Background: Better and more rapid tests are needed for the diagnosis of tuberculous pleural effusion (TPE), given the known limitations of conventional diagnostic tests. Objectives: To estimate diagnostic accuracy of the QuantiFERON-TB Gold In-Tube (QFT-GIT) test (and its components) using data-derived cutoffs in pleural fluid. Methods: The QFT-GIT test was performed on whole blood and pleural fluid from 43 patients with TPE and 29 control subjects (non-TPE). To achieve the objective, QFT-GIT test, estimating likelihood ratios and receiver operating curve analysis were performed. Results: The sensitivity and specificity using the QFT-GIT for the diagnosis of TPE were 48.8% and 79.3%, respectively, in pleural fluid. The best cutoff points for tuberculosis (TB) antigen, nil and TB antigen minus nil results were estimated at 0.70, 0.90 and 0.30 IU/ml, respectively. Area under the curve of TB antigen IFN-γ response was 0.86 (CI: 0.76–0.93), nil tube was 0.80 (CI: 0.69–0.89) and TB antigen minus nil tube was 0.82 (CI: 0.72–0.90). When the best cutoff scores of the nil tubes were set at this value, the results of a likelihood ratio of a positive and a negative test were 9.44 (7.4–12.0) and 0.37 (0.09–1.5), respectively. The percentages of indeterminate results in pleural fluid among the TPE cases were 42% (most of them caused by high nil IFN-γ values) using the QFT-GIT test. Conclusion: QFT-GIT test or its components have poor accuracy in the diagnosis of TPE, largely because of a high number of indeterminate results due to high background IFN-γ production in the TPE.

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