Multicentre double-blind randomised placebo-controlled trial evaluating the efficacy of the meningococcal B vaccine, 4CMenB (Bexsero), against Neisseria gonorrhoeae infection in men who have sex with men: the GoGoVax study protocol.

INTRODUCTION: Gonorrhoea, the sexually transmissible infection caused by Neisseria gonorrhoeae, has a substantial impact on sexual and reproductive health globally with an estimated 82 million new infections each year worldwide. N. gonorrhoeae antimicrobial resistance continues to escalate, and disease control is largely reliant on effective therapy as there is no proven effective gonococcal vaccine available. However, there is increasing evidence from observational cohort studies that the serogroup B meningococcal vaccine four-component meningitis B vaccine (4CMenB) (Bexsero), licensed to prevent invasive disease caused by Neisseria meningitidis, may provide cross-protection against the closely related bacterium N. gonorrhoeae. This study will evaluate the efficacy of 4CMenB against N. gonorrhoeae infection in men (cis and trans), transwomen and non-binary people who have sex with men (hereafter referred to as GBM+). METHODS AND ANALYSIS: This is a double-blind, randomised placebo-controlled trial in GBM+, either HIV-negative on pre-exposure prophylaxis against HIV or living with HIV (CD4 count >350 cells/mm3), who have had a diagnosis of gonorrhoea or infectious syphilis in the last 18 months (a key characteristic associated with a high risk of N. gonorrhoeae infection). Participants are randomised 1:1 to receive two doses of 4CMenB or placebo 3 months apart. Participants have 3-monthly visits over 24 months, which include testing for N. gonorrhoeae and other sexually transmissible infections, collection of demographics, sexual behaviour risks and antibiotic use, and collection of research samples for analysis of N. gonorrhoeae-specific systemic and mucosal immune responses. The primary outcome is the incidence of the first episode of N. gonorrhoeae infection, as determined by nucleic acid amplification tests, post month 4. Additional outcomes consider the incidence of symptomatic or asymptomatic N. gonorrhoeae infection at different anatomical sites (ie, urogenital, anorectum or oropharynx), incidence by N. gonorrhoeae genotype and antimicrobial resistance phenotype, and level and functional activity of N. gonorrhoeae-specific antibodies. ETHICS AND DISSEMINATION: Ethical approval was obtained from the St Vincent's Hospital Human Research Ethics Committee, St Vincent's Hospital Sydney, NSW, Australia (ref: 2020/ETH01084). Results will be disseminated in peer-reviewed journals and via presentation at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04415424.

Management of acute sexual assault presenting to a large Australian sexual health clinic in 2012-2021: a retrospective clinical audit.

Background The incidence of sexual assault continues to rise in Australia. This study aimed to describe the nature of assault, HIV/STI positivity, and its management at a sexual health clinic. Methods We performed a chart review of 516 sexual assault cases presenting to Melbourne Sexual Health Centre between 2012 and 2021, collecting data on victim demographics, details of assault, HIV/STI testing and positivity, police involvement, and offer of counselling. Results We included 516 cases: 124 males (24.0%); 384 females (74.4%); and eight transgender (1.6%) victims. The proportion of assault cases presenting to Melbourne Sexual Health Centre increased from 0.1% (37/37,070) in 2012 to 0.2% (56/36,514) in 2021 (P trend =0.006). HIV post-exposure prophylaxis was prescribed for 64.5% (80/124) of males and 12.5% (48/384) of females. Among victims, 69.4% (358/516) were tested for HIV and no one tested positive, while 71.9% (371/516) were tested for syphilis, with 1.6% (6/371) positive. Gonorrhoea and chlamydia were tested at the oropharynx (44.8% [231/516] vs 28.7% [148/516]), genitals (83.7% [432/516] vs 92.4% [477/516]) and anorectum (35.3% [182/516] vs 35.3% [182/516]). Positivity for gonorrhoea and chlamydia were: 2.6% (6/231) vs 2.0% (3/148) at oropharynx, 1.4% (6/432) vs 2.9% (14/477) at genitals, and 5.5% (10/182) vs 7.1% (13/182) at anorectum. According to clinical records, 25.2% (130/516) of victims sought police involvement, and 71.7% (370/516) were offered counselling. Conclusions Sexual assault was an uncommon presentation at Melbourne Sexual Health Centre, with diverse circumstances surrounding assault; however, clinical documentation varied, indicating a need for a standard primary care protocol for clients presenting with acute sexual assault.

