Objective : analysis of clinical and economic efficiency of various etiotropic chemotherapy regimes in patients with respiratory tuberculosis with multidrug- and extensively drug-resistant (MDR and XDR) pathogen using the pharmacoeconomic modeling method (Markov model). Material and methods . A single-centre, observational, retrospective, cohort study was performed, which included patients who received treatment in clinics and affiliated organizations of the main Moscow tuberculosis institution during 2014–2019 regarding respiratory tuberculosis with the MDR/XDR pathogen. The data of 1387 patients were analysed, of which 1093 patients received “optimized basic regimen” (OBR) in accordance with the Federal Clinical Recommendations of 2015, 294 patients received etiotropic therapy in accordance with the recommendations of the World Health Organization of 2018–2019. To evaluate economic efficiency, the pharmacoeconomic costeffectiveness analysis and pharmacoeconomic modeling were used. When assessing the economic costs of treatment, the direct costs (medical and non-medical) were taken into account. Results . The study results showed that 68.4% of patients in the group with bedaquiline-containing chemotherapy regimens reached the outcome of “treatment successfully completed” (patient was cured or transfered into the III group of dispensary follow-up) compared to 51.8% in the OBR group. The use of “new” etiotropic therapy regimens is most economically justified in patients with ХDR-tuberculosis with repeated treatment courses: incremental cost-effectiveness ratios (ICER) were 24,530.20 and 21,526.50 rubles per 1 patient. Markov model was developed, transitions from one state to another were evaluated according to the results of clinical observations during the first 2 years of research. Conclusion . The use of the dynamic model of the patient state made it possible to refine the estimates of the effectiveness of the compared etiotropic chemotherapy regimens for tuberculosis with MDR/XDR pathogen. Based on the results of modeling the dynamics of patients in the interval of 2 to 10 years of treatment, the use of “new” regimens provides a significant increase in the proportion of treatment success (by 16.1–29.8% in different groups of patients and at different times), a decrease in mortality (by 6.1–11.0%), and in the proportion of those who interrupted treatment (by 8.0–21.8%) in comparison with OBR.

The experience of the centralized control of the appointment and implementation of chemotherapy regimens for MDR/XDR TB by subcommittee of the head TB-physicians board of the Moscow Scientific and Practical Center for Tuberculosis Control in 2014-2021 presented. Totally, 6023 cases considered, 30% – primary diagnosis and treatment, 70% – monitoring of treatment. As a result of measures carried out under centralized control, the number of patients with respiratory MDR/XDR TB decreased by 4 times: from 752 in 2011 to 189 in 2021, mainly due to the cure of patients. There was a significant increase in the effectiveness of treatment of patients with MDR/XDR TB: in the 2013 cohort, the effective treatment courses was 45.9%, in the 2018 cohort. – 69.6%, while there was a decrease in the proportion of ineffective courses by almost 2 times – from 14.0 to 7.9%, a decrease of interrupted treatment by more than 2 times – from 12.2% to 4.8%, a decrease in the proportion of deaths from tuberculosis by 3 times – from 8.7% to 2.8%. The main difficulties of implementing new regimens of MDR/XDR TB chemotherapy have also been identified. The presence of comorbidity prevents the appointment of at least one of the most effective anti-tuberculosis drugs (bedaquiline, linezolid, moxifloxacin, cycloserine) in at least 25% of patients. The frequency of adverse events (AE) in MDR/XDR TB patients was 2nd stage severity was 33.2%, 3-4 stage – 5.3%. Correction of chemotherapy regimens with the exclusion and/or replacement of anti-tuberculosis drugs was necessary due to AE in general in 52.5% (95% CI 41.7-63.1%) of patients, and in 2.5% of cases chemotherapy was canceled completely, for a period of a week to 1.5 months. In at least 20% of patients, an important task is to ensure proper adherence of the patient to treatment, which requires counseling by a psychologist.

