Developing a model to predict individualised treatment for gonorrhoea: a modelling study.

OBJECTIVE: To develop a tool predicting individualised treatment for gonorrhoea, enabling treatment with previously recommended antibiotics, to reduce use of last-line treatment ceftriaxone. DESIGN: A modelling study. SETTING: England and Wales. PARTICIPANTS: Individuals accessing sentinel health services. INTERVENTION: Developing an Excel model which uses participants' demographic, behavioural and clinical characteristics to predict susceptibility to legacy antibiotics. Model parameters were calculated using data for 2015-2017 from the Gonococcal Resistance to Antimicrobials Surveillance Programme. MAIN OUTCOME MEASURES: Estimated number of doses of ceftriaxone saved, and number of people delayed effective treatment, by model use in clinical practice. Model outputs are the predicted risk of resistance to ciprofloxacin, azithromycin, penicillin and cefixime, in groups of individuals with different combinations of characteristics (gender, sexual orientation, number of recent sexual partners, age, ethnicity), and a treatment recommendation. RESULTS: Between 2015 and 2017, 8013 isolates were collected: 64% from men who have sex with men, 18% from heterosexual men and 18% from women. Across participant subgroups, stratified by all predictors, resistance prevalence was high for ciprofloxacin (range: 11%-51%) and penicillin (range: 6%-33%). Resistance prevalence for azithromycin and cefixime ranged from 0% to 13% and for ceftriaxone it was 0%. Simulating model use, 88% of individuals could be given cefixime and 10% azithromycin, saving 97% of ceftriaxone doses, with 1% of individuals delayed effective treatment. CONCLUSIONS: Using demographic and behavioural characteristics, we could not reliably identify a participant subset in which ciprofloxacin or penicillin would be effective. Cefixime resistance was almost universally low; however, substituting ceftriaxone for near-uniform treatment with cefixime risks re-emergence of resistance to cefixime and ceftriaxone. Several subgroups had low azithromycin resistance, but widespread azithromycin monotherapy risks resistance at population level. However, this dataset had limitations; further exploration of individual characteristics to predict resistance to a wider range of legacy antibiotics may still be appropriate.

Genomic and Phenotypic Variability in Neisseria gonorrhoeae Antimicrobial Susceptibility, England.

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global concern. Phylogenetic analyses resolve uncertainties regarding genetic relatedness of isolates with identical phenotypes and inform whether AMR is due to new mutations and clonal expansion or separate introductions by importation. We sequenced 1,277 isolates with associated epidemiologic and antimicrobial susceptibility data collected during 2013-2016 to investigate N. gonorrhoeae genomic variability in England. Comparing genetic markers and phenotypes for AMR, we identified 2 N. gonorrhoeae lineages with different antimicrobial susceptibility profiles and 3 clusters with elevated MICs for ceftriaxone, varying mutations in the penA allele, and different epidemiologic characteristics. Our results indicate N. gonorrhoeae with reduced antimicrobial susceptibility emerged independently and multiple times in different sexual networks in England, through new mutation or recombination events and by importation. Monitoring and control for AMR in N. gonorrhoeae should cover the entire population affected, rather than focusing on specific risk groups or locations.

Detection in the United Kingdom of the Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, October to December 2018.

We describe detection in the United Kingdom (UK) of the drug-resistant Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate azithromycin resistance. Two female patients developed infection following contact with UK-resident men from the same sexual network linked to travel to Ibiza, Spain. One case failed treatment with ceftriaxone, and azithromycin and gentamicin, before successful treatment with ertapenem. Both isolates had indistinguishable whole-genome sequences. Urgent action is essential to contain this drug-resistant strain.

Is previous azithromycin treatment associated with azithromycin resistance in Neisseria gonorrhoeae? A cross-sectional study using national surveillance data in England.

OBJECTIVES: It has been suggested that treatment of STIs with azithromycin may facilitate development of azithromycin resistance in Neisseria gonorrhoeae (NG) by exposing the organism to suboptimal doses. We investigated whether treatment history for non-rectal Chlamydia trachomatis (CT), non-gonococcal urethritis (NGU) or NG (proxies for azithromycin exposure) in sexual health (GUM) services was associated with susceptibility of NG to azithromycin. METHODS: Azithromycin susceptibility data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP 2013-2015, n=4606) and additional high-level azithromycin-resistant isolates (HL-AziR) identified by the Public Health England reference laboratory (2013-2016, n=54) were matched to electronic patient records in the national GUMCAD STI surveillance dataset (2012-2016). Descriptive and regression analyses were conducted to examine associations between history of previous CT/NGU/NG and subsequent susceptibility of NG to azithromycin. RESULTS: Modal azithromycin minimum inhibitory concentration (MIC) was 0.25 mg/L (one dilution below the resistance breakpoint) in those with and without history of previous CT/NGU/NG (previous 1 month/6 months). There were no differences in MIC distribution by history of CT/NGU (P=0.98) or NG (P=0.85) in the previous 1 month/6 months or in the odds of having an elevated azithromycin MIC (>0.25 mg/L) (Adjusted OR for CT/NGU 0.97 (95% CI 0.76 to 1.25); adjusted OR for NG 0.82 (95% CI: 0.65 to 1.04)) compared with those with no CT/NGU/NG in the previous 6 months. Among patients with HL-AziR NG, 3 (4%) were treated for CT/NGU and 2 (3%) for NG in the previous 6 months, compared with 6% and 8%, respectively for all GRASP patients. CONCLUSIONS: We found no evidence of an association between previous treatment for CT/NGU or NG in GUM services and subsequent presentation with an azithromycin-resistant strain. As many CT diagnoses occur in non-GUM settings, further research is needed to determine whether azithromycin-resistant NG is associated with azithromycin exposure in other settings and for other conditions.

