Bacterial vaginosis-associated bacteria in cisgender men who have sex with women: prevalence, association with non-gonococcal urethritis and natural history.

OBJECTIVES: Bacterial vaginosis-associated bacterium 2 (BVAB2), Mageeibacillus indolicus and Sneathia spp are highly predictive of bacterial vaginosis (BV) in cisgender women. They have been associated with non-gonococcal urethritis (NGU) in cisgender men in some but not all populations. We evaluated this association in a cross-sectional study of cisgender men who have sex with women only (MSW). METHODS: MSW without gonorrhoea attending a sexual health clinic (SHC) from 2014 to 2018 completed a computer-assisted self-interview, clinical interview and examination. NGU was defined as ≥5 polymorphonuclear leucocytes/high-power field in urethral exudates plus either urethral symptoms or visible discharge. Urine was tested for Chlamydia trachomatis and Mycoplasma genitalium using Aptima (Hologic) and for BVAB2, M. indolicus, Sneathia spp, Trichomonas vaginalis, Ureaplasma urealyticum, Haemophilus influenzae, herpes simplex virus and adenovirus using quantitative PCR. RESULTS: Of 317 MSW age 17-71, 67 (21.1%) had Sneathia spp, 36 (11.4%) had BVAB2, and 17 (5.4%) had M. indolicus at enrolment. Having ≥3 partners in the past 2 months was the only characteristic that was more common among MSW with than those without these bacteria (BVAB2: 47% vs 23%, M. indolicus: 53% vs 24%, Sneathia spp: 42% vs 22%; p≤0.03 for all). One-hundred seventeen men (37%) were diagnosed with NGU at enrolment. There was no significant association of BVAB2, M. indolicus or Sneathia spp with NGU (adjusted OR=0.59, 95% CI 0.14 to 2.43; aOR=3.40, 95% CI 0.68 to 17.06; aOR=0.46, 95% CI 0.16 to 1.27). Of 109 MSW with monthly samples, 34 (31.2%) had one of the bacteria at one or more follow-up visits, 22 of which were co-colonised with >1. Median persistence over 6 months did not differ significantly (BVAB2=30.5 days, IQR=28-87; M. indolicus=87 days, IQR=60-126; Sneathia spp=70 days, IQR=30-135; p≥0.20 for each comparison). CONCLUSIONS: Neither BVAB2, M. indolicus nor Sneathia spp were associated with increased risk of prevalent NGU in MSW attending an SHC.

The Incidence Rate of Sexual Behaviors Among Cisgender Men Who Have Sex with Men Attending a Sexual Health Clinic.

Although nuanced parameterization of sexual behavior may improve estimates from mathematical models of human immunodeficiency virus and sexually transmitted infection transmission, prospective estimates of the incidence of specific sexual behaviors among men who have sex with men (MSM) are limited. From December 2014 to July 2018, MSM with and without nongonococcal urethritis (NGU) completed weekly diaries over 3-12 weeks. Incidence rates of any sex, receptive anal sex, insertive anal sex, insertive oral sex, receptive rimming, and receptive hand-penile contact were 1.19, 0.28, 0.66, 0.90, 0.24, and 0.85 episodes per person-week, respectively, among 104 MSM with NGU at baseline, and 1.33, 0.54, 0.32, 0.95, 0.44, and 0.88 episodes per person-week, respectively, among 25 MSM without NGU at baseline. Most receptive anal sex (NGU + 83%, NGU - 86%) and insertive anal sex (NGU + 85%, NGU - 76%) episodes were condomless. MSM engaged in sex just over once per week, and condom use was infrequent. Insertive oral sex and receptive hand-penile contact were the most common behaviors.

Incidence of Nongonococcal Urethritis in Men Who Have Sex With Women and Associated Risk Factors.

