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Issue. Articles

3(18) // 2014



1. Editorial


Analysis of gaps in the organization of treatment of drug-resistant tuberculosis

V.M. Melnyk, I.O. Novozhylova, V.G. Matusevych, T.M. Martsinyuk

The article presents the results of the analysis of gaps in organization of the treatment of drug-resistant tuberculosis according to the survey among the tuberculocis experts of 27 administrative territories. Organization of the treatment of those patients is proved to be imperfective. Its main gaps are: disparity of departments (wards) for the treatment of patients with drug-resistant tuberculosis to established requirements for their construction, lack of facilities for the treatment of that patients in sanatoriums, not sufficient social support, difficulties in comparsory treatment due to lack of closed type departments, and no clear mechanism of enrollment of patients in cases of refusal. Among all causes f ineffective organization of the treatment of that patients two most important are low adherence to the treatment and lack of functional infrastructure and human resource capacity. Doctors of health services fulfill their responsibi­lities for providing treatment of TB patients not fully, often due to objective factors, including the lack of material and technical security and inadequate legislation.
Revealed gaps in the organization of treatment of patients with drug-resistant tuberculosis, as well as comments and suggestions of tuberculosis experts from administrative areas are very relevant right now, when there is a need of reforming the healthcare industry, and the effective functioning of TB services in the future will depend on its proper integration into the overall health care delivery system.

Keywords: drugresistant tuberculosis, organization of treatment, gap and constraints.

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2. Original research


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

I.B. Bialyk

Objective — to study the efficacy and tolerance of the intensive anti-tuberculosis treatment with 5—7 anti-tuberculosis drugs at multidrug-resistant destructive pulmonary tuberculosis patients with simultaneous and equable during the day administration of antituberculosis drugs.
Materials and methods. The intensive anti-tuberculosis treatment, containing 5—7 antituberculous drugs mainly the 2-nd line, fluoruquinolones and reserve medications was performed at 455 multidrug-resistant destructive pulmonary tuberculosis patients during 6—12 months. Subjects have been segregated to 2 groups, which were identical by the nature of process, duration of treatment and combinations of antimycobacterial drugs: the main group of 225 patients, who received anti-tuberculous drugs equably during the day and control group of 230 patients, who received all anti-tuberculous drugs simultaneously or almost simultaneously.
Results and discussion. Intensive anti-tuberculosis treatment in main group resulted in smear conver­sion at 73.3 % of patients during the (3.43 ± 0.21) months, caverns healed at 29.8% of patients during the (5.67 ± 0.38) months, partially regressed at 58.6 % of patients, and in generally, the summary regression of caverns occurred at 88.4 % of patients. The efficacy of anti-tuberculosis treatment in control group was only insignificantly lower (p > 0.1—0.5): smear conversion at 70.0 % of patients during the (3.62 ± 0.24) months, healing of caverns at 27.8 of patients during the (5.77 ± 0.41) months, partially regression of caverns at 56.1 % of patients, and the summary regression of caverns at 83.9 % of patients. Adverse reactions from antimycobacterial medications, which were administered equably during the day, occurred at 40.9 % of patients, among them the significant adverse reactions, which lead to the discontinuation of one or more drugs, occurred at 18.2 % of patients. Patients, who received antimycobacterial medications simultaneously or quite simultaneously, experienced adverse reactions significantly more frequently — at 50.9 %, including the significant adverse reactions — at 26.1 % (p < 0.05). Indicated differences concerned to all spectrum of adverse reactions — dyspeptic, neurological, hepatotoxic, vestibule-ototoxic, allergic and other.
Conclusions. The most advisable drugs administration during the intensive anti-tuberculosis treatment of multidrug-resistant destructive pulmonary tuberculosis containing 5—7 antituberculosis drugs is equab­le during the all day, but not simultaneous.

Keywords: multidrug-resistant destructive pulmonary tuberculosis, simultaneous and equable during the day administration of 57 antituberculous drugs, smear conversion, healing of caverns, adverse reactions.

