Nicole H. T. M. Dukers-Muijrers

High performance and acceptability of self-collected rectal swabs for diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae in men who have sex with men and women.

Background: Identification of sexually transmitted infections (STI) is limited by the infrequent assessment of rectal STI. This study assesses usability of self-collected rectal swabs (SRS) in diagnosing rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). Methods: In 2006 to 2007, clients of the Amsterdam and South Limburg STI outpatient clinics reporting receptive anal intercourse were asked to fill out a questionnaire and provide SRS. A standard provider-collected rectal swab (PRS) was also taken, and both were tested for CT and NG by a nucleic acid amplification tests. SRS performance was compared with PRS as to agreement, sensitivity, and specificity. Results: Prevalence of rectal CT was 11% among the 1458 MSM and 9% among the 936 women. Rectal NG prevalence was 7% and 2%. In 98% of both MSM and women, SRS and PRS yielded concordant CT test results, for NG agreement was 98% for MSM and 99.4% for women. SRS performance for CT and NG diagnosis was good in both groups and was comparable for both study regions. Slightly more (57% of MSM, 62% of women) preferred SRS to PRS or had no preference; 97% would visit the STI clinic again if SRS was standard practice. Conclusions: Because anal sex is a common practice for MSM and women, and anal STI are frequently present, rectal screening should be an essential part of an STI consultation. SRS is a feasible, valid, and acceptable alternative for MSM and women attending STI clinics, and hence should be considered for other settings as well.

High co-occurrence of anorectal chlamydia with urogenital chlamydia in women visiting an STI clinic revealed by routine universal testing in an observational study; a recommendation towards a better anorectal chlamydia control in women

BackgroundSymptom- 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.MethodsWomen (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.ResultsOf 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.ConclusionsCurrent 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.

Standard Symptom- and Sexual History-Based Testing Misses Anorectal Chlamydia trachomatis and Neisseria gonorrhoeae Infections in Swingers and Men Who Have Sex With Men

Background Currently, individuals at risk for sexually transmitted diseases (STDs) are tested extragenitally only if indicated, most often when there is a history of self-reported symptoms or self-reported anal sex. The sensitivity of such selective symptom- and sexual history–based testing for detection of anorectal STD has not been determined. Methods All men having sex with men (MSM) and swingers (heterosexual couples who have sex with other heterosexual couples and their self-identified heterosexual sex partners) attending our STD clinic (consults: n = 1690) from January 2010 until February 2011 were universally tested for urogenital, anorectal, and oropharyngeal Chlamydia trachomatis and Neisseria gonorrhoeae infections (STD). We compared STD prevalence at anorectal site based on universal versus selective testing. Results Sensitivity of selective symptom- and sexual history–based testing for anorectal STD was 52% for homosexual MSM, 40% for bisexual MSM, 43% for bisexual male swingers, 40% for heterosexual male swingers, and 47% for female swingers. Conclusions Universal testing of STD clinic clients who were MSM and swingers yielded more than half of all anorectal STD infections and is more sensitive for identifying anorectal STD infections compared with selective testing. Universal testing may be a more effective strategy for interrupting the ongoing transmission in high-risk sexual networks.

The value of testing multiple anatomic sites for gonorrhoea and chlamydia in sexually transmitted infection centres in the Netherlands, 2006–2010

National surveillance data from 2006 to 2010 of the Dutch sexually transmitted infection (STI) centres were used to analyse current practices on testing extragenital sites for chlamydia and gonorrhoea in men who have sex with men (MSM) and women. In MSM, 76.0% and 88.9% were tested at least at one extragenital site (pharyngeal and/or anorectal) for chlamydia and gonorrhoea, respectively; for women this was 20.5% and 30.2%. Testing more than one anatomic site differed by STI centre, ranging from 2% to 100%. In MSM tested at multiple sites, 63.0% and 66.5% of chlamydia and gonorrhoea diagnoses, respectively, would have been missed if screened at the urogenital site only, mainly anorectal infections. For women tested at multiple sites, the proportions of missed chlamydia and gonorrhoea diagnoses would have been 12.9% and 30.0%, respectively. Testing extragenital sites appears warranted, due to the numerous infections that would have been missed. Adding anorectal screening to urogenital screening for all MSM visiting an STI centre should be recommended. Since actual testing practices differ by centre, there is a need for clearer guidelines. Routine gonorrhoea and chlamydia screening at multiple sites in STI centres should be investigated further as this might be a more effective approach to reduce transmission than current practice.

Q Fever: Single-Point Source Outbreak With High Attack Rates and Massive Numbers of Undetected Infections Across an Entire Region

