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. Author manuscript; available in PMC: 2025 Nov 1.
Published in final edited form as: Sex Transm Dis. 2024 Jul 16;51(11):750–755. doi: 10.1097/OLQ.0000000000002056

Mycoplasma genitalium infections among participants in a HIV pre-exposure prophylaxis program in Hanoi, Vietnam

Khanh D Nguyen 1,*, Paul C Adamson 2,*, Hao TM Bui 1, Loc Q Pham 1, Phuong T Truong 3, Ngan T Le 3, Giang M Le 1, Jeffrey D Klausner 4
PMCID: PMC11560684  NIHMSID: NIHMS2009117  PMID: 39008624

Abstract

Background.

Mycoplasma genitalium causes a sexually transmitted infection and is also emerging as an important antimicrobial resistant pathogen. Data on M. genitalium infections among men who have sex with men (MSM) in low-resource settings are sparse.

Methods.

From January to December 2022, participants in an HIV pre-exposure prophylaxis (PrEP) program in Hanoi, Vietnam were enrolled into the study. Demographic, behavioral, and clinical characteristics were collected. Self-collected urine, rectal, and pharyngeal specimens were tested for M. genitalium using the Alinity m STI Assay (Abbott Molecular, USA). Univariate and multivariate logistic regression were performed to assess for factors associated with infections.

Results.

Among 477 participants, the median age was 25.3 years (21.7–29.6) and 92.2% (n=440) identified as MSM; 48.6% had ≥2 sex partners and 38.1% reported condomless anal sex in the prior month. The overall prevalence of M. genitalium infection was 10.9% (52/477); 7.3% (34/464) rectal, 3.2% (15/476) urethral, and 1.9% (9/476) pharyngeal. Infections were asymptomatic in 71.2% (37/52). Among those with M. genitalium, 30.7% (16/52) were co-infected with either N. gonorrhoeae or C. trachomatis. Among those reporting rectal (n=51) or urethral (n=35) symptoms, but without C. trachomatis or N. gonorrhoeae co-infections, five (9.8%) had rectal infections and one (2.9%) had urethral infection. Participants with M. genitalium were more likely to be asymptomatic than participants without M. genitalium (aOR 1.93; 95% CI 1.01–3.71).

Conclusions.

M. genitalium infections were common among primarily MSM engaged in an HIV PrEP program in Vietnam. The prevalence was highest in rectal specimens and nearly three quarters of M. genitalium infections were asymptomatic. Testing for M. genitalium infections among those with symptoms is important to enable pathogen-directed therapy. Additional research on antimicrobial resistance and treatment strategies for M. genitalium in low-resource settings is needed.

Keywords: Mycoplasma genitalium, Sexually transmitted infections, men who have sex with men, HIV pre-exposure prophylaxis

Summary:

A study among participants in an HIV PrEP program in Hanoi, Vietnam found the prevalence of Mycoplasma genitalium infections was high, but infections were primarily asymptomatic.

Introduction

Mycoplasma genitalium is a bacterial sexual transmitted infection (STI), which primarily causes urethritis in males and cervicitis in females. It is a leading cause of nongonococcal urethritis (NGU), accounting for 19.8% to 28.7% of bacterial infections among men with NGU,[13] and is also the etiology of 18.4 to 45.5% nonchlamydial nongonococcal urethritis cases.[4] The prevalence of M. genitalium infections among men who have sex with men (MSM) can range from 3.2% to 10.5%,[59] and is estimated to range from 10–17.5% among MSM on HIV pre-exposure prophylaxis (PrEP).[6] Asymptomatic infections among MSM are also common, with the prevalence being highest in rectal infections, followed by urethral infections, and pharyngeal infections.[812] M. genitalium infections are rarely associated with chronic complications among men, such as epididymitis, prostatitis, or infertility. [13,14]

