Vaccine value profile for Neisseria gonorrhoeae.

Neisseria gonorrhoeae infection (gonorrhoea) is a global public health challenge, causing substantial sexual and reproductive health consequences, such as infertility, pregnancy complications and increased acquisition or transmission of HIV. There is an urgency to controlling gonorrhoea because of increasing antimicrobial resistance to ceftriaxone, the last remaining treatment option, and the potential for gonorrhoea to become untreatable. No licensed gonococcal vaccine is available. Mounting observational evidence suggests that N. meningitidis serogroup B outer membrane vesicle-based vaccines may induce cross-protection against N. gonorrhoeae (estimated 30%-40% effectiveness using the 4CMenB vaccine). Clinical trials to determine the efficacy of the 4CMenB vaccine against N. gonorrhoeae are underway, as are Phase 1/2 studies of a new gonococcal-specific vaccine candidate. Ultimately, a gonococcal vaccine must be accessible, affordable and equitably dispensed, given that those most affected by gonorrhoea are also those who may be most disadvantaged in our societies, and most cases are in less-resourced settings. This vaccine value profile (VVP) provides a high level, holistic assessment of the current data to inform the potential public health, economic and societal value of pipeline vaccines. This was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations. All contributors have extensive expertise on various elements of the N. gonorrhoeae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using published data obtained from peer-reviewed journals or reports.

"How PrEPared are you?": Knowledge of and attitudes toward PrEP among overseas-born and newly arrived gay, bisexual, and other men who have sex with men in Australia.

Introduction: Overseas-born and newly arrived gay and bisexual men and men who have sex with men (GBMSM) are at higher risk of acquiring HIV in comparison to Australian-born GBMSM. Pre-exposure prophylaxis (PrEP) is subsidized by the Australian government under Medicare, Australia's universal health insurance scheme, however many members of this population are Medicare-ineligible, which could prevent them from accessing PrEP. We wanted to explore participants' knowledge of and attitudes toward PrEP and their opinions of new PrEP modalities, namely injectable PrEP and PrEP implants. Methods: We conducted in-depth qualitative interviews between February 2021 to September 2021 with 22 overseas-born, newly arrived (<5 years in Australia) GBMSM of varying PrEP use. We asked their opinions of PrEP and their preferences of new PrEP modalities. Interviews were audio recorded and transcribed verbatim. We conducted a reflexive thematic analysis to interpret the data. Results: Participants' views reflect the intersections between systemic factors, such as Medicare ineligibility and the high cost of PrEP, with socio-cultural factors, such as lack of knowledge about PrEP, internalized stigma stemming from homo- and sex-negativity, and stigmatizing attitudes toward PrEP and PrEP users. For participants who were on PrEP, being community connected, having a positive relationship with doctors and nurses, and being informed of the option to purchase PrEP from overseas pharmacies at a low cost helped them to overcome some of these barriers. Additionally, there was a strong preference for injectable PrEP but not PrEP implants. Participants stressed the importance of providing a comprehensive information about PrEP specific to this population and to make PrEP free for all. Conclusions: We concluded that resources about PrEP specific to this population that address both systemic and socio-cultural factors are needed, and for these resources to be available in languages other than English. This is to coincide with on-going advocacy to increase the capacity of publicly funded sexual health clinics to provide multilingual PrEP services for people without Medicare, and to make PrEP free for all. These combined strategies have the potential to increase PrEP knowledge and uptake among this population.

Combination Therapy for Mycoplasma genitalium, and New Insights Into the Utility of parC Mutant Detection to Improve Cure.

