The daily updated Dutch national database on COVID-19 epidemiology, vaccination and sewage surveillance.

The Dutch national open database on COVID-19 has been incrementally expanded since its start on 30 April 2020 and now includes datasets on symptoms, tests performed, individual-level positive cases and deaths, cases and deaths among vulnerable populations, settings of transmission, hospital and ICU admissions, SARS-CoV-2 variants, viral loads in sewage, vaccinations and the effective reproduction number. This data is collected by municipal health services, laboratories, hospitals, sewage treatment plants, vaccination providers and citizens and is cleaned, analysed and published, mostly daily, by the National Institute for Public Health and the Environment (RIVM) in the Netherlands, using automated scripts. Because these datasets cover the key aspects of the pandemic and are available at detailed geographical level, they are essential to gain a thorough understanding of the past and current COVID-19 epidemiology in the Netherlands. Future purposes of these datasets include country-level comparative analysis on the effect of non-pharmaceutical interventions against COVID-19 in different contexts, such as different cultural values or levels of socio-economic disparity, and studies on COVID-19 and weather factors.

Infection risks of city canal swimming events in the Netherlands in 2016.

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.

Entero- and parechovirus distributions in surface water and probabilities of exposure to these viruses during water recreation.

Numerous studies have reported quantitative data on viruses in surface waters generated using different methodologies. In the current study, the impact of the use of either cell culture-based or molecular-based methods in quantitative microbial risk assessment was assessed. Previously and newly generated data on the presence of infectious human enteroviruses (HEV) and enterovirus and parechovirus RNA were used to estimate distributions of virus concentrations in surface waters. Because techniques for the detection of infectious human parechoviruses (HPeV) in surface waters were not available, a 'Parallelogram Approach' was used to estimate their concentrations based on the ratio infectious HEV/HEV RNA. The obtained virus concentrations were then used to estimate the probability of exposure for children during recreation in such virus contaminated surface waters. Human enterovirus cell culture/PCR ratios ranged from 2.3 × 10(-3) to 0.28. This broad range of ratios indicates that care should be taken in assuming a fixed ratio for assessing the risk with PCR based virus concentrations. The probabilities of exposure to both enteroviruses and parechoviruses were calculated, using our Parallelogram Approach for the calculation of infectious parechoviruses. For both viruses it was observed that the detection method significantly influenced the probability of exposure. Based on the calculated culture data, PCR data, and the ingestion volume, it was estimated that the mean probabilities of exposure, of recreating children, to surface water containing viruses were 0.087 (infectious enteroviruses), 0.71 (enterovirus particles), 0.28 (parechovirus particles) and 0.025 (calculated infectious parechoviruses) per recreation event. The mean probabilities of exposure of children recreating in surface water from which drinking water is produced to infectious enteroviruses were estimated for nine locations and varied between 1.5 × 10(-4) - 0.09 per recreation event. In this study, the use of the rotavirus dose response relationship as a surrogate was avoided. Instead, the probabilities of exposure were derived as a function of the distributions of the calculated doses. Our 'Parallelogram Approach' was used to estimate the unavailable infectious parechovirus concentrations using Monte Carlo simulations, and the exposure assessment carried out showed that virus concentrations present in surface waters could pose a health risk for children and other vulnerable populations.

Detection of extranodal spread in head and neck cancer with [18F]FDG PET and MRI: improved accuracy?

AIM: Preoperative detection of extranodal spread (ENS) in head and neck cancer can have important consequences for patient management. The aim of this study was to determine whether 18-fluorodeoxyglucose positron emission tomography ([18F]FDG PET) or a combination with Magnetic Resonance Imaging (MRI) could more accurately predict ENS, especially with the near availability of fully integrated [18F]FDG PET/MRI scanners. METHODS: In retrospective cohort design a total of twelve patients, with 18 lymphnode metastases were studied with [18F]FDG PET and MRI. Presence of ENS was scored on MRI, and [18F]FDG PET images using a SUV max cut-off point of 12. Histopathology results were used as reference standard. Sensitivity, specificity and accuracy were calculated. RESULTS: The sensitivity, specificity and accuracy of [18F]FDG PET for ENS reached 70%,100% and 83%, respectively. The mean SUVmax of ENS positive lymphnodes was 13.6 versus 8.7 for lymphnode metastases without ENS (P=0.03). The sensitivity, specificity and accuracy of MRI for ENS were 70%, 100% and 83%, respectively. When the [18F]FDG PET and MRI findings were combined sensitivity, specificity and accuracy were 80%, 100% and 89%, respectively. Thus, accuracy increased from 83% to 89%. CONCLUSION: When there is no ENS or doubt of ENS on MRI, [18F]FDG PET seems to have additional value since it improves sensitivity and resolves uncertainty in case of high FDG uptake. This benefit needs to be confirmed prospectively in a larger cohort.

