Relevance of Campylobacter to public health—The need for a One Health approach

International Journal of Medical Microbiology 304 (2014) 817–823

Contents lists available at ScienceDirect

International Journal of Medical Microbiology journal homepage: www.elsevier.com/locate/ijmm

Mini Review

Relevance of Campylobacter to public health—The need for a One Health approach Greta Gölz a , Bettina Rosner b , Dirk Hofreuter c , Christine Josenhans c , Lothar Kreienbrock d , Anna Löwenstein a , Anika Schielke b , Klaus Stark b , Sebastian Suerbaum c , Lothar H. Wieler e , Thomas Alter a,∗ a

Institute of Food Hygiene, Freie Universität Berlin, Berlin, Germany Robert Koch-Institute, Department for Infectious Disease Epidemiology, Berlin, Germany c Institute for Medical Microbiology and Hospital Epidemiology, Hanover Medical School, Hanover, Germany d Department of Biometry, Epidemiology and Information Processing, WHO Collaborating Centre for Research and Training in Veterinary Public Health, University of Veterinary Medicine, Hanover, Germany e Centre for Infection Medicine, Institute of Microbiology and Epizootics, Freie Universität Berlin, Berlin, Germany b

a r t i c l e

i n f o

Keywords: Campylobacter Public health Food safety Transmission Animal health

a b s t r a c t Campylobacter species belong to the most important foodborne bacteria which cause gastroenteritis in humans in both developed and developing countries. With increasing reporting rates, the public awareness towards Campylobacter infections is growing continuously. This strengthens the necessity to establish intervention measures for prevention and control of thermophilic Campylobacter spp. along the food chain, as in particular poultry and poultry meat represent a major source of human infections. An interdisciplinary One Health approach and a combined effort of all stakeholders are necessary to ultimately reduce the burden of campylobacteriosis cases in humans. Numerous studies point out, however, that at present a complete elimination of Campylobacter in the food chain is not feasible. The present aim should therefore be to establish control measures and intervention strategies to minimize the occurrence of Campylobacter spp. in livestock (e.g. poultry flocks) and to reduce the quantitative Campylobacter burden in animals and foods. To this end, a combination of intervention methods at different stages of the food chain appears most promising. That has to be accompanied by targeted consumer advice and education campaigns to raise the awareness towards Campylobacter infections. © 2014 Elsevier GmbH. All rights reserved.

Introduction Even though intestinal Campylobacter spp. were presumably described as early as 1886 by Theodor Escherich, they have only been recognized as important human gastrointestinal pathogens for the past 30 years (Kist, 2002). As of today, intestinal Campylobacter species belong to the most important foodborne bacteria, which cause gastroenteritis in humans in both developed and developing countries (WHO, 2011). In many countries, the number of human campylobacteriosis cases

∗ Corresponding author at: Institute of Food Hygiene, Department of Veterinary Medicine, Freie Universität Berlin, Koenigsweg 69, 14163 Berlin, Germany. Tel.: +49 30 838 62550. E-mail address: [email protected] (T. Alter). http://dx.doi.org/10.1016/j.ijmm.2014.08.015 1438-4221/© 2014 Elsevier GmbH. All rights reserved.

has increased considerably to exceed the number of Salmonella infections in humans by about two- to threefold. Although various pathogenic Campylobacter species in humans have been identified as causative species in localized and systemic human diseases, the thermophilic intestinal species Campylobacter (C.) jejuni and C. coli are nowadays responsible for the majority of human campylobacteriosis cases (Moore et al., 2005). With increasing reporting rates, the public awareness towards Campylobacter infections is growing continuously. Both developments strengthen the necessity to establish intervention measures for prevention and control of thermophilic enteropathogenic Campylobacter spp. along the food chain. The major risk of human campylobacteriosis has generally been linked to the consumption of animal products, in particular poultry meat. Nevertheless, contact with pets and other animals, drinking of raw or improperly pasteurized milk, and different environmental sources have also to be considered for an adequate risk assessment.

818

G. Gölz et al. / International Journal of Medical Microbiology 304 (2014) 817–823

Fig. 1. Mean annual incidence of campylobacteriosis cases notified in Germany by age group and sex, 2001–2013 (RKI, 2014). Please note that age group ranges vary.

In many cases the direct link between a specific source and the human infection is missing. To complicate matters, the genetic instability of Campylobacter spp. makes epidemiological source studies difficult. Human campylobacteriosis occurs world-wide, with incidences showing significant regional differences. In the EU, Campylobacter are reported as the most common bacterial diarrheal pathogens with an incidence of approx. 55.5 per 100,000 population in the year 2012 (EFSA and ECDC, 2014). Even among the EU countries, a large variation in the notification rate is detectable: the highest rate was reported in the Czech Republic (174 cases per 100,000), followed by Slovakia, Luxembourg and the United Kingdom (106–117 per 100,000 population), while the lowest rates were reported in Bulgaria, Latvia, Italy, Poland and Romania (<2 per 100,000). For Germany, the rate of confirmed cases per 100,000 was 76.5. In the US, Campylobacter infections are second to Salmonella, with a notification rate of 13.8 per 100,000 population (Crim et al., 2014). In New Zealand, after peaking in the year 2006 with 379 per 100,000 population, the reporting rate was 161.5 per 100,000 in 2008 (Sears et al., 2011). Due to the predominantly self-limiting course of the human intestinal disease, which frequently leads to underreporting, it can be assumed that actual incidences are approx. 8–30-fold higher (Samuel et al., 2004). In several industrialized countries, including Germany, higher Campylobacter incidences are observed in young infants (<4 years) and young adults (20–29 years) (Fig. 1). This may be due to age-specific differences in risk factors, such as the incompletely matured mucosal and systemic immunity in young children or age-specific patterns concerning food preparation (e.g. higher levels of exposures to contaminated food, animal and environmental reservoirs; insufficient hand and food hygiene). In general, across most age groups, males are more frequently affected than females (Cody et al., 2012). Behavioural (e.g. differences in nutritional habits, leading to different exposures and risks) and physiological/immunological differences have been suggested as a cause of that gender bias. The latter was supported by Strachan et al. (2008) who demonstrated a similar sexual dimorphism in a mouse model, where infection and shedding rates were higher in male mice.

