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Tuberculosis and Lung Diseases

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Vol 103, No 6 (2025)
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ORIGINAL ARTICLES

8-16 99
Abstract

The objective: to compare effectiveness and safety of treatment of drug-susceptible tuberculosis when using four-month and six-month chemotherapy regimens.

Subjects and Methods. A multicenter cohort study was conducted from October 2023 to August 2025 to study treatment of drug-susceptible tuberculosis using a short-course (four-month) regimen (SC Group) of chemotherapy (CT) compiled of the following agents: rifapentine (900 mg daily), isoniazid, pyrazinamide, and levofloxacin in the intensive phase for two months and rifapentine (900 mg daily), isoniazid, and pyrazinamide in the continuation phase. Comparison Group (CG) included patients who received a six-month chemotherapy regimen for drug-susceptible tuberculosis during the same period. Effectiveness was assessed by sputum conversion and clinical and radiological changes.

Results. Effective treatment was achieved in 92.0% (46/50) of patients in Short-Course Regimen Group versus 76.6% (46/60) in Comparison Group (p = 0.038). Sputum conversion by smear according to microscopy data by the end of therapy was registered in 96.0% (48/50) and 76.7% (46/60), respectively (p = 0.005); and sputum conversion by culture was reported in 94.0% (47/50) and 73.3% (44/60) (p = 0.004). The overall frequency of adverse reactions was significantly lower in the Short-Course Regimen Group (57.7% vs. 74.6%; p = 0.045). 

17-23 75
Abstract

The objective: evaluation of potential of modern methods of rifampicin susceptibility testing in detection of heteroresistance of Mycobacterium tuberculosis cultures.

Subjects and Methods. Mixtures of susceptible (H37Rv) and resistant (strain 5521 with XDR, with the rpoB Ser531Leu mutation) Mycobacterium tuberculosis strains were artificially created in proportions from 0% to 100%. Phenotypic methods (BACTEC MGIT 960, proportion method on Middlebrook 7H10 medium) and molecular genetic tests (TB-TEST, Amplitub-MLU-RV, AmpliTest MBT-Resist I) were used to test resistance to rifampicin.

Results. Phenotypic methods revealed resistance to rifampicin with 1% resistant cells in the mixture. Molecular genetic methods showed variable detection thresholds: 5% (AmpliTest MBT-Resist I), 20% (TB-TEST), and 30% (Amplitub-MDR-RV). The authors demonstrate possibility of enhancing the sensitivity of domestic molecular genetic test systems by improving PCR data interpretation software, as well as the need to develop algorithms for tuberculosis diagnosing, taking into account limitations of the methods used. 

24-29 94
Abstract

The objective: to identify early factors of unfavorable course of TB/HIV co-infection in order to improve approaches to treatment of such patients.

Subjects and Methods. The study included 105 HIV-positive patients diagnosed with tuberculosis for the first time and M.tuberculosis (MTB) DNA was detected in a biological sample by a molecular genetic test. Patients were divided into two groups: a group with a favorable course of TB/HIV co-infection (78 people) and a group with an unfavorable course (27 people).

Results. Significant factors influencing the course of TB/HIV co-infection and easily assessible in each patient (levels of leukocyte (x), hemoglobin (y), albumin (z), and iron (w)) were identified. A discriminant model was developed representing formula D = -8.263-0.110x + 0.012y + 0.197z + 0.024w. The accuracy of the model is 83.3%. If this parameter D ≥ -0.301, then a patient has a low risk of an unfavorable course of the co-infection; if D < -0.301, a patient faces a high risk of an unfavorable course of TB/HIV co-infection. In case of an unfavorable prognosis, an extended molecular genetic testing of M. tuberculosis drug susceptibility will allow choosing an adequate anti-tuberculosis treatment regimen. If no data about M. tuberculosis are available, treatment regimens for drug-resistant tuberculosis should be used. 

30-40 63
Abstract

The objective: to evaluate the effectiveness and safety of recombinant interferon gamma in the combination therapy of drug-resistant pulmonary tuberculosis.

Subjects and Methods. 84 patients with drug-resistant tuberculosis were enrolled in the study, who were randomized equally into two groups: Main Group (MG) and Control Group (CG). In both groups, patients received anti-tuberculosis chemotherapy in accordance with the individual drug susceptibility of Mycobacterium tuberculosis. Patients in MG additionally received recombinant interferon gamma (rIFN-γ) (intramuscularly, 500,000 IU once a day daily for 3 months). The patients were followed up for 6 months.

