scholarly journals Tuberculosis Risk Stratification of Psoriatic Patients Before Anti-TNF-α Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Farida Benhadou ◽  
Violette Dirix ◽  
Fanny Domont ◽  
Fabienne Willaert ◽  
Anne Van Praet ◽  
...  
Keyword(s):  
Interferon Γ ◽  
Added Value ◽  
Skin Tests ◽  
Mycobacterial Antigen ◽  
Heparin Binding ◽  
Biological Drugs ◽  
Risk Levels ◽  
Tb Treatment ◽  
Specificity And Sensitivity ◽  
Broad Array

Psoriasis is a skin inflammatory condition for which significant progress has been made in its management by the use of targeted biological drugs. Detection of latent M. tuberculosis infection (LTBI) is mandatory before starting biotherapy that is associated with reactivation risk. Together with evaluation of TB risk factors and chest radiographs, tuberculin skin tests (TST) and/or blood interferon-γ-release assays (IGRA), like the QuantiFERON (QFT), are usually performed to diagnose M. tuberculosis infection. Using this approach, 14/49 psoriatic patients prospectively included in this study were identified as LTBI (14 TST+, induration size ≥ 10mm, 8 QFT+), and 7/14 received prophylactic anti-TB treatment, the other 7 reporting past-treatment. As the specificity and sensitivity of these tests were challenged, we evaluated the added value of an IGRA in response to a mycobacterial antigen associated with latency, the heparin-binding haemagglutinin (HBHA). All but one TST+ patient had a positive HBHA-IGRA, indicating higher sensitivity than the QFT. The HBHA-IGRA was also positive for 12/35 TST-QFT- patients. Measurement for 15 psoriatic patients (12 with HBHA-IGRA+) of 8 chemokines in addition to IFN-γ revealed a broad array of HBHA-induced chemokines for TST+QFT- and TST-QFT- patients, compared to a more restricted pattern for TST+QFT+ patients. This allowed us to define subgroups within psoriatic patients characterized by different immune responses to M. tuberculosis antigens that may be associated to different risk levels of reactivation of the infection. This approach may help in prioritizing patients who should receive prophylactic anti-TB treatment before starting biotherapies in order to reduce their number.

scholarly journals Influence of replacing tuberculin skin test with ex vivo interferon γ release assays on decision to administer prophylactic antituberculosis antibiotics before anti-TNF therapy

2012 ◽  
Vol 71 (11) ◽  
pp. 1783-1790 ◽  
Author(s):  
Xavier Mariette ◽  
Gabriel Baron ◽  
Florence Tubach ◽  
Frédéric Lioté ◽  
Bernard Combe ◽  
...  
Keyword(s):  
Antibiotic Prophylaxis ◽  
Tuberculin Skin Test ◽  
Skin Test ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Tertiary Care ◽  
Latent Tuberculosis ◽  
Interferon Γ ◽  
Specificity And Sensitivity ◽  
Immune Mediated

BackgroundThe recommendations for detecting latent tuberculosis infection (LTBI) before antitumour necrosis factor (anti-TNF) therapy are based on the tuberculin skin test (TST), which lacks both specificity and sensitivity and can lead to unnecessary treatment with antibiotics. A study was undertaken to investigate the effect of replacing TST with interferon γ (IFNγ) release assays (IGRA) in screening for LTBI and deciding to begin prophylactic antituberculosis (TB) antibiotics before anti-TNF therapy in immune-mediated inflammatory diseases.MethodsIn 15 tertiary care hospitals, consecutive patients with rheumatoid arthritis, spondylarthropathies or Crohn's disease were screened for LTBI before anti-TNF therapy with TST, QuantiFERON TB Gold in tube (QTF-Gold IT) and T-SPOT.TB at the same time. The potential diagnosis of LTBI and the effect on the decision to begin antibiotic prophylaxis were assessed.ResultsAmong 429 patients, 392 had results for the three tests. The results for TST, T-SPOT.TB and QTF Gold IT were positive for 35.2%, 15.1% and 9.9% of patients, respectively (p<0.0001). Antibiotics were required for 177 patients (45.2%) if positive TST results were included in the LTBI definition, 107 patients (27.3%) if TST results were replaced with results from one of the IGRA tests and 84 patients (21.4%) if TST results were replaced with QTF-Gold IT results (p<0.0001). The decision on the use of antibiotic prophylaxis was changed for 113 patients (28.8%, 95% CI 24.4% to 33.6%) if TST results were replaced with QTF-Gold IT results.ConclusionsReplacing TST with IGRA for determining LTBI allowed the proportion of patients with immune-mediated inflammatory diseases needing prophylactic anti-TB antibiotics before beginning anti-TNF agents to be reduced by half.TrialRegNo: NCT00811343.

