Single nucleotide polymorphisms in immune response genes in acute Q fever cases with differences in self-reported symptoms.

Genes involved in human immune response are well recognized to influence the clinical course of infection. The association of host genetics with susceptibility to and severity of clinical symptoms in acute Q fever was investigated. Single nucleotide polymorphisms (SNPs) in the IFNG (rs2430561/rs1861493), STAT1 (rs1914408), and VDR (rs2228570) genes were determined in 85 patients from the 2007 Dutch acute Q fever outbreak, and a symptom score was calculated. IFNG rs1861493 showed a significant association with the symptom score; IFNG rs2430561 showed a similar trend. These SNPs were then used to reproduce results in a 2009 outbreak population (n = 123). The median symptom score differed significantly in both populations: 2 versus 7. The significant association of IFNG rs1861493 with symptom score in the first population was not reproduced in the second population. We hypothesize that individuals in the second outbreak were exposed to a higher Coxiella burnetii dose compared to the first, which overruled the protection conferred by the A-allele of IFNG rs1861493 in the first population.

Campylobacter seroconversion rates in selected countries in the European Union.

As a major foodborne pathogen, Campylobacter is frequently isolated from food sources of animal origin. In contrast, human Campylobacter illness is relatively rare, but has a considerable health burden due to acute enteric illness as well as severe sequelae. To study silent transmission, serum antibodies can be used as biomarkers to estimate seroconversion rates, as a proxy for infection pressure. This novel approach to serology shows that infections are much more common than disease, possibly because most infections remain asymptomatic. This study used antibody titres measured in serum samples collected from healthy subjects selected randomly in the general population from several countries in the European Union (EU). Estimates of seroconversion rates to Campylobacter were calculated for seven countries: Romania, Poland, Italy, France, Finland, Denmark and The Netherlands. Results indicate high infection pressures in all these countries, slightly increasing in Eastern EU countries. Of these countries, the differences in rates of notified illnesses are much greater, with low numbers in France and Poland, possibly indicating lower probability of detection due to differences in the notification systems, but in the latter case it cannot be excluded that more frequent exposure confers better protection due to acquired immunity.

Detection of Coxiella burnetii DNA on small-ruminant farms during a Q fever outbreak in the Netherlands.

During large Q fever outbreaks in the Netherlands between 2007 and 2010, dairy goat farms were implicated as the primary source of human Q fever. The transmission of Coxiella burnetii to humans is thought to occur primarily via aerosols, although available data on C. burnetii in aerosols and other environmental matrices are limited. During the outbreak of 2009, 19 dairy goat farms and one dairy sheep farm were selected nationwide to investigate the presence of C. burnetii DNA in vaginal swabs, manure, surface area swabs, milk unit filters, and aerosols. Four of these farms had a positive status during the Coxiella burnetii bulk milk monitoring program in 2009 and additionally reported abortion waves in 2008 or 2009. Eleven farms were reported as having positive bulk milk only, and five selected (control) farms had a bulk milk-negative status in 2009 and no reported Q fever history. Screening by quantitative PCR (qPCR) revealed that on farms with a history of abortions related to C. burnetii and, to a lesser extent, on farms positive by bulk milk monitoring, generally higher proportions of positive samples and higher levels of C. burnetii DNA within positive samples were observed than on the control farms. The relatively high levels of C. burnetii DNA in surface area swabs and aerosols sampled in stables of bulk milk-positive farms, including farms with a Q fever-related abortion history, support the hypothesis that these farms can pose a risk for the transmission of C. burnetii to humans.

Biomarker dynamics: estimating infection rates from serological data.

