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Importance: This study is important because it shows the potential epidemiological silence associated with the use of culture as the primary diagnostic method for the laboratory identification of human campylobacteriosis. Also, we show how polymerase chain reaction methods are associated with a systematic increase in the number of human campylobacteriosis episodes as reported by routine disease surveillance. These findings are operationally relevant and have public health implications because they tell how crucial it is to consider changes in diagnostic methods, e.g., in the epidemiological analysis of historical data and in the interpretation of future data in light of the past. We also believe that this study highlights how the synergy between microbiology and epidemiology is essential for disease surveillance., Competing Interests: The authors declare no conflict of interest.

Background Campylobacter is one of the most frequent causes of bacterial gastroenteritis. Campylobacter outbreaks are rarely reported, which could be a reflection of a surveillance without routine molecular typing. We have previously shown that numerous small outbreak-like clusters can be detected when whole genome sequencing (WGS) data of clinical Campylobacter isolates was applied.AimTyping-based surveillance of Campylobacter infections was initiated in 2019 to enable detection of large clusters of clinical isolates and to match them to concurrent retail chicken isolates in order to react on ongoing outbreaks.MethodsWe performed WGS continuously on isolates from cases (n = 701) and chicken meat (n = 164) throughout 2019. Core genome multilocus sequence typing was used to detect clusters of clinical isolates and match them to isolates from chicken meat.ResultsSeventy-two clusters were detected, 58 small clusters (2-4 cases) and 14 large clusters (5-91 cases). One third of the clinical isolates matched isolates from chicken meat. One large cluster persisted throughout the whole year and represented 12% of all studied Campylobacter cases. This cluster type was detected in several chicken samples and was traced back to one slaughterhouse, where interventions were implemented to control the outbreak.ConclusionOur WGS-based surveillance has contributed to an improved understanding of the dynamics of the occurrence of Campylobacter strains in chicken meat and the correlation to clusters of human cases.

Campylobacteriosis is a disease of worldwide importance, but aspects of its transmission dynamics, particularly risk factors, are still poorly understood. We used data from a matched case-control study of 4,269 men who have sex with men (MSM) and 26,215 controls, combined with national surveillance data on Campylobacter spp., Salmonella spp., and Shigella spp., to calculate matched odds ratios (mORs) for infection among MSM and controls. MSM had higher odds of Campylobacter (mOR 14, 95% CI 10-21) and Shigella (mOR 74, 95% CI 27-203) infections, but not Salmonella (mOR 0.2, 95% CI 0-13), and were less likely than controls to have acquired Campylobacter infection abroad (χ 2  = 21; p<0.001). Our results confirm that sexual contact is a risk factor for campylobacteriosis and also suggest explanations for unique features of Campylobacter epidemiology. These findings provide a baseline for updating infection risk guidelines to the general population.

Aims: This study aimed to describe the demographic and geographic patterns of campylobacteriosis in Denmark, Finland, Norway and Sweden during 2000-2015. Methods: All Campylobacter infections notified to national authorities in the four countries during the study period were included. Background data for each notification consisted of patient age, sex, geographical location, presumed origin of infection and date of sample taken or date of sample received in the laboratory. These data were analysed in order to investigate annual trends, age group and sex patterns, as well as variations in the geographical and seasonal distribution of infections. Results: During the study period, a total of 164,001 Campylobacter infections, excluding travel-related cases, were registered, representing a mean annual incidence of 42.3 cases/100,000 population (ranging from 28.5 in Norway to 60.4 in Denmark). The incidence increased significantly from 2004 onwards in all countries, apart from Denmark. Males had higher infection rates in general. The highest incidences were observed in 0-4 year olds and those aged 20-29 years, apart from in Finland where there was no peak of infections in children aged 0-4 years. Seasonality of disease was distinct in all four countries, showing peaks of infection between July and August. In Sweden and Norway, incidences of campylobacteriosis were significantly higher in municipalities with high degrees of coastline or inland water. Conclusions: Campylobacter in the Nordic countries mostly follows known patterns with respect to demography and seasonality. Our study demonstrates new insights concerning geographical patterns of disease, highlighting possible future vulnerable population groups and locations.

Global climate change is predicted to alter precipitation and temperature patterns across the world, affecting a range of infectious diseases and particularly foodborne infections such as Campylobacter. In this study, we used national surveillance data to analyse the relationship between climate and campylobacteriosis in Denmark, Finland, Norway and Sweden and estimate the impact of climate changes on future disease patterns. We show that Campylobacter incidences are linked to increases in temperature and especially precipitation in the week before illness, suggesting a non-food transmission route. These four countries may experience a doubling of Campylobacter cases by the end of the 2080s, corresponding to around 6,000 excess cases per year caused only by climate changes. Considering the strong worldwide burden of campylobacteriosis, it is important to assess local and regional impacts of climate change in order to initiate timely public health management and adaptation strategies.

