Objective : to develop a reproducible model of tuberculous enterocolitis in laboratory animals comparable in its pathomorphological characteristics to intestinal tuberculosis in humans. Materials and methods . The experiment was conducted on 10 male Soviet Chinchilla rabbits. One day before infection, the animals were administered infliximab (16 mg/kg) intravenously to simulate immunosuppression. Laparotomy was performed under general anesthesia, followed by the introduction of a suspension of the international reference virulent Mycobacterium tuberculosis H 37 Rv strain (10 6 CFU in 0.5 ml of normal saline) into the cranial mesenteric artery and the fiber of the mesentery of the small intestine. During the 72–90–day observation, behavioral patterns and body weight were monitored, and an intradermal test with recombinant tuberculosis allergen (RTA, Diaskintest®) was performed. At the end of the experiment, pathomorphological (hematoxylin and eosin staining and Ziehl-Neelsen staining) and molecular genetic (PCR) studies of the abdominal and thoracic organs were conducted. Results . A positive RTA skin test on day 30 confirmed the development of a specific immune response. All infected animals (100%) exhibited specific granulomatous changes in the intestinal wall, mesentery and omentum (80%), with the formation of epithelial cellular granulomas, caseous necrosis and the presence of acid-fast mycobacteria (AFB). Specific lung lesions were detected in 90% of rabbits, 70% had enlarged intraabdominal lymph nodes, with caseous necrosis observed in 40% of the animals. PCR analysis detected MBT DNA in 80% of intestinal samples and 90% of lung samples. Conclusion . A reproducible model of tuberculous enterocolitis was established, characterized by the development of specific granulomatous inflammation within the intestine and mesentery.
Objective : to evaluate the impact of employment in the coal mining industry on tuberculosis (TB) incidence amid the implementation of preventive measures for dust-induced lung diseases and TB. Materials and methods . We analyzed data from a patient-level TB registry that allows for the identification of coal mining industry workers, employees of other industries, and the general population between 2014 and 2022. When comparing TB incidence rates, we evaluated age groups comparable to coal miners (21-68 years) and performed sex-stratification and sex-standardization of TB incidence rates. Results . Between 2015 and 2022, TB incidence rates among coal mining industry workers ranged from 37.3 to 51.6 per 100,000 population, including from 40.7 to 70.2 per 100,000 among men. Their incidence rates did not differ statistically significantly from those in workers of other industries ( p > 0.2) and were statistically significantly lower than the TB incidence in the general population of the Kemerovo region of comparable age (21–68 years) ( p < 0.0001). Conclusion. Employment in the coal mining industry does not constitute a TB risk factor amid advanced labor legislation, provision of personal and collective protective equipment, and regular preventive medical examinations.
Objective : to evaluate the impact of Gln27Glu polymorphism in the β₂-adrenergic receptor gene on immune status parameters and lipid metabolism in patients with asthma stratified by obesity phenotype. Materials and methods . The study included 156 Uzbek patients with bronchial asthma (BA) aged 18-65 years. Group 1 comprised patients with obesity ( n = 71), Group 2 included patients without obesity ( n = 85). The control group consisted of 47 healthy individuals. Genotyping of the Gln27Glu polymorphism in the β₂-adrenergic receptor gene was performed. Serum levels of total immunoglobulin E (IgE), interleukin-4 (IL-4), and interferon-γ (IFN-γ) were measured, along with the lipid profile parameters, including total cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and the atherogenic index. Results : Patients with BA exhibited a shift in the immune response toward a Th2 phenotype: IgE and interleukin-4 levels were significantly increased, while IFN-γ was decreased compared to the control group ( p < 0.01). The most pronounced alterations were observed in Group 1, particularly in patients carrying the Gln27Gln genotype, who exhibited the highest levels of IgE and IL-4, reduced IFN-γ levels, and atherogenic lipid profile abnormalities. In the absence of obesity (Group 2), the Gln27Gln polymorphism was not associated with significant differences in immunological or lipid parameters among the genotypes, suggesting that the effect of this genetic variant is primarily manifested in the presence of obesity.
