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Background: Human papillomavirus (HPV) vaccination for gay, bisexual and other men who have sex with men (GBMSM) aged up to 45 years attending sexual health clinics (SHC) and HIV clinics began in England as a pilot in June 2016, with national roll-out from April 2018. The recommended course is three doses of the quadrivalent HPV vaccine over one to 2 years. We present the methodology and results of monitoring vaccination uptake (initiation and completion), and attendance patterns, during the pilot phase., Methods: Total numbers of eligible GBMSM receiving HPV vaccine doses were extracted from routine datasets from pilot start to end of March 2018. Numbers of attendances since January 2009 were extracted and tested for trends before and after introduction of HPV vaccination., Results: Overall, first dose uptake was 49.1 % (23 619/48 095), with clinics with highest data completeness achieving close to 90% uptake during the pilot period. Refusals were very low (3.5%). There was no evidence of increases in the number of GBMSM attendances at pilot SHC., Conclusions: HPV vaccination has not caused important deviations to expected attendance patterns of GBMSM at SHC throughout the pilot phase. Overall, recorded initiation has been encouraging given known issues with data recording, as is current status of second and third dose completion. Attendances, vaccination initiation and completion will continue to be monitored alongside surveillance of anogenital warts diagnoses and of rectal HPV prevalence., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The 1916 Royal Commission on Venereal Diseases was established in response to epidemics of syphilis and gonorrhoea in the UK. In the 100 years since the Venereal Diseases Act (1917), the UK has experienced substantial scientific, economic and demographic changes. We describe historical and recent trends in STIs in the UK., Methods: We analysed surveillance data derived from STI clinics' statistical returns from 1917 to 2016., Results: Since 1918, gonorrhoea and syphilis diagnoses have fluctuated, reflecting social, economic and technological trends. Following spikes after World Wars I and II, rates declined before re-emerging during the 1960s. At that time, syphilis was more common in men, suggestive of transmission within the men who have sex with men (MSM) population. Behaviour change following the emergence of HIV/AIDS in the 1980s is thought to have facilitated a precipitous decline in diagnoses of both STIs in the mid-1980s. Since the early 2000s, gonorrhoea and syphilis have re-emerged as major public health concerns due to increased transmission among MSM and the spread of antimicrobial-resistant gonorrhoea. Chlamydia and genital warts are now the most commonly diagnosed STIs in the UK and have been the focus of public health interventions, including the national human papillomavirus vaccination programme, which has led to substantial declines in genital warts in young people, and the National Chlamydia Screening Programme in England. Since the 1980s, MSM, black ethnic minorities and young people have experienced the highest STI rates., Conclusion: Although diagnoses have fluctuated over the last century, STIs continue to be an important public health concern, often affecting more marginalised groups in society. Prevention must remain a public health priority and, as we enter a new era of sexual healthcare provision including online services, priority must be placed on maintaining prompt access for those at greatest risk of STIs., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Gastrointestinal infections (GII) can cause serious ill health and morbidity. Although primarily transmitted through faecal contamination of food or water, transmission through sexual activity is well described, especially among men who have sex with men (MSM)., Methods: We investigated the prevalence of GIIs among a convenience sample of MSM who were consecutively diagnosed with rectal Chlamydia trachomatis (CT) at 12 UK genitourinary medicine clinics during 10 weeks in 2012. Residual rectal swabs were coded, anonymised and tested for Shigella , Campylobacter , Salmonella , shiga toxin-producing Escherichia coli and enteroaggregative E. coli (EAEC) using a real-time PCR. Results were linked to respective coded and anonymised clinical and demographic data. Associations were investigated using Fisher's exact tests., Results: Of 444 specimens tested, overall GII prevalence was 8.6% (95% CI 6.3% to 11.6%): 1.8% (0.9% to 3.6%) tested positive for Shigella , 1.8% (0.9% to 3.6%) for Campylobacter and 5.2% (3.5% to 7.7%) for EAEC. No specimens tested positive for Salmonella or other diarrhoeagenic E. coli pathotypes. Among those with any GII, 14/30 were asymptomatic (2/7 with Shigella , 3/6 with Campylobacter and 9/17 with EAEC). Shigella prevalence was higher in MSM who were HIV-positive (4.7% (2.1% to 10.2%) vs 0.5%(0.1% to 3.2%) in HIV-negative MSM; p=0.01)., Conclusions: In this small feasibility study, MSM with rectal CT appeared to be at appreciable risk of GII. Asymptomatic carriage may play a role in sexual transmission of GII., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

To inform mathematical modelling of the impact of chlamydia screening in England since 2000, a complete picture of chlamydia testing is needed. Monitoring and surveillance systems evolved between 2000 and 2012. Since 2012, data on publicly funded chlamydia tests and diagnoses have been collected nationally. However, gaps exist for earlier years. We collated available data on chlamydia testing and diagnosis rates among 15-44-year-olds by sex and age group for 2000-2012. Where data were unavailable, we applied data- and evidence-based assumptions to construct plausible minimum and maximum estimates and set bounds on uncertainty. There was a large range between estimates in years when datasets were less comprehensive (2000-2008); smaller ranges were seen hereafter. In 15-19-year-old women in 2000, the estimated diagnosis rate ranged between 891 and 2,489 diagnoses per 100,000 persons. Testing and diagnosis rates increased between 2000 and 2012 in women and men across all age groups using minimum or maximum estimates, with greatest increases seen among 15-24-year-olds. Our dataset can be used to parameterise and validate mathematical models and serve as a reference dataset to which trends in chlamydia-related complications can be compared. Our analysis highlights the complexities of combining monitoring and surveillance datasets., (This article is copyright of The Authors, 2017.)

