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BackgroundIn Toronto, gonorrhea is the second most commonly reported sexually transmitted infection, after chlamydia. From 2000 to 2012, rates of gonorrhea in Toronto were stable, ranging from 56/100,000 to 72/100,000. However, rates started to rise in 2013. In 2018, rates increased by 37% from 2017, the largest observed annual increase since 2000, reaching a high of 158/100,000. This study aimed to describe gonorrhea trends in Toronto between 2012 and 2018.MethodsData for gonorrhea cases reported between 2012 and 2018 were extracted from the integrated Public Health Information System on January 29 2019. Analyses were conducted in SAS 9.4.ResultsIn 2018, 4,549 gonorrhea cases were reported in Toronto, 135% higher than 1,939 cases (71/100,000) reported in 2012. The increase was driven by a rise in reports among males, increasing by 192% while females increased by 24%; males comprised 81% of cases in 2018. Males most commonly reported engaging in sex with men (MSM), and the proportion with this risk factor increased from 55% in 2012 to 69% in 2018. Conversely, the proportion of males reporting sex with women declined from 25% in 2012 to 17% in 2018. Females in 2018 most commonly reported not using a condom (77%) in the last sexual encounter, slightly higher than 2012 (71%). In 2018, 38% of cases (44% of males, 9% of females) had rectum and/or pharyngeal gonorrhea, higher than 20% of cases in 2017.ConclusionThe rising rates in gonorrhea, particularly among MSM, may be due to changes in screening guidelines in 2013 that included extragenital screening of gonorrhea. In April 2018, both rectal and pharyngeal specimens were approved for Nucleic Acid Amplification Testing in Ontario, potentially playing a role in the additional increase in 2018. This study demonstrates that it is important that physicians continue to screen for extragenital gonorrhea among MSM.DisclosureNo significant relationships.

BackgroundThe emergence and spread of multidrug resistance to antibiotics used to treat gonorrhoea has resulted in a dramatic loss of effective regimens for the condition. Currently, the extended spectrum cephalosporin, ceftriaxone, is the only viable monotherapy option available, however, resistance to this last line treatment is now emerging globally. Herein, we assessed the in vitro activity of a novel small molecule antimicrobial with a new mechanism of action, SMT-571, against a large collection of N. gonorrhoeae clinical isolates and reference strains including numerous MDR and XDR gonococcal isolates.MethodsMICs (mg/L) of SMT-571 were determined by agar dilution according to current CLSI guidelines. The MICs of ceftriaxone, cefixime, azithromycin, ciprofloxacin, spectinomycin, tetracycline, and ampicillin were determined using the Etest method (AB bioMérieux, Marcy l’Etoile, France).ResultsSMT-571 showed potent in vitro activity against all the tested N. gonorrhoeae isolates (n=262) with MICs ranging from 0.064 to 0.125 mg/L, and the MIC50, MIC90 and modal MIC were all 0.125 mg/L. The compound was not influenced by pre-existing resistance mechanisms with no cross-resistance or correlation between the MICs of SMT-571 and comparator agents being observed.ConclusionThis study is the first broad evaluation of the in vitro activities of a new mechanism, novel small molecule antimicrobial for the treatment of gonorrhoea. SMT-571 demonstrated high in vitro activity against a large geographically, temporally and genetically diverse collection of clinical N. gonorrhoeae isolates and international reference strains, including various types of high-level resistant, MDR and XDR gonococcal isolates.DisclosureNo significant relationships.

