C J P A Hoebe

Prevalence of urogenital Chlamydia trachomatis increases significantly with level of urbanisation and suggests targeted screening approaches: results from the first national population based study in the Netherlands

Objectives:Chlamydia trachomatis (Chlamydia) is the most prevalent sexually transmitted bacterial infection and can cause considerable reproductive morbidity in women. Chlamydia screening programmes have been considered but policy recommendations are hampered by the lack of population based data. This paper describes the prevalence of Chlamydia in 15–29 year old women and men in rural and urban areas, as determined through systematic population based screening organised by the Municipal Public Health Services (MHS), and discusses the implications of this screening strategy for routine implementation. Methods: Stratified national probability survey according to “area address density” (AAD). 21 000 randomly selected women and men in four regions, aged 15–29 years received a home sampling kit. Urine samples were returned by mail and tested by polymerase chain reaction (PCR). Treatment was via the general practitioner, STI clinic, or MHS clinic. Results: 41% (8383) responded by sending in urine and questionnaire. 11% (2227) returned a refusal card. Non-responders included both higher and lower risk categories. Chlamydia prevalence was significantly lower in rural areas (0.6%, 95% CI 0.1 to 1.1) compared with very highly urbanised areas (3.2%, 95% CI 2.4 to 4.0). Overall prevalence was 2.0% (95% CI 1.7 to 2.3): 2.5% (95% CI 2.0 to 3.0%) in women and 1.5% (95% CI 1.1 to 1.8) in men. Of all cases 91% were treated. Infection was associated with degree of urbanisation, ethnicity, number of sex partners, and symptoms. Conclusion: This large, population based study found very low prevalence in rural populations, suggesting that nationwide systematic screening is not indicated in the Netherlands and that targeted approaches are a better option. Further analysis of risk profiles will contribute to determine how selective screening can be done.

A prediction rule for selective screening of Chlamydia trachomatis infection

Background: Screening for Chlamydia trachomatis infections is aimed at the reduction of these infections and subsequent complications. Selective screening may increase the cost effectiveness of a screening programme. Few population based systematic screening programmes have been carried out and attempts to validate selective screening criteria have shown poor performance. This study describes the development of a prediction rule for estimating the risk of chlamydial infection as a basis for selective screening. Methods: A population based chlamydia screening study was performed in the Netherlands by inviting 21 000 15–29 year old women and men in urban and rural areas for home based urine testing. Multivariable logistic regression was used to identify risk factors for chlamydial infection among 6303 sexually active participants, and the discriminative ability was measured by the area under the receiver operating characteristic curve (AUC). Internal validity was assessed with bootstrap resampling techniques. Results: The prevalence of C trachomatis (CT) infection was 2.6% (95% CI 2.2 to 3.2) in women and 2.0% (95% CI 1.4 to 2.7) in men. Chlamydial infection was associated with high level of urbanisation, young age, Surinam/Antillian ethnicity, low/intermediate education, multiple lifetime partners, a new contact in the previous two months, no condom use at last sexual contact, and complaints of (post)coital bleeding in women and frequent urination in men. A prediction model with these risk factors showed adequate discriminative ability at internal validation (AUC 0.78). Conclusion: The prediction rule has the potential to guide individuals in their choice of participation when offered chlamydia screening and is a promising tool for selective CT screening at population level.

Evaluation of a rapid one-step immunochromatographic test and two immunoenzymatic assays for the detection of anti-Treponema pallidum antibodies

Background: The control of syphilis depends on screening of the population at risk and is usually performed using the Treponema pallidum particle agglutination test (TPPA). Outside Europe the rapid plasma reagin test (RPR) or venereal disease research laboratory test is most often used for screening purposes. Because of the drawbacks in current diagnostic procedures, ie, long turnaround time, the need is felt for a rapid and simple test that can potentially be performed on whole blood. Objective and study design: In this study a one-step immunochromatographic test (Biorapid Syphilis) and two ELISA, the Bioelisa Syphilis 3.0 and ETI-Treponema Plus, were evaluated. Methods: Serum samples were collected between February 2000 and May 2006 at the University Hospital in Maastricht, The Netherlands. 145 TPPA-positive sera, confirmed by fluorescent treponemal antibody absorption (FTA-Abs, treponemal test) and/or RPR (non-treponemal) were included. Furthermore, 41 sera from healthy controls and 144 TPPA-negative sera from controls with underlying conditions that might interfere with T pallidum serology were collected. Results: The sensitivity and specificity of the Biorapid Syphilis, Bioelisa Syphilis 3.0 and ETI-Treponema Plus were 92% and 79%, 100% and 100% and 100% and 100%, respectively, with our selected sera. Conclusions: The performance of both ELISA was excellent in our study and is favoured over the TPPA because of its ability to be run on an automated system. The sensitivity and specificity of the Biorapid Syphilis were considered too low to implement the test in a hospital laboratory in a developed country but it might be useful in primary healthcare settings in developing countries.