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3. Original research


Lymphocytic protection system of children with pulmonary tuberculosis caused by the different susceptibility of pathogens to antimycobacterial drugs

I.L. Platonov, M.I. Sakhelashvili, T.M. Balyta, G.D. Shtybel

Objective — a comparative study of the mechanisms of lymphocyte protection in children with pulmonary tuberculosis caused by drug-susceptible/resistant strains of Mycobacterium tuberculosis.
Materials and methods. Studies of the pool of lymphocytic cells: CD3+, CD3+CD56+, CD3+HLA-DR+, CD3+CD4+, CD4+45RA+, CD3+CD8+, CD3+CD4+/CD3+CD8+, CD16/56+, CD16/56+CD8+, CD19+ held in children with drug-resistant (study group) and pulmonary tuberculosis with suscebtibility of the pathogen to the antimycobacterial drugs (control group). The average age of the patients was — (8 ± 1.5) years.
Results and discussion. Children in the control group revealed a decrease of the total amount of lymphocytes, amount of CD3+ T-lymphocytes (p < 0,01), CD3+CD4+ T-helper lymphocytes (p > 0.05), rate immunoregulatory index CD3+CD4+/CD3+CD8+ (IRI < 1; p < 0.05), increase of the pool of CD16/56+CD8+ activated natural killer (p < 0,01). Significant decrease in subpopulations of CD3+CD4+, CD3+CD4+/CD3+CD8+, increase of D3+D8+ and D16/56+CD8+ count was stated in the patients of the main group in comparison to the control group and healthy children.
Conclusions. Children with pulmonary tuberculosis experience lack of specific cellular immunity due to the loss of dynamic balance between lymphocyte subpopulation pool of cells and nonspecific activation of cellular defense. Intensity abnormalities in lymphocyte protection system in children with anti-tuberculosis treatment-resistant tuberculosis are greatly enhanced.

Keywords: pulmonary tuberculosis, children, lymphocyte immunity.

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4. Original research


Efficacy and tolerance of gemifloxacin and other fluoroquinolones in the regimens of antimycobacterial therapy in patients with destructive pulmonary multidrug-resistant tuberculosis

G.V. Radysh

Objective — to evaluate gemifloxacin clinical efficacy and tolerance in the regimens of antimycobacterial therapy in patients with destructive pulmonary MDR tuberculosis, including enhanced resistance.
Materials and methods. 138 patients with destructive pulmonary MDR tuberculosis were examined in an open, prospective, randomized study. General group comprised 65 patients who received standard treatment with the inclusion of gemifloxacin during the initial phase, and during the continuation phase of the study group gemifloxacin was replaced with the default fluoroquinolone. The comparison group comprised 73 patients who received standard treatment including standard fluoroquinolones. Evaluation of treatment results carried out on the basis of comprehensive study of clinical and radiographic and microbiological parameters: frequency and time of the disappearance of intoxication syndrome and other manifestations, smear conversion, regression of radiological changes in the lungs, the state unchanged (bacteriaexcretion continues) and deterioration (death).
Results and discussion. Inclusion of gemifloxacin or gatifloxacin into the regimen for MDR-TB increases the effectiveness of treatment (disappearance of intoxication syndrome, clinical signs and radiological signs of regression of destructive pulmonary tuberculosis and smear converion) in the initial phase by 38 % and 64 % (35 % and 61 % at XDR-TB) in comparison with the regimens that include levofloxacin or ofloxacin. At the end of the main course of treatment indicator «cure» was achieved respectively in 69 % and 61 % cases using gemifloxacin or gatifloxacin in comparosin to the 38 % and 27 % cases when using levofloxacin or ofloxacin.
Conclusions. The use of fluoroquinolones of the last (fourth) generation — gemifloxacin or gatifloxacin during the initial phase of the treatment of MDR-TB in the absence of data to the DST for the second-line drugs allows you to significantly improve the clinical efficacy of treatment compared with fluoroquinolones of the prior generations — levofloxacin or ofloxacin, only in cases of (later confirmed) TB with enhanced resistance.

Keywords: multidrug-resistant tuberculosis, gemifloxacin, fluoroquinolones, antituberculosis treatment.

