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Symptoms, Sites, and Significance of Mycoplasma genitalium in Men Who Have Sex with Men.

Mycoplasma genitalium causes nongonococcal urethritis (NGU) in men and is associated with pelvic inflammatory disease (PID), spontaneous abortion, and premature labor in women (1,2). Most guidelines recommend azithromycin as a first-line treatment; however, macrolide resistance is widespread and increasing in many countries (3-5). In a recent study of M. genitalium urethritis in Melbourne, Victoria, Australia, 39% of cases were in men who have sex with men (MSM); macrolide resistance was detected almost twice as often in MSM as in women or heterosexual men (76% of MSM vs. 39% for women and heterosexual men combined; p = 0.005) (6). We hypothesized that this difference may have arisen from frequent treatment of MSM for Chlamydia trachomatis and Neisseria gonorrhoeae infections, resulting in exposure of asymptomatic M. genitalium infections to azithromycin.

M. genitalium has been proposed as a cause of proctitis in MSM, but few studies have examined this association. Soni et al. found M. genitalium in 4.4% of rectal swabs from 438 MSM in England and found no association with rectal symptoms (7). Francis et al. foundM. genitalium in 5.4% of rectal swabs from 500 MSM in the United States but found only a weak association with rectal symptoms (8). Bissessor et al. reported that bacterial load of rectal M. genitalium was higher in MSM with proctitis compared with those with asymptomatic infection, and detection was more common in HIV-positive than HIV-negative MSM (21% vs. 8%; p = 0.006) (9). A meta-analysis in 2009 of 19 mostly cross-sectional or case-control studies found an association between M. genitalium and HIV infection, particularly in studies from sub-Saharan Africa (10). Subsequently, M. genitalium was detected twice as commonly in women who seroconverted to HIV in a prospective study in Africa (11), but no equivalent studies in MSM are available.

We aimed to determine the proportion of asymptomatic MSM who had M. genitalium in the urethra or rectum and the prevalence of macrolide resistance and risk factors for infection. We compared these data with the proportion of tests positive for M. genitalium in MSM with symptoms of proctitis and nongonococcal urethritis to further examine the contribution of M. genitalium to these syndromes in MSM.

Methods

This cross-sectional study was undertaken during August 23, 2016-September 27, 2017, at Melbourne Sexual Health Centre (MSHC), the only public sexual health clinic in Melbourne, a city of 4.5 million. MSM [greater than or equal to] 18 years of age who were asymptomatic at both triage and clinician consultations and reported receptive anal sex within the preceding year were eligible to participate. To minimize the impact of this study on clinical and laboratory services, recruitment was restricted to 8 of 49 clinical staff members, who offered the study to consecutive eligible clients. To determine how representative participants were of all asymptomatic MSM attending MSHC, we compared positivity for rectal C. trachomatis and N. gonorrhoeae in recruited and nonrecruited MSM. We asked participants to complete a questionnaire about recent sexual risk practices and to record any anogenital symptoms experienced in the preceding week. Participants provided urine and a rectal swab specimen (self- or clinician-collected) for M. genitalium screening.

We agitated the rectal swabs in 0.6 mL of phosphate-buffered saline to release cellular material, vortexed them briefly, and centrifuged them at low speed (8,000 rcf, 10 min) to remove PCR inhibitors. This step was required to reduce inhibition that differentially affected rectal samples; in early evaluations, the internal control failed in 9 (20.5%) of 44 uncentrifuged rectal samples but in none of 106 samples subjected to centrifugation. We transferred 0.2 mL of supernatant for nucleic acid isolation using the MagNA Pure 96 DNA and viral small volume kit on the automated MagNA Pure 96 system (Roche Diagnostics, https://www. roche.com). We prepared urine samples as described previously (12). We detected M. genitalium and macrolide resistance mutations in the 23S rRNA gene using the ResistancePlus MG test (SpeeDx Pty Ltd, Australia, https:// plexpcr.com). Published evaluations of this assay report specificity for the detection of M. genitalium of 100% and sensitivities of 94.9%, 98.5%, and 98.9% (13-15).

Participants provided additional samples for C. trachomatis and N. gonorrhoeae screening of the throat, urethra, and rectum; we performed serologic testing for syphilis and HIV as indicated. We tested samples for N. gonorrhoeae and C. trachomatis by transcription-mediated amplification (Aptima Combo 2, Hologic, https://www.hologic.com).

MSM who were recalled for treatment of M.genitalium completed another questionnaire about antimicrobial drug use. We also collected throat swab specimens from men with rectal M. genitalium infection so we could perform pharyngeal M. genitalium testing. Resources were not available for testing all participants, particularly since published studies have rarely detected M. genitalium at this site. However, we hypothesized that M. genitalium may be more common in the pharynx in men with rectal M. genitalium. We agitated the throat swabs in 0.6 mL of phosphate buffered saline to release cellular material and performed nucleic acid isolation as described for the other samples.

Statistical Methods

With a sample size of 1,000, a prevalence of M. genitalium of 10% would provide 80% power ([alpha] = 0.05) to detect an odds ratio of [greater than or equal to] 1.9 for a characteristic present in 30% of those who did not have M. genitalium. We assessed associations between M. genitalium, C. trachomatis, and N. gonorrhoeae and risk factors, as well as mild urethral and anorectal symptoms reported in the questionnaire, using logistic regression.

