Search Results (239)

Latent tuberculosis infection (LTBI) remains an important public health issue, as individuals can harbor Mycobacterium tuberculosis without symptoms and later develop active disease. This study aimed to assess the prevalence and risk factors associated with LTBI positivity among tuberculosis (TB) contacts in congregate settings in Gyeongsan City, the Republic of Korea (ROK), from 2014 to 2023. A total of 213 index cases and 3666 contacts were analyzed using data from the Korea Tuberculosis Infection Control System (KTB-NET). Overall, 20.7% of contacts tested positive for LTBI, with the highest rates observed among contacts aged ≥65 years (50.4%) and in healthcare facilities (34.8%). Binary logistic regression analyses revealed that age ≥65 years (OR: 2.93; 95% CI: 1.95–4.39; p < 0.001), social welfare facilities (OR: 2.75; 95% CI: 2.10–3.58; p < 0.001), workplaces (OR: 2.42; 95% CI: 1.88–3.10; p < 0.001), and healthcare facilities (OR: 3.42; 95% CI: 2.63–4.43; p < 0.001) were significantly associated with increased LTBI risk. These findings highlight the importance of targeted interventions and prevention strategies focused on older adults and high-risk groups to prevent future TB outbreaks by reducing the burden of LTBI. Full article

Mycobacterium tuberculosis—an acid-fast staining bacterium—is a serious global health challenge that can have both short-term and long-term complications. Although the immune response helps trap the infection, it can also cause necrosis and calcification, leading to lung tissue damage. Calcification is a known outcome of chronic granuloma evolution in TB. Multiple pathways contribute to fibrosis and calcification; some examples are IL-1β, TGF-β, and TNF-α. Current antifibrotic drugs, such as nintedanib and pirfenidone, are effective but may increase the risk of latent tuberculosis reactivation in certain patients. Experimental therapies such as artemisinin derivatives have shown promise in preclinical TB fibrosis models, while cell-based therapies like bone marrow-derived mononuclear cells are also under early investigation for dual antifibrotic and immunomodulatory effects. This literature review will explore recent studies on the pathogenesis of M. tuberculosis, the mechanisms underlying calcification in granuloma formation, and subsequent complications of the disease process. Full article

Background/Objectives: Patients with immune-mediated inflammatory diseases (IMIDs) treated with disease-modifying antirheumatic drugs (DMARDs) are at increased risk of latent tuberculosis infection (LTBI) reactivation, influenced by DMARD type. This study aimed to determine LTBI prevalence using interferon-gamma release assays (IGRAs) and identify associated risk factors in IMID patients in a middle-high TB burden setting in Mexico. Methods: A cross-sectional study was conducted from July 2024 to April 2025 at an IMID clinic. Patients aged ≥18 years, either receiving DMARDs or prior to initiating treatment, were included. LTBI was diagnosed using the QuantiFERON-TB Gold Plus assay. Bivariate analysis was performed using the chi-square test, and multivariate analysis was conducted. Results: LTBI prevalence was 34.2% (95% CI 29.1–39.7%) according to QFT-Plus and 35.6% (95% CI 29.7–42.0%) according to TSTs (n = 230). Prior TB exposure was the strongest risk factor (aOR 4.20, 95% CI 1.74–10.12, p = 0.001), while rheumatoid arthritis was associated with a lower LTBI likelihood (aOR 0.31, 95% CI 0.16–0.59, p < 0.001). Conclusions: A high prevalence of LTBI was observed in patients with IMIDs treated with DMARDs. Prior tuberculosis exposure was strongly associated with LTBI. These findings highlight the importance of LTBI screening in this population to prevent reactivation. Full article

