Incidence and economic burden of community-acquired gastroenteritis in the Netherlands: Does having children in the household make a difference?

This study aimed at estimating gastroenteritis (GE) incidence in all age groups of the Netherlands' general population, with special emphasis on the role of children in GE burden, and the associated costs. Monthly from November 2014 to November 2016, a random sample of 2000 residents in the Netherlands was invited to complete a questionnaire on household characteristics and health complaints. We calculated GE incidence rates standardized to the Dutch population and used multivariable logistic regression models to identify potential risk factors. We calculated the costs related to resources used within the healthcare sector, the resources used by patients and their families, and productivity losses (paid worktime) due to GE. The overall standardized incidence rate was 0.81 GE episodes/person-year, with the highest rate in children ≤4 years (1.96 episodes/person-year). GE was observed more often in households with children (≤17 years), especially if children attended out-of-home childcare services, and among individuals with non-native Dutch ethnic background. Less GE was observed among employed persons aged 25-64 years, compared with those unemployed, but the opposite was observed in persons ≥65 years. The average costs per GE episode was €191, resulting in €945 million annual total costs for GE in the Netherlands (€55 per inhabitant). The majority of costs (55%) were attributable to productivity losses of the ill or their caregivers. In conclusion, GE still poses a significant burden, particularly in preschool children and adults living in households with children. Similar to other industrialized countries, the major factor driving the costs due to GE was the loss of productivity. This study also provides up-to-date baseline GE incidence rates and associated societal costs to better contextualize the burden of the disease in support of policy making.

Accounting for long-term manifestations of Cryptosporidium spp infection in burden of disease and cost-of-illness estimations, the Netherlands (2013-2017).

BACKGROUND: Burden 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. METHODS: We 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). RESULTS: In 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. CONCLUSION: Current 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.

Surveillance perspective on Lyme borreliosis across the European Union and European Economic Area.

Lyme borreliosis (LB) is the most prevalent tick-borne disease in Europe. Erythema migrans (EM), an early, localised skin rash, is its most common presentation. Dissemination of the bacteria can lead to more severe manifestations including skin, neurological, cardiac, musculoskeletal and ocular manifestations. Comparison of LB incidence rates in the European Union (EU)/European Economic Area (EEA) and Balkan countries are difficult in the absence of standardised surveillance and reporting procedures. We explored six surveillance scenarios for LB surveillance in the EU/EEA, based on the following key indicators: (i) erythema migrans, (ii) neuroborreliosis, (iii) all human LB manifestations, (iv) seroprevalence, (v) tick bites, and (vi) infected ticks and reservoir hosts. In our opinion, neuroborreliosis seems most feasible and useful as the standard key indicator, being one of the most frequent severe LB manifestations, with the possibility of a specific case definition. Additional surveillance with erythema migrans as key indicator would add value to the surveillance of neuroborreliosis and lead to a more complete picture of LB epidemiology in the EU/EEA. The other scenarios have less value as a basis for EU-level surveillance, but can be considered periodically and locally, as they could supply complementary insights.

The cost of Lyme borreliosis.

Background: Lyme borreliosis (LB) is the most frequently reported tick-borne infection in Europe and North America. The aim of this study was to estimate the cost-of-illness of LB in the Netherlands. We used available incidence estimates from 2010 for tick bite consultations and three symptomatic LB outcomes: erythema migrans (EM), disseminated LB and Lyme-related persisting symptoms. The cost was estimated using these incidences and the average cost per patient as derived from a patient questionnaire. We estimated the cost from a societal perspective, including healthcare cost, patient cost and production loss, using the friction cost method and a 4% annual discount rate. Tick bites and LB in 2010 led to a societal cost of €19.3 million (95% CI 15.6-23.4; 16.6 million population) for the Netherlands. Healthcare cost and production loss each constituted 48% of the total cost (€9.3 and €9.2 million/year), and patient cost 4% (€0.8 million/year). Of the total cost, 37% was related to disseminated LB, followed by 27% for persisting symptoms, 22% for tick bites and 14% for EM. Per outcome, for an individual case the mean cost of disseminated LB and Lyme-related persisting symptoms was both around €5700; for EM and GP consultations for tick bites this was €122 and €53. As an alternative to the friction cost method, the human capital method resulted in a total cost of €23.5 million/year. LB leads to a substantial societal cost. Further research should therefore focus on additional preventive interventions.

