S37 Dual step interferon-gamma release assay testing can improve tuberculosis (TB) risk stratification in contacts of pulmonary TB: a prospective adult household contact cohort study

<h3>Introduction</h3> Studies report modest and variable predictive value of an interferon-gamma release assay (IGRA) test performed 8–12 weeks after index notification, to identify latent tuberculosis (TB) infection at risk of progressing to active TB. There is limited data evaluating predictive value of changes in the IGRA response with serial testing following recent exposure in a low-TB burden setting. <h3>Objectives</h3> To quantify the risk of progression to active TB using the serial IGRA response between baseline and 3 months in pulmonary TB contacts. <h3>Methods</h3> We performed an ethically approved prospective cohort study of pulmonary TB contacts between September 2015 and May 2018. Participants were recruited immediately after index case notification and had IGRA (QuantiFERON-TB Gold, QFT) test at baseline and 3 months. QFT+ve contacts did not receive chemoprophylaxis, but were followed prospectively up to 4 years with three monthly review during the first 2 years. In contacts developing TB (progressors), whole genome sequencing (WGS) was performed to inform case linkage. We defined changes in serial IGRA response as conversion (QFT negative to positive); or in contacts QFT+ve at baseline, as &gt; 0.27IU/L change in the QFT response, representing &gt;2 standard deviations of the mean serial QFT variability observed in a control group without recent TB exposure. <h3>Results</h3> 297 contacts were followed for a median of 1437 days (IQR 1159–1460). 124 contacts (41.8%) were QFT+ve at 3 months, of which 19 seroconverted from baseline. 20 progression events occurred and 6 diagnoses (30%) were made within 3 months of index notification including two QFT-ve cases. The remaining 14 cases were QFT+ve at baseline, and diagnosed after a median of 285 days. All 9 culture confirmed progressors were WGS matched to their index. For QFT+ve contacts, 2-year risk of incident TB was 10.8%, with no significant difference according to index smear status or quantitative QFT value (Table). Serial QFT identified greatest risk in seroconverters (2-year risk =33.6%) but no increased risk in QFT+ve contacts with a significant change after 3 months (table 1). <h3>Conclusions</h3> Our data suggests serial QFT testing at baseline and 3 months after index notification improves risk stratification in pulmonary TB contacts. Please refer to page A188 for declarations of interest related to this abstract.