Factors associated with HIV pre-exposure prophylaxis use among Asian men who have sex with men in Sydney and Melbourne, Australia: a cross-sectional study.

Background: Asian-born MSM are a priority population as Australia aims to end HIV transmission, but they reported additional barriers to access PrEP and other HIV prevention methods. This study investigates factors associated with PrEP use among Asian MSM in Sydney and Melbourne, Australia, to inform strategies to improve PrEP uptake in this population. Methods: This was a sub-analysis of a community-based cross-sectional survey conducted from March to June 2021. We recruited participants online in Sydney and Melbourne, Australia. Univariable and multivariable logistic regression analyses were performed to identify the factors associated with PrEP use in the last six months and lifetime. Latent class analyses were used to identify subgroups of Asian MSM sharing similar characteristics related to their risk practices for HIV. Findings: Overall, 870 Asian MSM were included: 288 Oceanian-born Asian MSM and 582 Asian-born MSM. Three latent classes were identified: 1) Asian-born MSM who recently arrived in Australia with limited English, were less likely to use PrEP and at higher risk of HIV infection (e.g., had condomless anal sex with a casual sex partner in the last six months) (4.6%); 2) Asian MSM who were at lower risk of HIV infection and less likely to use PrEP (69.3%) and; 3) Asian MSM who were at substantial risk of HIV infection and more likely to use PrEP (26.1%). Compared to Oceanian-born Asian MSM, those who were born in Southeast Asia (adjusted odds ratio (aOR) = 0.5, 95% confidence interval (CI) 0.3-0.7) and South Asia (aOR = 0.4, 95% CI 0.2-0.8) were less likely to ever use PrEP. Compared to Oceanian-born Asian MSM, those who were born in Southeast Asia (aOR = 0.4, 95% CI 0.3-0.7), Northeast Asia (aOR = 0.5, 95% CI 0.3-0.8) and South Asia (aOR = 0.4, 95% CI 0.2-0.7) were less likely to use PrEP in the last six months. Interpretation: To end HIV transmission in Australia, it will be necessary to develop strategies to improve PrEP access for the significant minority of Asian-born MSM who are at substantial risk of HIV infection. Funding: EPFC and JJO are supported by an Australian National Health and Medical Research Council (NHMRC) Emerging Leadership Investigator Grant (EPFC: GNT1172873 and JJO: GNT1193955). CKF is supported by an Australian National Health and Medical Research Council (NHMRC) Leadership Investigator Grant (GNT1172900).

Identifying Individuals at High Risk for HIV and Sexually Transmitted Infections With an Artificial Intelligence-Based Risk Assessment Tool.

Background: We have previously developed an artificial intelligence-based risk assessment tool to identify the individual risk of HIV and sexually transmitted infections (STIs) in a sexual health clinical setting. Based on this tool, this study aims to determine the optimal risk score thresholds to identify individuals at high risk for HIV/STIs. Methods: Using 2008-2022 data from 216 252 HIV, 227 995 syphilis, 262 599 gonorrhea, and 320 355 chlamydia consultations at a sexual health center, we applied MySTIRisk machine learning models to estimate infection risk scores. Optimal cutoffs for determining high-risk individuals were determined using Youden's index. Results: The HIV risk score cutoff for high risk was 0.56, with 86.0% sensitivity (95% CI, 82.9%-88.7%) and 65.6% specificity (95% CI, 65.4%-65.8%). Thirty-five percent of participants were classified as high risk, which accounted for 86% of HIV cases. The corresponding cutoffs were 0.49 for syphilis (sensitivity, 77.6%; 95% CI, 76.2%-78.9%; specificity, 78.1%; 95% CI, 77.9%-78.3%), 0.52 for gonorrhea (sensitivity, 78.3%; 95% CI, 77.6%-78.9%; specificity, 71.9%; 95% CI, 71.7%-72.0%), and 0.47 for chlamydia (sensitivity, 68.8%; 95% CI, 68.3%-69.4%; specificity, 63.7%; 95% CI, 63.5%-63.8%). High-risk groups identified using these thresholds accounted for 78% of syphilis, 78% of gonorrhea, and 69% of chlamydia cases. The odds of positivity were significantly higher in the high-risk group than otherwise across all infections: 11.4 (95% CI, 9.3-14.8) times for HIV, 12.3 (95% CI, 11.4-13.3) for syphilis, 9.2 (95% CI, 8.8-9.6) for gonorrhea, and 3.9 (95% CI, 3.8-4.0) for chlamydia. Conclusions: Risk scores generated by the AI-based risk assessment tool MySTIRisk, together with Youden's index, are effective in determining high-risk subgroups for HIV/STIs. The thresholds can aid targeted HIV/STI screening and prevention.

