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김지황Jee Whang Kim

University of Leicester

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Lancet Microbe, Jan 17 2024, S2666-5247(23)00289-6 | https://doi.org/10.1016/S2666-5247(23)00289-6 PET-CT-guided characterisation of progressive, preclinical tuberculosis infection and its association with low-level circulating Mycobacterium tuberculosis DNA in household contacts in Leicester, UK: a prospective cohort study

Jee Whang Kim MBChB^a,b, Karen Bowman PhD ^a, Joshua Nazareth MBBS ^a,b, Joanne Lee ^a,b, Prof Gerrit Woltmann MD ^a,b, Raman Verma PhD ^a,b, Meedya Sharifpour MBChB^c, Christopher Shield MSc ^d, Prof Catherine Rees PhD ^e, Anver Kamil MBChB ^c, Benjamin Swift PhD ^d, Pranabashis Haldar MD^a,b

^aNIHR Leicester Biomedical Research Centre, Department of Respiratory Sciences, University of Leicester, Leicester, UK

^bDepartment of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK

^cDepartment of Nuclear Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK

^dDepartment of Pathobiology and Population Sciences, Royal Veterinary College, London, UK

^eSchool of Biosciences, University of Nottingham, Nottingham, UK

Correspondence to: Dr Pranabashis Haldar

Abstract

Incipient tuberculosis, a progressive state of Mycobacterium tuberculosis infection with an increased risk of developing into tuberculosis disease, remains poorly characterised. Animal models suggest an association of progressive infection with bacteraemia. Circulating M tuberculosis DNA has previously been detected in pulmonary tuberculosis by use of Actiphage, a bacteriophage-based real-time PCR assay. We aimed to investigate whether serial [ ¹⁸F]fluorodeoxyglucose ([ ¹⁸F]FDG)-PET-CT could be used to characterise the state and progressive trajectory of incipient tuberculosis, and examine whether these PET-CT findings are associated with Actiphage-based detection of circulating M tuberculosis DNA. We did a prospective 12-month cohort study in healthy, asymptomatic adults (aged ≥16 years) who were household contacts of patients with pulmonary tuberculosis, and who had a clinical phenotype of latent tuberculosis infection, in Leicester, UK. Actiphage testing of participants' blood samples was done at baseline, and [ ¹⁸F]FDG PET-CT at baseline and after 3 months. Baseline PET-CT features were classified as positive, indeterminate, or negative, on the basis of the quantitation (maximum standardised uptake value [SUV _max]) and distribution of [ ¹⁸F]FDG uptake. Microbiological sampling was done at amenable sites of [ ¹⁸F]FDG uptake. Changes in [ ¹⁸F]FDG uptake after 3 months were quantitatively categorised as progressive, stable, or resolving. Participants received treatment if features of incipient tuberculosis, defined as microbiological detection of M tuberculosis or progressive PET-CT change, were identified. 20 contacts were recruited between Aug 5 and Nov 5, 2020; 16 of these participants had a positive result on IFNγ release assay (QuantiFERON-TB Gold Plus [QFT]) indicating tuberculosis infection. Baseline PET-CT scans were positive in ten contacts (all QFT positive), indeterminate in six contacts (three QFT positive), and negative in four contacts (three QFT positive). Four of eight PET-CT-positive contacts sampled had M tuberculosis identified (three through culture, one through Xpert MTB/RIF Ultra test) from intrathoracic lymph nodes or bronchial wash and received full antituberculosis treatment. Two further unsampled PET-CT-positive contacts were also treated: one with [ ¹⁸F]FDG uptake in the lung (SUV _max 9·4) received empirical antituberculosis treatment and one who showed progressive [ ¹⁸F]FDG uptake received preventive treatment. The ten untreated contacts with [ ¹⁸F]FDG uptake at baseline (seven QFT positive) had stable or resolving changes at follow-up and remained free of tuberculosis disease after 12 months. A positive baseline Actiphage test was associated with the presence of features of incipient tuberculosis requiring treatment (p=0·018). Microbiological and inflammatory features of incipient tuberculosis can be visualised on PET-CT and are associated with M tuberculosis detection in the blood, supporting the development of pathogen-directed blood biomarkers of tuberculosis risk. MRC Confidence in Concept.

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형식Research article
게재일2024년 01월 (BRIC 등록일 2024-02-05)
연구진국외 연구진
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