Cost-effectiveness of resistance-guided therapy for Mycoplasma genitalium in Australia.

The recommended first-line treatment for Mycoplasma genitalium infections is azithromycin. However, the prevalence of macrolide resistance for M. genitalium has increased to more than 50% worldwide. In 2013, Australia introduced a resistance-guided therapy (RGT) strategy to manage M. genitalium infections. This study assesses the cost-effectiveness of the RGT approach compared to no RGT (i.e., without macrolide resistance profile test) in women, men who have sex with men (MSM), and men who have sex with women (MSW) in Australia. We constructed dynamic transmission models of M. genitalium infections in women, MSM, and MSW in Australia, each with a population of 100,000. These models compared the costs and quality-adjusted life-years (QALYs) gained between RGT and no RGT scenarios from a healthcare perspective over ten years. All costs are reported in 2022 Australian dollars (Australian $). In our model, RGT is cost saving in women and MSM, with the incremental net monetary benefit of $1.3 million and $17.9 million, respectively. In MSW, the RGT approach is not cost-effective, with an incremental cost-effectiveness ratio of -$106.96 per QALY gained. RGT is cost saving compared to no RGT for M. genitalium infections in women and MSM, supporting its adoption as the national management strategy for these two population groups.

Vaginal anaerobes are associated with cervicitis: A case-control study.

OBJECTIVES: Cervicitis is associated with important reproductive sequelae. Primary causes include chlamydia and gonorrhoea, but a known sexually transmitted infection (STI) is not identified in >50% of cases (i.e. STI-negative cervicitis). Bacterial vaginosis (BV) and specific BV-associated bacteria have also been associated with cervicitis, but data are limited. We investigated the association between STI-negative cervicitis and vaginal microbiota composition. METHODS: This was a case-control sub-study of the OhMG study conducted at the Melbourne Sexual Health Centre. Cases were women with cervicitis who tested negative for STIs (STI-negative cervicitis, n = 64). Controls were STI-negative asymptomatic women attending for STI-screening (n = 128). The vaginal microbiota was characterised using 16S rRNA gene sequencing. Vaginal community state types were compared between cases and controls using logistic regression. Differential abundance analysis was performed to identify taxa associated with STI-negative cervicitis. RESULTS: STI-negative cervicitis cases were more likely than controls to have a Lactobacillus-deficient non-optimal microbiota (adjusted-odds-ratio 2.55, 95% CI 1.18-5.50). Compared to controls, cases had increased abundance of four BV-associated bacteria (Gardnerella, Fannyhessea vaginae, Prevotella bivia, Dialister micraerophilus) and decreased abundance of optimal lactobacilli. CONCLUSIONS: We report a positive association between non-optimal vaginal microbiota composition and STI-negative cervicitis. Specific anaerobic BV-associated bacteria may represent infectious causes of cervicitis.

Economic evaluation alongside a clinical trial of near-to-patient testing for sexually transmitted infections.

BACKGROUND: Current clinical care for common bacterial STIs (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Mycoplasma genitalium (MG)) involves empiric antimicrobial therapy when clients are symptomatic, or if asymptomatic, waiting for laboratory testing and recall if indicated. Near-to-patient testing (NPT) can improve pathogen-specific prescribing and reduce unnecessary or inappropriate antibiotic use in treating sexually transmitted infections (STI) by providing same-day delivery of results and treatment. METHODS: We compared the economic cost of NPT to current clinic practice for managing clients with suspected proctitis, non-gonococcal urethritis (NGU), or as an STI contact, from a health provider's perspective. With a microsimulation of 1000 clients, we calculated the cost per client tested and per STI- and pathogen- detected for each testing strategy. Sensitivity analyses were conducted to assess the robustness of the main outcomes. Costs are reported as Australian dollars (2023). RESULTS: In the standard care arm, cost per client tested for proctitis, NGU in men who have sex with men (MSM) and heterosexual men were the highest at $247.96 (95% Prediction Interval (PI): 246.77-249.15), $204.23 (95% PI: 202.70-205.75) and $195.01 (95% PI: 193.81-196.21) respectively. Comparatively, in the NPT arm, it costs $162.36 (95% PI: 161.43-163.28), $158.39 (95% PI: 157.62-159.15) and $149.17 (95% PI: 148.62-149.73), respectively. Using NPT resulted in cost savings of 34.52%, 22.45% and 23.51%, respectively. Among all the testing strategies, substantial difference in cost per client tested between the standard care arm and the NPT arm was observed for contacts of CT or NG, varying from 27.37% to 35.28%. CONCLUSION: We found that NPT is cost-saving compared with standard clinical care for individuals with STI symptoms and sexual contacts of CT, NG, and MG.

