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We developed an agent-based transmission model that simulates infection with HIV or Neisseria gonorrhoeae (NG) among MSM. We examined scenarios with increased percentages of MSM getting tested six monthly, among all MSM or only specific subgroups of MSM (defined according to recent gonorrhoea, number of partners and engagement in condomless anal intercourse (CAI)) and scenarios with reduced intervals between HIV/STI tests.

Chlamydia trachomatis (Ct) whole-proteome microarrays were utilized to identify antibody patterns associated with infection; pelvic inflammatory disease (PID), tubal factor infertility, chronic pelvic pain (CPP) and ectopic pregnancy in a subsample of the Netherlands Chlamydia cohort study. Serum pools were analyzed on whole-proteome arrays. The 121 most reactive antigens identified during whole-proteome arrays were selected for further analysis with minimized microarrays that allowed for single sera analysis. From the 232 single sera; 145 (62.5%) serum samples were reactive for at least one antigen. To discriminate between positive and negative serum samples; we created a panel of in total 18 antigens which identified 96% of all microarray positive samples. Antigens CT_858; CT_813 and CT_142 were most reactive. Comparison of antibody reactivity's among women with and without Ct related sequelae revealed that the reactivity of CT_813 and CT_142 was less common among women with PID compared to women without (29.0% versus 58.6%, p = 0.005 and 25.8% versus 50.6%, p = 0.017 respectively). CT_858 was less common among CPP cases compared to controls (33.3% versus 58.6; p = 0.028). Using a whole-proteome array to select antigens for minimized arrays allows for the identification of novel informative antigens as general infection markers or disease associated antigens.

IntroductionLymphogranuloma venereum (LGV), an invasive form of Chlamydia trachomatis infection, has been reported among (mainly HIV-positive) men who have sex with men (MSM) since 2003. In the Netherlands, LGV testing recommendations changed from selective to universal testing in 2015. Changes in tested populations could have led to incomparable LGV positivity rates over time.AimWe investigated LGV trends among MSM attending Centres for Sexual Health using surveillance data between 2011 and 2017.MethodsLGV positivity was calculated among MSM tested for rectal Chlamydia infection and MSM tested specifically for LGV. With multivariable logistic regression analysis, the association between years and LGV was adjusted for testing indicators and determinants.ResultsWe included 224,194 consultations. LGV increased from 86 in 2011 to 270 in 2017. Among LGV-positives, proportions of HIV-negative and asymptomatic MSM increased from 17.4% to 45.6% and from 31.4% to 49.3%, respectively, between 2011 and 2017. Among MSM tested for rectal chlamydia, LGV positivity increased from 0.12% to 0.33% among HIV-negatives and remained stable around 2.5% among HIV-positives. Among LGV-tested MSM, LGV positivity increased from 2.1% to 5.7% among HIV-negatives and from 15.1% to 22.1% among HIV-positives. Multivariable models showed increased odds ratios and significant positive associations between years and LGV.ConclusionsAlthough increased testing and changes in LGV incidence are difficult to disentangle, we found increasing LGV trends, especially when corrected for confounding. LGV was increasingly attributed to HIV-negative and asymptomatic MSM, among whom testing was previously limited. This stresses the importance of universal testing and continuous surveillance.

