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.

Autor: Kim JW; NIHR Leicester Biomedical Research Centre, Department of Respiratory Sciences, University of Leicester, Leicester, UK; Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK., Bowman K; NIHR Leicester Biomedical Research Centre, Department of Respiratory Sciences, University of Leicester, Leicester, UK., Nazareth J; NIHR Leicester Biomedical Research Centre, Department of Respiratory Sciences, University of Leicester, Leicester, UK; Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK., Lee J; NIHR Leicester Biomedical Research Centre, Department of Respiratory Sciences, University of Leicester, Leicester, UK; Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK., Woltmann G; NIHR Leicester Biomedical Research Centre, Department of Respiratory Sciences, University of Leicester, Leicester, UK; Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK., Verma R; NIHR Leicester Biomedical Research Centre, Department of Respiratory Sciences, University of Leicester, Leicester, UK; Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK., Sharifpour M; Department of Nuclear Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK., Shield C; Department of Pathobiology and Population Sciences, Royal Veterinary College, London, UK., Rees C; School of Biosciences, University of Nottingham, Nottingham, UK., Kamil A; Department of Nuclear Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK., Swift B; Department of Pathobiology and Population Sciences, Royal Veterinary College, London, UK., Haldar P; NIHR Leicester Biomedical Research Centre, Department of Respiratory Sciences, University of Leicester, Leicester, UK; Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK. Electronic address: ph62@leicester.ac.uk.
Jazyk: angličtina
Zdroj: The Lancet. Microbe [Lancet Microbe] 2024 Feb; Vol. 5 (2), pp. e119-e130. Date of Electronic Publication: 2024 Jan 17.
DOI: 10.1016/S2666-5247(23)00289-6
Abstrakt: Background: 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 [ 18 F]fluorodeoxyglucose ([ 18 F]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.
Methods: 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 [ 18 F]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 [ 18 F]FDG uptake. Microbiological sampling was done at amenable sites of [ 18 F]FDG uptake. Changes in [ 18 F]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.
Findings: 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 [ 18 F]FDG uptake in the lung (SUV max 9·4) received empirical antituberculosis treatment and one who showed progressive [ 18 F]FDG uptake received preventive treatment. The ten untreated contacts with [ 18 F]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).
Interpretation: 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.
Funding: MRC Confidence in Concept.
Competing Interests: Declaration of interests PH has received consultancy fees for two advisory board meetings with PBD Biotech since study inception. CR and BS hold stocks in PBD Biotech, the company commercialising the Actiphage technology. CR and BS have a pending patent on Actiphage bacteriophage-mediated mycobacterial DNA release assay testing (PCT/GB2020/050524). PBD Biotech supplied PCR reagents and components of the Actiphage kit for use in the study but had no role in design, execution, analysis, or reporting. All other authors declare no competing interests.
(Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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