Prevalence of cefixime-resistant Neisseria gonorrhoeae in Melbourne, Australia, 2021-2022.

While ceftriaxone remains the first-line treatment for gonorrhoea, the US CDC recommended cefixime as a second-line treatment in 2021. We tested 1176 Neisseria gonorrhoeae isolates among clients attending the Melbourne Sexual Health Centre in 2021-2022. The prevalence of cefixime resistance was 6.3% (74/1176), azithromycin resistance was 4.9% (58/1176) and ceftriaxone resistance was 0% (0/1176). Cefixime resistance was the highest among women (16.4%, 10/61), followed by men-who-have-sex-with-women (6.4%, 7/109), and men-who-have-sex-with-men (5.8%, 57/982). The prevalence of cefixime-resistant N. gonorrhoeae exceeds the threshold of the 5% resistance level recommended by the World Health Organization; and thus, cefixime treatment would have limited benefits in Australia.

Systematic review and meta-analysis of the association between Mycoplasma genitalium and Pelvic inflammatory disease (PID).

BACKGROUND: Differences in opinion concerning the contribution of M. genitalium to pelvic inflammatory disease (PID) has resulted in inconsistencies across global testing and treatment guidelines. We conducted a systematic review and meta-analysis to determine the association between M. genitalium and PID and M. genitalium positivity within PID cases to provide a contemporary evidence base to inform clinical practice (PROSPERO registration: CRD42022382156). METHODS: PubMed, Embase, Medline and Web of Science were searched to Dec 1, 2023 for studies that assessed women for PID using established clinical criteria and used nucleic acid amplification tests to detect M. genitalium. We calculated summary estimates of the 1) association of M. genitalium with PID (pooled odds ratio [OR]) and 2) proportion of PID cases with M. genitalium detected (pooled M. genitalium positivity in PID), using random-effects meta-analyses, with 95% confidence intervals (CI). RESULTS: Nineteen studies were included: 10 estimated M. genitalium association with PID, and 19 estimated M. genitalium positivity in PID. M. genitalium infection was significantly associated with PID (pooled OR=1.67 [95%CI: 1.24-2.24]). The pooled positivity of M. genitalium in PID was 10.3% [95%CI: 5.63-15.99]. Subgroup and meta-regression analyses showed that M. genitalium positivity in PID was highest in the Americas, in studies conducted in both inpatient and outpatient clinic settings, and in populations at high risk of sexually transmitted infections. CONCLUSIONS: M. genitalium was associated with a 67% increase in odds of PID and was detected in about one in ten clinical diagnoses of PID. These data support testing women for M. genitalium at initial PID diagnosis.

Bacterial vaginosis after menopause: factors associated and women's experiences: a cross-sectional study of Australian postmenopausal women.

