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Increased fluoroquinolone resistance in the two most common non-typhoidalSalmonella(NTS) serotypes among travellers returning to the Netherlands. ResistantSalmonella Enteritidisinfections are most likely to be acquired abroad, specifically outside Europe. This study highlights the importance of travel history when patients with NTS infections require empiric antimicrobial treatment.

In the Netherlands, more than half of domestic shigellosis cases are among men who have sex with men (MSM), particularly in the Amsterdam region. However, there is limited insight into which Shigella strains circulate in the Netherlands. Our objective was to assess the added value of whole-genome sequencing (WGS)-based surveillance for Shigella . To this end, we determined the relatedness among Shigella spp. isolates from patients in the Amsterdam region, as well as in an international context, including antimicrobial resistance markers, using WGS. The following criteria were used: it should provide insight into (1) clustering of shigellosis cases and the affected population, (2) the extent of admixture of MSM-associated isolates with those from the broader population and (3) the presence of antimicrobial resistance. It should then lead to more opportunities for targeted control measures. For this study, Shigella isolates from three laboratories in the Amsterdam region obtained between February 2019 and October 2021 were subjected to Illumina WGS at the National Institute for Public Health and the Environment (RIVM). Raw data were quality-checked and assembled, the Shigella serotype was determined with ShigaTyper, and antimicrobial resistance markers were detected using ResFinder and PointFinder. For Shigella sonnei , subclades were determined using Mykrobe. Relatedness of isolates, including 21 international reference genomes, was assessed with core genome multilocus sequence typing. In total, 109 isolates were included, of which 27 were from females (25 %) and 66 were from males (61 %), with which the majority (n=48, 73 %) being from MSM. No information on sex was available for the remaining 16 cases. The WGS data for all isolates, comprising 55 S . sonnei , 52 Shigella flexneri , 1 Shigella boydii and 1 Shigella dysenteriae , met the quality criteria. In total, 14 clusters containing 51 isolates (49 %) were identified, with a median cluster size of 2.5 cases (range: 2–15). Nine out of 14 clusters were MSM-associated, and 8 clusters (57 %) were travel-related. Six of the MSM clusters were related to international reference genomes. The prevalence of antimicrobial resistance markers was higher among isolates from MSM than non-MSM patients, particularly for ciprofloxacin (89 vs 33 %) and azithromycin (58 vs 17 %). In conclusion, about half of Shigella spp. patients were part of a cluster, of which a substantial part were related to international reference genomes, particularly among MSM, and a high prevalence of antimicrobial resistance markers was found. These findings indicate widespread international circulation of Shigella spp., particularly among MSM, with multidrug resistance that hampers treatment of patients. Moreover, the results of this study led to the implementation of a national WGS-based laboratory surveillance programme for Shigella spp. that started in April 2022.

BackgroundSalmonellosis remains the second most common zoonosis in the European Union despite a long-term decreasing trend. However, this trend has been reported to have stagnated in recent years, particularly for

Following the report of an excess in paediatric cases of severe acute hepatitis of unknown aetiology by the United Kingdom (UK) on 5 April 2022, 427 cases were reported from 20 countries in the World Health Organization European Region to the European Surveillance System TESSy from 1 January 2022 to 16 June 2022. Here, we analysed demographic, epidemiological, clinical and microbiological data available in TESSy. Of the reported cases, 77.3% were 5 years or younger and 53.5% had a positive test for adenovirus, 10.4% had a positive RT-PCR for SARS-CoV-2 and 10.3% were coinfected with both pathogens. Cases with adenovirus infections were significantly more likely to be admitted to intensive care or high-dependency units (OR = 2.11; 95% CI: 1.18–3.74) and transplanted (OR = 3.36; 95% CI: 1.19–9.55) than cases with a negative test result for adenovirus, but this was no longer observed when looking at this association separately between the UK and other countries. Aetiological studies are needed to ascertain if adenovirus plays a role in this possible emergence of hepatitis cases in children and, if confirmed, the mechanisms that could be involved.

Description of basis epidemiological characteristics of human S. Enteritidis cases and other relevant serovars.Extended report on epidemiological characteristics with results from the rarefaction analyses, the refined attribution models, but also with data on food consumption patterns

The objective of WP3 Task 1 is to describe (D-JRPFBZ-4-WP3.1) and evaluate (D-JRPFBZ-4-WP3.3) Member States (MS) national surveillance systems for Salmonella Enteritidis in humans, using an adapted version of the 2014 ECDC evaluation framework of public health surveillance systems, to assess whether the recent plateau of S. Enteritidis cases could be related to changes in the performance of the human surveillance systems and/or diagnostic standards that are in place.

