The Ukraine ranks among the top 20 countries with the highest number of multidrug-resistant (MDR) and extensively drug resistant (XDR) cases in the world. However, little is known of the genetic diversity, i.e., resistance signatures, in clinical isolates from this region. We analyzed seven of most prevalent MDR/XDR antibiotic resistance-conferring genes from clinical isolates ( = 75) collected from geographically diverse Ukrainian oblasts and the southern Crimean peninsula. Genomic analysis revealed that 6 (8%) were sensitive, 3 (4%) were resistant to at least one antibiotic but were not MDR, 40 (53%) were MDR, and 26 (35%) were XDR. The majority of isolates (81%) were of the Beijing-like lineage. This is the first study to use next-generation sequencing (NGS) of clinical isolates from the Ukraine to characterize mutations in genes conferring drug resistance. Several isolates harbored drug resistance signatures that have not been observed in other countries with high-burden tuberculosis. Most notably, the absence of gene promoter mutations, a diversity of mutation types in the resistance-determining region, and detection of heteroresistance provide a broader understanding of MDR/XDR from this area of the world.

Genotypic variation in Beijing lineages of Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB), has been associated with hyper virulence and the spread of extensively and multiple drug (X/MDR) resistant MTB strains in Eastern Europe, Central Asia, and East Asia. The clinical outcomes of 215 new cases of TB among the population of the Kharkiv region of Eastern Ukraine were analyzed to uncover factors associated with severe infection. Infecting MTB strains were profiled by 5 locus exact tandem repeats (ETRs) and 15 locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) genotyping. Among diverse MTB genotypes discovered in Ukraine, the Beijing genotype (MIRU-VNTR 42425) was significantly associated with risk factors for severe outcomes of disease in the study population, including TB/HIV co-infection and treatment failure. Strain replacement (superinfection) was observed in 10 patients, suggesting repeated exposure to novel MTB strains in hospital or community settings. Inclusion of MTB genotyping data may identify at-risk patients and improve treatment adherence to prevent X/MDR development for effective public health response against tuberculosis in Ukraine.

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Метою роботи було дослідження клініко-лабораторних даних хворих на вперше діагностований туберкульоз легень в умовах різного рівня споживання алкоголю. Матеріали і методи. У дослідження було долучено 102 хворих на вперше діагностований туберкульоз легень зі збереженою чутливістю до протитуберкульозних препаратів, які вживають алкоголь. Активність гамма-глутамілтранспептидази визначали кінетичним методом. Рівні С-реактивного білка визначали методом латексної аглютинації. Для аналізу параметрів якості життя пацієнтів використовувалася анкета SF-36. Оцінки характеру споживання алкоголю проводили за допомогою тесту Alcohol Use Disorders Identification Test. Отримані дані оброблені з використанням програми Statistica. Результати дослідження. За результатами опитувальника AUDIT пацієнти були поділені на три групи. Група 1-особи, які набрали 0-7 балів, група 2-8-15 балів, група 3-16 балів і більше. Показники якості життя в перших двох групах були на досить високому рівні з переважанням фізичної складової здоров'я. У третій групі середні показники за обома складовим виявилися достовірно нижче перших двох груп. Пацієнти групи 3 є більш соціально дезадаптованими. У групі зловживаючих алкоголем пацієнтів переважали процеси, що уражали більше однієї долі легень з ознаками деструктивних процесів легеневої тканини. У 82,1 % пацієнтів групи 3 були виявлені мікобактерії туберкульозу в мокротинні вже на етапі мікроскопічного дослідження. У хворих з туберкульозом зі зростанням рівня споживання алкоголю спостерігається збільшення рівнів в крові лейкоцитів, СРБ і показника ШОЕ, проявів анемії і зниження активності клітинного імунітету за рахунок зниження рівня лімфоцитів. Максимальні порушення мали місце в групі 3. Показники функціонального стану печінки, крім АЛТ, в групі 3 були достовірно вище, ніж в групі 1. Висновки. У хворих на туберкульоз, які вживають алкоголь мають місце зниження соціальної адаптації, рівня якості життя, наявність більш вираженого інтоксикаційного синдрому, превалювання поширених форм туберкульозу з масивним бактеріовиділенням, а також порушення функцій печінки.

