You are here

Article Text

Article menu
Tuberculosis
Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis
Free
  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.

https://doi.org/10.1136/thx.2009.116376

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Supplementary materials

    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