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Objectives: Chlamydia trachomatis (chlamydia) is one of the most reported bacterial sexually transmitted infections (STI) worldwide. Chlamydia can cause long term complications such as pelvic inflammatory disease (PID), ectopic pregnancy (EP) and tubal factor infertility (TFI). Changing testing strategies, for example reduced asymptomatic testing, influence chlamydia surveillance, highlighting the need for exploring alternative ways of monitoring chlamydia. We investigated the possibility of introducing routine surveillance of chlamydia related long term complications., Methods: A qualitative study including 15 in-depth interviews with a purposive sample of gynaecologists, general practitioners (GP), sexual health and emergency doctors was conducted in the Netherlands in 2021-2022. A semi-structured interview guide focused on experiences with diagnosis and registration of PID, EP and TFI and how a change in asymptomatic chlamydia testing strategy might influence this. Interviews were transcribed and analysed using a thematic approach., Results: Analysis showed that gynaecologists most frequently reported diagnosing PID, EP and TFI. Other professions rarely diagnose these complications, with emergency doctors only diagnosing EP. Most respondents reported unique registration codes for PID and EP, but the coding for TFI is more ambiguous. They reflected that diagnosis and registration of PID, EP and TFI are handled differently within their professions. Most respondents acknowledged registration in diagnostic codes as a useful surveillance tool. They expressed concerns in representativeness (e.g. differences in interpretation of diagnosis criteria) and data quality for surveillance., Conclusions: Patient files of gynaecologists are likely to be most complete for monitoring trends of diagnosed chlamydia related long term complications in the Netherlands. However, when establishing a chlamydia complication surveillance system, professionals should be engaged in further standardizing diagnosis and registration practices. This will improve the quality and interpretability of complication surveillance and facilitate comparison between countries., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Boogert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Pre-exposure prophylaxis (PrEP) users are routinely tested four times a year (3 monthly) for asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections on three anatomical locations. Given the high costs of this testing to the PrEP programme, we assessed the impact of 3 monthly screening(current practice), compared with 6 monthly on the disease burden. We quantified the difference in impact of these two testing frequencies on the prevalence of CT and NG among all men who have sex with men (MSM) who are at risk of an STI, and explored the cost-effectiveness of 3-monthly screening compared with a baseline scenario of 6-monthly screening., Methods: A dynamic infection model was developed to simulate the transmission of CT and NG among sexually active MSM (6500 MSM on PrEP and 29 531 MSM not on PrEP), and the impact of two different test frequencies over a 10-year period. The difference in number of averted infections was used to calculate incremental costs and quality-adjusted life-years (QALY) as well as an incremental cost-effectiveness ratio (ICER) from a societal perspective., Results: Compared with 6-monthly screening, 3-monthly screening of PrEP users for CT and NG cost an additional €46.8 million over a period of 10 years. Both screening frequencies would significantly reduce the prevalence of CT and NG, but 3-monthly screening would avert and extra ~18 250 CT and NG infections compared with 6-monthly screening, resulting in a gain of ~81 QALYs. The corresponding ICER was ~€430 000 per QALY gained, which exceeded the cost-effectiveness threshold of €20 000 per QALY., Conclusions: Three-monthly screening for CT and NG among MSM on PrEP is not cost-effective compared with 6-monthly screening. The ICER becomes more favourable when a smaller fraction of all MSM at risk for an STI are screened. Reducing the screening frequency could be considered when the PrEP programme is established and the prevalence of CT and NG decline., Competing Interests: Competing interests: EH obtained advisory board fees and a research grant from Gilead Sciences; both of which were paid to her institute., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Antenatal screening for HIV, syphilis and HBV has been successfully implemented in The Netherlands, but data on other STI among pregnant women or male partners are limited. Our objectives: (i) to assess the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) among pregnant women and male partners, (ii) to identify risk factors for these STI during pregnancy, and (iii) to identify adverse perinatal outcomes (APO) associated with STI., Methods: Cross-sectional study. Pregnant women aged ≤ 30 years (n = 548) and male partners (n = 425) were included at 30 midwifery practices during 2012-2016. Participants provided a self-collected vaginal swab (women) or urine sample (men) and completed a questionnaire. Perinatal data were derived from pregnancy cards. APO was defined as premature rupture of membranes, preterm delivery, low birthweight, stillbirth, neonatal conjunctival and respiratory infections. Data were analysed by logistic regression., Results: STI were present in 2.4% of pregnant women (CT 1.8%, NG 0.4%, TV 0.4%), and in 2.2% of male partners (CT 2.2%, NG 0.2%, TV 0%). Of young women (≤ 20 years), 12.5% had a CT infection. Prevalent STI during pregnancy was associated with female young age (≤ 20 years vs ≥ 21 years) (adjusted OR 6.52, CI 95%: 1.11-38.33), male non-Western vs Western background (aOR 9.34, CI 2.34-37.21), and female with ≥ 2 sex partners < 12 months vs 0-1 (aOR 9.88, CI 2.08-46.91). APO was not associated with STI, but was associated with female low education (aOR 3.36, CI 1.12-10.09), complications with previous newborn (aOR 10.49, CI 3.21-34.25 vs no complications) and short duration (0-4 years) of relationship (aOR 2.75, CI 1.41-5.39 vs ≥ 5 years). Small-for-gestational-age was not associated with STI, but was associated with female low education (aOR 7.81, 2.01-30.27), female non-Western background (aOR 4.41, 1.74-11.17), and both parents smoking during pregnancy (aOR 2.94, 1.01-8.84 vs both non-smoking)., Conclusions: Prevalence of STI was low among pregnant women and male partners in midwifery practices, except for CT among young women. The study could not confirm previously observed associations between STI and APO, which is probably due to low prevalence of STI, small study sample, and presumed treatment for STI.

Objectives: Women attending STI clinics are not routinely tested for oropharyngeal Chlamydia trachomatis (CT) infections. We aimed to assess spontaneous clearance of oropharyngeal CT and cure after antibiotic treatment in women., Methods: Women with vaginal or rectal CT (n=560) were recruited at STI clinics in 2016-2017, as part of the FemCure study (prospective cohort study). We included participants' data from week -1, that is, the diagnosis at initial visit, when clinics applied selective oropharyngeal testing. At week -1, a total of 241 women were oropharyngeally tested (30 positive) and 319 were untested. All FemCure participants provided nurse-collected oropharyngeal samples at study enrolment, that is, week 0, just prior to treatment (n=560), and after treatment at weeks 4 (n=449), 8 (n=433) and 12 (n=427). Samples were tested by nucleic acid amplification test, and at week 0 also by viability testing by viability PCR. Proportions of oropharyngeal CT test results were presented to represent spontaneous clearance and cure., Results: Of 30 women diagnosed with oropharyngeal CT at week -1, fifteen (50%) were negative at week 0 after a median of 9 days, that is, 'spontaneous clearance'. At week 0, a total of 560 participants were tested, and 46 (8.8%) were oropharyngeal CT positive; 12 of them (26.1%) had viable CT. Of the 46 positive, 36 women had an oropharyngeal test after treatment; 97.2% (35/36) were negative at week 4, that is, 'cure'. Of all women with follow-up visits, the proportion of oropharyngeal CT positive was between 0.5% and 1.6% between weeks 4 and 12. Of those not tested at week -1 (n=319), 8.5% (n=27) were oropharyngeal positive at week 0., Conclusions: The clinical importance of oropharyngeal CT in women is debated. We demonstrated that spontaneous clearance of oropharyngeal CT among women is common; of those who did not clear for CT, three-quarters had non-viable CT. After regular treatment with azithromycin or doxycycline, cure rate (97%) of oropharyngeal CT is excellent., Trial Registration Number: NCT02694497., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: In this study, we report the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) amongst clinical specimens of patients suspected for sexually transmitted infections received at our laboratory and in addition report the prevalence of resistance-associated mutations (RAM) for ciprofloxacin in NG and azithromycin and moxifloxacin in MG., Methods: All specimens received from December 2018 to May 2019 were tested for the four pathogens. In addition, the presence of RAM associated with resistance to ciprofloxacin in NG and to azithromycin and moxifloxacin in MG was determined by different real-time PCR assays on all NG- and MG-positive specimens., Results: CT was detected most often (267/2613, 10.2%), followed by MG (106/2592, 4.1%), NG (41/2613, 1.6%) and TV (10/2592, 0.4%) amongst all specimens. The prevalence of ciprofloxacin RAM in NG was 21.2%, and the prevalence of RAM in MG was 40.6% for azithromycin and 8.1% for moxifloxacin. Nearly all specimens containing moxifloxacin-resistant MG also contained azithromycin-resistant MG., Conclusion: CT is found most often in our population followed by MG and NG. By using molecular assays to detect RAM supplementary to pathogen identification of NG and MG, optimal therapy can be advised.