scholarly journals A fuller picture of COVID-19 prognosis: the added value of vulnerability measures to predict mortality in hospitalised older adults

2020 ◽  
Author(s):  
Márlon Juliano Romero Aliberti ◽  
Kenneth E Covinsky ◽  
Flavia Barreto Garcez ◽  
Alexander K Smith ◽  
Pedro Kallas Curiati ◽  
...  
Keyword(s):  
Older Adults ◽  
Prediction Models ◽  
Mortality Prediction ◽  
Added Value ◽  
University Hospital ◽  
Early Warning Score ◽  
Risk Levels ◽  
Time To Death ◽  
Mortality Prediction Models ◽  
Key Aspects

Abstract Background Although coronavirus disease 2019 (COVID-19) disproportionally affects older adults, the use of conventional triage tools in acute care settings ignores the key aspects of vulnerability. Objective This study aimed to determine the usefulness of adding a rapid vulnerability screening to an illness acuity tool to predict mortality in hospitalised COVID-19 patients. Design Cohort study. Setting Large university hospital dedicated to providing COVID-19 care. Participants Participants included are 1,428 consecutive inpatients aged ≥50 years. Methods Vulnerability was assessed using the modified version of PRO-AGE score (0–7; higher = worse), a validated and easy-to-administer tool that rates physical impairment, recent hospitalisation, acute mental change, weight loss and fatigue. The baseline covariates included age, sex, Charlson comorbidity score and the National Early Warning Score (NEWS), a well-known illness acuity tool. Our outcome was time-to-death within 60 days of admission. Results The patients had a median age of 66 years, and 58% were male. The incidence of 60-day mortality ranged from 22% to 69% across the quartiles of modified PRO-AGE. In adjusted analysis, compared with modified PRO-AGE scores 0–1 (‘lowest quartile’), the hazard ratios (95% confidence interval) for 60-day mortality for modified PRO-AGE scores 2–3, 4 and 5–7 were 1.4 (1.1–1.9), 2.0 (1.5–2.7) and 2.8 (2.1–3.8), respectively. The modified PRO-AGE predicted different mortality risk levels within each stratum of NEWS and improved the discrimination of mortality prediction models. Conclusions Adding vulnerability to illness acuity improved accuracy of predicting mortality in hospitalised COVID-19 patients. Combining tools such as PRO-AGE and NEWS may help stratify the risk of mortality from COVID-19.

scholarly journals Relevance of QuantiFERON-TB Gold Plus and Heparin-Binding Hemagglutinin Interferon-γ Release Assays for Monitoring of Pulmonary Tuberculosis Clearance: A Multicentered Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Carole Chedid ◽  
Eka Kokhreidze ◽  
Nestani Tukvadze ◽  
Sayera Banu ◽  
Mohammad Khaja Mafij Uddin ◽  
...  
Keyword(s):  
Immune Cell ◽  
Interferon Γ ◽  
Sputum Culture ◽  
Heparin Binding ◽  
Monitoring Methods ◽  
Blood Samples ◽  
Sputum Culture Conversion ◽  
Cell Counts ◽  
Release Assay ◽  
Culture Conversion