All patients attending MSHC who have symptoms of nongonococcal urethritis or proctitis are tested for M. genitalium. During the 13-month study period, we also extracted test results from the clinic database for M. genitalium, C. trachomatis, and N. gonorrhoeae from MSM who received diagnoses of proctitis or urethritis (based on symptoms and signs, not microscopic criteria). Using univariate logistic regression, we then used corresponding test results from the asymptomatic study population as controls to assess any association between detection of each organism in the rectum and urine and diagnoses of proctitis and urethritis. For men with M. genitalium detected, we compared risk factors for macrolide resistance mutations using [chi square] or Fisher exact tests, where appropriate. We also recorded the proportions of M. genitalium patients co-infected with C. trachomatis or N. gonorrhoeae in the urethra and rectum. We compared associations between the detection of M. genitalium and that of C. trachomatis or N. gonorrhoeae in the rectum or urine in the asymptomatic study population using logistic regression, as we did with associations between M. genitalium and C. trachomatis in cases of nongonococcal urethritis diagnosed during the same period.

This project was approved by the ethics committee of the Alfred Hospital in Melbourne (project no. 278/16). All participants gave written informed consent.

Results

During August 23, 2016-September 27, 2017, a total of 1,028 MSM were triaged as asymptomatic and invited to participate in the study. Of these, 17 declined: 3 declined the additional rectal swab specimen collection, and 14 declined for reasons unrelated to the study (distress or being unable to return to the clinic). Of the remaining 1,011, a total of 6 rectal swabs were unassessable (internal control failed), and 4 did not provide a urine sample. These 10 patients were excluded from the analysis, leaving 1,001 men with assessable samples from both collection sites.

Participants had a median age of 28.8 (interquartile range 24.3-34.1). A total of 107 (10.7%) were HIV positive, and 142 (15.9%) of the HIV-negative men were taking or commencing HIV preexposure prophylaxis medication (PrEP) (Table 1).

Of the 1,001 men, 95 (9.5% [95% CI 7.7%-11.5%]) had M. genitalium detected at any site. Twenty-seven (2.7% [95% CI: 1.8%--3.9%]) had M. genitalium detected in the urine and 70 (7.0% [95% CI 5.5%-8.8%]) in the rectum; 2 men were infected at both sites. C. trachomatis was detected in 91 (9.6% [95% CI 7.8%-1L7%]) of 948 men tested at both sites, and N. gonorrhoeae was detected in 64 (6.7% [95% CI 5.2%-8.5%]) of 952 men tested at both sites (Table 2). For urine samples, M. genitalium was detected in 2.7%, C. trachomatis in 1.7%, and N. gonorrhoeae in 0.7%. For rectal samples, M. genitalium was detected in 7.0%, C. trachomatis in 8.5%, and and N. gonorrhoeae in 6.2%.

During the study period, 4,228 MSM were triaged as asymptomatic at MSHC and not offered the study but were tested for rectal C. trachomatis and N. gonorrhoeae at least once. After excluding repeat tests, positivity for C. trachomatis did not differ between nonrecruited (7.4%) and recruited (8.5%) MSM (p = 0.25), but N. gonorrhoeae was lower in nonrecruited (4.2%) than in recruited (6.2%) MSM (p = 0.006).

Detection of M. genitalium was significantly associated with younger age (odds ratio [OR] 0.96 [95% CI 0.93-0.99]) per year of increasing age. Detection of M. genitalium in the rectum was significantly associated with receptive anal sex with [greater than or equal to] 2 partners within the past 3 months (OR 1.88 [95% CI 1.08-3.3]) and inconsistent condom use for receptive anal sex (OR 2.36 [95%CI 1.24-4.81]). M. genitalium was less common in HIV-infected men than in uninfected men (4.7% vs 10.1%, p = 0.08) but was not associated with taking or commencing PrEP.

The study population of 1,001 asymptomatic MSM completed a questionnaire about the presence of any anogenital or urethral symptoms in the week before presentation (all participants were asymptomatic at recruitment). Of these, 8.7% reported any recent symptoms in the urethra (itch, discomfort, discharge, or dysuria) and 25.5% in the anorectum (itch, discomfort, pain, or bleeding). Recent symptoms were not associated with detection of M. genitalium, C. trachomatis, or N. gonorrhoeae at either site (p>0.5 for all symptoms, individually or combined; Table 3).

We compared rectal test positivity for M. genitalium, C. trachomatis, and N. gonorrhoeae in the asymptomatic study population (n = 1,001) with rectal positivity in MSM who had symptoms of proctitis (n = 355) during the study period (Table 4). M. genitalium detection was similar in MSM with proctitis and asymptomatic MSM (5.6% for proctitis vs. 7.0% for asymptomatic; OR 0.79 [95% CI 0.45-1.35]; p = 0.38). However, rectal detection of both C. trachomatis (21.3% vs. 8.5%, OR 2.93 [95% CI 2.05-4.18]) and N. gonorrhoeae (28.4% vs. 6.2%, OR 5.97 [95% CI 4.15-8.61]) was significantly more common in MSM with symptoms of proctitis than in asymptomatic MSM.

