Remko Enserink

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.

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.

Comparative Analysis of Avian Influenza Virus Diversity in Poultry and Humans during a Highly Pathogenic Avian Influenza A (H7N7) Virus Outbreak

ABSTRACT 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.

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.

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.

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

BackgroundDay 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/designThe 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.DiscussionThe 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

To describe the epidemiological, virological, and institutional characteristics of influenza‐like illness (ILI) in nursing homes (NHs).

Risk factors for gastroenteritis in child day care.

The child day-care centre (DCC) is often considered as one risk factor for gastroenteritis (GE) rather than a complex setting in which the interplay of many factors may influence the epidemiology of GE. This study aimed to identify DCC-level risk factors for GE and major enteropathogen occurrence. A dynamic network of 100 and 43 DCCs participated in a syndromic and microbiological surveillance during 2010-2013. The weekly incidence of GE events and weekly prevalence of five major enteropathogens (rotavirus, norovirus, astrovirus, Giardia lamblia, Cryptosporidium hominis/parvum) were modelled per DCC using mixed-effects negative binomial/Poisson regression models. Sixteen hundred children were surveyed up to 3 years, during which 1829 GE episodes were reported and 5197 faecal samples were analysed. Identified risk factors were: large DCC capacity, crowding, having animals, nappy changing areas, sandpits, paddling pools, cleaning potties in normal sinks, cleaning vomit with paper towels (but without cleaner), mixing of staff between child groups, and staff members with multiple daily duties. Protective factors were: disinfecting fomites with chlorine, cleaning vomit with paper towels (and cleaner), daily cleaning of bed linen/toys, cohorting and exclusion policies for ill children and staff. Targeting these factors may reduce the burden of DCC-related GE.

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.

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.