Comprehensive observational study evaluating the enduring effectiveness of 4CMenB, the meningococcal B vaccine against gonococcal infections in the Northern Territory and South Australia, Australia: study protocol.

INTRODUCTION: The effectiveness of antibiotics for treating gonococcal infections is compromised due to escalating antibiotic resistance; and the development of an effective gonococcal vaccine has been challenging. Emerging evidence suggests that the licensed meningococcal B (MenB) vaccine, 4CMenB is effective against gonococcal infections due to cross-reacting antibodies and 95% genetic homology between the two bacteria, Neisseria meningitidis and Neisseria gonorrhoeae, that cause the diseases. This project aims to undertake epidemiological and genomic surveillance to evaluate the long-term protection of the 4CMenB vaccine against gonococcal infections in the Northern Territory (NT) and South Australia (SA), and to determine the potential benefit of a booster vaccine doses to provide longer-term protection against gonococcal infections. METHODS AND ANALYSES: This observational study will provide long-term evaluation results of the effectiveness of the 4CMenB vaccine against gonococcal infections at 4-7 years post 4CMenB programme implementation. Routine notifiable disease notifications will be the basis for assessing the impact of the vaccine on gonococcal infections. Pathology laboratories will provide data on the number and percentage of N. gonorrhoeae positive tests relative to all tests administered and will coordinate molecular sequencing for isolates. Genome sequencing results will be provided by SA Pathology and Territory Pathology/New South Wales Health Pathology, and linked with notification data by SA Health and NT Health. There are limitations in observational studies including the potential for confounding. Confounders will be analysed separately for each outcome/comparison. ETHICS AND DISSEMINATION: The protocol and all study documents have been reviewed and approved by the SA Department for Health and Well-being Human Research Ethics Committee (HREC/2022/HRE00308), and the evaluation will commence in the NT on receipt of approval from the NT Health and Menzies School of Health Research Human Research Ethics Committee. Results will be published in peer-reviewed journals and presented at scientific meetings and public forums.

Multicentre double-blind randomised placebo-controlled trial evaluating the efficacy of the meningococcal B vaccine, 4CMenB (Bexsero), against Neisseria gonorrhoeae infection in men who have sex with men: the GoGoVax study protocol.

INTRODUCTION: Gonorrhoea, the sexually transmissible infection caused by Neisseria gonorrhoeae, has a substantial impact on sexual and reproductive health globally with an estimated 82 million new infections each year worldwide. N. gonorrhoeae antimicrobial resistance continues to escalate, and disease control is largely reliant on effective therapy as there is no proven effective gonococcal vaccine available. However, there is increasing evidence from observational cohort studies that the serogroup B meningococcal vaccine four-component meningitis B vaccine (4CMenB) (Bexsero), licensed to prevent invasive disease caused by Neisseria meningitidis, may provide cross-protection against the closely related bacterium N. gonorrhoeae. This study will evaluate the efficacy of 4CMenB against N. gonorrhoeae infection in men (cis and trans), transwomen and non-binary people who have sex with men (hereafter referred to as GBM+). METHODS AND ANALYSIS: This is a double-blind, randomised placebo-controlled trial in GBM+, either HIV-negative on pre-exposure prophylaxis against HIV or living with HIV (CD4 count >350 cells/mm3), who have had a diagnosis of gonorrhoea or infectious syphilis in the last 18 months (a key characteristic associated with a high risk of N. gonorrhoeae infection). Participants are randomised 1:1 to receive two doses of 4CMenB or placebo 3 months apart. Participants have 3-monthly visits over 24 months, which include testing for N. gonorrhoeae and other sexually transmissible infections, collection of demographics, sexual behaviour risks and antibiotic use, and collection of research samples for analysis of N. gonorrhoeae-specific systemic and mucosal immune responses. The primary outcome is the incidence of the first episode of N. gonorrhoeae infection, as determined by nucleic acid amplification tests, post month 4. Additional outcomes consider the incidence of symptomatic or asymptomatic N. gonorrhoeae infection at different anatomical sites (ie, urogenital, anorectum or oropharynx), incidence by N. gonorrhoeae genotype and antimicrobial resistance phenotype, and level and functional activity of N. gonorrhoeae-specific antibodies. ETHICS AND DISSEMINATION: Ethical approval was obtained from the St Vincent's Hospital Human Research Ethics Committee, St Vincent's Hospital Sydney, NSW, Australia (ref: 2020/ETH01084). Results will be disseminated in peer-reviewed journals and via presentation at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04415424.

