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Background: Thymomas belong to rare tumors giving rise to thymic epithelial tissue. There is a classification of several forms of thymoma: A, AB, B1, B2, B3, thymic carcinoma (TC) and thymic neuroendocrine thymoma. In this meta-analysis study, we have focused on thymoma using articles based on the disease's next-generation sequencing (NGS) genomic profiling., Materials and Methods: We conducted a systematic review and meta-analysis of the prevalence of studies that discovered the genes and variants occurring in the less aggressive forms of the thymic epithelial tumors. Studies published before 12 th December 2022 were identified through PubMed, Web of Science (WoS), and SCOPUS databases. Two reviewers have searched for the bases and selected the articles for the final analysis, based on well-defined exclusion and inclusion criteria., Results: Finally, 12 publications were included in the qualitative as well as quantitative analysis. The three genes, GTF2I , TP53 , and HRAS , emerged as disease-significant in the observed studies. The Odds Ratio for all three extracted genes GTF2I (OR = 1.58, CI [1.51, 1.66] p < 0.00001) , TP53 (OR = 1.36, CI [1.12, 1.65], p < 0.002), and HRAS (OR = 1.02, CI [1.00, 1.04], p < 0.001)., Conclusions: According to obtained data, we noticed that the GTF2I gene exhibits a significant prevalence in the cohort of observed thymoma patients. Moreover, analyzing published articles NGS has suggested GTF2I, TP53 , and HRAS genes as the most frequently mutated genes in thymoma that have pathogenic single nucleotide variants (SNV) and Insertion/Deletion (InDel), which contribute to disease development and progression. These variants could be valuable biomarkers and target points specific to thymoma., (© 2023 Jelena Kostic Peric, Andja Cirkovic, Sanja Srzentic Drazilov, Natalija Samardzic, Vesna Skodric Trifunovic, Dragana Jovanovic, Sonja Pavlovic, published by Sciendo.)

Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity, currently is the focus of multiple genome-wide association studies (GWAS) in populations affected by the pandemic. This is the first study from Serbia that performed a GWAS of COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128 hospitalized COVID-19 patients from the Serbian population was enrolled in the study. We conducted a GWAS comparing (1) patients with pneumonia ( n = 80) against patients without pneumonia ( n = 48), and (2) severe ( n = 34) against mild disease ( n = 48) patients, using a genotyping array followed by imputation of missing genotypes. We have detected a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with a peak residing upstream of the gene KLHL1 ( p = 1.91 × 10 -8 ). Our study also replicated a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L and LZTFL1 genes suggestively associated with pneumonia ( p = 7.54 × 10 -6 ) and severe COVID-19 ( p = 6.88 × 10 -7 ), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 ( IRX, NDUFS6, MRPL36, p = 2.81 × 10 -6 ), 5q11.2 ( ESM1, p = 6.59 × 10 -6 ), and 9p23 ( TYRP1, LURAP1L , p = 8.69 × 10 -6 ). The genes located in or near the risk loci are expressed in neural or lung tissues, and have been previously associated with respiratory diseases such as asthma and COVID-19 or reported as differentially expressed in COVID-19 gene expression profiling studies. Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which could contribute to a better understanding of the COVID-19 host genetics in different populations., Competing Interests: Author MZ was employed by the company Seven Bridges. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zecevic, Kotur, Ristivojevic, Gasic, Skodric-Trifunovic, Stjepanovic, Stevanovic, Lavadinovic, Zukic, Pavlovic and Stankovic.)

