High resolution imaging and five-year tuberculosis contact outcomes
Author:
Esmail HanifORCID, Coussens Anna KORCID, Thienemann FriedrichORCID, Sossen BiancaORCID, Mukasa Sandra LORCID, Warwick JamesORCID, Goliath Rene T.ORCID, Davies Nashreen Omar, Douglass EmilyORCID, Jackson Amanda, Lakay Francisco, Streicher ElizabethORCID, Munro Jacob E.ORCID, Barrios Marilou HORCID, Heinsohn Torben, Macpherson LianaORCID, Sheerin DylanORCID, Aziz Saalikha, Serole Keboile, Daroowala Remy, Taliep ArshadORCID, Ahlers PetriORCID, Malherbe Stephanus T.ORCID, Bowden RoryORCID, Warren RobinORCID, Walzl GerhardORCID, Via Laura E.ORCID, Bahlo MelanieORCID, Jacobson Karen R.ORCID, Horsburgh C. RobertORCID, Salgame PadminiORCID, Alland DavidORCID, Barry Clifton EarlORCID, Flynn JoAnne L.ORCID, Ellner Jerrold JORCID, Wilkinson Robert JORCID
Abstract
AbstractBackgroundThe evolution of tuberculosis (TB) disease during the clinical latency period remains incompletely understood.Methods250 HIV-uninfected, adult household contacts of rifampicin-resistant TB with a negative symptom screen underwent baseline18F-Fluorodeoxyglucose positron emission and computed tomography (PET/CT), repeated in 112 after 5-15 months. Following South African and WHO guidelines, participants did not receive preventive therapy. All participants had intensive baseline screening with spontaneous, followed by induced, sputum sampling and were then observed for an average of 4.7 years for culture-positive disease. Baseline PET/CT abnormalities were evaluated in relation to culture-positive disease.ResultsAt baseline, 59 (23.6%) participants had lung PET/CT findings consistent with TB of which 29 (11.6%) were defined as Subclinical TB, and 30 (12%) Subclinical TB-inactive. A further 83 (33.2%) had other lung parenchymal abnormalities and 108 (43.2%) had normal lungs. Over 1107-person years of follow-up 14 cases of culture-positive TB were diagnosed. Six cases were detected by intensive baseline screening, all would have been missed by the South African symptom-based screening strategy and only one detected by a WHO-recommended chest X-Ray screening strategy. Those with baseline Subclinical TB lesions on PET/CT were significantly more likely to be diagnosed with culture-positive TB over the study period, compared to those with normal lung parenchyma (10/29 [34.5%] vs 2/108 [1.9%], Hazard Ratio 22.37 [4.89-102.47, p<0.001]).ConclusionsThese findings challenge the latent/active TB paradigm demonstrating that subclinical disease exists up to 4 years prior to microbiological detection and/or symptom onset. There are important implications for screening and management of TB.
Publisher
Cold Spring Harbor Laboratory
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