Understanding dynamics and overlapping epidemiologies of HIV, HSV-2, chlamydia, gonorrhea, and syphilis in sexual networks of men who have sex with men.

Introduction: We aimed to investigate the overlapping epidemiologies of human immunodeficiency virus (HIV), herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhea, and syphilis in sexual networks of men who have sex with men (MSM), and to explore to what extent the epidemiology of one sexually transmitted infection (STI) relates to or differs from that of another STI. Methods: An individual-based Monte Carlo simulation model was employed to simulate the concurrent transmission of STIs within diverse sexual networks of MSM. The model simulated sexual partnering, birth, death, and STI transmission within each specific sexual network. The model parameters were chosen based on the current knowledge and understanding of the natural history, transmission, and epidemiology of each considered STI. Associations were measured using the Spearman's rank correlation coefficient (SRCC) and maximal information coefficient (MIC). Results: A total of 500 sexual networks were simulated by varying the mean and variance of the number of partners for both short-term and all partnerships, degree correlation, and clustering coefficient. HSV-2 had the highest current infection prevalence across the simulations, followed by HIV, chlamydia, syphilis, and gonorrhea. Threshold and saturation effects emerged in the relationship between STIs across the simulated networks, and all STIs demonstrated moderate to strong associations. The strongest current infection prevalence association was between HIV and gonorrhea, with an SRCC of 0.84 (95% CI: 0.80-0.87) and an MIC of 0.81 (95% CI: 0.74-0.88). The weakest association was between HSV-2 and syphilis, with an SRCC of 0.54 (95% CI: 0.48-0.59) and an MIC of 0.57 (95% CI, 0.49-0.65). Gonorrhea exhibited the strongest associations with the other STIs while syphilis had the weakest associations. Across the simulated networks, proportions of the population with zero, one, two, three, four, and five concurrent STI infections were 48.6, 37.7, 11.1, 2.4, 0.3, and < 0.1%, respectively. For lifetime exposure to these infections, these proportions were 13.6, 21.0, 22.9, 24.3, 13.4, and 4.8%, respectively. Conclusion: STI epidemiologies demonstrate substantial overlap and associations, alongside nuanced differences that shape a unique pattern for each STI. Gonorrhea exhibits an "intermediate STI epidemiology," reflected by the highest average correlation coefficient with other STIs.

Minimum inhibitory concentrations of Neisseria gonorrhoeae strains in clients of the Amsterdam sexual health clinic with a Dutch versus an international sexual network.

OBJECTIVES: International travel combined with sex may contribute to dissemination of antimicrobial-resistant (AMR) Neisseria gonorrhoeae (Ng). To assess the role of travel in Ng strain susceptibility, we compared minimum inhibitory concentrations (MICs) for five antibiotics (ie, azithromycin, ceftriaxone, cefotaxime, cefixime and ciprofloxacin) in strains from clients with an exclusively Dutch sexual network and clients with an additional international sexual network. METHODS: From 2013 to 2019, we recorded recent residence of sexual partners of clients (and of their partners) with Ng at the Center for Sexual Health of Amsterdam. We categorised clients as having: (1) exclusively sexual partners residing in the Netherlands ('Dutch only') or (2) at least one partner residing outside the Netherlands. We categorised the country of residence of sexual partners by World Bank/EuroVoc regions. We analysed the difference of log-transformed MIC of Ng strains between categories using linear or hurdle regression for each antibiotic. RESULTS: We included 3367 gay and bisexual men who had sex with men (GBMSM), 516 women and 525 men who exclusively had sex with women (MSW) with Ng. Compared with GBMSM with a 'Dutch only' network, GBMSM with: (1) a Western European network had higher MICs for ceftriaxone (ß=0.19, 95% CI=0.08 to 0.29), cefotaxime (ß=0.19, 95% CI=0.08 to 0.31) and cefixime (ß=0.06, 95% CI=0.001 to 0.11); (2) a Southern European network had a higher MIC for cefixime (ß=0.10, 95% CI=0.02 to 0.17); and (3) a sub-Saharan African network had a lower MIC for ciprofloxacin (ß=-1.79, 95% CI=-2.84 to -0.74). In women and MSW, higher MICs were found for ceftriaxone in clients with a Latin American and Caribbean network (ß=0.26, 95% CI=0.02 to 0.51). CONCLUSIONS: For three cephalosporin antibiotics, we found Ng strains with slightly higher MICs in clients with partner(s) from Europe or Latin America and the Caribbean. International travel might contribute to the spread of Ng with lower susceptibility. More understanding of the emergence of AMR Ng is needed.