Chlamydia retesting remains low among young women in Australia: an observational study using sentinel surveillance data, 2018-2022.

BACKGROUND: Chlamydia remains the most notified bacterial sexually transmissible infection in Australia with guidelines recommending testing for re-infection at 3months post treatment. This paper aimed to determine chlamydia retesting and repeat positivity rates within 2-4months among young women in Australia, and to evaluate what factors increase or decrease the likelihood of retesting. METHODS: Chlamydia retesting rates among 16-29-year-old women were analysed from Australian Collaboration for Coordinated Enhanced Sentinel Surveillance of sexually transmissible infection and bloodborne virus (ACCESS) sentinel surveillance data (n =62 sites). Among women with at least one positive test between 1 January 2018 and 31 August 2022, retesting counts and proportions within 2-4months were calculated. Logistic regression was performed to assess factors associated with retesting within 2-4months. RESULTS: Among 8758 women who were positive before 31 August 2022 to allow time for follow up, 1423 (16.2%) were retested within 2-4months, of whom 179 (12.6%) tested positive. The odds of retesting within 2-4months were 25% lower if tested in a coronavirus disease 2019 (COVID-9) pandemic year (2020-2022) (aOR=0.75; 95% CI 0.59-0.95). Among 9140 women with a positive test before 30 November 2022, 397 (4.3%) were retested too early (within 7days to 1month) and 81 (20.4%) of those were positive. CONCLUSIONS: Chlamydia retesting rates remain low with around a sixth of women retested within 2-4months in line with guidelines. Re-infection is common with around one in eight retesting positive. An increase in retesting is required to reduce the risk of reproductive complications and onward transmission.

Sexual health clinic attendees' views on antibiotic post-exposure prophylaxis and vaccinations for sexually transmitted infections prevention: A qualitative study.

Background: The rising prevalence of bacterial sexually transmitted infections (STIs) is cause for concern in the context of antimicrobial resistance and the potential health outcomes of untreated infections. Objective: The Community Awareness and Surveillance of Transmission (CAST) study sought sexual health service users' views on reducing the prevalence of STIs. Methods: Semi-structured interviews were conducted with sexual health clinic attendees who had received a diagnosis of chlamydia, gonorrhea or syphilis in the previous six months. Participant comments relating to antibiotic post-exposure prophylaxis (APEP) and vaccination were inductively coded, then compared using comparative qualitative data analysis methods described by Miles and Huberman. Findings: Twenty-one participants with differing genders, ages, nationalities and sexual orientations, were interviewed. Participants across informant groups expressed concerns about APEP for STI prevention because of potential antimicrobial resistance and personal health impacts. Vaccination against bacterial STIs was more acceptable. Common factors mentioned in relation to both interventions included perception of individual STI risk over time, safety, effectiveness and accessibility. Conclusions: The views of sexual health service users support efforts to find alternatives to more frequent use of antibiotics, such as vaccinations against bacterial STIs, to reduce STI incidence and support antimicrobial stewardship.

Optimising HIV pre-exposure prophylaxis and testing strategies in men who have sex with men in Australia, Thailand, and China: a modelling study and cost-effectiveness analysis.