We compared the urine test positivity for M. genitalium and C. trachomatis in the asymptomatic study population (n = 1,001) with the positivity in 1,019 MSM presenting with symptoms of NGU during the study period. Both M. genitalium (8.1% vs. 2.7%; OR 3.20 [95% CI 2.03-5.18]) and C. trachomatis (14.5% vs. 1.7%, OR 9.99 [95% CI 5.89-18.07]) were more commonly detected in MSM with symptoms of NGU than in asymptomatic MSM (Table 4).

We detected macrolide resistance mutations in 80 (84.2% [95% CI 75.3%-90.9%]) of 95 men who had positive M. genitalium tests (Table 5). We found no significant association between resistance and site of infection, and although these mutations were more common in MSM reporting recent use of antimicrobial drugs, particularly azithromycin, this difference was not significant. Macrolide resistance mutations were found in all HIV-negative men taking or commencing PrEP (p = 0.06).

Table 6 shows the proportion of asymptomatic MSM with M. genitalium who were co-infected with C. trachomatis and N. gonorrhoeae, by anatomic site. Rectal C. trachomatis and rectal N. gonorrhoeae were detected with similar frequency in MSM with rectal M. genitalium compared with men without rectal M. genitalium (C. trachomatis, 9.2% vs. 8.4%, p = 0.82; N. gonorrhoeae, 6.1% vs. 6.2%; p = 0.98). However, C. trachomatis and N. gonorrhoeae were detected significantly more often in the urine of asymptomatic men with M. genitalium compared with men without urethral M. genitalium (C. trachomatis, 7.4% vs. 1.5%, p = 0.03; N. gonorrhoeae, 7.4% vs. 0.5%, p = 0.002).

In contrast, in MSM with NGU, detection of C. trachomatis was uncommon in men with urethral M. genitalium (2.5%) compared with men without urethral M. genitalium (15.5%; p = 0.001). Overall, of 89 MSM with M. genitalium infection detected at any site and tested for all 3 infections, 15 (16.9% [95% CI 9.7-26.3]) were co-infected with either C. trachomatis or N. gonorrhoeae. Of 143 MSM with either C. trachomatis or N. gonorrhoeae, 15 (10.5% [95% CI 5.9%-16.7%]) were co-infected with M. genitalium.

Throat swabs were collected from 54 (77.1%) of 70 MSM with rectal M. genitalium, all 60 MSM with rectal N. gonorrhoeae, and 37 (45.7%) of 81 MSM with rectal C. trachomatis (routine clinic testing for pharyngeal C. trachomatis commenced halfway through the study). Only 1 (1.9% [95% CI 0.05-9.9]) of 54 MSM with rectal M. genitalium had pharyngeal M. genitalium. In contrast, 8 (21.6% [95% CI 9.8-38.2]) of 37 MSM with rectal chlamydia had pharyngeal chlamydia, and 21 (35% [95% CI 23.1-48.4]) of 60 MSM with rectal gonorrhea had pharyngeal gonorrhea. Thus, dual pharyngeal and rectal infection with M. genitalium was significantly less common than was observed for C. trachomatis (p = 0.002) and N. gonorrhoeae (p<0.001). Of all men tested, 12 (3.0%) of 407 had pharyngeal chlamydia and 62 (6.4%) of 963 had pharyngeal gonorrhea.

Discussion

Almost 1 in 10 asymptomatic MSM attending a sexual health center in Melbourne, Victoria, Australia, during a 13-month period were infected with M. genitalium, and 84% of these infections were macrolide resistant. M. genitalium was detected in 7% of asymptomatic MSM at the rectum, 2.7% at the urethra, and only 0.2% at both sites. Overall, M. genitalium was as common as chlamydia and more common than gonorrhea in asymptomatic MSM. The proportion of asymptomatic MSM with M. genitalium in the rectum was no different from that in MSM with symptoms of proctitis during the same period. Co-infection with C. trachomatis or N. gonorrhoeae was common and present in 17% of M. genitalium infections. Screening MSM for C. trachomatis and N. gonorrhoeae will identify these infections, but if they are treated, asymptomatic M. genitalium infections, present in 10% of these cases, may be inadvertently exposed to azithromycin, exerting selection pressure for macrolide resistance, which may explain the rapid escalation of resistance in M. genitalium in MSM. The situation facing clinicians is challenging, because the recommended treatment for macrolide-resistant M. genitalium, moxifloxacin, is expensive, potentially toxic, and difficult to obtain and may generate further antimicrobial resistance, all of which should be considered before screening asymptomatic MSM for M. genitalium.

The detection of M. genitalium in 9.5% of asymptomatic MSM contrasts with a recent meta-analysis finding lower average prevalence estimates among MSM of 3.2% (95% CI 2.1%-5.1%) in 5 community-based studies and 3.7% (95% CI 2.4%-5.6%) in 4 clinic-based studies (16). This discrepancy may be because the meta-analysis included several studies that tested only urine, where M. genitalium is less common, or because of geographic or temporal differences. A recent Sydney study reported M. genitalium in 13.4% of MSM (rectum 8.9%, urine 4.7%) (17).

