Risk factors associated with influenza A (H1N1)pdm09: a nested case control study of TB patients with ILI in Lahore District, Pakistan.

BACKGROUND: Co-morbidity with respiratory viruses including influenza A, cause varying degree of morbidity especially in TB patients compared to general population. This study estimates the risk factors associated with influenza A (H1N1)pdm09 in TB patients with ILI. METHODS: A cohort of tuberculosis (TB) patients who were admitted to and enrolled in a TB Directly Observed Therapy Program (DOTs) in tertiary care hospitals of Lahore (Mayo Hospital and Infectious Disease Hospital) were followed for 12 weeks. At the start of study period, to record influenza-like illness (ILI), a symptom card was provided to all the participants. Every participant was contacted once a week, in person. When the symptoms were reported by the participant, a throat swab was taken for the detection of influenza A (H1N1)pdm09. A nested case control study was conducted and TB patients with ILI diagnosed with influenza A (H1N1)pdm09 by conventional RT-PCR were selected as cases, while those who tested negative by conventional RT-PCR were enrolled as controls. All cases and controls in the study were interviewed face-to-face in the local language. Epidemiological data about potential risk factors were collected on a predesigned questionnaire. Logistic analysis was conducted to identify associated risk factors in TB patients with ILI. RESULTS: From the main cohort of TB patients (n = 152) who were followed during the study period, 59 (39%) developed ILI symptoms; of them, 39 tested positive for influenza A (H1N1)pdm09, while 20 were detected negative for influenza A (H1N1)pdm09. In univariable analysis, four factors were identified as risk factors (p < 0.05). The final multivariable model identified one risk factor (sharing of towels, P = 0.008)) and one protective factor (wearing a face mask, p = < 0.001)) for influenza A (H1N1)pdm09 infection. CONCLUSION: The current study identified the risk factors of influenza A (H1N1)pdm09 infection among TB patients with ILI.

Long-term outcomes of surgical reconstruction for post-tuberculosis tracheobronchial stenosis: a 7-year follow-up in a tuberculosis-endemic region.

Background: Surgical reconstruction is often necessary for severe tracheobronchial stenosis resulting from tuberculosis (TB). However, the long-term efficacy of this approach remains unclear. This study investigated the safety and long-term outcomes of surgery for severe post-TB tracheobronchial stenosis. Methods: We conducted a retrospective study of 48 patients with severe post-TB tracheobronchial stenosis who underwent surgical reconstruction between 2015 and 2018 in a TB-endemic region. Pre- and postoperative evaluations included Karnofsky performance status, modified Medical Research Council (mMRC) dyspnea scale, spirometry, chest computed tomography (CT) scan, and bronchoscopy. The primary outcome was intervention-requiring restenosis over the long term. Results: The mean patient age was 30.6±9.9 years, with 91.7% females. Airway fibrosis was the predominant lesion (93.8%), affecting the bronchi (93.8%) and trachea (6.2%). All the patients underwent resection and anastomosis, and 56.2% required lobectomy. Postoperative complications occurred in 13 patients (27.1%), with prolonged air leaks being the most prevalent (12.5%). All complications resolved with conservative management. Significant improvements in performance status, dyspnea, and lung function were observed postoperatively and sustained for over 5 years. Within a median follow-up of 69 months, five cases of intervention-requiring restenosis occurred within the first year. The freedom from restenosis rate was 90% from 1 year onwards. Conclusions: Surgical reconstruction is safe and effective in treating severe post-TB tracheobronchial stenosis. Larger studies are required to validate these findings.

Mycobacterium tuberculosis and host interactions in the manifestation of tuberculosis.