Background Bacterial vaginosis (BV) is the most common cause of vaginal discharge in reproductive age women; however, little is known about it after menopause. We aimed to learn more about BV in Australian postmenopausal women. Methods We conducted an online survey (July-September 2021). Participants were recruited via social media and professional networks and asked about demographic characteristics, sexual history and BV experiences. Outcomes of interest were the proportion who had heard of BV, had BV ever, or had BV after menopause. Factors associated with these outcomes were assessed using logistic regression. Results Of 906 participants, 83% were included in the analysis. Overall, 37.9% had heard of BV, 11.0% reported having a BV diagnosis ever, 6.3% reported having a BV diagnosis after menopause and 4.4% reported having a BV diagnosis only after menopause. Multivariable analysis found that among all women the odds of having a BV diagnosis after menopause were increased for those who had BV before menopause, had douched in the past 12months, or had a previous STI diagnosis. Among those in a sexual relationship, a BV diagnosis after menopause was associated with a BV diagnosis before menopause, or being in a sexual relationship of 5years or less in duration. About half who reported BV after menopause described recurrences, distress, and a detrimental effect on sexual relationships. Conclusions BV in postmenopausal women is associated with sexual activity, and impacts negatively on their lives. Research into BV should not be limited to reproductive age women.

Near-to-patient-testing to inform targeted antibiotic use for sexually transmitted infections in a public sexual health clinic: the NEPTUNE cohort study.

Background: Empiric treatment of sexually transmitted infections can cause unnecessary antibiotic use. We determined if near-to-patient-testing (NPT) for Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium (MG) improved antibiotic-use for a range of clinical presentations. Methods: Clients attending with non-gonococcal urethritis (NGU), proctitis, as STI-contacts, or for an MG-test-of-cure (MG-TOC) between March and December 2021 were recruited. Participants received near-to-patient-testing (NPT-group) for the three STIs using the GeneXpert® System (Cepheid), and concurrent routine-testing by transcription-mediated-amplification (TMA; Aptima, Hologic). Antibiotic-use among NGU or proctitis cases in the NPT-group was compared to clinic-controls undergoing routine-testing only. The proportion in the NPT-group who notified partners <24 hrs of their STI-specific result was calculated. Findings: Among 904 consults by 808 NPT-participants, ≥1 STI was detected in 63/252 (25.0%) with NGU, 22/51 (43.1%) with proctitis, and 167/527 (31.7%) STI-contacts. MG was detected among 35/157 (22.3%) MG-TOC consults. Among NGU and proctitis cases, fewer in the NPT-group received empiric treatment compared to clinic-controls (29.4% [95% CI: 24.3-34.9%] vs 83.8% [95% CI: 79.2-87.8%], p < 0.001), resulting in more NPT-group cases appropriately treated (STI-specific drug/no drug appropriately; 80.9% [95% CI: 76.0-85.1%] vs 33.0% [95% CI: 27.7-38.6%], p < 0.001) and fewer mistreated (incorrect drug/treated but pathogen-negative; 17.8% [13.7-22.6%] vs 61.4% [55.6-66.9%], p < 0.001). Of 167/264 in the NPT-group with an STI who responded regarding partner-notification, 95.2% notified all/some partners; 85.9% notified them <24 hrs of the STI-specific result. Interpretation: Near-to-patient-testing significantly improved antibiotic use and a high proportion of individuals rapidly notified partners of STI-specific results, highlighting the broad benefits of timely diagnostic strategies for STIs in clinical decision making and partner notification. Funding: ARC ITRP Hub-grant; NHMRC.

Efficacy of Sitafloxacin for Mycoplasma genitalium in an Era of Increasing Antimicrobial Resistance.

Antimicrobial resistance in Mycoplasma genitalium is rising globally and antimicrobial options are limited. We evaluated the efficacy of sitafloxacin regimens for macrolide-resistant M genitalium at Melbourne Sexual Health Centre, Australia, between January 2017 and February 2022. Before June 2017, patients received doxycycline followed by sitafloxacin; subsequently, patients received doxycycline followed by combined doxycycline + sitafloxacin. Of 229 patients treated with a sitafloxacin regimen, 80.6% experienced microbial cure. Sitafloxacin cured 94.2% of infections that had not previously failed moxifloxacin and 69.5% of infections that had; prior failure of moxifloxacin was associated with an 8-fold odds of sitafloxacin failure. There was no difference in cure between sequential monotherapy and combination therapy when patients were stratified by past failure of moxifloxacin (P > .05); however, small numbers limited comparisons. Sitafloxacin was well tolerated and still achieved 70% cure in patients in whom moxifloxacin had failed. These data highlight the benefit of incorporating relevant fluoroquinolone resistance markers into assays to assist clinical decision making.

