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BACKGROUND Investigation was undertaken to determine the genetic relatedness of Neisseria gonorrhoeae (NG) isolates of young (

Women are not routinely tested for oropharyngeal Neisseria gonorrhoeae. At present, selective testing based on sexual behaviour or risk groups is advocated by international guidelines. Many oropharyngeal infections are asymptomatic and thus remain undetected, establishing a reservoir for ongoing transmission. Data on effectiveness of routine testing are scarce, thus we aimed to assess the optimal testing strategy for oropharyngeal N gonorrhoeae in women.In this retrospective cohort study, we used surveillance data obtained from all sexually transmitted infection (STI) clinics in the Netherlands between Jan 1, 2008, and Dec 31, 2017. We collected consultation-level data, and individual-level patient data from 2016 onwards, on sociodemographic characteristics, sexual behaviour in the past 6 months, self-reported symptoms, and STI diagnoses. We compared the prevalence of oropharyngeal N gonorrhoeae between women who attended clinics that offered routine universal testing (defined as85% of women tested per clinic-year) and women who attended clinics that offered selective testing (defined as 5-85% of women tested per clinic-year) or incidental testing (5% of women tested per clinic-year). We calculated the number of infections missed by selective testing by extrapolating prevalence for the routine universal testing group to that of weighted and unweighted samples of all selectively tested women. We used multivariable generalised estimating equations to identify independent risk factors for oropharyngeal N gonorrhoeae to identify the optimal selective testing strategy.554 266 consultations with at least one N gonorrhoeae test were recorded, of which 545 750 consultations (including repeat visits) were included in the analyses. Of 545 750 consultations, routine universal testing was used in 57 359 (10·5%), selective testing in 444 283 (81·4%), and incidental testing in 44 108 (8·1%). The prevalence of oropharyngeal N gonorrhoeae was 1·4% (95% CI 1·3-1·5; 703 of 50 962 consultations) in the routine testing group compared with 1·4% (1·3-1·5; 1858 of 132 276) in the selective testing group (p=0·68) and 2·8% (1·9-3·9; 30 of 1088) in the incidental testing group (p0·0001). The prevalence of oropharyngeal-only infections was 47·7% (335 of 703 women) in the routine testing group, 53·3% (991 of 1858) in the selective testing group, and 60·0% (18 of 30) in the incidental testing group. Selective testing would have missed an estimated 4363 (70%; 95% CI 69-71) of all 6221 oropharyngeal N gonorrhoeae infections. Independent risk factors for oropharyngeal N gonorrhoeae were being notified for any STI (adjusted odds ratio 2·1, 95% CI 1·5-3·0), reporting sex work (4·0, 2·3-6·7), and having concurrent genital (51·5, 34·1-77·7) or anorectal (2·6, 1·4-4·8) N gonorrhoeae. Selective testing of women notified for any STI, or who reported sex work, would have led to 5418 (27·8%) of 19 455 women being tested and would have identified 119 (55·6%) of 214 oropharyngeal N gonorrhoeae infections.Selective testing potentially misses more than two-thirds of oropharyngeal N gonorrhoeae infections in women, of whom half have oropharyngeal infections without concurrent genital or anorectal infections. Using independent risk factors for oropharyngeal infection to guide testing is a minimal testing strategy. Routine universal testing is the optimum scenario to detect the majority of infections. However, future studies are needed to assess the cost-effectiveness of routine testing and its effect on antimicrobial resistance.Public Health Service South Limburg.

Background The Chlamydia trachomatis bacterial load could have impact on transmission and sequelae. This is the first study providing comparison of C. trachomatis load at 3 anatomic sites estimated by cycle quantification (Cq) values. Methods Data from 7900 C. trachomatis-positive samples were included (2012–2018). Cq value was used as an inversely proportional measure for C. trachomatis load. Multivariable linear regression analyses assessed differences in mean Cq values. Results Vaginal swabs had the lowest Cq values (31.0) followed by urine (32.5), anorectal swabs (34.0), and oropharyngeal swabs (36.8) (P < .001). Men and women had similar oropharyngeal (36.4 vs 37.3; P = .13) and anorectal (34.2 vs 33.9; P = .19) Cq values. Men (32.2) and women (30.7) aged Conclusions Men and women have a similar C. trachomatis load at extragenital locations arguing for similar transmission potential and clinical relevance. Older patients and HIV-coinfected patients had lower C. trachomatis load, suggesting exposure to previous C. trachomatis infections potentially leading to partial immunity reducing load.

AIMS: Previous uncontrolled studies suggested a possible benefit of intravenous immunoglobulin (IVIg) in parvovirus B19 (B19V)-related dilated cardiomyopathy (DCM). This randomized, double-blind, placebo-controlled, single-centre trial investigated the benefits of IVIg beyond conventional therapy in idiopathic chronic DCM patients with B19V persistence. METHODS AND RESULTS: Fifty patients (39 men; mean age 54 ± 11 years) with idiopathic chronic (>6 months) DCM on optimal medical therapy, left ventricular ejection fraction (LVEF) 200 copies/µg DNA were blindly randomized to either IVIg (n = 26, 2 g/kg over 4 days) or placebo (n = 24). The primary outcome was change in LVEF at 6 months after randomization. Secondary outcomes were change in functional capacity assessed by 6-min walk test (6MWT), quality of life [Minnesota Living with Heart Failure Questionnaire (MLHFQ)], left ventricular end-diastolic volume (LVEDV), and EMB B19V load at 6 months after randomization. LVEF significantly improved in both IVIg and placebo groups (absolute mean increase 5 ± 9%, P = 0.011 and 6 ± 10%, P = 0.008, respectively), without a significant difference between groups (P = 0.609). Additionally, change in 6MWT [median (interquartile range) IVIg 36 (13;82) vs. placebo 32 (5;80) m; P = 0.573], MLHFQ [IVIg 0 (-7;5) vs. placebo -2 (-6;6), P = 0.904] and LVEDV (IVIg -16 ± 49 mL/m2 vs. placebo -29 ± 40 mL/m2 ; P = 0.334) did not significantly differ between groups. Moreover, despite increased circulating B19V antibodies upon IVIg administration, reduction in cardiac B19V did not significantly differ between groups. CONCLUSION: Intravenous immunoglobulin therapy does not significantly improve cardiac systolic function or functional capacity beyond standard medical therapy in patients with idiopathic chronic DCM and cardiac B19V persistence. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID NCT00892112. ispartof: EUROPEAN JOURNAL OF HEART FAILURE vol:23 issue:2 pages:302-309 ispartof: location:England status: published

