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This study was important to improve proper biosecurity measures and controlling the spread of Aeromonas to prevent future outbreaks. This research sought to determine whether virulent Aeromans species were present in morbid rainbow trout, their resistance and their genetic relatedness. A total number of 542 tissue lesion specimens were collected from gill, liver, heart and kidneys in morbid domesticated fish in Duhok province, Iraq. The gyrB DNA sequence analysis was used to determine the species classification. Drug susceptibility testing was conducted for all isolated strains using disc diffusion technique. The genotyping analysis was carried out using enterobacterial repetitive intergenic consensus-polymerase chain reaction. Thirty-four isolates were found and they were classified into three species ( Aeromonas veronii, Aeromonas sorbia, and Aeromonas allosaccharophila) , where A. veronii stand as one of the most prevalent species. The most frequently affected organ by Aeromonas was the gills among four different organs. The detection frequencies of the virulence genes aerolysin, outer membrane protein, glycerophospholipid-cholesterol acyltransferase, elastase, flagella, serine protease, cytotonic heat- labile , and hemolysin  were 100%, 100%, 79.41%, 64.70%, 76.47%, 67.64%, 70.58%, and 41.17, respectively. None of the strains possessed all of the virulence markers. All isolates were completely resistant to ceftazidime, amoxicillin and doxycycline. All isolates were found to be multi-drug-resistant. Regardless of the nearest geographic source area of samples and the same Aeromonas species, there was a high genetic diversity. The results of this study could help farmers and researchers make informed decisions about measures of biosecurity and proper therapeutic drugs to apply to prevent current outbreaks and prevent them from recurring again., Competing Interests: The authors declare that there is no conflict of interest that affects the publication of this work., (© 2024 Urmia University. All rights reserved.)

Point-of-care tests (POCTs) to diagnose sexually transmitted infections (STIs) have potential to positively impact patient management and patient perceptions of clinical services. Yet there remains a disconnect between development of new technologies and their implementation into clinical care. With the advent of new STI POCTs arriving to the global market, guidance for their successful adoption and implementation into clinical services is urgently needed. We conducted qualitative in-depth interviews with professionals prior to and post-implementation of a Chlamydia trachomatis/Neisseria gonorrhoeae POCT into clinical services in England to define key stakeholder roles and explore the process of POCT integration. Participants self-identified themselves as key stakeholders in the STI POCT adoption and/or implementation processes. Data consisted of interview transcripts, which were analysed thematically using NVIVO 11. Six sexual health services were included in the study; three of which have implemented POCTs. We conducted 40 total interviews: 31 prior to POCT implementation and 9 follow-up post-implementation. Post-implementation data showed that implementation plans required little or no change during service evaluation. Lead clinicians and managers self-identified as key stakeholders for the decision to purchase, while nurses self-identified as "change champions" for implementation. Many identified senior clinical staff as those most likely to introduce and drive change. However, participants stressed the importance of engaging all clinical staff in implementation. While the accuracy of the POCT, its positive impact on patient management and the ease of its integration within existing pathways were considered essential, costs of purchasing and utilising the technology were identified as central to the decision to purchase. Our study shows that key decision-makers for adoption and implementation require STI POCTs to have laboratory-comparable accuracy and be affordable for purchase and ongoing use. Further, successful integration of POCTs into sexual health services relies on supportive interpersonal relationships between all levels of staff., Competing Interests: The authors have read the journal’s policy and have the following competing interests to declare: At the time this research was being conducted, all authors were employed by the Applied Diagnostic Research and Evaluation Unit (ADREU) at St George’s University of London; ADREU has received funding from Abbott (https://www.abbott.com/), binx health (https://mybinxhealth.com/), Cepheid (https://www.cepheid.com/), SpeedDx (https://plexpcr.com/), Mologic (https://mologic.co.uk/), Revolugen (https://revolugen.co.uk/), and Sekisui (https://sekisuidiagnostics.com/), for the research and evaluation of their diagnostics. The present study was funded by a collaborative grant (ref: no. 90174-463338; awarded to STS, SSF, EMHE) between binx health and St George’s University of London. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Objectives: To develop a simple DNA sequencing test for simultaneous identification and antimicrobial resistance (AMR) detection of multiple sexually transmitted infections (STIs)., Methods: Real-time PCR (qPCR) was initially performed to identify Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) infections among a total of 200 vulvo-vaginal swab samples from female sex workers in Ecuador. qPCR positive samples plus qPCR negative controls for these STIs were subjected to single gene targeted PCR MinION-nanopore sequencing using the smartphone operated MinIT., Results: Among 200 vulvo-vaginal swab samples 43 were qPCR positive for at least one of the STIs. Single gene targeted nanopore sequencing generally yielded higher pathogen specific read counts in qPCR positive samples than qPCR negative controls. Of the 26 CT, NG or MG infections identified by qPCR, 25 were clearly distinguishable from qPCR negative controls by read count. Discrimination of TV qPCR positives from qPCR negative controls was poorer as many had low pathogen loads (qPCR cycle threshold >35) which produced few specific reads. Real-time AMR profiling revealed that 3/3 NG samples identified had gyrA mutations associated with fluoroquinolone resistance, 2/10 of TV had mutations related to metronidazole resistance, while none of the MG samples possessed 23S rRNA gene mutations contributing to macrolide resistance., Conclusions: Single gene targeted nanopore sequencing for diagnosing and simultaneously identifying key antimicrobial resistance markers for four common genital STIs shows promise. Further work to optimise accuracy, reduce costs and improve speed may allow sustainable approaches for managing STIs and emerging AMR in resource poor and laboratory limited settings., Competing Interests: LZ and STS are inventors on the patent: Detection and antibiotic resistance profiling of microorganisms, WO/2020/178575. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: There are limited published data on factors related to risky sexual practices (RSP) affecting sexually transmitted infections (STIs) among female sex workers (FSWs) in Ecuador., Methods: Cross-sectional study of FSWs presenting for a consultation in a primary health care centre during 2017. A questionnaire was administered to collect information on RSP and potential risk factors including age, membership of an FSW association, self-report of previous STI diagnosis, previous treatment for suspected STI and temporary migration for sex work. Associations between RSP and potential risk factors were estimated by logistic regression. The proportion of STI was estimated from vaginal swabs by real-time PCR for four sexually transmitted pathogens (Neisseria gonorrhoeae, Trichomonas vaginalis, Chlamydia trachomatis, and Mycoplasma genitalium)., Results: Of 249 FSWs recruited, 22.5% had reported RSPs at least once during sex work. Among FSWs reporting unprotected vaginal sex in the previous three months, 25.5% had at least one other RSP type. 17.6% (95%CI 13.3-22.8) had at least one active STI. Prevalence of co-infections was 2.4% (95%CI 1.1-5.2). In multivariable analysis, RSP was associated with age (adjusted OR 1.06; 95%CI 1.02-1.10), membership of an FSWs association (aOR 3.51; 95%CI 1.60-7.72) and self-reported previous STI (aOR 3.43; 95%CI 1.28-9.17)., Conclusions: Among a population of female sex workers with high proportion of STIs, increasing age and belonging to an FSWs association was associated with a higher likelihood of engaging in RSP with clients. Engaging with FSWs organisations may reduce the burden of STI among sex workers., Competing Interests: The authors have declared that no competing interests exist.

