Cell-free Mycobacterium tuberculosis DNA test in pleural effusion for tuberculous pleurisy: a diagnostic accuracy study

Clin Microbiol Infect. 2020 Aug;26(8):1089.e1-1089.e6. doi: 10.1016/j.cmi.2019.11.026. Epub 2019 Dec 2.

Abstract

Objectives: Tuberculous pleurisy (TP) diagnosis remains difficult, with the sensitivity of Xpert MTB/RIF (Xpert) and mycobacterial culture (culture) only about 30-50%. We aimed to assess the diagnostic performance of a cell-free Mycobacterium tuberculosis DNA test (cf-TB) in pleural effusion for TP.

Methods: Adults (≥18 years) with suspected TP presenting with pleural effusion were consecutively recruited, and pleural effusion specimens were prospectively collected in Beijing Chest Hospital, Beijing, China. After centrifuging pleural effusion, sediments were used for culture, Xpert and T-SPOT.TB assay, whereas supernatants were used for cf-TB and adenosine deaminase assay. The diagnostic performance was assessed against a composite reference standard.

Results: From June 2015 to December 2018, we prospectively evaluated 286 adults with suspected TP. One hundred twenty-two participants were classified as definite TP based on the prespecified composite reference standard. The cf-TB produced a sensitivity of 79.5% (97/122, 95% confidence interval (CI) 72.4- 86.7) for definite TP, which was superior to Xpert (38.5% (29.9-47.2); 47/122; p < 0.001) and culture (27.1% (19.2-34.9); 33/122; p < 0.001). With pleural effusion Xpert and/or culture as the reference standard, cf-TB showed 96.6% (57/59, 95% CI 92.0-100.0) sensitivity, which was also significantly higher than Xpert (79.7%, 95% CI 69.4-89.9; 47/59; p 0.004) and culture (55.9%, 95% CI: 43.3-68.6; 33/59; p < 0.001).

Conclusions: The cf-TB clearly showed improved sensitivity compared with Xpert and culture. We recommend cf-TB as the first-line test for TP diagnosis.

Keywords: Cell-free DNA; Diagnosis; Mycobacterium tuberculosis; Tuberculous pleurisy; Xpert MTB/RIF.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Bacteriological Techniques
  • Cell-Free Nucleic Acids / analysis*
  • DNA, Bacterial / analysis
  • Diagnostic Tests, Routine
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / growth & development
  • Mycobacterium tuberculosis / isolation & purification*
  • Pleural Effusion / microbiology*
  • Prospective Studies
  • Reagent Kits, Diagnostic
  • Sensitivity and Specificity
  • Tuberculosis, Pleural / diagnosis*

Substances

  • Cell-Free Nucleic Acids
  • DNA, Bacterial
  • Reagent Kits, Diagnostic