Increased syphilis testing and detection of late latent syphilis among women after switching from risk-based to opt-out testing strategy in an urban Australian sexual health clinic: a retrospective observational study.

Background: The Melbourne Sexual Health Centre (MSHC) implemented an opt-out syphilis test for women in December 2017. We aimed to examine the differences in syphilis testing uptake and confirmed syphilis cases among women after switching from risk-based to opt-out testing strategies. Methods: This was a retrospective study examining all women attending the MSHC for the first time in periods of risk-based testing (2015-2017) and opt-out testing (2018-2020). We calculated the proportion of women who tested for syphilis and the proportion of women with confirmed syphilis in each period. A chi-square test was performed to determine the differences in proportion between the risk-based testing and opt-out periods. Findings: A total of 27,481 women (i.e. 13,059 in the risk-based testing period and 14,422 in the opt-out period) were included in the final analysis, and the mean age was 26.8 years (standard deviation = 6.9). The proportion of women who were tested for syphilis at their first consultation increased from 52.8% (6890/13,059) in the risk-based testing period to 67.4% (9725/14,422) in the opt-out period (p < 0.0001). Syphilis positivity did not differ between the two periods (0.48% [33/6890] vs 0.71% [69/9725], p = 0.061) but late latent causes increased from 36.4% [12/33] to 60.9% [42/69] (p = 0.033). Interpretation: The opt-out testing strategy increased syphilis testing among women with increased detection of asymptomatic late latent syphilis. The opt-out syphilis testing strategy is beneficial in sexual health services. Health education and awareness may be required to improve syphilis testing uptake. Funding: National Health and Medical Research Council.

Efficacy of Minocycline for the Treatment of Mycoplasma genitalium.

Background: High levels of macrolide resistance and increasing fluoroquinolone resistance are making Mycoplasma genitalium increasingly difficult to treat. Minocycline is an alternative treatment for patients with macrolide-resistant M genitalium infections that have failed moxifloxacin, or for those with fluoroquinolone contraindications or resistance. Published efficacy data for minocycline for M genitalium are limited. Methods: We evaluated minocycline 100 mg twice daily for 14 days at Melbourne Sexual Health Centre (MSHC). Microbial cure was defined as a negative test of cure within 14-90 days after completing minocycline. The proportion cured and 95% confidence intervals (CIs) were calculated, and logistic regression was used to explore factors associated with treatment failure. We pooled data from the current study with a prior adjacent case series of patients with M genitalium who had received minocycline 100 mg twice daily for 14 days at MSHC. Results: Minocycline cured 60 of 90 (67% [95% CI, 56%-76%]) infections. Adherence was high (96%) and side effects were mild and self-limiting. No demographic or clinical characteristics were associated with minocycline failure in regression analyses. In the pooled analyses of 123 patients, 83 (68% [95% CI, 58%-76%]) were cured following minocycline. Conclusions: Minocycline cured 68% of macrolide-resistant M genitalium infections. These data provide tighter precision around the efficacy of minocycline for macrolide-resistant M genitalium and show that it is a well-tolerated regimen. With high levels of macrolide resistance, increasing fluoroquinolone resistance, and the high cost of moxifloxacin, access to nonquinolone options such as minocycline is increasingly important for the clinical management of M genitalium.

Prevotella and Gardnerella Are Associated With Treatment Failure Following First-line Antibiotics for Bacterial Vaginosis.

