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通过快速分子检测加速肺外结核病诊断

Accelerating extrapulmonary tuberculosis diagnosis with a rapid molecular assay.

作者信息

Guillet-Caruba Christelle, Bénet Caroline, Jmel Haroun, Doucet-Populaire Florence, Bourgeois-Nicolaos Nadège

机构信息

AP-HP Université Paris-Saclay Hôpital Antoine Béclère, Service de Bactériologie-Hygiène, Clamart, France.

Laboratoire de Biologie Médicale de Référence, AP-HP Université Paris-Saclay, Orsay, France.

出版信息

Microbiol Spectr. 2025 Aug 5;13(8):e0010425. doi: 10.1128/spectrum.00104-25. Epub 2025 Jun 12.

DOI:10.1128/spectrum.00104-25
PMID:40503841
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12323321/
Abstract

Extrapulmonary tuberculosis (EPTB) is characterized by a very low bacterial load and could remain undiagnosed for a long time in a number of cases due to atypical presentation. Conventional methods and their time to results are not always helpful in rapidly making an EPTB diagnosis and initiating appropriate treatment. In order to accelerate the bacteriological confirmation, we evaluated the benefits of systematically using nucleic acid amplification test (NAAT) on extrapulmonary specimens for TB diagnosis in a developed country. From November 2017 to March 2021, all extrapulmonary samples received at the mycobacteriology department were subjected to both conventional methods and Xpert MTB/RIF Ultra. The time savings and the diagnostic performance of reflex tests were evaluated. During the study period, 691 samples were included, 85 (12.3%) were NAAT positive for complex (MTBC), and only 1 for a mutation. The overall rate of invalid NAAT results was low, 0.9%. The average time to results of NAAT was 1.3 days compared to 18 days for positive culture, allowed to accelerate the EPTB diagnosis by 16 days. Overall NAAT sensitivity and specificity were 87.9% and 94.6%, respectively. No discrepancy was found among the 67 results involving the detection of rifampicin resistance. NAAT is a quick and consistent diagnostic test for EPTB with a potential turnaround time of 2 hours. Its systematic use could allow EPTB diagnosis and treatment faster by revealing results days to weeks before culture and drug susceptibility testing.IMPORTANCETuberculosis is considered the deadliest infectious disease in the world. Although tuberculosis most commonly affects the lungs, it also affects other sites referred to as extrapulmonary tuberculosis (EPTB). Diagnosis of EPTB is difficult and often delayed. We evaluated the benefits of systematically and routinely using a nucleic acid amplification test on all extrapulmonary specimens received at the mycobacterial core laboratory for EPTB diagnosis. Using a rapid (80 minutes) and easy-to-perform test, we accelerated the definitive diagnosis by an average of 16 days.

摘要

肺外结核(EPTB)的特点是细菌载量非常低,在许多情况下,由于临床表现不典型,可能长时间无法确诊。传统方法及其出结果的时间并不总是有助于快速做出EPTB诊断并开始适当治疗。为了加快细菌学确诊,我们评估了在一个发达国家系统地使用核酸扩增试验(NAAT)检测肺外标本以诊断结核病的益处。2017年11月至2021年3月,分枝杆菌科接收的所有肺外样本均采用传统方法和Xpert MTB/RIF Ultra进行检测。评估了节省的时间和复检试验的诊断性能。在研究期间,共纳入691份样本,其中85份(12.3%)NAAT检测结果为结核分枝杆菌复合群(MTBC)阳性,只有1份检测到突变。NAAT无效结果的总体发生率较低,为0.9%。NAAT的平均出结果时间为1.3天,而阳性培养的平均出结果时间为18天,这使得EPTB诊断能够提前16天加速。总体而言,NAAT的敏感性和特异性分别为87.9%和94.6%。在67份涉及利福平耐药检测的结果中未发现差异。NAAT是一种快速且结果一致的EPTB诊断试验,潜在周转时间为2小时。系统地使用该试验可以在培养和药物敏感性试验前数天至数周得出结果,从而更快地进行EPTB诊断和治疗。重要性结核病被认为是世界上最致命的传染病。虽然结核病最常影响肺部,但它也会影响其他部位,称为肺外结核(EPTB)。EPTB的诊断困难且常常延迟。我们评估了在分枝杆菌核心实验室系统且常规地使用核酸扩增试验检测所有接收的肺外标本以诊断EPTB的益处。通过使用一种快速(80分钟)且易于操作的试验,我们将确诊平均提前了16天。

