Point-of-care testing and treatment of sexually transmitted and genital infections to improve birth outcomes in high-burden, low-resource settings (WANTAIM): a pragmatic cluster randomised crossover trial in Papua New Guinea.

BACKGROUND: Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and bacterial vaginosis have been associated with adverse maternal and perinatal outcomes, but there is conflicting evidence on the benefits of antenatal screening and treatment for these conditions. We aimed to determine the effect of antenatal point-of-care testing and immediate treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis on preterm birth, low birthweight, and other adverse maternal and perinatal outcomes compared with current standard of care, which included symptom-based treatment without laboratory confirmation. METHODS: In this pragmatic cluster randomised crossover trial, we enrolled women (aged ≥16 years) attending an antenatal clinic at 26 weeks' gestation or earlier (confirmed by obstetric ultrasound), living within approximately 1 h drive of a study clinic, and able to provide reliable contact details at ten primary health facilities and their catchment communities (clusters) in Papua New Guinea. Clusters were randomly allocated 1:1 to receive either the intervention or control (standard care) in the first phase of the trial. Following an interval (washout period) of 2-3 months at the end of the first phase, each cluster crossed over to the other group. Randomisation was stratified by province. Individual participants were informed about trial group allocation only after completing informed consent procedures. The primary outcome was a composite of preterm birth (livebirth before 37 weeks' gestation), low birthweight (<2500 g), or both, analysed according to the intention-to-treat population. This study is registered with ISRCTN Registry, ISRCTN37134032, and is completed. FINDINGS: Between July 26, 2017, and Aug 30, 2021, 4526 women were enrolled (2210 [63·3%] of 3492 women in the intervention group and 2316 [62·8%] of 3687 in the control group). Primary outcome data were available for 4297 (94·9%) newborn babies of 4526 women. The proportion of preterm birth, low birthweight, or both, in the intervention group, expressed as the mean of crude proportions across clusters, was 18·8% (SD 4·7%) compared with 17·8% in the control group (risk ratio [RR] 1·06, 95% CI 0·78-1·42; p=0·67). There were 1052 serious adverse events reported (566 in the intervention group and 486 in the control group) among 929 trial participants, and no differences by trial group. INTERPRETATION: Point-of-care testing and treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis did not reduce preterm birth or low birthweight compared with standard care. Within the subgroup of women with N gonorrhoeae, there was a substantial reduction in the primary outcome. FUNDING: UK Department of Health and Social Care; UK Foreign, Commonwealth and Development Office; UK Medical Research Council; the Wellcome Trust; the Australian National Health and Medical Research Council; and Swiss National Science Foundation.

Elimination and eradication goals for communicable diseases: a systematic review.

Objective: To consolidate recent information on elimination and eradication goals for infectious diseases and clarify the definitions and associated terminology for different goals. Methods: We conducted a systematic search of the World Health Organization's Institutional Repository for Information Sharing (WHO IRIS) and a customized systematic Google advanced search for documents published between 2008 and 2022 on elimination or eradication strategies for infectious conditions authored by WHO or other leading health organizations. We extracted information on names of infectious conditions, the elimination and eradication goals and timelines, definitions of goals, non-standardized terminology, targets and assessment processes. Findings: We identified nine goals for 27 infectious conditions, ranging from disease control to eradication. In comparison with the hierarchy of disease control, as defined at the Dahlem Workshop in 1997, six goals related to disease control with varying levels of advancement, two related to elimination and one to eradication. Goals progressed along a disease-control continuum, such as end of disease epidemic to pre-elimination to elimination as a public health problem or threat. We identified the use of non-standardized terminology with certain goals, including virtual elimination, elimination of disease epidemics, public health threat and public health concern. Conclusion: As we approach the 2030 target date to achieve many of the goals related to disease control and for other infections to become candidates for elimination in the future, clarity of definitions and objectives is important for public health professionals and policy-makers to avoid misperceptions and miscommunication.

National Surveillance of Home-Based HIV Testing Among Australian Gay and Bisexual Men, 2018-2020: Uptake After Commercial Availability of HIV Self-Tests.

