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AbstractObjectiveStudy designMethodsResultsConclusionOur objective was to assess trends in three sexually transmitted infections (STIs) – gonorrhoea, chlamydia and syphilis – in Spain, by age group and sex from 2016 to 2022.Retrospective observational studyData from epidemiological surveillance system were used to calculate the incidence rate for each STIs by age group and sex. Poisson regression was employed to examine the trends for 2016 to 2022.For gonorrhoea, higher incidence rates were observed among men than women for all period. The incidence rate ratio (IRR) varied between 1.14 (95% CI 1.12–1.16) for the 15–19 age group to 1.24 (1.23–1.25) for the 35–44 age group among men, and between 1.14 (1.09–1.19) for 55 years or more to 1.27 (1.24–1.29) for the 15–19 age group among women. For chlamydia, women showed higher incidence rate for all age groups than men during the period. Individuals aged 55 years and over showed the highest increase, IRR = 1.30 (1.27–1.34) for men, while it was the lowest for women, IRR = 1.22 (1.16–1.27). The incidence rates for syphilis were lower than for the other STIs. IRR values varied between 1.04 (1.02–1.06) in the 20–24 age group and 1.15 (1.14–1.16) in the 35–44 age group for males; and between 1.13 (1.06–1.16) for the 25–34 age group and 1.18 (1.13–1.25) for the 25–34 age group for females.STIs are more frequent in people aged 25–34 and are increasing in all age groups. However, the rise is most pronounced among older men and among younger women. [ABSTRACT FROM AUTHOR]

Background 4CMenB appears to be effective in reducing Neisseria gonorrhoeae (Ng) infections. Aims are to assess factors associated with breakthrough rectal Ng after 4CMenB and evaluate clinical and microbiological characteristics of breakthrough infections compared with before vaccination. Methods This was a retrospective study of gay, bisexual, and other men who have sex with men (GBMSM) vaccinated with 4CMenB (2 doses) between 2017 and 2023 at the San Raffaele Scientific Institute for Research, Hospitalization and Healthcare (IRCCS San Raffaele Scientific Institute), Milan, Italy, and tested for rectal Ng. Rectal Ng infection is considered breakthrough if it occurs >1 month after the second 4CMenB dose and with positive nucleic acid amplification test (NAAT) result. Follow-up was from July 2017 (first 4CMenB vaccination) to November 2023 (data freeze). Rectal Ng was screened with both NAAT and gonococcal-specific cultures. Characteristics of individuals with or without breakthrough Ng and of Ng infections before or after 4CMenB were compared using Mann-Whitney and χ2/Fisher tests. Results Overall, 473 GBMSM vaccinated with 4CMenB were included, with a median age (interquartile range) of 43 (37–51) years; 451 of 473 were living with human immunodeficiency virus. The percentage of NAAT-positive rectal Ng swab samples was 76 of 957 (7.7%) after 4CMenB and 51 of 456 (11.1%) before. Breakthrough rectal Ng after baseline were 76 in 57 of 473 people. People with rectal Ng after 4CMenB were younger, more likely to have a previous sexually transmitted infection, and had more sexual partners than those without (all P <.001). Breakthrough rectal Ng infections were less frequently symptomatic (34.2% vs 66.7%; P =.001) and more likely with negative gonococcal-specific culture (55.3% vs 19.6%; P <.001) compared with before vaccination. Conclusions Breakthrough rectal Ng infections after 4CMenB were 76 in 57/473 people, preferentially identified in GBMSM with higher-risk sexual behaviors, were less often symptomatic, and more often with negative gonococcal-specific cultures, suggesting lower infection virulence. [ABSTRACT FROM AUTHOR]

New, first-in-class oral antibiotics like zoliflodacin, developed in a public–private partnership, require an optimal introduction strategy while ensuring antibiotic stewardship. Zoliflodacin, given as a single dose for uncomplicated urogenital gonorrhoea, recently demonstrated non-inferiority to ceftriaxone plus azithromycin and safety in a phase 3 randomised controlled trial. Following regulatory approval, zoliflodacin could improve sexually transmitted infection (STI) management and help address the threat of untreatable gonorrhoea, as levels of resistance to current first-line treatments increase. The Global Antibiotic Research & Development Partnership (GARDP) convened an expert meeting during the 2023 STI and HIV World Congress to discuss key questions about the introduction of zoliflodacin in low- and middle-income countries (LMICs). The questions included: which patients to treat in which situations, the timing of introduction, and what additional evidence is needed to change policy for the use of new antibiotics for gonorrhoea. Recommendations from the expert group included: the generation of evidence for the role of a drug like zoliflodacin in clinical treatment failures; the need for additional antimicrobial resistance surveillance; investigation of the role of novel diagnostic approaches, such as point-of-care tests, to improve stewardship; study of preferences and values among the population in need; and modelling of the emergence of N. gonorrhoeae resistance and transmission in different scenarios. Forthcoming World Health Organization (WHO) global guidelines could outline recommendations for a new oral antibiotic like zoliflodacin based on existing evidence, and rational approaches for certain populations or use cases, while the evidence base is further strengthened. [ABSTRACT FROM AUTHOR]

Background: Men who have sex with men (MSM) are more vulnerable to acquiring sexually transmitted infections (STIs). In 2019, for instance, 74% of European Neisseria gonorrhoeae (Ng) cases among males affected MSM. A recent report by the World Health Organization showed that most of the 2020' interim targets to end STIs by 2030 had not been met. A broadened understanding of STI transmission networks could guide future elimination strategies and reduce the STI burden. Therefore, we used whole-genome sequencing (WGS) to determine Ng-clusters and assess sexual mixing. Methods: WGS was performed on Ng-isolates collected at the Medical University of Vienna, Austria and was used for core genome multi-locus sequencing typing cluster analysis. Epidemiologic and infection-specific details were extracted from medical records. Results: Genomic analysis and demographic data were available for 415 isolates, and 43.9% (182/415) were allocated to 31 Ng-clusters. Nine clusters comprised samples from heterosexual individuals only (women N = 4, human immunodeficiency virus (HIV)-negative men N = 49, HIV-positive man N = 1), nine clusters included MSM only (HIV-negative N = 22, HIV-positive N = 13) and 13 clusters included both heterosexuals and MSM (HIV-negative N = 75, HIV-positive N = 18). Current use of HIV pre-exposure prophylaxis (PrEP) was reported by 22.8% of MSM. In multivariate analysis, only 'MSM' predicted clustering with isolates from HIV-positive individuals (adjusted odds ratio 10.24 (95% CI 5.02–20.90)). Conclusions: Sexual mixing of HIV-positive, HIV-negative MSM and non-MSM was frequently observed. Furthermore, HIV-serodiscordant clustering highlights the importance of PrEP rollout to avert HIV transmission. Our findings can inform future STI prevention strategies and continuous surveillance efforts are required to keep up with transmission dynamics. [ABSTRACT FROM AUTHOR]

An effective prophylactic vaccine for prevention of Neisseria gonorrhoeae infection would have a major impact on sexual and reproductive health worldwide. Interest in developing gonorrhoea vaccines is growing due to the reported high rates of N. gonorrhoeae infections globally, and the threat of antimicrobial resistance. Several gonorrhoea vaccine candidates are currently under evaluation and various mathematical models have been used to assess the potential population-level impact a gonorrhoea vaccine may have once available. Here we review key aspects of gonorrhoea vaccine mathematical modelling studies, including model structures, populations considered, and assumptions used as well as vaccine characteristics and implementation scenarios investigated. The predicted vaccine impact varied between studies, ranging from as little as ∼17 % reduction in N. gonorrhoeae prevalence after 30 years up to 100 % reduction after 5 years. However, all studies predicted that even a partially effective gonorrhoea vaccine could have a substantial impact in reducing N. gonorrhoeae prevalence or incidence, particularly when high coverage is achieved within either important risk groups or the overall sexually active population. As expected, higher vaccine efficacy against acquisition of N. gonorrhoeae and longer duration of protection were linked to greater reductions in infections. A vaccine that alters onward transmission could also substantially reduce infections. Several gaps and research needs have been identified by researchers in the field and via this narrative literature review. For example, future modelling to inform gonorrhoea vaccine development and implementation should consider additional populations that are at high risk of N. gonorrhoeae infection, especially in low- and middle-income settings, as well as the impact of vaccination on the potential adverse sexual and reproductive health outcomes of infection. In addition, more detailed and robust epidemiological, biological, and behavioural data is needed to enable more accurate and robust modelling of gonorrhoea vaccine impact to inform future scientific and public health decision-making. [ABSTRACT FROM AUTHOR]

Neisseria gonorrhoeae infection (gonorrhoea) is a global public health challenge, causing substantial sexual and reproductive health consequences, such as infertility, pregnancy complications and increased acquisition or transmission of HIV. There is an urgency to controlling gonorrhoea because of increasing antimicrobial resistance to ceftriaxone, the last remaining treatment option, and the potential for gonorrhoea to become untreatable. No licensed gonococcal vaccine is available. Mounting observational evidence suggests that N. meningitidis serogroup B outer membrane vesicle-based vaccines may induce cross-protection against N. gonorrhoeae (estimated 30%–40% effectiveness using the 4CMenB vaccine). Clinical trials to determine the efficacy of the 4CMenB vaccine against N. gonorrhoeae are underway, as are Phase 1/2 studies of a new gonococcal-specific vaccine candidate. Ultimately, a gonococcal vaccine must be accessible, affordable and equitably dispensed, given that those most affected by gonorrhoea are also those who may be most disadvantaged in our societies, and most cases are in less-resourced settings. This vaccine value profile (VVP) provides a high level, holistic assessment of the current data to inform the potential public health, economic and societal value of pipeline vaccines. This was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations. All contributors have extensive expertise on various elements of the N. gonorrhoeae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using published data obtained from peer-reviewed journals or reports. [ABSTRACT FROM AUTHOR]