The final step of epigenetic processes is changing the gene expression in a new microenvironment in the body, such as neuroendocrine changes, active infections, oncogenes, or chemical agents. The case of tuberculosis (TB) is an outcome of Mycobacterium tuberculosis (M.tb) and host interaction in the manifestation of active and latent TB or clearance. This comprehensive review explains and interprets the epigenetics findings regarding gene expressions on the host-pathogen interactions in the development and progression of tuberculosis. This review introduces novel insights into the complicated host-pathogen interactions, discusses the challengeable results, and shows the gaps in the clear understanding of M.tb behavior. Focusing on the biological phenomena of host-pathogen interactions, the epigenetic changes, and their outcomes provides a promising future for developing effective TB immunotherapies when converting gene expression toward appropriate host immune responses gradually becomes attainable. Overall, this review may shed light on the dark sides of TB pathogenesis as a life-threatening disease. Therefore, it may support effective planning and implementation of epigenetics approaches for introducing proper therapies or effective vaccines.

Breaking the Cycle: Matrix Metalloproteinase Inhibitors as an Alternative Approach in Managing Tuberculosis Pathogenesis and Progression.

Mycobacterium tuberculosis (Mtb) has long posed a significant challenge to global public health, resulting in approximately 1.6 million deaths annually. Pulmonary tuberculosis (TB) instigated by Mtb is characterized by extensive lung tissue damage, leading to lesions and dissemination within the tissue matrix. Matrix metalloproteinases (MMPs) exhibit endopeptidase activity, contributing to inflammatory tissue damage and, consequently, morbidity and mortality in TB patients. MMP activities in TB are intricately regulated by various components, including cytokines, chemokines, cell receptors, and growth factors, through intracellular signaling pathways. Primarily, Mtb-infected macrophages induce MMP expression, disrupting the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs), thereby impairing extracellular matrix (ECM) deposition in the lungs. Recent research underscores the significance of immunomodulatory factors in MMP secretion and granuloma formation during Mtb pathogenesis. Several studies have investigated both the activation and inhibition of MMPs using endogenous MMP inhibitors (i.e., TIMPs) and synthetic inhibitors. However, despite their promising pharmacological potential, few MMP inhibitors have been explored for TB treatment as host-directed therapy. Scientists are exploring novel strategies to enhance TB therapeutic regimens by suppressing MMP activity to mitigate Mtb-associated matrix destruction and reduce TB induced lung inflammation. These strategies include the use of MMP inhibitor molecules alone or in combination with anti-TB drugs. Additionally, there is growing interest in developing novel formulations containing MMP inhibitors or MMP-responsive drug delivery systems to suppress MMPs and release drugs at specific target sites. This review summarizes MMPs' expression and regulation in TB, their role in immune response, and the potential of MMP inhibitors as effective therapeutic targets to alleviate TB immunopathology.

Diagnostic accuracy of the Xpert® MTB/XDR assay for detection of Isoniazid and second-line antituberculosis drugs resistance at central TB reference laboratory in Tanzania.

INTRODUCTION: Early diagnosis of tuberculosis (TB) and universal access to drug-susceptibility testing (DST) are critical elements of the WHO End TB Strategy. Current rapid tests (e.g., Xpert® MTB/RIF and Ultra-assays) can detect rifampicin resistance-conferring mutations, but cannot detect resistance to Isoniazid and second-line anti-TB agents. Although Line Probe Assay is capable of detecting resistance to second-line anti-TB agents, it requires sophisticated laboratory infrastructure and advanced skills which are often not readily available in settings replete with TB. A rapid test capable of detecting Isoniazid and second-line anti-TB drug resistance is highly needed. METHODS: We conducted a diagnostic accuracy study to evaluate a new automated Xpert MTB/XDR 10-colour assay for rapid detection of Isoniazid and second-line drugs, including ethionamide, fluoroquinolones, and injectable drugs (Amikacin, Kanamycin, and Capreomycin). Positive Xpert MTB/RIF respiratory specimens were prospectively collected through routine diagnosis and surveillance of drug resistance at the Central TB Reference Laboratory in Tanzania. Specimens were tested by both Xpert XDR assay and LPA against culture-based phenotypic DST as the reference standard. FINDINGS: We analysed specimens from 151 TB patients with a mean age (SD) of 36.2 (12.7) years. The majority (n = 109, 72.2%) were males. The sensitivity for Xpert MTB/XDR was 93.5% (95% CI, 87.4-96.7); for Isoniazid, 96.6 (95% CI, 92.1-98.6); for Fluoroquinolone, 98.7% (95% Cl 94.8-99.7); for Amikacin, 96.6%; and (95% CI 92.1-98.6) for Ethionamide. Ethionamide had the lowest specificity of 50% and the highest was 100% for Fluoroquinolone. The diagnostic performance was generally comparable to that of LPA with slight variations between the two assays. The non-determinate rate (i.e., invalid M. tuberculosis complex detection) of Xpert MTB/XDR was 2·96%. CONCLUSION: The Xpert MTB/XDR demonstrated high sensitivity and specificity for detecting resistance to Isoniazid, Fluoroquinolones, and injectable agents. This assay can be used in clinical settings to facilitate rapid diagnosis of mono-isoniazid and extensively drug-resistant TB.