Currently, many national and international guidelines recommended against screening and treatment for M. genitalium in asymptomatic individuals, given the uncertain benefit of treating asymptomatic infections and due to the emergence of antimicrobial resistance (AMR).[1517] AMR to macrolides through macrolide-resistant mutations (MRMs) are a major concern, where the estimated prevalence can be as high as 67.6 – 75%,[6,18] but resistance to fluoroquinolones is also a concern, though the prevalence is lower.[6] Macrolide and fluoroquinolone resistance in M. genitalium infections is significantly higher among MSM compared with women and heterosexual men.[19] One proposed mechanism of resistance is through increased consumption of antibiotics, and a higher prevalence of macrolide resistance was found in M. genitalium infections among patients with recent macrolide consumption.[20,21]

Detection of M. genitalium infections is through the use of nucleic acid amplification tests (NAATs).[16] Recently, NAATs for M. genitalium have become available in many high-income countries, but access to these tests in low- and middle-income countries (LMICs) in many parts of Asia, like Vietnam, have been limited.[22] Therefore, data regarding the prevalence of M. genitalium infections are sparse and clinicians are often limited to syndromic case management for NGU. One study among symptomatic, heterosexual men in Vietnam found a prevalence of urethral M. genitalium infections to be 19.5% and emphasized important role of diagnostic testing.[23] Data on M. genitalium infections among MSM in Vietnam are lacking, though a prior study in Vietnam found 28.5% of MSM were infected with either Chlamydia trachomatis or Neisseria gonorrhoeae.[24]

The aims of this study were to describe the prevalence, anatomic distribution, and symptom status of M. genitalium infections, as well as to investigate the factors associated with M. genitalium infections among MSM in an HIV PrEP program in Hanoi, Vietnam.

Materials and Methods

Study design and population

This was a secondary analysis of a cross-sectional study within the PrEP program at the Sexual Health Promotion Clinic in Hanoi, Vietnam. Study participants were recruited from January to December 2022 into a study screening for C. trachomatis and N. gonorrhoeae. Participants were eligible if they were male at birth, aged 16 years or older, reported having sex with men or transgender women in prior 12 months and enrolled in the HIV PrEP program at the SHP clinic; exclusion criteria were if they had C. trachomatis or N. gonorrhoeae testing done in the prior 3 months. Participants were referred to the study based on the eligibility criteria, as well as staff and clinic availability. Information was not collected for those who were not referred or refused to participate.

Data collection

Following enrollment, participants completed a self-administered survey collecting demographic, behavioral, and clinical characteristics. Sexual behaviors were self-reported and included: number of sex partners in the prior month as the combined number of male, female and transgender sex partners, anal sex position(s), condomless anal intercourse in the prior month, group sex (defined as having sex with two or more partners in the same encounter) or having sex with partners met via mobile apps in the prior 6 months. Drug use associated with sex in the prior 6 months was considered if the participant reported using at least one substance (heroin, ketamine, ecstasy, methamphetamine, cannabis, 3,4-methylenedioxymethamphetamine (MDMA), gamma hydroxybutyrate or gamma butyrolactone (GHB/GHL), popper or erectile dysfunction medications) before or during sex to enhance sexual pleasure.

Symptoms were self-reported. Rectal symptoms included pain/burning when defecating, itching, bleeding, discharge, ulcers, or diarrhea; genital symptoms included pain/burning when urinating, itching, discharge, testicular pain, swollen lymph nodes or ulcers; and pharyngeal symptoms included pain or itching in the throat.

Sample collection and testing

Participants provided a urine sample and self-collected oral and rectal swabs for C. trachomatis and N. gonorrhoeae testing. Molecular testing was performed using the Alinity m STI Assay (Abbott Molecular, USA), a United States Food and Drug Administration-cleared assay which uses multiplex real-time polymerase chain reaction (PCR) for amplification and detection of C. trachomatis, N. gonorrhoeae, as well as M. genitalium and Trichomonas vaginalis. The testing was performed at the Department of Microbiology at Bach Mai Hospital. Test results for M. genitalium and T. vaginalis were initially blinded; participants received test results for C. trachomatis and N. gonorrhoeae and infections were managed according to local treatment guidelines. M. genitalium test results were later unblinded and we conducted a retrospective analysis on the prevalence of M. genitalium among pharyngeal, rectal and urethral specimens. M. genitalium test results were either positive, negative, or inconclusive, in the event of failed internal controls or the presence of inhibitors.