The marginal distribution of serum antibody titres in a cross-sectional population sample can be expressed as a function of the infection rate, taking into account heterogeneity in peak levels and decay rates. This marginal model allows estimation of incidences, as well as simple tests for homogeneity across age, gender or geographic strata, using likelihood ratio tests. An example is given using Campylobacter serum antibody data. Using a hierarchical dynamic model to analyse data from a follow-up study in patients with symptomatic Campylobacter infection, we show that the serum antibody response consists of a rapid increase to peak levels followed by a slow decline with a geometric mean halftime of 1.4, 0.6 and 0.3 years for IgG, IgM and IgA, respectively. Antibody peak levels and decay rates were highly variable among subjects. Incidence estimates are consistent among different antibody classes (IgG, IgM and IgA). High seroconversion rates indicate that Campylobacter infection is a frequent event, occurring approximately once every year in any adult person, in the Netherlands, supporting the conclusion that a small fraction of infections leads to symptoms severe enough for notification.

Costs of gastroenteritis in the Netherlands, with special attention for severe cases.

In 1999, the costs of gastroenteritis in the Netherlands were estimated using data on hospitalizations from national registries, together with data on etiology and self-reported data on health care resource use in a community-based study. Now, more information on hospitalizations is available and these data were used to update the total costs of gastroenteritis in the Netherlands. The costs of severe gastroenteritis in the Netherlands were estimated in more depth using a hospital-based study, with patient questionnaires including a follow-up period of 6 months. The overall costs of gastroenteritis were calculated taking direct medical costs, direct non-medical costs, and indirect non-medical costs into account. The costs for severe gastroenteritis in 2009 were estimated at 2,203 per hospitalized child and 6,834 per hospitalized adult. The overall costs of gastroenteritis in 2009 were estimated at 611-695 million, which is 133-151 per gastroenteritis case or 37-42 per inhabitant. The total health care costs for gastroenteritis were about 50% higher in 2009 compared to 1999, which is mostly due to the rise in health care costs. The costs per gastroenteritis episode in adults are higher compared to children, mainly due to differences in the reasons for hospitalization and course of disease, and productivity losses.

Etiology of acute gastroenteritis in children requiring hospitalization in the Netherlands.

Infectious gastroenteritis causes a considerable burden of disease worldwide. Costs due to gastroenteritis are dominated by the hospitalized cases. Effective control of gastroenteritis should be targeted at the diseases with the highest burden and costs. For that, an accurate understanding of the relative importance of the different bacterial, viral, and parasitic pathogens is needed. The objective of the present study was to determine the incidence and etiology of gastroenteritis requiring hospital admission in the Netherlands. Six hospitals enrolled patients admitted with gastroenteritis for approximately one year over the period May 2008 to November 2009. Participants provided questionnaires and a fecal sample, and the hospital filled out a clinical questionnaire. In total, 143 children hospitalized for gastroenteritis and 64 matched controls were included in the study. Overall incidence of gastroenteritis requiring hospitalization was estimated at 2.92 per 1,000 children aged 0-17 years per year, with the highest incidence in children under the age of 5 years. The full diagnostic panel of pathogens could be studied in fecal samples of 96 cases. One or more pathogens were found in 98% of these cases. Co-infections were observed relatively often (40%). Viruses were detected in 82% of the samples, with rotavirus being most common (56%), bacteria in 32% and parasites in 10%. The present study emphasizes the importance of viral pathogens, especially rotavirus, in hospitalizations of children with gastroenteritis. Policies to reduce (costs of) hospitalizations due to gastroenteritis should therefore be first targeted at rotavirus.

Aetiology of acute gastroenteritis in adults requiring hospitalization in The Netherlands.

SUMMARY Infectious gastroenteritis causes a considerable burden of disease worldwide. Effective control should be targeted at diseases with the highest burden and costs. Therefore, an accurate understanding of the relative importance of the different microorganisms is needed. The objective of this study was to determine the incidence and aetiology of gastroenteritis in adults requiring hospital admission in The Netherlands. Five hospitals enrolled patients admitted with gastroenteritis for about 1 year during the period May 2008 to November 2009. Participants completed questionnaires and provided a faecal sample. The hospital completed a clinical questionnaire. In total, 44 adults hospitalized for gastroenteritis were included in the study. The cases had serious symptoms, with 31% subsequently developing kidney failure. One or more pathogens were found in 59% of cases. Overall, rotavirus (22%) was the most common infection. Co-infections were observed relatively often (22%). This study emphasizes that rotavirus can also cause serious illness in adults.