Viable Legionella pneumophila bacteria in natural soil and rainwater puddles.

AIMS: For the majority of sporadic Legionnaires' disease cases the source of infection remains unknown. Infection may possible result from exposure to Legionella bacteria in sources that are not yet considered in outbreak investigations. Therefore, potential sources of pathogenic Legionella bacteria--natural soil and rainwater puddles on roads--were studied in 2012. METHODS AND RESULTS: Legionella bacteria were detected in 30% (6/20) of soils and 3·9% (3/77) of rainwater puddles by amoebal coculture. Legionella pneumophila was isolated from two out of six Legionella positive soil samples and two out of three Legionella positive rainwater samples. Several other species were found including the pathogenic Leg. gormanii and Leg. longbeachae. Sequence types (ST) could be assigned to two Leg. pneumophila strains isolated from soil, ST710 and ST477, and one strain isolated from rainwater, ST1064. These sequence types were previously associated with Legionnaires' disease patients. CONCLUSIONS: Rainwater and soil may be alternative sources for Legionella. SIGNIFICANCE AND IMPACT OF THE STUDY: The detection of clinically relevant strains indicates that rainwater and soil are potential sources of Legionella bacteria and future research should assess the public health implication of the presence of Leg. pneumophila in rainwater puddles and natural soil.

Environmental surveillance of human parechoviruses in sewage in The Netherlands.

The circulation of human parechoviruses (HPeVs) in the population was studied by environmental surveillance comprising of molecular analyses of sewage samples (n = 89) that were collected from 15 different locations in The Netherlands. Samples were taken from sewage originating from schools (n = 9) or from parts of municipalities (n = 6) during the Dutch school year 2010-2011. At 13/15 locations HPeV1, HPeV3, or HPeV6 RNA was detected at least once; however, sequence diversity did not reflect associations in time or place. A higher percentage of positives was observed in the samples originating from the municipalities. It was demonstrated that HPeV circulated in the studied population to a higher extent than would be expected from the current knowledge on infections predominating in young children.

Reduction of bacteriophage MS2 by filtration and irradiation determined by culture and quantitative real-time RT-PCR.

Molecular methods are increasingly applied for virus detection in environmental samples without rendering data on viral infectivity. Infectivity data are important for assessing public health risks from exposure to human pathogenic viruses in the environment. Here, treatment efficiencies of three (drinking) water treatment processes were estimated by quantification of the indicator virus bacteriophage MS2 with culture and real-time reverse transcription polymerase chain reaction (qRT-PCR). We studied the virus reduction by slow sand filtration at a pilot plant. No decay of MS2 RNA was observed, whereas infectious MS2 particles were inactivated at a rate of 0.1 day(-1). Removal of MS2 RNA and infectious MS2 particles was 1.2 and 1.6 log10-units, respectively. Virus reduction by UV and gamma irradiation was determined in laboratory-scale experiments. The reduction of MS2 RNA based on qRT-PCR data was negligible. Reduction of infectious MS2 particles was estimated at 3.0-3.6 log10-units (UV dose up to 400 or 800 J/m(2)) and 4.7-7 log10-units (gamma dose up to 200 Gray). As shown in this study, estimations of viral reduction, both inactivation and removal, obtained by molecular methods should be interpreted carefully when considering treatment options to provide virus-safe drinking water. Combining culture-based methods with molecular methods may provide supplementary information on mechanisms of virus reduction.

Value of MR and CT Imaging for Assessment of Internal Carotid Artery Encasement in Head and Neck Squamous Cell Carcinoma.