Background: A Chlamydia trachomatis infection (chlamydia) can result in tubal factor infertility in women. To assess if this association results in fewer pregnant women, we aimed to assess pregnancy incidences and time to pregnancy among women with a previous chlamydia infection compared with women without one and who were participating in the Netherlands Chlamydia Cohort Study (NECCST)., Methods: The NECCST is a cohort of women of reproductive age tested for chlamydia in a chlamydia screening trial between 2008 and 2011 and reinvited for NECCST in 2015 to 2016. Chlamydia status (positive/negative) was defined using chlamydia screening trial-nucleic acid amplification test results, chlamydia immunoglobulin G presence in serum, or self-reported chlamydia infections. Data on pregnancies were collected via questionnaires in 2015-2016 and 2017-2018. Overall pregnancies (i.e., planned and unplanned) and time to pregnancy (among women with a pregnancy intention) were compared between chlamydia-positive and chlamydia-negative women using Cox regressions., Results: Of 5704 women enrolled, 1717 (30.1%; 95% confidence interval [CI], 28.9-31.3) women was chlamydia positive. Overall pregnancy proportions were similar in chlamydia-positive and chlamydia-negative women (49.0% [95% CI, 46.5-51.4] versus 50.5% [95% CI, 48.9-52.0]). Pregnancies per 1000 person-years were 53.2 (95% CI, 51.5-55.0) for chlamydia negatives and 83.0 (95% CI, 78.5-87.9) for chlamydia positives. Among women with a pregnancy intention, 12% of chlamydia-positive women had a time to pregnancy of >12 months compared with 8% of chlamydia negatives (P < 0.01)., Conclusions: Overall pregnancy rates were not lower in chlamydia-positive women compared with chlamydia-negative women, but among women with a pregnancy intention, time to pregnancy was longer and pregnancy rates were lower in chlamydia-positive women., Trial Registration Number: Dutch Trial Register NTR-5597.

Objectives: Spontaneous 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., Methods: Three 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., Results: 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 (p<0.001).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., Conclusions: 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., Trial Registration Number: NCT02694497., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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 < 25 years (OR: 1.83; 95%CI:1.38-2.43), co-infected with HIV (OR: 2.07; 95%CI: 1.02-4.22) or co-infected with 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 < 25 years and patients coinfected with HIV or NG had more frequent repeat CT infections, accounting for ~ 20% of the diagnosed CT infections. These patients are likely at the highest risk for transmitting and acquiring CT. Therefore, testing and retesting this group remains important to enhance CT control.

Objectives: Pathogen 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., Methods: 188 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., Results: The 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., Conclusion: Standardisation 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Most 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., Methods: A 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 χ 2 test and linear regression were used to compare genital and anorectal C. trachomatis loads and identify determinants associated with load., Results: The overall median C. trachomatis load was higher in genital (median 5.3 log 10 C. 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., Conclusions: Although 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Host immunogenetic factors can affect late complications of urogenital infections with Chlamydia trachomatis . These findings are creating new avenues for updating existing risk prediction models for C. trachomatis -associated tubal factor infertility (TFI). Research into host factors and its utilization may therefore have future implications for diagnosing C. trachomatis -induced infertility. We outline the epidemiological situation regarding C. trachomatis and TFI in high-income countries. Thereupon, we review the main characteristics of the population undergoing fertility work-up and identify screening and diagnostic strategies for TFI currently in place. The Netherlands is an exemplary model for the state of the art in high-income countries. Within the framework of existing clinical approaches, we propose a scenario for the translation of relevant genome-based information into triage of infertile women, with the objective of implementing genetic profiling in the routine investigation of TFI. Furthermore, we describe the state of the art in relevant gene- and single nucleotide polymorphism (SNP) based clinical prediction models and place our perspectives in the context of these applications. We conclude that the introduction of a genetic test of proven validity into the assessment of TFI should help reduce patient burden from invasive and costly examinations by achieving a more precise risk stratification.

Objectives: To assess to what extent triage criteria, client and regional characteristics explain regional differences in Chlamydia trachomatis (Ct) and Neisseria gonorrhoeae (Ng) positivity in sexually transmitted infection (STI) clinics., Design: Retrospective cross-sectional study on the Dutch STI surveillance database of all 24 STI clinics., Participants: STI clinic visits of heterosexual persons in 2015 with a Ct (n=101 495) and/or Ng test (n=101 081)., Primary Outcome Measure: Ct and Ng positivity and 95% CI was assessed for each STI clinic. Two-level logistic regression analyses were performed to calculate the percentage change in regional variance (PCV) after adding triage criteria (model 1), other client characteristics (model 2) and regional characteristics (model 3) to the empty model. The contribution of single characteristics was determined after removing them from model 3., Results: Ct positivity was 14.9% and ranged from 12.6% to 20.0% regionally. Ng positivity was 1.7% and ranged from 0.8% to 3.8% regionally. For Ct, the PCV was 11.7% in model 1, 32.2% in model 2% and 59.3% in model 3. Age, notified for Ct (triage), level of education (other characteristics) and regional degree of urbanisation (region) explained variance most. For Ng, the PCV was 38.7% in model 1, 61.2% in model 2% and 69.1% in model 3. Ethnicity (triage), partner in risk group, level of education and neighbourhood (other characteristics) and regional socioeconomic status (SES) explained variance most. A significant part of regional variance remained unexplained., Conclusions: Regional variance was explained by differences in client characteristics, indicating that triage and self-selection influence positivity rates in the surveillance data.Clustering of Ng in low SES regions additionally explained regional variance in Ng; targeted interventions in low SES regions may assist Ng control. Including educational level as triage criterion is recommended. Studies incorporating prevalence data are needed to assess whether regional clustering underlies unexplained regional variance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Although anorectal Chlamydia trachomatis (CT) infections are frequently diagnosed in men who have sex with men (MSM) and women, the reason for this infection often remains unexplained, as anal sex is not always reported. Oropharyngeal infections inoculating the gastrointestinal (GI) tract may contribute to anorectal-CT infections, as evidence in animals suggests that chlamydia bacteria undergo GI passage; however, no evidence exists in humans. Longitudinal patient clinic-registry data from MSM (n = 17 125) and women (n = 4120) from two Dutch sexually transmitted infection clinics were analysed. When adjusting for confounding socio-demographics, co-infections and risk behaviour, previous (from 3 weeks up to 24 months) oropharyngeal CT was not a risk factor for subsequent anorectal CT in women (odds ratio (OR) 0.46; 95% confidence interval (CI) 0.18-1.18; P = 0.11) and MSM (OR 1.33; 95% CI 0.86-2.07; P = 0.204). Despite the large dataset, the numbers did not allow for the estimation of risk in specific subgroups of interest. The role of the GI tract cannot be excluded with this epidemiological study, but the impact of preceding oropharyngeal CT on anorectal-CT infection is likely limited.

Background: In the Netherlands, there are strong disparities in Chlamydia trachomatis (CT) prevalence between ethnic groups. The current study aims to identify whether socioeconomic status, sexual risk behavior and sexual healthcare seeking behavior may explain differences in CT seroprevalence between ethnic groups., Methods: We used 2011-2014 baseline data of the HELIUS (HEalthy LIfe in an Urban Setting) study, a multi-ethnic population-based cohort study in Amsterdam, the Netherlands, including participants from Dutch, African Surinamese, South-Asian Surinamese, Ghanaian, Moroccan and Turkish origin. For this analysis, we selected sexually active, heterosexual participants aged 18-34 years old. CT seroprevalence was determined using a multiplex serology assay. The CT seroprevalence ratios between different ethnicities are calculated and adjusted for potential indicators of socioeconomic status, sexual risk behavior and sexual healthcare seeking behavior., Results: The study population consisted of 2001 individuals (52.8% female) with a median age of 28 years (IQR 24-31). CT seropositivity differed by ethnicities and ranged from 71.6% (African Surinamese), and 67.9% (Ghanaian) to 31.1% (Turkish). The CT seroprevalence ratio of African Surinamese was 1.72 (95% CI 1.43-2.06) and 1.52 (95% CI 1.16-1.99) of Ghanaian as compared to the Dutch reference group, after adjustment for socioeconomic status, sexual risk behavior and sexual healthcare seeking behavior., Conclusions: Indicators of socioeconomic status, sexual risk behavior, and sexual health seeking behavior could not explain the higher CT seroprevalence among African Surinamese and Ghanaian residents of Amsterdam.

