Tuberculosis and COVID-19 co-infection in Serbia: Pandemic challenge in a low-burden country.

Introduction: COVID-19 and tuberculosis (TB) represent global threats to the public health system. The impact of COVID-19 on TB results in a reduction in the number of notified TB cases, delayed diagnosis and treatment, and increased case fatality and mortality rates. The aim of the study was to analyze the TB/COVID-19 co-infected cohort in Serbia as a low-burden country and compare it to the global TB/COVID-19 cohort. Methods: A retrospective analysis was done on 53 TB and COVID-19 co-infected patients treated in COVID hospital "Batajnica" in Belgrade and Special Hospital for Pulmonary Diseases "Ozren" Sokobanja in the period from 6 March 2020 to 1 April 2022. A comparative analysis with the global cohort published recently was also performed. Results: TB/COVID-19 cohort in Serbia included significantly fewer migrants and diabetes cases, but more cases with chronic respiratory diseases compared to the global. Descriptive analysis of TB cases in the Serbian TB/COVID-19 cohort showed fewer cases diagnosed with sputum smear and Gene Xpert/HAIN, fewer EPTB and mono-resistant cases, and more cases diagnosed with solid culture, unilateral pulmonary infiltrate (with bilateral cavity lesions), and bilateral pulmonary infiltrate (no cavities) compared to TB/COVID-19 cases worldwide. Nasal congestion and fever were more common COVID-19 symptoms in the global cohort. Radiology was more commonly used for the diagnosis of COVID-19 in Serbia. Typical bilateral ground opacities were less common among Serbian patients. Serbian patients spent fewer days in the hospital and achieved a higher PCR conversion rate and TB treatment success rate. Conclusion: The Serbian TB/COVID-19 cohort achieved a higher treatment success rate compared to the global cohort. Encouraging vaccination against SARS-CoV-2 for people with a current or past TB disease, as well as rapid diagnosis and targeted treatment of TB in highly specialized pulmonology institutions, presents key points to avoid excessive morbidity and mortality.

Association between active pulmonary tuberculosis and miRNA-146a: A preliminary study from Serbia.

INTRODUCTION: Tuberculosis (TB) continues to be a significant public health problem. The role of small non-coding RNAs, such as microRNAs (miRNAs), was investigated extensively in Mycobacterium tuberculosis (MTB) infection as well as in a variety of other pathophysiological processes in recent years. It was found that miRNAs act as regulators of both early reaction to MTB infection and in process of adaptation of the host immune cells during latent course of the disease. Molecule miRNA-146a is expressed exclusively in immune cells and it has the most prominent role in modulation of innate immunity. METHODOLOGY: We investigated the level of expression of miRNA-146a using an RT-qPCR technique in peripheral blood mononuclear cells of 44 patients with active pulmonary TB and 17 healthy individuals. We also analyzed the significance of miRNA-146a rs2910164 SNV for expression profile of miRNA-146a, in order to investigate potential usage of miRNA-146a as a biomarker for TB. RESULTS: There was statistically significant decrease of expression of miRNA-146a in TB group compared to control group. When gender cohorts were analyzed, the expression levels in TB male and TB female subgroup were significantly lower than the expression levels in the same gender control subgroups. CONCLUSIONS: Our results indicate that miRNA-146a plays a significant role in the pathogenesis of TB, suggesting that miRNA-146a could be used as a biomarker for active pulmonary TB.

Trends in tuberculosis notification and mortality and factors associated with treatment outcomes in Serbia, 2005 to 2015.