A strong seasonality with a peak of Campylobacter incidences in the summer months is seen world-wide (Nichols, 2005; Schielke et al., 2014). It is speculated that the higher detection rates in poultry flocks and foods of animal origin in the summer period as well as the specific seasonal leisure behaviour of humans (barbecues, picnics) during that period contribute to the increase of transmission of Campylobacter to humans. Increased vector-borne transmission by flies was suspected as a possible seasonal driver as well (Nichols, 2005). Climate changes with increasing temperatures might have an impact on the human campylobacter cases (Stark et al., 2009). It is estimated that an average increase in the ambient temperature by 1 ◦ C will generally lead to increased incidences of food-borne gastrointestinal infections by 4–5% (Health Protection Agency, 2008). In order to reduce human Campylobacter spp. infections, a combined effort of all stakeholders is necessary. This review summarizes current information of public health challenges related to Campylobacter. Campylobacter in animals and the environment Thermophilic Campylobacter occur almost ubiquitously in the environment. In large numbers, they can be found in the intestinal tract of warm-blooded animals, usually without showing clinical symptoms. However, C. jejuni can cause abortions in sheep. Recently, a highly virulent clone causing outbreaks of ovine abortions has emerged in the US. Its zoonotic potential has recently been suggested (Sahin et al., 2012). A primary cause of Campylobacter contamination of food and water are Campylobacter-shedding animals such as food animals and possibly environmental bird species. Poultry flocks are highly colonized with Campylobacter spp. with prevalences ranging from 30% to 100%. An EU baseline survey detected a prevalence of 71.2% in broiler batches at EU level (Member states prevalence in caecal content ranging from 2% to 100%) and a prevalence of 75.8% on broiler carcasses (prevalences on carcasses ranging from 4.9% to 100%) (EFSA, 2010). The distribution of Campylobacter counts on carcasses during that study is shown in Fig. 2. In addition to a high variety of Campylobacter counts between countries, a tendency for high counts in countries with high prevalences was observed.

G. Gölz et al. / International Journal of Medical Microbiology 304 (2014) 817–823

819

Fig. 2. Distribution of Campylobacter counts on broiler carcasses (EU baseline survey, 2008) (EFSA, 2010).

Seasonality with a peak of Campylobacter prevalence in broiler flocks in summer and autumn has already been established in several studies (Hartnack et al., 2009; Meldrum et al., 2005; Miller et al., 2004). That seasonal pattern and the dependence on latitude indicate that climatic factors might play a role either directly or indirectly. Investigations showed that the strongest increase in the incidence of poultry flocks occurred at outdoor temperatures of 13–20 ◦ C, while higher temperatures resulted in smaller increases (but at a higher level). It is thereby assumed that a “threshold” to the end of spring exists, after which the prevalence dramatically increases in poultry flocks (Louis et al., 2005). Usually, chicks are infected in the first days of life and remain mainly asymptomatic carriers of Campylobacter, during a relatively short life-span in broilers (due to current intensive husbandry practices) and longer in laying hens. The prevalence in poultry flocks can increase within a week from <5% to >95% (Hartnett et al., 2001; Katsma et al., 2005). Sources of entry into poultry flocks are manifold (including drinking water, environment for free-range poultry, wild birds, rodents, flies or staff). A direct correlation between the activity of flies in the farm area and the colonization of poultry flocks with Campylobacter spp. is suggested (with >30,000 flies per production cycle) (Hald et al., 2008; Näther et al., 2009). A number of studies have performed risk-factor analysis for poultry flock colonization. Increased animal age, number of houses on the farm, production type, flock size, presence of other animals on the farm, partial depopulation (thinning) or type of nipple drinkers are associated with the degree of colonization (Näther et al., 2009). The common denominator explaining most of these divergent risk factors is biosecurity or the lack of such measures (Wagenaar et al., 2013). In principle, a high biosecurity level on a poultry farm may prevent introduction of Campylobacter into a poultry flock. However, it does not guarantee a Campylobacter-free flock at slaughter. Currently, the slaughter process might contribute to intense cross-contamination taking place at different stages of the slaughter line. That phenomenon (higher prevalence on broiler skin than in caeca) has already been described (Hue et al., 2010). Such slaughterhouse effects are related to technology and hygiene standards during slaughter practices that influence caecal and faecal contamination of the carcasses (Alter et al., 2005a). Heavily contaminated broiler skin samples originate mostly from Campylobacter-positive flocks. Such heavily contaminated flocks might act as source of cross-contamination during the slaughter process. Based on the