BACKGROUND: Bacterial vaginosis (BV) is a common vaginal dysbiosis that often recurs following first-line antibiotics. We investigated if vaginal microbiota composition was associated with BV recurrence. METHODS: We analyzed samples and data from 121 women who participated in 3 published trials evaluating novel interventions for improving BV cure, including concurrent antibiotic treatment of regular sexual partners (RSPs). Women diagnosed with BV received first-line antibiotics and self-collected vaginal swabs pretreatment and the day after finishing antibiotics (immediately posttreatment). 16S rRNA gene sequencing was performed on vaginal samples. Logistic regression explored associations between BV recurrence and features of the vaginal microbiota pre- and posttreatment. RESULTS: Sixteen women (13% [95% confidence interval {CI}, 8%-21%]) experienced BV recurrence within 1 month of treatment. Women with an untreated RSP were more likely to experience recurrence than women with no RSP (P = .008) or an RSP who received treatment (P = .011). A higher abundance of Prevotella pretreatment (adjusted odds ratio [AOR], 1.35 [95% CI, 1.05-1.91]) and Gardnerella immediately posttreatment (AOR, 1.23 [95% CI, 1.03-1.49]) were associated with increased odds of BV recurrence. CONCLUSIONS: Having specific Prevotella spp prior to recommended treatment and persistence of Gardnerella immediately posttreatment may contribute to the high rates of BV recurrence. Interventions that target these taxa are likely required to achieve sustained BV cure.

gyrA Mutations in Mycoplasma genitalium and Their Contribution to Moxifloxacin Failure: Time for the Next Generation of Resistance-Guided Therapy.

BACKGROUND: Although single nucleotide polymorphisms (SNPs) in Mycoplasma genitalium parC contribute to fluoroquinolone treatment failure, data are limited for the homologous gene, gyrA. This study investigated the prevalence of gyrA SNPs and their contribution to fluoroquinolone failure. METHODS: Samples from 411 patients (male and female) undergoing treatment for M. genitalium infection (Melbourne Sexual Health Centre, March 2019-February 2020) were analyzed by Sanger sequencing (gyrA and parC). For patients treated with moxifloxacin (n = 194), the association between SNPs and microbiologic treatment outcome was analyzed. RESULTS: The most common parC SNP was G248T/S83I (21.1% of samples), followed by D87N (2.3%). The most common gyrA SNP was G285A/M95I (7.1%). Dual parC/gyrA SNPs were found in 8.6% of cases. One third of infections harboring parC G248T/S83I SNP had a concurrent SNP in gyrA conferring M95I. SNPs in gyrA cooccurred with parC S83I variations. Treatment failure was higher in patients with parC S83I/gyrA dual SNPs when compared with infections with single S83I SNP alone from analysis of (1) 194 cases in this study (81.2% vs 45.8%, P = .047), and (2) pooled analysis of a larger population of 535 cases (80.6% vs 43.2%; P = .0027), indicating a strong additive effect. CONCLUSIONS: Compared with parC S83I SNP alone, M. genitalium infections with dual mutations affecting parC/gyrA had twice the likelihood of failing moxifloxacin. Although antimicrobial resistance varies by region globally, these data indicate that gyrA should be considered as a target for future resistance assays in Australasia. We propose a strategy for the next generation of resistance-guided therapy incorporating parC and gyrA testing.

Comparison of Seegene AnyPlexTM II STI-7e with standard-of-care diagnostic methods for the detection of Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis.

