Pregnancies and Time to Pregnancy in Women With and Without a Previous Chlamydia trachomatis Infection.

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.

Chlamydia trachomatis and the Risk of Pelvic Inflammatory Disease, Ectopic Pregnancy, and Female Infertility: A Retrospective Cohort Study Among Primary Care Patients.

BACKGROUND: We evaluated the risk of pelvic inflammatory disease (PID), ectopic pregnancy, and infertility in women with a previous Chlamydia trachomatis (CT) diagnosis compared with women who tested negative for CT and CT untested women, considering both targeted and incidental (ie, prescribed for another indication) use of CT-effective antibiotics. METHODS: This was a retrospective study of women aged 12-25 years at start of follow-up within the Clinical Practice Research Datalink GOLD database linked to index of multiple deprivation quintiles, 2000-2013. CT test status and antibiotic use were determined in a time-dependent manner. Risk of PID, ectopic pregnancy, or female infertility were evaluated using of Cox proportional hazard models. RESULTS: We studied 857 324 women, contributing 6 457 060 person-years. Compared with women who tested CT-negative, women who tested CT-positive had an increased risk of PID (adjusted hazard ratio [aHR], 2.36; 95% confidence interval [CI], 2.01-2.79), ectopic pregnancy (aHR, 1.87; 95% CI, 1.38-2.54), and infertility (aHR, 1.85; 95% CI, 1.27-2.68). The PID risk was higher for women with 2 or more positive CT tests than those with 1 positive test. PID risk increased with the number of previous antibiotic prescriptions, regardless of CT test status. CONCLUSIONS: We showed an association between CT-positive tests and 3 adverse reproductive health outcomes. Moreover, this risk increased with repeat CT infections. CT-effective antibiotic use showed no decreased risks of subsequent PID regardless of CT history. Our results confirm the reproductive health burden of CT, which requires adequate public health interventions.

Relation between Chlamydia trachomatis infection and pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility in a Dutch cohort of women previously tested for chlamydia in a chlamydia screening trial.

OBJECTIVES: A better understanding of Chlamydia trachomatis infection (chlamydia)-related sequelae can provide a framework for effective chlamydia control strategies. The objective of this study was to estimate risks and risk factors of pelvic inflammatory disease (PID), ectopic pregnancy and tubal factor infertility (TFI) with a follow-up time of up until 8 years in women previously tested for chlamydia in the Chlamydia Screening Implementation study (CSI) and participating in the Netherlands Chlamydia Cohort Study (NECCST). METHODS: 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. RESULTS: 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 <20 versus >24 years at first infection (HR 4.35, 1.1 to 16.8). CONCLUSION: 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. TRIAL REGISTRATION: NTR-5597.

Evaluation and enumeration of online test providers for sexually transmitted infections, specifically chlamydia, in the Netherlands.

OBJECTIVES: Online testing for STIs might complement regular care provided by general practitioners or STI clinics. Two types of online testing can be distinguished, self-testing and self-sampling (sending sample to a laboratory for diagnosis). Online testing can occur without consultation with a healthcare professional, therefore information given by providers is essential for informed decision-making. We aimed to enumerate online test providers in the Netherlands focusing on chlamydia tests, to evaluate information using quality indicators and to gain insight on the proportion of online testing in the STI testing arena. METHODS: We performed a systematic internet search to identify online STI test providers. Twenty quality indicators were evaluated on their websites; indicator scores were weighted by level of importance (expert opinion). High scoring providers were recommended, on the condition that the sensitivity and specificity of the test were above 95% and providers included a follow-up procedure in case of a positive result. Finally, providers were contacted to inquire about the number of sold tests, positivity rates and demographic characteristics of testers. RESULTS: Five out of 12 identified self-sample test providers could be recommended, versus zero out of eight self-test providers. Self-sample test providers gave complete and correct information on more indicators (67%) compared with self-test providers (38%). In 2015, an estimated 30 000-40 000 self-sample tests were purchased, and 12 000-25 000 self-tests, which is roughly 10%-15% of the total number of STI tests. CONCLUSION: This evaluation shows that some online self-sample test providers could be put forward as way of STI testing complementing regular testing options. None of the self-test providers were recommended. Regularly evaluating online test providers is advised to improve quality of the information on the websites. Finally, self-testing might not be suited for all populations as most information is provided in written format only.