BACKGROUND: Mycoplasma genitalium (MG) infection is challenging to cure because of rising antimicrobial resistance and limited treatment options. METHODS: This was a prospective evaluation of the efficacy and tolerability of resistance-guided combination antimicrobial therapy for MG treatment at Melbourne Sexual Health Centre (August 2019-December 2020). All patients received 7 days of doxycycline before combination therapy based on the macrolide-resistant profile. Macrolide-susceptible infections received combination doxycycline + azithromycin (1 g, day 1; 500 mg, days 2-4) and macrolide-resistant infections combination doxycycline + moxifloxacin (400 mg daily for 7 days). Adherence and adverse effects were recorded at test-of-cure, recommended 14-28 days after antimicrobial completion. Sequencing was performed to determine the prevalence of single nucleotide polymorphisms (SNPs) in the parC gene and their association with moxifloxacin treatment outcomes in macrolide-resistant infections. RESULTS: Of 100 patients with macrolide-susceptible MG treated with doxycycline + azithromycin, 93 were cured (93.0%; 95% confidence interval [CI], 86.1-97.1). Of 247 patients with macrolide-resistant MG receiving doxycycline + moxifloxacin, 210 were cured (85.0%; 95% CI, 80.0-89.2). parC sequencing was available for 164 (66%) macrolide-resistant infections; 29% had SNPs at parC S83 or D87 (23% S83I). The absence of SNPs at parC S83/D87 was associated with 98.3% cure (95% CI, 93.9-99.8) following doxycycline + moxifloxacin. The presence of the parC S83I-SNP was associated with failure in 62.5% (95% CI, 45.8-77.3). Side effects were common (40%-46%) and predominantly mild and gastrointestinal. CONCLUSIONS: Combination doxycycline + azithromycin achieved high cure for macrolide-susceptible infections. However, in the context of a high prevalence of the parC S83I mutation (23%) in macrolide-resistant infections, doxycycline + moxifloxacin cured only 85%. Infections that were wild-type for S83/D87 experienced high cure following doxycycline + moxifloxacin, supporting the use of a parC-resistance/susceptibility testing strategy in clinical care.

Antiseptic mouthwash for gonorrhoea prevention (OMEGA): a randomised, double-blind, parallel-group, multicentre trial.

BACKGROUND: To address the increasing incidence of gonorrhoea and antimicrobial resistance, we compared the efficacy of Listerine and Biotène mouthwashes for preventing gonorrhoea among men who have sex with men (MSM). METHODS: The OMEGA trial was a multicentre, parallel-group, double-blind randomised controlled trial among MSM, done at three urban sexual health clinics and one general practice clinic in Australia. Men were eligible if they were diagnosed with oropharyngeal gonorrhoea by nucleic acid amplification test (NAAT) in the previous 30 days or were aged 16-24 years. They were randomly assigned to receive Listerine (intervention) or Biotène (control) via a computer-generated sequence (1:1 ratio, block size of four). Participants, clinicians, data collectors, data analysts, and outcome adjudicators were masked to the interventions after assignment. Participants were instructed to rinse and gargle with 20 mL of mouthwash for 60 s at least once daily for 12 weeks. Oropharyngeal swabs were collected by research nurses every 6 weeks, and participants provided saliva samples every 3 weeks, to be tested for Neisseria gonorrhoeae with NAAT and quantitative PCR. The primary outcome was proportion of MSM diagnosed with oropharyngeal N gonorrhoeae infection at any point over the 12-week period, defined as a positive result for either oropharyngeal swabs or saliva samples by NAAT, and the cumulative incidence of oropharyngeal gonorrhoea at the week 12 visit. A modified intention-to-treat analysis for the primary outcome was done that included men who provided at least one follow-up specimen over the 12-week study period. The trial was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12616000247471). FINDINGS: Between March 30, 2016, and Oct 26, 2018, 786 MSM were screened and 256 were excluded. 264 MSM were randomly assigned to the Biotène group and 266 to the Listerine group. The analysis population included 227 (86%) men in the Biotène group and 219 (82%) in the Listerine group. Oropharyngeal gonorrhoea was detected in ten (4%) of 227 of MSM in the Biotène group and in 15 (7%) of 219 in the Listerine group (adjusted risk difference 2·5%, 95% CI -1·8 to 6·8). The cumulative incidence of oropharyngeal gonorrhoea at the week 12 visit did not differ between the two mouthwash groups (adjusted risk difference 3·1%, 95% CI -1·4 to 7·7). INTERPRETATION: Listerine did not reduce the incidence of oropharyngeal gonorrhoea compared with Biotène. However, previous research suggests that mouthwash might reduce the infectivity of oropharyngeal gonorrhoea; therefore, further studies of mouthwash examining its inhibitory effect on N gonorrhoeae are warranted to determine if it has a potential role for the prevention of transmission. FUNDING: Australian National Health and Medical Research Council.