Objective : to evaluate the efficacy and safety of a rifapentine-containing regimen in treatment of patients with drug-susceptible respiratory tuberculosis and gastrointestinal comorbidities, compared to the standard 6-8 month regimen. Materials and Methods . An analysis of treatment efficacy and safety was performed in 204 patients with drug-susceptible respiratory tuberculosis who completed a full course of therapy. Inclusion criteria: male and female patients aged 18 years and older, newly diagnosed with respiratory tuberculosis with preserved susceptibility of Mycobacterium tuberculosis to the first line drugs, and concomitant gastrointestinal diseases. Exclusion criteria: HIV infection, acute liver diseases of various etiologies, decompensated liver cirrhosis, grade II–III pulmonary heart failure, and chronic renal failure. Patients in the main group (MG, n=77) received a modified chemotherapy regimen for drug-susceptible tuberculosis, where rifapentine replaced rifampicin in both the intensive and continuation phases. The comparison group (CG, n= 127) received standard chemotherapy regimens. Results . By the end of month 4, sputum culture conversion was achieved in 77.8% of patients in the main group and 46.5% of patients in the comparison group. Lung cavity scarring within 6 months of chemotherapy was observed in 84.4% of patients in the main group, versus 51.5% in the comparison group. Adverse events were reported in 2.6% of patients in the main group and 14.2% in the comparison group (p < 0.05). Conclusion . A modified rifapentine-containing regimen for treatment of drug susceptible tuberculosis is effective and safe in patients with gastrointestinal comorbidities.
Objective : to identify risk factors associated with the development of acute progressive tuberculosis (TB) in HIV-negative patients. Materials and methods : A case-control study included 342 HIV-negative patients with newly diagnosed TB, who were hospitalized at the I.F. Kopylova Kuzbass Clinical Phthisiopulmonology Medical Center (Kemerovo, Russia) in 2022–2025. Group 1 (n=135) comprised patients with acute progressive forms of TB (disseminated TB, caseous pneumonia), whereas Group 2 (n=207) consisted of patients with non-acute forms of TB (focal, infiltrative, cavernous TB, tuberculoma). A total of 66 variables were analyzed, encompassing sociodemographic, anamnestic, clinical, and genetic factors (38 polymorphic variants in genes of the vitamin D system and the NF-kB1 – 20S proteasome system). Genotyping was performed using real-time polymerase chain reaction (PCR). Results : Medical and social risk factors associated with the development of acute progressive forms of TB included unemployment among working-age individuals ( p = 0.01; OR = 1.8), alcohol dependence syndrome ( p = 0.03; OR = 1.8), rural residence ( p = 0.01; OR = 2.0), and the presence of chronic non-communicable diseases ( p = 0.005; OR = 1.9). Among comorbid conditions, diabetes mellitus was identified as the most significant risk factor ( p = 0.01; OR = 3.35). The risk of acute progressive TB was particularly associated with decompensation of carbohydrate metabolism (HbA1c >9%, p =0.02; OR=5.33) and poor patient adherence to regular medical follow-up ( p =0.01; OR = 7.19). In patients with acute progressive TB, pre-XDR and XDR strains of Mycobacterium tuberculosis were detected more frequently ( p = 0.001; OR = 3.63). Molecular genetic analysis revealed that the risk of acute progression of TB is associated with polymorphisms in genes involved in vitamin D transport and binding (GC rs3755967-CT genotype, OR=2.12; rs7041-AC genotype, OR=2.17), primary activation (CYP2R1 rs10741657-AA genotype, OR=0.43), degradation of active forms (CYP24A1 rs2209314-TT genotype, OR=0.54; rs2296241-AA genotype, OR=0.51), as well as with the pro-inflammatory factor gene NFKB1 (rs4648050-TC genotype, OR=1.81).
