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PloS One 2023A mechanistic understanding of uncommon immune outcomes such as resistance to infection has led to the development of novel therapies. Using gene level analytic methods,...
BACKGROUND
A mechanistic understanding of uncommon immune outcomes such as resistance to infection has led to the development of novel therapies. Using gene level analytic methods, we previously found distinct monocyte transcriptional responses associated with resistance to Mycobacterium tuberculosis (Mtb) infection defined as persistently negative tuberculin skin test (TST) and interferon gamma release assay (IGRA) reactivity among highly exposed contacts (RSTR phenotype).
OBJECTIVE
Using transcript isoform analyses, we aimed to identify novel RSTR-associated genes hypothesizing that previous gene-level differential expression analysis obscures isoform-specific differences that contribute to phenotype.
MATERIALS AND METHODS
Monocytes from 49 RSTR versus 52 subjects with latent Mtb infection (LTBI) were infected with M. tuberculosis (H37Rv) or left unstimulated (media) prior to RNA isolation and sequencing. RSTR-associated gene expression was then identified using differential transcript isoform analysis.
RESULTS
We identified 81 differentially expressed transcripts (DETs) in 70 genes (FDR <0.05) comparing RSTR and LTBI phenotypes with the majority (n = 79 DETs) identified under Mtb-stimulated conditions. Seventeen of these genes were previously identified with gene-level bulk RNAseq analyses including genes in the IFNγ response that had increased expression among LTBI subjects, findings consistent with a clinical phenotype based on IGRA reactivity. Among the subset of 23 genes with positive differential expression among Mtb-infected RSTR monocytes, 13 were not previously identified. These novel DET genes included PDE4A and ZEB2, which each had multiple DETs with higher expression among RSTR subjects, and ACSL4 and GAPDH that each had a single transcript isoform associated with RSTR.
CONCLUSION AND LIMITATIONS
Transcript isoform-specific analyses identify transcriptional associations, such as those associated with resistance to TST/IGRA conversion, that are obscured when using gene-level approaches. These findings should be validated with additional RSTR cohorts and whether the newly identified candidate resistance genes directly influence the monocyte Mtb response requires functional study.
Topics: Humans; Interferon-gamma Release Tests; Tuberculin Test; Latent Tuberculosis; Mycobacterium tuberculosis; Phenotype; Latent Infection
PubMed: 37058459
DOI: 10.1371/journal.pone.0284498 -
Revue Scientifique Et Technique... Dec 2012Tuberculosis is a chronic, contagious, granulomatous disease caused by mycobacterial species belonging to the Mycobacterium tuberculosis complex. Camelids were not... (Review)
Review
Tuberculosis is a chronic, contagious, granulomatous disease caused by mycobacterial species belonging to the Mycobacterium tuberculosis complex. Camelids were not considered highly susceptible to tuberculosis, but in recent years increased numbers of cases have been experienced in some countries. In most of the cases, transmission probably occurs through contact with infected cattle or wildlife. None of the ante-mortem tests currently available can consistently provide accurate diagnosis of the infection in live camelids. Recently developed serological assays have the potential for rapid and accurate diagnosis of tuberculosis but still need to be validated.
Topics: Animals; Camelids, New World; Camelus; Humans; Mycobacterium; Tuberculin Test; Tuberculosis; Zoonoses
PubMed: 23520743
DOI: 10.20506/rst.31.3.2161 -
Chest Dec 2010After more than a century of relying on skin testing for the diagnosis of latent TB infection, clinicians now have access to blood-based diagnostics in the form of... (Comparative Study)
Comparative Study Review
After more than a century of relying on skin testing for the diagnosis of latent TB infection, clinicians now have access to blood-based diagnostics in the form of interferon γ release assays (IGRAs). These tests are generally associated with higher sensitivity and specificity for diagnosis of latent TB infection. This article reviews the indications for testing and treatment of latent TB infection in the overall context of a TB control program and describes how IGRAs might be used in specific clinical settings and populations, including people having close contact with an active case of TB, the foreign born, and health-care workers.
Topics: Antigens, Bacterial; Female; Forecasting; Humans; Immunologic Tests; Interferon-gamma; Latent Tuberculosis; Male; Sensitivity and Specificity; Tuberculin Test; United States
PubMed: 21138881
DOI: 10.1378/chest.10-0366 -
Journal of Microbiology, Immunology,... Oct 2023To assess associations between disease severity in index TB patients and QuantiFERON-TB Gold Plus (QFT-Plus) results in contacts, and predictors for QFT-Plus conversion...
OBJECTIVES
To assess associations between disease severity in index TB patients and QuantiFERON-TB Gold Plus (QFT-Plus) results in contacts, and predictors for QFT-Plus conversion in contacts over 6-12 months.
