented in the article and the analysis of the major trends has been made. The spread of HIV infection among pregnant women in Ukraine has been traced. An increase in the AIDS-related illnesses mortality in 2011 in comparison to the previous years is emphasized. Annual increase of TB/HIV co-morbidity, as well as mortality is observed against the background of the growing of the prevalence of HIV-infected persons in Ukraine. Prevalence of children born by HIV-infec­ted mothers is also annually increasing. HIV-infected infants are the most susceptible to TB, presented by the rapid spread with hematogenous dissemination and complications development.

Keywords: children, tuberculosis, HIV infection.

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15. to help a general practitioner

 

Recommendations on HIV counseling and testing among tuberculosis patients

O.O. Neduzhko, L.G. Averbukh, O.V. Postnov, T.K. Kiriazova, S.V. Esipenko

Objective – to determine the features and to provide recommendations regarding HIV counseling and testing among TB patients.
Materials and methods. Analyzed the main international guidelines for the provision of counseling and testing for HIV patients with tuberculosis.
Results and discussion. HIV counseling and testing is an important structural component of medical care for tuberculosis patients. Timely identification of HIV status improves the effectiveness of medical care and ensures patients access to HIV services in case of positive HIV test result.
Conclusions. The provision of integrated medical care using provider-initiated HIV testing and counseling approach is a priority combination in organization of treatment of patients with co-morbidity. HIV testing and counseling among TB patients has some additional requirements to address, especially during the post-test counseling procedure.

Keywords: HIV, tuberculosis, counseling and testing, recommendations.

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16. Clinical case

 

Tumor-like infiltrative pulmonary tuberculosis

E.N. Raznatovskaya, A.A. Mihaylova, V.V. Fomenko, H.V. Zubov

The article presents a case of an extremely rare form of infiltrative tuberculosis — tumor-like tuberculosis.

Keywords: infiltrative tuberculosis, tumor-like form, case history.

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17. Clinical case

 

Peculiarities of congenital HIV/TB co-infection course in newborns and infants

N.V. Rymarenko

The article presents two cases of congenital HIV/TB co-infection in newborns and infants. The analysis describes the main clinical and laboratory features and the clinical course of the disease.

Keywords: congenital tuberculosis, HIV infection, children.

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