Screening of bioactive compounds from selected mushroom species against putative drug targets in Mycobacterium tuberculosis: a multi-target approach.

Mycobacterium tuberculosis (Mtb) is a notorious pathogen that causes one of the highest mortalities globally. Due to a pressing demand to identify novel therapeutic alternatives, the present study aims to focus on screening the putative drug targets and prioritizing their role in antibacterial drug development. The most vital proteins involved in the Biotin biosynthesis pathway and the Lipoarabinomannan (LAM) pathway such as biotin synthase (bioB) and alpha-(1->6)-mannopyranosyltransferase A (mptA) respectively, along with other essential virulence proteins of Mtb were selected as drug targets. Among these, the ones without native structures were modelled and validated using standard bioinformatics tools. Further, the interactions were performed with naturally available lead molecules present in selected mushroom species such as Agaricus bisporus, Pleurotus djamor, Hypsizygus ulmarius. Through Gas Chromatography-Mass Spectrometry (GC-MS), 15 bioactive compounds from the methanolic extract of mushrooms were identified. Further, 4 were selected based on drug-likeness and pharmacokinetic screening for molecular docking analysis against our prioritized targets wherein Benz[e]azulene from Pleurotus djamor illustrated a good binding affinity with a LF rank score of -9.036 kcal mol -1 against nuoM (NADH quinone oxidoreductase subunit M) and could be used as a prospective candidate in order to combat Tuberculosis (TB). Furthermore, the stability of the complex are validated using MD Simulations and subsequently, the binding free energy was calculated using MM-GBSA analysis. Thus, the current in silico analysis suggests a promising role of compounds extracted from mushrooms in tackling the TB burden.Communicated by Ramaswamy H. Sarma.

Pharmacists' Role in Global TB Elimination: Practices, Pitfalls, and Potential.

Tuberculosis (TB) is the top infectious killer in the world despite efforts to eliminate it. Pharmaceutical care roles are pillars of pharmacy practice, and pharmacists are well equipped to serve a unique role in the pathway to provide education about TB. Previous systematic reviews emphasize pharmacists' role in treating TB; however, pharmacists can and do play much broader roles in overall TB elimination efforts. Five researchers searched five electronic databases (PubMed, PsychInfo, CINAHL, Academic Search Premier, and Embase). Search terms included pharmacy, pharmacist, tuberculosis, antitubercular agents, supply, distribution, and drug therapy. Inclusion criteria were studies published from 2010 through March 2023, in English or Spanish, addressed a specific TB-related role for pharmacists/pharmacies, and were peer-reviewed. Exclusion criteria included pharmacology, pharmacokinetics, clinical trials on drug efficacy, and editorials. Two researchers conducted each level of review; for discordance, a third researcher reviewed, and a decision was reached by consensus. Roles were extracted and cross-referenced with traditional pharmaceutical care steps. Of the initial 682 hits, 133 were duplicates. After further review, we excluded 514 records, leaving 37 articles for full extraction. We found nine roles for pharmacists in TB prevention and classified them as implemented, not implemented, or recommended. These roles were: (1) TB symptom screening; (2) Referring to TB care systems; (3) TB testing; (4) Dispensing TB medication correctly and/or directly observed therapy; (5) Counseling; (6) Looking to reduce socioeconomic barriers; (7) Procurement of TB medications; (8) Quality assurance of TB medications; (9) Maintaining and using pharmacy data systems. Pharmacists are well situated to play a vital role in the global fight against TB. Findings suggested pharmacists in many settings have already expanded their roles related to TB elimination beyond traditional pharmaceutical care. Still others need to increase the understanding of TB procurement and treatment, their power to improve TB care, and their contributions to data systems that serve population health. Pharmacy curricula should increase TB-related training to better equip future pharmacists to contribute to TB elimination.