BackgroundWidespread ceftriaxone antimicrobial resistance (AMR) threatens Neisseria gonorrhoeae (NG) treatment, with few alternatives available. AMR point-of-care tests (AMR POCT) may enable alternative treatments, including abandoned regimens, sparing ceftriaxone use. We assessed cost-effectiveness of five hypothetical AMR POCT strategies: A-C included a second antibiotic alongside ceftriaxone; and D and E consisted of a single antibiotic alternative, compared with standard care (SC: ceftriaxone and azithromycin).AimAssess costs and effectiveness of AMR POCT strategies that optimise NG treatment and reduce ceftriaxone use.MethodsThe five AMR POCT treatment strategies were compared using a decision tree model simulating 38,870 NG-diagnosed England sexual health clinic (SHC) attendees; A micro-costing approach, representing cost to the SHC (for 2015/16), was employed. Primary outcomes were: total costs; percentage of patients given optimal treatment (regimens curing NG, without AMR); percentage of patients given non-ceftriaxone optimal treatment; cost-effectiveness (cost per optimal treatment gained).ResultsAll strategies cost more than SC. Strategy B (azithromycin and ciprofloxacin (azithromycin preferred); dual therapy) avoided most suboptimal treatments (n = 48) but cost most to implement (GBP 4,093,844 (EUR 5,474,656)). Strategy D (azithromycin AMR POCT; monotherapy) was most cost-effective for both cost per optimal treatments gained (GBP 414.67 (EUR 554.53)) and per ceftriaxone-sparing treatment (GBP 11.29 (EUR 15.09)) but with treatment failures (n = 34) and suboptimal treatments (n = 706).ConclusionsAMR POCT may enable improved antibiotic stewardship, but require net health system investment. A small reduction in test cost would enable monotherapy AMR POCT strategies to be cost-saving.

Background: Low uptake of sexually transmitted infection testing by sexually active young people is a worldwide public health problem. Screening in non-medical settings has been suggested as a method to improve uptake. The "Test n Treat" feasibility trial offered free, on-site rapid chlamydia/gonorrhoea tests with same day treatment for chlamydia (and gonorrhoea treatment at a local clinic,) to sexually active students (median age 17 years) at six technical colleges in London. Despite high rates of chlamydia (6% prevalence), uptake of testing was low (< 15%). In a qualitative study we explored the acceptability, including barriers and facilitators to uptake, of on-site chlamydia screening., Methods: In 2016-17 we conducted a qualitative study in the interpretative tradition using face to face or telephone semi-structured interviews with students (n = 26), teaching staff (n = 3) and field researchers (n = 4). Interviews were digitally recorded, transcribed and thematically analysed., Results: From the student perspective, feelings of embarrassment and the potential for stigma were deterrents to sexually transmitted infection testing. While the non-medical setting was viewed as mitigating against stigma, for some students volunteering to be screened exposed them to detrimental judgements by their peers. A small financial incentive to be screened was regarded as legitimising volunteering in a non-discrediting way. Staff and researchers confirmed these views. The very low level of knowledge about sexually transmitted infections influenced students to not view themselves as candidates for testing. There were also suggestions that some teenagers considered themselves invulnerable to sexually transmitted infections despite engaging in risky sexual behaviours. Students and researchers reported the strong influence peers had on uptake, or not, of sexually transmitted infection testing., Conclusions: This study offers new insights into the acceptability of college-based sexually transmitted infection screening to young, multi-ethnic students. Future studies in similar high risk, hard to reach groups should consider linking testing with education about sexually transmitted infections, offering non stigmatising incentives and engaging peer influencers.