Type-specific human papillomavirus infections among young heterosexual male and female STI clinic attendees

Background: Baseline genotype-specific human papillomavirus (HPV) prevalence rates and associated risk factors per gender enable future assessment of the impact of vaccination on HPV dynamics. Methods: Before the start of national HPV vaccination for girls, data were collected cross-sectionally in nationwide Dutch sexually transmitted infections (STI) clinics among heterosexual males (n = 430) and females (n = 1136) aged 16 to 24 years. Self-collected vaginal or penile swabs were analyzed by a sensitive polymerase chain reaction (SPF10) and genotyped with line probe assay. Logistic regression was applied to estimate determinants of HPV prevalent infections. Results: HPV prevalence was 54% among males and 72% among females. High-risk (HR) HPV was present in males and females, 40% and 58%, respectively. Independent risk factors for HR-HPV infection were female gender, number of lifetime sex partners and a history of chlamydia or gonorrhea. In addition, not having a casual partner and consistent condom use were protective factors in women, but not in men. For low-risk (LR) HPV, the odds were smaller. Multiple HR-HPV and sexual risk behavior showed a stronger association compared with a single HR-HPV infection. Conclusions: Prevalence of HR-HPV is high in both genders. Infection with multiple HR-HPV types was more associated with high-risk sexual behavior than infection with LR-HPV types or a single HR-HPV type.

P3.023* Geographical Clustering of Repeat Positive Tests with Chlamydia Trachomatis Among Young People (16–29 Years); Identification of a Hidden Key Chlamydia Population

Background Young patients with repeat infections of Chlamydia trachomatis(Ct) are a key population for prevention as they indicate ongoing risk for spread and complications in women. We estimated the hidden key population, i.e. missed repeat testers and repeat positives, to effectively focus screening strategies. Methods Data covered all youngsters (16–29 years,n = 42,894) in Eastern South-Limburg, the Netherlands (2006–2010) including all their genital Ct tests by any care provider. Using logistic regression, determinants (age, sex, socio-economic status (SES)) for not having a repeat test (in positives) and for having a positive repeat test (in repeated testers) were evaluated. Using Geographic-Information-Systems and spatial statistics (SaTScan purely spatial Poisson model, Bivariate Local Moran`s I), spatial clusters and correlations with SES of repeat (positive) tests were evaluated. Results Overall 10,044 (23.4%) youngsters were tested of whom 944(9.4%) were positive. Of positives, 423(44.8%) had no repeat test (more often older, ORperyear 0.96 95% CI 0.92–1.00, and male, OR2.26 95% CI 1.69–3.02). Of repeat testers, 111(21.3%) were repeat positive. Spatial clusters were found in four municipalities(3 low SES) and low SES correlated with repeat positive tests. We estimate that 230 repeat positives (0.5% of total youngsters) are missed in care. These include 90 (21.3% of 423) who were lost in care for repeat testing follow-up and 140 repeat positives in the 32,850 youngsters who were never tested before (assuming 2.0% positivity and 21.3% repeat positivity). Overall, an estimated 67.4%(230/(230+111)) of all repeat positive patients is thereby missed in current care. Conclusion Two-thirds of repeat positive patients are hidden to current care, some (–40%) because they missed a repeat test and others (–60%) because they are never tested. As they comprise a central but small part of the total young population, control strategies targeting this key population should be highly acuminated. Geo-spatial analysis, which pointed to low SES high prevalence areas informs more effective Ct control.