Decreased prevalence and age-specific risk factors for Toxoplasma gondii IgG antibodies in The Netherlands between 1995/1996 and 2006/2007.

To estimate the change in the seroprevalence and risk factors for toxoplasmosis in The Netherlands, a study was conducted in the general population in 2006/2007, similarly designed as a previous study in 1995/1996. Testing 5541 sera for IgG antibodies against Toxoplasma gondii showed a marked decrease of the overall seroprevalence to 26·0% [95% confidence interval (CI) 24·0-28·0], compared to 40·5% (95% CI 37·5-43·4) in 1995/1996. In women of reproductive age the seroprevalence decreased from 35·2% (95% CI 32·9-38·6) in 1995/1996 to 18·5% (95% CI 16·2-20·7) in 2006/2007, leaving the majority of pregnant women susceptible to primary infection with T. gondii and their babies to congenital toxoplasmosis. In participants aged ≥20 years, Toxoplasma seropositivity was associated with living in the Northwest, living in urban areas, low educational level, consumption of raw pork, keeping a cat, and not having occupational contact with clients or patients. For younger participants, risk factors were keeping sheep or cattle, consumption of raw unwashed vegetables and putting sand in the mouth.

Risk factors for indigenous Campylobacter jejuni and Campylobacter coli infections in The Netherlands: a case-control study.

A case-control study comprising 1315 Campylobacter jejuni cases, 121 Campylobacter coli cases and 3409 frequency-matched controls was conducted in The Netherlands in 2002-2003. Risk factors for both C. jejuni and C. coli enteritis were consumption of undercooked meat and barbecued meat, ownership of cats and use of proton pump inhibitors. Consumption of chicken was a predominant risk factor for C. jejuni enteritis, but many additional risk factors were identified. Unique risk factors for C. coli infections were consumption of game and tripe, and swimming. Contact with farm animals and persons with gastroenteritis were predominant risk factors for C. jejuni enteritis in young children (0-4 years). Important risk factors for the elderly (>or=60 years) were eating in a restaurant, use of proton pump inhibitors and having a chronic intestinal illness. Consumption of chicken in spring, steak tartare in autumn and winter and barbecued meat in rural areas showed strong associations with C. jejuni infections. This study illustrates that important differences in risk factors exist for different Campylobacter spp. and these may differ dependent on age, season or degree of urbanization.

A prolonged outbreak of Salmonella Typhimurium infection related to an uncommon vehicle: hard cheese made from raw milk.

In 2006, in The Netherlands, an outbreak of Salmonella Typhimurium phage type 561 (STM DT7, corresponding to the rare DT7 in the international typing scheme) was detected, accumulating to over 200 cases. By telephone interviews, data were collected from all laboratory-confirmed cases. In addition, in August 2006, a case-control study was performed in a subset of cases. Environmental and microbiological investigation was performed on a suspected dairy farm. In the case-control study (51 cases, 105 matched controls), hard cheese purchased from a farm, specifically farm X, and from a market stall were found to be associated with infection. The dairy production room of farm X tested STM DT7-positive in August. However, it was only in November, after earlier unsuccessful attempts, that a low-level contamination was confirmed in the hard farmhouse cheese, triggering control measures. A timely and adequate response was hampered during this outbreak for several reasons. Measures for improvement in handling future similar incidents are discussed.

Norovirus outbreaks in nursing homes: the evaluation of infection control measures.

Effective infection control measures during norovirus outbreaks are urgently needed in places where vulnerable individuals gather. In the present study, the effect of a number of measures was investigated in daily practice. Forty-nine Dutch nursing homes were monitored prospectively for norovirus outbreaks during two winter seasons. A total of 37 norovirus outbreaks were registered. Control measures were most effective when implemented within 3 days after onset of disease of the first patient. Measures targeted at reduced transmission between persons, via aerosols, and via contaminated surfaces reduced illness in staff and in residents. Reducing illness in staff results in fewer costs for sick leave and substitution of staff and less disruption in the care of residents. The effect of control measures on outbreak duration was limited. This is the first intervention study examining the effect of control measures. Further research is needed to extend and refine the conclusions.