An extensive multi-country outbreak of multidrug-resistant monophasic

In this deliverable, the association between human exposure to Salmonella Enteritidis (SE) through chicken eggs and the number of human salmonellosis cases was explored. The rationale was that changes in human exposure to SE could potentially explain the levelling off of the decreasing trend of human SE cases in Europe. For the exposure assessment, a simplified approach of the pre-treatment load was used, which was calculated as the product of egg SE prevalence and egg consumption rate. Due to the limited availability of egg SE prevalence data, we also investigated the suitability of laying hen flock level SE prevalence as a proxy for egg SE prevalence. However, the correlation between the two was limited, and flock level SE prevalence was therefore not included in further analysis. Annual data on egg SE prevalence could only be obtained from Spain. Pooled sample egg SE prevalence’s from Spain were first transformed to annual egg SE prevalence’s. Next, annual egg SE prevalence was compared with the annual incidence rate of salmonellosis in Spain. We found a weak correlation between the pre-treatment SE load and the number of human SE cases, which indicates that changes in human exposure to SE through consumption of chicken eggs cannot explain the stagnating SE incidence in humans. However, several other factors could be at play that we could not take into account, such as: the obtained dataset on egg SE prevalence in Spain is not representative for the true egg SE prevalence in Spain; egg SE prevalence was measured on the shell of the egg and not for the content, which might not fully represent the true human SE exposure; humans might be exposed to SE via other transmission routes than chicken eggs. This study also looked at the importance of SE exposure from imported eggs, but that seemed to be negligible for Spain as eggs mainly originated from in-land. This study found no indication that the changing trend in human salmonellosis incidence is related to changes human exposure to SE from chicken eggs. However, data availability was limited, and analyses could only be performed for Spain, of which it is unknown whether results are generalizable to other countries. Therefore, based on results in this study, we could not fully determine whether the EU-wide reversal of the decreasing SE trend in humans could be due to changes in exposure to SE through eggs.

The public health measures implemented to control coronavirus disease 2019 (COVID-19) may influence also other infectious diseases. Using national laboratory surveillance data, we assessed the impact of the COVID-19 pandemic on human salmonellosis in the Netherlands until March 2021. Salmonellosis incidence decreased significantly after March 2020: in the second, third and fourth quarters of 2020, and in the first quarter of 2021, the incidence decreased by 55%, 57%, 47% and 37%, respectively, compared to the same quarters of 2016–2019. The decrease was strongest among travel-related cases (94%, 84%, 79% and 93% in the aforementioned quarters, respectively). Other significant changes were: increased proportion of cases among older adults and increased proportion of invasive infections, decreased proportion of trimethoprim resistance and increased proportion of serovar Typhimurium monophasic variant vs. Enteritidis. This led to decreased contributions of laying hens and increased contributions of pigs and cattle as sources of human infections. The observed changes probably reflect a combination of reduced exposure to Salmonella due to restrictions on international travels and gatherings, closure of dine-in restaurants, catering and hospitality sectors at large and changes in healthcare-seeking and diagnostic behaviours.

The impact of COVID-19 on population health is recognised as being substantial, yet few studies have attempted to quantify to what extent infection causes mild or moderate symptoms only, requires hospital and/or ICU admission, results in prolonged and chronic illness, or leads to premature death. We aimed to quantify the total disease burden of acute COVID-19 in the Netherlands in 2020 using the disability-adjusted life-years (DALY) measure, and to investigate how burden varies between age-groups and occupations. Using standard methods and diverse data sources (mandatory notifications, population-level seroprevalence, hospital and ICU admissions, registered COVID-19 deaths, and the literature), we estimated years of life lost (YLL), years lived with disability, DALY and DALY per 100,000 population due to COVID-19, excluding post-acute sequelae, stratified by 5-year age-group and occupation category. The total disease burden due to acute COVID-19 was 286,100 (95% CI: 281,700-290,500) DALY, and the per-capita burden was 1640 (95% CI: 1620-1670) DALY/100,000, of which 99.4% consisted of YLL. The per-capita burden increased steeply with age, starting from 60 to 64 years, with relatively little burden estimated for persons under 50 years old. SARS-CoV-2 infection and associated premature mortality was responsible for a considerable direct health burden in the Netherlands, despite extensive public health measures. DALY were much higher than for other high-burden infectious diseases, but lower than estimated for coronary heart disease. These findings are valuable for informing public health decision-makers regarding the expected COVID-19 health burden among population subgroups, and the possible gains from targeted preventative interventions.