Background: Chlamydia trachomatis (chlamydia), the most commonly reported sexually transmitted infection (STI) in the Netherlands, can lead to severe reproductive complications. Reasons for the sustained chlamydia prevalence in young individuals, even in countries with chlamydia screening programs, might be the asymptomatic nature of chlamydia infections, and high reinfection rates after treatment. When individuals are unaware of their infection, preventive behaviour or health-care seeking behaviour mostly depends on psychological determinants, such as risk perception. Furthermore, behaviour change after a diagnosis might be vital to reduce reinfection rates. This makes the incorporation of psychological determinants and behaviour change in mathematical models estimating the impact of interventions on chlamydia transmission especially important. Therefore, quantitative real-life data to inform these models is needed., Methods: A longitudinal cohort study will be conducted to explore the link between psychological and behavioural determinants and chlamydia (re)infection among heterosexual STI clinic visitors aged 18-24 years. Participants will be recruited at the STI clinics of the public health services of Amsterdam, Hollands Noorden, Kennemerland, and Twente. Participants are enrolled for a year, and questionnaires are administrated at four time points: baseline (before an STI consultation), three-week, six-month and at one-year follow-up. To be able to link psychological and behavioural determinants to (re)infections, participants will be tested for chlamydia at enrolment and at six-month follow-up. Data from the longitudinal cohort study will be used to develop mathematical models for curable STI incorporating these determinants to be able to better estimate the impact of interventions., Discussion: This study will provide insights into the link between psychological and behavioural determinants, including short-term and long-term changes after diagnosis, and chlamydia (re)infections. Our mathematical model, informed by data from the longitudinal cohort study, will be able to estimate the impact of interventions on chlamydia prevalence, and identify and prioritise successful interventions for the future. These interventions could be implemented at STI clinics tailored to psychological and behavioural characteristics of individuals., Trial Registration: Dutch Trial Register NTR-6307 . Retrospectively registered 11-nov-2016.

Background: For Chlamydia trachomatis (CT), a test of cure (TOC) within 3-5 weeks is not recommended. International guidelines differ in advising a Neisseria gonorrhoeae (NG) TOC. Retesting CT and NG positives within 3-12 months is recommended in international guidelines. We assessed TOC and retesting practices including extragenital testing in general practitioner (GP) practices located in different socioeconomic status (SES) areas to inform and optimize local test practices., Methods: Laboratory data of 48 Dutch GP practices between January 2011 and July 2016 were used. Based on a patient's first positive CT or NG test, the proportion of TOC (<3 months) and retests (3-12 months) were calculated. Patient- and GP-related factors were assessed using multivariate logistic regression analyses., Results: For CT (n = 622), 20% had a TOC and 24% had a retest at the GP practice. GP practices in low SES areas were more likely to perform a CT TOC (OR:1.8;95%CI:1.1-3.1). Younger patients (<25 years) were more likely to have a CT TOC (OR:1.6;95%CI:1.0-2.4). For CT (n = 622), 2.4% had a TOC and 6.1% had a retest at another STI care provider. For NG (n = 73), 25% had a TOC and 15% had a retest at the GP practice. For NG (n = 73), 2.7% had a TOC and 12.3% had a retest at another STI care provider. In only 0.3% of the consultations patients were tested on extragenital sites., Conclusion: Almost 20% of the patients returned for a CT TOC, especially at GP practices in low SES areas. For NG, 1 out of 4 patients returned for a TOC. Retesting rates were low for both CT (24%) and NG (15%), (re)infections including extragenital infections may be missed. Efforts are required to focus TOC and increase retesting practices of GPs in order to improve CT/NG control.