data from the EU Campylobacter baseline survey, it was concluded that a Campylobacter-colonized broiler batch was about 30 times more likely to have the sampled carcass contaminated with Campylobacter, compared to a non-colonized batch, and a higher Campylobacter count on carcasses was strongly associated with Campylobacter colonization of the batch (EFSA, 2010). In addition to poultry as a major reservoir for Campylobacter, cattle, pigs, sheep and goats are to be considered as an important source of human infections, e.g. the cattle prevalence reached on average 6.2% (animal based) and 24.3% (herd based) in the EU (EFSA, 2012). Scientific studies have shown very high prevalences in pig herds: C. coli predominates in this host species with up to 100% of the herds and 80% of the serological samples being positive (Weijtens et al., 1999; Alter et al., 2005b; von Altrock et al., 2006; Nathues et al., 2013). Despite the high prevalence in pig herds, several studies assessed the risk arising from pork for human infection as rather low (Nielsen et al., 1997; Guevremont et al., 2004). In contrast to poultry carcasses, where the swelling of the skin during slaughter and processing allows the survival of Campylobacter, the rapid drying (water activity < 0.97) of the pig skin causes a massive reduction of thermophilic Campylobacter on pig carcasses. Campylobacter can survive especially in feather follicles and the pores of the poultry skin at a depth of 20–30 ␮m. In these niches, the bacteria meet a preferred micro-climate which allows them to survive stress conditions better with little exposure to oxygen and a sufficient protection against dehydration (Chantarapanont and Berrang, 2003). The relatively smooth surface of the pig skin and the rapid dehydration prevents such survival rates during the cooling process on pig carcasses. Dogs and cats or other pet animals must also be considered as possible sources of human infection in the immediate household (Wieland et al., 2006). In many cases, dogs and cats can asymptomatically carry thermophilic Campylobacter spp., with prevalences ranging up to about 40%. Own data (generated during an epidemiological study on Campylobacter prevalence in different sources) showed a prevalence of 15.3% in dogs and 11.3% in cats (Table 1). Usually, C. upsaliensis and C. helveticus are the dominant species in these animals, but C. jejuni is routinely diagnosed as well. In particular, close contact with Campylobacter-shedding young cats and dogs allows the transmission of Campylobacter to humans. Campylobacter spp. have been isolated from several water sources. Studies of surface waters showed prevalences of

820

G. Gölz et al. / International Journal of Medical Microbiology 304 (2014) 817–823

Table 1 Campylobacter prevalence in various sources in Germany (Lehmann et al., 2013). Source

Prevalence

Dogs Cats Pigeons Quails Mussels Rodents Surface water Children’s playgrounds

15.3% (25/163) 11.3% (20/177) 20.0% (10/50) 62.5% (25/40) 15.4% (20/130) 2.6% (1/39) 5.5% (6/109) 11.8% (16/136)

For detection, a combination of ISO 10272-1 and the Cape Town protocol (Le Roux and Lastovica, 1998) was used.

thermophilic Campylobacter of up to 45% in lakes and rivers (Schindler et al., 2003). In a case-control study carried out by Schönberg-Norio et al. (2004), swimming in natural lakes was identified as risk factor for domestically acquired sporadic Campylobacter infections in Finland. In addition, waterways should be considered in the migration routes of Campylobacter (Meinersmann and Berrang, 2013). As a result of the ability of Campylobacter spp. to survive for a short period in salt water, mussels and crustaceans can become contaminated with Campylobacter (especially C. lari) (Table 1). The primary cause of these contaminations are seabirds (particularly gulls, which show also a high prevalence of C. lari; Endtz et al., 1997; van Doorn et al., 1998). In its epidemiology, C. coli and C. jejuni are significantly different. Different prevalences of C. jejuni and C. coli in various foods and data from different surveys and models suggest that the risk factors for human C. coli infections might be different than for C. jejuni infections (Gillespie et al., 2002; Roux et al., 2013). That assumption has to be taken into account when developing strategies to reduce campylobacteriosis cases. Source attribution Microbiological source attribution approaches have been used to estimate the contribution of different sources and transmission pathways to Campylobacter infections. For this, the epidemiology of campylobacteriosis at the genotype level is usually investigated by comparing Campylobacter genotypes from humans with those from food and environmental sources by using mainly MLST analysis. Even though it is difficult to compare the outcome of different source attribution models (differences in the data sets used, different mathematical models applied), Table 2 tries to summarize the major findings of selected source attribution models. All models agree that the majority of strains infecting humans originate from the poultry reservoir, followed by ruminants and other reservoirs such as environmental sources, pigs or wild birds (Wagenaar et al., 2013). Studies from New Zealand and Scotland demonstrated that intestinal campylobacteriosis cases in urban and rural areas have different epidemiological patterns (Strachan et al., 2009; Mullner et al., 2010), with poultry-associated cases more likely to be found in urban areas and ruminant- or avian (non-poultry)-associated genotypes posing a higher risk in rural areas (esp. for young children). Nonetheless, it might be difficult to generalize these findings: more country- or region-specific data are clearly needed to establish and take into account specific local epidemiological patterns. Risk assessments Although risk assessment in campylobacteriosis is difficult, it is clear that handling and consumption of contaminated poultry meat are a major risk of infection as indicated by several studies undertaken in different countries (Lindqvist and Lindblad,

Table 2 Proportion of human campylobacteriosis (C. jejuni and C. coli) cases attributed to different sources (selected studies). Sources

Origin of human C. jejuni infections Sheppard et al. (2009) (%)

Mughini Gras et al. (2012) (%)

Levesque et al. (2013) (%)

Chicken Turkeys Cattle Sheep Pigs Wild birds Environment

58–78

66.1

64.5

∼10–20 ∼10–20

21.2 2.4 0.01

25.8

Sources

Origin of human C. coli infections

4 4

10.2

Sheppard et al. (2009) (%) Chicken Turkeys Cattle Sheep Pigs Wild birds Environment a

40–56 1 2–14 40 1–6

Mughini Gras et al. (2012) (%)

2.3 7.4a

Roux et al. (2013) (%)

69.6

40

12.2 5.0 4.9

14 41 6

8.9

Water.

