Introduction: Tuberculosis (TBC) is a contagious chronic respiratory disease which despite the known cause, Mycobacterium tuberculosis (Mtb), and many decades of successful therapy, remains one of the leading global health problems. Immune responses against Mtb infection involve both of types of immunity, but cellular immunity, in which certain cytokines and Th1 cells play a key role, is crucial. A better understanding of the functions of the cytokine network involved in the state and progression of TBC could identify specific molecular markers for monitoring of disease activity as well as therapy outcomes in TBC patients. Methodology: We investigated expression of TNF-α, IL-6 and IRAK1 genes using an RT-qPCR technique in peripheral blood mononuclear cells of 33 TBC patients and 10 healthy individuals. Results: Comparison between TBC patients and healthy individuals revealed statistically significant differences for all analyzed genes. The levels of expression of TNF-α and IL-6 mRNA were higher, while the level of IRAK1 mRNA was lower in the TBC group compared to controls. Moreover, a strong positive correlation was observed between TNF-α and IL-6 gene expression. When clinical parameters were analyzed, increased levels of TNF-α mRNA were detected in patients with a longer duration of therapy (>2 months) compared to those with a shorter therapy duration (< 2 months), and in patients without anemia. Conclusions: Our results indicate that the inflammatory genes we examined play a crucial role in the pathogenesis of tuberculosis, and that the expression of the TNF-α gene could be a marker for monitoring the clinical effect of the ant-tuberculosis drugs during therapy.

Introduction. COVID-19 is responsible for the current global pandemic. Globally, over 15 million people are currently infected, and just over 600,000 have died due to being infected. It is known that people with chronic illnesses and compromised immune systems can develop more severe clinical presentation. Tuberculosis is still one of the biggest epidemiological problems worldwide. Both of these diseases can be misdiagnosed and can manifest in a similar way. We will present a case study of a patient who was initially treated as a COVID-19 infection, with Tuberculosis being diagnosed later on. The recovery began only after being treated for both diseases simultaneously. Case report. The patient is a 27-year-old male, non-smoker, with no history of any significant diseases. He presented with fever, fatigue and hemoptysis. Computed tomography pulmoangiography had shown massive consolidations and excavations, which could be caused by COVID-19. Despite being treated for COVID-19, there was no clinical improvement. On the follow-up chest X-radiograohy, beside signs of COVID-19, there were also changes that could indicate Tuberculosis. Tuberculosis was detected in sputum, using PCR and Mycobacteria Growth Indicator Tube, and only after being treated for both diseases did his condition improve. Conclusion. There are a few reported cases of COVID-19 and Tuberculosis coinfections, and we believe that there are many more patients with this coinfection being unrecognized.

SUMMARY – Currently, topical are studies that examine different reasons for delay of tuberculosis (TB) diagnosis and its impact on disease prognosis. The aim was to examine three time periods associated with treatment delay: patient related, health system related and total delay. This retrospective-prospective study included 100 consecutive patients hospitalized at Department of Pulmonology, Clinical Center of Serbia, in the period from March to December 2015. Study results showed median patient delay to be 92.5 days. Total delay was affected by patient related delay. Median healthcare delay was 18.5 days. Patients that reported excessive alcohol consumption were more likely to have prolonged time to seek medical help. Years of alcohol consumption yielded moderate positive correlation with patient related delay (r=0.362, p<0.001). Correlation between the number of cigarettes and patient delay was moderate, positive and statistically significant (r=0.314, p=0.001). Delay in seeking medical help was more likely in patients with negative family history of TB. There was no difference in the effect of the presence of symptoms on patient related delay (p>0.05). Clinical characteristics such as patient TB category and chest radiograph abnormalities were not associated with prolonged patient related delay (p>0.05). Study results point to the importance of health education and/or health intervention in the population group at a high risk of TB.