Estimates of the incidence, prevalence, and factors associated with common sexually transmitted infections among Lebanese women.

BACKGROUND: We analyzed the prevalence of active infection with common curable sexually transmitted infections (STIs) including N. gonorrhea, C. trachomatis, T. vaginalis, and T. pallidum, as well as active infection with HPV, herpes simplex virus types I (HSV-1) and II (HSV-2), M. hominis, M. genitalium, C. albicans, and Ureaplasma in 351 Lebanese women. METHODS: A cross-sectional study, involving 351 sexually active women, 40 years or younger, who were recruited from outpatient Obstetrics and Gynecology clinic attendees between September 2016 and November 2017. RESULTS: The prevalence of active infection was low at 0.3% for N. gonorrhea, 0.6% for HSV-2, 2.8% for C. trachomatis, and 2.9% for any curable STIs. Prevalence of active HPV infection was high assessed at 15.7% for high-risk and 12.2% for low-risk genotypes. Furthermore, the prevalence was 2.0% for M. genitalium, 6.8% for ureaplasma, 13.7% for Candida albicans, and 20.5% for M. hominis. No active infections with T. vaginalis, T. pallidum, or HSV-1 were observed. Significant age differences were noted in the prevalence of high-risk and low-risk HPV genotypes, but no such differences were noted in the prevalence of other infections. No appreciable variations were identified in the prevalence of key STIs based on smoking, marital status, or the number of sexual partners. CONCLUSIONS: The study documented active infection with substantial prevalence for multiple STIs among women attending outpatient gynecology and obstetrics clinics in Lebanon. These findings underscore the importance of strengthening STI surveillance, linkage to care, and prevention interventions in reducing STI incidence among women.

Management of acute sexual assault presenting to a large Australian sexual health clinic in 2012-2021: a retrospective clinical audit.

Background The incidence of sexual assault continues to rise in Australia. This study aimed to describe the nature of assault, HIV/STI positivity, and its management at a sexual health clinic. Methods We performed a chart review of 516 sexual assault cases presenting to Melbourne Sexual Health Centre between 2012 and 2021, collecting data on victim demographics, details of assault, HIV/STI testing and positivity, police involvement, and offer of counselling. Results We included 516 cases: 124 males (24.0%); 384 females (74.4%); and eight transgender (1.6%) victims. The proportion of assault cases presenting to Melbourne Sexual Health Centre increased from 0.1% (37/37,070) in 2012 to 0.2% (56/36,514) in 2021 (P trend =0.006). HIV post-exposure prophylaxis was prescribed for 64.5% (80/124) of males and 12.5% (48/384) of females. Among victims, 69.4% (358/516) were tested for HIV and no one tested positive, while 71.9% (371/516) were tested for syphilis, with 1.6% (6/371) positive. Gonorrhoea and chlamydia were tested at the oropharynx (44.8% [231/516] vs 28.7% [148/516]), genitals (83.7% [432/516] vs 92.4% [477/516]) and anorectum (35.3% [182/516] vs 35.3% [182/516]). Positivity for gonorrhoea and chlamydia were: 2.6% (6/231) vs 2.0% (3/148) at oropharynx, 1.4% (6/432) vs 2.9% (14/477) at genitals, and 5.5% (10/182) vs 7.1% (13/182) at anorectum. According to clinical records, 25.2% (130/516) of victims sought police involvement, and 71.7% (370/516) were offered counselling. Conclusions Sexual assault was an uncommon presentation at Melbourne Sexual Health Centre, with diverse circumstances surrounding assault; however, clinical documentation varied, indicating a need for a standard primary care protocol for clients presenting with acute sexual assault.

Screening for Chlamydia and Gonorrhea in Youth Correctional Facilities, Utah, USA.