Ethnic variations in sexual behaviours and sexual health markers: findings from the third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

BACKGROUND: Sexual health entails the absence of disease and the ability to lead a pleasurable and safe sex life. In Britain, ethnic inequalities in diagnoses of sexually transmitted infections (STI) persist; however, the reasons for these inequalities, and ethnic variations in other markers of sexual health, remain poorly understood. We investigated ethnic differences in hypothesised explanatory factors such as socioeconomic factors, substance use, depression, and sexual behaviours, and whether they explained ethnic variations in sexual health markers (reported STI diagnoses, attendance at sexual health clinics, use of emergency contraception, and sexual function). METHODS: We analysed probability survey data from Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3; n=15 162, conducted in 2010-12). Reflecting Britain's current ethnic composition, we included in our analysis participants who identified in 2011 as belonging to one of the following seven largest ethnic groups: white British, black Caribbean, black African, Indian, Pakistani, white other, and mixed ethnicity. We calculated age-standardised estimates and age-adjusted odds ratios for all explanatory factors and sexual health markers for all these ethnic groups with white British as the reference category. We used multivariable regression to examine the extent to which adjusting for explanatory factors explained ethnic variations in sexual health markers. FINDINGS: We included 14 563 (96·0%) of the 15 162 participants surveyed in Natsal-3. Greater proportions of black Caribbean, black African, and Pakistani people lived in deprived areas than those of other ethnic groups (36·9-55·3% vs 16·4-29·4%). Recreational drug use was highest among white other and mixed ethnicity groups (25·6-27·7% in men and 10·3-12·9% in women in the white other and mixed ethnicity groups vs 4·1-15·6% in men and 1·0-11·2% in women of other ethnicities). Compared with white British men, the proportions of black Caribbean and black African men reporting being sexually competent at sexual debut were lower (32·9% for black Caribbean and 21·9% for black African vs 47·4% for white British) and the number of partners in the past 5 years was greater (median 2 [IQR 1-4] for black Caribbean and 2 [1-5] for black African vs 1 [1-2] for white British), and although black Caribbean and black African men reported greater proportions of concurrent partnerships (26·5% for black Caribbean and 38·9% for black African vs 14·8% for white British), these differences were not significant after adjusting for age. Compared with white British women, the proportions of black African and mixed ethnicity women reporting being sexually competent were lower (18·0% for black African and 35·3% for mixed ethnicity vs 47·9% for white British), and mixed ethnicity women reported larger numbers of partners in the past 5 years (median 1 [IQR 1-4] vs 1 [1-2]) and greater concurrency (14·3% vs 8·0%). Reporting STI diagnoses was higher in black Caribbean men (8·7%) and mixed ethnicity women (6·7%) than white British participants (3·6% in men and 3·2% in women). Use of emergency contraception was most commonly reported among black Caribbean women (30·7%). Low sexual function was most common among women of white other ethnicity (30·1%). Adjustment for explanatory factors only partly explained inequalities among some ethnic groups relative to white British ethnicity but did not eliminate ethnic differences in these markers. INTERPRETATION: Ethnic inequalities in sexual health markers exist, and they were not fully explained by differences in their broader determinants. Holistic interventions addressing modifiable risk factors and targeting ethnic groups at risk of poor sexual health are needed. FUNDING: Medical Research Council, the Wellcome Trust, the Economic and Social Research Council, UK Department of Health, and The National Institute for Health Research.

EFFECTS OF "SWIM WITH THE TURTLES" TOURIST ATTRACTIONS ON GREEN SEA TURTLE (CHELONIA MYDAS) HEALTH IN BARBADOS, WEST INDIES.

Along the West Coast of Barbados a unique relationship has developed between endangered green sea turtles (Chelonia mydas) and humans. Fishermen began inadvertently provisioning these foraging turtles with fish offal discarded from their boats. Although initially an indirect supplementation, this activity became a popular attraction for visitors. Subsequently, demand for this activity increased, and direct supplementation or provisioning with food began. Food items offered included raw whole fish (typically a mixture of false herring [Harengula clupeola] and pilchard [Harengula humeralis]), filleted fish, and lesser amounts of processed food such as hot dogs, chicken, bread, or various other leftovers. Alterations in behavior and growth rates as a result of the provisioning have been documented in this population. The purpose of this study was to determine how tourism-based human interactions are affecting the overall health of this foraging population and to determine what potential health risks these interactions may create for sea turtles. Juvenile green sea turtles (n=29) were captured from four sites off the coast of Barbados, West Indies, and categorized into a group that received supplemental feeding as part of a tour (n=11) or an unsupplemented group (n=18) that consisted of individuals that were captured at sites that did not provide supplemental feeding. Following capture, a general health assessment of each animal was conducted. This included weight and morphometric measurements, a systematic physical examination, determination of body condition score and body condition index, epibiota assessment and quantification, and clinical pathology including hematologic and biochemical testing and nutritional assessments. The supplemented group was found to have changes to body condition, vitamin, mineral, hematologic, and biochemical values. Based on these results, recommendations were made to decrease negative behaviors and health impacts for turtles as a result of this provisioning.