Introduction: This prospective study aimed to study the composition and structure of the vaginal microbiota prior to Chlamydia trachomatis infection., Methods: A nested case-control study was performed in 122 women, half of which acquired C. trachomatis within a year after their first visit. At the first visit, the composition and structure of vaginal microbial communities were analysed using 16S rRNA sequencing in the context of the sociodemographic and sexual risk behaviour information using logistic regression., Results: Five vaginal community state types (CSTs) were identified. Four CSTs were dominated by Lactobacillus spp., of which L. crispatus (37%) and L. iners (33%) were the most common. One CST was characterised by the absence of Lactobacillus spp. (25%) and the presence of an array of strict and facultative anaerobes. Multivariate logistic regression analysis revealed that women with a L. iners- dominated CST had an increased risk of C. trachomatis infection (p=0.04; OR: 2.6, 95% CI 1.0 to 6.6)., Conclusions: The distribution of CSTs dominated by Lactobacillus spp. agreed with previous studies. However, the frequency of dysbiosis among Caucasian women was relatively high (24%). Having vaginal microbiota dominated by L. iners was associated with an increased risk for C. trachomatis infection. Therefore, we hypothesise that specific signatures of vaginal microbiota are indicative of increased host predisposition to acquiring STIs., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To develop prediction models for Chlamydia trachomatis (Ct) infection with different levels of detail in information, that is, from readily available data in registries and from additional questionnaires., Methods: All inhabitants of Rotterdam and Amsterdam aged 16-29 were invited yearly from 2008 until 2011 for home-based testing. Their registry data included gender, age, ethnicity and neighbourhood-level socioeconomic status (SES). Participants were asked to fill in a questionnaire on education, sexually transmitted infection history, symptoms, partner information and sexual behaviour. We developed prediction models for Ct infection using first-time participant data-including registry variables only and with additional questionnaire variables-by multilevel logistic regression analysis to account for clustering within neighbourhoods. We assessed the discriminative ability by the area under the receiver operating characteristic curve (AUC)., Results: Four per cent (3540/80 385) of the participants was infected. The strongest registry predictors for Ct infection were young age (especially for women) and Surinamese, Antillean or sub-Saharan African ethnicity. Neighbourhood-level SES was of minor importance. Strong questionnaire predictors were low to intermediate education level, ethnicity of the partner (non-Dutch) and having sex with casual partners. When using a prediction model including questionnaire risk factors (AUC 0.74, 95% CI 0.736 to 0.752) for selective screening, 48% of the participating population needed to be screened to find 80% (95% CI 78.4% to 81.0%) of Ct infections. The model with registry risk factors only (AUC 0.67, 95% CI 0.656 to 0.675) required 60% to be screened to find 78% (95% CI 76.6% to 79.4%) of Ct infections., Conclusions: A registry-based prediction model can facilitate selective Ct screening at population level, with further refinement at the individual level by including questionnaire risk factors., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives: To evaluate and compare Chlamydia trachomatis (CT) diagnostic test practices of different sexually transmitted infection (STI) care providers in 16-29 year olds from one defined geographic Dutch region (280,000 inhabitants). Both number and proportion of positive CT tests (ie, test positivity) were assessed, and factors associated with these outcomes., Methods: Data on laboratory testing and diagnosis of urogenital, anorectal and oropharyngeal CT between 2006 and 2010 were retrieved from general practitioners (GPs), gynaecologists, an STI clinic and a population-based chlamydia screening programme. Multivariable regression analyses explored associations between age, sex, test year, socio-economic status (SES) and STI care provider and the outcomes being the number of tests and test positivity., Results: Overall, 22,831 tests were performed (1868 positive; 8.2%). Extragenital (ie, anorectal and oropharyngeal) tests accounted for 4% of all tests (7.5% positive) and were almost exclusively (99%) performed by the STI clinic. STI clinics tested most men (37.2% of all tested men), whereas GPs tested most women (29.9% of all tested women). GPs and STI clinics accounted for 73.3% (1326/1808) of urogenital CT diagnoses. In women, the number of tests increased with age, whereas test positivity decreased for all STI care providers. Lower SES was associated with higher test positivity in GP and gynaecology patients., Conclusions: STI clinics performed most CT tests in men, whereas GPs performed most CT tests in women. GPs and STI clinics accounted for the majority of positives. Extragenital CT testing is rarely performed outside the STI clinic and needs to be promoted, especially in men who have sex with men., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives: The objective of this study is to assess the effect of reminder text messages 6 months after the initial treatment on retest and chlamydia reinfection rates in young heterosexuals compared with a historical control group and to assess factors associated with both outcomes., Methods: Heterosexual people (aged 16-23 years), testing positive for urogenital chlamydia, were offered a retest after 6 months. Participants received a text message reminder at 6 months after the initial chlamydia diagnosis. Rates of retest uptake and the result of the retest were analysed using Cox regression. Prevalence ratios (PRs) were calculated to identify factors associated with these outcomes. Furthermore, the retest rate was compared with the retest rate of a historical control group., Results: 30.6% (253/838) of the study group returned within 5-8 months compared with 9.2% (140/1530) in the historical control group. Women and persons who were not notified for a sexually transmitted infection (STI) at inclusion were more likely to return for a retest. 20.4% (56/275) of participants had a chlamydia reinfection upon retesting. Reinfection was higher in participants reporting STI-related symptoms (PR 3.2, 95% CI 1.8 to 5.6) and in participants who were notified for an STI at retest (PR 5.3, 95% CI 2.4 to 11.5)., Conclusions: A text message reminder appeared to have a clear, positive impact on the resulting retest rate. These results also indicate that retesting is necessary to identify chlamydia reinfections., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives: Recently, we reported a high prevalence (16%) of urogenital Chlamydia trachomatis infections among women in a rural setting in South Africa. Molecular epidemiological studies on C. trachomatis infections could provide insights into the characteristics of this epidemic, yet such data are not available. The objective of this study was therefore to assess the distribution of C. trachomatis strains among women from a South African rural community, the Mopani district, and to compare it with strains from Amsterdam, the Netherlands., Methods: High-resolution multilocus sequence typing (hr-MLST) was used to study urogenital C. trachomatis infections in women visiting primary healthcare facilities across rural Mopani District in Limpopo Province, South Africa. Sequence types (STs) were compared with 100 strains from women visiting the sexually transmitted infection clinic in Amsterdam, the Netherlands., Results: Full hr-MLST data were obtained for C. trachomatis infection in 43 women from Mopani district. Using the complete hr-MLST profile of all 43 women from Mopani district, 26 STs could be identified, of which 18 (69%) were novel to the hr-MLST database. The remaining STs clustered together with strains from Amsterdam., Conclusions: Hr-MLST data revealed a diverse molecular epidemiology with novel STs and a specific cluster for the Mopani district. Also C. trachomatis types that occur worldwide were detected., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: To measure the effect of changing the point-of-care (POC) testing algorithm of urogenital chlamydia for all male high-risk patients to those with only symptoms with respect to: diagnostic accuracy, loss to follow-up, correctly managed consultations and costs., Methods: Retrospective comparison of the diagnostic accuracy and cost-effectiveness of Gram-stained urethral smear analysis for the POC management of urogenital Chlamydia trachomatis infections. Between 2008 and 2009 Gram-stained urethral smear analysis was offered to all men irrespective of symptoms; between 2010 and 2011 only to those with symptoms. The Aptima CT assay was the reference diagnostic test., Results: The number of examined Gram-stained smears in the two periods was respectively 7185 (2008-2009 period) and 18,852 (2010-2011 period). The sensitivity of the Gram stain analysis was respectively 83.8% (95% CI 81.2% to 86.1%) and 91.0% (95% CI 89.5% to 92.3%) (p<0.001). The specificity was respectively 74.1% (95% CI 73.0% to 75.2%) and 53.1% (95% CI 51.8% to 54.4%) (p<0.001). The positive predictive value was low in both periods, respectively 31.7% (95% CI 29.8% to 33.6%) and 35.6% (95% CI 34.1% to 37.1%) (p=0.002), whereas the negative predictive value was high, respectively 97.0% (95% CI 96.4% to 97.4%) and 95.4% (95% CI 94.6% to 96.1%) (p=0.002). The loss to follow-up rate between 2008-2009 and 2010-2011 was, respectively, 1.8% (95% CI 1.0% to 2.9%) vs 2.3% (95% CI 1.7% to 3.0%) (p=0.36). There was a small difference in overtreatment, 68.0% (95% CI 66.0% to 69.8%) vs 64.1% (95% CI 62.6% to 65.5%) (p=0.001). The cost per correctly managed consultation was 14.3% lower in the 2010-2011 period (€94.31 vs €80.82). The percentage of delayed treated infections was significantly lower in the 2008-2009 period (10.5%) compared with the 2010-2011 period (22.8%) (p<0.001)., Conclusions: With a high sensitivity in male high-risk patients, the Gram-stained urethral smear is a useful POC test to detect urogenital C. trachomatis. When offered only to men with urogenital symptoms the specificity decreases but the cost per correctly managed consultation is reduced with 14.3% without a significant difference in loss to follow-up but with a significantly higher rate of delayed treatment., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

We assessed whether infection with chlamydia increases the incidence of carcinogenic human papillomavirus (HPV) infections and if HPV persistence is affected by chlamydia co-infection. For 1982 women (16-29 years-old) participating in two consecutive rounds of a chlamydia screening implementation trial, swabs were polymerase chain reaction tested to detect chlamydia and 14 carcinogenic HPV genotypes. HPV type-specific incidence and persistence rates were stratified for chlamydia positivity at follow-up. Associations were assessed by multilevel logistic regression analyses with correction for sexual risk factors. HPV type-specific incidence ranged from 1.4% to 8.9% and persistence from 22.7% to 59.4% after a median follow-up of 11 months (interquartile range: 11-12). Differences in 1-year HPV persistence rates between chlamydia -infected and noninfected women were less distinct than differences in HPV incidence rates (pooled adjusted odds ratios of 1.17 [95% CI: 0.69-1.96] and 1.84 [95% CI: 1.36-2.47], respectively). The effect of chlamydia co-infection on HPV-infection risk did not significantly differ by HPV genotype. In conclusion, infection with chlamydia increases the risk of infection by carcinogenic HPV types and may enhance persistence of some HPV types. Although these findings could reflect residual confounding through unobserved risk factors, our results do give reason to explore more fully the association between chlamydia and HPV type-specific acquisition and persistence., (© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Previous studies found conflicting results regarding associations between urogenital Chlamydia trachomatis infections and ethnicity or urogenital symptoms among at-risk populations using either ompA-based genotyping or high-resolution multilocus sequence typing (MLST). This study applied high-resolution MLST on samples of individuals from a selected young urban screening population to assess the relationship of C. trachomatis strain types with ethnicity and self-reported urogenital symptoms. Demographic and sexual risk behaviour characteristics of the identified clusters were also analysed., Methods: We selected C. trachomatis-positive samples from the Dutch Chlamydia Screening Implementation study among young individuals in Amsterdam, the Netherlands. All samples were typed using high-resolution MLST. Clusters were assigned using minimum spanning tree analysis and were combined with epidemiological data of the participants., Results: We obtained full MLST data for C. trachomatis-positive samples from 439 participants and detected nine ompA genovars. MLST analysis identified 175 sequence types and six large clusters; in one cluster, participants with Surinamese/Antillean ethnicity were over-represented (58.8%) and this cluster predominantly consisted of genovar I. In addition, we found one cluster with an over-representation of participants with Dutch ethnicity (90.0%) and which solely consisted of genovar G. No association was observed between C. trachomatis clusters and urogenital symptoms., Conclusions: We found an association between urogenital C. trachomatis clusters and ethnicity among young screening participants in Amsterdam, the Netherlands. However, no association was found between C. trachomatis clusters and self-reported urogenital symptoms., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: In three pilot regions of The Netherlands, all 16-29 year olds were invited to participate in three annual rounds of Chlamydia screening. The aim of the present study is to evaluate the cost-effectiveness of repeated Chlamydia screening, based on empirical data., Methods: A mathematical model was employed to estimate the influence of repeated screening on prevalence and incidence of Chlamydial infection. A model simulating the natural history of Chlamydia was combined with cost and utility data to estimate the number of major outcomes and quality-adjusted life-years (QALYs) associated with Chlamydia. Six screening scenarios (16-29 years annually; 16-24 years annually; women only; biennial screening; biennial screening women only; screening every five years) were compared with no screening in two sexual networks, representing both lower ('national network') and higher ('urban network') baseline prevalence. Incremental cost-effectiveness ratios (ICERs) for the different screening scenarios were estimated. Uncertainty and sensitivity analyses were performed., Results: In all scenarios and networks, cost per major outcome averted are above €5000. Cost per QALY are at least €50,000. The default scenario as piloted in the Netherlands was least cost-effective, with ICERs of €232,000 in the national and €145,000 in the urban sexual network. Results were robust in sensitivity analyses., Conclusions: It is unlikely that repeated rounds of Chlamydia screening will be cost-effective. Only at high levels of willingness to pay for a QALY (>€50,000) screening may be more cost-effective than no screening., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: With the aim of targeting high-risk hidden heterosexual young people for Chlamydia trachomatis (CT) testing, an innovative web-based screening strategy using Respondent Driven Sampling (RDS) and home-based CT testing, was developed, piloted and evaluated., Methods: Two STI clinic nurses encouraged 37 CT positive heterosexual young people (aged 16-25 years), called index clients, to recruit peers from their social and sexual networks using the web-based screening strategy. Eligible peers (young, living in the study area) could request a home-based CT test and recruit other peers., Results: Twelve (40%) index clients recruited 35 peers. Two of these peers recruited other peers (n = 7). In total, 35 recruited peers were eligible for participation; ten of them (29%) requested a test and eight tested. Seven tested for the first time and one (13%) was positive. Most peers were female friends (80%). Nurses were positive about using the strategy., Conclusions: The screening strategy is feasible for targeting the hidden social network. However, uptake among men and recruitment of sex-partners is low and RDS stopped early. Future studies are needed to explore the sustainability, cost-effectiveness, and impact of strategies that target people at risk who are not effectively reached by regular health care.

