Search Results (1,258)

Tuberculosis (TB) continues to be the world’s deadliest infectious disease, with an estimated 10.8 million new cases reported in 2023, of which India alone accounted for 28% of the global burden. This study aims to evaluate the impact of tuberculosis on pulmonary function and exercise tolerance, and to examine how these impairments affect health-related quality of life (HRQoL). In a cross-sectional design, 96 bacteriologically confirmed TB patients and 96 age- and sex-matched community controls underwent spirometry, six-minute-walk test (6 MWT), and HRQoL evaluation. DR-TB was detected in 27 patients (28.1%): Isoniazid monoresistance 59.3%, rifampicin monoresistance 11.1%, and XDR-TB 29.6%. Dyspnoea (70.8%) and cough (37.5%) were the most commonly reported symptoms among TB patients. Mean values of FEV₁, FVC, and FEV₁/FVC were significantly lower in TB patients compared to controls (62.8%, 65.97%, and 70.08% vs. 82.55%, 80.09%, and 78.08%, respectively; p < 0.001). Recurrent or DR-TB was associated with reduced spirometric indices and 6 MWT distances (241 m vs. 358 m in drug-sensitive TB). St. George’s respiratory questionnaire (SGRQ) scores indicated significantly poorer health-related quality of life (HRQoL) in patients compared to controls across all domains—symptoms (23.7 vs. 10.7), activity (33.3 vs. 14.2), and impact (20.6 vs. 9.4; p < 0.05). SGRQ scores were inversely correlated with lung function parameters (r = −0.42 to −0.56). These findings underscore the persistent health burden TB poses post-therapy, highlighting the need for routine post-TB functional screening and robust DR-TB control to achieve End-TB goals. Full article

Tuberculosis (TB) remains a formidable global public health challenge. The rising prevalence of drug-resistant TB and increased human immunodeficiency virus(HIV) co-infection further exacerbate TB control efforts. Mycobacterium tuberculosis (Mtb) achieves highly heterogeneous infection outcomes (active disease, latency, or clearance) through immune evasion and host metabolic reprogramming. While conventional diagnostic techniques offer cost-effectiveness and accessibility without complex infrastructure, they are constrained by low sensitivity, prolonged turnaround times, and an inability to distinguish latent TB infection (LTBI) from active TB disease (ATB). Recent research into host-derived biomarkers provides a promising strategy to overcome diagnostic bottlenecks by deciphering characteristic molecular changes in host–pathogen interactions. This review systematically reviews advances in host-derived biomarkers for TB diagnosis, critically discussing the clinical potential, translational challenges, and future research directions of integrated multi-omics biomarker panels to enhance diagnostic sensitivity and specificity, differentiate ATB from LTBI, and guide precision therapy. Full article

Background/Objectives: Effective prophylaxis for Mycobacterium tuberculosis (Mtb) requires greater understanding of immune correlates of protection. With renewed interest in BCG as an Mtb vaccine, particularly via the intravenous (IV) route, our objective was to characterize both innate and adaptive immune correlates of vaccine-induced pulmonary immunity as potential biomarkers for protective efficacy in a murine model of Mtb infection. Methods: Mice were given BCG via different routes and some boosted with recombinant virus constructs encoding Mtb Ag85B. Responding innate lymphoid cell (ILC) populations, T cells and B cells were analyzed by fluorescence activated cell sorting (FACS) for surface markers and by intracellular cytokine staining or antibody ELISPOT. Some immunized mice were challenged with aerosolized Mtb and monitored for bacterial growth in the lungs and spleen. Results: BCG given IV, but not intranasally or subcutaneously, resulted in marked increases in IFNγ expression at 72 h by pulmonary CD49⁺ NK cells, CD69⁺ ILC1, and two ILC3 populations, NCR-ILC3 and LTi cells, the latter also producing IL-22. Pulmonary ILC2 populations in these mice had significantly increased IL-13 expression at 24 h compared to the other routes. Interestingly, high levels of NK cells and ILC1 expressing IFNγ and/or TNFα were sustained at 8 wk, with sustained expression of IL-17A by pulmonary NCR-ILC3 and pronounced tissue-resident and effector memory CD4⁺ and CD8⁺ T cell responses. Intranasal boosting with Ad-Ag85B enhanced these T cell responses and generated Mtb-specific pulmonary IgA and IgG B cells, correlating with significantly reduced bacterial loads following Mtb challenge. Conclusions: BCG given IV primed for both early and persistent pulmonary ILC1/ILC3 responses of a predominantly Th1/Th17-type profile along with local Mtb-specific memory T cell and B cell populations, correlating with enhanced protective efficacy. These are worthy of further study as compartmentalized biomarkers for effective vaccine-induced local immunity against Mtb. Full article