We analysed hepatitis A (HepA) notifications and hospitalisations in Italy, the Netherlands, Norway, Spain, and Sweden for available periods between 1995 and 2014. We aimed to investigate whether decreasing HepA incidence is associated with increasing age at infection and worsening HepA presentation and to identify groups at risk of severe disease.We performed a retrospective cohort study including 36 734 notified and 36 849 hospitalised patients. We used negative binomial regressions to identify over time: i) trends in hospitalisation and notification rates; ii) proportion of hospitalised and notified patients aged ≥40 years; iii) proportion of "severe hospitalisations"; and iv) risk factors for severe hospitalisation.During the study period both HepA notifications and hospitalisations decreased, with notification rates decreasing faster, patients aged ≥40 years increased, however, the proportion of severe HepA hospitalisations remained stable. Older patients and patients with comorbidities, particularly liver diseases, were more likely to experience severe disease.We used digitalised health information to confirm decreasing trends in HepA hospitalisations and notifications, and the increasing age of patients with HepA in Europe. We did not identify an increase in the severity of the clinical presentation of patients with HepA. Older patients with liver diseases are at increased risk of severe disease and should be prioritised for vaccination.

Summary Background Salmonella spp are a major cause of food-borne outbreaks in Europe. We investigated a large multi-country outbreak of Salmonella enterica serotype Enteritidis in the EU and European Economic Area (EEA). Methods A confirmed case was defined as a laboratory-confirmed infection with the outbreak strains of S Enteritidis based on whole-genome sequencing (WGS), occurring between May 1, 2015, and Oct 31, 2018. A probable case was defined as laboratory-confirmed infection with S Enteritidis with the multiple-locus variable-number tandem repeat analysis outbreak profile. Multi-country epidemiological, trace-back, trace-forward, and environmental investigations were done. We did a case-control study including confirmed and probable cases and controls randomly sampled from the population registry (frequency matched by age, sex, and postal code). Odds ratios (ORs) for exposure rates between cases and controls were calculated with unmatched univariable and multivariable logistic regression. Findings 18 EU and EEA countries reported 838 confirmed and 371 probable cases. 509 (42%) cases were reported in 2016, after which the number of cases steadily increased. The case-control study results showed that cases more often ate in food establishments than did controls (OR 3·4 [95% CI 1·6–7·3]), but no specific food item was identified. Recipe-based food trace-back investigations among cases who ate in food establishments identified eggs from Poland as the vehicle of infection in October, 2016. Phylogenetic analysis identified two strains of S Enteritidis in human cases that were subsequently identified in salmonella-positive eggs and primary production premises in Poland, confirming the source of the outbreak. After control measures were implemented, the number of cases decreased, but increased again in March, 2017, and the increase continued into 2018. Interpretation This outbreak highlights the public health value of multi-country sharing of epidemiological, trace-back, and microbiological data. The re-emergence of cases suggests that outbreak strains have continued to enter the food chain, although changes in strain population dynamics and fewer cases indicate that control measures had some effect. Routine use of WGS in salmonella surveillance and outbreak response promises to identify and stop outbreaks in the future. Funding European Centre for Disease Prevention and Control; Directorate General for Health and Food Safety, European Commission; and National Public Health and Food Safety Institutes of the authors' countries (see Acknowledgments for full list).

To determine whether children play a role in the transmission of SARS-CoV-2 to other children and adults, and to gain insight into symptomatic and asymptomatic infections in children.Analysis of national COVID-19 notifications and prospective observational study in families with children.Information about COVID-19 patients and their contacts was obtained from the registration systems used by the public health services. In an ongoing study, patients with COVID-19 were asked to participate if they have a family with children. On two occasions nose-throat swabs and blood were collected for PCR analysis and determination of antibodies against SARS-CoV-2.The notifications suggest that transmission finds place mainly between adults and to a lesser extent between parents and children. For the family study, data were available from 54 households with a total of 227 participants. In families of a confirmed COVID-19 patient, children between 1 and 11 years were less often positive in PCR and serology than older children and adults.The study gives no indications that children play an important role in the transmission of SARS-CoV-2. Children can indeed become infected, but transmission mainly takes place between adult peers and from adult family members to children. Transmission among children or from children to adults, as is known in influenza, appears to be less common. Ongoing studies should provide important information for further decision-making on control measures, such as closure of schools.