National prevalence estimates of chlamydia and gonorrhoea in the Netherlands.

OBJECTIVES: National prevalence estimates of Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoeae (gonorrhoea) are important for providing insights in the occurrence and control of these STIs. The aim was to obtain national prevalence estimates for chlamydia and gonorrhoea and to investigate risk factors associated with infection. METHODS: Between November 2016 and January 2017, we performed a national population-based cross-sectional probability sample survey among men and women aged 18-34 years in the Netherlands. Individuals were invited to complete a questionnaire about sexual health. At the end of the questionnaire, sexually active individuals could request a home-based sampling kit. Samples were tested for chlamydia and gonorrhoea using nucleic acid amplification test (NAAT). Logistic regression analyses were performed for predictors of participation and chlamydia infection. RESULTS: Of the 17 222 invited individuals, 4447 (26%) participated. Of these, 3255 were eligible for prevalence survey participation and 550 (17%) returned a sample. Participation in the prevalence survey was associated with age (20+) and risk factors for STI. We did not detect any gonorrhoea. The overall weighted prevalence of chlamydia was 2.8% (95% CI 1.5% to 5.2%); 1.1% (0.1% to 7.2%) in men and 5.6% (3.3% to 9.5%) in women. Risk factors for chlamydia infections in women aged 18-24 years were low/medium education level, not having a relationship with the person you had most recent sex with and age at first sex older than 16. CONCLUSIONS: Chlamydia and gonorrhoea prevalence were low in the general Dutch population, as was the participation rate. Repeated prevalence surveys are needed to analyse trends in STI prevalences and to evaluate control policies.

A pill for the partner via the chlamydia patient? Results from a mixed method study among sexual health care providers in the Netherlands.

BACKGROUND: Chlamydia prevalence in the Netherlands remains high despite targeted efforts. Effective Partner Notification (PN) and Partner Treatment (PT) can interrupt transmission and prevent re-infections. Patient Initiated Partner Treatment (PIPT) may strengthen chlamydia control. This study explores the current practice of PN and PT, and benefits of, and barriers and facilitators for PIPT among professionals in sexual health care in the Netherlands. METHODS: A qualitative study was performed among GPs, GP-assistants (GPAs), physicians and nurses working at Sexual Health Clinics (SHC) and key-informants on ethnical diversity using topic lists in focus groups (N = 40) and semi-structured questionnaires in individual interviews (N = 9). Topics included current practices regarding PN and PT, attitude regarding PIPT, and perceived barriers and facilitators for PIPT. Interviews were taped, transcribed verbatim, and coded using ATLAS.ti. A quantitative online questionnaire on the same topics was sent to all physicians and nurses employed at Dutch SHC (complete response rate 26% (84/321)). RESULTS: The qualitative study showed that all professionals support the need for more attention to PN, and that they saw advantages in PIPT. Mentioned barriers included unwilling PN-behaviour, Dutch legislation, several medical considerations and inadequate skills of GPs. Also, concerns about limited knowledge of cultural sensitivity around PN and PT were raised. Mentioned facilitators of PIPT were reliable home based test-kits, phone-contact between professionals and notified partners, more consultation time for GPs or GPAs and additional training. The online questionnaire showed that SHC employees agreed that partners should be treated as soon as possible, but also that they were reluctant towards PIPT without counselling and testing. CONCLUSIONS: Professionals saw advantages in PIPT, but they also identified barriers hampering the potential introduction of PIPT. Improving PN and counselling skills with specific focus on cultural sensitivity is needed. PIPT could be considered for specific partners. PIPT in combination with home based testing and using e-healthcare should be further explored and developed.

STIs in sex partners notified for chlamydia exposure: implications for expedited partner therapy.

