Azithromycin or Doxycycline for Asymptomatic Rectal Chlamydia trachomatis.

BACKGROUND: Rectal chlamydia is a common bacterial sexually transmissible infection among men who have sex with men. Data from randomized, controlled trials are needed to guide treatment. METHODS: In this double-blind trial conducted at five sexual health clinics in Australia, we randomly assigned men who have sex with men and who had asymptomatic rectal chlamydia to receive doxycycline (100 mg twice daily for 7 days) or azithromycin (1-g single dose). Asymptomatic chlamydia was selected as the trial focus because more than 85% of men with rectal chlamydia infection are asymptomatic, and clinical guidelines recommend a longer treatment course for symptomatic infection. The primary outcome was a negative nucleic acid amplification test for rectal chlamydia (microbiologic cure) at 4 weeks. RESULTS: From August 2016 through August 2019, we enrolled 625 men (314 in the doxycycline group and 311 in the azithromycin group). Primary outcome data were available for 290 men (92.4%) in the doxycycline group and 297 (95.5%) in the azithromycin group. In the modified intention-to-treat population, a microbiologic cure occurred in 281 of 290 men (96.9%; 95% confidence interval [CI], 94.9 to 98.9) in the doxycycline group and in 227 of 297 (76.4%; 95% CI, 73.8 to 79.1) in the azithromycin group, for an adjusted risk difference of 19.9 percentage points (95% CI, 14.6 to 25.3; P<0.001). Adverse events that included nausea, diarrhea, and vomiting were reported in 98 men (33.8%) in the doxycycline group and in 134 (45.1%) in the azithromycin group (risk difference, -11.3 percentage points; 95% CI, -19.5 to -3.2). CONCLUSIONS: A 7-day course of doxycycline was superior to single-dose azithromycin in the treatment of rectal chlamydia infection among men who have sex with men. (Funded by the National Health and Medical Research Council; RTS Australian New Zealand Clinical Trials Registry number, ACTRN12614001125617.).

The changing epidemiology of Neisseria gonorrhoeae genogroups and antimicrobial resistance in Queensland, Australia, 2010-15: a case series analysis of unique Neisseria gonorrhoeae isolates.

BACKGROUND: Neisseria gonorrhoeae (NG) can lead to serious reproductive and sexual health outcomes, and the annual number of NG notifications in Australia increased steadily from 10329 in 2010 to 29549 by 2020. Australian populations most affected are urban men who have sex with men and First Nations peoples living in remote areas, and a resurgence in urban heterosexuals has been observed since 2012. METHODS: A case series analysis of Queensland NG isolates (2010-15) exploring temporal trends and antimicrobial resistance by demographic and geographic distribution and genotype was performed. Proportions describe age, sex, strain, genogroup (NG multi-antigen sequence typing), region, swab site, antimicrobial sensitivity and isolate rates per 100000 population. Dominant genogroups were identified. RESULTS: Among 3953 isolates, the median age was 25years (IQR 20-34years) and most (n =2871/3915, 73%) were men. Brisbane city (68.8) and Far North Queensland (54.1) excluding Cairns showed the highest rates. Forty-six genogroups were documented, seven (G2992, G6876, G1415, G4186, G5, G1407 and G6937) comprised half of all isolates. The predominant male genogroup was G2992 (16%), and G6876 (20%) for females; G5 was predominantly male from 2010 to 2011, but equal in both sexes from 2012 to 2015. CONCLUSION: Considerable temporal, geographical and demographical diversity was observed in Queensland NG isolates, which has public health implications. Certain genogroups are more transient than others, and evidence suggests bridging from male-dominant networks to heterosexual networks. Molecular surveillance can enhance tracking the epidemiology and movement of NG in Australia, highlighting the necessity of genotyping to expose potentially prevalent strains circulating in undetected or underrepresented networks by current screening methods.

A Gonococcal Vaccine Has the Potential to Rapidly Reduce the Incidence of Neisseria gonorrhoeae Infection Among Urban Men Who Have Sex With Men.

