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Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis
  1. Keertan Dheda (keertan.dheda{at}uct.ac.za)
  1. University of Cape Town, South Africa
    1. Richard N van Zyl-Smit (rvzs{at}iafrica.com)
    1. University of Cape Town, South Africa
      1. Richard Meldau (richard.meldau{at}uct.ac.za)
      1. University of Cape Town, South Africa
        1. Surita Meldau (surita.meldau{at}uct.ac.za)
        1. University of Cape Town, South Africa
          1. Greg Symons (gregsymons{at}webmail.co.za)
          1. University of Cape Town, South Africa
            1. Hoosain Khalfey (hkhalfey{at}yahoo.com)
            1. University of Cape Town, South Africa
              1. Neville Govender (drgovender{at}mweb.co.za)
              1. University of Cape Town, South Africa
                1. Valentina Rosu
                1. University of Sardinia, Italy
                  1. Leonardo A Sechi
                  1. University of Sardinia, Italy
                    1. Alice Maredza (alice.maredza{at}uct.ac.za)
                    1. University of Cape Town, South Africa
                      1. Patricia L Semple (lynn.semple{at}uct.ac.za)
                      1. University of Cape Town, South Africa
                        1. Andrew Whitelaw (andrew.whitelaw{at}uct.ac.za)
                        1. University of Cape Town, South Africa
                          1. Helen Wainright (helen.wainwright{at}uct.ac.za)
                          1. University of Cape Town, South Africa
                            1. Motasim Badri (motasim.badri{at}uct.ac.za)
                            1. University of Cape Town, South Africa
                              1. Rodney Dawson (rodney.dawson{at}uct.ac.za)
                              1. University of Cape Town, South Africa
                                1. Eric D Bateman (eric.bateman{at}uct.ac.za)
                                1. University of Cape Town, South Africa
                                  1. Alimuddin Zumla (a.zumla{at}ucl.ac.uk)
                                  1. University College London, United Kingdom

                                    Abstract

                                    Background: The diagnosis of smear-negative pulmonary tuberculosis is problematic. There are limited data on the profile of alveolar tuberculosis antigen-specific T-cells and their utility for the rapid immunodiagnosis of pulmonary tuberculosis is unclear.

                                    Methods: We evaluated antigen-specific IFN- γresponses to ESAT-6 and CFP-10 (T-SPOT.®TB and QuantiFERON®-TB-Gold-In-Tube), heparin-binding-haemagglutinin and purified-protein-derivative, using alveolar-lavage cells, in 91 consecutively recruited South-African tuberculosis suspects.

                                    Results: Of 85 evaluable patients (28% HIV+), 24, 11, 48, 2 had definite tuberculosis, probable tuberculosis, non-tuberculosis and an uncertain diagnosis, respectively. Between 34% (T-SPOT.®TB) and 41% (QuantiFERON®-TB-Gold-In-Tube) of all test results were inconclusive. Failure of the positive control was significantly higher with the QuantiFERON®-TB-Gold-In-Tube than T-SPOT.®TB (85 vs. 46% of inconclusive results; p=0.001). Using staphylococcal-enterotoxin-B, compared with phytohaemaglutinin, reduced failure of the positive control substantially (25% to 3%; p= 0.02). In evaluable samples, when the definite and non-tuberculosis groups were used for outcome analysis, the [sensitivity; specificity; PPV; NPV%] for T-SPOT.®TB (>20 spots/million alveolar mononuclear cells) and QuantiFERON®-TB-Gold-In-Tube ( 0.35 IU/ml), was [88; 94; 89; 94 (n=55)] and [55; 86; 77; 69 (n=46)], respectively. Rapid diagnosis of TB was achieved more frequently with T-SPOT.®TB than smear-microscopy [14/24 (58%) vs. 7/24 (29%) of definite TB cases; p=0.02]. Heparin-binding-haemagluttinin and purified-protein-derivative alveolar lymphocyte IFN-γresponses had poor performance outcomes.

                                    Conclusion: Provided evaluable results are obtained the RD-1, but not the heparin-binding-haemagglutinin or purified-protein-derivative, alveolar-lymphocyte IFN-γ ELISPOT response is a useful rapid immunodiagnostic test for tuberculosis. However, test utility in high-burden settings may be limited by the high proportion of inconclusive results.

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