Data analysis

The primary outcome was the prevalence of M. genitalium infections at any site, which was defined as number of participants who were M. genitalium positive in at least one site over the number of participants who had M. genitalium test results in at least one specimen. Descriptive statistics were performed for demographic, behavioral and clinical data; percentages for categorical variables, or median and interquartile range for continuous variables, were reported. Categorical variables between M. genitalium positive and M. genitalium negative groups were compared using Pearson’s Chi-squared test and Fisher’s exact test, and nonparametric continuous variables were compared using Wilcoxon rank-sum tests. Univariate logistic regression was performed, and variables with a p-value <0.25, or any variable that was a potential confounder were included in a multivariate logistic regression model; backward elimination was used to select the final model by Akaike’s and Bayesian information criterion, Hosmer-Lemeshow goodness of fit tests, and variance inflation factor for multicollinearity checking. Multicollinearity was found between age and education, though these were maintained in the final model as exclusion or inclusion did not strongly impact the model. We performed data analyses using STATA version 14 (StataCorp LLC, College Station, TX, USA).

Our study was approved by the Institutional Review Boards (IRB) of Hanoi Medical University (HMUIRB580), the University of California, Los Angeles, and University of Southern California. All study participants provided written informed consent.

Results

Participant demographics

Overall, 477 participants had M. genitalium test results. The median age was 25.3 (21.7–29.6) years. All participants were male, 92.2% (n=440) identified as men, while 1.9% (n=9) self-identified as transgender women, and 5.9% (n=28) were unsure of their gender identification, gender nonconforming or gender incongruent. Vocational training, college, university or higher was completed by 61.0% (n=291). Among 412 participants who reported their prior month income, 58.5% earned more than 7 million VND (approx. 287 $US), which was the GPD per capita of Vietnam according to the World Bank 2021 report. Regarding sexual behaviors, 48.6% (n=232) reported two or more sex partners in the prior month; 38.1% (n=182) reported condomless anal intercourse in the prior month; and in the prior 6 months, 12.4% (n=59) engaged in group sex, 45.7% (n=218) reported drug use associated with sex, and 56.6% (n=270) met sex partners via mobile applications (Table 1).

Table 1.

Prevalence of M. genitalium infections and associated demographic, behavioral, and clinical characteristics among participants in an HIV PrEP program in Hanoi, Vietnam

Characteristic Overall (N=477) M. genitalium positive (n=52) p value*

n n %

Median age (IQR) 25.3 (21.7–29.6) 25.2 (20.9–28.1) - 0.42

Age, years 0.93
16–24 232 25 10.8
25–62 245 27 11.0

Gender identity 0.08
Man 440 47 10.7
Transgender woman 9 3 33.3
Other/Unsure** 28 2 7.1

Highest education 0.35
Up to high school 45 7 15.6
In vocational training/ college/university 141 19 13.5
Finished vocational training/college/university 241 22 9.1
Post-graduation training 50 4 8.0

Last month income (n=412) 0.74
7 million VND or lower 171 18 10.5
Higher than 7 million VND 241 23 9.5

Group sex in the prior 6 months 59 7 11.9 0.80

Drug use associated with sex in the prior 6 months 218 25 11.5 0.71

Sex with male partners met via mobile apps in the prior 6 months 270 27 10.0 0.47

Number of sex partners of any gender in the last month 0.37
0 60 6 10.0
1 185 16 8.7
≥ 2 232 30 12.9

Anal sex position with male partners in the last month 0.26
No anal sex last month 122 10 8.2
Insertive only 118 15 12.7
Receptive only 133 19 14.3
Both insertive and receptive 104 8 7.7

Condomless anal sex with male or transgender partners in the prior month 182 26 14.3 0.06

Antibiotic use in the last 6 months 0.51
No 292 30 10.3
Yes 126 17 13.5
Unsure 59 5 8.5

Episodes of antibiotic use in the prior 6 months (n=126) 0.79
One 83 13 15.7
Two 23 3 13.0
Three to five 17 1 5.9
More than five 3 0 0