Prevalence, characterisation and clinical profiles of Shiga toxin-producing Escherichia coli in The Netherlands.

Detection of Shiga toxin-producing Escherichia coli (STEC) in The Netherlands is traditionally limited to serogroup O157. To assess the relative importance of STEC, including non-O157 serogroups, stool samples submitted nationwide for investigation of enteric pathogens or diarrhoea were screened with real-time PCR for the presence of the Shiga toxin genes. Patients were selected if their stool contained blood upon macroscopic examination, if they had a history of bloody diarrhoea, were diagnosed with haemolytic uraemic syndrome, or were aged <6 years (irrespective of the bloody aspect of the stool). PCR-positive stools were forwarded to a central laboratory for STEC isolation and typing. In total, 4069 stools were examined, with 68 (1.7%) positive PCR results. The highest prevalence was for stools containing macroscopic blood (3.5%), followed by stools from patients with a history of bloody diarrhoea (2.4%). Among young children, the prevalence (1.0%) was not significantly higher than among random, non-bloody, stool samples from diarrhoeal patients (1.4%). STEC strains were isolated from 25 (38%) PCR-positive stools. Eleven O-serogroups were detected, including five STEC O157 strains. As serogroup O157 represented only 20% of the STEC isolates, laboratories should be encouraged to use techniques enabling them to detect non-O157 serogroups, in parallel with culture, for isolation and subsequent characterisation of STEC strains for public health surveillance and detection of outbreaks.

Cercarial dermatitis in the Netherlands caused by Trichobilharzia spp.

Outbreaks of cercarial dermatitis which occurred in recreational lakes in the Netherlands were studied and a method for direct rapid detection of the parasite Trichobilharzia in water samples was developed. A standardized questionnaire with questions on health complaints and exposure was distributed to individuals who developed symptoms of cercarial dermatitis after visiting fresh water lakes. Snails from the suspected lakes were examined for the presence of Trichobilharzia by microscopy and PCR. Water samples were concentrated by filtration and examined by PCR. Water quality was tested according to European Bathing Water Directive 76/160/EEG. Trichobilharzia was detected in snails and water samples from lakes which met European bathing water standards. Despite a response of 25.5%, epidemiological data suggested that longer and more frequent exposure to the water resulted in increased reporting of symptoms of cercarial dermatitis and confirmed the importance of exposure as a risk factor. A novel method for direct detection of Trichobilharzia, which includes concentration of water samples by filtration and detection of the parasite by PCR proved to be a valuable and simple tool for confirmation of presumptive outbreaks, particularly when snails could not be found in the suspected water and public health protecting measures were necessary.

Shiga toxin-producing Escherichia coli (STEC) O157 outbreak, The Netherlands, September-October 2005.

In September 2005, the first national food-related outbreak of Shiga toxin (Stx)-producing Escherichia coli (STEC) O157 was investigated in the Netherlands. A total of 21 laboratory-confirmed cases (including one secondary case), and another 11 probable cases (two primary and nine secondary cases) were reported in patients who became ill between 11 September and 10 October 2005. Preliminary investigation suggested consumption of a raw beef product, steak tartare (in the Netherlands also known as "filet americain"), and contact with other symptomatic persons as possible risk factors. A subsequent case-control study supported the hypothesis that steak tartare was the source of the outbreak (matched odds ratio (OR) 272, 95% confidence interval (CI) 3-23,211). Consumption of ready-to-eat vegetables was also associated with STEC O157 infection (matched OR 24, 95% CI 1.1-528), but was considered a less likely source, as only 40% of the cases were exposed. Samples of steak tartare collected from one chain of supermarkets where it is likely that most patients (67%) bought steak tartare, all tested negative for STEC O157. However, sampling was done three days after the date of symptom onset of the last reported case. Since 88% of the cases became ill within a two week period, point source contamination may explain these negative results. It is concluded that steak tartare was the most likely cause of the first national food-related outbreak of STEC O157 in the Netherlands.