Background: COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The emerging amount of data indicates that vitamin D, zinc and selenium could be important for clinical presentation of COVID-19. Here, we investigated association of genetic variants related to the altered level and bioavailability of vitamin D, zinc and selenium with clinical severity of COVID-19. Methods: We analyzed variants in genes significant for the status of vitamin D ( DHCR7 / NADSYN1 rs12785878, GC rs2282679, CYP2R1 rs10741657, and VDR rs2228570), zinc ( PPCDC rs2120019) and selenium ( DMGDH rs17823744) in 120 Serbian adult and pediatric COVID-19 patients using allelic discrimination. Furthermore, we carried out comparative population genetic analysis among European and other worldwide populations to investigate variation in allelic frequencies of selected variants. Results: Study showed that DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 variants were associated with severe COVID-19 in adults ( p = 0.03, p = 0.017, respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the odds for developing severe disease, OR 0.21 (0.05-0.9) and OR 5.9 (1.4-25.2), respectively. There were no associations between selected genetic variants and disease severity in pediatric patients. Comparative population genetic analysis revealed that Serbian population had the lowest frequency of CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and 0.66 in Spanish and Italian population, respectively), suggesting that other populations should also investigate the relationship of CYP2R1 variant and the COVID-19 disease course. Conclusion: The results of the study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults. This could direct prevention strategies based on population specific nutrigenetic profiles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kotur, Skakic, Klaassen, Gasic, Zukic, Skodric-Trifunovic, Stjepanovic, Zivkovic, Ostojic, Stevanovic, Lavadinovic, Pavlovic and Stankovic.)

Introduction: Single nucleotide variants (SNVs) represent important genetic risk factors for susceptibility to posttraumatic sepsis and a potential target for immunotherapy. We aimed to evaluate the association between 8 different SNVs within tumor necrosis factor alpha (TNFA), lymphotoxin alpha (LTA) and Toll-like receptor (TLR2 and TLR4) genes and the risk of posttraumatic sepsis., Methods: Nested case-control study was conducted in the emergency department of the Clinical Centre of Serbia including 228 traumatized patients (44 with sepsis and 184 without sepsis). To compare the results of trauma subjects with the data from the general population, a control group of 101 healthy persons was included in the study. Genotyping of TNFA (rs1800629 and rs361525), LTA (rs909253), TLR2 (rs3804099, rs4696480 and rs3804100), and TLR4 (rs4986790 and rs4986791) was performed for all patients within all three groups using the real-time PCR method. MutationTaster database and in silico software SIFT were used to predict the variant pathogenic effect., Results: Carriage of the G allele of the TNFA rs1800629 gene variant (OR 2.1, 95%CI 1.06-4.16) and T allele-carriage of the TLR4 rs4986791 genetic variant (OR 3.02, 95%CI 1.31-6.57) were associated with significantly higher risk of sepsis in trauma patients when compared to the general population prone to sepsis and traumatized patients without developing a sepsis, respectively. Of these two variants, only variant in TLR4 gene (rs4986791) has been labeled as disease causing by both the MutationTaster database and the in-silico software SIFT, which further supports the role of this variant in various pathologies including sepsis. For the remaining six variants no significant association with the susceptibility to sepsis was detected., Conclusions: Carriage of the G allele of the TNFA rs1800629 gene variant and T allele-carriage of the TLR4 rs4986791 genetic variant confer significant risk of posttraumatic sepsis. TLR4 gene variants (rs4986790 and rs4986791) has been labelled as disease causing., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Thymomas and thymic carcinoma (TC) are the most common neoplasms localised in the thymus. These diseases are poorly understood, but progress made in next-generation sequencing (NGS) technology has provided novel data on their molecular pathology., Material and Methods: Genomic DNA was isolated from formalin-fixed paraffin-embedded tumour tissue. We investigated somatic variants in 35 thymoma patients using amplicon-based TruSeq Amplicon Cancer Panel (TSACP) that covers 48 cancer related genes. We also analysed three samples from healthy individuals by TSACP platform and 32 healthy controls using exome sequencing., Results: The total number of detected variants was 4447, out of which 2906 were in the coding region (median per patient 83, range: 2-300) and 1541 were in the non-coding area (median per patient 44, range: 0-172). We identified four genes, APC , ATM , ERBB4 , and SMAD4 , having more than 100 protein-changing variants. Additionally, more than 70% of the analysed cases harboured protein-changing variants in SMAD4, APC, ATM, PTEN, KDR , and TP53 . Moreover, this study revealed 168 recurrent variants, out of which 15 were shown to be pathogenic. Comparison to controls revealed that the variants we reported in this study were somatic thymoma-specific variants. Additionally, we found that the presence of variants in SMAD 4 gene predicted shorter overall survival in thymoma patients., Conclusions: The most frequently mutated genes in thymoma samples analysed in this study belong to the EGFR, ATM, and TP53 signalling pathways, regulating cell cycle check points, gene expression, and apoptosis. The results of our study complement the knowledge of thymoma molecular pathogenesis., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia & Banach.)