Background Longitudinal cohort data of patients with tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19. Methods We collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk-regression models, and the log-rank test was used to compare survival and mortality attributed to TB, COVID-19 or both. Results Overall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19 versus those dying because of either TB or COVID-19 alone (p<0.001). Significant adjusted risk factors for TB mortality were higher age (hazard ratio (HR) 1.05, 95% CI 1.03-1.07), HIV infection (HR 2.29, 95% CI 1.02-5.16) and invasive ventilation (HR 4.28, 95% CI 2.34-7.83). For COVID-19 mortality, the adjusted risks were higher age (HR 1.03, 95% CI 1.02-1.04), male sex (HR 2.21, 95% CI 1.24-3.91), oxygen requirement (HR 7.93, 95% CI 3.44- 18.26) and invasive ventilation (HR 2.19, 95% CI 1.36-3.53). Conclusions In our global cohort, death was the outcome in >10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes.

OBJECTIVES:Although evidence is growing on the overall impact of the COVID-19 pandemic on tuberculosis (TB) services, global studies based on national data are needed to better quantify the extent of the impact and the countries' preparedness to tackle the two diseases. The aim of this study was to compare the number of people with new diagnoses or recurrence of TB disease, the number of drug-resistant (DR)-TB, and the number of TB deaths in 2020 vs 2019 in 11 countries in Europe, Northern America, and Australia. METHODS:TB managers or directors of national reference centers of the selected countries provided the agreed-upon variables through a validated questionnaire on a monthly basis. A descriptive analysis compared the incidence of TB and DR-TB and mortality of the pre-COVID-19 year (2019) vs the first year of the COVID-19 pandemic (2020). RESULTS:Comparing 2020 vs 2019, lower number of TB cases (new diagnosis or recurrence) was notified in all countries (except USA-Virginia and Australia), and fewer DR-TB notifications (apart from France, Portugal, and Spain). The deaths among TB cases were higher in 2020 compared to 2019 in most countries with three countries (France, The Netherlands, USA-Virginia) reporting minimal TB-related mortality. CONCLUSIONS:A comprehensive evaluation of medium-term impact of COVID-19 on TB services would benefit from similar studies in multiple settings and from global availability of treatment outcome data from TB/COVID-19 co-infected patients.

The objective: to justify the optimal duration of chemotherapy with Lzd and Bdq by evaluating the long-term treatment outcomes in patients with multiple/pre-extensive drug resistant (MDR/preXDR) tuberculosis who interrupted treatment at different time points. Subjects and Methods. 800 patients with MDR/preXDR tuberculosis were enrolled in the study, they were from all regions of the Russian Federation and they started a course of chemotherapy with regimens containing Lzd and Bdq in 2017-2018. All patients who interrupted their chemotherapy (124) were divided at 4 groups. Group 1-43 patients who received less than 90 doses, Group 2-37 patients who received from 91 to 180 doses, Group 3-39 patients who received from 181 to 270 doses, and Group 4-5 patients who received from 271 to 360 doses of anti-tuberculosis drugs. Results. In Group 3, the effectiveness of reaching a favorable outcome during observation for 3-4 years made 53.8% in 21/39, which was comparable to the effectiveness of treatment with a 24-month course of chemotherapy (2017 – 58.0 and 2018 – 52.1%). The treatment duration of patients from Group 3 was additionally analyzed, the arithmetic mean of the number of administered doses makes 262 ± 15, which allowed recommending 9-month courses of chemotherapy.

Background:The control of tuberculosis (TB) may benefit from a prospective identification of areas where the incidence may increase in addition to the traditionally identified foci of high incidence. We aimed to identify residential areas with growing tuberculosis incidence rates and assess their significance and stability.Methods:We analysed the changes in TB incidence rates using case data georeferenced with spatial granularity to apartment buildings in the territory of Moscow from 2000 to 2019. We identified sparsely distributed areas with significant increases in the incidence rate inside residential areas. We tested the stability of found growth areas to case underreporting via stochastic modelling.Results:For 21 350 cases with smear- or culture-positive pulmonary TB among residents from 2000 to 2019, we identified 52 small-scale clusters of growing incidence rate responsible for 1% of all registered cases. We tested clusters of disease growth for underreporting and found them to be relatively unstable to resampling with case drop-out, but their spatial displacement was small. Territories with a stable increase in TB incidence rate were identified and compared to the rest of the city, which is characterised by a significant decrease in incidence.Conclusions:Identified areas with a tendency for an increase in the TB incidence rate may be important targets for disease control services.

