An outbreak of Legionnaires' disease linked to a municipal and industrial wastewater treatment plant, The Netherlands, September-October 2022.

Wastewater treatment plants (WWTPs) are increasingly identified as Legionnaires' disease (LD) sources. An outbreak investigation was initiated following five LD cases reported in September 2022 in Houten, the Netherlands. Case identification was based on the European LD case definition, with symptom onset from 1 September 2022, residence in or within 5 km of Houten, or visit to Houten within the incubation period, without other likely sources. We sampled potential sources and genotyped environmental and clinical isolates. We identified 15 LD cases with onset between 13 September and 23 October 2022. A spatial source identification and wind direction model suggested an industrial (iWWTP) and a municipal WWTP (mWWTP) as potential sources, with the first discharging water into the latter. Both tested positive for Legionella pneumophila serogroups 1 and 6 with multiple sequence types (ST). We detected L. pneumophila sg1 ST42 in the mWWTP, matching with one of three available clinical isolates. Following control measures at the WWTPs, no further cases were observed. This outbreak underlines that municipal and industrial WWTPs can play an important role in community LD cases and outbreaks, especially those with favourable conditions for Legionella growth and dissemination, or even non-favourable conditions for growth but with the influx of contaminated water.

Cross-border differences in the prevalence and risk factors for carriage of antimicrobial resistance in children attending daycare centers: a point prevalence study in the Netherlands and Belgium.

BACKGROUND: Day care centres (DCCs) are ideal settings for drug-resistant bacteria to emerge. Prevalence numbers of faecal carriage of antimicrobial resistant bacteria in these settings are rare. We aimed to determine the prevalence of faecal antimicrobial resistant bacteria carriage in children attending DCCs and to assess and identify infection risk factors within DCCs in The Netherlands and Belgium. METHODS: A point-prevalence study was conducted in 28 Dutch (499 children) and 18 Belgian (448 children) DCCs. Stool samples were taken from the children's diapers and a questionnaire was filled in by their parents. Hygiene related to stool and toilet use, hygiene related to food, environmental contamination, hand hygiene and hygiene guidelines were assessed conform a standardized questionnaire by the infection prevention and control expert visiting the DCC. Multilevel logistical regression analyses were used to define which characteristics predicted the presence of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E), carbapenemase-producing Enterobacterales (CPE), vancomycin-resistant enterococci (VRE), and ciprofloxacin-resistant Enterobacterales (CipR-E). RESULTS: The ESBL-E prevalence was 16% (n = 71) in Belgium and 6% (n = 30) in the Netherlands. The CipR-E prevalence was 17% (n = 78) in Belgium and 8% (n = 38) in the Netherlands. Antimicrobial use (RR: 0.30; 95% CI: 0.33-0.48) and hospital admissions (RR: 0.37; 95% CI: 0.25-0.54) were lower in the Netherlands. Children travelling to Asia were at higher risk of being an ESBL-E carrier. Children using antimicrobials were at higher risk of being a CipR-E carrier. Cleaning the changing mat after each use was found as a protective factor for CipR-E carriage. CONCLUSIONS: We established a significant difference in ESBL-E and CipR-E carriage and antimicrobial use and hospital admissions between the Netherlands and Belgium among children attending DCCs. The differences between both countries should be further studied to improve the policy on anti-microbial use and hospital admissions in children.

Time Scales of Human Mpox Transmission in The Netherlands.

Mpox has spread rapidly to many countries in nonendemic regions. After reviewing detailed exposure histories of 109 pairs of mpox cases in the Netherlands, we identified 34 pairs where transmission was likely and the infectee reported a single potential infector with a mean serial interval of 10.1 days (95% credible interval, 6.6-14.7 days). Further investigation into pairs from 1 regional public health service revealed that presymptomatic transmission may have occurred in 5 of 18 pairs. These findings emphasize that precaution remains key, regardless of the presence of recognizable symptoms of mpox.