Non-adherence to tuberculosis contact screening and its associated factors in Kuching, Sarawak: A cross-sectional study.

Introduction: Tuberculosis (TB) contacts in Malaysia undergo follow-up screening to reduce their risk of active or latent TB. However, adherence to this screening is low. Limited studies have explored the factors contributing to non-adherence to follow-up screening. This study aimed to determine the non-adherence rate and reasons in a government health clinic. Methods: Participants were TB contacts due for their 2nd contact screening (including those who attended their first contact screening at Petra Jaya Health Clinic from November 2018 to March 2019), were aged at least 18 years and were able to understand English or Malay. Data were collected during the second contact screening from August 2019 to January 2020. Results: A total of 383 TB contacts were included. Of them, 56.6% (n=217) were aged 20-39 years, and the sex distribution was equal (men: 44.1%, n=169). The majority were non-household contacts (82.2%, n=315). The rate of non-adherence to follow-up screening was 19.1% (n=73). Approximately 52.1% (n=36) reported forgetting their scheduled appointment date as the primary reason for non-adherence. The influencing factors included employment and ethnicity. Only 39.1% (n=27) were aware of their risk for active TB, while 49.5% (n=189) were unsure whether TB can be cured with proper treatment. Conclusion: The findings highlight the need to improve the reminder system for TB contacts. Although direct association between knowledge and adherence could not be established, the low percentage of correct answers to most basic knowledge questions associated with TB indicates a need to improve health education for TB contacts.

Deciphering the Correlation between the Emergence of Lung Carcinoma Associated with Tuberculosis-related Inflammation.

Lung cancer and tuberculosis (TB) are classified as the second-most life-threatening diseases globally. They both are exclusively represented as major public health risks and might exhibit similar symptoms, occasionally diagnosed simultaneously. Several epidemiological studies suggest that TB is a significant risk factor for the progression of lung cancer. The staggering mortality rates of pulmonary disorders are intrinsically connected to lung cancer and TB. Numerous factors play a pivotal role in the development of TB and may promote lung carcinogenesis, particularly among the geriatric population. Understanding the intricacies involved in the association between lung carcinogenesis and TB has become a crucial demand of current research. Consequently, this study aims to comprehensively review current knowledge on the relationship between tuberculosis-related inflammation and the emergence of lung carcinoma, highlighting the impact of persistent inflammation on lung tissue, immune modulation, fibrosis, aspects of reactive oxygen species, and an altered microenvironment that are linked to the progression of tuberculosis and subsequently trigger lung carcinoma.

Primary Tuberculosis of Tonsils: Interesting Case Detected During the Histopathological Examination.