IntroductionGentamicin is effective against N. gonorrhoeae in vitro and systematic reviews have reported cure rates of 62%–98% but the quality of studies was low and there are few data on pharyngeal or rectal infections. A recent large non comparative trial reported a cure rate of 100% when gentamicin was combined with 2g oral azithromycin, but a high incidence of gastrointestinal adverse effects limited tolerability and few extra-genital infections were included. The aim of this study was to evaluate the efficacy and safety of gentamicin versus ceftriaxone, each combined with 1g of azithromycin, for the treatment of gonorrhoea.MethodsA multi-centre, blinded, randomised controlled trial in participants with genital, pharyngeal or rectal gonorrhoea who received either gentamicin 240 mg or ceftriaxone 500 mg (each as a single intramuscular injection). The diagnosis of gonorrhoea was based on a positive nucleic acid amplification test (NAAT) or gram stained smear on microscopy. The primary endpoint was microbiological cure based on NAAT two weeks after treatment. The trial had 90% power to detect non-inferiority with a lower CI for an absolute risk difference of 5%. Data collection was completed in March 2017.Results720 patients from 14 sexual health clinics in England were randomised to receive ceftriaxone (n=362) or gentamicin (n=358). Baseline characteristics of the two groups were well balanced. 306 participants randomised to ceftriaxone (85%) and 292 randomised to gentamicin (82%) had primary outcome data available. 98% (299/306) and 91% (267/292) of participants randomised respectively had clearance of gonorrhoea at 2 weeks – adjusted risk difference −6.4% (95% CI −10.4%, −2.4%). Pre-specified sensitivity analyses supported this result. Clearance at the genital site was 98% and 94%, at pharynx 96% and 80% and at rectum 98% and 90%. The frequency of side effects was similar between treatment groups.ConclusionGentamicin is not non-inferior to ceftriaxone for the treatment of gonorrhoea.

IntroductionGonorrhoea 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. MethodsWe 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 behavioural data. We estimated the contribution of various sexual acts to gonorrhoea incidence and evaluate the potential impacts of screening scale-up and utilisation of mouthwash on the gonorrhoea epidemic. ResultsWe calibrated the model to prevalence of oropharyngeal, anal and urethral gonorrhoea of 8.6% (7.7%–9.5%), 8.3% (7.4%–10.4%) 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. ConclusionOur model suggests that kissing may play a key role in NG transmission among MSM. Focusing on STI screening alone is not sufficient to control the rising epidemic. Promotion of regular mouthwash may achieve near elimination of gonorrhoea in MSM.

New approaches are urgently required to address increasing rates of gonorrhoea and the emergence and global spread of antibiotic-resistant Neisseria gonorrhoeae. We used whole-genome sequencing to study transmission and track resistance in N gonorrhoeae isolates. We did whole-genome sequencing of isolates obtained from samples collected from patients attending sexual health services in Brighton, UK, between Jan 1, 2011, and March 9, 2015. We also included isolates from other UK locations, historical isolates from Brighton, and previous data from a US study. Samples from symptomatic patients and asymptomatic sexual health screening underwent nucleic acid amplification testing; positive samples and all samples from symptomatic patients were cultured for N gonorrhoeae, and resulting isolates were whole-genome sequenced. Cefixime susceptibility testing was done in selected isolates by agar incorporation, and we used sequence data to determine multi-antigen sequence types and penA genotypes. We derived a transmission nomogram to determine the plausibility of direct or indirect transmission between any two cases depending on the time between samples: estimated mutation rates, plus diversity noted within patients across anatomical sites and probable transmission pairs, were used to fit a coalescent model to determine the number of single nucleotide polymorphisms expected. 1407 (98%) of 1437 Brighton isolates between Jan 1, 2011, and March 9, 2015 were successfully sequenced. We identified 1061 infections from 907 patients. 281 (26%) of these infections were indistinguishable (ie, differed by zero single nucleotide polymorphisms) from one or more previous cases, and 786 (74%) had evidence of a sampled direct or indirect Brighton source. We observed multiple related samples across geographical locations. Of 1273 infections in Brighton (including historical data), 225 (18%) were linked to another case elsewhere in the UK, and 115 (9%) to a case in the USA. Four lineages initially identified in Brighton could be linked to 70 USA sequences, including 61 from a lineage carrying the mosaic penA XXXIV allele, which is associated with reduced cefixime susceptibility. We present a whole-genome-sequencing-based tool for genomic contact tracing of N gonorrhoeae and demonstrate local, national, and international transmission. Whole-genome sequencing can be applied across geographical boundaries to investigate gonorrhoea transmission and to track antimicrobial resistance. Oxford National Institute for Health Research Health Protection Research Unit and Biomedical Research Centre.

