Christian J. P. A. Hoebe

Association of Histo–Blood Group Antigens and Susceptibility to Norovirus Infections

BACKGROUND Noroviruses (NoVs) are the leading cause of viral gastroenteritis in humans of all ages. Challenge studies that used the NoV prototype strain Norwalk virus (NV) have shown that some individuals are not susceptible to infection, suggesting the absence of a receptor. Recent studies have identified histo-blood group antigens (HBGAs) as possible receptors. Being a nonsecretor and presence of HBGA type B were associated with protection against infection with NV, a genogroup (GG) I NoV. METHODS In the present retrospective study, we investigated the association between presence of HBGAs and the risk of infection with another NoV belonging to GGI (Hu/NV/I/Birmingham/93/UK). The study was done as part of an investigation of a waterborne outbreak in a group of schoolchildren and of a cohort of healthy adults. The ABH histo-blood group phenotype was determined by use of saliva or serum samples from these individuals. RESULTS Presence of HBGA type B was significantly correlated with a lack of susceptibility to infection with GGI NoV and with an absence of antibodies. No correlation was found with GGII NoV. Although the infection rate in nonsecretors was lower, this difference was not statistically significant, and several children lacking HBGAs in saliva were found to be infected. CONCLUSIONS Individuals with the HBGA type B may be protected against infection with GGI (but not GGII) NoVs. The association between susceptibility to NoV infection and being a secretor may be restricted to GGI NoV.

Norovirus Outbreak among Primary Schoolchildren Who Had Played in a Recreational Water Fountain

BACKGROUND A gastroenteritis outbreak was associated with playing in a norovirus-contaminated recreational fountain. OBJECTIVE AND STUDY DESIGN A retrospective cohort study was performed to estimate the magnitude of the outbreak and identify its source. Epidemiological investigation included standardized questionnaires about sex, age, school, class, risk exposures, and illness characteristics. Stool samples and environmental water samples were analyzed for the presence of bacteria, viruses, and parasites. RESULTS Questionnaires were returned for 191 schoolchildren (response rate, 83%) with a mean age of 9.2 years, of whom 47% were ill (diarrhea and/or vomiting). Children were more likely to have been ill if they had played in the recreational fountain (relative risk, 10.4). Norovirus (Birmingham) was detected in 22 (88%) stool specimens from ill children and in 6 (38%) specimens from healthy children. The water sample from the fountain contained a norovirus strain that was identical to the RNA sequence found in stools. CONCLUSIONS Recreational water may be the source of gastroenteritis outbreaks. Adequate water treatment can prevent these types of outbreak.

Effectiveness of yearly, register based screening for chlamydia in the Netherlands: controlled trial with randomised stepped wedge implementation

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

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 Rates of Antimicrobial Drug Resistance Gene Acquisition After International travel, the Netherlands

We investigated the effect of international travel on the gut resistome of 122 healthy travelers from the Netherlands by using a targeted metagenomic approach. Our results confirm high acquisition rates of the extended-spectrum β-lactamase encoding gene blaCTX-M, documenting a rise in prevalence from 9.0% before travel to 33.6% after travel (p<0.001). The prevalence of quinolone resistance encoding genes qnrB and qnrS increased from 6.6% and 8.2% before travel to 36.9% and 55.7% after travel, respectively (both p<0.001). Travel to Southeast Asia and the Indian subcontinent was associated with the highest acquisition rates of qnrS and both blaCTX-M and qnrS, respectively. Investigation of the associations between the acquisitions of the blaCTX-M and qnr genes showed that acquisition of a blaCTX-M gene was not associated with that of a qnrB (p = 0.305) or qnrS (p = 0.080) gene. These findings support the increasing evidence that travelers contribute to the spread of antimicrobial drug resistance.

Lack of evidence for the role of human adenovirus-36 in obesity in a European cohort.

Adenovirus infection has been shown to increase adiposity in chickens, mice, and nonhuman primates. Adenovirus type 36 (Ad‐36) DNA was detected in adipose tissues in these animal trials. In the United States, Ad‐36 significantly correlates with obesity as illustrated by an Ad‐36 seroprevalence of 30% in obese individuals and 11% in nonobese individuals. We investigated the possibility of a similar correlation of Ad‐36 in Dutch and Belgian persons. In total, 509 serum samples were analyzed for Ad‐36 antibodies using a serum neutralization assay. In addition, PCR was used to detect adenoviral DNA in visceral adipose tissue of 31 severely obese surgical patients. Our results indicated an overall Ad‐36 seroprevalence of 5.5% increasing with age. BMI of Ad‐36 seropositive humans was not significantly different from seronegative humans. No adenoviral DNA could be found using PCR on visceral adipose tissue. In conclusion, this first Ad‐36 study in the Netherlands and in Belgium indicates that Ad‐36 does not play a role as a direct cause of BMI increase and obesity in humans in Western Europe.

Acceptability of Self-Taken Vaginal Swabs and First-Catch Urine Samples for the Diagnosis of Urogenital Chlamydia trachomatis and Neisseria gonorrhoeae With an Amplified DNA Assay in Young Women Attending a Public Health Sexually Transmitted Disease Clinic

Objectives: Public health efforts are needed to encourage young women to get tested for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC). Goal: To assess the acceptability and feasibility of 2 noninvasive diagnostic approaches. Study Design: Participants of this cross-sectional survey were 413 young women (age 16–35) who underwent STD testing by self-taken vaginal swab (SVS) and a first-catch urine sample (FCU) by nucleic acid amplification test (BDProbTec) and filled out a questionnaire. Results: CT and GC were diagnosed in 10.9% (45/413) and 1.5% (6/413). Eleven percent of the participants who never previously had an STD examination (68%) tested STD positive. SVS and FCU were almost uniformly reported as easy to perform and preferred above gynecologic examination. Conclusions: Using SVS combined with FCU can be an important enhancing tool in public health approaches. Acceptability among potential patients is high, enabling the noninvasive detection of STDs that would otherwise remain undetected and untreated.

Rationale, design, and results of the first screening round of a comprehensive, register-based, Chlamydia screening implementation programme in the Netherlands

BackgroundImplementing Chlamydia trachomatis screening in the Netherlands has been a point of debate for several years. The National Health Council advised against implementing nationwide screening until additional data collected from a pilot project in 2003 suggested that screening by risk profiles could be effective. A continuous increase in infections recorded in the national surveillance database affirmed the need for a more active approach. Here, we describe the rationale, design, and implementation of a Chlamydia screening demonstration programme.MethodsA systematic, selective, internet-based Chlamydia screening programme started in April 2008. Letters are sent annually to all 16 to 29-year-old residents of Amsterdam, Rotterdam, and selected municipalities of South Limburg. The letters invite sexually active persons to login to http://www.chlamydiatest.nl with a personal code and to request a test kit. In the lower prevalence area of South Limburg, test kits can only be requested if the internet-based risk assessment exceeds a predefined value.ResultsWe sent invitations to 261,025 people in the first round. One-fifth of the invitees requested a test kit, of whom 80% sent in a sample for testing. The overall positivity rate was 4.2%.ConclusionsThis programme advances Chlamydia control activities in the Netherlands. Insight into the feasibility, effectiveness, cost-effectiveness, and impact of this large-scale screening programme will determine whether the programme will be implemented nationally.

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.