title: Detection of transrenal DNA for the diagnosis of pulmonary tuberculosis and treatment monitoring.
abstract: OBJECTIVE
  Molecular diagnostics of patients with MTB tuberculosis from urine samples.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Alere Technologies GmbH, Jena, Germany.
authors: Ines
authors: I
authors: Labugger
authors: Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany. jheyckendorf@fz-borstel.de.|German Center for Infection Research (DZIF), partner site Borstel, Research Center Borstel, Borstel, Germany. jheyckendorf@fz-borstel.de.|International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany. jheyckendorf@fz-borstel.de.
authors: Jan
authors: http://orcid.org/0000-0003-4203-8421
authors: J
authors: Heyckendorf
authors: Alere Technologies GmbH, Jena, Germany.
authors: Stefan
authors: S
authors: Dees
authors: Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany.
authors: Emilia
authors: E
authors: Häussinger
authors: Center for Clinical Studies, Research Center Borstel, Borstel, Germany.
authors: Christian
authors: C
authors: Herzmann
authors: Division of Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany.
authors: Thomas A
authors: TA
authors: Kohl
authors: Division of Mycobacteriology, Research Center Borstel, Borstel, Germany.|Laboratory Dr. Limbach, Heidelberg, Germany.
authors: Elvira
authors: E
authors: Richter
authors: Alere Technologies GmbH, Jena, Germany.
authors: Eric
authors: E
authors: Rivera-Milla
authors: Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany.|German Center for Infection Research (DZIF), partner site Borstel, Research Center Borstel, Borstel, Germany.|International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany.|Department of Medicine, Karolinska Institute, Stockholm, Sweden.|Department of Medicine, University of Namibia School of Medicine, Windhoek, Namibia.
authors: Christoph
authors: C
authors: Lange
mesh_terms: D019411:Clinical Laboratory Techniques / Q000379:methods*; D004269:DNA, Bacterial / Q000652:urine*; D005260:Female; D006801:Humans; D007668:Kidney / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000302:isolation & purification*; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000382:microbiology / Q000628:therapy / Q000652:urine*; D016482:Urinalysis
chemical_list: D004269:DNA, Bacterial
keywords: Extra-pulmonary TB; Mycobacterium tuberculosis; Personalized therapy; TB diagnostics; TB in children; Therapy response; Tuberculosis; Urine TB diagnostics