Tuberculosis infection under anti-TNF alpha treatment

2021 ◽  
Vol 16 ◽  
Author(s):  
Salma Athimni ◽  
Maroua Slouma ◽  
Rim Dhahri ◽  
Imen Gharsallah ◽  
Leila Metouia ◽  
...  

Background: Anti-tumor necrosis factor-α (TNF-α) is a life-changing treatment leading to quality-of-life improvement. Nonetheless, this treatment is associated with a high risk of infection, especially tuberculosis. Objective: Our study aimed to determine the frequency of active tuberculosis in our patients with chronic rheumatic disease and treated with TNF-α. Methods: We conducted a retrospective study including patients with Rheumatoid Arthritis and Spondylarthritis diagnosed according to ACR/EULAR 2009 criteria and ASAS 2010, respectively, and treated with biological agents for at least 6 months. We collected data regarding tuberculosis screening and the occurrence of active tuberculosis during follow-up. Results: 82 patients were included (37 men and 45 women). The mean age was 42 ± 3.4 years. At inclusion, no patient had a medical history of tuberculosis. The diagnosis of latent tuberculosis infection was established in 17 patients (20.7%). Prophylactic treatment was prescribed in all these cases for three months. Two cases (2.4%) of active tuberculosis occurred under biologic (infliximab). It was two severe forms of tuberculosis. The first case had miliary tuberculosis associated with hepatic and peritoneal involvement. The second one had pleural tuberculosis. These two patients received anti-tuberculosis therapy, and the biological treatment was interrupted. Given the high disease activity, the anti-TNF-α was restarted after 3 and 4 months. There was no recurrence of tuberculosis after 7 years of follow-up. Conclusion: The use of TNF-α blockers is associated with a risk of disseminated forms of tuberculosis. Tuberculosis screening, which is recommended before the biological onset, is also necessary under this treatment. Restarting the anti-TNF-α after appropriate treatment of tuberculosis seemed to be safe.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lifan Zhang ◽  
Shijun Wan ◽  
Ziyue Zhou ◽  
Yueqiu Zhang ◽  
Xiaoqing Liu

Abstract Background The differential diagnosis of active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains challenging in clinical practice. We aimed to evaluate the diagnostic accuracy of the IFN-γ/TNF-α FluoroSpot assay for differentiating ATB from LTBI. Methods We conducted a pilot study of case-control design, using the FluoroSpot assay to simultaneously detect IFN-γ and TNF-α secretion at the single-cell level. The frequencies of antigen-specific single TNF-α-, total TNF-α-, single IFN-γ-, total IFN-γ- and dual IFN-γ/TNF-α-secreting T cells were detected. The optimal cutoffs value of frequencies for differentiating ATB from LTBI were determined according to receiver operating characteristic curve analysis. The sensitivity, specificity, predictive values (PV) and likelihood ratios (LR) of the FluoroSpot assay were calculated. Results Thirty patients diagnosed microbiologically with ATB, 36 healthcare workers with LTBI and 36 healthy controls were enrolled. After stimulated by ESAT-6 or CFP-10 peptides, the median frequencies of single TNF-α-, total TNF-α-, single IFN-γ-, total IFN-γ- and dual IFN-γ/TNF-α-secreting T cells in ATB patients were all significantly higher than those in LTBI and HC groups (P < 0.01). The frequencies of total IFN-γ-secreting T cells detected by FluoroSpot assay correlated significantly with those of T-SPOT.TB (r = 0.910 for ESAT-6, P < 0.001, r = 0.845 for CFP-10, P < 0.001). After stimulated by ESAT-6 peptides, with total TNF-α-secreting T cells frequencies at a cut off value of 21 iSFCs/250,000 PBMCs, the sensitivity, specificity, PLR, NLR, PPV, NPV of IFN-γ/TNF-α FluoroSpot assay in differentiating ATB from LTBI were 96.7% (95%CI, 82.8–99.9%), 94.3% (95%CI, 80.8–99.3%), 16.92 (95%CI, 4.40–65.08), 0.04 (95%CI, 0.01–0.24), 93.6% (95%CI,78.6–99.2%) and 97.1% (95%CI, 84.7–99.9%), respectively. With the frequencies of total TNF-α- and total IFN-γ-secreting T cells stimulated by ESAT-6 peptides combined, the specificity was increased to 97.1%, and the positive likelihood ratio to 31.5. The combination with CFP-10 might not improve the diagnostic accuracy of the ESAT-6 for differentiating ATB from LTBI. Conclusions IFN-γ/TNF-α FluoroSpot assay might have potential to help differentiate ATB from LTBI, but the findings need to be further verified by cross-sectional or prospective cohort studies.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ying Luo ◽  
Ying Xue ◽  
Liyan Mao ◽  
Qun Lin ◽  
Guoxing Tang ◽  
...  