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.

Objectives: We conducted a cluster-randomized feasibility trial of 90-minute Chlamydia trachomatis tests and same day on-site treatment ('Test n Treat/TnT') in six technical colleges in London, England, to assess TnT uptake rates; follow-up rates; prevalence of C. trachomatis at baseline and 7 months; time to treatment; acceptability of TnT., Methods: Participants completed questionnaires and provided genitourinary samples at baseline and 7 months. Participants were informed that baseline samples would not be tested for 7 months and were advised to get screened independently. Colleges were randomly allocated 1:1 to intervention (TnT) or control (no TnT). One month and 4 months post recruitment, participants at intervention colleges were texted invitations for on-site free C. trachomatis tests. A purposive sample of students who did/did not attend for screening were interviewed (n = 26)., Results: Five hundred and nine sexually active students were recruited: median age 17.9 years, 47% male, 50% black ethnicity, 55% reporting two or more sexual partners in the previous year. TnT uptake was 13% (33/259; 95% CI 8.9-17.4%) at 1 month and 10% (26/259; 6.7-14.4%) at 4 months with overall C. trachomatis positivity 5.1% (3/59; 1.1-14.2%). Follow-up at 7 months was 62% (317/509) for questionnaires and 52% (264/509) for samples. C. trachomatis prevalence was 6.2% (31/503) at baseline and 6.1% (16/264) at 7 months. Median time from test to treatment was 15 h. Interviews suggested low test uptake was associated with not feeling at risk, perceptions of stigma, and little knowledge of sexually transmitted infections (STIs)., Conclusions: Despite high C. trachomatis rates at baseline and follow-up, uptake of testing was low. Like many countries, England urgently needs better sex education, including making STI testing routine/normal. Trial registration ISRCTN58038795., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Young people aged 16-24 years are disproportionately affected by sexually transmitted infections (STIs). STIs can have serious health consequences for affected individuals and the estimated annual cost of treatment to the National Health Service is £620 million. Accordingly, the UK government has made reducing the rates of STIs among this group a priority. A missed opportunity to intervene to increase condom use is when young people obtain self-sampling kits for STIs via the internet., Objective: Our aim was to develop a theory-based tailored intervention to increase condom use for 16-24-years-olds accessing chlamydia self-sampling websites., Methods: The intervention, Wrapped, was developed using Intervention Mapping and was co-designed with young people. The following steps were performed: (1) identification of important determinants of condom use and evidence of their changeability using computer and digital interventions; (2) setting the intervention goal, performance objectives, and change objectives; (3) identification of Behavior Change Principles (BCPs) and practical strategies to target these determinants; and (4) development of intervention materials able to deliver the BCPs and practical strategies., Results: Users of existing chlamydia self-sampling websites are signposted to Wrapped after placing an order for a sampling kit. Salient barriers to condom use are identified by each user and relevant intervention components are allocated to target these. The components include the following: (1) a sample box of condoms, (2) an online condom distribution service, (3) a product for carrying condoms, (4) a condom demonstration video, (5) a series of videos on communication about condom use, and (6) erotic films of real couples discussing and demonstrating condom use., Conclusions: This intervention will be directed at young people who may be particularly receptive to messages and support for behavior change due to their testing status., (©Katie Newby, Rik Crutzen, Katherine Brown, Julia Bailey, John Saunders, Ala Szczepura, Jonny Hunt, Tim Alston, S Tariq Sadiq, Satyajit Das. Originally published in JMIR Formative Research (http://formative.jmir.org), 01.05.2019.)