Data on the impact of human papillomavirus (HPV) vaccination on the population HPV prevalence are largely obtained from women. We assessed the impact of the girls‐only HPV16/18 vaccination program in the Netherlands that started in 2009, on trends in HPV prevalence among women and heterosexual men, using data from the PASSYON study. In this cross‐sectional study, the HPV prevalence among 16‐ to 24‐year‐old visitors to sexually transmitted infection clinics was assessed in 2009, 2011, 2013, and 2015. We compared the genital postvaccination HPV prevalence with the prevaccination prevalence (2009) using Poisson GEE models. In total, we included 4,996 women and 1,901 heterosexual men. The percentage of women who reported to be vaccinated increased from 2.3% in 2009 to 37% in 2015. Among all women, the HPV16/18 prevalence decreased from 23% prevaccination to 15% in 2015 (adjusted prevalence ratio [aPR] 0.62, p trend < 0.01). Among heterosexual men, the HPV16/18 prevalence decreased from 17% prevaccination to 11% in 2015 (aPR 0.52, p trend < 0.01). Of the heterosexual men with a steady partner, HPV16/18 prevalence was lower among those whose steady partner had been vaccine‐eligible in the national immunization program (aPR 0.13). Among unvaccinated women, the HPV16/18 prevalence in 2015 was not different from prevaccination. The decreasing HPV16/18 prevalence among heterosexual men and the reduced HPV16/18 prevalence among heterosexual men with a vaccine‐eligible steady partner strongly suggests herd protection from girls‐only vaccination. Absence of notable herd effects among unvaccinated women 6 years postvaccination may be due to the moderate vaccine uptake among girls in the Netherlands., What's new? Human papillomavirus (HPV) is a sexually transmitted virus that plays a causal role in the development of anogenital and oropharyngeal cancers in both men and women. The population‐level impact of HPV vaccination programs on the HPV prevalence has however mainly been studied in women. This study shows decreasing trends in the HPV16 and HPV18 prevalence among both women and heterosexual men after the introduction of a girls‐only HPV16/18 vaccination program in the Netherlands. The findings provide compelling evidence for herd protection in men. Because HPV16/18 are the most oncogenic types, HPV‐related cancers are expected to decline in both sexes after girls‐only HPV vaccination.

Euro-GASP network: Angelika Stary, Maria Haller, Ruth Verbrugge, Tania Crucitti, Soteroulla Soteriou, Despo Pieridou, Susan Cowan, Steen Hoffmann, Jevgenia Epstein, Jelena Viktorova, Ndeindo Ndeikoundam, Agathe Goubard, Peter Kohl, Susanne Buder, Viviane Bremer, Eva Tzelepi, Vasileia Konte, Eszter Balla, Mária Dudás, Guðrún Sigmundsdóttir, Guðrún Svanborg Hauksdóttir, Derval Igoe, Brendan Crowley, Barbara Suligoi, Paola Stefanelli, Gatis Pakarna, Violeta Mavcutko, Christopher Barbara, Jackie Maistre Melillo, Alje Van Dam, Birgit Van Benthem, Ineke Linde, Hilde Kløvstad, Thea Bergheim, Slawomir Majewski, Beata Mlynarczyk-Bonikowska, Jacinta Azevedo, Maria José Borrego, Peter Pavlik, Peter Truska, Irena Klavs, Samo Jeverica, Julio Vazquez, Mercedes Diez, Inga Velicko, Magnus Unemo, Gwenda Hughes, Kirstine Eastick Euro-GASP network: Maria José Borrego (Departamento de Doenças Infeciosas do INSA) Background: European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) antimicrobial resistance (AMR) data are used to inform gonorrhoea treatment guidelines; therefore the data need to be robust and representative. We assessed the extent to which Euro-GASP reflects national measures of the AMR situation for Neisseria gonorrhoeae across the European Union/European Economic Area (EU/EEA). Methods: We compared data from Euro-GASP with published national gonococcal AMR data from 15 countries for azithromycin, cefixime and ciprofloxacin for the period 2009 to 2013 and performed Poisson regression to identify differences (p < 0.05) between the proportions of resistant isolates. The 2014 Euro-GASP AMR data for each country (n = 19) were weighted to account for differences in the distribution of patient characteristics between Euro-GASP and EU/EEA epidemiological gonorrhoea surveillance data. Data were compared to determine whether estimates of resistance levels differed with regards to the 5% threshold used to assess the clinical utility of first-line gonorrhoea treatments. We assessed the quality of decentralised testing by comparing AMR data for isolates tested both centrally and in the participating laboratories, and by evaluating external quality assessment (EQA) performance. Results: There was no significant difference for azithromycin, cefixime and ciprofloxacin resistance when Euro-GASP country data were compared with data from national reports. Weighting slightly altered the Euro-GASP AMR estimates (by between - 4.7 and 4.7% from the unweighted estimates). Weighting resulted in greater changes in estimates of resistance to azithromycin (from - 9.5 to 2.7%) and ciprofloxacin (from - 14.8 to 17.9%) in countries with low isolate numbers and low completeness of reporting (n = 3). Weighting caused AMR levels to fall below or above the 5% threshold for cefixime or azithromycin, respectively in only two countries. Susceptibility category data submitted from the decentralised Euro-GASP laboratories were concordant with the Euro-GASP data (> 90%). EQA performance was also good; < 5% of the minimum inhibitory concentration (MIC) results differed by > 4-fold from the modal MIC of the EQA isolate. Conclusions: The overall prevalence of AMR reported by Euro-GASP reflects closely the AMR situation for N. gonorrhoeae in the EU/EEA. Euro-GASP data can be used to provide robust AMR estimates to inform the European guideline for the management of gonorrhoea. The study was funded by the European Centre for Disease Prevention and Control (Framework Contract No. ECDC/2013/015). The funding body contributed to the design of the study, the analysis and interpretation of the data and to the writing of the manuscript. info:eu-repo/semantics/publishedVersion

