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Frontiers in Cellular and Infection... 2024Tuberculosis (TB) persists as a global health challenge, with its treatment hampered by the side effects of long-term combination drug therapies and the growing issue of...
BACKGROUND
Tuberculosis (TB) persists as a global health challenge, with its treatment hampered by the side effects of long-term combination drug therapies and the growing issue of drug resistance. Therefore, the development of novel therapeutic strategies is critical. This study focuses on the role of immune checkpoint molecules (ICs) and functions of CD8+ T cells in the search for new potential targets against TB.
METHODS
We conducted differential expression genes analysis and CD8+ T cell functional gene analysis on 92 TB samples and 61 healthy individual (HI) samples from TB database GSE83456, which contains data on 34,603 genes. The GSE54992 dataset was used to validated the findings. Additionally, a cluster analysis on single-cell data from primates infected with mycobacterium tuberculosis and those vaccinated with BCG was performed.
RESULTS
The overexpression of LAG-3 gene was found as a potentially important characteristic of both pulmonary TB (PTB) and extrapulmonary TB (EPTB). Further correlation analysis showed that LAG-3 gene was correlated with GZMB, perforin, IL-2 and IL-12. A significant temporal and spatial variation in LAG-3 expression was observed in T cells and macrophages during TB infection and after BCG vaccination.
CONCLUSION
LAG-3 was overexpressed in TB samples. Targeting LAG-3 may represent a potential therapeutic target for tuberculosis.
Topics: Lymphocyte Activation Gene 3 Protein; Humans; Mycobacterium tuberculosis; CD8-Positive T-Lymphocytes; Tuberculosis; Animals; Antigens, CD; BCG Vaccine; Macrophages; Interleukin-2; Gene Expression Profiling; Tuberculosis, Pulmonary; Interleukin-12; Perforin; Male
PubMed: 38957797
DOI: 10.3389/fcimb.2024.1410015 -
Frontiers in Public Health 2024We aimed to determine the trend of TB-related deaths during the COVID-19 pandemic.
BACKGROUND
We aimed to determine the trend of TB-related deaths during the COVID-19 pandemic.
METHODS
TB-related mortality data of decedents aged ≥25 years from 2006 to 2021 were analyzed. Excess deaths were estimated by determining the difference between observed and projected mortality rates during the pandemic.
RESULTS
A total of 18,628 TB-related deaths were documented from 2006 to 2021. TB-related age-standardized mortality rates (ASMRs) were 0.51 in 2020 and 0.52 in 2021, corresponding to an excess mortality of 10.22 and 9.19%, respectively. Female patients with TB demonstrated a higher relative increase in mortality (26.33 vs. 2.17% in 2020; 21.48 vs. 3.23% in 2021) when compared to male. Female aged 45-64 years old showed a surge in mortality, with an annual percent change (APC) of -2.2% pre-pandemic to 22.8% (95% CI: -1.7 to 68.7%) during the pandemic, corresponding to excess mortalities of 62.165 and 99.16% in 2020 and 2021, respectively; these excess mortality rates were higher than those observed in the overall female population ages 45-64 years in 2020 (17.53%) and 2021 (33.79%).
CONCLUSION
The steady decline in TB-related mortality in the United States has been reversed by COVID-19. Female with TB were disproportionately affected by the pandemic.
Topics: Humans; COVID-19; Female; Middle Aged; Male; United States; Adult; Aged; Tuberculosis; Sex Factors; Aged, 80 and over; Pandemics
PubMed: 38957204
DOI: 10.3389/fpubh.2024.1413604 -
BMC Infectious Diseases Jul 2024To investigate risk factors associated with long-term mortality in patients with stage II and III tuberculous meningitis (TBM).
OBJECTIVE
To investigate risk factors associated with long-term mortality in patients with stage II and III tuberculous meningitis (TBM).
METHODS
This retrospective analysis examined patients who were first diagnosed with stage II and III TBM at West China Hospital of Sichuan University between January 1, 2018 and October 1, 2019. Patients were followed via telephone and categorized into survival and mortality groups based on 4-year outcomes. Multivariate logistic regression identified independent risk factors for long-term mortality in stage II and III TBM.