Any symptoms in the prior week
Pharyngeal symptoms 105 9 8.6 0.39
Rectal symptoms 76 8 10.5 0.91
Genitourinary symptoms 61 3 4.9 0.13
No symptoms 288 37 12.8 0.09

Any symptoms in the prior week, without N. gonorrhoeae or C. trachomatis in that site
Pharyngeal symptoms 87 0 0 0.35
Rectal symptoms 51 5 9.8 0.40
Genitourinary symptoms 45 1 2.2 1.00

Co-infections
N. gonorrhoeae 71 12 16.9 0.08
C. trachomatis 92 7 7.6 0.26
Any N. gonorrhoeae or C. trachomatis co-infections 136 16 11.8 0.70
*

Using chi-square or Fischer’s exact test for categorical variables, and Wilcoxon-ranksum test for continuous variables.

**

Participants who were gender nonconforming or gender incongruent, or unsure of their gender identity.

Any symptoms in the pharynx, rectum or urethra in the prior week were reported by 39.6% (189/477) participants, of whom pharyngeal symptoms were the most frequently reported (22.0%; 105/477), followed by rectal symptoms (15.9%; 76/477) and urethral symptoms (12.8%; 61/477) (Table 1).

M. genitalium prevalence and anatomic distribution

Among 477 participants with M. genitalium test results, 10.9% (52/477) were infected with M. genitalium at any site. The prevalence was highest in the rectum (7.3%, 34/464), followed by urethra (3.2%, 15/476) and pharynx (1.9%, 9/476); 1.0% (5/477) were M. genitalium-positive in multiple sites and one participant was infected with M. genitalium in all three anatomic sites. Inconclusive results were present in 5.2% (24/464) of rectal specimens and 0.2% (1/476) of oral specimens, but not in urine specimens. Among those with M. genitalium, 30.7% (16/52) were co-infected with either N. gonorrhoeae or C. trachomatis (Table 1).

Asymptomatic M. genitalium infections accounted for 71.2% (37/52) of all infections. Among those reporting pharyngeal symptoms, but without N. gonorrhoeae and C. trachomatis, no M. genitalium infections were detected; while among those without N. gonorrhoeae and C. trachomatis reporting rectal symptoms (n=51) and urethral symptoms (n=45), 9.8% (5/51) tested positive for rectal and 2.2% (1/45) for urethral M. genitalium, respectively (Table 2).

Table 2.

Anatomic site and symptom status of M. genitalium infections, including C. trachomatis and N. gonorrhoeae co-infections, among participants in an HIV PrEP clinic in Hanoi, Vietnam.

Anatomic site Asymptomatic at that site Symptomatic at that site p-value*

# positive/ # tested** % # positive/ # tested** %

Rectum
N. gonorrhoeae or C. trachomatis infections 66/390 16.9 18/74 24.3 0.12
M. genitalium infections 28/390 7.2 6/74 8.1 0.76
M. genitalium, excluding participants with N. gonorrhoeae or C. trachomatis infections 21/306 6.9 5/51 9.8 0.45

Pharynx
N. gonorrhoeae or C. trachomatis infections 55/371 14.8 18/105 17.1 0.56
M. genitalium infections 9/371 2.4 0/105 0 0.39
M. genitalium, excluding participants with N. gonorrhoeae or C. trachomatis infections 7/315 2.2 0/87 0 0.36

Genitourinary
N. gonorrhoeae or C. trachomatis infections 15/415 3.6 16/61 26.2 <0.01
M. genitalium infections 13/415 3.1 2/61 3.3 1.00
M. genitalium, excluding participants with N. gonorrhoeae or C. trachomatis infections 12/400 3.0 1/45 2.2 1.00
*

Using chi-square or Fischer’s exact test

**

Numerators are number of samples at the given anatomic site that were positive with pathogens of interest, denominators are number of participants with samples tested at the given anatomic site.

In univariate analysis, there were no associations between M. genitalium infections and demographic or behavioral factors, including drug use associated with sex or group sex, N. gonorrhoeae or C. trachomatis co-infections, and any symptoms in the pharynx, urethra and rectum. In multivariate analysis, participants with M. genitalium were more likely to be asymptomatic than those without M. genitalium (aOR 1.93; 95% CI 1.01–3.71) (Table 3). The p-value (0.49) from Hosmer-Lemeshow test indicated the model fits well.