In industrialized countries, the leading cause of bacterial gastroenteritis is Campylobacter jejuni. However, outbreaks are rarely reported, which may reflect limitations of surveillance, for which molecular typing is not routinely performed. To determine the frequency of genetic clusters among patients and to find links to concurrent isolates from poultry meat, broiler chickens, cattle, pigs, and dogs, we performed whole-genome sequencing on 1,509 C. jejuni isolates from 774 patients and 735 food or animal sources in Denmark during 2015-2017. We found numerous clusters; 366/774 (47.3%) clinical isolates formed 104 clusters of >2 isolates. A total of 41 patient clusters representing 199/366 (54%) patients matched a potential source, primarily domestic chickens/broilers. This study revealed serial outbreaks and numerous matches to concurrent food and animal isolates and highlighted the potential of whole-genome sequencing for improving routine surveillance of C. jejuni by enhancing outbreak detection, source tracing, and potentially prevention of human infections.

Campylobacter is the most frequently occurring cause of bacterial gastroenteritis in Europe. Unlike other zoonotic diseases, European-wide incidences of Campylobacter infections have increased during the past decade, resulting in a significant disease burden. In Denmark, campylobacteriosis is notifiable by laboratory and a unique registration system of electronic transfer and storage of notified Campylobacter cases linked to the national person register of age, gender and geographical location allows collection of comprehensive case data. Using national surveillance data, we describe Campylobacter infections in Denmark from 2000 to 2015, focusing on age-specific incidences, geography, seasonality and outbreaks. During the observed period, a total of 60,725 Campylobacter infections were registered with a mean annual incidence of 69.3 cases/100,000 population. From 2000 to 2014, the incidence of campylobacteriosis decreased by 20%, followed by an apparent increase of 20% from 2014 to 2015. Approximately one-third of cases were travel-related. Incidences were highest in males, young adults aged 20-29 years and children under 5 years of age. Generally, children under 10 years of age living in rural areas were at higher risk of infection. Infection patterns were seasonal with an increase from May to October, peaking in August. Outbreaks were identified each year, including four large waterborne outbreaks which all occurred following heavy rainfall events. For the most part, patterns of Campylobacter infection in Denmark during 2000 to 2015 remained remarkably constant and followed what is known about the disease with respect to demographic, temporal and spatial characteristics. To establish better targeted prevention and control measures, the current knowledge gaps regarding both Campylobacter microbiology (degree of clonal diversity and clustering) and the importance of different risk factors (food versus environment/climate) need to be filled., (© 2017 Blackwell Verlag GmbH.)

Following an unusually heavy rainfall in June 2009, a community-wide outbreak of Campylobacter gastroenteritis occurred in a small Danish town. The outbreak investigation consisted of (1) a cohort study using an e-questionnaire of disease determinants, (2) microbiological study of stool samples, (3) serological study of blood samples from cases and asymptomatic members of case households, and (4) environmental analyses of the water distribution system. The questionnaire study identified 163 cases (respondent attack rate 16%). Results showed a significant dose-response relationship between consumption of tap water and risk of gastroenteritis. Campylobacter jejuni belonging to two related flaA types were isolated from stool samples. Serum antibody levels against Campylobacter were significantly higher in cases than in asymptomatic persons. Water samples were positive for coliform bacteria, and the likely mode of contamination was found to be surface water leaking into the drinking-water system. This geographically constrained outbreak presented an ideal opportunity to study the serological response in persons involved in a Campylobacter outbreak. The serology indicated that asymptomatic persons from the same household may have been exposed, during the outbreak period, to Campylobacter at doses that did not elicit symptoms or alternatively had been exposed to Campylobacter at a time prior to the outbreak, resulting in residual immunity and thus absence of clinical signs.

By building reconstruction models for a case of gastroenteritis in the general population moving through different steps of the surveillance pyramid we estimated that millions of illnesses occur annually in the European population, leading to thousands of hospitalizations. We used data on the healthcare system in seven European Union member states in relation to pathogen characteristics that influence healthcare seeking. Data on healthcare usage were obtained by harmonized cross-sectional surveys. The degree of under-diagnosis and underreporting varied by pathogen and country. Overall, underreporting and under-diagnosis were estimated to be lowest for Germany and Sweden, followed by Denmark, The Netherlands, UK, Italy and Poland. Across all countries, the incidence rate was highest for Campylobacter spp. and Salmonella spp. Incidence estimates resulting from the pyramid reconstruction approach are adjusted for biases due to different surveillance systems and are therefore a better basis for international comparisons than reported data.