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According to the World Health Organization, each year 10 million people are diagnosed with tuberculosis for the first time and 1.5 million people die from it. The death rate from this disease has increased in the world for the first time in more than ten years. Unfortunately, Ukraine is in the TOP-10 countries with the largest number of tuberculosis cases among population. Only in December 2021, 1,229 cases of tuberculosis were registered in Ukraine. To date, the course of the tuberculosis process has undergone significant changes. The infiltrative form (IF) of pulmonary tuberculosis accounts for the majority of new cases. Standardized treatment (60 doses in the intensive phase and 120 doses in the continuation phase) is not always sufficient for effective recovery and requires prolongation. That is why it is necessary to study the predictors that maximally reflect the need in therapy prolongation. The objective: to analyze the dynamics of clinical, laboratory and radiological parameters in patients with IF of newly diagnosed pulmonary tuberculosis (NDPT) under conditions of varying treatment effectiveness. Materials and methods. 120 men of working age with IF NDPT were examined in KNP of the Kharkiv Regional Council “Regional TB Dispancer N1” during 2019–2021. Patients were divided into two groups: Group 1 (n=89) included patients with positive clinical and radiological dynamics of the tuberculosis process, and as a result of treatment clearing of Mycobacterium tuberculosis (MBT) from the sputum; Group 2 included patients (n=31) with weak positive dynamics, as a result of which IF was extended to 90 doses. Comparison of clinical, laboratory and radiological data at the beginning and end of IF treatment in patients with different therapy efficiency was performed. The study was conducted in accordance with the requirements of good clinical practice, the Declaration of Helsinki of the World Medical Association, and was approved by the local ethic committee of the Kharkiv Medical Academy of Postgraduate Education. Results. An analysis of the dynamics of clinical, radiological and laboratory data showed that the decrease of immuno-inflammatory indicators levels (C-reactive protein, IL-4, IL-10, circulating immune complexes; CD4/CD8 ratio) was more pronounced in the group of patients who did not need treatment prolongation. At the same time this group was also characterized by significant increase in the level of IFN-γ by the end of the IF treatment, which could indicate activation of cellular immunity together with decrease in the levels of IL-4 and IL-10 which indicated the suppression of humoral immunity. Due to the predominance of cellular immunity over humoral, macrophage activation and their phagocytic activity were accelerated, as a result of which the process of MBT elimination was much faster and more efficient in Group 1 patients. Changes in cytokine levels were observed in patients of Group 1, who showed positive dynamics after IF treatment, but not in patients of Group 2, who demonstrated signs of cytokine dysregulation due to continuing specific inflammatory process. Conclusions. Tuberculosis remains one of the global health problems. The general trend in the spread of tuberculosis and mortality from it throughout the world requires urgent efforts to the detection and treatment of this disease. In patients with IF pulmonary TB standard treatment was less effective in case of slow insufficient decrease in the levels of CRP, IL-10, γ-INF, and the CD4/CD8 ratio which was associated with slow cavities healing, continuing spreading of the infiltrative process. These patients needed prolonged treatment regimen.

Patients with ACO have significant poorer health-related quality of life and more severe functional limitations compared to asthma and COPD alone. Most commonly, chronic respiratory disease is associated with cardiovascular disease, such as arterial hypertension. However, the impact of concomitant cardiac diseases on the quality of life and functional status of patients with ACO remains poorly understood. The aim of the work was to study dynamics of functional condition and quality of life in with ACO and concomitant AH against the background of complex therapy. Materials and methods. We selected for participating in the study 100 patients with ACO and concomitant AH. Examination of the patients included: clinical methods, spirometry, and questinaries – mMRS, CAT, SGRQ, performing 6MWT. Results. After 16 weeks of treatment there were no changes in lung functional status in patients on standard treatment, at the same time, in group of patients who had an active rehabilitation program, there was a significant improvement in the bronchial response to the action of bronchodilators, although other indicators of the functional status of the lungs didn't show significant changes. Patients who additionally used an active rehabilitation program had a significant improvement in clinical symptoms, shortness of breath, and quality of life according to CAT, mMRC, and SGRQ scores, respectively. There was also a significant increase in distance during the 6MWT in this group of patients. Conclusions. Conducting an active rehabilitation program (physical rehabilitation in combination with an educational program and self-management) in group of patients with ACO and concomitant AH, who are on standard medical treatment, significantly improves the bronchial response to the action of bronchodilators, decreases clinical manifestations, shortness of breath and improve quality of life and exercise tolerance, according to CAT, mMRC, SGRQ and 6MWT questionnaires, respectively.

The study of the human immune system state in infection with M. tuberculosis is relevant because the course and outcome of this disease are largely determined by the immune status of the patient. However, 98 % of patients with pulmonary tuberculosis have an immune imbalance. It is known that in the protection against tuberculosis an important role belongs to the body's natural resistance, which is provided by a variety of cellular and humoral factors, physicochemical characteristics of tissues, lymphoid cells, leukocyte and macrophage responses and genetic resistance. When mycobacteria enter the body, polymorphonuclear leukocytes, monocytes and macrophages are the main phagocytic cells. Optimally high level of resistance to the pathogen develops only in the coordinated interaction of T−lymphocytes with macrophages. Studies of cellular immunity and genetic markers have shown that the course of tuberculosis infection is associated with suppression of their functional activity. Immune response deregulation is closely related to oxidative stress, which results from an imbalance between free reactive oxygen species and antioxidant mechanisms, with a higher risk of developing it rather in lungs than other organs. Many studies have presented the results of studying the state of the immune system and the "oxidative stress − antioxidant protection" system in tuberculosis. This is an important component, because the clinical course and outcome of treatment is largely determined by the status of these systems. A number of experts point out that the study of immunological and oxidative parameters in tuberculosis is of a great importance for deciding on the tactics of treatment and the choice of direction of influence on the course of the disease. Key words: M. Tuberculosis, immunity in tuberculosis, oxidative stress, antioxidant protection.