Case series on acute HCV in HIV-negative men in regular clinical practice: a call for action.

BACKGROUND: The evidence that HIV treatment as prevention (TasP) and HIV pre-exposure prophylaxis (PrEP) reduces the risk of HIV transmission is overwhelming. But as PrEP and TasP can lead to increased sexual mixing between HIV positive and negative men who have sex with men (MSM), sexually transmitted infections such as acute hepatitis C (HCV), which were thought to be limited to HIV-infected MSM, could become more frequent in HIV uninfected MSM as well. The objective of this study was to describe a series of cases of sexually transmitted HCV infections in HIV-uninfected MSM in the Netherlands and Belgium. METHODS: Through the Dutch Acute HCV in HIV Study (a Dutch-Belgian prospective multicentre study on the treatment of acute HCV infection, NCT02600325) and the Be-PrEP-ared study (a PrEP project in Antwerp, EudraCT2015-000054-37) several acute HCV infections were detected in HIV-negative men. RESULTS: A newly acquired HCV infection was diagnosed in ten HIV-negative MSM. HCV was diagnosed at a sexually transmitted infection (STI) clinic (n = 2), by their general practitioner (n = 2), by their HIV physician (n = 1) or at a PrEP clinic (n = 5). Ten patients reported unprotected anal intercourse and four had a concomitant STI at the time of HCV diagnosis. Six patients reported using drugs during sex. CONCLUSIONS: Our observation calls for a larger nationwide epidemiological study on the prevalence, incidence and risk factors of HCV infection in HIV-uninfected MSM. In the changing landscape of TasP and PrEP, reliable and up-to-date epidemiological data on HCV among HIV-uninfected MSM are needed and will help in developing evidence-based testing policies.

The Netherlands Chlamydia cohort study (NECCST) protocol to assess the risk of late complications following Chlamydia trachomatis infection in women.

BACKGROUND: Chlamydia trachomatis (CT), the most common bacterial sexually transmitted infection (STI) among young women, can result in serious sequelae. Although the course of infection is often asymptomatic, CT may cause pelvic inflammatory disease (PID), leading to severe complications, such as prolonged time to pregnancy, ectopic pregnancy, and tubal factor subfertility. The risk of and risk factors for complications following CT-infection have not been assessed in a long-term prospective cohort study, the preferred design to define infections and complications adequately. METHODS: In the Netherlands Chlamydia Cohort Study (NECCST), a cohort of women of reproductive age with and without a history of CT-infection is followed over a minimum of ten years to investigate (CT-related) reproductive tract complications. This study is a follow-up of the Chlamydia Screening Implementation (CSI) study, executed between 2008 and 2011 in the Netherlands. For NECCST, female CSI participants who consented to be approached for follow-up studies (n = 14,685) are invited, and prospectively followed until 2022. Four data collection moments are foreseen every two consecutive years. Questionnaire data and blood samples for CT-Immunoglobulin G (IgG) measurement are obtained as well as host DNA to determine specific genetic biomarkers related to susceptibility and severity of infection. CT-history will be based on CSI test outcomes, self-reported infections and CT-IgG presence. Information on (time to) pregnancies and the potential long-term complications (i.e. PID, ectopic pregnancy and (tubal factor) subfertility), will be acquired by questionnaires. Reported subfertility will be verified in medical registers. Occurrence of these late complications and prolonged time to pregnancy, as a proxy for reduced fertility due to a previous CT-infection, or other risk factors, will be investigated using longitudinal statistical procedures. DISCUSSION: In the proposed study, the occurrence of late complications following CT-infection and its risk factors will be assessed. Ultimately, provided reliable risk factors and/or markers can be identified for such late complications. This will contribute to the development of a prognostic tool to estimate the risk of CT-related complications at an early time point, enabling targeted prevention and care towards women at risk for late complications. TRIAL REGISTRATION: Dutch Trial Register NTR-5597 . Retrospectively registered 14 February 2016.

Ethnic and regional differences in STI clinic use: a Dutch epidemiological study using aggregated STI clinic data combined with population numbers.