Contribution of sexual health services to hepatitis B detection and control (Netherlands, 2008-2016).

OBJECTIVES: Case finding is one of the priority actions to reduce the disease burden of chronic hepatitis B (CHB). We estimated the contribution of CHB case finding at sexual health centres (SHCs) to the total national number of newly diagnosed CHB cases in the Netherlands and determined the characteristics of CHB cases detected at SHCs. METHODS: This observational study used surveillance data from all outpatient SHCs in the Netherlands (SOAP database) and the number of CHB from national notification data (Osiris) from 2008 to 2016. The proportion of CHB notifications (hepatitis B surface antigen positive serology) detected at SHCs was calculated. SHC consultations without hepatitis B virus (HBV) testing (n=669 308), with acute hepatitis B diagnosis (n=73), with HBV vaccination only (n=182) or an inconclusive hepatitis B diagnosis (n=24) were excluded. Univariable and multivariable logistic regression analyses were performed, stratified by gender and sexual preference, to analyse patient characteristics associated with CHB. RESULTS: During the study period, 12 149 CHB cases were notified. 405 646 SHC consultations were included in the analysis and 1452 CHB cases (0.4%) were detected at SHCs. The proportion of CHB cases detected at SHCs in relation to the national notified number ranged between 12.4% (200 of 1613) in 2008 and 10.8% (106 of 980) in 2016. 87% of CHB cases were among first-generation migrants (FGMs) originating from high endemic countries for sexually transmitted infections or men who have sex with men (MSM). In multivariable analysis, an older age category, migration background and being a commercial sex worker (CSW) were associated with CHB in all stratified analyses. CONCLUSIONS: The contribution of SHCs is relevant to case finding of CHB in the Netherlands. SHCs should therefore be considered as an important health setting to screen for HBV in high-risk groups, especially among MSM, CSW and FGM, to achieve a reduction in the HBV-related disease burden.

COVID-19 vaccine effectiveness against SARS-CoV-2 infection during the Delta period, a nationwide study adjusting for chance of exposure, the Netherlands, July to December 2021.

BackgroundDifferential SARS-CoV-2 exposure between vaccinated and unvaccinated individuals may confound vaccine effectiveness (VE) estimates.AimWe conducted a test-negative case-control study to determine VE against SARS-CoV-2 infection and the presence of confounding by SARS-CoV-2 exposure.MethodsWe included adults tested for SARS-CoV-2 at community facilities between 4 July and 8 December 2021 (circulation period of the Delta variant). The VE against SARS-CoV-2 infection after primary vaccination with an mRNA (Comirnaty or Spikevax) or vector-based vaccine (Vaxzevria or Janssen) was calculated using logistic regression adjusting for age, sex and calendar week (Model 1). We additionally adjusted for comorbidity and education level (Model 2) and SARS-CoV-2 exposure (number of close contacts, visiting busy locations, household size, face mask wearing, contact with SARS-CoV-2 case; Model 3). We stratified by age, vaccine type and time since vaccination.ResultsVE against infection (Model 3) was 64% (95% CI: 50-73), only slightly lower than in Models 1 (68%; 95% CI: 58-76) and 2 (67%; 95% CI: 56-75). Estimates stratified by age group, vaccine and time since vaccination remained similar: mRNA VE (Model 3) among people ≥ 50 years decreased significantly (p = 0.01) from 81% (95% CI: 66-91) at < 120 days to 61% (95% CI: 22-80) at ≥ 120 days after vaccination. It decreased from 83% to 59% in Model 1 and from 81% to 56% in Model 2.ConclusionSARS-CoV-2 exposure did not majorly confound the estimated COVID-19 VE against infection, suggesting that VE can be estimated accurately using routinely collected data without exposure information.

Epidemiological evaluation of mass testing in a small municipality in the Netherlands during the SARS-CoV-2 epidemic.