We reviewed data obtained in October 2021-May 2023 from youth who reported a history of sexual activity upon admission to 1 of 12 juvenile justice facilities in Utah, USA, that offered screening for Chlamydia trachomatis and Neisseria gonorrhoeae. Urinalysis revealed C. trachomatis positivity of 10.77%, N. gonorrhoeae positivity of 1.08%, and coinfection C. trachomatis N. gonorrhoeae) of 0.90%. Prevalence of infection was similar for youths in rural and urban facilities. A total of 12.01% of those identifying as male and 14.01% of those identifying as female tested positive for C. trachomatis, N. gonorrhoeae, or coinfection. Of young adults who tested positive, 74.65% received their results while incarcerated, all of whom accepted treatment. Our research underscores the feasibility of providing prompt C. trachomatis/N. gonorrhoeae screening and treatment in juvenile correctional facilities. The pervasiveness of infection emphasizes the urgent need for early identification and treatment for C. trachomatis and N. gonorrhoeae in incarcerated youth nationwide.

Evaluation of a new CT/NG/TV/MG Real-Time PCR Kit (Vircell) versus the Allplex STI Essential Assay (Seegene) for the diagnosis of sexually transmitted infections.

Sexually transmitted infections (STI) are a public health problem. Real-time PCR assays are the most sensitive test for screening and diagnosis of these infections. The aim of this study was to evaluate a new CT/NG/TV/MG Real-Time PCR (RT-PCR) kit (Vircell) for the detection of Chamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Trichomonas vaginalis for the diagnosis of sexual transmitted infections using the Allplex STI Essential Assay (Seegene) as the reference's method. A total of 497 samples from different anatomical sites (endocervical, urethral, rectal, pharyngeal and urine) were analysed from October 2022 to February 2023. A total of 108 (21.73 %) and 106 (21.33 %) positive samples were found for any of the assays used. The most commonly detected pathogen was N. gonorrhoeae (52 samples; 10.46 %), and the least commonly detected was T. vaginalis (three samples; 0.60 %). The anatomical site with the highest prevalence of micro-organisms was a non-urogenital site, the pharynx (26 positive samples; 5.23 %). Using the Allplex STI Essential Assay (Seegene) as the reference method, the diagnosis performance showed that the average specificity of CT/NG/TV/MG RT-PCR Kit (Vircell) was 99.84 % and the sensitivity was 99.53 %. The overall concordance was k=0.98 (CI95 %; 0.96-1). In conclusion, the CT/NG/TV/MG RT-PCR Kit (Vircell) assay shows a good sensitivity and specificity and constitutes a promising and additional alternative to routine procedures for distinct types of clinical specimen in diagnosis STI.

Chlamydia trachomatis and Neisseria gonorrhoeae rectal infections: Interplay between rectal microbiome, HPV infection and Torquetenovirus.

Men having sex with men (MSM) represent a key population, in which sexually transmitted rectal infections (STIs) caused by Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and high-risk HPV (HR-HPV) are very common and linked to significant morbidity. Investigating the anorectal microbiome associated with rectal STIs holds potential for deeper insights into the pathogenesis of these infections and the development of innovative control strategies. In this study, we explored the interplay at the rectal site between C. trachomatis, N. gonorrhoeae, HR-HPV infection, and the anorectal microbiome in a cohort of 92 MSM (47 infected by CT and/or NG vs 45 controls). Moreover, we assessed the presence of Torquetenovirus (TTV), a non-pathogenic endogenous virus, considered as a possible predictor of immune system activation. We found a high prevalence of HR-HPV rectal infections (61%), especially in subjects with a concurrent CT/NG rectal infection (70.2%) and in people living with HIV (84%). In addition, we observed that TTV was more prevalent in subjects with CT/NG rectal infections than in non-infected ones (70.2% vs 46.7%, respectively). The anorectal microbiome of patients infected by CT and/or NG exhibited a reduction in Escherichia, while the presence of TTV was significantly associated with higher levels of Bacteroides. We observed a positive correlation of HR-HPV types with Escherichia and Corynebacterium, and a negative correlation with the Firmicutes phylum, and with Prevotella, Oscillospira, Sutterella. Our findings shed light on some of the dynamics occurring within the rectal environment involving chlamydial/gonococcal infections, HPV, TTV, and the anorectal microbiome. These data could open new perspectives for the control and prevention of STIs in MSM.

Australian Gonococcal Surveillance Programme, 1 January to 31 March 2023.