Sarcoidosis is a multi-organ granulomatosis of unknown origin. Modern diagnostic methods allow detecting this disease at an early stage. The absence of specific markers requires a comprehensive approach to diagnosis based on comparison of radiation, clinical, morphological and functional data. The course of sarcoidosis without damage to the respiratory system presents significant difficulties. It is extremely important to understand the time and means of starting Sarcoidosis’s treatment to avoid the early initiation of hormones and cytostatics and, on the other hand, to timely respond to progression and threatening conditions. Methods. Clinical recommendations are based on the analysis of Russian and English publications of the latest sarcoidosis research. The target audience of these clinical guidelines are therapists, general practitioners, pulmonologists, TB doctors, rheumatologists, dermatologists, radiation diagnosticians, immunologists, and clinical pharmacologists. Each thesis-recommendation for diagnosis and treatment is evaluated on an 1 to 5 scale of levels of evidence and an A, B, C scale of the grades of recommendations. The clinical guidelines also contain comments and explanations for the theses-recommendations, diagnostic algorithms, treatment strategies, reference materials on the use of recommended drugs. Conclusion. Current information on epidemiology, clinical manifestations, diagnosis and management strategies for patients with sarcoidosis are covered in the presented clinical guidelines. Approved by the decision of the Scientific and Practical Council of the Ministry of Health of the Russian Federation (2022).

BACKGROUND The bedaquiline-pretomanid-linezolid regimen has been reported to have 90% efficacy against highly drug-resistant tuberculosis, but the incidence of adverse events with 1200 mg of linezolid daily has been high. The appropriate dose of linezolid and duration of treatment with this agent to minimize toxic effects while maintaining efficacy against highly drug-resistant tuberculosis are unclear. METHODS We enrolled participants with extensively drug-resistant (XDR) tuberculosis (i.e., resistant to rifampin, a fluoroquinolone, and an aminoglycoside), pre-XDR tuberculosis (i.e., resistant to rifampin and to either a fluoroquinolone or an aminoglycoside), or rifampin-resistant tuberculosis that was not responsive to treatment or for which a second-line regimen had been discontinued because of side effects. We randomly assigned the participants to receive bedaquiline for 26 weeks (200 mg daily for 8 weeks, then 100 mg daily for 18 weeks), pretomanid (200 mg daily for 26 weeks), and daily linezolid at a dose of 1200 mg for 26 weeks or 9 weeks or 600 mg for 26 weeks or 9 weeks. The primary end point in the modified intention-to-treat population was the incidence of an unfavorable outcome, defined as treatment failure or disease relapse (clinical or bacteriologic) at 26 weeks after completion of treatment. Safety was also evaluated. RESULTS A total of 181 participants were enrolled, 88% of whom had XDR or pre-XDR tuberculosis. Among participants who received bedaquiline-pretomanid-linezolid with linezolid at a dose of 1200 mg for 26 weeks or 9 weeks or 600 mg for 26 weeks or 9 weeks, 93%, 89%, 91%, and 84%, respectively, had a favorable outcome; peripheral neuropathy occurred in 38%, 24%, 24%, and 13%, respectively; myelosuppression occurred in 22%, 15%, 2%, and 7%, respectively; and the linezolid dose was modified (i.e., interrupted, reduced, or discontinued) in 51%, 30%, 13%, and 13%, respectively. Optic neuropathy developed in 4 participants (9%) who had received linezolid at a dose of 1200 mg for 26 weeks; all the cases resolved. Six of the seven unfavorable microbiologic outcomes through 78 weeks of follow-up occurred in participants assigned to the 9-week linezolid groups. CONCLUSIONS A total of 84 to 93% of the participants across all four bedaquiline-pretomanid-linezolid treatment groups had a favorable outcome. The overall risk-benefit ratio favored the group that received the three-drug regimen with linezolid at a dose of 600 mg for 26 weeks, with a lower incidence of adverse events reported and fewer linezolid dose modifications. (Funded by the TB Alliance and others; ZeNix ClinicalTrials.gov number, NCT03086486.).