Purpose: Single doses of gentamicin have demonstrated clinical efficacy in the treatment of urogenital gonorrhea, but lower cure rates for oropharyngeal and anorectal gonorrhea. Formulations selectively enriched in specific gentamicin C congeners have been proposed as a less toxic alternative to gentamicin, potentially permitting higher dosing to result in increased plasma exposures at the extragenital sites of infection. The purpose of the present study was to compare the antibacterial activity of individual gentamicin C congeners against Neisseria gonorrhoeae to that of other aminoglycoside antibiotics. Methods: Antimicrobial susceptibility of three N. gonorrhoeae reference strains and 152 clinical isolates was assessed using standard disk diffusion, agar dilution, and epsilometer tests. Results: Gentamicin C1, C2, C1a, and C2a demonstrated similar activity against N. gonorrhoeae. Interestingly, susceptibility to the 1-N-ethylated aminoglycosides etimicin and netilmicin was significantly higher than the susceptibility to their parent compounds gentamicin C1a and sisomicin, and to any other of the 25 aminoglycosides assessed in this study. Propylamycin, a 4'-propylated paromomycin analogue, was significantly more active against N. gonorrhoeae than its parent compound, too. Conclusion: Selectively enriched gentamicin formulations hold promise for a less toxic but equally efficacious alternative to gentamicin. Our study warrants additional consideration of the clinically established netilmicin and etimicin for treatment of genital and perhaps extragenital gonorrhea. Additional studies are required to elucidate the mechanism behind the advantage of alkylated aminoglycosides. [ABSTRACT FROM AUTHOR]

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 nontetracycline 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 resist‑ ance in Neisseria gonorrhoeae, but this efect was not statistically signifcant (Pooled OR 2.3, 95% CI 0.93.4). PEP had a marked efect on the N. gonorrhoeae tetracycline MIC distribution in the one study where this was assessed. Pro‑ phylactic efcacy was 100% at low MICs and 0% at high MICs. In the one study where this was assessed, PEP resulted in a signifcant increase in tetracycline resistance in commensal Neisseria species compared to the control group (OR 2.9, 95% CI 1.55.5) but no signifcant efect 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. [ABSTRACT FROM AUTHOR]

Neisseria gonorrhea is a sexually transmitted disease from gonorrhea that lacks treatment; despite the urgency, the absence of adequate drugs, lack of human correlates of protection, and inadequate animal models of infection have delayed progress toward the prevention of gonococcal infection. Lactobacillus crispatus is a lactic acid bacterium typically found in the human vaginal microbiota. Peptides from L. crispatus have shown a potential therapeutic option for targetting N. gonorrhea. Bioinformatics analysis is important for speeding up drug target acquisition, screening refinement, and evaluating adverse effects and drug resistance prediction. Therefore, this study identified an antimicrobial peptide from the bacteriocin immunity protein (BIP) of L. crispatus using the bioinformatics tool and Collection of Antimicrobial Peptide (CAMPR3). Based on the AMP score and highest ADMET properties, the peptide SM20 was chosen for docking analysis. SM20 was docked against multiple proteins from the genome of the AMR bacterium N. gonorrhea using an online tool; protein-peptide interactions were established and visualized using the PyMol visualizing tool. Molecular docking was carried out using the CABSdock tool, and multiple conformations were obtained against the membrane proteins of N. gonorrhoea. The peptide SM20 exhibited higher docking scores and ADMET properties. Therefore, SM20 could be further encapsulated with cellulose; it can be applied topically to the genital tract to target N. gonorrhea infection. The controlled release of the antimicrobial peptide from the gel can provide sustained delivery of the treatment, increasing its efficacy and reducing the risk of resistance development. [ABSTRACT FROM AUTHOR]

The growing threat of antibiotic-resistant Neisseria gonorrhoeae, which causes gonorrhea, presents a current public health challenge. Over the years, the pathogen has developed resistance to different antibiotics, leaving few effective treatment options. High-level resistance to key drugs, including ceftriaxone, has become a concerning reality. This article primarily focuses on the treatment of gonorrhea and the current clinical trials aimed at providing new antibiotic treatment options. We explore ongoing efforts to assess new antibiotics, including zoliflodacin, and gepotidacin. These drugs offer new effective treatment options, but their rapid availability remains uncertain. We delve into two ongoing clinical trials: one evaluating the efficacy and safety of gepotidacin compared to the standard ceftriaxone–azithromycin combination and the other assessing the non-inferiority of zoliflodacin versus the combination therapy of ceftriaxone–azithromycin. These trials represent crucial steps in the search for alternative treatments for uncomplicated gonorrhea. Notably, gonorrhea has been included in the "WHO Priority Pathogens List for Research and Development of New Antibiotics". In conclusion, the urgent need for innovative treatment strategies is underscored by the rising threat of antibiotic resistance in N. gonorrhoeae; collaboration among researchers, industries, and healthcare authorities is therefore essential. [ABSTRACT FROM AUTHOR]

Background: The management and control of gonorrhea are hampered by the widespread resistance to the diverse strains of Neisseria gonorrhea. Resistance to sulfonamides, penicillins, tetracyclines, macrolides, fluoroquinolones, and early cephalosporins has emerged rapidly. Purpose: This systematic review aimed to assess what antibiotics can be used as an alternative therapy for gonorrhea infections that are resistant to antibiotics. Methods: The study was conducted using the Web of Science, PubMed, Embase, and CENTRAL databases, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines. Risk of Bias for Randomized Trials (RoB2) was utilized to evaluate study quality. Results: This review included 28 articles from randomized controlled trials between 2013 and 2023, distributed across five nations. The studies included 2.380 patients and clinical isolates from men and women diagnosed with gonorrhea infection at various sites. Sample testing by treatment with alternative antibiotics. Discussion: Zoliflodacin, tigecycline, and ertapenem in single or dual therapy with ceftriaxone could be considered as a potential option in treating gonorrhea resistant to antibiotics. Gentamicin cannot be recommended to replace ceftriaxone as first-line therapy. Gepotidacin is effective for the Gyr A A92T mutation in gonorrhea infection. Summary: The effectiveness of these antibiotics, zoliflodacin, ceftriaxone, gentamicin, gepotidacin, solithromycin, tigecycline, and ertapenem is considered a solution to gonorrhea resistance. Researchers should study how to provide antibiotics with intervening multidrug efflux pumps to overcome gonococcal antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Treatment of Neisseria gonorrhoeae is under threat with the emergence and spread of antimicrobial resistance. Thus, there is a growing interest in the development of a gonorrhoea vaccine. We used mathematical modelling to assess the impact of a hypothetical vaccine in controlling gonorrhoea among heterosexuals living in a setting of relatively high N. gonorrhoeae prevalence (∼3 %). We developed a mathematical model of N. gonorrhoeae transmission among 15–49-year-old heterosexuals, stratified by age and sex, and calibrated to prevalence and sexual behaviour data from South Africa as an example of a high prevalence setting for which we have data available. Using this model, we assessed the potential impact of a vaccine on N. gonorrhoeae prevalence in the entire population. We considered gonorrhoea vaccines having differing impacts on N. gonorrhoeae infection and transmission and offered to different age-groups. The model predicts that N. gonorrhoeae prevalence can be reduced by ∼50 % in 10 years following introduction of a vaccine if annual vaccination uptake is 10 %, vaccine efficacy against acquisition of infection is 25 % and duration of protection is 5 years, with vaccination available to the entire population of 15–49-year-olds. If only 15–24-year-olds are vaccinated, the predicted reduction in prevalence in the entire population is 25 % with equivalent vaccine characteristics and uptake. Although predicted reductions in prevalence for vaccination programmes targeting only high-activity individuals and the entire population are similar over the same period, vaccinating only high-activity individuals is more efficient as the cumulative number of vaccinations needed to reduce prevalence in the entire population by 50 % is ∼3 times lower for this programme. Provision of a gonorrhoea vaccine could lead to substantial reductions in N. gonorrhoeae prevalence in a high prevalence heterosexual setting, even with moderate annual vaccination uptake of a vaccine with partial efficacy. [ABSTRACT FROM AUTHOR]

Introduction: Neisseria gonorrhoeae causes gonorrhoea, a globally neglected but increasing disease. This systematic review and meta-analysis reviewed the epidemiology and economic burden of gonorrhoea in Latin America and the Caribbean (LAC). Methods: We searched PubMed, EMBase, Cochrane Library, EconLIT, CINAHL, CRD, LILACS, Global Health, Global Dissertations and Theses, SciELO, Web of Science databases, countries' ministries of health, and the IHME's Global Burden of Disease databases. Studies published in the last 10 years (20 years for economic studies) were included if conducted in any LAC country, without language restrictions. The main outcome measures were incidence/prevalence, proportion of co-infections, case fatality rates, specific mortality/hospitalisation rates, direct/indirect costs, and impact of gonorrhoea on quality of life. To assess evidence quality, we used a checklist developed by the US National Heart, Lung, and Blood Institute for observational studies and trial control arms, the Cochrane Effective Practice Organization of Care Group tool for randomised controlled trials, and the CICERO checklist for economic studies. Results: We identified 1290 articles; 115 included epidemiological studies and one included an economic study. Ministry of health data from Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay were identified. Gonorrhoea prevalence was 1.46% (95% confidence interval [CI] 1.00–2.00%) from 48 studies and 5.68% (95% CI 4.23–7.32%) from 58 studies for non-high-risk and high-risk populations, respectively. Cumulative incidence for the high-risk population was 2.05 cases per 100 persons/year. Few published studies were rated as "good" in the risk of bias assessments. Variations in the methodology of the sources and limited information found in the countries' surveillance systems hinder the comparison of data. Conclusion: The burden of gonorrhoea in LAC is not negligible. Our results provide public health and clinical decision support to assess potential interventions to prevent gonorrhoea. Trial Registration: The protocol is registered on PROSPERO (CRD42021253342). The study was funded by GlaxoSmithKline Biologicals SA (GSK study identifier VEO-000025). [ABSTRACT FROM AUTHOR]