BACKGROUND: Men who have sex with men (MSM) in the Asia-Pacific region have a disproportionately high burden of HIV infection compared with the general population. Although pre-exposure prophylaxis (PrEP) for HIV is highly effective at preventing new HIV infections, the cost-effectiveness of PrEP for MSM in different countries in the Asia-Pacific region with varying PrEP coverage and HIV testing frequencies remains unstudied. We aimed to analyse the economic and health benefits of long-acting injectable cabotegravir (CAB-LA) compared with oral PrEP in high-income countries and low-income and middle-income countries within the Asia-Pacific region. METHODS: We developed a decision-analytic Markov model to evaluate the population impact and cost-effectiveness of PrEP scale-up among MSM in Australia, Thailand, and China. We assumed a static cohort of 100 000 MSM aged 18 years or older who were at risk of HIV infection, with a monthly cycle length over a 40-year time period. We evaluated hypothetical scenarios with universal PrEP coverage of 80% among 100 000 suitable MSM in each country. We modelled oral PrEP and CAB-LA for MSM with diverse HIV testing frequency strategies. We adopted the health-care system's perspective with a 3% annual discount rate. We calculated the incremental cost-effectiveness ratio (ICER), measured as additional cost per quality-adjusted life-year (QALY) gained, to compare different strategies with the status quo in each country. All costs were reported in 2021 US$. We also performed one-way, two-way, and probabilistic sensitivity analyses to assess the robustness of our findings. FINDINGS: Compared with the status quo in each country, expanding oral PrEP to 80% of suitable MSM would avert 8·1% of new HIV infections in Australia, 14·5% in Thailand, and 26·4% in China in a 40-year period. Expanding oral PrEP use with 6-monthly HIV testing for both PrEP and non-PrEP users was cost-saving for Australia. Similarly, expanding oral PrEP use remained the most cost-effective strategy in both Thailand and China, but optimal testing frequency varied, with annual testing in Thailand (ICER $4707 per QALY gained) and 3-monthly testing in China (ICER $16 926 per QALY gained) for both PrEP and non-PrEP users. We also found that replacing oral PrEP with CAB-LA for MSM could avert more new HIV infections (12·8% in Australia, 27·6% in Thailand, and 32·8% in China), but implementing CAB-LA was not cost-effective due to its high cost. The cost of CAB-LA would need to be reduced by 50-90% and be used as a complementary strategy to oral PrEP to be cost-effective in these countries. INTERPRETATION: Expanding oral PrEP use for MSM, with country-specific testing frequency, is cost-effective in Australia, Thailand, and China. Due to the high cost, CAB-LA is currently not affordable as a single-use strategy but might be offered as an additional option to oral PrEP. FUNDING: Ministry of Science and Technology of the People's Republic of China, the Australian National Health and Medical Research Council, National Key Research and Development Program of China, and National Natural Science Foundation of China.

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.

STI pathogens in the oropharynx: update on screening and treatment.

PURPOSE OF REVIEW: The rise in antimicrobial resistance in several STI pathogens such as Neisseria gonorrhoeae has become a public health threat as only one first-line treatment remains. Reducing screening interval for gonorrhoea and chlamydia in high-prevalence populations has been proposed to address antimicrobial stewardship, but this remains controversial. This review aimed to revisit the epidemiology of infections at the oropharynx and review the current screening recommendations and treatment guidelines in different populations. RECENT FINDINGS: Emerging evidence suggests that the oropharynx is the primary anatomical site for gonorrhoea transmission but maybe not for chlamydia transmission. Most international guidelines recommend 3-monthly oropharyngeal gonorrhoea and chlamydia screening for high-prevalence populations (e.g. men who have sex with men) but not low-prevalence populations (e.g. heterosexuals) given the clinical and public health benefits of screening in low-prevalence populations are still unclear. Doxycycline remains the first-line treatment for oropharyngeal chlamydia in most guidelines. However, some countries have moved from dual therapy (ceftriaxone and azithromycin) to monotherapy (ceftriaxone) for oropharyngeal gonorrhoea treatment to address antimicrobial stewardship. SUMMARY: The transmission of gonorrhoea and chlamydia is still not fully understood. Further work will be required to evaluate the benefits and harms of reducing screening in high-prevalence populations.

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.

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.

Australian Sexual Health Service Users' Perspectives on Reducing the Oral Transmission of Bacterial STIs: A Qualitative Study.

Growing rates of bacterial sexually transmitted infections (STIs) demand new approaches to STI prevention. Sexual practices involving saliva or direct contact with the mouth increase the risk of STI transmission, but community awareness remains largely unexplored in the literature. The Community Awareness and Surveillance of STI Transmission study sought to explore sexual health clinic attendees' awareness of oral STIs; experiences when seeking testing and treatment; and acceptable educational and clinical interventions. Twenty-one semi-structured interviews were conducted with a diverse group of Melbourne Sexual Health Center attendees'. Reflective thematic analysis was undertaken, revealing key themes across people of different genders, sexual identities, ages, and nationalities. All participants emphasized the importance of understanding how their sexual practices might put them at risk of an oral STI. They also sought care from specialist sexual health services with the expectation that health-care providers (HCPs) in these settings had more understanding of diverse sexual practices. Participants' decisions to protect themselves against oral STIs were primarily driven by the effect the decision had on pleasure and intimacy. Comfort during the health-care encounter and trust in HCPs facilitated better understanding of individual STI risk. Differences in awareness and risk reduction strategies were noted based on past experience with oral testing and STIs. These findings highlight the importance of HCPs and public health interventions providing solutions that recognize the central role of pleasure and intimacy in our sexual lives.