Background Information on tuberculosis (TB) and coronavirus disease 2019 (COVID-19) is still limited. The aim of this study was to describe the features of the TB/COVID-19 co-infected individuals from a prospective, anonymised, multicountry register-based cohort with special focus on the determinants of mortality and other outcomes. Methods We enrolled all patients of any age with either active TB or previous TB and COVID-19. 172 centres from 34 countries provided individual data on 767 TB-COVID-19 co-infected patients, (>50% population-based). Results Of 767 patients, 553 (74.0%) out of 747 had TB before COVID-19 (including 234 out of 747 with previous TB), 71 (9.5%) out of 747 had COVID-19 first and 123 (16.5%) out of 747 had both diseases diagnosed within the same week (n=35 (4.6%) on the same day). 85 (11.08%) out of 767 patients died (41 (14.2%) out of 289 in Europe and 44 (9.2%) out of 478 outside Europe; p=0.03): 42 (49.4%) from COVID-19, 31 (36.5%) from COVID-19 and TB, one (1.2%) from TB and 11 from other causes. In the univariate analysis on mortality the following variables reached statistical significance: age, male gender, having more than one comorbidity, diabetes mellitus, cardiovascular disease, chronic respiratory disease, chronic renal disease, presence of key symptoms, invasive ventilation and hospitalisation due to COVID-19. The final multivariable logistic regression model included age, male gender and invasive ventilation as independent contributors to mortality. Conclusion The data suggest that TB and COVID-19 are a "cursed duet" and need immediate attention. TB should be considered a risk factor for severe COVID disease and patients with TB should be prioritised for COVID-19 preventative efforts, including vaccination.

Objective. Тo study the features of humoral immunity to SARS-CoV-2 among the medical stuff of an antitubercular hospital in the context of the spread of a new coronavirus infection. Materials and methods. The interim results of a single-center prospective observational study involving 350 employees of a pulmonary tuberculosis hospital that was not repurposed to work with COVID-19 are presented. The results of weekly monitoring of IgM and IgG levels for the period from May 15 to November 28, 2020, were analyzed in comparison with the results of diagnosis of COVID-19 cases (identification of the pathogen in a smear from the oropharynx and nasopharynx, changes in lung tissue according to computed tomography). Results. During the observation period, COVID-19 was detected in 106 people (30.3%). Antibodies to SARS-CoV-2 (IgG and/or IgM) were detected at the start of monitoring in 30 people (8.6%, 95%CI 5.8-12.2%), by the end of the follow – up period-in 95 people (27.1%, 95%CI 22.7- 32.0%). The frequency of detection of antibodies in the patients was 70.8% (95%CI 55.6-88.7%): IgM class in 23 (21.7%), G class in 73 (68.9%). The median time from disease detection to IgM detection was 1.5 weeks. (interquartile range 0-4 weeks), before the discovery of IgG – 4 weeks. (interquartile range 2-5 weeks). At any follow-up period, the chances of IgG production in the protective titer were higher in the case of moderate or severe disease with the development of pneumonia compared to the mild course (OR 2.6, 95%CI 1.1-6.3); the IgG titer was also higher (p < 0.01). «Atypical» variants of the antibody response were identified in individuals with confirmed COVID-19: no antibody formation (31 people), production of class M antibodies only (4 people); long-term persistence of IgG in a titer of less than 30 g/l, long ahead of the disease manifestation (6 people). The sensitivity of serological testing as a method for detecting current and / or transmitted coronavirus infection was 70.8% (95%CI 61.1-79.2%), and the specificity was 91.8% (95%CI 87.6-94.9%). Conclusion. The frequency of detection of antibodies to SARS-CoV-2 among employees of the TB hospital corresponds to the dynamics of the incidence of COVID-19. Virus-specific antibodies were detected in 70.8% of COVID-19 survivors (IgG in 68.9%); in the absolute majority of patients, the antibodies remained in a significant titer (IgG > 10 g/l) for 6 months or more at the start of testing. When the disease occurs without the development of viral pneumonia, the chances of forming a significant and persistent antibody response are significantly lower. Serological testing is a sensitive and highly specific method for detecting a previous COVID-19 disease.

