现有和第二代干扰素-γ 释放试验在结核病诊断评估中的临床应用：一项观察性队列研究。

Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study.

机构信息

Tuberculosis Research Centre, National Heart and Lung Institute, Imperial College London, London, UK; Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK.

Tuberculosis Research Centre, National Heart and Lung Institute, Imperial College London, London, UK; National Institute for Health Research Health Protection Research Unit in Respiratory Infections, Imperial College London, London, UK.

出版信息

Lancet Infect Dis. 2019 Feb;19(2):193-202. doi: 10.1016/S1473-3099(18)30613-3. Epub 2019 Jan 14.

DOI:10.1016/S1473-3099(18)30613-3

PMID:30655049

Abstract

BACKGROUND

The clinical utility of interferon-γ release assays (IGRAs) for diagnosis of active tuberculosis is unclear, although they are commonly used in countries with a low incidence of tuberculosis. We aimed to resolve this clinical uncertainty by determining the accuracy and utility of commercially available and second-generation IGRAs in the diagnostic assessment of suspected tuberculosis in a low-incidence setting.

METHODS

We did a prospective cohort study of adults with suspected tuberculosis in routine secondary care in England. Patients were tested for Mycobacterium tuberculosis infection at baseline with commercially available (T-SPOT.TB and QuantiFERON-TB Gold In-Tube [QFT-GIT]) and second-generation (incorporating novel M tuberculosis antigens) IGRAs and followed up for 6-12 months to establish definitive diagnoses. Sensitivity, specificity, positive and negative likelihood ratios, and predictive values of the tests were determined.

FINDINGS

Of the 1060 adults enrolled in the study, 845 were included in the analyses and 363 were diagnosed with tuberculosis. Sensitivity of T-SPOT.TB for all tuberculosis diagnosis, including culture-confirmed and highly probable cases, was 81·4% (95% CI 76·6-85·3), which was higher than QFT-GIT (67·3% [62·0-72·1]). Second-generation IGRAs had a sensitivity of 94·0% (90·0-96·4) for culture-confirmed tuberculosis and 89·2% (85·2-92·2) when including highly probable tuberculosis, giving a negative likelihood ratio for all tuberculosis cases of 0·13 (95% CI 0·10-0·19). Specificity ranged from 86·2% (95% CI 82·3-89·4) for T-SPOT.TB to 80·0% (75·6-83·8) for second-generation IGRAs.

INTERPRETATION

Commercially available IGRAs do not have sufficient accuracy for diagnostic evaluation of suspected tuberculosis. Second-generation tests, however, might have sufficiently high sensitivity, low negative likelihood ratio, and correspondingly high negative predictive value in low-incidence settings to facilitate prompt rule-out of tuberculosis.

FUNDING

National Institute for Health Research.

摘要

背景

干扰素-γ 释放试验（IGRAs）在诊断活动性结核病方面的临床应用价值尚不清楚，尽管在结核病发病率较低的国家中，此类检测常被应用。我们旨在通过确定在低发病率环境下，市售和第二代 IGRAs 用于疑似结核病诊断评估的准确性和实用性，来解决这一临床不确定性问题。

方法

我们进行了一项在英国常规二级保健中疑似结核病成人患者的前瞻性队列研究。在基线时，患者接受了市售（T-SPOT.TB 和 QuantiFERON-TB Gold In-Tube[QFT-GIT]）和第二代（纳入新型结核分枝杆菌抗原）IGRAs 的检测，以评估结核分枝杆菌感染，并随访 6-12 个月以明确诊断。我们确定了这些检测的敏感性、特异性、阳性和阴性似然比及预测值。

结果

在纳入的 1060 名成人中，845 名被纳入分析，363 名被诊断为结核病。T-SPOT.TB 对所有结核病（包括培养确诊和高度疑似病例）的诊断敏感性为 81.4%（95%CI76.6-85.3），高于 QFT-GIT（67.3%[62.0-72.1]）。第二代 IGRAs 对培养确诊结核病的诊断敏感性为 94.0%（90.0-96.4），对包括高度疑似结核病在内的所有结核病的诊断敏感性为 89.2%（85.2-92.2），所有结核病病例的阴性似然比为 0.13（95%CI0.10-0.19）。特异性范围从 T-SPOT.TB 的 86.2%（95%CI82.3-89.4）到第二代 IGRAs 的 80.0%（75.6-83.8）。