BACKGROUND In early 2009, a dairy-goat annex care farm in South Limburg, the Netherlands, reported 220 Coxiella burnetii-related abortions in 450 pregnant goats. These preceded human cases and occurred in a region that was Q-fever free before 2009, providing a unique quasi-experimental setting for investigating regional transmission patterns associated with a Q-fever point source. METHODS Index-farm residents/employees, visitors, and their household contacts were traced and screened for C. burnetii. Distribution of community cases was analysed using a geographic information system. True incidence, including undetected infections, was estimated regionwide by seroprevalence in a pre- versus postoutbreak sample, and near-farm by immunoglobulin M seroprevalence in a municipal population sample. Environmental bacterial load was repeatedly measured in surface and aerosol samples. RESULTS Serological attack rate was 92% (24/26) in index-farm residents/employees, 56% (28/50) in visitors, and 50% (7/14) in household contacts, and the clinical attack rate (ie, the proportion of persons seropositive for acute infection who also had clinical illness) was ≥ 80%. Notified symptomatic community cases (n = 253) were scattered downwind from the index farm, following a significant exposure-response gradient. Observed incidence ranged from 6.3% (0-1 km) to 0.1% (4-5 km), and remained high beyond. True incidence of infections was estimated at 2.9% regionwide, extrapolating to 8941 infections; estimated near-farm incidence was 12%. Coxiella burnetii load was high on-farm (2009), and lower off-farm (2009-2010). CONCLUSIONS Linking a single dairy-goat farm to a human Q-fever cluster, we show widespread transmission, massive numbers of undetected infections, and high attack rates on- and off-farm, even beyond a 5-km high-risk zone. Our investigation may serve as an essential case study for risk assessment in public health and related fields such as bioterrorism response and preparedness.

Waterborne gastroenteritis outbreak at a scouting camp caused by two norovirus genogroups: GI and GII.

BACKGROUND A cross-border gastroenteritis outbreak at a scouting camp was associated with drinking water from a farmers well. OBJECTIVES A retrospective cohort study was performed to identify size and source of the outbreak, as well as other characteristics. STUDY DESIGN Epidemiological investigation included standardized questionnaires about sex, age, risk exposures, illness and family members. Stool and water (100mL) samples were analyzed for bacteria, viruses and parasites. RESULTS Questionnaires were returned by 84 scouts (response rate 82%), mean age of 13 years. The primary attack rate was 85% (diarrhoea and/or vomiting). Drinking water was the strongest independent risk factor showing a dose-response effect with 50%, 75%, 75%, 93% and 96% case prevalence for 0, 1, 2-3, 4-5 and >5 glasses consumed, respectively. Norovirus (GI.2 Southampton and GII.7 Leeds) was detected in 51 stool specimens (75%) from ill scouts. Water analysis showed fecal contamination, but no norovirus. The secondary attack rate was 20%. CONCLUSIONS This remarkable outbreak was caused by a point-source infection with two genogroups of noroviruses most likely transmitted by drinking water from a well. Finding a dose-response relationship was striking. Specific measures to reduce the risk of waterborne diseases, outbreak investigation and a good international public health network are important.

High non-responsiveness of males and the elderly to standard hepatitis B vaccination among a large cohort of healthy employees

BACKGROUND Hepatitis B virus infection is a major health problem. Although non-response is known to increase with age, hepatitis B vaccinations are considered to have only minor non-response rates (anti-HBs<10IU/L) in healthy subjects. OBJECTIVES The aim of this study was to quantify immunosenescence in a large retrospective cohort of 11,439 healthy adults who received HBV immunisation according to the standard vaccination regime. STUDY DESIGN We evaluated the response to the standard three-dose vaccination regimen, consisting of 20-μg doses of the HbsAg recombinant DNA hepatitis B vaccine, among 11,439 healthy employees using a retrospective cohort design. Logistic regression was applied to predict the non-response rate, and multivariate regression analysis was applied to predict antibody response. Predictors of responsiveness included sex, age and time between the last vaccination and antibody titre measurement. RESULTS From the age of 29 on in men and 43 on in women, more than 5% of subjects did not respond. Compared with women, men had a higher risk of non-response and exhibited a steeper decline in antibody titres produced with increasing age. CONCLUSIONS This retrospective cohort study demonstrates that immunosenescence starts at young age, especially among men, underlining the importance of vaccination at a young age to achieve long-lasting immunity. Moreover, HBV vaccination should always include testing for antibodies to facilitate the performance of necessary interventions to prevent long-term fatal complications.

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.

Seroprevalence and determinants of eight high-risk human papillomavirus types in homosexual men, heterosexual men, and women: a population-based study in Amsterdam.

Background: To determine differences in the seroprevalence of high-risk human papillomavirus (hrHPV) types between men having sex with men (MSM), heterosexual men and women, we analyzed seroprevalence and risk factors for 8 hrHPV in the general population of Amsterdam, the Netherlands. Methods: We interviewed 1349 inhabitants aged ≥17 years and tested sera for antibodies against L1 capsid proteins of 8 hrHPV using Luminex-based multiplex serology. Risk factors for hrHPV were determined by multivariate Poisson analysis. RESULTS: Seroprevalences for 8 hrHPV ranged from 13.1% for HPV-45 to 31.4% for HPV-35. Seropositivity for HPV-16 and HPV-18 was more common in women and MSM than in heterosexual men. HPV-16 and -18 were more common in subjects also having antibodies against other hrHPV types (prevalence rate ratio [PRR], 2.12, 95% confidence interval [CI] 1.52–2.97; and PRR, 2.00; 95% CI, 1.43–2.81, respectively) and/or herpes simplex virus type 2 (PRR, 1.69; 95% CI, 1.32–2.16; and PRR, 1.47; 95% CI, 1.13–1.92, respectively). HPV-18 was more common in persons with a history of sexually transmitted infections (STI) (PRR, 1.64; 95% CI, 1.20–2.25). HPV-35, -45, and -58 were more common in non-European ethnic groups. Conclusions: Prevalence of 8 hrHPV antibodies was high in the Amsterdam population, especially in MSM.

Evaluation of the anatomical site distribution of chlamydia and gonorrhoea in men who have sex with men and in high-risk women by routine testing: cross-sectional study revealing missed opportunities for treatment strategies

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.