A-184 DiaSorin LIAISON® QuantiFERON®-TB Gold Plus conjugate formulation change improves rate of low positive test results

Abstract Background Tuberculosis (TB) is a slow-progressing yet highly contagious disease, posing a significant global healthcare challenge. Latent TB infection (LTBI), where individuals are infected but asymptomatic, remains a diagnostic challenge and therefore requires continuous effort to improve test performance. Our previous study on DiaSorin LIAISON® QuantiFERON®-TB Gold Plus test, one of the LTBI diagnostic platforms, demonstrated a high rate of low positive results (Antigen-Nil results between 0.35-1.00 IU/mL) when compared to the ELISA-based QFT-plus test, and higher than expected low positive result reported in a mixed risk population (1.3-5.4% compared to 2-3%). This result prompted the manufacturer to investigate the issue and confirmed our finding. Such investigation subsequently resulted in the replacement of the lyophilized conjugate with liquid conjugate in 2023. In this study, we aimed to determine if the new liquid conjugate reduced low positive rates compared to lyophilized conjugate. Methods To evaluate percent agreement of the test results between lyophilized and liquid conjugates, we performed the test on 100 samples using both conjugate formulations. Positive and negative percent agreement were calculated using a 2x2 table. The 95% confidence interval (95% CI) for each percent agreement were calculated using Wilson score method. To assess test performance in real-world clinical data, we compared the low positive rates before switching the conjugate formulation (July 2023-March 2024) and after (April-December 2024). The high positive, negative, and indeterminate result rates were also compared between the two time periods. The medians of the result rates were compared using Wilcoxon rank-sum test. Results Among 100 samples tested by both conjugate formulations, 39 samples showed concordant positive results, while 58 samples demonstrated concordant negative results. Three samples tested negative with the liquid conjugate but positive with the lyophilized conjugate. No sample tested negative with the lyophilized conjugate but positive with the liquid conjugate. Therefore, the positive percent agreement was 100% (39/39) (95% CI: 96.4-100%) and the negative percent agreement was 95.1% (58/61) (95% CI: 88.9-97.9%). As for the real-world test performance data, we reviewed 15,297 test results, including 7,301 from before switching (from lyophilized conjugate) and 7,996 from after switching to liquid conjugate. Statistically significant differences were noted for the low positive rates (2.85% before versus 2.08% after switching; p=0.005), the total positive rates (6.65% before versus 5.36% after switching; p=0.008) and the negative rates (91.4% before versus 93.1% after switching; p=0.006). There was no statistical difference of the medians of high positive and indeterminate result rates before and after the formulation switch. Conclusion Switching from lyophilized to liquid conjugate resulted in a statistically significant difference in the low positive, total positive and negative rates, whereas the high positive and indeterminate rates remained unchanged. These results demonstrate a reduction in low positive rates, which translated to less work-up to confirm LTBI and a reduced delay in new employees starting new jobs, as QuantiFERON is commonly used in pre-employment testing.