Predictive performance of interferon-gamma release assays and the tuberculin skin test for incident tuberculosis: an individual participant data meta-analysis
Yohhei Hamada, Rishi K Gupta, Matteo Quartagno, Abbie Izzard, Carlos Acuña-Villaorduña, Neus Altet, Roland Diel, José Domínguez, Sian Floyd, Amita Gupta, Helena Huerga, Edward C. Jones‐López, Aarti Kinikar, Christoph Lange, Frank van Leth, Qiao Liu, Wei Lu, Peng Lü, Irene Latorre Rueda, Leonardo Martínez, Stanley Kimbung Mbandi, Laura Muñoz, Elisabeth Sánchez Padilla, Mandar Paradkar, Thomas J. Scriba, Martina Sester, Kwame Shanaube, Surendra K. Sharma, Rosa Sloot, Giovanni Sotgiu, Kannan Thiruvengadam, Richa Vashishtha, Ibrahim Abubakar, Molebogeng X. Rangaka
Abstract
Background: Evidence on the comparative performance of purified protein derivative tuberculin skin tests (TST) and interferon-gamma release assays (IGRA) for predicting incident active tuberculosis (TB) remains conflicting. We conducted an individual participant data meta-analysis to directly compare the predictive performance for incident TB disease between TST and IGRA to inform policy. Methods: We searched Medline and Embase from 1 January 2002 to 4 September 2020, and studies that were included in previous systematic reviews. We included prospective longitudinal studies in which participants received both TST and IGRA and estimated performance as hazard ratios (HR) for the development of all diagnoses of TB in participants with dichotomised positive test results compared to negative results, using different thresholds of positivity for TST. Secondary analyses included an evaluation of the impact of background TB incidence. We also estimated the sensitivity and specificity for predicting TB. We explored heterogeneity through pre-defined sub-group analyses (e.g. country-level TB incidence). Publication bias was assessed using funnel plots and Egger's test. This review is registered with PROSPERO, CRD42020205667. Findings: and p = 0.68 for QFT-GIT). Interpretation: IGRA appears to have higher predictive performance than the TST in low TB incidence countries, but the difference was driven by a single study. Any advantage in clinical performance may be small, given the numerically similar positive and negative predictive values. Both IGRA and TST had lower performance in countries with high TB incidence. Test choice should be contextual and made considering operational and likely clinical impact of test results. Funding: YH, IA, and MXR were supported by the National Institute for Health and Care Research (NIHR), United Kingdom (RP-PG-0217-20009). MQ was supported by the Medical Research Council [MC_UU_00004/07].