Rectal positivity for M. genitalium in men with symptoms of proctitis was no higher than in asymptomatic MSM. Furthermore, a report of mild anorectal symptoms over the preceding week was not associated with rectal M. genitalium and presumably reflected nonspecific self-limiting symptoms. In contrast, rectal C. trachomatis and N. gonorrhoeae were significantly associated with current symptoms of proctitis (OR 3 and 6, respectively). Two previous studies found no association between rectal M. genitalium and symptoms, whereas 1 reported a weak association of borderline significance (7,8,17). Other studies suggesting that M. genitalium may cause proctitis have not compared frequency of detection in symptomatic and asymptomatic patients (18,19).

The high proportion of cases with macrolide resistance in this study (84%) is consistent with recent MSHC data. MSHC has been using the same resistance assay for M. genitalium since June 20, 2016; by March 27, 2018, a total of 943 patients with NGU, cervicitis, PID, proctitis, or contacts of infection had M. genitalium detected. Macrolide resistance mutations were routinely detected in 265 (51.5% [95% CI 47.0-55.9]) of 515 heterosexual men and women compared with 349 (81.5% [95% CI 77.5-85.1]) of 428 MSM (p<0.0001). This difference between MSM and heterosexuals was also seen in a recent study in Spain, which reported macrolide resistance in 71% of MSM compared with 13% of heterosexuals (p<0.001); prior azithromycin exposure was a significant risk factor for resistance (20). Other recent studies in MSM report macrolide resistance in 74%-80% of M. genitalium infections (17,21). The high proportion of cases with resistance reduced our ability to identify risk factors; we detected resistance in 90% of infected men who recalled taking any antimicrobial drug within the previous 3 months and 100% of those who recalled taking azithromycin, but this difference was not significant.

Asymptomatic urethral co-infections with C. trachomatis and N. gonorrhoeae were significantly associated with detection of M. genitalium, but this association was not seen with rectal co-infections. Although the association between M. genitalium and urethral co-infections was significant, we found only 4 cases of co-infection. Specific host factors might possibly lead some men to tolerate, and therefore accumulate, urethral infections. The proportion of asymptomatic men with M. genitalium detected in their urine was higher than for C. trachomatis and for N. gonorrhoeae, again consistent with the hypothesis that M. genitalium might be less pathogenic than C. trachomatis or N. gonorrhoeae.

Pharyngeal M. genitalium is reported as rare (22-26), so to optimize detection, we limited pharyngeal testing to MSM with rectal infection because other pharyngeal sexually transmitted infections (STIs) are commonly concurrent with rectal infections. Of patients with rectal M. genitalium, only 1.9% had pharyngeal M. genitalium, which was much lower than for pharyngeal C. trachomatis (22%) and N. gonorrhoeae (35%) in MSM with these rectal infections. However, C. trachomatis and N. gonorrhoeae were detected by transcription mediated amplification. A recent Sydney study using the ResistancePlus PCR assay also found no pharyngeal M. genitalium infections in 508 MSM (rectal prevalence 8.9%), providing further evidence that M. genitalium is rarely detected in pharyngeal specimens (17).

Of concern, 17% of MSM with M. genitalium were co-infected with C. trachomatis or N. gonorrhoeae, predominantly reflecting rectal infections. The rectum appears likely to be a reservoir for asymptomatic M. genitalium, and treatment of concurrent STIs promotes macrolide resistance, which is estimated to develop de novo in 12% of wild-type cases exposed to single-dose azithromycin (6). The high proportion of macrolide-resistant M. genitalium in MSM may be caused by the combination of a high background prevalence of asymptomatic rectal M. genitalium, a high frequency of concurrent chlamydia or gonorrhea, and the resulting use of azithromycin in this population.

This study has limitations, including reliance on recall of antimicrobial drug exposure, recruitment from a sexual health center where findings may not reflect MSM elsewhere, and restricted testing for pharyngeal M. genitalium. Centrifugation to remove PCR inhibitors was undertaken on rectal samples because of higher levels of inhibition, which could have reduced the sensitivity of rectal M. genitalium detection. Furthermore, we were unable to approach all MSM attending the clinic. The study population had a higher proportion with rectal gonorrhea, but not chlamydia, compared with those who were not recruited, possibly because our inclusion criteria required receptive anal sex in the previous year and the nonrecruited group included MSM attending an express service for lower-risk men. This difference suggests that the study population may have had a slightly elevated risk of infection, which should be considered alongside our findings. Diagnoses of nongonococcal urethritis and proctitis were predominantly clinical, based on symptoms and sexual risk, which is likely to lead to a lower prevalence of STIs in these groups compared with studies that required microscopic criteria for case definitions. However, clinical diagnoses are commonly used in primary care and are supported by the strong associations we observed between detection of C. trachomatis and N. gonorrhoeae and the symptom-based definitions of proctitis and urethritis.

