TUBERCULOSIS

Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis

K Dheda^1,2,3, R N van Zyl-Smit¹, R Meldau¹, S Meldau¹, G Symons⁴, H Khalfey⁴, N Govender⁴, V Rosu⁵, L A Sechi⁵, A Maredza¹, P Semple¹, A Whitelaw⁶, H Wainwright⁷, M Badri⁴, R Dawson¹, E D Bateman¹, A Zumla³

¹ Lung Infection and Immunity Unit & CTBRI, UCT Lung Institute & Division of Pulmonology, Department of Medicine, University of Cape Town, South Africa
² Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa
³ Centre for Infectious Diseases and International Health, University College Medical School, London, UK
⁴ Department of Medicine, University of Cape Town, South Africa
⁵ Dipartimento di Scienze Biomediche, University of Sardinia, Sassari, Italy
⁶ Division of Medical Microbiology, University of Cape Town, South Africa
⁷ Department of Anatomical Pathology, University of Cape Town, South Africa

^{Correspondence to} K Dheda, Department of Medicine, Groote Schuur Hospital, Observatory, Cape Town, South Africa, 7925; keertan.dheda{at}uct.ac.za

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 (IFN) 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 IFN 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 IFN 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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