HIV self-testing allows people to collect samples and test themselves at home, addressing known barriers to facility-based testing. We aimed to measure the uptake of home HIV testing among Australian gay and bisexual men (GBM). Using national cross-sectional data from the Australian Gay Community Periodic Surveys, we assessed trends in home HIV testing among non-HIV positive GBM between 2018 and 2020. Overall, the use of home HIV testing was low, but slightly increased during 2018-2020 (from 0.3 to 0.8%, RR = 1.54, 95%CI = 1.23-1.92, p-trend < 0.001). Testing at home was more likely among non-HIV-positive GBM who were born overseas and recently arrived in Australia, at higher risk of HIV, and infrequent HIV testers. Given the greater use of home testing by men at higher risk of HIV, recent migrants and infrequent testers, all priority groups in Australia's HIV epidemic, we recommend increasing access to HIV self-testing to enhance uptake in these and other groups of GBM.

A population-level application of a method for estimating the timing of HIV acquisition among migrants to Australia.

INTRODUCTION: Australia has set the goal for the virtual elimination of HIV transmission by the end of 2022, yet accurate information is lacking on the level of HIV transmission occurring among residents. We developed a method for estimating the timing of HIV acquisition among migrants, relative to their arrival in Australia. We then applied this method to surveillance data from the Australian National HIV Registry with the aim of ascertaining the level of HIV transmission among migrants to Australia occurring before and after migration, and to inform appropriate local public health interventions. METHODS: We developed an algorithm incorporating CD4+ T-cell decline back-projection and enhanced variables (clinical presentation, past HIV testing history and clinician estimate of the place of HIV acquisition) and compared it to a standard algorithm which uses CD4+ T-cell back-projection only. We applied both algorithms to all new HIV diagnoses among migrants to estimate whether HIV infection occurred before or after arrival in Australia. RESULTS: Between 1 January 2016 and 31 December 2020, 1909 migrants were newly diagnosed with HIV in Australia, 85% were men, and the median age was 33 years. Using the enhanced algorithm, 932 (49%) were estimated to have acquired HIV after arrival in Australia, 629 (33%) before arrival (from overseas), 250 (13%) close to arrival and 98 (5%) were unable to be classified. Using the standard algorithm, 622 (33%) were estimated to have acquired HIV in Australia, 472 (25%) before arrival, 321 (17%) close to arrival and 494 (26%) were unable to be classified. CONCLUSIONS: Using our algorithm, close to half of migrants diagnosed with HIV were estimated to have acquired HIV after arrival in Australia, highlighting the need for tailored culturally appropriate testing and prevention programmes to limit HIV transmission and achieve elimination targets. Our method reduced the proportion of HIV cases unable to be classified and can be adopted in other countries with similar HIV surveillance protocols, to inform epidemiology and elimination efforts.

Infectious syphilis in women and heterosexual men in major Australian cities: sentinel surveillance data, 2011-2019.