OBJECTIVES: Expedited partner therapy (EPT) may reduce chlamydia reinfection rates. However, the disadvantages of EPT for chlamydia include missing the opportunity to test for other STIs and unnecessary use of antibiotics among non-infected partners. As part of a larger study that investigated the feasibility of EPT in the Netherlands, we explored the frequency of STI among a potential EPT target population of chlamydia-notified heterosexual men and women attending STI clinics for testing. METHODS: Cross-sectional national STI/HIV surveillance data, which contain information on all consultations at STI clinics, were used to calculate STI positivity rates stratified by chlamydia notification and gender, and proportions of STI that were attributable to clients notified for chlamydia. RESULTS: Of all consultations in 2015 (n=101 710), 14 445 (14.4%) clients reported to be notified exclusively for chlamydia. Among chlamydia-notified clients, the chlamydia positivity rate was 34.2% (n=4947), and consequently 65.8% (n=9488) of them tested negative for chlamydia. Chlamydia-notified clients contributed to 10.2% of all gonorrhoea infections (n=174/1702) and 10.9% of all infectious syphilis, HIV and/or infectious hepatitis B infections (n=15/173). CONCLUSION: Implementing EPT without additional STI testing for all partners of chlamydia-infected index patients implies that STIs other than chlamydia will be missed. Although the chlamydia positivity rate was high among chlamydia-notified partners, two-thirds would unnecessarily use azithromycin. An evaluation of EPT against the current partner treatment strategy is needed to carefully weigh the potential health gains against the potential health losses and to explore the characteristics of EPT-eligible partners.

Partner notification and partner treatment for chlamydia: attitude and practice of general practitioners in the Netherlands; a landscape analysis.

BACKGROUND: Chlamydia prevalence remains high despite scaling-up control efforts. Transmission is not effectively interrupted without partner notification (PN) and (timely) partner treatment (PT). In the Netherlands, the follow-up of partners is not standardized and may depend on GPs' time and priorities. We investigated current practice and attitude of GPs towards PN and PT to determine the potential for Patient-Initiated Partner Treatment, which is legally not supported yet. METHODS: Multiple data-sources were combined for a landscape analysis. Quantitative data on (potential) PT were obtained from prescriptions in the national pharmacy register (2004-2014) and electronic patient data from NIVEL-Primary Care Database (PCD) and from STI consultations in a subgroup of sentinel practices therein. Furthermore, we collected information on current practice via two short questionnaires at a national GP conference and obtained insight into GPs' attitudes towards PN/PT in a vignette study among GPs partaking in NIVEL-PCD. RESULTS: Prescription data showed Azithromycin double dosages in 1-2% of cases in the pharmacy register (37.000 per year); probable chlamydia-specific repeated prescriptions or double dosages of other antibiotics in NIVEL-PCD (115/1078) could not be interpreted as PT for chlamydia with certainty. STI consultation data revealed direct PT in 6/100 cases, via partner prescription or double doses. In the questionnaires the large majority of GPs (>95% of 1411) reported to discuss PN of current and ex-partner(s) with chlamydia patients. Direct PT was indicated as most common method by 4% of 271 GPs overall and by 12% for partners registered in the same practice. Usually, GPs leave further steps to the patients (83%), advising patients to tell partners to get tested (56%) or treated (28%). In the vignette study, 16-20% of 268 GPs indicated willingness to provide direct PT, depending on patient/partner profile, more (24-45%) if patients would have the chance to notify their partner first. CONCLUSION: GPs in the Netherlands already treat some partners of chlamydia cases directly, especially partners registered in the same practice. Follow-up of partner notification and treatment in general practice needs more attention. GPs may be open to implement PIPT more often, provided there are clear guidelines to arrange this legally and practically.

The need to scale up HIV indicator condition-guided testing for early case-finding: a case-control study in primary care.