Abstract: The Australian National Neisseria Network (NNN) comprises reference laboratories in each state and territory that report data on antimicrobial susceptibility testing to an agreed group of antimicrobial agents for the Australian Gonococcal Surveillance Programme (AGSP). The AGSP data are presented quarterly in tabulated form, as well as in the AGSP annual report. This report presents national gonococcal antimicrobial resistance surveillance data from 1 January to 31 March 2023.

Australian Gonococcal Surveillance Programme, 1 April to 30 June 2023.

Abstract: The Australian National Neisseria Network (NNN) comprises reference laboratories in each state and territory that report data on antimicrobial susceptibility testing to an agreed group of antimicrobial agents for the Australian Gonococcal Surveillance Programme (AGSP). The AGSP data are presented quarterly in tabulated form, as well as in the AGSP annual report. This report presents national gonococcal antimicrobial resistance surveillance data from 1 April to 30 June 2023.

Australian Gonococcal Surveillance Programme, 1 July to 30 September 2023.

Abstract: The Australian National Neisseria Network (NNN) comprises reference laboratories in each state and territory that report data on antimicrobial susceptibility testing to an agreed group of antimicrobial agents for the Australian Gonococcal Surveillance Programme (AGSP). The AGSP data are presented quarterly in tabulated form, as well as in the AGSP annual report. This report presents national gonococcal antimicrobial resistance surveillance data from 1 July to 30 September 2023.

45 years of tetracycline post exposure prophylaxis for STIs and the risk of tetracycline resistance: a systematic review and meta-analysis.

There is considerable interest in the use of doxycycline post exposure prophylaxis (PEP) to reduce the incidence of bacterial sexually transmitted infections (STIs). An important concern is that this could select for tetracycline resistance in these STIs and other species. We searched PubMed and Google Scholar, (1948-2023) for randomized controlled trials comparing tetracycline PEP with non-tetracycline controls. The primary outcome was antimicrobial resistance (AMR) to tetracyclines in all bacterial species with available data. Our search yielded 140 studies, of which three met the inclusion criteria. Tetracycline PEP was associated with an increasedprevalence of tetracycline resistance in Neisseria gonorrhoeae, but this effect was not statistically significant (Pooled OR 2.3, 95% CI 0.9-3.4). PEP had a marked effect on the N. gonorrhoeae tetracycline MIC distribution in the one study where this was assessed. Prophylactic efficacy was 100% at low MICs and 0% at high MICs. In the one study where this was assessed, PEP resulted in a significant increase in tetracycline resistance in commensal Neisseria species compared to the control group (OR 2.9, 95% CI 1.5-5.5) but no significant effect on the prevalence of tetracycline resistance in Staphylococcus aureus. The available evidence suggests that PEP with tetracyclines could be associated with selecting tetracycline resistance in N. gonorrhoeae and commensal Neisseria species.

Antimicrobial-resistant Neisseria gonorrhoeae in Europe in 2020 compared with in 2013 and 2018: a retrospective genomic surveillance study.

BACKGROUND: Regular quality-assured whole-genome sequencing linked to antimicrobial resistance (AMR) and patient metadata is imperative to elucidate the shifting gonorrhoea epidemiology, both nationally and internationally. We aimed to examine the gonococcal population in the European Economic Area (EEA) in 2020, elucidate emerging and disappearing gonococcal lineages associated with AMR and patient metadata, compare with 2013 and 2018 whole-genome sequencing data, and explain changes in gonococcal AMR and gonorrhoea epidemiology. METHODS: In this retrospective genomic surveillance study, we analysed consecutive gonococcal isolates that were collected in EEA countries through the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) in 2020, and made comparisons with Euro-GASP data from 2013 and 2018. All isolates had linked AMR data (based on minimum inhibitory concentration determination) and patient metadata. We performed whole-genome sequencing and molecular typing and AMR determinants were derived from quality-checked whole-genome sequencing data. Links between genomic lineages, AMR, and patient metadata were examined. FINDINGS: 1932 gonococcal isolates collected in 2020 in 21 EEA countries were included. The majority (81·2%, 147 of 181 isolates) of azithromycin resistance (present in 9·4%, 181 of 1932) was explained by the continued expansion of the Neisseria gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) clonal complexes (CCs) 63, 168, and 213 (with mtrD/mtrR promoter mosaic 2) and the novel NG-STAR CC1031 (semi-mosaic mtrD variant 13), associated with men who have sex with men and anorectal or oropharyngeal infections. The declining cefixime resistance (0·5%, nine of 1932) and negligible ceftriaxone resistance (0·1%, one of 1932) was largely because of the progressive disappearance of NG-STAR CC90 (with mosaic penA allele), which was predominant in 2013. No known resistance determinants for novel antimicrobials (zoliflodacin, gepotidacin, and lefamulin) were found. INTERPRETATION: Azithromycin-resistant clones, mainly with mtrD mosaic or semi-mosaic variants, appear to be stabilising at a relatively high level in the EEA. This mostly low-level azithromycin resistance might threaten the recommended ceftriaxone-azithromycin therapy, but the negligible ceftriaxone resistance is encouraging. The decreased genomic population diversity and increased clonality could be explained in part by the COVID-19 pandemic resulting in lower importation of novel strains into Europe. FUNDING: European Centre for Disease Prevention and Control and Örebro University Hospital.

