Societal Burden and Correlates of Acute Gastroenteritis in Families with Preschool Children.

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.

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.

Prevalence and Risk Factors for Colonization With Extended-Spectrum Cephalosporin-Resistant Escherichia coli in Children Attending Daycare Centers: A Cohort Study in the Netherlands.

BACKGROUND: The purpose of this study was to determine the prevalence and risk factors for colonization with extended-spectrum cephalosporin-resistant (ESC-R) Escherichia coli in daycare center (DCC)-attending children. METHODS: This is a prospective cohort study including 44 DCCs in the Netherlands, combining DCC characteristics and monthly collected stool samples from their attendees, and was performed in 2010-2012. During a 22-month study period, 852 stool samples were collected and screened for ESC-R E coli. Risk factors were studied using logistic regression analysis. RESULTS: In DCC-attending children (<4 years old), the overall prevalence of ESC-R E coli was 4.5%, and it was 8% in <1-year-old attendees. Among the 38 children carrying ESC-R E coli, the most common types were blaCMY-2 (26%), blaCTX-M-1 (16%), and chromosomal AmpC type 3 promoter mutants (13%). Extended-spectrum cephalosporin-resistant E coli was less common in DCCs where stricter hygiene protocols were enforced, eg, not allowing ill children to enter the DCC (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.14-0.84), performing extra checks on handwashing of ill children (OR, 0.42; 95% CI, 0.20-0.87), and reporting suspected outbreaks to local health authorities (OR, 0.27; 95% CI, 0.11-0.69). CONCLUSIONS: The distribution of ESC-R E coli types in DCCs differs from that of the general population. Extended-spectrum cephalosporin-resistant E coli carriage in DCC-attending children is associated with the hygiene policies enforced in the DCC. Although our results are not conclusive enough to change current DCC practice beyond ensuring compliance with standing policies, they generated hypotheses and defined the degree of ESC resistance among DCC attendees, which may influence empiric antibiotic therapy choices, and tracked the increasing trend in ESC resistance.

Transient and sustained effects of child-care attendance on hospital admission for gastroenteritis.

BACKGROUND: There is evidence that children experience a transient increase in mild episodes of gastroenteritis when they start attending out-of-home child care. We assessed the transient and sustained effects of cumulative day-care attendance, age at first enrolment and type of child care facility attended on hospitalization rates for gastroenteritis. METHODS: Cox proportional hazard models were used to estimate the risk of being hospitalized for gastroenteritis in two large cohorts of preschool (<6 years old) and elementary school-going (6-10 years old) children in Denmark. Day-by-day child-level registry data were used. Together, the two cohorts comprised 443,872 children, 21,038 hospitalizations and 1742,284 child-years (1994-2011). RESULTS: From first day-care attendance until 12 months of cumulated attendance, preschool children attending day-care centres, but not those attending day-care homes, had an increased risk of hospitalization for gastroenteritis compared with children never attending registered day-care. Such increased risk was highest shortly after starting day-care attendance and then gradually declined. After 12 months of attendance, attending either day-care centres or day-care homes was associated with a lower risk for hospitalization. Such decreased risk was confined to children starting day-care attendance before the age of one year and extended throughout, but not beyond, their preschool years. CONCLUSIONS: Attending day-care centres is associated with a higher risk for gastroenteritis hospitalization until completing 1 year of attendance. However, if children start attending day-care before the age of 1 year, they experience a lower risk of being hospitalized during their preschool years. This apparent protective effect does not last into the elementary school years.

Gastroenteritis attributable to 16 enteropathogens in children attending day care: significant effects of rotavirus, norovirus, astrovirus, Cryptosporidium and Giardia.

BACKGROUND: Children attending day care experience substantial gastrointestinal morbidity due to circulating seasonal enteropathogens in the day-care environment. The lack of a distinct clinical presentation of gastroenteritis (GE) in these children, in combination with the high diversity of enteropathogenic agents, complicates the assessment of the individual contributions of enteropathogens that may cause GE. We aimed to estimate the proportion of day-care attendees experiencing GE that could be attributed to a range of enteropathogens circulating in day care in the Netherlands in 2010-2013. METHODS: Using time-series data from a national laboratory-based and syndrome-based surveillance system in Dutch day-care centers and generalized estimating equation analysis, we modelled the variation in prevalence of 16 enteropathogens of bacterial (8), viral (5) and parasitic origin (3) circulating in day care to the variation of GE incidence among children attending day care. RESULTS: Rotavirus, norovirus, astrovirus, Giardia and Cryptosporidium were significantly associated with GE morbidity among day-care attendees in our time-series analysis. Together, these enteropathogens accounted for 39% of the GE morbidity: 11% by rotavirus, 10% by norovirus, 8% by Giardia, 7% by astrovirus and 3% by Cryptosporidium. CONCLUSIONS: We demonstrate that circulating viruses and parasites, rather than bacteria, contribute to seasonal GE experienced by children in day care.

