Exhaled Mycobacterium tuberculosis output and detection of subclinical disease by face-mask sampling: prospective observational studies

Exhaled Mycobacterium tuberculosis output and detection of subclinical disease by face-mask sampling: prospective observational studies
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DOI:
10.1016/s1473-3099(19)30307-8
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发表时间:
2020-05-01
影响因子:
56.3
通讯作者:
Barer, Michael R.
Barer, Michael R.
中科院分区:
医学1区
文献类型:
--
作者:
Williams, Caroline M.;Abdulwhhab, Mohamad;Barer, Michael R.

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结核病仍然是一个全球性的健康挑战,早期诊断是减少结核病的关键。口罩采样检测呼出的结核分枝杆菌。我们的目的是调查肺结核患者的细菌输出,并评估潜在的口罩采样作为一种诊断方法,在积极的casefinding.Methods,我们做了24小时的纵向研究,从三家医院在比勒陀利亚,南非,与微生物学确诊的肺结核患者。患者在24小时内进行了8次1小时的面罩采样,同时进行痰液采样。用定量PCR检测结核分枝杆菌。我们还在比勒陀利亚附近一个非正式定居点的居民中进行了积极的病例调查试点研究。我们招募了WHO筛查问卷上有结核病症状的个体。参与者提供痰液和面罩样本,使用Xpert MTB/RIF Ultra分子检测试剂盒进行检测。结果2015年9月22日至2015年12月3日,本纵向研究共筛选了78例肺结核患者,其中24例完成了研究(20例合并HIV感染)。在24小时内获得的192份面罩样本中有166份(86%)和184份可评估痰液样本中有38份(21%)检出结核分枝杆菌。呼出的结核分枝杆菌排出量没有昼夜模式,与咳嗽频率、痰菌含量或胸部放射学疾病严重程度无关。2018年5月16日,45人接受了前瞻性主动病例发现试点研究的筛查,其中20人有结核病症状并愿意参加。8名参与者被前瞻性诊断为肺结核,其中6人在筛选时仅为面罩阳性。其中4名参与者(其中3人为HIV阳性)胸部X线检查结果正常,但PET-CT扫描显示有治疗反应的早期结核病相容性病变,6周后痰液样本Xpert阳性。解释面罩采样提供了一种检测呼出的结核分枝杆菌的高效和非侵入性方法,与痰样本相比,以更高的一致性和更早的疾病阶段告知活动性感染的存在。该方法显示出诊断和筛查的潜力,特别是在难以到达的社区。版权所有(C)2020作者。爱思唯尔有限公司出版
Background Tuberculosis remains a global health challenge, with early diagnosis key to its reduction. Face-mask sampling detects exhaled Mycobacterium tuberculosis. We aimed to investigate bacillary output from patients with pulmonary tuberculosis and to assess the potential of face-mask sampling as a diagnostic method in active case-finding.Methods We did a 24-h longitudinal study in patients from three hospitals in Pretoria, South Africa, with microbiologically confirmed pulmonary tuberculosis. Patients underwent 1 h of face-mask sampling eight times over a 24-h period, with contemporaneous sputum sampling. M tuberculosis was detected by quantitative PCR. We also did an active case-finding pilot study in inhabitants of an informal settlement near Pretoria. We enrolled individuals with symptoms of tuberculosis on the WHO screening questionnaire. Participants provided sputum and face-mask samples that were tested with the molecular assay Xpert MTB/RIF Ultra. Sputum-negative and face-mask-positive individuals were followed up prospectively for 20 weeks by bronchoscopy, PET-CT, and further sputum analysis to validate the diagnosis.Findings Between Sept 22, 2015, and Dec 3, 2015, 78 patients with pulmonary tuberculosis were screened for the longitudinal study, of whom 24 completed the study (20 had HIV co-infection). M tuberculosis was detected in 166 (86%) of 192 face-mask samples and 38 (21%) of 184 assessable sputum samples obtained over a 24-h period. Exhaled M tuberculosis output showed no diurnal pattern and did not associate with cough frequency, sputum bacillary content, or chest radiographic disease severity. On May 16, 2018, 45 individuals were screened for the prospective active case-finding pilot study, of whom 20 had tuberculosis symptoms and were willing to take part. Eight participants were diagnosed prospectively with pulmonary tuberculosis, of whom six were exclusively face-mask positive at screening. Four of these participants (three of whom were HIV-positive) had normal findings on chest radiography but had treatment-responsive early tuberculosis-compatible lesions on PET-CT scans, with Xpert-positive sputum samples after 6 weeks.Interpretation Face-mask sampling offers a highly efficient and non-invasive method for detecting exhaled M tuberculosis, informing the presence of active infection both with greater consistency and at an earlier disease stage than with sputum samples. The approach shows potential for diagnosis and screening, particularly in difficult-to-reach communities. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.