Objectives: Pharyngeal Chlamydia trachomatis (chlamydia) might contribute to ongoing chlamydia transmission, yet data on spontaneous clearance duration are rare. We examined the prevalence, spontaneous clearance, chlamydial DNA concentration and genotypes of pharyngeal chlamydia among clinic patients with sexually transmitted infection (STI)., Methods: Female patients at high risk for an STI who reported active oral sex and male patients who have sex with men (MSM) were screened for pharyngeal chlamydia RNA using a nucleic acid amplification test. A repeat swab was obtained to evaluate spontaneous clearance in untreated patients with pharyngeal chlamydia. Quantitative chlamydia DNA load was determined by calculating the chlamydia/human cell ratio., Results: Pharyngeal chlamydia was detected in 148/13 111 (1.1%) MSM and in 160/6915 (2.3%) women. 53% of MSM and 32% of women with pharyngeal chlamydia did not have a concurrent anogenital chlamydia infection. In 16/43 (37%) MSM and in 20/55 (36%) women, the repeat pharyngeal swab was negative (median follow-up 10 days, range 4-58 days). Patients with an initial chlamydial DNA concentration above the median were less likely to clear. Of 23 MSM with pharyngeal chlamydia who had sex with a lymphogranuloma venereum (LGV)-positive partner recently or in the past, two were LGV biovar positive (8.7%)., Conclusions: The pharynx is a reservoir for chlamydia and LGV, and may play a role in ongoing transmission. Although delay in ribosomal RNA decline after resolution of the infection might have led to an underestimation of spontaneous clearance, in high-risk STI clinic patients, testing the pharynx for chlamydia should be considered., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: Chlamydia trachomatis (CT) reporting rates from sexually transmitted infection clinics and general practitioners have shown a rising trend in the Netherlands. It is unknown to what extent this reflects increased CT transmission or improved case finding. To achieve more insight into the CT epidemic, we explored the CT IgG seroprevalence (a marker of past CT infection) in the general population of the Netherlands in 1996 and in 2007., Methods: From two population-based studies in 1996 and 2007, serum samples, demographic and sexual behaviour outcomes were examined, including 1246 men and 1930 women aged 15-39 years. Serum CT IgG antibodies were analysed using the Medac CT IgG ELISA test. Multivariate logistic regression analyses explored the seroprevalence and determinants over time., Results: The CT IgG seroprevalence was higher in women than in men (10% vs 6%). Among women aged 25-39 years the seroprevalence was lower in 2007 (9%) than in 1996 (14%; adjusted OR (aOR) 0.6, 95% CI 0.4 to 0.8). There was no statistical evidence of a difference in seroprevalence within birth cohorts. Factors associated with seropositivity were male gender (aOR 0.4, 95% CI 0.3 to 0.7), a self-reported history of CT infection (aOR 5.1, 95% CI 2.6 to 10.0), age 25-39 years (aOR 1.7, 95% CI 1.1 to 2.7), non-Western ethnicity (aOR 2.2, 95% CI 1.4 to 3.3) and ≥ 2 recent sexual partners (aOR 2.2, 95% CI 1.3 to 3.5)., Conclusions: Between 1996 and 2007 the proportion of individuals in the general population with CT IgG antibodies was lower among women aged 25-39 years, but remained similar among younger women and men., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: In recent years a few cases of lymphogranuloma venereum (LGV) in heterosexuals in Europe have been reported. It is not known whether LGV transmission among heterosexuals occurs on a wider scale., Methods: Heterosexual male and female STI clinic clients (n = 587) in Amsterdam, the Netherlands, with a positive nucleic acid amplification test (NAAT) result for Chlamydia trachomatis (CT) were screened for IgA anti-MOMP in serum. If the value was above the cut-off index (2.0) the patient's CT positive urogenital, ocular or rectal sample(s) were selected and tested for LGV by an in-house LGV-specific NAAT., Results: Sera of 126 patients were above 2.0 COI. Some patients had >1 CT positive sample. Samples could not be retrieved from 15 of the 126 persons, and 7 samples that were found positive for CT in the diagnostic amplification process could not be confirmed and hence not typed. We did not find a single case of LGV infection in 123 urogenital, ocular or rectal samples from 104 patients., Conclusion: We found no indications for significant spread of LGV infection in heterosexuals in Amsterdam. Surveillance in females with cervical or anal CT infection is indicated to monitor LGV occurrence in heterosexuals.

Lymphogranuloma venereum (LGV) is a sexually transmitted infection, previously only seen in tropical regions. This changed in 2003 when the first endemically acquired LGV cases were reported in Rotterdam, the Netherlands, among predominantly HIV positive men who have sex with men (MSM). Early diagnosis is important to prevent irreversible complications and to stop further transmission in the community. In contrast to earlier reports, approximately 25% of LGV infections are asymptomatic and form an easily missed undetected reservoir. The majority of reported infections in MSM are found in the anorectal canal and not urogenital, which leaves the mode of transmission within the MSM network unclear. Given the increasing trend, the LGV endemic is clearly not under control. Therefore directed screening must be intensified.

Background: Symptom- and sexual history-based testing i.e., testing on indication, for anorectal sexually transmitted infections (STIs) in women is common. Yet, it is unknown whether this strategy is effective. Moreover, little is known about alternative transmission routes i.e. by fingers/toys. This study assesses anorectal STI prevalence and infections missed by current testing practice, thereby informing the optimal control strategy for anorectal STIs in women., Methods: Women (n = 663) attending our STI-clinic between May 2012-July 2013 were offered routine testing for anorectal and urogenital Chlamydia trachomatis and Neisseria gonorrhoeae. Data were collected on demographics, sexual behaviour and symptoms. Women were assigned to one of the categories: indication (reported anal sex/symptoms), fingers/toys (only reported use of fingers/toys), or without indication., Results: Of women, 92% (n = 654) participated. There were 203 reports (31.0%) of anal sex and/or symptoms (indication), 48 reports (7.3%) of only using fingers/toys (fingers/toys), and 403 reports (61.6%) of no anal symptoms, no anal sex and no anal use of fingers/toys (without indication). The overall prevalence was 11.2% (73/654) for urogenital chlamydia and 8.4% (55/654) for anorectal chlamydia. Gonorrhoea infections were not observed. Prevalence of anorectal chlamydia was 7.9% (16/203) for women with indication and 8.6% (39/451) for all other women (P = 0.74). Two-thirds (39/55) of anorectal infections were diagnosed in women without indication. Isolated anorectal chlamydia was rare (n = 3): of all women with an anorectal infection, 94.5% (52/55) also had co-occurrence of urogenital chlamydia. Of all women with urogenital chlamydia, 71.2% (52/73) also had anorectal chlamydia., Conclusions: Current selective testing on indication of symptoms and sexual history is not an appropriate control strategy for anorectal chlamydia in women visiting an STI clinic. Routine universal anorectal testing is feasible and may be a possible control strategy in women. Yet costs may be a problem. When more restricted control measures are preferred, possible alternatives include (1) anorectal testing only in women with urogenital chlamydia (problem: treatment delay or loss to follow up), and (2) direct treatment for urogenital chlamydia that is effective for anorectal chlamydia as well.