IntroductionThe incidence of Neisseria Gonorrhoeae (GC) and multi drug resistant variants are increasing. Culture can be performed by direct plating or via a transport media tube with subsequent automated rapid plating (e.g., ESwab™). Direct inoculation was the favoured mode of culture however in response to the COVID-19 pandemic there was a shift towards ESwab™, to reduce workload. This exploratory study compared both methods head-to-head.MethodThe study ran in a metropolitan clinic over 6 months. Patients with confirmed or suspected GC had cultures taken via direct inoculation and ESwabTM by the same clinician at the same time. A descriptive analysis was undertaken.Results• 67 anatomical sites were NAAT positive, from 50 patients.• Not all NAAT positive samples had both direct inoculation and ESwabTM collected unfortunately.• In direct comparison of both methods 6, out of a total of 24, positive Direct Inoculations had a negative corresponding ESwabTM.• 2, out of a total of 21, ESwabTM had a negative corresponding Direct Inoculation.• Table 1 shows the comparative sensitivity of Direct Inoculation & ESwabTMcompared to NAAT byanatomical sites.Abstract P139 Table 1Head-to-Head comparison by anatomical site Anatomical Site NAAT positive swabs Direct Inoculation Sensitivity compared to NAAT ESwabTM Sensitivity compared to NAAT Pharyngeal 32 30.7%(8/26) 18.52%(5/27) Rectal 18 50%(7/14) 53.33%(8/15) Urethral 7 85.71%(5/6) 85.71%(5/6) Vaginal 10 50%(4/8) 37.5%(3/8) Total from all sites 67 44.44%(24/54) 37.5%(21/56) DiscussionUnfortunately, recruitment was poor, largely due to the emergence of Monkeypox. Both methods had demonstrated low sensitivity but direct inoculation tended toward increased sensitvity. Unsurprisingly, urethral swabs produced higher sensitivity and pharyngeal lower sensitivity.While direct inoculation appears more sensitive this needs to be balanced against the ease of EswabsTM. Direct inoculation is more costly, requires more equipment and training and has the potential to grow Neisseria meningitidis with a theoretical risk to staff.

Declining antimicrobial susceptibility to current gonorrhoea antibiotic treatment and inadequate treatment options have raised the possibility of untreatable gonorrhoea. New prevention approaches, such as vaccination, are needed. Outer membrane vesicle meningococcal serogroup B vaccines might be protective against gonorrhoea. We evaluated the effectiveness of a serogroup B meningococcal outer membrane vesicle vaccine (MenB-4C) against gonorrhoea in individuals aged 16–23 years in two US cities. We identified laboratory-confirmed gonorrhoea and chlamydia infections among individuals aged 16–23 years from sexually transmitted infection surveillance records in New York City and Philadelphia from 2016 to 2018. We linked gonorrhoea and chlamydia case records to immunisation registry records to determine MenB-4C vaccination status at infection, defined as complete vaccination (two MenB-4C doses administered 30–180 days apart), partial vaccination (single MenB-4C vaccine dose), or no vaccination (serogroup B meningococcal vaccine naive). Using log-binomial regression with generalised estimating equations to account for correlations between multiple infections per patient, we calculated adjusted prevalence ratios (APR) and 95% CIs to determine if vaccination was protective against gonorrhoea. We used individual-level data for descriptive analyses and infection-level data for regression analyses. Between Jan 1, 2016, and Dec 31, 2018, we identified 167 706 infections (18 099 gonococcal infections, 124 876 chlamydial infections, and 24 731 gonococcal and chlamydial co-infections) among 109 737 individuals linked to the immunisation registries. 7692 individuals were vaccinated, of whom 4032 (52·4%) had received one dose, 3596 (46·7%) two doses, and 64 (<1·0%) at least three doses. Compared with no vaccination, complete vaccination series (APR 0·60, 95% CI 0·47–0·77; p<0·0001) and partial vaccination series (0·74, 0·63–0·88; p=0·0012) were protective against gonorrhoea. Complete MenB-4C vaccination series was 40% (95% CI 23–53) effective against gonorrhoea and partial MenB-4C vaccination series was 26% (12–37) effective. MenB-4C vaccination was associated with a reduced gonorrhoea prevalence. MenB-4C could offer cross-protection against Neisseria gonorrhoeae. Development of an effective gonococcal vaccine might be feasible with implications for gonorrhoea prevention and control. None.