Objectives Non-typhoid Salmonella (NTS) may invade beyond the intestine, causing bacteraemia, sepsis, and infection of normally sterile sites. The epidemiology of invasive NTS (iNTS) infection is under-researched. We determined trends, risk factors, serotype distribution, antimicrobial resistance (AMR), and attributable sources of iNTS infection in a high-income setting. Methods 22,837 records of culture-confirmed human salmonellosis cases and 10,008 serotyped Salmonella isolates from five putative animal reservoirs (pigs, cattle, broilers, layers, reptiles) in the Netherlands during 2005–2018 were retrieved from national surveillance registries. Risk factors for iNTS infection were identified using logistic regression analysis. Source attribution modelling was based on serotyping, prevalence, and exposure data. Results The average annual percentage of iNTS infections was 4.6% (range 3.5–5.7%). An increase in iNTS infections was observed since 2012 (odds ratio (OR) 1.09, 95% confidence interval (95% CI) 1.04–1.14). Increased iNTS infection risk was associated with wintertime (OR 1.37, 95% CI 1.12–1.66), male sex (OR 1.73, 95% CI 1.51–1.99), older age (ORs: 3.27 to 16.33, depending on age groups), and living in rural areas (OR 1.54, 95% CI 1.23–1.93). While 52% of iNTS infections (n = 950) were caused by serotypes Enteritidis and Typhimurium, those displaying the highest invasiveness relative to their occurrence were Dublin (32.9%, n = 163), Panama (21.6%, n = 106), and Poona (14.1%, n = 71). Cattle were a larger source of iNTS than non-iNTS infections (12.2% vs. 7.6%). Lower AMR and multi-resistance rates were observed among iNTS (37.9%) than non-iNTS isolates (48.6%). Discussion The increase in iNTS infections, which is reported also in other countries, is of public health and clinical concern. The underlying reasons seem to be multi-factorial in nature. iNTS infection risk depends more on the infecting serotypes and patient demographics, and less on the attributable reservoirs and AMR profiles.

SUMMARYOn 12 July 2015, a triathlon competition with 900 participants took place in Utrecht, the Netherlands. An outbreak investigation was initiated after 56 participants reported health complaints. An online questionnaire was sent to 700 participants. Stool specimens from six participants and four water specimens were collected from the swimming location. A total of 239 participants completed the questionnaire (response rate: 34%), 73 (31%) of them met the case definition for acute gastrointestinal illness (AGI). A total of 67% of the respondents were male and the median age was 38 years. Almost half (42%) of swimmers reported health complaints. Consumption of energy drinks and ingesting ⩾3 mouthfuls of canal water were identified as risk factors for AGI among swimmers only (adjusted relative risks (aRR) 1·6; 95% confidence intervals (CI) 1·0–2·5 and aRR 2·6; 95% CI 1·5–4·8). The collected water specimens tested positive for norovirus genogroup I and rotavirus and stool specimens tested positive for norovirus genogroup II. Our findings indicate that the outbreak could have been caused by exposure to norovirus during swimming. Swimmers should get information about the health risks for making an informed choice about participating. For future events, the organisers decided to change the swimming location from a canal to a recreational lake.

Background: Shigella spp. and entero-invasive Escherichia coli (EIEC) can cause mild diarrhea to dysentery. In the Netherlands, although shigellosis is a notifiable disease, there is no laboratory surveillance for Shigella spp. and EIEC in place. Consequently, the population structure for circulating Shigella spp. and EIEC isolates is not known. This study describes the phenotypic and serological characteristics, the phenotypic and genetic antimicrobial resistance profiles, the virulence gene profiles, the classic multi-locus sequence types (MSLT) and core genome MLST (cgMLST) types, and the epidemiology of Shigella spp. and EIEC isolates collected during a cross-sectional study in the Netherlands in 2016 and 2017. Results: S. sonnei, S. flexneri and EIEC were predominantly detected in the Netherlands. A substantial part of the characterized isolates was resistant to antimicrobials advised for treatment, i.e., 73% was phenotypically resistant to co-trimoxazol and 19% to ciprofloxacin. Antimicrobial resistance was particularly observed in isolates from male patients who had sex with men or from patients that had travelled to Asia. Furthermore, isolates related to international clusters were also circulating in the Netherlands. Travel-related isolates formed clusters with isolates from patients without travel history, indicating their emergence into the Dutch population. Conclusions: In conclusion, laboratory surveillance using whole genome sequencing for genetic characterization of isolates complements the current epidemiological surveillance, as the latter is not sufficient to detect all (inter)national clusters, emphasizing the importance of multifactorial public health approaches.