During 6 weeks in February-March 2021, the Dutch municipal health service Utrecht studied the epidemiological effects on test incidence and the detection of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mass testing (MT). During MT, inhabitants of Bunschoten could repeatedly test regardless of symptoms and as often as desired at the close-by test facilities in the municipality. Data from the regular COVID-19 registration was used for analysis. In Bunschoten, MT caused a significant increase in test incidence and an immediate increase in the number of detected active infections, in contrast to a stabilisation in the rest of the province of Utrecht. Age distribution of test incidence shifted to the older population in Bunschoten during MT. During MT, there was a 6.8 percentage point increase in detected asymptomatic cases, a 0.4 percentage point increase in pre-symptomatic cases and a decrease of 0.5 days between onset of symptoms and test date. This study has shown that MT increases test incidence and helps to obtain a more complete view of the presence of SARS-CoV-2 in a community, which can be useful in specific situations with a defined target group or goal. However, the question remains open whether the use of MT is proportionate to the overall gain.

Evaluation of a personalized, dose-sparing revaccination strategy in hepatitis B vaccine non-responders.

OBJECTIVES: The detection of low levels of antibodies against HBsAg (anti-HBs) below 10 IU/L in non-responders after a primary hepatitis B vaccination, is associated with seroconversion after revaccination. We compared the diagnostic performance of four anti-HBs assays in non-responders in their ability to differentiate between absence or presence of low levels of anti-HBs and propose a revaccination strategy guided by anti-HBs titres. METHODS: Non-responders were revaccinated with Fendrix 20 µg at 0, 1 and 2 months. Anti-HBs titres were determined by Abbott Architect, Diasorin Liaison, Roche Cobas and Siemens ADVIA Centaur. Inter-assay agreement was evaluated with Cohen's Kappa (k) in baseline samples between zero-responders without detectable antibodies and poor-responders with detectable antibodies < 10 IU/L. Seroconversion rates and geometric mean titres were analysed at 0, 1 and 3 months. A titre-based strategy (one revaccination dose and anti-HBs measurement followed by two more revaccination doses if required) was compared with the standard revaccination series of 3 doses. RESULTS: 57 participants were included in the analysis. k was ≥ 0.65 for all assays except ADVIA (k ≤ 0.41). After one revaccination dose all assays detected a mean seroconversion rate in zero-responders of 42.9%, compared to 85.1% in poor-responders. The difference between zero- and poor-responders in seroconversion rate per assay was significant (p < 0.05). After three revaccination doses the mean seroconversion rate was 88.2% in zero-responders and 98.5% in poor-responders (p > 0.286 per assay). A titre-based strategy reduced the amount of revaccinations by 17% compared with the standard. CONCLUSIONS: All assays demonstrated a comparable difference in seroconversion rate between zero- and poor-responders after one revaccination dose. The revaccination strategy could be optimised by differentiation between zero- and poor-responders followed by a titre-guided schedule.

First autochthonous human West Nile virus infections in the Netherlands, July to August 2020.

In October 2020, the first case of autochthonous West Nile virus neuroinvasive disease was diagnosed in the Netherlands with a presumed infection in the last week of August. Investigations revealed five more cases of local West Nile virus (WNV) infection. The cases resided in a region where WNV was detected in a bird and mosquitoes in August 2020. Molecular analysis was successful for two cases and identified the presence of WNV lineage 2.

Serological response to three alternative series of hepatitis B revaccination (Fendrix, Twinrix, and HBVaxPro-40) in healthy non-responders: a multicentre, open-label, randomised, controlled, superiority trial.

