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Abstract N. gonorrhoeae, which causes the sexually transmissible infection gonorrhoea, remains a significant public health threat globally, with challenges posed by increasing transmission and antimicrobial resistance (AMR). The COVID-19 pandemic introduced exceptional circumstances into communicable disease control, impacting the transmission of gonorrhoea and other infectious diseases. Through phylogenomic and phylodynamic analysis of 5881 N. gonorrhoeae genomes from Australia, we investigated N. gonorrhoeae transmission over five years, including a time period during the COVID-19 pandemic. Using a novel cgMLST-based genetic threshold, we demonstrate persistence of large N. gonorrhoeae genomic clusters over several years, with some persistent clusters associated with heterosexual transmission. We observed a decline in both N. gonorrhoeae transmission and genomic diversity during the COVID-19 pandemic, suggestive of an evolutionary bottleneck. The longitudinal, occult transmission of N. gonorrhoeae over many years further highlights the urgent need for improved diagnostic, treatment, and prevention strategies for gonorrhoea.

Abstract Background Sexually transmitted infections (STIs) pose a significant global public health challenge. Early diagnosis and treatment reduce STI transmission, but rely on recognising symptoms and care-seeking behaviour of the individual. Digital health software that distinguishes STI skin conditions could improve health-seeking behaviour. We developed and evaluated a deep learning model to differentiate STIs from non-STIs based on clinical images and symptoms. Methods We used 4913 clinical images of genital lesions and metadata from the Melbourne Sexual Health Centre collected during 2010–2023. We developed two binary classification models to distinguish STIs from non-STIs: (1) a convolutional neural network (CNN) using images only and (2) an integrated model combining both CNN and fully connected neural network (FCN) using images and metadata. We evaluated the model performance by the area under the ROC curve (AUC) and assessed metadata contributions to the Image-only model. Results Our study included 1583 STI and 3330 non-STI images. Common STI diagnoses were syphilis (34.6%), genital warts (24.5%) and herpes (19.4%), while most non-STIs (80.3%) were conditions such as dermatitis, lichen sclerosis and balanitis. In both STI and non-STI groups, the most frequently observed groups were 25–34 years (48.6% and 38.2%, respectively) and heterosexual males (60.3% and 45.9%, respectively). The Image-only model showed a reasonable performance with an AUC of 0.859 (SD 0.013). The Image + Metadata model achieved a significantly higher AUC of 0.893 (SD 0.018) compared to the Image-only model (p

Abstract 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.

Objective: HIV pre-exposure prophylaxis (PrEP) became available in Victoria, Australia, in 2016. We examined non-occupational post-exposure prophylaxis (nPEP) usage among gay, bisexual and other men who have sex with men (MSM) before and after PrEP became available. Methods: We included MSM attending Melbourne Sexual Health Centre for nPEP between 2011 and 2021. We analysed three periods: the ‘pre-PrEP’ (01 Jan 2011 to 25 Jul 2016), ‘PrEP before COVID-19’ (26 Jul 2016 to 31 Dec 2019), and ‘PrEP during COVID-19’ (01 Jan 2020 to 31 Dec 2021). Results: There were 222,978 consultations for MSM; 8292 (3.7%) were nPEP consultations. The proportion of nPEP consultations increased from 3.3% (3093/94263) in the pre-PrEP period to 4.3% (3843/89251) in the PrEP before COVID-19 period then dropped to 3.4% (1356/39464) during the COVID-19 period. Compared to Australian-born MSM, MSM born in Central/South America (adjusted odds ratio [aOR]: 1.75; 95% confidence interval [CI]: 1.27–2.40) had the highest odds of accessing nPEP, followed by Asian-born MSM (aOR: 1.47; 95% CI: 1.27–1.71) after adjusting for PrEP availability and COVID-19. Those newly arrived in Australia in ≤4 years had higher odds (aOR: 1.14; 95% CI: 1.05–1.22) of accessing nPEP than those living in Australia for >4 years. Conclusion: nPEP prescriptions declined with PrEP availability. Newly arrived overseas-born MSM who are unlikely to have access to subsidised PrEP have a higher demand of nPEP. Implications for Public Health: Increasing PrEP education and ensuring equal access is vital in the drive to reduce new HIV diagnoses.

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.

Abstract Background Syphilis is a sexually transmitted infection causing significant global morbidity and mortality. To inform policymaking and economic evaluation studies for syphilis, we summarised utility and disability weights for health states associated with syphilis. Methods We conducted a systematic review, searching six databases for economic evaluations and primary valuation studies related to syphilis from January 2000 to February 2022. We extracted health state utility values or disability weights, including identification of how these were derived. The study was registered in the international prospective register of systematic reviews (PROSPERO, CRD42021230035). Findings Of 3401 studies screened, 22 economic evaluations, two primary studies providing condition-specific measures, and 13 burden of disease studies were included. Fifteen economic evaluations reported outcomes as disability-adjusted life years (DALYs) and seven reported quality-adjusted life years (QALYs). Fourteen of 15 economic evaluations that used DALYS based their values on the original Global Burden of Disease (GBD) study from 1990 (published in 1996). For the seven QALY-related economic evaluations, the methodology varied between studies, with some studies using assumptions and others creating utility weights or converting them from disability weights. Interpretation We found a limited evidence base for the valuation of health states for syphilis, a lack of transparency for the development of existing health state utility values, and inconsistencies in the application of these values to estimate DALYs and QALYs. Further research is required to expand the evidence base so that policymakers can access accurate and well-informed economic evaluations to allocate resources to address syphilis and implement syphilis programs that are cost-effective.

The Victorian Government introduced a time-limited human papillomavirus (HPV) catch-up program for gay, bisexual, and other men who have sex with men (GBMSM) aged ≤ 26 years in 2017–2019. We conducted a retrospective observational study to examine the accuracy of the self-report of HPV vaccination status using computer-assisted self-interviewing versus their immunization history via electronic health records. We included GBMSM aged 23–30 years visiting the Melbourne Sexual Health Centre (MSHC) in 2020–2021 because they were age-eligible for the HPV catch-up program in Victoria, Australia. Individuals who were unsure about their vaccination status were categorized as ‘unvaccinated’. Of the 1,786 eligible men, 1,665 men self-reported their HPV vaccination status: 48.8% (n = 812) vaccinated, 17.4% (n = 289) unvaccinated, and 33.9% (n = 564) unsure. Self-reported HPV vaccination had a sensitivity of 61.3% (95%CI: 58.3 to 64.2%; 661/1079), a specificity of 74.2% (95%CI: 70.5 to 77.7%; 435/586), a positive predictive value of 81.4% (95%CI: 78.6 to 84.0%; 661/812), a negative predictive value of 51.0% (95%CI: 47.6 to 54.4%; 435/853), and an accuracy of 52.6% (95%CI: 50.1 to 55.0%). Our results showed that only half of GBMSM know and report their HPV vaccination status correctly. Novel approaches such as digital vaccine passports may be useful for individuals to accurately report their vaccination status to guide accurate clinical decisions and management.

