© 2006 American Thoracic Society
Tuberculosis Diagnostic Tests: Sensitivity, Specificity, and Comparing Apples with ApplesTo the Editor:In his recent pulmonary perspective, Dr. Richeldi (1) purportedly compared two commercially available tests for Mycobacterium tuberculosis infection (QuantiFERON-TB Gold and T-SPOT.TB), but unfortunately defined any ELISpot performed by Lalvani and colleagues as a T-SPOT.TB test. Although the author correctly noted that comparing results from experimentally based tests with commercial tests is a mistake, he does not distinguish the many differences of "Lalvani" tests from the commercial test. ELISpot studies reported by Lalvani and colleagues used heterogeneous antigen sources for ESAT-6 and CFP-10 (peptides of different sizes and purity and recombinant antigens with possible impurities) and used these antigens in numerous combinations (up to 35) with varying cutoffs. In comparison, the commercial T-SPOT.TB test uses only two peptide pools representing ESAT-6 and CFP-10. These variations between the experimental ELISpot and the commercial T-SPOT.TB test can lead to major differences in clinical results (2). Consequently, the comparative analysis by Richeldi does not accurately reflect the "real world" performance of the T-SPOT.TB test and can be misleading to the uninitiated reader. A contact investigation using ELISpot, reported by Richeldi and coworkers (3), and the corresponding T-SPOT.TB patent by Lalvani and Ewer (2) highlights the marked differences in diagnostic outcome depending on whether peptide or protein antigens are used. Since results from these "Lalvani" ELISpot studies, which have included recombinant antigens, substantially disagree with their commercial counterpart, they cannot be used to typify results of the peptide-based commercial test. Based on the available literature, specificity of the commercial T-SPOT.TB test has yet to be determined using methods and cutoffs proposed by the manufacturer. Furthermore, as recently noted by Davies and Drobniewski, a possible trade-off for sensitivity away from specificity may also be attributable to the T-SPOT.TB test (4). Although quoting an independent Korean study (5), Richeldi neglects data demonstrating that T-SPOT.TB appears less specific than QuantiFERON-TB Gold and that when specificity parameters are equalized, sensitivity is very similar. It should also be noted that the study of Goletti and coworkers (6), which is not cited by Richeldi, performed an independent comparison of both commercial tests and found little difference in outcome.
The use of either commercial assay will result in major changes in how tuberculosis infection is defined, eliminating the need for treating large numbers of people falsely identified as infected by the skin test. Collectively, a large and rapidly growing body of evidence shows that these new IFN-
Cellestis Limited Victoria, Australia FOOTNOTES Conflict of Interest Statement: A.J.R. is an employee of Cellestis Ltd and owns stock in Cellestis Ltd. J.S.R. is an employee of Cellestis Ltd and owns stock in Cellestis Ltd. S.L.J. is an employee of Cellestis Ltd and owns stock in Cellestis Ltd. G.S. is an employee of Cellestis Ltd. REFERENCES
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tests are a major advance in the accuracy of diagnosis of tuberculosis infection.