BackgroundTuberculosis (TB) is a leading infectious cause of death. To improve treatment efficacy, quicker monitoring methods are needed. The objective of this study was to monitor the response to a heparin-binding hemagglutinin (HBHA) interferon-γ (IFN-γ) release assay (IGRA) and QuantiFERON-TB Gold Plus (QFT-P) and to analyze plasma IFN-γ levels according to sputum culture conversion and immune cell counts during treatment.MethodsThis multicentered cohort study was based in Bangladesh, Georgia, Lebanon, Madagascar, and Paraguay. Adult, non-immunocompromised patients with culture-confirmed pulmonary TB were included. Patients were followed up at baseline (T0), after two months of treatment (T1), and at the end of therapy (T2). Clinical data and blood samples were collected at each timepoint. Whole blood samples were stimulated with QFT-P antigens or recombinant methylated Mycobacterium tuberculosis HBHA (produced in Mycobacterium smegmatis; rmsHBHA). Plasma IFN-γ levels were then assessed by ELISA.FindingsBetween December 2017 and September 2020, 132 participants completed treatment, including 28 (21.2%) drug-resistant patients. rmsHBHA IFN-γ increased significantly throughout treatment (0.086 IU/ml at T0 vs. 1.03 IU/ml at T2, p &lt; 0.001) while QFT-P IFN-γ remained constant (TB1: 0.53 IU/ml at T0 vs. 0.63 IU/ml at T2, p = 0.13). Patients with low lymphocyte percentages (&lt;14%) or high neutrophil percentages (&gt;79%) at baseline had significantly lower IFN-γ responses to QFT-P and rmsHBHA at T0 and T1. In a small group of slow converters (patients with positive cultures at T1; n = 16), we observed a consistent clinical pattern at baseline (high neutrophil percentages, low lymphocyte percentages and BMI, low TB1, TB2, and MIT IFN-γ responses) and low rmsHBHA IFN-γ at T1 and T2. However, the accuracy of the QFT-P and rmsHBHA IGRAs compared to culture throughout treatment was low (40 and 65% respectively). Combining both tests improved their sensitivity and accuracy (70–80%) but not their specificity (&lt;30%).ConclusionWe showed that QFT-P and rmsHBHA IFN-γ responses were associated with rates of sputum culture conversion. Our results support a growing body of evidence suggesting that rmsHBHA IFN-γ discriminates between the different stages of TB, from active disease to controlled infection. However, further work is needed to confirm the specificity of QFT-P and rmsHBHA IGRAs for treatment monitoring.

scholarly journals Alternative Splicing of MR1 regulates antigen presentation to MAIT cells

2019 ◽  
Author(s):  
Gitanjali A. Narayanan ◽  
Abhinav Nellore ◽  
Jessica G. Tran ◽  
Aneta H. Worley ◽  
Erin W. Meermeier ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Cell Activation ◽  
Splice Variants ◽  
The United States ◽  
United States Government ◽  
Mycobacterial Antigen ◽  
Department Of Veterans Affairs ◽  
Double Positive ◽  
Mait Cells ◽  
Broad Array

AbstractMucosal Associated Invariant T (MAIT) cells can sense intracellular infection by a broad array of pathogens. These cells are activated upon encountering microbial antigen(s) displayed by MR1 on the surface of an infected cell. Human MR1 undergoes alternative splicing. The full length isoform, MR1A, can activate MAIT cells, while the function of the isoforms, MR1B and MR1C, are not well characterized.In this report, we sought to characterize these splice variants. Using a transcriptomic analysis in conjunction with qPCR, we find that that MR1A and MR1B transcripts are widely expressed. Despite the widespread expression of MR1A and MR1B, only MR1A can present mycobacterial antigen to MAIT cells. Coexpression of MR1B with MR1A serves to decrease MAIT cell activation following bacterial infection. However, expression of MR1B prior to MR1A lowers total MR1A abundance, suggesting competition between MR1A and MR1B for either ligands or chaperones required for folding and/or trafficking. Finally, we evaluated CD4/CD8 double positive thymocytes expressing surface MR1. Relative MR1A/MR1B expression in MR1-expressing thymocytes is associated with their prevalence.Our results suggest alternative splicing of MR1 represents a means of regulating MAIT activation in response to microbial ligand.FundingThis work was supported by NIH T32HL083808 (EK, GAN, EM), VA Merit Award I01CX001562 (MJH), NIH R01AI29976 (MJH), NIH R01AI048090 (DML), NIH R21AI124225-01A1 (FT) and VA Merit Award I01BX000533 (DML). The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.

scholarly journals Prevalence of latent tuberculosis among refugee children in Malaysia

2020 ◽  
Vol 6 (1) ◽  
pp. 00254-2019 ◽  
Author(s):  
Yen Jun Wong ◽  
Shaun Wen Huey Lee
Keyword(s):  
Latent Tuberculosis ◽  
Interferon Γ ◽  
Cross Sectional Study ◽  
Preventive Therapy ◽  
Skin Tests ◽  
Refugee Children ◽  
High Risk Population ◽  
Tuberculosis Screening ◽  
Cross Sectional ◽  
Increased Risk

