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.

Risk of Primary Incident Hepatitis C Infection Following Bacterial Sexually Transmissible Infections Among Gay and Bisexual Men in Australia From 2016 to 2020.

Background: In Australia, the incidence of hepatitis C virus (HCV) has declined among gay and bisexual men (GBM) with human immunodeficiency virus (HIV) since 2015 and is low among GBM using HIV preexposure prophylaxis (PrEP). However, ongoing HCV testing and treatment remains necessary to sustain this. To assess the potential utility of sexually transmissible infections (STIs) to inform HCV testing among GBM with HIV and GBM using PrEP, we examined the association between bacterial STI diagnoses and subsequent primary HCV infection. Methods: Data were from a national network of 46 clinics participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance. GBM included had ≥1 HCV antibody negative test result and ≥1 subsequent HCV antibody and/or RNA test. Discrete time survival analysis was used to estimate the association between a positive syphilis, rectal chlamydia, and rectal gonorrhea diagnosis in the previous 2 years and a primary HCV diagnosis, defined as a positive HCV antibody or RNA test result. Results: Among 6529 GBM with HIV, 92 (1.4%) had an incident HCV infection. A prior positive syphilis diagnosis was associated with an incident HCV diagnosis (adjusted hazard ratio, 1.99 [95% confidence interval, 1.11-3.58]). Among 13 061 GBM prescribed PrEP, 48 (0.4%) had an incident HCV diagnosis. Prior rectal chlamydia (adjusted hazard ratio, 2.75 [95% confidence interval, 1.42-5.32]) and rectal gonorrhea (2.54 [1.28-5.05]) diagnoses were associated with incident HCV. Conclusions: Diagnoses of bacterial STIs in the past 2 years was associated with HCV incidence. These findings suggest that STIs might be useful for informing HCV testing decisions and guidelines for GBM with HIV and GBM using PrEP.

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.

Optimizing health resource allocation for improving timely HIV diagnosis in China.

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.

Clinical features-based machine learning models to separate sexually transmitted infections from other skin diagnoses.

INTRODUCTION: Many sexual health services are overwhelmed and cannot cater for all the individuals who present with sexually transmitted infections (STIs). Digital health software that separates STIs from non-STIs could improve the efficiency of clinical services. We developed and evaluated a machine learning model that predicts whether patients have an STI based on their clinical features. METHODS: We manually extracted 25 demographic features and clinical features from 1315 clinical records in the electronic health record system at Melbourne Sexual Health Center. We examined 16 machine learning models to predict a binary outcome of an STI or a non-STI diagnosis. We evaluated the models' performance with the area under the ROC curve (AUC), accuracy and F1-scores. RESULTS: Our study included 1315 consultations, of which 36.8% (484/1315) were diagnosed with STIs and 63.2% (831/1315) had non-STI conditions. The study population predominantly consisted of heterosexual men (49.5%, 651/1315), followed by gay, bisexual and other men who have sex with men (GBMSM) (25.7%), women (21.6%) and unknown gender (3.2%). The median age was 31 years (intra-quartile range (IQR) 26-39). The top 5 performing models were CatBoost (AUC 0.912), Random Forest (AUC 0.917), LightGBM (AUC 0.907), Gradient Boosting (AUC 0.905) and XGBoost (AUC 0.900). The best model, CatBoost, achieved an accuracy of 0.837, sensitivity of 0.776, specificity of 0.831, precision of 0.782 and F1-score of 0.778. The key important features were lesion duration, type of skin lesions, age, gender, history of skin disorders, number of lesions, dysuria duration, anorectal pain and itchiness. CONCLUSIONS: Our best model demonstrates a reasonable performance in distinguishing STIs from non-STIs. However, to be clinically useful, more detailed information such as clinical images, may be required to reach sufficient accuracy.

Predictors of liver disease progression in people living with HIV-HBV co-infection on antiretroviral therapy.

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.

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.

Ignored and undervalued in public health: a systematic review of health state utility values associated with syphilis infection.

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.

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.

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.

Neisseria gonorrhoeae vaccines: a contemporary overview.

Neisseria gonorrhoeae infection is an important public health issue, with an annual global incidence of 87 million. N. gonorrhoeae infection causes significant morbidity and can have serious long-term impacts on reproductive and neonatal health and may rarely cause life-threatening disease. Global rates of N. gonorrhoeae infection have increased over the past 20 years. Importantly, rates of antimicrobial resistance to key antimicrobials also continue to increase, with the United States Centers for Disease Control and Prevention identifying drug-resistant N. gonorrhoeae as an urgent threat to public health. This review summarizes the current evidence for N. gonorrhoeae vaccines, including historical clinical trials, key N. gonorrhoeae vaccine preclinical studies, and studies of the impact of Neisseria meningitidis vaccines on N. gonorrhoeae infection. A comprehensive survey of potential vaccine antigens, including those identified through traditional vaccine immunogenicity approaches, as well as those identified using more contemporary reverse vaccinology approaches, are also described. Finally, the potential epidemiological impacts of a N. gonorrhoeae vaccine and research priorities for further vaccine development are described.

Hepatitis C virus reinfection incidence among gay and bisexual men with HIV in Australia from 2016 to 2020.