Introduction: Sarcoidosis is a rare multisystem granulomatous disease with unknown etiology. The interplay of vitamin D deficiency and genetic polymorphisms in genes coding for the proteins relevant for metabolism of vitamin D is an important, but unexplored area. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in CYP2R1 (rs10741657), CYP27B1 (rs10877012), DBP (rs7041; rs4588), and VDR (rs2228570 ) genes and sarcoidosis, as well as the association between these SNPs and 25(OH)D levels in sarcoidosis patients., Material and Methods: For that purpose we genotyped 86 sarcoidosis patients and 50 healthy controls using the PCR-RFLP method., Results: Subjects carrying the CC genotype of CYP27B1 rs10877012 have 10 times lower odds of suffering from sarcoidosis. Moreover, DBP rs4588 AA genotype was shown to be a susceptibility factor, where carriers of this genotype had eight times higher odds for developing sarcoidosis. In addition, the A allele of the DBP gene (rs4588) was associated with lower levels of 25(OH)D in sarcoidosis patients., Conclusions: These results suggest that patients with vitamin D deficiency should be regularly tested for genetic modifiers that are related to sarcoidosis in order to prevent development of serious forms of sarcoidosis., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2018 Termedia & Banach.)

Purpose: Neuroendocrine lung tumors (NET) include typical carcinoids (TC), atypical carcinoids (AC), large cell NE carcinoma (LCNEC) and small-cell carcinoma (SCLC), with different clinicopathological profiles and relative grades of malignancy. Although differences between carcinoids and high grade carcinomas are recognized, precise differences and behavior of TC and AC have not been clearly defined. The aim of this study was to better define the differences in the clinical behavior of TC and AC, and to establish new prognostic factors of overall survival (OS), by determining the levels of genetic expression of IGF1R, ERCC1, Bax, p53, Bcl2 and Bcl2/Bax ratio., Methods: The histopathological diagnosis of 52 surgically resected pulmonary carcinoid tumors was made according to the WHO classification. Gene expressions were evaluated by quantitative real-time PCR., Results: The confirmed prognostic factors for overall survival (OS) were pTNM T (p<0.01), pTNM N (p<0.05), clinical stage (p<0.05), type of surgery (p<0.01) and histopathological (HP) tumor type (p<0.05). Bcl2 mRNA level and Bcl2/Bax ratio were found to have a potential for discrimination of the HP type of tumor (AC vs TC, Receiver Operating Characteristics (ROC) cut-off values 0.1451 and 0.3015, respectively), but without statistically significant impact on OS., Conclusions: In patients with NETs, smaller primary tumor, absence of positive lymph nodes, and TC type of tumor predicted longer OS. Type of resection has influence on OS. Bcl2 expression and Bcl2/Bax ratio might be valuable as independent diagnostic parametars in lung carcinoids. Therapeutic approaches using attenuation of Bcl2 or upregulation of Bax might prove useful in lung NETs.