Summary: Background: Gay and bisexual men (GBM) remain overrepresented among syphilis diagnoses in Australia and globally. The extent to which changes in sexual networks associated with HIV pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) may have influenced syphilis transmission among GBM at the population-level is poorly understood. We describe trends in syphilis testing and incidence among GBM in Australia over eleven years spanning widespread uptake of HIV PrEP and TasP. Methods: We analysed linked clinical data from GBM aged 16 years or older across a sentinel surveillance network in Australia from January 1, 2012, to December 31, 2022. Individuals with at least two clinic visits and with at least two syphilis tests during the observations period were included in testing and incidence analyses, respectively. Annual rates of testing and infectious syphilis incidence from 2012 to 2022 were disaggregated by HIV status and PrEP use (record of PrEP prescription; retrospectively categorised as ever or never-PrEP user). Cox regression explored associations between demographics, PrEP use and history of bacterial sexually transmissible infections (STIs) and infectious syphilis diagnosis. Findings: Among 129,278 GBM (mean age, 34.6 years [SD, 12.2]) included in testing rate analyses, 7.4% were living with HIV at entry and 31.1% were prescribed PrEP at least once during the study period. Overall syphilis testing rate was 114.0/100 person-years (py) and highest among GBM with HIV (168.4/100 py). Syphilis testing increased from 72.8/100 py to 151.8/100 py; driven largely by increases among ever-PrEP users. Among 94,710 GBM included in incidence analyses, there were 14,710 syphilis infections diagnosed over 451,560 person-years (incidence rate = 3.3/100 py). Syphilis incidence was highest among GBM with HIV (6.5/100 py), followed by ever-PrEP users (3.5/100 py) and never-PrEP users (1.4/100 py). From 2012 to 2022, syphilis incidence increased among ever-PrEP users from 1.3/100 py to 5.1/100 py, and fluctuated between 5.4/100 py and 6.6/100 py among GBM with HIV. In multivariable Cox regression, previous syphilis diagnosis (adjusted hazard ratio [aHR] = 1.98, 95% CI = 1.83–2.14), living with HIV (aHR = 1.83, 95% CI = 1.12–1.25) and recent (past 12 m) prescription of PrEP (aHR = 1.78, 95% CI = 1.61–1.97) were associated with syphilis diagnosis. Interpretation: Syphilis trends between GBM with HIV and GBM with evidence of PrEP use have converged over the past decade in Australia. Our findings recommend targeting emergent syphilis control strategies (e.g. doxycycline post-exposure prophylaxis) to GBM with prior syphilis diagnoses, using HIV PrEP or who are living with HIV. Funding: Australian Department of Health and Aged Care, National Health and Medical Research Council.

Summary: Background: In Australia the incidence of HIV has declined steadily, yet sustained reduction of HIV transmission in this setting requires improved public health responses. As enhanced public health responses and prioritisation of resources may be guided by molecular epidemiological data, here we aimed to assess the applicability of these approaches in Victoria, Australia. Methods: A comprehensive collection of HIV-1 pol sequences from individuals diagnosed with HIV in Victoria, Australia, between January 1st 2000 and December 31st 2020 were deidentified and used as the basis of our assessment. These sequences were subtyped and surveillance drug resistance mutations (SDRMs) identified, before definition of transmission groups was performed using HIV-TRACE (0.4.4). Phylodynamic methods were applied using BEAST (2.6.6), assessing effective reproductive numbers for large groups, and additional demographic data were integrated to provide a high resolution view of HIV transmission in Victoria on a decadal time scale. Findings: Based on standard settings for HIV-TRACE, 70% (2438/3507) of analysed HIV-1 pol sequences were readily assigned to a transmission group. Individuals in transmission groups were more commonly males (aOR 1.50), those born in Australia (aOR 2.13), those with probable place of acquisition as Victoria (aOR 6.73), and/or those reporting injectable drug use (aOR 2.13). SDRMs were identified in 375 patients (10.7%), with sustained transmission of these limited to a subset of smaller groups. Informative patterns of epidemic growth, stabilisation, and decline were observed; many transmission groups showed effective reproductive numbers (Re) values reaching greater than 4.0, representing considerable epidemic growth, while others maintained low Re values. Interpretation: This study provides a high resolution view of HIV transmission in Victoria, Australia, and highlights the potential of molecular epidemiology to guide and enhance public health responses in this setting. This informs ongoing discussions with community groups on the acceptability and place of molecular epidemiological approaches in Australia. Funding: National Health and Medical Research Council, Australian Research Council.

Summary: Background: High coverage of pre-exposure prophylaxis (PrEP) will reduce HIV transmission and help end the HIV/AIDS pandemic. However, PrEP users face challenges, including long-term adherence. The study aimed to document the proportions of individuals who restart HIV PrEP after they stop and the reasons for restarting PrEP. Methods: This study is a systematic review and meta-analysis. We systematically searched CINAHL, Embase, Emcare, Global Health, Medline, Scopus, and PsychINFO for peer-reviewed with no date restrictions. A grey literature search was conducted through Google search, a search of abstract books of AIDS conferences and the websites of WHO and UNAIDS. The data search was conducted in April 2023 and updated in February 2024. Two authors extracted data on the proportion of people who stopped and then restarted PrEP, reasons for restarting, and strategies to support people restarting PrEP. Two authors appraised the data using the Joanna Briggs Institute Appraisal Tools. We used a random-effects meta-analysis to pool estimates of restarting. We conducted meta-regression to determine potential sources of heterogeneity. This study is registered with PROSPERO, CRD42023416777. However, we deviated from our original plan as we did not identify enough studies for strategies to support restarting PrEP (primary objective). Subsequently, we revised our plan to strengthen our secondary objective to quantify the proportion of people who stopped and restarted PrEP, and explore possible reasons for its heterogeneity. Findings: Of 988 studies, 30 unique studieswere included: 27 reported the proportion restarting PrEP, and of these, 7 also reported reasons for restarting PrEP, and 3 studies reported only on the reasons for restarting PrEP. No study evaluated interventions for restarting PrEP. For the meta-analysis, we included 27 studies. Most studies were from high-income countries (17/27, 63%) or the USA (15/27, 56%). Overall, 23.8% (95% CI: 15.9–32.7, I2 = 99.8%, N = 85,683) of people who stopped PrEP restarted PrEP. There was a lower proportion of restarting in studies from middle-income countries compared to high-income countries (adjusted odds ratio (aOR) 0.6, 95% CI: 0.50–0.73, p 1 month compared to those who stopped

Summary: Background: In people living with HIV-HBV, liver fibrosis progression can occur even with suppressive antiretroviral therapy (ART). We investigated the relationship between liver fibrosis and biomarkers of inflammation, apoptosis, and microbial translocation. Methods: In this observational cohort study adults living with HIV-HBV already on effective ART were recruited in Australia and Thailand and followed for 3 years including 6 monthly clinical review and blood tests and annual transient elastography. Differences in clinical and laboratory predictors of liver fibrosis progression were tested followed by regression analysis adjusted for CD4+ T-cells at study entry. A linear mixed model was fitted to longitudinal data to explore changes over time. Findings: 67 participants (85% male, median age 49 y) were followed for 175 person-years. Median duration of ART was 10 years (interquartile range (IQR) 8–16 years). We found 11/59 (19%) participants during 3-years follow-up (6/100 person-years) met the primary endpoint of liver disease progression, defined as increased Metavir stage from baseline to final scan. In regression analysis, progressors compared to non-progressors had higher levels of high mobility group box 1 protein (HGMB1), (median (IQR) 3.7 (2.6–5.0) and 2.4 ng/mL (1.5–3.4) respectively, adjusted relative risk 1.47, 95% CI [1.00, 2.17]) and lower nadir CD4+ T-cell percentage (median 4% (IQR 2–8) and 11% (4–15) respectively (relative risk 0.93, 95% CI [0.88, 0.98]). Interpretation: Progression in liver fibrosis occurs in people with HIV-HBV on suppressive ART. Fibrosis progression was associated with higher HMGB1 and lower percentage nadir CD4+ T-cell count, highlighting the importance of early initiation of HBV-active ART. Funding: This work was supported by NHMRC project grant 1101836; NHMRC practitioner fellowship 1138581 and NHMRC program grant 1149990. The funder had no role in study design, data collection, data analysis, interpretation, writing of this manuscript or decision to submit for publication.

