Search Results (900)

Tuberculosis (TB) is an ancient and re-emerging granulomatous infectious disease that continues to challenge public health. Early diagnosis and prompt effective treatment are crucial for preventing disease progression and reducing both morbidity and mortality. These steps play a vital role in infection control and in lowering death rates at both individual and population levels. Although diagnostic methods have improved sufficiently in recent decades, TB can still present with ambiguous laboratory and imaging features. This ambiguity can lead to diagnostic pitfalls and potentially disastrous outcomes due to delayed diagnosis. In this article, we present a case of TB that was difficult to diagnose. The disease had invaded the mediastinum, right atrium, right coronary artery, and inferior vena cava (IVC), resulting in Budd–Chiari syndrome. This rare presentation created clinical, laboratory, and radiological confusion, resulting in a diagnostic dilemma that ultimately led to open cardiac surgery. The patient initially presented with progressive shortness of breath on exertion and fatigue, which suggested possible heart disease. This suspicion was reinforced by computed tomography (CT) imaging, which showed infiltrative mass lesions predominantly in the right side of the heart, invading the right coronary artery and IVC, with imaging features mimicking angiosarcoma. Although laboratory findings revealed an exudative effusion with lymphocyte predominance and elevated adenosine deaminase (ADA), the Gram stain was negative for bacteria, and an acid-fast bacilli (AFB) smear was also negative. These findings contributed to diagnostic uncertainty and delayed the confirmation of TB. Open surgery with excisional biopsy and histopathological analysis ultimately confirmed TB. We conclude that TB should not be ruled out solely based on negative Mycobacterium bacteria in pericardial effusion or AFB smear. TB can mimic aggressive tumors such as angiosarcoma or lymphoma with invasion of the surrounding tissues and blood vessels. Awareness of the clinical presentation, imaging findings, and potential diagnostic pitfalls of TB is essential, especially in endemic regions. Full article

Background: Disease-modifying drugs (DMDs) for multiple sclerosis (MS) slightly increase the risk of tuberculosis (TB) disease. The QuantiFERON-TB-Plus (QFT-Plus) test is approved for TB infection (TBI) screening. Currently, there are no data available regarding the characterization of QFT-Plus response in patients with MS. Objectives: This study aimed to compare the magnitude of QFT-Plus responses between patients with MS and TBI (MS-TBI) and TBI subjects without MS (NON-MS-TBI). Additionally, discordant responses to TB1/TB2 stimulation were documented. Results were evaluated considering demographic and clinical data, particularly the impact of DMDs and the type of TB exposure. Methods: Patients with MS (N = 810) were screened for TBI (2018–2023). Thirty (3.7%) had an MS-TBI diagnosis, and 20 were recruited for the study. As a control group, we enrolled 106 NON-MS-TBI. Results: MS-TBI showed significantly lower IFN-γ production in response to TB1 (p = 0.01) and TB2 stimulation (p = 0.02) compared to NON-MS-TBI. The 30% of TB2 results of MS-TBI fell into the QFT-Plus grey zone (0.2–0.7 IU/mL). Only 7% of NON-MS-TBI showed this profile (p = 0.002). Conclusions: MS-TBI had a lower QFT-Plus response and more borderline results compared to NON-MS-TBI. Future studies should clarify the significance of the borderline results in this vulnerable population to improve QFT-Plus accuracy regarding sensitivity, specificity, and TB prediction. Full article