BACKGROUND: European guidelines recommend offering an HIV test to individuals who display HIV indicator conditions (ICs). We aimed to investigate the incidence of ICs in primary care reported in medical records prior to HIV diagnosis. METHODS: We did a cross-sectional search in an electronic general practice database using a matched case-control design to identify which predefined ICs registered by Dutch GPs were most associated with an HIV-positive status prior to the time of diagnosis. RESULTS: We included 224 HIV cases diagnosed from 2009 to 2013, which were matched with 2,193 controls. Almost two thirds (n = 136, 60.7%) of cases were diagnosed with one or more ICs in the period up to five years prior to the index date compared to 18.7% (n = 411) of controls. Cases were more likely to have an IC than controls: in the one year prior to the index date, the odds ratio (OR) for at least one condition was 11.7 (95% CI: 8.3 to 16.4). No significant differences were seen in the strength of the association between HIV diagnosis and ICs when comparing genders, age groups or urbanisation levels. There is no indication that subgroups require a different testing strategy. CONCLUSIONS: Our study shows that there are opportunities for IC-guided testing in primary care. We recommend that IC-guided testing be more integrated in GPs' future guidelines and that education strategies be used to facilitate its implementation in daily practice.

Correlation between viral load, multiplicity of infection, and persistence of HPV16 and HPV18 infection in a Dutch cohort of young women.

BACKGROUND: Persistent high-risk human papillomavirus infection precedes the development of cervical cancer. Here we evaluated the contribution of HPV16/18 viral load and the presence of infections with multiple HPV types to persistence and clearance of HPV16/18 infections. METHODS: Vaginal self-swabs were obtained from young women (16-29 y) with one year interval. HPV genotyping was performed using the highly sensitive SPF10-DEIA-LiPA25 system. HPV16/18 DNA loads were quantified via an adapted, highly sensitive qPCR protocol targeting the L1 gene. RESULTS: We identified 227 HPV16 and 111 HPV18 infections with follow-up. For HPV16 132/227 (58%) were persistent and 95/227 cleared. For HPV18 49/111 (44%) infections were persistent and 62/111 cleared. Baseline viral load was significantly higher in persistent infections than in clearing infections for both HPV16 (p=0.022) and HPV18 (p=0.013). At baseline, only HPV16 viral load was significantly higher in multiple HPV infections compared with single infections (p=0.003). In logistic regression analysis HPV16 and HPV18 viral load were found to contribute to persistency with OR=1.279 (95%CI=1.074-1.524) and OR=1.256 (95%CI=1.028-1.533) per log-unit increase HPV16 and HPV18 viral load respectively. The presence of multiple HPV type infections was not associated with higher persistency. CONCLUSION: HPV16/18 viral load might be used as a marker for persisting infections and is affected by the presence of multiple HPV infections. Evaluation of these parameters at the population level may be of value to assess the presence of persistent or clearing HPV16/18 infections as an early marker, and may provide useful quantitative information in (epidemiological) vaccine monitoring studies.

Changes in chlamydia control activities in Europe between 2007 and 2012: a cross-national survey.

BACKGROUND: In 2012, the levels of chlamydia control activities including primary prevention, effective case management with partner management and surveillance were assessed in 2012 across countries in the European Union and European Economic Area (EU/EEA), on initiative of the European Centre for Disease Control (ECDC) survey, and the findings were compared with those from a similar survey in 2007. METHODS: Experts in the 30 EU/EEA countries were invited to respond to an online questionnaire; 28 countries responded, of which 25 participated in both the 2007 and 2012 surveys. Analyses focused on 13 indicators of chlamydia prevention and control activities; countries were assigned to one of five categories of chlamydia control. RESULTS: In 2012, more countries than in 2007 reported availability of national chlamydia case management guidelines (80% vs. 68%), opportunistic chlamydia testing (68% vs. 44%) and consistent use of nucleic acid amplification tests (64% vs. 36%). The number of countries reporting having a national sexually transmitted infection control strategy or a surveillance system for chlamydia did not change notably. In 2012, most countries (18/25, 72%) had implemented primary prevention activities and case management guidelines addressing partner management, compared with 44% (11/25) of countries in 2007. CONCLUSION: Overall, chlamydia control activities in EU/EEA countries strengthened between 2007 and 2012. Several countries still need to develop essential chlamydia control activities, whereas others may strengthen implementation and monitoring of existing activities.