METHODS
TB patients (n = 295) and the contacts (n = 1051) were enrolled during 2018-2021 with QFT-Plus performed at baseline and months 6 and 12. A strong CD8 response was defined as TB2 interferon gamma (IFN-γ) response minus TB1 >0.6 IU/ml and stringent conversion as change from QFT-plus negative to high-positive QFT-Plus (TB1 or TB2 IFN-γ responses >0.7 IU/ml).
RESULTS
Contacts with index TB patients with sputum smear >1+ was associated with positive QFT-Plus compared to those without (p < 0.001). Contacts with index TB patients with bilateral lung disease were more likely to have strong CD8 responses than those without (p = 0.038). QFT-Plus stringent conversion occurred in 9.7% of contacts over 6-12 months. A TB1 IFN-γ response ≥0.03 IU/ml combined with a TB2 ≥0.06 IU/ml was predictive of a 19-fold increased risk for QFT-Plus stringent conversion in contacts (odd ratio 19.565 [8.484-45.116], p < 0.001).
CONCLUSION
Bacterial burden and bilateral lung disease of index TB patients were associated with positive QFT-Plus and strong CD8 responses in contacts. TB1 and TB2 IFN-γ responses were synergistically predictive of stringent conversion in contacts.
Topics: Humans; Latent Tuberculosis; Interferon-gamma Release Tests; Tuberculosis; Interferon-gamma; Lung Diseases; Mycobacterium tuberculosis; Tuberculin Test
PubMed: 37580184
DOI: 10.1016/j.jmii.2023.07.014 -
Respiratory Medicine Nov 2006Tuberculosis has claimed its victims throughout much of known human history. It reached epidemic proportions in Europe and North America during the 18th and 19th...
Tuberculosis has claimed its victims throughout much of known human history. It reached epidemic proportions in Europe and North America during the 18th and 19th centuries, earning the sobriquet, "Captain Among these Men of Death." Then it began to decline. Understanding of the pathogenesis of tuberculosis began with the work of Théophile Laennec at the beginning of the 19th century and was further advanced by the demonstration of the transmissibility of Mycobacterium tuberculosis infection by Jean-Antoine Villemin in 1865 and the identification of the tubercle bacillus as the etiologic agent by Robert Koch in 1882. Clemens von Pirquet developed the tuberculin skin test in 1907 and 3 years later used it to demonstrate latent tuberculous infection in asymptomatic children. In the late 19th and early 20th centuries sanatoria developed for the treatment of patients with tuberculosis. The rest provided there was supplemented with pulmonary collapse procedures designed to rest infected parts of lungs and to close cavities. Public Health measures to combat the spread of tuberculosis emerged following the discovery of its bacterial cause. BCG vaccination was widely employed following World War I. The modern era of tuberculosis treatment and control was heralded by the discovery of streptomycin in 1944 and isoniazid in 1952.
Topics: Anti-Bacterial Agents; Antitubercular Agents; BCG Vaccine; Europe; History, 18th Century; History, 19th Century; History, 20th Century; Humans; Isoniazid; Male; Mycobacterium tuberculosis; Public Health; Streptomycin; Tuberculin Test; Tuberculosis
PubMed: 16949809
DOI: 10.1016/j.rmed.2006.08.006 -
Pneumonologia I Alergologia Polska 2015
Topics: Humans; Interferon-gamma; Interferon-gamma Release Tests; Latent Tuberculosis; Tuberculin Test
PubMed: 25754049
DOI: 10.5603/PiAP.2015.0015 -
The Veterinary Record Sep 2015A novel method for estimating specificity of the Single Intradermal Comparative Cervical Tuberculin (SICCT) test for bovine tuberculosis (bTB) using surveillance tests...
A novel method for estimating specificity of the Single Intradermal Comparative Cervical Tuberculin (SICCT) test for bovine tuberculosis (bTB) using surveillance tests results is reported. The specificity of the SICCT test at three cut-offs was estimated from the dates, locations and skinfold measurements of all routine tests carried out in Officially TB Free (OTF) cattle herds in Great Britain (GB) between 2002 and 2008, according to their separation (by distance and time) from known infected (OTF-withdrawn) herds. The proportion of animals that tested positive was constant (P>0.20) when the distance between tested herds and nearest infected herd exceeded 8 km. For standard cut-off, calculated specificity was 99.98 per cent (95 per cent confidence interval ±0.004 per cent), equating to one false positive result per 5000 uninfected animals tested. For severe cut-off it was 99.91 per cent (±0.013 per cent) and for ultrasevere cut-off (selecting all reactors and inconclusive reactors) it was 99.87 per cent (±0.017 per cent). The estimated positive predictive value of the test averaged 91 per cent and varied by regional prevalence. This study provides further evidence of the high specificity of the SICCT test under GB conditions, suggests that over 90 per cent of cattle currently culled using this test in GB were infected, and endorses slaughter of at least these cattle for bTB control.