Objectives: Repeated infections of Chlamydia trachomatis may be new infections or persistent infections due to treatment failure or due to unresolved infections in sexual partners. We aimed to establish the value of using high-resolution multilocus sequence typing (CT-MLST) to discriminate repeated C trachomatis infections., Methods: Paired C trachomatis positive samples (baseline (T0) and after 6 months (T1)) were selected from two Dutch screening implementation studies among young heterosexual people. Typing with six CT-MLST loci included the ompA gene. The uniqueness of strains was assessed using 256 reference CT-MLST profiles., Results: In 27 out of 34 paired cases, full sequence types were obtained. A multilocus (13 cases) or single locus variant (4 cases) was seen, indicating 17 new C trachomatis infections at T1. The ompA genovar was identical for 5 of 17 discordant cases. The 10 cases with concordant typing results were categorised as treatment failure (5 cases) versus persistent or recurrent infections (5 cases). Surprisingly, these concordant cases had C trachomatis strains that were either unique or found in small clusters. The median time between T0 and T1 did not differ between the concordant and discordant cases., Conclusions: High-resolution typing was superior in discriminating new infections compared with only using ompA genovar typing. Many cases (37%) showed exactly the same C trachomatis strain after 6 months. CT-MLST is not conclusive in distinguishing recurrent infections from treatment failure.

Objectives: Current strategies for controlling non-urogenital chlamydia and gonorrhoea are not uniform. It is assumed that present anorectal/oropharyngeal infections are coincidentally treated with urogenital infections. However, it is not clear whether this control strategy is effective. To inform current debate, we evaluated the anatomical site distribution of chlamydia and gonorrhoea by routine testing in men who have sex with men (hereafter men) and in high-risk women (prostitutes and swingers, hereafter women)., Methods: Between January 2010 and November 2012, all men (n=2436) and women (n=1321) attending our sexually transmitted infection clinic were routinely tested for anorectal, oropharyngeal and urogenital Chlamydia trachomatis and Neisseria gonorrhoeae. Data were collected on demographics and sexual behaviour., Results: Overall chlamydia positivity was 10.4% (254/2436) in men and 7.0% (92/1321) in women, for gonorrhoea this was 6.3% (154/2436) and 3.1% (41/1321), respectively. Isolated non-urogenital infections amounted to 76% of all infections in men and for up to 59% of all infections in women. For combined urogenital and anorectal infections, this amounted to 14% for men and up to 54% for women., Conclusions: Testing only for non-urogenital infections is insufficient, as it overlooks many infections. The use of coincidental treatment is therefore a suboptimal control strategy in high-risk groups for halting complications and transmission. There is an urgent need to optimise the testing guidelines for chlamydia and gonorrhoea at different anatomical sites.

Background: Chlamydia trachomatis infection in pregnancy may lead to adverse pregnancy outcomes. In the Netherlands, testing for C. trachomatis is based on risk assessment. We assessed midwives' knowledge, test practices, assessment of risk behavior, and attitudes regarding testing for C. trachomatis infection during pregnancy. We evaluated the association between midwives' characteristics and their knowledge of C. trachomatis infection in terms of symptomatology and outcomes., Methods: This was a cross-sectional study among primary care midwives in the Netherlands. Between September and November 2011, midwives from all Dutch primary care midwifery practices were invited to complete a questionnaire about C. trachomatis infection., Results: Of the 518 midwives invited to participate in this study, 331 (63.9%) responded. The overall median knowledge score for questions about symptomatology and outcomes was 10 out of a maximum score of 15. The median knowledge score was higher among midwives in urban areas. In total, 239 (72.2%) midwives reported testing pregnant women for C. trachomatis. The primary reason for testing was a request by the woman herself (96.2%), followed by symptoms of infection (89.1%), risk behavior (59.3%), and risk factors for infection (7.3%). Almost 25% of midwives showed positive attitudes towards universal screening for C. trachomatis., Conclusions: Midwives were knowledgeable about symptoms of infection, but less about outcomes. Midwives test pregnant women for C. trachomatis mainly on the women's request. Otherwise, testing is based on symptoms of infection rather than on known risk factors. This may contribute to under-diagnosis and under-treatment, leading to maternal, perinatal, and neonatal morbidity.

Background: In The Netherlands, a national chlamydia screening program started in 2008, but the participation was low and the screening was not cost-effective. This study aimed to explore unconscious and conscious associations with chlamydia screening (16-29 year-olds). In addition, we examined whether information presented in chlamydia screening invitation letters had an effect on the evaluation of these determinants compared to a no-letter group., Methods: An Internet survey was conducted that included self-report measures of attitude, susceptibility, severity, unrealistic optimism, subjective, moral, and descriptive norm, perceived behavioral control, outcome expectations, barriers, intention, and a response time measure to assess unconscious associations of chlamydia screening with annoyance, threat and reassurance., Results: On the unconscious level, participants (N = 713) who received no information letter associated testing for chlamydia with annoyance and threat, but also with reassurance (all p's < .001). On the self-report measures, participants showed a low intention towards chlamydia screening (M = 1.42, range 1-5). Subjective norm, moral norm, perceived susceptibility and attitude were the most important predictors of the intention to screen (R2 = .56). Participants who rated their susceptibility as high also reported more risky behaviors (p < .001).In the groups that received a letter (N = 735), a weaker unconscious association of chlamydia screening with annoyance was found compared with the no-letter group (p < .001), but no differences were found in reassurance or threat. Furthermore, the letters caused a higher intention (p < .001), but intention remained low (M = 1.74). On a conscious level, giving information caused a more positive attitude, higher susceptibility, a higher subjective and moral norm, and more positive outcome expectations (all p's < .001)., Conclusion: Subjective norm, moral norm, susceptibility, and attitude towards chlamydia might be crucial targets to increase chlamydia screening behavior among sexually active young people. This study shows that informational invitation letters increase the intention and the intention-predicting variables. More evidence is needed on whether screening behavior can be increased by the use of an alternative information letter adapted to the specific unconscious and conscious determinants revealed in this study, or that we need other, more interactive behavior change methods.

Objectives: To examine lymphogranuloma venereum (LGV) trends over time among men who have sex with men (MSM) visiting the Amsterdam sexually transmitted infection (STI) clinic; to investigate anal LGV symptomatology; and to examine the positivity and characteristics of anorectal and inguinal LGV., Methods: We included MSM consultations from whom a swab (from anorectum, bubo or an genital ulcer) was taken for Chlamydia trachomatis (Ct) screening. Anorectal swabs were taken from all MSM who reported receptive anorectal intercourse in the preceding 6 months. Ct positive samples were further tested with a pmpH PCR to identify L-genovars. Patient symptoms, clinical and anoscopic inflammatory signs, and STI co-infections were noted; Gram-stained anorectal mucosal smears were examined., Results: Between January 2005 and June 2012, 48 570 consultations among MSM were conducted. In 3628/35 650 visits, anorectal Ct infections were diagnosed, including 411 anal LGV (1.2%). Moreover, 65/1649 genital ulcer swabs were Ct positive; 10 were inguinal LGV (0.6%) Since January 2011 a significant increase in the positivity of LGV occurred (p<0.0001). 89 (27.2%) anorectal LGV cases were asymptomatic. HIV prevalence among anorectal LGV cases was significantly higher (p=0.008) than among inguinal LGV cases. STI co-morbidity in anorectal LGV cases remained invariably high during the study period., Conclusions: Since January 2011, LGV positivity in MSM consultations in Amsterdam has risen significantly. The great majority comprise anal LGV; inguinal LGV is rare. Anal LGV is asymptomatic in a quarter of cases. In all MSM with anal Ct infections LGV should be excluded, irrespective of symptoms or inflammatory signs.