ObjectivesSpontaneous clearance of Chlamydia trachomatis (CT) infections can occur between diagnosis and treatment. We followed CT patients to assess clearance using a conventional definition (no total CT-DNA, assessed by routine quantitative PCR methods) and a definition accounting for viability, assessed by viability PCR testing.MethodsThree outpatient STI clinics included CT-diagnosed women (The Netherlands, 2016–2017, FemCure study); participants had vaginal CT (vCT) and rectal CT (rCT) (group A: n=155), vCT and were rectally untested (group B: n=351), single vCT (group C: n=25) or single rCT (group D: n=29). Follow-up (median interval 9 days) vaginal and rectal samples underwent quantitative PCR testing (detecting total CT-DNA). When PCR positive, samples underwent V-PCR testing to detect ‘viable CT’ (CT-DNA from intact CT organisms; V-PCR positive). ‘Clearance’ was the proportion PCR-negative patients and ‘clearance of viable CT’ was the proportion of patients testing PCR negative or PCR positive but V-PCR negative. We used multivariable logistic regression analyses to assess diagnosis group (A–D), age, days since initial CT test (diagnosis) and study site (STI clinic) in relation to clearance and clearance of viable CT.ResultsClearance and clearance of viable CT at both anatomic sites were for (A) 0.6% and 3.9%; (B) 5.4% and 9.4%; (C) 32.0% and 52.0% and (D) 27.6% and 41.4%, respectively. In multivariate analyses, women with single infections (groups C and D) had higher likelihood of clearance than women concurrently infected with vCT and rCT (pOf rectally untested women (group B), 76.9% had total CT-DNA and 46.7% had viable CT (V-PCR positive) at the rectal site.ConclusionsOf untreated female vCT patients who had CT also at the rectal site, or who were rectally untested, only a small proportion cleared CT (in fact many had viable CT) at their follow-up visit (median 9 days). Among single site infected women clearance was much higher.Trial registration numberNCT02694497.

ObjectivesIn recent years, studies have demonstrated frequent rectal Chlamydia trachomatis (CT) detection in women, irrespective of reported anal sex or rectal symptoms. However, the clinical relevance and public health implication of rectal CT detection in women remain under debate. Therefore, evaluating CT viability may provide more insight into the relevance of standard routine nucleic acid amplification test (NAAT)–positive results.MethodsIn this cross-sectional explorative study, a convenience sample of female patients at our STI clinic aged 18 years or older, diagnosed with vaginal and/or rectal CT, were invited to participate. On return for treatment, rectal CT-diagnosed women were instructed to self-collect rectal swab samples before being treated. Standard COBAS 4800 CT/NG routine NAAT testing was applied for CT diagnosis. Rectal viable CT load was evaluated by using viability-PCR (V-PCR).Results53 women with rectal CT were included in this study; 86.8% (46/53) had a quantifiable rectal total CT load. Of women with quantifiable samples, 52.2% (24/46) had viable CT detected from rectal swabs by V-PCR, with a mean rectal viable CT load of 3.31 log10 CT/mL (range 1.16–6.22). No statistically significant difference (p=0.73) was observed in the mean rectal viable CT load of women with an indication for rectal testing (n=9) and without (n=15), 3.20 log10 CT/mL (range 2.06–4.36) and 3.38 log10 CT/mL (range 1.16–6.22), respectively. CT culture yielded positive test results from rectal swabs in 22.6% (12/53) of rectal CT NAAT-diagnosed women. Of women with viable rectal CT by V-PCR (n=24), 50% (12/24) were positive by CT culture.ConclusionsOverall, the detection of high rectal viable CT loads in this study indicates that rectal CT in some women might represent a currently ongoing infection rather than just the presence of remnant DNA from dead bacteria or only contamination from an active vaginal CT infection.

BackgroundChlamydia trachomatis (CT) is routinely diagnosed by nucleic acid amplification tests (NAATs), which are unable to distinguish between nucleic acids from viable and non-viable CT organisms.ObjectivesWe applied our recently developed sensitive PCR (viability PCR) technique to measure viable bacterial CT load and explore associated determinants in 524 women attending Dutch sexual health centres (STI clinics), and who had genital or rectal CT.MethodsWe included women participating in the FemCure study (Netherlands, 2016–2017). At the enrolment visit (pre-treatment), 524 were NAAT positive (n=411 had genital and rectal CT, n=88 had genital CT only and n=25 had rectal CT only). We assessed viable rectal and viable genital load using V-PCR. We presented mean load (range 0 (non-viable) to 6.5 log10 CT/mL) and explored potential associations with urogenital symptoms (coital lower abdominal pain, coital blood loss, intermenstrual bleeding, altered vaginal discharge, painful or frequent micturition), rectal symptoms (discharge, pain, blood loss), other anatomical site infection and sociodemographics using multivariable regression analyses.ResultsIn genital (n=499) CT NAAT-positive women, the mean viable load was 3.5 log10 CT/mL (SD 1.6). Genital viable load was independently associated with urogenital symptoms—especially altered vaginal discharge (Beta=0.35, p=0.012) and with concurrent rectal CT (aBeta=1.79; p10 CT/mL (vs 3.3 in women without symptoms). Of 436 rectal CT NAAT-positive women, the mean rectal viable load was 2.2 log10 CT/mL (SD 2.0); rectal symptoms were reported by 2.5% (n=11) and not associated with rectal viable load.ConclusionAmong women diagnosed with CT in an outpatient clinical setting, viable genital CT load was higher in those reporting urogenital symptoms, but the difference was small. Viable genital load was substantially higher when women also had a concurrent rectal CT.Trial registration numberClinicalTrials.gov NCT02694497.

Purpose: The putative presence of SARS-CoV-2 in ocular specimen puts healthcare workers at risk. We thoroughly examined conjunctival swabs and tear fluid in a large cohort of COVID-19 patients. Methods: A total of 243 symptomatic laboratory-confirmed COVID-19 patients were included in this observational multicenter study. Conjunctival swabs were analyzed by reverse transcription polymerase chain reaction for detection of SARS-CoV-2 RNA. Next-generation sequencing and phylogenetic analysis were performed to identify viral strains and to determine tissue tropism. Schirmer tear samples from 43 hospitalized COVID-19 patients and 25 healthy controls were analyzed by multiplex cytokine immunoassays. Results: Viral SARS-CoV-2 RNA was detected in conjunctival swabs from 17 (7.0%) of 243 COVID-19 patients. Conjunctival samples were positive for viral SARS-CoV-2 RNA as long as 12 days after disease onset. Cycle threshold (Ct) values for conjunctival swabs (mean 34.5 +/- 5.1) were significantly higher than nasopharyngeal swabs (mean 16.7 +/- 3.6). No correlation between Ct values of conjunctival and nasopharyngeal swabs was observed. The majority of positive conjunctival samples were detected only once and primarily during the first visit. Next-generation sequencing analysis revealed that the virus strain found in the conjunctiva was most often identical to the one found in the nasopharynx. Tear cytokine levels IL-1 beta and IL-6 were elevated in COVID-19 patients compared to healthy controls. Conclusions: Conjunctival samples that were positive for SARS-CoV-2 RNA contained the same viral strain as the nasopharynx. Translational Relevance: The presence of SARS-CoV-2 viral RNA and elevated cytokines in tear fluid confirm the involvement of the ocular surface in COVID-19 disease.