IntroductionTuberculosis remains one of the top 10 major causes of global mortality, imposing social–economic and medical challenges in Malaysia. Refugees sheltered in Malaysia are a high-risk population but basic health checks upon their arrival, including tuberculosis screening, are not practised. This study aimed to identify the prevalence and risk factors of tuberculosis and latent tuberculosis infection (LTBI) among refugee children in Malaysia.MethodsA cross-sectional study was performed in three refugee schools in the Klang Valley, Malaysia, using tuberculin skin tests or interferon-γ release assays. Participants who tested positive were sent for further examination with chest radiography to confirm the tuberculosis diagnosis.ResultsFrom April 2018 to April 2019, we screened 430 refugee children with a median age of 13.0 years. Most of the children were born in Myanmar (n=274, 63.7%) and Pakistan (n=60, 14.0%). No children were diagnosed with active tuberculosis but 55 of the children (12.8%) were diagnosed with LTBI. Children with LTBI were generally older (OR 3.01, 95% CI 1.71–5.29; p<0.001) than those without LTBI infection. Sex, history of bacille Calmette–Guérin vaccination and country of birth were not associated with increased risk of LTBI.ConclusionThe relatively high LTBI burden among refugee children in this study poses an indication of possible LTBI risk among this population nationwide, and thus would be an important group to target for preventive therapy. This provides a unique opportunity for researchers to further examine and implement well-structured preventive strategies in combating the endemic infectious disease in Malaysia.

scholarly journals Annual risk of tuberculosis infection in rural China: a population-based prospective study

2016 ◽  
Vol 48 (1) ◽  
pp. 168-178 ◽  
Author(s):  
Lei Gao ◽  
Liqiong Bai ◽  
Jianmin Liu ◽  
Wei Lu ◽  
Xinhua Wang ◽  
...  
Keyword(s):  
Prospective Study ◽  
Rural China ◽  
Population Data ◽  
Interferon Γ ◽  
Population Based ◽  
Skin Tests ◽  
Baseline Survey ◽  
Release Assay ◽  
Annual Risk

Prospective population data on the incidence of tuberculosis (TB) infection has been sparsely reported in the global literature.A population-based prospective study was conducted in rural China to investigate the annual risk of TB infection, and its persistence using serial tuberculin skin tests (TSTs) and an interferon-γ release assay. In total, 13 580 eligible participants from four rural sites, identified as TST negative (<10 mm) or QuantiFERON-TB Gold In-Tube (QFT) (an interferon-γ release assay) negative from a baseline survey, were included in the first year's follow-up examination.The annual conversion rate of QFT among the study sites ranged between 2.1% and 4.9% (average 3.1%), and the incidence of TST conversion ranged between 6.0% and 31.1% (average 14.5%). During the second year's follow-up, infection persistence was investigated using 390 subjects with QFT conversions. Among them, 49.7% (164 out of 330) were found to be consistently QFT positive. Both the conversion and the persistence of QFT positivity were found to be significantly increased with increasing age.In conclusion, the annual TB infection rate was suggested to be ∼1.5% based on persistent positive results after QFT conversion in rural China. Therefore, infection control among those high-risk populations, including the elderly, should be prioritised for TB control in China.

scholarly journals GENNO-INZhENERNYE BIOLOGIChESKIE PREPARATY V TERAPII OSTEOPOROZA U BOL'NYKhREVMATOIDNYM ARTRITOM

2013 ◽  
Vol 16 (2) ◽  
pp. 12-17 ◽  
Author(s):  
I S DYDYKINA ◽  
P S DYDYKINA ◽  
E L NASONOV
Keyword(s):  
High Efficiency ◽  
Proteolytic Enzymes ◽  
Interleukin 1 ◽  
Interferon Γ ◽  
Genetically Engineered ◽  
Mineral Density ◽  
Biological Drugs ◽  
Leading Role ◽  
Inflammatory Processes ◽  
Inflammatory Changes

The authors review the current literature data on the influence of the genetically engineered biological drugs on the bone mineral density, bone exchange and remodeling of bone are submitted. Due to high efficiency these drugs received the deserved popularity in spite of the fact that are applied in rheumatology rather recently. The leading role in pathogenesis of local and generalized bone resorption and destruction in rheumatoid arthritis is realized by mediators of immune and inflammatory processes (pro-inflammatory cytokinins): tumor necrosis factor a, interleukin 1, 2, 12, 17, interferon γ, and also prostaglandins, proteolytic enzymes (a collagenase, other proteases), etc. There are described RANKL — dependent and RANKL — independent mechanisms of activation the osteoclastogenesis. In recent years it is established that the inhibition of pro-inflammatory cytokinins not only reduces inflammatory changes of joints, but also constrains destruction development, interferes with development of bone erosions and generalized bone loss. In the present review results of these works are discussed and questions for future researches are brought up.

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