Abstract Background Multimorbidity is better prevented in younger ages than in older ages. This study aims to identify the differences in comorbidity patterns in middle-aged inpatients from China and the United Kingdom (UK). Methods We utilized 184,133 and 180,497 baseline hospitalization records in middle-aged populations (40–59 years) from Shaanxi, China, and UK Biobank. Logistic regression was used to calculate odds ratios and P values for 43,110 unique comorbidity patterns in Chinese inpatients and 21,026 unique comorbidity patterns in UK inpatients. We included the statistically significant (P values adjusted by Bonferroni correction) and common comorbidity patterns (the pattern with prevalence > 1/10,000 in each dataset) and employed network analysis to construct multimorbidity networks and compare feature differences in multimorbidity networks for Chinese and UK inpatients, respectively. We defined hub diseases as diseases having the top 10 highest number of unique comorbidity patterns in the multimorbidity network. Results We reported that 57.12% of Chinese inpatients had multimorbidity, substantially higher than 30.39% of UK inpatients. The complete multimorbidity network for Chinese inpatients consisted of 1367 comorbidities of 341 diseases and was 2.93 × more complex than that of 467 comorbidities of 215 diseases in the UK. In males, the complexity of the multimorbidity network in China was 2.69 × more than their UK counterparts, while the ratio was 2.63 × in females. Comorbidities associated with hub diseases represented 68.26% of comorbidity frequencies in the complete multimorbidity network in Chinese inpatients and 55.61% in UK inpatients. Essential hypertension, dyslipidemia, type 2 diabetes mellitus, and gastritis and duodenitis were the hub diseases in both populations. The Chinese inpatients consistently demonstrated a higher frequency of comorbidities related to circulatory and endocrine/nutritional/metabolic diseases. In the UK, aside from these comorbidities, comorbidities related to digestive and genitourinary diseases were also prevalent, particularly the latter among female inpatients. Conclusions Chinese inpatients exhibit higher multimorbidity prevalence and more complex networks compared to their UK counterparts. Multimorbidity with circulatory and endocrine/nutritional/metabolic diseases among both Chinese and UK inpatients necessitates tailored surveillance, prevention, and intervention approaches. Targeted interventions for digestive and genitourinary diseases are warranted for the UK.

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.

Abstract Introduction The Joint United Nations Programme on HIV/AIDS (UNAIDS) updated the 95‐95‐95 targets for the HIV endgame in 2030. To achieve the first target in a timely manner, we investigate the optimized strategy of resource allocation to maximize timely HIV diagnosis in 14 populations in China. Methods We developed a mathematical model by integrating epidemiological, demographical and behavioural data from 12 high‐risk and two general populations to evaluate the impact of various resource allocation strategies of HIV testing on HIV incidence in China. We identified the optimized allocation strategy that maximizes the number of HIV diagnoses at an estimated total spending on HIV tests in China and calculated the per‐capita cost of new HIV case detection. Results We estimated that 144,795 new HIV cases may occur annually in 14 populations in China, with a total annual spending of US$2.8 billion on HIV testing. The largest proportion of spending was allocated to general males (44.0%), followed by general females (42.6%) and pregnant women (5.1%). Despite this allocation strategy, only 45.5% (65,867/144,795, timely diagnosis rate) of annual new infections were diagnosed within a year of acquisition, with a cost of $42,852 required for each new HIV case detection. By optimizing the allocation of HIV testing resources within the same spending amount, we found that general females received the highest proportion of spending allocation (45.1%), followed by low‐risk men who have sex with men (13.9%) and pregnant women (8.4%). In contrast, the proportion of spending allocation for the general males decreased to 0.2%. With this optimized strategy, we estimated that 120,755 (83.4%) of annual new infections would be diagnosed within a year of acquisition, with the cost required for one HIV case detection reduced to $23,364/case. Further spending increases could allow for significant increases in HIV testing among lower‐risk populations. Conclusions Optimizing resource allocation for HIV testing in high‐risk populations would improve HIV timely diagnosis rate of new infections and reduce cost per HIV case detection.

Summary: 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

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.

ABSTRACT: Objectives: Although the World Health Organization recommends ‘frequent’ screening of sexually transmitted infections (STI) for people who use pre-exposure prophylaxis for HIV, there is no evidence for optimal frequency. Methods: We searched five databases and used random-effects meta-analysis to calculate pooled estimates of STI test positivity. We narratively synthesized data on secondary outcomes, including adherence to recommended STI screening frequency and changes in STI epidemiology. Results: Of 7477 studies, we included 38 for the meta-analysis and 11 for secondary outcomes. With 2-3 monthly STI screening, the pooled positivity was 0.20 (95% confidence interval [CI]: 0.15-0.25) for chlamydia, 0.17 (95% CI: 0.12-0.22) for gonorrhea, and 0.07 (95% CI: 0.05-0.08) for syphilis. For chlamydia and gonorrhea, the positivity was approximately 50% and 75% lower, respectively, in studies that screened 4-6 monthly vs 2-3 monthly. There was no significant difference in the positivity for syphilis in studies that screened 4-6 monthly compared to 2-3 monthly. Adherence of clients to recommended screening frequency varied significantly (39-94%) depending on population and country. Modeling studies suggest more frequent STI screening could reduce incidence. Conclusion: Although more frequent STI screening could reduce delayed diagnoses and incidence, there remain significant knowledge gaps regarding the optimal STI screening frequency.

ABSTRACT 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.

Abstract Introduction Of 37.7 million people living with HIV in 2020, 6.1 million still do not know their HIV status. We synthesize evidence on concurrent HIV testing among people who tested for other sexually transmitted infections (STIs). Methods We conducted a systematic review using five databases, HIV conferences and clinical trial registries. We included publications between 2010 and May 2021 that reported primary data on concurrent HIV/STI testing. We conducted a random‐effects meta‐analysis and meta‐regression of the pooled proportion for concurrent HIV/STI testing. Results We identified 96 eligible studies. Among those, 49 studies had relevant data for a meta‐analysis. The remaining studies provided data on the acceptability, feasibility, barriers, facilitators, economic evaluation and social harms of concurrent HIV/STI testing. The pooled proportion of people tested for HIV among those attending an STI service (n = 18 studies) was 71.0% (95% confidence intervals: 61.0–80.1, I2 = 99.9%), people tested for HIV among those who were tested for STIs (n = 15) was 61.3% (53.9–68.4, I2 = 99.9%), people tested for HIV among those who were diagnosed with an STI (n = 13) was 35.3% (27.1–43.9, I2 = 99.9%) and people tested for HIV among those presenting with STI symptoms (n = 3) was 27.1% (20.5–34.3, I2 = 92.0%). The meta‐regression analysis found that heterogeneity was driven mainly by identity as a sexual and gender minority, the latest year of study, country‐income level and region of the world. Discussion This review found poor concurrent HIV/STI testing among those already diagnosed with an STI (35.3%) or who had symptoms with STIs (27.1%). Additionally, concurrent HIV/STI testing among those tested for STIs varied significantly according to the testing location, country income level and region of the world. A few potential reasons for these observations include differences in national STI‐related policies, lack of standard operation procedures, clinician‐level factors, poor awareness and adherence to HIV indicator condition‐guided HIV testing and stigma associated with HIV compared to other curable STIs. Conclusions Not testing for HIV among people using STI services presents a significant missed opportunity, particularly among those diagnosed with an STI. Stronger integration of HIV and STI services is urgently needed to improve prevention, early diagnosis and linkage to care services.