Results. During treatment in the patients from both groups, clinical manifestations of tuberculosis decreased, but in MG this occurred faster. In MG, sputum conversion was reported on average after 18.6 days of treatment (by smear) and 16.8 days (by culture) versus 28.8 days and 25.5 days, respectively, in the CG (p0.05). A total of 87 AEs were reported: in 48 patients in MG and in 39 patients in CG. The majority of patients developed 1-2 AEs. The most common AEs were abnormal laboratory rates. In all patents from MG, the tolerability of rIFN-γ was assessed as excellent. The study revealed that rIFN-γ as a 3-month course in addition to anti-tuberculosis chemotherapy could shorten the treatment time and improve effectiveness of treatment in patients with drug-resistant tuberculosis. 

41-47 64
Abstract

The objective: to study factors influencing treatment outcomes in new tuberculosis patients from indigenous populations of the North (IPN) living in the Yamalo-Nenets Autonomous Area (YNAA).

Subjects and Methods. A retrospective cohort study of treatment outcomes of new patients registered for treatment with drug-susceptible tuberculosis regimens in the Yamalo-Nenets Autonomous Area in 2010-2022 was conducted. A factor analysis of predictors of unfavorable chemotherapy outcomes in patients from indigenous population was performed.

Results. Among patients from indigenous population, there is a lower proportion of successful treatment (58.79%) than among non-native permanent residents (68.45%; p = 0.001) due to high level of consequent drug resistance detection and a higher proportion of patients transferred for treatment with relevant chemotherapy regimens (p < 0.0001), as well as a higher proportion of chemotherapy failures (p = 0.001), in some patients it was associated with alcohol dependence syndrome (aOR = 2.80; p = 0.045), and late detection of tuberculosis (p = 0.01). To reduce the proportion of treatment failures among indigenous populations, it is advisable to consider their annual fluorographic examination. 

48-56 66
Abstract

The objective: comparative assessment of hepatotoxicity of combinations of anti-tuberculosis drugs (ATBDs) including those recommended for short-course chemotherapy and analysis of protective properties of Semax and ascorbigen.

Subjects and Methods. The study consisted of 2 experiments with different combinations of anti-tuberculosis drugs and the accompanying drug. In Experiment 1, rats in the experimental groups received Mxf Lzd Pto Cs Z and Mxf Lzd Pto Cs Z + Semax; in Experiment 2, they received Mxf Lzd Pto Bdq Cfz and Mxf Lzd Pto Bdq Cfz + ascorbigen. Rats in control groups were administered 1% starch gel orally. The duration of administration made 14 days in all groups. Hepatotoxicity was assessed by biochemical parameters and pathomorphological criteria.

Results. In rats, receiving Mxf Lzd Pto Cs Z, a statistically significant increase in transaminase and total bilirubin levels as well as profound changes in liver tissue were detected versus Control Group. In rats receiving Mxf Lzd Pto Bdq Cfz, despite the elevated transaminase activity, pathomorphological changes in the liver were less severe. The use of Semax and ascorbigen contributed to the improvement of enzymatic activity and lower liver tissue damage. It has been shown that the toxicity modifying properties of ascorbigen are more pronounced, however, the hepatoprotective potential of Semax was manifested when the structural liver disorders were more severe. 

58-65 55
Abstract

The objective: to evaluate the use of two-stage arthroplasty in the treatment of a destructive form of septic gonitis of tuberculous and non-specific etiology including HIV-positive patients.

Subjects and Methods. 15 patients with a destructive form of septic gonitis of both non-specific and tuberculous etiology were enrolled in the study, all those patients underwent surgical treatment. In 7/15 (46.67%) patients, the disease was caused by M. tuberculosis, in 8 (53.33%) it was a non-specific disease, and 5/15 (33.33%) patients were HIV-positive. The patients were planned to undergo a two-stage endoprosthetics using cemented articulating spacers saturated with antimicrobial drugs, according to the drug susceptibility of the pathogen. 10 patients (66.67%) underwent a full cycle of two-stage endoprosthetics, and 5 cases (33.33%) underwent the first stage only.

Results. In all 15 cases, sustained eradication of the infection was achieved. In 10 patients who completed the entire cycle of surgical treatment, a statistically significant improvement in the KSS scores was obtained from 35.4 ± 15.4 to 78.2 ± 15.1 (p<0.05), the observation period ranged from 1 year to 14 years. No significant impact of HIV infection on the treatment results was observed.

66-73 62
Abstract

The objective: to assess the functional outcomes of extrapleural thoracoplasty among patients with destructive tuberculosis and comorbid human immunodeficiency virus (HIV) 6 months after the performed surgery.

