Spatial Effects of Livestock Farming on Human Infections With Shiga Toxin-Producing Escherichia coli O157 in Small but Densely Populated Regions: The Case of the Netherlands.

The role of environmental transmission of typically foodborne pathogens like Shiga toxin-producing Escherichia coli (STEC) O157 is increasingly recognized. To gain more insights into spatially restricted risk factors that play a role in this transmission, we assessed the spatial association between sporadic STEC O157 human infections and the exposure to livestock (i.e. small ruminants, cattle, poultry, and pigs) in a densely populated country: the Netherlands. This was done for the years 2007-2016, using a state-of-the-art spatial analysis method in which hexagonal areas with different sizes (90, 50, 25 and 10 km2) were used in combination with a novel probability of exposure metric: the population-weighted number of animals per hexagon. To identify risk factors for STEC O157 infections and their population attributable fraction (PAF), a spatial regression model was fitted using integrated nested Laplace approximation (INLA). Living in hexagonal areas of 25, 50 and 90 km2 with twice as much population-weighted small ruminants was associated with an increase of the incidence rate of human STEC O157 infections in summer (RR of 1.09 [95%CI;1.01-1.17], RR of 1.17 [95%CI;1.07-1.28] and RR of 1.13 [95%CI;1.01-1.26]), with a PAF of 49% (95%CI;8-72%). Results suggest exposure to small ruminants to be a risk factor, although no evidence on the mode of transmission is provided. Therefore, the underlying mechanisms warrant further investigation and could offer new targets for control. The newly proposed exposure metric has potential to improve existing spatial modeling studies on infectious diseases related to livestock exposure, especially in densely populated countries like the Netherlands.

Changing epidemiology of invasive non-typhoid Salmonella infection: a nationwide population-based registry study.

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

Clinical relevance of enteropathogen co-infections in preschool children-a population-based repeated cross-sectional study.

OBJECTIVES: This study aimed to (i) determine risk factors for enteropathogen co-infections, (ii) determine whether enteropathogen co-infections influence gastroenteritis risk, and (iii) determine whether enteropathogen co-infection occurred randomly in preschool children. METHODS: A monthly-repeated cross-sectional survey in Dutch children aged 0-48 months was conducted during October 2012 to October 2014. A total of 981 stool samples were collected along with questionnaires collecting data on gastrointestinal symptoms and potential risk factors; 822 samples were successfully tested for 19 enteropathogens using real-time multiplex PCRs. Logistic regression analysis assessed co-infections in relation to gastroenteritis and potential risk factors. RESULTS: In all, 598/822 (72.7%) stool samples tested positive for at least one enteropathogen, of which 290 (48.5%) were positive for two or more enteropathogens. Risk factors for two or more enteropathogen co-infections were young age (<12 months, OR 1.9, 95% CI 1.1-3.3; 13-36 months, OR 1.7, 95% CI 1.1-2.5, versus 37-48 months), day-care attendance (OR 1.8, 95% CI 1.3-2.5), households with three or more children versus those with one child (OR 1.7, 95% CI 1.1-2.8). Stool samples collected in spring less often had two or more enteropathogens versus summer (OR 0.4, 95% CI 0.2-0.7). Food allergy was a risk factor for three or more enteropathogen co-infections (OR 3.2, 95% CI 1.1-8.9). The frequency of co-infection was higher than expected for norovirus GI/norovirus GII, Clostridium difficile/norovirus GI, C. difficile/rotavirus, astrovirus/Dientamoeba fragilis, atypical enteropathogenic Escherichia coli/adenovirus, typical enteropathogenic E. coli/adenovirus, and enteroaggregative E. coli/astrovirus. No co-infection was associated with increased gastroenteritis risk. CONCLUSIONS: Risk factors for enteropathogen co-infections were identified and specific enteropathogens co-occurred significantly more often than expected by chance. Enteropathogen co-infections were not associated with increased gastroenteritis risk, calling into question their clinical relevance in preschool children.

Chikungunya virus outbreak in Sint Maarten: Long-term arthralgia after a 15-month period.

BACKGROUND & OBJECTIVES: The first chikungunya (CHIK) epidemic in the Americas was reported in December 2013. Chikungunya virus (CHIKV) causes an acute febrile illness and is transmitted to humans by Aedes mosquitoes. Although earlier studies have described long-term clinical manifestations of CHIK patients infected with the East/Central/South African (ECSA) genotype, little is known about persistent manifestations in the Caribbean region, for which the Asian genotype is responsible. The objective of this study was to describe the presence of persisting clinical manifestations, specifically arthralgia, in CHIKV-infected patients on the Caribbean Island, Sint Maarten, 15 months after onset of the disease. METHODS: This retrospective cohort study included confirmed CHIK patients that were recorded by the participating general practitioners (GPs) during the chikungunya outbreak in 2014 in Sint Maarten. Between March and July 2015, 15 months after the onset of disease, patients were interviewed via telephone about the presence, duration and impact of clinical CHIKV manifestations. RESULTS: In total, 56 patients were interviewed (median age 47 yr), of which 30 (54%) were females. Out of the total interviewed patients, 52 (93%) reported arthralgia for the first three months after the disease onset, of which 23 (44%) patients reported to have persistent arthralgia, 15 months after the disease onset. Pain intensity of persistent arthralgia was perceived as mild in the majority of patients (n = 14; 60%), moderate in 7 (30%) patients and severe in 2 (9%) patients. During the acute phase of disease, most patients had to miss school or work (n = 39; 72%) due to clinical CHIKV manifestations and reported a negative impact on daily activities (n = 36; 57%). INTERPRETATION & CONCLUSION: Results suggested that persisting arthralgia is a frequent complication in CHIK patients included in the study. Future research on strain-specific clinical long-term manifestations and on their impact on daily life of patients, in the form of a comparative study between patients and controls, is recommended.

Updated cost-effectiveness and risk-benefit analysis of two infant rotavirus vaccination strategies in a high-income, low-endemic setting.

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

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.

Outbreak of diarrhoea among participants of a triathlon and a duathlon on 12 July 2015 in Utrecht, the Netherlands.

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

[Tularaemia in a boy following participation in a mud race]. / Een jongen met tularemie na een modderrace.

BACKGROUND: Tularaemia is a rare disease. In Europe it mostly occurs in Scandinavia. Since 2011 more cases are being reported in the Netherlands. Tularaemia may manifest itself in various ways. It is important to take strict precautions during biopsy, drainage and biopsy processing in order to prevent transmission. CASE DESCRIPTION: A 10-year-old boy presented to the paediatrician with a left inguinal lymphadenitis. A week before the onset of symptoms he had participated in a children's mud race. Serology and PCR of pus from the lymph node tested positive for Francisella tularensis. Treatment with ciprofloxacin was insufficiently effective, so surgical drainage of the gland was performed under strict isolation conditions. Water from the mud race location contained genetic material from F. tularensis. CONCLUSION: Given the rising incidence of tularaemia in the Netherlands, it is important to consider 'tularaemia' in the differential diagnosis in patients with lymphadenitis and epidemiological clues in their case history. Since 1 November 2016 it has been mandatory to report tularaemia in the Netherlands.

Different risk factors for infection with Giardia lamblia assemblages A and B in children attending day-care centres.

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

Characteristics of child daycare centres associated with clustering of major enteropathogens.

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

Potential causative agents of acute gastroenteritis in households with preschool children: prevalence, risk factors, clinical relevance and household transmission.

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