Campylobacteriosis is the most common cause of bacterial foodborne illness in the European Union and the United States. Infection with Campylobacter spp. is frequently associated with different sequelae including neuropathies and reactive arthritis. Diagnosis is mainly by bacterial culturing which is time consuming, expensive, and not well suited for diagnosing sequelae or identifying infections from stool samples with nonviable bacteria. Serologic assays, in particular ELISAs, are well suited for this purpose, but, at present, there is no international consensus on antibody assays for human campylobacteriosis. In an extensive literature review, 19 studies validating such assays were identified of which 13 were more than 10 years old. We conclude that the best validated of these assays are developed and used in-house for research purposes rather than for routine diagnostics. Considering the burden of disease and potential long-term severity of Campylobacter infections, developing a standardized, commercially available antibody assay could be of great benefit for diagnostic and surveillance purposes worldwide., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: In Denmark, large-scale waterborne outbreaks are rare. This report describes the investigation of an outbreak that occurred in the town of Køge in May 2010., Methods: The epidemiological investigation consisted of hypothesis generating telephone interviews, followed by a cohort study among approximately 20,000 residents using an online questionnaire. Odds ratios were calculated for exposures including the number of glasses of tap water consumed. Geographical spreading was assessed using a geographical information system. The microbiological investigation included cultures of stool samples and flagellin-typing. In the environmental investigation, water samples were tested for Escherichia coli and coliform counts and for DNA of Campylobacter, Enterococcus, and Bacteroides. During the outbreak investigation a water boiling order was enforced, as tap water was considered a potential source., Results: Of 45 patients with laboratory confirmed Campylobacter infection in the municipality of Køge in May, 43 lived in the area covered by the central water supply. Of 61 patients with laboratory confirmed Campylobacter jejuni by 8 June, 50 shared a common flagellin gene type--flaA type 36 (82%). The epidemic curve from the cohort study showed a wave of diarrhoea onset from 14 to 20 May (n = 176). Among these patients, the development of diarrhoea was associated with drinking tap water with a dose-response pattern (linear increase by 2 glasses: odds ratio 1.40, 95% confidence interval 1.16-1.70). No bacterial DNA was found in water samples., Conclusions: These findings indicated a point source contamination of tap water with a single clone of C. jejuni which likely occurred on 12-13 May. The water boiling order was lifted on 18 June.

Objective: Enteric pathogens have been implicated in the aetiology of inflammatory bowel disease (IBD), but increased rates of stool testing of patients with unclear gastrointestinal symptoms might cause detection bias. Hence, the objective of this study was to analyse incidence rates of Crohn's disease and ulcerative colitis among patients with Salmonella- or Campylobacter-positive and negative stool tests and to study the incidence of positive and negative stool tests among patients already diagnosed with IBD., Methods: The Danish population was followed for 94.3 million person-years during 1992-2008 using national registers to identify persons with positive and negative stool tests and patients with IBD. Using Poisson regression, incidence rate ratios (IRRs) for IBD after positive or negative stool tests and, conversely, IRRs for positive and negative stool tests following IBD, were calculated., Results: IRRs for IBD were significantly high in the first year after Salmonella- or Campylobacter-positive stool tests (IRRs 5.4-9.8), and they remained moderately increased 1-10 years later (IRRs 1.6-2.2), and less so >10 years later (IRRs 0.8-1.8). However, IRRs for IBD <1 year after a negative stool test were several-fold higher (IRRs 53.2-57.5), and a decreasing incidence pattern over time was parallel to that following positive test results. Among patients with IBD, IRRs for subsequent positive and-most notably-negative stool test results were also significantly high., Conclusion: Similarities in temporal risk patterns for IBD following positive or negative stool tests indicate that the increased occurrence of Salmonella- or Campylobacter-positive results around the time of first IBD hospitalisation results from detection bias.