Topics: Animals; Cattle; Population Surveillance; Sensitivity and Specificity; Tuberculin Test; Tuberculosis, Bovine; United Kingdom
PubMed: 26338518
DOI: 10.1136/vr.102961 -
British Medical Journal Dec 1970
Topics: False Negative Reactions; Humans; Hypersensitivity, Delayed; Tuberculin Test; Tuberculosis
PubMed: 5485173
DOI: No ID Found -
American Journal of Public Health Jul 2019To characterize the cascade of care for latent tuberculosis infection (LTBI) in persons experiencing homelessness (PEH) and evaluate the effect of screening by... (Comparative Study)
Comparative Study
To characterize the cascade of care for latent tuberculosis infection (LTBI) in persons experiencing homelessness (PEH) and evaluate the effect of screening by QuantiFERON-TB Gold (QFT) versus tuberculin skin test (TST). We performed a retrospective cohort study of all PEH screened for LTBI by QFT and TST from May 2015 to April 2017 in Fulton County, Georgia. There were 3504 PEH screened by QFT and 5509 by TST, with 2925 TSTs administered on site at community shelters and 2584 at the health department. More valid test results were obtained in those screened by QFT (99.0% vs 69.0%; < .001) because of low return rates for reading in both TST arms. For tests administered on site, testing by QFT versus TST improved retention in care with significantly more estimated LTBI cases following up for a medical examination (67.8% vs 51.0%; < .001) and starting LTBI treatment (58.4% vs 39.8%; < .001). A QFT-based screening strategy in PEH improved diagnosis and retention in care for new LTBI cases compared with TST and may be an effective strategy to limit progression to active tuberculosis.
Topics: Adult; Female; Georgia; Ill-Housed Persons; Humans; Interferon-gamma Release Tests; Latent Tuberculosis; Male; Mass Screening; Middle Aged; Retrospective Studies; Tuberculin Test
PubMed: 31095412
DOI: 10.2105/AJPH.2019.305069 -
Infection Control and Hospital... Mar 2009We compared a whole-blood interferon-gamma release assay (QuantiFERON-TB Gold In-Tube test, hereafter "QFT-in tube test") with a tuberculin skin test (TST) to determine... (Comparative Study)
Comparative Study
Comparison of QuantiFERON-TB Gold In-Tube Test and tuberculin skin test for identification of latent Mycobacterium tuberculosis infection in healthcare staff and association between positive test results and known risk factors for infection.
OBJECTIVE
We compared a whole-blood interferon-gamma release assay (QuantiFERON-TB Gold In-Tube test, hereafter "QFT-in tube test") with a tuberculin skin test (TST) to determine which test more accurately identified latent Mycobacterium tuberculosis infection in healthcare staff.
METHODS
A total of 481 hospital staff members were recruited from 5 hospitals in Melbourne, Australia. They provided information about demographic variables and tuberculosis (TB) risk factors (ie, birth or travel in a country with a high prevalence of TB, working in an occupation likely to involve contact with M. tuberculosis or individuals with TB, or being a household contact of an individual with a proven case of pulmonary TB). The QFT-in tube test and the TST were administered in accordance with standardized protocols. Concordance between the test results and positive risk factors was analyzed using the kappa statistic, the McNemar test, and logistic regression.
RESULTS
A total of 358 participants had both a TST result and a QFT-in tube test result available for comparison. There were fewer positive QFT-in tube test results than positive TST results (6.7% vs. 33.0%; P<.001). Agreement between the tests was poor (71%; kappa=0.16). A positive QFT-in tube test result was associated with birth in a country with a high prevalence of TB, the number of years an individual had lived in a country with a high prevalence of TB (ie, the effect of each additional year, treated as a continuous variable), and high-risk occupational contact. A positive TST result was associated with older age, receipt of bacille Calmette-Guérin (BCG) vaccination, and working in an occupation that involved patient contact. Receipt of BCG vaccination was most strongly associated with discordant results in instances in which the TST result was positive and the QFT-in tube test result was negative.
CONCLUSION
In a population of healthcare staff with a low prevalence of TB and a significant rate of BCG vaccination, a positive QFT-in tube test result was associated with the presence of known risk factors for TB exposure, whereas a positive TST result was more strongly associated with a prior history of BCG vaccination.
Topics: Adult; Aged; Female; Health Personnel; Humans; Logistic Models; Male; Middle Aged; Mycobacterium tuberculosis; Reagent Kits, Diagnostic; Risk Factors; Tuberculin Test; Tuberculosis; Young Adult
PubMed: 19191484
DOI: 10.1086/595695