Background: Idiopathic pulmonary fibrosis (IPF) has common risk factors with cancer and significant similarities in the pathobiology process, both diseases having poor outcomes. Immune checkpoint PD-L1 has become the target of checkpoint inhibitory therapy that unleashes antitumor T cells and has revolutionized cancer treatment. This is a pilot study exploring membrane immune checkpoint PD-L1 expression in human IPF lung tissue samples and its soluble form, soluble PD-L1 (sPD-L1) plasma concentrations in IPF patients, in order to investigate potential role of PD-L1 as an IPF biomarker., Methods: Twelve human IPF lung tissue samples (formalin-fixed, paraffin-embedded) obtained by surgical biopsy, have been tested for PD-L1 expression by PD-L1 IHC 22C3 pharmDx assay, while plasma samples for examination of sPD-L1 forms, PD-L1 (B7-H1/CD274) blood concentration, originated from 23 patients with IPF who did not undergo surgical biopsy., Results: Membrane PD-L1 expression in IPF lung tissue samples was positive to overexpression of PD-L1 in 9 samples out of 12. Only very few cells in the interstitium have shown a discrete PD-L1 expression, but not of a membrane type. As for sPD-L1 forms, we have found elevated concentrations of sPD-L1 in the serum of IPF patients 314.3 ng/L (117.7-483.1 ng/L), significantly higher compared with healthy control group 91.0 ng/L (52.4-119.7 ng/L), P<0.01., Conclusions: For IPF with PD-L1 expression on alveolar macrophages, further studies are necessary to elucidate this phenomenon. Serum sPD-1/PD-L1 is easily detected in clinical practice and should be further evaluated as a potential prognostic or/and predictive biomarker in IPF., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Primary ciliary dyskinesia (PCD) is a rare inherited autosomal recessive or X-linked disorder that mainly affects lungs. Dysfunction of respiratory cilia causes symptoms such as chronic rhinosinusitis, coughing, rhinitis, conductive hearing loss and recurrent lung infections with bronchiectasis. It is now well known that pathogenic genetic changes lead to ciliary dysfunction. Here we report usage of clinical-exome based NGS approach in order to reveal underlying genetic causes in cohort of 21 patient with diagnosis of PCD. By detecting 18 (12 novel) potentially pathogenic genetic variants, we established the genetic cause of 11 (9 unrelated) patients. Genetic variants were detected in six PCD disease-causing genes, as well as in SPAG16 and SPAG17 genes, that were not detected in PCD patients so far, but were related to some symptoms of PCD. The most frequently mutated gene in our cohort was DNAH5 (27.77%). Identified variants were in homozygous, compound heterozygous and trans-heterozygous state. For detailed characterization of one novel homozygous genetic variant in DNAI1 gene (c. 947&#95;948insG, p. Thr318TyrfsTer11), RT-qPCR and Western Blot analysis were performed. Molecular diagnostic approach applied in this study enables analysis of 29 PCD disease-causing and related genes. It resulted in mutation detection rate of 50% and enabled discovery of twelve novel mutations and pointed two possible novel PCD candidate genes., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Non-tuberculous mycobacteria (NTM) are ubiquitous organisms associated with various infections. The aim of the study was to determine the most relevant clinical characteristics of NTM during the 7-year period., Methodology: A retrospective study of NTM infections was conducted between January 2009 and December 2016. The American Thoracic Society/Infectious Disease Society of America criteria were used to define cases of pulmonary or an extrapulmonary site., Results: A total of 85 patients were included in the study. Pulmonary cases predominated 83/85 (98%), while extrapulmonary NTM were present in 2/95 (2%) patients. Overall, ten different NTM species were isolated. The most common organisms were slow-growing mycobacteria (SGM) presented in 70/85 (82.35%) patients. Isolated SGM strains were Mycobacterium avium complex (MAC) in 25/85 (29.41%) patients, M. xenopi in 20/85 (23.53%) patients, M. kansasii in 15/85 (17.65%) patients and M. peregrinum and M. gordonae in 5/85 (5.88%) patients each. Isolated rapid-growing mycobacteria (RGM) strains were M. abscessus in 8/85 (9.41%) patients, M. fortuitum in 4/85 (4.71%) patients and M. chelonae in 3/85 (3.53%) patients. Almost all patients (98%; 83/85) had comorbidities. Among 75 (88.24%) patients who completed follow-up, 59 (69.41%), 10 (11.76%) and 6 (7%), were cured, experienced relapse and died, respectively., Conclusion: In the present study, pulmonary NTM infections were more frequent compared to extrapulmonary disease forms. SGM were most common isolates with MAC pulmonary disease the most frequently found. Comorbidities have an important role in NTM occurrence. Further investigation should focus on an NTM drug susceptibility testing.

