Articles 1328 www.thelancet.com Vol 367 April 22, 2006 Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study Giovanni Ferrara, Monica Losi, Roberto D’Amico, Pietro Roversi, Roberto Piro, Marisa Meacci, Barbara Meccugni, Ilaria Marchetti Dori, Alessandro Andreani, Barbara Maria Bergamini, Cristina Mussini, Fabio Rumpianesi, Leonardo M Fabbri, Luca Richeldi Summary Background Two commercial blood assays for the diagnosis of latent tuberculosis infection—T-SPOT.TB and QuantiFERON-TB Gold—have been separately compared with the tuberculin skin test. Our aim was to compare the efficacy of all three tests in the same population sample. Methods We did a prospective study in 393 consecutively enrolled patients who were tested simultaneously with T-SPOT.TB and QuantiFERON-TB Gold because of suspected latent or active tuberculosis. 318 patients also had results available for a tuberculin skin test. Findings Overall agreement with the skin test was similar (T-SPOT.TB κ=0·508, QuantiFERON-TB Gold κ=0·460), but fewer BCG-vaccinated individuals were identified as positive by the two blood assays than by the tuberculin skin test (p=0·003 for T-SPOT.TB and p<0.0001 for QuantiFERON-TB Gold). Indeterminate results were significantly more frequent with QuantiFERON-TB Gold (11%, 43 of 383) than with T-SPOT.TB (3%, 12 of 383; p<0·0001) and were associated with immunosuppressive treatments for both tests. Age younger than 5 years was significantly associated with indeterminate results with QuantiFERON-TB Gold (p=0.003), but not with T-SPOT.TB. Overall, T-SPOT.TB produced significantly more positive results (38%, n=144, vs 26%, n=100, with QuantiFERON-TB Gold; p<0·0001), and close contacts of patients with active tuberculosis were more likely to be positive with T-SPOT.TB than with QuantiFERON-TB Gold (p=0·0010). Interpretation T-SPOT.TB and QuantiFERON-TB Gold have higher specificity than the tuberculin skin test. Rates of indeterminate and positive results, however, differ between the blood tests, suggesting that they might provide different results in routine clinical practice. Introduction Eradication of tuberculosis in low-prevalence countries is judged a realistic aim. 1,2 Even in areas with a decreasing prevalence of the disease, however, several important concerns need to be resolved before the disease can be controlled. 3,4 A key factor is the number of asymptomatic individuals with latent disease, who are a reservoir of future cases. As the prevalence of tuberculosis, and the risk of future re-infection, decreases, diagnosis and treatment of these individuals becomes increasingly important. There are an estimated 9–14 million people in the USA who have latent infection, 5 and the number continues to increase as immigrants from high- prevalence areas move to America and person–person transmission of Mycobacterium tuberculosis occurs. Evidence suggests that treatment of latent infection reduces the risk of progression to active tuberculosis, especially in high-risk groups, such as patients infected with HIV. 6,7 Individuals with radiological evidence of inactive tuberculosis, close contacts of patients with active disease, patients receiving infliximab and other immunosuppressive therapy, and children aged 5 years and younger are also priority groups that could benefit from treatment of latent disease. 8 Unfortunately, the standard diagnostic test for latent tuberculosis infection— the tuberculin skin test (also known as the intradermal Mantoux test)—is unreliable, often providing false- negative results in these high-risk groups, especially in immunosuppressed patients and young children. 9 Furthermore, the specificity of the test is low; false- positive results in individuals vaccinated against BCG and in those infected by non-tuberculous mycobacteria are common. 9,10 As such, high-risk patients who stand to benefit most from preventive chemotherapy might not be diagnosed, and resources are being wasted on treatment of individuals incorrectly identified as having latent infection. Two new blood tests, based on detection of interferon γ produced by T cells in response to antigens specific to M tuberculosis and encoded by the RD1 region, might be more accurate than the tuberculin skin test. 11,12 Both tests are commercially available in regulatory agency-approved formats. T-SPOT.TB (Oxford Immunotec, Abingdon, UK) is based on the ex vivo overnight enzyme-linked immunospot (ELISPOT) assay. It has been approved for in-vitro diagnostic use in Europe and is being assessed by the US Food and Drug Administration (FDA). QuantiFERON-TB Gold (Cellestis, Carnegie, Australia) is based on a whole-blood ELISA and has been approved for in-vitro diagnostic use by the FDA. Guidelines for the Lancet 2006; 367: 1328–34 Section of Respiratory Disease (G Ferrara MD, M Losi PhD, P Roversi MD, R Piro MD, A Andreani MD, Prof L M Fabbri MD, L Richeldi MD) and Section of Statistics (R D’Amico PhD), Department of Oncology, Haematology, and Respiratory Disease, University of Modena and Reggio Emilia, Via del Pozzo, 71-41100 Modena, Italy; Laboratory of Microbiology and Virology, Azienda Ospedaliera Policlinico di Modena, Modena, Italy (M Meacci BSc, B Meccugni BSc, I Marchetti Dori BSc, F Rumpianesi BSc); and Department of Paediatrics (B M Bergamini MD) and Clinic of Infectious and Tropical Diseases (C Mussini MD), University of Modena and Reggio Emilia, Modena, Italy Correspondence to: Dr Luca Richeldi richeldi.luca@unimore.it