The asymptomatic course of Chlamydia trachomatis (CT) infections can result in underestimated CT lifetime prevalence. Antibody testing might improve this estimate. We assessed CT antibody positivity and predictive factors thereof in the Netherlands Chlamydia Cohort Study. Women who had ≥1 CT Nucleic Acid Amplification Test (NAAT) in the study (2008-2011) and who provided self-reported information on NAATs were tested for CT major outer membrane protein specific IgG in serum (2016). CT antibody positivity was assessed and predictive factors were identified using multivariable logistic regressions, separately for CT-positive women (≥1 positive NAAT or ≥1 self-reported positive CT test) and CT-negative women (negative by study NAAT and self-report). Of the 3,613 women studied, 833 (23.1%) were CT -positive. Among the CT-negative women, 208 (7.5%, 95%CI 6.5-8.5) tested positive for CT antibodies. This increased CT lifetime prevalence with 5.8% (95%CI 5.0-6.5). Among women with a CT-positive history, 338 (40.6%, 95%CI 38.5-44.1) tested positive. Predictive factors for antibody positivity related to lower social economic status, sexual risk behavior, multiple infections, higher body mass index, and non-smoking. CT antibody testing significantly increased the lifetime prevalence. Combining NAAT outcomes, self-reported positive tests, and antibody testing reduced misclassification in CT prevalence estimates.

A better understanding of Women who participated in the CSI 2008-2011 (n=13 498) were invited in 2015-2016 for NECCST. Chlamydia positive was defined as a positive CSI-PCR test, positive chlamydia serology and/or self-reported infection (time dependent). Data on PID, ectopic pregnancy and TFI were collected by self-completed questionnaires. Incidence rates and HRs were compared between chlamydia-positive and chlamydia-negative women corrected for confounders. Of 5704 women included, 29.5% (95% CI 28.3 to 30.7) were chlamydia positive. The incidence rate of PID was 1.8 per 1000 person-years (py) (1.6 to 2.2) overall, 4.4 per 1000 py (3.3 to 5.7) among chlamydia positives compared with 1.4 per 1000 py (1.1 to 1.7) for chlamydia negatives. For TFI, this was 0.4 per 1000 py (0.3 to 0.5) overall, 1.3 per 1000 py (0.8 to 2.1) and 0.2 per 1000 py (0.1 to 0.4) among chlamydia positives and negatives, respectively. And for ectopic pregnancy, this was 0.6 per 1000 py (0.5 to 0.8) overall, 0.8 per 1000 py (0.4 to 1.5) and 0.6 per 1000 py (0.4 to 0.8) for chlamydia negatives. Among chlamydia-positive women, the strongest risk factor for PID was symptomatic versus asymptomatic infection (adjusted HR 2.88, 1.4 to 4.5) and for TFI age 24 years at first infection (HR 4.35, 1.1 to 16.8). We found a considerably higher risk for PID and TFI in chlamydia-positive women, but the incidence for ectopic pregnancy was comparable between chlamydia-positive and chlamydia-negative women. Overall, the incidence rates of sequelae remained low.

