Background
The role of interferon-gamma release assays (IGRAs) in diagnosis of active tuberculosis (TB) is unclear, yet they are commonly used in low-TB-incidence countries. This study sought to resolve this clinical uncertainty by determining the diagnostic accuracy and role of current and second-generation IGRAs in the diagnostic assessment of suspected TB in a low-incidence setting.
Methods
This was a prospective cohort study of 1,060 adults with suspected TB, conducted in routine secondary care in England. Patients were tested for M. tuberculosis (Mtb) infection at baseline using current and second-generation IGRAs, the latter incorporating novel Mtb antigens, and followed up for 6-12m to establish definitive diagnoses. Sensitivity, specificity and positive and negative likelihood ratios (LRs) and predictive values (PVs) of the tests for TB were determined.
Findings
TB was diagnosed in 363 (43%) of 845 patients included in analyses. Sensitivity of T-SPOT.TB was 81.4% (95%CI 76.6-85.3%), higher than Quantiferon-Gold In-Tube at 67.3% (95%CI 62.0-72.1%). Second-generation IGRA had higher sensitivity than current tests, at 94.0% (95%CI 90.0–96.4%) for culture-confirmed TB and 89.2% (95%CI 85.2–92.2%) when including highly-probable TB, giving a negative LR for all TB of 0.13 (95%CI 0.10-0.19). Specificity ranged from 86.2% (95%CI 82.3-89.4%) for T-SPOT.TB to 80.0% (95%CI 75.6-83.8%) for second-generation IGRA.
Interpretation
Currently-available IGRAs lack sufficient accuracy for diagnostic evaluation of suspected TB. Second-generation tests, however, may have sufficiently high sensitivity, low negative LR and correspondingly high negative PV in low-incidence settings to facilitate prompt rule-out of TB.