BACKGROUND: A gonococcal vaccine is urgently needed due to increasing gonorrhea incidence and emerging multidrug-resistant gonococcal strains worldwide. Men who have sex with men (MSM) have among the highest incidences of gonorrhea and may be a key target population for vaccination when available. METHODS: An individual-based, anatomical site-specific mathematical model was used to simulate Neisseria gonorrhoeae transmission in a population of 10 000 MSM. The impact of vaccination on gonorrhea prevalence was assessed. RESULTS: With a gonococcal vaccine of 100% or 50% protective efficacy, gonorrhea prevalence could be reduced by 94% or 62%, respectively, within 2 years if 30% of MSM are vaccinated on presentation for sexually transmitted infection (STI) testing. Elimination of gonorrhea is possible within 8 years with vaccines of ≥ 50% efficacy lasting 2 years, providing a booster vaccination is available every 3 years on average. A vaccine's impact may be reduced if it is not effective at all anatomical sites. CONCLUSIONS: Our study indicates that with a vaccine of modest efficacy and an immunization strategy that targets MSM presenting for STI screening, the prevalence of gonorrhea in this population could be rapidly and substantially reduced.

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.

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.

Modelling testing and response strategies for COVID-19 outbreaks in remote Australian Aboriginal communities.

BACKGROUND: Remote Australian Aboriginal and Torres Strait Islander communities have potential to be severely impacted by COVID-19, with multiple factors predisposing to increased transmission and disease severity. Our modelling aims to inform optimal public health responses. METHODS: An individual-based simulation model represented SARS-CoV2 transmission in communities ranging from 100 to 3500 people, comprised of large, interconnected households. A range of strategies for case finding, quarantining of contacts, testing, and lockdown were examined, following the silent introduction of a case. RESULTS: Multiple secondary infections are likely present by the time the first case is identified. Quarantine of close contacts, defined by extended household membership, can reduce peak infection prevalence from 60 to 70% to around 10%, but subsequent waves may occur when community mixing resumes. Exit testing significantly reduces ongoing transmission. Concurrent lockdown of non-quarantined households for 14 days is highly effective for epidemic control and reduces overall testing requirements; peak prevalence of the initial outbreak can be constrained to less than 5%, and the final community attack rate to less than 10% in modelled scenarios. Lockdown also mitigates the effect of a delay in the initial response. Compliance with lockdown must be at least 80-90%, however, or epidemic control will be lost. CONCLUSIONS: A SARS-CoV-2 outbreak will spread rapidly in remote communities. Prompt case detection with quarantining of extended-household contacts and a 14 day lockdown for all other residents, combined with exit testing for all, is the most effective strategy for rapid containment. Compliance is crucial, underscoring the need for community supported, culturally sensitive responses.

Factors Associated With Early Resumption of Condomless Anal Sex Among Men Who Have Sex With Men After Rectal Chlamydia Treatment.

BACKGROUND: The resumption of sexual activity shortly after commencing treatment for sexually transmitted infections (STIs) is poorly described despite contributing to onward transmission. With azithromycin remaining an option for rectal Chlamydia trachomatis, resuming sex too early after treatment may contribute to antimicrobial resistance because of exposure of newly acquired STIs to subinhibitory concentrations. METHODS: Clinical and sexual behavioral data were collected from men participating in a trial assessing treatment efficacy for rectal chlamydia. Data were collected at recruitment and weekly for 3 weeks after commencing treatment. Outcome measures were resumption of any sexual activity or condomless receptive anal sex within 1, 2, or 3 weeks after commencing treatment. Generalized linear regression was used to calculate adjusted risk ratios (aRR) to identify associated factors. RESULTS: Almost 1 in 10 men (9.5%; 95% confidence interval [CI], 7.2-12.1) resumed condomless receptive anal sex within 1 week of commencing treatment. This was associated with current preexposure prophylaxis use (aRR, 3.4; 95% CI, 2.5-4.8]) and having 9 or more sexual partners in the last 3 months (aRR, 3.2; 95% CI, 1.6-5.0). Most men (75.0%; 95% CI, 71.3-78.5) resumed any sexual activity within 3 weeks; this was associated with a greater number of sexual partners (4-8 partners; aRR, 1.2; 95% CI, 1.1-1.5; ≥9 partners; aRR, 1.5; 95% CI, 1.3-1.7). CONCLUSIONS: Resuming condomless receptive anal sex early after treatment may facilitate onward transmission and promote antimicrobial resistance for STIs. Although azithromycin remains a treatment option, this analysis highlights the need for new health promotion messages regarding early resumption of sex and continued surveillance for antimicrobial resistance.

Modelling the decline and future of hepatitis A transmission in Australia.

