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Uncertainty in the risk of reproductive complications (pelvic inflammatory disease, ectopic pregnancy, and tubal factor infertility) following chlamydia infection and repeat infection hampers the design of evidence-based chlamydia control programmes. We estimate the association between diagnosed chlamydia and episodes of hospital health care (inpatient, outpatient, and emergency department) for a reproductive complication. We constructed and analysed a retrospective population-based cohort of women aged 15–44 years from administrative records in Denmark (1995–2012). We used a subset of the national Danish Chlamydia Study. The master dataset contains all residents of Denmark (including Greenland) who had a positive chlamydia test recorded by a public health microbiology laboratory from Jan 1, 1992, to Nov 2, 2011. Individuals were randomly matched (by age and sex) to four individuals drawn from the population register (Danish Civil Registration System) who did not have a positive chlamydia test during this interval. The outcomes in the study were hospital episodes of health-care (inpatient, outpatient, and emergency department) with a diagnosis of pelvic inflammatory disease, ectopic pregnancy, or tubal factor infertility. The 516 720 women (103 344 positive, 182 879 negative, 230 497 never-tested) had a mean follow-up of 7·96 years. Compared with women with only negative tests, the risk of each complication was 30% higher in women with one or more positive tests (pelvic inflammatory disease, adjusted hazard ratio [AHR] 1·50 [95% CI 1·43–1·57]; ectopic pregnancy, AHR 1·31 [1·25–1·38]; tubal factor infertility, AHR 1·37 [1·24–1·52]) and 60% lower in women who were never-tested (pelvic inflammatory disease, AHR 0·33 [0·31–0·35]; ectopic pregnancy, AHR 0·42 [0·39–0·44]; tubal factor infertility AHR 0·29 [0·25–0·33]). A positive test had a minor absolute impact on health as the difference in the lifetime incidence of complications was small between women who tested positive and those who tested negative (pelvic inflammatory disease, 0·6%; ectopic pregnancy, 0·2%; tubal factor infertility, 0·1%). Repeat infections increased the risk of pelvic inflammatory disease by a further 20% (AHR 1·20, 95% CI 1·11–1·31). A single diagnosed chlamydia infection increased the risk of all complications and a repeat diagnosed infection further increased the risk of pelvic inflammatory disease. Therefore, control programmes must prevent first and repeat infections to improve women's reproductive health. Unrestricted partial funding from Frederiksberg Kommune, Frederiksberg, Denmark. BD held an Medical Research Council Population Health Scientist Fellowship (G0902120). KT held an National Institute for Health Research Post-Doctoral Fellowship 2009-02-055.

Despite being among the largest and most charismatic species in the marine environment, considerable gaps remain in our understanding of the behavioural ecology of manta rays ( Mobula alfredi , M . birostris ). Manta rays are often sighted in association with an array of smaller hitchhiker fish species, which utilise their hosts as a sanctuary for shelter, protection, and the sustenance they provide. Species interactions, rather than the species at the individual level, determine the ecological processes that drive community dynamics, support biodiversity and ecosystem health. Thus, understanding the associations within marine communities is critical to implementing effective conservation and management. However, the underlying patterns between manta rays, their symbionts, and other hitchhiker species remain elusive. Here, we explore the spatial and temporal variation in hitchhiker presence with M . alfredi and M . birostris throughout the Maldives and investigate the factors which may influence association using generalised linear mixed effects models (GLMM). For the first time, associations between M . alfredi and M . birostris with hitchhiker species other than those belonging to the family Echeneidae are described. A variation in the species of hitchhiker associated with M . alfredi and M . birostris was identified, with sharksucker remora ( Echeneis naucrates ) and giant remora ( Remora remora) being the most common, respectively. Spatiotemporal variation in the presence of manta rays was identified as a driver for the occurrence of ephemeral hitchhiker associations. Near-term pregnant female M . alfredi , and M . alfredi at cleaning stations, had the highest likelihood of an association with adult E . naucrates . Juvenile E . naucrates were more likely to be associated with juvenile M . alfredi , and a seasonal trend in E . naucrates host association was identified. Remora were most likely to be present with female M . birostris , and a mean number of 1.5 ± 0.5 R . remora were observed per M . birostris . It is hoped these initial findings will serve as the basis for future work into the complex relationships between manta rays and their hitchhikers.

