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Background: Tuberculosis (TB) poses a significant public health challenge, particularly because it can exist in an asymptomatic latent phase. Latent TB infection indicates the presence of Mycobacterium tuberculosis without clinical symptoms. Effectively distinguishing between active and latent TB is essential, especially in regions with high TB prevalence, as it may help reduce transmission rates. This study aims to evaluate C1q as a potential biomarker for differentiating active TB from latent forms., Methods: This prospective cross-sectional study was conducted from January 2017 to February 2018, involving HIV-negative adults aged 18 and older attending TB clinics. Participants were categorized based on clinical symptoms, imaging results, and laboratory tests into active or latent TB. Blood samples were collected to assess serum C1q levels, which were then compared between the two groups., Results: Out of 81 patients referred for TB evaluation, 38 were diagnosed with active TB. The overall median C1q level was 6.46 μg/ml (interquartile range 4.66-10). The active TB group exhibited significantly elevated C1q levels (10.21 μg/ml) compared to the latent TB group (6.03 μg/ml, P < 0.001). The area under the receiver operating characteristic curve for C1q in distinguishing active from latent TB was 0.74 (95% confidence interval, 0.63-0.85), with sensitivity varying between 61% and 82% at different threshold values., Conclusions: C1q shows potential as a reliable and easily obtainable biomarker for differentiating active TB from latent infection, demonstrating high sensitivity. These results underscore the need for further research to explore the clinical application of C1q in TB diagnostics., (Copyright © 2024 International Journal of Mycobacteriology.)

Background: There are two main causes of exudative effusion including malignancy-induced effusion and tuberculosis. Considering that in reactive ejections, such as tuberculosis-induced effusion, the role of B lymphocytes and in the malignant effusion, the role of T lymphocytes are more important, in this study we analyzed the frequency of CD4, CD8, CD19, CD56-16, CD64, QuantiFERON in the pleural and serum samples of patients with exudative lymphocytic-dominant effusion., Methods: In total, 73 patients were enrolled in the study by exudative lymphocyte effusion, and finally, 63 patients had definite diagnoses. The patients were sorted into three groups including malignant, tuberculosis, and none. The sample of blood plasma and pleural effusion were collected and CD markers were analyzed using flow cytometry., Results: The mean age in the malignancy and tuberculous (TB) groups was 63.16 ± 12 and 52.15 ± 22.62, respectively. There was no significant difference in the frequency of CD8, CD4, and CD16-56 cells in blood samples of patients with tuberculosis and malignancy. Compared to those with tuberculosis, the percentage of CD64 cells was significantly higher in patients with tuberculosis than in malignant subjects. Moreover, a comparison of the frequency of cells with CD8, CD4, CD19, CD64, CD16-56, and CD14 markers in pleural samples showed no significant difference between groups. Other inflammatory factors were also investigated. The erythrocyte sedimentation rate (ESR) value for tuberculosis patients was significantly higher than malignancy. Also, QuantiFERON was positive in 14.3% of malignant patients, and 62.5% of patients with TB, which had a significant difference., Conclusion: Considering that there are many confounding variables in the study, such as previous medications, subtypes of Mycobacterium , and race of patients conducting studies in different groups and performing data mining for using a set of parameters can be used to detect the exact diagnosis., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Background: Tuberculosis (TB) still remains a major health threat worldwide. The current TB diagnostics are suboptimal, and there is a high clinical need for identifying novel biomarkers of disease prevalence. Circulating exosomes have been currently attractive as novel biomarkers in a wide range of pathological conditions., Methods: In this study, we performed bioinformatics analysis on the downstream targets of a dysregulated microRNA (miRNA) cluster induced by Bacillus Calmette-Guerin infection of human macrophages to provide greater understanding of their potential roles in disease pathogenesis., Results: Our analysis demonstrated that these dysregulated miRNAs have central roles in the host metabolic and energy pathways., Conclusion: This suggests that the host miRNA network is perturbed by Mycobacterium to re-patterning host metabolism machinery to favor its intracellular survival. The dysregulated miRNAs can be delivered to local and distal cells by exosomes and thereby modulate their function., Competing Interests: None