The economic burden of a Salmonella Thompson outbreak caused by smoked salmon in the Netherlands, 2012-2013.

Background: In 2012, the Netherlands experienced the most extensive food-related outbreak of Salmonella ever recorded. It was caused by smoked salmon contaminated with Salmonella Thompson during processing. In total, 1149 cases of salmonellosis were laboratory confirmed and reported to RIVM. Twenty percent of cases was hospitalised and four cases were reported to be fatal. The purpose of this study was to estimate total costs of the Salmonella Thompson outbreak. Methods: Data from a case-control study were used to estimate the cost-of-illness of reported cases (i.e. healthcare costs, patient costs and production losses). Outbreak control costs were estimated based on interviews with staff from health authorities. Using the Dutch foodborne disease burden and cost-of-illness model, we estimated the number of underestimated cases and the associated cost-of-illness. Results: The estimated number of cases, including reported and underestimated cases was 21 123. Adjusted for underestimation, the total cost-of-illness would be €6.8 million (95% CI €2.5-€16.7 million) with productivity losses being the main cost driver. Adding outbreak control costs, the total outbreak costs are estimated at €7.5 million. Conclusion: In the Netherlands, measures are taken to reduce salmonella concentrations in food, but detection of contamination during food processing remains difficult. As shown, Salmonella outbreaks have the potential for a relatively high disease and economic burden for society. Early warning and close cooperation between the industry, health authorities and laboratories is essential for rapid detection, control of outbreaks, and to reduce disease and economic burden.

Hepatitis E virus: Assessment of the epidemiological situation in humans in Europe, 2014/15.

BACKGROUND: Hepatitis E virus (HEV) is endemic in EU/EEA countries, but the understanding of the burden of the infection in humans is inconsistent as the disease is not under EU surveillance but subject to national policies. STUDY: Countries were asked to nominate experts and to complete a standardised questionnaire about the epidemiological situation and surveillance of HEV in their respective EU/EEA country. This study reviewed surveillance systems for human cases of HEV in EU/EEA countries and nominated experts assessed the epidemiology in particular examining the recent increase in the number of autochthonous cases. RESULTS: Surveillance systems and case definitions across EU/EEA countries were shown to be highly variable and testing algorithms were unreliable. Large increases of autochthonous cases were reported from Western EU/EEA countries with lower case numbers seen in Northern and Southern European countries. Lack of clinical awareness and variability in testing strategies might account for the observed differences in hepatitis E incidence across EU/EEA countries. Infections were predominantly caused by HEV genotype 3, the most prevalent virus type in the animal reservoirs. CONCLUSION: Discussions from the expert group supported joint working across countries to better monitor the epidemiology and possible changes in risk of virus acquisition at a European level. There was agreement to share surveillance strategies and algorithms but also importantly the collation of HEV data from human and animal populations. These data collected at a European level would serve the 'One Health' approach to better informing on human exposure to HEV.

Influenza-like Illness in Households with Children of Preschool Age.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 for >24 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. CONCLUSION: 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 for >2 years acquire some protection to ILI.

The burden of Lyme borreliosis expressed in disability-adjusted life years.