С целью совершенствования медицинской помощи населению г. Москвы при заболевании микобактериозами (МБ) проведены ретро- и проспективное исследования 165 больных в 2004–2018 гг. Для систематизации этиотропной терапии проведено детальное исследование лекарственной чувствительности (ЛЧ) нетуберкулезных микобактерий (НТМБ), и обнаружена широкая вариабельность спектров лекарственной устойчивости (ЛУ). Методом кластерного анализа предположили схему химиотерапии (ХТ) пациентов. Отметили важную роль хирургического лечения в комплексной терапии больных МБ. Отмечена зависимость эффективности лечения от некоторых клинических параметров, а хронический характер микобактериального воспаления определил длительное, иногда пожизненное наблюдение больных.

Background: Moscow, 13 million populated city, has one of the lowest tuberculosis (TB) notification rate in the Russia (17.7 per 100 K, 2020). City's TB control system was temporarily reorganized in accordance with the needs of isolation and treatment TB/COVID-19 patients (TBC19P). TBC19P database was organized to analyze the COVID-19 prevalence in TB patients. Aims: To analyzed the information about COVID-19 confection in the TB patients population. Methods: Data of 642 TBC19P and 3083 new and retreatment TB cases, all which were notified in the city in 2020 were analyzed. Results: Prevalence of COVID-19 among all TB patients registered for treatment in 2020 was 21.0%. TBC19P included 324 new TB cases (50.5% or 15.4% in all new TB cases), 73 relapses (11.3%) and 245 retreatment cases (38.3%). There are only 22.9% retreatment cases among all 2020 TB cohort (p < 0.01). Share of HIV was 20.7% and 21.9% in new TBC19P cases (14.4% among all new TB cases, p < 0.01). The median age was 42 (IQR=33-54), which more than for all TB cases (38, p <0.05). 39.6% of TBC19P patients were city resident, 19.5% homeless, 16.0% foreigners, 50.5% of TBC19P were unemployment. 49.4% cases had COVID-19 with not severe acute respiratory viral infection, 46.3% - pneumonia without respiratory distress and 3% with acute respiratory failure, 1.6% with ARDS syndrome. 14.7% TBC19P were detected by CT scan only, and other – by laboratory tests. 30.4% TBC19P had IgM >1 and 45.2% - IgG> 10. 92.7% of COVID-19 cases were cured and 6.4% (41) died: 31, 9 and 1 from COVID-19, TB, HIV, respectively. Conclusions: Analysis allows assessing the part of the TB patient population who are more susceptible to the disease, which is important for COVID-19 prevention and treatment.

Tuberculosis (TB) does not respect borders, and migration confounds global TB control and elimination. Systematic screening of immigrants from TB high burden settings and-to a lesser degree TB infection (TBI)-is recommended in most countries with a low incidence of TB. The aim of the study was to evaluate the views of a diverse group of international health professionals on TB management among migrants. Participants expressed their level of agreement using a six-point Likert scale with different statements in an online survey available in English, French, Mandarin, Spanish, Portuguese and Russian. The survey consisted of eight sections, covering TB and TBI screening and treatment in migrants. A total of 1055 respondents from 80 countries and territories participated between November 2019 and April 2020. The largest professional groups were pulmonologists (16.8%), other clinicians (30.4%), and nurses (11.8%). Participants generally supported infection control and TB surveillance established practices (administrative interventions, personal protection, etc.), while they disagreed on how to diagnose and manage both TB and TBI, particularly on which TBI regimens to use and when patients should be hospitalised. The results of this first knowledge, attitude and practice study on TB screening and treatment in migrants will inform public health policy and educational resources.