Objective: The goal of this multi-cohort study is to investigate the positivity rate of Trichomonas vaginalis (TV) among three distinct Dutch patient populations and its relation with Chlamydia trachomatis (CT) positivity. Few studies have been performed in Europe where TV positivity rate seems to be low. Additionally, the majority of earlier studies have focused on high risk or specific populations., Methods: A random selection of men and women from a national population-based chlamydia screening, attendees of a sexually transmitted infections (STI) clinic and a non-selected population from general practitioners (GPs) were systematically screened for TV and CT using PCR. The associations among TV and CT co-infection, age and gender were studied., Results: A total of 2079 individuals were studied. A TV positivity rate of 1.5% was observed in the medium risk GP cohort followed by 0.7% in the low risk population-based cohort and 0.6% in the high risk STI clinic. TV was found in 0.7% of CT positives and a similar 1.1% among CT negatives. All TV positive individuals in this study were women., Conclusions: The positivity rate of TV was low (<2%) and comparable in all three populations studied. We found no association between TV and CT infection.

Since 2003, an epidemic of lymphogranuloma venereum (LGV) has been ongoing in men who have sex with men (MSM) in Europe. Of 92,271 MSM consulting sexually transmitted disease (STI) clinics in the Netherlands between 2006 and 2011, 63,228 (68%) were tested for anorectal Chlamydia infection, with 6,343 (10%) positive diagnoses. In 4,776 of those (75%), LGV testing was performed, with regional variation from 7% to 97%. In total 414 LGV cases were diagnosed, a mean annual positivity rate of 8.7%, decreasing from 14% in 2007 to 6% in 2011, but increasing to 13.1% during 2012 (184 new cases). Risk factors for LGV were human immunodeficiency virus (HIV) positivity (odds ratio (OR)=4.1; 95% confidence interval (CI): 3.2–5.3), STI symptoms (OR=4.1; 95% CI: 3.1–5.4), more than 50 sex partners in the past six months (OR=3.7; 95% CI: 1.1–12.4), older age (40–44 years: OR=2.1; 95% CI: 1.5–2.8), no condom use (OR=2.2; 95% CI: 1.2–3.9) and homosexuality (as opposed to bisexuality; OR=2.2; 95% CI: 1.1–4.2). Regional differences in LGV testing rates limit national LGV surveillance, leading to an underestimation of the real incidence. Characteristics of MSM with LGV did not change over time, so existing prevention strategies should be intensified.

We investigated Chlamydia trachomatis strains from Nanjing, China, and whether these strains differed from Amsterdam, the Netherlands. C. trachomatis type was determined with multilocus sequence typing. Most strains were specific to Nanjing, but some clustered with strains from Amsterdam. This demonstrates a geographical variation in C. trachomatis previously left undetected.

Urethral lymphogranuloma venereum (LGV) is not screened routinely. We found that in 341 men having sex with men with anorectal LGV, 7 (2.1%) had concurrent urethral LGV. Among 59 partners, 4 (6.8%) had urethral LGV infections. Urethral LGV is common, probably key in transmission, and missed in current routine LGV screening algorithms.

High-resolution genotyping of Chlamydia trachomatis improves the characterization of strains infecting different patient groups and sexual networks. In this study, multilocus sequence typing (MLST) and ompA sequence determination were used for an analysis of C. trachomatis strains from 203 men who have sex with men (MSM) from Sweden, the Netherlands, and the United States. The results obtained were compared with data from 153 heterosexual women from Sweden and the Netherlands. The overlap in MLST/ompA profiles between MSM from Sweden and the Netherlands was 68%, while the overlap between heterosexual populations from these countries was only 18%. The distribution of genotypes in MSM from the United States was less similar to that in MSM from the European countries, with 45% and 46% overlaps for MSM in Sweden and the Netherlands, respectively. Minimum-spanning-tree analysis of MLST/ompA sequence types identified two large clusters that contained almost exclusively samples from MSM and comprised 74% of all MSM samples. Three other clusters were predominated by samples from women but also contained MSM specimens. Of 19 detected variants of the MLST target CT144, three variants were highly associated with MSM. Our study supports the hypotheses of both tissue tropism as well as epidemiological network structures as explanations for the linkage between specific genetic variants and sexual orientation.

Since 2003, a lymphogranuloma venereum epidemic has been reported in The Netherlands and other European countries. This epidemic is caused by Chlamydia trachomatis serovariant L2b and has only been seen in men having sex with men. The authors investigated a woman presenting with a bubo in her right groin. The authors showed by real-time PCR that the woman was infected with C trachomatis, serovariant L2b. This is the first reported case study of a female patient with bubonic lymphogranuloma venereum caused by serovariant L2b, which was probably contracted via her bisexual male partner.

Objective: To evaluate the effectiveness of register based, yearly chlamydia screening., Design: Controlled trial with randomised stepped wedge implementation in three blocks., Setting: Three regions of the Netherlands: Amsterdam, Rotterdam, and South Limburg., Participants: 317 304 women and men aged 16-29 years listed on municipal registers at start of trial., Intervention: From March 2008 to February 2011, the Chlamydia Screening Implementation programme offered yearly chlamydia screening tests. Postal invitations asked people to use an internet site to request a kit for self collection of samples, which would then be sent to regional laboratories for testing. Treatment and partner notification were done by the general practitioner or at a sexually transmitted infection clinic., Main Outcome Measures: Primary outcomes were the percentage of chlamydia tests positive (positivity), percentage of invitees returning a specimen (uptake), and estimated chlamydia prevalence. Secondary outcomes were positivity according to sex, age, region, and sociodemographic factors; adherence to screening invitations; and incidence of self reported pelvic inflammatory disease., Results: The participation rate was 16.1% (43 358/269 273) after the first invitation, 10.8% after the second, and 9.5% after the third, compared with 13.0% (6223/48 031) in the control block invited at the end of round two of the intervention. Chlamydia positivity in the intervention blocks at the first invitation was the same as in the control block (4.3%) and 0.2% lower at the third invitation (odds ratio 0.96 (95% confidence interval 0.83 to 1.10)). No substantial decreases in positivity were seen after three screening rounds in any region or sociodemographic group. Among the people who participated three times (2.8% of all invitees), positivity fell from 5.9% to 2.9% (odds ratio 0.49 (0.47 to 0.50))., Conclusions: There was no statistical evidence of an impact on chlamydia positivity rates or estimated population prevalence from the Chlamydia Screening Implementation programme after three years at the participation levels obtained. The current evidence does not support a national roll out of this register based chlamydia screening programme., Trial Registration: NTR 3071 (Netherlands Trial Register, www.trialregister.nl).

Objectives: Systematic screening for Chlamydia trachomatis by individual invitation can be optimised by filtering participants on risk profile, excluding people at no or low risk. The authors investigated this technique in a large-scale chlamydia screening programme in The Netherlands in one rural region where relatively low prevalence was expected (<2%)., Methods: Invitees were alerted by personal letter to log in to http://www.chlamydiatest.nl and fill in an 8-item questionnaire. Only invitees with sufficient score could proceed to request a test kit. The authors investigated the effect of selection on participation, positivity and acceptability in three screening rounds and on the number needed to invite and the number needed to screen., Results: The selection led to exclusion of 36% of potential participants and a positivity rate of 4.8% among participants, achieving similar number needed to screen values in the rural and urban areas. Higher scores were clearly related to higher positivity rates. Persons who were excluded from participation did not have a lower response in the next round. The acceptability study revealed disappointment about exclusion of 30% of excluded participants but most approved of the screening set-up., Conclusions: Systematic selection of screening participants by risk score is feasible and successful in realising higher positivity rates. A somewhat stricter selection could be applied in the rural and urban areas of the screening programme. Multiple-item selection with a cut-off total score may work better than, more commonly used, selection by single criteria, especially in low-risk populations. Acceptability of selection is high but could still be improved by better communication on expectations.

