Predicting tuberculosis risk – Authors’ reply

摘要

Sandra V Kik and colleagues question the potential value of our RNA signature of tuberculosis risk for targeted intervention on a population basis.1 They point out that the positive predictive value (PPV) of the RNA signature depends on the rate of progression to active tuberculosis disease; prognostic utility would therefore be greatest in settings of high tuberculosis incidence. The Foundation for Innovative New Diagnostics and the New Diagnostics Working Group of the Stop TB Partnership have drafted an intervention target product profile (iTPP) for a new prognostic test for tuberculosis risk. This iTPP proposes that a new test would have to be compared with an interferon gamma release assay (IGRA). The test would need a sensitivity and specificity in the range 75–90% in order to at least double the PPV, and halve the number needed to treat with preventive therapy, compared with IGRA.2 As Kik and colleagues explain, the RNA signature achieves this goal, and therefore is likely to be substantially more useful than an IGRA. It should be noted that other iTPP characteristics such as practicality and low cost would have to be addressed for ultimate application. The signature had higher sensitivity at the timepoints most proximal to tuberculosis diagnosis, suggesting that timing of the test is a key factor in performance. Disease resolution has been recognised since the prechemotherapy era, and arrest or even reversal of disease without therapy—particularly in children with subclinical, culture-positive, or radiographic tuberculosis—has been described.