Dheda, Keertan and Zyl-Smit, Richard N. van and Sechi, Leonardo Antonio and Badri, Motasim and Meldau, Richard and Meldau, Surita and Symons, Gregory and Semple, Patricia L. and Maredza, Alice and Dawson, Rodney and Wainright, Helen and Whitelaw, Andrew and Vallie, Y. and Raubenheimer, Peter and Bateman, Eric D. and Zumla, Alimuddin (2009) Utility of quantitative T-cell responses versus unstimulated interferon-γ for the diagnosis of pleural tuberculosis. European Respiratory Journal, Vol. 34 (5), p. 1118-1126. eISSN 1399-3003. Article.
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The clinical utility of antigen-specific interferon (IFN)-γ release assays (IGRAs) using pleural mononuclear cells, for the diagnosis of tuberculosis (TB), requires clarification.
We compared the diagnostic utility of unstimulated pleural IFN-γ levels with several pleural antigen-specific T-cell IGRAs (early secretory antigenic target-6 and culture filtrate protein-10 (T-SPOT.®TB, QuantiFERON®-TB Gold In-tube), purified protein derivative (PPD) and heparin-binding 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.®TB: 86, 60, 84 and 64%, respectively; QuantiFERON®-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-γ: 97, 100, 100 and 94%, respectively.
Unstimulated IFN-γ 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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