BACKGROUND: There is some concern that hepatitis C virus (HCV) reinfection might impact HCV micro-elimination efforts among gay and bisexual men (GBM) with HIV. However, there is a limited understanding of reinfection incidence in the context of unrestricted government-funded HCV treatment. We aimed to estimate HCV reinfection incidence among GBM with HIV in Australia from 2016 to 2020. METHODS: Data were from 39 clinics participating in ACCESS, a sentinel surveillance network for blood borne viruses and sexually transmissible infections across Australia. GBM with HIV who had evidence of treatment or spontaneous clearance with at least one positive HCV RNA test, a subsequent negative HCV RNA test, and at least one additional HCV RNA test between 1st January 2016 and 31st December 2020 were eligible for inclusion. A new HCV RNA positive test and/or detectable viral load was defined as a reinfection. Generalised linear modelling was used to examine trends in reinfection. RESULTS: Among 12 213 GBM with HIV who had at least one HCV test, 540 were included in the reinfection incidence analysis, of whom 38 (7%) had evidence of reinfection during the observation period. Over 1124 person-years of follow-up, the overall rate of reinfection was 3.4/100PY (95% CI 2.5-4.6). HCV reinfection incidence declined on average 30% per calendar year (Incidence Rate Ratio 0.70, 95% CI 0.54-0.91). CONCLUSION: HCV reinfection incidence has declined among GBM with HIV in Australia since government-funded unrestricted DAAs were made available. Ongoing HCV RNA testing following cure and prompt treatment for anyone newly diagnosed is warranted to sustain this.

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.

Human papillomavirus and p16INK4a in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis.

We intended to update human papillomavirus (HPV) prevalence and p16INK4a positivity in oropharyngeal squamous cell carcinomars (SCC), and calculate HPV attributable fraction (AF) for oropharyngeal SCC by geographic region. We searched Medline, Embase, and the Cochrane Library to identify published studies of HPV prevalence and p16INK4a positivity alone or together in oropharyngeal SCC before December 28, 2021. Studies that reported type-specific HPV DNA prevalence using broad-spectrum PCR-based testing methods were included. We estimated pooled HPV prevalence, type-specific HPV prevalence, and p16INK4a positivity. AF of HPV was calculated by geographic region. One hundred and thirty-four studies including 12 139 cases were included in our analysis. The pooled HPV prevalence estimate for oropharyngeal SCC was 48.1% (95% confidence interval [CI] 43.2-53.0). HPV prevalence varied significantly by geographic region, and the highest HPV prevalence in oropharyngeal SCC was noted in North America (72.6%, 95% CI 63.8-80.6). Among HPV positive cases, HPV 16 was the most common type with a prevalence of 40.2% (95% CI 35.7-44.7). The pooled p16INK4a positivity in HPV positive and HPV16 positive oropharyngeal SCC cases was 87.2% (95% CI 81.6-91.2) and 91.7% (84.3-97.2). The highest AFs of HPV and HPV16 were noted in North America at 69.6% (95% CI 53.0-91.5) and 63.0% (48.0-82.7). [Correction added on 31 October 2023, after first online publication: the percentage symbol (%) was missing and has been added to 63.0% (48.0-82.7) in the Abstract and Conclusion.] A significant proportion of oropharyngeal SCC was attributable to HPV. HPV16 accounts for the majority of HPV positive oropharyngeal SCC cases. These findings highlight the importance of HPV vaccination in the prevention of a substantial proportion of oropharyngeal SCC cases.

Cost-Effectiveness of the Second COVID-19 Booster Vaccination in the USA.

OBJECTIVE: To assess the cost effectiveness of the second COVID-19 booster vaccination with different age groups. METHODS: We developed a decision-analytic Susceptible-Exposed-Infected-Recovered (SEIR)-Markov model by five age groups (0-4 years, 5-11 years 12-17 years, 18-49 years, and 50+ years) and calibrated the model by actual mortality in each age group in the USA. We conducted five scenarios to evaluate the cost effectiveness of the second booster strategy and incremental benefits if the strategy would expand to 18-49 years and 12-17 years, from a health care system perspective. The analysis was reported according to the Consolidated Health Economic Evaluation Reporting Standards 2022 statement. RESULTS: Implementing the second booster strategy for those aged ≥ 50 years cost $823 million but reduced direct medical costs by $1166 million, corresponding to a benefit-cost ratio of 1.42. Moreover, the strategy also resulted in a gain of 2596 quality-adjusted life-years (QALYs) during the 180-day evaluation period, indicating it was dominant. Further, vaccinating individuals aged 18-49 years with the second booster would result in an additional gain of $1592 million and 8790 QALYs. Similarly, expanding the vaccination to individuals aged 12-17 years would result in an additional gain of $16 million and 403 QALYs. However, if social interaction between all age groups was severed, vaccination expansion to ages 18-49 and 12-17 years would no longer be dominant but cost effective with an incremental cost-effectiveness ratio (ICER) of $37,572 and $26,705/QALY gained, respectively. CONCLUSION: The second booster strategy was likely to be dominant in reducing the disease burden of the COVID-19 pandemic. Expanding the second booster strategy to ages 18-49 and 12-17 years would remain dominant due to their social contacts with the older age group.

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.

Exploring multimorbidity profiles in middle-aged inpatients: a network-based comparative study of China and the United Kingdom.

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.

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.