Background: Tuberculosis (TB) remains a major global health challenge, including in Thailand, where both asymptomatic and symptomatic cases sustain transmission. The disease burden increases treatment complexity and mortality, requiring integrated care and coordinated policies. Methods: We developed a deterministic compartmental model to examine the transmission dynamics of TB in Thailand, incorporating both latent and active stages of infection, as well as vaccination coverage. The model was calibrated using national TB incidence data, and sensitivity analysis revealed that the TB transmission rate was the most influential parameter affecting the basic reproduction number (R₀). We evaluated the impact of several intervention strategies, including increased treatment coverage for latent and active TB infections and improved vaccination rates. Results: Our analysis indicates that among the single interventions, scaling up effective treatment for latent TB infections produced the greatest reduction in asymptomatic and symptomatic cases, while enhanced treatment for active TB cases was second most effective for reducing both asymptomatic and symptomatic cases. Importantly, our results indicate that combining multiple interventions yields significantly greater reductions in overall TB incidence than any single approach alone. Our findings suggest that a modest investment in integrated TB control can substantially reduce TB transmission and disease burden in Thailand. However, complete eradication of TB would require a comprehensive and sustained investment to achieve near-universal coverage of both preventive and curative strategies. Conclusions: TB remains a significant public health threat in Thailand. Targeted interventions and integrated strategies are key to reducing disease burden and improving treatment outcomes. Full article

Sexually transmitted infections (STIs) are a significant global health concern, affecting millions of people worldwide, particularly sexually active adolescents and young adults. These infections, caused by various pathogens, including bacteria, viruses, parasites, and fungi, can have profound implications for women’s reproductive health and fertility. This review explores the role of vaginal and uterine infections in women’s infertility, focusing on the most common pathogens and their impact on reproductive outcomes. Bacterial infections, such as those caused by intracellular bacteria (Mycoplasma, Ureaplasma, and Chlamydia), Neisseria gonorrhoeae, and bacterial vaginosis, are among the most prevalent causes of infertility in women. Studies have shown that these infections can lead to pelvic inflammatory disease, tubal occlusion, and endometrial damage, all of which can impair fertility. Mycobacterium tuberculosis, in particular, is a significant cause of genital tuberculosis and infertility in high-incidence countries. Viral infections, such as Human papillomavirus (HPV) and Herpes simplex virus (HSV), can also affect women’s fertility. While the exact role of HPV in female infertility remains unclear, studies suggest that it may increase the risk of endometrial implantation issues and miscarriage. HSV may be associated with unexplained infertility. Parasitic infections, such as trichomoniasis and schistosomiasis, can directly impact the female reproductive system, leading to infertility, ectopic pregnancy, and other complications. Fungal infections, such as candidiasis, are common but rarely have serious outcomes related to fertility. The vaginal microbiome plays a crucial role in maintaining reproductive health, and alterations in the microbial balance can increase susceptibility to STIs and infertility. Probiotics have been proposed as a potential therapeutic strategy to restore the vaginal ecosystem and improve fertility outcomes, although further research is needed to establish their efficacy. In conclusion, vaginal and uterine infections contribute significantly to women’s infertility, with various pathogens affecting the reproductive system through different mechanisms. Early diagnosis, appropriate treatment, and preventive measures are essential to mitigate the impact of these infections on women’s reproductive health and fertility. Full article

This review addresses the urgent need for alternative strategies to combat drug-resistant mycobacterial infections, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, as well as non-tuberculous mycobacterial (NTM) diseases. Traditional antibiotics are increasingly limited by resistance, toxicity, and poor efficacy, particularly in immunocompromised patients. A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar, covering publications primarily from 2000 to 2025. Only articles published in English were included to ensure consistency in data interpretation. Search terms included “mycobacteriophages,” “phage therapy,” “drug-resistant mycobacteria, “diagnostic phages,” and “phage engineering.” The review examines the therapeutic and diagnostic potential of mycobacteriophages—viruses that specifically infect mycobacteria—focusing on their molecular biology, engineering advances, delivery systems, and clinical applications. Evidence suggests that mycobacteriophages offer high specificity, potent bactericidal activity, and adaptability, positioning them as promising candidates for targeted therapy. Although significant obstacles remain—including immune interactions, limited host range, and regulatory challenges—rapid progress in synthetic biology and delivery platforms continues to expand their clinical potential. As research advances and clinical frameworks evolve, mycobacteriophages are poised to become a valuable asset in the fight against drug-resistant mycobacterial diseases, offering new precision-based solutions where conventional therapies fail. 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

