Search Results (26)

The article analyzes the effects of psychosocial interventions on adherence to tuberculosis (TB) treatment among vulnerable populations in Romania. The study includes 4104 patients from disadvantaged groups (rural, injecting drug users, homeless), beneficiaries of a national multidisciplinary support program. Multivariate analyses conducted on drug-susceptible TB (DS-TB) patients within this cohort identified some predictors of therapeutic success, such as extrapulmonary diagnosis, peer-to-peer educational support, and a higher level of education. At the same time, men, occupationally inactive people and those in the initial phase of treatment at project entry showed lower adherence. The results support the integration of psychosocial interventions in TB management. 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

Early detection of tuberculosis plays a critical role in effective treatment management. Like active tuberculosis, early identification of inactive forms such as latent or healed tuberculosis is essential to prevent future reactivation. In this study, we developed a deep-learning-based binary classification model to distinguish between active and inactive tuberculosis cases. Our model architecture incorporated an EfficientNet backbone with an MLP-Mixer classification head and was fine-tuned on a dataset annotated by Cheonan Soonchunhyang Hospital. To enhance predictive performance, we applied transfer learning using weights pre-trained on the JFT-300M dataset via the Noisy Student training method. Unlike conventional models, our approach achieved competitive results, with an accuracy of 96.3%, a sensitivity of 95.9%, and a specificity of 96.6% on the test set. These promising outcomes suggest that our model could serve as a valuable asset to support clinical decision-making and streamline early screening workflows for latent tuberculosis. Full article

Background: Tuberculosis (TB) is a bacterial disease that mainly affects the lungs, but it can also impact other parts of the body, such as the brain, bones, and kidneys. The disease is caused by a bacterium called Mycobacterium tuberculosis and spreads through the air when an infected person coughs or sneezes. TB can be inactive or active; in its active state, noticeable symptoms appear, and it can be transmitted to others. There are ongoing challenges in fighting TB, including resistance to medications, co-infections, and limited resources in areas heavily affected by the disease. These issues make it challenging to eradicate TB. Objective: Timely and precise diagnosis is essential for effective control, especially since TB often goes undetected and untreated, particularly in remote and under-resourced locations. Chest X-ray (CXR) images are commonly used to diagnose TB. However, difficulties can arise due to unusual findings on X-rays and a shortage of radiologists in high-infection areas. Method: To address these challenges, a computer-aided diagnosis (CAD) system that uses the vision transformer (ViT) technique has been developed to accurately identify TB in CXR images. This innovative hybrid CAD approach combines ViT with Principal Component Analysis (PCA) and machine learning (ML) techniques for TB classification, introducing a new method in this field. In the hybrid CAD system, ViT is used for deep feature extraction as a base model, PCA is used to reduce feature dimensions, and various ML methods are used to classify TB. This system allows for quickly identifying TB, enabling timely medical action and improving patient outcomes. Additionally, it streamlines the diagnostic process, reducing time and costs for patients and lessening the workload on healthcare professionals. The TB chest X-ray dataset was utilized to train and evaluate the proposed CAD system, which underwent pre-processing techniques like resizing, scaling, and noise removal to improve diagnostic accuracy. Results: The performance of our CAD model was assessed against existing models, yielding excellent results. The model achieved remarkable metrics: an average precision of 99.90%, recall of 99.52%, F1-score of 99.71%, accuracy of 99.84%, false negative rate (FNR) of 0.48%, specificity of 99.52%, and negative predictive value (NPV) of 99.90%. Conclusions: This evaluation highlights the superior performance of our model compared to the latest available classifiers. Full article

Mycobacterium tuberculosis causes 6.4 million cases of tuberculosis and claims 1.6 million lives annually. Mycobacterial adhesion, invasion of host cells, and subsequent intracellular survival are crucial for the infection and dissemination process, yet the cellular mechanisms underlying these phenomena remain poorly understood. This study created a Bacillus Calmette–Guérin (BCG) transposon library using a MycomarT7 phage carrying a Himar1 Mariner transposon to identify genes related to mycobacteria adhesion and invasion. Using adhesion and invasion model screening, we found that the mutant strain B2909 lacked adhesion and invasion abilities because of an inactive fadD18 gene, which encodes a fatty-acyl CoA ligase, although the specific function of this gene remains unclear. To investigate the role of FadD18, we constructed a complementary strain and observed that fadD18 expression enhanced the colony size and promoted the formation of a stronger cord-like structure; FadD18 expression also inhibited BCG growth and reduced BCG intracellular survival in macrophages. Furthermore, FadD18 expression elevated levels of the proinflammatory cytokines IL-6, IL-1β, and TNF-α in infected macrophages by stimulating the NF-κB and MAPK signaling pathways. Overall, the FadD18 plays a key role in the adhesion and invasion abilities of mycobacteria while modulating the intracellular survival of BCG by influencing the production of proinflammatory cytokines. Full article

