Performance evaluation of automated urine microscopy as a rapid, non-invasive approach for the diagnosis of non-gonococcal urethritis

Abstract

ObjectivesGram-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.MethodsReceiver 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.ResultsAn 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).ConclusionsAUFC 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.

A Systematic Review of Point of Care Testing forChlamydia trachomatis,Neisseria gonorrhoeae, andTrichomonas vaginalis

“…For CT, the ten diagnostics evaluated were the Gram stained urethral smear [ 19 , 20 ], GeneXpert® Xpert CT/NG (Xpert CT/NG) (Cepheid, Sunnyvale, CA, USA) [ 21 ], aQcare Chlamydia TRF kit (Medisensor, Inc., Daegu, Korea) [ 22 ], Chlamydia Rapid Test (CRT) (Diagnostics for the Real World (Europe), Cambridge, UK) [ 23 , 24 ], ACON Plate CT Rapid Test (ACON CT) (ACON Laboratories, San Diego, CA, USA) [ 23 , 25 ], ACON NG and CT Duo test combo (ACON Duo) (ACON Laboratories, San Diego, CA, USA) [ 25 ], QuickVue Chlamydia Rapid Test (QuickVue) (Quidel Corporation, San Diego, CA, USA) [ 25 , 26 ], Automated Urine Flow Cytometry (AUFC) of first void urine [ 20 ], Handilab-C (Zonda, Dallas, TX, USA) [ 26 ], and Biorapid Chlamydia Ag test (Biokit, S.A., Barcelona, Spain) [ 26 ]. The performance results are summarized in Table 1 .…”

“…The best performing test was the Xpert CT/NG, an FDA cleared real-time PCR platform, which consistently had sensitivities and specificities >97% across sample types [ 21 ]. The aQcare Chlamydia TRF kit and AUFC also performed well, with sensitivities and specificities above 90%, although they were each evaluated in one study [ 20 , 22 ]. The remainder of the diagnostics did not perform adequately, with either sensitivities or specificities <75% and often <50% [ 19 , 20 , 23 – 26 ].…”

Validation and verification of automated urine particle analysers

“…Some studies looked at other possible specific uses, such as the ability to discriminate between glomerular and non-glomerular haematuria62–64 or at whether automated urine microscopy of first-void urines could be used to diagnose non-gonococcal urethritis 65…”

“…In other studies, the time for completing the microscopy was given in relation to the receipt time in the laboratory, and it ranged between 1 hour,11 18 30 31 33 35 2 hours,12 13 16 19 34 3 hours58 and 4 hours after receipt 21 24 62. In some of the studies, there was only a generic statement that urines had been tested without much delay9 17 27 38 39 50 54 56 65 or no clear statements 14 15 23 26 36 37 40–45 49 55 57…”

Highlights from this issue

“…Clinicians will be interested to see the evaluation of automated urine microscopy for the diagnosis of non-gonococcal urethritis, reported by Pond et al 3. The authors report that this approach improves on the specificity of microscopy to detect Chlamydia trachomatis or Mycoplasma genitalium .…”