OBJECTIVES: Ethnic minorities (EM) from STI-endemic countries are at increased risk to acquire an STI. The objectives of this study were to investigate the difference in STI clinic consultation and positivity rates between ethnic groups, and compare findings between Dutch cities. METHODS: Aggregated population numbers from 2011 to 2013 of 15-44 year-old citizens of Amsterdam, Rotterdam, The Hague and Utrecht extracted from the population register (N=3 129 941 person-years) were combined with aggregated STI clinic consultation data in these cities from the national STI surveillance database (N=113 536). Using negative binomial regression analyses (adjusted for age and gender), we compared STI consultation and positivity rates between ethnic groups and cities. RESULTS: Compared with ethnic Dutch (consultation rate: 40.3/1000 person-years), EM from Eastern Europe, Sub-Sahara Africa, Suriname, the Netherlands Antilles/Aruba and Latin America had higher consultation rates (range relative risk (RR): 1.27-2.26), whereas EM from Turkey, North Africa, Asia and Western countries had lower consultation rates (range RR: 0.29-0.82). Of the consultations among ethnic Dutch, 12.2% was STI positive. Positivity rates were higher among all EM groups (range RR: 1.14-1.81). Consultation rates were highest in Amsterdam and lowest in Utrecht independent of ethnic background (range RR Amsterdam vs Utrecht: 4.30-10.30). Positivity rates differed less between cities. CONCLUSIONS: There were substantial differences in STI clinic use between ethnic groups and cities in the Netherlands. Although higher positivity rates among EM suggest that these high-risk individuals reach STI clinics, it remains unknown whether their reach is optimal. Special attention should be given to EM with comparatively low consultation rates.

Delayed linkage to care in one-third of HIV-positive individuals in the Netherlands.

OBJECTIVES: To determine time to linkage to HIV care following diagnosis and to identify risk factors for delayed linkage. METHODS: Patients newly diagnosed with HIV at sexually transmitted infections (STI) clinics in the Netherlands were followed until linkage to care. Data were collected at the time of diagnosis and at first consultation in care, including demographics, behavioural information, CD4+ counts and HIV viral load (VL) measurements. Delayed linkage to care was defined as >4 weeks between HIV diagnosis and first consultation. RESULTS: 310 participants were included; the majority (90%) being men who have sex with men (MSM). For 259 participants (84%), a date of first consultation in care was known; median time to linkage was 9 days (range 0-435). Overall, 95 (31%) of the participants were not linked within 4 weeks of diagnosis; among them, 44 were linked late, and 51 were not linked at all by the end of study follow-up. Being young (<25 years), having non-Western ethnicity or lacking health insurance were independently associated with delayed linkage to care as well as being referred to care indirectly. Baseline CD4+ count, VL, perceived social support and stigma at diagnosis were not associated with delayed linkage. Risk behaviour and CD4+ counts declined between diagnosis and linkage to care. CONCLUSIONS: Although most newly diagnosed patients with HIV were linked to care within 4 weeks, delay was observed for one-third, with over half of them not yet linked at the end of follow-up. Vulnerable subpopulations (young, uninsured, ethnic minority) were at risk for delayed linkage. Testing those at risk is not sufficient, timely linkage to care needs to be better assured as well.

Lymphogranuloma venereum among men who have sex with men in the Netherlands: regional differences in testing rates lead to underestimation of the incidence, 2006-2012.

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): 3.2­5.3), STI symptoms (OR=4.1; 95% CI: 3.1­5.4), more than 50 sex partners in the past six months (OR=3.7; 95% CI: 1.1­12.4), older age (40­44 years: OR=2.1; 95% CI: 1.5­2.8), no condom use (OR=2.2; 95% CI: 1.2­3.9) and homosexuality (as opposed to bisexuality; OR=2.2; 95% CI: 1.1­4.2). 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.

Comparing two definitions of ethnicity for identifying young persons at risk for chlamydia.

Ethnic disparities in chlamydia infections in The Netherlands were assessed, in order to compare two definitions of ethnicity: ethnicity based on country of birth and self-defined ethnicity. Chlamydia positivity in persons aged 16-29 years was investigated using data from the first round of the Chlamydia Screening Implementation (CSI, 2008-2009) and surveillance data from STI centres (2009). Logistic regression modelling showed that being an immigrant was associated with chlamydia positivity in both CSI [adjusted odds ratio (aOR) 2·3, 95% confidence interval (CI) 2·0-2·6] and STI centres (aOR 1·4, 95% CI 1·3-1·5). In both settings, 60% of immigrants defined themselves as Dutch. Despite the difference, classification by self-defined ethnicity resulted in similar associations between (non-Dutch) ethnicity and chlamydia positivity. However, ethnicity based on country of birth explained variation in chlamydia positivity better, and is objective and constant over time and therefore more useful for identifying young persons at higher risk for chlamydia infection.

Outbreak investigation in two groups of coach passengers with gastroenteritis returning from Germany to the Netherlands in February 2009.