The identification of a type I interferon-induced transcriptomic signature in active tuberculosis suggests a potential role for these interferons in the pathogenesis of tuberculosis. Comorbidities such as human immunodeficiency virus, diabetes, systemic lupus erythematosus, end-stage renal disease, and coronavirus disease are epidemiologically linked to an increased risk for reactivation of latent tuberculosis infection. Notably, type I interferons are also implicated in the pathogenesis of these conditions, with a recognizable type I interferon transcriptomic signature. The mechanisms by which type I interferons in tuberculosis-risk-associated comorbidities may drive the progression of tuberculosis or maintenance of latent infection however remain largely unknown. This review summarizes the existing literature on the increased association between type I interferons, focusing on interferon-α and -β, and the heightened risk of tuberculosis reactivation. It also underscores the similarities in the immunopathogenesis of these comorbidities. A better understanding of these mechanisms is essential to guide the development of host-directed interferon therapies and improving diagnostic biomarkers in M. tuberculosis infection. Full article

Background: This study aims to reveal the demographic and clinical data of patients receiving TNF-α blockers, to compare the characteristics of those who received latent tuberculosis infection (LTBI) treatment and those who did not, and to evaluate and determine potential risk factors for developing active TB disease. Methods: A systematic retrospective study was conducted in a tertiary university hospital examining all patients receiving at least one TNF-α blocker between January 2019 and October 2024. The incidence of tuberculosis (TB) was analyzed across various TNF-α blocker medications in patients, both with and without LTBI treatment. Results: A total of 519 patients had TNF-α blockers: 452 (87.09%) underwent TST, 193 (37.1%) underwent booster TST, and 33 (6.3%) underwent IGRA/TST; 362 (69.7%) were treated for LTBI, and 7 (1.3%) developed TB. Comparing all TNF-α blockers, adalimumab showed a higher risk of TB. Patients with and without LTBI treatment did not significantly differ in TB incidence after biologic therapy. Conclusions: The incidence of TB in people taking TNF-α blockers was higher compared to the incidence in the general population. LTBI screening, including both TST and IGRA, should be performed with TST and IGRA tests, and LTBI-positive individuals should be started on preventive treatment. However, it should not be forgotten that active TB disease may also develop in LTBI-negative individuals. Full article

Background: Tuberculosis (TB) remains a major global public health challenge, and diagnosing it can be difficult due to issues such as distinguishing active TB from latent TB infection (LTBI), as well as the sample collection process, which is often time-consuming and lacks sensitivity and specificity. Ferroptosis is emerging as an important factor in TB pathogenesis; however, its underlying molecular mechanisms are not fully understood. Thus, there is a critical need to establish ferroptosis-related diagnostic biomarkers for tuberculosis (TB). Methods: This study aimed to identify and validate potential ferroptosis-related genes in TB infection while enhancing clinical diagnostic accuracy through bioinformatics-driven gene identification. The microarray expression profile dataset GSE28623 from the Gene Expression Omnibus (GEO) database was used to identify ferroptosis-related differentially expressed genes (FR-DEGs) associated with TB. Subsequently, these genes were used for immune cell infiltration, Gene Set Enrichment Analysis (GSEA), functional enrichment and correlation analyses. Hub genes were identified using Weighted Gene Co-expression Network Analysis (WGCNA) and validated in independent datasets GSE37250, GSE39940, GSE19437, and GSE31348. Results: A total of 21 FR-DEGs were identified. Among them, four hub genes (ACSL1, PARP9, TLR4, and ATG3) were identified as diagnostic biomarkers. These biomarkers were enriched in immune-response related pathways and were validated. Immune cell infiltration, GSEA, functional enrichment and correlation analyses revealed that multiple immune cell types could be activated by FR-DEGs. Throughout anti-TB therapy, the expression of the four hub gene signatures significantly decreased in patients cured of TB. Conclusions: In conclusion, ferroptosis plays a key role in TB pathogenesis. These four hub gene signatures are linked with TB treatment effectiveness and show promise as biomarkers for differentiating TB from LTBI. Full article