The impact of HIV preexposure prophylaxis on bacterial sexually transmitted infection occurrence in MSM: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of preexposure prophylaxis (PrEP) initiation on bacterial sexually transmitted infection (STI) occurrence (overall; chlamydia; gonorrhea; syphilis), in MSM. DESIGN: Systematic review and meta-analysis. METHODS: Systematic searches were performed in PubMed, Embase, and Scopus without language restrictions until 1 February 2023. We sought studies reporting data for the estimation of incidence rate ratios (IRR), prevalence ratios or cumulative incidence ratios (the latter in equal time periods before and after PrEP initiation) regarding bacterial STI occurrence. Separate analyses were performed overall for any STI, syphilis, chlamydia and gonorrhea (overall; rectal; urethral; pharyngeal for the two latter conditions); ratios greater than unity denoted increase in STI occurrence after PrEP initiation. RESULTS: Twenty-three eligible studies with 11 776 participants (age range: 18-71 years) with a median follow-up of 12 months were included. Overall, PrEP initiation was associated with a significant increase in the occurrence of any STI (pooled effect size: 1.15, 95% confidence interval (CI): 1.04-1.26), any gonorrhea (pooled effect size: 1.17, 95% CI: 1.02-1.34), any chlamydia (pooled effect size: 1.31, 95% CI: 1.09-1.58) and rectal chlamydia (pooled effect size: 1.31, 95% CI: 1.05-1.64), whereas a borderline increase was found in urethral chlamydia (pooled effect size: 1.25, 95% CI: 0.99-1.60, P  = 0.064). Changes in pharyngeal chlamydia and site-specific gonorrhea occurrence did not reach statistical significance. Syphilis showed virtually no change after PrEP initiation (pooled effect size: 0.99, 95% CI: 0.72-1.37). CONCLUSION: These results highlight the need for more comprehensive, accessible STI testing to tackle bacterial STI infections in PrEP users.

Antibiotic overuse, poor antimicrobial stewardship, and low specificity of syndromic case management in a cross section of men with urethral discharge syndrome in Kampala, Uganda.

OBJECTIVE: High prevalence of sexually transmitted infections (STIs) combined with poor antimicrobial stewardship are drivers of STI antimicrobial resistance (AMR) especially in resource-limited settings where syndromic case management (SCM) is the norm. We characterized patterns of antibiotic use prior to clinic attendance and study enrollment in Ugandan men with urethral discharge syndrome (UDS), evaluated in-clinic prescribing, and the performance characteristics of SCM. METHODS: Participants were recruited from government clinics participating in an existing gonococcal surveillance program in Kampala, Uganda. Questionnaires including antimicrobial use prior to attendance, prior episodes of UDS, penile swabs, and blood samples were collected. Bivariable and multivariable logistic regression models were used to estimate odds ratios (OR) for preselected factors likely to be associated with antibiotic use. In-clinic antibiotic treatment data were extracted from clinical notes, and the performance of SCM against laboratory-based STI diagnoses was evaluated. FINDINGS: Between October 2019 and November 2020, 100(40%) of 250 men with UDS reported taking antibiotics in the 14days prior to attending the clinic. Of these 210(84%) had at least one curable STI and 20% had a reactive point-of-care HIV test. Multivariable analysis demonstrated significant associations between recent antimicrobial use and duration of UDS symptoms <6 days (OR 2.98(95%CI 1.07,8.36), p = 0.038), and sex with women only (OR 0.08(95%CI 0.01,0.82),p = 0.038). The sensitivity of SCM ranged from 80.0% to 94.4%; specificity was low between 5.6% and 33.1%. The positive predictive value of SCM ranged from 2.4(95%CI 0.7,6.0) for trichomoniasis to 63.4(95%CI 56.5,69.9) for gonorrhea. CONCLUSION: Pre-enrollment antibiotic use was common in this population at high risk of STI and HIV. Combined with the poor specificity of SCM for male UDS, extensive antibiotic use is a likely driver of STI-AMR in Ugandan men. Interventions to improve antimicrobial stewardship and deliver affordable diagnostics to augment SCM and decrease overtreatment of STI syndromes are required.