Disparities in characteristics in accessing public Australian sexual health services between Medicare-eligible and Medicare-ineligible men who have sex with men.

OBJECTIVES: Accessible health services are a key element of effective human immunodeficiency virus (HIV) and sexually transmitted infection (STI) control. This study aimed to examine whether there were any differences in accessing sexual health services between Medicare-eligible and Medicare-ineligible men who have sex with men (MSM) in Melbourne, Australia. METHODS: We conducted a retrospective, cross-sectional study of MSM attending Melbourne Sexual Health Centre between 2016 and 2019. Demographic characteristics, sexual practices, HIV testing practices and STI diagnoses were compared between Medicare-eligible and Medicare-ineligible MSM. RESULTS: We included 5,085 Medicare-eligible and 2,786 Medicare-ineligible MSM. Condomless anal sex in the past 12 months was more common in Medicare-eligible compared to Medicare-ineligible MSM (74.4% vs. 64.9%; p<0.001) although the number of partners did not differ between groups. There was no difference in prior HIV testing practices between Medicare-eligible and Medicare-ineligible MSM (76.1% vs. 77.7%; p=0.122). Medicare-ineligible MSM were more likely to have anorectal chlamydia compared to Medicare-eligible MSM (10.6% vs. 8.5%; p=0.004). CONCLUSIONS: Medicare-ineligible MSM have less condomless sex but a higher rate of anorectal chlamydia, suggesting they might have limited access to STI testing or may be less willing to disclose high-risk behaviour. Implications for public health: Scaling up access to HIV and STI testings for Medicare-ineligible MSM is essential.

Prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium: a systematic review and meta-analysis.

BACKGROUND: Mycoplasma genitalium is now recognised as an important bacterial sexually transmitted infection. We summarised data from studies of mutations associated with macrolide and fluoroquinolone resistance in M genitalium to establish the prevalence of resistance. We also investigated temporal trends in resistance and aimed to establish the association between resistance and geographical location. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, and MEDLINE for studies that included data for the prevalence of mutations associated with macrolide and fluoroquinolone resistance in M genitalium published in any language up to Jan 7, 2019. We defined prevalence as the proportion of M genitalium samples positive for key mutations associated with azithromycin resistance (23S rRNA gene, position 2058 or 2059) or moxifloxacin resistance (S83R, S83I, D87N, or D87Y in parC), or both, among all M genitalium samples that were successfully characterised. We used random-effects meta-analyses to calculate summary estimates of prevalence. Subgroup and meta-regression analyses by WHO region and time period were done. This study was registered with PROSPERO, number CRD42016050370. RESULTS: Overall, 59 studies from 21 countries met the inclusion criteria for our study: 57 studies of macrolide resistance (8966 samples), 25 of fluoroquinolone resistance (4003 samples), and 22 of dual resistance to macrolides and fluoroquinolones (3280 samples). The summary prevalence of mutations associated with macrolide resistance among M genitalium samples was 35·5% (95% CI 28·8-42·5); prevalence increased from 10·0% (95% CI 2·6-20·1%) before 2010, to 51·4% (40·3-62·4%) in 2016-17 (p<0·0001). Prevalence of mutations associated with macrolide resistance was significantly greater in samples in the WHO Western Pacific and Americas regions than in those from the WHO European region. The overall prevalence of mutations associated with fluoroquinolone resistance in M genitalium samples was 7·7% (95% CI 4·5-11·4%). Prevalence did not change significantly over time, but was significantly higher in the Western Pacific region than in the European region. Overall, the prevalence of both mutations associated with macrolide resistance and those associated with fluoroquinolone resistance among M genitalium samples was 2·8% (1·3-4·7%). The prevalence of dual resistance did not change significantly over time, and did not vary significantly by geographical region. INTERPRETATION: Global surveillance and measures to optimise the efficacy of treatments-including resistance-guided strategies, new antimicrobials, and antimicrobial combination approaches-are urgently needed to ensure cure in a high proportion of M genitalium infections and to prevent further spread of resistant strains. FUNDING: Australian National Health and Medical Research Council.