Tracing the sources of human salmonellosis: a multi-model comparison of phenotyping and genotyping methods.

Salmonella source attribution is usually performed using frequency-matched models, such as the (modified) Dutch and Hald models, based on phenotyping data, i.e. serotyping, phage typing, and antimicrobial resistance profiling. However, for practical and economic reasons, genotyping methods such as Multi-locus Variable Number of Tandem Repeats Analysis (MLVA) are gradually replacing traditional phenotyping of salmonellas beyond the serovar level. As MLVA-based source attribution of human salmonellosis using frequency-matched models is problematic due to the high variability of the genetic targets investigated, other models need to be explored. Using a comprehensive data set from the Netherlands in 2005-2013, this study aimed at attributing sporadic and domestic cases of Salmonella Typhimurium/4,[5],12:i:- and Salmonella Enteritidis to four putative food-producing animal sources (pigs, cattle, broilers, and layers/eggs) using the modified Dutch and Hald models (based on sero/phage typing data) in comparison with a widely applied population genetics model - the asymmetric island model (AIM) - supplied with MLVA data. This allowed us to compare model outcomes and to corroborate whether MLVA-based Salmonella source attribution using the AIM is able to provide sound, comparable results. All three models provided very similar results, confirming once more that most S. Typhimurium/4,[5],12:i:- and S. Enteritidis cases are attributable to pigs and layers/eggs, respectively. We concluded that MLVA-based source attribution using the AIM is a feasible option, at least for S. Typhimurium/4,[5],12:i:- and S. Enteritidis. Enough information seems to be contained in the MLVA profiles to trace the sources of human salmonellosis even in presence of imperfect temporal overlap between human and source isolates. Besides Salmonella, the AIM might also be applicable to other pathogens that do not always comply to clonal models. This would add further value to current surveillance activities by performing source attribution using genotyping data that are being collected in a standardized fashion internationally.

Effectiveness of post-exposition prophylaxis with oseltamivir in nursing homes: a randomised controlled trial over four seasons.

BACKGROUND: Oseltamivir has been registered for use as post-exposition prophylaxis (PEP) following exposure to influenza, based on studies among healthy adults. Effectiveness among frail elderly nursing home populations still needs to be properly assessed. METHODS: We conducted a randomised double-blind placebo-controlled trial of PEP with either oseltamivir (75 mg once daily) or placebo among nursing home units where influenza virus was detected; analysis was unblinded. The primary outcome was laboratory-confirmed influenza among residents in units on PEP; the secondary outcome was clinical diagnosis of influenza-like illness (ILI). RESULTS: 42 nursing homes were recruited, in which 17 outbreaks occurred from 2009 through 2013, two caused by influenza virus B, the others caused by influenza virus A(H3N2). Randomisation was successful in 15 outbreaks, with a few chance differences in baseline indicators. Six outbreaks were assigned to oseltamivir and nine to placebo. Influenza virus positive secondary ILI cases were detected in 2/6 and 2/9 units respectively (ns); secondary ILI cases occurred in 2/6 units on oseltamivir, and 5/9 units on placebo (ns). Logistical challenges in ensuring timely administration were considerable. CONCLUSION: We did not find statistical evidence that PEP with oseltamivir given to nursing home residents in routine operational settings exposed to influenza reduced the risk of new influenza infections within a unit nor that of developing ILI. Power however was limited due to far fewer outbreaks in nursing homes than expected since the 2009 pandemic. (RCT nr NL92738).

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.

High detection rates of enteropathogens in asymptomatic children attending day care.