Background: Linezolid, bedaquiline, and newer fluoroquinolones are currently placed as priority Group A drugs for the treatment of drug-resistant tuberculosis. The number of reported linezolid-resistant clinical strains is still low, and the correlation of molecular determinants with phenotype is not perfect. Methods: We determined the linezolid MICs for clinical isolates from the Moscow region and identified mutations in rplC and rrl genes. Results: All 16 linezolid-resistant isolates had previously reported mutations in the rplC or rrl loci, and 13 of them bore a RplC C154R substitution. Detection of this substitution in a heteroresistant state was not successful, probably, due to the more stable DNA secondary structure of the mutated fragment, which precludes its amplification in mixes with the wild-type DNA. Strains with an rplC mutation had higher linezolid MIC compared to isolates with rrl mutations. Conclusions: Linezolid resistance mostly emerged during treatment with the latest regimen. Three primary cases with linezolid resistance question the possible transmission of totally drug-resistant tuberculosis in the Moscow region, which demands further investigation.

Tuberculosis (TB) is still common in many parts of the world, and requires monitoring, clinical assessment, testing, contact tracing, confirmation of diagnosis, and treatment regimens that are either supervised or unsupervised for effective eradication. We examine the problems posed by the COVID-19 pandemic to tuberculosis management and the current policies in place to address them. There are some similarities between tuberculosis and respiratory viral infectious illnesses, such as COVID-19. They mostly infect susceptible populations by droplet transfer or other infectious source transmission pathways. Acute respiratory infectious illnesses affect patients with tuberculosis and as Tuberculosis is one of the top ten causes of death worldwide patients with active tuberculosis more likely to have covid -19 infection, in this review paper we examine when two infection clash.

Introduction: Traditional methods of tuberculosis (TB) treatment outcomes assessment, based on laboratory results at the end of the therapy, does not permit distinguish advantage of surgery TB treatment. Long-term effectiveness such as TB relapses (RL), conversion to chronic cases (CHR), death from TB, HIV or concomitant diseases (CD), can be used as more vivid indicators of surgery effectiveness. Methods: Data of 2 cohorts of new and re-treatment TB cases from Moscow residents, who had treatment in 2010-2012 (A) and 2013-2016 (B), were analyzed. Each cohort, containing 10143 and 9807 respiratory TB patients, included 2 subgroups: 1) having and 2) not having surgery treatment for RTB (SG and NS, accordingly). Long-term indicators included share of RL, CHR, deaths from TB, HIV or CD, which were happened until 01/01/2016 and 01/01/2020 for A and B cohort respectively. Expansion of indications for surgical treatment in the B period compared with A has led to an increase in the number of surgery treated TB patients from 343 to 624. Results: Patients from A cohorts in SG and NS groups, respectively, accounted for: 2.3% and 1.7% RL (p > 0.05), 5.5% and 9.4% CHR (p < 0.05), 8.5% and 21.6% deaths (p < 0.01), including 1.7% and 5.4% death from TB (p < 0.01), 2.6% and 10.5% death from HIV and CD (p < 0.01). Patients from B cohorts in SG and NS groups, respectively, accounted for: 2.1% and 7.4% RL (p < 0.01), 3.5% and 9.4% CHR (p < 0.01), 5.6% and 23.0% deaths (p < 0.01), including 1.1% and 5.6% death from TB (p < 0.01), 1.6% and 11.3% death from HIV and CD (p < 0.01). Conclusion: Surgery treatment, evaluated by long-term indicators, demonstrates a high effectiveness both in general and after significant expansion of indications for surgery.

The authors categorised the patients with TB and COVID-19 co-infection into 3 groups based on timing of their diagnosis. However, in view of the difference in the natural history of TB (chronic course) and COVID-19 (acute), categorising 14 patients as having COVID-19 prior to TB (median time interval of 4 days between the two diagnosis) and nine as diagnosed simultaneously (within the same week) seems inappropriate. Since TB has an insidious onset, it is obvious that TB was present before COVID-19 infection in both the subgroups, although the diagnosis was made at different times. In fact, it may be right to say that all the three subgroups actually constitute a single group of old/active TB patients who developed COVID-19 infection. COVID-19 has probably just unmasked some of the subtle active TB cases that were responsible for hidden transmission in the general population [2]. Superimposed COVID-19 has brought them to the hospital to get a timely diagnosis.