Agreement and systematic bias between QuantiFERON chemiluminescent immunoassay and QuantiFERON enzyme-linked immunosorbent assay in the detection of latent tuberculosis infection: A systematic review and meta-analysis.

OBJECTIVES

Enzyme-linked immunosorbent assay (ELISA)-based QuantiFERON-TB Gold Plus (QFT-Plus ELISA) testing is associated with manual variability and indeterminate results. The transition from QFT-Plus ELISA to chemiluminescent immunoassay (CLIA) for QuantiFERON-TB Gold Plus (QFT-Plus CLIA) testing represents a significant methodological evolution that requires comprehensive evaluation. This systematic review and meta-analysis aimed to assess method agreement, characterize systematic bias patterns, evaluate clinical concordance between DiaSorin's QFT-Plus CLIA and QIAGEN's (QFT-Plus ELISA) methodologies, and determine sources of heterogeneity across diverse populations for latent tuberculosis infection (LTBI) detection.

METHODS

We searched the PubMed, Embase, and Google Scholar databases from January 2019 to January 2025 for studies comparing QFT-Plus CLIA and QFT-Plus ELISA methodologies for LTBI detection. Two reviewers independently screened the studies and assessed their quality using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. We conducted a meta-analysis of agreement measures using random-effects models, systematic bias characterization, meta-regression analysis of the sources of heterogeneity, and clinical subgroup analysis. Evidence certainty was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). The review was registered with PROSPERO (CRD420251031884).

RESULTS

A total of 16 studies comprising 4169 participants were included. A meta-analysis of 10 studies (n = 2932) revealed a substantial overall concordance of 88.76% (95% confidence interval [CI] 83.57-93.95). Among the seven studies with complete data to calculate positive and negative agreement measures (n = 1305), the pooled positive agreement was 91.3% (95% CI 88.95-93.65) and the negative agreement was 93.89% (95% CI 92.18-95.6). The comparative analysis revealed a mean discordance rate of 6.56% (range: 0.44-16.67%), with a weighted mean directional bias of +0.2% (showing minimal overall directional preference between platforms). Significant heterogeneity was observed (I² = 95.8%, P <0.0001), and evidence certainty was rated "very low" due to methodological limitations.

CONCLUSIONS

Diasorin's QFT-Plus CLIA and QIAGEN's QFT-Plus ELISA demonstrated substantial overall agreement in detecting LTBI, with the strongest concordance for clearly positive and negative results. Laboratories implementing QFT-Plus CLIA platforms should consider verification studies, and future research should evaluate the clinical significance of discordant results and optimize interpretive algorithms for diverse epidemiologic settings.