Sexually transmitted infections (STIs) continue to be a major public health concern in the United Kingdom (UK). Epidemiological models have shown that narrowing the time between STI diagnosis and treatment may reduce the population burden of infection, and rapid, accurate point-of-care tests (POCTs) have potential for increasing correct treatment and mitigating the spread of antimicrobial resistance (AMR). We developed the Precise social science programme to incorporate clinician and patient opinions on potential designs and implementation of new POCTs for multiple STIs and AMR detection. We conducted qualitative research, consisting of informal interviews with clinicians and semi-structured in-depth interviews with patients, in six sexual health clinics in the UK. Interviews with clinicians focused on how the new POCTs would likely be implemented into clinical care; these new clinical pathways were then posed to patients in in-depth interviews. Patient interviews showed acceptability of POCTs, however, willingness to wait in clinic for test results depended on the context of patients' sexual healthcare seeking. Patients reporting frequent healthcare visits often based their expectations and opinions of services and POCTs on previous visits. Patients' suggestions for implementation of POCTs included provision of information on service changes and targeting tests to patients concerned they are infected. Our data suggests that patients may accept new POCT pathways if they are given information on these changes prior to attending services and to consider implementing POCTs among patients who are anxious about their infection status and/or who are experiencing symptoms., Competing Interests: ADREU has received funding from Binx Health (formerly Atlas Genetics Ltd), Alere, Cepheid, SpeedDx, Mologic, Revolugen and Sekisui. SSF and EHE have been members of the BD Diagnostics Advisory Panel on UK Provision of Sexual Health Services. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: Rapid and accurate sexually transmitted infection diagnosis can reduce onward transmission and improve treatment efficacy. We evaluated the accuracy of a 15-minute run-time recombinase polymerase amplification-based prototype point-of-care test (TwistDx) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG)., Methods: Prospective, multicentre study of symptomatic and asymptomatic patients attending three English sexual health clinics. Research samples provided were additional self-collected vulvovaginal swab (SCVS) (female participants) and first-catch urine (FCU) aliquot (female and male participants). Samples were processed blind to the comparator (routine clinic CT/NG nucleic acid amplification test (NAAT)) results. Discrepancies were resolved using Cepheid CT/NG GeneXpert., Results: Both recombinase polymerase amplification and routine clinic NAAT results were available for 392 male and 395 female participants. CT positivity was 8.9% (35/392) (male FCU), 7.3% (29/395) (female FCU) and 7.1% (28/395) (SCVS). Corresponding NG positivity was 3.1% (12/392), 0.8% (3/395) and 0.8% (3/395). Specificity and positive predictive values were 100% for all sample types and both organisms, except male CT FCU (99.7% specificity (95% confidence interval (CI) 98.4-100.0; 356/357), 97.1% positive predictive value (95% CI 84.7-99.9; 33/34)). For CT, sensitivity was ≥94.3% for FCU and SCVS. CT sensitivity for female FCU was higher (100%; 95% CI, 88.1-100; 29/29) than for SCVS (96.4%; 95% CI, 81.7-99.9; 27/28). NG sensitivity and negative predictive values were 100% in FCU (male and female)., Conclusions: This prototype test has excellent performance characteristics, comparable to currently used NAATs, and fulfils several World Health Organization ASSURED criteria. Its rapidity without loss of performance suggests that once further developed and commercialized, this test could positively affect clinical practice and public health., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To quantify the costs, benefits and cost-effectiveness of three multipathogen point-of-care (POC) testing strategies for detecting common sexually transmitted infections (STIs) compared with standard laboratory testing., Design: Modelling study., Setting: Genitourinary medicine (GUM) services in England., Population: A hypothetical cohort of 965 988 people, representing the annual number attending GUM services symptomatic of lower genitourinary tract infection., Interventions: The decision tree model considered costs and reimbursement to GUM services associated with diagnosing and managing STIs. Three strategies using hypothetical point-of-care tests (POCTs) were compared with standard care (SC) using laboratory-based testing. The strategies were: A) dual POCT for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); B) triplex POCT for CT-NG and Mycoplasma genitalium (MG); C) quadruplex POCT for CT-NG-MG and Trichomonas vaginalis (TV). Data came from published literature and unpublished estimates., Primary and Secondary Outcome Measures: Primary outcomes were total costs and benefits (quality-adjusted life years (QALYs)) for each strategy (2016 GB, £) and associated incremental cost-effectiveness ratios (ICERs) between each of the POC strategies and SC. Secondary outcomes were inappropriate treatment of STIs, onward STI transmission, pelvic inflammatory disease in women, time to cure and total attendances., Results: In the base-case analysis, POC strategy C, a quadruplex POCT, was the most cost-effective relative to the other strategies, with an ICER of £36 585 per QALY gained compared with SC when using microcosting, and cost-savings of £26 451 382 when using tariff costing. POC strategy C also generated the most benefits, with 240 467 fewer clinic attendances, 808 fewer onward STI transmissions and 235 135 averted inappropriate treatments compared with SC., Conclusions: Many benefits can be achieved by using multipathogen POCTs to improve STI diagnosis and management. Further evidence is needed on the underlying prevalence of STIs and SC delivery in the UK to reduce uncertainty in economic analyses., Competing Interests: Competing interests: All authors have completed the Unified Competing Interest Form and declare financial support from Innovate UK; EJA, SEH, MJH are employees of Aquarius Population Health (APH), which reports grants from Innovate UK grant to Atlas Genetics, during the conduct of the study; other from Cepheid, St Georges University of London, Enigma Diagnostics and AstraZeneca, on STI and POC research outside the submitted work; RMB is a Lecturer and Programme Director of Economics at St. Angela’s College Sligo/NUI Galway and an academic staff member of the Health Economics and Policy Analysis Centre (HEPAC) at NUI Galway, providing health economic support to Aquarius Population Health on an ad hoc consultancy basis. STS, EH-E, SSF are members of the Applied Diagnostic Research and Evaluation Unit at St George’s, University of London, which has received funding from Atlas Genetics, Alere, Cepheid, SpeeDx and Sekisui. STS has received NIHR funding to develop a POCT with Atlas., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Non-specific genital infection (NSGI; non- Chlamydia trachomatis , non- Neisseria gonorrhoeae -associated urethritis) is a common diagnosis in symptomatic heterosexual men attending UK sexual health clinics (SHCs). but little is known about the psychosocial impact of this diagnosis., Methods: We conducted an observational study among symptomatic heterosexual men attending SHCs to evaluate the psychosocial impact of an NSGI diagnosis compared with a diagnosis of Chlamydia trachomatis (CT), Neisseria gonorrhoeae or no abnormalities detected focusing on the feasibility of our study methodology. Participants completed a computer-assisted self-interviewing (CASI) including two validated measures of psychosocial impact: the EQ-5D-5L health-related quality of life and Rosenberg Self-Esteem Scale, before diagnostic testing and 2 weeks after receiving test results (follow-up 1 (FU-1)) and a qualitative interview. We compared scores between diagnostic groups using paired t-tests, qualitative data were analysed thematically and feasibility was assessed by process analysis., Results: 60 men completed the baseline CASI (75% response rate). 46 (76.6%) were eligible for follow-up; 11/46 (23.9%) completed the follow-up CASI, and 3/11 (27.3%) completed the qualitative interview. 81.7% of all participants left CASI feedback at baseline: 73.5% reported the questionnaire as 'fine' or 'very good'. Qualitative interview participants reported the study was acceptable. Compared with baseline, among patients completing FU-1, only patients with a diagnosis of NSGI (p<0.05) or CT (p<0.05) showed increased EQ-5D-5L Index, whereas patients with a diagnosis of NSGI (p=0.05) showed decreased mean Rosenberg Self-Esteem Scale score., Conclusions: Although most participants indicated study acceptability at baseline, and we employed measures to increase retention (CASI questionnaires, reminder messages and a focus on men's health), we experienced high loss to follow-up. We found that heterosexual men attending SHCs with symptoms of urethritis experience both positive and negative psychosocial impacts following their clinic attendance, which warrants further investigation., Competing Interests: Competing interests: The Applied Diagnostic Research and Evaluation Unit at St George’s, University of London (STS, EMH-E, SF and AP) receives funding from the National Institute of Health Research (NIHR) i4i Programme (grant number II-LB-0214-20005), Atlas Genetics, Alere, Hologic Cepheid, SpeeDx, Sekisui and Becton Dickinson to develop Point of Care Tests for STIs., (© 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.)