Hepatitis A incidence has declined in most countries through a combination of prevention measures, augmented through the use of a highly effective vaccine. In Australia, the proportion of the population susceptible to hepatitis A infection has declined over time due to high rates of opportunistic vaccination as well as the sustained inflow of seropositive immigrants from high-endemicity countries. These factors have contributed to a rapid decline in incidence. An age-structured hepatitis A transmission model incorporating demographic changes was fitted to seroprevalence and disease notification data and used to project incidence trends and transmission potential for hepatitis A in the general population. Robustness of findings was assessed through worst-case scenarios regarding vaccine uptake, migration and the duration of immunity. The decline in age-specific seroprevalence until the introduction of hepatitis A vaccine in 1994 was well explained through a declining basic reproduction number (R0 ) that remained >1. Accounting for existing immunity, we estimated that the effective reproduction number (Reff ) <1 in the general population of Australia since the early 1990s, declining more rapidly after the introduction of the hepatitis A vaccine. Future projections under a variety of scenarios support Reff remaining <1 with continued low incidence in the general population. In conclusion, our results suggest that sustained endemic transmission in the general Australian population is no longer possible although risks of sporadic outbreaks remain. This suggests potential for local elimination of hepatitis A infection in Australia, provided that elimination criteria can be defined and satisfied in risk groups. The methodology used here to investigate elimination potential can easily be replicated in settings such as in the USA where sequential seroprevalence studies are supported by routine notification data.

Impact of replacing cytology with human papillomavirus testing for cervical cancer screening on the prevalence of Trichomonas vaginalis: a modelling study.

OBJECTIVES: Trichomonas vaginalis (TV) is the most common curable STI worldwide and is associated with increased risk of HIV acquisition and serious reproductive morbidities. The prevalence of TV infection is very low in Australian cities, and this is thought to be at least partly due to incidental detection and treatment of TV in women participating in the cervical cytology screening programme. In 2017, the national cervical screening programme will transition to a new model based on testing for high-risk (HR) human papillomavirus (HPV), with a reduced frequency and commencement at an older age. We model the potential impact of this transition on TV prevalence in Australia. METHODS: A mathematical model was developed to describe the transmission of TV in the general population and used to evaluate scenarios that capture the switch from cytology-based screening to HR HPV testing. Under these scenarios, individuals with asymptomatic TV who test negative for HR HPV will remain undiagnosed and untreated. We estimate the change in TV prevalence expected to occur due to the switch from cytology to HR HPV testing and changes to the frequency and age at commencement of screening. RESULTS: Our results suggest that with the transition to HR HPV testing, TV prevalence may increase from the current ~0.4% to 2.8% within 20 years if TV testing coverage is not increased and HR HPV prevalence does not decline further. If HR HPV prevalence continues to decline at its current rate with ongoing vaccination, TV prevalence is predicted to increase to 3.0% within this time frame. CONCLUSIONS: Our modelling suggests that in a setting like Australia, where TV can be detected incidentally through cytology-based cervical screening, a transition to HPV testing is likely to result in increasing TV prevalence over time unless additional measures are implemented to increase TV testing and treatment.

Molecular test for chlamydia and gonorrhoea used at point of care in remote primary healthcare settings: a diagnostic test evaluation.

OBJECTIVES: A new molecular test for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) (GeneXpert CT/NG) has been demonstrated to be as accurate as conventional nucleic acid amplification tests (NAAT), but performance has not been evaluated in routine primary care, performed at the point of care by clinicians. We aimed to examine its diagnostic performance when used by clinicians in remote community health services in Australia with high prevalences of CT and NG infection. The trial was registered with the Australian and New Zealand Clinical Trials Registry (#12613000808741) METHODS: At 12 health services, training was provided to 99 clinicians in the use of the GeneXpert CT/NG assay who tested specimens from all patients undergoing STI screening. Specimens were also sent in parallel for conventional laboratory-based NAATs and the concordance of results was evaluated. RESULTS: Clinicians conducted 2486 tests: CT concordance was 99.4% (95% CI 99.1 to 99.7) with a positive concordance of 98.6% (95% CI 95.9 to 99.7) and negative concordance of 99.5% (95% CI 99.1 to 99.8); NG concordance was 99.9% (95% CI 99.7 to 100.0) with a positive concordance of 100.0% (95% CI 97.5 to 100.0) and negative concordance of 99.9% (95% CI 99.7 to 100.0). CONCLUSIONS: In this first study reporting routine point-of-care use of GeneXpert CT/NG by primary care clinicians, we found excellent concordance with conventional NAATs. The use of the GeneXpert CT/NG at the point of care could potentially transform management and control of these infections in many endemic settings, including low/middle-income countries.