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5. Original research


Modern features of deaths in pulmonary tuberculosis among hospitalized adults of tertiary hospitals (according to the clinical and post-mortem analysis)

I.V. Liskina

Objective — a retrospective analysis of the features of mortality structure among those who died with the final clinical diagnosis of the underlying disease — «pulmonary tuberculosis» for the period 2006—2012 years.
Materials and methods. Autopsy protocols, clinical histories of all deaths with underlying disease «pulmonary tuberculosis» were analyzed in the hospital of the Institute for 2006—2012 years. The form and character of lesion in pulmonary tuberculosis, options of generalization of infection were taken into account. The cohort of the dead with severe pulmonary lesions was analyzed in more details. The types of the treatment, the cause of death, complications of the underlying disease were examined. The final clinical and post-mortem diagnosis were compared.
Results and discussion. During the period there 229 deaths were stated, of which 75 (32.75 %) cases were diagnosed with pulmonary tuberculosis. Of these, an autopsy was performed in 60 (32.09 %) cases. In all cases the diagnosis of «pulmonary tuberculosis» was established intra vitam. At the time of death 61 (81.3 %) patients remained smear positive. In 57 (76.0 %) among 75 cases the diagnosis of severe course of tuberculosis was established, namely, the development of hematogenous-disseminated tuberculosis, including generalized form. A detailed study of this cohort revealed that 51 (89.5 %) patients remaine smear positive. In the cases with revealed drug-resistance multidrug-resistant MTB strains and strains with extended resistance dominated. Co-infection of TB/HIV was present in 7 (12.3 %) cases. The most frequent immediate causes of death were progression of tuberculous process (31 (54.4 %) cases), profuse pulmonary hemorrhage (8 (14.04 %) cases) and pulmonary embolism and/or acute thrombosis of the right heart (9 (15.59 %) cases). Additionally the incidence of serious complications of pulmonary tuberculosis and comorbidity were studied. Complete coincidence of the final clinical and postmortem diagnoses occurred in 12 (25.53 %) of 47 autopsies. Most often tuberculosis of intrathoracic lymph nodes wasn’t diagnosed (23 cases, 48.94 %) in the clinic.
Conclusions. Currently, the increasing incidence of co-infection TB/HIV cases and cases with multidrug-resistant MBT strains or extensively drug-resistant strains largely determine the structure of TB deaths in specialized hospitals. These circumstances explain the development of severe, generalized forms of tuberculosis, in particular, to our knowledge; they made up 76.0 % of all deaths in hospital. Clinical diagnostics of nature and prevalence of tuberculous lesions, mainly affecting the lungs in severe forms of tuberculosis remained unsatisfactory. The diagnosis of tuberculous lesions of peripheral lymph nodes is established in vivo extremely rarely (the discrepancy on autopsy — 48.94 %), especially in the therapeutic treatment, form and phase of pulmonary tuberculosis is not correctly defined (38.30 % difference), the preva­lence of infection, as typically, its generalization is underestimated (the discrepancy according to autopsy findings — 17.0 %).

Keywords: mortality, hematogenous-disseminated tuberculosis, pathological diagnosis.

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6. Original research


Alterations of left ventricular function in patients with bronchial obstruction

V.E. Horodetsky

Objective – the present study evaluated left ventricular (LV) function in patients with chronic obstruc­tive pulmonary disease (COPD).
Materials and methods. Ninety patients with COPD were studied by electrocardiography, Doppler echocardiography and spirography.
Results and discussion. Compared with controls, patients with COPD had significantly lower transmitral E/A values and longer DecT and IVRT. Overall, 42 (46 %) patients had clear impaired relaxa­tion pattern of LV diastolic dysfunction. Mean pulmonary artery pressure correlated significantly with LV filling parameters. Pulmonary hypertension appeared to be an independent predictor of LV diastolic dysfunction in patients with COPD.
Conclusions. Patients with bronchial obstruction characterized by diastolic left ventricular dysfunction. The presence of pulmonary hypertension is an independent predictor of left ventricular dysfunction. Doppler-echocardiographic examination should be indicated for patients with COPD in order to identify possible pulmonary hypertension and diastolic dysfunction.

Keywords: chronic obstructive pulmonary disease, left ventricle, doppler-echocardiographic examination.