Resistance-Guided Antimicrobial Therapy Using Doxycycline-Moxifloxacin and Doxycycline-2.5 g Azithromycin for the Treatment of Mycoplasma genitalium Infection: Efficacy and Tolerability.

BACKGROUND: Macrolide resistance in Mycoplasma genitalium (MG) exceeds 50% in many regions, and quinolone resistance is increasing. We recently reported that resistance-guided therapy (RGT) using doxycycline followed by sitafloxacin or 2.5 g azithromycin cured 92% and 95% of macrolide-resistant and macrolide-susceptible infections, respectively. We present data on RGT using doxycycline-moxifloxacin, the regimen recommended in international guidelines, and extend data on the efficacy of doxycycline-2.5 g azithromycin and de novo macrolide resistance. METHODS: Patients attending Melbourne Sexual Health Centre between 2017 and 2018 with sexually transmitted infection syndromes were treated with doxycycline for 7 days and recalled if MG-positive. Macrolide-susceptible cases received 2.5 g azithromycin (1 g, then 500 mg daily for 3 days), and resistant cases moxifloxacin (400 mg daily, 7 days). Test of cure was recommended 14-28 days post-antimicrobials. RESULTS: There were 383 patients (81 females/106 heterosexual males/196 men who have sex with men) included. Microbial cure following doxycycline-azithromycin was 95.4% (95% confidence interval [CI], 89.7-98.0) and doxycycline-moxifloxacin was 92.0% (95% CI, 88.1-94.6). De novo macrolide resistance was detected in 4.6% of cases. Combining doxycycline-azithromycin data with our prior RGT study (n = 186) yielded a pooled cure of 95.7% (95% CI, 91.6-97.8). ParC mutations were present in 22% of macrolide-resistant cases. CONCLUSIONS: These findings support the inclusion of moxifloxacin in resistance-guided strategies and extend the evidence for 2.5 g azithromycin and presumptive use of doxycycline. These data provide an evidence base for current UK, Australian, and European guidelines for the treatment of MG.

Clinical Characteristics of Anorectal Mycoplasma genitalium Infection and Microbial Cure in Men Who Have Sex With Men.

BACKGROUND: We report clinical characteristics of proctitis caused solely by Mycoplasma genitalium (MG) compared with chlamydia and gonococcus. We determined the proportions cured with first-line (azithromycin) and second-line antimicrobials (moxifloxacin, pristinamycin). METHODS: A total of 166 patients attending Melbourne Sexual Health Centre from 2012 to 2016 with symptoms of proctitis were tested for MG, Chlamydia trachomatis, and Neisseria gonorrhoeae. Demographic characteristics, sexual behaviors, clinical symptoms, and signs were recorded. Multinomial multivariable logistic regression was used to test for significant differences in symptoms and signs for the pathogens detected. RESULTS: Seventeen percent of men had MG (95% confidence interval, 12-24), 21% had chlamydia (15-27), and 40% had gonococcal monoinfection (32-48), whereas 22% had MG coinfection (16-29). Relative to men with MG monoinfection, those with chlamydial monoinfection reported more anal pain (adjusted prevalence odds ratio (aPOR), 4.68 [1.41-14.19]), whereas men with gonococcal monoinfection reported more anal pain (aPOR, 6.75 [2.21-20.55]) and tenesmus (aPOR, 15.44 [1.62-146.90]), but less anal itch (aPOR, 0.32 [0.11-0.93]). The microbiological cure for MG using azithromycin was low at 35% (22-50), whereas moxifloxacin subsequently cured 92% (64-100) and pristinamycin cured 79% (54-94) of infections. CONCLUSIONS: M. genitalium was almost as common as chlamydia in men presenting to a sexual health center with symptoms of proctitis. Men with anorectal MG monoinfection were less likely to have symptoms and signs compared with those with chlamydia or gonococcus monoinfection. Cure for men with symptomatic anorectal MG by azithromycin was low. We suggest routine testing for MG in cases of proctitis, with test of cure after treatment being essential.