Latent tuberculosis infection (LTBi) affects nearly a quarter of the global population, yet current diagnostic methods are limited by low sensitivity and specificity. This study applied an integrative bioinformatics framework, incorporating machine learning techniques, to identify robust gene expression biomarkers associated with LTBi. We analyzed four publicly available transcriptomic datasets from peripheral blood mononuclear cells (PBMCs), representing latent, active, and healthy states. Differentially expressed genes (DEGs) were identified, followed by gene ontology (GO) enrichment, functional clustering, and miRNA interaction analysis. Semantic similarity, unsupervised clustering, and pathway enrichment were applied to refine the gene list. Key biomarkers were prioritized using receiver operating characteristic (ROC) curve analysis, with CCL2 and CXCL10 emerging as top candidates (AUC > 0.85). This multi-step approach demonstrates the potential of combining transcriptomic profiling with established machine learning and bioinformatics tools to uncover candidate biomarkers for improved LTBi detection, and it also provides a foundation for future experimental validation. Full article

Dormancy occurs when Mycobacterium tuberculosis (Mtb) enters a non-replicating and metabolically inactive state in response to hostile environment. During this state, it is highly resistant to conventional antibiotics, which increase the urgency to develop new potential drugs against dormant bacilli. In view of this, the dormancy survival regulator (DosR) protein is thought to be an essential component that plays a key role in bacterial adaptation to dormancy during hypoxic conditions. Herein, the NP-lib database containing natural product compounds was screened virtually against the binding site of the DosR protein using the MTiopen screen web server. A series of computational analyses were performed, including redocking, intermolecular interaction analysis, and MDS, followed by binding free energy analysis. Through screening, 1000 natural product compounds were obtained with docking energy ranging from −8.5 to −4.1 kcal/mol. The top four lead compounds were then selected for further investigation. On comparative analysis of intermolecular interaction, dynamics simulation and MM/GBSA calculation revealed that M3 docked with the DosR protein (docking score = −8.1 kcal/mol, RMSD = ~7 Å and ΔG Bind = −53.51 kcal/mol) exhibited stronger stability than reference compound Ursolic acid (docking score = −6.2 kcal/mol, RMSD = ~13.5 Å and ΔG Bind = −44.51 kcal/mol). Hence, M3 is recommended for further validation through in vitro and in vivo studies against latent tuberculosis infection. Full article

Latent tuberculosis infection (LTBI) is prevalent in patients with type 2 diabetes. We aimed to examine the relationship between serum levels of aryl hydrocarbon receptor (AhR) and LTBI in patients with type 2 diabetes. In this cross-sectional study, patients with type 2 diabetes were screened for LTBI using the QuantiFERON-TB (QFT) test. Of 543 patients screened for LTBI, 133 (24.5%) were QFT-positive. The QFT-positive patients had higher AhR levels than the QFT-negative patients (44.6 [interquartile range: 25.4–58.6] pg/mL vs. 37.8 [interquartile range: 17.4–55.0] pg/mL; p = 0.004). According to the receiver operating characteristic curve, the area under the curve was 0.584 (95% confidence interval: 0.528–0.639; p = 0.004) and the optimal cutoff value for serum AhR levels was of 37.7 pg/mL for differentiating a QFT-positive result. By a multivariable logistic regression analysis, the patients with high AhR levels had a greater risk of being QFT positive than those with low AhR levels (odds ratio = 1.902, 95% confidence interval: 1.254–2.886; p = 0.003). In conclusion, in patients with type 2 diabetes, a high serum AhR level was associated with LTBI. Full article

