Assessing the Diagnostic Performance of New Commercial Interferon-gamma Release Assays for Mycobacterium tuberculosis Infection: A Systematic Review and Meta-analysis

Background We compared 6 new interferon-gamma release assays (IGRAs; hereafter index tests: QFT-Plus, QFT-Plus CLIA, QIAreach, Wantai TB-IGRA, Standard E TB-Feron, and T-SPOT.TB/T-Cell Select) with World Health Organization (WHO)-endorsed tests for tuberculosis infection (hereafter reference tests). Methods Data sources (1 January 2007-18 August 2021) were Medline, Embase, Web of Science, Cochrane Database of Systematic Reviews, and manufacturers' data. Cross-sectional and cohort studies comparing the diagnostic performance of index and reference tests were selected. The primary outcomes of interest were the pooled differences in sensitivity and specificity between index and reference tests. The certainty of evidence (CoE) was summarized using the GRADE approach. Results Eighty-seven studies were included (44 evaluated the QFT-Plus, 4 QFT-Plus CLIA, 3 QIAreach, 26 TB-IGRA, 10 TB-Feron [1 assessing the QFT-Plus], and 1 T-SPOT.TB/T-Cell Select). Compared to the QFT-GIT, QFT Plus's sensitivity was 0.1 percentage points lower (95% confidence interval [CI], -2.8 to 2.6; CoE: moderate), and its specificity 0.9 percentage points lower (95% CI, -1.0 to -.9; CoE: moderate). Compared to QFT-GIT, TB-IGRA's sensitivity was 3.0 percentage points higher (95% CI, -.2 to 6.2; CoE: very low), and its specificity 2.6 percentage points lower (95% CI, -4.2 to -1.0; CoE: low). Agreement between the QFT-Plus CLIA and QIAreach with QFT-Plus was excellent (pooled kappa statistics of 0.86 [95% CI, .78 to .94; CoE: low]; and 0.96 [95% CI, .92 to 1.00; CoE: low], respectively). The pooled kappa statistic comparing the TB-Feron and the QFT-Plus or QFT-GIT was 0.85 (95% CI, .79 to .92; CoE: low). Conclusions The QFT-Plus and the TB-IGRA have very similar sensitivity and specificity as WHO-approved IGRAs. We compared the diagnostic performance of the QFT-Plus, QIAreach, QFT-Plus CLIA, TB-IGRA, TB-Feron, and T-SPOT.TB/T-Cell Select with that of WHO-endorsed tests. The QFT-Plus and the Wantai TB-IGRA showed similar performance as their comparators; studies assessing other new tests are limited.