Corrigendum to: Optimising the delivery of sexual health services in Australia: a qualitative study.

BACKGROUND: With a rise in sexually transmitted infections in Australia, it is important to evaluate and optimise current sexual health services to reduce barriers to access and increase testing. We aimed to describe the range of sexual health services in Australia, focusing on strategies to improve testing among priority populations, and any future strategies participants believed would improve service delivery. METHODS: We conducted 20 semi-structured interviews with key informants working in Australian sexual health services from July to December 2020, and collected data on service characteristics and strategies to improve access. We used content analysis, then coded and categorised the data into recurring themes and sub-themes. RESULTS: We identified two major themes: 'Expanding Traditional Service Delivery' and 'Thinking Outside the Box'. The first theme outlines strategies that build upon pre-existing service delivery models, such as express clinics and an increased focus on confidentiality. The second theme outlines new strategies introduced to fill gaps in service delivery, such as self-testing and outreach. CONCLUSIONS: To improve access to HIV/STI testing, there is a need for multiple access points to cater for a range of populations and their preferences. Establishing strategies to accomplish this involves utilising a combination of expanding traditional service models and implementing new approaches to service delivery.

Rapid detection of monkeypox virus using a CRISPR-Cas12a mediated assay: a laboratory validation and evaluation study.

BACKGROUND: The 2022 outbreak of mpox (formerly known as monkeypox) led to the spread of monkeypox virus (MPXV) in over 110 countries, demanding effective disease management and surveillance. As current diagnostics rely largely on centralised laboratory testing, our objective was to develop a simple rapid point-of-care assay to detect MPXV in clinical samples using isothermal amplification coupled with CRISPR and CRISPR-associated protein (Cas) technology. METHODS: In this proof-of-concept study, we developed a portable isothermal amplification CRISPR-Cas12a-based assay for the detection of MPXV. We designed a panel of 22 primer-guide RNA sets using pangenome and gene-agnostic approaches, and subsequently shortlisted the three sets producing the strongest signals for evaluation of analytical sensitivity and specificity using a fluorescence-based readout. The set displaying 100% specificity and the lowest limit of detection (LOD) was selected for further assay validation using both a fluorescence-based and lateral-flow readout. Assay specificity was confirmed using a panel of viral and bacterial pathogens. Finally, we did a blind concordance study on genomic DNA extracted from 185 clinical samples, comparing assay results with a gold-standard quantitative PCR (qPCR) assay. We identified the optimal time to detection and analysed the performance of the assay relative to qPCR using receiver operating characteristic (ROC) curves. We also assessed the compatibility with lateral-flow strips, both visually and computationally, where strips were interpreted blinded to the fluorescence results on the basis of the presence or absence of test bands. FINDINGS: With an optimal run duration of approximately 45 min from isothermal amplification to CRISPR-assay readout, the MPXV recombinase polymerase amplification CRISPR-Cas12a-based assay with the selected primer-guide set had an LOD of 1 copy per µL and 100% specificity against tested viral pathogens. Blinded concordance testing of 185 clinical samples resulted in 100% sensitivity (95% CI 89·3-100) and 99·3% specificity (95% CI 95·7-100) using the fluorescence readout. For optimal time to detection by fluorescence readout, we estimated the areas under the ROC curve to be 0·98 at 2 min and 0·99 at 4 min. Lateral-flow strips had 100% sensitivity (89·3-100) and 98·6% specificity (94·7-100) with both visual and computational assessment. Overall, lateral-flow results were highly concordant with fluorescence-based readouts (179 of 185 tests, 96·8% concordant), with discrepancies associated with low viral load samples. INTERPRETATION: Our assay for the diagnosis of mpox displayed good performance characteristics compared with qPCR. Although optimisation of the assay will be required before deployment, its usability and versatility present a potential solution to MPXV detection in low-resource and remote settings, as well as a means of community-based, on-site testing. FUNDING: Victorian Medical Research Accelerator Fund and the Australian Government Department of Health.

