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Dr. Piana and colleagues comment on the low sensitivity of the tuberculin skin test (TST) in patients with active tuberculosis as reported in our study, which examined routine use of the new interferon- (IFN-) QuantiFERON-TB Gold (Cellestis Ltd., Carnegie, Victoria, Australia) test for the diagnosis of tuberculosis infection (1). They also compare the 33.3% rate of positive TST in our report with the 87.0% rate of positive TST that they observed among 46 patients with tuberculosis in an unpublished study. Further, they highlight the special characteristics of our inpatients with active disease. In fact, out of the 11 patients with tuberculosis, 4 had extrapulmonary or disseminated disease while three others had concomitant cancer or were taking immunosuppressive drugs; all these medical conditions are known to significantly reduce the rate of positive TST results (2, 3). Moreover, the low proportion of patients with positive microbiology results was also due to the significant fraction of cases with extrapulmonary localization or with concomitant immunosuppression.

Piana and colleagues also refer to the results of a contact tracing investigation among 138 immunosuppressed patients in a hematology unit, where they used the T-SPOT.TB test (Oxford Immunotec Ltd.) to detect infected contacts (4). In that study, they identified 35 contacts who were positive with T-SPOT.TB and negative with the TST, thus suggesting a higher sensitivity of T-SPOT.TB. These results are consistent with recent reports on the use of T-SPOT.TB (5, 6), showing high sensitivity for the diagnosis of tuberculosis infection in immunosuppressed patients. This does not seem to be the case with the QuantiFERON-TB Gold test used in our study, as we observed a high proportion of indeterminate results, which were strongly associated with immunosuppression (1).

As discussed in our article, at the present time, only data from preselected cohorts of patients have been published for QuantiFERON-TB Gold. QuantiFERON-TB Gold (a whole blood test based on the ELISA technique) and T-SPOT.TB (using the ELISPOT technology on preseparated blood cells) have some methodological differences (7). Only the ELISPOT test has been used in those patients in whom the TST is most often falsely negative, such as HIV-infected patients (6) and newborns (8). Data in these vulnerable groups are lacking for QuantiFERON-TB Gold, and direct comparative studies of both blood tests in parallel have not yet been published. Therefore, in our paper, we focus on the rate of indeterminate results of the QuantiFERON-TB Gold in patients routinely tested for tuberculosis infection in a hospital setting. We did not infer any conclusions regarding the other commercially available test.

Luca Richeldi, Giovanni Ferrara, Monica Losi, Roberto Piro, Pietro Roversi and Leonardo M. Fabbri

University of Modena and Reggio Emilia, Modena, Italy

FOOTNOTES

Conflict of Interest Statement: L.R. received $1,500 in 2005 for serving on an Advisory Board for Oxford Immunotec Ltd. G.F. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. M.L. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. R.P. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. P.R. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. L.M.F. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

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