Molecular Antimicrobial Resistance Surveillance for Neisseria gonorrhoeae, Northern Territory, Australia.

Neisseria gonorrhoeae antimicrobial resistance (AMR) is a globally recognized health threat; new strategies are needed to enhance AMR surveillance. The Northern Territory of Australia is unique in that 2 different first-line therapies, based primarily on geographic location, are used for gonorrhea treatment. We tested 1,629 N. gonorrhoeae nucleic acid amplification test-positive clinical samples, collected from regions where ceftriaxone plus azithromycin or amoxicillin plus azithromycin are recommended first-line treatments, by using 8 N. gonorrhoeae AMR PCR assays. We compared results with those from routine culture-based surveillance data. PCR data confirmed an absence of ceftriaxone resistance and a low level of azithromycin resistance (0.2%), and that penicillin resistance was <5% in amoxicillin plus azithromycin regions. Rates of ciprofloxacin resistance and penicillinase-producing N. gonorrhoeae were lower when molecular methods were used. Molecular methods to detect N. gonorrhoeae AMR can increase the evidence base for treatment guidelines, particularly in settings where culture-based surveillance is limited.

Changes in the rates of Neisseria gonorrhoeae antimicrobial resistance are primarily driven by dynamic fluctuations in common gonococcal genotypes.

Objectives: To examine how gonococcal genotypes and associated changes over time influence rates of Neisseria gonorrhoeae antimicrobial resistance. Methods: All available N. gonorrhoeae isolates collected in New South Wales, Australia in the first half of both 2012 and 2014 were genotyped using the Agena MassARRAY iPLEX platform. Genotypic data were compared with phenotypic antimicrobial resistance profiles over time. We focused on penicillin and ciprofloxacin as significant increases in resistance to both antibiotics were observed over this time period. Results: Genotyping data were obtained for 760 and 782 isolates in 2012 and 2014, respectively. A total of 162 distinct genotypes were identified in the study, including 36 (22.2%) genotypes present in both years ( persisting genotypes), 54 (33.3%) observed in 2012 only and 72 (44.4%) observed in 2014 only (s ingle-year genotypes). Overall, persisting genotypes comprised 15 of the 20 most common genotypes, 8 of which showed a significant change in proportion from 2012 to 2014. Persisting genotypes also comprised the majority (>70%) of ciprofloxacin- and penicillin-resistant isolates in both years. Significant fluctuations in the most common persisting genotypes accounted for the majority of observed increases in both ciprofloxacin and penicillin resistance. Single-year genotypes contributed to ∼20% of ciprofloxacin and penicillin resistance in each year. Conclusions: The results show that the gonococcal genotypes persisting in the study population fluctuated significantly within a 3 year period, with numerous other genotypes appearing or disappearing. It is the net effect of these changes that determines N. gonorrhoeae antimicrobial resistance levels within the population.

Identifying factors that lead to the persistence of imported gonorrhoeae strains: a modelling study.

OBJECTIVE: The importation of Neisseria gonorrhoeae (NG) strains from overseas is believed to be the main source of antimicrobial resistance in Australia. With recent sporadic cases of ceftriaxone-resistant gonorrhoea reported in Australia and elsewhere, we sought to model the potential for imported NG strains to persist in the men who have sex with men (MSM) population in Australia. METHODS: We developed an individual-based model to simulate the transmission of NG in a population of urban MSM, and used this model to investigate factors contributing to the probability that an imported NG strain will persist. RESULTS: The probability of the imported NG strain persisting as the result of a single importation event is less than 1%, but the probability increases to 1% if the imported NG strain is resistant to treatment, and further increases to 3.1% if the imported NG strain can also form mixed infections with the local NG strain. The probability of the imported NG strain persisting increases to 4.4% if there are at least three importation events per month within a 1-year period. CONCLUSION: The imported NG strain is unlikely to persist as a result of a single importation event. However, the probability of persistence increases if the imported NG strain is resistant to treatment, can form mixed infections with the local NG strain or there are frequent importation events. Identification of the factors that determine the likelihood of persistence of an imported NG strain could contribute to our capacity to respond appropriately and in a timely fashion.