Objective/background: Tuberculosis (TB) is a major global health problem and poses immense threats to many populations. The association between tobacco smoke and TB has already been studied. Water-pipe smoking has become an increasing problem not only in Middle Eastern countries but also globally as it is considered by users as being safer than cigarettes. The presence of high levels of toxic substances in water-pipe smoke may be predisposing factors that enhance the incidence of pulmonary disorders in water-pipe smokers. For example, uncontrolled macropinocytosis occurs in alveolar epithelial cells following exposure to water-pipe smoke, which may predispose individuals to pulmonary infection. In this work, we studied the effects of water-pipe condense (WPC) on the internalization of Mycobacterium bovis (bacillus Calmette-Guérin [BCG]) by macropinocytosis in Type II alveolar epithelial cells (A549)., Methods: A549 cells were treated by WPC (4mg/mL) for 24 h, 48 h, 72 h, and 96 h, respectively. The effect on cell proliferation was studied using a methylthiazolyldiphenyl-tetrazolium bromide (MTT) reduction assay. Cells were exposed to fluorescein isothiocyanate (FITC)-dextran (1mg/mL; control) and FITC-BCG (multiplicity of infection, 10) for 20min at 37°C before their collection and the uptake of BCG-FITC was determined by flow cytometry. Similar experiments were performed at 4°C as a control., Results: WPC (4mg/mL) after 72h (1.4±0.2-fold, p<0.05) and 96h (1.6±0.2-fold, p<0.05) hours increased the uptake of BCG-FITC. No effect on BCG-FITC uptake was observed at 24h or 48h. WPC also significantly increased the uptake of FITC-dextran (2.9±0.3-fold, p<0.05) after 96h. WPC also significantly decreased cell proliferation after 24h (84±2%), 48h (78±3%), 72h (64±2%, p<0.05), and 96h (45±2%, p<0.05)., Conclusion: WPC exposure increased epithelial cells' permeability and death and enhanced their capacity for macropinocytosis. Our in vitro data suggest possible harmful effects of WPC on the ability of lung epithelial cells to phagocytose mycobacteria. Further studies will be conducted to understand the mechanism of action of WPC., (Copyright © 2016.)

Objective/background: Tuberculosis (TB) is a major global threat to human health, especially in low-income countries. The diagnosis of TB is challenging because of the limitations of specificity and sensitivity with the current diagnostics. Novel, selective biomarkers for TB would be of great practical value. Exosomes are bioactive vesicles with 30-100nm in diameter, which are secreted from almost all cell types and are found in virtually every human body fluid. Exosomes transport micro-RNAs (miRNAs), which are post-transcriptional regulators of gene expression, around the body and allow miRNAs to modulate biological pathways in target cells. Our aim was to investigate the potential of exosomal miRNAs as biomarkers by examining their release from human monocyte-derived macrophages (MDMs) after infection with Mycobacterium using miRNA sequencing., Methods: Human monocytes were obtained from blood and driven to an MDM phenotype using standard protocols. MDMs were infected with Mycobacterium bovis Bacillus Calmette-Guérin (BCG) or left uninfected as control. Exosomes were collected 72 h postinfection from the cell culture medium and subjected to RNA isolation. Small RNA libraries were constructed and RNA sequencing performed. The raw reads were filtered to eliminate adaptor and primer sequences, and the sequences in FASTQ format were run against the mature human miRNA sequences available in miRBase using BLAST software using a Linux operating system. Micro-RNAs were identified using E=0.01 or 1., Results: Infection of MDMs with BCG lead to the release of a number of exosomal miRNAs. These mainly consisted with Let-7 family members, miR-155, miR-146a, miR-145, and miR-21 all of which were predicted to target important immune-related genes and pathways., Conclusion: This study provides evidence for the release of specific miRNAs from BCG-infected MDMs. These results need to be confirmed and the presence of this panel of miRNAs tested in the blood of patients to determine their selectivity and specificity as a diagnostic in patients with TB., (Copyright © 2016.)

Objective/background: Tuberculosis (TB) remains the leading cause of AIDS-related deaths among adults in countries with resource limitations. The emergence of the Xpert MTB/RIF rapid molecular assay and its subsequent World Health Organization endorsement in 2010 transformed the TB-diagnostic landscape. Xpert provided diagnostic accuracy that was far superior to that of the sputum-smear microscopy test previously used. The detection of mycobacterial lipoarabinomannan (LAM) antigen in urine has emerged as a potential point-of-care test for TB. LAM antigen is a lipopolysaccharide present in mycobacterial cell walls which is released from metabolically active or degenerating bacterial cells and appears to be present only in people with active TB. Urine-based testing has advantages over sputum-based testing because urine is easy to collect and store and lacks the infection control risks associated with sputum collection. A previously study reported that urinary-LAM testing is a rapid, low-cost, ante-mortem diagnosis for human immunodeficiency virus (HIV)-associated TB. The objective of this study was to investigate the levels of LAM in HIV patients referred to the Mashih Daneshvari Hospital Tehran, Iran., Methods: Urine from 31 HIV patients without TB, 33 HIV patients with pulmonary TB, and eight HIV patients with extrapulmonary TB was analyzed for LAM using enzyme-linked immunosorbent assay kits (Mybiosource, San Diego, CA, USA)., Results: The plasma levels of LAM in pulmonary TB/HIV patients was 7.67±2.3ng/ml compared with 4.5±1.6ng/ml in extrapulmonary TB/HIV and 6.7±1.2ng/ml in HIV patients without TB. There was no significant difference in urine LAM levels between the three groups., Conclusion: Our results highlight the limitations of using urine LAM levels for differentiating HIV-associated TB patients in Iran., (Copyright © 2016.)