The AnyPlexTM II STI-7e panel assay (Seegene) detects seven sexually transmitted organisms (Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, M. hominis, Ureaplasma urealyticum, U. parvum, and Trichomonas vaginalis). This study compared the performance of AnyPlexTM II STI-7e with standard-of-care diagnostic methods. Samples (cervical or vaginal swabs, or urine) from 1330 women were tested on standard-of-care assays; 83/1318 (6.3%) tested positive for M. genitalium (ResistancePlus® MG), 99/1317 (7.5%) positive for C. trachomatis and 11/1316 (0.8%) positive for N. gonorrhoeae (Hologic® Aptima Combo 2®), and 6/689 (0.9%) positive for T. vaginalis (wet mount microscopy). AnyPlexTM II STI-7e had good agreement for the detection of M. genitalium [Cohen's kappa of 0.80, 95% confidence intervals (CI) 0.74-0.87] and C. trachomatis (kappa of 0.87, 95% CI 0.82-0.92), with positive and negative % agreement >96% for both infections. There was lower agreement for the detection of N. gonorrhoeae (kappa of 0.37, 95%CI 0.19-0.55) and T. vaginalis (kappa of 0.521, 95%CI 0.25-0.80). In summary, the test performed well in this comparison for M. genitalium and C. trachomatis detection, but results were less conclusive for N. gonorrhoeae and T. vaginalis due to low prevalence in the population.

Time to healthcare seeking following the onset of symptoms among men and women attending a sexual health clinic in Melbourne, Australia.

Background: Timely diagnosis and treatment of sexually transmitted infections (STIs) underpin their control by reducing the duration of infectiousness. There are currently limited data exploring healthcare seeking among individuals with STI symptoms. Methods: We analyzed data on individuals reporting STI symptoms at the Melbourne Sexual Health Centre (MSHC) between August 2017 and December 2020. We calculated the time between symptom onset and clinic attendance by risk group for 13 STI diagnoses. We performed univariable and multivariable logistic regression analyses to explore factors associated with delayed healthcare seeking (greater than 7 days). Results: Among 7,032 symptomatic clinic attendances, the shortest time to healthcare seeking was among individuals diagnosed with gonococcal urethritis (median 3 days), and the longest was among individuals diagnosed with genital warts (median 60 days). Individuals diagnosed with gonococcal urethritis sought care earlier than individuals diagnosed with non-gonococcal urethritis (median 3 vs. 6 days, p < 0.001), and individuals diagnosed with genital herpes sought care earlier than individuals diagnosed with primary syphilis (median 4 vs. 14 days, p < 0.001). Men who have sex with men, and men taking human immunodeficiency virus pre-exposure prophylaxis (PrEP), were least likely to delay healthcare seeking. Both men and women who delayed healthcare seeking were more likely to live further from the clinic than those who did not delay their presentation [p trend < 0.001 (men) and p trend = 0.049 (women)]. Conclusion: Improved local access to healthcare alongside targeted strategies to encourage early healthcare seeking among groups at increased likelihood of delay may reduce STI-associated morbidity and transmission.

The Urethral Microbiota of Men with and without Idiopathic Urethritis.