Despite being a preventable and curable disease, tuberculosis, which mainly affects the lungs, is still a major cause of illness and death worldwide, with more than one million people dying from it each year. The affliction of the tonsils is uncommon, and isolated tonsillar tuberculosis in the absence of active pulmonary disease is an extremely rare condition that requires early and accurate diagnosis to provide proper management. Microscopic examination is one of the gold-standard tools for diagnosing tuberculosis. However, routine histopathological investigation for tonsillectomy specimens is not justified except in cases of unusual clinical or postoperative presentations. A 20-year-old female patient who experienced recurrent episodes of infections with enlarged tonsils and adenoids and showed a slightly unusual presentation was sent for a histopathology examination. Upon microscopic examination, a caseating granulomatous reaction was found, and staining for acid-fast bacilli tested positive. The patient was treated for tuberculosis of the tonsils, and their condition improved.

Sequencing by Binding rivals error-corrected Sequencing by Synthesis technology for accurate detection and quantification of minor (<0.1%) subpopulation variants.

Detecting very minor (< 1%) subpopulations using next-generation sequencing is a critical need for multiple applications including detection of drug resistant pathogens and somatic variant detection in oncology. To enable these applications, wet lab enhancements and bioinformatic error correction methods have been developed for 'sequencing by synthesis' technology to reduce its inherent sequencing error rate. A recently available sequencing approach termed 'sequencing by binding' claims to have higher base calling accuracy data "out of the box." This paper evaluates the utility of using 'sequencing by binding' for the detection of ultra-rare subpopulations down to 0.001%.

Circular RNAs in tuberculosis and lung cancer.

This review signifies the role of circular RNAs (circRNAs) in tuberculosis (TB) and lung cancer (LC), focusing on pathogenesis, diagnosis, and treatment. CircRNAs, a newly discovered type of non-coding RNA, have emerged as key regulators of gene expression and promising biomarkers in various bodily fluids due to their stability. The current review discusses circRNA biogenesis, highlighting their RNase-R resistance due to their loop forming structure, making them effective biomarkers. It details their roles in gene regulation, including splicing, transcription control, and miRNA interactions, and their impact on cellular processes and diseases. For LC, the review identifies circRNA dysregulation affecting cell growth, motility, and survival, and their potential as therapeutic targets and biomarkers. In TB, it addresses circRNAs' influence on host anti-TB immune responses, proposing their use as early diagnostic markers. The paper also explores the interplay between TB and LC, emphasizing circRNAs as dual biosignatures, and the necessity for differential diagnosis. It concludes that no single circRNA biomarker is universally applicable for both TB and LC. Ultimately, the review highlights the pivotal role of circRNAs in TB and LC, encouraging further research in biomarker identification and therapeutic development concomitant for both diseases.

A case of pulmonary tuberculosis that developed during nivolumab and ipilimumab treatment for pulmonary adenocarcinoma that recurred two months after completion of anti-tuberculous treatment.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become key agents in the treatment of non-small cell lung cancer worldwide. However, immune-related adverse events (irAEs) must be addressed to maximize the efficacy of ICIs. Mycobacterium tuberculosis (Mtb) infection is considered as a type of irAE associated with ICIs, but the underlying mechanism is not completely understood. Here, we present a case of pulmonary tuberculosis (TB) that developed during administration of nivolumab and ipilimumab for pulmonary adenocarcinoma that recurred just 2 months after completion of anti-TB treatment. CASE DESCRIPTION: A 67-year-old man with lung adenocarcinoma was referred to our hospital for chemotherapy. He was a former smoker and had been diagnosed with stage IVA (cT4N1M1a) lung adenocarcinoma. Interferon-gamma release assay (IGRA) yielded positive results at the start of treatment. One month after initiating treatment with nivolumab and ipilimumab, he presented with productive cough and Mtb complex was cultured from sputum samples. Two months after completing anti-TB treatment, recurrence of TB was observed. The series of strains were found to be identical. CONCLUSIONS: This represents the first report of pulmonary TB that developed during nivolumab and ipilimumab treatment, and recurred 2 months after completing anti-TB treatment. Physicians should be mindful of the potential for TB recurrence following the use of ICIs, particularly in patients showing positive results from IGRA.

Tuberculosis in Poland in 2021. / Gruzlica w Polsce w 2021 r.