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

Human leukocyte extract (HLE), a non-immunogenic dialyzable leukocyte preparation (<10 kDa), may serve as a safe adjuvant in immunotherapy. We investigated the effects of albendazole (ABZ), HLE, and their combination in Mesocestoides vogae infected mice, focusing on lymphoid cells in the peritoneal cavity, the site of larval proliferation and parasite-induced immunosuppression. Peritoneal lymphoid cells were analysed by flow cytometry and qPCR. Cells proliferative responses to ConA, LPS, and parasite excretory/secretory (E/S) antigens, cytokine production (ELISA), IgM and IgG isotypes in exudates and parasite antigen recognition (Western blot) were assessed. Efficacy was measured by larval burden and 14-3-3 gene expression in larvae. HLE combined with ABZ enhanced larval clearance and suppressed 14-3-3 gene expression in larvae. HLE and combination therapy increased CD3⁺ T cell frequencies, especially CD3^+high, reduced regulatory CD3+/IL-10 Tregs and expression of Foxp3⁺. All treatments diminished CD19⁺/IL-10⁺ Bregs, correlating with lower CD9 and Atf3 mRNA levels compared to infected mice. Transcription factors T-bet expression was strongly upregulated, while GATA3 was moderately elevated. IFN-γ production and T/B cell proliferation were restored after HLE and combination therapy, partially, even in the presence of E/S antigens. IgM and total IgG levels against parasite antigens declined, while Th1-associated IgG2a increased in ABZ+HLE and HLE-treated groups. Albendazole failed to reverse the immunosuppressive Treg-type immunity but was more effective in reducing Breg populations and their functions. HLE enhanced ABZ efficacy by restoring Th1 responsiveness, reducing Treg/Breg activity, and modulating antibody profiles. It represents a promising immunomodulatory adjuvant in the treatment of the infections associated with Th2/Treg-driven immunosuppression. 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: Dendritic cells (DCs) play an important role as a bridge between innate and adaptive immunity, and changes in gene expression of DCs during the immune response to Mycobacterium tuberculosis (M.tb) may affect the development of tuberculosis. Methods: Using systems biology methods, mRNA and miRNA expression profile data of DCs infected with M.tb were obtained. A total of 1398 differentially expressed mRNAs and 79 differentially expressed miRNAs were identified, and a corresponding miRNA–mRNA regulatory network was constructed using Cytoscape 3.9.1 software. The functional annotations and pathway classifications of the miRNA–mRNA network were identified using the DAVID tool. Then, the key pathway modules in the miRNA–mRNA network were screened and subjected to PPI network analysis to identify hub nodes. Subsequently the miRNA/mRNA axis was determined, validated by qRT-PCR, and evaluated through ROC curve analysis. Results: The TNF signaling pathway and the Tuberculosis pathway were key pathway modules, with miR-34a-3p/TNF and miR-190a-3p/IL1B being the greatest correlations with the two pathway modules. qRT-PCR results showed that IL1B and miR-190a-3p exhibited significant differences in both the H37Ra and BCG infection groups. The AUC of two factors (IL1B and miR-190a-3p) was 0.9561 and 0.9625, respectively, showing high sensitivity and specificity. Conclusions: Consequently, miR-190a-3p/IL1B might be a good candidate marker to characterize the immune response of DCs to M.tb and a transition signal from innate to adaptive immunity. 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

Background: Accurate differentiation between Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM) is essential for proper diagnosis and treatment. This study compares the diagnostic performance of two commercial real-time PCR kits, AdvanSure^TM TB/NTM and Kogene PowerChek^TM MTB/NTM, for detecting MTB, NTM, and negative (no growth, NG) clinical specimens. Methods: A total of 390 clinical residual specimens were collected from patients between December 2022 and June 2023. The samples, including sputum, bronchoalveolar lavage, tracheal aspirate and body fluid, were initially tested with MGIT culture and then analyzed using both PCR kits. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were evaluated. Discrepant results between the two PCR assays were further investigated using sequencing to identify the detected mycobacterial species, and final diagnoses were verified by culture results and review of electronic medical records. Results: Of the 390 specimens, both AdvanSure^TM and PowerChek^TM real-time PCR assays demonstrated 100% sensitivity for both MTB and NTM detection. For MTB detection, AdvanSure^TM demonstrated a specificity of 100%, with a PPV, NPV, and overall accuracy all reaching 100%. In comparison, PowerChek^TM showed a specificity of 98.62%, a PPV of 96.15%, an NPV of 100%, and an overall accuracy of 98.97%. For NTM detection, both AdvanSure^TM and PowerChek^TM exhibited identical performance metrics. The specificity was 99.58% for both assays, with a PPV of 99.34%, NPV of 100%, and an overall accuracy of 99.74%. Five discrepant results were finally confirmed as four NTM detection cases and one negative case by culture and clinical diagnosis which showed four cases of PowerChek^TM MTB+NTM detection and one case of NTM detection, respectively. Conclusions: The PowerChek^TM MTB/NTM real-time PCR kit demonstrated excellent diagnostic performance for the detection of MTB and NTM, with high sensitivity, specificity, and accuracy. Minor discrepancies, particularly in detecting MTB+NTM mixed infections, highlight the importance of complementary sequencing analysis for resolving uncertain results. These findings support the clinical utility of both PCR assays as reliable tools for rapid diagnosis of mycobacterial infections. PowerChek^TM showed occasional false positives, suggesting that optimizing the assay’s cutoff threshold or amplification parameters could enhance its specificity and reduce false-positive results in clinically ambiguous cases. Full article