Objective. This study was conducted to assess the value of CT and MR imaging in the preoperative evaluation of ICA encasement. Methods. Based upon three patient groups this study was performed. Retrospective analysis of 260 neck dissection reports from 2001 to 2010 was performed to determine unexpected peroperative-diagnosed encasement. Two experienced head and neck radiologists reviewed 12 scans for encasement. Results. In four out of 260 (1.5%) patients undergoing neck dissection, preoperative imaging was false negative as there was peroperative encasement of the ICA. Of 380 patients undergoing preoperative imaging, the radiologist reported encasement of the ICA in 25 cases. In 342 cases no encasement was described, 125 of these underwent neck dissection, and 2 had encasement peroperatively. The interobserver variation kappa varied from 0.273 to 1 for the different characteristics studied. Conclusion. These retrospectively studied cohorts demonstrate that preoperative assessment of encasement of the ICA using MRI and/or CT was of value in evaluation of ICA encasement and therefore contributively in selecting operable patients (without ICA encasement), since in only 1.5% encasement was missed. However, observer variation affects the reliability of this feature.

Isolation of Legionella pneumophila from pluvial floods by amoebal coculture.

Viable Legionella pneumophila bacteria were isolated by amoebal coculture from pluvial floods after intense rainfall and from water collected at sewage treatment plants. Several isolated L. pneumophila strains belonged to sequence types that have been previously identified in patients.

Feasibility of quantitative environmental surveillance in poliovirus eradication strategies.

The progress of the Global Polio Eradication Initiative is monitored by acute flaccid paralysis (AFP) surveillance supplemented with environmental surveillance in selected areas. To assess the sensitivity of environmental surveillance, stools from (re)vaccinated elderly persons with a low seroprevalence and from wastewater were concurrently collected and analyzed in the Netherlands over a prolonged period of time. A total number of 228 healthy individuals with different levels of immunity were challenged with monovalent oral polio vaccine serotype 1 or 3. Poliovirus concentrations were determined by the titration of fecal suspensions on poliovirus-sensitive L20B cells and of sewage concentrates by L20B monolayer plaque assay. Almost half of the individuals (45%) shed poliovirus on day 3 after challenge, which peaked (57%) on day 8 with an average poliovirus excretion of 1.3 × 10(5) TCID(50) per g of feces and gradually decreased to less than 5% on day 42. The virus concentrations in sewage peaked on days 6 to 8 at approximately 100 PFU per liter, remained high until day 14, and subsequently decreased to less than 10 PFU per liter on day 29. The estimated poliovirus concentration in sewage approximated the measured initial virus excretion in feces, within 1 log(10) variation, resulting in a sensitivity of detection of 100 infected but mostly asymptomatic individuals in tens of thousands of individuals. An additional second peak observed in sewage may indicate secondary transmission missed by enterovirus or AFP surveillance in patients. This enables the detection of circulating poliovirus by environmental surveillance, supporting its feasibility as an early warning system.

Prognostic significance of radiologically determined neck node volume in head and neck cancer: a systematic review.

This systematic review addresses the prognostic significance of neck node volume in head and neck cancer. Primary tumor volume evolved as an independent significant factor for survival in head and neck cancer patients. Besides primary tumor volume, multiple prognostic features related to the regional lymph nodes were studied in literature. In literature, some authors showed the significance of total tumor volume/nodal volume for survival and loco-regional control. Articles reporting prognosis and survival in nodal tumor volumes were collected by systematically reviewing publications listed in the Pubmed and Embase databases. Publications were included when they at least reported on total tumor volume (TTV) or nodal volume and survival. In this systematic review we studied 21 articles. For measurement of nodal volume different formulas were used. Until now, there's no clear statistical evidence for the use of either TTV or nodal volume versus primary tumor volume to predict the individual loco-regional control or survival after treatment. There is wide variety of tumor measuring systems in the literature. The cut-off value for local tumor response also shows large variation. Firstly consensus should be accomplished on standardization of volume measurements, preferably automatic, and secondly large study groups are needed with identical treatment modalities to further unravel the role of neck node volume as separate staging tool.

Presence of enteric viruses in source waters for drinking water production in The Netherlands.