BACKGROUND: Incidence and risk factors for nongonococcal urethritis (NGU) remain poorly defined. We conducted a cohort study to estimate the incidence of NGU and identify risk factors in men who have sex with women. METHODS: We enrolled cisgender male sexually transmitted disease clinic attendees 16 years or older who reported exclusively female partners. At enrollment and 6 monthly follow-up visits, men underwent a clinical examination, provided urethral swab and urine specimens, completed a sexual behavior survey and biweekly diaries, and were tested for Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) using Aptima assays (Hologic, Inc). Nongonococcal urethritis was defined as ≥5 polymorphonuclear leukocytes per high-power field plus either urethral symptoms or visible discharge. We estimated the incidence of NGU overall, asymptomatic and symptomatic NGU, non-CT/non-MG NGU, and CT/MG-associated NGU using Poisson regression for clustered outcomes. We performed relative risk binomial regression for clustered data to identify characteristics associated with incident NGU. RESULTS: From August 2014 to July 2018, 307 participants at risk for NGU contributed 109.4 person-years. Median age was 32 years, and 52% were White. At enrollment, 107 men had NGU; of these, 88% were symptomatic, 27% had CT, and 22% had MG. Fifty men had 60 cases of incident NGU (incidence rate, 56 per 100 person-years; 95% confidence interval, 43-74). Unlike prevalent NGU at enrollment, CT/MG-associated incident NGU was rare (incidence rate, 7; 95% confidence interval [CI], 4-15), and most (78%) incident NGU was asymptomatic. Risk factors for incident NGU were ≤ high school education (adjusted rate ratio [ARR], 2.45; 95% CI, 1.19-5.00), history of CT (ARR, 2.15; 95% CI, 1.08-4.27), history of NGU (ARR, 2.67; 95% CI, 1.27-5.62), and NGU at enrollment (ARR, 2.03; 95% CI, 1.04-3.98). Neither condom use nor having a new partner was associated with incident NGU; Black race was only associated with incident symptomatic and non-CT/non-MG NGU. CONCLUSIONS: Incidence of NGU was high, predominantly non-CT/non-MG and asymptomatic. Future studies should investigate the etiology and clinical significance of asymptomatic NGU.

Long Duration of Asymptomatic Mycoplasma genitalium Infection After Syndromic Treatment for Nongonococcal Urethritis.

BACKGROUND: Although Mycoplasma genitalium (MG) is an acknowledged cause of nongonococcal urethritis (NGU), access to diagnostic testing is limited. Syndromic management is common, yet little is known about natural history. METHODS: Between August 2014 and April 2016, 13 heterosexual men aged ≥16 years with MG were identified within a cohort study of men with and without NGU attending an urban sexually transmitted diseases clinic. Men had 6-7 monthly visits. NGU was defined as ≥5 polymorphonuclear leukocytes per high-power field on urethral Gram stain plus either visible urethral discharge or urethral symptoms. Men with NGU received 1 g of azithromycin. Men with persistent NGU received moxifloxacin 400 mg for 14 days. First-void urine was retrospectively tested for MG using transcription-mediated amplification. Resistance-associated mutations were detected by polymerase chain reaction (PCR) and sequencing. Organism load was determined by quantitative PCR. RESULTS: Sixty-two percent of MG-positive men had macrolide resistance-mediating mutations (MRMM) at enrollment; 31% had parC mutations (all outside the quinolone resistance-determining region). MG persisted after azithromycin in 7 men, 6 of whom had MRMM. The median duration of persistence in the absence of curative therapy was 143 days (range, 21-228). Five men experienced symptom resolution after azithromycin, but MG persisted for another 89-186 days before moxifloxacin. Organism load was somewhat lower in MRMM than wild-type infections (P = .16). CONCLUSIONS: The high prevalence of macrolide resistance and long duration of infection after symptom resolution highlights the need for diagnostic MG testing of men with NGU to direct therapy.

Cross-sectional study of urethral exposures at last sexual episode associated with non-gonococcal urethritis among STD clinic patients.