AIM OF THE STUDY: To evaluate the main features of epidemiology of tuberculosis (TB) in 2021 in Poland and to compare with the situation in the European Union and European Economic Area (EU/EEA) countries. MATERIAL AND METHODS: Analysis of case-based data on TB patients from National TB Register, data on anti-TB drug susceptibility in cases notified in 2021, data from Statistics Poland on deaths from tuberculosis in 2020, data from National Institute of Public Health NIH - National Research Institute (NIPH NIH - NRI) on HIV-positive subjects for whom TB was an AIDS-defining disease, data from the report "European Centre for Disease Prevention and Control, WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2022 - 2021 data. Copenhagen: WHO Regional Office for Europe and Stockholm: European Centre for Disease Prevention and Control; 2022." RESULTS: In 2021, 3704 TB cases were reported in Poland. The incidence rate was 9.7 cases per 100,000 with large variability between voivodeships from 5.4 to 12.6 per 100,000. A decrease in the incidence with respect to 2020 was found in 8 voivodeships, the most significant in lubuskie voivodship (42.6%). The number of all pulmonary tuberculosis cases was 3,553 i.e. 9.3 per 100,000. Pulmonary cases represented 95.9% of all TB cases. In 2021, 151 extrapulmonary TB cases were notified (4.1% of all TB cases). Pulmonary tuberculosis was bacteriologically confirmed in 2,970 cases (83.6% of all pulmonary TB cases, the incidence rate 7.8 per 100,000). The number of smear-positive pulmonary TB cases was 2,085 i.e. 5.5 per 100,000 (58.7% of all pulmonary TB cases). In 2021, there were 54 cases (25 of foreign origin) with multidrug resistant TB (MDR-TB) representing 1.9% of cases with known drug sensitivity. The incidence rates of tuberculosis were growing along with the age group from 0.6 per 100,000 among children (0-14 years) to 15.8 per 100,000 among subjects in the age group 45-64 years, the incidence rate in the age group ≥65 years was 11.7 per 100,000. There were 37 cases in children up to 14 years of age (1.0% of the total) and 51 cases in adolescents between 15 and 19 years of age - rates 0.6 and 2.8 per 100,000 respectively. In 2021, there were 2,690 cases of tuberculosis in men and 1,014 in women. The TB incidence in men - 14.6 per 100,000 was almost 3.0 times higher than among women - 5.1. The biggest difference in the TB incidence between the two sex groups occurred in persons aged 55-59 years, 30.5 vs. 6.6 and in age group 60 to 64 years, 26.0 vs. 5.7. In 2021, there were 132 patients of foreign origin among all cases of tuberculosis in Poland (3.6%). In 2020, TB was the cause of death for 474 people (mortality rate - 1.2 per 100,000). CONCLUSIONS: The incidence of tuberculosis in Poland in 2021 was 10.2% higher than in 2020. The percentage of tuberculosis cases with bacteriological confirmation was 82.6%, higher than the average in EU/EEA countries (72.0%). The percentage of MDR-TB cases was lower than the average in EU/EEA countries (1.9% vs. 3.8%). The highest incidence rates are found in Poland in the older age groups (in EU/EEA countries in people aged 25 to 44). The percentage of children up to 14 years of age among the total number of TB patients was 1.0%, the average in the EU/EEA countries was 3.5%. The incidence of tuberculosis in men was nearly three times higher than in women in Poland. The impact of migration on the epidemiological situation of tuberculosis in Poland in 2021 was smaller than in the EU/EEA countries (in Poland, the percentage of foreigners among all TB patients was 3.6 vs. 33.8% in the EU/EEA).

Tuberculosis Infection Control: Experiences and Considerations from a Web Based Tool Implementation.

