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American Journal of Respiratory and Critical Care Medicine Vol 173. pp. 130, (2006)
© 2006 American Thoracic Society

Correspondence

Use of Commercial Interferon-{gamma} Assays in Immunocompromised Patients for Tuberculosis Diagnosis

To the Editor:

We read with interest the recent article by Ferrara and colleagues (1) describing the routine use of QuantiFERON-TB Gold (QFTGold) (1, 4) for tuberculosis (TB) diagnosis. The authors report sensitivity of the tuberculin skin test (TST) as 33.3% and for QFT-Gold as 66.7%. The authors also report a high number of indeterminate results with the QFT-Gold test (23%) related, in particular, to the extent of immunosuppression in the patient groups. This paper (1) opens discussion on some important issues:

  1. 1. In a prospective study, we have evaluated the other new blood test for tuberculosis, T-SPOT.TB (Oxford-Immunotec, Oxford, UK), against the TST. T-SPOT.TB enumerates individual activated TB-specific T cells using enzyme-linked immunospot (ELISPOT) methodology (3). A total of 500 patients who were referred to the Lombardia Centre for Tuberculosis Control as TB suspects or during routine contact tracing were enrolled.
  2. The sensitivity of the TST found in those later confirmed with TB disease was 87.0% (40/46). This is much higher than the 33% sensitivity reported by Ferrara and colleagues, and more consistent with the usual reported sensitivity for the TST (6). Given the unusually low sensitivity found for the TST by Ferrara and coworkers, it would be useful for them to set out any underlying immunosuppression of these patients. In addition, as only 6 of the 11 reported subjects with TBdisease were confirmed by culture, it would be useful for them to set out the basis of diagnosis for the remaining 5.
  3. The sensitivity of the T-SPOT.TB test in our population was found to be 95.3%. This is significantly higher than that reported for the QFT-Gold test, and this difference in sensitivity appears to be a consistently emerging observation (2, 3, 5).
  4. Comparison of numbers of indeterminate results between QFT-Gold and T-SPOT.TB is also illuminating. In our study, the tested population included a group of 138 immunocompromised hematology patients exposed to an infectious case during their chemotherapy and 32 patients immunosuppressed for other reasons (immunological diseases, cancer, HIV). In this (often severely) immunosuppressed subpopulation, the indeterminate rate for T-SPOT.TB was only 4.7%.

The authors conclude that commercial interferon-{gamma} tests are suitable for routine diagnosis of TB infection, but the performance of the tests is negatively affected by patients' immunosuppression. We would caution the authors to the evident methodological and clinical differences between the two new blood tests for TB; our results would suggest that T-SPOT.TB performs successfully even in immunosuppressed patient groups.

Federica Piana

Fondazione San Raffaele, Milan, Italy

Luigi R. Codecasa

Istituto Villa Marelli, Milan, Italy

Giorgio Besozzi

A.O. Morelli, Sondalo, Italy

G. B. Migliori

Fondazione S. Maugeri, Tradate, Italy

Daniela M. Cirillo

Fondazione San Raffaele, Milan, Italy

FOOTNOTES

Conflict of Interest Statement: None of the authors have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

REFERENCES

  1. Ferrara G, Losi M, Meacci M, Meccugni B, Piro R, Roversi P, Bergamini BM, D'Amico R, Marchegiano P, Rumpianesi F, et al. Routine hospital use of a commercial whole blood interferon-{gamma} assay for tuberculosis infection. Am J Respir Crit Care Med 2005;172:163–165.
  2. Piana F, Codecasa LR, Cavallerio P, Orfeo N, Barbarano L, Morra E, Cirillo DM. Use of IFN-{gamma} test in contact tracing in a haematology department for identifying nosocomial spreading of tuberculosis. Presented at 26th Annual Congress of the European Society of Mycobacteriology; June 26-29, 2005; Istanbul, Turkey. Abstract book, p. 59.
  3. Lalvani A, Pathan AA, McShane H, Wilkinson RJ, Latif M, Conlon CP, Pasvol G, Hill AV. Rapid detection of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. Am J Respir Crit Care Med 2001;163:824–828.[Abstract/Free Full Text]
  4. Pai M, Riley LW, Colford JM. Interferon-{gamma} assays in the immunodiagnosis of tuberculosis: a systematic review. Lancet Infect Dis 2004;4:761–776.[CrossRef][Medline]
  5. Mori T, Sakatani M, Yamagishi F, Takashima T, Kawabe Y, Nagao K, Shigeto E, Harada N, Mitarai S, Okada M, et al. Specific detection of tuberculosis infection with an interferon-{gamma}–based assay using new antigens. Am J Respir Crit Care Med 2004;170:59–64.[Abstract/Free Full Text]
  6. Huebner RE, Schein MF, Bass JB. The tuberculin skin test. Clin Infect Dis 1993;17:968–975.[Medline]



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