Neisseria gonorrhoeae Transmission Among Men Who Have Sex With Men: An Anatomical Site-Specific Mathematical Model Evaluating the Potential Preventive Impact of Mouthwash.

BACKGROUND: Gonorrhoea notifications are rapidly rising in men who have sex with men (MSM). We developed a model to assess mouthwash as a novel intervention for gonorrhoea control. METHODS: We developed a model of Neisseria gonorrhoeae (NG) transmission to explain anatomic site-specific prevalence of gonorrhoea among MSM. The model was calibrated to available epidemiological and behavioral data. We estimated the contribution of various sexual acts to gonorrhoea incidence and evaluate the potential impacts of screening scale-up and utilization of mouthwash on the gonorrhoea epidemic. RESULTS: We calibrated the model to prevalence of oropharyngeal, anal, and urethral gonorrhoea of 8.6% (7.7-9.5%), 8.3% (7.4-9.1%), and 0.20% (0.04-0.35%), respectively, among MSM. Oropharynx to oropharynx transmission through kissing is estimated to account for nearly three quarters of all incident cases (71.6% [64.4-80.5%]) of gonorrhoea in MSM. Substantially increasing annual oropharynx screening for gonorrhoea from the current 40% to 100% may only halve the prevalence of gonorrhoea in MSM. In contrast, the use of mouthwash with moderate efficacy (additional 1% clearance per daily use) would further reduce the corresponding prevalence rates to 3.1% (2.2-4.4%), 3.8% (2.3-4.9%), and 0.10% (0.06-0.11%), and a high-efficacy mouthwash (additional 1.5% clearance per daily use) may further halve the gonorrhoea prevalence. Without oropharynx to oropharynx transmission, we could not replicate current prevalence data. CONCLUSIONS: Despite a dearth of empirical data, our model suggests that kissing could potentially play an important role in NG transmission among MSM. Control through sexually transmitted infection screening alone is unlikely to have a substantial impact on the gonorrhoea epidemic in MSM.

Treatment efficacy of azithromycin 1 g single dose versus doxycycline 100 mg twice daily for 7 days for the treatment of rectal chlamydia among men who have sex with men - a double-blind randomised controlled trial protocol.

BACKGROUND: Rectal infection with Chlamydia trachomatis is one of the most common bacterial sexually transmissible infections among men who have sex with men (MSM) with diagnosis rates continuing to rise. Current treatment guidelines recommend either azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days. However, there are increasing concerns about treatment failure with azithromycin. We are conducting the first randomised controlled trial (RCT) to compare treatment efficacy of azithromycin versus doxycycline for the treatment of rectal chlamydia in MSM. METHODS/DESIGN: The Rectal Treatment Study will recruit 700 MSM attending Australian sexual health clinics for the treatment of rectal chlamydia. Participants will be asked to provide rectal swabs and will be randomised to either azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days. Participants will be asked to complete questionnaires about adverse drug reactions, sexual behaviour and drug adherence via short message service and online survey. The primary outcome is the treatment efficacy as determined by a negative chlamydia nucleic acid amplification test at 4 weeks post treatment. Secondary outcomes will utilise whole genome sequencing and mRNA assay to differentiate between treatment failure, reinfection or false positive results. DISCUSSION: Rectal chlamydia is an increasing public health concern as use of pre-exposure prophylaxis against HIV becomes commonplace. Optimal, evidence-based treatment is critical to halting ongoing transmission. This study will provide the first RCT evidence comparing azithromycin and doxycycline for the treatment of rectal chlamydia. The results of this trial will establish which treatment is more efficacious and inform international management guidelines. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614001125617.

Human papillomavirus vaccination and genital warts in young Indigenous Australians: national sentinel surveillance data.

