Abstract：
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains one of the deadliest infectious diseases globally. Timely diagnosis is a key step in the management of TB patients and in the prevention of further transmission events. Current diagnostic tools are limited in these regards. There is an urgent need for new accurate non-sputum-based diagnostic tools for the detection of symptomatic as well as subclinical TB. In this study, we recruited 52 symptomatic TB patients (sputum Xpert MTB/RIF positive) and 58 household contacts to assess the accuracy of a sequence-specific hybridization assay that detects the presence of Mtb cell-free DNA in urine. Using sputum Xpert MTB/RIF as a reference test, the magnetic bead-capture assay could discriminate active TB from healthy household contacts with an overall sensitivity of 72.1% [confidence interval (CI) 0.59-0.86] and specificity of 95.5% (CI 0.90-1.02) with a positive predictive value of 93.9% and negative predictive value of 78.2%. The detection of Mtb-specific DNA in urine suggested four asymptomatic TB infection cases that were confirmed in all instances either by concomitant Xpert MTB/RIF sputum testing or by follow-up investigation raising the specificity of the index test to 100%. We conclude that sequence-specific hybridization assays on urine specimens hold promise as non-invasive tests for the detection of subclinical TB.
OBJECTIVE: There is an urgent need for a non-sputum-based diagnostic tool allowing sensitive and specific detection of all forms of tuberculosis (TB) infections. In that context, we performed a case-control study to assess the accuracy of a molecular detection method enabling the identification of cell-free DNA from Mycobacterium tuberculosis that is shed in the urine of tuberculosis patients. We present accuracy data that would fulfill the target product profile for a non-sputum test. In addition, recent epidemiological data suggested that up to 50% of individuals secreting live bacilli do not present with symptoms at the time of screening. We report, here, that the investigated index test could also detect instances of asymptomatic TB infections among household contacts.
OBJECTIVE: There is an urgent need for a non-sputum-based diagnostic tool allowing sensitive and specific detection of all forms of tuberculosis (TB) infections. In that context, we performed a case-control study to assess the accuracy of a molecular detection method enabling the identification of cell-free DNA from Mycobacterium tuberculosis that is shed in the urine of tuberculosis patients. We present accuracy data that would fulfill the target product profile for a non-sputum test. In addition, recent epidemiological data suggested that up to 50% of individuals secreting live bacilli do not present with symptoms at the time of screening. We report, here, that the investigated index test could also detect instances of asymptomatic TB infections among household contacts.
摘要：
由结核分枝杆菌（Mtb）引起的结核病（TB）仍然是全球最致命的传染病之一。及时诊断是结核病患者管理和预防进一步传播事件的关键步骤。目前的诊断工具在这些方面是有限的。迫切需要新的准确的非基于痰的诊断工具来检测有症状的和亚临床的TB。在这项研究中,我们招募了52例有症状的TB患者(痰XpertMTB/RIF阳性)和58名家庭接触者,以评估检测尿液中Mtb无细胞DNA的序列特异性杂交试验的准确性.使用痰XpertMTB/RIF作为参考测试，磁珠捕获试验可将活动性TB与健康家庭接触者区分开,总体灵敏度为72.1%[置信区间(CI)0.59~0.86],特异性为95.5%(CI0.90~1.02),阳性预测值为93.9%,阴性预测值为78.2%.尿液中Mtb特异性DNA的检测表明有4例无症状的TB感染病例，在所有情况下都通过伴随的XpertMTB/RIF痰检测或通过随访调查得到证实，将指数检测的特异性提高到100％。我们得出的结论是，尿液标本上的序列特异性杂交试验有望作为检测亚临床结核病的非侵入性试验。
目的：迫切需要一种非基于痰的诊断工具，可以对所有形式的结核病（TB）感染进行敏感和特异性的检测。在这种情况下，我们进行了一项病例对照研究,以评估一种分子检测方法的准确性,该方法能够从结核分枝杆菌中鉴定出在结核病患者尿液中脱落的无细胞DNA.我们提供的准确性数据可以满足非痰检测的目标产品概况。此外,最近的流行病学数据表明，多达50％的分泌活杆菌的个体在筛查时没有症状。我们报告,在这里，所调查的指数测试还可以检测家庭接触者中无症状结核病感染的实例。
目的：迫切需要一种非基于痰的诊断工具，可以对所有形式的结核病（TB）感染进行敏感和特异性的检测。在这种情况下，我们进行了一项病例对照研究,以评估一种分子检测方法的准确性,该方法能够从结核分枝杆菌中鉴定出在结核病患者尿液中脱落的无细胞DNA.我们提供的准确性数据可以满足非痰检测的目标产品概况。此外,最近的流行病学数据表明，多达50％的分泌活杆菌的个体在筛查时没有症状。我们报告,在这里，所调查的指数测试还可以检测家庭接触者中无症状结核病感染的实例。