Tuberculosis (TB) remains a significant global health challenge. Indeed, according to the World Health Organization (WHO), TB is classified as the second most common cause of death worldwide due to a single infectious agent in 2022, following COVID-19. To effectively manage tuberculosis patients, it is necessary to ensure accurate diagnosis, prompt treatment initiation, and vigilant monitoring of patients' progress. In 2017, the TB Ge network was implemented and launched in two primary hospitals within the Liguria Region in Italy, with the main purpose to manage tuberculosis infections. This system, organized as a web-based tool, simplifies the manual input of patient's data and therapies, while automating the integration of test results from hospitals' Laboratory Information Systems (LIS), without requiring human intervention. The goal of this paper is to highlight the outcomes achieved through the implementation of the TB Ge network in a period seriously affected by the COVID-19 pandemia and outline future directions. More specifically, the aim is to extend its adoption to all hospitals in the Liguria Region, thus improving the management of tuberculosis infections across healthcare facilities.

Safety of pyrazinamide in elderly patients with tuberculosis in Japan: A nationwide cohort study.

BACKGROUND AND OBJECTIVE: Pyrazinamide (PZA) is the standard first-line treatment for tuberculosis (TB); however, its safety in elderly patients has not been thoroughly investigated. METHODS: This retrospective study used data from the Japanese Diagnosis Procedure Combination inpatient database. We identified patients who were admitted for TB between July 2010 and March 2022. Patients were categorized into HRE (isoniazid, rifampicin and ethambutol) and HREZ (isoniazid, rifampicin, ethambutol and PZA) groups. Primary outcomes included in-hospital mortality and overall adverse events (characterized by a composite of hepatotoxicity, gout attack, allergic reactions and gastrointestinal intolerance). Secondary outcomes included the length of hospital stay, 90-day readmission and use of drugs related to the primary outcome adverse events. Data were analysed using propensity score matching; we also conducted a subgroup analysis for those aged ≥75 years. RESULTS: Among 19,930 eligible patients, 8924 received HRE and 11,006 received HREZ. Propensity score matching created 3578 matched pairs with a mean age of approximately 80 years. Compared with the HRE group, the HREZ group demonstrated a higher proportion of overall adverse events (3.1% vs. 4.7%; p < 0.001), allergic reactions (1.4% vs. 2.5%; p < 0.001) and antihistamine use (21.9% vs. 27.6%; p < 0.001). No significant differences were observed regarding in-hospital mortality, hepatotoxicity or length of hospital stay between the groups. Subgroup analysis for those aged ≥75 years showed consistent results. CONCLUSION: Medical practitioners may consider adding PZA to an initial treatment regimen even in elderly patients with TB.

Enhancing multi-class lung disease classification in chest x-ray images: A hybrid manta-ray foraging volcano eruption algorithm boosted multilayer perceptron neural network approach.

One of the most used diagnostic imaging techniques for identifying a variety of lung and bone-related conditions is the chest X-ray. Recent developments in deep learning have demonstrated several successful cases of illness diagnosis from chest X-rays. However, issues of stability and class imbalance still need to be resolved. Hence in this manuscript, multi-class lung disease classification in chest x-ray images using a hybrid manta-ray foraging volcano eruption algorithm boosted multilayer perceptron neural network approach is proposed (MPNN-Hyb-MRF-VEA). Initially, the input chest X-ray images are taken from the Covid-Chest X-ray dataset. Anisotropic diffusion Kuwahara filtering (ADKF) is used to enhance the quality of these images and lower noise. To capture significant discriminative features, the Term frequency-inverse document frequency (TF-IDF) based feature extraction method is utilized in this case. The Multilayer Perceptron Neural Network (MPNN) serves as the classification model for multi-class lung disorders classification as COVID-19, pneumonia, tuberculosis (TB), and normal. A Hybrid Manta-Ray Foraging and Volcano Eruption Algorithm (Hyb-MRF-VEA) is introduced to further optimize and fine-tune the MPNN's parameters. The Python platform is used to accurately evaluate the proposed methodology. The performance of the proposed method provides 23.21%, 12.09%, and 5.66% higher accuracy compared with existing methods like NFM, SVM, and CNN respectively.