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7. Original research


Immuno-endocrine changes in patients with HIV infection depending on the clinical stage and immunosuppression severity

D.G. Zhyvytsia, O.V. Samoylenko

HIV infection is a prolonged infectious disease that develops as a result of infection with human immunodeficiency virus (HIV) and is characterized by progressive damage the immune system. Disturban­ce in the functioning of the immune system that occurs during HIV infection can cause disturbances in the secretion of hormones and thus lead to dysregulation of many organs and systems.
Objective — to investigate endocrine status in patients with HIV infection by serum hormone para­meters depending on the stage of the disease and the number of CD4- lymphocytes.
Matherials and methods. The study included 64 patients and examined for HIV control group that consisted of 15 HIV-negative healthy individuals . Immunological examination included the determination of the absolute and relative levels of T lymphocytes (CD3+), T helper cells (CD4+), T-killer cells (CD8+), index immunoreactivity (CD4+/CD8+) using monoclonal antibodies for flow cytometry COULTER® EPISS® XL (Beckmon Coulter, France). Determination of adrenal hormones (cortisol, dehidroepiandos­teron sulfate — DHEA) thyrotropin (TSH), thyroid hormones (free thyroxine — T4, free triiodothyroni­ne — T3) in serum was carried out by ELISA using kits Ltd. «Companies AlkorBio» (RF).
Results and discussion. The assessment of changes in levels of adrenal hormones and thyroid hormones and immune status in 64 patients with HIV — infection was carried out. When comparing the performance level of serum hormones in patients with HIV infection in the control group downward trend in the average level of thyroid hormones (T3) was observed: level decreased by 2.6 times at the level of CD4-lymphocyte less than 100 ml –1, and 1.6 times at the level of CD4-lymphocytes from 100 to 350 ml –1, at the level of CD4-lymphocytes more than 350 ml –1 below 2.6 times, TSH and T4 decreased in almost all patients on the same level. When comparing the level of adrenal hormones in patients with HIV infection and control group regardless of immunodeficiency we found significantly (p < 0.05) lower dehidroepiandosterone. Immunological studies revealed significant reduction in the absolute number of CD4+-lymphocytes in 8 times and the relative amount in 3.6 times. The study of hormone level revealed significant increasing of cortisol with increasing of immunodeficiency severity. The average level of cortisol level was increases by 1—3 stages, but also decreased at disease stage 4.
Conclusions. Patients with HIV infection revealed decrease in dehidroepiandosterone and thyroid hormones serum level. In severe immunodeficiency there is a tendency to cortisol level increasing. Progression of HIV infection is accompanied by a decrease in the absolute number of CD3-lymphocytes, the absolute and relative number of CD4-lymphocyte and index immunoreactivity. In patients with clinical stage IV these figures reach minimum values (4—9 times lower in comparison with the normal).

Keywords: HIV infection, dehidroepiandosteron, thyroxine, triiodothyronine, thyrotropin, cortisol, CD4-lymphocyte.

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8. Original research


Elimination of viral particles of HIV in blood and improvement of CD4 count in three patients in Ukraine who were administered Enercel or Enercel in combination with antiretroviral and anti-tuberculosis therapy for the treatmnet of HIV/TB co-infectio

V.P. Dubrov, T.. Dubrova, D. Kristner, S. Sanseverino, D. Loren

Human Immunodeficiency Virus [HIV] causes progressive immune system destruction and eventually death from opportunistic infections. Combination of antiretroviral treatment is effective and results in normal life-span of affected individuals but is limited by side-effects, cost and the development of drug resistance.
Objective — this preliminary study was designed to evaluate whether the complex homeopathic immunomodulator Enercel® is of benefit in patients with HIV and tuberculosis co-infection.
Materials and methods. One patient was treated with Enercel® without antiretrovirals for 4 months on the following schedule: 50 ml IV twice daily for 1 month followed by 50 ml IV once daily for 3 months; 20 drops under the tongue twice daily; 5 ml via nebulizer once per day and 2 puffs into each nostril three times per day.Two patients were treated with Enercel® on the same schedule + antiretrovirals [Abacavir 300 mg twice daily; Lamivudine (3TC) 150 mg twice daily and Efavirenz 600 mg daily] for 3 months. All patients received standard anti-tuberculosis treatment.
Results and discussion. At baseline, the patient on Enercel® alone had a CD4 count of 360 cells/mm3 and a viral load of 35,428 copies/ml. After 4 months of treatment CD4 count was 458 cells/mm3 and his viral load was undetectable (< 40 copies/ml) [> 2 log10 suppression]. Both patients on combination therapy had significant increase in CD4 count and elimination of detectable HIV particles in the bloodstream [> 4 log10 and > 5 log10] after 3 months. No side effects or toxicity were observed.
Conclusions. Whereas the use of immunomodulators in HIV/AIDS has had variable results, Enercel® was safe and effective in 3 patients with Clinical Stage IV AIDS. This encouraging result is now being followed by a more extensive evaluation of Enercel® in HIV/AIDS.