Background Nucleic acid amplification tests (NAATs) have revolutionized our ability to diagnose Chlamydia trachomatis (CT). Sometimes, in addition, assessment of CT viability would help to gain more insight in the clinical impact of a positive NAAT. Methods to assess the CT viability have become available in research settings (e.g. viability-PCR; V-PCR). Here we assess viability in six different anatomic sites in women. Methods Immediately prior to treatment (STI clinic South Limburg), 28 vaginal NAAT-CT-positive (COBAS4800 CT/NG) adult women, were included in the ‘CHLAMOUR’ study. We used V-PCR to assess CT viable load (log10 CT/ml) in same clinician taken standardized samples from the cervix, vagina, perineum, anus, optional rectum, and pharynx. Mean loads were compared using t-tests. Results Twenty-eight women were included of whom 68% (19/28) consented to proctoscopic examination (rectal). NAAT-CT-positive rate was 75% for cervix, 79% vagina, 64% perineum, 64% anus, 74% rectum, and 21% for pharynx. Viable load was detected in 90% (19/21) CT positive cervix, 77% (17/22) vagina, 11% (2/18) perineum, 61% (11/18) anal, 93% (13/14) rectal, and 0% (0/6) pharynx samples. The mean viable load was marginally higher in cervical compared to vaginal samples (4.37 [SD:1.35] vs. 3.45 [SD:1.05], p=0.055). Mean viable load was higher in rectal compared to anal samples (3.51 [SD:0.51] vs. 2.70 [SD:0.42], p=0.01). Viable load was 2.72 [SD:1.69] CT positive perineum samples. Conclusions The amount of viable CT varied by anatomic site, and were highest ‘upward in the body’, which is thus likely to represent actual site of infection. Still, the vaginal and anal sites (that are usually self-sampled) had high concordance with the cervical and rectal sites. CT at the perineum may indicate autoinoculation. Notably, the presence of viable CT in anorectal samples indicated the presence of an active anorectal infection, which should be accounted for in comprehensive CT management.

Background Anorectal infections with Chlamydia trachomatis (CT) are prevalent in women visiting STI-clinics. In women, azithromycin treatment in anorectal chlamydia is unsuccessful in about 20%, with the potential of subsequent re-infection of the vagina through autoinoculation. We evaluated the risk for incident urogenital CT, by exposure from the own anorectal site and exposure by sex; and similarly evaluated risks for incident anorectal CT. Methods Prospective multicenter cohort study, FemCure. At 4, 6, 8, 10, and 12 weeks after azithromycin or doxycycline CT treatment, women self-collected anorectal and urogenital swabs for CT-DNA testing. We calculated the proportion with incident CT, at week 6–12, by 2-week time-periods. Compared to no exposure (A), risk of incident urogenital CT was estimated for sexual exposure (B), anorectal CT exposure (C), and both exposures (D), adjusted for confounders by adjusted odds ratios (OR) and 95% confidence intervals (CI). We similarly assessed incident anorectal CT. Results Data comprised 385 participants contributing 1540 two-week periods. Urogenital incidence was 3·3% (47/1428) [95%CI: 2·4–4·4]; 0·7% (A), 1·9% (B), 13·9% (C), and 25·4 (D). ORs were: 2·7 [95%CI:0·9–8·6] (B), 21·8 [95%CI:6·7–70·7] (C), 49·7 [95%CI:15·4–160·4] (D). Anorectal incidence was 2·9% (39/1343) [95CI:1·8–3·6]; 1·3% (A), 1·3% (B), 27·8% (C), and 36·7% (D). ORs were: 0·91 [95%CI:0·32–2·60] (B), 26·0 [95%CI:7·16–94·34] (C), 44·3 [95%CI:14·4–136·2] (D). Of incident CT, 55% urogenital and 70% anorectal infections persisted (>two weeks). Conclusion Between 6–12 weeks after initial treatment, the risk for incident urogenital CT in women increased when women had a recent anorectal CT, especially when also sex was reported. Likewise, the risk for incident anorectal CT increased with urogenital CT and sex exposure. Findings may suggest a key role for auto-inoculation in the re-establishment or persistence of urogenital and anorectal chlamydia infections in treated women, especially in case of suboptimal initial treatment or lack of anorectal testing.

One Health (OH) is an increasingly popular approach for addressing antimicrobial resistance (AMR) which is often presented as a shared health concern at the interface of human-animal-environment relations. OH is widely adopted as a framework for collaboration between organisations like the World Health Organisation and the World Organisation for Animal Health; furthermore it occupies a central position in international AMR policy documents. Scholars like Craddock and Hinchliffe have raised questions about whether a unified OH understanding of health allows us to comprehend the diversity of practices and knowledge involved in interdisciplinary and interorganisational collaborations. In this article, we aim to explore how the OH idea as a shared health concern is conceptualised in international responses to AMR. Therefore, we conducted a constructivist policy analysis of two types of international policy documents–11 documents dedicated to AMR and a OH approach to it, and 12 documents with a focus on more general health issues that AMR regulations are built upon. The analysis of this policy arena makes clear that both sets of documents put human health at the centre, while the animal and environmental sectors are primarily framed as a risk for human health. Although human health is, more or less explicitly, considered to be the main problem, the animal and environmental health sectors are assigned responsibility for addressing this problem. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

ObjectivesMost international STI guidelines recommend Chlamydia trachomatis anorectal testing in women after self-reported sexual exposure or symptoms in women. However, it has been shown that the prevalence of anorectal C. trachomatis is as high (7%–17 %) in women who do not report anorectal intercourse (AI) as in women who do. This study assessed the correlation between the genital and anorectal C. trachomatis load in concurrently infected women for increased microbiological insight.MethodsA convenience sample of 105 women with a concurrent (genital and anorectal) C. trachomatis infection was included from the STI clinic in South Limburg, the Netherlands. Women provided self-collected vaginal and anorectal swabs. The C. trachomatis load was quantified with qPCR and the human cell load was assessed to ensure sample adequacy. Genital and anorectal C. trachomatis loads were divided into tertiles for comparison. The χ2 test and linear regression were used to compare genital and anorectal C. trachomatis loads and identify determinants associated with load.ResultsThe overall median C. trachomatis load was higher in genital (median 5.3 log10C. trachomatis/ml) than anorectal samples (median 3.4, p ≤ 0.001), but both loads were within the same range. The genital and anal load categories were not related within one woman (p = 0.99), both in women with and without AI. The anorectal C. trachomatis load was in the same or higher load category than the genital load in 56% of women without AI, and 79% of women with AI.ConclusionsAlthough no cut-off for clinical relevance is known, an anorectal C. trachomatis load in the same or higher load category than the genital C. trachomatis load is likely to be clinically relevant. Other measurements should also be taken into account, such as leucocytes or bacterial viability to distinguish infection from contamination or exposure.