Incidence and persistence of carcinogenic genital human papillomavirus infections in young women with or without Chlamydia trachomatis co-infection.

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.

Comparison of STI-related consultations among ethnic groups in the Netherlands: an epidemiologic study using electronic records from general practices.

BACKGROUND: Currently, surveillance of sexually transmitted infections (STIs) among ethnic minorities (EM) in the Netherlands is mainly performed using data from STI centers, while the general practitioner (GP) is the most important STI care provider. We determined the frequency of STI-related episodes at the general practice among EM, and compared this with the native Dutch population. METHODS: Electronic medical records from 15-to 60-year-old patients registered in a general practice network from 2002 to 2011 were linked to the population registry, to obtain (parental) country of birth. Using diagnoses and prescription codes, we investigated the number of STI-related episodes per 100,000 patient years by ethnicity. Logistic regression analyses (crude and adjusted for gender, age, and degree of urbanization) were performed for 2011 to investigate differences between EM and native Dutch. RESULTS: The reporting rate of STI-related episodes increased from 2004 to 2011 among all ethnic groups, and was higher among EM than among native Dutch, except for Turkish EM. After adjustment for gender, age, and degree of urbanization, the reporting rate in 2011 was higher among Surinamese [Odds Ratio (OR) 1.99, 95 % confidence interval (CI) 1.70-2.33], Antillean/Aruban (OR 2.48, 95 % CI 2.04-3.01), and Western EM (OR 1.24, 95 % CI 1.11-1.39) compared with native Dutch, whereas it was lower among Turkish EM (OR 0.48, 95 % CI 0.37-0.61). Women consulted the GP relatively more frequently regarding STIs than men, except for Turkish and Moroccan women. CONCLUSIONS: Most EM consult their GP more often for STI care than native Dutch. However, it remains unclear whether this covers the need of EM groups at higher STI risk. As a first point of contact for care, GPs can play an important role in reaching EM for (proactive) STI/HIV testing.

Chlamydia screening is not cost-effective at low participation rates: evidence from a repeated register-based implementation study in The Netherlands.

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.

Urogenital Chlamydia trachomatis strain types, defined by high-resolution multilocus sequence typing, in relation to ethnicity and urogenital symptoms among a young screening population in Amsterdam, The Netherlands.

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.

Genital chlamydia prevalence in Europe and non-European high income countries: systematic review and meta-analysis.

BACKGROUND: Accurate information about the prevalence of Chlamydia trachomatis is needed to assess national prevention and control measures. METHODS: We systematically reviewed population-based cross-sectional studies that estimated chlamydia prevalence in European Union/European Economic Area (EU/EEA) Member States and non-European high income countries from January 1990 to August 2012. We examined results in forest plots, explored heterogeneity using the I² statistic, and conducted random effects meta-analysis if appropriate. Meta-regression was used to examine the relationship between study characteristics and chlamydia prevalence estimates. RESULTS: We included 25 population-based studies from 11 EU/EEA countries and 14 studies from five other high income countries. Four EU/EEA Member States reported on nationally representative surveys of sexually experienced adults aged 18-26 years (response rates 52-71%). In women, chlamydia point prevalence estimates ranged from 3.0-5.3%; the pooled average of these estimates was 3.6% (95% CI 2.4, 4.8, I² 0%). In men, estimates ranged from 2.4-7.3% (pooled average 3.5%; 95% CI 1.9, 5.2, I² 27%). Estimates in EU/EEA Member States were statistically consistent with those in other high income countries (I² 0% for women, 6% for men). There was statistical evidence of an association between survey response rate and estimated chlamydia prevalence; estimates were higher in surveys with lower response rates, (p = 0.003 in women, 0.018 in men). CONCLUSIONS: Population-based surveys that estimate chlamydia prevalence are at risk of participation bias owing to low response rates. Estimates obtained in nationally representative samples of the general population of EU/EEA Member States are similar to estimates from other high income countries.