BackgroundPreviously a country with medium tuberculosis (TB) burden, Serbia almost reached a low TB burden during the period 2005 to 2015.AimThe aim of this study was to analyse the trends in notification rates and treatment success rates as well as to identify predictors of treatment outcomes.MethodsWe performed a trend analysis and logistic regression analysis of 17,441 TB cases registered from 2005 to 2015 in all health facilities in Serbia, to identify predictors of treatment success, loss to follow-up and mortality.ResultsFrom 2005 to 2015, TB notification rate and mortality in Serbia decreased but treatment success remained below the global target. Loss to follow-up was associated with retreatment (odds ratio (OR) = 2.38; 95% confidence interval (CI): 2.08-2.77), male sex (OR = 1.57; 95% CI: 1.39-1.79), age younger than 65 years (OR = 1.37; 95% CI: 1.20-1.51), lower education level (OR = 2.57; 95% CI: 1.74-3.80) and pulmonary TB (OR = 1.28; 95% CI: 1.06-1.56). Deaths were more frequent in retreatment cases (OR = 1.39; 95% CI: 1.12-1.61), male patients (OR = 1.34; 95% CI: 1.19-1.52), those 65 years and older (OR = 4.34; 95% CI: 4.00-5.00), those with lower education level (OR = 1.63; 95% CI: 1.14-2.33) and pulmonary TB (OR = 2.24; 95% CI: 1.78-2.83).ConclusionsSpecial interventions should be implemented to address groups at risk of poor treatment outcome.

Risk factors for multidrug-resistant tuberculosis among tuberculosis patients in Serbia: a case-control study.

BACKGROUND: Multidrug resistant (MDR) tuberculosis (TB) represents TB which is simultaneous resistant to at least rifampicin (R) and isoniazid (H). Identifying inadequate therapy as the main cause of this form of the disease and explaining the factors leading to its occurrence, numerous social determinants that affect the risk of developing resistance are highlighted. The objectives of the study was to identify independent factors of MDR-TB among tuberculosis patients. METHODS: Case-control study was conducted from 1st September 2009 to 1st June 2014 in 31 healthcare institutions in Serbia where MDR-TB and TB patients were treated. TB patients infected with MDR- M. tuberculosis and non MDR- M. tuberculosis strain were considered as cases and controls, respectively. Cases and controls were matched by the date of hospitalization. The data was collected using structured questionnaire with face to face interview. Bivariate and multivariable logistic regression analysis (MLRA) were used to identify determinants associated with MDR-TB. RESULTS: A total of 124 respondents, 31 cases and 93 controls were participated in the study. MLRA identified six significant independent risk factors for the occurrence of MDR-TB as follows: monthly income of the family (Odds ratio (OR) = 3.71; 95% Confidence Interval (CI) = 1.22-11.28), defaulting from treatment (OR = 3.33; 95% CI = 1.14-9.09), stigma associated with TB (OR = 2.97; 95% CI = 1.18-7.45), subjective feeling of sadness (OR = 4.05; 95% CI = 1.69-9.70), use of sedatives (OR = 2.79; 95% CI = 1.02-7.65) and chronic obstructive pulmonary disease (OR = 4.51; 95% CI = 1.07-18.96). CONCLUSION: In order to reduce burden of drug resistance, strategies of controlling MDR-TB in Serbia should emphasize multi-sectorial actions, addressing health care and social needs of TB patients.

A rating instrument for fear of hospitalisation.

AIMS AND OBJECTIVES: To develop and validate a reliable instrument that can measure fear of hospitalisation experienced by outpatients. BACKGROUND: After having a diagnosis established, some patients experience sense of fear, unpleasantness and embarrassment due to the possibility to be admitted to a hospital. Currently, there is no available instrument for measuring fear of hospitalisation. DESIGN: Cross-sectional study for assessing reliability and validity of a questionnaire. METHOD: The questionnaire with 17 items and answers according to the Likert scale was developed during two brainstorming sessions of the research team. Its reliability, validity and temporal stability were tested on the sample of 330 outpatients. The study was multicentric, involving patients from seven cities and three countries. RESULTS: Fear of hospitalisation scale showed satisfactory reliability, when rated both by the investigators (Cronbach's alpha .799) and by the patients themselves (Cronbach's alpha .760). It is temporally stable, and both divergent and convergent validity tests had good results. Factorial analysis revealed three domains: fear of being injured, trust to medical staff and fear of losing privacy or autonomy. CONCLUSIONS: This study developed new reliable and valid instrument for measuring fear of hospitalisation. RELEVANCE TO CLINICAL PRACTICE: Identification of patients with high level of fear of hospitalisation by this instrument should help clinicians to administer measures which may decrease fear and prevent avoidance of healthcare utilisation.