Acute urethritis (i.e., inflammation of the male urethra) affects millions of men within
the United States annually. In young sexually active men, urethritis is most commonly
caused by the sexually transmitted infections (STI) Neisseria gonorrhoeae (GC, causes
gonorrhea) and Chlamydia trachomatis (CT, causes chlamydia), but can also be caused by a
lengthening list of known and emerging pathogens that cause "nongonococcal urethritis"
(NGU). STI management has proven challenging due to the prevalence of asymptomatic
infections and because men often fail to seek STI care until they experience pronounced
symptoms. However, even without urethral symptoms, most men with a urethral STI have
measurable evidence of urethritis. Thus, a cheap, simple, and non-invasive point of care
(POC) test (i.e., results available within 30 minutes) that accurately detects urethritis
could be a game changer in STI management as asymptomatic infections could be detected
and treated, potentially decreasing the risk of spreading STIs to sexual partners.
Currently, the only widely used POC test available for diagnosis of urethritis in men in
the US is Gram stain microscopy of a urethral swab smear. This approach has been shown to
be highly effective for identifying men who have urethritis and has 95% sensitivity for
diagnosing GC in symptomatic men [4]. Although the urethral swab remains the gold
standard test to diagnose urethritis at the POC, it is rarely used outside of specialized
STI clinics given its many limitations, which include: (1) it often elicits severe pain,
and in rare cases can permanently damage the urethra; (2) it requires specialized
instrumentation (an inverted microscope with a 1000x objective) and Gram stain reagents;
(3) it must also be administered and interpreted by trained personnel that have different
inter-operator accuracy in reporting results, and (4) anxiety associated with this
procedure is a common reason men cite for delaying STI care and failing to return for
follow-up visits. In many other clinical settings, POC screening for STIs would be highly
desirable, for example during annual wellness exams of high-risk male adolescents;
screening with specific STI nucleic acid amplification tests (NAATs) is not
cost-effective in low-risk populations and the urethral swab procedure is unacceptable in
these populations. As an alternative approach, a few investigators have evaluated
Leukocyte esterase (LE) testing as part of a routine urinalysis using first-catch urine
to diagnose urethritis, but the low sensitivity and specificity of this approach has
limited its use to resource-limited settings.
Flow cytometry is routinely used in clinical settings to identify populations of cells
(e.g., neutrophils, red blood cells for whole blood counts) from blood and urine. Modern
flow cytometers are highly automated, rapid, and inexpensive to run, which makes them an
optimal assay for screening for urethritis by detecting elevated neutrophils in
asymptomatic men. Interestingly, several recent publications have shown that flow
cytometric analysis of urine can be used to diagnose urethritis with comparable
sensitivity and specificity to the urethral Gram stain smear. However, most of these
studies did not use state-of-the-art flow cytometers, did not calibrate Gram stain to
flow cytometric results directly, and did not diagnose the sensitivity/specificity of
this approach for detection of a broad section of urethral STI. The investigators
hypothesize that the state-of-the-art flow cytometer analyzer, Sysmex UF-5000, may be
able to similarly provide a non-invasive and cost-effective approach for urethritis
diagnosis in men using first-catch urine when compared to Gram stain and urinalysis. A
prior version, the Sysmex UF-1000i, has been shown to be promising in detection of
urinary tract infections, but has not yet been studied in STIs. The UF-5000 could be a
powerful screening approach for urethral STI that could be employed in a broad range of
clinical settings, not just specialized STI clinics. Separately, if urine flow cytometry
could be optimized to yield similar sensitivity to the Gram stain smear, the
investigators suspect this approach would rapidly replace the Gram stain smear in
clinical practice which in turn would improve patient capture and retention.
The investigators will recruit healthy men aged 18 to 50 who, after consenting to
participate, will be assigned to start collecting a urine specimen three times week
(typically, Monday, Wednesday, and Friday) for two weeks.
The device used to collect urine will be either a Colli-Pee or a standard-of-care 60 ml
sterile urine cup. Participants with an odd birth year will use the Colli-Pee during the
first week; even birth year participants will use the Colli-Pee during the second week.