ObjectiveChlamydia trachomatis(CT) andNeisseria gonorrhoeae(NG) infections can clear without treatment. Despite high prevalence of anorectal infections in men who have sex with men (MSM) and women, studies on anorectal clearance are scarce. Moreover it is unknown whether bacterial load affects urogenital/anorectal CT clearance. In this prospective cohort study, CT and NG clearance is assessed at three anatomical sites of men and women.MethodsCT-positive and NG-positive MSM, heterosexual men and women ≥18 years of age visiting our STI clinic between 2011 and 2013 underwent a repeat test when returning for treatment (n=482). The primary outcome was clearance, defined as a positive nucleic acid amplification test (NAAT) at screening-consultation, followed by a negative NAAT at treatment-consultation. Sociodemographics, sexual risk behaviour and CT bacterial load (inhouse quantitative PCR) were tested as determinants for clearance using multivariable logistic regression for CT and Fisher’s exact test for NG.ResultsCT clearance was 9.1% (10/110) for urine, 6.8% (20/292) for vaginal swabs, 12.7% (8/63) for anorectal swabs (ie, 4.0% [1/25] in MSM and 18.4% [7/38] in women) and 57.1% (4/7) for oropharyngeal swabs. For NG this was 33.3% (2/6), 28.6% (2/7), 20.0% (2/10) and 27.3% (6/22), respectively. The number of days between tests (median 10, IQR 7–14) was not associated with clearance. Lower bacterial load at screening was the only predictor for CT clearance (urine mean 1.2 vs 2.6 log CT/mL, p=0.001; vaginal swabs mean 2.1 vs 5.2 log CT/mL pConclusionsThis study reports the largest number of anorectal infections tested for CT and NG clearance to date. Clearance in all sample types was substantial: between 7% and 57% for CT, and between 20% and 33% for NG (notwithstanding low absolute numbers). CT clearance was associated with a lower load at screening. However, not all individuals with low bacterial CT load cleared the infection, hampering STI guideline change.

ObjectivesPathogen load has been linked to disease severity in patients infected with HIV, resulting in international standards to adequately and reproducibly quantify load.Chlamydia trachomatis(CT) load has been inconsistently linked to disease severity since extensive differences exist in quantification methods (14 methods in 28 articles). Differences include normalisation for human cell load due to CT’s intracellular nature, despite the inability to distinguish inflammatory cells from epithelial cells with molecular techniques. We compared the human cell load in CT-positive men and women at the genital and anal site to a CT-negative control group to estimate the impact of inflammatory cells in these samples.Methods188 women (tested at genital and anal site) and 519 men (207 tested at the anal site and 312 tested at the urogenital site) were included from our STI-clinic in the Netherlands. Specimens were self-collected vaginal swabs, anal swabs and urine samples. Quantitative-PCR targeting the HLA-gene quantified human cell load. Mann-Whitney-U-test was used for statistical analyses.ResultsThe genital cell load had a similar range and median (6.5 log10) between CT-negative and CT-positive women . The urogenital cell load was significantly higher than the anal cell load (median 3.6 log10). The anal cell load was significantly higher in men with- than without anal CT infection (median 4.5 versus 3.9 respectively). The anal cell load is significantly higher in CT-positive men than in women. Both Neisseria gonorrhoeae-co-infections and reported anal intercourse significantly increased the human cell load in anal samples.ConclusionStandardisation in CT load studies is necessary as current studies show 14 different quantification methods in 28 studies . In this study we demonstrate the inappropriateness of normalising the CT load for the human cell load using molecular techniques, as the presence of inflammatory cells cannot be excluded.

Sexual healthcare aims to reduce HIV and sexually transmitted infections (STIs) by promoting testing and prevention. To better reach men who have sex with men (MSM), additional strategies are needed. Here, we describe development of an intervention, which is part of a broader HIV/STI home-care program, targeted to reach MSM and motivate them to use self-sampling tests. Self-sampling includes blood sampling (finger prick) for HIV, hepatitis B, and syphilis, and a urine sample and oral and anorectal swab samples for chlamydia and gonorrhea. Intervention mapping, a systematic six-step approach, was used to guide the development process: (1) needs assessment including interviews with MSM, (2) create a matrix of change, (3) selection of theory-based methods and practical strategies, (4) intervention development, (5) implementation plan, and (6) evaluation (not included in this paper). Stakeholders were involved to increase program support and feasibility. The needs assessment revealed that testing barriers among MSM related to stigma, time, and privacy concerns. Barriers among healthcare providers related to time, competing priorities, lack of expertise, and guideline restrictions. Included intervention components are designed to overcome these barriers, e.g., engaging role models, with a website with a role model story, and providing tailored information. Methods to reach MSM were a variety of information channels (posters, flyers, and audio-visual displays) and delivery modes, such as advertisements on websites and invitational cards (online and paper) distributed by healthcare providers and MSM themselves (social network testing/peer testing). Our intervention aims to encourage MSM to engage in testing, re-testing, and providing a test to peer MSM. Evidence-based methods to overcome barriers were included to reach and motivate an increased number of MSM. Using intervention mapping stimulated systematic evidence-based decision making and adapting the intervention to the target audience and setting. The next step (step 6) is to implement and evaluate the intervention.

Antimicrobial resistance control programmes often aim to “fix” the behaviour of antibiotic users and prescribers. Such behavioural interventions have been widely criticised in social science literature for being inefficient and too narrow in scope. Drawing on these criticisms, this article analyses how political programmes for fixing antibiotic behaviours were adapted into the practices of health‐care professionals and patients in Russia. In 2018, we conducted interviews with medical doctors, pharmacists and patients in a Russian city; focusing on their practices around the policy requirement introduced in 2017 which obligated medical prescriptions of antibiotics. We conceptualised the obligatory medical prescription as a political technique which sought to change practices of self‐treatment and over‐the‐counter sales of medications by establishing doctors as an obligatory passage point to access antibiotics. Our analysis shows that the requirement for medical prescriptions does not fulfil the infrastructural gaps that influence antibiotic practices. By navigating the antibiotic prescriptions, doctors, pharmacists and patients informally compensate for the gaps in the existing infrastructure creating informal networks of antibiotic care parallel to the requirement of obligatory prescriptions. Following these informal practices, we could map the inconsistencies in the current policy approaches to tackle AMR as a behavioural rather than infrastructural problem.

Oropharyngeal Chlamydia trachomatis (CT) infections and, especially, Neisseria gonorrhoeae (NG) infections are common, but few commercial nucleic acid amplification tests (NAAT5) specify extragenital samples for intended use. The test characteristics of the cobas 4800 CT/NG assay were evaluated for oropharyngeal swabs. The technical validation included analysis of the specificity, sensitivity, dynamic range, linearity, efficiency, and precision. The probability of detection curve combined with historical data enabled the estimation of potentially missed diagnoses. A clinical evaluation was performed on a subset of 2,798 clinical samples available from routine diagnostics. Results of the cobas 4800 were compared with those from in-house C. trachomatis/N. gonorrhoeae PCR assays. Discrepant samples were tested with resolver assays, and these results were considered decisive. No cross- reactivity was seen in the analytical specificity analysis. High linearity (R-2 >= 0.983), efficiency (89% to 99%), and precision (cycle threshold [C-T] value of 0.1 to 0.9) were seen for both C. trachomatis and N. gonorrhoeae. The limit of detection in oropharyngeal samples was 3.2 x 10(2) inclusion-forming units (IFU)/ml for C. trachomatis and 6.7 x 10(2) CFU/ml for N. gonorrhoeae. Estimates on potentially missed diagnoses were up to 7.2% for C. trachomatis and up to 24.7% for N. gonorrhoeae. Clinical sensitivity and specificity were evaluated with 25 C. trachomatis-positive, 86 N. gonorrhoeae-positive, and 264 negative samples, resulting in 100% and 99.6% for C. trachomatis and 100% and 96.7% for N. gonorrhoeae, respectively. The findings in this study demonstrate the utility of the cobas 4800 CT/NG assay for oropharyngeal samples. Despite its being a highly accurate test, the range of reported C-T values, especially for N. gonorrhoeae, suggests relatively low oropharyngeal loads. Hence, consistent detection over the full range of oropharyngeal loads could be impaired.