BackgroundBurden of disease (BoD) estimations are increasingly used to prioritize public health interventions. Previous Cryptosporidium BoD models accounted only for acute episodes, while there is increasing evidence of long-term manifestations. Our objective was to update Cryptosporidium BoD and cost-of-illness (COI) models and to estimate BoD and COI for the Netherlands in years 2013-2017.MethodsWe performed a scoping literature review and drew an outcome tree including long-term manifestations for which sufficient evidence was found, such as recurrent diarrhea and joint pain. We chose the Disability-Adjusted Life Year (DALY) metric to synthesize years of life lost due mortality (YLLs) and years lived with disability due to non-fatal outcomes (YLDs). For the costs, we adopted a societal perspective accounting for direct healthcare costs, patient costs and productivity losses. Uncertainty was managed using Latin Hypercube sampling (30,000 iterations).ResultsIn the Netherlands in 2017, we estimated 50,000 Cryptosporidium cases (95% uncertainty interval (UI): 15,000-102,000), 7,000 GP visits, 300 hospitalizations and 3 deaths, resulting in 137 DALYs (95%UI: 54-255) and €19.2 million COI (95%UI: €7.2 million- €36.2 million). Estimates were highest for 2016 (218 DALYs and €31.1 million in COI), and lowest in 2013 (100 DALYs and €13.8 million in COI). Most of the BoD was attributable to YLD (≈80% of DALYs). The most important cost was productivity losses (≈90% of total COI). Long-term manifestations, including recurring diarrhea and joint pain, accounted for 9% of the total DALYs and 7% of the total COI.ConclusionCurrent evidence supports the inclusion of long-term manifestations in Cryptosporidium models, which contribute close to 10% of the total DALYs and costs. This may be an underestimation, as we were conservative in our assumptions. Cryptosporidium should be considered a priority organism with respect to public health surveillance, even in industrialized countries with high hygiene standards.

Giardia lamblia is a major cause of diarrhoea in children, especially those attending day-care centres (DCCs). Only Giardia assemblages A and B infect humans. Given the lack of assemblage-specific epidemiological data, we aimed to identify risk factors for infection by assemblages A and B in DCC attendees. During 2010-2013, 5,015 faecal samples from ≤4-year-old children attending 40 DCCs participating in laboratory surveillance in the Netherlands were tested for Giardia using RT-PCR. Giardia-positive samples were typed for identification of assemblages A and B. We compared child- and DCC-level characteristics of Giardia-positive children with those of Giardia-negative children using mixed-effects logistic regression. Overall, 226 samples (4.5 %) tested positive for Giardia, and assemblages were determined for 138 of them: 62 (45 %) were assemblage A and 76 (55 %) were B. The only risk factor for assemblage A infection was attending DCCs with indoor sandpits and cats during spring/summer (odds ratio [OR] 13.5; 95% CI 1.8-101.3). For assemblage B, risk factors were attending DCCs with dedicated diaper-changing (OR 3.6; 95% CI 1.7-7.6) and laundry (OR 2.3; 95% CI 1.1-4.9) areas. Preventing sick children from attending day-care and having cloth-towels at the DCC decreased the risk of assemblage B infection (OR 0.0; 95% CI 0.0-0.5 and OR 0.3; 95% CI 0.1-0.6 respectively). Risk factors for assemblages A and B infection in DCC-attending children were different, with assemblage B being mainly related to anthroponotic transmission, and assemblage A being related to zoonotic transmission. Given these differences, interventions to reduce the burden of childhood giardiasis cannot ignore those assemblage-specific preferred reservoirs and transmission routes.

Acute gastroenteritis (AGE) morbidity remains high amongst preschool children, posing a significant societal burden. Empirical data on AGE-causing agents is needed to gauge their clinical relevance and identify agent-specific targets for control. We assessed the prevalence, risk factors and association with symptoms for enteropathogens in households with preschool children. A monthly-repeated cross-sectional survey of enteropathogens in households with preschool children was performed. A parent-child pair per household (n = 907 households) provided faecal samples and reported their symptoms and potential risk exposures. Samples were tested by multiplex reverse transcription polymerase chain reaction (RT-PCR) for 19 enteropathogens. Associations were assessed using logistic regression. 28.3 % of children (n = 981) and 15.6 % of parents (n = 971) carried pathogenic bacteria and/or Escherichia coli-associated pathogenicity genes, and 6.5 % and 3.3 % carried viruses, respectively. Giardia lamblia (4.6 % of children, 2.5 % of parents) and Dientamoeba fragilis (36 %, 39 %, respectively) were the main parasites, and were associated with pet exposure. Living in rural areas was associated with carriage of pathogenic E. coli, norovirus I and D. fragilis. Pathogenic E. coli was associated with summertime and livestock exposure. Attending day-care centres increased the risk of carrying norovirus, sapovirus and G. lamblia. Viruses occurred mainly in winter and were associated with AGE symptoms. Childparent associations were found for bacterial pathogenicity genes, viruses, G. lamblia and D. fragilis. Enteropathogens spread widely in households with preschool children, particularly viruses, which more often cause symptoms. While bacteria predominate during summer and in those exposed to livestock, viruses predominate in wintertime and, like G. lamblia, are widespread amongst day-care centre attendees.