Abstract Timely and regular testing for HIV and sexually transmitted infections (STI) is important for controlling HIV and STI (HIV/STI) among men who have sex with men (MSM). We established multiple machine learning models (e.g., logistic regression, lasso regression, ridge regression, elastic net regression, support vector machine, k-nearest neighbour, naïve bayes, random forest, gradient boosting machine, XGBoost, and multi-layer perceptron) to predict timely (i.e., within 30 days) clinic attendance and HIV/STI testing uptake after receiving a reminder message via short message service (SMS) or email). Our study used 3044 clinic consultations among MSM within 12 months after receiving an email or SMS reminder at the Melbourne Sexual Health Centre between April 11, 2019, and April 30, 2020. About 29.5% [899/3044] were timely clinic attendance post reminder messages, and 84.6% [761/899] had HIV/STI testing. The XGBoost model performed best in predicting timely clinic attendance [mean [SD] AUC 62.8% (3.2%); F1 score 70.8% (1.2%)]. The elastic net regression model performed best in predicting HIV/STI testing within 30 days [AUC 82.7% (6.3%); F1 score 85.3% (1.8%)]. The machine learning approach is helpful in predicting timely clinic attendance and HIV/STI re-testing. Our predictive models could be incorporated into clinic websites to inform sexual health care or follow-up service.

Abstract Studies suggest men who have sex with men (MSM) practising receptive anal sex are more likely to present with secondary syphilis, implying primary anorectal lesions are likely to be missed. If men could detect anorectal lesions in the primary stage by regular anal self-examination (ASE), transmission could be reduced by early diagnosis and treatment. We aimed to explore the attitudes of MSM on performing ASE to detect primary anorectal syphilis. An online anonymous cross-sectional survey among MSM over 18 years of age living in Australia, was conducted between July and November 2020 and recruitment was from a sexual health clinic and social media. A total of 568 MSM completed the survey (median age: 34 [IQR 27–45]): 32% (183) had previously performed ASE. Among 66% (374) who had never performed ASE, 68% (250) would consider performing ASE in the future with a preferred median frequency of 2 times per 4 weeks (IQR 1–4), whilst men who were already performing ASE were performing it at median 1 per 4 weeks (IQR 0.2–3). Almost two-thirds of MSM who had never performed ASE were willing to adopt ASE practice in the future. Studies are required to determine the effectiveness of ASE for syphilis detection.

ABSTRACT: Objectives: Molecular testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is costly. Therefore, we appraised the evidence regarding pooling samples from multiple individuals to test for CT/NG. Methods: In this systematic review, we searched 5 databases (2000-2021). Studies were included if they contained primary data describing pooled testing. We calculated the pooled sensitivities and specificities for CT and NG using a bivariate mixed-effects logistic regression model. Results: We included 22 studies: most were conducted in high-income countries (81.8%, 18 of 22), among women (73.3%, 17 of 22), and pooled urine samples (63.6%, 14 of 22). Eighteen studies provided 25 estimates for the meta-analysis of diagnostic accuracy, with data from 6,913 pooled specimens. The pooled sensitivity for CT was 98.4% (95% confidence intervals [CI]: 96.8-99.2%, I2=77.5, p

BackgroundChlamydia trachomatis (chlamydia) is one of the most common sexually transmitted infections (STI) globally, and re-infections are common. Current Australian guidelines recommend re-testing for chlamydia 3 months after treatment to identify possible re-infection. Patient-delivered partner therapy (PDPT) has been proposed to control chlamydia re-infection among heterosexuals. We aimed to identify determinants and the prediction of chlamydia re-testing and re-infection within 1 year among heterosexuals with chlamydia to identify potential PDPT candidates.MethodsOur baseline data included 5,806 heterosexuals with chlamydia aged ≥18 years and 2,070 re-tested for chlamydia within 1 year of their chlamydia diagnosis at the Melbourne Sexual Health Center from January 2, 2015, to May 15, 2020. We used routinely collected electronic health record (EHR) variables and machine-learning models to predict chlamydia re-testing and re-infection events. We also used logistic regression to investigate factors associated with chlamydia re-testing and re-infection.ResultsAbout 2,070 (36%) of 5,806 heterosexuals with chlamydia were re-tested for chlamydia within 1 year. Among those retested, 307 (15%) were re-infected. Multivariable logistic regression analysis showed that older age (≥35 years old), female, living with HIV, being a current sex worker, patient-delivered partner therapy users, and higher numbers of sex partners were associated with an increased chlamydia re-testing within 1 year. Multivariable logistic regression analysis also showed that younger age (18–24 years), male gender, and living with HIV were associated with an increased chlamydia re-infection within 1 year. The XGBoost model was the best model for predicting chlamydia re-testing and re-infection within 1 year among heterosexuals with chlamydia; however, machine learning approaches and these self-reported answers from clients did not provide a good predictive value (AUC < 60.0%).ConclusionThe low rate of chlamydia re-testing and high rate of chlamydia re-infection among heterosexuals with chlamydia highlights the need for further interventions. Better targeting of individuals more likely to be re-infected is needed to optimize the provision of PDPT and encourage the test of re-infection at 3 months.

ObjectivesGay, bisexual and other men who have sex with men (GBMSM) and trans and gender diverse (TGD) people are disproportionately affected by poorer sexual health outcomes compared to heterosexual populations. We aimed to explore the preferences of GBMSM and TGD for using eHealth for sexual health (eSexualHealth).MethodsWe distributed an anonymous online survey from April to August 2021among the lesbian, gay, bisexual, transgender, intersex, queer and other people of diverse sexuality or gender (LGBTIQA+) community in Australia. The survey collected data on sociodemographic characteristics and sexual behaviors, their preferences for app/website functions and preferred HIV and sexually transmitted infection (STI) testing reminders. We used descriptive statistics to summarize the characteristics of the study population. Free-text responses were thematically analyzed.ResultsOf 466 participants included, most identified as cisgender males (92.7%). The median age was 48 [interquartile range (IQR): 37–56]. For accessing sexual health-related information, 160 (34.6%) would use either a website or an app, 165 (32.7%) would prefer a website, 119 (25.8%) would prefer an app, and 33 (7.1%) would not use either platform. There was no significant difference between GBMSM and TGD people. Participants were most interested in information about STI clinics, HIV/STI hotspots, and sexual health education. Participants stressed the need for privacy and anonymity when using eHealth. Regarding reminders to test for HIV/STIs, receiving regular SMS was most popular (112/293, 38.2%), followed by regular emails (55/293 18.8%) and a reminder function on their phone (48/293, 16.4%).ConclusionOur study suggests a promising future for eHealth among GBMSM and TGD people. Sexual health is still a stigmatized area, and eHealth may circumvent barriers this population faces.