Chlamydia trachomatis (CT) increases its plasmid numbers when stressed, as occurs in clinical trachoma samples. Most CT tests target the plasmid to increase the test sensitivity, but some only target the chromosome. We investigated clinical urogenital samples for total plasmid copy numbers to assess its diagnostic value and intra-bacterial plasmid copy numbers to assess its natural variation. Both plasmid and chromosome copies were quantified using qPCR, and the plasmid:chromosome ratio (PCr) calculated in two cohorts: (1) 383 urogenital samples for the total PCR (tPCr), and (2) 42 vaginal swabs, with one half treated with propium-monoazide (PMA) to prevent the quantification of extracellular DNA and the other half untreated to allow for both tPCr and intra-bacterial PCr (iPCr) quantification. Mann–Whitney U tests compared PCr between samples, in relation to age and gender. Cohort 1: tPCr varied greatly (1–677, median 16). Median tPCr was significantly higher in urines than vaginal swabs (32 vs. 11, p

Neisseria gonorrhoeae is a common bacterial sexually transmitted infection (STI). Currently, there are limited data on the bacterial load in both men and women and on both genital and extragenital sites. Therefore, we quantified N. gonorrhoeae bacterial loads in a large population of women, heterosexual men, and men who have sex with men (MSM) at three different anatomical sites. N. gonorrhoeae-positive samples (n = 1265) of STI clinic consultations (n = 944) were tested for N. gonorrhoeae with the Roche Cobas 4800 system, and quantification cycle (Cq) values were used as an inversely proportional measure for N. gonorrhoeae bacterial load after interpolation from a standard curve. Bacterial loads were compared between sample materials and sexes using t tests. The following mean N. gonorrhoeae loads were observed: urine, 4.5 +/- 1.0 log(10) CFU/ml; vaginal swabs, 4.3 +/- 1.1 log(10) CFU/ml; anorectal swabs (women), 4.0 +/- 1.2 logic, CFU/ml; anorectal swabs (men), 4.5 +/- 1.3 log(10) CFU/ml; oropharyngeal swabs (women), 2.8 +/- 0.9 log(10) CFU/ml; and oropharyngeal swabs (men), 3.2 +/- 1.0 log(10) CFU/ml. Oropharyngeal swabs had a significantly lower N. gonorrhoeae load (P

We assessed whether patients repeatedly infected with Chlamydia trachomatis (CT) have a lower urogenital or anorectal CT load. A CT-positive retest was independently associated with higher vaginal and higher urine Cq values (P

Purpose: To assess enzymatic digestion rate after Riboflavin (RF) and Water-Soluble-Taurine (WST11) based corneal cross-linking (CXL), with or without the addition of high molecular weight dextran (RF-D and WST-D).Methods: Eighty-eight paired porcine corneas were cross-linked by either RF (n = 11) or RF-D (n = 11) and ultraviolet light (UVA), or WST11 (n = 11) or WST-D (n = 11) and near-infrared (NIR) light, or used as paired control (n = 44). Corneal buttons of treated and paired control eyes were placed in a 0.3% collagenase solution. Time to full digestion and remaining dry sample weight after six hours were compared.Results: A strong treatment effect was seen with all four formulations, as all controls had been fully digested whilst all treated samples were still visible at the experiment's endpoint. After irradiation, central corneal thickness was significantly higher in samples treated with hypo-osmolar formulations, compared to dextran enriched formulations (P < 0.001). Dry sample weight after digestion was nonsignificantly different between corneas treated by the four different formulations (P = 0.102). Average dry sample weight was 1.68 ± 0.6 (n = 10), 2.19 ± 0.50 (n = 8), 1.48 ± 0.76 (n = 11), and 1.54 ± 0.60 (n = 9) mg, for RF, RF-D, WST11, and WST-D treated samples, respectively. Enzymatic resistance was similar for RF and WST based CXL (P = 0.61) and was not affected by the addition of dextran (P = 0.221).Conclusions: Both RF and WST11 based CXL significantly increases resistance to enzymatic digestion, with similar effect for hypo-osmolar and hyperosmolar (dextran enriched) formulations.Translational Relevance: Our findings indicate these formulations are interchangeable, paving the way for the development of novel PACK-CXL protocols for thin corneas and deep-seated infections.

Background The Dutch province of Limburg borders the German district of Heinsberg, which had a large cluster of COVID-19 cases linked to local carnival activities before any cases were reported in the Netherlands. However, Heinsberg was not included as an area reporting local or community transmission per the national case definition at the time. In early March, two residents from a long-term care facility (LTCF) in Sittard, a Dutch town located in close vicinity to the district of Heinsberg, tested positive for COVID-19. In this study we aimed to determine whether cross-border introduction of the virus took place by analysing the LTCF outbreak in Sittard, both epidemiologically and microbiologically. Methods Surveys and semi-structured oral interviews were conducted with all present LTCF residents by health care workers during regular points of care for information on new or unusual signs and symptoms of disease. Both throat and nasopharyngeal swabs were taken from residents suspect of COVID-19, based on regional criteria, for the detection of SARS-CoV-2 by Real-time Polymerase Chain Reaction. Additionally, whole genome sequencing was performed using a SARS-CoV-2 specific amplicon-based Nanopore sequencing approach. Moreover, twelve random residents were sampled for possible asymptomatic infections. Results Out of 99 residents, 46 got tested for COVID-19. Out of the 46 tested residents, nineteen (41%) tested positive for COVID-19, including 3 asymptomatic residents. CT-values for asymptomatic residents seemed higher compared to symptomatic residents. Eleven samples were sequenced, along with three random samples from COVID-19 patients hospitalized in the regional hospital at the time of the LTCF outbreak. All samples were linked to COVID-19 cases from the cross-border region of Heinsberg, Germany. Conclusions Sequencing combined with epidemiological data was able to virtually prove cross-border transmission at the start of the Dutch COVID-19 epidemic. Our results highlight the need for cross-border collaboration and adjustment of national policy to emerging region-specific needs along borders in order to establish coordinated implementation of infection control measures to limit the spread of COVID-19.