BACKGROUND: Gastroenteritis morbidity is high among children under the age of four, especially amongst those who attend day care. OBJECTIVE: To determine the prevalence of a range of enteropathogens in the intestinal flora of children attending day care and to relate their occurrence with characteristics of the sampled child and the sampling season. METHODS: We performed three years of enteropathogen surveillance in a network of 29 child day care centers in the Netherlands. The centers were instructed to take one fecal sample from ten randomly chosen children each month, regardless of gastrointestinal symptoms at time of sampling. All samples were analyzed for the molecular detection of 16 enteropathogenic bacteria, parasites and viruses by real-time multiplex PCR. RESULTS: Enteropathogens were detected in 78.0% of the 5197 fecal samples. Of the total, 95.4% of samples were obtained from children who had no gastroenteritis symptoms at time of sampling. Bacterial enteropathogens were detected most often (most prevalent EPEC, 19.9%), followed by parasitic enteropathogens (most prevalent: D. fragilis, 22.1%) and viral enteropathogens (most prevalent: norovirus, 9.5%). 4.6% of samples related to children that experienced symptoms of gastroenteritis at time of sampling. Only rotavirus and norovirus were significantly associated with gastroenteritis among day care attendees. CONCLUSIONS: Our study indicates that asymptomatic infections with enteropathogens in day care attendees are not a rare event and that gastroenteritis caused by infections with these enteropathogens is only one expression of their presence.

Risk factors for human salmonellosis originating from pigs, cattle, broiler chickens and egg laying hens: a combined case-control and source attribution analysis.

Several case-control studies have investigated risk factors for human salmonellosis while others have used Salmonella subtyping to attribute human infections to different food and animal reservoirs. This study combined case-control and source attribution data into a single analysis to explore risk factors at the point of exposure for human salmonellosis originating from four putative food-producing animal reservoirs (pigs, cattle, broilers and layers/eggs) in the Netherlands. We confirmed that most human cases (∼ 90%) were attributable to layers/eggs and pigs. Layers/eggs and broilers were the most likely reservoirs of salmonellosis in adults, in urban areas, and in spring/summer, whereas pigs and cattle were the most likely reservoirs of salmonellosis in children, in rural areas, and in autumn/winter. Several reservoir-specific risk factors were identified. Not using a chopping board for raw meat only and consuming raw/undercooked meat were risk factors for infection with salmonellas originating from pigs, cattle and broilers. Consuming raw/undercooked eggs and by-products were risk factors for layer/egg-associated salmonellosis. Using antibiotics was a risk factor for pig- and cattle-associated salmonellosis and using proton-pump inhibitors for salmonellosis attributable to any reservoir. Pig- and cattle-associated infections were also linked to direct contact with animals and environmental exposure (e.g. playing in sandboxes). Eating fish, meat in pastry, and several non-meat foods (fruit, vegetables and pasteurized dairy products) were protective factors. Consuming pork and occupational exposure to animals and/or raw meats were protective against layer/egg-associated salmonellosis. We concluded that individuals acquiring salmonellosis from different reservoirs have different associated risk factors, suggesting that salmonellas may infect humans through various transmission pathways depending on their original reservoirs. The outcome of classical case-control studies can be enhanced by incorporating source attribution data and vice versa.

Infectious disease burden related to child day care in the Netherlands.

BACKGROUND: Studying day-care-associated infectious disease dynamics aids in formulating evidence-based guidelines for disease control, thereby supporting day-care centers in their continuous efforts to provide their child population with a safe and hygienic environment. The objective of this study was to estimate the (excess) infectious disease burden related to child day-care attendance in the Netherlands. METHODS: A Dutch surveillance network of child day-care centers (DCCs) prospectively reported on infectious disease episodes and related use of health care among their child population on a daily basis from March 2010 to March 2012. RESULTS: Gastroenteritis (387 per 1000 child-years) and influenza-like illness (247 per 1000 child-years) were the most frequently reported infectious diseases. DCCs reported these infectious diseases to occur twice as often among children aged 0-2 years compared with children aged 2-4 years. Antibiotic treatment was required in 6%, a general practitioner visit in 29% and hospitalization in 2% of infectious disease episodes. DCC incidences of gastroenteritis and influenza-like illness requiring children to visit a general practitioner were approximately twice as high as general population estimates for this age group. Part of the DCCs indicated to not always wash the hands of children before eating (34%) or after a toilet visit (15%) or to not always clean the toilet and kitchen areas (17%) on a daily basis. CONCLUSION: The infectious disease risk associated with child day-care attendance is substantial, particularly among the very young attendees, in excess of general population estimates for this age group and potentially partly preventable.

The KIzSS network, a sentinel surveillance system for infectious diseases in day care centers: study protocol.