A recent article in the Journal of Travel Medicine discusses three novel pentavalent meningococcal vaccines. Invasive meningococcal disease (IMD) can have severe consequences, including long-term disability and even death. The distribution of serogroups associated with IMD varies globally, with different serogroups predominating in different regions. The article highlights the development of pentavalent vaccines that offer protection against multiple serogroups, as well as the potential use of these vaccines for travelers attending mass gatherings or in high-risk situations. However, more research is needed to determine the effectiveness and appropriate dosing schedules for these vaccines in travelers. [Extracted from the article]

Background: Gonorrhoea is an ongoing public health concern due to its rising incidence and the emergence of antibiotic resistance. There are an estimated 82 million new Neisseria gonorrhoeae infections each year, with several populations at higher risk for gonococcal infection, including gay and bisexual men (GBM). If left untreated, infection can lead to serious morbidity including infertility, sepsis and increased risk of HIV acquisition. Development of a gonorrhoea vaccine has been challenging, however there is observational evidence that serogroup B meningococcal vaccines, used to protect against the closely related bacteria Neisseria meningitidis, could provide cross-protection against N. gonorrhoeae. Methods: The MenGO (Meningococcal vaccine efficacy against Gonorrhoea) study is a phase III open-label randomised control trial in GBM to evaluate the efficacy of the four-component meningococcal serogroup B vaccine, 4CMenB, against gonorrhoea. A total of 130 GBM will be recruited at the Gold Coast Sexual Health Clinic, Australia, and randomised to either receive 2 doses of 4CMenB or no intervention. Participants will be followed up for 24 months with testing for N. gonorrhoeae and other sexually transmissible infections every three months. Demographics, sexual behaviour risk, antibiotic use, and blood samples for analysis of N. gonorrhoeae-specific immune responses, will be collected during the study. The primary outcome is the number of N. gonorrhoeae infections in participants over 2 years measured by nucleic acid amplification test (NAAT). Secondary outcomes are vaccine-induced N. gonorrhoeae-specific immune responses, and adverse events in trial participants. Discussion: This trial will determine if the 4CMenB vaccine is able to reduce N. gonorrhoeae infection. If shown to be effective, 4CMenB could be used in gonococcal prevention. Analysis of 4CMenB-induced immune responses will increase understanding of the type of immune response needed to prevent N. gonorrhoeae, which may enable identification of a potential correlate of protection to aid future gonorrhoea vaccine development. Trial registration: The trial has been registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12619001478101) on 25 October 2019. [ABSTRACT FROM AUTHOR]

• Half of urethral gonorrhoea in the population was attributable to insertive anal sex. • Insertive anal sex was the only independent risk factor for urethral gonorrhoea. • One of two men who only used saliva to masturbate also had throat gonorrhoea. • This suggests that autoinoculation of gonorrhoea may be biologically plausible. The saliva of individuals with oropharyngeal gonorrhoea can contain viable Neisseria gonorrhoeae. This study examined if using saliva as a lubricant for masturbation is a risk factor for urethral gonorrhoea among men who have sex with men (MSM). In this cross-sectional study, MSM aged ≥18 years attending the Melbourne Sexual Health Centre between February 2021 and December 2023 were surveyed. Data were collected on sexual activities in the past 7 days, including receiving fellatio, condomless insertive anal sex, docking, and using saliva for masturbation. Multivariable logistic regression examined associations between these exposures and urethral gonorrhoea. The median age of the 3114 men was 32 (IQR: 27-40), with 4.7% (n = 145) testing positive for urethral gonorrhoea. Urethral gonorrhoea was independently associated with an increasing number of partners for condomless insertive anal sex (P < 0.001). It was not significantly associated with receiving fellatio (P = 0.613), docking (P = 0.207), or using saliva for masturbation (P = 0.117). However, of the 110 men who only used saliva for masturbation, two (1.8%) had urethral gonorrhoea, and one (0.9%) had both urethral and oropharyngeal gonorrhoea. Condomless insertive anal sex is the leading risk factor for urethral gonorrhoea and not using saliva as a lubricant for masturbation. [ABSTRACT FROM AUTHOR]

Introduction: Diagnoses of gonorrhoea in England rose by 26% between 2018 and 2019. Recent evidence that a vaccine against meningococcal B disease currently offered to infants in the UK (4CMenB) could additionally protect (with 31% efficacy) against gonorrhoea has led to renewed hope for a vaccine. A Phase 2 proof-of-concept trial of 4CMenB vaccination against gonorrhoea in adults is currently underway. Objectives: To investigate the potential public health impact of adolescent gonorrhoea vaccination in England, considering different implementation strategies. Methods: We developed a deterministic transmission-dynamic model of gonorrhoea infection among heterosexual 13–64-year-olds stratified by age, sex and sexual activity. We explored the impact of a National Immunisation Programme (NIP) among 14-year-olds for a vaccine with 31% efficacy, 6 years' duration of protection, and 85% uptake. We also explored how impact might change for varying efficacy (20–50%) and uptake (75–95%), the addition of a catch-up programme, the use of boosters, and varying duration of protection. Results: An NIP against gonorrhoea could lead to 50,000 (95% credible interval, CrI 31,000-80,000) and 849,000 (95%CrI 476,000-1,568,000) gonorrhoea infections being averted over 10 and 70 years, respectively, in England, for a vaccine with 31% efficacy and 85% uptake. This is equivalent to 25% (95%CrI 17–33%) of heterosexual infections being averted over 70 years. Vaccine impact is predicted to increase over time and be greatest among 13–18-year-olds (39% of infections 95%CrI 31–49% averted) over 70 years. Varying vaccine efficacy and duration of protection had a noticeable effect on impact. Catch-up and booster vaccination increased the short- and long-term impact, respectively. Conclusions: A partially-effective vaccine against gonorrhoea infection, delivered to 14-year-olds alongside the MenACWY vaccine, could have an important population impact on gonorrhoea. Catch-up and booster vaccination could be considered alongside cohort vaccination to increase impact. [ABSTRACT FROM AUTHOR]

Background: Partner notification (PN) after a sexually transmitted infection (STI) diagnosis is being promoted as a means to interrupt transmission chains. We investigated whether Internalised Homonegativity (IH) is associated with PN among men having sex with men (MSM). Methods: PN, defined as notifying at least one partner after diagnosis of syphilis and gonorrhoea, was queried in two internet-based self-completion surveys conducted between Oct 2017 and May 2018 in 68 countries in Europe, Latin America, Canada, and the Philippines. IH is defined by a man's level of agreement or disagreement with negative social beliefs about male homosexuality. Covariates included in a multivariate regression model with a random intercept at country level were age, HIV diagnosis, partnership status, sexual self-efficacy, HIV serostatus communication during last sex with a non-steady partner, place where this partner was met, and PN-related socio-historical background of the country of residence. We grouped countries in three areas: North- and Central-Western European countries plus Canada, former socialist countries, and Latin-American/Mediterranean countries plus the Philippines. In each of the three areas individuals were assigned to 4 subgroups based on IH quartiles and PN rates were determined for each subgroup. Results: PN rates were calculated for 49 countries (excluding countries with less than 10 diagnoses). Mean proportions of MSM notifying their partners were 68.1% and 72.9% after syphilis and gonorrhoea diagnoses, respectively. PN rates were lower in Latin American countries and the Philippines compared to European countries. Within Europe, a North–South divide with lower PN rates in Mediterranean countries was observed. In each of the three regions we mostly observed a stepwise increase of PN rates with decreasing IH. Regression analysis showed lower IH scores associated with higher PN rates. Higher perceived self-efficacy, living in a partnership, and HIV status communication were positively associated with PN. Men who had met their last partner in a gay social venue were more likely to have notified their partners of a syphilis diagnosis compared to men who had met this partner online. Men with diagnosed HIV were less likely to report PN. Conclusions: We could demonstrate that IH was associated with PN among MSM across all countries included in our analysis. Reducing cultural homophobia and ensuring inclusive policies may contribute to STI prevention and control. [ABSTRACT FROM AUTHOR]

The gonorrhoea caused by the bacterium Neisseria gonorrhoeae remains a major global public health problem with high morbidity. Gonorrhoea can affect both women and men, being more prevalent in sexually active young individuals. Even after infection from N. gonorrhoeae, many patients may remain asymptomatic, making the diagnosis and adequate treatment of the disease difficult. The treatment and control of gonorrhoea have been difficult in recent years in most populations, being an example of how behavioural, social, and demographic factors can influence the epidemiology of an infectious disease. The emergence of strains of N. gonorrhoeae resistant to multiple antimicrobials, especially to extended-spectrum cephalosporins, indicates that gonorrhoea has the potential to become untreatable in the current reality of treatment options, especially in places that have a high prevalence of gonococcal infections. The loss of available and effective treatment options can lead to significant increases in new cases of the disease, as well as increased morbidity and mortality. This review provides an overview of current therapeutic options for gonorrhoea, as well as ongoing experimental studies and clinical trials with new antigonococcal agents. [ABSTRACT FROM AUTHOR]

This study aimed to investigate what impact the COVID-19 pandemic and its associated restrictions had on Chlamydia trachomatis and Neisseria gonorrhoeae infections in Sweden, Denmark and Norway, countries with very different governmental strategies for handling this pandemic. Retrospective analysis of data collected via requests to Swedish regions and to health authorities in Denmark and Norway. The data were collected for the years 2018–2020 and the data from Sweden were more detailed. When the pandemic restrictions were installed in 2020, the number of reported chlamydia cases decreased. The decline was most pronounced in Norway 10.8% (2019: n = 28,446; 2020: n = 25,444) while it was only 3.1% in Denmark (2019: n = 35,688; 2020: n = 34,689) and 4.3% in Sweden (2019: n = 34,726; 2020: n = 33,339). Nucleic acid amplifications tests for chlamydia decreased in Sweden (10%) and Norway (18%) in 2020 compared to 2019, while in Denmark a 21% decrease was noted in April 2020 but thereafter increased to a higher level than 2019. The number of reported gonorrhoea cases decreased in Sweden (17%) and in Norway (39%) in 2020 compared to 2019, while a 21% increase was noted in Denmark. Pandemic restrictions had an impact on the number of reported chlamydia infections in all three countries, but only temporarily and did not seem to be correlated to the restriction levels. The number of reported gonorrhoea infections in Sweden and Norway significantly decreased but not in Denmark. Pandemic restrictions appear to have had a limited effect on the spread of chlamydia and gonorrhoea. [ABSTRACT FROM AUTHOR]