Abstract Background Asian-born gay, bisexual and other men who have sex with men (gbMSM) newly arrived in Australia are more than four times as likely than their Australian-born counterparts to be diagnosed with incident HIV. Our aim was to explore experiences of Asian-born gbMSM newly arrived in Australia and attending a sexual health centre with regards to their knowledge of and preference for HIV prevention strategies. Results Twenty-four gbMSM aged 20–30 years attending Melbourne Sexual Health Centre who were born in Asia and arrived in Australia in the preceding four years, participated in semi-structured face-to-face interviews from 8th May 2019 and 23rd December 2019. Men were excluded if they were living with HIV. Interviews were recorded, transcribed verbatim and analysed thematically. Men reported little knowledge of HIV prevention strategies outside of condom use prior to coming to Australia. Although participants reported basic knowledge of HIV transmission and treatment, exposure to sexual identity and HIV-related stigma in their countries of birth meant they imagined a HIV diagnosis would be devastating. Most relied on condoms to stay HIV negative however their consistency of use varied. Seven men were on pre-exposure prophylaxis (PrEP); all but one started PrEP after coming to Australia. Many indicated interest in PrEP but described it as too expensive given they do not have access to government-subsidized healthcare. Sexual health counselling and connections with LGBTQI community groups appeared to facilitate PrEP and consistent condom use. Conclusions Asian-born gbMSM newly-arrived to Australia may have limited knowledge of HIV prevention strategies aside from condom use. Increased connections with sexual health services and LGBTQI communities may facilitate more effective HIV prevention strategies.

Objectives: The exact characteristics of a coronavirus disease 2019 (COVID-19) outbreak that trigger public health interventions are poorly defined. The aim of this study was to assess the critical timing and extent of public health interventions to contain COVID-19 outbreaks in Australia. Methods: A practical model was developed using existing epidemic data in Australia. The effective combinations of public health interventions and the critical number of daily cases for intervention commencement under various scenarios of changes in transmissibility of new variants and vaccination coverage were quantified. Results: In the past COVID-19 outbreaks in four Australian states, the number of reported cases on the day that interventions commenced strongly predicted the size and duration of the outbreaks. In the early phase of an outbreak, containing a wildtype-dominant epidemic to a low level (≤10 cases/day) would require effective combinations of social distancing and face mask use interventions to be commenced before the number of daily reported cases reaches six. Containing an Alpha-dominant epidemic would require more stringent interventions that commence earlier. For the Delta variant, public health interventions alone would not contain the epidemic unless the vaccination coverage was ≥70%. Conclusions: This study highlights the importance of early and decisive action in the initial phase of an outbreak. Vaccination is essential for containing variants.

Abstract Background There is a significant global burden of herpes simplex virus (HSV) related genital ulcer disease yet little is known about its impact on quality of life. This systematic review aimed to identify studies that quantitatively evaluated the effect of genital herpes on various aspects of health-related quality of life. Methods Six databases were searched (MEDLINE, EMBASE, NHS Economic Evaluation Database, Health Technology Assessment, Database of Abstracts of Reviews of Effects, Web of Science Core Collection) for primary quality of life and economic evaluations of genital herpes from January 1, 2000 to January 7, 2021. Qualitative studies or those without primary data were excluded. Two authors independently extracted data from the publications. The study’s registration number with PROSPERO was CRD42021239410. Findings We identified 26 relevant publications: 19 presented primary quality of life data, and seven were economic evaluations. The primary studies presented a range of condition-specific tools for describing the quality of life in individuals with genital herpes, but only one study used a direct valuation that could be used to generate utility weights. All economic evaluations of HSV infection were from high-income country settings. Most (6 of 7) focused on neonatal HSV infection with utilities adopted from studies prior to 2000. Interpretation The extant literature on genital herpes-related quality of life is limited and requires updating. We recommend future studies be conducted in geographic- and population- diverse settings, and use preference-based condition-specific or generic-instruments to better inform economic modelling.

Abstract Objective: Examine the changes in service delivery Australian public sexual health clinics made to remain open during lockdown. Methods: A cross‐sectional survey designed and delivered on Qualtrics was emailed to 21 directors of public sexual health clinics across Australia from July‐August 2020 and asked about a variety of changes to service delivery. Descriptive statistics were calculated. Results: Twenty clinics participated, all remained open and reported service changes, including suspension of walk‐in services in eight clinics. Some clinics stopped offering asymptomatic screening for varying patient populations. Most clinics transitioned to a mix of telehealth and face‐to‐face consultations. Nineteen clinics reported delays in testing and 13 reported limitations in testing. Most clinics changed to phone consultations for HIV medication refills (n=15) and eleven clinics prescribed longer repeat prescriptions. Fourteen clinics had staff redeployed to assist the COVID‐19 response. Conclusion: Public sexual health clinics pivoted service delivery to reduce risk of COVID‐19 transmission in clinical settings, managed staffing reductions and delays in molecular testing, and maintained a focus on urgent and symptomatic STI presentations and those at higher risk of HIV/STI acquisition. Implications for public health: Further research is warranted to understand what impact reduced asymptomatic screening may have had on community STI transmission.

Abstract Background HIV self-testing was proved as an effective tool for increasing testing frequency in gay and bisexual men at high risk of infection. Questions remain about understanding why HIVST encouraged testing and how such success can be translated to programmatic implementation. Methods We conducted a qualitative investigation of how FORTH participants experienced and perceived HIVST. Stratified sampling was used to recruit gay and bisexual men participating in the FORTH HIVST intervention to take part in interviews, focusing on infrequent testers and those who had received inaccurate HIVST results. Results Our analysis identified several prominent themes organized into two overarching domains from the 15 interviews: (i) aspects of HIVST contributing to HIV testing frequency, and (ii) sustaining HIVST into the future. Participants also believed that their use of HIVST in the future would depend on the test kit’s reliability, particularly when compared with highly reliable clinic-based testing. Conclusion HIVST increases the frequency of HIV testing among gay and bisexual men due, in part, to the practical, psychological, and social benefits it offers. To capitalize fully on these benefits, however, strategies to ensure the availability of highly reliable HIVST are required to sustain benefits beyond the confines of a structured research study.

Abstract Background Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) at genital and extragenital sites is needed for most key populations, but molecular diagnostic tests for CT/NG are costly. We aimed to determine the accuracy of pooled samples from multiple anatomic sites from one individual to detect CT/NG using the testing of a single sample from one anatomic site as the reference. Methods In this systematic review and meta-analysis, we searched five databases for articles published from January 1, 2000, to February 4, 2021. Studies were included if they contained original data describing the diagnostic accuracy of pooled testing compared with single samples, resource use, benefits and harms of pooling, acceptability, and impact on health equity. We present the pooled sensitivities and specificities for CT and NG using a bivariate mixed-effects logistic regression model. The study protocol is registered in PROSPERO, an international database of prospectively registered systematic reviews (CRD42021240793). We used GRADE to evaluate the quality of evidence. Results Our search yielded 7814 studies, with 17 eligible studies included in our review. Most studies were conducted in high-income countries (82.6%, 14/17) and focused on men who have sex with men (70.6%, 12/17). Fourteen studies provided 15 estimates for the meta-analysis for CT with data from 5891 individuals. The pooled sensitivity for multisite pooling for CT was 93.1% [95% confidence intervals (CI) 90.5–95.0], I 2 =43.3, and pooled specificity was 99.4% [99.0–99.6], I 2 =52.9. Thirteen studies provided 14 estimates for the meta-analysis for NG with data from 6565 individuals. The pooled sensitivity for multisite pooling for NG was 94.1% [95% CI 90.9–96.3], I 2 =68.4, and pooled specificity was 99.6% [99.1–99.8], I 2 =83.6. Studies report significant cost savings (by two thirds to a third). Conclusion Multisite pooled testing is a promising approach to improve testing coverage for CT/NG in resource-constrained settings with a small compromise in sensitivity but with a potential for significant cost savings.

