title: Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous pericarditis compared to adenosine deaminase and unstimulated interferon-γ in a high burden setting: a prospective study.
abstract: BACKGROUND
  Tuberculous pericarditis (TBP) is associated with high morbidity and mortality, and is an important treatable cause of heart failure in developing countries. Tuberculous aetiology of pericarditis is difficult to diagnose promptly. The utility of the new quantitative PCR test (Xpert MTB/RIF) for the diagnosis of TBP is unknown. This study sought to evaluate the diagnostic accuracy of the Xpert MTB/RIF test compared to pericardial adenosine deaminase (ADA) and unstimulated interferon-gamma (uIFNγ) in suspected TBP.
  
  
  METHODS
  From October 2009 through September 2012, 151 consecutive patients with suspected TBP were enrolled at a single centre in Cape Town, South Africa. Mycobacterium tuberculosis culture and/or pericardial histology served as the reference standard for definite TBP. Receiver-operating-characteristic curve analysis was used for selection of ADA and uIFNγ cut-points.
  
  
  RESULTS
  Of the participants, 49% (74/151) were classified as definite TBP, 33% (50/151) as probable TBP and 18% (27/151) as non TBP. A total of 105 (74%) participants were human immunodeficiency virus (HIV) positive. Xpert-MTB/RIF had a sensitivity and specificity (95% confidence interval (CI)) of 63.8% (52.4% to 75.1%) and 100% (85.6% to 100%), respectively. Concentration of pericardial fluid by centrifugation and using standard sample processing did not improve Xpert MTB/RIF accuracy. ADA (≥35 IU/L) and uIFNγ (≥44 pg/ml) both had a sensitivity of 95.7% (88.1% to 98.5%) and a negative likelihood ratio of 0.05 (0.02 to 0.10). However, the specificity and positive likelihood ratio of uIFNγ was higher than ADA (96.3% (81.7% to 99.3%) and 25.8 (3.6 to 183.4) versus 84% (65.4% to 93.6%) and 6.0 (3.7 to 9.8); P = 0.03) at an estimated background prevalence of TB of 30%. The sensitivity and negative predictive value of both uIFNγ and ADA were higher than Xpert-MT/RIF (P < 0.001).
  
  
  CONCLUSIONS
  uIFNγ offers superior accuracy for the diagnosis of microbiologically confirmed TBP compared to the ADA assay and the Xpert MTB/RIF test.
authors.forename: Shaheen
authors.initials: S
authors.lastname: Pandie
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Peter
authors.forename: Zita S
authors.initials: ZS
authors.lastname: Kerbelker
authors.forename: Richard
authors.initials: R
authors.lastname: Meldau
authors.forename: Grant
authors.initials: G
authors.lastname: Theron
authors.forename: Ureshnie
authors.initials: U
authors.lastname: Govender
authors.forename: Mpiko
authors.initials: M
authors.lastname: Ntsekhe
authors.forename: Keertan
authors.initials: K
authors.lastname: Dheda
authors.affiliation: The Cardiac Clinic, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Groote Schuur Drive, Observatory, Cape Town 7925, South Africa. bongani.mayosi@uct.ac.za.
authors.forename: Bongani M
authors.initials: BM
authors.lastname: Mayosi
mesh_terms: D000243:Adenosine Deaminase / Q000032:analysis*; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D017281:Cost of Illness; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D010490:Pericardial Effusion / Q000737:chemistry* / Q000201:enzymology / Q000276:immunology; D010495:Pericarditis, Tuberculous / Q000175:diagnosis* / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D016133:Polymerase Chain Reaction / Q000379:methods / Q000592:standards*; D015995:Prevalence; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013019:South Africa; D014376:Tuberculosis / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D007371:Interferon-gamma; D000243:Adenosine Deaminase