We conducted our study at the Melbourne Sexual Health Centre, the largest public STI clinic in Victoria, Australia. Starting August 2008, the clinic began treating sexual contacts of M. genitalium–infected patients and recording these cases in the clinic database. We defined a contact as someone who reported anal or vaginal sex with or without condoms with a person reporting a recent diagnosis of M. genitalium infection. Persons reporting only oral sex did not meet our definition of a contact. Persons were included at first report of being a contact, and repeat presentations were excluded. MSM were defined as men reporting any sex with men within the preceding 12 months.

We tested contacts by using an in-house real-time PCR assay targeting the 16s rRNA gene (27). Men were predominantly tested by using a first-pass urine sample, rarely with a urethral swab, and with an anorectal swab if anal sex was reported. Women were tested using a high vaginal swab or cervical swab, but a first-pass urine sample was used if patients preferred, and an anorectal swab was taken if anal sex was reported. We did not test for pharyngeal M. genitalium in men or women because of the absence of published evidence for infection at this anatomic site (15,28).

We recorded all sexual contacts of the M. genitalium–infected patients who attended the clinic during August 2008–July 2016 in the clinic database. We extracted demographic, behavioral, laboratory, and clinical data from the clinic’s electronic medical records, including number and sex of sex partners, sexual practices within the preceding 3 months, whether these partners were considered casual or regular partners, and consistency of condom use. Data were routinely obtained by clinicians and computer-assisted self-interview. Signs and symptoms among men reporting sexual contact with an infected person were urethral discharge, irritation, dysuria, rectal pain, and bleeding. Signs and symptoms among women reporting sexual contact with an infected person were abnormal vaginal discharge, dysuria, abnormal bleeding, and lower abdominal pain.

We performed statistical analyses by using Stata version 12 (StataCorp LLP, College Station, TX, USA). We calculated the proportion of contacts infected with M. genitalium, including 95% CIs, for 3 groups: women, heterosexual men, and MSM. We examined factors associated with infection for 2 groups: 1) heterosexual men and women, and 2) MSM. We conducted univariate logistic regression for each group by using demographic and behavioral characteristics as independent variables and detection of M. genitalium as the dependent variable. We treated age as a binary variable, with a cutoff at 27 years for all groups. We also treated the number of sex partners as a binary variable, with a cutoff at 1 for all groups. We used the χ² or Fisher exact test, where appropriate, to assess the statistical significance of these associations. We calculated crude odds ratios (ORs) with 95% CIs, entered variables with p values <0.10 in the univariate analysis in the multivariate analysis by using forward stepwise logistic regression, and calculated adjusted ORs (aORs) with 95% CIs. In multivariate analyses, we omitted the binary variable for number of partners because of collinearity with the variable indicating whether the notifying partner was a regular or casual partner. Because some MSM had urine tests, others had rectal swabs, and some had both, we entered each test, rather than each person, into a multivariate model examining risk factors for infection in MSM by using robust SEs to account for clustering around persons.

In a subset of contacts, we were able to identify the referring partner in the clinic’s electronic medical record system. If this partner’s M. genitalium infection was diagnosed at the clinic within 40 days of the contact’s presentation, we included the contact in a further analysis of sexual partnerships (dyads).

Figure

Figure. Flowchart for 441 persons examined at Melbourne Sexual Health Centre who reported sexual contact with a Mycoplasma genitalium–infected partner, Melbourne, Victoria, Australia, August 2008–July 2016. Dashed lines indicate persons excluded for...

During the study period, a total of 441 presentations to the clinic were made by patients reporting sexual contact with a person with M. genitalium infection (Figure). We excluded repeat presentations by the same person (n = 25), those missing laboratory test results (n = 16), those missing >50% of the queried behavioral data (n = 1), and those not meeting our definition of a contact (n = 22). These exclusions left 377 (85.5%) persons (139 women, 126 heterosexual men, and 112 MSM) for analysis.

In this study, a high proportion of persons reporting contact with an M. genitalium–infected partner were infected, including 48% of women, 31% of heterosexual men, and 42% of MSM tested at both the rectum and urethra. The sample size for this study exceeds the combined total of sample sizes in previously published studies, adding precision to estimates of the probability of infection and transmissibility of M. genitalium between sex partners (8–14). These findings will inform guidelines for the management of sexual contacts of M. genitalium–infected patients and provide an evidence base for informed discussion between clinicians and their patients regarding the appropriateness of presumptive treatment for contacts of infected patients or recommending testing and return for treatment.