2008; Nauta et al., 2009; Sears et al., 2011). Several quantitative risk assessments, in particular on Campylobacter in poultry meat, have been carried out in recent years and are summarized by Nauta et al. (2009). These models cover either single or all stages of the production chain (primary production, slaughtering and processing, consumer behaviour, human disease). The first risk assessments on Campylobacter in poultry meat have been created in the United Kingdom (Hartnett et al., 2001) and Denmark (Rosenquist et al., 2003). These models served as the basis for the international FAO/WHO risk assessment report (FAO/WHO, 2007). In recent years, models from the Netherlands (Mylius et al., 2007), New Zealand (Lake et al., 2007) and Germany (Brynestad et al., 2008) were added. Even though a unified and harmonized risk assessment model would be highly desirable, it is currently not feasible due to differences in production practices and consumer behaviour among countries. In addition, the mathematical constraints of such risk models combined with a lack of data currently limit the generalization of the results (Stellbrink, 2009). Nonetheless, several concordances between these risk assessments are visible: - Logistic slaughter appears to have a negligible influence on the Campylobacter load in poultry meat and ultimately on the human health risk. - Measures to reduce the prevalence in poultry flocks appear to make only a minor contribution to the reduction of the incidence in humans. - A reduction in the quantitative load of poultry flocks will not necessarily lead to a reduction of the prevalence in the herds. - To conclude this current assessment, it may be one of the most effective measures to concentrate on the quantitative reduction of Campylobacter along the food chain (especially when these processes can help to reduce the Campylobacter loads in meat and meat products, such as by freezing carcasses or meat). Rosenquist et al. (2003) were able to calculate a correlation between the reduction of the quantitative Campylobacter contamination of poultry carcasses and a reduction in the incidence of human campylobacteriosis. Simulations showed that a reduction of Campylobacter counts on chicken carcasses by two orders of magnitude can lead to a 30-fold decrease in human campylobacteriosis

G. Gölz et al. / International Journal of Medical Microbiology 304 (2014) 817–823

cases. A reduction in the flock prevalence by a factor of 30 would be necessary to achieve the same reduction in the incidence in humans. So far, quantitative risk assessment models do not account for the emerging scientific finding that, due to their high genetic and phenotypic variability and flexibility (Gripp et al., 2011), not all intestinal Campylobacter spp., currently grouped in various phylogenetic lineages such as clonal complexes or sequence types, are equally virulent in all possible settings of human infection. In order to develop more accurate risk assessment models, the tools to distinguish between different phenotypes which might lead to a different extent of virulence of the organism, taking into account individual host differences such as the immune status of the infected person, need to be improved. The same holds true for bacterial tenacity and survival capabilities: It is well established that strains within an individual Campylobacter sp. vary considerably in their ability to survive in the environment and along the food chain and can exhibit large differences in their stress response (Jasson et al., 2007; Sampers et al., 2010; Riedel et al., 2013). Nonetheless, the mechanisms and infection outcome of such potential fitness advantages have not been elucidated yet. Cost of illness and burden of disease Only sporadic data are available on the costs of Campylobacter infections. Annual costs for the US were calculated to range between 1.2 and 4 billion $ (Eberle and Kiess, 2012; Batz et al., 2014). The cost of food-borne campylobacteriosis to public health systems and to loss of individual health and productivity in the EU is estimated to be around 2.4 billion D per year (EFSA, 2014). In this context, measures of disease burden (by calculating e.g. disability-adjusted life years-DALY, quality-adjusted life yearsQALY, years of potential life lost-YPLL) are becoming increasingly important parameters to set priorities in healthcare or to assess and shape risk-based food safety policy. Batz et al. (2014) estimated 16 QALY lost per 1000 campylobacteriosis cases, summing up to 13,256 QALY losses annually in the US. For the Netherlands, an undiscounted disease burden of 41 DALY per 1000 cases was estimated. Based on that, the DALY per year was 2060–3250 for this country (Havelaar et al., 2012; Mangen et al., 2013). Sequelae accounted for 82% of the total burden of Campylobacter. Risk management options To provide a scientific basis for risk management decisions with regard to intestinal Campylobacter infections, information from risk assessments, epidemiology and the efficiency of intervention methods has to be taken into account (Mangen et al., 2007). Most of these data are available for poultry and poultry meat. Several publications already investigated the efficiency and the cost-benefit of different intervention methods in the poultry production chain and included that information into risk assessment models (Havelaar et al., 2007). In addition, information from Iceland (Stern et al., 2003), Norway (Hofshagen and Kruse, 2005), Denmark and New Zealand (New Zealand Ministry for Primary Industries, 2013) on risk management approaches is available. In most cases, a combination of different intervention methods from farm-to-fork was proposed or applied. By carrying out cost-effectiveness analysis of different intervention strategies to control Campylobacter in the New Zealand poultry supply, it was suggested that the most cost-effective interventions are applied in the primary processing stage, including phage-based control in broiler flocks (if efficacy of Campylobacter reduction is proven in