Surveillance data from sexual health clinics indicate recent increases in sexually transmitted infections, particularly among men who have sex with men. The largest annual increase in syphilis diagnoses in a decade was reported in 2014. Less condom use may be the primary reason for these increases.

Objectives: To investigate use of dual tests for Chlamydia trachomatis and Neisseria gonorrhoeae on samples collected through the National Chlamydia Screening Programme (NCSP) in England., Design and Setting: During May-July 2013, we delivered an online survey to commissioners of sexual health services in the 152 upper-tier English Local Authorities (LAs) who were responsible for commissioning chlamydia screening in people aged 15-24 years., Main Outcome Measures: (1) The proportion of English LAs using dual tests on samples collected by the NCSP; (2) The estimated number of gonorrhoea tests and false positives from samples collected by the NCSP, calculated using national surveillance data on the number of chlamydia tests performed, assuming the gonorrhoea prevalence to range between 0.1% and 1%, and test sensitivity and specificity of 99.5%., Results: 64% (98/152) of LAs responded to this national survey; over half (53% (52/98)) reported currently using dual tests in community settings. There was no significant difference between LAs using and not using dual tests by chlamydia positivity, chlamydia diagnosis rate or population screening coverage. Although positive gonorrhoea results were confirmed with supplementary tests in 93% (38/41) of LAs, this occurred after patients were notified about the initial positive result in 63% (26/41). Approximately 450-4500 confirmed gonorrhoea diagnoses and 2300 false-positive screens might occur through use of dual tests on NCSP samples each year. Under reasonable assumptions, the positive predictive value of the screening test is 17-67%., Conclusions: Over half of English LAs already commission dual tests for samples collected by the NCSP. Gonorrhoea screening has been introduced alongside chlamydia screening in many low prevalence settings without a national evidence review or change of policy. We question the public health benefit here, and suggest that robust testing algorithms and clinical management pathways, together with rigorous evaluation, be implemented wherever dual tests are deployed., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Laboratory studies were conducted to investigate potential adverse effects on development, growth, reproduction and biomarker responses (vitellogenin [VTG] and gonad histology) in fathead minnows (Pimephales promelas) exposed to tamoxifen citrate. Based on the results of a partial life cycle study (nominal [mean measured] concentrations ranged from 0.18 [0.11] to 18 [15.74] microg/L), a 284-d fish full life-cycle (FFLC) flow-through study was conducted using newly fertilized embryos (<24 h postfertilization) exposed to nominal (mean measured) concentrations of 14C-tamoxifen citrate that ranged from 0.01 (0.007) to 5.12 (4.08) microg/L. Triethylene glycol (2.0 microl/L) was used as a solvent carrier, with 17beta-estradiol (E2) as a positive control (nominal 0.1 microg/L). Among the biomarkers measured, significant effects on VTG and gonad histology were observed, although these results required care in their interpretation. Among important population-relevant endpoints, no effects on reproduction were observed at nominal concentrations < or = 5.12 microg/L. Effects on growth (length and weight) were observed in some treatments; however, some of these showed irregular concentration-response relationships, which made interpretation uncertain, or were deemed transient in nature (e.g., reduction in growth of F1 28-d posthatch larval fish at nominal concentrations of 0.08, 0.64, and 5.12 microg/L) and judged not to be biologically significant. Interpretation of results from fish chronic studies is challenging and frequently calls for scientific judgement about statistical and biological significance and what constitutes an adverse effect. Using the principles used in mammalian toxicology studies, data from partial and FFLC studies were evaluated from both statistical and biological perspectives in order to determine no-observed-adverse effect concentrations (expressed as (adverse)NOEC) for use in environmental risk assessment. Careful consideration of both biological and statistical outcomes from these studies suggested overall (adverse)NOEC concentration and lowest-observed-effect concentration ((adverse)LOEC) values for tamoxifen citrate of 5.12 microg/L and 5.6 microg/L, respectively.

Previous studies have shown that L-2-chloropropionic acid (L-CPA) produces necrosis to cerebellar granule cells with some associated Purkinje cell damage in the rat. We have re-evaluated the neuropathology using the original sections and fresh sections from archived brain material from rats treated with L-CPA at different ages, times after dosing and the following prior treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801. In addition we have determined the lobular distribution of cerebellar granule cell necrosis produced by L-CPA. Using Fluoro-Jade staining to detect degenerating neurons, we have identified three new brain regions that show neuronal cell necrosis as a result of exposure to L-CPA, these are the medial habenular nucleus, pontine gray and inferior olivary nucleus. The neuronal cell degeneration was confirmed in conventional haematoxylin and eosin stained sections and in some cases by glial fibrillary acidic protein staining for reactive gliosis. The neuronal cell necrosis at these new sites was both time and dose dependent; young 22-day-old rats, which are refractory to L-CPA-induced cerebellar granule cell necrosis, did however show some neuronal cell degeneration in the medial habenular, pontine gray and inferior olivary nuclei. Treatment of rats with MK-801 30 min prior to L-CPA, afforded complete protection against the neuronal cell injury in the medial habenular, pontine gray and inferior olivary nuclei, similar to that previously reported for the cerebellum, supporting an excitotoxic mechanism of neuronal cell death. In the cerebellum the lobular distribution of the granule cell loss was not uniform, more severe granule cell loss occurring in lobules 1-4 and 9a + b. This localization exactly mirrors that seen previously in the cerebellum of rats given L-CPA and examined by magnetic resonance imaging (MRI). The basis for the neuronal cell loss in the medial habenular nucleus, pontine gray and inferior olivary nucleus, in addition to the major site in the cerebellum, and the sensitivity of particular cerebellar lobes is not currently understood. Anatomical connections between the sites of injury and their likely neurotransmitter use are discussed.