Background and Objectives: Abnormal blood and biochemical indicators could increase the risk of infectious diseases. However, the association between blood together with biochemical indicators and latent tuberculosis infection (LTBI) has not been well confirmed. Materials and Methods: Our aim was to assess the role of blood and biochemical indicators in the risk of LTBI. We enrolled 965 freshmen who were originating from tuberculosis key areas of a college in Nanjing. We used logistic regression models, restricted cubic spline (RCS), and nomograms to evaluate the association between blood and biochemical indicators and LTBI. In addition, calibration curves were performed to evaluate the quality of the model. Results: Among these 965 participants, 311 were diagnosed as LTBI according to TST. Multivariate models showed that the population with an eosinophils percentage around <0.5% (OR: 2.82, 95% CI: 1.39–5.74, p = 0.004) and 0.5–5% (OR: 2.78, 95% CI: 1.07–7.23, p = 0.036) were positively associated with LTBI. Elevated uric acid levels (OR: 1.01, 95% CI: 1.00–1.02, p = 0.047) were significantly associated with LTBI. In addition, participants with a history of tuberculosis exposure (OR: 3.26, 95% CI: 1.39–7.66) and a history of tuberculosis (OR: 10.92, 95% CI: 1.24–96.08) were also positively correlated with LTBI. Conclusions: Eosinophils percentage and uric acid are associated with LTBIs. Participants who have tuberculosis exposure history and tuberculosis history are the critical target population. Full article

Background/Objectives: Healthcare workers (HCWs) are globally recognized as a high-risk group for tuberculosis (TB) infection. However, limited data exist on the prevalence of latent TB infection (LTBI) and associated occupational risk factors in the Mexican context. Identifying the burden of LTBI is essential for effective prevention. This study aimed to estimate the prevalence of LTBI among HCWs in a tertiary care hospital in Mexico and to explore associated risk factors. Methods: An analytical cross-sectional study was conducted among 300 HCWs (including physicians, nurses, and stretcher-bearers) at a tertiary-level hospital in Mexico. Sociodemographic and occupational data were collected through a structured questionnaire. LTBI screening was performed using the tuberculin skin test (TST), with positive results confirmed via the QuantiFERON-TB Gold assay. Associations between relevant variables and LTBI were assessed using logistic regression models, adjusted for potential confounders. Results: The prevalence of LTBI was 16.7%. After adjusting for confounders, male HCWs had significantly higher odds of LTBI compared to females (adjusted odds ratio [aOR] = 2.02; 95% confidence interval [CI]: 1.06–3.80). Although elevated odds of LTBI were also observed among physicians, stretcher-bearers, and those with direct contact with TB patients, these associations were not statistically significant. Conclusion: LTBI represents a relevant occupational health issue among HCWs, with nearly one in six workers affected. Early detection and prevention of TB in healthcare settings are critical to protecting individual workers and public health. These findings highlight the need to strengthen occupational TB surveillance and prevention strategies in similar healthcare environments. Full article

Healthcare workers (HCWs) face an increased risk of tuberculosis (TB) due to occupational exposure. This study aimed to estimate the point prevalence of TB infection (TBI) from the initial test performed, while the reversion and conversion were done by subsequent testing at one year among HCWs in Puducherry, India. A prospective cohort study was conducted among a sample of proportionately chosen HCWs based on their occupational strata of a tertiary hospital in 2022. TBI was assessed using IGRA (4th generation QuantiFeron—TB gold plus kits) after TB symptom screening. The IGRA test was repeated at the end of one year. Reversion was defined as a positive IGRA test at the baseline and had values < 0.2 IU/L in TB1 or TB2 tubes during follow-up. Conversion was defined as a negative IGRA result at the baseline and had values of >0.7 IU/L in TB1 or TB2 tubes during follow-up. Of the 400 HCWs included, the mean (SD) age was 37 (7) years. Median (IQR) work experience was 15.7 (10–21) years. TBI was seen in 150 HCWs (37.7%, 95% CI: 33.0–42.7), and one had active TB. A total of 128/150 HCWs with TBI at baseline were followed up, and 15 had TBI reversion (11.7 per 100 person-years; 95% CI: 6.7–18.5). Thirteen HCWs (5.6 per 100 person-years; 95% CI: 3.3–9.8) had TBI conversion. Full article

