S122 PET-CT identifies early inflammatory changes of metabolically active Mycobacterium tuberculosis infection in household TB contacts with a clinical phenotype of latent infection: A descriptive case series

<h3>Introduction</h3> Tuberculosis infection (TBI) comprises a spectrum of infection states poorly characterised by clinical screening with chest X-ray (CXR) and interferon gamma release assays (IGRA). Here we report utility of PET-CT as a highly sensitive imaging modality to visualise the heterogeneity of TBI. <h3>Objectives</h3> A descriptive account of findings after serial PET-CT scans with targeted invasive sampling in six immunocompetent household pulmonary TB contacts (HHCs) with normal CXRs recruited to a larger prospective observational study. <h3>Methods</h3> All recruited HHCs underwent routine CXR and IGRA testing (QuantiFERON-TB Gold Plus (QFT)), followed by ¹⁸F-FDG PET-CT soon after index notification. Invasive sampling with bronchoalveolar lavage (BAL) and/or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was performed if there was significant PET-CT tracer uptake. QFT-negative participants with baseline ¹⁸F-FDG-avid lesions had follow-up PET-CT and repeat QFT after 3 months. <h3>Results</h3> Three QFT-positive patients with ¹⁸F-FDG-avid abnormalities in lung parenchyma and/or intrathoracic lymph nodes that underwent bronchoscopic sampling yielded positive <i>Mycobacterium tuberculosis</i> cultures in BAL (N=2) and EBUS-TBNA (N=1). Time to positive culture ranged from 25 days to 34 days (figure 1). Linkage to index cases was confirmed in two out of three patients on whole genome sequencing. Post-treatment PET-CT showed partial or complete resolution of metabolic activity. Three QFT negative patients that had ¹⁸F-FDG-avid intrathoracic lymph nodes at baseline demonstrated QFT conversion after 3 to 6 months. Follow-up PET-CT at the time of QFT conversion showed increasing avidity at baseline sites of tracer uptake (N=2) or appearance of additional ¹⁸F-FDG-avid lesions in the mediastinal lymph nodes (N=1) (figure 1). <h3>Conclusions</h3> PET-CT identifies intrathoracic inflammation in HHCs with a clinical phenotype of latent TBI that predominates in mediastinal nodes and is evident prior to IGRA conversion. Sampling detects metabolically active, culturable TBI in a subset with PET-CT avidity that may be representative of incipient TB. These observations also support the view that <i>M.tuberculosis</i> is transmitted in a metabolically active state. PET-CT offers a tool for characterising the heterogeneity of latent TBI that has utility to support studies of biomarker development and infection pathogenesis.