We detected M. genitalium in 9.5% of asymptomatic MSM; although it was as common as chlamydia or gonorrhoea, 84% of these infections were macrolide resistant. The high proportion of MSM with macrolide-resistant M. genitalium might be considered a reason to screen for this infection but would not meet the criteria for screening established by Wilson and Jungner (27). For example, the natural history of M. genitalium infection, particularly in the rectum, is poorly understood. Testing is not widely available and the high prevalence of antimicrobial drug resistance also limits the availability of treatment. If we screened this population, 8% of MSM (84% of 9.5%) would require moxifloxacin or a similar agent. Moxifloxacin is expensive, difficult to obtain in many parts of the world, and associated with uncommon but concerning toxicities. Resistance to quinolone antimicrobial drugs is now detected in 16% of patients coming to MSHC (mixed heterosexual and MSM population) in ongoing unpublished work (G.L. Murray, unpub. data). Increasing the use of moxifloxacin as a result of screening would be expected to generate more resistance.

Rectal M. genitalium infection may not warrant treatment. It was not associated with current anorectal symptoms in this study; most published literature suggests no association or only a weak association. No prospective studies have associated M. genitalium with increased risk for HIV infection in MSM, in contrast to women; such an association may become less critical when HIV PrEP and treatment are widely used. Therefore, screening asymptomatic MSM for M. genitalium would result in considerable expense and adverse events for uncertain benefit. Although M. genitalium has been identified in cases of proctitis, it is predominantly asymptomatic in the rectum, and there appears to be insufficient evidence to suggest that M. genitalium is a cause of proctitis.

Acknowledgments

We thank Mieken Grant, Colin Denver, the staff at MSHC, and the study participants for their important contributions to this study.

T.R.H.R. and E.P.F.C. are funded by Australian National Health and Medical Research Council early career fellowships (nos. 1091536 and 1091226).

Dr. Read was a sexual health physician at Melbourne Sexual Health Centre and a research fellow at Monash University, Melbourne, Victoria, Australia. He was elected to the Parliament of Victoria in 2018 and no longer works in medical research.

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(27.) Wilson JWG, Jungner G. Principles and practice of screening for disease. Geneva: World Health Organization; 1968.

Address for correspondence: Catriona S. Bradshaw, Melbourne Sexual Health Centre, 580 Swanston St, Carlton, VIC 3053, Australia; email: cbradshaw@mshc.org.au

Author affiliations: Melbourne Sexual Health Centre, Carlton, Victoria, Australia (T.R.H. Read, C.K. Fairley, M. Doyle, K. Worthington, D. Lee, L.A. Vodstrcil, E.P.F. Chow, M.Y Chen, C.S. Bradshaw); Monash University, Melbourne, Victoria, Australia (T.R.H. Read, C.K. Fairley, L.A. Vodstrcil, E.P.F. Chow, M.Y. Chen, C.S. Bradshaw); Monash Biomedicine Discovery Institute, Melbourne (G.L. Murray); Murdoch Children's Research Institute, Parkville, Victoria, Australia (G.L. Murray, J.A. Danielewski, J. Su, S.M. Garland); Royal Women's Hospital, Melbourne (G.L. Murray, J. A. Danielewski, S.M. Garland); Royal Children's Hospital, Melbourne (G.L. Murray, S.M. Garland); SpeeDx Pty Ltd, Eveleigh, Sydney, New South Wales, Australia (E. Mokany, L. T. Tan); University of Melbourne, Melbourne (S.M. Garland)

DOI: https://doi.org/10.3201/eid2504.181258
Table 1. Characteristics associated with urethral or rectal
Mycoplasma genitalium in asymptomatic men who have sex with men,
Australia *

Characteristic                 All patients        M. genitalium
                                                    not detected

Detected in urine,
rectum, or both

Prevalence                        1,001              906 (90.5)

Median age, y (IQR)          28.8 (24.3-34.1)     28.9 (24.5-34.3)

HIV status
([double dagger])

Negative                           894               804 (88.7)

Positive                           107               102 (11.3)

On/commencing PrEP([section])

No                                 752               678 (84.3)

Yes                                142               126 (15.7)

Detected in urine only

Urine prevalence                                     974 (97.3)
Insertive oral sex
partners in previous 3
mo, n = 984 ([paragraph])

<4                                 431               421 (44.0)
[greater than or                   553               536 (56.0)
equal to] 4

Insertive anal sex
partners in previous 3
months, n = 941 (#)

<2                                 428               418 (45.7)
[greater than or                   513               497 (54.3)
equal to]2

Condom use insertive anal
sex in previous 3 mo

Always                             287               280 (38.7)
Not always                         460               443 (61.3)

Detected in rectum only
Rectal prevalence                                    931 (93.0)
Receptive anal sex
partners in previous 3
mo, n = 945 (#)

<2                                 367               349 (39.8)
[greater than or                   578               527 (60.2)
equal to] 2

Condom use receptive anal
sex in previous 3 mo

Always                             301               288 (37.1)
Not always                         540               488 (62.9)

Characteristic                 M. genitalium       Crude OR (95% CI)
                            detected ([dagger])

Detected in urine,
rectum, or both

Prevalence                   95 (9.5, 7.7-11.5)

Median age, y (IQR)           27.4 (23.3-32.3)      0.96 (0.93-0.99)

HIV status
([double dagger])

Negative                         90 (94.7)

Positive                     5 (5.3, 1.7-11.9)      0.44 (0.17-1.10)

On/commencing PrEP([section])

No                               74 (82.2)

Yes                         16 (17.8, 10.5-27.3)    1.16 (0.66-2.06)

Detected in urine only

Urine prevalence             27 (2.7, 1.8-3.9)