821

practice; Lake et al., 2013). However, phages can also be applied at other time points (Hertwig et al., 2013). Even though it is generally agreed that on-farm biosecurity measures need to be enhanced, it is not always clear which specific measure needs to be applied and the costs can be very high. Obviously, not one method is likely to eliminate Campylobacter carriage in broilers on-farm, but a number of methods (single or in combination) can reduce the bacterial load sufficiently to have an effect on human health (Wassenaar, 2011). Controlling Campylobacter on-farm will not only influence transmission via meat but also via environmental pathways, leading to a higher public health impact than interventions performed later in the food chain (at slaughter and processing). But for short term, such interventions later in the chain are considered more feasible (Swart et al., 2013). At slaughter and processing, faecal leakage should be minimized and cross-contamination of carcasses reduced. Several post-harvest decontamination methods were successfully applied, incl. freezing of broiler carcasses (Iceland and Denmark), hot water carcass decontamination, application of hyperchlorinated water to cool birds post dressing (New Zealand) or lactic acids. These measures can be combined with scheduling (applying intervention measures only on products originating from Campylobacter-positive flocks). However, most currently applied decontamination methods can only reduce the Campylobacter number on chicken carcasses or chicken meat, but will not eliminate Campylobacter completely. Regional differences must be considered as well when discussing decontamination methods in broiler meat production: chemical treatments and some physical treatments (e.g. irradiation) are not accepted in the EU, but are used in other parts of the world (in general, the EU follows a top-down approach, whereas in the US the primary control is applied in the processing plant) (FAO/WHO, 2009). Many authors have stressed the need for strengthening public education on household measures such as kitchen hygiene and general microbial hazards, even though such intensification of consumer education alone is not expected to resolve the problem.

Conclusions An interdisciplinary One Health approach and a combined effort of all stakeholders (e.g. veterinary authorities, human medical experts and personnel, scientists, policymakers, public health authorities, and industry) is necessary to ultimately reduce the burden of campylobacteriosis cases in humans. The implementation of efficient regulatory Campylobacter control measures in broiler production proved to be useful in New Zealand and was intensively discussed by a recent EFSA opinion (EFSA, 2011). Recently, Swart et al. (2013) calculated for the Netherlands, that an introduction of a process hygiene criterion of e.g. 1000 cfu Campylobacter per gram chicken meat would lead to a reduction of the number of human cases by two-thirds. The costs to the poultry industry to meet such a criterion (estimated at approx. 2 million D per year) would be considerably lower than the averted costs of illness (approx. 9 million D per year). Concerted efforts to improve attribution of campylobacteriosis cases to sources are needed to place and monitor intervention strategies in an efficient manner. Based on available data, these source attributions have to be carried out regionally to describe the specific epidemiological situation. Numerous studies point out, however, that currently a complete elimination of Campylobacter in the food chain is not feasible in most countries. Truly effective and commonly applicable solutions for the eradication of Campylobacter in the food chain are still missing (Wagenaar et al., 2006, 2013). The present aim should therefore be to establish control measures and intervention strategies to minimize the occurrence of Campylobacter spp. in livestock (esp. poultry flocks) and to reduce

822

G. Gölz et al. / International Journal of Medical Microbiology 304 (2014) 817–823

the quantitative Campylobacter burden in animals and foods. To this end, a combination of intervention methods at different stages of the food chain appears most promising (with special focus on the poultry sector). A strict implementation of on-farm biosecurity measures is needed. These intervention strategies have to be accompanied by additional control measures to reduce transmission along the food chain. By optimizing slaughter and processing steps, the Campylobacter concentration on slaughter carcasses (and subsequently meat) can be reduced (e.g. by reduction of faecal contamination during slaughter; post-harvest decontamination, such as freezing, crust freezing or usage of antimicrobial agents). Last but not least, public health authorities should provide targeted consumer advice and set up education campaigns to raise the awareness towards Campylobacter infection and the importance of different sources (e.g. food, environment) in the epidemiology of Campylobacter. Acknowledgements This work was supported by the German Federal Ministry of Education and Research (project: FBI-Zoo/Food-Borne Zoonotic Infections of Humans, grant 01Kl1012). References Alter, T., Gaull, F., Froeb, A., Fehlhaber, K., 2005a. Distribution of Campylobacter jejuni strains at different stages of a turkey slaughter line. Food Microbiol. 22, 345–351. Alter, T., Gaull, F., Kasimir, S., Gürtler, M., Mielke, H., Linnebur, M., Fehlhaber, K., 2005b. Prevalence and transmission routes of Campylobacter spp. strains within multiple pig farms. Vet. Microbiol. 108, 251–261. Batz, M., Hoffmann, S., Morris Jr., J.G., 2014. Disease-outcome trees EQ-5D scores, and estimated annual losses of Quality-Adjusted Life Years (QALYs) for 14 foodborne pathogens in the United States. Foodborne Pathog. Dis. 11, 395–402. Brynestad, S., Braute, L., Luber, P., Bartelt, E., 2008. Quantitative microbiological risk assessment of campylobacteriosis cases in the German population due to consumption of chicken prepared in homes. Int. J. Risk Assess. Manag. 8, 191–210. Chantarapanont, W., Berrang, M., Frank, J.F., 2003. Direct microscopic observation and viability determination of Campylobacter jejuni on chicken skin. J. Food Prot. 66, 2222–2230. Cody, A.J., McCarthy, N.M., Wimalarathna, H.L., Colles, F.M., Clark, L., Bowler, I.C., Maiden, M.C., Dingle, K.E., 2012. A longitudinal 6-year study of the molecular epidemiology of clinical Campylobacter isolates in Oxfordshire United Kingdom. J. Clin. Microbiol. 50, 3193–3201. Crim, S.M., Iwamoto, M., Huang, J.Y., Griffin, P.M., Gilliss, D., Cronquist, A.B., Cartter, M., Tobin-D’Angelo, M., Blythe, D., Smith, K., Lathrop, S., Zansky, S., Cieslak, P.R., Dunn, J., Holt, K.G., Lance, S., Tauxe, R., Henao, O.L., 2014. Incidence and trends of infection with pathogens transmitted commonly through food-Foodborne Diseases Active Surveillance Network, 10 U.S. sites, 2006–2013. MMWR 63, 328–332. Eberle, K.N., Kiess, A.S., 2012. Phenotypic and genotypic methods for typing Campylobacter jejuni and Campylobacter coli in poultry. Poult. Sci. 91, 255–264. EFSA, 2010. Analysis of the baseline survey on the prevalence of Campylobacter in broiler batches and of Campylobacter and Salmonella on broiler carcasses in the EU, 2008, Part A: Campylobacter and Salmonella prevalence estimates. EFSA J. 8, 1503, http://dx.doi.org/10.2903/j.efsa.2010.1503. EFSA, 2011. Scientific opinion on Campylobacter in broiler meat production: control options and performance objectives and/or targets at different stages of the food chain. EFSA J. 9, 2105, http://dx.doi.org/10.2903/j.efsa.2011.2105. EFSA, 2012. The European union summary report on trends and sources of zoonoses, zoonotic agents and food-borne outbreaks in 2010. EFSA J. 10, 2597, http://dx.doi.org/10.2903/j.efsa.2012.2597. EFSA, 2014. EFSA explains zoonotic diseases: Campylobacter. Fact Sheet, http://dx.doi.org/10.2805/59450. EFSA, ECDC, 2014. The European union summary report on trends and sources of zoonoses, zoonotic agents and food-borne outbreaks in 2012. EFSA J. 12, 3547, http://dx.doi.org/10.2903/j.efsa.2014.3547, 312 pp. Endtz, H.P., Vliegenthart, J.S., Vandamme, P., Weverink, H.W., van den Braak, N.P., Verbrugh, H.A., van Belkum, A., 1997. Genotypic diversity of Campylobacter lari isolated from mussels and oysters in The Netherlands. Int. J. Food Microbiol. 34, 79–88. FAO/WHO, 2007. Risk Assessment of Campylobacter spp. in Broiler Chickens: Technical Report. Microbiological Risk Assessment Series 12, Rome, Geneva. FAO/WHO, 2009. Salmonella and Campylobacter in Chicken Meat: Meeting Report. Microbiological Risk Assessment Series 19, Rome, Geneva. Gillespie, I.A., O’Brien, S.J., Frost, J.A., Adak, G.K., Horby, P., Swan, A.V., Painter, M.J., Neal., K.R., 2002. A case-case comparison of Campylobacter coli and Campylobacter jejuni infection: a tool for generating hypotheses. Emerg. Infect. Dis. 8, 937–942.

