Labugger Ines, Heyckendorf Jan, Dees Stefan, Häussinger Emilia, Herzmann Christian, Kohl Thomas A, Richter Elvira, Rivera-Milla Eric, Lange Christoph
Alere Technologies GmbH, Jena, Germany.
Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany.
Infection. 2017 Jun;45(3):269-276. doi: 10.1007/s15010-016-0955-2. Epub 2016 Oct 31.
Molecular diagnostics of patients with MTB tuberculosis from urine samples.
We developed a new molecular assay based on the detection of M. tuberculosis-specific transrenal DNA (trDNA) and tested it for the diagnosis of active tuberculosis at the initiation of anti-tuberculosis therapy and during treatment follow-up.
The overall sensitivity of trDNA was 96 and 100% when smear-microscopy and trDNA was combined. In a subset of TB treatment naïve patients (n = 11) sensitivity and specificity of trDNA was 64 and 100%, respectively. For this subset of patients the sensitivity was 91% when smear-microscopy and trDNA diagnosis were combined. After treatment initiation, trDNA showed a significant reduction in concentration over time reaching undetectable trDNA values at week 12 in 9 of 11 accessible patients (82%). Kinetics in treatment-naïve patients showed low base-line trDNA levels, which increased to maximal trDNA levels within one week indicating bactericidal activity of anti-tuberculosis drugs after the initiation of effective therapy. Maximal trDNA levels correlated positively with a radiological score, suggesting that the process of DNA excretion may reflect the extent of pulmonary disease. Matched samples showed an inverse correlation between the time to positivity of solid culture with maximum trDNA levels as well as the expected positive correlation between smear grade and maximum trDNA values.
The detection of M. tuberculosis trDNA from urine specimen is a promising method for the diagnosis tuberculosis. The assay may be a candidate diagnostic tool for patients with paucibacillary and extrapulmonary disease, as method to assess treatment responses and could be helpful to diagnose tuberculosis in children.
对尿样中结核分枝杆菌（MTB）结核病患者进行分子诊断。
我们基于检测结核分枝杆菌特异性经肾DNA（trDNA）开发了一种新的分子检测方法，并在抗结核治疗开始时和治疗随访期间对其进行了活性结核病诊断测试。
当涂片显微镜检查和trDNA联合使用时，trDNA的总体敏感性分别为96%和100%。在一组未接受过结核病治疗的患者（n = 11）中，trDNA的敏感性和特异性分别为64%和100%。对于这组患者，当涂片显微镜检查和trDNA诊断联合使用时，敏感性为91%。治疗开始后，trDNA浓度随时间显著降低，在11名可获取样本的患者中有9名（82%）在第12周时trDNA值降至检测不到。未接受过治疗的患者的动力学显示基线trDNA水平较低，在一周内升至最高trDNA水平，表明有效治疗开始后抗结核药物的杀菌活性。最高trDNA水平与放射学评分呈正相关，提示DNA排泄过程可能反映肺部疾病的程度。匹配样本显示固体培养阳性时间与最高trDNA水平呈负相关，以及涂片分级与最高trDNA值之间预期的正相关。
从尿标本中检测结核分枝杆菌trDNA是一种有前景的结核病诊断方法。该检测方法可能是少菌型和肺外疾病患者的候选诊断工具，可作为评估治疗反应的方法，并且可能有助于儿童结核病的诊断。