OBJECTIVE: Although Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) are major causes of non-gonococcal urethritis (NGU), up to 50% of cases are of unknown aetiology. We sought to identify urethral exposures at last sexual episode associated with NGU and non-CT/non-MG NGU to identify anatomical sites from which aetiologically relevant micro-organisms may be acquired. METHODS: We enrolled STD clinic patients with and without NGU assigned male sex at birth and age ≥16 into a cross-sectional study. NGU was urethral symptoms or visible discharge plus ≥5 polymorphonuclear leucocytes without Neisseria gonorrhoeae. Urine was tested for CT and MG (Aptima). We used logistic regression to estimate the association between urethral exposures at last sex and NGU separately among cisgender men and transgender women who have sex with men (MSM/TGWSM) and cisgender men who have sex with women (MSW). RESULTS: Between 8 August 2014 and 1 November 2017, we enrolled 432 patients, including 183 MSM/TGWSM (118 NGU+, 65 NGU-) and 249 MSW (126 NGU+, 123 NGU-). The mean age was 34; 59% were white. CT and MG were detected in 72 (30%) and 49 (20%) NGU+ participants, respectively. Compared with MSM/TGWSM reporting only non-urethral exposures at last sex, those reporting insertive anal intercourse (IAI) only (adjusted OR (AOR)=4.46, 95% CI 1.09 to 18.19) and IAI with insertive oral sex (IOS) (AOR=7.88, 95% CI 2.67 to 23.26) had higher odds of NGU. MSM/TGWSM reporting IOS only had no significant increased odds (AOR=1.67, 95% CI 0.58 to 4.85). Compared with MSW whose only urethral exposure at last sex was vaginal sex (VS), MSW reporting IOS and VS had similar odds of NGU (OR=0.84, 95% CI 0.50 to 1.41). The results were similar for non-CT/non-MG NGU. CONCLUSIONS: Among MSM/TGWSM, IAI may lead to transmission of yet-unidentified rectal micro-organisms that cause non-CT/non-MG NGU, in addition to transmission of known pathogens. Sites of urethral exposure appear less important for understanding NGU risk among MSW due to minimal variation in behaviour.

Lack of Association Between the S83I ParC Mutation in Mycoplasma genitalium and Treatment Outcomes Among Men Who Have Sex With Men with Nongonococcal Urethritis.

From February 2015 to October 2017, among 20 men who have sex with men with Mycoplasma genitalium-associated nongonococcal urethritis, 15% had macrolide resistance and S83I ParC mutations. Azithromycin followed by moxifloxacin cleared Mycoplasma genitalium in 2 of 2 with and 11 of 13 without S83I mutations. Dual failures were cleared after doxycycline. S83I mutations were not associated with moxifloxacin failure.

Resolution of Symptoms and Resumption of Sex After Diagnosis of Nongonococcal Urethritis Among Men Who Have Sex With Men.

BACKGROUND: Standard counseling at nongonococcal urethritis (NGU) diagnosis includes advice to abstain from sex for at least 7 days and until symptoms resolve. METHODS: From December 2014 to July 2018, we enrolled men who have sex with men and received azithromycin (1 g) for NGU at the Public Health-Seattle and King County STD Clinic. Over 12 weeks of follow-up, participants reported daily urethral symptoms and sexual activity on web-based diaries. Nongonococcal urethritis was defined as urethral symptoms or visible urethral discharge plus 5 or greater polymorphonuclear leukocytes per high-power field. Time of symptom resolution was defined as the first of 5 consecutive asymptomatic days. RESULTS: Of 100 participants with NGU and no Chlamydia trachomatis (CT)/Mycoplasma genitalium (MG) coinfection, 36 (36%), 22 (22%), and 42 (42%) had CT-NGU, MG-NGU, and non-CT/non-MG NGU, respectively. Among men with MG-NGU, 94% had a macrolide resistance mutation. For all etiologies, median time to symptom resolution after azithromycin was 7 days (95% confidence interval [CI], 5-9); 37% had symptoms lasting longer than 7 days. For men with CT-NGU, MG-NGU, and non-CT/non-MG NGU, median time to symptom resolution was 4 days (95% CI, 2-6; 16% >7 days), undefined days (95% CI, 7 to undefined; 60% >7 days), and 7 days (95% CI, 5-11; 46% >7 days), respectively. Median time to first sexual activity (any type) was 12 days (95% CI, 11-17); it was 16 days (95% CI, 12-18) to first urethral sexual exposure. Twenty-seven percent did not avoid urethral exposure for the recommended period. CONCLUSIONS: Counseling at NGU diagnosis should educate patients that symptoms may persist more than 7 days, particularly for non-CT NGU, and emphasize the rationale for the 7-day abstinence period.

Estimated Performance of Transvaginal Ultrasonography for Evaluation of Postmenopausal Bleeding in a Simulated Cohort of Black and White Women in the US.