Introduction: Sexual and gender minority populations are disproportionately affected by the global syndemic of HIV and other sexually transmitted infections (STIs). We hypothesized that transgender women (TGW) and non‐binary individuals in Nigeria have more STIs than cis‐gender men who have sex with men (cis‐MSM), and that experiences of stigma and sexual practices differ between these three groups. Methods: From 2013 to 2020, TRUST/RV368 enrolled adults assigned male sex at birth who reported anal sex with men in Abuja and Lagos, Nigeria. Participants were tested for STIs and completed questionnaires about sexual behaviours and social stigma every 3 months. Participants were categorized as cis‐MSM, TGW or non‐binary/other based on self‐reported gender identity. Gender group comparisons were made of HIV, gonorrhoea and chlamydia prevalence and incidence; stigma indicators; and condom use during anal sex. Results: Among 2795 participants, there were 2260 (80.8%) cis‐MSM, 284 (10.2%) TGW and 251 (9.0%) non‐binary/other individuals with median age of 23 years (interquartile range 20–27). HIV prevalence among cis‐MSM, TGW and non‐binary/other participants was 40.8%, 51.5% and 47.6%, respectively (p = 0.002). HIV incidence was 8.7 cases per 100 person‐years (PY) (95% confidence interval [CI] 6.9–10.8), 13.1 cases/100 PY (95% CI 6.5–23.4) and 17.6 cases/100 PY (95% CI 9.8–29.0, p = 0.025), respectively. Anorectal gonorrhoea incidence was lower in cis‐MSM than TGW (22.2 [95% CI 19.6–25.0] vs. 35.9 [95% CI 27.3–46.3]). TGW were more likely than cis‐MSM to report being affected by stigma, including assault (47.2% vs. 32.3%), fear of walking around (32.4% vs. 19.2%) and healthcare avoidance (25.0% vs. 19.1%; all p < 0.05). TGW were more likely to report always using condoms than non‐binary/other individuals (35.3% vs. 26.2%, p = 0.041) during receptive anal sex. Conclusions: Sexual and gender minorities in Nigeria have heterogeneous sexual behaviours and experiences of social stigma that may influence the vulnerability to HIV and other STIs. There is a need for tailored interventions that acknowledge and are informed by gender. Further research is needed, particularly among understudied non‐binary individuals, to better understand disparities and inform tailored interventions to improve outcomes among these communities. [ABSTRACT FROM AUTHOR]

Background: The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the European Union/European Economic Area (EU/EEA). We present the Euro-GASP results from 2019 (26 countries), linked to patient epidemiological data, and compared with data from previous years.Methods: Agar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST clinical breakpoints, where available) of 3239 N. gonorrhoeae isolates from 26 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-test and the Pearson's χ2 test was used to assess significance of odds ratios for associations between patient epidemiological data and antimicrobial resistance.Results: European N. gonorrhoeae isolates collected between 2016 and 2019 displayed shifting MIC distributions for; ceftriaxone, with highly susceptible isolates increasing over time and occasional resistant isolates each year; cefixime, with highly-susceptible isolates becoming increasingly common; azithromycin, with a shift away from lower MICs towards higher MICs above the EUCAST epidemiological cut-off (ECOFF); and ciprofloxacin which is displaying a similar shift in MICs as observed for azithromycin. In 2019, two isolates displayed ceftriaxone resistance, but both isolates had MICs below the azithromycin ECOFF. Cefixime resistance (0.8%) was associated with patient sex, with resistance higher in females compared with male heterosexuals and men-who-have-sex-with-men (MSM). The number of countries reporting isolates with azithromycin MICs above the ECOFF increased from 76.9% (20/26) in 2016 to 92.3% (24/26) in 2019. Isolates with azithromycin MICs above the ECOFF (9.0%) were associated with pharyngeal infection sites. Following multivariable analysis, ciprofloxacin resistance remained associated with isolates from MSM and heterosexual males compared with females, the absence of a concurrent chlamydial infection, pharyngeal infection sites and patients ≥ 25 years of age.Conclusions: Resistance to ceftriaxone and cefixime remained uncommon in EU/EEA countries in 2019 with a significant decrease in cefixime resistance observed between 2016 and 2019. The significant increase in azithromycin "resistance" (azithromycin MICs above the ECOFF) threatens the effectiveness of the dual therapy (ceftriaxone + azithromycin), i.e., for ceftriaxone-resistant cases, currently recommended in many countries internationally and requires close monitoring. [ABSTRACT FROM AUTHOR]

Medicinal plants used by traditional healers (THs) in managing gonorrhea and syphilis in Urambo District, Tabora Region, Tanzania, were documented. A semi-structured questionnaire was used to gather information on the use of medicinal plants. The findings revealed that 33 medicinal plants belonging to 18 families were used by the THs to manage gonorrhea and/or syphilis in Urambo District. Among the listed plants, Ximenia caffra, Friesodielsia obovata and Clerodendrum myricoides were frequently used by THs to manage gonorrhea while Ozoroa reticulata, Catunaregam spinosa, Annona senegalensis and Aloe vera were used to manage syphilis. Cassia abreviata, Strychnos spinosa, Strychnos potatorum and Entanda abyssinica were frequently used for the management of both ailments. Five species namely Oldfieldia dactylophylla, Flaucortia indica, Strophanthus eminii, Musa sapeintum and Phyllanthus engleri were recorded for the first time in the country's ethnobotanical literature as a treatment of STIs. Many of the recorded plants also possessed antimicrobial properties. [ABSTRACT FROM AUTHOR]

Background: Point-of-care testing for sexually transmitted infections (STIs) may improve diagnosis and treatment of STIs in low- and middle-income counties. We explored the facilitators and barriers to point-of-care testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoea (NG) for youth in community-based settings in Zimbabwe.Methods: This study was nested within a cluster randomised trial of community-based delivery of integrated HIV and sexual and reproductive health services for youth aged 16 to 24 years. On-site CT/NG testing on urine samples using the Xpert® CT/NG test was piloted in four intervention clusters, with testing performed by service providers. On-site testing was defined as sample processing on the same day and site as sample collection. Outcomes included proportion of tests processed on-site, time between sample collection and collection of results, and proportion of clients receiving treatment. In-depth interviews were conducted with nine service providers and three staff members providing study co-ordination or laboratory support to explore facilitators and barriers to providing on-site CT/NG testing.Results: Of 847 Xpert tests, 296 (35.0%) were performed on-site. Of these, 61 (20.6%) were positive for CT/NG; one (1.6%) received same day aetiological treatment; 33 (54.1%) presented later for treatment; and 5 (8.2%) were treated as a part of syndromic management. There was no difference in the proportion of clients who were treated whether their sample was processed on or off-site (64% (39/61) vs 60% (66/110); p = 0.61). The median (IQR) number of days between sample collection and collection of positive results was 14 (7-35) and 14 (7-52.5) for samples processed on and off-site, respectively, The interviews revealed four themes related to the provision of on-site testing associated with the i) diagnostic device ii) environment, iii) provider, and iv) clients. Some of the specific barriers identified included insufficient testing capacity, inadequate space, as well as reluctance of clients to wait for their results.Conclusions: In addition to research to optimise the implementation of point-of-care tests for STIs in resource-limited settings, the development of new platforms to reduce analytic time will be necessary to scale up STI testing and reduce the attrition between testing and treatment.Trial Registration: Registered in clinical trials.gov ( NCT03719521 ). [ABSTRACT FROM AUTHOR]

Neisseria gonorrhoeae causes the sexually transmitted disease gonorrhoea. The treatment of gonorrhoea is becoming increasingly challenging, as N. gonorrhoeae has developed resistance to antimicrobial agents routinely used in the clinic. Resistance to penicillin is wide-spread partly due to the acquisition of β-lactamase genes. How N. gonorrhoeae survives an initial exposure to β-lactams before acquiring resistance genes remains to be understood. Here, using a panel of clinical isolates of N. gonorrhoeae we show that the β-lactamase enzyme is packaged into outer membrane vesicles (OMVs) by strains expressing blaTEM-1B or blaTEM-106, which protects otherwise susceptible clinical isolates from the β-lactam drug amoxycillin. We characterized the phenotypes of these clinical isolates of N. gonorrhoeae and the time courses over which the cross-protection of the strains is effective. Imaging and biochemical assays suggest that OMVs promote the transfer of proteins and lipids between bacteria. Thus, N. gonorrhoeae strains secret antibiotic degrading enzymes via OMVs enabling survival of otherwise susceptible bacteria. The secretion of β-lactamase protects otherwise susceptible Neisseria gonorrhoeae pathogens from antibiotics. [ABSTRACT FROM AUTHOR]

The coronavirus SARS-CoV-2 (COVID-19) pandemic led to major restrictions in daily life and social contacts in Finland in March 2020. The effect of these restrictions on sexually transmitted infections (STIs) is unclear. The aim of this study was to analyse the incidence and positive rates of sexually transmitted infections in Northern Finland between 2020 and 2021 and compare these with the years prior to the pandemic. Numbers of positive Chlamydia trachomatis, HIV and hepatitis C samples were lower in 2020 to 2021 than in previous years, whereas more gonorrhoea and syphilis was found during pandemic than in previous years. The number of new cases of C. trachomatis reported each month decreased in the first months of the pandemic, but exceeded the prior pandemic-level in autumn 2020. When the mean positive sample rates were compared with the years 2015 to 2019, there was a significant decrease in positive C. trachomatis (p < 0.001) and hepatitis C (p < 0.001) sample rates in both 2020 and 2021. The positive rates for Treponema pallidum in 2020 did not differ significantly (p = 0.38) from previous years. In conclusion, these results show that sexually transmitted infections occurred despite recommendations for social distancing during the COVID-19 pandemic. Thus, easy access to STI testing should always be available, even during exceptional circumstances. [ABSTRACT FROM AUTHOR]