In February 2009, an outbreak of 38 cases of gastroenteritis occurred among the participants of two Dutch coach trips (A and B) who visited the same hotel in Germany. We initiated an outbreak investigation to determine possible risk of food-borne infection. A retrospective cohort study was performed among 87 passengers using a self-administered questionnaire. The response rate was 75 of 87 (86%). Mean age was 65 years. Cases were defined as participants of the two coach trips who had diarrhoea and/or vomiting at least once within 24 hours in the period between 7 and 14 February 2009. We distinguished early and late cases, with symptoms starting within or after 72 hours of arrival in the hotel. Overall attack-rate was 38 of 75 (51%). Microbiological investigation was performed on stool samples of two passengers from Coach A and two passengers from Coach B. Identical norovirus genotype II.4 sequences were detected in all four samples. Univariate analysis revealed a potential risk for early cases from juice consumption , which was most clearly seen for Coach B on day of arrival (juice at lunch: relative risk (RR): 3.9, 95% confidence interval (CI): 1.3-11.7; juice at dinner: RR: 5.5, 95% CI: 1.6-18.1). A dose-response relationship was found. This outbreak was probably caused by using the taps of juice served in large containers with a tap for self-service, due to environmental contamination through person-to-person transmission. Still the role of either contaminated juice or contact with contaminated juice cannot be ruled out.

Significance of isolated antibody to hepatitis B core antigen in Dutch national vaccination campaign of behavioural high-risk groups.

In the Dutch national vaccination campaign for behavioural risk groups, anti-HBcore is used as the primary HBV screening test. Samples with positive results undergo testing for active infection (HBsAg) but are otherwise accepted as indicating past infection, thereby assuming immunity. This study evaluated evidence for immunity in the target population screened on the basis of this algorithm, by re-analysing 1000 anti-HBcore-positive blood samples equally divided among risk groups: 14.7% of confirmed anti-HBcore lacked anti-HBs ('isolated' anti-HBcore). Independent risk factors for isolated anti-HBcore were risk group, HCV infection in hard-drug users (DU) and origin from Sub-Saharan Africa. After extrapolation, the proportion of participants who were said to be immune but lacked any additional evidence of immunity amounted to 9.6% (ranging from 12.5% in DU to 6.5% in men who have sex with men). It is recommended that as a minimum anti-HBs screening is included in testing algorithms used to determine vaccination programmes for risk groups, in particular in DU.

A cluster of hepatitis B infections associated with incorrect use of a capillary blood sampling device in a nursing home in the Netherlands, 2007.

In July 2007, two residents of a nursing home were diagnosed with acute Hepatitis B virus infection. To identify risk factors for HBV infection a retrospective cohort study among residents was performed. Case finding included discharged diabetes patients and those receiving home care. Among 32 residents one case of chronic hepatitis B was found that could be identified by genotyping as the source patient for the acute cases. Diabetes and finger sticks were risk factors for HBV infection. Most likely the cause of transmission was a multiclix finger stick device developed for use in individual patients but used in multiple patients. Education and training in the use of new equipment and hygiene audits remain the cornerstones in infection control practices.

[The molecular epidemiology of hepatitis A in The Netherlands; the usefulness of typing isolated viral strains]. / Moleculaire epidemiologie van hepatitis A in Nederland; het nut van het typeren van geïsoleerde virusstammen.

OBJECTIVE: To investigate the epidemiological links between several outbreaks of hepatitis A in The Netherlands (2001-2004). DESIGN: Descriptive. METHOD: Blood samples taken in connection with reports of hepatitis A to municipal health centres from 2001-2004, were typed by determining the nucleotide sequence of the VP3-VP1 and the VP1-P2A regions of the genome of the hepatitis A virus (HAV). Genetic distances were represented graphically by means of a phylogenetic tree. RESULTS: The study into the spread of various subtypes of HAV showed a clear link between the HAV-(sub)genotype and risk of transmission: in men that have sex with men only genotype 1A occurred, in travellers to African countries genotype 1B was predominantly seen. CONCLUSION: A database containing various viral strains from people with hepatitis A in The Netherlands could, if kept up to date, be used as an aid in confirming the classical way of tracing sources as well as for the evaluation of preventative measures.

A slow epidemic of LGV in the Netherlands in 2004 and 2005.

In 2004, an outbreak of LGV was detected in MSM in the Netherlands. By January 2006, 179 confirmed cases of LGV had been reported; 65 (retrospectively) in 2002/2003, 76 in 2004 and 38 in 2005. The evolution of the LGV outbreak appears to have slowed down and only a few cases were found in the first months of 2006.