Online testing for sexually transmitted infections has a lower unit cost than testing in clinical services and economic analysis has focused on the cost per test and cost per diagnosis in clinics and online. However, online services generate new demand for testing and shift activity between services, requiring system-level analysis to effectively predict cost-effectiveness. Routinely collected, anonymised, retrospective data on sexual health service activity from all specialist services (clinic and online) within an inner London sexual health economy were collated and harmonised to generate a complete dataset of individual level clinic attendances. Clinic activity and diagnoses were coded using nationally standardised codes assigned by clinicians. Costs were taken from locally or regionally agreed sexual health tariffs. The introduction of online services changed patterns of testing. In an inner London sexual health economy, online STI testing increased total number of tests, the total cost of testing and total diagnoses while slightly reducing the average cost per diagnosis. Two years after the introduction of online services 37% of tests in the were provided online and total diagnoses increased. The positivity of online services is generally lower than that in clinics but varies between contexts. Where the positivity ratio between clinic and online is less than the cost ratio, online services will reduce cost per diagnosis. In this analysis, areas with different classifications as urban and rural had different clinic/online positivity ratios changing the cost effectiveness between areas. Even after the introduction of online services, simple STI testing activity continues in clinics and providers should consider online-first options where clinically appropriate. Online services for STI testing are not 'stand alone'. They change STI testing behaviour with impacts on all elements of the sexual health economy. Planning, development and monitoring of such services should reference the dynamic nature of these systems and the role of online services within them.

Background On admission to hospital, patients with community-acquired pneumonia (CAP), undergo extensive diagnostic testing. Two high-throughput laboratory-based PCR panels which return a result in 5.5 hours (h) have been developed to test for pathogens commonly associated with upper (Respiratory 1 Panel) and lower (Respiratory 3 Panel) respiratory tract infections (GeneFirst, Oxford). These could replace multiple diagnostic tests currently used. Methods An online survey, completed by senior clinicians in the UK, France and Spain, was used to collect data on the diagnostic testing of immunocompetent and immunocompromised adults admitted to hospital with CAP, including the cost of diagnostics. Data were used to inform a cost-comparison model. For each country, the average cost of diagnostic testing per patient was calculated separately for immunocompetent and immunocompromised patients. The model compared three testing strategies with standard of care (SoC). In the Panel 1 strategy, the Respiratory 1 Panel was used for patients that would otherwise have tests which could be replaced by Respiratory 1 Panel, equivalent strategies for Respiratory 3 Panel and for both panels combined were assessed. Results In total, 48 surveys were completed (UK = 17; France = 15; Spain = 16). Compared with SoC, the Panel 1 + 3 strategy was most favourable, resulting in cost savings for immunocompetent and immunocompromised patients respectively, of €22.09 (£18.50) and €26.12 (£21.88) in the UK, €99.60 and €108.77 in France and €27.07 and €51.87 in Spain. Conclusion In all three countries, the use of these respiratory panels could reduce the average cost of diagnostics used for patients admitted to hospital with CAP.

The impact of Chlamydia trachomatis (chlamydia) control on the incidence of pelvic inflammatory disease (PID) is theoretically limited by the proportion of PID caused by chlamydia. We estimate the population excess fraction (PEF) of treated chlamydia infection on PID at 12-months in settings with widespread chlamydia control (testing and treatment) and compare this to the estimated PEF of untreated chlamydia. We used two large retrospective population-based cohorts of women of reproductive age from settings with widespread chlamydia control to calculate the PEF of treated chlamydia on PID at 12-months. We undertook a systematic review to identify further studies that reported the risk of PID in women who were tested for chlamydia (infected and uninfected). We used the same method to calculate the PEF in eligible studies then compared all estimates of PEF. The systematic review identified a single study, a randomised controlled trial of chlamydia screening (POPI-RCT). In the presence of testing and treatment <10% of PID at 12-months was attributable to treated (baseline) chlamydia infections (Manitoba: 8.86%(95%CI 7.15-10.75); Denmark: 3.84%(3.26-4.45); screened-arm POPI-RCT: 0.99%(0.00-29.06)). In the absence of active chlamydia treatment 26.44%(11.57-46.32) of PID at 12-months was attributable to untreated (baseline) chlamydia infections (deferred-arm POPI-RCT). The PEFs suggest that eradicating baseline chlamydia infections could prevent 484 cases of PID at 12-months per 100,000 women in the untreated setting and 13-184 cases of PID per 100,000 tested women in the presence of testing and treatment. Testing and treating chlamydia reduced the PEF of chlamydia on PID by 65% compared to the untreated setting. But in the presence of testing and treatment over 90% of PID could not be attributed to a baseline chlamydia infection. More information is needed about the aetiology of PID to develop effective strategies for improving the reproductive health of women.