Table 3.

Univariate and multivariate logistic regression for factors associated with M. genitalium infections.

N M. genitalium positive (n, %) OR (95% CI) aOR (95% CI) p-value
Age, years 477 52 (10.9) 0.99 (0.95–1.04) 0.99 (0.95–1.04) 0.81
Gender identity
Man 440 47 (10.7) REF REF
Transgender woman 9 3 (33.3) 4.18 (1.01–17.27) 3.29 (0.73–14.88) 0.12
Other/Unsure 28 2 (7.1) 0.64 (0.15–2.80) 0.53 (0.12–2.37) 0.41
Highest education
Up to high school 45 7 (15.6) REF REF
In vocational training/ college/university 141 19 (13.5) 0.85 (0.33–2.16) 0.97 (0.35–2.67) 0.95
Finished vocational training/college/university 241 22 (9.1) 0.55 (0.22–1.37) 0.60 (0.23–1.56) 0.30
Post-graduation training 50 4 (8.0) 0.47 (0.13–1.73) 0.53 (0.14–2.03) 0.36
Number of sex partners of any gender in the last month
0 60 6 (10.0) REF REF
1 185 16 (8.7) 0.85 (0.32–2.29) 0.72 (0.25–2.06) 0.54
≥ 2 232 30 (12.9) 1.33 (0.53–3.38) 1.16 (0.41–3.28) 0.78
Condomless anal sex with male or transgender partners in the prior month 182 26 (14.3) 1.72 (0.97–3.07) 1.87 (0.97–3.58) 0.06
No STI symptoms in the prior week 288 37 (31.4) 1.71 (0.91–3.21) 1.93 (1.01–3.71) 0.04
Any N. gonorrhoeae or C. trachomatis co-infections 136 16 (11.8) 1.12 (0.60–2.11) 1.00 (0.52–1.94) 0.99

Discussion

In our study of primarily MSM in an HIV PrEP program in Hanoi, Vietnam, we found the overall prevalence of M. genitalium to be 10.9%. The prevalence of rectal infections was higher than urethral or pharyngeal infections. Nearly three-quarters of all M. genitalium infections were asymptomatic. The prevalence of symptomatic M. genitalium was 9.8% for rectal and 2.2% for urethral sites, in the absence of C. trachomatis or N. gonorrhoeae co-infections. These data help to understand the epidemiology of M. genitalium among populations of MSM in Vietnam.

The overall prevalence of M. genitalium within our study population of primarily MSM on PrEP was fairly similar to a previous study among MSM in an HIV PrEP trial (10.5%)[6] and a study on the prevalence of STIs among HIV-uninfected MSM PrEP users in Germany (14.2%)[9], but much higher than the prevalence of M. genitalium among MSM in a meta-analysis from five studies (3.2%).[5] The anatomic distribution of M. genitalium is similar to the estimates from a meta-analysis among MSM from 46 studies (6.2% at the rectum, 5.0% at the urethra and 1.0% at the pharynx).[10] However, we found a higher prevalence of asymptomatic M. genitalium infections in our study (12.8% overall, 9.2% in rectum, 2.8% in pharynx and 3.1% in urethra) compared to a study of asymptomatic MSM in Australia (9.5% overall, 7.0% in rectum and 2.7% in urethra)[8], and another study on rectal M. genitalium among asymptomatic MSM in Australia (7.0%).[18] While the exact reason for a higher M. genitalium prevalence among asymptomatic MSM in our study, compared to prior studies, is not known, the reasons might be multi-factorial, including the inclusion of the pharyngeal site, the relatively small number of infections, and the prior reliance of syndromic management for STIs, as prior research has shown long duration of M. genitalium infections following syndromic treatment of NGU.[25]