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis. Despite the availability of novel therapeutic approaches, TB is considered as one of the leading causes of death due to infectious diseases worldwide. Alveolar macrophages are the first line of defense against M. tuberculosis; they ingest and sequester the bacilli within granulomatous structures. Control and resolution of the infection requires activated T lymphocytes as well as Th1 cytokines. There are two forms of TB: active TB and latent TB. Latent TB is a state in which M. tuberculosis survives in the body without causing overt signs and symptoms. People with latent TB are noncontagious. However, M. tuberculosis can become active in the body, multiply, and cause overt TB. Sarcoidosis, on the other hand, is an autoimmune disease of unknown etiology which can affect multiple systems of the body. Nonspecific constitutional symptoms, such as fever, fatigue, malaise, and weight loss, are present in approximately one-third of patients. Chest X-ray usually shows hilar and mediastinal lymphadenopathy. Although the lungs are the most common sites of inflammation, sarcoidosis can also involve other organs, such as the eyes (intraocular and adnexal), skin, lymph nodes, salivary glands, heart, spleen, liver, and the nervous system. Recent investigations have provided further insights into the genetic basis of sarcoidosis and the way genotype determines the clinical presentation and phenotype of patients. Histopathologic features are usually insufficient for diagnosis of sarcoidosis. Diagnosis of sarcoidosis in endemic areas for TB can become a great challenge. Both TB and sarcoidosis are granulomatous diseases; TB is characterized by caseating granulomas, whereas sarcoidosis is characterized by noncaseating granulomas. New cases of sarcoidosis are increasingly being diagnosed in areas endemic for TB due to increased orientation of physicians and availability of diagnostic modalities. However, it is often difficult to differentiate sarcoidosis from TB, especially when caseous necrosis is not seen and acid-fast staining is negative in the biopsy specimen of patient with TB. Granulomatous inflammation in sarcoidosis is believed to be caused by the presence of a persistent poorly degradable unknown antigen in combination with a nonresolving host response. M. tuberculosis has been extensively studied as a possible cause of sarcoidosis. Results suggest that granulomas form in the lungs as a result of the immune response to inhaled M. tuberculosis and serve as the central site of host-pathogen interaction during M. tuberculosis infection. M. tuberculosis DNA detection in sarcoidosis samples by traditional polymerase chain reaction (PCR) has been used for the pathological study of sarcoidosis; however, it is likely that real time quantitative PCR analysis of specific mRNAs and microRNAs will be necessary as a sensitive, precise, and rapid diagnostic test for detecting trace of TB in Sarcoidosis. In conclusion, diagnosis of sarcoidosis in areas with a high burden of TB poses a significant challenge. Improved diagnostic tests including genetic tests can improve our knowledge and help in distinguishing these two diseases., (Copyright © 2016.)

Sarcoidosis is a granulomatous inflammatory disease that is induced by unknown antigen(s) in a genetically susceptible host. Although the direct link between Mycobacterium tuberculosis (MTB) infection and sarcoidosis can be excluded on the basis of current knowledge, non-infectious mechanisms may explain the causative role of mycobacterial antigens. Ever since sarcoidosis was first described, its relationship with tuberculosis (TB) has been under-investigated. Whereas some researchers consider sarcoidosis and TB as two examples of the same disease process, others have rejected mycobacteria as playing any causative role in sarcoidosis. Whether they are linked causally or not, clinical evidence makes a differential diagnosis between the two conditions very challenging, particularly in countries with high burden of TB. The present study analyzes the relationship between sarcoidosis and TB and its implications in clinical practice. The coincidence of TB and sarcoidosis and the higher incidence of mycobacterial DNA in biological samples of sarcoid patients have been reported by many authors. In addition, new evidence of a similarity in MTB phenotype in sarcoidosis is provided. Overall, these observations suggest that TB and sarcoidosis may not only share the same etiology, but may even be different aspects of one disease., (Copyright © 2014 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.)