Background: Rapid Point-Of-Care Tests for Chlamydia trachomatis (CT) may reduce onward transmission and reproductive sexual health (RSH) sequelae by reducing turnaround times between diagnosis and treatment. The io® single module system (Atlas Genetics Ltd.) runs clinical samples through a nucleic acid amplification test (NAAT)-based CT cartridge, delivering results in 30min., Methods: Prospective diagnostic accuracy study of the io® CT-assay in four UK Genito-Urinary Medicine (GUM)/RSH clinics on additional-to-routine self-collected vulvovaginal swabs. Samples were tested "fresh" within 10days of collection, or "frozen" at -80°C for later testing. Participant characteristics were collected to assess risk factors associated with CT infection., Results: CT prevalence was 7.2% (51/709) overall. Sensitivity, specificity, positive and negative predictive values of the io® CT assay were, respectively, 96.1% (95% Confidence Interval (CI): 86.5-99.5), 97.7% (95%CI: 96.3-98.7), 76.6% (95%CI: 64.3-86.2) and 99.7% (95%CI: 98.9-100). The only risk factor associated with CT infection was being a sexual contact of an individual with CT., Conclusions: The io® CT-assay is a 30-min, fully automated, high-performing NAAT currently CE-marked for CT diagnosis in women, making it a highly promising diagnostic to enable specific treatment, initiation of partner notification and appropriately intensive health promotion at the point of care., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Self-directed and internet-based care are key elements of eHealth agendas. We developed a complex online clinical and public health intervention, the eSexual Health Clinic (eSHC), in which patients with genital chlamydia are diagnosed and medically managed via an automated online clinical consultation, leading to antibiotic collection from a pharmacy. Partner notification, health promotion, and capture of surveillance data are integral aspects of the eSHC. We aimed to assess the safety and feasibility of the eSHC as an alternative to routine care in non-randomised, exploratory proof-of-concept studies., Methods: Participants were untreated patients with chlamydia from genitourinary medicine clinics, untreated patients with chlamydia from six areas in England in the National Chlamydia Screening Programme's (NCSP) online postal testing service, or patients without chlamydia tested in the same six NCSP areas. All participants were aged 16 years or older. The primary outcome was the proportion of patients with chlamydia who consented to the online chlamydia pathway who then received appropriate clinical management either exclusively through online treatment or via a combination of online management and face-to-face care. We captured adverse treatment outcomes., Findings: Between July 21, 2014, and March 13, 2015, 2340 people used the eSHC. Of 197 eligible patients from genitourinary medicine clinics, 161 accessed results online. Of the 116 who consented to be included in the study, 112 (97%, 95% CI 91-99) received treatment, and 74 of those were treated exclusively online. Of the 146 eligible NCSP patients, 134 accessed their results online, and 105 consented to be included. 93 (89%, 95% CI 81-94) received treatment, and 60 were treated exclusively online. In both groups, median time to collection of treatment was within 1 day of receiving their diagnosis. 1776 (89%) of 1936 NCSP patients without chlamydia accessed results online. No adverse events were recorded., Interpretation: The eSHC is safe and feasible for management of patients with chlamydia, with preliminary evidence of similar treatment outcomes to those in traditional services. This innovative model could help to address growing clinical and public health needs. A definitive trial is needed to assess the efficacy, cost-effectiveness, and public health impact of this intervention., Funding: UK Clinical Research Collaboration., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Background: Control of sexually transmitted infections (STI) is a global public health priority. Despite the UK's free, confidential sexual health clinical services, those at greatest risk of STIs, including young people, report barriers to use. These include: embarrassment regarding face-to-face consultations; the time-commitment needed to attend clinic; privacy concerns (e.g. being seen attending clinic); and issues related to confidentiality. A smartphone-enabled STI self-testing device, linked with online clinical care pathways for treatment, partner notification, and disease surveillance, is being developed by the eSTI(2) consortium. It is intended to benefit public health, and could do so by increasing testing among populations which underutilise existing services and/or by enabling rapid provision of effective treatment. We explored its acceptability among potential users., Methods: In-depth interviews were conducted in 2012 with 25 sexually-experienced 16-24 year olds, recruited from Further Education colleges in an urban, high STI prevalence area. Thematic analysis was undertaken., Results: Nine females and 16 males participated. 21 self-defined as Black; three, mixed ethnicity; and one, Muslim/Asian. 22 reported experience of STI testing, two reported previous STI diagnoses, and all had owned smartphones. Participants expressed enthusiasm about the proposed service, and suggested that they and their peers would use it and test more often if it were available. Utilizing sexual healthcare was perceived to be easier and faster with STI self-testing and online clinical care, which facilitated concealment of STI testing from peers/family, and avoided embarrassing face-to-face consultations. Despite these perceived advantages to privacy, new privacy concerns arose regarding communications technology: principally the risk inherent in having evidence of STI testing or diagnosis visible or retrievable on their phone. Some concerns arose regarding the proposed self-test's accuracy, related to self-operation and the technology's novelty. Several expressed anxiety around the possibility of being diagnosed and treated without any contact with healthcare professionals., Conclusions: Remote STI self-testing and online care appealed to these young people. It addressed barriers they associated with conventional STI services, thus may benefit public health through earlier detection and treatment. Our findings underpin development of online care pathways, as part of ongoing research to create this complex e-health intervention.