Background/Objectives: Pediatric drug administration is hindered by difficulties in swallowing conventional medications and the unpalatable taste of many drugs. Among diseases highlighting the need for improved pediatric delivery, tuberculosis (TB) stands out. One form of the disease is latent TB infection (LTBI), which is concerning in children. Effective LTBI treatment is crucial for prevention, with isoniazid (INH) widely used for its proven efficacy and safety. This study aims to develop innovative 3D-printed chewable gels containing INH for LTBI treatment. Methods: The gels were formulated using gelatin and carrageenan gum, sugar-free sweeteners, and flavoring. Two batches were prepared, and using 3D printing (3DP) with a semi-solid extrusion (SSE) module, chewable gels were produced. Rheological properties were measured to assess the feasibility of 3DP-SSE, evaluating the structural integrity and adequate fluidity of the formulation. The 3D-printed chewable gels were evaluated by visual, mass, and dimensional characteristics. In addition, the water activity, texture profile, INH and degradation product content, in vitro release, and taste-masking were investigated. Results: The optimized formulation maintained suitable rheological properties for 3DP-SSE, demonstrating consistent weight, dimensions, and stability after the process. The texture achieved a balance between printing parameters and shape maintenance, and the INH presented an immediate-release profile (>85% within 30 min). The chewable gels showed an improvement in palatability compared to conventional INH tablets. Conclusions: This innovative approach offers a promising solution for pediatric LTBI treatment, as it improves efficacy, medication acceptability, and on-demand access. Full article

Background: This case is unique in demonstrating the reactivation of latent tuberculosis (TB) following co-infection with SARS-CoV-2 and Epstein–Barr virus (EBV) in an otherwise healthy young adult. It highlights a rare clinical scenario in which viral immune dysregulation likely facilitated TB progression. To date, few reports have explored the complex interplay between COVID-19, EBV reactivation, and TB in a single patient, particularly with isolated extrapulmonary involvement. Case Presentation: A 24-year-old woman presented with persistent low-grade fever, fatigue, night sweats, unintentional weight loss, and progressive cervical and supraclavicular lymphadenopathy. These symptoms emerged shortly after a moderate COVID-19 infection. Laboratory studies revealed elevated inflammatory markers and pronounced lymphopenia. EBV reactivation was confirmed via serology and PCR. Despite antiviral therapy, symptoms persisted, and imaging revealed necrotic lymphadenopathy. Tuberculous lymphadenitis was diagnosed through fine-needle aspiration cytology and PCR detection of Mycobacterium tuberculosis. The patient was treated with a standard anti-tuberculosis regimen, resulting in clinical, radiological, and immunological improvement. Conclusions: This case underscores the importance of considering latent TB reactivation in patients with persistent lymphadenopathy and recent viral infections, particularly in regions with high TB prevalence. It also emphasizes the need for thorough immunological and microbiological assessment in complex post-viral syndromes. The main clinical takeaway is that COVID-19 and EBV co-infection may create a permissive environment for TB reactivation through immune system compromise. Full article

Tumor necrosis factor (TNF) is a key immunoregulatory cytokine with a dual role in the host response to Mycobacterium tuberculosis. While essential for granuloma formation, macrophage activation, and containment of latent infection, TNF can also contribute to tissue damage and immune pathology. This review systematically analyzes over 300 peer-reviewed studies published between 1980 and 2024, highlighting the molecular and cellular mechanisms of TNF action in tuberculosis (TB). Particular attention is given to TNF receptor signaling pathways, the balance between protective and pathological immune responses, and the modulation of TNF activity during anti-TNF therapy in patients with autoimmune diseases. We discuss how different TNF inhibitors vary in their capacity to interfere with host defense mechanisms, with monoclonal antibodies carrying a higher reactivation risk than receptor-based agents. To enhance conceptual clarity, we provide newly developed schematic representations that integrate current knowledge on TNF-driven immune dynamics, including its interaction with other cytokines, effects on granuloma stability, and role in intracellular bacterial control. Understanding the pleiotropic functions of TNF in tuberculosis pathogenesis is crucial for developing safe immunomodulatory strategies and optimizing the clinical management of patients at risk of latent TB reactivation. Full article