In this study, among heterosexual contacts, women were twice as likely as men to be infected with M. genitalium, after adjusting for condom use and nature of relationship. This finding could be attributable to the female genital tract’s greater susceptibility to STIs, with the larger surface area of the cervico-vaginal mucosa compared with the urethral mucosa (29), and female sex hormones thought to enhance susceptibility to STIs (30). Heterosexual contacts notified by a regular partner were twice as likely to be infected, suggesting that multiple sexual acts or events of exposure might increase risk for acquisition of M. genitalium. Less than 100% condom use for penile-vaginal sex with a regular partner appeared to double the risk for M. genitalium infection among heterosexual contacts, and although this increased risk was not significant (p = 0.07), it does suggest that condoms provide protection against M. genitalium infection, as has been shown for other bacterial STIs. Concordance for M. genitalium infection in heterosexual dyads in which both partners were tested at our service was 47%, reflecting the high risk for concurrent infection in heterosexual partnerships. Overall, the prevalence of M. genitalium infection in heterosexual men and women was within the range reported for chlamydial infection in published studies (23–26).

The prevalence of M. genitalium that was observed among contacts in this study is substantially higher than the prevalence reported in comparable study populations in Melbourne. Reported prevalence estimates from these studies were 2.4% (95% CI 1.5%–3.3%) in young women attending clinics, including the site of this study (4); 1.3% (95% CI 0.3%–3.7%) in urine samples from asymptomatic heterosexual men (31); and (2.1%; 95% CI 1.1%–3.6%) in rectal swabs and urine samples from asymptomatic MSM (15), all of which are much lower than the respective prevalence estimates reported in our study of 48.2% (95% CI 39.7%–56.8%), 31.0% (95% CI 23.0%–39.8%), and 41.7% (95% CI 27.6%–56.8%).

MSM contacts had a similar likelihood of being infected with M. genitalium as women when they were tested at both the urethra and the rectum. This study highlights the importance of rectal testing for M. genitalium in MSM. Urethral positivity was only 8% in MSM, compared with 31% in heterosexual men. However, overall rectal positivity was high at 38%, and when MSM were tested at both urethral and rectal sites, 42% were positive for M. genitalium, and most of these had rectal infections. The clinic records do not indicate why some men were not tested at both sites. The higher rate of rectal infection compared with urethral infection is consistent with studies of chlamydial infection among MSM but is also likely to be influenced by the notifying partner’s reason for seeking care. When this factor was examined among MSM dyads, 29 of 34 MSM notifying partners sought care for urethral infections, suggesting that urethral infections might be more likely than rectal infections to cause symptoms.

Our study has several limitations. The study is retrospective and relies on self-report of exposure to infection without laboratory confirmation. As such, the data reflect the prevalence of infection only among those persons who seek care reporting exposure to M. genitalium rather than among all of those exposed. We have no information on contacts of infected patients who did not attend the clinic, and these persons are likely to be systematically different from those who did seek out testing and treatment. These findings might also not be generalizable to non–STI clinic populations or to other populations with a different background prevalence of M. genitalium infection. Although we considered the notifying partner the index patient for analytical purposes, we cannot ascertain the transmission direction between sex partners or whether transmission occurred through a third person. Sexual behavioral data were self-reported and hence subject to recall bias. The most notable limitation was the lack of dual-site testing for MSM contacts, which limited our ability to report precise estimates of infection among MSM and to examine concordance in MSM dyads.

Presumptive treatment of sexual contacts reduces the risk for reinfection and is recommended for STI syndromes such as nongonococcal urethritis (20). In the contacts of M. genitalium­–infected persons in this study, presumptive treatment would have treated 1 infection for every 2–3 treatments. However, the decision to recommend presumptive treatment must also take into account potential harms and benefits to the contact and their sex partners. Although heterosexual men had a slightly lower prevalence of positivity, presumptive treatment might be more important in reducing the risk for serious sequelae, such as pelvic inflammatory disease, in female partners.

The alternate approach of treating contacts only after confirmation of M. genitalium infection represents better stewardship of antimicrobial drugs but relies on access to sensitive testing practices and a high rate of return of patients to be effective. An important consideration before presumptively treating contacts for M. genitalium infection is the increasing prevalence of macrolide resistance, which is >40% in Europe, Japan, and the United States and >75% among MSM in Australia (32–35). Furthermore, macrolide resistance is selected in 12%–18% of seemingly susceptible infections after treatment with 1 g azithromycin and extended azithromycin regimens (35). Presumptive use of macrolides for M. genitalium–infected contacts might therefore not only be ineffective in those patients with detectable resistance but also contribute to development and spread of resistance, particularly in asymptomatic contacts who believe they have been effectively treated. The only recommended treatments for macrolide-resistant M. genitalium are fourth-generation fluoroquinolones, which are expensive and can cause tendinopathy, neuropathy, and adverse central nervous system effects, which are major considerations for determining their use in persons who do not have confirmed infection. Overall, a prudent approach entails managing sexual contacts according to the informed preferences of the person and, if known, the resistance status of the notifying partner. The results of our study provide an evidence base for informed discussions between clinicians and patients at risk for infection and can inform international treatment and partner-notification guidelines.