The Ukraine ranks among the top 20 countries with the highest number of multidrug-resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis 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 ( n = 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 M. tuberculosis 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 inhA gene promoter mutations, a diversity of mutation types in the rpoB 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.

Background. Co-infection of tuberculosis and HIV is a global challenge exacerbated by the mutual influence of these diseases. HIV increases the risk of tuberculosis by 25–30 times, while tuberculosis accelerates HIV progression. According to WHO, 443,000 tuberculosis cases were reported among HIV-infected individuals in 2023. In Ukraine, 18,140 TB cases were recorded in 2024, with 14.7% being HIV-positive, and one in three co-infected individuals dies from tuberculosis. Tuberculosis-associated immune reconstitution inflammatory syndrome is a serious issue, complicating the management of both diseases and increasing mortality. Purpose – to evaluate the immunological features of HIV/tuberculosis co-infection, pathogenesis, and challenges in diagnosing, preventing, and treating tuberculosisassociated immune reconstitution inflammatory syndrome. Materials and Methods. A systematic literature review for 2015–2025 was conducted using PubMed, Scopus, and Web of Science with the terms: «HIV», «tuberculosis», «tuberculosis-associated immune reconstitution inflammatory syndrome», «immunopathogenesis», and «antiretroviral therapy». Abstracts, full texts, and relevance were analyzed. Results. HIV depletes CD4+ T-cells, reducing IFN-γ and TNF-α, which promotes tuberculosis progression. Tuberculosis-associated immune reconstitution inflammatory syndrome results from hypercytokinemia, inflammasome activation (NLRP3, AIM2), and tissue damage by metalloproteinases MMP-8 and MMP-9. Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome is linked to Th1 responses (IFN-γ, IL-2, IL-12, TNF-α), hyperactivation of CD4+ cells (PD-1+, HLA-DR+), reduced PGL-Tb1 antibodies, and monocyte activation (CD163+). Risk factors include low CD4 counts, short intervals before initiating antiretroviral therapy, and extrapulmonary tuberculosis. Diagnosis is challenging due to the lack of biomarkers (CRP, IL-6, IL-18). Treatment involves prednisone, NSAIDs, and TNF-α inhibitors; prevention includes isoniazid and optimized antiretroviral therapy. Conclusions. Tuberculosis-associated immune reconstitution inflammatory syndrome complicates the management of HIV/tuberculosis co-infection due to hypercytokinemia and inflammasome activation. Diagnosing non-manifest tuberculosis-associated immune reconstitution inflammatory syndrome is problematic due to the lack of biomarkers. Corticosteroids are effective in managing this condition, but targeted therapies are needed.

Multidrug-resistant tuberculosis (MDR TB) has found in 22 % new cases of tuberculosis (TB) and in 56% of retreated cases in Ukraine (WHO, 2015). The aim: of the study was to estimate resistant of different M.tuberculosis (MBT) strains of MDR-TB patients. Materials and methods: In 2014-2015, the 93 cases of MDR TB had studied in Kharkiv, Ukraine. MBT identification and drug susceptibility testing (DST) had performed as recommended by WHO. VNTR genotyping was done by using sets of primers for amplification of five exact tandem repeats ETR loci (A, B, C, D, E). Results and discussion: It was determined the variability of each locus by PCR from all 93 strains. By the VNTR-genotyping, the most common genotype was Beijing (69%). It was also demonstrated genotype LAM (13%), Africanum (3%) and Harlem (2%). 12 strains had not identified because of unique VNTR profiles. Among the 93 patients with MDR-TB in 52 (56%) cases was found tuberculosis with enhanced resistance (XDR-TB). There were no significant statistical differences in resistance frequency to the first-line anti-TB drugs among MBT strains (p>0.05). In 26 cases MBT from Beijing clade were resistant to all first-line anti-TB drugs. In 69% and 60% cases respectively were found the resistance to Kanamycin (Km) and Ofloxacin (Ofx). The frequency of resistance to Km, Para-aminosalicilic acid (PAS) and Ethionamid (Et) was revealed significantly higher for LAM in compare to Beijing (p<0.05). Conclusions: It is dificulte situation with MDR TB in Kharkiv region, Ukraine. Dominant strain of MDR TB is Bejing - 69% of cases. The resistance to the second-line anti-TB drugs revealed significantly higher for LAM strain in compare to Beijing strain.