Background Repeat Chlamydia trachomatis (CT) infections are common. To better understand the characteristics of patients frequently infected with CT at our sexually transmitted infection (STI) care services, we assessed the differences between patients repeatedly infected with CT and those who repeatedly tested negative. Methods In this cross-sectional analysis of cohort data, we assessed individuals tested for CT at different STI care providers between 2011 and mid-2018 in Southwest Limburg, the Netherlands (n = 17,616). Patients with ≥2 repeat CT infections in the study period were categorized as “patients with repeat CT infections.” Multivariable logistic regression analyses were performed for the binary outcome measure: patients with repeat CT infections versus patients who repeatedly tested negative (reference group). Additional analyses were performed for only the STI clinic population. Results Patients aged Neisseria gonorrhoeae (NG) (OR: 5.04; 95%CI: 3.33–7.63) had more repeat CT infections. In additional analyses among exclusively STI clinic visitors, patients with urogenital symptoms (OR: 2.17; 95%CI: 1.41–3.35), and patients notified for STIs (OR: 4.55; 95%CI: 3.17–6.54) had more frequent repeat CT infections. Conclusions Patients aged

Objectives Maintenance treatment with macrolide antibiotics has shown to be effective in reducing exacerbations in COPD patients. A major concern with prolonged treatment with antibiotics is the development of bacterial resistance. In this study we determined the effect of azithromycin on the development and acquisition of resistance to macrolides in the nasopharyngeal flora in COPD patients. Methods This study was part of the COLUMBUS trial, a randomised, double-blind, placebo-controlled trial to measure the effect of maintenance treatment with azithromycin in 92 COPD patients on the exacerbation rates during a 12-month period. In order to determine resistance to macrolides, we used a targeted metagenomic approach to measure the presence and relative abundance of specific macrolide resistance genes ermB, ermF and mefA in throat samples collected at different time-points during this 12-month period. Results There was no increased risk for acquisition of macrolide resistance genes in the azithromycin group compared to the placebo group in COPD patients. However, loss of the macrolide resistance gene ermB was increased overtime in the placebo treated group compared to the azithromycin group (n = 5 for the placebo group versus n = 0 for the azithromycin group at 12 months; p = 0.012). The change in relative abundance of the three macrolide-resistance genes showed that all but one (ermF) increased during treatment with azithromycin. Conclusions The acquisition rate of macrolide resistance genes in COPD patients treated with azithromycin maintenance therapy was limited, but the relative abundance of macrolide resistance genes increased significantly over time compared to placebo. This study was part of the COLUMBUS trial (Clinicaltrials.gov, NCT00985244).

We applied our recently developed sensitive PCR (viability PCR) technique to measure viable bacterial CT load and explore associated determinants in 524 women attending Dutch sexual health centres (STI clinics), and who had genital or rectal CT.We included women participating in the FemCure study (Netherlands, 2016-2017). At the enrolment visit (pre-treatment), 524 were NAAT positive (n=411 had genital and rectal CT, n=88 had genital CT only and n=25 had rectal CT only). We assessed viable rectal and viable genital load using V-PCR. We presented mean load (range 0 (non-viable) to 6.5 logIn genital (n=499) CT NAAT-positive women, the mean viable load was 3.5 logAmong women diagnosed with CT in an outpatient clinical setting, viable genital CT load was higher in those reporting urogenital symptoms, but the difference was small. Viable genital load was substantially higher when women also had a concurrent rectal CT.ClinicalTrials.gov NCT02694497.

We assessed whether patients repeatedly infected with Neisseria gonorrhoeae (NG) were different compared to patients repeatedly tested negative, to obtain insight into the characteristics of patients frequently tested and infected with NG. All patients tested for NG (n = 16,662) between January 2011 and July 2018 were included. Multivariable logistic regression analyses were performed for the outcomes &ldquo, repeat NG infections&rdquo, and &ldquo, once NG positive and not retested&rdquo, versus patients &ldquo, repeatedly tested NG negative&rdquo, Of the individuals tested for NG, 0.2% (40/16,662) had repeat (&ge, 2) NG infections, and accounted for 23% of all diagnosed NG infections. STI clinic patients, men (mostly men who have sex with men (MSM)), patients aged &ge, 25 years, and patients co-infected with HIV or Chlamydia trachomatis (CT) more often had repeat NG infections. The number of patients not retested after their initial NG diagnosis was 29.9% (92/308). Men (mostly MSM), HIV positive patients, and patients notified for sexually transmitted infections (STIs) were more often NG positive and not retested. Concluding, only 40 patients tested for NG accounted for one in four diagnosed NG infections. However, re-infections are likely to be missed among MSM and HIV positive patients, as they were mainly not retested after NG infection. It remains important to test and re-test for NG, especially in MSM, in order to halt transmission.

Prospective studies are key study designs when attempting to unravel health mechanisms that are widely applicable. Understanding the internal validity of a prospective study is essential to judge a study's quality. Moreover, insights in possible sampling bias and the external validity of a prospective study are useful to judge the applicability of a study's findings. We evaluated participation, retention, and associated factors of women in a multicenter prospective cohort (FemCure) to understand the study's validity.Chlamydia trachomatis (CT) infected adult women, negative for HIV, syphilis, and Neisseria gonorrhoeae were eligible to be preselected and included at three sexually transmitted infection (STI) clinics in the Netherlands (2016-2017). The planned follow-up for participants was 3 months, with two weekly rectal and vaginal CT self-sampling and online questionnaires administered at home and at the clinic. We calculated the proportions of preselected, included, and retained (completed follow-up) women. Associations with non-preselection, noninclusion, and non-retention (called attrition) were assessed (logistic and Cox regression).Among the 4,916 women, 1,763 (35.9%) were preselected, of whom 560 (31.8%) were included. The study population had diverse baseline characteristics: study site, migration background, high education, and no STI history were associated with non-preselection and noninclusion. Retention was 76.3% (n = 427). Attrition was 10.71/100 person/month (95% confidence interval 9.97, 12.69) and was associated with young age and low education. In an outpatient clinical setting, it proved feasible to include and retain women in an intensive prospective cohort. External validity was limited as the study population was not representative (sampling bias), but this did not affect the internal validity. Selective attrition, however (potential selection bias), should be accounted for when interpreting the study results.

Diagnostics, including those that work at point-of-care, are an essential part of successful public health responses to infectious diseases and pandemics. Yet, they are not always used or fit intended use settings. This paper reports on key insights from a qualitative study on how those engaged with developing and implementing new point-of-care (POC) diagnostics for tuberculosis (TB) and HIV ensure these technologies work at POC. Ethnographic fieldwork between 2015 and 2017 consisting of 53 semistructured interviews with global stakeholders and visits to workshops, companies, and conferences was combined with 15 semistructured interviews with stakeholders in India including providers, decision-makers, scientists and developers and visits to companies, clinics and laboratories. Our results show how developers and implementer of HIV and TB POC diagnostics aim to know and align their diagnostics to elements in more settings than just intended use, but also the setting of the developer, the global intermediaries, the bug/disease and the competitor. Actors and elements across these five settings define what a good diagnostic is, yet their needs might conflict or change and they are difficult to access. Aligning diagnostics to the POC requires continuous needs assessment throughout development and implementation phases as well as substantive, ongoing investment in relationships with users. The flexibility required for such continuous realigning and iteration clashes with established evaluation procedures and business models in global health and risks favouring certain products over others. The paper concludes with suggestions to strengthen this alignment work and applies this framework to research needs in the wake of COVID-19.