BACKGROUND: Serological non-response can be present after hepatitis B vaccination in healthy adults. We aimed to establish which of three revaccination regimens is most effective at inducing protective immunity METHODS: Healthy adults (aged 18-80 years) from 16 Dutch centres (13 public health services, two university hospitals, and one travel clinic) were included in this multicentre, parallel group, randomised, controlled, superiority trial. The inclusion criterion was vaccine non-response (hepatitis B surface antibody [anti-HBs] titre <10 IU/L) after a primary series with three doses of one type of recombinant vaccine against hepatitis B virus (either HBVaxPro-10 or Engerix-B at months 0, 1, and 6). Participants were individually randomly assigned (1:1:1:1) to a vaccination series of repeated initial vaccination (HBVaxPro 10 µg or Engerix-B 20 µg) as the control, or to Twinrix 20 µg, Fendrix 20 µg, or HBVaxPro 40 µg. We used a web-based randomisation programme, stratified by centre, with a block size of four. Participants and centres were unmasked to assignment after randomisation. Laboratory staff and investigators were masked to vaccine-group assignment. All revaccination schedules were identical, with intramuscular vaccinations at 0, 1, and 2 months. Anti-HBs was measured at 0, 1, 2, and 3 months. The primary outcome was the percentage of responders (anti-HBs titres ≥10 IU/L) at 3 months. Immunogenicity and safety analyses were based on an intention-to-vaccinate analysis, the immunogenicity analysis with last observation carried forward for missing data, and the Bonferroni and the Benjamini-Hochberg method were applied to correct for multiple testing. The trial was registered in the Dutch National Trial Register and inclusion has been stopped (identifier NL3011; EudraCT-number 2011-005627-40). FINDINGS: The participants were recruited between Nov 1, 2012, and Sept 1, 2017. 480 participants were randomly assigned and included in intention-to-vaccinate analyses: 124 (26%) to control, 118 (25%) to Twinrix, 114 (24%) to HBVaxPro-40, and 124 (26%) to Fendrix. At month 3 the percentage of responders was 83 (67%) of 124 (95% CI 57·9-75·1 in the control group, 94 (80%) of the 118 (71·3-86·5) in the Twinrix group, 95 (83%) of 114 (75·2-89·7) in the HBVaxPro-40 group, and 108 (87%) of 124 (79·9-92·4) in the Fendrix group. Compared with the control group, the percentage of responders was superior for the HBVaxPro-40 group (adjusted difference 21·6% [95% CI 10·4-32·7], p=0·0204 [Bonferroni corrected p value]) and the Fendrix group (26·3% [15·4-37·3], p=0·0006), but not the Twinrix group (25·0% [13·0-37·0]; p=0·0846). One serious adverse event occurred (herpes zoster ophthalmicus) in the Fendrix group, which was not attributed to the vaccine. INTERPRETATION: Revaccinating healthy non-responders with Fendrix or HBVaxPro-40 resulted in significantly higher proportions of responders and therefore indication for these vaccines should be expanded to enable revaccination of non-responders. FUNDING: National Institute for Public Health and the Environment.

Predictors of hepatitis B vaccination completion among people who use drugs participating in a national program of targeted vaccination.

BACKGROUND: Targeted vaccination strategies are necessary to prevent people who use drugs (PWUD) becoming infected with hepatitis B virus (HBV). The aims of this study were to provide an overview of the activities for PWUD in a decentralised vaccination program in the Netherlands and to explore the determinants associated with completing a standard hepatitis B vaccination series. METHODS: We used data for behavioural risk groups from the register of the national vaccination program. The data concerned PWUD who were immunised against hepatitis B in the Netherlands between 2002 and 2011. A standard series of three vaccinations (at 0, 1, and 6 months) was offered at inclusion and was continued if serological markers for past or chronic HBV infection were absent. Completion of a vaccination series (at least three vaccinations, irrespective of timing) was a dependent variable in our logistic regression analysis. RESULTS: The program reached 18,054 PWUD. Of the 15,746 participants eligible for vaccination (i.e. they were neither carriers of hepatitis B nor immune to hepatitis B), 9089 (58%) completed a series of three hepatitis B vaccinations. Factors associated with a higher completion rate of a vaccination series (p < 0.01) were: starting vaccination in the earlier years of the program, older age of PWUD, intravenous drug use, vaccine administration by addiction care centres, and flexibility in location of vaccine delivery. CONCLUSION: Despite using a standard HBV vaccination schedule and no financial incentives, vaccination completion among PWUD was relatively high. Our results suggest that flexibility of vaccination location and administration of vaccines by healthcare workers with sustainable contact with PWUD could improve vaccination programs for this risk group.