Insertive oral sex
partners in previous 3
mo, n = 984 ([paragraph])

<4                               10 (37.0)
[greater than or                 17 (63.0)          1.34 (0.61-2.95)
equal to] 4

Insertive anal sex
partners in previous 3
months, n = 941 (#)

<2                               10 (38.5)
[greater than or                 16 (61.5)          1.34 (0.60-3.0)
equal to]2

Condom use insertive anal
sex in previous 3 mo

Always                            7 (29.2)
Not always                       17 (70.8)          1.53 (0.63-3.75)

Detected in rectum only

Rectal prevalence                                 70 (7.0, 5.5-8.8)
Receptive anal sex
partners in previous 3
mo, n = 945 (#)

<2                               18 (26.1)
[greater than or                 51 (73.9)          1.88 (1.08-3.3)
equal to] 2

Condom use receptive anal
sex in previous 3 mo

Always                           13 (20.0)
Not always                       52 (80.0)          2.36 (1.24-4.81)

Characteristic              p value

Detected in urine,
rectum, or both

Prevalence

Median age, y (IQR)          0.006

HIV status
([double dagger])

Negative

Positive                     0.08

On/commencing PrEP([section])

No

Yes                          0.60

Detected in urine only

Urine prevalence

Insertive oral sex
partners in previous 3
mo, n = 984 ([paragraph])

<4
[greater than or             0.47
equal to] 4

Insertive anal sex
partners in previous 3
months, n = 941
([paragraph])

<2
[greater than or             0.47
equal to]2

Condom use insertive anal
sex in previous 3 mo

Always
Not always                   0.35

Detected in rectum only
Receptive anal sex
partners in previous 3
mo, n = 945#

<2
[greater than or             0.026
equal to] 2

Condom use receptive anal
sex in previous 3 mo

Always
Not always                   0.006

* Values are no. (%, 95% CI) except as indicated.
This table should be viewed in conjunction with
Table 2. IQR, interquartile range; OR, odds ratio; PrEP,
preexposure prophylaxis.

([dagger]) in 2 of 97 infected men, M. genitalium was
detected in both the urine and the rectum.

([double dagger]) Includes 5 men with unknown HIV infection
status. M. genitalium was detected in 4.7% of HIV-positive
men vs. 10.1 % of HIV-negative men (p = 0.08).

([section]) HIV-negative men only.

([paragraph]) Median 4.

(#) Median 2.

Table 2. Detection of urethral or rectal Chlamydia trachomatis
or Neisseria gonorrhoeae in asymptomatic men who have sex with
men, Australia *

                                                      C. trachomatis
Characteristic                     All patients        not detected

Detected in urine, rectum,
or both

STI prevalence                         1,001            857 (90.4)
Median age, y (IQR)              28.8 (24.3-34.1)    28.8 (24.3-34.0)
HIV status
Negative ([double dagger])              894             782 (91.3)
Positive                                107              75 (8.8)

On/commencing PrEP ([section])

No                                      752             666 (85.2)
Yes                                     142             116 (14.8)

Detected in urine only

Urine prevalence                        958             942 (98.3)

Insertive oral sex partners
in previous 3 mo, n = 984
([paragraph])

<4                                      431             407 (44.0)
[greater than or equal to] 4            553             519 (56.0)

Insertive anal sex partners in
previous 3 mo, n = 941 (#)

<2                                      428             406 (45.9)
[greater than or equal to] 2            513             479 (54.1)

Condom use insertive anal sex
in previous 3 mo

Always                                  287             273 (39.1)
Not always                              460             425 (60.9)

Detected in rectum only
Rectal prevalence                     958-963           877 (91.5)
Receptive anal sex partners in
previous 3 mo, n = 945 (#)

<2                                      367             336 (40.8)
[greater than or equal to] 2            578             488 (59.2)

Condom use receptive anal sex
in previous 3 mo

Always                                  301             270 (37.1)
Not always                              540             458 (62.9)

                                   C. trachomatis
Characteristic                   detected ([dagger])

Detected in urine, rectum,
or both

STI prevalence                   91 (9.6, 7.8-11.7)
Median age, y (IQR)               27.6 (23.8-35.2)
HIV status
Negative ([double dagger])            72 (79.1)
Positive                              19 (20.9)

On/commencing PrEP ([section])

No                                    57 (79.2)
Yes                                   15 (20.8)

Detected in urine only

Urine prevalence                  16 (1.7, 1.0-2.7)

Insertive oral sex partners
in previous 3 mo, n = 984
([paragraph])

<4                                    4 (25.0)
[greater than or equal to] 4          12 (75.0)

Insertive anal sex partners in
previous 3 mo, n = 941 (#)

<2                                    4 (25.0)
[greater than or equal to] 2          12 (75.0)

Condom use insertive anal sex
in previous 3 mo

Always                                 5(31.3)
Not always                            11 (68.7)

Detected in rectum only
Rectal prevalence                81 (8.5, 6.8-10.4)
Receptive anal sex partners in
previous 3 mo, n = 945 (#)

<2                                    20 (24.7)
[greater than or equal to] 2          61 (75.3)

Condom use receptive anal sex
in previous 3 mo

Always                                18 (23.4)
Not always                            59 (76.6)