OBJECTIVES: To examine changes in the positive infectious syphilis test rate among women and heterosexual men in major Australian cities, and rate differences by social, biomedical, and behavioural determinants of health. DESIGN, SETTING: Analysis of data extracted from de-identified patient records from 34 sexual health clinics participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance of Sexually Transmissible Infections and Blood Borne Viruses (ACCESS). PARTICIPANTS: First tests during calendar year for women and heterosexual men aged 15 years or more in major cities who attended ACCESS sexual health clinics during 2011-2019. MAIN OUTCOME MEASURES: Positive infectious syphilis test rate; change in annual positive test rate. RESULTS: 180 of 52 221 tested women (0.34%) and 239 of 36 341 heterosexual men (0.66%) were diagnosed with infectious syphilis. The positive test rate for women was 1.8 (95% confidence interval [CI], 0.9-3.2) per 1000 tests in 2011, 3.0 (95% CI, 2.0-4.2) per 1000 tests in 2019 (change per year: rate ratio [RR], 1.12; 95% CI, 1.01-1.25); for heterosexual men it was 6.1 (95% CI, 3.8-9.2) per 1000 tests in 2011 and 7.6 (95% CI, 5.6-10) per 1000 tests in 2019 (RR, 1.10; 95% CI, 1.03-1.17). In multivariable analyses, the positive test rate was higher for women (adjusted RR [aRR], 1.85; 95% CI, 1.34-2.55) and heterosexual men (aRR, 2.39; 95% CI, 1.53-3.74) in areas of greatest socio-economic disadvantage than for those in areas of least socio-economic disadvantage. It was also higher for Indigenous women (aRR, 2.39; 95% CI, 1.22-4.70) and for women who reported recent injection drug use (aRR, 4.87; 95% CI, 2.18-10.9) than for other women; it was lower for bisexual than heterosexual women (aRR, 0.48; 95% CI, 0.29-0.81) and for women who reported recent sex work (aRR, 0.35; 95% CI, 0.29-0.44). The positive test rate was higher for heterosexual men aged 40-49 years (aRR, 2.11; 95% CI, 1.42-3.12) or more than 50 years (aRR, 2.36; 95% CI, 1.53-3.65) than for those aged 15-29 years. CONCLUSION: The positive test rate among both urban women and heterosexual men tested was higher in 2019 than in 2011. People who attend reproductive health or alcohol and drug services should be routinely screened for syphilis.

The acceptability and usability of two HIV self-test kits among men who have sex with men: a randomised crossover trial.

OBJECTIVES: To compare the usability and acceptability of oral fluid- and blood-based HIV self-test kits among men who have sex with men in Australia. DESIGN: Randomised crossover trial. SETTING, PARTICIPANTS: Gay, bisexual, and other men aged 18 years or older who have sex with men, who attended two metropolitan sexual health clinics in Sydney and Melbourne, 7 January - 10 December 2019. MAIN OUTCOME MEASURES: Ease of use of HIV self-test kits; preferred HIV self-test type; difficulties encountered during HIV self-testing. RESULTS: 170 men were recruited (median age, 34 years; interquartile range, 29-43 years); 144 identified as gay (85%), 96 were born outside Australia (57%). Participants were more likely to report the oral fluid HIV self-test was easy to use than the blood-based self-test (oral fluid, 99%; blood, 86%; odds ratio [OR], 3.0; 95% confidence interval [CI], 1.4-6.6). The oral fluid test was preferred by 98 participants (58%; 95% CI, 50-65%), the blood-based test by 69 (41%; 95% CI, 33-48%). Difficulties with the oral fluid test kit identified by observing nurses included problems placing the buffer solution into the stand (40 of 170 participants, 24%) and not swabbing both gums (23 of 169, 14%); difficulties with the blood-based test kit included problems filling the device test channel (69 of 170, 41%) and squeezing the finger firmly enough to generate a blood drop (42 of 170, 25%). No participant received an invalid result with the oral fluid self-test; two of 162 participants (1%) received invalid results with the blood self-test. After adjusting for age, education level, and ethnic background, characteristics associated with higher odds of using HIV self-testing in the future were overseas birth (adjusted OR, 3.07; 95% CI, 1.42-6.64), and self-evaluated ease of use and confidence in using the kits. CONCLUSION: It is important to provide options for obtaining both oral fluid- and blood-based HIV self-tests. The usability and acceptability of both kits were high, but the ease of use and perceived accuracy influenced test kit preference.

Assessing the Impact of HIV Preexposure Prophylaxis Scale-Up on Gonorrhea Incidence Among Gay and Bisexual Men in Sydney: A Mathematical Modeling Study.