Keywords: tuberculosis, TB/HIV co-infection, antiretroviral therapy, Enercel.

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9. Original research


Effectiveness of clofazimine in complex treatment of patients with extensively drug-resistant tuberculosis

N.I. Kibizova, S.O. Cherenko, O.P. Chobotar

Objective — study the efficacy and safety of clofazimine in patients with extensively drug-resistant tuberculosis (XDRTB).
Materials and methods. The efficacy and tolerability of individualized anti-tuberculosis treatment regimens that included clofazimine in 45 patients with XDR TB were investigated in a controlled study. In the comparison group, which was formed according to the method of selecting a pair of cases and drug resistance profile, underwent the same individualized anti-tuberculosis treatment regimens without clarithromycin. The most patients in each group were with retreatment cases — 36 (80.0 %).
Results and discussion. In the study group smear conversion was observed in 26 (57.8 %) of patients with XDR TB. In control group smear conversion was reached in 55.6 % of cases, that significantly differed from treatment results in the study group. Adverse reactions of complex anti-tuberculosis treatment including gastrointestinal adverse reactions were observed in 40.0 % and 13.3 % patients respectively of the study group and in 42.2 % and 17.8 % patients of the control group.
Conclusions. Adding clofazimine to anti-tuberculosis treatment regimens does not increase the effectiveness of treatment of XDR-TB, but significantly doesn’t increase the incidence of adversere actions including gastrointestinal.

Keywords: extensively drug resistant tuberculosis, clofazimine.

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10. Original research


Carcinoids and carcinoid syndrome in phthisiopulmonology

I.D. Duzhyi, O.B. Kravec, I.Ya. Gresko, E.V. Yashukova

The differential diagnostics of circular-shaped mass is rather difficult in phthisiopulmonology because there are known about 80 variants of such lesion. The most important forms among them in prognostic value are tuberculoma, carcinoids and cancer. Timely diagnostics of the latter influence the long-term results of surgical treatment.
Objective – to present an experience of diagnostics and surgical treatment tactics for carcinoid of lungs.
Materials and methods. The study included 225 persons who were operated for circulated-shaped mass.
Results and discussion. 5 (2.22 %) patients had carcinoids among 225 persons operated for circulated-shaped mass. In 2 of these 5 patients, development of carcinoid syndrome was observed. Metastases appeared after 18-month and 24-month postoperating periods, but 3 patients without carcinoid syndrome had no relapses of the disease in 5-year follow-up.
Conclusions. Surgical treatment should be applied not later than 2—3 months after detection of syndromic diagnosis in patients with circulated-shaped masses of lungs. To identify possible metastases it is needed to use ultrasound or computer tomography in case of carcinoid syndrome.

Keywords: circular-shaped lesions of lungs, carcinoids, tactics.

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11. Reviews


Disease caused by the Ebola virus: current state of the problem

O.A. Golubovska

This article presents basic information on the etiology, pathogenesis, modern methods of diagnosis and prevention of the disease. Currently known outbreaks of the disease are characterized and an emphasis on the major known sources of infection and routes of transmission are made. Particular attention is paid to modern Ebola outbreak in 2014 and to the international response efforts for its elimination. It is noted that now there are no reliable methods for the treatment and prevention of the diseasewhich makes timely isolation of patients and the prevention of contact the most effective protection factors. The attention is also focused on the work of WHO and other global communities to overcome the epidemic.

Keywords: Ebola disease, Ebola outbreak.