RESULTS
In total, 178 patients were included, comprising 108 (60.7%) males and 36 (20.2%) non-survivors. Mean age was 36 ± 17 years. Compared to survivors, non-survivors demonstrated significantly higher age, heart rate, diastolic blood pressure, blood glucose, rates of headache, neurological deficits, cognitive dysfunction, impaired consciousness, hydrocephalus, and basal meningeal inflammation. This group also exhibited significantly lower Glasgow Coma Scale (GCS) scores, blood potassium, albumin, and cerebrospinal fluid chloride. Multivariate analysis revealed age (OR 1.042; 95% CI 1.015-1.070; P = 0.002), GCS score (OR 0.693; 95% CI 0.589-0.814; P < 0.001), neurological deficits (OR 5.204; 95% CI 2.056-13.174; P < 0.001), and hydrocephalus (OR 2.680; 95% CI 1.081-6.643; P = 0.033) as independent mortality risk factors. The ROC curve area under age was 0.613 (95% CI 0.506-0.720; P = 0.036) and 0.721 (95% CI 0.615-0.826; P < 0.001) under GCS score.
CONCLUSION
Advanced age, reduced GCS scores, neurological deficits, and hydrocephalus were identified as independent risk factors for mortality in stage II and III TBM patients.
Topics: Humans; Male; Tuberculosis, Meningeal; Female; Adult; Risk Factors; Retrospective Studies; Middle Aged; Young Adult; China; Glasgow Coma Scale; Adolescent
PubMed: 38956526
DOI: 10.1186/s12879-024-09561-0 -
BMC Pulmonary Medicine Jul 2024Immunoglobulin light chain (AL) amyloidosis presents a clinical spectrum characterized by diverse manifestations and involvement of multiple organs, posing a significant...
INTRODUCTION
Immunoglobulin light chain (AL) amyloidosis presents a clinical spectrum characterized by diverse manifestations and involvement of multiple organs, posing a significant diagnostic challenge for physicians.
METHODS AND RESULTS
We present a case of a patient admitted to our hospital due to recurrent cough and sputum, which was initially diagnosed as refractory tuberculosis. Throughout his hospitalization, the patient experienced distressing symptoms, including uncontrollable chest tightness, hypotension, and fever. Noteworthy observations included a persistent elevation in cardiac biomarkers, indicative of cardiac damage. Bronchoalveolar lavage revealed the presence of various pathogenic microorganisms, while bone marrow flow cytometry demonstrated the existence of clonal plasma cells. Additionally, the urine free light chain assay detected the presence of M protein, and the positive congo red staining of the abdominal wall fat biopsy confirmed amyloid deposition in the tissues. Taking into account the patient's clinical presentation and the examination findings, we reached a conclusive diagnosis of immunoglobulin light chain (AL) amyloidosis.
CONCLUSION
This case serves as a reminder for physicians to consider rare diseases like AL amyloidosis when patients present with symptoms involving multiple organ systems such as heart, lung and kidney that are unresponsive to conventional treatment options.
Topics: Humans; Male; Immunoglobulin Light-chain Amyloidosis; Hypotension; Diagnosis, Differential; Middle Aged; Tuberculosis; Cough; Aged
PubMed: 38956518
DOI: 10.1186/s12890-024-03127-1 -
BMC Infectious Diseases Jul 2024Tuberculosis is a global health problem that causes 1. 4 million deaths every year. It has been estimated that sputum smear-negative diagnosis but culture-positive... (Comparative Study)
Comparative Study
Comparison of microscopic and xpert MTB diagnoses of presumptive mycobacteria tuberculosis infection: retrospective analysis of routine diagnosis at Cape Coast Teaching Hospital.
INTRODUCTION
Tuberculosis is a global health problem that causes 1. 4 million deaths every year. It has been estimated that sputum smear-negative diagnosis but culture-positive pulmonary TB diagnosis contribute to 12.6% of pulmonary TB transmission. TB diagnosis by smear microscopy smear has a minimum detection limit (LOD) of 5,000 to 10,000 bacilli per milliliter (CFU/ml) of sputum result in missed cases and false positives. However, GeneXpert technology, with a LOD of 131-250 CFU/ml in sputum samples and its implementation is believe to facilitate early detection TB and drug-resistant TB case. Since 2013, Ghana health Service (GHS) introduce GeneXpert MTB/RIF diagnostic in all regional hospitals in Ghana, however no assessment of performance between microscopy and GeneXpert TB diagnosis cross the health facilities has been reported. The study compared the results of routine diagnoses of TB by microscopy and Xpert MTB from 2016 to 2020 at the Cape Coast Teaching Hospital (CCTH).
METHODS
The study compared routine microscopic and GeneXpert TB diagnosis results at the Cape Coast Teaching Hospital (CCTH) from 2016 to 2020 retrospectively. Briefly, sputum specimens were collected into 20 mL sterile screw-capped containers for each case of suspected TB infection and processed within 24 h. The samples were decontaminated using the NALC-NaOH method with the final NaOH concentration of 1%. The supernatants were discarded after the centrifuge and the remaining pellets dissolved in 1-1.5 ml of phosphate buffer saline (PBS) and used for diagnosis. A fixed smears were Ziehl-Neelsen acid-fast stain and observed under microscope and the remainings were used for GeneXpert MTB/RIF diagnosis. The data were analyze using GraphPad Prism.