Introduction: Information about whether Salmonella and Campylobacter infections are acquired during foreign travel has previously been incomplete. We collected such information systematically for 2008., Methods: Information from all laboratory-confirmed cases of Salmonella and Campylobacter-cases from three laboratory catchment areas were prospectively collected by telephone interviews., Results: Of the overall 3,675 cases of Salmonella infection in 2008, information about recent travel was obtained in 3,152 (86%). Among these, 61% of S. Enteritidis, 6% of S. Typhimurium, and 34% of individuals infected with other serotypes were acquired abroad. Among the isolates that were tested for antimicrobial drug sensitivity, 21% of the isolates acquired during foreign travel were resistant and 9% were multidrug-resistant compared with 7% and 2%, respectively, of the indigenous strains. Nearly a quarter of the 3,455 registered Campylobacter cases were included in the survey, and information about recent travel was obtained from 82%. Among these, 33% were acquired abroad., Discussion: The proportion of Salmonella infections acquired abroad varies by serotype. S. Enteritidis used to be the most frequent serotype, predominantly acquired from contaminated Danish egg, but S. Enteritidis is today primarily an imported infection. By contrast, S. Typhimurium is predominately acquired in Denmark. The latter observation should be interpreted on the background of the unprecedented large outbreaks of S. Typhimurium in 2008. There was a clear association between a history of foreign travel and the risk of acquiring an infection with a drug-resistant strain.

The objective of this study was to examine incidences of Campylobacter in broilers and humans, and to describe seasonal variation and long-term trends by comparing longitudinal surveillance data in six Northern European countries (Denmark, Finland, Iceland, Norway, Sweden and the Netherlands). Due to high degree of seasonality and autocorrelation, seasonally adjusted (de-seasonalized) and trend adjusted data (de-trended) were used for comparing incidences within and between the six countries. De-seasonalized time series were obtained by fitting the incidence time series to mean monthly temperature and then removing this effect from the data. Long-term trends were fitted to the de-seasonalized time series. The incidence of Campylobacter colonization in broiler flocks and incidence of campylobacteriosis in humans showed a concordant seasonality for all the countries. There was a strong association between the incidence in both broilers and humans in a given month and the mean temperature of the northern hemisphere in the same month, as well as the preceding month, as shown by the cross-correlations and the chosen Generalized Additive Model. Denmark and Sweden showed a steadily decreasing trend for Campylobacter in broilers and human campylobacteriosis in the period 2001-2007. In Iceland, there was a decreasing trend for campylobacteriosis in humans from 1999 to 2007, whilst the broiler trend for Campylobacter was stable from 2001 to 2004, then falling thereafter. In Norway, the human campylobacteriosis trend showed a steady increase throughout the period. On the other hand, the Norwegian broiler trend for Campylobacter showed a decrease from 2001 until 2004, but was thereafter stable. There was no significant decrease or increase in incidence for human campylobacteriosis in the Netherlands, and the trend for Campylobacter in broilers was close to stable. The seasonality seen in broiler and human closely follows the temperature, and was probably caused, at least partly, by temperature related factors.

Campylobacter jejuni is a frequent cause of bacterial gastroenteritis. Often it causes self-limiting disease but severe or prolonged cases may require antimicrobial treatment. The agricultural use of antimicrobial agents selects for resistance among C. jejuni which is transmitted to humans via food. In Denmark, the use of fluoroquinolones in animal husbandry has been restricted since 2003. The purpose of the present study was to look at trends in occurrence of resistance among C. jejuni from broiler chickens, broiler chicken meat and human domestically acquired or travel associated cases. From 1997 through 2007, C. jejuni isolates were obtained from The Danish Integrated Antimicrobial Resistance Monitoring and Research Programme (DANMAP) and susceptibility tested for ciprofloxacin, erythromycin, nalidixic acid, and tetracycline. Erythromycin resistance was at a low level in all the reservoirs during the study period. Resistance to ciprofloxacin, nalidixic acid and tetracycline was significantly higher in C. jejuni from imported broiler chicken meat compared to Danish broiler chicken meat. In domestically acquired human C. jejuni isolates, resistance to ciprofloxacin and nalidixic acid was for most years significantly higher compared to the level found in isolates from Danish broiler chicken meat, whereas the resistance level was similar to the level found in isolates from imported broiler chicken meat. Imported broiler chicken meat may therefore contribute to the high level of ciprofloxacin and nalidixic acid resistance in C. jejuni isolates from domestically acquired human infections. In 2006 and 2007, the occurrence of resistance to ciprofloxacin, nalidixic acid and tetracycline was significantly higher in travel associated C. jejuni isolates compared to isolates acquired domestically. Even though the use of fluoroquinolones is restricted for animal use in Denmark, Danes are still often infected by fluoroquinolone resistant C. jejuni from imported chicken meat or by travelling.

