Non-gonococcal urethritis and its relationship to three novel bacterial vaginosis (BV) associated bacteria

Objective: Non-gonococcal urethritis (NGU) is the most common urethral syndrome in the United States, yet up to 50% of cases are of unknown etiology. Bacterial-vaginosis associated bacteria (BVAB), highly predictive of BV in cisgender women, have been detected in cisgender men and may explain some cases of NGU. We sought to determine the frequency and correlates of three BVAB in cisgender men and evaluate whether they were associated with NGU. Methods: We enrolled cisgender men who have sex with women (MSW) from a sexually transmitted disease (STD) clinic in Seattle, WA. Participants completed a computer-assisted self-interview (CASI), underwent a clinical interview and examination, and provided a urethral swab and urine specimen. We quantitated polymorphonuclear leukocytes (PMNs) on a Gram stained urethral smear and defined NGU as ≥5 PMNs per high power field plus either urethral symptoms or visible discharge in the absence of Neisseria gonorrhoeae. First void urine specimens were tested for Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG), using Aptima assays (Hologic, Inc. San Diego, CA) and for BVAB2, Mageeibacillus indolicus, and Sneathia spp. using laboratory-developed quantitative polymerase chain reaction (qPCR) assays. We also tested a subset of men for Trichomonas vaginalis (TV), Ureaplasma urealyticum (UU), herpes simplex virus, and adenovirus using qPCR. We used logistic regression to evaluate potential associations between BVAB and NGU. Results: A total of 317 MSW met inclusion criteria and were included in these analyses. Of these, thirty-six (11.4%) had BVAB2, 17 (5.4%) had M. indolicus and 67 (21.1%) had Sneathia spp. No sociodemographic characteristics were associated with any of the BVAB. However, men with each of these three BVAB were significantly more likely to report ≥3 sex partners in the past two months (BVAB2: 47.2% vs. 23.0%, p=0.01; M. indolicus: 52.9% vs. 24.2%, p=0.03; Sneathia spp.: 42.2% vs. 21.5%, p<0.01). In the subset of 174 men with UU test results, UU was significantly more common among men with BVAB2 (68.4% vs. 21.3%, p <0.001), M. indolicus (66.7% vs. 25.0%, p =0.04), and Sneathia spp. (54.1% vs. 19.0%, p<0.001). There was no association of NGU with BVAB2 or with M. indolicus in bivariate or multivariable analyses. Men with Sneathia spp. were significantly less likely to have NGU (25.4% vs. 40.0%, AOR=0.36, 95% CI=0.13-0.97). Results were similar when restricting the analysis to men without other known pathogens, although the association with Sneathia spp. was no longer significant. In a subset of men with longitudinal data, all three BVAB were frequently detected over multiple visits and often detected together. Conclusions: This analysis did not confirm prior observations of increased risk of NGU associated with any of these three BVAB. More research investigating how the number of female partners influences BVAB colonization in MSW may inform our understanding of acquisition and clearance in women.