RESULTS
50.11% (48.48-51.38%) were females with an odd ratio (95% CI) of 1.004 (0.944-1.069) more likely to report to the TB clinic for suspected TB diagnosis. The smear-positive cases for the first sputum were 6.6% (5.98-7.25%), and the second sputum was 6.07% (5.45-6.73%). The Xpert MTB-RIF diagnosis detected 2.93% (10/341) (1.42-5.33%) in the first and 5.44% (16/294) (3.14-8.69%) in the second smear-negative TB samples. The prevalence of Xpert MTB-RIF across smear positive showed that males had 56.87% (178/313) and 56.15% (137/244) and females had 43.13% (135/313) and 43.85% (107/244) for the first and second sputum. Also, false negative smears were 0.18% (10/5607) for smear 1 and 0.31% (16/5126) for smear 2.
CONCLUSION
In conclusion, the study highlights the higher sensitivity of the GeneXpert assay compared to traditional smear microscopy for detecting MTB. The GeneXpert assay identified 10 and 16 positive MTB from smear 1 and smear 2 samples which were microscopic negative.
Topics: Humans; Mycobacterium tuberculosis; Retrospective Studies; Sputum; Ghana; Female; Hospitals, Teaching; Adult; Male; Microscopy; Middle Aged; Tuberculosis, Pulmonary; Young Adult; Adolescent; Sensitivity and Specificity; Aged; Molecular Diagnostic Techniques; Child; Child, Preschool
PubMed: 38956504
DOI: 10.1186/s12879-024-09566-9 -
BMC Infectious Diseases Jul 2024Multi-drug or rifamycin-resistant tuberculosis (MDR/RR-TB) is an important public health concern, including in settings with high HIV prevalence. TB drug resistance can... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multi-drug or rifamycin-resistant tuberculosis (MDR/RR-TB) is an important public health concern, including in settings with high HIV prevalence. TB drug resistance can be directly transmitted or arise through resistance acquisition during first-line TB treatment. Limited evidence suggests that people living with HIV (PLHIV) might have an increased risk of acquired rifamycin-resistance (ARR).
METHODS
To assess HIV as a risk factor for ARR during first-line TB treatment, a systematic review and meta-analysis was conducted. ARR was defined as rifamycin-susceptibility at treatment start with rifamycin-resistance diagnosed during or at the end of treatment, or at recurrence. PubMed/MEDLINE, CINAHL, Cochrane Library, and Google Scholar databases were searched from inception to 23 May 2024 for articles in English; conference abstracts were also searched from 2004 to 2021. The Mantel-Haenszel random-effects model was used to estimate the pooled odds ratio of any association between HIV and ARR among individuals receiving first-line TB treatment.
RESULTS
Ten studies that included data collected between 1990 and 2014 were identified: five from the United States, two from South Africa and one each from Uganda, India and Moldova. A total of 97,564 individuals were included across all studies, with 13,359 (13.7%) PLHIV. Overall, 312 (0.32%) acquired rifamycin-resistance, among whom 115 (36.9%) were PLHIV. The weighted odds of ARR were 4.57 (95% CI, 2.01-10.42) times higher among PLHIV compared to HIV-negative individuals receiving first-line TB treatment.
CONCLUSION
The available data, suggest that PLHIV have an increased ARR risk during first-line TB treatment. Further research is needed to clarify specific risk factors, including advanced HIV disease and TB disease severity. Given the introduction of shorter, 4-month rifamycin-based regimens, there is an urgent need for additional data on ARR, particularly for PLHIV.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022327337.
Topics: Humans; HIV Infections; Rifamycins; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Risk Factors; Mycobacterium tuberculosis; South Africa
PubMed: 38956461
DOI: 10.1186/s12879-024-09514-7 -
Scientific Reports Jul 2024Using ultrasound findings and clinical characteristics, we constructed and validated a new nomogram for distinguishing epididymal tuberculosis from nontuberculous...