Background: Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) at genital and extragenital sites is needed for most key populations, but molecular diagnostic tests for CT/NG are costly. We aimed to determine the accuracy of pooled samples from multiple anatomic sites from one individual to detect CT/NG using the testing of a single sample from one anatomic site as the reference.Methods: In this systematic review and meta-analysis, we searched five databases for articles published from January 1, 2000, to February 4, 2021. Studies were included if they contained original data describing the diagnostic accuracy of pooled testing compared with single samples, resource use, benefits and harms of pooling, acceptability, and impact on health equity. We present the pooled sensitivities and specificities for CT and NG using a bivariate mixed-effects logistic regression model. The study protocol is registered in PROSPERO, an international database of prospectively registered systematic reviews (CRD42021240793). We used GRADE to evaluate the quality of evidence.Results: Our search yielded 7814 studies, with 17 eligible studies included in our review. Most studies were conducted in high-income countries (82.6%, 14/17) and focused on men who have sex with men (70.6%, 12/17). Fourteen studies provided 15 estimates for the meta-analysis for CT with data from 5891 individuals. The pooled sensitivity for multisite pooling for CT was 93.1% [95% confidence intervals (CI) 90.5-95.0], I2=43.3, and pooled specificity was 99.4% [99.0-99.6], I2=52.9. Thirteen studies provided 14 estimates for the meta-analysis for NG with data from 6565 individuals. The pooled sensitivity for multisite pooling for NG was 94.1% [95% CI 90.9-96.3], I2=68.4, and pooled specificity was 99.6% [99.1-99.8], I2=83.6. Studies report significant cost savings (by two thirds to a third).Conclusion: Multisite pooled testing is a promising approach to improve testing coverage for CT/NG in resource-constrained settings with a small compromise in sensitivity but with a potential for significant cost savings. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the compliance of laboratory diagnostics of gonorrhoea in Ukraine with the World Health Organization (WHO) laboratory manual. Materials and Methods: A quantitative non-randomised cross-sectional descriptive postal survey was conducted to evaluate the diagnostics of gonorrhoea in sexually transmitted infections (STI) clinics in Ukraine. Results: The survey provided data about diagnostics of Neisseria gonorrhoeae in STI clinics from 14 regions of Ukraine from January 2013 to September 2014. The clinics performed microscopy, culture, and point-ofcare- testing in 100%, 85.7%, and 7.1% of the cases, respectively. None of the respondents had the option of performing nucleic acid amplification tests and antimicrobial susceptibility testing. Two regions reported their participation in the collaborative project by WHO on antimicrobial resistance investigation, as national antimicrobial susceptibility surveillance program had not been established in Ukraine. A "three-site testing" (urogenital, pharyngeal, and rectal specimens) in symptomatic heterosexuals was conducted by 25%, "twosite testing" (urogenital and pharyngeal specimens) was conducted by 41.7%, and "one-site testing" (urogenital specimen) was conducted by 33.3% of the respondents. External quality control of laboratory tests for the detection of N. gonorrhoeae was not performed in 50% of the regions in Ukraine. Non-selective culture media for isolation of N. gonorrhoeae and culture media in tubes instead of the recommended Petri dishes were used in 16.7% and 58.3% of the laboratories, respectively. Conclusion: Increased adherence to evidence-basedWHO and/or nationally adapted management guidelines is essential for monitoring gonorrhoea and preventing antimicrobial resistance of N. gonorrhoeae in Ukraine. [ABSTRACT FROM AUTHOR]

Background: Systematic and scoping literature searches are increasingly resource intensive. We present the results of a scoping review which combines the use of a novel artificial-intelligence-(AI)-assisted Medline search tool with two other 'traditional' literature search methods. We illustrate this novel approach with a case study to identify and map the range of conditions (clinical presentations, complications, coinfections and health problems) associated with gonorrhoea infection.Methods: To fully characterize the range of health outcomes associated with gonorrhoea, we combined a high yield preliminary search with a traditional systematic search, then supplemented with the output of a novel AI-assisted Medline search tool based on natural language processing methods to identify eligible literature.Results: We identified 189 health conditions associated with gonorrhoea infection of which: 53 were identified through the initial 'high yield' search; 99 through the systematic search; and 124 through the AI-assisted search. These were extracted from 107 unique references and 21 International Statistical Classification of Diseases and Related Health Problems Ninth and Tenth Revision (ICD 9/10) or Read codes. Health conditions were mapped to the urogenital tract (n = 86), anorectal tract (n = 6) oropharyngeal tract (n = 5) and the eye (n = 14); and other conditions such as systemic (n = 61) and neonatal conditions (n = 7), psychosocial associations (n = 3), and co-infections (n = 7). The 107 unique references attained a Scottish Intercollegiate Guidelines Network (SIGN) score of ≥2++ (n = 2), 2+ (14 [13%]), 2- (30 [28%]) and 3 (45 [42%]), respectively. The remaining papers (n = 16) were reviews.Conclusions: Through AI screening of Medline, we captured - titles, abstracts, case reports and case series related to rare but serious health conditions related to gonorrhoea infection. These outcomes might otherwise have been missed during a systematic search. The AI-assisted search provided a useful addition to traditional/manual literature searches especially when rapid results are required in an exploratory setting. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the association between institution-delivered sex education given under real-world conditions and sexually transmitted infection (STI) rates, STI fatalism, and prior STI testing among African American men aged 15–24 who have sex with women. Participants were tested at community venues for Chlamydia and gonorrhoea and undertook a survey to elicit history of sex education and sexual health information. Among 1196 participants, 73.0% reported having received institution-delivered sex education topics including STI information (90.5%), condoms (89.2%), pregnancy/birth (72.1%) and birth control (67.1%). Among a subset of participants asked about the quality of sex education, 85.7% reported it was 'very good' or 'OK'. The prevalence rate for Chlamydia and/or gonorrhoea was 10.5%. Those who received sex education were more likely to have lower STI fatalism (51.0% vs. 42.4%, p = 0.01) and more likely to report previous Chlamydia screening (44.1% vs. 31.6%, p < 0.01), but did not have a significantly lower rate of Chlamydia and/or gonorrhoea (9.9% vs. 12.4%, p = 0.20) compared to those who did not receive sex education. These findings suggest that institution-delivered sex education given under real-world conditions has beneficial effects on STI risk factors among young African American men. [ABSTRACT FROM AUTHOR]

Background: Antenatal screening for HIV, syphilis and HBV has been successfully implemented in The Netherlands, but data on other STI among pregnant women or male partners are limited. Our objectives: (i) to assess the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) among pregnant women and male partners, (ii) to identify risk factors for these STI during pregnancy, and (iii) to identify adverse perinatal outcomes (APO) associated with STI. Methods: Cross-sectional study. Pregnant women aged ≤ 30 years (n = 548) and male partners (n = 425) were included at 30 midwifery practices during 2012–2016. Participants provided a self-collected vaginal swab (women) or urine sample (men) and completed a questionnaire. Perinatal data were derived from pregnancy cards. APO was defined as premature rupture of membranes, preterm delivery, low birthweight, stillbirth, neonatal conjunctival and respiratory infections. Data were analysed by logistic regression. Results: STI were present in 2.4% of pregnant women (CT 1.8%, NG 0.4%, TV 0.4%), and in 2.2% of male partners (CT 2.2%, NG 0.2%, TV 0%). Of young women (≤ 20 years), 12.5% had a CT infection. Prevalent STI during pregnancy was associated with female young age (≤ 20 years vs ≥ 21 years) (adjusted OR 6.52, CI 95%: 1.11–38.33), male non-Western vs Western background (aOR 9.34, CI 2.34–37.21), and female with ≥ 2 sex partners < 12 months vs 0–1 (aOR 9.88, CI 2.08–46.91). APO was not associated with STI, but was associated with female low education (aOR 3.36, CI 1.12–10.09), complications with previous newborn (aOR 10.49, CI 3.21–34.25 vs no complications) and short duration (0–4 years) of relationship (aOR 2.75, CI 1.41–5.39 vs ≥ 5 years). Small-for-gestational-age was not associated with STI, but was associated with female low education (aOR 7.81, 2.01–30.27), female non-Western background (aOR 4.41, 1.74–11.17), and both parents smoking during pregnancy (aOR 2.94, 1.01–8.84 vs both non-smoking). Conclusions: Prevalence of STI was low among pregnant women and male partners in midwifery practices, except for CT among young women. The study could not confirm previously observed associations between STI and APO, which is probably due to low prevalence of STI, small study sample, and presumed treatment for STI. Plain language summary: Antenatal screening for HIV, syphilis and HBV has been successfully implemented in The Netherlands, but data on other STI among pregnant women or male partners are limited. Our objectives were: (i) to assess the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) among pregnant women and male partners, (ii) to identify risk factors for these STI during pregnancy, and (iii) to identify adverse perinatal outcomes (APO) associated with STI. Pregnant women aged ≤ 30 years and male partners were included at 30 midwifery practices. Women provided a vaginal swab, partners a urine sample; both completed a questionnaire. Perinatal data were derived from midwives. STI were present in 2.4% of pregnant women (CT 1.8%, NG 0.4%, TV 0.4%), and in 2.2% of male partners (CT 2.2%, NG 0.2%, TV 0%). Of women ≤ 20 years, 12.5% had a CT infection. Prevalent STI during pregnancy was associated with female young age, male non-Western background, and female with ≥ 2 sex partners < 12 months. APO was not associated with STI, but was associated with female low education, complications with previous newborn, and short duration of the relationship. Small-for-gestational-age was not associated with STI, but was associated with female low education, female non-Western background, and both parents smoking during pregnancy. Prevalence of STI was low among pregnant women and male partners in midwifery practices, except for CT among young women. The study could not confirm previously observed associations between STI and APO. Probably due to low prevalence of STI, small study sample, and presumed treatment for STI. [ABSTRACT FROM AUTHOR]