OBJECTIVES: To examine the impact of the national human papillomavirus (HPV) vaccination program (available to girls and women [12-26 years] since 2007 and to boys [12-15 years] since 2013) on the number of diagnoses of genital warts in Australian Aboriginal and Torres Strait Islander (Indigenous) people. DESIGN, SETTING, PARTICIPANTS: Analysis of routinely collected data from patients attending 39 sexual health clinics (SHCs) in the Genital Warts Surveillance Network for the first time.Major outcome: The average annual proportion of Indigenous and non-Indigenous SHC patients diagnosed with genital warts during the pre-vaccination (2004-2007) and vaccination periods (2008-2014), stratified by age group and sex. RESULTS: 7.3% of the 215 599 Australian-born patients with known Indigenous status and seen for the first time at participating SHCs during 2004-2014 were Indigenous Australians. The average proportion of female Indigenous patients diagnosed with warts was lower during the vaccination period than during the pre-vaccination period (in those under 21, summary rate ratio [SRR], 0.12; 95% CI, 0.07-0.21; P < 0.001); in 21-30-year olds: SRR, 0.41; 95% CI, 0.27-0.61; P < 0.001); there was no significant difference for women over 30 (SRR, 0.84; 95% CI, 0.51-1.36; P = 0.47). The proportion of male Indigenous heterosexual SHC patients under 21 diagnosed with warts was also lower during the vaccination period (SRR, 0.25; 95% CI, 0.12-0.49; P < 0.001), with no significant changes among older Indigenous men over 30. CONCLUSIONS: There were marked declines in the proportions of diagnoses of genital warts in young Indigenous women and men attending SHCs after the introduction of the HPV vaccination program. If high levels of HPV vaccine coverage are sustained, HPV-related cancer rates should also decline.

The Molecular Epidemiology and Antimicrobial Resistance of Neisseria gonorrhoeae in Australia: A Nationwide Cross-Sectional Study, 2012.

BACKGROUND: Antimicrobial resistance (AMR) by Neisseria gonorrhoeae is considered a serious global threat. METHODS: In this nationwide study, we used MassARRAY iPLEX genotyping technology to examine the epidemiology of N. gonorrhoeae and associated AMR in the Australian population. All available N. gonorrhoeae isolates (n = 2452) received from Australian reference laboratories from January to June 2012 were included in the study. Genotypic data were combined with phenotypic AMR information to define strain types. RESULTS: A total of 270 distinct strain types were observed. The 40 most common strain types accounted for over 80% of isolates, and the 10 most common strain types accounted for almost half of all isolates. The high male to female ratios (>94% male) suggested that at least 22 of the top 40 strain types were primarily circulating within networks of men who have sex with men (MSM). Particular strain types were also concentrated among females: two strain types accounted for 37.5% of all isolates from females. Isolates harbouring the mosaic penicillin binding protein 2 (PBP2)-considered a key mechanism for cephalosporin resistance-comprised 8.9% of all N. gonorrhoeae isolates and were primarily observed in males (95%). CONCLUSIONS: This large scale epidemiological investigation demonstrated that N. gonorrhoeae infections are dominated by relatively few strain types. The commonest strain types were concentrated in MSM in urban areas and Indigenous heterosexuals in remote areas, and we were able to confirm a resurgent epidemic in heterosexual networks in urban areas. The prevalence of mosaic PBP2 harboring N. gonorrhoeae strains highlight the ability for new N. gonorrhoeae strains to spread and become established across populations.

A real-time PCR assay for direct characterization of the Neisseria gonorrhoeae GyrA 91 locus associated with ciprofloxacin susceptibility.

OBJECTIVES: The objective of this study was to develop a real-time PCR method for specific detection of the gonococcal GyrA amino acid 91 locus directly in clinical samples so as to predict Neisseria gonorrhoeae ciprofloxacin susceptibility. METHODS: The real-time PCR assay, GyrA91-PCR, was designed using two probes, one for detection of the WT S91 sequence and the other for detection of the S91F alteration. The performance of the assay was initially assessed using characterized N. gonorrhoeae isolates (n = 70), a panel of commensal Neisseria and Moraxella species (n = 55 isolates) and clinical samples providing negative results by a commercial N. gonorrhoeae nucleic acid amplification test (NAAT) method (n = 171). The GyrA91-PCR was then applied directly to N. gonorrhoeae NAAT-positive clinical samples (n = 210) from the year 2014 for which corresponding N. gonorrhoeae isolates with susceptibility results were also available. RESULTS: The GyrA91-PCR accurately characterized the GyrA 91 locus of all 70 N. gonorrhoeae isolates (sensitivity = 100%, 95% CI = 94.9%-100%), whereas all non-gonococcal isolates and N. gonorrhoeae NAAT-negative clinical samples gave negative results by the GyrA91-PCR (specificity = 100%, 95% CI = 98.4%-100%). When applied to the 210 N. gonorrhoeae NAAT-positive clinical samples, the GyrA91-PCR successfully characterized 195 samples (92.9%, 95% CI = 88.5%-95.9%). When compared with the corresponding bacterial culture results, positivity by the GyrA91-PCR WT probe correctly predicted N. gonorrhoeae susceptibility to ciprofloxacin in 161 of 162 (99.4%, 95% CI = 96.6%-99.9%) samples. CONCLUSIONS: The use of a PCR assay for detection of mutation in gyrA applied directly to clinical samples can predict ciprofloxacin susceptibility in N. gonorrhoeae.