                                  N. gonorrhoeae
Characteristic                     not detected

Detected in urine, rectum,
or both

STI prevalence                      888 (93.3)
Median age, y (IQR)              28.8 (24.3-34.1)
HIV status
Negative ([double dagger])          801 (90.2)
Positive                             87 (9.8)

On/commencing PrEP ([section])

No                                  683 (85.3)
Yes                                 118 (14.7)

Detected in urine only

Urine prevalence                    951 (99.3)

Insertive oral sex partners
in previous 3 mo, n = 984
([paragraph])

<4                                  408 (43.6)
[greater than or equal to] 4        527 (56.4)

Insertive anal sex partners in
previous 3 mo, n = 941 (#)

<2                                  409 (45.8)
[greater than or equal to] 2        485 (54.2)

Condom use insertive anal sex
in previous 3 mo

Always                              273 (38.6)
Not always                          434 (61.4)

Detected in rectum only
Rectal prevalence                   903 (93.8)
Receptive anal sex partners in
previous 3 mo, n = 945 (#)

<2                                  342 (40.1)
[greater than or equal to] 2        511 (59.9)

Condom use receptive anal sex
in previous 3 mo

Always                              277 (36.7)
Not always                          477 (63.3)

                                   N. gonorrhoeae
Characteristic                   detected ([dagger])

Detected in urine, rectum,
or both

STI prevalence                    64 (6.7, 5.2-8.5)
Median age, y (IQR)               27.2 (24.1-33.1)
HIV status
Negative ([double dagger])            55 (85.9)
Positive                              9 (14.1)

On/commencing PrEP ([section])

No                                    39 (70.9)
Yes                                   16 (29.1)

Detected in urine only

Urine prevalence                  7 (0.7, 0.3-1.4)

Insertive oral sex partners
in previous 3 mo, n = 984
([paragraph])

<4                                    2 (28.6)
[greater than or equal to] 4           5(71.4)

Insertive anal sex partners in
previous 3 mo, n = 941 (#)

<2                                        0
[greater than or equal to] 2           7 (100)

Condom use insertive anal sex
in previous 3 mo

Always                                4 (57.1)
Not always                            3 (42.9)

Detected in rectum only
Rectal prevalence                 60 (6.2, 4.8-7.9)
Receptive anal sex partners in
previous 3 mo, n = 945 (#)

<2                                    15 (26.3)
[greater than or equal to] 2          42 (73.7)

Condom use receptive anal sex
in previous 3 mo

Always                                11 (20.0)
Not always                            44 (80.0)

* Values are no. (%) or no. (%, 95% CI) except as indicated. This
table should be viewed in conjunction with Table 1. All 1,001 men
had urine and rectal swabs tested for Mycoplasma genitalium, but
only 948 were tested at both sites for C. trachomatis and 952 for
N. gonorrhoeae. IQR, interquartile range; PrEP, preexposure
prophylaxis.

([dagger]) Denominators varied based on numbers tested; 958 men had
urine tests for both infections; 948 men were screened at both
sites and 958 men had rectal tests for C. trachomatis; and 952 men
were screened at both sites and 963 men had rectal tests for N.
gonorrhoeae.

([double dagger]) Includes 5 men of unknown HIV infection status.
M. genitalium was detected in 4.7% of HIV-positive men vs. 10.1% of
HIV-negative men (p = 0.08).

([section]) HIV-negative men only.

([paragraph]) Median 4.

(#) Median 2.

Table 3. Detection of Mycoplasma genitalium, Chlamydia trachomatis,
and Neisseria gonorrhoeae in asymptomatic men who have sex with
men according to reports of symptoms during the preceding week,
Australia *

                  Urethral symptoms ([dagger])
                  None, no.    Mild, no.   Odds ratio
Characteristic    (%)          (%)         (95% CI)       p value

M. genitalium,
n = 1,001

Not detected      889 (97.3)   85 (97.7)   0.84
Detected          25 (2.7)     2 (2.3)     (0.19-3.59)    0.81

C. trachomatis,
n = 958

Not detected      861 (98.4)   81 (97.6)   1.52
Detected          14 (1.6)     2 (2.4)     (0.34-6.80)    0.59

Neisseria
gonorrhoeae,
n = 958

Not detected      868 (99.3)   83 (98.8)   1.74
Detected          6 (0.7)      1 (1.2)     (0.21-14.65)   0.61

                  Anorectal symptoms ([double dagger])
                  None, no.    Mild, no.    Odds ratio
Characteristic    (%)          (%)          (95% CI)      p value

M. genitalium,
n = 1,001

Not detected      692 (92.7)   239 (93.7)   0.86
Detected          54 (7.2)     16 (6.3)     (0.48-1.53)   0.60

C. trachomatis,
n = 958

Not detected      657 (91.4)   220 (92.1)   0.92
Detected          62 (8.6)     19 (7.9)     (0.54-1.56)   0.75

Neisseria
gonorrhoeae,
n = 958

Not detected      675 (93.8)   228 (93.8)   0.99
Detected          45 (6.3)     15 (6.2)     (0.54-1.80)   0.97

* All participants were triaged as asymptomatic. This table reports
answers to a questionnaire about "any symptoms (even if mild) in
the past week."