Background: Tuberculosis (TB) infection is a life-threatening infection caused by certain bacteria belonging to the Mycobacterium tuberculosis complex. More than 10 million subjects are newly sick from this infection every year globally. At the same time, TB is quite prevalent among subjects who come from lower socioeconomic layers of general population, and marginalized sections and areas. Sarcopenia is a muscle disease that derives from adverse muscle alterations and is related to the loss of muscle strength and mass. It is a major medical issue due to its increased adverse outcomes including falls, functional decline, frailty, hospitalizations, increased mortality, and healthcare costs. Methods: This study examined the potential interplay between the TB infection and sarcopenia through conducting a non-systematic review of the current literature. Results: It has been recorded that the prevalence of sarcopenia among TB survivors is high, whilst the danger of TB among the elderly increases with sarcopenia and physical inactivity. Nevertheless, sufficient protein and total energy intake are associated with a low risk of sarcopenia in TB survivors. Conclusions: Further studies are needed to validate these findings and shed more light on the upcoming different aspects of this intriguing association. Full article

Gastrointestinal tuberculosis (GITB) and Crohn’s disease (CD) are close mimics. This prospective study aimed to evaluate the diagnostic performance of perfusion computed tomography (CT) in differentiating GITB from CD. Consecutive patients with ileocaecal thickening underwent perfusion CT of the ileocaecal region between January 2019 and July 2020. Two radiologists (blinded to the final diagnosis) independently assessed blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability at perfusion CT. These parameters were compared among the patients with GITB as well as active and inactive CD. Receiver operating characteristic curves were utilized for determining the diagnostic performance of perfusion CT. Interclass correlation coefficient and Bland–Altman analysis were performed to compare the observations of the two radiologists. During the study period, 34 patients underwent perfusion CT. Eight patients had diagnoses other than intestinal tuberculosis or CD. Thus, 26 patients (mean age 36 ± 14 years, 18 males) with GITB (n = 11), active CD (n = 6), and inactive CD (n = 9) were evaluated. BF, MTT, and permeability showed significant differences among the groups, while BV did not differ significantly among the groups. BF and permeability had 100% sensitivity and 100% specificity, while MTT had 61.5–100% sensitivity and 70–100% specificity for differentiating GITB from active CD and active from inactive CD. The interclass correlation coefficient for perfusion CT parameters was 0.88–1. Perfusion CT is a novel imaging technique that can improve the diagnostic performance of differentiating tuberculosis from CD. Full article

Mycobacterium kansasii (Mkn) causes tuberculosis-like lung infection in both immunocompetent and immunocompromised patients. Current standard therapy against Mkn infection is lengthy and difficult to adhere to. Although β-lactams are the most important class of antibiotics, representing 65% of the global antibiotic market, they have been traditionally dismissed for the treatment of mycobacterial infections, as they were considered inactive against mycobacteria. A renewed interest in β-lactams as antimycobacterial agents has shown their activity against several mycobacterial species, including M. tuberculosis, M. ulcerans or M. abscessus; however, information against Mkn is lacking. In this study, we determined the in vitro activity of several β-lactams against Mkn. A selection of 32 agents including all β-lactam chemical classes (penicillins, cephalosporins, carbapenems and monobactams) with three β-lactamase inhibitors (clavulanate, tazobactam and avibactam) were evaluated against 22 Mkn strains by MIC assays. Penicillins plus clavulanate and first- and third-generation cephalosporins were the most active β-lactams against Mkn. Combinatorial time-kill assays revealed favorable interactions of amoxicillin–clavulanate and cefadroxil with first-line Mkn treatment. Amoxicillin–clavulanate and cefadroxil are oral medications that are readily available, and well tolerated with an excellent safety and pharmacokinetic profile that could constitute a promising alternative option for Mkn therapy. Full article