BackgroundEmerging data suggest tongue-kissing may transmit gonorrhea. We aim to examine the duration or body position of heterosexual men and women during tongue-kissing (henceforth, known as kissing).MethodsA cross-sectional survey among heterosexual men and women attending the Melbourne Sexual Health Centre in Australia between May 2019 and March 2020 collected data on the duration and body position (i.e., on top of or lying down underneath) of their most recent kissing partner in the past 3 months. Univariable and multivariable linear regressions were performed to examine the association between gender and kissing duration.ResultsOf 2,866 individuals, 93.6% (n = 2,683) had at least one kissing partner in the past 3 months, which included 1,342 (50.1%) men and 1,341 (49.9%) women, and 87.2% (n = 2,339) had sex with their opposite-gender kissing partner. The adjusted mean duration of kissing with the most recent opposite-gender kissing partner did not differ between men and women (12.2 vs. 11.5 min, p = 0.170). More men were on top of their most recent opposite-gender kissing partner compared to women (87.9 vs. 82.9%, p < 0.001). Men reported a longer kissing duration than women when they were on top of the opposite-gender kissing partner (8.3 vs. 7.4 min, p = 0.006). More women had same-gender kissing partners than men (9.6 vs. 2.8%, p < 0.001).ConclusionMen spending longer than women on top of their opposite-gender kissing partner suggests a potential alternative explanation for oropharyngeal gonorrhea being seen more commonly in women. Further research should investigate whether body positioning and duration of kissing influence the risk of gonorrhea transmission.

We aimed to investigate the sexual mixing by human papillomavirus (HPV) vaccination status in male-male partnerships and estimate the proportion of male-male partnerships protected against HPV. We analyzed male-male partnerships attending the Melbourne Sexual Health Center between 2018 and 2019. Data on self-reported HPV vaccination status were collected. Newman’s assortativity coefficient was used to examine the sexual mixing by HPV vaccination status. Assortativity refers to the tendency of individuals to have partners with similar characteristics (i.e. same vaccination status). Of 321 male-male partnerships where both men reported their HPV vaccination status, 52.6% (95% CI: 47.0–58.2%) partnerships had both men vaccinated, 32.1% (95% CI: 27.0–37.5%) partnerships had only one man vaccinated, and 15.3% (95% CI: 11.5–19.7%) had both men unvaccinated. The assortativity on HPV vaccination status was moderate (assortativity coefficient = 0.265, 95% CI: 0.196–0.335). There were about 15% of male-male partnerships where both men were not protected against HPV. Interventions targeting vaccinated individuals to encourage their unvaccinated partners to be vaccinated might increase the HPV vaccine coverage.

Summary: Background: People on the move, including international migrants, may face health inequities that expose them to a higher risk for HIV than native-born populations. We conducted a systematic review to calculate the HIV prevalence ratio of international migrants compared with native-born populations. Methods: We searched five databases between January 2010 and March 2022. Using random-effects meta-analysis, we calculated the pooled HIV prevalence ratios (PR) by comparing the HIV prevalence of migrants with native-born populations. Our research protocol is registered in the International prospective register of systematic reviews (PROSPERO, CRD42021250867). Findings: In total, 5,121 studies were screened, and 38 were included in the final analysis: 7,121,699 migrants and more than 270 million natives were included in the analysis. The pooled PR for any foreign-born migrants was 1·70 (95% CI 1·11 – 2·61, I2=99·67%, n = 33 studies), refugees was 2·37 (95% CI 0·33–16·99, I2=99·5%, n = 5), undocumented people was 3·98 (95% CI 0·11–143·01, I2=94·6%, n = 3), whilst asylum seekers was 54·79 (95% CI 17·23–174·23, I2=90·2%, n = 2). Meta-regression revealed that population type (adjusted R-squared 11.5%), region of origin (11.3%) and migrant type (10.8%) accounted for heterogeneity more than country-income (2.4%) and study setting (2.3%). Interpretation: Although it was not possible to assess if HIV infection occurred in the country of origin or destination, the HIV prevalence ratio was higher among migrants than in native-born populations. Inclusive health policies and strategies for delivering HIV testing, prevention and treatment services for migrant populations tailored to their needs are urgently needed. Funding: J.J.O. and E.P.F.C. are supported by the Australian National Health and Medical Research Council (NHMRC) Emerging Leader Fellowship (GNT1193955 and GNT1172873, respectively).

ABSTRACT 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.

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.

BackgroundTimely 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.MethodsWe 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).ResultsAmong 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 [ptrend < 0.001 (men) and ptrend = 0.049 (women)].ConclusionImproved 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.

Abstract Background Studies show men who have sex with men (MSM) practising receptive anal sex are more likely to present with secondary syphilis, suggesting anorectal primary lesions are being missed. Regular anal self-examination might be able to detect anorectal syphilis lesions, hence potentially reducing transmission. This study aimed to explore the attitudes of MSM on performing anal self-examination to detect primary syphilis. Methods In this qualitative study, 20 MSM over 18 years of age were purposively sampled from a sexual health clinic to participate in semi-structured interviews. Interviews were recorded, transcribed verbatim and data analysed thematically. Results Four major themes and 12 sub-themes were generated from the study: (1) reasons for performing anal self-examination, (2) preferred educational resources for anal self-examination, (3) attitudes towards partner anal examination, and (4) acceptability of anal self-examination. Most participants had performed some form of anal self-examination in the past, and, just over half performed regularly for mostly health-related concerns. Most participants who infrequently or never performed anal self-examination were agreeable to perform regularly if it was recommended by health professionals with appropriate guidance. Participants preferred education on anal self-examination from health professionals and trusted online learning resources. Conclusion Our study showed MSM were agreeable to anal self-examination however would like to receive education and training to gain more confidence in conducting anal self-examination as a screening tool. Further studies are required to explore the adherence and acceptability of anal self-examination for syphilis prior to studies examining efficacy. The study provides foundation for any future policy aiming at utilising anal self-examination as a screening tool for syphilis among MSM.

ObjectivesWe assessed nonconventional interventions that did not traditionally focus on increasing condom use and/or testing among men who have sex with men (MSM) and the evidence for these interventions.MethodsGuided by the Participants, Concept and Context (PCC) framework, we searched five online databases from inception to 9 August 2021 for original research on interventions that do not focus on increasing condom use and/or testing to prevent gonorrhea and/or syphilis in MSM. Two researchers screened titles and abstracts to assess eligibility, reviewed articles' full text and resolved discrepancies through discussion. We charted relevant study information, and the included studies were critically appraised.ResultsOf 373 articles retrieved, 13 studies were included. These studies were conducted in Australia (n = 3), Belgium (n = 2), China (n = 3), the Netherlands (n = 1) and the US (n = 4). Two randomized controlled trials (RCTs) of doxycycline as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) reduced any STI incidence (gonorrhea, syphilis, or chlamydia), but only doxycycline PEP significantly reduced syphilis incidence. Six studies of interventions that facilitated self-collection, self-examination, and self-testing, found varied evidence for gonorrhea and/or syphilis prevention. Four RCTs and one single-arm trial examined the efficacy of mouthwash, but the evidence remains inconclusive on whether mouthwash use can prevent transmission between men.ConclusionWe found evidence for doxycycline PEP in reducing syphilis incidence, evidence on the use of mouthwash to prevent gonorrhea transmission between men remains inconclusive. More evidence is needed for interventions that do not focus on increasing condom use and/or testing to prevent gonorrhea and/or syphilis.

