Prevalence, incidence and characteristics associated with asymptomatic urethral inflammation in men who have sex with women

Background: Despite the potential to increase risk for acquisition of HIV and other sexually transmitted pathogens, the frequency with which men experience asymptomatic urethral inflammation is unknown. To better understand the full spectrum of perturbations to the male urethra, we aimed to determine the prevalence, incidence, and risk factors for asymptomatic urethral inflammation in men who have sex with women (MSW) attending a sexually transmitted infections clinic in Seattle.

Methods: We performed a secondary analysis of data collected during a cohort study designed to investigate the contribution of the male urethral microbiota to non-gonococcal urethritis (NGU). At enrollment, participants underwent a physical exam with assessment for urethral discharge and collection of urethral swab and first void urine specimens. Participants also completed a routine computer assisted interview (CASI) that collected information on STI
history, sexual history, urogenital symptoms, and sociobehavioral data. Urethral discharge was transferred to a slide which was Gram-stained to assess polymorphonuclear (PMN) cell count and the presence of diplococci indicating Neisseria gonorrhoeae (GC) infection. First void urine specimens were tested for GC, Chlamydia trachomatis (CT), and Mycoplasma genitalium (MG) using Aptima Assays (Hologic, Inc., San Diego, CA). Participants also completed a series of follow-up visits at four-week intervals and underwent the same study procedures as at the enrollment visit. We estimated the prevalence of asymptomatic urethral inflammation at enrollment in a cross-sectional study and identified characteristics associated with asymptomatic urethral inflammation in a case control study. Cases were defined as ≥5 polymorphonuclear cells on microscopic examination of a Gram-stained urethral smear without reported urethral symptoms and without urethral discharge on genital exam. Controls were men who had no urethral inflammation, no urethral symptoms, and no urethral discharge on genital exam. We used a cohort study design to estimate the incidence of asymptomatic urethral inflammation over time and identify characteristics associated with the incidence of this condition.

Results: Twenty-one of the 317 MSW had asymptomatic urethral inflammation at enrollment (6.6%; 95% CI 4.1%-9.9%). Relative to controls (n=134), cases (n=21) were significantly more likely to have a lifetime history of NGU (20% vs. 5% p=0.04). Cases were also somewhat more likely than controls to have a lifetime history of Chlamydia trachomatis (CT) (29% vs. 16% p=0.19), somewhat more likely than controls to have ≥ 2 sex partners in the past two months (74% vs. 52%, p=0.09), and somewhat less likely to be non-Hispanic white (38% vs. 52%, p=0.26), although these differences were not statistically significant. Men met criteria for asymptomatic urethral inflammation at 121 of 1444 eligible follow-up visits over 106.6 person-years at risk for an estimated incidence rate of 1.14 cases per person-year (95% CI: 0.94-1.4). Non-Hispanic Black MSW [aRR 1.84 (1.24-2.72), p=0.002), those who reported ≥ 2 sex partners in the two months prior to enrollment [aRR 1.62 (1.06-2.47), p=0.02], and those who had NGU at enrollment [aRR 1.64 (1.08-2.50), p=0.02] were significantly more likely to experience an incident episode of asymptomatic urethral inflammation. In contrast, having CT at enrollment was not associated with asymptomatic urethral inflammation [aRR 0.75 (0.44-1.27), p=0.28].

Discussion: In these MSW attending an urban sexual health clinic, the prevalence of asymptomatic urethral inflammation was low but incidence was high. Significant associations with non-Hispanic Black race/ethnicity, NGU at enrollment, and ≥2 partners in the past two months but not prior CT infection suggest that persistent inflammation may occur frequently in men subsequent to non-chlamydial urethral infections. Whether asymptomatic urethral
inflammation is associated with adverse health consequences is unknown and should be investigated.