Subjects and Methods. 49 HIV/TB co-infected patients were subjected to a retrospective study 6 months after the extrapleural thoracoplasty. A control group comprised similar 49 patients with destructive pulmonary tuberculosis but without HIV infection. The following functional characteristics were analyzed: dynamics of dyspnea, vital capacity of lungs (VC), forced expiratory volume of the air exhaled in the first second (FEV1), the Tiffeneau-Pinelli index and indicators of the pulmonary capillary blood flow (PCB).

Results. In MG, extrapleural thoracoplasty contributed to the healing of cavities by 6 months in 30.6% (15/49 patients) and sputum conversion in 46.9% (23/49 patients). Those parameters did not differ significantly from those in patients from Comparison Group (with HIV-negative status). Deterioration of spirometry results was recorded in 28.3±14.6% of patients in MG and 29.5±14.6% in CG, p>0.05; PCB remained at the preoperative level in both groups. A subgroup of 14 (28.6%) patients with limited (insufficient) effect after extrapleural thoracoplasty showed a significant decrease in the degree of dyspnea as well no significant changes in the spirometric values. Thus, extrapleural thoracoplasty can be considered functionally safe.

CLINICAL OBSERVATIONS

74-81 63
Abstract

The article describes a clinical case of successful treatment of a 13-year-old female patient with post-tuberculous stenosis of the left main bronchus of grade 3-4 using a self-fixing endoprosthesis. As a result of 24 months of anti-tuberculosis chemotherapy and 18 months of endoprosthetics, it was possible to cure tuberculosis of the lungs and bronchi, restore the function of the left main bronchus, and avoid organ-removing surgery in the child. The method of treatment with self-fixing endoprostheses in a pediatric phthisiological practice was used for the first time. 

82-87 56
Abstract

Tuberculosis of the female genital organs mostly affects women of the reproductive age; less often, the disease develops in postmenopausal women. The article describes a clinical case of diagnosis of genital tuberculosis in a 72-year-old woman. The ultrasound examination of her abdomen revealed intrauterine fluid collection and fluid formations in the right ovary. No data relevant for diagnosis were provided through testing of scrapings from the walls and cervix of the uterus. Laparoscopy detected pronounced adhesions and an encapsulated lesion. Histological testing of surgical specimens confirmed tuberculosis. 

REVIEWS

88-95 59
Abstract

In recent years, much attention has been paid to phage technologies as promising methods for rapid testing of drug susceptibility of bacteria, including Mycobacterium tuberculosis. Mycobacteriophages are capable to infect specifically M. tuberculosis, which makes it possible to develop new effective, cost-efficient diagnostic tests, as well as fundamentally new drugs for tuberculosis treatment. This review analyzes twenty-seven publications describing main methods for testing the spectrum of drug susceptibility of M. tuberculosis based in mycobacteriophages. The advantages of these methods are the following: rapidness (results are obtained within 24-96 hours from the test start), and specificity (based on a strict host range of the phage). This allows for the rapid detection of M. tuberculosis and its susceptibility to anti-tuberculosis drugs. 

96-103 90
Abstract

Trehalose probes seem to be a promising area of tuberculosis diagnosis, these probes are capable of selectively penetrating Mycobacterium tuberculosis. These probes generate a fluorescent signal, enabling detection of mycobacteria. To analyze the current state of knowledge and prospects of trehalose probes as a new approach for rapid detection of Mycobacterium tuberculosis, a systematic review of scientific literature was conducted. The main types of probes include fluorogenic probes, "fluorophore-quencher" based probes, and photoactivatable probes. Trehalose probes enable selective detection of mycobacteria due to specific trehalose uptake and incorporation into the cell wall, followed by fluorescence activation. These probes allow for the detection of mycobacteria in sputum samples without complex sample preparation or washing. The method allows differentiation of viable and non-viable cells and can also be applied for drug susceptibility testing. 

104-116 73
Abstract

Pharmacogenetic testing is the most promising tool in personalized medicine aimed at enhancing effectiveness and safety of treatment, especially in complicated cases with comorbidities. The review analyzes 122 publications devoted to theoretical and applied aspects of pharmacogenetic testing in the treatment of tuberculosis patients. It considers the role of genetic polymorphisms in the response to treatment, and presents data on proteins involved in pharmacokinetics and pharmacodynamics of main anti-tuberculosis drugs and the genes encoding these proteins. The review analyzes the list of the most significant markers associated with the risk of adverse reactions during treatment of drug-sensitive and drug-resistant tuberculosis, and it characterizes prospects for their use in clinical practice. The list of references contains 56 key publications cited in the text. 



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ISSN 2075-1230 (Print)
ISSN 2542-1506 (Online)