BACKGROUND: The rollout of preexposure prophylaxis (PrEP) for HIV prevention among gay and bisexual men (GBM) is associated with increases in condomless anal intercourse, potentially increasing the incidence of other sexually transmissible infections (STIs). METHODS: We developed an individual-based mathematical model to simulate the transmission of Neisseria gonorrhoeae among GBM in Sydney, accounting for changes in sexual practices, STI testing, and PrEP use. We calibrated and validated the model using reported incidence rates for HIV-positive and HIV-negative GBM from 2010 to 2019. Scenarios were run with varying PrEP uptake, PrEP-related STI testing, and PrEP-related sexual behavior and testing intervals up to 2030 to assess the impact of PrEP use on gonorrhea incidence. RESULTS: Preexposure prophylaxis uptake and associated 3-monthly STI testing from 2015 onward resulted in a predicted increase from 20 to 37 N. gonorrhoeae infections per 100 person-years among HIV-negative GBM by the end of 2020. This is lower than the counterfactual predictions of 45 per 100 person-years if PrEP were not scaled up and 48 per 100 person-years with nonadherence to 3-monthly STI testing. Increasing the time between STI tests for PrEP users by 1 month from 2018 results in the incidence rate among HIV-negative GBM increasing by 8% by 2030. If PrEP coverage doubles from 24% to 53%, incidence among HIV-negative GBM declines by ~25% by 2030. CONCLUSIONS: Behavior change due to widespread PrEP use may lead to significant increases in gonorrhea incidence in GBM, but the recommended quarterly STI testing recommended for PrEP users should reduce incidence by 18% by 2030.

Surveillance systems to monitor antimicrobial resistance in Neisseria gonorrhoeae: a global, systematic review, 1 January 2012 to 27 September 2020.

BackgroundEffective surveillance of antimicrobial resistance (AMR) in Neisseria gonorrhoeae is required for the early detection of resistant strains and to ensure that treatment guidelines are appropriate for the setting in which they are implemented. AMR in N. gonorrhoeae has been identified as a global health threat.AimWe performed a systematic review to identify and describe surveillance systems targeting AMR in N. gonorrhoeae.MethodsWe searched Medline, PubMed, Global Health, EMBASE, CINAHL, Web of Science and ProQuest databases and grey literature between 1 January 2012 and 27 September 2020. Surveillance systems were defined as the continuous, systematic collection, analysis and interpretation of N. gonorrhoeae resistance data. The key components of surveillance systems were extracted, categorised, described and summarised.ResultsWe found 40 publications reporting on N. gonorrhoeae AMR surveillance systems in 27 countries and 10 multi-country or global surveillance reports. The proportion of countries with surveillance systems in each of the WHO's six regions ranged from one of 22 countries in the Eastern Mediterranean and five of 54 in Africa, to three of 11 countries in South East Asia. Only four countries report systems which are both comprehensive and national. We found no evidence of a current surveillance system in at least 148 countries. Coverage, representativeness, volume, clinical specimen source, type and epidemiological information vary substantially and limit interpretability and comparability of surveillance data for public health action.ConclusionGlobally, surveillance for N. gonorrhoeae AMR is inadequate and leaves large populations vulnerable to a major public health threat.

Sustaining success: a qualitative study of gay and bisexual men's experiences and perceptions of HIV self-testing in a randomized controlled trial.

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.

Modelling response strategies for controlling gonorrhoea outbreaks in men who have sex with men in Australia.

The ability to treat gonorrhoea with current first-line drugs is threatened by the global spread of extensively drug resistant (XDR) Neisseria gonorrhoeae (NG) strains. In Australia, urban transmission is high among men who have sex with men (MSM) and importation of an XDR NG strain in this population could result in an epidemic that would be difficult and costly to control. An individual-based, anatomical site-specific mathematical model of NG transmission among Australian MSM was developed and used to evaluate the potential for elimination of an imported NG strain under a range of case-based and population-based test-and-treat strategies. When initiated upon detection of the imported strain, these strategies enhance the probability of elimination and reduce the outbreak size compared with current practice (current testing levels and no contact tracing). The most effective strategies combine testing targeted at regular and casual partners with increased rates of population testing. However, even with the most effective strategies, outbreaks can persist for up to 2 years post-detection. Our simulations suggest that local elimination of imported NG strains can be achieved with high probability using combined case-based and population-based test-and-treat strategies. These strategies may be an effective means of preserving current treatments in the event of wider XDR NG emergence.

The longer-term effects of access to HIV self-tests on HIV testing frequency in high-risk gay and bisexual men: follow-up data from a randomised controlled trial.