Diagnostic performance of serological assays for anti-HBs testing: Results from a quality assessment program.

BACKGROUND: Post-vaccination testing after hepatitis B vaccination is indispensable to evaluate long-term immunological protection. Using a threshold level of antibodies against hepatitis B surface antigen (anti-HBs) to define serological protection, implies reproducible and valid measurements of different diagnostic assays. OBJECTIVES: In this study we assess the performance of currently used anti-HBs assays. STUDY DESIGN: In 2013, 45 laboratories participated in an external quality assessment program using pooled anti-HBs serum samples around the cutoff values 10IU/l and 100IU/l. Laboratories used either Axsym (Abbott Laboratories), Architect (Abbott Laboratories), Access (Beckman-Coulter), ADVIA Centaur anti-HBs2 (Siemens Healthcare Diagnostics), Elecsys, Modular or Cobas (Roche Diagnostics) or Vidas Total Quick (Biomerieux) for anti-HBs titre quantification. We analysed covariance using mixed-model repeated measures. To assess sensitivity/specificity and agreement, a true positive or true negative result was defined as an anti-HBs titre respectively above or below the cutoff value by ≥4 of 6 assays. RESULTS: Different anti-HBs assays were associated with statistically significant (P<0.05) differences in anti-HBs titres in all dilutions. Sensitivity and specificity ranged respectively from 64%-100% and 95%-100%. Agreement between assays around an anti-HBs titre cutoff value of 10IU/l ranged from 93%-100% and was 44% for a cutoff value of 100IU/l. CONCLUSIONS: Around a cutoff value of 10IU/l use of the Access assay may result in false-negative results. Concerning the cutoff value of 100IU/l, a sample being classified below or above this cutoff relied heavily on the specific assay used, with both the Architect and the Access resulting in false-negative results.

Fluctuation of Viremia in Hepatitis B Virus-Infected Healthcare Workers Performing Exposure-Prone Procedures in the Netherlands.

OBJECTIVE: To determine the longitudinal changes in viral load of hepatitis B virus (HBV)-infected healthcare workers (HCWs) and its consequences for exclusion of infected HCWs performing exposure-prone procedures, various HBV DNA safety thresholds, and the frequency of monitoring. DESIGN: Retrospective cohort study June 1, 1996-January 31, 2013. Participants In the Netherlands, chronically HBV-infected HCWs performing exposure-prone procedures are notified to the Committee for Prevention of Iatrogenic Hepatitis B. Of the 126 notified HCWs, 45 had 2 or more HBV DNA levels determined without antiviral therapy. METHODS: A time-to-event analysis for HBV-infected HCWs categorized in various viremia levels surpassing a HBV DNA threshold level of 1×105 copies/mL, above which exposure-prone procedures are not allowed in the Netherlands. RESULTS: Fluctuations of HBV DNA in follow-up samples ranged from -5.4 to +2.2 log10 copies/mL. A high correlation was seen for each HBV DNA level with the 3 previous levels. In a time-to-event analysis, after 6 months 7.2%, 6.5%, and 14.3% of individuals had surpassed the threshold of 1×105 copies/mL for viral load categories 4.8×103 to 1.5×104; 1.5×104 to 4.0×104; and 4.0×104 to 1.0×105, respectively. CONCLUSIONS: We propose standard retesting every 6 months, with more frequent retesting just below the high threshold value (1×105 copies/mL), and prolonging this standard interval to 1 year after 3 consecutive levels below the threshold in policies with lower safety thresholds (1×103 or 1×104 copies/mL). Infect Control Hosp Epidemiol 2016;37:655-660.