Campylobacter infections are the main cause of bacterial gastroenteritis in Denmark. While primarily foodborne, Campylobacter infections are also to some degree acquired through other sources which may include contact with animals or the environment, locally contaminated drinking water and more. We analyzed Campylobacter cases for clustering in space and time for the large Danish island of Funen in the period 1995-2003, under the assumption that infections caused by 'environmental' factors may show persistent clustering while foodborne infections will occur randomly in space. Input data were geo-coded datasets of the addresses of laboratory-confirmed Campylobacter cases and of the background population of Funen County. The dataset had a spatial extent of 4.900 km2. Data were aggregated into units of analysis (so-called features) of 5 km by 5 km times 1 year, and the Campylobacter incidence calculated. We used a modified form of local Moran's I to test if features with similar incidence rates occurred next to each other in space and time, and compared the observed clusters with simulated clusters. Because clusters may be caused by a high tendency among local GPs to submit stool samples, we also analyzed a dataset of all submitted stool samples for comparison. The results showed a significant persisting clustering of Campylobacter incidence rates in the Western part of Funen. Results were visualized using the Netlogo software. The underlying causes of the observed clustering are not known and will require further examination, but may be partially explained by an increased rate of stool samples submissions by physicians in the area. We hope, by this approach, to have developed a tool which will allow for analyses of geographical clusters which may in turn form a basis for further epidemiological examinations to cast light on the sources of infection.

In May/June 2005 an outbreak of diarrhoeal illness occurred among company employees in Copenhagen. Cases were reported from seven of eight companies that received food from the same catering kitchen. Stool specimens from three patients from two companies were positive for Campylobacter jejuni. We performed a retrospective cohort study among employees exposed to canteen food in the three largest companies to identify the source of the outbreak and to prevent further spread. Using self-administered questionnaires we collected information on disease, days of canteen food eaten and food items consumed. The catering kitchen was inspected and food samples were taken. Questionnaires were returned by 295/348 (85%) employees. Of 247 employees who ate canteen food, 79 were cases, and the attack rate (AR) was 32%. Consuming canteen food on 25 May was associated with illness (AR 75/204, RR=3.2, 95%CI 1.3-8.2). Consumption of chicken salad on this day, but not other types of food, was associated with illness (AR=43/97, RR=2.3, 95%CI 1.3-4.1). Interviews with kitchen staff indicated the likelihood of cross-contamination from raw chicken to the chicken salad during storage. This is the first recognised major Campylobacter outbreak associated with contaminated chicken documented in Denmark. It is plausible that food handling practices contributed to transmission, and awareness of safe food handling and storage has since been raised among kitchen staff. The low number of positive specimens accrued in this outbreak suggests a general underascertainment of adult cases in the laboratory reporting system by a factor of 20.

Using data from an 11-year period (1991-2001), the authors analyzed available information on location of residence for all registered, laboratory-confirmed, domestically acquired cases of campylobacteriosis in Denmark. Patient data were merged with data from a national register on housing and addresses, and a population density index was constructed using the Danish population register. The study was performed as a register-based case-control study; 15 age-matched controls for each case were selected from the national population register. A total of 22,066 cases were compared with 318,958 controls in logistic regression analysis. Living in types of housing found in rural areas and living in areas with a low population density were both associated with an increased risk of infection. This relation concerned children in particular and explained one third of cases among children in the countryside. Furthermore, in some counties there was an association between infection and type of drinking-water company serving the home. This study indicated that contact with animals or the environment is the source of a substantial proportion of sporadic Campylobacter infections in the Danish countryside, particularly among children.

Campylobacter infections are increasing and pose a serious public health problem in Denmark. Infections in humans and broiler flocks show similar seasonality, suggesting that climate may play a role in infection. We examined the effects of temperature, precipitation, relative humidity, and hours of sunlight on Campylobacter incidence in humans and broiler flocks by using lag dependence functions, locally fitted linear models, and cross validation methods. For humans, the best model included average temperature and sunlight 4 weeks prior to infection; the maximum temperature lagged at 4 weeks was the best single predictor. For broilers, the average and maximum temperatures 3 weeks prior to slaughter gave the best estimate; the average temperature lagged at 3 weeks was the best single predictor. The combined effects of temperature and sunlight or the combined effects of temperature and relative humidity predicted the incidence in humans equally well. For broiler flock incidence these factors explained considerably less. Future research should focus on elements within the broiler environment that may be affected by climate, as well as the interaction of microclimatic factors on and around broiler farms. There is a need to quantify the contribution of broilers as a source of campylobacteriosis in humans and to further examine the effect of temperature on human incidence after this contribution is accounted for. Investigations should be conducted into food consumption and preparation practices and poultry sales that may vary by season.