Shiga toxin-producing Escherichia coli (STEC) O157 outbreak, The Netherlands, September - October 2005.

In September 2005, the first national food-related outbreak of Shiga toxin (Stx)-producing Escherichia coli (STEC) O157 was investigated in the Netherlands. A total of 21 laboratory-confirmed cases (including one secondary case), and another 11 probable cases (two primary and nine secondary cases) were reported in patients who became ill between 11 September and 10 October 2005. Preliminary investigation suggested consumption of a raw beef product, steak tartare (in the Netherlands also known as 'filet américain'), and contact with other symptomatic persons as possible risk factors. A subsequent case-control study supported the hypothesis that steak tartare was the source of the outbreak (matched odds ratio (OR) 272, 95% confidence interval (CI) 3 - 23211). Consumption of ready-to-eat vegetables was also associated with STEC O157 infection (matched OR 24, 95% CI 1.1 - 528), but was considered a less likely source, as only 40% of the cases were exposed. Samples of steak tartare collected from one chain of supermarkets where it is likely that most patients (67%) bought steak tartare, all tested negative for STEC O157. However, sampling was done three days after the date of symptom onset of the last reported case. Since 88% of the cases became ill within a two week period, point source contamination may explain these negative results. It is concluded that steak tartare was the most likely cause of the first national food-related outbreak of STEC O157 in the Netherlands.

Detection of a nosocomial outbreak of salmonellosis may be delayed by application of a protocol for rejection of stool cultures.

In October 2001 an outbreak of Salmonella enterica serovar enteritidis phage-type 6 occurred in a hospital and a nursing home, both served by the same hospital kitchen. Five nursing home residents died during the outbreak. S. enteritidis was isolated from three of them. Of 231 stool samples from nursing home residents, hospital patients and employees, 82 were culture-positive. All symptomatic patients were treated with oral ciprofloxacin. Inspection of the kitchen showed that during preparation of the desserts implicated in causing the outbreak, temperatures were not measured and storage temperatures were too high. No left-over food samples were available for analysis. According to the 'four-day rule' in use in this hospital, the stool samples related to the first outbreak were not cultured for Salmonella spp., whereas culturing afterwards from both stored specimens and repeats, showed that some of these samples would have been positive for S. enteritidis. Thus without the application of stool culture rejection criteria the outbreak would have been detected one day earlier. With the four-day rule in effect, the outbreak might have been detected much later, if an unusually high number of nursing home residents with gastroenteritis had not been noticed by nursing home physicians. The rule was revised to prevent a possible delay in the future. As a result of this outbreak, the government has announced legislation forbidding the sale of Salmonella-contaminated eggs. An official ban on the use of raw eggs will be included in several hygiene codes.

Explosive increase of Salmonella Java in poultry in the Netherlands: consequences for public health.

In the Netherlands Salmonella Paratyphi B variant Java increased in poultry from less than 2% of all isolates before 1996 to 60% in 2002. Despite exposure to contaminated meat is high, human patients with Java infection are rare (0.3% of all isolates). However, 50% of the human isolates showed PFGE profiles identical to the poultry clone. Resistance to flumequin in S. Java increased from 3% between 1996-2000 to 19% in 2001, and 39% in 2002, while that of other serotypes in poultry remained at about 7%. S. Java is also fast becoming less sensitive to ciprofloxacin.

[Surveillance of hepatitis A in the Netherlands 1993-2002]. / Surveillance van hepatitis A in Nederland, 1993-2002.

