Search Results (4,064)

Tuberculosis is a zoonotic chronic respiratory infectious disease caused by the Mycobacterium tuberculosis complex. The outbreak and epidemic of tuberculosis can seriously threaten human and veterinary health. To investigate the effects of environmental factors on tuberculosis in domestic ruminants, we collected data regarding the prevalence of tuberculosis in cattle, buffaloes, sheep, and goats in China (1956–2024) from publicly published literature and available databases. We identified the key risk factors among six major air pollutants and 19 bioclimatic variables; simulated the risk distribution of tuberculosis in cattle, buffaloes, sheep, and goats in China using the maximum entropy ecological niche model; and evaluated the effects of environmental factors. The area under the curve of the model was 0.873 (95% confidence interval, 0.851–0.895). The risk factors that most significantly influenced the prevalence of tuberculosis were the nitrogen dioxide (NO₂) level, mean temperature of the coldest quarter, cattle distribution density, sheep distribution density, ozone (O₃) level, and precipitation of the driest month. The predicted map of tuberculosis risk in cattle, buffaloes, sheep, and goats indicated that the high-risk regions were mainly distributed in South, North, East, and Northwest China. Improved surveillance is needed in these high-risk areas, and early preventive measures must be implemented based on the risk factors identified to reduce the future prevalence of tuberculosis in cattle, buffaloes, sheep, and goats. Full article

Comorbidities in tuberculosis patients are increasing annually. Autoimmune pathology may influence the diagnosis and treatment of tuberculosis (TB). However, the molecular mimicry between Mycobacterium tuberculosis (Mtb) and human autoantigens is an important provocative factor in the development of autoimmunity on one hand. Mtb has already been widely discussed as a provocateur of autoimmunity in humans. The aim of this study was to determine whether molecular mimicry exists between Mtb antigens and human autoantigens previously demonstrated as targets of autoimmunity. Materials and Methods: We analyzed the level of antibodies in 19 patients with pulmonary tuberculosis. In all cases ELISA assays was used. Also, in parallel, we identified 29 similar pentapeptides between key Mtb antigens and human autoantigens. Bioinformatic methods were used in this study. All amino acid sequences of MT antigens and human autoantigens were obtained from the UniProt database, and similar epitopes between Mtb antigens and human autoantigens were identified using the original “Alignmentaj” program. The immunoreactivity of the shared pentapeptides in Mtb antigens was evaluated with use of the IEDB database. Results: The high level of antibodies to modified citrulinated vimentin (anti-MCV) was most frequently detected (57%) in comparison with other antibodies. Elevated levels of antibodies to C3 complement fragments (47%) and rheumatoid factors (21%) in the absence of any rheumatic or autoimmune diseases are noteworthy. Several of the shared pentapeptides belong to the immunoreactive epitopes of Mtb antigens. The bioinformatic data correlated with our earlier studies of the levels of corresponding autoantibodies in the sera of TB patients. Conclusion: Our findings on cross-reactivity and sequence similarity between the Mtb proteins and human autoantigens provide support for the role of antigen mimicry in TB-related autoimmunity. Full article

Mycobacterial infections, caused by various species within the Mycobacterium genus, remain one of the main challenges to global health across the world. Understanding the complex interplay between the host and mycobacterial pathogens is essential for developing effective diagnostic and therapeutic strategies. Host long noncoding RNAs (lncRNAs) have emerged as key regulators in cellular response to bacterial infections within host cells. This review provides an overview of the intricate relationship between mycobacterial infections and host lncRNAs in the context of Mycobacterium tuberculosis and non-tuberculous mycobacterium (NTM) infections. Accumulation of evidence indicates that host lncRNAs play a critical role in regulating cellular response to mycobacterial infection within host cells, such as macrophages, the primary host cells for mycobacterial intracellular survival. The expression of specific host lncRNAs has been implicated in the pathogenesis of mycobacterial infections, providing potential targets for the development of novel host-directed therapies and biomarkers for TB diagnosis. In summary, this review aims to highlight the current state of knowledge regarding the involvement of host lncRNAs in mycobacterial infections. It also emphasizes their potential application as novel diagnostic biomarkers and therapeutic targets. Full article