While the majority of M. genitalium infections in our study were detected among those without symptoms, the utility of screening for asymptomatic infections is expected to be low. The benefit of treating asymptomatic infections is not established and is likely outweighed by the cost of treatment, antibiotic side effects, and potential risks associated with increasing AMR through increased antimicrobial consumption.[1517,26] A natural experiment among MSM in an HIV PrEP program in Belgium showed that screening was not associated with decreased incidence, but was associated with increased AMR.[27] However, a recent modeling study from Australia estimated that higher screening coverage for M. genitalium among MSM could reduce its prevalence.[7] They estimated a 20–30% reduction in the prevalence of M. genitalium among MSM could be achieved through screening for M. genitalium infection among MSM with symptoms and those at increased susceptibility for infections, but without symptoms.[7] While the evidence does not yet support screening for M. genitalium among asymptomatic patients, diagnosing symptomatic M. genitalium infections is recommended by international guidelines.[16,17] Therefore, access to NAATs for M. genitalium testing is critical, in addition to those capable of detecting resistance mutations that can lead to improved treatment outcomes through resistance-guided therapy.[28] This is particularly important in the Western Pacific Region, where Vietnam is located, as the prevalence of AMR in M. genitalium infections is high.[21] Currently, M. genitalium testing is available in some settings in Vietnam, and costs approximately $20 USD for each NAAT. However, as of our knowledge, M. genitalium resistance testing is not routinely available.

We did not find any demographic or behavioral factors associated with M. genitalium infections in multivariate analysis. However, study participants with M. genitalium were more likely to be asymptomatic, compared to those without M. genitalium infections, even when controlling for N. gonorrhoeae or C. trachomatis co-infections. While this is a somewhat surprising finding, it was likely driven by the inclusion of pharyngeal site infections. There was a high proportion of asymptomatic pharyngeal M. genitalium infections (all nine pharyngeal infections were asymptomatic), which, together with the relatively small number of infections, likely skews the association towards those who are asymptomatic. In our study, 71% of the total M. genitalium infections were asymptomatic, and other reports estimate this to be 54–93%.[29,30] While some studies have found an association of M. genitalium infections with N. gonorrhoeae or C. trachomatis co-infections,[8,23] we did not see an association with co-infections; the prevalence of M. genitalium was slightly higher among those with N. gonorrhoeae infections, but this did not meet statistical significance. Similar to other studies, we did not find significant association between M. genitalium infections and behaviors such as multiple sex partners, history of a past STI, or substance use.[18,23]

Our study has several limitations, including a convenience sampling of MSM recruited from a single HIV PrEP program, where findings might not be generalizable to MSM in other settings. In addition, there might be some selection bias of study participants who were symptomatic, or who self-selected based on behaviors thought to increase vulnerability for infections, to participate in a study testing for STIs, which might overestimate the prevalence of M. genitalium among MSM in the HIV PrEP program. Surveys were self-collected to minimize interviewer-bias, but could still be impacted by recall or social desirability bias, which might underestimate the association with some risk factors.

Conclusion

In summary, we found a 10.9% prevalence of M. genitalium infection among MSM in an HIV PrEP program in Hanoi, Vietnam. The prevalence was highest among rectal specimens and infections were associated with asymptomatic status. A minority of M. genitalium infections occurred in those who were symptomatic and without N. gonorrhoeae and C. trachomatis co-infections. While our data does not support the routine screening and treatment of M. genitalium among asymptomatic men, using NAATs for detection of M. genitalium infections among those with symptoms and negative N. gonorrhoeae and C. trachomatis tests is an important tool to enable pathogen-directed therapy of M. genitalium infections, which must take into account growing concerns about AMR. Additional research is needed to understand risk factors for AMR in M. genitalium in low and middle-income countries, where the prevalence of AMR is higher and access to diagnostic testing is limited, in order to optimize the testing and treatment approach to M. genitalium in these settings.

Conflicts of Interest and Source of Funding:

This work was supported by the US National Institute of Allergy and Infectious Diseases (R21 AI157817 to G. M. L and J. D. K.) and the Fogarty International Center (K01TW012170 to P. C. A). The funders had no role in the data collection, analysis, manuscript preparation, or decision to publish. All authors report a no charge donation of study materials from Abbott Molecular (Des Plaines, IL, USA). In addition, JDK reports consulting fees from Abbott in the prior 12 months. All other authors report no potential conflicts of interest.

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