title: Performance evaluation of automated urine microscopy as a rapid, non-invasive approach for the diagnosis of non-gonococcal urethritis.
abstract: OBJECTIVE
  Gram-stained urethral smear (GSUS), the standard point-of-care test for non-gonococcal urethritis (NGU) is operator dependent and poorly specific. The performance of rapid automated urine flow cytometry (AUFC) of first void urine (FVU) white cell counts (UWCC) for predicting Mycoplasma genitalium and Chlamydia trachomatis urethral infections was assessed and its application to asymptomatic infection was evaluated.
  
  
  METHODS
  Receiver operating characteristic curve analysis, determining FVU-UWCC threshold for predicting M. genitalium or C. trachomatis infection was performed on 208 'training' samples from symptomatic patients and subsequently validated using 228 additional FVUs obtained from prospective unselected patients.
  
  
  RESULTS
  An optimal diagnostic threshold of >29 UWC/µL gave sensitivities and specificities for either infection of 81.5% (95% CI 65.1% to 91.6%) and 85.8% (79.5% to 90.4%), respectively, compared with 86.8% (71.1% to 95%) and 64.7% (56.9% to 71.7%), respectively, for GSUS, using the training set samples. FVU-UWCC demonstrated sensitivities and specificities of 69.2% (95% CI 48.1% to 84.9%) and 92% (87.2% to 95.2%), respectively, when using validation samples. In asymptomatic patients where GSUS was not used, AUFC would have enabled more infections to be detected compared with clinical considerations only (71.4% vs 28.6%; p=0.03). The correlation between UWCC and bacterial load was stronger for M. genitalium compared with C. trachomatis (τ=0.426, p≤0.001 vs τ=0.295, p=0.022, respectively).
  
  
  CONCLUSIONS
  AUFC offers improved specificity over microscopy for predicting C. trachomatis or M. genitalium infection. Universal AUFC may enable non-invasive diagnosis of asymptomatic NGU at the PoC. The degree of urethral inflammation exhibits a stronger association with pathogen load for M. genitalium compared with C. trachomatis.
authors.affiliation: Institute for Infection and Immunity, St George's University of London, London, UK.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Pond
authors.affiliation: Institute for Infection and Immunity, St George's University of London, London, UK Department of Genitourinary & HIV Medicine, St George's Healthcare NHS Trust, London, UK.
authors.forename: Achyuta V
authors.initials: AV
authors.lastname: Nori
authors.affiliation: Department of Genitourinary & HIV Medicine, St George's Healthcare NHS Trust, London, UK.
authors.forename: Sheel
authors.initials: S
authors.lastname: Patel
authors.affiliation: Institute for Infection and Immunity, St George's University of London, London, UK.
authors.forename: Ken
authors.initials: K
authors.lastname: Laing
authors.affiliation: Institute for Infection and Immunity, St George's University of London, London, UK.
authors.forename: Margarita
authors.initials: M
authors.lastname: Ajayi
authors.affiliation: Research Department of Infection and Population Health, University College London, Mortimer Market Centre, London, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Copas
authors.affiliation: Institute for Infection and Immunity, St George's University of London, London, UK.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Butcher
authors.affiliation: Institute for Infection and Immunity, St George's University of London, London, UK Department of Genitourinary & HIV Medicine, St George's Healthcare NHS Trust, London, UK.
authors.forename: Phillip
authors.initials: P
authors.lastname: Hay
authors.affiliation: Institute for Infection and Immunity, St George's University of London, London, UK Department of Genitourinary & HIV Medicine, St George's Healthcare NHS Trust, London, UK.
authors.forename: Syed Tariq
authors.initials: ST
authors.lastname: Sadiq
mesh_terms: D000328:Adult; D057205:Automation, Laboratory / Q000379:methods*; D002690:Chlamydia Infections / Q000175:diagnosis*; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D007958:Leukocyte Count / Q000379:methods; D008297:Male; D008853:Microscopy / Q000379:methods*; D009175:Mycoplasma Infections / Q000175:diagnosis*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D014526:Urethritis / Q000175:diagnosis*; D014556:Urine / Q000166:cytology*
keywords: CHLAMYDIA TRACHOMATIS; DIAGNOSIS; M GENITALIUM; MOLECULAR TECHNIQUES; URETHRITIS