Accuracy of Immunodiagnostic Tests for Active Tuberculosis Using Single and Combined Results: A Multicenter TBNET-Study

The clinical application of IFN-gamma release assays (IGRAs) has recently improved the diagnosis of latent tuberculosis infection. In a multicenter study of the Tuberculosis Network European Trialsgroup (TBNET) we aimed to ascertain in routine clinical practice the accuracy of a novel assay using selected peptides encoded in the mycobacterial genomic region of difference (RD) 1 for the diagnosis of active tuberculosis in comparison with tuberculin skin test (TST), QuantiFERON-TB GOLD In-Tube (Cellestis Ltd., Carnegie, Australia) and T-SPOT.TB (Oxfordimmunotec, Abingdon, UK)

Estimates of likelihood ratios for the combination of the diagnostic tests studied according to the disease status.

<p><b>Abbreviations:</b></p><p>TB: tuberculosis; RD: region of difference; RD1 test: test based on the RD1 selected peptides; TST: tuberculin skin test; CI: confidence interval; pos: positive; neg: negative; QuantiFERON: QuantiFERON-TB GOLD In-Tube.</p

Estimates of sensitivities for the combination of the diagnostic tests studied.

<p><b>Abbreviations:</b></p><p>RD: region of difference; TST: tuberculin skin test; CI: confidence interval.</p

Study flow diagram.

<p>Abbreviations: TB: tuberculosis; RD: Region of Difference; Indeterm: indeterminate; TST: tuberculin skin test; QF: QuantiFERON-TB GOLD In-Tube.</p

Demographic and clinical characteristics of the subjects enrolled in the study.

<p><b>Abbreviations:</b></p><p>TB: tuberculosis; BCG: Bacillus Calmette and Guerin; HIV: Human Immunodeficiency Virus.</p

Risk Assessment of Tuberculosis in Immunocompromised Patients A TBNET Study

Rationale: In the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-gamma release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test results may vary depending on immunodeficiency. Objectives: This study compared the performance of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis. Methods: Immunocompromised patients with HIV infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation, and healthy control subjects were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA), and T-SPOT. TB test (enzyme-linked immunospot) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up. Measurements and Main Results: Frequencies of positive test results varied from 8.7 to 15.9% in HIV infection (n = 768), 25.3 to 30.6% in chronic renal failure (n = 270), 25.0% to 37.2% in rheumatoid arthritis (n = 199), 9.0 to 20.0% in solid-organ transplant recipients (n = 197), 0% to 5.8% in stem-cell transplant recipients (n = 103), and 11.2 to 15.2% in immunocompetent control subjects (n = 211). Eleven patients (10 with HIV infection and one solid-organ transplant recipient) developed tuberculosis during a median follow-up of 1.8 (interquartile range, 0.2-3.0) years. Six of the 11 patients had a negative or indeterminate test result in all three tests at the time of screening. Tuberculosis incidence was generally low, but higher in HIV-infected individuals with a positive TST (3.25 cases per 100 person-years) than with a positive ELISA (1.31 cases per 100 person-years) or enzyme-linked immunospot result (1.78 cases per 100 person-years). No cases of tuberculosis occurred in patients who received preventive chemotherapy. Conclusions: Among immunocompromised patients evaluated in this study, progression toward tuberculosis was highest in HIV-infected individuals and was poorly predicted by TST or IGRAs