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12. Reviews


Characteristics of digestive system concomitant pathology and its role in the formation of resistant pulmonary tuberculosis

L.D. Todoriko

haracteristics of the most common diseases of the digestive system in patients with pulmonary tuberculosis and their role in the formation of drug-resistane is presented in the literature review and analysis of own experimental results. The number of patients with pulmonary tuberculosis with hepatitis, having acute and reciprocally aggravate course, tends to increase. The problem of forming a drug-induced hepatitis is created by significant duration and toxicity of multidrug-resistant tuberculosis (MDR TB) treatment.
More than in half of the cases the use of anti-tuberculosis treatment in patients with resistant tubercu­losis leads to the affect of the gastric and duodenum mucosa, of the pancreas structure and function, formation of the malabsorption syndrome. The presence of digestive system pathology in patients with active tuberculosis in most cases is accompanied with the failure to complete the TB regimen, and treat­ment result may be ineffective. Comorbidity of pulmonary tuberculosis with digestive diseases has every reason to be considered in the appointment of the basic course of anti-tuberculosis treatment for newly diagnosed TB cases, as well as in the dynamics of the use of the basic course of anti-tuberculosis treatment (especially for MDR TB), and in the period of residual effects after pulmonary tuberculosis treatment as well.

Keywords: tuberculosis, digestive system, chronic hepatitis, chronic pancreatitis, drug resistance, anti-TB drugs.

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13. Original research


Co-infection: HIV/AIDS with TB and hepatotropic viruses. Current view on complicated question

V.E. Krasiuk

HIV/TB co-infection complicates clinical course, treatment and management of patients with HIV. The affected individuals represent a treatment challenge with controversies among doctors associated with drug resistance, cross-resistance, hepatotoxicity and low response to treatment. Studies have shown that HIV co-infection accelerates hepatotropic viruses and increase risk of liver cirrhosis, hepatocellular carcinoma, and decompensated liver disease, affects and significantly complicates course of tuberculosis in co-infected individuals. Many studies showed the presence of increased risk of progression of acquired immunodefici­ency syndrome (AIDS) and AIDS-related mortality in co-infected individuals. HIV is one of the main risk factors for tuberculosis. On the other hand TB significantly accelerates the progression of HIV. Analyzis of epidemiological indicators showed the trend that HIV prevalence is highly correlated with high incidence of tuberculosis.

Keywords: tuberculosis, HIV/AIDS, hepatitis and , co-infection.

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14. Reviews


Possibilities of immunological disorders correction by using Glutamyl-Cysteinyl-Glycine disodium and world experience of its using in patients with drug-resistant pulmonary tuberculosis

O.S. Shalmin, O.M. Raznatovska, R.M. Yasinskiy

The article provides a review of the literature on the possibilities of immunological disorders correction using Glutamyl-Cysteinyl-Glycine disodium and world experience of its using in patients with drug-resistant pulmonary tuberculosis.

Keywords: Glutamyl-Cysteinyl-Glycine disodium, immunological disorders, drug-resistant pulmonary tuberculosis.

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Causes analysis for the prevalence of multidrug-resistant tuberculosis in the Odesa region

S.V. Yesipenko, V.V. Filyuk, N.A. Gerasimova

The article presents an analysis of the reasons for the high prevalence of multidrug-resistant tuberculosis in the Odesa region. Accent is made on the evaluation of the selection of patients for the treatment of second-line drugs. We compared characteristic of the efficacy of treatment of MDR TB cases according to cohort analysis. It was established that patients with MDR TB in order to increase motivation for treat­ment need qualified psychological care, individual approach to the appointment of second-line drug treatment for patients with co-infection of TB/HIV on a background of deep immunosuppression and providing a controlled outpatient therapy.

Keywords: multidrug-resistant tuberculosis (MDR TB), cohort analysis, a controlled therapy, treatment efficacy.

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16. Organization of medical care


Current approach to the organization of the health care for the patients with co-infection HIV/TB in Ukraine using the principle two diseases one patient

T.L. Haborets

Recently, Ukraine has seen growth in the incidence of comorbidity HIV/TB. As of 01.01.2014, 16 175 HIV-infected individuals diagnosed with tuberculosis were under supervision. Modern approach to the organization of medical care for patients with HIV/TB co-infection uses the principle of «two diseases — one patient», ie at the treatment of the two diseases at the same time patient should be at the focus. Isonia­zid preventive therapy is a safe and effective treatment for people living with HIV in order to prevent the progression of recent mycobacterial infection and reactivation of latent mycobacterial infection.

Keywords: HIV/tuberculosis co-infection, health care organization, principl two diseases one patient.

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