BACKGROUND: Day care-associated infectious diseases are widely recognized as a public health problem but rarely studied. Insights into their dynamics and their association with the day care setting are important for effective decision making in management of infectious disease control. This paper describes the purpose, design and potential of our national multi-center, day care-based sentinel surveillance network for infectious diseases (the KIzSS network). The aim of the KIzSS network is to acquire a long-term insight into the syndromic and microbiological aspects of day care-related infectious diseases and associated disease burden and to model these aspects with day care setting characteristics. METHODS/DESIGN: The KIzSS network applies a prospective cohort design, following day care centers rather than individual children or staff members over time. Data on infectious disease symptoms and related morbidity (children and staff), medical consumption, absenteeism and circulating enteric pathogens (children) are collected on a daily, weekly or monthly basis. Every two years, a survey is performed to assess the characteristics of participating day care centers. DISCUSSION: The KIzSS network offers a unique potential to study infectious disease dynamics in the day care setting over a sustained period of time. The created (bio)databases will help us to assess day care-related disease burden of infectious diseases among attending children and staff and their relation with the day care setting. This will support the much needed development of evidence-based and pragmatic guidelines for infectious disease control in day care centers.

Absence of influenza A(H1N1) during seasonal and pandemic seasons in a sentinel nursing home surveillance network in the Netherlands.

OBJECTIVES: To describe the epidemiological, virological, and institutional characteristics of influenza-like illness (ILI) in nursing homes (NHs). DESIGN: Continuous clinical surveillance of ILI and virological surveillance of ILI and other acute respiratory infections (ARIs) during four influenza seasons. SETTING: National sentinel NH surveillance network. PARTICIPANTS: National sentinel residents. MEASUREMENTS: Weekly registration of ILI cases (influenza seasons 2008/09-2009/10), influenza virus detection (influenza seasons 2006/07-2009/10), and collection of institutional characteristics of NHs at start of participation. RESULTS: During the 2008/09 influenza season, ILI incidence started to rise in Week 49 of 2008, peaked in Week 3 of 2009 (158 cases per 10,000 resident weeks), and flattened out by Week 16 of 2009 (mean ILI incidence during epidemic: 73 cases per 10,000 resident weeks). During the 2009/10 influenza pandemic, there was no epidemic peak. Influenza virus type and subtype varied throughout virological surveillance but was limited to influenza A(H3N2) and B viruses. Higher staff vaccination coverage (>15%) was associated with lower ILI-incidence in the 2008/09 influenza season in a univariate negative binomial regression analysis (incidence rate ratio = 0.3, 95% confidence interval = 0.1-0.8)). CONCLUSION: Neither seasonal nor pandemic influenza A(H1N1) viruses were detected in the network, despite widespread community transmission of seasonal and influenza A(H1N1) virus. ILI incidence trends corresponded to virological trends. Sentinel surveillance of ILI combining clinical and virological data in NHs increases understanding of transmission risks in this specific vulnerable population.

Comparative analysis of avian influenza virus diversity in poultry and humans during a highly pathogenic avian influenza A (H7N7) virus outbreak.

Although increasing data have become available that link human adaptation with specific molecular changes in nonhuman influenza viruses, the molecular changes of these viruses during a large highly pathogenic avian influenza virus (HPAI) outbreak in poultry along with avian-to-human transmission have never been documented. By comprehensive virologic analysis of combined veterinary and human samples obtained during a large HPAI A (H7N7) outbreak in the Netherlands in 2003, we mapped the acquisition of human adaptation markers to identify the public health risk associated with an HPAI outbreak in poultry. Full-length hemagglutinin (HA), neuraminidase (NA), and PB2 sequencing of A (H7N7) viruses obtained from 45 human cases showed amino acid variations at different codons in HA (n=20), NA (n=23), and PB2 (n=23). Identification of the avian sources of human virus infections based on 232 farm sequences demonstrated that for each gene about 50% of the variation was already present in poultry. Polygenic accumulation and farm-to-farm spread of known virulence and human adaptation markers in A (H7N7) virus-infected poultry occurred prior to farm-to-human transmission. These include the independent emergence of HA A143T mutants, accumulation of four NA mutations, and farm-to-farm spread of virus variants harboring mammalian host determinants D701N and S714I in PB2. This implies that HPAI viruses with pandemic potential can emerge directly from poultry. Since the public health risk of an avian influenza virus outbreak in poultry can rapidly change, we recommend virologic monitoring for human adaptation markers among poultry as well as among humans during the course of an outbreak in poultry.