BackgroundRapid and effective discrimination between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains a challenge. There is an urgent need for developing practical and affordable approaches targeting this issue.MethodsParticipants with ATB and LTBI were recruited at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort) based on positive T-SPOT results from June 2020 to January 2021. The expression of activation markers including HLA-DR, CD38, CD69, and CD25 was examined on Mycobacterium tuberculosis (MTB)-specific CD4+ T cells defined by IFN-γ, TNF-α, and IL-2 expression upon MTB antigen stimulation.ResultsA total of 90 (40 ATB and 50 LTBI) and another 64 (29 ATB and 35 LTBI) subjects were recruited from the Qiaokou cohort and Caidian cohort, respectively. The expression patterns of Th1 cytokines including IFN-γ, TNF-α, and IL-2 upon MTB antigen stimulation could not differentiate ATB patients from LTBI individuals well. However, both HLA-DR and CD38 on MTB-specific cells showed discriminatory value in distinguishing between ATB patients and LTBI individuals. As for developing a single candidate biomarker, HLA-DR had the advantage over CD38. Moreover, HLA-DR on TNF-α+ or IL-2+ cells had superiority over that on IFN-γ+ cells in differentiating ATB patients from LTBI individuals. Besides, HLA-DR on MTB-specific cells defined by multiple cytokine co-expression had a higher ability to discriminate patients with ATB from LTBI individuals than that of MTB-specific cells defined by one kind of cytokine expression. Specially, HLA-DR on TNF-α+IL-2+ cells produced an AUC of 0.901 (95% CI, 0.833–0.969), with a sensitivity of 93.75% (95% CI, 79.85–98.27%) and specificity of 72.97% (95% CI, 57.02–84.60%) as a threshold of 44% was used. Furthermore, the performance of HLA-DR on TNF-α+IL-2+ cells for differential diagnosis was obtained with validation cohort data: 90.91% (95% CI, 72.19–97.47%) sensitivity and 68.97% (95% CI, 50.77–82.73%) specificity.ConclusionsWe demonstrated that HLA-DR on MTB-specific cells was a potentially useful biomarker for accurate discrimination between ATB and LTBI.


2020 ◽  
Vol 26 (9) ◽  
pp. 1315-1318 ◽  
Author(s):  
Jana G Hashash ◽  
Carla Abou Fadel ◽  
Mohammad Hosni ◽  
Lara Hassoun ◽  
Zeina Kanafani ◽  
...  

Abstract The use of biological agents for the treatment of chronic inflammatory conditions such as inflammatory bowel diseases (IBD) has been on the rise.1,2 Current biological therapies include antitumor necrosis factor-α (anti-TNF-α), anti-interleukin-12/23, and anti-integrin agents. Before initiation of biological drugs, screening for Mycobacterium tuberculosis infection is required to avoid reactivation or worsening of disease after immunosuppression. It has been shown that anti-TNF-α treated patients have a 14-fold increased risk of tuberculosis (TB) infection/reactivation compared with healthy controls.3 The methods for screening for TB have evolved over time and vary from region to region.


2018 ◽  
Vol 77 (4) ◽  
pp. 314-320 ◽  
Author(s):  
Ji Yeun Kim ◽  
Joung Ha Park ◽  
Min-Chul Kim ◽  
Hye Hee Cha ◽  
Na-Young Jeon ◽  
...  

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 857.1-857
Author(s):  
C. Pávez Perales ◽  
A. Quiles Roger ◽  
E. Grau García ◽  
M. De la Rubia Navarro ◽  
S. Leal Rodriguez ◽  
...  

Background:Patients with rheumatic diseases (RD) are at higher risk of latent tuberculosis infection (LTBI) reactivation. To detect and treat it before starting treatment, especially with biological therapies, decrease the reactivation risk. Diagnosis is carried out by the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs), IGRAs might be more specific and sensitive.Objectives:We aim to analyze the concordance between QuantiFERON-TB Gold In-Tube (QTF) and TST for the diagnosis of LTBI in patients with rheumatic diseases.Methods:A retrospective observational study was conducted including patients diagnosed with RD screened for LTBI with both TST and QTF (2014-2018). Demographical and clinical variables at screening and at follow-up were collected. The concordance between both tests has been estimated as categorical variables using Cohen´s Kappa test, considering “poor” if it is ≤ 0,20; “low” if 0,20 < k ≤ 0,40, “moderate” if 0,40 < k ≤ 0,60, “substantial” if 0,60 < k ≤ 0,80 and “optimal” if k > 0,80.Results:167 patients were included (57% women) with a mean age of 52±16 years. 42% of them had systemic autoimmune diseases, 22% spondyloarthropathies and 36% other RD. 2 had history of past active tuberculosis (TB). At the time of screening, 46.11% were treated with GC.LTBI was diagnosed in 35 patients: 15 had both QTF and TST positive, 16 only QTF positive and 4 only TST positive. 12 from 31 QTF positive patients were treated with GC at the time of screening. 3 from 19 TST positive patients were treated with GC at the time of screening.After LTBI screening 62 patients received biological treatment, 4 of them had both test positive, 6 only QTF positive and 2 only TST positive. 11 received LTBI treatment according to the hospital protocol (isoniazid for 6 to 9 months). 10 completed treatment, 1 did not because of intolerance and did not receive other treatment. 1 patient with only TST positive was considered a false positive and did not receive treatment. During follow-up no TB reactivation was reported.23 patients with LBTI received treatment other than biological therapy during follow-up, of them 8 received LBTI treatment. There was no TB reactivation during follow up.The Kappa concordance between QTF and TST was estimated: moderated in the whole sample, poor in the patients treated with GC at screening, and substantial when the patients treated with GC at screening were excluded. Results are shown in Table 1.Table 1.Kappa concordance between QTF and TST.Conclusion:QTF seems to be the most appropriate LTBI screening test in patients with RD treated with GC. Screening and treatment of LTBI in patients with RD treated with or without biological agents was effective in reducing TB reactivation.Disclosure of Interests:None declared.


2013 ◽  
Vol 1 ◽  
pp. 112-117 ◽  
Author(s):  
Jolanta Paluch-Oleś ◽  
Agnieszka Magryś ◽  
Maria Kozioł-Montewka ◽  
Arkadiusz Koszarny ◽  
Maria Majdan

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