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-γ 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. Clinical trial registered with www.clinicaltrials.gov (NCT 00707317).

Rational use of immunodiagnostic tools for tuberculosis infection: guidelines and cost effectiveness studies.

Tuberculosis (TB) remains a public health challenge and its control requires the use efficient diagnostic tools. Mycobacterium tuberculosis (MTB) elicits a strong immune response upon infection, a phenomenon measured by the old tuberculin skin test (TST). However, this test has many limitations and a high rate of positivity in BCG-vaccinated subjects. Recent studies have identified several MTB-antigens for diagnostic use, including the ESAT-6 and CFP-10 proteins. Based on these antigens, one of the most significant developments in the diagnostic armamentarium for TB has been the assays based on IFN- determination (IGRAs). The assays stem from the principle that T-cells of infected individuals produce IFN-gamma when they re-encounter the MTB antigens in vitro and this can be measured by a conventional ELISA test. The evaluation of IGRAs in different clinical settings showed many advantages over TST. The worldwide diffusion of IGRAs has increased the knowledge on their clinical use and a number of guidelines have been devised for their application. The two-step approach (first using TST followed by IGRA for confirmation) is the most favored strategy for IGRA-use in the general population, while the use of IGRAs alone is suggested in particular clinical settings and/or patient groups. Even if these tests are still costly there are a number of cost effective advantages in the "targeted" use of IGRAs over the TST. The work we present summarises all these aspects.