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PET-CT benchmarked detection and 5-year progression of asymptomatic tuberculosis: a longitudinal, prospective cohort study

Author(s): Esmail, H; Thienemann, F; Sossen, B; Mukasa, SL; Lakay, F; Munro, JE; MacPherson, L; Warwick, JM; Goliath, RT; Omar-Davies, N; Douglass, E; Jackson, A; Streicher, EM; Heinsohn, T; Sheerin, D; Barrios, MH; Aziz, S; Serole, KC; Daroowala, R; Taliep, A; Ahlers, P; Malherbe, ST; Bowden, R; Warren, RM; Walzl, G; Via, LE; Bahlo, M; Kik, SV; Ruhwald, M; Jacobson, KR; Horsburgh, CR, Jr; Salgame, P; Alland, D; Barry, CE, 3rd; Flynn, JL; Ellner, JJ; Coussens, AK; Wilkinson, RJ;
Journal Title: Lancet Respiratory Medicine
Publication Type: Mar 23
Abstract: BACKGROUND: To understand how lung pathology relates to symptoms, microbiology, and progression risk in tuberculosis and to advance diagnostic development, we determined the frequency at screening of tuberculosis-consistent lesions in asymptomatic individuals within 5 years of tuberculosis diagnosis using highly sensitive imaging ([(18)F]-fluorodeoxyglucose PET-CT) and compared with chest x-ray computer-aided detection (CAD). METHODS: We enrolled a prospective longitudinal cohort in Khayelitsha, Cape Town, South Africa, of asymptomatic, HIV-uninfected contacts aged 18-65 years of patients with rifampicin-resistant tuberculosis, a tuberculosis high-risk group not eligible for chemoprophylaxis. Participants underwent baseline PET-CT, chest x-ray, phlebotomy, and intensive sputum collection, and were classified into four PET-CT lung categories: consistent with tuberculosis, inactive tuberculosis, other lesions, and normal. Chest x-ray was processed by three types of CAD software (CAD4TB [version 7.0], qXR [version 3.0.0], and Lunit [version 3.1.4.111]). Follow-up included symptom-agnostic tuberculosis screening (23-38 months) and provincial register review (≤74 months), and a subgroup had repeat PET-CT (5-15 months). Tuberculosis was defined as bacteriologically confirmed or clinically diagnosed. The primary outcome measures were hazard ratio (HR) for tuberculosis diagnosis and treatment by baseline PET-CT lung abnormality category with normal as the reference group, and diagnostic performance of chest x-ray CAD software using area under the receiver operator characteristic curve (AUC). FINDINGS: 250 asymptomatic adults were enrolled between March 3, 2015, and Oct 11, 2017, irrespective of tuberculosis history or previous infection, and followed up for 1107 person-years (median 4·7 years [IQR 4·0-5·1]). 18 (7%) participants were treated for tuberculosis (16 [89%] of 18 bacteriologically confirmed). Six of 18 participants were diagnosed at baseline (four requiring induced sputum culture) and 12 of 18 after a median of 32 months (IQR 12-35). By baseline PET-CT category, tuberculosis was diagnosed and treated in 12 (41%) of 29 participants with scans consistent with tuberculosis, two (7%) of 30 with scans consistent with inactive tuberculosis, two (2%) of 83 with scans showing other lesions, and two (2%) of 108 with scans showing normal lungs. Participants with baseline PET-CT scans consistent with tuberculosis had the highest risk of 5-year tuberculosis diagnosis (HR 28·54 [95% CI 6·37-127·81] compared with those with scans showing normal lungs, p<0·0001), with no significant risk for scans consistent with inactive tuberculosis (3·55 [0·50-25·21], p=0·21) or other lung lesions (1·30 [0·18-9·23], p=0·79). 11 (69%) of the 16 participants with bacteriologically confirmed tuberculosis were asymptomatic at bacteriological confirmation, and ten (91%) of 11 had baseline PET-CT scans consistent with tuberculosis. Using baseline PET-CT classification as reference, the AUC for chest x-ray CAD software ranged from 0·86 (95% CI 0·72-0·99) to 0·89 (0·75-1·00) for bacteriologically confirmed tuberculosis. INTERPRETATION: Most adult asymptomatic contacts diagnosed with tuberculosis over 5 years had baseline radiographically evident disease, not radiographically negative incipient tuberculosis. Although PET-CT is not feasible for routine screening, it provides a highly sensitive reference benchmark for diagnostic development, with chest x-ray CAD performing comparatively well. FUNDING: South Africa Medical Research Council, US National Institutes of Health, Gates Foundation, Wellcome, UK Research and Innovation Medical Research Council, and Walter and Eliza Hall Institute of Medical Research.
Publisher: Elsevier
Research Division(s): Genetics and Gene Regulation; Advanced Technology and Biology
PubMed ID: 41887246
Publisher's Version: https://doi.org/10.1016/s2213-2600(26)00056-1
Open Access at Publisher's Site: https://doi.org/10.1016/S2213-2600(26)00056-1
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-04-27 02:50:38

Last Modified: 2026-04-27 02:50:51