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

Abstract

BackgroundThe clinical application of IFN-γ 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).Principal Findings425 individuals from 6 different European centres were prospectively enrolled. We found that sensitivity of the novel test, TST, QuantiFERON-TB GOLD In-Tube and T-SPOT.TB was respectively 73.1%, 85.3%, 78.1%, and 85.2%; specificity was respectively 70.6%, 48.0%, 61.9% and 44.3%; positive likelihood ratios were respectively 2.48, 1.64, 2.05, and 1.53; negative likelihood ratios were respectively 0.38, 0.31, 0.35, 0.33. Sensitivity of TST combined with the novel test, QuantiFERON-TB GOLD In-Tube and T-SPOT.TB increased up to 92.4%, 97.7% and 97.1%, respectively. The likelihood ratios of combined negative results of TST with, respectively, the novel test, QuantiFERON-TB GOLD In-Tube and T-SPOT.TB were 0.19, 0.07 and 0.10.ConclusionsThe assay based on RD1 selected peptides has similar accuracy for active tuberculosis compared with TST and commercial IGRAs. Then, independently of the spectrum of antigens used in the assays to elicit mycobacterial specific immune responses, the novel test, IGRAs, and the TST do not allow an accurate identification of active tuberculosis in clinical practice. However, the combined use of the novel assay or commercial IGRAs with TST may allow exclusion of tuberculosis.

Interferon- release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis

“…In nine of these, TST positivity was significantly associated with BCG vaccination as an independent predictor in multivariate analysis [47,50,55,62,67,71,72,74,77] with odd ratios ranging between 3.8 (95% CI 1.0-13.9) [50] [35] GOLETTI [36] JAFARI [37] JAFARI [38] KAMPMANN [39] KANG [40] LEE [41] MARKOVA [42] WANG [43] DETJEN [26] DHEDA [34] GOLETTI [36] KAMPMANN [39] KANG [40] MARKOVA [42] odds for test positivity with M. tuberculosis exposure gradients, or using chest radiography lesions as a surrogate of prior exposure, the IGRAs associated better with exposure than the TST, irrespective of the setting's disease burden. Furthermore, there was generally a poor agreement between IGRAs and TST results (for k statistics, see table 3).…”

“…NPV in patients with active tuberculosis 18 articles satisfied our inclusion criteria for evaluating the NPV; 13 assessed the NPV among confirmed tuberculosis cases [22,26,[34][35][36][37][38][39][40][41][42][43][44] and six assessed the prospective outcome in IGRA-negative individuals after an average of 2 yrs [19-22, 45, 46]. Among the studies in which the NPV was evaluated in patients with confirmed tuberculosis (387 tuberculosis cases with a valid T-SPOT1.TB result and 304 with valid QFT-G-IT result), the NPV varied greatly, irrespective of the IGRA used.…”

“…Among the studies in which the NPV was evaluated in patients with confirmed tuberculosis (387 tuberculosis cases with a valid T-SPOT1.TB result and 304 with valid QFT-G-IT result), the NPV varied greatly, irrespective of the IGRA used. Among the 13 articles, the NPV ranged between 74.4% [36] and 100% [22,34], with a pooled value of 94% (95% CI 92.1-95.6%) for the T-SPOT1.TB and 88% (95% CI 84.6-91.5%) for the QFT-G-IT (figs 2 and 3).…”

IP-10 release assays in the diagnosis of tuberculosis infection: current status and future directions

“…Two of the greatest obstacles for the IGRAs are the inability to discriminate between active and latent TB infection, as well as suboptimal sensitivity [83]. In immunocompromised individuals and children, who have the greatest risk of progression to active disease and would benefit the most from an accurate diagnosis of latent TB infection, the IGRA performance is compromised.…”

Response to Rv2628 latency antigen associates with cured tuberculosis and remote infection

“…There is evidence that commercial IGRAs are highly sensitive for detecting LTBI [2], and have a high specificity that is unaffected by bacille Calmette-Guérin (BCG) vaccination. Although IGRAs were designed as assays for LTBI, these tests do not discriminate between active disease and LTBI [5,6]. Moreover, IGRAs do not distinguish between a recently acquired infection and remote LTBI [7].…”