Influenza-like illness (ILI) is the leading cause of medical consultation amongst preschool children, who may contribute to spreading ILI-causing agents within the household. We aimed to determine the societal burden (incidence, health-care consumption and productivity loss) and correlates of ILI in households with preschool children.A survey was performed in the Netherlands during October 2012 to October 2014. Monthly, 2000 households with children younger than 4 years were invited to report their symptoms and related medical care, productivity loss and putative risk exposures for 1 preschool child and 1 parent.Eight thousand seven hundred and sixty-eight child-parent pairs were enrolled. ILI incidence was 2.81 episodes/child-year and 1.72 episodes/parent-year. Amongst those with ILI, health-care utilization was 35.7% (children) and 17.7% (parents). Work absenteeism was 45.7% (median 2 workdays lost) and day-care absenteeism was 22.8% (median 1 day missed). Chronic respiratory conditions, developmental disabilities, parental occupation in health care/child care, having a sibling and attending day care for ≤12 months increased childhood ILI risk. Parental ILI risk increased with having chronic respiratory conditions, developmentally disabled day-care-attending children and female gender in interaction with unemployment and multiple day-care-attending children. Breastfeeding infants 6-month-old or younger and attending day care for24 months decreased childhood ILI risk. Pregnancy, occupation in health care and having ≥3 children decreased parental ILI risk. Parents of ILI-affected children had a concurrent 4-fold higher ILI risk.ILI in households with preschool children has a considerable societal impact. Risk-mitigating initiatives seem justified for day-care attendees, mothers, people with chronic respiratory conditions, and children with developmental disabilities. Children attending day care for2 years acquire some protection to ILI.

Table S3. Additional analysis of AGE and ARI with regard to their risk factors with and without individuals having chronic diseases. (DOCX 18 kb)

Table S1. Results of univariate analyses for AGE in all age categories (overall), children (

Table S2. Results of univariate analyses for ARI in all age categories (overall), children (

Figure S1. Flowchart discarded information. (DOCX 47 kb)

Background and objective Since 2013, a biennial rotavirus pattern has emerged in the Netherlands with alternating high and low endemic years and a nearly 50% reduction in rotavirus hospitalization rates overall, while infant rotavirus vaccination has remained below 1% throughout. As the rotavirus vaccination cost-effectiveness and risk-benefit ratio in high-income settings is highly influenced by the total rotavirus disease burden, we re-evaluated two infant vaccination strategies, taking into account this recent change in rotavirus epidemiology. Methods We used updated rotavirus disease burden estimates derived from (active) surveillance to evaluate (1) a targeted strategy with selective vaccination of infants with medical risk conditions (prematurity, low birth weight, or congenital conditions) and (2) universal vaccination including all infants. In addition, we added herd protection as well as vaccine-induced intussusception risk to our previous cost-effectiveness model. An age- and risk-group structured, discrete-time event, stochastic multi-cohort model of the Dutch pediatric population was used to estimate the costs and effects of each vaccination strategy. Results The targeted vaccination was cost-saving under all scenarios tested from both the healthcare payer and societal perspective at rotavirus vaccine market prices (€135/child). The cost-effectiveness ratio for universal vaccination was €51,277 at the assumed vaccine price of €75/child, using a societal perspective and 3% discount rates. Universal vaccination became cost-neutral at €32/child. At an assumed vaccine-induced intussusception rate of 1/50,000, an estimated 1707 hospitalizations and 21 fatal rotavirus cases were averted by targeted vaccination per vaccine-induced intussusception case. Applying universal vaccination, an additional 571 hospitalizations and

Introduction Swimming events in city canals are gaining popularity in the Netherlands, even though canal water is usually not officially designated for recreational use. Knowledge regarding the risk of infection after swimming in canals is limited. An outbreak was reported in 2015 following a canal swimming event in Utrecht, the Netherlands. Local governments were concerned about the health risks of such events. In order to assess the safety of canal swimming, the Public Health Service (PHS) prospectively investigated two city canal swimming events in 2015. In 2016, we repeated this study, aiming to prospectively determine the risks of infection during two urban swimming events, the Utrecht SingelSwim 2016 (USS) and the Amsterdam City Swim 2016 (ACS). Methods We sent online questionnaires to 271 USS participants and 2697 ACS participants, concerning personal characteristics, symptoms, and exposure. Participants were asked to forward the questionnaire to three relatives, i.e., non-exposed. We analyzed water samples from the USS venue taken during the event, as well as stool samples of USS participants with acute gastrointestinal illness (AGI). AGI was defined as diarrhea and/or vomiting within seven days after the event. We calculated adjusted risk ratios (RR) for AGI in the exposed group compared with non-exposed respondents, using binomial regression models. Results The questionnaire was returned by 160 USS participants (exposed) (59%) and 40 non-exposed relatives. Five percent of the exposed (n = 17) and 3% of non-exposed (n = 1) reported AGI (RR = 1.69; 95% CI: 0.23–12.46). Norovirus genogroup II was detected in two of six USS water samples and in none of the three stool samples. In one of three stool samples, rotavirus was detected. The questionnaire was returned by 1169 ACS participants (exposed) (43%) and 410 non-exposed relatives. Six percent of the exposed (n = 71) and 1% of non-exposed (n = 5) reported AGI (RR 4.86; 95% CI: 1.98–11.97). Conclusion Results of the ACS event showed a higher risk for AGI among the exposed, indicating that participants of events in urban canals in the Netherlands could be at a higher risk for AGI than those not participating. The inconclusive results from the USS are likely due to the small sample size. Swimming in non-monitored open water can bring health risks and more knowledge about environmental and human risk factors helps reduce the risk by being able to more specifically advise organizations and governments.