The quality of drinking water in The Netherlands has to comply with the Dutch Drinking Water Directive: less than one infection in 10,000 persons per year may occur due to consumption of unboiled drinking water. Since virus concentrations in drinking waters may be below the detection limit but entail a public health risk, the infection risk from drinking water consumption requires the assessment of the virus concentrations in source waters and of the removal efficiency of treatment processes. In this study, samples of source waters were taken during 4 years of regular sampling (1999 to 2002), and enteroviruses, reoviruses, somatic phages, and F-specific phages were detected in 75% (range, 0.0033 to 5.2 PFU/liter), 83% (0.0030 to 5.9 PFU/liter), 100% (1.1 to 114,156 PFU/liter), and 97% (0.12 to 14,403 PFU/liter), respectively, of 75 tested source water samples originating from 10 locations for drinking water production. By endpoint dilution reverse transcription-PCR (RT-PCR), 45% of the tested source water samples were positive for norovirus RNA (0.22 to 177 PCR-detectable units [PDU]/liter), and 48% were positive for rotavirus RNA (0.65 to 2,249 PDU/liter). Multiple viruses were regularly detected in the source water samples. A significant correlation between the concentrations of the two phages and those of the enteroviruses could be demonstrated. The virus concentrations varied greatly between 10 tested locations, and a seasonal effect was observed. Peak concentrations of pathogenic viruses occur in source waters used for drinking water production. If seasonal and short-term fluctuations coincide with less efficient or failing treatment, an unacceptable public health risk from exposure to this drinking water may occur.

Seroprevalence and molecular detection of hepatitis E virus in wild boar and red deer in The Netherlands.

To date, sources of hepatitis E virus (HEV) in the Netherlands, including swine and wild boar, have been identified, but no direct attribution to Dutch hepatitis E cases have been demonstrated. Other animal sources may exist. To identify these species, HEV RNA detection by RT-PCR is required, but complicated. A preselection based on serology may be useful. Therefore, wildlife species were studied by serology and molecular methods. Using a species-independent double-antigen sandwich ELISA, HEV-specific antibodies were detected in sera from 12% of 1029 wild boar (Sus scrofa scrofa), in 5% of 38 red deer (Cervus elaphus) and in none of 8 studied roe deer (Capreolus capreolus). Differences in background signals were observed between species and accounted for by fitting finite mixture distributions. HEV RNA was detected in 8% of 106 wild boars, in 15% of 39 red deer and in none of 8 roe deer. In conclusion, HEV was shown to be present in European red deer for the first time. This preselection based on species-independent serological assays may be beneficial to identify new potential animal reservoirs of HEV. The consumption of Dutch undercooked wild boar and red deer meat may lead to human exposure to HEV.

Transmission of methicillin-resistant Staphylococcus aureus to household contacts.

The frequency of and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) transmission from a MRSA index person to household contacts were assessed in this prospective study. Between January 2005 and December 2007, 62 newly diagnosed MRSA index persons (46 patients and 16 health care workers) and their 160 household contacts were included in the study analysis. Transmission of MRSA from an index person to household contacts occurred in nearly half of the cases (47%; n = 29). These 29 index persons together had 84 household contacts, of which two-thirds (67%; n = 56) became MRSA positive. Prolonged exposure time to MRSA at home was a significant risk factor for MRSA transmission to household contacts. In addition, MRSA colonization at least in the throat, younger age, and eczema in index persons were significantly associated with MRSA transmission; the presence of wounds was negatively associated with MRSA transmission. Furthermore, an increased number of household contacts and being the partner of a MRSA index person were household-related risk factors for MRSA acquisition from the index person. No predominant pulsed-field gel electrophoresis (PFGE) type was observed to be transmitted more frequently than other PFGE types. To date, screening household contacts and providing MRSA eradication therapy to those found positive simultaneously with the index person is not included in the "search-and-destroy" policy. We suggest including both in MRSA prevention guidelines, as this may reduce further spread of MRSA.

Confirmation of the presence of Trichobilharzia by examination of water samples and snails following reports of cases of cercarial dermatitis.

In case of cercarial dermatitis after exposure to fresh water lakes, managers responsible for bathing water quality wish to confirm the presence of Trichobilharzia, which substantiates taking measures to protect bathers from further exposure. A novel approach, including concentration of suspected water samples by filtration and PCR detection of the parasite, is proposed. This approach has been applied to bathing sites with a history of cercarial dermatitis, sampled from 2005 to 2008. Examination of snails, the standard procedure for confirmation of the parasite's presence, and analysis of water samples, appear to be complementary procedures that enhance the chance of parasite detection in implicated bathing water. Water analysis is particularly valuable when snails cannot be found; it confirmed the presence of Trichobilharzia on 25% of sampling days with reported skin conditions and no snails found. PCR of the ToSau3A repeat directly confirmed the parasite in the water. The application of the combination of analysis of water samples and examination of snails is suggested when cases of (presumptive) cercarial dermatitis are reported or when lakes with a history of cercarial dermatitis are inspected prior to the bathing season, in order to guide interventions to prevent (further) cases of swimmers' itch.