Treponema pallidum Detection at Asymptomatic Oral, Anal, and Vaginal Sites in Adults Reporting Sexual Contact with Persons with Syphilis.

We investigated Treponema pallidum PCR positivity at mucosal sites (oral, anal, and vaginal sites) among adults who had sexual contact with a person with syphilis (syphilis contacts). All syphilis contacts had oral rinse and swab samples collected for testing. Men who have sex with men had anal swab and women had vaginal swab samples collected for testing, regardless of the presence of lesions. Of 407 persons tested, 42 (10%) had early syphilis diagnosed; of those, 19 (45%) tested positive by PCR from any anatomic site and had a positive serologic test. T. pallidum was positive from vaginal samples in 3 women, anal samples in 3 men, and oral cavity samples in 2 women and 3 men, without symptoms at those sites. Three women had no prior syphilis serologic test. T. pallidum detection at asymptomatic mucosal sites suggests early syphilis infections, particularly in cases that would conventionally be staged as latent syphilis of unknown duration.

Emerging sexual and reproductive health in Australia and New Zealand: gaps, challenges and solutions.

This Virtual Special Issue explores emerging topics in reproductive health in the Australian and New Zealand context. The included manuscripts cover pregnancy and termination of pregnancy, priority populations for sexual and reproductive health, digital technology and its impact on reproductive health, and perspectives from clinicians.

Treponema pallidum PCR screening at mucosal sites of asymptomatic men who have sex with men taking HIV pre-exposure prophylaxis.

Early detection and treatment of syphilis will reduce the infectious period and transmission. We aimed to determine whether screening men who have sex with men (MSM) taking HIV pre-exposure prophylaxis (PrEP) for syphilis using Treponema pallidum polymerase chain reaction (PCR) could detect syphilis before the appearance of syphilis antibodies in serology. MSM attending 3-monthly PrEP clinic visits in Melbourne, Australia, were screened with a PCR assay targeting the polA gene of T. pallidum from an anal swab and an oral rinse between November 2019 and March 2020. Participants were serologically screened for syphilis using chemiluminescence immunoassay. A total of 309 asymptomatic participants provided an anal swab and oral rinse sample for T. pallidum PCR screening. Two syphilis cases (0.6%) were detected: one man had a positive serology only; another man had T. pallidum detected by PCR from an anal swab and a positive serology. PCR positivity was 0.3% (n = 1) for anal swabs and 0% (n = 0) for oral rinse. In this study, T. pallidum PCR screening at routine PrEP clinic visits did not identify additional cases of early syphilis over serological screening performed at these visits. IMPORTANCE With the ongoing syphilis epidemic in men who have sex with men (MSM), we investigated the role of using Treponema pallidum polymerase chain reaction (PCR) testing at the oral cavity and anus in MSM taking pre-exposure prophylaxis for the early detection of syphilis. We evaluated whether the PCR tests from these mucosal sites can detect syphilis infection early, before the development of syphilis antibodies in serology. Our study found two syphilis cases among 309 MSM, and only one syphilis case had a positive anal PCR swab, although serology was positive. We conclude that additional PCR testing is likely to be expensive and would not be cost effective for individuals who regularly screen for syphilis. However, future studies with a larger sample size are required.

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.

Intra- and interhost genomic diversity of monkeypox virus.

The impact and frequency of infectious disease outbreaks demonstrate the need for timely genomic surveillance to inform public health responses. In the largest known outbreak of mpox, genomic surveillance efforts have primarily focused on high-incidence nations in Europe and the Americas, with a paucity of data from South-East Asia and the Western Pacific. Here we analyzed 102 monkeypox virus (MPXV) genomes sampled from 56 individuals in Melbourne, Australia. All genomes fell within the 2022 MPXV outbreak lineage (B.1), with likely onward local transmission detected. We observed within-host diversity and instances of co-infection, and highlight further examples of structural variation and apolipoprotein B editing complex-driven micro-evolution in the current MPXV outbreak. Updating our understanding of MPXV emergence and diversification will inform public health measures and enable monitoring of the virus' evolutionary trajectory throughout the mpox outbreak.