Evaluation of Adapted Whole-Blood Interferon-γ Release Assays for the Diagnosis of Pleural Tuberculosis

Chegou, Novel N.; Walzl, Gerhard; Bolliger, Chris T.; Diacon, Andreas H.; Heuvel, Michel M. van den

doi:10.1159/000128575

Cited by 69 publications

(88 citation statements)

References 49 publications

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“…A recent meta-analysis of 7 studies that included 213 patients with TB pleural effusions found the sensitivity and specificity of IGRA measurements in pleural fluid to be 0.75 and 0.82, respectively [51]. Moreover, another study showed that measuring γ-interferon levels in pleural fluid was superior to IGRA in regards to both sensitivity and specificity [52]. Using IGRAs for blood or pleural fluid is not recommended for making a diagnosis of TB pleuritis [53].…”

Section: Interferon-gammamentioning

confidence: 99%

Tuberculous Pleural Effusion

Cohen

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2015

Tur Toraks Der

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When a patient presents with new pleural effusion, the diagnosis of tuberculous (TB) pleuritis should be considered. The patient is at risk for developing pulmonary or extrapulmonary TB if the diagnosis is not made. Between 3% and 25% of patients with TB will have TB pleuritis. The incidence of TB pleuritis is higher in patients who are human immunodeficiency virus (HIV)-positive. Pleural fluid is an exudate that usually has a predominance of lymphocytes. The easiest way to diagnose TB pleuritis in a patient with lymphocytic pleural effusion is to demonstrate a pleural fluid adenosine deaminase level above 40 IU/L. The treatment for TB pleuritis is the same as that for pulmonary TB. Tuberculous empyema is a rare occurrence, and the treatment is difficult. KEY WORDS:Tuberculosis, pleural effusions, adenosine deaminase, gamma interferon, pleural biopsy, empyema INTRODUCTION Tuberculosis (TB) remains a major public health problem in developing countries. Most patients with TB have pulmonary TB; however, 25% of adults can present with extrapulmonary TB, which mainly involves the lymph nodes and pleura but can affect any organ system, including the central nervous system (CNS), cardiovascular system, and gastrointestinal (GI) tract [1]. The most common form of extrapulmonary TB is infection of the pleura. In a patient who presents with undiagnosed pleural effusion, the diagnosis of TB pleuritis should be considered. Pleural effusion, as an isolated manifestation of TB, may be selflimited and of little immediate concern, but untreated, it can lead to serious disease many years later. Pathogenesis and Pathologic FeaturesTuberculous pleural effusion may occur in the absence of radiologically apparent TB [2]. The effusion may result as a sequela to a primary infection from 6-12 weeks earlier, or it may represent the reactivation of TB [2]. In developed countries, TB pleural effusions present more often in older patients. The median age in one North American study was 56, suggesting reactivation of the disease [3]. However, a study from 2004 in San Francisco showed that pleural TB cases were 2 times more likely to be clustered (when assessed by genotyping of the mycobacterial organisms) than pulmonary TB and 3 times more likely to be clustered than nonrespiratory TB cases [4]. The observations made in the San Francisco study suggest that the majority of patients has a postprimary infection [4]. This was not confirmed in studies performed in both Houston [5] and Baltimore [6] or in a study in sub-Saharan Africa, in which the prevalence of pleural TB was 63.2% in patients with a primary TB infection [7].The pathogenesis of TB pleural effusion is thought to be related to the rupture of a subpleural caseous focus in the lung into the pleural space [8]. The basis for this was the observation that a caseous TB focus could be demonstrated in the lung, contiguous with the diseased pleural, in 12 to 15 patients with TB pleuritis [9]. The 3 other patients in this study had parenchymal disease but did not have caseous foci adjacent...

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Section: Interferon-gammamentioning

confidence: 99%

Tuberculous Pleural Effusion

Cohen

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2015

Tur Toraks Der

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“…In the last several months, two case-control studies from high-burden countries (South Africa) and using QFT-TB-GIT have been published [15,16]. Both showed that the QFT-TB-GIT assay had suboptimal sensitivity (27 and 57%, respectively).…”

Section: Pleural Hbha and Ppd Elispot Responsesmentioning

confidence: 99%

“…We therefore hypothesised that TB antigen-specific responses could distinguish active pleural TB from alternative diagnoses and should have better discriminatory value than unstimulated IFN-c, a nonspecific biomarker of inflammation. A recent case-control study from Europe showed a high diagnostic accuracy with the T-SPOT.1TB assay (Oxford Immunotec, Abingdon, UK) [13] but overall data on the utility of two known IFN-c release assays (IGRAs), T-SPOT.1TB and QuantiFERON1-TB Gold In-tube (QFT-TB-GIT; Cellestis, Carnegie, Australia), including a head-to-head comparison, for the diagnosis of TB-PE are limited [13][14][15][16]. There are several other unresolved questions, including the optimal cell number and pleural fluid volume required, optimal cut-off point and utility in high HIV-prevalence settings [17].…”

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confidence: 99%

Utility of quantitative T-cell responsesversusunstimulated interferon-γ for the diagnosis of pleural tuberculosis