BACKGROUND: Lyme borreliosis (LB) is the most commonly reported tick-borne infection in Europe and North America. In the last 15 years a 3-fold increase was observed in general practitioner consultations for LB in the Netherlands. To support prioritization of prevention and control efforts for LB, we estimated its burden expressed in Disability-Adjusted Life Years (DALYs). METHODS: We used available incidence estimates for three LB outcomes: (i) erythema migrans (EM), (ii) disseminated LB and (iii) Lyme-related persisting symptoms. To generate DALYs, disability weights and duration per outcome were derived using a patient questionnaire including health-related quality of life as measured by the EQ-5D. RESULTS: We estimated the total LB burden for the Netherlands in 2010 at 10.55 DALYs per 100,000 population (95% CI: 8.80-12.43); i.e. 0.60 DALYs for EM, 0.86 DALYs for disseminated LB and 9.09 DALYs for Lyme-related persisting symptoms. Per patient this was 0.005 DALYs for EM, 0.113 for disseminated LB and 1.661 DALYs for a patient with Lyme-related persisting symptoms. In a sensitivity analysis the total LB burden ranged from 7.58 to 16.93 DALYs per 100,000 population. CONCLUSIONS: LB causes a substantial disease burden in the Netherlands. The vast majority of this burden is caused by patients with Lyme-related persisting symptoms. EM and disseminated Lyme have a more modest impact. Further research should focus on the mechanisms that trigger development of these persisting symptoms that patients and their physicians attribute to LB.

Cost-of-illness and disease burden of food-related pathogens in the Netherlands, 2011.

To inform risk management decisions on control and prevention of food-related disease, both the disease burden expressed in Disability Adjusted Life Years (DALY) and the cost-of-illness of food-related pathogens are estimated and presented. Disease burden of fourteen pathogens that can be transmitted by food, the environment, animals and humans was previously estimated by Havelaar et al. (2012). In this paper we complement these by cost-of-illness estimates. Together, these present a complete picture of the societal burden of food-related diseases. Using incidence estimates for 2011, community-acquired non-consulting cases, patients consulting their general practitioner, hospitalized patients and the incidence of sequelae and fatal cases, estimates were obtained for DALYs, direct healthcare costs (e.g. costs for doctor's fees, hospitalizations and medicines), direct non-healthcare costs (e.g. travel costs to and from the doctor), indirect non-healthcare costs (e.g. productivity loss, special education) and total costs. The updated disease burden for 2011 was equal to 13,940 DALY/year (undiscounted) or 12,650 DALY/year (discounted at 1.5%), and was of the same magnitude as previous estimates. At the population-level thermophilic Campylobacter spp., Toxoplasma gondii and rotavirus were associated with the highest disease burden. Perinatal listeriosis infection was associated with the highest DALY per symptomatic case. The total cost-of-illness in 2011 of fourteen food-related pathogens and associated sequelae was estimated at € 468 million/year, if undiscounted, and at € 416 million/year if discounted by 4%. Direct healthcare costs accounted for 24% of total costs, direct non-healthcare costs for 2% and indirect non-healthcare costs for 74% of total costs. At the population-level, norovirus had the highest total cost-of-illness in 2011 with € 106 million/year, followed by thermophilic Campylobacter spp. (€ 76 million/year) and rotavirus (€ 73 million/year). Cost-of-illness per infected case varied from € 150 for Clostridium perfringens intoxications to € 275,000 for perinatal listeriosis. Both incident cases and fatal cases are more strongly correlated with COI/year than with DALY/year. More than 40% of all cost-of-illness and DALYs can be attributed to food, in total € 168 million/year and 5,150 DALY/year for 2011. Beef, lamb, pork and poultry meat alone accounted for 39% of these costs. Products of animal origin accounted for € 86 million/year (or 51% of the costs attributed to food) and 3,320 DALY/year (or 64% of the disease burden attributed to food). Among the pathogens studied Staphylococcus aureus intoxications accounted for the highest share of costs attributed to food (€ 47.1 million/year), followed by Campylobacter spp. (€ 32.0 million/year) and norovirus (€ 17.7 million/year).

Extension of traditional infectious disease surveillance with a repeated population survey.