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the leading infectious causes of death globally, with drug resistance presenting a significant challenge to control efforts. The interplay between type 2 diabetes mellitus (T2DM) and TB introduces additional complexity, as T2DM triples the risk of active TB and exacerbates drug resistance development. This review explores how T2DM-induced metabolic and immune dysregulation fosters the survival of Mtb, promoting persistence and the emergence of multidrug-resistant strains. Mechanisms such as efflux pump activation and the subtherapeutic levels of isoniazid and rifampicin in T2DM patients are highlighted as key contributors to resistance. We discuss the dual syndemics of T2DM–TB, emphasizing the role of glycemic control and innovative therapeutic strategies, including efflux pump inhibitors and host-directed therapies like metformin. This review underscores the need for integrated diagnostic, treatment, and management approaches to address the global impact of T2DM–TB comorbidity and drug resistance. Full article

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a leading cause of global mortality. While TB detection can be performed through chest X-ray (CXR) analysis, numerous studies have leveraged AI to automate and enhance the diagnostic process. However, existing approaches often focus on partial or incomplete lesion detection, lacking comprehensive multi-class and multi-label solutions for the full range of TB-related anomalies. To address this, we present a hybrid AI model combining vision transformer (ViT) and convolutional neural network (CNN) architectures for efficient multi-class and multi-label classification of 14 TB-related anomalies. Using 133 CXR images from Dr. Cipto Mangunkusumo National Central General Hospital and 214 images from the NIH datasets, we tackled data imbalance with augmentation, class weighting, and focal loss. The model achieved an accuracy of 0.911, a loss of 0.285, and an AUC of 0.510. Given the complexity of handling not only multi-class but also multi-label data with imbalanced and limited samples, the AUC score reflects the challenging nature of the task rather than any shortcoming of the model itself. By classifying the most distinct TB-related labels in a single AI study, this research highlights the potential of AI to enhance both the accuracy and efficiency of detecting TB-related anomalies, offering valuable advancements in combating this global health burden. Full article

mRNA vaccines represent a milestone in the history of vaccinology, because they are safe, very effective, quick and cost-effective to produce, easy to adapt should the antigen vary, and able to induce humoral and cellular immunity. Methods: To date, only two COVID-19 mRNA and one RSV vaccines have been approved. However, several mRNA vaccines are currently under development for the prevention of human viral (influenza, human immunodeficiency virus [HIV], Epstein–Barr virus, cytomegalovirus, Zika, respiratory syncytial virus, metapneumovirus/parainfluenza 3, Chikungunya, Nipah, rabies, varicella zoster virus, and herpes simplex virus 1 and 2), bacterial (tuberculosis), and parasitic (malaria) diseases. Results: RNA viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV)-2, HIV, and influenza, are characterized by high variability, thus creating the need to rapidly adapt the vaccines to the circulating viral strain, a task that mRNA vaccines can easily accomplish; however, the speed of variability may be higher than the time needed for a vaccine to be adapted. mRNA vaccines, using lipid nanoparticles as the delivery system, may act as adjuvants, thus powerfully stimulating innate as well as adaptive immunity, both humoral, which is rapidly waning, and cell-mediated, which is highly persistent. Safety profiles were satisfactory, considering that only a slight increase in prognostically favorable anaphylactic reactions in young females and myopericarditis in young males has been observed. Conclusions: The COVID-19 pandemic determined a shift in the use of RNA: after having been used in medicine as micro-RNAs and tumor vaccines, the new era of anti-infectious mRNA vaccines has begun, which is currently in great development, to either improve already available, but unsatisfactory, vaccines or develop protective vaccines against infectious agents for which no preventative tools have been realized yet. Full article