Nucleic Acid Amplification Tests (NAATs) are the recommended test type for diagnosing Chlamydia trachomatis (chlamydia). However, less sensitive diagnostic methods-including direct immunofluorescence (IF) and enzyme-linked immunoassay (ELISA)-remain in use in lower resourced settings. We estimate the risk of pelvic inflammatory disease (PID) following undiagnosed infection in women tested with non-NAATs and estimate the health gain from using accurate diagnostic tests. We used Denmark's national Chlamydia Study dataset to extract all chlamydia tests performed in women aged 15-34 years (1998-2001). Tests were categorised as non-NAAT (IF/ELISA) or NAAT and limited to each woman's first test in the study period. We linked test data to hospital presentations for PID within 12 months from the Danish National Patient Register. The study included 272,105 women with a chlamydia test, just under half (44.78%, n = 121,857) were tested using NAATs. Overall, 6.38% (n = 17,353) tested positive for chlamydia and 0.64% (n = 1,732) were diagnosed with PID within 12 months. The risk of PID following a positive chlamydia test did not differ by test type (NAAT 0.81% [95% CI 0.61-1.00], non-NAAT 0.78% [0.59-0.96]). The risk of PID following a negative test was significantly lower in women tested with NAATs compared to non-NAATs (0.55% [0.51-0.59] compared to 0.69% [0.64-0.73]; adjusted odds ratio (AOR) 0.83 [0.75-0.93]). We estimate that 18% of chlamydia infections in women tested with a non-NAAT were undiagnosed and that the risk of progression from undiagnosed chlamydia infection to PID within 12 months was 9.52% (9.30-9.68). Using non-NAATs could lead to an excess 120 cases of PID per 100,000 women tested compared to using NAATs. The key limitations of this study are under ascertainment of PID cases, misclassification bias in chlamydia and PID exposure status, bias to the association between clinical presentation and test type and the presence of unmeasured confounders (including other sexually transmitted infection [STI] diagnoses and clinical indication for chlamydia test). This retrospective observational study estimates the positive impact on women's reproductive health from using accurate chlamydia diagnostic tests and provides further evidence for restricting the use of inferior tests. Women with a negative chlamydia test have a 17% higher adjusted risk of PID by 12 months if they are tested using a non-NAAT compared to a NAAT.

ObjectiveTo develop a tool predicting individualised treatment for gonorrhoea, enabling treatment with previously recommended antibiotics, to reduce use of last-line treatment ceftriaxone.DesignA modelling study.SettingEngland and Wales.ParticipantsIndividuals accessing sentinel health services.InterventionDeveloping 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 measuresEstimated 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.ResultsBetween 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.ConclusionsUsing 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.

Detecting hypermethylation of tumour suppressor genes could provide an alternative to liquid-based cytology (LBC) triage within HPV primary cervical screening. The impact of using the QIAsure® FAM19A4/mir124-2 DNA Methylation Test (QIAGEN, N.V, Hilden, Germany) on CIN3+ diagnoses, retention, unnecessary colposcopies, and programme costs is unknown. A decision-tree model was developed to compare LBC with the QIAsure Methylation testing to guide colposcopy referral. Incorporating clinician- and self-sampling pathways the model was informed by the Dutch cervical cancer screening programme, published studies, and manufacturer data. Clinical and cost outcomes were assessed using two scenarios for DNA methylation testing and LBC relative performance. Sensitivity analyses (deterministic and probabilistic) were performed to assess model and parameter uncertainty. A range of self-sampling uptake was assessed in scenario analyses. For the screening cohort (n = 807,269) where 22.1% self-sampled, the number of unnecessary colposcopies and CIN3+ diagnoses varied according to the relative performance of methylation testing and LBC. Irrespective of relative performance, the cost per complete screen was lower and fewer people were lost to follow-up when using DNA methylation testing. The results indicate that, within an HPV primary screening programme that incorporates self-sampling, using the QIAsure Methylation Test for triage reduces the cost per screen compared to LBC.

Background. Human immunodeficiency virus (HIV)–infected people who inject drugs (PWID) frequently encounter barriers accessing and remaining on antiretroviral therapy (ART). Some studies have suggested that opioid substitution therapy (OST) could facilitate PWID's engagement with HIV services. We conducted a systematic review and meta-analysis to evaluate the impact of concurrent OST use on ART-related outcomes among HIV-infected PWID. Methods. We searched Medline, PsycInfo, Embase, Global Health, Cochrane, Web of Science, and Social Policy and Practice databases for studies between 1996 to November 2014 documenting the impact of OST, compared to no OST, on ART outcomes. Outcomes considered were coverage and recruitment onto ART, adherence, viral suppression, attrition from ART, and mortality. Meta-analyses were conducted using random-effects modeling, and heterogeneity assessed using Cochran Q test and I2 statistic. Results. We identified 4685 articles, and 32 studies conducted in North America, Europe, Indonesia, and China were included. OST was associated with a 69% increase in recruitment onto ART (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.32–2.15), a 54% increase in ART coverage (odds ratio [OR], 1.54; 95% CI, 1.17–2.03), a 2-fold increase in adherence (OR, 2.14; 95% CI, 1.41–3.26), and a 23% decrease in the odds of attrition (OR, 0.77; 95% CI, .63–.95). OST was associated with a 45% increase in odds of viral suppression (OR, 1.45; 95% CI, 1.21–1.73), but there was limited evidence from 6 studies for OST decreasing mortality for PWID on ART (HR, 0.91; 95% CI, .65–1.25). Conclusions. These findings support the use of OST, and its integration with HIV services, to improve the HIV treatment and care continuum among HIV-infected PWID.