Purpose: This study aimed to summarize and analyze the clinical data of intestinal tuberculosis (ITB) in order to provide guidance for accurate diagnosis and treatment of ITB. Methods: This study consecutively included patients with ITB who were admitted to our hospital from 2008 to 2021 and retrospectively analyzed their clinical features. Results: Forty-six patients were included. The most common clinical symptom was weight loss (67.4%). Seventy percent of 20 patients were positive for tuberculin skin test; 57.1% of 14 patients were positive for mycobacterium tuberculosis specific cellular immune response test, while 84.6% of 26 patients were positive for tuberculosis infection T cell spot test. By chest computed tomography (CT) examination, 25% and 5.6% of 36 patients were diagnosed with active pulmonary tuberculosis and with inactive pulmonary tuberculosis, respectively. By abdominal CT examination, the most common sign was abdominal lymph node enlargement (43.2%). Forty-two patients underwent colonoscopy, and the most common endoscopic manifestation was ileocecal ulcer (59.5%), followed by colonic ulcer (35.7%) and ileocecal valve deformity (26.2%). ITB most frequently involved the terminal ileum/ileocecal region (76.1%). Granulomatous inflammation with multinucleated giant cells and caseous necrosis was found via endoscopic biopsies, the ultrasound-guided percutaneous biopsy of enlarged mesentery lymph nodes, and surgical interventions. The acid-fast bacilli were discovered in 53.1% of 32 samples. Twenty-one cases highly suspected of ITB were confirmed after responding to empiric anti-tuberculosis therapy. Conclusions: It was necessary to comprehensively analyze clinical features to make an accurate diagnosis of ITB and aid in distinguishing ITB from diseases such as Crohn’s disease and malignant tumors. Full article

A method to identify molecular scaffolds potentially active against the Mycobacterium tuberculosis complex (MTBC) is developed. A set of structurally heterogeneous agents against MTBC was used to obtain a mathematical model based on topological descriptors. This model was statistically validated through a Leave-n-Out test. It successfully discriminated between active or inactive compounds over 86% in database sets. It was also useful to select new potential antituberculosis compounds in external databases. The selection of new substituted pyrimidines, pyrimidones and triazolo[1,5-a]pyrimidines was particularly interesting because these structures could provide new scaffolds in this field. The seven selected candidates were synthesized and six of them showed activity in vitro. Full article

A series of eleven benzylated intermediates and eleven target compounds derived from salicylanilide were tested against Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 as reference strains and against three clinical isolates of methicillin-resistant S. aureus (MRSA) and three isolates of vancomycin-resistant E. faecalis. In addition, the compounds were evaluated against Mycobacterium tuberculosis H37Ra and M. smegmatis ATCC 700084. The in vitro cytotoxicity of the compounds was assessed using the human monocytic leukemia cell line THP-1. The lipophilicity of the prepared compounds was experimentally determined and correlated with biological activity. The benzylated intermediates were found to be completely biologically inactive. Of the final eleven compounds, according to the number of amide groups in the molecule, eight are diamides, and three are triamides that were inactive. 5-Chloro-2-hydroxy-N-[(2S)- 4-(methylsulfanyl)-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino}butan-2-yl]benzamide (3e) and 5-chloro-2-hydroxy-N-[(2S)-(4-methyl-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino)pentan-2-yl)benzamide (3f) showed the broadest spectrum of activity against all tested species/isolates comparable to the used standards (ampicillin and isoniazid). Six diamides showed high antistaphylococcal activity with MICs ranging from 0.070 to 8.95 μM. Three diamides showed anti-enterococcal activity with MICs ranging from 4.66 to 35.8 μM, and the activities of 3f and 3e against M. tuberculosis and M. smegmatis were MICs of 18.7 and 35.8 μM, respectively. All the active compounds were microbicidal. It was observed that the connecting linker between the chlorsalicylic and 4-CF₃-anilide cores must be substituted with a bulky and/or lipophilic chain such as isopropyl, isobutyl, or thiabutyl chain. Anticancer activity on THP-1 cells IC₅₀ ranged from 1.4 to >10 µM and increased with increasing lipophilicity. Full article