BackgroundNeisseria gonorrhoeae antibiotic resistance surveillance is important to maintain adequate treatment. We analysed 2007-15 data from the Gonococcal Resistance to Antimicrobials Surveillance (GRAS), which currently includes 19 of 25 sexually transmitted infection (STI) centres in the Netherlands. Methods: From each patient with a gonorrhoea culture, the minimum inhibitory concentration (MIC) for several antibiotics was determined. Time trends were assessed by geometric means and linear regression of logarithmic MIC. Determinants for decreased susceptibility to ceftriaxone (MIC > 0.032 mg/L) and resistance to cefotaxime (MIC > 0.125 mg/L) and azithromycin (MIC > 0.5 mg/L) were assessed using stratified logistic regression. Results: 11,768 isolates were analysed. No ceftriaxone resistance was found. In 2015, 27 of 1,425 isolates (1.9%) were resistant to cefotaxime and 176 of 1,623 (10.9%) to azithromycin. Ceftriaxone susceptibility showed no trend (p = 0.96) during the study period, but cefotaxime MIC decreased (p

Euro-GASP study group: INSA - Maria José Borrego Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010626/ Background: Traditional methods for molecular epidemiology of Neisseria gonorrhoeae are suboptimal. Whole-genome sequencing (WGS) offers ideal resolution to describe population dynamics and to predict and infer transmission of antimicrobial resistance, and can enhance infection control through linkage with epidemiological data. We used WGS, in conjunction with linked epidemiological and phenotypic data, to describe the gonococcal population in 20 European countries. We aimed to detail changes in phenotypic antimicrobial resistance levels (and the reasons for these changes) and strain distribution (with a focus on antimicrobial resistance strains in risk groups), and to predict antimicrobial resistance from WGS data. Methods: We carried out an observational study, in which we sequenced isolates taken from patients with gonorrhoea from the European Gonococcal Antimicrobial Surveillance Programme in 20 countries from September to November, 2013. We also developed a web platform that we used for automated antimicrobial resistance prediction, molecular typing (N gonorrhoeae multi-antigen sequence typing [NG-MAST] and multilocus sequence typing), and phylogenetic clustering in conjunction with epidemiological and phenotypic data. Findings: The multidrug-resistant NG-MAST genogroup G1407 was predominant and accounted for the most cephalosporin resistance, but the prevalence of this genogroup decreased from 248 (23%) of 1066 isolates in a previous study from 2009–10 to 174 (17%) of 1054 isolates in this survey in 2013. This genogroup previously showed an association with men who have sex with men, but changed to an association with heterosexual people (odds ratio=4·29). WGS provided substantially improved resolution and accuracy over NG-MAST and multilocus sequence typing, predicted antimicrobial resistance relatively well, and identified discrepant isolates, mixed infections or contaminants, and multidrug-resistant clades linked to risk groups. Interpretation: To our knowledge, we provide the first use of joint analysis of WGS and epidemiological data in an international programme for regional surveillance of sexually transmitted infections. WGS provided enhanced understanding of the distribution of antimicrobial resistance clones, including replacement with clones that were more susceptible to antimicrobials, in several risk groups nationally and regionally. We provide a framework for genomic surveillance of gonococci through standardised sampling, use of WGS, and a shared information architecture for interpretation and dissemination by use of open access software. The European Centre for Disease Prevention and Control, The Centre for Genomic Pathogen Surveillance, Örebro University Hospital, and Wellcome. info:eu-repo/semantics/publishedVersion