Background and Objectives: Coinfection with SARS-CoV-2 and extrapulmonary tuberculosis (extraPTB) presents unique clinical challenges due to dual inflammatory responses and potential differences in patient profiles compared to those with SARS-CoV-2 infection alone. This study uniquely contributes to the underexplored interaction between extraPTB and SARS-CoV-2, focusing on systemic inflammation as a critical determinant of outcomes. Materials and Methods: This retrospective, cross-sectional study included 123 patients aged 19–91 years, hospitalized at Victor Babeș Hospital in Timișoara from March 2020 to March 2022. We compared 23 extraPTB and SARS-CoV-2 coinfected patients with 100 age-matched SARS-CoV-2-only patients. Clinical records were examined for demographic, clinical, and laboratory data. Results: The coinfected group was younger, with 65% under 40 years, and presented significantly higher IL-6, PCT, and transaminase levels. Coexisting COPD and type 2 diabetes were independent predictors of coinfection. A higher SpO2 at diagnosis was positively associated with coinfection likelihood (OR = 5.37), while CT scores indicated less pulmonary involvement in coinfected patients. Non-fatal outcomes were more frequent in the coinfection group (95.7% sensitivity), and only one coinfected patient had a fatal outcome versus 17 in the SARS-CoV-2-only group. Low SpO2 and elevated IL-6 were significant predictors of mortality, with severe symptoms tripling fatality odds. Conclusions: Coinfection with extraPTB and SARS-CoV-2 is associated with younger age, heightened systemic inflammation, and longer hospital stays but does not significantly increase mortality risk compared to SARS-CoV-2 alone. These findings underscore the importance of monitoring systemic inflammatory markers and developing tailored management strategies to improve long-term care outcomes for coinfected patients, especially in resource-limited settings. Full article

Background: Serum C-reactive protein (CRP) levels vary depending on radiological and bacteriological findings at the time of tuberculosis (TB) diagnosis. However, the utility of this biomarker in monitoring response to anti-TB treatment and identifying patients at risk of treatment failure is not well established. Objectives: This study evaluated the impact of patients’ baseline characteristics and anti-TB drug plasma exposure on the early reduction in serum CRP levels and its relationship with treatment response. Methods: We enrolled 42 patients with drug-susceptible pulmonary TB, who received a standard six-month regimen. The plasma concentrations of four anti-TB drugs were analysed using LC-MS/MS. Clinically relevant data, including serum CRP levels before and 10–12 days after treatment initiation (CRP_10–12d), were obtained from electronic medical records and patient questionnaires. Results: In 10–12 days, the median serum CRP level decreased from 21.9 to 6.4 mg/L. Lower body mass index, positive sputum-smear microscopy results, and lung cavitations at diagnosis were related to higher biomarker levels at both time points; smoking had a more pronounced effect on serum CRP_10–12d levels. Variability in anti-TB drug plasma exposure did not significantly affect the reduction in serum CRP levels. The serum CRP_10–12d levels, or fold change from the baseline, did not predict the time to sputum culture conversion. Conclusions: Disease severity and patient characteristics may influence the pattern of early CRP reduction, while anti-TB drug plasma exposure had no significant effect at this stage. These early changes in serum CRP levels were not a predictor of response to anti-TB therapy. Full article

Multiple human and plant pathogens are dispersed and transmitted as bioaerosols (e.g., Mycobacterium tuberculosis, SARS-CoV-2, Legionella pneumophila, Aspergillus fumigatus, Phytophthora spp., and Fusarium graminearum). Rapid, on-site methods to detect airborne pathogens would greatly enhance our ability to monitor exposure and trigger early mitigation measures across different settings. Analysis of air samples for microorganisms in a regulatory context is often based on culture-based methods, which are slow, lack specificity, and are not suitable for detecting viruses. Molecular methods (based on nucleic acids) could overcome these challenges. For example, loop-mediated isothermal amplification (LAMP) is rapid, sensitive, specific, and may detect microbial pathogens from air samples in under 60 min. However, the low biomass in air samples makes recovering sufficient nucleic acids for detection challenging. To overcome this, we present a simple method for concentrating bioaerosols collected through liquid impingement (one of the most common methods for bioaerosol collection). This method paired with LAMP (or other molecular approaches) offers simple, rapid, and sensitive detection of pathogens. We validated this method using three airborne pathogens (Mycobacterium tuberculosis, Legionella pneumophila, and Aspergillus fumigatus), and we were able to detect fewer than five cells in a 15 mL liquid impinger air sample in under 60 min. This simple method offers rapid pathogen detection without the use of specialist equipment, and it can be used across healthcare, education, environmental monitoring, and military settings. Full article