Mycobacterium (M.) tuberculosis mostly spreads from active tuberculosis (TB) patients to human contacts, although human-to-animal and animal-to-human transmission has been described. Here, we present a rare case of rifampicin-resistant tuberculosis (RR-TB) transmission from a companion dog to its owner, highlighting the zoonotic potential of the pathogen. Namely, a 37-year-old Croatian man was diagnosed with RR-TB, with whole-genome sequencing analysis revealing a close genetic link to the strain isolated from his dog, which had died of miliary TB six years earlier. This case emphasizes the complexity of TB transmission dynamics, particularly involving companion animals, and underlines the importance of integrated “One Health” approaches for TB control. Awareness of zoonotic TB risks is essential for the early detection and prevention of cross-species transmission, especially in vulnerable populations and households with close human–animal contact. Full article

The pivotal component in the protection against TB is the tissue macrophages (Mф). These cells have been demonstrated to play a crucial role in the elimination of pathogens and mycobacterial killing. Elucidation of the molecular and phenotypic events that determine the outcome of infection in Mф is fundamental to understanding the key features of these cells that are so important in fighting infection. Mф activation is driven by cytokines and other inflammatory mediators secreted by T lymphocytes. The interaction between Mycobacterium tuberculosis (Mtb) and host Мф has been the subject of extensive in vitro research. This dynamic interplay represents a pivotal step in the progression of mycobacterial infection because pulmonary macrophages constitute the primary line of defense against the pathogen, thereby serving as the initial immune cells to which Mtb must adapt to establish a replicative foothold within the host. Our studies have demonstrated that highly differentiated Th1 effectors with the CD27^low phenotype exhibit superior efficacy in activating both peritoneal (Mф: T cell ratio ranging from 125:1 to 625:1) and pulmonary macrophages (Mф: T cell ratio = 5:1) compared to cells with the CD27^high phenotype. Furthermore, our findings indicate that this activation mechanism is not contingent upon the production of reactive nitrogen species. To effectively activate the bacteriostatic function of macrophages, CD27^high T lymphocytes must differentiate into effectors with the CD27^low phenotype. 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: Acute respiratory distress syndrome (ARDS) secondary to tuberculosis (TB) is rare and associated with high mortality. Management is further complicated by comorbidities and ICU-related complications. Methods: We report a 43-year-old woman with post-polio sequelae and uncontrolled diabetes who developed ARDS due to pulmonary TB, complicated by recurrent nosocomial infections and gastrointestinal bleeding. Early bronchoscopy and GeneXpert MTB/RIF PCR were performed on ICU Day 2, enabling anti-TB therapy initiation by ICU Day 3. The patient received lung-protective ventilation, prone positioning, tailored antibiotics, and multidisciplinary care. Results: The patient’s clinical course was complicated by two episodes of ventilator-associated pneumonia and gastrointestinal bleeding, but with individualized management, she achieved ventilator weaning and functional recovery. Conclusions: Early TB recognition in ARDS is crucial. Multidisciplinary ICU management, including prudent steroid use, improves outcomes. Full article