Background: Secukinumab is a fully human monoclonal antibody that targets interleukin (IL)-17A and is used to treat axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Treating axSpA and PsA can be challenging in patients with comorbidities. In this multicenter retrospective study, we aimed to evaluate the efficacy and safety of secukinumab treatment in patients with axSpA and PsA who had a history of tuberculosis, multiple sclerosis (MS), or congestive heart failure (CHF). Methods: The study included 44 patients with a diagnosis of axSpA and PsA and a history of tuberculosis, MS, or CHF who received secukinumab treatment at 13 centers in our country. Erythrocyte sedimentation rate, C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index, Ankylosing Spondylitis Disease Activity Score CRP, visual analog scale, and Disease Activity Score-28 CRP markers at months 0, 3, and 12 of secukinumab treatment were analyzed. Alongside this, tuberculosis, MS, and CHF were evaluated at follow-up using clinical assessments and imaging methods such as chest radiographs, brain magnetic resonance, and echocardiography. Results: A statistically significant improvement in inflammatory markers and disease activity scores was observed in patients treated with secukinumab. There was no reactivation in patients with a history of tuberculosis. In most MS patients, the disease was stable, while clinical and radiological improvement was observed in one patient. No worsening of CHF stage was observed in patients with a history of CHF. Conclusions: With regular clinical monitoring, secukinumab may be an effective and safe treatment option for axSpA and PsA patients with a history of tuberculosis, MS, or CHF. Full article

Background/Objectives: The integration of machine learning (ML) and artificial intelligence (AI) has revolutionized the pharmaceutical industry by improving drug discovery, development and manufacturing processes. Based on literature data, an ML model was developed by our group to predict the formation of binary co-amorphous systems (COAMSs) for inhalation therapy. The model’s ability to develop a dry powder formulation with the necessary properties for a predicted co-amorphous combination was evaluated. Methods: An extended experimental validation of the ML model by co-milling and X-ray diffraction analysis for 18 API-API (active pharmaceutical ingredient) combinations is presented. Additionally, one COAMS of rifampicin (RIF) and ethambutol (ETH), two first-line tuberculosis (TB) drugs are developed further for inhalation therapy. Results: The ML model has shown an accuracy of 79% in predicting suitable combinations for 35 APIs used in inhalation therapy; experimental accuracy was demonstrated to be 72%. The study confirmed the successful development of stable COAMSs of RIF-ETH either via spray-drying or co-milling. In particular, the milled COAMSs showed better aerosolization properties (higher ED and FPF with lower standard deviation). Further, RIF-ETH COAMSs show much more reproducible results in terms of drug quantity dissolved over time. Conclusions: ML has been shown to be a suitable tool to predict COAMSs that can be developed for TB treatment by inhalation to save time and cost during the experimental screening phase. 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

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: 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) poses a persistent global health threat exacerbated by the emergence of drug-resistant strains; hence, there is a continuous quest for novel antimicrobial agents. Despite efforts to develop effective therapies, existing treatments require a relatively long duration of therapy to eradicate the pathogen due to its virulence factors, pathogenesis patterns, and ability to enter dormant states. This can lead to a higher risk of treatment failure due to poor patient adherence to the complex regimen. As a result, considerable research is necessary to identify alternative antituberculosis agents. The marine environment, particularly marine-derived fungi, has recently gained interest due to its potential as an abundant source of bioactive natural products. This review covers 19 genera of marine-derived fungi and 139 metabolites, 131 of which exhibit antimycobacterial activity. The integrated dataset pinpoints the fungal genera and chemical classes that most frequently yield potent antimycobacterial hits while simultaneously exposing critical gaps, such as the minimal evaluation of compounds against dormant bacilli and the presence of underexplored ecological niches and fungal genera. Several compounds exhibit potent activity through uncommon mechanisms, including the inhibition of mycobacterial protein tyrosine phosphatases (MptpB/MptpA), protein kinase PknG, ATP synthase and the disruption of mycobacterial DNA via G-quadruplex stabilization. Structure–activity relationship (SAR) trends are highlighted for the most potent agents, illuminating how specific functional groups underpin target engagement and potency. This review also briefly proposes a dereplication strategy and approaches for toxicity mitigation in the exploration of marine-derived fungi’s natural products. Through this analysis, we offer insights into the potency and challenges of marine-derived fungi’s natural products as hit compounds or scaffolds for further antimycobacterial research. Full article