Nongonococcal urethritis (NGU) is a common genital tract syndrome in men, and up to 50% of cases are considered idiopathic, i.e., no etiological agent is identified. This poses challenges for clinicians in the diagnosis and treatment of NGU and often results in antibiotic misuse and overuse. Therefore, to identify potential infectious causes of urethritis and inform clinical management of urethritis cases, we characterized and compared the urethral microbiota of men with and without idiopathic urethritis. Participants were derived from a case-control study that examined viral and bacterial pathogens and sexual practices associated with NGU. Men with NGU who tested negative for established causes of NGU (Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, adenoviruses, herpes simplex virus [HSV]-1, and/or HSV-2) were classified as idiopathic cases, and the controls were men reporting no current urethral symptoms. Men provided a urine sample that was used to characterize the urethral microbiota using 16S rRNA gene sequencing. Bacterial taxa associated with idiopathic urethritis were identified using analysis of compositions of microbiomes with bias correction. When stratified by sex of sexual partner, we found that the abundance of Haemophilus influenzae was significantly increased in men who have sex with men with idiopathic urethritis, and the abundance of Corynebacterium was significantly increased in men who have sex with women with idiopathic urethritis. Other taxa, including Ureaplasma, Staphylococcus haemolyticus, Streptococcus pyogenes, Escherichia, and Streptococcus pneumoniae/pseudopneumoniae, dominated the urethral microbiota of idiopathic urethritis cases but not controls, suggesting that these organisms may also contribute to urethritis. Importantly, the taxa we identified represent biologically plausible causes of urethritis and should be prioritized for future study. IMPORTANCE Nongonococcal urethritis (NGU) is the commonest genital tract syndrome in men and is nearly universally presumptively treated with an antibiotic. Common causes of NGU include Chlamydia trachomatis and Mycoplasma genitalium, but in more than 50% of cases, an infectious cause is not identified. In this case-control study, we found that the urethral microbiota composition differed between men with and without idiopathic urethritis and differed by sex of sexual partner. We identified specific bacterial taxa that were associated with idiopathic urethritis, including Haemophilus influenzae and Corynebacterium. These data, together with the finding that key bacterial taxa were found to dominate the urethral microbiota of cases but not controls, suggest that a range of bacteria contribute to urethritis and that these organisms may be influenced by sexual practices. Through identifying the infectious causes of urethritis, we can inform appropriate targeted diagnostic and treatment practices and importantly reduce misuse and overuse of antibiotics.

Repeat infections with chlamydia in women may be more transcriptionally active with lower responses from some immune genes.

Chlamydia trachomatis, the most common bacterial sexually transmitted infection worldwide, is responsible for considerable health burden due to its significant sequelae. There are growing concerns about chlamydial treatment and management due to widely documented increasing burden of repeat infections. In the current study, a cohort study design of 305 women with urogenital chlamydial infections demonstrated that 11.8% of women experienced repeat infections after treatment with azithromycin. The chlamydial DNA load measured by quantitative PCR was higher in women who experienced a repeat infection (p = 0.0097) and repeat infection was associated with sexual contact. There was no genomic or phenotypic evidence of azithromycin resistance within the chlamydial isolates. During repeat infection, or repeat positive tests during follow up, vaginal chlamydial gene expression (ompA, euo, omcB, htrA, trpAB) was markedly higher compared to baseline, and two of the selected immune genes analyzed had significantly lower expression at the time of repeat infection. Overall, there are two implications of these results. The results could be generalized to all recent infections, or repeat positive events, and indicate that chlamydial infections are have higher transcriptional activity of select genes early in the infection in women. Alternatively, after azithromycin treatment, repeat infections of Chlamydia may be more transcriptionally active at certain genes, and there may be post-treatment immunological alterations that interplay into repeat exposures establishing an active infection. The potential that recent infections may involve a higher level of activity from the organism may have implications for management by more regular testing of the most at risk women to reduce the risk of sequelae.

Positivity and Risk Factors for Trichomonas vaginalis Among Women Attending a Sexual Health Clinic in Melbourne, 2006 to 2019.

BACKGROUND: Trichomonas vaginalis is not a notifiable disease in Australia in most states, resulting in limited Australian epidemiological studies. This study aimed to examine the positivity of T. vaginalis in women attending the Melbourne Sexual Health Centre (MSHC) and identify associated factors. METHODS: All women 16 years or older who were tested for T. vaginalis at MSHC from 2006 to 2019 were included. The diagnostic method changed from culture to nucleic acid amplification test in August 2018. The annual positivity of T. vaginalis was calculated. Because of the data completeness, we performed a generalized estimating equations multivariable logistic regression using data from 2011 to 2019 to examine factors associated with T. vaginalis positivity. RESULTS: From 2006 to 2019, 69,739 tests for T. vaginalis were conducted, and 294 tested positive (0.42%; 95% confidence interval [CI], 0.37%-0.47%). Approximately 60% of women tested reported symptoms. After adjusting for potential confounders including the change in diagnostic method, there was a 21% (95% CI, 12%-31%) annual increase in T. vaginalis positivity between 2011 and 2019. Women with concurrent syphilis had the highest odds of testing positive for T. vaginalis (adjusted odds ratio [aOR], 21.55; 95% CI, 6.96-66.78), followed by women who had injected drugs in the last 12 months (aOR, 6.99; 95% CI, 4.11-11.87), were 35 years or older (aOR, 3.47; 95% CI, 2.26-5.35), or had concurrent chlamydia (aOR, 1.77; 95% CI, 1.05-2.99). CONCLUSIONS: The rising positivity of T. vaginalis at MSHC irrespective of change in diagnostic method suggests a concurrent community-wide rise in Melbourne. Given the rising positivity, testing informed by risk factors should be considered.

