Predictive value of interferon-gamma release assays and tuberculin skin test for latent tuberculosis infection: A systematic review and meta-analysis of head-to-head comparative tests

BACKGROUND: This study aimed to evaluate the ability of tuberculin skin test (TST) and interferon-gamma release assay (IGRA) to predict progression of latent tuberculosis (LTBI) to active tuberculosis. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library for cohort studies published until October 6, 2024, that used both IGRA and TST to detect LTBI and reported data on active TB development. We assessed the predictive value of IGRA and TST for disease progression by calculating the risk ratio (RR), which compares the progression rates between positive and negative individuals for each test. RESULTS: Out of 2650 potentially eligible studies, 260 were reviewed in full text, and 44 studies with 25637 individuals were included. The pooled RR for disease progression was higher with IGRA than with TST (5.38 [95 % CI: 3.44-8.40] vs. 3.03 [95 % CI: 1.20-4.10]), although this difference did not reach statistical significance (p = 0.0713). PPV with IGRA vs TST: 2.50 % [95 % CI: 1.20 %-4.10 %] vs 1.30 % [95 % CI: 0.60 %-2.40 %] (p = 0.4852). NPV with IGRA vs TST: 99.70 % [95 % CI: 99.40 %-99.90 %] vs 99.60 % [95 % CI: 99.30 %-99.90 %] (p = 0.9630). Furthermore, the PPV of IGRA was similar to the progression rate of IGRA+/TST+ (2.00 % [95 % CI: 0.05 %-4.40 %] vs. 2.50 % [95 % CI: 0.40 %-6.10 %]). Finally, while IGRA identified fewer positive individuals (23.90 % [95 % CI: 18.50 %-29.80 %] vs. 52.20 % [95 % CI: 34.30 %-69.80 %]), the number of positive individuals progressing was similar (265 vs. 268), with similar results also observed in the untreated population. CONCLUSIONS: IGRA appears to have superior predictive value for TB progression compared to TST. Additionally, incorporating TST alongside IGRA does not seem to significantly enhance predictive accuracy. IGRA effectively reduces the number of individuals requiring treatment while seemingly not missing those at risk of progression.