BACKGROUND: A wait-list randomised controlled trial in Australia (FORTH) in high-risk gay and bisexual men (GBM) showed access to free HIV self-tests (HIVSTs) doubled the frequency of HIV testing in year 1 to reach guideline recommended levels of 4 tests per year, compared to two tests per year in the standard-care arm (facility-based testing). In year 2, men in both arms had access to HIVSTs. We assessed if the effect was maintained for a further 12 months. METHODS: Participants included GBM reporting condomless anal intercourse or > 5 male partners in the past 3 months. We included men who had completed at least one survey in both year 1 and 2 and calculated the mean tests per person, based on the validated self-report and clinic records. We used Poisson regression and random effects Poisson regression models to compare the overall testing frequency by study arm, year and testing modality (HIVST/facility-based test). FINDINGS: Overall, 362 men completed at least one survey in year 1 and 343 in year 2. Among men in the intervention arm (access to HIVSTs in both years), the mean number of HIV tests in year 2 (3⋅7 overall, 2⋅3 facility-based tests, 1⋅4 HIVSTs) was lower compared to year 1 (4⋅1 overall, 1⋅7 facility-based tests, 2⋅4 HIVSTs) (RR:0⋅84, 95% CI:0⋅75-0⋅95, p=0⋅002), but higher than the standard-care arm in year 1 (2⋅0 overall, RR:1⋅71, 95% CI:1⋅48-1.97, p<0⋅001). Findings were not different when stratified by sociodemographic characteristics or recent high risk sexual history. INTERPRETATION: In year 2, fewer HIVSTs were used on average compared to year 1, but access to free HIVSTs enabled more men to maintain higher HIV testing frequency, compared with facility-based testing only. HIV self-testing should be a key component of HIV testing and prevention strategies. FUNDING: This work was supported by grant 568971 from the National Health and Medical Research Council of Australia.

Genital warts trends in Australian and overseas-born people in Australia: A cross-sectional trend analysis to measure progress towards control and elimination.

Background: Substantial declines in genital warts have been observed in countries with quadrivalent/nonavalent human papillomavirus (q/n HPV) vaccination programmes, with Australia showing the most pronounced and long-term reductions. No study has assessed progress towards elimination of genital warts in a nation-wide sample of patients, and migrants' contribution to population-level control of genital warts. We assessed Australia's progress towards genital warts elimination by examining trends in diagnoses in Australian- and overseas-born patients of sexual health clinics (SHCs) across Australia. Methods: A cross-sectional trend analysis of new genital warts diagnoses among first-time patients of 34 SHCs, between 2004 and 2018, was performed. Rate ratios (RR) were calculated using Poisson regression models, for comparing trends in proportions of new genital warts diagnoses in Australian- and overseas-born patients during the pre-vaccination era (2004-2007) and the vaccination era (2008-2018), and by 2018 relative to 2004-2007. Findings: A total of 439,957 new patients (Australian-born: 230,230; overseas-born: 209,727) were seen at SHCs, 6•4% were diagnosed with genital warts (Australian-born: 7•1%; overseas-born: 5•6%). By 2018, there had been a 64% reduction in the proportion of all SHC patients with a genital warts diagnosis relative to 2004-2007 (RR: 0•36, 95% CI: 0•35-0•38). The decline was more pronounced at 72% (RR: 0•28, 95% CI: 0 •27-0•30) among Australian-born patients, with the greatest reduction in women and men aged <21 years, at 98% (RR: 0•02, 95% CI: 0•01-0•03) and 92% (RR: 0•08, 95% CI: 0•06-0•11), respectively. By 2018, there was a 49% reduction in the proportion of overseas-born patients diagnosed with genital warts (RR: 0•51, 95% CI:0•48-0•54), and a 21% reduction in overseas-born patients from countries with no or bivalent HPV (bHPV) vaccination programme (RR: 0•79, 95% CI: 0•71-0•90). Interpretation: The substantial reductions in Australian-born people is a testament to the efficacy of quadrivalent (qHPV) and nonavalent (nHPV) vaccines and the high and wide-spread vaccination coverage in Australia. However, population-wide elimination of genital warts in Australia is dependent on other countries initiating or expanding their own HPV vaccination programmes. Funding: The Australian Government Department of Health and Seqirus Australia.