Gripp, E., Hlahla, D., Didelot, X., Kops, F., Maurischat, S., Tedin, K., Alter, T., Ellerbroek, L., Schreiber, K., Schomburg, D., Janssen, T., Bartholomaus, P., Hofreuter, D., Woltemate, S., Uhr, M., Brenneke, B., Gruning, P., Gerlach, G., Wieler, L., Suerbaum, S., Josenhans, C., 2011. Closely related Campylobacter jejuni strains from different sources reveal a generalist rather than a specialist lifestyle. BMC Genomics 12, 584. Guevremont, E., Higgins, R., Quessy, S., 2004. Characterization of Campylobacter isolates recovered from clinically healthy pigs and from sporadic cases of campylobacteriosis in humans. J. Food Prot. 67, 228–234. Hald, B., Skovgard, H., Pedersen, K., Bunkenborg, H., 2008. Influxed insects as vectors for Campylobacter jejuni and Campylobacter coli in Danish broiler houses. Poult. Sci. 87, 1428–1434. Hartnack, S., Doherr, M.G., Alter, T., Toutounian-Mashad, K., Greiner, M., 2009. Campylobacter monitoring in German broiler flocks: an explorative time series analysis. Zoonoses Public Health 56, 117–128. Hartnett, E., Kelly, L., Newell, D., Wooldridge, M., Gettinby, G., 2001. A quantitative risk assessment for the occurrence of Campylobacter in chickens at the point of slaughter. Epidemiol. Infect. 127, 195–206. Havelaar, A.H., Mangen, M.J., de Koeijer, A.A., Bogaardt, M.J., Evers, E.G., JacobsReitsma, W.F., van Pelt, W., Wagenaar, J.A., de Wit, G.A., van der Zee, H., Nauta, M.J., 2007. Effectiveness and efficiency of controlling Campylobacter on broiler chicken meat. Risk Anal. 27, 831–844. Havelaar, A.H., Haagsma, J.A., Mangen, M.J., Kemmeren, J.M., Verhoef, L.P., Vijgen, S.M., Wilson, M., Friesema, I.H., Kortbeek, L.M., van Duynhoven, Y.T., van Pelt, W., 2012. Disease burden of foodborne pathogens in the Netherlands, 2009. Int. J. Food Microbiol. 156, 231–238. Health Protection Agency, 2008. Health Effects of Climate Change in the United Kingdom 2008. Department of Health Report. Hertwig, S., Hammerl, J.A., Appel, B., Alter, T., 2013. Post-harvest application of lytic bacteriophages for biocontrol of foodborne pathogens and spoilage bacteria. Berl. Munch. Tierarztl. Wochenschr. 125, 357–369. Hofshagen, M., Kruse, H., 2005. Reduction in flock prevalence of Campylobacter spp. in broilers in Norway after implementation of an action plan. J. Food Prot. 68, 2220–2223. Hue, O., Le Bouquin, S., Laisney, M.J., Allain, V., Lalande, F., Petetin, I., Rouxel, S., Quesne, S., Gloaguen, P.Y., Picherot, M., Santolini, J., Salvat, G., Bougeard, S., Chemaly, M., 2010. Prevalence of and risk factors for Campylobacter spp. contamination of broiler chicken carcasses at the slaughterhouse. Food Microbiol. 27, 992–999. Jasson, V., Uyttendaele, M., Rajkovic, A., Debevere, J., 2007. Establishment of procedures provoking sub-lethal injury of Listeria monocytogenes, Campylobacter jejuni and Escherichia coli O157 to serve method performance testing. Int. J. Food Microbiol. 118, 241–249. Katsma, W.E.A., de Koeijer, A.A., Fischer, E.A.J., Jacobs-Reitsma, W., Wagenaar, J., 2005. Campylobacter Prevalence in Broiler Flocks in the Netherlands Modelling Transmission within and between Flocks and Efficacy of Interventions. Animal Sciences Group (ASG), Wageningen. Kist, M., 2002. Lebensmittelbedingte Infektionen durch Campylobacter. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 45, 497–506. Lake, R., Hudson, A., Cressey, P., Bane., G., 2007. Quantitative Risk Model: Campylobacter spp. in the Poultry Food Chain, Christchurch, New Zealand. Lake, R.J., Horn, B.J., Dunn, A.H., Parris, R., Green, F.T., McNickle, D.C., 2013. Costeffectiveness of interventions to control Campylobacter in the New Zealand poultry meat food supply. J. Food Prot. 76, 1161–1167. Le Roux, E., Lastovica, A.J., 1998. The Cape Town protocol: how to isolate the most campylobacters for your dollar, pound, frank yen. In: Lastovica, A.J., Newell, D., Lastovica, E.E. (Eds.), Campylobacter, Helicobacter and Related Organisms. Institute of Child Health, University of Cape Town, Rondebosch, Cape Town, South Africa. Lehmann, L., Löwenstein, A., Lehnert, F., Gölz, G., Alter, T., 2013. Nachweis und Charakterisierung von Campylobacter spp. aus unterschiedlichen Matrizes [abstract]. In: Abstract-Band 54. Arbeitstagung des Arbeitsgebietes Lebensmittelhygiene, Garmisch-Partenkirchen. Amtstierärztlicher Dienst, Germany, pp. 167. Levesque, S., Fournier, E., Carrier, N., Frost, E., Arbeit, R.D., Michaud, S., 2013. Campylobacteriosis in urban versus rural areas: a case-case study integrated with molecular typing to validate risk factors and to attribute sources of infection. PLOS ONE 8, e83731. Lindqvist, R., Lindblad, M., 2008. Quantitative risk assessment of thermophilic Campylobacter spp. and cross-contamination during handling of raw broiler chickens evaluating strategies at the producer level to reduce human campylobacteriosis in Sweden. Int. J. Food Microbiol. 121, 41–52. Louis, V.R., Gillespie, I.A., O’Brien, S.J., Russek-Cohen, E., Pearson, A.D., Colwell, R.R., 2005. Temperature-driven Campylobacter seasonality in England and wales. Appl. Environ. Microbiol. 71, 85–92. Mangen, M.J., Havelaar, A.H., Poppe, K.P., de Wit., G.A., 2007. Cost-utility analysis to control Campylobacter on chicken meat: dealing with data limitations. Risk Anal. 27, 815–830. Mangen, M.J., Plass, D., Havelaar, A.H., Gibbons, C.L., Cassini, A., Muhlberger, N., van Lier, A., Haagsma, J.A., Brooke, R.J., Lai, T., de Waure, C., Kramarz, P., Kretzschmar, M.E., 2013. The pathogen- and incidence-based DALY approach: an appropriate methodology for estimating the burden of infectious diseases. PLOS ONE 8, e79740. Meinersmann, R.J., Berrang, M.E., Little., E., 2013. Campylobacter spp. recovered from the Upper Oconee River Watershed Georgia in a 4-year study. Microb. Ecol. 65, 22–27.