Recent dynamics in Neisseria gonorrhoeae genomic epidemiology in Brazil: antimicrobial resistance and genomic lineages in 2017-20 compared to 2015-16.

OBJECTIVES: Regular quality-assured WGS with antimicrobial resistance (AMR) and epidemiological data of patients is imperative to elucidate the shifting gonorrhoea epidemiology, nationally and internationally. We describe the dynamics of the gonococcal population in 11 cities in Brazil between 2017 and 2020 and elucidate emerging and disappearing gonococcal lineages associated with AMR, compare to Brazilian WGS and AMR data from 2015 to 2016, and explain recent changes in gonococcal AMR and gonorrhoea epidemiology. METHODS: WGS was performed using Illumina NextSeq 550 and genomes of 623 gonococcal isolates were used for downstream analysis. Molecular typing and AMR determinants were obtained and links between genomic lineages and AMR (determined by agar dilution/Etest) examined. RESULTS: Azithromycin resistance (15.6%, 97/623) had substantially increased and was mainly explained by clonal expansions of strains with 23S rRNA C2611T (mostly NG-STAR CC124) and mtr mosaics (mostly NG-STAR CC63, MLST ST9363). Resistance to ceftriaxone and cefixime remained at the same levels as in 2015-16, i.e. at 0% and 0.2% (1/623), respectively. Regarding novel gonorrhoea treatments, no known zoliflodacin-resistance gyrB mutations or gepotidacin-resistance gyrA mutations were found. Genomic lineages and sublineages showed a phylogenomic shift from sublineage A5 to sublineages A1-A4, while isolates within lineage B remained diverse in Brazil. CONCLUSIONS: Azithromycin resistance, mainly caused by 23S rRNA C2611T and mtrD mosaics/semi-mosaics, had substantially increased in Brazil. This mostly low-level azithromycin resistance may threaten the recommended ceftriaxone-azithromycin therapy, but the lack of ceftriaxone resistance is encouraging. Enhanced gonococcal AMR surveillance, including WGS, is imperative in Brazil and other Latin American and Caribbean countries.

Antimicrobial resistance and heterogeneity of Neisseria gonorrhoeae isolated from patients attending sexually transmitted infection clinics in Lusaka, Zambia.