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本文引用的文献

1
Xpert MTB/RIF Ultra for the rapid diagnosis of extrapulmonary tuberculosis in a clinical setting of high tuberculosis prevalence country and interpretation of 'trace' results.在结核病高流行国家的临床环境中,使用Xpert MTB/RIF Ultra快速诊断肺外结核病及对“微量”结果的解读。
Tuberculosis (Edinb). 2024 Mar;145:102478. doi: 10.1016/j.tube.2024.102478. Epub 2024 Jan 8.
2
Effects of sputum bacillary load and age on GeneXpert and traditional methods in pulmonary tuberculosis: a 4-year retrospective comparative study.痰菌载量和年龄对 GeneXpert 与传统方法诊断肺结核的影响:一项 4 年回顾性对比研究。
BMC Infect Dis. 2023 Nov 27;23(1):831. doi: 10.1186/s12879-023-08832-6.
3
Efficacy of Xpert in tuberculosis diagnosis based on various specimens: a systematic review and meta-analysis.
基于各种标本的 Xpert 在结核病诊断中的疗效:系统评价和荟萃分析。
Front Cell Infect Microbiol. 2023 May 2;13:1149741. doi: 10.3389/fcimb.2023.1149741. eCollection 2023.
4
Xpert MTB/RIF Ultra Trace Results: Decision Support for the Treatment of Extrapulmonary Tuberculosis in Low TB Burden Countries.Xpert MTB/RIF Ultra微量检测结果:低结核病负担国家肺外结核病治疗的决策支持
J Clin Med. 2023 Apr 27;12(9):3148. doi: 10.3390/jcm12093148.
5
Xpert MTB/RIF Ultra CT value provides a rapid measure of sputum bacillary burden and predicts smear status in patients with pulmonary tuberculosis.Xpert MTB/RIF Ultra CT 值可快速衡量痰菌载量,并可预测肺结核患者的涂片状态。
Sci Rep. 2023 Jan 28;13(1):1591. doi: 10.1038/s41598-023-28869-6.
6
Xpert MTB/RIF Ultra outperformed the Xpert assay in tuberculosis lymphadenitis diagnosis: a prospective head-to-head cohort study.Xpert MTB/RIF Ultra 在诊断结核性淋巴结炎方面优于 Xpert 检测:一项前瞻性头对头队列研究。
Int J Infect Dis. 2022 Sep;122:741-746. doi: 10.1016/j.ijid.2022.07.039. Epub 2022 Jul 22.
7
Tracing TB: Are there predictors for active TB disease in patients with Xpert Ultra trace results?追踪结核:Xpert Ultra 痕量结果阳性的患者中,有活动性结核病的预测因素吗?
Int J Infect Dis. 2022 Jan;114:115-123. doi: 10.1016/j.ijid.2021.10.056. Epub 2021 Nov 2.
8
Extrapulmonary tuberculosis.肺外结核。
Expert Rev Respir Med. 2021 Jul;15(7):931-948. doi: 10.1080/17476348.2021.1927718. Epub 2021 Jul 14.
9
Xpert MTB/RIF Ultra and Xpert MTB/RIF assays for extrapulmonary tuberculosis and rifampicin resistance in adults.Xpert MTB/RIF Ultra 检测和 Xpert MTB/RIF 检测在成人肺外结核和利福平耐药检测中的应用。
Cochrane Database Syst Rev. 2021 Jan 15;1(1):CD012768. doi: 10.1002/14651858.CD012768.pub3.
10
Extrapulmonary tuberculosis among migrants in Europe, 1995 to 2017.1995 年至 2017 年欧洲移民中的肺外结核。
Clin Microbiol Infect. 2021 Sep;27(9):1347.e1-1347.e7. doi: 10.1016/j.cmi.2020.12.006. Epub 2020 Dec 19.