Background: Despite considerable international eHealth impetus, there is no guidance on the development of online clinical care pathways. Advances in diagnostics now enable self-testing with home diagnosis, to which comprehensive online clinical care could be linked, facilitating completely self-directed, remote care. We describe a new framework for developing complex online clinical care pathways and its application to clinical management of people with genital chlamydia infection, the commonest sexually transmitted infection (STI) in England., Methods: Using the existing evidence-base, guidelines and examples from contemporary clinical practice, we developed the eClinical Care Pathway Framework, a nine-step iterative process. Step 1: define the aims of the online pathway; Step 2: define the functional units; Step 3: draft the clinical consultation; Step 4: expert review; Step 5: cognitive testing; Step 6: user-centred interface testing; Step 7: specification development; Step 8: software testing, usability testing and further comprehension testing; Step 9: piloting. We then applied the Framework to create a chlamydia online clinical care pathway (Online Chlamydia Pathway)., Results: Use of the Framework elucidated content and structure of the care pathway and identified the need for significant changes in sequences of care (Traditional: history, diagnosis, information versus Online: diagnosis, information, history) and prescribing safety assessment. The Framework met the needs of complex STI management and enabled development of a multi-faceted, fully-automated consultation., Conclusion: The Framework provides a comprehensive structure on which complex online care pathways such as those needed for STI management, which involve clinical services, public health surveillance functions and third party (sexual partner) management, can be developed to meet national clinical and public health standards. The Online Chlamydia Pathway's standardised method of collecting data on demographics and sexual behaviour, with potential for interoperability with surveillance systems, could be a powerful tool for public health and clinical management.

Background: The annual number of new human immunodeficiency virus (HIV) infections in the United Kingdom among men who have sex with men (MSM) has risen, and remains high among heterosexuals. Increasing HIV transmission among MSM is consistent with evidence of ongoing sexual risk behavior in this group, and targeted prevention strategies are needed for those at risk of acquiring HIV., Objective: The Attitudes to and Understanding of Risk of Acquisition of HIV (AURAH) study was designed to collect information on HIV negative adults at risk of HIV infection in the United Kingdom, based on the following parameters: physical and mental health, lifestyle, patterns of sexual behaviour, and attitudes to sexual risk., Methods: Cross-sectional questionnaire study of HIV negative or undiagnosed sexual health clinic attendees in the United Kingdom from 2013-2014., Results: Of 2630 participants in the AURAH study, 2064 (78%) were in the key subgroups of interest; 580 were black Africans (325 females and 255 males) and 1484 were MSM, with 27 participants belonging to both categories., Conclusions: The results from AURAH will be a significant resource to understand the attitudes and sexual behaviour of those at risk of acquiring HIV within the United Kingdom. AURAH will inform future prevention efforts and targeted health promotion initiatives in the HIV negative population.

Advances in microfluidics and the introduction of isothermal nucleic acid amplification assays have resulted in a range of solutions for nucleic acid amplification tests suited for point of care and field use. However, miniaturisation of instrumentation for such assays has not seen such rapid advances and fluorescence based assays still depend on complex, bulky and expensive optics such as fluorescence microscopes, photomultiplier tubes and sensitive lens assemblies. In this work we demonstrate a robust, low cost platform for isothermal nucleic acid amplification on a microfluidic device. Using easily obtainable materials and commercial off-the-shelf components, we show real time fluorescence detection using a low cost photodiode and operational amplifier without need for lenses. Temperature regulation on the device is achieved using a heater fabricated with standard printed circuit board fabrication methods. These facile construction methods allow fabrications at a cost compatible with widespread deployment to resource poor settings.