Background: Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are significant public health concerns globally. Nearly no gonococcal AMR data are available from Central Asia, and no data from Kyrgyzstan has been published. We examined, for the first time, AMR and molecular epidemiology of N. gonorrhoeae isolates cultured in Kyrgyzstan in 2012 and 2017, in order to inform refinements of the Kyrgyz national gonorrhoea management guidelines.Methods: N. gonorrhoeae isolates cultured in 2012 (n = 84) and 2017 (n = 72) in Kyrgyzstan were examined. MICs of nine antimicrobials were determined using Etest and, where available, clinical breakpoints from the EUCAST were applied. N. gonorrhoeae multiantigen sequence typing (NG-MAST) was also performed.Results: The overall resistance levels were high to ciprofloxacin (88.5%), tetracycline (56.9%), benzylpenicillin (39.1%), and kanamycin (4.7%). Resistance to cefixime (0.6%, n = 1 isolate), azithromycin (0.6%, n = 1), and gentamicin (0.6%, n = 1) was rare. No resistance to ceftriaxone or spectinomycin was found. However, the proportion of isolates with decreased susceptibility (MIC = 0.125 mg/L) to ceftriaxone and cefixime was 12.8 and 11.5%, respectively. Gonococcal isolates were assigned 69 sequence types, of which 52 (75.4%) were new.Conclusions: The gonococcal population in Kyrgyzstan in 2012 and 2017 showed a high genetic diversity. Ceftriaxone, 500-1000 mg, in combination with azithromycin 2 g or doxycycline, particularly when chlamydial infection has not been excluded, should be recommended as empiric first-line treatment. Spectinomycin 2 g could be an alternative treatment, and given with azithromycin 2 g if pharyngeal gonorrhoea has not been excluded. Fluoroquinolones, aminoglycosides, benzylpenicillin, or tetracyclines should not be used for empiric treatment of gonorrhoea in Kyrgyzstan. Timely updating and high compliance to national gonorrhoea treatment guidelines based on quality-assured AMR data is imperative. Expanded and improved gonococcal AMR surveillance in Kyrgyzstan is crucial. [ABSTRACT FROM AUTHOR]

We aimed to estimate how often urethral gonorrhoea is symptomatic among men in the Pre-Exposure Prophylaxis Expanded Victoria study. Eighty-seven percent of 213 cases of urethral gonorrhoea were symptomatic. Ensuring men with urethral gonorrhoea both recognize and present early for treatment is critical to reduce transmission. [ABSTRACT FROM AUTHOR]

Background: The emergence and spread of antimicrobial resistance (AMR) in Neisseria gonorrhoeae, nationally and internationally, is a serious threat to the management and control of gonorrhoea. Limited and conflicting data regarding the epidemiological drivers of gonococcal AMR internationally have been published. We examined the antimicrobial susceptibility/resistance of gonococcal isolates (n = 15,803) collected across 27 European Union/European Economic Area (EU/EEA) countries in 2009–2016, in conjunction to epidemiological and clinical data of the corresponding patients, to elucidate associations between antimicrobial susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection. Methods: In total, 15,803 N. gonorrhoeae isolates from the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), 2009–2016, were examined. Associations between gonococcal susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection were investigated using univariate and multivariate logistic regression analysis. Statistical significance was determined by Pearson χ2-test or Fisher's exact test with two-tailed p-values of < 0.05 indicating significance. Results: The overall gonococcal resistance from 2009 to 2016 was 51.7% (range during the years: 46.5–63.5%), 7.1% (4.5–13.2%), 4.3% (1.8–8.7%), and 0.2% (0.0–0.5%) to ciprofloxacin, azithromycin, cefixime, and ceftriaxone, respectively. The level of resistance combined with decreased susceptibility to ceftriaxone was 10.2% (5.7–15.5%). Resistance to cefixime and ciprofloxacin, and resistance combined with decreased susceptibility to ceftriaxone were positively associated with urogenital infections and heterosexual males, males with sexual orientation not reported and females (except for ciprofloxacin), i.e. when compared to men-who-have-sex-with-men (MSM). Azithromycin resistance was positively associated with heterosexual males, but no association was significant regarding anatomical site of infection. Conclusions: Overall, sexual orientation was the main variable associated with gonococcal AMR. Strongest positive associations were identified with heterosexual patients, particularly males, and not MSM. To provide evidence-based understanding and mitigate gonococcal AMR emergence and spread, associations between antimicrobial susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection need to be further investigated in different geographic settings. In general, these insights will support identification of groups at increased risk and targeted public health actions such as intensified screening, 3-site testing using molecular diagnostics, sexual contact tracing, and surveillance of treatment failures. [ABSTRACT FROM AUTHOR]

Background: The emergence and spread of antimicrobial resistance (AMR) in Neisseria gonorrhoeae, nationally and internationally, is a serious threat to the management and control of gonorrhoea. Limited and conflicting data regarding the epidemiological drivers of gonococcal AMR internationally have been published. We examined the antimicrobial susceptibility/resistance of gonococcal isolates (n = 15,803) collected across 27 European Union/European Economic Area (EU/EEA) countries in 2009-2016, in conjunction to epidemiological and clinical data of the corresponding patients, to elucidate associations between antimicrobial susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection.Methods: In total, 15,803 N. gonorrhoeae isolates from the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), 2009-2016, were examined. Associations between gonococcal susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection were investigated using univariate and multivariate logistic regression analysis. Statistical significance was determined by Pearson χ2-test or Fisher's exact test with two-tailed p-values of < 0.05 indicating significance.Results: The overall gonococcal resistance from 2009 to 2016 was 51.7% (range during the years: 46.5-63.5%), 7.1% (4.5-13.2%), 4.3% (1.8-8.7%), and 0.2% (0.0-0.5%) to ciprofloxacin, azithromycin, cefixime, and ceftriaxone, respectively. The level of resistance combined with decreased susceptibility to ceftriaxone was 10.2% (5.7-15.5%). Resistance to cefixime and ciprofloxacin, and resistance combined with decreased susceptibility to ceftriaxone were positively associated with urogenital infections and heterosexual males, males with sexual orientation not reported and females (except for ciprofloxacin), i.e. when compared to men-who-have-sex-with-men (MSM). Azithromycin resistance was positively associated with heterosexual males, but no association was significant regarding anatomical site of infection.Conclusions: Overall, sexual orientation was the main variable associated with gonococcal AMR. Strongest positive associations were identified with heterosexual patients, particularly males, and not MSM. To provide evidence-based understanding and mitigate gonococcal AMR emergence and spread, associations between antimicrobial susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection need to be further investigated in different geographic settings. In general, these insights will support identification of groups at increased risk and targeted public health actions such as intensified screening, 3-site testing using molecular diagnostics, sexual contact tracing, and surveillance of treatment failures. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the characteristics of patients co-infected with Chlamydia trachomatis and Neisseria gonorrhoea. A retrospective case-control study was performed, which included 399 co-infected patients seen at a sexually transmitted infection clinic in Copenhagen, Denmark. Case-control groups included 300 patients who tested positive only for N. gonorrhoea, 300 who tested positive only for C. trachomatis, and 300 who tested negative for both N. gonorrhoea and C. trachomatis in the same study period. For men, non-Danish origin (odds ratio (OR) 2.3, 95% confidence interval (Cl) 1.34-4.12), previous sexually transmitted infections with C. trachomatis (OR 3.3, 95% CI 1.94-5.92) and N. gonorrhoea (OR 10.6, 95% CI 6.36-17.76), and higher number of sex partners (OR 1.7, 95% Cl 1.40-2.28) were significantly associated with diagnosis of co-infection. For women, previous sexually transmitted infections with C. trachomatis (OR 6.7, 95% CI 3.89-11.78) and N. gonorrhoea (OR 10.4, 95% CI 4.99-21.71), and higher number of sex partners (OR 1.8, 95% CI 1.28-2.56) were significantly associated with a diagnosis of co-infection, whereas being of non-Danish origin was, in some cases, a protective factor (OR 0.3, 95% CI 0.17-0.69). Furthermore, this study demonstrated sex-associated characteristics that should raise concern about coinfection, including: for men, being of non-Danish origin, men who have sex with men status, and higher age, and, for women, young age, in particular, and previous sexually transmitted infections. [ABSTRACT FROM AUTHOR]

Background: Up to 18% of genital Chlamydia infections and 9% of Gonorrhoea infections in England are diagnosed in Primary Care. Evidence suggests that a substantial proportion of these cases are not managed appropriately in line with national guidelines. With the increase in sexually transmitted infections and the emergence of antimicrobial resistance, their timely and appropriate treatment is a priority. We investigated feasibility and acceptability of extending the National Chlamydia Screening Programme's centralised, nurse-led, telephone management (NLTM) as an option for management of all cases of chlamydia and gonorrhoea diagnosed in Primary Care. Methods: Randomised feasibility trial in 11 practices in Bristol with nested qualitative study. In intervention practices patients and health care providers (HCPs) had the option of choosing NLTM or usual care for all patients tested for Chlamydia and Gonorrhoea. In control practices patients received usual care. Results: One thousand one hundred fifty-four Chlamydia/gonorrhoea tests took place during the 6-month study, with a chlamydia positivity rate of 2.6% and gonorrhoea positivity rate of 0.8%. The NLTM managed 335 patients. Interviews were conducted with sixteen HCPs (11 GPs, 5 nurses) and 12 patients (8 female). HCPs were positive about the NLTM, welcomed the partner notification service, though requested more timely feedback on the management of their patients. Explaining the NLTM to patients didn't negatively impact on consultations. Patients found the NLTM acceptable, more convenient and provided greater anonymity than usual care. Patients appreciated getting a text message regarding a negative result and valued talking to a sexual health specialist about positive results. Conclusion: Extension of this established NLTM intervention to a greater proportion of patients was both feasible and acceptable to both patients and HCP, could provide a better service for patients, whilst decreasing primacy care workload. The study provides evidence to support the wider implementation of this NLTM approach to managing chlamydia and gonorrhoea diagnosed in primary care. [ABSTRACT FROM AUTHOR]