Summary: Background: We aimed to systematically review the health preference literature using discrete choice experiments (DCEs), an attribute-based stated preference method, to investigate patient preferences for HIV pre-exposure prophylaxis (PrEP). Methods: A search in PubMed, Scopus, CINAHL, and Embase was conducted on July 1, 2021, and updated on November 3, 2021. We used two concepts to create our search strategy: (1) discrete choice experiments/conjoint analysis/best-worst scaling, and (2) HIV PrEP.The study is registered in PROSPERO (CRD42021267026). Findings: In total, 1060 studies were identified, and 18 were included in the analysis. Various attributes were examined, including dosing regimen, type of PrEP products, side effects, other side benefits, cost, effectiveness, dispensing venue, and additional support services. Dosing frequency, cost, the effectiveness of PrEP, dispensing venue, and side effects were the most common attributes examined in DCEs. Despite significant heterogeneity in preferences across subpopulations, overall, the most important attributes were cost (28%, 5/18), effectiveness (28%, 5/18) followed by dosing frequency (17%, 3/18). Interpretation: Notably, in studies where all of these three attributes were examined, some individuals would trade effectiveness for cost or vice versa. Ensuring PrEP is low cost or free, widely disseminating information of its effectiveness and advancements in reducing dosing frequency could accelerate the uptake of PrEP for those who would benefit from PrEP the most. Funding: None.

Summary: Background: Our aim was to determine whether exposure to the anatomical sites (oropharynx, penis, or anus) of male partners of men who have sex with men (MSM) were independent risk factors for oropharyngeal gonorrhoea after adjusting for exposures to these sites. Methods: In this cross-sectional study, we invited MSM who attended the Melbourne Sexual Health Centre (MSHC) in Victoria, Australia between 26-November 2018 and 31-December 2020 to complete a survey of their sexual practices in the past three months. We collected data on the number of male partners with whom men engaged in sexual activities that exposed their oropharynx to their partners’ oropharynx (kissing), penis (fellatio), and anus (rimming or analingus). Only men who were aged ≥16 years, tested for oropharyngeal gonorrhoea and did not have indeterminate or invalid results were included in the final analysis. We conducted univariable and multivariable logistic regression analyses to investigate associations between oropharyngeal gonorrhoea and the three exposures to the oropharynx. Findings: The median age of the 2,322 men who completed the survey was 31 years (IQR: 26-40), and 5·2% (n = 120) were diagnosed with oropharyngeal gonorrhoea. Our univariate analysis showed that oropharyngeal gonorrhoea was significantly associated with increasing number of kissing (ptrend

IntroductionOverseas-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.MethodsWe conducted in-depth qualitative interviews between February 2021 to September 2021 with 22 overseas-born, newly arrived (

BackgroundMen who have sex with men (MSM) practicing exclusively receptive anal sex are more likely to present with secondary than primary syphilis, implying primary anorectal lesions may be missed. If men could detect anorectal lesions by regular anal self-examination, the duration of infectiousness could be reduced. This study aimed to examine adherence to weekly anal self-examination.MethodWe conducted a longitudinal feasibility study examining the adherence to weekly anal self-examinations among MSM attending a sexual health clinic in Melbourne, Australia between December 2020 and June 2021. Adherence to weekly anal self-examinations over 12 weeks was assessed from a logbook and 4-weekly surveys. Participants who identified abnormalities in their anus were recommended to seek medical review.ResultsOf the 30 men who completed the study, anal self-examination was performed at least weekly for 308 of 360 person-weeks (86% of the weeks, 95% CI: 82–89). The mean adherence was 3.6 (95% CI: 3.3–3.9) examinations per 4-weeks per person in Weeks 1–4, 3.5 (95% CI: 3.1–3.8) in Weeks 5–8 and 3.3 (95% CI: 2.9–3.7) in Weeks 9–12 (Ptrend = 0.06). Six men (20%, 6/30) were seen for medical review after they identified abnormalities, whilst eight men (27%, 8/30) reported abnormalities, but did not seek medical review. No participants were diagnosed with syphilis during the study period.ConclusionWe conclude that men adhered well to weekly anal self-examination. Therefore, it is feasible to trial this as a routine practice among MSM. Future studies should investigate possible reductions in adherence over time and ways to increase medical review for abnormalities that men find.

ObjectivesTo illustrate the epidemiologic and cost-effectiveness impact of shifting the focus from population-based screening toward a targeted management approach for genital chlamydia infection.DesignModeling study, implementing an individual-based, stochastic, dynamic network model.SettingHong Kong.PopulationA hypothetical sample network of 10,000 people with a partnership distribution based on Hong Kong's sexually active population of reproductive age (age 18–49 years).InterventionsIn this study, we present several scenarios with different implementations of universal vs. targeted screening (based on partner numbers). We also explored the impact of (1) screening only, (2) screening plus expedited partner therapy, and (3) screening plus partner testing.Primary outcome measuresChange of chlamydia prevalence before and after implementing the different strategies. The cost-effectiveness analysis reports total direct cost from a health provider perspective, the QALYs gained, and incremental cost-effectiveness ratios (ICER).ResultsIn comparing the effects of universal screening only and targeted screening of the high-risk population, the mean prevalence during the 10th year of intervention was 2.75 ± 0.30% and 2.35 ± 0.21%, respectively (compared with 3.24 ± 0.30% and 3.35 ± 0.21% before the interventions, respectively). The addition of contact tracing to the latter targeted screening scenario reduces the mean prevalence during the 10th year of intervention to 1.48 ± 0.13% (compared with 3.31 ± 0.33% at baseline) in the best-case of testing before treatment and maximal contact-tracing effectiveness (40%). Overall, the most effective scenarios were those for which interventions focused on the high-risk population defined by the number of partners, with contact tracing included. The ICER for targeted screening with contact tracing at 20% and 40% efficiency was $4,634 and $7,219 per QALY gained, respectively (10-year time horizon). Expedited partner therapy did not significantly impact overall chlamydia prevalence and caused overtreatment.ConclusionsOur study suggests that targeted screening with strengthened contact tracing efforts is the most cost-effective strategy to reduce the prevalence of chlamydia in Hong Kong.

Abstract Mycoplasma genitalium (M. genitalium) is a recently recognised and important sexually transmitted infection among men who have sex with men (MSM). The role of oral sex, rimming, and kissing on M. genitalium transmission in MSM is unclear. We created four deterministic susceptible-infectious-susceptible epidemic models to examine the role that different sexual behaviours play in transmitting M. genitalium at the oropharynx, urethra anorectum among men who have sex with men in Australia. Our results suggest that oral and anal sex without other sexual practices (model 1) replicate well single site infection at the oropharynx, urethra and anorectum and also multi-site infection. If kissing or rimming are added to model 1 (i.e., model 2–4) no substantial improvements in the calibration of the models occur. Model 1 estimates that 3.4% of infections occur at the oropharynx, 34.8% at the urethra and 61.8% at the anorectum. Model 1 also estimates that the proportion of incident M. genitalium transmitted by anal sex was 82.4%, and by oral sex was about 17.6%. Our findings could provide an enhanced understanding of M. genitalium transmission in MSM, thus providing insights into what sexual practices contribute most to transmission.