Background: In the Netherlands, no guidelines exist for routine sexually transmitted infection (STI) screening of human immunodeficiency virus (HIV)-infected men having sex with men (MSM). We assessed prevalence and factors associated with asymptomatic STI., Methods: MSM visiting HIV outpatient clinics of academic hospitals were tested for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), syphilis, and hepatitis B and C infection. Prevalence and risk factors were studied using logistic regression., Results: In total, 659 MSM were included between 2007 and 2008. STI were found in 16.0% of patients, mostly anal CT and syphilis. One new hepatitis B and 3 new hepatitis C infections were identified. In multivariate analyses, any STI (syphilis, CT, or NG) was associated with patient's age below 40 years (odds ratio [OR]: 2.5, 95% confidence interval [CI]: 1.3-5.0), having had sex with 2 or more sexual partners (OR 2.1, 95% CI: 1.2-3.5), the use of the same sexual toys with a sexual partner (OR 2.2, 95% CI: 1.0-4.9), and enema use before sex (OR: 2.3, 95% 1.2-4.2). Syphilis was independently associated with fisting with gloves versus no fisting (OR: 4.9, 95% CI: 1.7-13.7) and with rimming (OR: 5.0, 95% CI: 1.7-15.0). CT or NG were associated with age below 45 years (age 40-44 years: OR: 2.4, 95% CI: 1.1-5.3; age <40 years: OR: 2.4, 95% CI: 1.1-5.4), enema use before sex (OR: 2.4, 95% CI: 1.3-4.4) and drug use during sex (OR: 2.4, 95% CI: 1.4-4.0)., Conclusions: High-risk sexual behavior was very common, and 16% of HIV-infected MSM in HIV care had an asymptomatic STI, mostly anal CT and syphilis. Development of STI screening guidelines is recommended.

Background: Chlamydia trachomatis infection (CT) is the most prevalent bacterial STD. Sexually active adolescents and young adults are the main risk group for CT. However, STD testing rates in this group are low since exposed individuals may not feel at risk, owing-at least in part-to the infection's largely asymptomatic nature. Designing new testing environments that are more appealing to young people who are most at risk of acquiring chlamydia can be an important strategy to improve overall testing rates. Here we evaluate the effect of a school-based sexual health program conducted among vocational school students, aiming to obtain better access for counseling and enhance students' STD testing behavior., Methods: Adolescents (median age 19 years) attending a large vocational school were provided with sexual health education. Students filled in a questionnaire measuring CT risk and were offered STD testing. Using univariate and multivariate analysis, we assessed differences between men and women in STD-related risk behavior, sexual problems, CT testing behavior and determinants of CT testing behavior., Results: Of 345 participants, 70% were female. Of the 287 sexually active students, 75% were at high risk for CT; one third of women reported sexual problems. Of sexually active participants, 61% provided a self-administered specimen for STD testing. Independent determinants for testing included STD related symptoms and no condom use. All CT diagnoses were in the high-CT-risk group. In the high-risk group, STD testing showed an increased uptake, from 27% (previous self-reported test) to 65% (current test). CT prevalence was 5.7%., Conclusions: Vocational school students are a target population for versatile sexual health prevention. When provided with CT testing facilities and education, self selection mechanisms seemed to increase CT testing rate dramatically in this high-CT-risk population expressing sexual problems. Considering the relative ease of testing and treating large numbers of young adults, offering tests at a vocational school is feasible in reaching adolescents for STD screening. Although cost-effectiveness remains an issue counseling is effective in increasing test rates.

Background: The relevance of screening of oropharynx and anorectum in addition to endocervical tests for detection of Chlamydia trachomatis and Neisseria gonorrhoeae infection is unclear in women, while there is a documented benefit of this approach in men who have sex with men., Methods: Female visitors to the sexually transmitted disease (STD) clinic were asked about their sexual practice as a part of the routine electronic patient file. In addition to tests for endocervical infection, swabs were taken from the oropharynx and anorectum to test for C. trachomatis and N. gonorrhoeae based on the history of sexual contact. Routinely, all electronic patient files are anonymously included in a database for surveillance purposes. In this observational study, we analyzed all consultations in the database over an 18 months period., Results: A total of 4299 consultations were registered; 10% of women had endocervical chlamydia and 1.1% had gonorrhea. The detection rates for C. trachomatis and N. gonorrhoeae from oropharyngeal samples were 1.9% and 0.8%, and from anorectal samples 8.7% and 1.7%, respectively. Except for 2 cases of pharyngeal gonorrhea, all oropharyngeal and anorectal infections were asymptomatic. Inclusion of oropharyngeal and anorectal tests in the screening protocol was associated with a percentage increase in prevalence of chlamydia by 9.5% and gonorrhea by 31%, relative to tests for endocervical tests alone. The percentage increase in prevalence was higher than that for the symptom-based approach (3.7% and 10.4%, respectively)., Conclusions: Inclusion of oropharyngeal and anorectal tests in the STD screening protocol increases the prevalence of chlamydia and gonorrhea in women. Screening of anatomical sites based on sexual history is preferred over a symptom-based protocol.

We aimed to compare conventional ompA typing of Chlamydia trachomatis with multilocus sequence typing (MLST) and multilocus variable-number tandem-repeat (VNTR) analysis (MLVA). Previously used MLST and MLVA systems were compared to modified versions that used shorter target regions and nested PCR. Heterosexual couples were selected from among persons with urogenital C. trachomatis infections visiting the sexually transmitted infection outpatient clinic in Amsterdam, The Netherlands. We identified 30 couples with a total of 65 C. trachomatis-positive samples on which MLST and MLVA for eight target regions were performed. All regions were successfully sequenced in 52 samples, resulting in a complete profile for 18 couples and 12 individuals. Nine ompA genovars from D to K, with two variants of genovar G, were found. The numbers of sequence type and MLVA type profiles were 20 for MLST and 21 for MLVA, and a combination of MLST and MLVA yielded 28 profiles, with discriminatory indexes (D) ranging from 0.95 to 0.99. Partners in 17 couples shared identical profiles, while partners in 1 couple had completely different profiles. Three persons had infections at multiple anatomical locations, and within each of these three individuals, all profiles were identical. The discriminatory capacity of all MLST and MLVA methods is much higher than that of ompA genotyping (D = 0.78). No genotype variation was found within the samples of the same person or from heterosexual couples with a putative single transmission. This shows that the chlamydial genome in clinical specimens has an appropriate polymorphism to enable epidemiological cluster analysis using MLST and MLVA.

Background: Sexually transmitted infection (STI) screening programmes are implemented in many countries to decrease burden of STI and to improve sexual health. Screening for Chlamydia trachomatis and Neisseria gonorrhoeae has a prominent role in these protocols. Most of the screening programmes concerning men having sex with men (MSM) are based on opportunistic urethral testing. In The Netherlands, a history-based approach is used. The aim of this study is to evaluate the protocol of screening anatomic sites for C. trachomatis and N. gonorrhoeae infection based on sexual history in MSM in routine practice in The Netherlands., Methods: All MSM visiting the clinic for STI in The Hague are routinely asked about their sexual practice during consulting. As per protocol, tests for urogenital, oropharyngeal and anorectal infection are obtained based on reported site(s) of sexual contact. All consultations are entered into a database as part of the national STI monitoring system. Data of an 18 months period were retrieved from this database and analysed., Results: A total of 1455 consultations in MSM were registered during the study period. The prevalence of C. trachomatis and N. gonorrhoeae per anatomic site was: urethral infection 4.0% respectively and 2.8%, oropharynx 1.5% and 4.2%, and anorectum 8.2% and 6.0%. The majority of chlamydia cases (72%) involved a single anatomic site, which was especially manifest for anorectal infections (79%), while 42% of gonorrhoea cases were single site. Twenty-six percent of MSM with anorectal chlamydia and 17% with anorectal gonorrhoea reported symptoms of proctitis; none of the oropharyngeal infections were symptomatic. Most cases of anorectal infection (83%) and oropharyngeal infection (100%) would have remained undiagnosed with a symptom-based protocol., Conclusions: The current strategy of sexual-history based screening of multiple anatomic sites for chlamydia and gonorrhoea in MSM is a useful and valid guideline which is to be preferred over a symptom-based screening protocol.