S121 Real-world diagnostic utility of Xpert MTB/RIF Ultra in pulmonary and extrapulmonary samples in TB hotspot of low TB incidence, high resource setting

<h3>Introduction</h3> Use of rapid molecular diagnostics such as Xpert MTB/RIF and Xpert MTB/RIF Ultra (Xpert-Ultra) is endorsed by World Health Organization for rapid diagnosis of TB. Xpert-Ultra has improved sensitivity, but utility in low TB-prevalent settings, where paucibacillary and extrapulmonary disease are more common, remains uncertain. Current UK National Institute for Health and Care Excellence guidance for use of rapid molecular diagnostics remains unclear. <h3>Objectives</h3> To examine utility of Xpert-Ultra as a clinical first-line diagnostic tool in pulmonary (PTB) and extrapulmonary TB (EPTB) and to investigate Xpert-Ultra grade as a biomarker of infectiousness in a low TB burden setting. <h3>Methods</h3> Retrospective analysis of all patients with suspected TB that were triple tested with Xpert-Ultra, smear microscopy and mycobacterial culture at the University Hospitals of Leicester NHS Trust between 01/03/2018 and 28/02/2019. Sensitivity and specificity analyses of all three diagnostic markers were performed using TB culture and TB diagnosis at the primary disease site as independent reference standards. We also investigated the association between Xpert-Ultra grade from index PTB respiratory tract samples, and infectiousness defined as the proportion of close contacts with QuantiFERON-TB Gold plus positive latent TB infection (LTBI). <h3>Results</h3> 251 samples (188 respiratory samples) were analysed, from 231 patients of whom 86 had TB. 64 samples (63 patients) were <i>Mycobacterium tuberculosis</i> (Mtb) culture positive. 26 samples were smear positive, including four with non-tuberculous mycobacteria. 71 were Xpert-Ultra positive. Compared with culture alone, Xpert-Ultra increased microbiological confirmation of TB diagnosis from 50.0% to 73.1% in EPTB, and from 87.7% to 89.5% in PTB (table 1). Combining both Xpert and culture as a composite for microbiological diagnosis yielded overall sensitivity of 84.6% and 94.7% for the diagnosis of EPTB and PTB, respectively. Overall, 28.6% of 224 screened PTB contacts from 49 PTB cases had LTBI. Stratifying by index Xpert-ultra grade (high/low/negative), the proportion of contacts with LTBI was 45.5%, 17.4% and 4.4% respectively. <h3>Conclusions</h3> Xpert-Ultra is a highly sensitive and specific TB diagnostic that usefully informs infectiousness of PTB. Our data support using Xpert-Ultra routinely with culture, in the diagnostic assessment of clinically relevant cohorts.