BACKGROUND: Public health surveillance is an important tool for monitoring cases of infectious diseases. Identification of risk factors requires the comparison of exposure between cases and controls. However, standard surveillance systems do not routinely collect information on controls. METHODS: Since 2008, we have extended the surveillance of infectious diseases in The Netherlands with a repeated population survey. This survey is based on the thrice-yearly administration of a questionnaire about potential risk factors for several gastrointestinal, foodborne and respiratory infections to a representative, dynamic sample of the Dutch population. The questionnaire contains questions similar to those used for interviewing cases. RESULTS: Over 14 mailing rounds, 4926 persons were approached with a response of 36%, with a small underrepresentation of men, young people, people living in large cities and persons with both parents born outside The Netherlands. Costs per completed questionnaire were around 15 euro. Muscle/joint pain in the past 4 weeks was the most reported symptom (44%), followed by running nose (39%) and headache (32%); 5.6% reported gastroenteritis, reflecting an incidence of 997 episodes per 1000 person-years. CONCLUSIONS: Extending traditional surveillance with a repeated population survey offers the unique opportunity to gather data for a multitude of purposes. The survey already has been used in two outbreak investigations and two case-control studies. It is cost-effective and may provide novel epidemiological insights towards risk group and risk factor identification and characterization for a variety of infectious diseases. The survey will be continued and expanded in use.

Gastrointestinal and respiratory illness in children that do and do not attend child day care centers: a cost-of-illness study.

BACKGROUND: Gastrointestinal and respiratory diseases are major causes of morbidity for young children, particularly for those children attending child day care centers (DCCs). Although both diseases are presumed to cause considerable societal costs for care and treatment of illness, the extent of these costs, and the difference of these costs between children that do and do not attend such centers, is largely unknown. OBJECTIVE: Estimate the societal costs for care and treatment of episodes of gastroenteritis (GE) and influenza-like illness (ILI) experienced by Dutch children that attend a DCC, compared to children that do not attend a DCC. METHODS: A web-based monthly survey was conducted among households with children aged 0-48 months from October 2012 to October 2013. Households filled-in a questionnaire on the incidence of GE and ILI episodes experienced by their child during the past 4 weeks, on the costs related to care and treatment of these episodes, and on DCC arrangements. Costs and incidence were adjusted for socioeconomic characteristics including education level, nationality and monthly income of parents, number of children in the household, gender and age of the child and month of survey conduct. RESULTS: Children attending a DCC experienced higher rates of GE (aIRR 1.4 [95%CI: 1.2-1.9]) and ILI (aIRR: 1.4 [95%CI: 1.2-1.6]) compared to children not attending a DCC. The societal costs for care and treatment of an episode of GE and ILI experienced by a DCC-attending child were estimated at €215.45 [€115.69-€315.02] and €196.32 [€161.58-€232.74] respectively, twice as high as for a non-DCC-attending child. The DCC-attributable economic burden of GE and ILI for the Netherlands was estimated at €25 million and €72 million per year. CONCLUSIONS: Although children attending a DCC experience only slightly higher rates of GE and ILI compared to children not attending a DCC, the costs involved per episode are substantially higher.

Disease burden of foodborne pathogens in the Netherlands, 2009.

To inform risk management decisions on control, prevention and surveillance of foodborne disease, the disease burden of foodborne pathogens is estimated using Disability Adjusted Life Years as a summary metric of public health. Fourteen pathogens that can be transmitted by food are included in the study (four infectious bacteria, three toxin-producing bacteria, four viruses and three protozoa). Data represent the burden in the Netherlands in 2009. The incidence of community-acquired non-consulting cases, patients consulting their general practitioner, those admitted to hospital, as well as the incidence of sequelae and fatal cases is estimated using surveillance data, cohort studies and published data. Disease burden includes estimates of duration and disability weights for non-fatal cases and loss of statistical life expectancy for fatal cases. Results at pathogen level are combined with data from an expert survey to assess the fraction of cases attributable to food, and the main food groups contributing to transmission. Among 1.8 million cases of disease (approx. 10,600 per 100,000) and 233 deaths (1.4 per 100,000) by these fourteen pathogens, approximately one-third (680,000 cases; 4100 per 100,000) and 78 deaths (0.5 per 100,000) are attributable to foodborne transmission. The total burden is 13,500 DALY (82 DALY per 100,000). On a population level, Toxoplasma gondii, thermophilic Campylobacter spp., rotaviruses, noroviruses and Salmonella spp. cause the highest disease burden. The burden per case is highest for perinatal listeriosis and congenital toxoplasmosis. Approximately 45% of the total burden is attributed to food. T. gondii and Campylobacter spp. appear to be key targets for additional intervention efforts, with a focus on food and environmental pathways. The ranking of foodborne pathogens based on burden is very different compared to when only incidence is considered. The burden of acute disease is a relatively small part of the total burden. In the Netherlands, the burden of foodborne pathogens is similar to the burden of upper respiratory and urinary tract infections.