Background: The increasing pervasiveness of mobile technologies has given potential to transform healthcare by facilitating clinical management using software applications. These technologies may provide valuable tools in sexual health care and potentially overcome existing practical and cultural barriers to routine testing for sexually transmitted infections. In order to inform the design of a mobile health application for STIs that supports self-testing and self-management by linking diagnosis with online care pathways, we aimed to identify the dimensions and range of preferences for user interface design features among young people., Methods: Nine focus group discussions were conducted (n = 49) with two age-stratified samples (16 to 18 and 19 to 24 year olds) of young people from Further Education colleges and Higher Education establishments. Discussions explored young people's views with regard to: the software interface; the presentation of information; and the ordering of interaction steps. Discussions were audio recorded and transcribed verbatim. Interview transcripts were analysed using thematic analysis., Results: Four over-arching themes emerged: privacy and security; credibility; user journey support; and the task-technology-context fit. From these themes, 20 user interface design recommendations for mobile health applications are proposed. For participants, although privacy was a major concern, security was not perceived as a major potential barrier as participants were generally unaware of potential security threats and inherently trusted new technology. Customisation also emerged as a key design preference to increase attractiveness and acceptability., Conclusions: Considerable effort should be focused on designing healthcare applications from the patient's perspective to maximise acceptability. The design recommendations proposed in this paper provide a valuable point of reference for the health design community to inform development of mobile-based health interventions for the diagnosis and treatment of a number of other conditions for this target group, while stimulating conversation across multidisciplinary communities.

Thousands of bacterial phylotypes colonise the human body and the host response to this bacterial challenge greatly influences our state of health or disease. The concept of infectogenomics highlights the importance of host genetic factors in determining the composition of human microbial biofilms and the response to this microbial challenge. We hereby introduce the term 'genetic dysbiosis' to highlight the role of human genetic variants affecting microbial recognition and host response in creating an environment conducive to changes in the normal microbiota. Such changes can, in turn, predispose to, and influence, diseases such as: cancer, inflammatory bowel disease, rheumatoid arthritis, psoriasis, bacterial vaginosis and periodontitis. This review presents the state of the evidence on host genetic factors affecting dysbiosis and microbial misrecognition (i.e. an aberrant response to the normal microbiota) and highlights the need for further research in this area.

Objective: To investigate frequency and risk factors for prevalent, incident, and persistent carcinogenic human papillomavirus (HPV) in young women before the introduction of immunisation against HPV types 16 and 18 for schoolgirls., Design: Cohort study, Setting: 20 London universities and further education colleges., Participants: 2185 sexually active female students, mean age 21 years (range 16-27), 38% from ethnic minorities, who took part in the POPI (prevention of pelvic infection) chlamydia screening trial in 2004-08 and who provided duplicate, self taken vaginal swabs and completed questionnaires at baseline. At follow-up, a median of 16 months later, 821 women (38%) returned repeat vaginal swabs by post. In 2009-10, stored samples were tested for HPV., Results: Samples from 404/2185 (18.5% (95% CI 16.9% to 20.2%)) of the cohort were positive for carcinogenic HPV at baseline, including 15.0% (327) positive for non-vaccine carcinogenic genotypes. Reporting two or more sexual partners in the previous year and concurrent Chlamydia trachomatis or bacterial vaginosis were independent risk factors for prevalent vaginal HPV infection. Infection with one or more new HPV types was found in 17.7% (145/821) of follow-up samples, giving an estimated annual incidence of carcinogenic HPV infection of 12.9% (95% CI 11.0% to 15.0%). Incident infection was more common in women reporting two or more partners in the previous year, aged<20, of black ethnicity, or with C trachomatis vaginosis at baseline. Multiple partners was the only independent risk factor for incident infection (adjusted relative risk 1.99 (95% CI 1.46 to 2.72)). Of 143 women with baseline carcinogenic HPV infection, 20 (14% (8.3% to 19.7%) had infection with the same carcinogenic HPV type(s) detected after 12-28 months. Of these women, 13 (65%) had redetected infection with HPV 16 or 18, and nine (45%) with non-vaccine carcinogenic HPV genotypes., Conclusion: In the first UK cohort study of carcinogenic HPV in young women in the community, multiple sexual partners was an independent predictor of both prevalent and incident infection. Infection with non-vaccine carcinogenic genotypes was common. Although current HPV vaccines offer partial cross protection against some non-vaccine carcinogenic HPV types, immunised women will still need cervical screening.

Background: To determine patient and treatment characteristics associated with vitamin D deficiency (VDD) in an UK inner city HIV-1-positive adult cohort., Methods: Two hundred twenty-seven HIV-positive patients attending prospectively for routine blood tests in winter had serum 25-hydroxyvitamin D and parathyroid hormone (PTH) concentrations and other routine chemistry measured. Those with and without VDD were defined as having serum 25-hydroxyvitamin D concentrations <50 nmol/L and >75 nmol/L, respectively. Characteristics were compared between patients with and without VDD. The effects of VDD, tenofovir use, and their interaction on chemical measures were investigated., Results: VDD was found in 57% (131 of 227) of patients. Independent associations included nonwhite ethnicity [adjusted odds ratio (95% confidence interval): 7.40 (2.52 to 21.7)], higher random blood glucose [2.38 (1.24 to 4.57) per mmol/L], higher estimated glomerular filtration rate [eGFR: 1.04 (1.01 to 1.06)], and higher PTH [1.19 (1.00 to 1.42)]. PTH was higher in those receiving tenofovir (median 7.2 pmol/L) than other patients (4.3; P < 0.001) overall, but high PTH with tenofovir occurred only in the context of VDD. Tenofovir use was not associated with serum creatinine or eGFR overall but interacted with vitamin D status (P = 0.05 and P = 0.08, respectively), being linked to somewhat higher creatinine and lower eGFR among patients without VDD but higher eGFR in VDD patients., Conclusions: 25(OH) VDD is associated with tenofovir-linked hyperparathyroidism and also with higher eGFR.