Nieuwe regeling en structuur aanvullende curatieve soa-bestrijding in Nederland

New regulations and structure for additional STD-care in the NetherlandsFrom January 2006 a new structure for additional STI care was introduced in the Netherlands. Previously, STI care was provided by a range of different physicians and institutions with inconsistent quality and at different costs. Since 2001, the STI clinics and Municipal Health Services (MHS) report a continuous increase in the number of consultations. Also, the financial structure was inadequate to cover the active testing policy with respect to STIs including HIV. In the new structure for additional STI care, the country has been divided in eight STI regions, representing all 29 Municipal Health Services (MHS). In each region, a coordinating MHS developed an STI control plan with the other MHS and clinics in the region. The Ministry of Health developed an innovative financial system based on the number of inhabitants per region and financial incentives for a higher STI positivity ratio (= number of diagnoses / number of consultations). The average positivity ratio was calculated from STI surveillance data. As such, diagnosis and treatment of 5 STI (Chlamydial infection gonorrhoea, syphilis, HIV, acute hepatitis B) will be financed. The financial incentive stimulates the MHS to focus on high risk groups.Key words: STI control, organisation

P3.234 Chlamydia trachomatis: geographical variation in test practices of general practitioners, 2011–2015

Introduction Retesting Chlamydia trachomatis (CT) treated people after 3–12 months is recommended as it can yield substantial numbers of reinfections. A test-of-cure (TOC) shortly after treatment (within 3 months) is not advisable due to the likelihood of false positive findings leading to overtreatment. Spatial analyses are useful to detect geographical areas of low guideline adherence to inform local testing policies and targeted interventions. The aim was to assess geographical variation in test practices of general practitioners (GPs) in The Netherlands. Methods Retrospective laboratory data containing CT tests of 48 GPs in 4 municipalities were obtained (2011–2015) from the public laboratory in the south western part of the Netherlands (183 thousand residents). First recorded urogenital positive CT tests of men (n=249; 39.2%) and women (n=386;60.8%)≥16 years between January 2011 and July 2015 were included in the analyses and TOC and retests were outcomes. Logistic regression was used for analyses. Results Overall, 8,275 CT tests were performed (positivity 8.4%;n=691);only 0.4% (n=43) from extra genital sites. On a GP level, the number of CT tests varied geographically from 1 to 2421 (p<0.001). A TOC was performed in 19.1% of the CT cases (n=123;13.8% positive). TOC was more often performed in south Maastricht in comparison with the centre of Maastricht (p=0.02,OR 3.0,95% CI 1.23–7.33). A retest was performed in 23% of the CT cases (n=146;10.3% positive). The rate of retests non-significantly varied geographically between 6.3% and 30.2% p=0.33. Patients with a TOC were more likely to have a retest in comparison with cases without a TOC (p=0.02). Conclusion Testing at extra genital sites and the overall proportion of retests was low at GP practices. Almost one out of five CT cases returned within three months, and many (re-)infections were probably missed. Moreover, it seems that there are geographical variations in test practices of GPs. Thus, targeted interventions at the local level are needed to increase CT testing and retesting practices of GPs.

P1-S6.12 The contribution of a Chlamydia screening programme to testing and case-finding in addition to regular STI-care in three regions of The Netherlands

Background The impact of a Chlamydia screening programme can be measured by the incremental amount of Chlamydia tests performed and cases detected as compared to the throughput in regular care. In the Netherlands, regular STI care is provided by specialised STI-centres (aimed at high-risk groups) and General Practitioners (GPs, basic opportunistic screening and care for symptomatic cases). An annual register-based Chlamydia screening programme is implemented in three regions since 2008. Methods The number of persons tested and cases detected in the Chlamydia Screening among 16–29 year olds in Amsterdam, Rotterdam and South Limburg, 2008–2010, were compared to consultations and diagnoses in this age group reported in surveillance data from STI centres in the regions and estimates of STI care in general practices in these regions, 2007–2010. Round 3 data are based on the first 6 months of the year. Results The baseline testing rates (at STI centers and by GPs in year pre-screening) were 10% in Rotterdam, 13% in Amsterdam and 6% in South-Limburg. CSI increased testing rates steeply in the first year to 26–30% in the cities and 17% in Limburg; this decreased to 20–21% and 13% in round 3, still doubling testing rates as compared to baseline. Positivity rates at regular STI-care facilities are higher than in CSI: 12–15% in regular care vs 4–5% in CSI; therefore the addition of CSI to case-finding in the three regions was lower than that to testing: the screening programme added about 41% on top of the cases found in regular care in round 1, but this decreased to 20% in round 3 due to lower participation and positivity rates in consecutive rounds. Conclusions By comparison to regular testing at STI centers and in general practice, the Chlamydia Screening had a major contribution towards the number of young people tested for Chlamydia in the three regions. The addition towards case-finding was lower, because the case-detection rate of the screening programme was lower than that in regular care. The Screening programme did not seem to affect the number of patients seen in regular care, but double “consumers” cannot be excluded.

