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.
Lancet Microbe
; 5(2): e119-e130, 2024 02.
Article
em En
| MEDLINE
| ID: mdl-38244554
ABSTRACT
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 [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.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 [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 [SUVmax]) 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.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 [18F]FDG uptake in the lung (SUVmax 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).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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
/
Tuberculose Pulmonar
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Tuberculose Latente
/
Mycobacterium tuberculosis
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Humans
País/Região como assunto:
Europa
Idioma:
En
Revista:
Lancet Microbe
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Reino Unido