Using ultrasound findings and clinical characteristics, we constructed and validated a new nomogram for distinguishing epididymal tuberculosis from nontuberculous epididymitis, both of which share similar symptoms. We retrospectively examined data of patients with epididymal tuberculosis and nontuberculous epididymitis hospitalized between January 1, 2013, and March 31, 2023. Eligible patients were randomly assigned to derivation and validation cohorts (ratio, 7:3). We drew a nomogram to construct a diagnostic model through multivariate logistic regression and visualize the model. We used concordance index, calibration plots, and decision curve analysis to assess the discrimination, calibration, and clinical usefulness of the nomogram, respectively. In this study, 136 participants had epididymal tuberculosis and 79 had nontuberculous epididymitis. Five variables-C-reactive protein level, elevated scrotal skin temperature, nodular lesion, chronic infection, and scrotal skin ulceration-were significant and used to construct the nomogram. Concordance indices of the derivation and validation cohorts were 0.95 and 0.96, respectively (95% confidence intervals, 0.91-0.98 and 0.92-1.00, respectively). Decision curve analysis of this nomogram revealed that it helped differentiate epididymal tuberculosis from nontuberculous epididymitis. This nomogram may help clinicians distinguish between epididymal tuberculosis and nontuberculous epididymitis, thereby increasing diagnosis accuracy.
Topics: Humans; Male; Epididymitis; Nomograms; Ultrasonography; Middle Aged; Adult; Diagnosis, Differential; Retrospective Studies; Epididymis; Tuberculosis, Male Genital; Tuberculosis; Aged
PubMed: 38956255
DOI: 10.1038/s41598-024-65682-1 -
Saudi Medical Journal Jul 2024To evaluate cytokine profiles and interferon-gamma release assay (IGRA) for their diagnostic capabilities in the differentiation of tuberculosis (TB) from non-TB...
OBJECTIVES
To evaluate cytokine profiles and interferon-gamma release assay (IGRA) for their diagnostic capabilities in the differentiation of tuberculosis (TB) from non-TB conditions, as well as smear-negative pulmonary tuberculosis (SNPT) from smear-positive pulmonary tuberculosis (SPPT).
METHODS
A total of 125 participants were included, 77 of whom had TB and 48 who didn't, and demographic, clinical, and laboratory data were collected, including cytokine levels and IGRA results. The TB patients were further divided into 2 subgroups: SNPT (n=42) and SPPT (n=35).
RESULTS
Compared to non-TB, the TB group had lower BMI, higher WBC, neutrophils, monocytes, ESR and CRP (<0.05). TB patients showed higher IL-2, IL-6, IFN-γ, IL-8 (<0.001) and higher IGRA positivity (88.3% versus [vs.] 29.2%, <0.001). Between SNPT and SPPT, moderate effect sizes were observed for IFN-α, IL-2, IL-10, IL-8 (Cohen's d 0.59-0.76), with lower IGRA positivity in SNPT (81.0% vs. 97.1%, =0.015). ROC analysis indicated IFN-α, IL-2, IL-10, IL-8 had moderate accuracy for SNPT diagnosis (AUCs 0.668-0.734), and combining these improved accuracy (AUC 0.759, 80% sensitivity, 64.2% specificity).
CONCLUSION
A multi-biomarker approach combining these cytokines demonstrates enhanced diagnostic accuracy for tuberculosis.
Topics: Humans; Tuberculosis, Pulmonary; Male; Female; Cytokines; Adult; Middle Aged; Retrospective Studies; Interferon-gamma Release Tests; Interleukin-2; Interleukin-8; ROC Curve; Interleukin-6; Interleukin-10
PubMed: 38955446
DOI: 10.15537/smj.2024.45.7.20240310 -
CMAJ : Canadian Medical Association... Jul 2024
Topics: Humans; Female; Bronchiectasis; Mycetoma; Middle Aged; Lung Diseases, Fungal; Tomography, X-Ray Computed
PubMed: 38955407
DOI: 10.1503/cmaj.231618-f -
BMJ Case Reports Jul 2024Lucio leprosy is a diffuse non-nodular form of lepromatous leprosy. Lucio phenomenon is a type of reactional state which occurs in untreated cases due to the bacillary...
Lucio leprosy is a diffuse non-nodular form of lepromatous leprosy. Lucio phenomenon is a type of reactional state which occurs in untreated cases due to the bacillary invasion of endothelial cells. We hereby describe a histopathologically confirmed case of Lucio leprosy with Lucio phenomenon. The patient presented with pleomorphic clinical features and started taking antileprosy treatment and systemic steroids. After few days of admission, she developed deep ulcers exposing the fascia. She also developed cardiogenic shock secondary to septicaemia. She was managed with inotropes and broad-spectrum antibiotics. The patient was given appropriate wound care and the ulcers healed within a period of 3 months and antileprosy drugs were continued. Our patient is a de novo case of Lucio leprosy with Lucio phenomenon and pleomorphic clinical features who developed near fatal septic shock. She was managed successfully. Despite the extensive disease manifestation, all the wounds healed completely.
Topics: Humans; Female; Leprosy, Lepromatous; Shock, Septic; Leprostatic Agents; Anti-Bacterial Agents; Shock, Cardiogenic; Middle Aged
PubMed: 38955383
DOI: 10.1136/bcr-2023-255477