Timor Leste is one of the top countries in Asia with a high incidence rate of pulmonary tuberculosis (TB). The success of TB treatment necessitated a more profound comprehension of adherence as a multifaceted behavioral issue, along with identifying the barriers that hinder and the factors that promote patient adherence. This study aimed to assess the rate of pulmonary TB medication adherence and identify its predictors among adults in Metinaro and Becora, Dili, Timor-Leste. A descriptive analytical cross-sectional study was conducted, and new patients with pulmonary TB aged 18 years and above were selected using a proportional sampling method. Quantitative data were collected from 398 patients with pulmonary tuberculosis. The medication adherence results were as follows: 73.6% low adherence, 18.3% moderate adherence, and only 8.1% high adherence. The study identified significant predictors of medication adherence, such as health service factors (OR = 14.024, 95% CI: 5.42–35.54, p = 0.001). Patients who perceived a high quality in the health service were 14 times more likely to exhibit higher medication adherence. Regarding individual behaviors, patients who consumed alcohol or occasionally engaged in physical exercise were significantly less likely to exhibit higher medication adherence (OR = 0.17, 95% CI: 0.091–0.312, p = 0.001). Similarly, patients experiencing high levels of stigma were less likely to achieve strong adherence (OR = 0.146, 95% CI: 0.058–0.326, p = 0.001).Both health service quality and individual factors, such as lifestyle behaviors and social stigma, were statistically significant predictors ofTB medication adherence. Enhancing the healthcare infrastructure, implementing multisectoral strategies for behavior change, and reducing stigma are crucial. Additionally, mobile health technologies, like SMS reminders and telehealth, might support real-time adherence improvements. Full article

The hospital-at-home (HaH) model delivers hospital-level acute care, including diagnostics, monitoring, and treatments, in a patient’s home. It is particularly effective for managing conditions such as pneumonia. Point-of-care ultrasonography (PoCUS) is a key diagnostic tool in the HaH model, and it often serves as a substitute for imaging-based diagnosis in the HaH setting. Both standard and handheld ultrasound equipment are suitable for lung ultrasound (LUS) evaluation. Curvelinear and linear probes are typically used. Patient positioning depends on their clinical condition and specific diagnostic protocols. To enhance sensitivity, we recommend using at least 10-point protocols supported by studies for pneumonia. Five essential LUS patterns should be identified, including A-line, multiple B-lines (alveolar-interstitial syndrome), confluent B-lines, subpleural consolidation, and consolidation with air bronchogram. Pleural effusion is common, and its internal echogenicity can indicate severity and the need for invasive procedures. The current evidence on various etiologies and types of pneumonia is limited, but LUS demonstrates good sensitivity in detecting abnormal sonographic patterns in atypical pneumonia, tuberculosis, and ventilator-associated pneumonia. Further LUS studies in the HaH setting are required to validate and generalize the findings. Full article

Background/Objectives: The combination of isoniazid (INH) and rifampicin (RIF) is indicated for the treatment maintenance phase of tuberculosis (TB) in adults and children. In Brazil, there is no current reference listed drug for this indication in children. Farmanguinhos has undertaken the development of an age-appropriate dispersible tablet to be taken with water for all age groups from birth to adolescence. The primary objective of this work was to develop and validate a physiologically-based biopharmaceutics model (PBBM) in GastroPlus^TM, to link the product’s in vitro performance to the observed pharmacokinetic (PK) data in adults and children. Methods: The PBBM was developed based on measured or predicted physico-chemical and biopharmaceutical properties of INH and RIF. The metabolic clearance was specified mechanistically in the gut and liver for both parent drugs and acetyl-isoniazid. The model incorporated formulation related measurements such as dosage form disintegration and dissolution as inputs and was validated using extensive literature as well as in house clinical data. Results: The model was used to predict the exposure in children across the targeted dosing regimen for each age group using the new age-appropriate formulation. Probabilistic models of efficacy and safety versus exposure, combined with real world data on children, were utilized to assess drug efficacy and safety in the target populations. Conclusions: The model predictions (systemic exposure) along with clinical data from the literature linking systemic exposure to clinical outcomes confirmed that the proposed dispersible pediatric tablet and dosing regimen are anticipated to be as safe and as effective as adult formulations at similar doses. Full article