Antimicrobial resistance (AMR) is often presented as a major public health problem globally. Screening for AMR usually takes place in clinical settings. Recent developments in microbiology stimulated a series of studies focusing on AMR in communities, and particularly in travelers (any mobile individual), which was argued to be important for identifying potential public health risks. Against this background, microbiologists have become interested in non-hospitalized refugees as one of the traveler groups. However, this attention to refugees has provoked some professional debates on potential stigmatization of refugees as dangerous “others”. To contribute to these debates, and to explore the idea of AMR screening of non-hospitalized refugees from different perspectives, we conducted a qualitative study among four groups of stakeholders who were chosen because of their associations with potential microbiological screening: microbiologists, public health physicians, public health nurses, and refugees. The study took place in a Dutch city from June to August 2016 and had 17 participants: five microbiologists, two public health nurses, four public health physicians, and six refugees. While microbiologists and public health physicians demonstrated a de-contextualized biomedical narrative in arguing that AMR screening among non-hospitalized refugees could be important for scientific research as well as for AMR prevention in communities, public health nurses displayed a more contextualized narrative bringing the benefits for individuals at the center and indicating that screening exclusively among refugees may provoke fear and stigmatization. Refugees were rather positive about AMR screening but stressed that it should particularly contribute to their individual health. We conclude that to design AMR prevention strategies, it is important to consider the complex meanings of AMR screening, and to design these strategies as a process of co-production by diverse stakeholders, including the target populations.

Honey is known for its wound healing potential. In this study we investigated free radical formation and inhibition in different honeys and the influence on bacterial growth inhibition. alpha-Oxaldehydes and free amino acids were shown to be present in manuka and non-manuka honeys. With electron spin resonance we measured that methylglyoxal (MG) and glyoxal (GO) form different carbon centered radicals under the influence of either hydrogen peroxide or arginine and lysine. These radicals were also formed in a combination of alpha-oxaldehydes and amino acids in artificial honey, which was quantified by the cytochrome C assay. Also, a strong bactericidal activity for MG and GO (minimum concentration 0.6 and 1.25 mM) was shown against different bacterial strains. Interestingly, honeys with a high MG content were shown to be better free radical scavengers for hydroxyl and superoxide radicals, implying a complex mechanism for free radical donation and scavenging in honey.

Background Chordomas are rare tumors assumed to derive from notochordal remnants. We believe that a molecular switch is responsible for their malignant behavior. The involvement of oncogenic viruses has not been studied, however. Thus, in the present study, we investigated the presence of oncogenic viruses in chordomas. Methods DNA and RNA from snap-frozen chordoma (n = 18) and chondrosarcoma (n = 15) specimens were isolated. Real-time PCR or RT-PCR was performed to assess the presence of multiple oncogenic viruses, including herpesviridea (herpes simplex virus [HSV]-1, HSV-2, Epstein-Barr virus [EBV], cytomegalovirus, human herpesvirus [HHV]- 6, HHV-7, and Kaposi's sarcoma–associated herpesvirus), polyomaviridea (parvovirus B19 [PVB19], BK virus, JC virus, Simian virus 40, Merkel cell polyomavirus, human polyomavirus [HPyV]-6, and HPyV-7), papillomaviridae, and respiratory viruses. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to validate the positive results. Results PVB19 DNA was detected in 4 of 18 chordomas (22%) and in 1 of 15 chondrosarcomas (7%). IHC recognizing the VP2 capsid protein of PVB19 showed a positive cytoplasmic staining in 44% of the cases (14 of 32). HHV7 DNA was present in 6 of the 18 chordomas (33%). Genomic DNA of EBV was found in 22% of the samples; however, no positive results were found on ISH. None of the chordoma cases showed any presence of DNA from the remaining viruses. Conclusions Viral involvement in the etiology of chordomas is likely, with PVB19 the most distinguishing.

Item does not contain fulltext Eczematous external otitis is a chronic inflammatory disease and often difficult to treat. Our objective was to investigate the clinical effect and in vitro antibacterial potential of medical honey eardrops as treatment of eczematous external otitis. In a prospective study, 15 patients diagnosed with recurrent eczematous external otitis were treated with medical honey eardrops for 2 weeks. The following clinical outcomes were evaluated: visual analog scale of ear complaints, score of eczema, and eradication of bacterial infection. Furthermore, the antibacterial effect of honey eardrops against different bacterial strains was tested in vitro. Treatment resulted in less discomfort and itching and decreased signs of eczema, with high patient satisfaction and without adverse reactions. Honey eardrops showed a strong in vitro inhibitory activity against all tested strains but did not eradicate Staphylococcus aureus infection in vivo. The results of this preliminary study indicate a possible role of honey eardrops in eczematous ear disease.

Spontaneous clearance ofThree outpatient STI clinics included CT-diagnosed women (The Netherlands, 2016-2017, FemCure study); participants had vaginal CT (vCT) and rectal CT (rCT) (group A: n=155), vCT and were rectally untested (group B: n=351), single vCT (group C: n=25) or single rCT (group D: n=29). Follow-up (median interval 9 days) vaginal and rectal samples underwent quantitative PCR testing (detecting total CT-DNA). When PCR positive, samples underwent V-PCR testing to detect 'viable CT' (CT-DNA from intact CT organisms; V-PCR positive). 'Clearance' was the proportion PCR-negative patients and 'clearance of viable CT' was the proportion of patients testing PCR negative or PCR positive but V-PCR negative. We used multivariable logistic regression analyses to assess diagnosis group (A-D), age, days since initial CT test (diagnosis) and study site (STI clinic) in relation to clearance and clearance of viable CT.Clearance and clearance of viable CT at both anatomic sites were for (A) 0.6% and 3.9%; (B) 5.4% and 9.4%; (C) 32.0% and 52.0% and (D) 27.6% and 41.4%, respectively. In multivariate analyses, women with single infections (groups C and D) had higher likelihood of clearance than women concurrently infected with vCT and rCT (p0.001).Of rectally untested women (group B), 76.9% had total CT-DNA and 46.7% had viable CT (V-PCR positive) at the rectal site.Of untreated female vCT patients who had CT also at the rectal site, or who were rectally untested, only a small proportion cleared CT (in fact many had viable CT) at their follow-up visit (median 9 days). Among single site infected women clearance was much higher.NCT02694497.

Background Surveillance of Neisseria gonorrhoeae (NG) is important to monitor antimicrobial resistance and detect outbreaks but is limited by the low NG culture success rate. Recently, we developed a culture-free NG multi-antigen sequence typing (NG-MAST) method. In 2018, an increase of 155% of genital NG cases in heterosexual men and women younger than 25 was observed in South Limburg, the Netherlands. We investigated the genetic relatedness of the NG strains with culture-free NG-MAST to characterize the 2018 increase and compared this with NG cases of heterosexual men and women younger than 25 in 2016 and 2017. Methods Residual routine nucleic acid amplification test diagnostic sample material was retrieved for 53/56 NG cases in 2018 (13 male urine and 40 vaginal swabs) and 36/38 control cases in 2016–2017 (13 male urine and 23 vaginal swabs). Total DNA was isolated and NG was genotyped using the culture-free NG-MAST protocol. Sanger sequence data was used to construct a phylogenetic tree. Results A total of 48/53 cases were genotyped of the 2018 increase, two failed and three samples showed a potentially mixed strain infection. We identified three clusters of closely related NG strains, a novel sequence type (n=15), G2 (n=14) and G13113 (n=10) respectively. No large clusters (n Conclusion We observed a potential NG outbreak in South Limburg using culture-free NG-MAST and identified three clusters of closely related strains. Using current culture-dependent surveillance methods we would not have identified the three clusters to enable intervention assessment. Disclosure No significant relationships.