Background: Brown rats (Rattus norvegicus) may carry pathogens that can be a risk for public health. Brown rats in the Netherlands were tested for the zoonotic pathogens Leptospira spp. and Seoul hantavirus (SEOV), in order to obtain insight in their prevalence. Methods and results: Cross-sectional studies were performed at four locations from 2011 to 2015. The rats were tested for Leptospira spp. using real-time PCR and/or culture resulting in a prevalence ranging between 33–57%. Testing for SEOV was done through an adapted human Seoul hantavirus ELISA and real-time RT-PCR. Although at several locations the ELISA indicated presence of SEOV antibodies, none could be confirmed by focus reduction neutralization testing. Conclusion: The results indicate a widespread presence of Leptospira spp. in brown rats in the Netherlands, including areas with a low leptospirosis incidence in humans. No evidence for circulation of SEOV was found in this study.

Background In the Netherlands, echovirus type 6 (E6) is identified through clinical and environmental enterovirus surveillance (CEVS and EEVS). Aim We aimed to identify E6 transmission clusters and to assess the role of EEVS in surveillance and early warning of E6. Methods We included all E6 strains from CEVS and EEVS from 2007 through 2016. CEVS samples were from patients with enterovirus illness. EEVS samples came from sewage water at pre-specified sampling points. E6 strains were defined by partial VP1 sequence, month and 4-digit postcode. Phylogenetic E6 clusters were detected using pairwise genetic distances. We identified transmission clusters using a combined pairwise distance in time, place and phylogeny dimensions. Results E6 was identified in 157 of 3,506 CEVS clinical episodes and 92 of 1,067 EEVS samples. Increased E6 circulation was observed in 2009 and from 2014 onwards. Eight phylogenetic clusters were identified; five included both CEVS and EEVS strains. Among these, identification in EEVS did not consistently precede CEVS. One phylogenetic cluster was dominant until 2014, but genetic diversity increased thereafter. Of 14 identified transmission clusters, six included both EEVS and CEVS; in two of them, EEVS identification preceded CEVS identification. Transmission clusters were consistent with phylogenetic clusters, and with previous outbreak reports. Conclusion Algorithms using combined time–place–phylogeny data allowed identification of clusters not detected by any of these variables alone. EEVS identified strains circulating in the population, but EEVS samples did not systematically precede clinical case surveillance, limiting EEVS usefulness for early warning in a context where E6 is endemic.

A hyperendemic rotavirus season was expected after a low-endemic 2014 season in the Netherlands. Rotavirus detections were however similar in 2015 and lower in 2016 compared with 2010-2013. Gastroenteritis consultation rates were also similar in 2015, but the age distribution shifted to older children because of an accumulation of noninfected children. Results indicate a possible shift to a biennial rotavirus pattern.

Background: Brown rats (Rattus norvegicus) may carry pathogens that can be a risk for public health. Brown rats in the Netherlands were tested for the zoonotic pathogens Leptospira spp. and Seoul hantavirus (SEOV), in order to obtain insight in their prevalence. Methods and results: Cross-sectional studies were performed at four locations from 2011 to 2015. The rats were tested for Leptospira spp. using real-time PCR and/or culture resulting in a prevalence ranging between 33–57%. Testing for SEOV was done through an adapted human Seoul hantavirus ELISA and real-time RT-PCR. Although at several locations the ELISA indicated presence of SEOV antibodies, none could be confirmed by focus reduction neutralization testing. Conclusion: The results indicate a widespread presence of Leptospira spp. in brown rats in the Netherlands, including areas with a low leptospirosis incidence in humans. No evidence for circulation of SEOV was found in this study.