Patterns of Sexual Practices, Sexually Transmitted Infections and Other Genital Infections in Women Who Have Sex with Women Only (WSWO), Women Who Have Sex with Men Only (WSMO) and Women Who Have Sex with Men and Women (WSMW): Findings from a Sexual Health Clinic in Melbourne, Australia, 2011-2019.

Despite rises in sexually transmitted infection (STI) notifications among Australian women in the last decade, limited STI surveillance data exist specifically for women who have sex with women. This study aimed to compare differences in sexual practices and positivity for STIs and other genital infections among women who have sex with men only (WSMO), women who have sex with women only (WSWO), and women who have sex with men and women (WSMW), and whether these changed over time. In this retrospective repeated cross-sectional study, women attending the Melbourne Sexual Health Centre for the first time between 2011 and 2019 were categorized as "WSMW," "WSWO," or "WSMO" according to self-reported sexual practices in the previous 12 months. Demographic information, sexual practices, and positivity for STIs and other genital infections were compared between the three groups and over time. A total of 36,147 women (2618 WSMW, 534 WSWO, and 32,995 WSMO) were included. WSMW reported more sexual partners (median = 6; IQR = 4-10) than WSMO (median = 3; IQR = 2-5) and WSWO (median = 2; IQR = 1-4) (p < .001). A higher proportion of WSMW always used condoms with casual male partners compared to WSMO (20.4% vs 15.9%; p < .001). The proportion of women who always used condoms with casual male partners decreased over time in WSMO, (19.9% in 2011 to 15.2% in 2019, ptrend < .001) but not in WSMW. Bacterial vaginosis was more common in WSWO (14.8%) than in WSMW (11.8%) and WSMO (7.7%) (p < .001). Chlamydia was more common in WSMO (9.3%) than in WSMW (6.6%) and WSWO (1.2%) (p < .001). Syphilis was more common in WSMO (1.0%) than in WSMW (0.3%) and WSWO (0.0%) (p = .004). Over time, chlamydia positivity in WSWO increased (from 0.0% to 2.7%, ptrend = .014), and syphilis positivity in WSMW increased (from 0.0% to 0.7%, ptrend = .028); however, positivity of these STIs did not change in other groups. Sexual practices and positivity for STIs and other genital infections differed according to the sex of women's partners in the previous 12 months. Knowledge of these differences is important to account for future changes in STI trends that may occur in these subpopulations.

parC Variants in Mycoplasma genitalium: Trends over Time and Association with Moxifloxacin Failure.

Prevalence, trends, and treatment outcome estimates were generated for parC variants in macrolide-resistant Mycoplasma genitalium. Among 539 cases, the most common amino acid change was S83I, which increased from 13% in 2012 to 2013, to 23% in 2019 to 2020 (Ptrend = 0.046). From 381 moxifloxacin treatments, failure occurred in 58.7% (95% confidence interval [CI], 46.7 to 69.9) of cases with S83I. Other changes affecting S83 or D87 were uncommon and minor contributors to failure. The absence of S83I was highly predictive of moxifloxacin cure (96.4%; 95% CI, 93.7 to 98.2), highlighting diagnostic potential.