Rare Case of Tubercular Serpiginous-Like Choroiditis.

Serpiginous choroiditis is a rare cause of posterior uveitis, included in the spectrum of white dot syndromes. It occurs as a result of an autoimmune process but could be associated with infections such as tuberculosis (TB) (serpiginous-like choroiditis). Tubercular serpiginous-like choroiditis is more commonly reported in Southeast Asian countries than in Western countries. We report a case of an Indian male in his late 30s with bilateral grey-yellowish subretinal infiltrates at the level of choroid with active scalloped edges having a positive TB-QuantiFERON Gold test (Cellestis Limited, Carnegie, Australia), who responded well to the treatment of intravenous methylprednisolone and systemic steroids (given initially to control the acute inflammation) while on anti-tubercular (anti-TB) therapy. The lesions finally completely healed on the anti-TB therapy.

Construction of novel multi-epitope-based diagnostic biomarker HP16118P and its application in the differential diagnosis of Mycobacterium tuberculosis latent infection.

Tuberculosis (TB) is an infectious disease that significantly threatens human health. However, the differential diagnosis of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) remains a challenge for clinicians in early detection and preventive intervention. In this study, we developed a novel biomarker named HP16118P, utilizing 16 helper T lymphocyte (HTL) epitopes, 11 cytotoxic T lymphocyte (CTL) epitopes, and 8 B cell epitopes identified from 15 antigens associated with LTBI-RD using the IEDB database. We analyzed the physicochemical properties, spatial structure, and immunological characteristics of HP16118P using various tools, which indicated that it is a hydrophilic and relatively stable alkaline protein. Furthermore, HP16118P exhibited good antigenicity and immunogenicity, while being non-toxic and non-allergenic, with the potential to induce immune responses. We observed that HP16118P can stimulate the production of high levels of IFN-γ+ T lymphocytes in individuals with ATB, LTBI, and health controls. IL-5 induced by HP16118P demonstrated potential in distinguishing LTBI individuals and ATB patients (p=0.0372, AUC=0.8214, 95% CI [0.5843 to 1.000]) with a sensitivity of 100% and specificity of 71.43%. Furthermore, we incorporated the GM-CSF, IL-23, IL-5, and MCP-3 induced by HP16118P into 15 machine learning algorithms to construct a model. It was found that the Quadratic discriminant analysis model exhibited the best diagnostic performance for discriminating between LTBI and ATB, with a sensitivity of 1.00, specificity of 0.86, and accuracy of 0.93. In summary, HP16118P has demonstrated strong antigenicity and immunogenicity, with the induction of GM-CSF, IL-23, IL-5, and MCP-3, suggesting their potential for the differential diagnosis of LTBI and ATB.

Real-time evaluation of a multi-agency TB-screening event for persons experiencing homelessness in a town with a low incidence of TB in England.

Real-time evaluation (RTE) supports populations (e.g., persons experiencing homelessness (PEH) to engage in evaluation of health interventions who may otherwise be overlooked. The aim of this RTE was to explore the understanding of TB amongst PEH, identify barriers/facilitators to attending screening for PEH alongside suggestions for improving TB-screening events targeting PEH, who have high and complex health needs. This RTE composed of free-text structured one-to-one interviews performed immediately after screening at a single tuberculosis (TB) screening event. Handwritten forms were transcribed for thematic analysis, with codes ascribed to answers that were developed into core themes. All RTE participants (n=15) learned about the screening event on the day it was held. Key concerns amongst screening attendees included: stigma around drug use, not understanding the purpose of TB screening, lack of trusted individuals/services present, too many partner organizations involved, and language barriers. Facilitators to screening included a positive welcome to the event, a satisfactory explanation of screening tests, and sharing of results. A need for improved event promotion alongside communication of the purpose of TB screening amongst PEH was also identified. A lack of trust identified by some participants suggests the range of services present should be reconsidered for future screening events.