Chlamydia trachomatis infections in multi-ethnic urban youth: a pilot combining STI health education and outreach testing in Rotterdam, Netherlands.

BACKGROUND/OBJECTIVES: Testing for Chlamydia trachomatis (Ct) is less accepted in people of non-Dutch ethnicity than Dutch people. We offered additional Ct and gonorrhoea testing through our outreach sexually transmitted infections (STI) prevention programme to determine whether this intervention strategy is feasible and efficient. METHODS: Outreach workers offered test kits to women and men aged 15-29 years, in group and street settings and in a vocational training school. Demographic and behavioural data and characteristics of non-responders were assessed. DNA was isolated (using the MagNA Pure LC system) from urine and tested using the Cobas Amplicor test. RESULTS: Among sexually active people, the test rate differed by venue (groups 80% (74/93), school 73% (49/67), street 17% (49/287); p<0.001). There was no difference in test rate between group and school settings by gender or ethnicity. Ct positivity was 14.5% (25/172); women 20.2% (20/99) versus men 6.8% (5/73); p = 0.01. Ct positivity was highest at school (24.5% (12/49)) and among Surinamese/Antillean people (17.5% (14/80)). Treatment rate of index cases and current partners was 100% and 78%, respectively. CONCLUSIONS: We found a high acceptance of chlamydia testing in group and school settings in both men and women of non-Dutch ethnicity. The prevalence indicates that we have accessed high risk people. Outreach testing and is feasible and most efficient in school and group settings. School screening may have an impact on community prevalence of Ct infections.

Acceptability and consequences of screening for chlamydia trachomatis by home-based urine testing.

OBJECTIVE: The objective of this study was to study the acceptability and consequences of home-based chlamydia (CT) screening by Municipal Health Services (MHS) among 15- to 29-year-old participants. STUDY: This study consisted of a cross-section of 156 CT-positives and 600 random sampled CT-negatives after receiving the result of their CT test. RESULTS: Thirty-eight percent of the men and 59% of the women responded. The screening method was well-accepted. Seventy percent (52) of the CT-positives were surprised about their result. Infected women more often than men reported a feeling of being dirty and of anxiety about infertility. Curiosity for the CT result was decisive for participation in 68% and perception of personal risk was poor. The willingness to be tested regularly was determined by present chlamydial infection, young age, multiple lifetime partners, short relationship, and earlier test for chlamydia. CONCLUSIONS: Chlamydia screening organised by MHS is acceptable for future screening. Participants with an elevated risk are interested in screening as long as test kits are easily available. Counseling with focus on effects of CT, especially on women, is essential. Alternative approaches are needed to motivate men and non-Dutch high-risk groups.

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.

[A cluster of lymphogranuloma venereum among homosexual men in Rotterdam with implications for other countries in Western Europe]. / Cluster van lymphogranuloma venereum onder homoseksuele mannen in Rotterdam, met grensoverschrijdende gevolgen.

In mid-December 2003, a cluster of 15 cases of lymphogranuloma venereum (LGV) among male homosexuals was reported to the Municipal Health Service in Rotterdam by the Erasmus Medical Centre's outpatient clinic for sexually transmitted infections (STI). Most patients presented with proctitis and some with constipation. All were Caucasian and between 26 and 48 years of age. Thirteen of them were HIV-positive and eight had a concomitant STI. All men reported having had unprotected insertive and receptive anal sexual contact. Many sexual contacts were anonymous and were reported to have taken place in Germany, Belgium, the United Kingdom and France. This outbreak of LGV may extend through a large part of western Europe. In view of the patients' international contacts, international warnings and alertness are needed. Concerted action of professionals in infectious disease control and curative care is called for.

Prevalence of STD and HIV infections among attenders of the Erasmus MC STD clinic, Rotterdam, The Netherlands, during the years 1996 to 2000.

The purpose of the study was to investigate possible changes in the prevalence of STD and HIV collected at a Dutch STD clinic in the period 1996 to 2000. Age, gender, ethnic background, sexual preference, intravenous drug use and STD or HIV infection in persons attending an STD outpatient clinic were analysed and compared. The prevalence of HIV infection among the clinic visitors remained stable. The prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis infections increased significantly among heterosexual men and heterosexual women. Among homo- and bisexual men a significant increase was seen in chlamydial infections only. Because of the increasing prevalence of gonococcal and chlamydial infections among STD clinic visitors in Rotterdam, more attention should be paid to coordinated preventive activities, such as health education and contact tracing. Further subgroup analyses should be done in order to get more information on risk behaviour in the different groups.