Increasing multidrug resistance rates in Neisseria gonorrhoeae have raised concerns and an urgent call for new antibiotics for treatment of gonorrhoea. Several decades of subdued drug development in this field and the recent failures of two new antibiotics to show non-inferiority compared with the current first-line antibiotics ceftriaxone plus azithromycin highlight the need for improved preclinical tools to predict clinical outcome of new drugs in the development process. To summarize current pharmacokinetic/pharmacodynamic (PK/PD) knowledge and dose-finding strategies for antibiotics against gonorrhoea. Literature review of published papers and discussions by global experts at a special workshop on this topic. We review current knowledge of gonococcal specific PK/PD principles and provide an update on new in vitro and in vivo models to correlate drug exposure with clinical outcome, and identify challenges and gaps in gonococcal therapeutic research. Identifying the ideal antimicrobial agent and dose for treating uncomplicated urogenital and pharyngeal gonococcal disease requires appropriate validated non-clinical PK/PD models. Recent advances in adapting in vitro and in vivo models for use in gonorrhoea are an important step for enabling the development of new drugs with reduced risk of failure in Phase 3 clinical development and diminish the risk of emergence of resistance. [ABSTRACT FROM AUTHOR]

Routine screening for Chlamydia and gonococcal infection in pregnancy is not widespread, especially in low- and middle-income countries (LMICs), despite their potential adverse consequences on pregnancy outcome. We conducted a systematic literature search of three major databases to review current literature surrounding Chlamydia trachomatis and Neisseria gonorrhoeae infections in pregnancy. We discuss the epidemiology and burden of both infections, detection methods, potential adverse feto-maternal and infant outcomes and provide an overview of treatment options. A total of 67 articles met the inclusion criteria. The prevalence of C. trachomatis and N. gonorrhoeae across all trimesters ranged between 1.0%-36.8% and 0-14.2% worldwide, respectively. The most common diagnostic method is the Nucleic acid amplification test (NAAT). In pregnancy, chlamydia is associated with preterm birth, spontaneous miscarriage, stillbirth and neonatal conjunctivitis, while gonorrhoea is mainly associated with preterm birth and stillbirth. Amoxicillin, erythromycin and azithromycin showed similar efficacy in the treatment of chlamydia in pregnancy, while ceftriaxone and cefixime were effective in treating gonorrhoea in pregnancy. Being largely asymptomatic infections in women, we opine that detection strategies with locally appropriate tools should be combined with the syndromic approach in LMICs, where there is a high burden of disease. [ABSTRACT FROM AUTHOR]

Introduction: The effective management of sexually transmitted infections (STIs) consists not only of antimicrobial therapy to receive treatment and reduce infectivity, but also in the overall attention and care for the patient's reproductive and sexual health. In July 2019, the WHO called for a concerted effort to ensure access to the services needed to prevent and treat these diseases to everyone and everywhere. Objective: to study and present European policies and the Bulgarian present situation as a basis for building effective, evidence-based interventions and services for the STIs spectrum with emphasis on syphilis to support the achievement of the WHO strategic goals. Material and methods: in this study we applied the documentary method: a review of official strategies, reports, articles on the discussed topic. Results: a review of European and national policies and practices were presented and discussed with emphasis on syphilis. Social, ethical, economic dimensions of the STIs spectrum management were discussed on a national level in order to support the achievement of WHO strategic goals. Conclusions: The presented review provides a good opportunity to define the priority issues related to the management of the spectrum of sexually transmitted infections for evidence-based health policy ideas, research, will and decisions in Bulgaria. [ABSTRACT FROM AUTHOR]

Background: Gonorrhoea is increasing in France since its resurgence in the late 1990's. Understanding trends of condomless sex is a requirement to tailor prevention toward most exposed individuals. This study aims to analyse trends and determinants of condomless penetrative sex (PS) in MSM and heterosexuals diagnosed with gonorrhoea in France.Methods: A standardized self-administered questionnaire filled by 3453 patients was used to monitor condomless sex through the sentinel surveillance network ResIST between 2005 and 2014. Trends were used to describe consistent condom use for penetrative sex (PS). A logistic regression model analysed patients' characteristics associated with condomless PS.Results: Between 2005 and 2014, condomless PS increased regardless of sexual orientation. Condomless PS was particularly common among HIV positive men who have sex with men (MSM (65%)). People living in metropolitan regions outside Paris area (adjusted odds-ratio (AOR) [95% CI] =1.33[1.12-1.58]) were more likely to engage in condomless PS. Conversely, MSM (AOR [95% CI] =0.21 [0.16-0.29]), HIV seronegative patients (AOR [95% CI] =0.68 [0.51-0.89]), patients diagnosed in hospital (AOR [95% CI] = 0.66 [0.45-0.97]) and multi-partners (≥ 10 partners, AOR [95% CI] = 0.54 [0.40-0.74]) were more likely to use condoms.Conclusions: These findings highlight a decreasing use of condom in MSM and heterosexuals diagnosed with gonorrhoea. Prevention strategies should take in account drivers of condomless sex in a context of uncontrolled STI epidemics. [ABSTRACT FROM AUTHOR]

Introduction: Men who have sex with men (MSM) and transgender women (TGW) experience high incidence and prevalence of sexually transmitted infections (STI), and data are needed to understand risk factors for STIs in these populations. The Sibanye Health Project was conducted in Cape Town and Port Elizabeth, South Africa from 2015 to 2016 to develop and test a package of HIV prevention interventions for MSM and TGW. We describe the incidence, prevalence and symptoms of Chlamydia trachomatis (CT), Neisseria gonorrhea (NG) and syphilis observed during the study. Methods: Participants completed HIV testing at baseline. All participants who were HIV negative were followed prospectively. Additionally, a sample of participants identified as living with HIV at baseline was selected to be followed prospectively so that the prospective cohort was approximately 20% HIV positive; the remaining participants identified as HIV positive at baseline were not followed prospectively. Prospective participants were followed for 12 months and returned for clinic‐based STI/HIV testing and assessment of STI symptoms at months 6 and 12. Additional HIV/STI testing visits could be scheduled at participant request. Results: Following consent, a total of 292 participants attended a baseline visit (mean age = 26 years), and 201 were enrolled for the 12‐month prospective study. Acceptance of screening for syphilis and urethral NG/CT was near universal, though acceptance of screening for rectal NG/CT was lower (194/292; 66%). Prevalence of urethral CT and NG at baseline was 10% (29/289) and 3% (8/288) respectively; incidence of urethral CT and NG was 12.8/100 person‐years (PY) and 7.1/100 PY respectively. Prevalence of rectal CT and NG at baseline was 25% (47/189) and 16% (30/189) respectively; incidence of rectal CT and NG was 33.4/100 PY and 26.8/100 PY respectively. Prevalence of syphilis at baseline was 17% (45/258) and incidence was 8.2/100 PY. 91%, 95% and 97% of diagnosed rectal NG/CT, urethral NG/CT and syphilis infections, respectively, were clinically asymptomatic. Conclusions: Prevalence and incidence of urethral and rectal STIs were high among these South African MSM and TGW, and were similar to rates in other settings in the world. Clinical symptoms from these infections were rare, highlighting limitations of syndromic surveillance and suggesting the need for presumptive testing and/or treatment to address the STI epidemic among MSM/TGW in South Africa. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major health threat compromising the gonorrhoea treatment globally. AMR surveillance including whole genome sequencing (WGS)‐based epidemiology provides ideal resolution to identify and describe AMR gonococcal clones, AMR determinants and populations, which can inform management guidelines and antimicrobial stewardship policies. Our aims were to, for the first time, elucidate the WGS‐based epidemiology and characterize AMR determinants of gonococcal strains spreading in Ukraine, 2013–2018. Gonococcal isolates (n = 150) from Ternopil and Dnipro, Ukraine (2013–2018), were subjected to AMR testing (Etest) for eight antimicrobials and WGS. Overall, 11.3% of isolates were resistant to ciprofloxacin, 6.0% to tetracycline, and 0.7% to benzylpenicillin. No isolates were resistant to azithromycin, spectinomycin, ceftriaxone, or cefixime, but one isolate was bordering resistance to both cephalosporins. Twenty‐five MLST STs, 50 NG‐MAST STs, and 34 NG‐STAR types were identified. The phylogenomic analysis revealed six main clusters, mostly associated with the internationally described multidrug‐susceptible gonococcal lineage. Resistance to ciprofloxacin was associated with GyrA S91F and ParC S87R mutations; tetracyclines with rpsJ V57M and tetM; penicillins with mosaic penA‐34.001 and β‐lactamase; mtrR; PorB1b G101D, and PBP1 L421P mutations. One isolate of the multidrug‐resistant NG‐MAST ST1407, MLST ST1901 was found, which was bordering resistance to ceftriaxone and cefixime. The antimicrobial susceptibility of gonococcal strains spreading in Ternopil and Dnipro, Ukraine, in 2013–2018 was surprisingly high. Continued and expanded gonococcal AMR surveillance, ideally including WGS, in Ukraine is essential. This could inform action plans and public health policies to control the spread of AMR gonococcal strains in Ukraine. [ABSTRACT FROM AUTHOR]

Background: It is unclear how important bystander selection is in the genesis of antimicrobial resistance (AMR) in Neisseria gonorrhoeae. Methods: We assessed bystander selection in a novel way. Mixed-effects linear regression was used to assess if country-level prevalence of gonococcal AMR in 30 European countries predicts homologous AMR in other bacteria. The data used was from the European Antimicrobial Resistance Surveillance Network. Results: The prevalence of gonococcal ciprofloxacin resistance was found to be positively associated with AMR prevalence in E. coli (coef. 0.52; P = 0.007), Acinetobacter spp. (coef. 0.13; P = 0.044) and Pseudomonas aeruginosa (coef. 0.36; P = 0.020) but not Klebsiella pneumoniae. Azithromycin resistance in N. gonorrhoeae was positively associated with macrolide resistance in Streptococcus pneumoniae (coef. 0.01; P = 0.018). No association was found for cephalosporins. Conclusions: Gonococcal AMR is linked to that in other bacteria. This finding is likely explained by high antimicrobial consumption in affected populations and provides additional motivation for strengthening antimicrobial stewardship programs. [ABSTRACT FROM AUTHOR]