Background: High throughput proteomic technology offers promise for the detection of disease biomarkers and proteomic signature patterns but biomarker discovery studies can be limited by cost factors when large sample size numbers are required. Pooling sera or plasma samples from disease cases potentially offers a solution to cost implications by reducing the standard errors of mass to charge values. Surface enhanced laser desorption/ionization time of flight (SELDI-ToF) mass spectra obtained from individual and pooled sera from invasive aspergillosis cases and controls were compared., Results: Pooling resulted in 50% loss of peak clusters detected in individual samples. Overall, loss was greatest for low intensity clusters. Peak intensities and case:control intensity ratios, among clusters not lost, demonstrated good reproducibility., Conclusion: Pooling sera results in significant potential biomarker loss when using SELDI-ToF MS.

Objective: To identify opportunities for earlier HIV diagnosis within primary and secondary care settings in the UK in Africans with newly diagnosed HIV infection., Methods: A survey of newly diagnosed HIV-positive Africans attending 15 HIV treatment centres across London was conducted between April 2004 and February 2006. The survey consisted of a confidential self-completed questionnaire linked to clinician-completed clinical records., Results: A total of 263 questionnaires were completed, representing an uptake rate of 79.5% of patients approached and 49.8% (131/263) of participants presented with advanced HIV disease (CD4 cell count < 200 cells/mul at diagnosis). In the year prior to HIV diagnosis 76.4% (181/237) had seen their GP, 38.3% (98/256) had attended outpatient services, and 15.2% (39/257) inpatient services, representing missed opportunities for earlier HIV diagnosis. Of those attending GP services the issue of HIV and/or HIV testing was raised for 17.6% (31/176) and 37.1% (78/210) had a previous negative HIV test, 32.5% of these within the UK. Medical attention was sought for wide ranging reasons, often not obviously connected to underlying HIV status. Despite the population predominantly coming from countries of high HIV prevalence personal appreciation of risk was comparatively low and knowledge of benefits of testing lacking., Conclusion: Africans are accessing health services but clinicians are failing to use these opportunities effectively for preventive and diagnostic purposes with regards to HIV infection. Comparatively low appreciation of personal risk and lack of perceived ill health within this community means clinicians need to be more proactive in addressing HIV.

Objective: To examine the effect of early syphilis on blood and semen plasma HIV-1 viral loads and CD4 counts., Methods: In a retrospective case-control study, blood plasma HIV-1 viral loads and CD4 counts in cases during early syphilis (n = 63, 27 receiving antiretroviral therapy) were compared to those before and after syphilis and with controls with non-systemic acute sexually transmitted infections (STI) (n = 104, 39 receiving antiretroviral therapy). In a prospective substudy in those not receiving antiretroviral therapy, semen plasma viral loads during early syphilis (n = 13) were compared with those 1 month, 3 months, and 6 months after treatment for syphilis and with controls with no STIs (n = 20)., Results: Retrospective study: CD4 counts were similar in cases (median 410, n = 139 counts) during early syphilis compared to before (485, n = 80) and after (475, n = 88). In a secondary analysis, a drop in CD4 count (21%) among those with early latent syphilis was observed compared with controls. Blood plasma viral loads did not change significantly overall or in those with primary, secondary, or early latent syphilis. Effects were similar on or off antiretroviral therapy. Prospective study: blood and semen viral loads were slightly higher in cases compared with controls but treatment of early syphilis did not reduce either., Conclusions: We detected no association between early syphilis and changes in blood or semen viral load or CD4 count. Increased HIV-1 infectivity associated with early syphilis is unlikely to be associated with increased levels of HIV-1 RNA in blood or semen.

Objectives: To examine the effects of urethritis and its treatment on semen plasma HIV-1 RNA load in HIV-1 infected men not receiving antiretroviral therapy (ART), in a developed world setting., Methods: Prospective case-control study. HIV-1 infected homosexual men, not receiving ART for at least 3 months, with (cases) and without (controls) symptomatic urethritis, were recruited. Blood and semen were collected for HIV-1 RNA quantification at presentation, before antibiotic therapy, and at 1 and 2 weeks., Results: 20 cases (13 gonococcal urethritis and/or chlamydial urethritis (GU/CU) and seven non-specific urethritis (NSU)) and 35 controls were recruited. Baseline characteristics and blood plasma viral load were similar in cases and controls. Mean log semen plasma viral loads were higher among those with GU/CU compared with controls (4.27 log versus 3.55 log respectively; p = 0.01) but not in those with NSU (3.48 log; p = 0.82). Following antibiotics, semen plasma viral loads fell by a mean of 0.25 log (95% CI: 0.03 to 0.47) in those with GU/CU. Semen plasma viral loads did not fall in those with NSU., Conclusions: In this study of 55 homosexual men not on ART, semen plasma viral loads were approximately fivefold higher in those with GU/CU, but not NSU, compared with controls. Treatment of GU/CU resulted in reduction in semen plasma viral loads. Although absolute effects were considerably lower when compared to patients from a similar study from sub-Saharan Africa, our data demonstrate the potential for sexually transmitted infections to enhance HIV infectivity of men not receiving ART in the developed world.