IMPORTANCE: Black women in the US with endometrial cancer (EC) are more likely to be diagnosed with advanced-stage disease independent of insured status and histologic type. The most common way of diagnosing EC at early stages is through screening of people with postmenopausal bleeding to detect endometrial thickness (ET). This approach may disproportionately underperform in Black women secondary to a higher prevalence of fibroids and nonendometrioid EC in this population, both of which affect the quality of ET measurement. OBJECTIVE: To compare the performance of recommended transvaginal ultrasonography (TVUS) ET thresholds as a screening method to prompt endometrial biopsy by race in a simulated cohort of symptomatic women. DESIGN, SETTING, AND PARTICIPANTS: In a simulated retrospective cohort study, based on data from Surveillance, Epidemiology, and End Results (SEER) national cancer registry 2012-2016; the US census; and published estimates of ET distribution and fibroid prevalence, diagnostic test characteristics of the 3-mm or more, 4-mm or more, and 5-mm or more ET thresholds for biopsy to capture EC diagnoses were calculated. The simulated cohort was constructed from February 2, 2020 (date of access to SEER data), to August 31, 2020. Analysis occurred from September 30, 2020, to March 30, 2021, including the primary analysis and the sensitivity calculations. MAIN OUTCOMES AND MEASURES: The main outcome measured was accuracy of the TVUS ET threshold to accurately identify cases of EC, measured by sensitivity, negative predictive value, and area under the curve (AUC). RESULTS: A total of 367 073 simulated Black and White women with postmenopausal bleeding were evaluated, including 36 708 with EC. Among Black women, the currently recommended 4-mm or greater ET threshold prompted biopsy for fewer than half of EC cases (sensitivity, 47.5%; 95% CI, 46.0%-49.0%); of women referred for biopsy, 13.1% were EC cases (positive predictive value, 13.1%; 95% CI, 12.5%-13.6%). The AUC for the 4-mm or more threshold was 0.57 (95% CI, 0.56-0.57). In contrast, among the White women, the 4-mm or more threshold led to biopsy for most with EC (sensitivity, 87.9%; 95% CI, 87.6%-88.3%). Of those referred for biopsy, 14.6% had EC (positive predictive value, 14.6%; 95% CI, 14.4%-14.7%); AUC was 0.73 (95% CI, 0.73-0.74). The same variations held for the 3-mm or more and 5-mm or more ET thresholds: sensitivity, positive predictive value, and AUC were consistently lower for Black women than White women. CONCLUSIONS AND RELEVANCE: The findings of this simulated cohort study suggest that use of ET as measured by TVUS to determine the need for EC diagnostic testing in symptomatic women may exacerbate racial disparities in EC stage at diagnosis. In simulated data, TVUS ET screening missed almost 5 times more cases of EC among Black women vs White women owing to the greater prevalence of fibroids and nonendometrioid histologic type in Black women.

The Impact of Fibroids and Histologic Subtype on the Performance of US Clinical Guidelines for the Diagnosis of Endometrial Cancer among Black Women.

Objective: To assess the predicted performance of the American College of Obstetrics and Gynecology (ACOG)'s recommended endometrial thickness (ET) of ≥4mm via transvaginal ultrasound (TVUS) for a simulated cohort of US Black women with postmenopausal bleeding (PMB). Main Outcome Measure: Performance characteristics of 3+, 4+, and 5+mm ET thresholds were assessed including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Receiver Operator Characteristic (ROC) curves, and the area under the curve (AUC). Methods: We used endometrial cancer parameters from ET studies upon which guidelines are based, as well as documented population characteristics of US Black women, to simulate a cohort of US Black women with PMB. Annual endometrial cancer (EC) prevalence overall and by histology type (I and II), history and current diagnosis of uterine fibroids, and visibility of endometria were estimated. Sensitivity analyses were performed to assess performance changes with quality of baseline parameters and impact of fibroids on ET visibility. Results: In the main model with the 4+mm recommended threshold, TVUS ET showed a sensitivity of 47.5% (95% CI: 46.0-49.0%); specificity of 64.9% (95% CI: 64.4-65.3%); PPV of 13.1% (95% CI: 12.5-13.6%); NPV of 91.7% (95% CI: 91.4-92.1%), and AUC of .57 (95% CI: .56-.57). Conclusions: Among a simulated cohort of US Black women, the recommended 4+mm ET threshold to trigger diagnostic biopsy for EC diagnosis performed poorly, with more than 50% of cases missed and an 8-fold higher frequency of false negative results than reported for the general population.