([dagger]) Urethral symptoms were any of the
following: dysuria, discharge, urethral itch, or discomfort. No
individual symptom was significantly associated with any organism.

([double dagger]) Anorectal symptoms were any of the following:
anal pain, bleeding, itch, or discomfort. No individual symptom was
significantly associated with any organism.

Table 4. Detection of Mycoplasma genitalium, Chlamydia trachomatis,
and Neisseria gonorrhoeae in asymptomatic men who have sex with men
compared with clinic attendees diagnosed with proctitis or NGU,
Australia *

                  Asymptomatic      Clinic
Characteristic    men tested at     attendees    Odds ratio    p value
                  the rectum for    with         95% CI)
                  STIs              symptoms
                                    of
                                    proctitis

M. genitalium
Not detected      931 (93.0)        335 (94.4)   0.79          0.38
Detected          70 (7.0)          20 (5.6)     (0.45-1.35)

C. trachomatis
Not detected      877 (91.5)        277 (78.7)   2.93          <0.0001
Detected          81 (8.5)           75 (21.3)   (2.05-4.18)

N. gonorrhoeae
Not detected      903 (93.8)        252 (71.6)   5.97          <0.0001
Detected          60 (6.2)          100 (28.4)   (4.15-8.61)

                  Asymptomatic      Clinic
Characteristic    men tested at     attendees    Odds ratio     p value
                  the rectum for    with         95% CI)
                  STIs              symptoms
                                    of
                                    proctitis

M. genitalium                                                   <0.0001
Not detected      974 (97.3)        936 (91.9)   3.2
Detected           27 (2.7)         83 (8.1)     (2.03-5.18)

C. trachomatis
Not detected      942 (98.3)        878 (85.5)   9.99           <0.0001
Detected          16 (1.7)          149 (14.5)   (5.89-18.07)

N. gonorrhoeae
Not detected
Detected

* Treated as NGU but not confirmed by urethral GraNGU, nongonococcal
urethritis; STI, sexually transmitted infection.

Table 5. Risk factors for detection of macrolide resistance mutations
in anogenital Mycoplasma genitalium infections detected in men who
have sex with men, Australia

Category                 Mutations      Mutations      p value
                        not detected,   detected,
                           no. (%)       no. (%)

Overall                   15 (15.8)     80 (84.2)

Antibiotic in the
preceding 3 months

None                      13 (86.7)     54 (67.5)
Yes, not azithromycin     2 (13.3)      17 (21.3)
Yes, azithromycin             0         9 (11.2)         0.39

HIV status

Negative                 15 (100.0)     75 (93.8)
Positive                      0          5 (6.2)         1.0

Taking or starting
PrEP *

No                       15 (100.0)     59 (78.7)
Yes                           0         16 (21.3)        0.06

Site of infection

Urine                     4 (26.7)      23 (28.0)
Rectum                    11 (73.3)     59 (72.2)        0.91

* PrEP, preexposure prophylaxis. HIV-positive men excluded.

Table 6. Mycoplasma genitalium detection in men who have sex
with men co-infected with Chlamydia trachomatis or Neisseria
gonorrhoeae and are asymptomatic or have symptoms of NGU,
Australia *

                        Rectal M. genitalium
Category                Not detected,   Detected,    Odds ratio
                        no. (%)          no. (%)     (95% CI)

Asymptomatic,
n = 1,001

Rectal C. trachomatis

Not detected            818 (91.6)      59 (90.8)    1.1
Detected                75 (8.4)        6 (9.2)      (0.46-2.65)

Rectal N. gonorrhoeae

Not detected            842 (93.8)      61 (93.9)    0.96
Detected                56 (6.2)        4 (6.1)      (0.35-2.81)

                        Urine M. genitalium

Urine C. trachomatis
Not detected            917 (98.5)      25 (92.6)    5.24
Detected                14 (1.5)        2 (7.4)      (1.13-24.29)

Urine N. gonorrhoeae

Not detected            926 (99.5)      25 (92.6)    14.82
Detected                5 (0.5)         2(7.4)       (2.74-80.07)

Men with NGU symptoms,  Urine M. genitalium
([dagger]) n = 1,001 *

Urine C. trachomatis
Not detected            777 (84.5)      79 (97.5)    0.14
Detected                143 (15.5)      2(2.5)       (0.03-0.57)

Category                p value

Asymptomatic,
n = 1,001

Rectal C. trachomatis

Not detected
Detected                0.82

Rectal N. gonorrhoeae

Not detected
Detected                0.98

Urine C. trachomatis
Not detected
Detected                0.03

Urine N. gonorrhoeae

Not detected
Detected                0.002

Men with NGU symptoms,
([dagger]) n = 1,001 *

Urine C. trachomatis
Not detected
Detected                0.001

* Although there are 1,001 men in each dataset, these 2 groups are
the same size only by coincidence. NGU, nongonococcal urethritis.

([dagger]) All men in this group received a clinical diagnosis of
urethritis.
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Title Annotation:RESEARCH
Author:Read, Tim R.H.; Murray, Gerald L.; Danielewski, Jennifer A.; Fairley, Christopher K.; Doyle, Michell
Publication:Emerging Infectious Diseases
Article Type:Report
Date:Apr 1, 2019
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