Leptospirosis is a globally emerging zoonotic disease, associated with various climatic, biotic and abiotic factors. Mapping and quantifying geographical variations in the occurrence of leptospirosis and the surrounding environment offer innovative methods to study disease transmission and to identify associations between the disease and the environment. This study aims to investigate geographic variations in leptospirosis incidence in the Netherlands and to identify associations with environmental factors driving the emergence of the disease. Individual case data derived over the period 1995-2012 in the Netherlands were geocoded and aggregated by municipality. Environmental covariate data were extracted for each municipality and stored in a spatial database. Spatial clusters were identified using kernel density estimations and quantified using local autocorrelation statistics. Associations between the incidence of leptospirosis and the local environment were determined using Simultaneous Autoregressive Models (SAR) explicitly modelling spatial dependence of the model residuals. Leptospirosis incidence rates were found to be spatially clustered, showing a marked spatial pattern. Fitting a spatial autoregressive model significantly improved model fit and revealed significant association between leptospirosis and the coverage of arable land, built up area, grassland and sabulous clay soils. The incidence of leptospirosis in the Netherlands could effectively be modelled using a combination of soil and land-use variables accounting for spatial dependence of incidence rates per municipality. The resulting spatially explicit risk predictions provide an important source of information which will benefit clinical awareness on potential leptospirosis infections in endemic areas.

This paper deals with modelling the relationship between human Puumala hantavirus (PUUV) infection, the abundance and prevalence of infection of the host (the bank vole), mast, and temperature. These data were used to build and parametrise generalised regression models, and parametrise them using datasets on these factors pertaining to the Netherlands. The performance of the models was assessed by considering their predictive power. Models including mast and monthly temperature performed well, and showed that mast intensity influences vole abundance and hence human exposure for the following year. Thus, the model can aid in forecasting of human illness cases, since (1) mast intensity influences the vole abundance and hence human exposure for the following year and (2) monitoring of mast is much more feasible than determining bank vole abundance.

SUMMARYInsights into transmission dynamics of enteropathogens in children attending daycare are limited. Here we aimed at identifying daycare centre (DCC) characteristics associated with time-clustered occurrence of enteropathogens in DCC-attending children. For this purpose, we used the KIzSS network, which comprises 43 DCCs that participated in infectious disease surveillance in The Netherlands during February 2010–February 2013. Space–time scan statistics were used to identify clusters of rotavirus, norovirus, astrovirus, Giardia lamblia and Cryptosporidium spp. in a two-dimensional DCC characteristic space constructed using canonical correlation analysis. Logistic regression models were then used to further identify DCC characteristics associated with increased or decreased odds for clustering of enteropathogens. Factors associated with increased odds for enteropathogen clustering in DCCs were having indoor/outdoor paddling pools or sandpits, owning animals, high numbers of attending children, and reporting outbreaks to local health authorities. Factors associated with decreased odds for enteropathogen clustering in DCCs were cleaning child potties in designated waste disposal stations, cleaning vomit with chlorine-based products, daily cleaning of toys, extra cleaning of toys during a suspected outbreak, and excluding children with gastroenteritis. These factors provide targets for reducing the burden of gastrointestinal morbidity associated with time-clustered occurrence of major enteropathogens in DCC attendees.

Rotavirus detection rates among preschool children sampled irrespective of symptoms during the rotavirus season (January-April) in the Netherlands were significantly lower in 2014 (0.6%) than in 2010 (11.2%), 2011 (6.9%), 2012 (6.8%) and 2013 (6.7%). This supports previous observations of a genuine drop in rotavirus circulation (without rotavirus vaccination) rather than a milder disease course.

Gastrointestinal infection morbidity remains high amongst preschool children in developed countries. We investigated the societal burden (incidence, healthcare utilization, and productivity loss) and correlates of acute gastroenteritis (AGE) in families with preschoolers. Monthly for 25 months, 2000 families reported AGE symptoms and related care, productivity loss, and risk exposures for one preschooler and one parent. Amongst 8768 child-parent pairs enrolled, 7.3% parents and 17.4% children experienced AGE (0.95 episodes/parent-year and 2.25 episodes/child-year). Healthcare utilization was 18.3% (children) and 8.6% (parents), with 1.6% children hospitalized. Work absenteeism was 55.6% (median 1.5 days) and day-care absenteeism was 26.2% (median 1 day). Besides chronic enteropathies, antacid use, non-breastfeeding, and toddling age, risk factors for childhood AGE were having developmental disabilities, parental occupation in healthcare, multiple siblings, single-parent families, and ≤12-month day-care attendance. Risk factors for parental AGE were female gender, having multiple or developmentally-disabled day-care-attending children, antimicrobial use, and poor food-handling practices. Parents of AGE-affected children had a concurrent 4-fold increased AGE risk. We concluded that AGE-causing agents spread widely in families with preschool children, causing high healthcare-seeking behaviours and productivity losses. Modifiable risk factors provide targets for AGE-reducing initiatives. Children may acquire some immunity to AGE after one year of day-care attendance.