O1-S01.03 High yield in reinfections during a chlamydia screening programme when automatically sending testkits after 6 months to previously infected

Background Reinfections remain challenging in the control of Chlamydia trachomatis (Ct). In a systematic internet-based Ct Screening programme (CSI) in the Netherlands, all Ct-positive participants automatically received a test kit after 6 months to facilitate discovery of reinfections. Determinants for reinfection for two screening rounds, treatment and partner notification are discussed. Methods CSI-home-based testkits can be requested online after register based postal invitation. Infected participants get a referral letter for their health provider to get treatment for themselves and their current partner; expartners can be alerted by the participant and request a test kit via the website. Participants fill in a questionnaire on sexual behaviour voluntarily. Ct-positives answer questions about treatment and partner notification 10 days after checking their results. Infected participants who do not check their result online receive it by postal letter. After 6 months retest kits are automatically sent to previously infected participants. Results Overall, 3185 participants (4.1%) tested positive; 7% of Ct-positives did not check their result online and received a postal letter. The majority (86%) of Ct-positive participants who answered the treatment questionnaire (response 43%) was treated within 2 weeks after checking their result online; 80% of those with a current relationship reported their partner had also been treated and 16% of those with past relationships notified ex-partners via the website. One third of the ex-partners participated, 28% of whom were Ct-positive. After 6 months, 3055 participants received a retest kit and 66% responded. The reinfection rate was 8.8%. Results of the questionnaire revealed 75% of retest-positives had been treated for the initial infection and 70% had had their partner treated, while these proportions were 87% and 80% among retest-negatives. At higher risk for reinfections were young people (<20 years 17%), specific ethnic minorities (Netherlands Antillean 16%, Turkish 17%, sub-Sahara African 18%), persons living in Rotterdam (11 vs 8% Amsterdam 4% Limburg), and in high-risk areas (14%). Conclusions The uptake of retesting was successful counting two third with automatically sent testkits 6 months after screening. Reinfection rates were high, especially among known risk-groups. Questionnaire results show that follow-up of (partner) treatment after Chlamydia infections could be improved.

P4-S1.07 Chlamydia trachomatis DNA stability independent of preservation temperature, type of medium en storage duration

Background In almost all diagnostic studies, stored samples are used. This is also the case in Chlamydia trachomatis research. The performance of diagnostic assays, such as nucleic acid amplification tests, is dependent on the preservation of C trachomatis DNA. However, the influence of different storage conditions on C trachomatis DNA has not been thoroughly explored yet. Therefore, we have studied the impact of temperature, type of medium and duration of storage on the preservation of C trachomatis DNA. Methods Phosphate buffered saline (PBS), 2-sucrose-phosphate medium (2-SP), COBAS Amplicor medium and urine samples were spiked with C trachomatis serovar D elementary bodies and stored at room temperature, 4°C, −20°C and −80°C. DNA was isolated using the Qiagen DNA mini kit (Qiagen GmbH, Hilden, Germany). Samples were tested in triplicate with a TaqMan PCR at day 0, 1, 7, 14 and 30. Furthermore, clinical C trachomatis positive urine samples were collected and pooled, and stored and tested in triplicate, at the same temperatures and time intervals. This same procedure was executed with pooled C trachomatis positive swab samples. Results C trachomatis was detected in all samples, irrespective of the different storage temperature conditions, different types of medium and the different durations of storage. Regarding storage time, the cycle threshold (ct) overall did not increase, in fact it tended to decrease within 30 days. If there was an increase in ct over time, this occurred in <10% of the experiments, it did not outreach three (corresponding to a decline in load of 1 log). This mainly occurred in the spiked COBAS samples which were frozen. Conclusions All samples tested positive for C trachomatis in our experiments, with on average no decrease in cycle threshold over time. We can therefore conclude that PBS, 2-SP, COBAS Amplicor medium and urine are all excellent media to preserve C trachomatis DNA for a longer period of time, independent of storage temperature.