Effect on genital warts in Australian female and heterosexual male individuals after introduction of the national human papillomavirus gender-neutral vaccination programme: an analysis of national sentinel surveillance data from 2004-18.

BACKGROUND: In Australia, the government-funded human papillomavirus (HPV) vaccination programme was introduced in April, 2007, for girls and young women, and in February, 2013, for boys. As of Dec 31, 2018, all Australian-born female individuals younger than 38 years and male individuals younger than 21 years have been eligible for the free quadrivalent or nonavalent HPV vaccine. We aimed to examine the trends in genital wart diagnoses among Australian-born female and heterosexual male individuals who attended sexual health clinics throughout Australia before and after the introduction of the gender-neutral HPV vaccination programme in February, 2013. METHODS: We did a serial cross-sectional analysis of genital wart diagnoses among Australian-born female and heterosexual male individuals attending a national surveillance network of 35 clinics between Jan 1, 2004, and Dec 31, 2018. We calculated prevalence ratios of genital warts, using log-binomial regression models, for the female-only vaccination period (July 1, 2007, to Feb 28, 2013), gender-neutral vaccination period (March 1, 2013, to Dec 31, 2018), and the whole vaccination period (July 1, 2007, to Dec 31, 2018) compared with the pre-vaccination period (Jan 1, 2004, to June 30, 2007). FINDINGS: We included 121 038 men and 116 341 women in the analysis. Overall, we observed a 58% reduction (prevalence ratio 0·42, 95% CI 0·40-0·44) in genital wart diagnoses in female individuals and a 45% reduction (0·55, 0·53-0·57) in genital wart diagnoses in heterosexual male individuals after the introduction of the vaccination programme in 2007. The largest reduction in genital warts was observed in younger individuals, and there was a decreasing magnitude of reduction with increasing age (80%, 72%, 61%, 41%, and 16% reductions in female individuals aged 15-20 years, 21-25 years, 26-30 years, 31-35 years, and ≥36 years, respectively; 70%, 61%, 49%, 37%, and 29% reductions in male individuals aged 15-20 years, 21-25 years, 26-30 years, 31-35 years, and ≥36 years, respectively). Significant reductions observed in female individuals (0·32, 0·28-0·36) and male individuals (0·51, 0·43-0·61) aged 15-20 years in the female-only vaccination period were followed by a more substantial reduction in female individuals (0·07, 0·06-0·09) and male individuals (0·11, 0·08-0·15) aged 15-20 years in the gender-neutral vaccination period. INTERPRETATION: The national gender-neutral HPV vaccination programme has led to substantial and ongoing reduction in genital warts among Australian female and heterosexual male individuals, with a marked reduction in young individuals who received the vaccine at school. FUNDING: Seqirus Australia and the Australian Government Department of Health.

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

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

A New Method for Estimating the Incidence of Infectious Diseases.

Ambitious World Health Organization targets for disease elimination require monitoring of epidemics using routine health data in settings of decreasing and low incidence. We evaluated 2 methods commonly applied to routine testing results to estimate incidence rates that assume a uniform probability of infection between consecutive negative and positive tests based on 1) the midpoint of this interval and 2) a randomly selected point in this interval. We compared these with an approximation of the Poisson binomial distribution, which assigns partial incidence to time periods based on the uniform probability of occurrence in these intervals. We assessed bias, variance, and convergence of estimates using simulations of Weibull-distributed failure times with systematically varied baseline incidence and varying trend. We considered results for quarterly, half-yearly, and yearly incidence estimation frequencies. We applied the methods to assess human immunodeficiency virus (HIV) incidence in HIV-negative patients from the Treatment With Antiretrovirals and Their Impact on Positive and Negative Men (TAIPAN) Study, an Australian study of HIV incidence in men who have sex with men, between 2012 and 2018. The Poisson binomial method had reduced bias and variance at low levels of incidence and for increased estimation frequency, with increased consistency of estimation. Application of methods to real-world assessment of HIV incidence found decreased variance in Poisson binomial model estimates, with observed incidence declining to levels where simulation results had indicated bias in midpoint and random-point methods.