Tuberculosis (TB) is a major global health threat, with the current Bacillus Calmette–Guérin (BCG) vaccine having limited efficacy against adult pulmonary disease. Trained immunity (TI) is a form of innate immune memory that enhances antimicrobial defense. It is characterized by the epigenetic and metabolic reprogramming of innate immune cells and holds promise as a promising approach to prevent TB. In this study, we investigated the capacity of heparin-binding hemagglutinin (HBHA), a methylated antigen of Mycobacterium tuberculosis, to induce TI in murine RAW264.7 macrophages, human-derived THP-1 macrophages, and human peripheral blood mononuclear cells (hPBMCs). HBHA-trained macrophages exhibited the enhanced expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) following secondary lipopolysaccharide stimulation. The epigenetic profiling indicated elevated levels of H3K4me1 and H3K4me3 histone marks at cytokine gene loci. Further, metabolic analysis revealed heightened lactate production and the increased expression of glycolytic enzymes. Functionally, HBHA-trained macrophages exhibited improved control of intracellular mycobacteria, as evidenced by a significant reduction in colony-forming units following BCG infection. These findings elucidate that HBHA induces a functional TI phenotype via coordinated epigenetic and metabolic changes, and suggest HBHA may serve as a valuable tool for studying TI and its relevance to host defense against mycobacterial infections, pending further in vivo and clinical validation. Full article

Background: Multidrug-resistant tuberculosis (MDR-TB) remains a significant public health threat in Central Asia, where rising resistance to first-line anti-TB drugs challenges control efforts. As of 2024, the World Health Organization (WHO) reports that over 2.5% of new TB cases and 18% of previously treated cases are resistant to first-line TB drugs worldwide. Objectives: This integrative review synthesizes current evidence on MDR-TB in Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan, with a focus on infection control, diagnostic advancements, and evolving treatment strategies. Methods: A comprehensive literature search was conducted across five electronic databases: PubMed, Scopus, Web of Science, Embase, World Health Organization (WHO) Global Tuberculosis Database, and ClinicalTrials.gov. A total of 29 articles from Central Asian countries met the inclusion criteria. Results: Four main themes were identified: “genetic variability and resistance patterns of MDR-TB strains”; “barriers to effective treatment”; “diagnostic tools”, and “infection control strategies”. Conclusions: This review underscores the importance of comprehensive, multifactorial approaches in addressing drug-resistant TB in the region. The implementation of early diagnosis and all-oral treatment regimens has improved adherence in recent studies. Full article

Background/Objectives: Tuberculosis (TB) and HIV co-infection pose significant challenges in resource-limited settings, contributing to multi-drug-resistant TB when treatment fails. This study aimed to identify determinants of TB treatment outcomes among HIV/TB co-infected patients in Lusaka, Zambia. Methods: A retrospective cohort study was conducted at Chilenje, Chipata, and Chawama level one hospitals, using systematic sampling to select 586 patient files. Data were analyzed with SPSS version 23, employing descriptive statistics, chi-square tests, and hierarchical logistic regression. Results: Among the study population (n = 586), consisting predominantly of working-age adults (25–44 years: 61.6%) and males (56.5%), treatment success was 81.3%, with a 12.5% mortality rate across treatment phases. Baseline smear-negative TB, viral load (100,000–199,999 copies/mL), diabetes without hypertension, and negative smear at follow-up independently predicted treatment outcomes. Higher treatment failure odds were linked to smear-negative TB, high viral load, and hypertension–diabetes comorbidity, while CD4 count and HIV treatment status showed no independent effects. Conclusions: These findings underscore the influence of viral load, TB type, comorbidities, and sputum conversion on treatment success, emphasizing the need for targeted monitoring and integrated care, particularly in the continuation phase, to enhance outcomes in this vulnerable population. Full article