Background: Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease of unknown etiology. A major limitation in transcriptomic profiling of lung tissue in IPF has been a dependence on snap-frozen fresh tissues (FF). In this project we sought to determine whether genome scale transcript profiling using RNA Sequencing (RNA-Seq) could be applied to archived Formalin-Fixed Paraffin-Embedded (FFPE) IPF tissues., Results: We isolated total RNA from 7 IPF and 5 control FFPE lung tissues and performed 50 base pair paired-end sequencing on Illumina 2000 HiSeq. TopHat2 was used to map sequencing reads to the human genome. On average ~62 million reads (53.4% of ~116 million reads) were mapped per sample. 4,131 genes were differentially expressed between IPF and controls (1,920 increased and 2,211 decreased (FDR < 0.05). We compared our results to differentially expressed genes calculated from a previously published dataset generated from FF tissues analyzed on Agilent microarrays (GSE47460). The overlap of differentially expressed genes was very high (760 increased and 1,413 decreased, FDR < 0.05). Only 92 differentially expressed genes changed in opposite directions. Pathway enrichment analysis performed using MetaCore confirmed numerous IPF relevant genes and pathways including extracellular remodeling, TGF-beta, and WNT. Gene network analysis of MMP7, a highly differentially expressed gene in both datasets, revealed the same canonical pathways and gene network candidates in RNA-Seq and microarray data. For validation by NanoString nCounter® we selected 35 genes that had a fold change of 2 in at least one dataset (10 discordant, 10 significantly differentially expressed in one dataset only and 15 concordant genes). High concordance of fold change and FDR was observed for each type of the samples (FF vs FFPE) with both microarrays (r = 0.92) and RNA-Seq (r = 0.90) and the number of discordant genes was reduced to four., Conclusions: Our results demonstrate that RNA sequencing of RNA obtained from archived FFPE lung tissues is feasible. The results obtained from FFPE tissue are highly comparable to FF tissues. The ability to perform RNA-Seq on archived FFPE IPF tissues should greatly enhance the availability of tissue biopsies for research in IPF.

Purpose: Cancer is the one of the leading cause of death worldwide. The aim of this study was to examine cancer mortality trends in the population of central Serbia in the period from 2002 to 2011., Methods: The descriptive epidemiological method was used. The mortality from all malignant tumors (code C00-C96 of the International Disease Classification) was registered. The source of mortality data was the published material of the Cancer Registry of Serbia. The source of population data was the census of 2002 and 2011 and the estimates for inter-census years. Non-standardized, age-adjusted and age-specific mortality rates were calculated. Age adjustment of mortality rates was performed by the direct method of standardization. Trend lines were estimated using linear regression., Results: During 2002-2011, cancer caused about 20% of all deaths each year in central Serbia. More men (56.9%) than women (43.1%) died of cancer. The average mortality rate for men was 1.3 times higher compared to women. A significant trend of increase of the age-adjusted mortality rates was recorded both for males (p<0.001) and for females (p=0.02). Except gastric cancer, the age-adjusted mortality rates in men were significantly increased for lung cancer (p=0.02), colorectal cancer (p<0.05), prostate cancer (p=0.01) and pancreatic cancer (p=0.01). Age-adjusted mortality rates for breast cancer in females were remarkably increased (p=0.01), especially after 2007., Conclusions: In central Serbia during the period from 2002 to 2011, there was an increasing trend in mortality rates due to cancers in both sexes. Cancer mortality in males was 1.3-fold higher compared to females.