Defining Elimination of Genital Warts-A Modified Delphi Study.

Background: Substantial declines in genital warts (GW) have been observed in countries with quadrivalent HPV vaccination programmes, with Australia showing the highest reductions due to early commencement and high vaccination coverage. There is a real potential to achieve GW elimination; however, no GW elimination definition exists. Taking Australia as a case study, we aimed to reach expert consensus on a proposed GW elimination definition using a modified Delphi process. Method: We used modelling and epidemiological data to estimate the expected number of new GW cases, from pre-vaccination (baseline) in 2006 to the year 2060 in Australian heterosexuals, men who have sex with men (MSM), and newly arrived international travellers and migrants. We used these data and the literature, to develop a questionnaire containing ten elimination-related items, each with 9-point Likert scales (1-strongly disagree; 9-strongly agree). The survey was completed by 18 experts who participated in a full day face-to-face modified Delphi study, in which individuals and then small groups discussed and scored each item. The process was repeated online for items where consensus (≥70% agreement) was not initially achieved. Median and coefficient of variation (COV) were used to describe the central tendency and variability of responses, respectively. Findings: There was a 95% participation rate in the face-to-face session, and 84% response rate in the final online round. The median item score ranged between 7.0 and 9.0 and the COV was ≤0.30 on all items. Consensus was reached that at ≥80% HPV vaccination coverage, GW will be eliminated as a public health problem in Australia by 2060. During this time period there will be a 95% reduction in population-level incidence compared with baseline, equivalent to <1 GW case per 10,000 population. The reductions will occur most rapidly in Australian heterosexuals, with 73%, 90% and 97% relative reductions by years 2021, 2030 and 2060, respectively. The proportion of new GW cases attributable to importation will increase from 3.6% in 2006 to ~49% in 2060. Interpretation: Our results indicate that the vaccination programme will minimise new GW cases in the Australian population, but importation of cases will continue. This is the first study to define GW elimination at a national level. The framework developed could be used to define GW elimination in other countries, with thresholds particularly valuable for vaccination programme impact evaluation. Funding: LK supported through an Australian Government Research Training Programme Scholarship; unconditional funding from Seqirus to support the Delphi Workshop.

Population-level diagnosis and care cascade for chlamydia in Australia.

OBJECTIVES: Key strategies to control chlamydia include testing, treatment, partner management and re-testing. We developed a diagnosis and care cascade for chlamydia to highlight gaps in control strategies nationally and to inform efforts to optimise control programmes. METHODS: The Australian Chlamydia Cascade was organised into four steps: (1) annual number of new chlamydia infections (including re-infections); (2) annual number of chlamydia diagnoses; (3) annual number of diagnoses treated; (4) annual number of diagnoses followed by a re-test for chlamydia within 42-180 days of diagnosis. For 2016, we estimated the number of infections among young men and women aged 15-29 years in each of these steps using a combination of mathematical modelling, national notification data, sentinel surveillance data and previous research studies. RESULTS: Among young people in Australia, there were an estimated 248 580 (range, 240 690-256 470) new chlamydia infections in 2016 (96 470 in women; 152 100 in men) of which 70 164 were diagnosed (28.2% overall: women 43.4%, men 18.6%). Of the chlamydia infections diagnosed, 65 490 (range, 59 640-70 160) were treated (93.3% across all populations), but only 11 330 (range, 7660-16 285) diagnoses were followed by a re-test within 42-180 days (17.3% overall: women 20.6%, men 12.5%) of diagnosis. CONCLUSIONS: The greatest gaps in the Australian Chlamydia Cascade for young people were in the diagnosis and re-testing steps, with 72% of infections undiagnosed and 83% of those diagnosed not re-tested: both were especially low among men. Treatment rates were also lower than recommended by guidelines. Our cascade highlights the need for enhanced strategies to improve treatment and re-testing coverage such as short message service reminders, point-of-care and postal test kits.