BACKGROUND: Antimicrobial resistance (AMR) of Neisseria gonorrhoeae is a threat to public health as strains have developed resistance to antimicrobials available for the treatment of gonorrhea. Whole genome sequencing (WGS) can detect and predict antimicrobial resistance to enhance the control and prevention of gonorrhea. Data on the molecular epidemiology of N. gonorrhoeae is sparse in Zambia. This study aimed to determine the genetic diversity of N. gonorrhoeae isolated from patients attending sexually transmitted infection (STI) clinics in Lusaka, Zambia. METHODS: A cross-sectional study that sequenced 38 N. gonorrhoeae isolated from 122 patients with gonorrhea from 2019 to 2020 was conducted. The AMR profiles were determined by the E-test, and the DNA was extracted using the NucliSens easyMaG magnetic device. Whole genome sequencing was performed on the Illumina NextSeq550 platform. The Bacterial analysis pipeline (BAP) that is readily available at: https://cge.cbs.dtu.dk/services/CGEpipeline-1.1 was used for the identification of the species, assembling the genome, multi-locus sequence typing (MLST), detection of plasmids and AMR genes. Phylogeny by single nucleotide polymorphisms (SNPs) was determined with the CCphylo dataset. RESULTS: The most frequent STs with 18.4% of isolates each were ST7363, ST1921 and ST1582, followed by ST1583 (13%), novel ST17026 (7.9%), ST1588 (7.9%), ST1596 (5.3%), ST11181 (5.3%), ST11750 (2.6/%) and ST11241 (2.6%) among the 38 genotyped isolates. The blaTeM-1B and tetM (55%) was the most prevalent combination of AMR genes, followed by blaTeM-1B (18.4%), tetM (15.8%), and the combination of blaTeM-1B, ermT, and tetL was 2.6% of the isolates. The AMR phenotypes were predicted in ciprofloxacin, penicillin, tetracycline, azithromycin, and cefixime. The combination of mutations 23.7% was gryA (S91F), parC (E91G), ponA (L421) and rpsJ (V57M), followed by 18.4% in gyrA (S91F), ponA (L421P), rpsJ (V57M), and 18.4% in gyrA (D95G, S91F), ponA (L421P), and rpsJ (V57M). The combinations in gyrA (D95G, S91F) and rpsJ (V57M), and gyrA (D95G, S91F), parC (E91F), ponA (L421P) and rpsJ (V57M) were 13.2% each of the isolates. Plasmid TEM-1 (84.2%), tetM (15.8%), and gonococcal genetic island (GGI) was detected in all isolates. CONCLUSION: This study revealed remarkable heterogeneity of N. gonorrhoeae with blaTEM-1, tetM, ponA, gyrA, and parC genes associated with high resistance to penicillin, tetracycline, and ciprofloxacin demanding revision of the standard treatment guidelines and improved antimicrobial stewardship in Zambia.

Independent clinic-based evaluation of point-of-care testing for the screening of Chlamydia trachomatis, Neisseria gonorrhoea and Trichomonas vaginalis in women-at-risk in Australia, Guatemala, Morocco, and South Africa.

BACKGROUND: In 2018, the World Health Organization commenced a multi-country validation study of the Cepheid GeneXpert for a range of molecular-based point-of-care (POC) tests in primary care settings. One study arm focused on the evaluation of POC tests for screening 'women at risk' for chlamydia (CT), gonorrhoea (NG) and trichomonas (TV) in four countries - Australia, Guatemala, Morocco and South Africa. METHODS: Study participants completed a pre-test questionnaire which included demographics, clinical information and general questions on POC testing (POCT). Two vaginal swab samples (either self-collected or clinician collected) from each patient were tested on the GeneXpert at the POC and at a reference laboratory using quality-assured nucleic acid amplification tests (NAATs). RESULTS: One thousand three hundred and eighty-three women were enrolled: 58.6% from South Africa, 29.2% from Morocco, 6.2% from Guatemala, and 6.0% from Australia. 1296 samples for CT/NG and 1380 samples for TV were tested by the GeneXpert and the reference NAAT. The rate of unsuccessful tests on the GeneXpert was 1.9% for CT, 1.5% for NG and 0.96% for TV. The prevalence of CT, NG and TV was 31%, 13% and 23%, respectively. 1.5% of samples were positive for all three infections; 7.8% were positive for CT and NG; 2.4% were positive for NG and TV; and 7.3% were positive for CT and TV. Compared to reference NAATs, pooled estimates of sensitivity for the GeneXpert tests were 83.7% (95% confidence intervals 69.2-92.1) for CT, 90.5% (85.1-94.1) for NG and 64.7% (58.1-70.7) for TV (although estimates varied considerably between countries). Estimates for specificity were ≥96% for all three tests both within- and between-countries. Pooled positive and negative likelihood ratios were: 32.7 ([CI] 21.2-50.5) and 0.17 (0.08-0.33) for CT; 95.3 (36.9-245.7) and 0.10 (0.06-0.15) for NG; and 56.5 (31.6-101.1) and 0.35 (0.27-0.47) for TV. CONCLUSION: This multi-country evaluation is the first of its kind world-wide. Positive likelihood ratios, as well as specificity estimates, indicate the GeneXpert POC test results for CT, NG and TV were clinically acceptable for ruling in the presence of disease. However, negative likelihood ratios and variable sensitivity estimates from this study were poorer than expected for ruling out these infections, particularly for TV. TRIAL REGISTRATION: Ethics approval to conduct the ProSPeRo study was granted by the WHO Ethics Review Committee, as well as local ethics committees from all participating countries.