Chlamydia trachomatis Antibody Testing in Vaginal Mucosal Material versus Blood Samples of Women Attending a Fertility Clinic and an STI Clinic.

Background. Chlamydia infections often follow an asymptomatic course but may damage the reproductive tract. Chlamydia antibodies in serum are used as markers for past infections and can relate to tubal pathology and infertility. This "proof of principle" study aimed to assess whether Chlamydia antibodies are detectable in easier to obtain, noninvasive, vaginal mucosa samples and relate to current or past infection. Methods. We compared outcomes of Chlamydia IgG and IgA antibody tests in serum and vaginal mucosal swabs in (a) 77 women attending a fertility clinic, of whom 25 tested positive for serum-IgG and (b) 107 women visiting an STI centre, including 30 Chlamydia PCR-positive subjects. Results. In the STI clinic, active Chlamydia infections were linked to serum-IgG and serum-IgA (P < 0.001) and mucosa-IgA (P < 0.001), but not mucosa-IgG. In the fertility clinic, mucosa-IgG had stronger correlations with serum-IgG (P = 0.02) than mucosa-IgA (P = 0.06). Women with tubal pathology or Chlamydia history more commonly had serum-IgG and mucosa-IgA (both P < 0.001), whereas this link was weaker for mucosa-IgG (P = 0.03). Conclusion. Chlamydia IgG and IgA are detectable in vaginal mucosal material. Serum-IgG had stronger associations with current or past infections. Mucosa-IgA also showed associations with (past) infection and complications. IgA presence in vaginal mucosa warrants further epidemiological studies.

Use of Chlamydia trachomatis high-resolution typing: an extended case study to distinguish recurrent or persistent infection from new infection.

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.

Detection of anorectal and cervicovaginal Chlamydia trachomatis infections following azithromycin treatment: prospective cohort study with multiple time-sequential measures of rRNA, DNA, quantitative load and symptoms.

BACKGROUND: Determination of Chlamydia trachomatis (Ct) treatment success is hampered by current assessment methods, which involve a single post-treatment measurement only. Therefore, we evaluated Ct detection by applying multiple laboratory measures on time-sequential post-treatment samples. METHODS: A prospective cohort study was established with azithromycin-treated (1000 mg) Ct patients (44 cervicovaginal and 15 anorectal cases). Each patient provided 18 self-taken samples pre-treatment and for 8 weeks post-treatment (response: 96%; 1,016 samples). Samples were tested for 16S rRNA (TMA), bacterial load (quantitative PCR; Chlamydia plasmid DNA) and type (serovar and multilocus sequence typing). Covariates (including behavior, pre-treatment load, anatomic site, symptoms, age, and menstruation) were tested for their potential association with positivity and load at 3-8 weeks using regression analyses controlling for repeated measures. FINDINGS: By day 9, Ct positivity decreased to 20% and the median load to 0.3 inclusion-forming units (IFU) per ml (pre-treatment: 170 IFU/ml). Of the 35 cases who reported no sex, sex with a treated partner or safe sex with a new partner, 40% had detection, i.e. one or more positive samples from 3-8 weeks (same Ct type over time), indicating possible antimicrobial treatment failure. Cases showed intermittent positive detection and the number of positive samples was higher in anorectal cases than in cervicovaginal cases. The highest observed bacterial load between 3-8 weeks post-treatment was 313 IFU/ml, yet the majority (65%) of positive samples showed a load of ≤ 2 IFU/ml. Pre-treatment load was found to be associated with later load in anorectal cases. CONCLUSIONS: A single test at 3-8 weeks post-treatment frequently misses Ct. Detection reveals intermittent low loads, with an unknown risk of later complications or transmission. These findings warrant critical re-evaluation of the clinical management of single dose azithromycin-treated Ct patients and fuel the debate on defining treatment failure. Clinicaltrials.gov Identifier: NCT01448876.