Is it cost-effective to introduce rotavirus vaccination in the Dutch national immunization program?

This study assessed whether the inclusion of two rotavirus (RV) vaccines in the Dutch national immunization programme is cost-effective. Costs and outcomes in unvaccinated and vaccinated populations are compared for a time period of 20 years. In the baseline, assuming competitive market forces in relation to vaccine costs, Rotarix is more cost-effective than RotaTeq, resulting in a cost-utility ratio (CUR) of euro 53,000 per DALY (third payer perspective) and euro 49,000 per DALY (societal perspective), but both considered as being not cost-effective. Vaccine-related costs, annual epidemic-size, and indirect protection are the major factors that determine cost-effectiveness of RV vaccination.

Immunity to Campylobacter: its role in risk assessment and epidemiology.

Acquired immunity is an important factor in the epidemiology of campylobacteriosis in the developing world, apparently limiting symptomatic infection to children of less than two years. However, also in developed countries the highest incidence is observed in children under five years and the majority of Campylobacter infections are asymptomatic, which may be related to the effects of immunity and/or the ingested doses. Not accounting for immunity in epidemiological studies may lead to biased results due to the misclassification of Campylobacter-exposed but apparently healthy persons as unexposed. In risk assessment studies, health risks may be overestimated when immunity is neglected.

Attributing the human disease burden of foodborne infections to specific sources.

Foodborne diseases are an important cause of human illness worldwide. Humans acquire these infections from a variety of sources and routes of transmission. Many efforts have been made in the last decades to prevent and control foodborne diseases, particularly foodborne zoonoses. However, information on the impact of these interventions is limited. To identify and prioritize successful food safety interventions, it is important to attribute the burden of human illness to the specific sources. Defining scientific concepts and harmonizing terminology for "source attribution" is essential for understanding and improving attribution methodologies and for sharing knowledge within the scientific community. We propose harmonized nomenclature, and describe the various approaches for human illness source attribution and their usefulness to address specific public health questions.

Effectiveness and efficiency of controlling Campylobacter on broiler chicken meat.

Campylobacter bacteria are an important cause of foodborne infections. We estimated the potential costs and benefits of a large number of possible interventions to decrease human exposure to Campylobacter by consumption of chicken meat, which accounts for 20-40% of all cases of human campylobacteriosis in the Netherlands. For this purpose, a farm-to-fork risk assessment model was combined with economic analysis and epidemiological data. Reduction of contamination at broiler farms could be efficient in theory. However, it is unclear which hygienic measures need to be taken and the costs can be very high. The experimental treatment of colonized broiler flocks with bacteriophages has proven to be effective and could also be cost efficient, if confirmed in practice. Since a major decrease of infections at the broiler farm is not expected in the short term, additional measures in the processing plant were also considered. At this moment, guaranteed Campylobacter-free chicken meat at the retail level is not realistic. The most promising interventions in the processing plant are limiting fecal leakage during processing and separation of contaminated and noncontaminated flocks (scheduling), followed by decontamination of the contaminated flock. New (faster and more sensitive) test methods to detect Campylobacter colonization in broilers flocks are a prerequisite for successful scheduling scenarios. Other methods to decrease the contamination of meat of colonized flocks such as freezing and heat treatment are more expensive and/or less effective than chemical decontamination.