Purpose of Review: Calcium metabolism impairments have long been recognized as a complication of sarcoidosis. For more than six decades physicians and investigators have been trying to elucidate this severe problem; nevertheless it seems puzzlingly new for both readers and researchers., Recent Findings: This review highlights the problems of calcium metabolism in sarcoidosis in relation to vitamin D synthesis, which is definitely altered by granulomatous inflammation. Increasing evidence suggests that vitamin D is an immunomodulating hormone that inhibits both antigen presentation by cells of the innate immune system, and the cytokine release and proliferation of Th1 cells. As calcium homeostasis is primary controlled by levels of vitamin D, parathyroid hormone (PTH) and calcitonin, this literature review emphasizes the role of general immunomodulating properties of vitamin D and the correlation with calcium metabolism impairments, with the special accent on already known interactions with sarcoidosis., Summary: Granuloma formation has been related to a failure of the innate immune system. One of the possible explanations is a vitamin D deficiency. The evidence-based findings on calcium metabolism impairments and the interactions with vitamin D might help both clinicians and researchers in developing new strategies.

Setting: Children's Hospital for Respiratory Diseases and Tuberculosis, Belgrade, Serbia., Objectives: To compare parents' educational level and smoking habits with asthma in children exposed to environmental tobacco smoke (ETS) and in those not exposed., Methods: In this cross-sectional study, 231 asthmatic children (average age 10.6 years, 49% boys) from smoking and non-smoking families were compared by birth weight, birth length, first episode of wheezing, number of respiratory infections and exacerbations per year, severity of asthma, number of hospitalisations, total serum immunoglobulin E (IgE), skin prick tests and allergic manifestations., Results: In our study, 77% of the children were from smoking families: 45.9% had active smoking mothers and 51% active smoking fathers. Smoking was more common among parents with lower education level. The mother being the only smoker in the family had a greater impact on respiratory infections and asthma exacerbations in the first years of life; however, after the third year, the effect of having both smoking parents was important. Children exposed to ETS had more allergic manifestations. The percentage of children with both non-smoking parents decreased and that of children with both smoking parents increased with increasing asthma severity (χ(2) = 17.73, P < 0.05)., Conclusion: ETS has a negative impact on illness among children with asthma.

Setting: Health care workers in the Clinical Center of Serbia., Objective: To evaluate tuberculosis (TB) incidence by job category comparing the rates of TB in health care workers (HCWs) working in pulmonary departments, other (non-pulmonary) departments, and in the general population in Serbia., Design: Prospective cohort study from 1992 to 2004. Assessment of the relationship between employment in different departments and TB incidence was expressed by relative risk (RR), which was calculated using the annual TB incidence in the population of Serbia as the baseline rate., Results: A total of 24 HCWs developed active TB in the study period. The mean incidence rate was 413.2 per 100000 persons (RR = 12.2) for hospital staff in the pulmonary department and 20.3/100000 (RR = 0.6) for other departments. Nurses and technicians were at 7.8 times higher risk of developing TB than doctors. The mean working period before the onset of illness was 15.1 years (95%CI 5.1-25.1) for HCWs in pulmonary departments and 8.1 years (95%CI 4.6-11.6) in non-pulmonary departments (P = 0.006)., Conclusion: This study indicates that HCWs were at an increased risk of TB, most likely from nosocomial transmission in high-risk departments.

Setting: Republic of Serbia, excluding Kosovo., Objective: To estimate the clinical and epidemiological pattern of tuberculosis (TB) in Serbia during the period 1990-2004., Design: A retrospective analysis of clinical and epidemiological data on TB patients registered in annual TB reports., Results: During the 15-year period, TB incidence levelled off in Serbia. The slightly decreasing trend occurred in both total pulmonary TB (PTB) and laboratory confirmed PTB (PTB+) incidence (P > 0.05), while the trend of extra-pulmonary TB (EPTB) incidence increased slightly (P > 0.05). During the same period, TB mortality showed a significantly decreasing trend (P < 0.05). The mean annual proportion of PTB+ cases among newly reported PTB cases was 62.7%. The mean proportion of EPTB cases among total TB cases was 6.1%. The mean percentage of cases with resistance to at least one anti-tuberculosis drug was 4.8%., Conclusion: Thanks to the good organisation and efficient work of anti-tuberculosis dispensaries in Serbia, as well as to the low incidence of AIDS and low frequency of Mycobacterium tuberculosis resistant strains, TB incidence did not increase during the period observed and TB mortality significantly decreased, despite markedly deteriorated socio-economic conditions during the 1990s.