Human papillomavirus (HPV) infection is common in women and also the main cause of cervical cancer. Based on a dynamic compartmental model, we aimed to evaluate the population impact and cost-effectiveness of strategies that combined cervical cancer screening and HPV schoolgirl vaccination for Chinese women. The effectiveness of interventions was assessed by comparing modeled scenarios to the status quo, where a 3-y cervical cancer screening program remained at a 20% coverage and without a universal HPV vaccination program. Our study demonstrated that increasing screening coverage from 20% to 50% would reduce the high-risk HPV (HR-HPV) prevalence to 5.4%, whereas a universal schoolgirl vaccination program using the quadrivalent vaccine (qHPV) with a coverage of 50% would reduce the prevalence to 2.9% by 2069. Scaling-up the cervical screening coverage to 50% will prevent 16,012 (95% CI: 8,791 to 25,913) Disability-Adjusted Life-Years (DALYs) per year, with an incremental cost-effectiveness ratio (ICER) of US$ 10,958 (95% CI: $169 to $26,973)/DALY prevented. At the current qHPV price, vaccinating 50% of school girls will prevent 13,854 (95% CI: 8,355 to 20,776) DALYs/year, but the corresponding incremental cost-effectiveness ratio (ICER, US$ 83,043, 95% CI: $52,234 to $138,025) exceeds cost-effectiveness threshold (i.e., 3 times GDP per-capita of China: $30,792). The qHPV vaccine requires at least a 50% price reduction to be cost-effective. Vaccinating schoolgirls will result in a large population health benefit in the long term, but such a universal HPV vaccination program can only be cost-effective with a substantial price reduction.

BackgroundIn Australia, undiagnosed HIV rates are much higher among migrant gay, bisexual, or other men who have sex with men (GBMSM) than Australian-born GBMSM. HIV self-testing is a promising tool to overcome barriers to HIV testing and improve HIV testing uptake among migrant GBMSM. We compared the preferences for HIV testing services, including HIV self-testing, among migrant and Australian-born GBMSM.MethodsPreferences were assessed via two discrete choice experiments (DCEs). Participants were recruited between December 2017 and January 2018 using online and offline advertising and randomly assigned to complete one of two online DCE surveys. Migrant GBMSM were classified as being born in a country with a reciprocal healthcare agreement (RHCA) with Australia (providing free or subsided health care) or not. Latent class analysis and mixed logit models were used to explore heterogeneity in preferences.FindingsWe recruited 1,606 GBMSM, including 583 migrant men of whom 419 (72%) were born in non-RHCA countries. Most participants preferred a free or cheap oral test with higher accuracy and a shorter window period to facilitate early detection of infections. Cost was more important for men born in non-RHCA countries than for men from RHCA countries or Australia. All groups preferred accessing kits through online distributers or off the shelf purchasing from pharmacies. Men born in RHCA countries least preferred accessing HIV self-testing kits from a medical clinic, while more than half of men from non-RHCA countries most preferred sourcing kits from a clinic. Sex-on-premises venues were the least preferred location to access test kits among all groups. In addition, two latent class analyses explored heterogeneity in preferences among men from non-RHCA countries and we found four latent classes for HIV testing services and two latent classes for HIVST distribution.InterpretationOur findings emphasise the need for high-performing and low-cost HIV self-testing kits that are accessible from a variety of distribution points as a component of Australia's HIV response, especially for those who do not have access to free or subsidised health care in Australia.

Summary: Background: Regular anal self-examination could potentially reduce syphilis transmission by detecting anal syphilis earlier among men who have sex with men (MSM). This study aimed to examine the preferences of MSM on performing anal self-examination to detect anal syphilis. Methods: An online survey with a discrete choice experiment (DCE) was distributed to MSM attending a sexual health clinic and through social media in Australia between June and November 2020. The DCE examined the preferred attributes of anal self-examination that would encourage MSM to perform anal self-examination. Data were analysed using a random parameters logit (RPL) model. Findings: The median age of 557 MSM who completed the survey was 35 (inter quartile range, 27-45). The choice to perform anal self-examination was most influenced by two attributes: the accuracy of anal self-examination to diagnose anal syphilis, and the frequency of anal self-examination, followed by the type of instruction materials to perform anal self-examination, waiting time for medical review, and type of support received if abnormalities were found. Using the most preferred attributes, 98% of people would conduct anal self-examination compared with 35% when the least preferred anal self-examination attributes were offered. Interpretation: If anal self-examination were recommended for anal syphilis screening, it will be important to consider preferences of MSM: men were more likely to undertake anal self-examination if the frequency was once a month and there was higher accuracy of detecting anal syphilis. Funding: Australian National Health And Medical Research Council.

BackgroundThere are few studies investigating group sex among female sex workers (FSWs). This study aimed to examine the typical number of group sex participants, sexual activities and condom use in group sex among FSWs attending a sexual health clinic in Melbourne, Australia.MethodsWe conducted a cross-sectional survey between May 1, 2019 and March 13, 2020 among FSWs in Melbourne. Participants were asked whether they had participated in group sex (sex involving more than two participants) within the past 3 months, the size of the most recent group sex event, sexual activities they engaged in and condom use. It is unknown whether this was a paid or unpaid event in our study.ResultsOf the 247 FSWs surveyed, the mean age was 28.9 years and 51.8% were born in Australia. More than a quarter (27.5%, n = 68) had had group sex in the past 3 months with the number of events ranging from 1 to 10 times. The median size of the group was 3 participants with one man and two women (including the FSW) being the most common combination. Kissing was the most common activity in group sex. Of 58 FSWs who had vaginal sex during group sex, 77.3% (51/58) reported their male partners always used condoms but 13.7% (7/51) of these did not change condoms between women.ConclusionThis study finds that group sex is common among FSWs. Although condoms are always used during group sex, one in six men did not change their condoms between partners, which may increase STI transmission between partners.

Abstract Objectives We aimed to identify high-risk factors for disease progression and fatality for coronavirus disease 2019 (COVID-19) patients. Methods We enrolled 2433 COVID-19 patients and used LASSO regression and multivariable cause-specific Cox proportional hazard models to identify the risk factors for disease progression and fatality. Results The median time for progression from mild-to-moderate, moderate-to-severe, severe-to-critical, and critical-to-death were 3.0 (interquartile range: 1.8–5.5), 3.0 (1.0–7.0), 3.0 (1.0–8.0), and 6.5 (4.0–16.3) days, respectively. Among 1,758 mild or moderate patients at admission, 474 (27.0%) progressed to a severe or critical stage. Age above 60 years, elevated levels of blood glucose, respiratory rate, fever, chest tightness, c-reaction protein, lactate dehydrogenase, direct bilirubin, and low albumin and lymphocyte count were significant risk factors for progression. Of 675 severe or critical patients at admission, 41 (6.1%) died. Age above 74 years, elevated levels of blood glucose, fibrinogen and creatine kinase-MB, and low plateleta count were significant risk factors for fatality. Patients with elevated blood glucose level were 58% more likely to progress and 3.22 times more likely to die of COVID-19. Conclusions Older age, elevated glucose level, and clinical indicators related to systemic inflammatory responses and multiple organ failures, predict both the disease progression and the fatality of COVID-19 patients.