Esmail Hanif, Coussens Anna K, Thienemann Friedrich, Sossen Bianca, Mukasa Sandra L, Warwick James, Goliath Rene T, Davies Nashreen Omar, Douglass Emily, Jackson Amanda, Lakay Francisco, Streicher Elizabeth, Munro Jacob E, Barrios Marilou H, Heinsohn Torben, Macpherson Liana, Sheerin Dylan, Aziz Saalikha, Serole Keboile, Daroowala Remy, Taliep Arshad, Ahlers Petri, Malherbe Stephanus T, Bowden Rory, Warren Robin, Walzl Gerhard, Via Laura E, Bahlo Melanie, Jacobson Karen R, Horsburgh C Robert, Salgame Padmini, Alland David, Barry Clifton Earl, Flynn JoAnne L, Ellner Jerrold J, Wilkinson Robert J
Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, Republic of South Africa.
MRC Clinical Trials Unit at University College London, WC1V 6LJ, United Kingdom.
medRxiv. 2023 Jul 3:2023.07.03.23292111. doi: 10.1101/2023.07.03.23292111.
The evolution of tuberculosis (TB) disease during the clinical latency period remains incompletely understood.
250 HIV-uninfected, adult household contacts of rifampicin-resistant TB with a negative symptom screen underwent baseline F-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.
At 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]).
These 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.
结核病（TB）在临床潜伏期的演变仍未完全明确。
250名未感染HIV、成年的耐利福平结核病患者的家庭接触者，症状筛查呈阴性，接受了基线氟脱氧葡萄糖正电子发射断层扫描和计算机断层扫描（PET/CT），其中112人在5至15个月后进行了复查。按照南非和世界卫生组织的指南，参与者未接受预防性治疗。所有参与者均进行了强化基线筛查，包括自发咳痰，随后诱导咳痰取样，然后平均观察4.7年以检测培养阳性疾病。评估基线PET/CT异常与培养阳性疾病的关系。
基线时，59名（23.6%）参与者的肺部PET/CT结果符合结核病表现，其中29名（11.6%）被定义为亚临床结核病，30名（12%）为亚临床非活动性结核病。另有83名（33.2%）有其他肺实质异常，108名（43.2%）肺部正常。在超过1107人年的随访中，诊断出14例培养阳性结核病。6例通过强化基线筛查检测到，所有这些病例都会被南非基于症状的筛查策略漏诊，只有1例通过世界卫生组织推荐的胸部X线筛查策略检测到。与肺实质正常的参与者相比，PET/CT上有基线亚临床结核病变的参与者在研究期间被诊断为培养阳性结核病的可能性显著更高（10/29 [34.5%] 对2/108 [1.9%]，风险比22.37 [4.89 - 102.47，p<0.001]）。
这些发现挑战了潜伏性/活动性结核病范式，表明亚临床疾病在微生物学检测和/或症状出现前长达4年就已存在。这对结核病的筛查和管理具有重要意义。
