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Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis
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  1. K Dheda1,2,3,
  2. R N van Zyl-Smit1,
  3. R Meldau1,
  4. S Meldau1,
  5. G Symons4,
  6. H Khalfey4,
  7. N Govender4,
  8. V Rosu5,
  9. L A Sechi5,
  10. A Maredza1,
  11. P Semple1,
  12. A Whitelaw6,
  13. H Wainwright7,
  14. M Badri4,
  15. R Dawson1,
  16. E D Bateman1,
  17. A Zumla3
  1. 1
    Lung Infection and Immunity Unit & CTBRI, UCT Lung Institute & Division of Pulmonology, Department of Medicine, University of Cape Town, South Africa
  2. 2
    Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa
  3. 3
    Centre for Infectious Diseases and International Health, University College Medical School, London, UK
  4. 4
    Department of Medicine, University of Cape Town, South Africa
  5. 5
    Dipartimento di Scienze Biomediche, University of Sardinia, Sassari, Italy
  6. 6
    Division of Medical Microbiology, University of Cape Town, South Africa
  7. 7
    Department of Anatomical Pathology, University of Cape Town, South Africa
  1. Correspondence to K Dheda, Department of Medicine, Groote Schuur Hospital, Observatory, Cape Town, South Africa, 7925; keertan.dheda{at}uct.ac.za

Abstract

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

Methods: Antigen-specific interferon γ (IFNγ) responses to the RD-1 antigens ESAT-6 and CFP-10 (T-SPOT.TB and QuantiFERON-TB-Gold-In-Tube), heparin-binding haemagglutinin and purified protein derivative were evaluated, using alveolar lavage cells, in 91 consecutively recruited South African patients suspected of having TB.

Results: Of 85 evaluable patients (29% HIV+), 24, 11, 48 and 2 had definite TB, probable TB, non-TB 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 with T-SPOT.TB (85% vs 46% of inconclusive results; p = 0.001). Using staphylococcal enterotoxin B, compared with phytohaemagglutinin, substantially reduced failure of the positive control (25% to 3%; p = 0.02). In evaluable samples, when the definite and non-TB groups were used for outcome analysis, the percentage sensitivity, specificity, positive predictive value and negative predictive value for T-SPOT.TB (⩾20 spots/million alveolar mononuclear cells) and QuantiFERON-TB-Gold-In-Tube (0.35 IU/ml) were 89, 94, 89 and 94% (n = 55) and 55, 86, 77 and 69% (n = 46), respectively. Rapid diagnosis of TB was achieved more frequently with T-SPOT.TB than with 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 IFNγ responses 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 IFNγ ELISPOT response is a useful rapid immunodiagnostic test for TB. However, test utility in high-burden settings may be limited by the high proportion of inconclusive results.

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Footnotes

  • Funding This work was supported by the South African National Research Foundation (SARChI), the South African Medical Research Council and the UCL–UCT Collaboration Initiative.

  • Competing interests None.

  • Provenance and Peer review Not commissioned; externally peer reviewed.

  • Ethics approval The study protocol was approved by the University of Cape Town Ethics Committee.

  • ▸ Additional methods, figures and tables are published online only at http://thorax.bmj.com/content/vol64/issue10

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