Dheda

Zyl-Smit²,

Sechi³

et al. 2009

Eur Respir J

110

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The clinical utility of antigen-specific interferon (IFN)-c release assays (IGRAs) using pleural mononuclear cells, for the diagnosis of tuberculosis (TB), requires clarification.We compared the diagnostic utility of unstimulated pleural IFN-c levels with several pleural antigen-specific T-cell IGRAs (early secretory antigenic target-6 and culture filtrate protein-10 (T-SPOT.1TB, QuantiFERON1-TB Gold In-tube), purified protein derivative (PPD) and heparinbinding haemagglutinin (HBHA)) in 78 South African TB suspects. Test results were compared against a clinical score and a reference standard.Out of 74 evaluable subjects 48, seven and 19 had definite, probable and no TB, respectively. 11 (15%) out of 74 pleural samples (nine (19%) out of 48 of the definite TB cases) had total cell counts that were inadequate for T-cell processing. In the remaining 63 samples, the sensitivity, specificity, positive predictive value and negative predictive value of different diagnostic methods were as follows. Maximal bioclinical score: 54, 89, 92 and 43%, respectively; T-SPOT.1TB: 86, 60, 84 and 64%, respectively; QuantiFERON1-TB Gold In-tube: 57, 80, 87 and 44%, respectively; HBHA-specific IGRA: 59, 31, 64 and 27%, respectively; PPD-specific IGRA: 81, 40, 76 and 46%, respectively; and pleural fluid unstimulated IFN-c: 97, 100, 100 and 94%, respectively. Unstimulated IFN-c was the most accurate test for distinguishing TB from non-TB effusions in a high-burden setting. The antigen-specific T-cell IGRAs were limited by suboptimal accuracy and the inability to isolate sufficient mononuclear cells to perform the assay.

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“…To date, Chegou and co-workers have shown that ex vivo pleural fluid IFN-y levels accurately identified TB in all patients in a high burden area, suggesting IGRA to have a poor additional diagnostic value (20). Detection of whole IFN-y was superior to QFT-IT using blood and pleural fluid (73% and 57% sensitivity, with 71% and 87% specificity, respectively) and to QFT-G (the predecessor of QFT-IT) applied to isolated pleural fluid cells (100% sensitivity and 67% specificity).…”

Section: Discussionmentioning

confidence: 99%

“…Despite the fact that IGRA do not discriminate LTBI from active TB, pooled sensitivity of blood assays has recently been estimated to be higher than 80% in detecting active TB disease as a surrogate of TB infection, at least in developed countries (11)(12). Some reports indicate that IGRAs might be helpful in selected cases of pulmonary TB cases (13)(14)(15)(16)(17) and in patients with extra-pulmonary TB, including plTB and TB meningitis, by detecting the release of IFN-y by antigen-specific T cells directly at the infection site (18)(19)(20)(21)(22)(23)(24)(25).…”

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confidence: 99%

Role of the Quantiferon-TB Test in Ruling Out Pleural Tuberculosis: A Multi-Centre Study

Losi

Bocchino

Matarese

et al. 2011

Int J Immunopathol Pharmacol

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The first two authors contributed equally to the study Diagnosing pleural tuberculosis (pITB) might be difficult due to limited sensitivity of conventional microbiology tools. As M. tuberculosis (MTB)-specific T cells are recruited into pleural space in pITB, their detection may provide useful clinical information. To this aim, in addition to standard diagnostic tests, we used the QuantiFERON-TB Gold In-Tube (QFT-IT) test in blood and pleural effusion (PE) samples from 48 patients with clinical suspicion of pITB, 18 (37.5%) of whom had confirmed pITB. Four of them (22.2%) tested positive with a nucleic acid amplification test for MTB. The tuberculin skin test was positive in most confirmed plTB cases (88.9%). Positive QFT-IT tests were significantly more frequent in patients with confirmed pITB, as compared to patients with an alternative diagnosis, both in blood (77.7 vs 36.6%, p=0.006) and in PE samples (83.3% vs 46.6%, p=0.02). In addition, both blood and PE MTB-stimulated IFN-y levels were significantly higher in plTB patients (p=0.03 and p=0.0049 vs non-pITB, respectively). In blood samples, QFT-IT had 77.8% sensitivity and 63.3% specificity, resulting in 56.0% positive (PPV) and 82.6% negative (NPV) predictive values. On PE, QFT-IT sensitivity was 83.3% and specificity 53.3% (PPV 51.7% and NPV 84.2%). The optimal AVe-derived cut-off for MTBstimulated pleural IFN-y level was 3.01 IU/mL (77.8% sensitivity, 80% specificity, PPV 68.4% and NPV 82.8%). These data suggest that QFT-IT might have a role in ruling out plTB in clinical practice.Pleural tuberculosis (pITB) is an extra-pulmonary manifestation of active tuberculosis (TB), representing about 4% of all TB cases (I). Despite the characteristic finding of increased count of lymphocytes in pleural effusion (PE), confirmation of pITB diagnosis based on PE analysis is problematic

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Evaluation of Adapted Whole-Blood Interferon-γ Release Assays for the Diagnosis of Pleural Tuberculosis

Cited by 69 publications

References 49 publications

Tuberculous Pleural Effusion

Tuberculous Pleural Effusion

Utility of quantitative T-cell responsesversusunstimulated interferon-γ for the diagnosis of pleural tuberculosis

Role of the Quantiferon-TB Test in Ruling Out Pleural Tuberculosis: A Multi-Centre Study

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