ObjectivePrevious studies have quantified bacterial loads of Neisseria gonorrhoeae in the pharynx and rectum of men but not the urethra. We quantified the bacterial load of N. gonorrhoeae in men with symptomatic and asymptomatic urethral gonorrhoea infections.MethodsConsecutive men diagnosed with urethral gonorrhoea by Aptima Combo 2 testing of urine at the Melbourne Sexual Health Centre between March and July 2016 were eligible for the study: symptomatic men with purulent urethral discharge and asymptomatic men with no urethral symptoms. The gonococcal bacterial load in both groups was measured by urethral swab using a standardised collection method and real-time quantitative PCR targeting the opa gene.ResultsTwenty men were recruited into the study: 16 had purulent urethral discharge and 4 had asymptomatic urethral gonorrhoea. The median gonococcal bacterial load was significantly higher among symptomatic men (3.7×106 copies per swab, IQR 2.5×106–4.7×106) compared with asymptomatic men (2.0×105 copies per swab, IQR 2.7×104–4.5×105) (p=0.002).ConclusionsGonococcal loads in men with urethral discharge were higher than loads seen with asymptomatic urethral gonorrhoea and loads seen in asymptomatic pharyngeal and rectal gonorrhoea infections in previous studies.

BackgroundThree randomised controlled trials have either reported that mouthwash may increase the susceptibility of the oropharynx to Neisseria gonorrhoeae or potentially decrease its transmissibility. We modelled these potential impacts on gonorrhoea incidence.MethodsWe calibrated a susceptible-infected-susceptible compartmental model to examine the effectiveness of antibacterial mouthwash on the transmission of Neisseria gonorrhoeae in men who have sex with men (MSM). Four scenarios include: (1) mouthwash had no effect; (2) mouthwash increased the susceptibility of the oropharynx to Neisseria gonorrhoeae; (3) mouthwash reduced the transmissibility of Neisseria gonorrhoeae from the oropharynx; (4) we combined the effect of mouthwash from scenarios 2 and 3.ResultsUnder scenario 1, the overall incidence of gonorrhoea was 44 (95% CI: 37–50)/100 person-years (PY). Site-specific incidence/100 PY at the oropharynx, anorectum and urethra were 26 (22–31), 9 (8–11) and 8 (5–12). Under scenario 2, with between 20–80% mouthwash coverage in the MSM population, the incidence increased at all three anatomical sites by between 7.4% (5.9–60.8%) and 136.6% (108.1–177.5%). Under scenario 3, with the same coverage, the incidence decreased at all anatomical sites by between 11.6% (10.2–13.5%) and 99.8% (99.2–100%). Under scenario 4, changes in the incidence depended on the efficacy of mouthwash on the transmissibility and susceptibility with both leading to large increases of nearly 130% or large declines of almost 100%.ConclusionsThe effect of mouthwash on gonorrhoea incidence is largely predictable depending on whether it increases the susceptibility to or reduces the transmissibility of Neisseria gonorrhoeae, highlighting an urgent need for further empirical investigation.

BackgroundNeisseria gonorrhoeae can be cultured from saliva in men with pharyngeal gonorrhoea and could theoretically be transmitted from the pharynx to the urethra when saliva is used as a lubricant for masturbation. To explore this issue, we developed mathematical models for the transmission of Neisseria gonorrhoeae at each of oropharynx, urethra and anorectum among men who have sex with men (MSM).MethodsModel 1 included transmission routes (oral sex, anal sex, rimming, kissing, and three sequential sex practices) we have previously validated. In Model 2, we added masturbation to model 1. In Model 3, we included masturbation but excluded the three sequential sex practices. We calibrated our data to six international studies. We evaluated the model performance using the Root Mean Squared Error (RMSE) and Cohen’s d statistic.ResultsModel 2 has significantly higher RMSE than model 1 (p-value <0.01 in five datasets, and p=0.47 in one dataset), but only p-values from two datasets revealed a substantially large effect (Cohen’s d > 0.8) compared with Model 1. This suggests performance of Model 1 and Model 2 are similar. In contrast, Model 3 has significantly higher RMSE than both Model 1 and Model 2 (p-value <0.01 for all six datasets), and p-value revealed a large effect (Cohen’s d > 0.8 for all six datasets) compared with the two models. This suggests performance of Model 3 is significantly worse than Model 1 and Model 2.ConclusionOur findings indicate that masturbation plays a moderate role in the transmission of Neisseria gonorrhoeae. Our model also suggests that sequential sexual practices may be more important than masturbation for explaining the site-specific prevalence in men with multi-site infection. Our model predicted that about 1 in 4 cases of urethral gonorrhoea might arise from masturbation if it transmits gonorrhoea.