G. Gölz et al. / International Journal of Medical Microbiology 304 (2014) 817–823 Meldrum, R.J., Griffiths, J.K., Smith, R.M., Evans, M.R., 2005. The seasonality of human campylobacter infection and Campylobacter isolates from fresh, retail chicken in Wales. Epidemiol. Infect. 133, 49–52. Miller, G., Dunn, G.M., Smith-Palmer, A., Ogden, I.D., Strachan, N.J., 2004. Human campylobacteriosis in Scotland: seasonality, regional trends and bursts of infection. Epidemiol. Infect. 132, 585–593. Moore, J.E., Corcoran, D., Dooley, J.S., Fanning, S., Lucey, B., Matsuda, M., McDowell, D.A., Megraud, F., Millar, B.C., O’Mahony, R., O’Riordan, L., O’Rourke, M., Rao, J.R., Rooney, P.J., Sails, A., Whyte, P., 2005. Campylobacter. Vet. Res. 36, 351–382. Mughini Gras, L., Smid, J.H., Wagenaar, J.A., de Boer, A.G., Havelaar, A.H., Friesema, I.H., French, N.P., Busani, L., van Pelt., W., 2012. Risk factors for campylobacteriosis of chicken, ruminant, and environmental origin: a combined case–control and source attribution analysis. PLOS ONE 7, e42599. Mullner, P., Shadbolt, T., Collins-Emerson, J.M., Midwinter, A.C., Spencer, S.E.F., Marshall, J., Carter, P.E., Campbell, D.M., Wilson, D.J., Hathaway, S., Pirie, R., French, N.P., 2010. Molecular and spatial epidemiology of human campylobacteriosis: source association and genotype-related risk factors. Epidemiol. Infect. 138, 1372–1383. Mylius, S.D., Nauta, M.J., Havelaar, A., 2007. Cross-contamination during food preparation: a mechanistic model applied to chicken-borne Campylobacter. Risk Anal. 27, 803–813. Näther, G., Alter, T., Martin, A., Ellerbroek, L., 2009. Analysis of risk factors for Campylobacter species infection in broiler flocks. Poult. Sci. 88, 1299–1305. Nathues, C., Grüning, P., Fruth, A., Verspohl, J., Blaha, T., Kreienbrock, L., Merle, R., 2013. Campylobacter spp., Yersinia enterocolitica, and Salmonella enterica and their simultaneous occurrence in German fattening pig herds and their environment. J. Food Prot. 76, 1704–1711. Nauta, M., Hill, A., Rosenquist, H., Brynestad, S., Fetsch, A., van der Logt, P., Fazil, A., Christensen, B., Katsma, E., Borck, B., Havelaar, A., 2009. A comparison of risk assessments on Campylobacter in broiler meat. Int. J. Food Microbiol. 129, 107–123. New Zealand Ministry for Primary Industries, 2013. Campylobacter Risk Management Strategy 2013–2014. Nichols, G.L., 2005. Fly transmission of Campylobacter. Emerg. Infect. Dis. 11, 361–364. Nielsen, E.M., Engberg, J., Madsen, M., 1997. Distribution of serotypes of Campylobacter jejuni and C. coli from Danish patients, poultry, cattle and swine FEMS Immunol. Med. Microbiol. 19, 47–56. Riedel, C., Gölz, G., Förstner, K.U., Sharma, C.M., Alter, T., 2013. Changes in gene expression as a heat shock response in Campylobacter jejuni, C. coli and C. lari [abstract]. In: 17th International Workshop on Campylobacter, Helicobacter and Related Organisms, CHRO 2013 Abstract Book, Aberdeen, UK, p. 80. RKI, 2014. SurvStat@RKI 2.0, https://survstat.rki.de (accessed 05.08.14). Rosenquist, H., Nielsen, N.L., Sommer, H.M., Norrung, B., Christensen, B.B., 2003. Quantitative risk assessment of human campylobacteriosis associated with thermophilic Campylobacter species in chickens. Int. J. Food Microbiol. 83, 87–103. Roux, F., Sproston, E., Rotariu, O., Macrae, M., Sheppard, S.K., Bessell, P., SmithPalmer, A., Cowden, J., Maiden, M.C., Forbes, K.J., Strachan, N.J., 2013. Elucidating the aetiology of human Campylobacter coli infections. PLOS ONE 8, e64504. Sahin, O., Fitzgerald, C., Stroika, S., Zhao, S., Sippy, R.J., Kwan, P., Plummer, P.J., Han, J., Yaeger, M.J., Zhang, Q., 2012. Molecular evidence for zoonotic transmission of an emergent, highly pathogenic Campylobacter jejuni clone in the United States. J. Clin. Microbiol. 50, 680–687. Sampers, I., Habib, I., De Zutter, L., Dumoulin, A., Uyttendaele, M., 2010. Survival of Campylobacter spp. in poultry meat preparations subjected to freezing, refrigeration, minor salt concentration, and heat treatment. Int. J. Food Microbiol. 137, 147–153. Samuel, M.C., Vugia, D.J., Shallow, S., Marcus, R., Segler, S., McGivern, T., Kassenborg, H., Reilly, K., Kennedy, M., Angulo, F., Tauxe, R.V., 2004. Epidemiology of sporadic Campylobacter infection in the United States and declining trend in incidence FoodNet 1996-1999. Clin. Infect. Dis. 38 (S3), 165–174.