OBJECTIVE: To survey trends in data on hepatitis A using information from the notification system of the Municipal Medical and Health Services 1993-2002. DESIGN: Retrospective, descriptive. METHOD: Data collected from the notification system of the Dutch Municipal and Medical Services were analyzed. RESULTS: From 1993 to 2002, 64.4%, 6.5% and 11.5% of infections were contracted in the Netherlands, Turkey and Morocco, respectively. Although the absolute number of cases was highest for young people under the age of 16 infected in the Netherlands, incidence rates showed that the children of immigrants infected in Turkey or Morocco were at highest risk, followed by adult immigrants from Turkey and Morocco. In addition, a seasonal trend was observed starting with an increase in the number of notifications of young travellers infected in Turkey and Morocco during their summer holiday, followed by a steep increase in notifications of young people infected in the Netherlands in autumn. This was followed later in the year by a slight increase in notifications of adults who acquired the infection in the Netherlands. However, between 1993-2002 the total number of notifications was halved. This decrease was mainly restricted to infections acquired in the Netherlands. In recent years, fewer outbreaks have been reported in schools, households and families. In 2001, a peak of notifications from the homosexual scene was observed. There was a continued trend in the rise of the mean age of hepatitis-A onset. CONCLUSION: Risk of hepatitis A is highest for the children of immigrants travelling to Turkey or Morocco in the summer months. Secondary cases in the Netherlands are in strong decline, especially in schools and families. However, the almost stable incidence of infections among young people of Turkish or Moroccan extraction stresses the continued importance of immunization of this group before they travel. The continuing trend in the rise of the mean age of hepatitis-A onset deserves attention because of the increasing risk of mortality of the disease amongst older people.

[Explosive increase in Salmonella java in poultry. Consequences for public health]. / Explosieve toename van Salmonella Java in pluimvee. Consequenties voor de volksgezondheid.

In the Netherlands S. Paratyphi B variation Java increased in poultry from less than 2% of all isolates before 1996 up to 40% in 2001. This development in poultry runs in parallel with that in Germany and appears not to occur in other European countries. A German study shows that in the late nineties it concerns isolates of only one multi-resistant clone of Java (in Holland as well) whilst isolates before the middle nineties were genetically much more heterogeneous and sensitive to antibiotics. Although the exposition of humans to contaminated poultry meat is relatively high, human patients with a Java infection are rare. Treatment of poultry flocks with quinolones was about 13% in 2000-2001. Resistance to flumequin of Java increased from 3% between 1996-1999 to 20% between 2000-2002 whilst that of other serotypes in poultry remained about 7%. Java is also fast becoming less sensitive to ciprofloxacin which is the antibiotic of first choice in serious cases of salmonellosis. The ministries of public health, agriculture and the production boards, with their research institutes, together with the poultry meat production chain integrations have recently decided to work together in order to determine the public health importance of the Java epidemic in poultry and finding measures for effective control in the poultry industry.

Coxiella burnetii seroprevalence and risk factors on commercial sheep farms in The Netherlands.

Coxiella burnetii seroprevalence was assessed on Dutch dairy and non-dairy sheep farms using ELISA. Risk factors for seropositivity on non-dairy sheep farms were identified at farm and sheep level by univariate and multivariate multilevel analyses. Based on 953 dairy and 5671 non-dairy serum samples, sheep seroprevalences were 18.7 per cent and 2.0 per cent, respectively, and 78.6 per cent and 30.5 per cent at farm level. Significant risk factors for non-dairy sheep farms were farm location in the south of the country, sheep kept on marginal grounds, one or several supply addresses for ewes during 2007-2009 and wearing farm boots and/or outfit by professional visitors. On sheep level, risk factors included among others farm location in the south of the country, lamb breeding as main farm purpose, goat density within 10 km farm radius, use of windbreak curtain or windshields, and presence of ≥6 stillborn lambs in 2009. Farm location in the south of the country and goat density suggests that infected goats have played a role in the transmission to non-dairy sheep. Other risk factors suggest introduction of the bacterium through sheep supply and professional visitors. Biosecurity measures should be strengthened, including avoiding infection during handling of stillborn lambs and birth products in the lambing period.