Vitamin D has an immunomodulatory function and is involved in eliminating pathogens. Vitamin D deficiencies reported in Type 2 diabetes mellitus (T2DM) patients make them more susceptible to developing tuberculosis (TB). The macrophages are the immune cells that control intracellular pathogens by producing the antimicrobial peptide cathelicidin-LL37. This pathway involves TLR activation by pathogens, vitamin D receptor (VDR) ligation, and the enzyme 1α-hydroxylase Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1). However, it is not clear whether the biological actions of vitamin D are affected by high glucose concentrations. This study aimed to evaluate the vitamin D contribution in the expression of VDR and CYP27B1, involved in the conversion of an inactive to an active form of vitamin D in the infected macrophages using M. tuberculosis as an infection model. The expression of LL37 and the nucleus translocation of VDR were evaluated as the readout of the response of vitamin D and determined if those processes are affected by glucose concentrations. Macrophages from healthy donors were cultured under glucose concentrations of 5.5, 15, or 30 mM, stimulated with vitamin D in inactive (25(OH)D₃) or active (1,25(OH)₂D₃) forms, and infected with M. tuberculosis. The vitamin D-dependent induction of LL37 and the expression of VDR and CYP27B1 genes were analyzed by qPCR, and VDR translocation was analyzed in nuclear protein extracts by ELISA. M. tuberculosis downregulated the expression of LL37 regardless of the glucose concentration, whereas VDR and CYP27B1 upregulated it regardless of the glucose concentration. After evaluating two concentrations of vitamin D, 1 nM or 1 μM, the high concentration (1 μM) was necessary to restore the induction of LL37 expression in M. tuberculosis-infected macrophages. High concentrations of the inactive form of vitamin D restore the infected macrophages’ ability to express LL37 regardless of the glucose concentration. This finding supports the idea that vitamin D administration in patients with T2DM could benefit TB control and prevention. Full article

Due to their non-specific diagnostic patterns of ocular infection, differential diagnosis between Mycobacterium (M.) chimaera and tuberculosis can be challenging. In both disorders, ocular manifestation can be the first sign of a systemic infection, and a delayed diagnosis might reduce the response to treatment leading to negative outcomes. Thus, it becomes imperative to distinguish chorioretinal lesions associated with M. chimaera, from lesions due to M. tuberculosis and other infectious disorders. To date, multimodal non-invasive imaging modalities that include ultra-wide field fundus photography, fluorescein and indocyanine green angiography, optical coherence tomography and optical coherence tomography angiography, facilitate in vivo examination of retinal and choroidal tissues, enabling early diagnosis, monitoring treatment response, and relapse detection. This approach is crucial to differentiate between active and inactive ocular disease, and guides clinicians in their decisional-tree during the patients’ follow-up. In this review, we summarized and compared the available literature on multimodal imaging data of M. chimaera infection and tuberculosis, emphasizing similarities and differences in imaging patterns between these two entities and highlighting the relevance of multimodal imaging in the management of the infections. Full article

The search for novel antimycobacterial drugs is a matter of urgency, since tuberculosis is still one of the top ten causes of death from a single infectious agent, killing more than 1.4 million people worldwide each year. Nine Amaryllidaceae alkaloids (AAs) of various structural types have been screened for their antimycobacterial activity. Unfortunately, all were considered inactive, and thus a pilot series of aromatic esters of galanthamine, 3-O-methylpancracine, vittatine and maritidine were synthesized to increase biological activity. The semisynthetic derivatives of AAs were screened for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Ra and two other mycobacterial strains (M. aurum, M. smegmatis) using a modified Microplate Alamar Blue Assay. The most active compounds were also studied for their in vitro hepatotoxicity on the hepatocellular carcinoma cell line HepG2. In general, the derivatization of the original AAs was associated with a significant increase in antimycobacterial activity. Several pilot derivatives were identified as compounds with micromolar MICs against M. tuberculosis H37Ra. Two derivatives of galanthamine, 1i and 1r, were selected for further structure optimalization to increase the selectivity index. Full article

Nature has been a source of inspiration for the development of new pharmaceutically active agents. A series of new unnatural gallotannins (GTs), derived from d-lyxose, d-ribose, l-rhamnose, d-mannose, and d-fructose have been designed and synthesized in order to study the protective and antimicrobial effects of synthetic polyphenols that are structurally related to plant-derived products. The structures of the new compounds were confirmed by various spectroscopic methods. Apart from spectral analysis, the antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging and iron reducing power (FRAP) assays. Antibacterial activity of compounds was tested in vitro against Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 (reference and control strains), three methicillin-resistant isolates of S. aureus, and three isolates of vancomycin-resistant E. faecalis. For screening of antimycobacterial effect, a virulent isolate of Mycobacterium tuberculosis and two non-tuberculous mycobacteria were used. Furthermore, antibiofilm activity of structurally different GTs against S. aureus, and their ability to inhibit sortase A, were inspected. Experimental data revealed that the studied GTs are excellent antioxidants and radical-scavenging agents. The compounds exhibited only a moderate antibacterial effect against Gram-positive pathogens S. aureus and E. faecalis and were practically inactive against mycobacteria. However, they were efficient inhibitors and disruptors of S. aureus biofilms in sub-MIC concentrations, and interacted with the quorum-sensing system in Chromobacteriumviolaceum. Overall, these findings suggest that synthetic GTs could be considered as promising candidates for pharmacological, biomedical, consumer products, and for food industry applications. Full article