Real-time PCR detection of Neisseria gonorrhoeae susceptibility to penicillin.

OBJECTIVES: The objective of this study was to develop a real-time PCR assay targeting the gonococcal porB gene (PorB-PCR) for predicting susceptibility of Neisseria gonorrhoeae to penicillin. This complements a previously described PCR assay for detecting penicillinase-producing N. gonorrhoeae (PPNG) developed by our laboratory (PPNG-PCR). METHODS: The PorB-PCR assay was designed using six probes to characterize various combinations of amino acids at positions 101 and 102 of the PorB1b class protein, including the WT G101/A102 and mutant G101K/A102D, G101K/A102N and G101K/A102G sequences, as well as the PorB1a sequence. The ability of these sequences to predict penicillin susceptibility was initially assessed using 2307 N. gonorrhoeae isolates from throughout Australia for which phenotypic susceptibility data were available. The assay was then applied to N. gonorrhoeae-positive clinical specimens (n = 70). Specificity was assessed by testing commensal Neisseria strains (n = 75) and N. gonorrhoeae-negative clinical specimens (n = 171). RESULTS: Testing of the 2307 N. gonorrhoeae isolates using PorB-PCR to detect G101/A102 and PorB1a sequences identified a total of 78.4% (61.2% and 17.2%, respectively) of penicillin-susceptible isolates with specificities of 97.4% and 99.3% and positive predictive values of 98.8% and 98.9%, where PPNG strains were simultaneously identified and excluded. Similar performance data were obtained when the PorB-PCR assay was applied to the N. gonorrhoeae-positive clinical specimens. No false-positive results were observed for the N. gonorrhoeae-negative samples and no cross-reactions were observed with the non-gonococcal species. CONCLUSIONS: When used in parallel with the previously described PPNG-PCR, the PorB-PCR approach has the potential to facilitate individualized treatment of gonorrhoea using penicillin.

Direct real-time PCR-based detection of Neisseria gonorrhoeae 23S rRNA mutations associated with azithromycin resistance.

OBJECTIVES: Surveillance for Neisseria gonorrhoeae azithromycin resistance is of growing importance given increasing use of ceftriaxone and azithromycin dual therapy for gonorrhoea treatment. In this study, we developed two real-time PCR methods for direct detection of two key N. gonorrhoeae 23S rRNA mutations associated with azithromycin resistance. METHODS: The real-time PCR assays, 2611-PCR and 2059-PCR, targeted the gonococcal 23S rRNA C2611T and A2059G mutations, respectively. A major design challenge was that gonococcal 23S rRNA sequences have high sequence homology with those of commensal Neisseria species. To limit the potential for cross-reaction, 'non-template' bases were utilized in primer sequences. The performance of the methods was initially assessed using a panel of gonococcal (n = 70) and non-gonococcal (n = 28) Neisseria species. Analytical specificity was further assessed by testing N. gonorrhoeae nucleic acid amplification test (NAAT)-negative clinical samples (n = 90), before being applied to N. gonorrhoeae NAAT-positive clinical samples (n = 306). RESULTS: Cross-reactions with commensal Neisseria strains remained evident for both assays; however, cycle threshold (Ct) values were significantly delayed, indicating reduced sensitivity for non-gonococcal species. For the N. gonorrhoeae NAAT-negative clinical samples, 7/21 pharyngeal samples provided evidence of cross-reaction (Ct values >40 cycles); however, the remaining urogenital and rectal swab samples were negative. In total, the gonococcal 2611 and 2059 23S rRNA nucleotides were both successfully characterized in 266/306 (87%) of the N. gonorrhoeae NAAT-positive clinical specimens. CONCLUSIONS: Real-time PCR detection of gonococcal 23S rRNA mutations directly from clinical samples is feasible and may enhance culture- and non-culture-based N. gonorrhoeae resistance surveillance.