Background Despite public-health efforts, men who have sex with men (MSM) are still not sufficiently reached with current HIV/STI care. We developed a regional MSM home-care program, used by public-health STI care, hospital HIV care, and general practitioners. The program combines home-based self-sampling testing for HIV, syphilis, chlamydia and gonorrhoea (anorectal, genital and oropharyngeal) with counselling, treatment and sexual health care after positive diagnosis. We developed this program using the systematic intervention mapping (IM) protocol (six steps). Here, we describe the development process. Methods Step1 (needs assessment): we conducted a literature review and interviews with 18 MSM and 19 healthcare professionals from public-health and hospital care. Step 2–5: specific objectives were formulated to achieve the program goal and methods were selected to address determinants that needed to be changed. Program production was done with evidence-based methods to overcome barriers identified in the needs assessment. A plan was made for implementation. Results Step 1 (needs assessment): Healthcare professionals and MSM expressed a positive attitude towards home-based self-sampling. Care providers raised concerns to missing face-to-face counselling and expected that MSM may experience difficulties with blood drawing (finger prick). Steps 2–4: Identified target change behaviors were 1) testing in MSM and 2) adoption of the program in care-providers. Solutions to decrease testing barriers in MSM in the program include: 1) home-based self-sampling 2) reminders (text messaging) 3) social network peer-dissemination of tests and 4) re-testing opportunities. To improve adoption and implementation, a sustainable collaborative infrastructure is set up between public-health service, hospital care providers and general practitioners. Conclusion The regional homecare program to motivate MSM to HIV/STI testing and to motivate care providers to use it was systematically developed for effective behavioral change. In the program, evidence-based methods to overcome barriers are included to reach an increased number of MSM and motivate care providers. The next step is to pilot implementation of the program. Disclosure No significant relationships.

Background Swingers are at high risk for acquiring sexual transmitted infections (STI). The prevalence of human papillomavirus (HPV) in this population is unknown. This information is necessary to assess whether this high risk population should be included in the HPV prevention strategies. In this case-control study the prevalence of HPV in female swingers was tested. Methods Vaginal swabs were collected from 94 female swingers (median age 45 years), visiting an STI clinic between October 2010 and December 2013 in South Limburg, the Netherlands. Ninety-three vaginal swabs from women visiting their general practitioner in this region, were matched in age and time of visit. Broad-spectrum HPV DNA amplification and mucosal HPV genotyping were performed using the highly sensitive SPF10 DEIA-LiPA25 system (DDL Diagnostic Laboratory, Rijswijk). Results In 98% of swingers HPV was detected compared to 18% of the matched controls. Of these HPV positive swingers, 75% carried at least one high risk type (hr-type). Twenty-eight percent carried hr-types only, 25% carried low risk types (lr-types) only and 47% carried one or more concurrent hr-types and lr-types. There were no significant differences between the control group and the swingers in type of carriage (hr-type, lr-type, mixed). Hr-type 52 was most prevalent in swingers, followed by hr-types 31 and 53 (23%). Hr-types 16 and 18 were detected in 15%, respectively 11% of swingers. In the control group most prevalent were hr-types 16, 51 and 53, detected in 18% of HPV positive women. Conclusion In this study an unprecedented high HPV prevalence of 98% was found in female swingers, which was 5 times as much as in matched controls. Of the HPV positive swingers, a worrisome 75% carried at least one hr-type, detected with this highly sensitive detection method. These prevalence rates suggest a potential high HPV disease burden in this population and therefore targeted HPV prevention strategies are necessary. Disclosure No significant relationships.

Background Symptoms have been associated with Chlamydia trachomatis (CT) infections in culture-based studies, in contrast to studies based on nucleic acid amplification tests (NAAT). This may be because NAAT also detect non-viable bacteria. As culturing techniques are insensitive, we developed a sensitive polymerase chain reaction (V-PCR) technique to measure the viable bacterial load. We here assess the association between symptoms and viable load in 524 women with vaginal or rectal CT. Methods Prior to treatment at three STI clinics, we included NAAT-CT-positive adult women (n=411 vaginal and rectal CT; n=88 only vaginal CT; n=25 only rectal CT), who were negative for HIV, syphilis and Neisseria gonorrhoeae (Netherlands, 2016–2017; FemCure). We assessed the viable rectal and vaginal load (log10 CT/ml) using V-PCR. We present the mean viable load (range 0 [non-viable] to 6.5) and tested associations with vaginal symptoms (coital lower abdominal pain, coital blood loss, intermenstrual bleeding, altered discharge, painful or frequent micturition) and rectal symptoms (discharge, pain, blood loss), using multivariable regression techniques adjusting for age and educational level. Results Of 499 vaginal CT NAAT-positive women, mean viable load was 3.5 log10 CT/ml (SD: 1.6). Vaginal symptoms were reported by 50.3% (n=251) of women; women reporting any vaginal symptoms had higher vaginal viable load (mean 3.6 log10 CT/ml) than women without symptoms (mean 3.3 log10CT/ml) (B=0.35, p=0.012) (mainly due to ‘altered discharge’). Of 436 rectal CT NAAT-positive women mean viable load was 2.2 log10 CT/ml (SD: 2.0); rectal symptoms were reported by 4.8% (n=21) and not associated with rectal viable load. Conclusion In an outpatient clinical setting, women diagnosed with vaginal CT have a higher viable load when they have symptoms. Yet, the difference is quite small (0.3 log10 CT/ml) and is therefore unlikely to have a major impact on clinical patient management in women. Disclosure No significant relationships.

Background Rectal infections with Chlamydia trachomatis (CT) are prevalent in women visiting a STI outpatient clinic. While azithromycin is the most used treatment, microbiological treatment failure in rectal CT is common and its drivers remain unclear. Methods This study is part of a prospective multicentre cohort study (FemCure). Current analyses included 112 women clinically-diagnosed (by nucleic acid amplification test [NAAT]) with rectal and vaginal CT, who not vomited and denied rectal and vaginal unprotected sex. Four weeks after azithromycin treatment (1g single dose) participants self-collected vaginal and rectal samples. Samples were tested for CT-DNA (NAAT) and viable CT-load (viability polymerase chain reaction [V-PCR]). We evaluated two endpoints: (1) failure by NAAT-positivity and (2) failure by V-PCR-positivity. Enrolment-risk-factors associated with failure were assessed using multivariable logistic regression; i.e., age, education, migratory-background, previous CT, NAAT Cq-value [marker CT-DNA load], culture, viable CT [V-PCR positive], viable load [log10 copies/ml], vaginal CT. Results (1) Failure by NAAT (21.4%; 24/112) was independently associated with both rectal and vaginal NAAT Cq-values; both aOR: 0.8 per unit decrease in the NAAT Cq-value (95%CI:0.7–0.9, p Conclusion In an outpatient clinical setting, azithromycin rectal CT microbiological treatment failure was common and associated with higher pre-treatment (viable) loads. The lower azithromycin treatment failure in patients with NAAT Cq-values≥36 or non-viable rectal CT might result in different treatment choices. Disclosure No significant relationships.