Detection of infectious rotavirus in naturally contaminated source waters for drinking water production.

AIMS: To assess public health risks of rotavirus via drinking water consumption, a cell culture-PCR assay was developed and optimized for the detection of infectious environmental rotavirus strains in naturally contaminated source waters for drinking water production. METHODS AND RESULTS: Infectious rotavirus concentrations were estimated by an optimized cell culture-PCR assay as most probable numbers by using the presence or absence of replicated virus in different sample volumes. Infectious rotavirus was detected in 11 of 12 source water samples in concentrations varying from 0.19 (0.01-0.87) to 8.3 (1.8-34.0) infectious PCR detectable units per litre (IPDU/l), which was not significantly different from the concentrations of infectious enterovirus in these samples. CONCLUSIONS: In 55% of the samples, rotavirus genomes were 1000 to 10 000 times (3 log(10)-4 log(10)) more abundantly present than infectious rotavirus particles, whereas in the remaining 45% of the samples, rotavirus genomes were less than 1000 times (<3 log(10)) more abundantly present. SIGNIFICANCE AND IMPACT OF THE STUDY: The broad variation observed in the ratios of rotavirus RNA and infectious particles demonstrates the importance of detecting infectious viruses instead of viral RNA for the purposes involving estimations of public health risks.

Long-term inactivation study of three enteroviruses in artificial surface and groundwaters, using PCR and cell culture.

Since the transmission of pathogenic viruses via water is indistinguishable from the transmission via other routes and since the levels in drinking water, although significant for health, may be too low for detection, quantitative viral risk assessment is a useful tool for assessing disease risk due to consumption of drinking water. Quantitative viral risk assessment requires information concerning the ability of viruses detected in drinking water to infect their host. To obtain insight into the infectivity of viruses in relation to the presence of virus genomes, inactivation of three different enteroviruses in artificial ground and surface waters under different controlled pH, temperature, and salt conditions was studied by using both PCR and cell culture over time. In salt-peptone medium, the estimated ratio of RNA genomes to infectious poliovirus 1 in freshly prepared suspensions was about 10(0). At 4 degrees C this ratio was 10(3) after 600 days, and at 22 degrees C it was 10(4) after 200 days. For poliovirus 1 and 2 the RNA/infectious virus ratio was higher in artificial groundwater than in artificial surface water, but this was not the case for coxsackievirus B4. When molecular detection is used for virus enumeration, it is important that the fraction of infectious virus (based on all virus genomes detected) decays with time, especially at temperatures near 22 degrees C.

Selective neck dissection for N0 and N1 oral cavity and oropharyngeal cancer: are skip metastases a real danger?

OBJECTIVES: To contribute to insight in therapeutic safety of selective neck dissections for oral cavity and oropharyngeal cancer with a special focus on the risk of skip metastases. DESIGN: Retrospective data analysis. SETTING: Tertiary referral centre. PARTICIPANTS: A total of 291 patients operated for oral cavity or oropharyngeal squamous cell cancer between 1999 and 2004. MAIN OUTCOME MEASURES: Incidence of skip metastases in both pathologically N0 and N+ necks for oral cavity and oropharyngeal cancer. RESULTS: Of all neck dissections (n = 226) performed for oral cavity cancer, skip metastases to level III or level IV occurred in 14 cases (6%). Ten skip metastases occurred in level III only (10/226 = 4%). Thus, four necks had metastases in level IV, which would not have been removed in case of a Selective neck dissection level I-III (supraomohyoid neck dissection). In case of oropharyngeal cancer, skip metastases to level III or level IV occurred in six of 92 cases (7%). Five skip metastases occurred in level III only (5/92 = 5%). This means that of the necks containing skip metastases, only one neck (1%): had metastases in level IV, which would not have been removed in case of a Selective neck dissection level I-III (Supraomohyoid neck dissection). CONCLUSIONS: The question whether level IV should be included in the treatment of N0 and even N1 necks of patients with cancer of the oral cavity and oropharynx cannot be answered by all data available to us now. The fear of skip metastases including level IV does not seem to be justified.