Pleural Fluid and Tuberculosis: Are All Interferon Gamma Release Assays Equal?

Abstract

c W e have read the recently published review of Aggarwal and colleagues (1) with great interest. The use of interferon gamma release assays (IGRA) in extrasanguineous body fluids as potential diagnostic tests for active tuberculosis (TB) does have our special attention. We would like to address two important methodological decisions made in this review with considerable consequences for the results.First, in the sensitivity analysis, the authors decided to categorize indeterminate results in tuberculous pleural effusion (TPE) patients as false negative, with the argument that this reflects the real-life clinical decision-making scenario, where any "nonpositive" report is indicative of the absence of disease. We do not recognize this argument in clinical practice of indeterminate IGRA results in the assessment of active TB, and moreover, this is not demonstrated in the review by Aggarwal et al., as 83% (50/60) of patients with indeterminate QuantiFERON results in pleural fluid and 52% (28/54) of patients with indeterminate T-SPOT.TB results in pleural fluid have pleural tuberculosis (1). According to the assay manufacturer's instructions, an indeterminate IGRA result should not have clinical consequences in the workup for a patient with active TB and therefore should be excluded from the calculation of diagnostic accuracy.Second, the authors decided to combine QuantiFERON and T-SPOT.TB results in pleural fluid to calculate pooled sensitivity and specificity. Since the value of IGRA in extrasanguineous body fluids is still under discussion, considering that the two tests are based on different laboratory techniques with different diagnostic accuracies reported in literature thus far (2), ánd because of the heterogeneity of the included studies, we suppose that it would be better to distinguish the accuracy of the two "pleural fluid" tests.In order to better comprehend the consequences for the results of the study by Aggarwal et al., we composed a new table (Table 1) based on the data presented in Table 1 of the recent review (1). In our table, we used the total of the true-positive, false-negative, and indeterminate test results of the QuantiFERON and T-SPOT.TB assays separately for the group of patients with TPE. For the non-TPE patients, we used the total of true-negative, false-positive, and indeterminate test results. Results of the IGRA in blood were excluded because we specifically aimed to address the accuracy of IGRA in pleural fluid.We observed that in Table 1 of the recent review (1) (according to the results of Zhang et al. [3]), the shown sum of true-negative (n ϭ 42), false-positive (n ϭ 75), and indeterminate (n ϭ 47) T-SPOT.TB results exceeds the total number of non-TPE patients (n ϭ 49). We tried to retrieve the correct numbers from the original article, which are, if we are correct, the following: true negative, 42; false positive, 7; and indeterminate, 0 (3). We cannot determine which numbers were used in the sensitivity and specificity analyses of Aggarwal and colleagues (1).After exclusion of ...

Positive predictive value of ELISpot in BAL and pleural fluid from patients with suspected pulmonary tuberculosis

“…Another systematic review about the diagnostic performance of MTB-specific IGRA in pleural fluid combined the results of ELISpot and Quantiferon Gold-in tube, resulting in the pooled sensitivity and specificity of 72% and 78%, respectively. [3,4] The results of both reviews indicate the diagnostic superiority of ELISpot compared with Quantiferon Gold-in tube in extra-sanguineous fluids; however, the clinical utility of IGRA in extra-sanguineous fluids is still under research. Especially, the limited positive predictive value (PPV), although not evaluated in both reviews, seems a limitation of this test as in a large, multicentre study in a low TBendemic area, the PPV of MTB-specific IGRA in bronchoalveolar lavage (BAL) was only 55%.…”

Expert Review on Contemporary Management of Common Benign Pleural Effusions

“…In brief, IGRAs performance is better in PF than in peripheral blood, 77 in geographical areas with high TB incidence, 78 if T-SPOT.TB is used instead of QuantiFERON, 78,79 and if undetermined results are excluded from the calculations. 80 Thus, according to a meta-analysis of 22 studies, the diagnostic yield of PF T-SPOT.TB in countries with high TB burden was: sensitivity 91%, specificity 87%, LR positive 7.89, and LR negative 0.12. 78 In clinical practice, IGRAs have limited value for diagnostic purposes and should not be routinely performed in the setting of suspected TB effusions.…”