SummaryVitamin D has an important role in numerous physiological functions. Vitamin D receptors are characterized by polymorphisms and presence in different tissues including a number of cells of the immune system. The role of vitamin D as a biological inhibitor of inflammatory hyper activity is of particular importance. Hypovitaminosis D has been associated with many serious chronic diseases, such as autoimmune, infectious and cardiovascular diseases as well as some types of cancer. Vitamin D has an influence on the immune res ponse to tuberculosis. Calcitriol (1,25-dihydro xycholecalciferol), the major active form of vitamin D, has shown in vitro activity against Mycobacterium tuberculosis. It has been found that susceptibility to chronic mycobacterial infections is strongly correlated with a low vi tamin D intake and particular VDR alleles. Vitamin D deficiency might predispose the individuals infected with Myco bacterium tuberculosis to develop tuber culosis. Calcitriol binds to vitamin D receptors and modulates immune responses by regulating the transcription of genes responsive to vitamin D. Faster conversion of sputum mycobacterial culture in patients with pulmonary tuberculosis is associated with being a carrier of the t allele of the TaqI vitamin D receptor polymorphism. On the contrary, slower spu tum culture conversion in pulmonary tuberculosis has been found in the carriers of the f allele of the FokI vitamin D receptor polymorphism. The results of in vitro studies, clinical research and population studies indicated that vitamin D Kratak sadr`ajVitamin D ima zna~ajnu ulogu u velikom broju fiziolo{kih funkcija, posebno kao biolo{ki inhibitor inflamatorne hiperreaktivnosti. Hipovitaminoza je povezana sa mnogim hroni~nim oboljenjima, uklju~uju}i autoimune, infektivne, kardiovaskularne bolesti i neke vrste tumora. Vitamin D uti~e na imuni odgovor kod tuber kuloze, te nedostatak vi tamina D mo`e biti zna~ajan faktor rizika za nastanak tuber kuloze me|u osobama koje su inficirane Mycobacte riumom tuberculosis. Postoji jaka povezanost izme|u ne dostatka vitamina D u ishrani i prisustva odre|enog VDR alela, i podlo` nosti mikobakterijskoj infekciji. Pokazano je da kalcitriol, glavni aktivni oblik vitamina D (1,25-dihidro ksiholekal ciferol) ima in vitro antimikobakterijsku aktivnost. Receptori za vitamin D su polimorfni i prisutni su u razli ~itim tkivima, uklju~uju}i i }elije imunog sistema. Kalcitriol se vezuje za odgovaraju}e receptore za vitamin D, modulira imunolo{ki odgovor i reguli{e transkripciju gena koji zavise od vitamina D. Br`a konverzija kulture mikobakterija iz sputuma kod pacijenata sa plu}nom tuberkulozom ukazuje na nosioce t alela polimorfizma TaqI receptora za vitamin D. Suprotno tome, sporija konverzija kulture miko bakterija iz sputuma u plu} noj tuberkulozi povezuje se sa nosiocima f alela polimorfizma FokI receptora za vitamin D. Rezultati bazi~nih nau~nih i klini~kih istra`ivanja i populacionih studija sugeri{u da nedostatak vitamina D mo`e predstavljati zna~ajan rizik za nastanak tub...

Tuberculosis (TB) is granulomatous diseases caused by Mycobacterium tuberculosis (MTB). TB is a highly infectious disease that primarily affects the lungs. One-third of human population is infected with MTB, therefore it is of utmost significance to determine the factors that influence the individual susceptibility to the disease. Host genetic factors have been recognized as essential for susceptibility to TB, since only 5% to 10% of infected individuals develop the disease. A number of candidate genes has been intensively studied, the most of which were connected with the function of macrophages, thus participating in immune response. Here we examined the gene variants of VDR (FokI) and NRAMP1 (INT4, D543N, 3?UTR) genes in aim to make the correlation between these genetic factors and risk of TB in Serbian patients. This study included 110 TB patients and 67 healthy controls. Pulmonary TB was diagnosed by clinical symptoms, radiological evidence of TB and bacteriological criteria (Culture- positive/ smear- positive). Genotyping was performed using PCR-RFLP method. Our findings revealed significant prevalence of ff genotype and variant allele f of the FokI VDR gene variant in patients compared to control group. Based on the our results the carriers of ff genotype are five times more at risk to tuberculosis than carriers of FF and Ff genotype in our population. The results of analyzed SNPs in NRAMP1 gene showed no statistically significant difference in distribution of the gene variants between patient and control groups. Therefore, we could conclude that the genotype ff of the VDR gene is factor that strongly contribute to susceptibility to TB in Serbian population. [Projekat Ministarstva nauke Republike Srbije, br. 175046 i br. III41004]