QTF-Gold assay for monitoring of anti-tuberculosis therapy in subjects with active TB

Introduction: The identification and characterization of two M. tuberculosis-specific antigens (ESAT-6 and CFP- 10) has led to the development of a whole blood new generation of M. tuberculosis specific diagnostic tests, that have several advantages over tuberculin skin test (TST), in terms of higher specificity, better correlation with surrogate measures of exposure to M. tuberculosis in low-incidence setting, and less cross-reactivity with M. bovis (BCG) vaccine and environmental mycobacteria.The role of these new tests in evaluating post-therapy tuberculosis eradication has not been investigated yet. Aim of this longitudinal study was to determinate changes of response to M. tuberculosis-specific antigens in patients during the standard tuberculosis treatment and to investigate the in vitro effects of tuberculosis drugs on the IFN-γ release. Methods: 23 individuals with active tuberculosis were enrolled and followed over time.They were tested with QuantiFERON TB-Gold (QFT-Gold) at four time points: at diagnosis (t0), after 3 and 6 months of treatment (t1- t2) and at the end of the specific treatment (t3). Results: At baseline all patients were positive by QFT-Gold.At second time-point 17 out of 23 (74%) were positive, at third time-point 11 of 23 (47%) were positive, at treatment completion 3/23 (13%) were positive.The conversion to negative response to M. tuberculosis-specific antigens was found in 87% patients analyzed after successful therapy. Longitudinal QFT-Gold testing shown a significant decrease (p<0.001) of IFN-γ response during the therapy. No inhibitory effect on IFN-γ release was noted in vitro for chemotherapy using at concentrations compatible with those achieved in serum of treated patients.We have revealed an inhibitory effect only at concentrations 2-3 times greater than those previously tested. Conclusion: A successful therapy for tuberculosis causes a significant decrease of the ESAT-6 and CFP-10 response and this data suggest that the QTF-Gold assay may have a role as a tool for evaluating tuberculosis eradication after standard tuberculosis treatment.