Worldwide, attempted suicide and suicide death are one of the leading causes of morbidity and mortality. Women in South-East Asia are especially vulnerable, as almost 50% of all global female suicides occur in the 11 countries of the WHO South-East Asia Region. This scoping literature analysis aimed to identify and analyze the predictors or risk factors for attempted suicide and suicide death among South-East Asian women. A scoping literature review was conducted. Five databases—PubMed, MEDLINE, EBSCOhost, PsycINFO, and EMBASE—were searched. Forty studies and twelve literature reviews were eligible for inclusion. Women in South-East Asia, particularly those who are young and married, living in poverty, with low or no education, living in rural areas, with no employment outside the home, with lower socioeconomic position, and living within joint families are highly vulnerable to suicidality. This review identified gender disadvantage, infertility, domestic abuse, intimate partner violence, family conflicts, husband’s alcohol misuse, child marriage, forced marriages, and dowry disputes as the most significant predictors of attempted suicide and suicide death among South-East Asian women. A better understanding of the phenomenon is essential to develop effective gender-specific and culturally appropriate suicide prevention strategies or interventions. Full article

Multidrug-resistant tuberculosis (MDR-TB) poses a significant global health threat, especially when it involves the central nervous system (CNS). Tuberculous meningitis (TBM), a severe manifestation of TB, is linked to high mortality rates and long-term neurological complications, further exacerbated by drug resistance and immune evasion mechanisms employed by Mycobacterium tuberculosis (Mtb). Although pulmonary TB remains the primary focus of research, MDR-TBM introduces unique challenges in diagnosis, treatment, and patient outcomes. The effectiveness of current treatments is frequently compromised by poor CNS penetration of anti-TB drugs and the necessity for prolonged therapy, which often involves considerable toxicity. This review explores the potential of cytokine-based adjunct immunotherapies for MDR-TBM, addressing the challenges of balancing pro-inflammatory and anti-inflammatory signals within the CNS. A central focus is the prospective role of glutathione, not only in reducing oxidative stress but also in enhancing host immune defenses against Mtb’s immune evasion strategies. Furthermore, the development of vaccines aimed at upregulating glutathione synthesis in macrophages represents a promising strategy to bolster the immune response and improve treatment outcomes. By integrating glutathione and innovative vaccine approaches into MDR-TBM management, this review proposes a comprehensive strategy that targets Mtb directly while supporting immune modulation, with the potential to enhance patient outcomes and reduce treatment related adverse effects. We underscore the urgent need for further research into adjunctive therapies and immunomodulatory strategies to more effectively combat MDR-TBM. Full article

The pulmonary route for drug administration has garnered a great deal of attention in therapeutics for treating respiratory disorders. It allows for the delivery of drugs directly to the lungs and, consequently, the maintenance of high concentrations at the action site and a reduction in systemic adverse effects compared to other routes, such as oral or intravenous. Nevertheless, the pulmonary administration of drugs is challenging, as the respiratory system tries to eliminate inhaled particles, being the main responsible mucociliary escalator. Nanomedicines represent a primary strategy to overcome the limitations of this route as they can be engineered to prolong pulmonary retention and avoid their clearance while reducing drug systemic distribution and, consequently, systemic adverse effects. This review analyses the use of pulmonary-administered nanomedicines to treat infectious diseases affecting the respiratory system and lung carcinoma, two pathologies that represent major health threats. Full article