Fannyhessea vaginae and Clearance of Lactobacillus iners Are Associated With Incident Nonchlamydial Non- Mycoplasma genitalium Urethritis in Men Who Have Sex With Women

Abstract

Background: The etiology of nongonococcal urethritis (NGU) is incompletely understood. We sought to determine if genitourinary bacterial diversity or specific taxa were associated with incident NGU.

Methods: From August 2014 to July 2018, men who have sex with women attending a sexual health clinic were clinically evaluated, including Mycoplasma genitalium (MG) and Chlamydia trachomatis (CT) testing, at enrollment and 6 monthly visits. New cases of NGU (≥5 polymorphonuclear leukocytes per high-power field in urethral exudates plus either symptoms or visible discharge) and their visit preceding NGU diagnosis were matched 1:1 to 2 sequential visits without NGU (controls). We determined associations with incident NGU and applied broad-range 16S rRNA gene polymerase chain reaction and sequencing to urine samples from each visit. We used conditional logistic regression to evaluate the association of Shannon Diversity Index, species richness, Haemophilus influenzae , Fannyhessea vaginae, Lactobacillus iners, and Streptococcus mitis group with incident non-CT-non-MG-NGU (NCNM-NGU).

Results: Of 62 matched case-control pairs, median age was 32 years. Higher Shannon Diversity Index the previous month was associated with higher odds of incident NCNM-NGU (adjusted odds ratio [aOR], 2.8 per unit increase; 95% confidence interval [CI], 1.03-7.47), as was F. vaginae at NGU diagnosis (aOR, 5.1; 95% CI, 1.28-20.15), F. vaginae acquisition (aOR, 13.8; 95% CI, 1.96-97.33), and consistent carriage of F. vaginae (aOR, 16.1; 95% CI, 1.66-156.29). Odds of NCNM-NGU were higher when L. iners cleared between visits (aOR, 18.0; 95% CI, 1.08-299.24). Neither the H. influenzae nor S. mitis group was associated with incident NCNM-NGU.

Conclusions: F. vaginae acquisition/detection and L. iners clearance were associated with urethritis. This merits investigation in larger longitudinal studies using species-specific detection methods.