Aims: It is unclear how economic factors impact on the epidemiology of infectious disease. We evaluated the relationship between incidence of selected infectious diseases and economic factors, including economic downturn, in 13 European countries between 1970 and 2010. Methods : Data were obtained from national communicable disease surveillance centres. Negative binomial forms of the generalised additive model (GAM) and the generalised linear model were tested to see which best reflected transmission dynamics of: diphtheria, pertussis, measles, meningococcal disease, hepatitis B, gonorrhoea, syphilis, hepatitis A and salmonella. Economic indicators were gross domestic product per capita (GDPpc), unemployment rates and (economic) downturn. Results : GAM models produced the best goodness-of-fit results. The relationship between GDPpc and disease incidence was often non-linear. Strength and directions of association between population age, tertiary education levels, GDPpc and unemployment were disease dependent. Overdispersion for almost all diseases validated the assumption of a negative binomial relationship. Downturns were not independently linked to disease incidence. Conclusions : Social and economic factors can be correlated with many infections. However, the trend is not always in the same direction, and these associations are often non-linear. Economic downturn or recessions as indicators of increased disease risk may be better replaced by GDPpc or unemployment measures. [ABSTRACT FROM AUTHOR]

Background: Community-based screening may be one solution to increase testing and treatment of sexually transmitted infections in sexually active teenagers, but there are few data on the practicalities and cost of running such a service. We estimate the cost of running a 'Test n Treat' service providing rapid chlamydia (CT) and gonorrhoea (NG) testing and same day on-site CT treatment in technical colleges.Methods: Process data from a 2016/17 cluster randomised feasibility trial were used to estimate total costs and service uptake. Pathway mapping was used to model different uptake scenarios. Participants, from six London colleges, provided self-taken genitourinary samples in the nearest toilet. Included in the study were 509 sexually active students (mean 85/college): median age 17.9 years, 49% male, 50% black ethnicity, with a baseline CT and NG prevalence of 6 and 0.5%, respectively. All participants received information about CT and NG infections at recruitment. When the Test n Treat team visited, participants were texted/emailed invitations to attend for confidential testing. Three colleges were randomly allocated the intervention, to host (non-incentivised) Test n Treat one and four months after baseline. All six colleges hosted follow-up Test n Treat seven months after baseline when students received a £10 incentive (to participate).Results: The mean non-incentivised daily uptake per college was 5 students (range 1 to 17), which cost £237 (range £1082 to £88) per student screened, and £4657 (range £21,281 to £1723) per CT infection detected, or £13,970 (range £63,842 to £5169) per NG infection detected. The mean incentivised daily uptake was 19 students which cost £91 per student screened, and £1408/CT infection or £7042/NG infection detected. If daily capacity for screening were achieved (49 students/day), costs including incentives would be £47 per person screened and £925/CT infection or £2774/NG infection detected.Conclusions: Delivering non-incentivised Test n Treat in technical colleges is more expensive per person screened than CT and NG screening in clinics. Targeting areas with high infection rates, combined with high, incentivised uptake could make costs comparable.Trial Registration: ISRCTN58038795, Assigned August 2016, registered prospectively. [ABSTRACT FROM AUTHOR]

Neisseria gonorrhoeae is an etiologic agent of gonorrhoea, one of the most common sexually transmitted diseases caused by bacteria. For many years, infections caused by N. gonorrhoeae were considered to be relatively easy to treat; however, resistance has emerged successively to all therapeutic agents used in treatment of the disease, e.g., penicillin, ciprofloxacin or azithromycin. Currently, the global problem is the emergence and a threat of spread of N. gonorrhoeae strains resistant to extended-spectrum cephalosporins (ESC), such as injectable ceftriaxone and oral-used cefixime. Especially, dangerous are multi-resistant strains resistant simultaneously to ESC and azithromycin. Three strains with high-level resistance to azithromycin and resistant to ESC were first time isolated in 2018. Moreover, in 2018, the first ESBL was described in N. gonorrhoeae and that makes the threat of appearing the ESBL mechanism of resistance in N. gonorrhoeae more real, even though the strain was sensitive to ceftriaxone. Molecular typing revealed that variants resistant to ESC occurred also among strains belonging to epidemic clonal complex CC1 (genogroup G1407) distinguished in NG-MAST typing system. The G1407 genogroup, in particular the ST1407 sequence type, is currently dominant in most European countries. The presence of different mechanisms of drug resistance significantly affects clinical practice and force changes in treatment regimens and introduction of new drugs. [ABSTRACT FROM AUTHOR]

Treatment options for gonorrhoea are scarce. Drug repurposing of bioactive molecules approved for other conditions might therefore be of value. We developed a method for wide‐scale, systematic drug repurposing screen to identify molecules with activity against Neisseria gonorrhoeae and screened the Prestwick Chemical Library (1200 FDA‐approved drugs). As a proof‐of‐concept, we further examined one promising and interesting screening hit (auranofin; antirheumatic agent). Three WHO gonococcal reference strains (WHO F, O, P) were used for the Library screening. The strains were grown in presence of a fixed concentration of the library drugs in 384‐well plates for 12 h, and the remaining bacterial respiration, to reflect growth, was then quantitatively measured using optical density (OD) 450 nm and a resazurin assay. The activity of auranofin was further examined using in vitro susceptibility testing (minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)) against genetically diverse antimicrobial‐resistant N. gonorrhoeae strains and time‐kill assays. Sixty‐eight molecules significantly inhibited bacterial growth of WHO F, O and P. Auranofin showed potent in vitro bactericidal activity (in MIC‐, MBC‐ and time‐kill assays) against four WHO reference strains. No cross‐resistance between auranofin and any antimicrobial currently or previously used for gonorrhoea treatment was found when examining 51 selected antimicrobial‐resistant gonococcal strains. In conclusion, this is the first wide‐scale systematic screening effort for repurposing drugs for future treatment of gonorrhoea. Additional studies examining mechanism(s) of action, resistance development, in vivo anti‐gonococcal activity and pharmacokinetics/pharmacodynamics for gonococcal infections of auranofin and several other significant screening hits would be valuable. [ABSTRACT FROM AUTHOR]

Background: European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) antimicrobial resistance (AMR) data are used to inform gonorrhoea treatment guidelines; therefore the data need to be robust and representative. We assessed the extent to which Euro-GASP reflects national measures of the AMR situation for Neisseria gonorrhoeae across the European Union/European Economic Area (EU/EEA).Methods: We compared data from Euro-GASP with published national gonococcal AMR data from 15 countries for azithromycin, cefixime and ciprofloxacin for the period 2009 to 2013 and performed Poisson regression to identify differences (p < 0.05) between the proportions of resistant isolates. The 2014 Euro-GASP AMR data for each country (n = 19) were weighted to account for differences in the distribution of patient characteristics between Euro-GASP and EU/EEA epidemiological gonorrhoea surveillance data. Data were compared to determine whether estimates of resistance levels differed with regards to the 5% threshold used to assess the clinical utility of first-line gonorrhoea treatments. We assessed the quality of decentralised testing by comparing AMR data for isolates tested both centrally and in the participating laboratories, and by evaluating external quality assessment (EQA) performance.Results: There was no significant difference for azithromycin, cefixime and ciprofloxacin resistance when Euro-GASP country data were compared with data from national reports. Weighting slightly altered the Euro-GASP AMR estimates (by between - 4.7 and 4.7% from the unweighted estimates). Weighting resulted in greater changes in estimates of resistance to azithromycin (from - 9.5 to 2.7%) and ciprofloxacin (from - 14.8 to 17.9%) in countries with low isolate numbers and low completeness of reporting (n = 3). Weighting caused AMR levels to fall below or above the 5% threshold for cefixime or azithromycin, respectively in only two countries. Susceptibility category data submitted from the decentralised Euro-GASP laboratories were concordant with the Euro-GASP data (> 90%). EQA performance was also good; < 5% of the minimum inhibitory concentration (MIC) results differed by > 4-fold from the modal MIC of the EQA isolate.Conclusions: The overall prevalence of AMR reported by Euro-GASP reflects closely the AMR situation for N. gonorrhoeae in the EU/EEA. Euro-GASP data can be used to provide robust AMR estimates to inform the European guideline for the management of gonorrhoea. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health concern globally. However, recent gonococcal AMR data from Eastern Europe are extremely limited and no AMR data for strains spreading in Ukraine have ever been internationally published. We investigated the AMR of N. gonorrhoeae isolates in two regions of Ukraine (Ternopil 2013–2018, Dnipropetrovsk 2013–2014), and, where information was available, the treatment administered to the corresponding gonorrhoea patients. Determination of minimum inhibitory concentration (MIC) of eight antimicrobials was performed using Etest and resistance breakpoints from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) were applied. Overall, 9.3% of the examined 150 isolates were resistant to ciprofloxacin, 6.0% to tetracycline, 2.0% to azithromycin, and 0.7% to benzylpenicillin. No isolates were resistant to ceftriaxone, cefixime, spectinomycin, or gentamicin. However, one (0.7%) isolate showed a MIC value of 0.125 mg/L for both ceftriaxone and cefixime, i.e., bordering resistance. Eighty‐eight (67.2%) of 131 patients were administered dual therapy (ceftriaxone 1 g plus doxycycline/clarithromycin/azithromycin/ofloxacin) and 22 (16.8%) ceftriaxone 1 g monotherapy. Worryingly, 21 (16.0%) patients received monotherapy with clarithromycin/doxycycline/azithromycin/ofloxacin/benzylpenicillin. In conclusion, the antimicrobial susceptibility of gonococcal strains spreading in Ternopil and Dnipropetrovsk, Ukraine during 2013–2018 was high. Low levels of resistance to ciprofloxacin, tetracycline, azithromycin, and benzylpenicillin were found, but no resistance to the internationally recommended ceftriaxone, cefixime, or spectinomycin. Ceftriaxone 1 g should remain as empiric first‐line treatment, in dual therapy with azithromycin or doxycycline or in monotherapy. Continued and expanded gonococcal AMR surveillance in Ukraine is essential to monitor the susceptibility to particularly extended‐spectrum cephalosporins, azithromycin and doxycycline. [ABSTRACT FROM AUTHOR]