823

Schielke, A., Rosner, B.M., Stark, K., 2014. Epidemiology of campylobacteriosis in Germany – insights from 10 years of surveillance. BMC Infect. Dis. 14, 30. Schindler, P.R.G., Elmer-Englhardt, D., Hörmansdorfer, S., 2003. Untersuchung zum mikrobiologischen Status südbayerischer Badegewässer unter besonderer Berücksichtigung des Vorkommens thermophiler Campylobacter-Arten. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 46, 483–487. Schönberg-Norio, D., Takkinen, J., Hanninen, M.L., Katila, M.L., Kaukoranta, S.S., Mattila, L., Rautelin, H., 2004. Swimming and Campylobacter infections. Emerg. Infect. Dis. 10, 1474–1477. Sears, A., Baker, M.G., Wilson, N., Marshall, J., Muellner, P., Campbell, D.M., Lake, R.J., French, N.P., 2011. Marked campylobacteriosis decline after interventions aimed at poultry, New Zealand. Emerg. Infect. Dis. 17, 1007–1015. Sheppard, S.K., Dallas, J.F., Strachan, N.J., MacRae, M., McCarthy, N.D., Wilson, D.J., Gormley, F.J., Falush, D., Ogden, I.D., Maiden, M.C., Forbes, K.J., 2009. Campylobacter genotyping to determine the source of human infection. Clin. Infect. Dis. 48, 1072–1078. Stark, K., Niedrig, M., Biederbick, W., Merkert, H., Hacker, J., 2009. Die Auswirkungen des Klimawandels Welche neuen Infektionskrankheiten und gesundheitlichen Probleme sind zu erwarten? Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 52, 699–714. Stellbrink, E., (thesis) 2009. Die Rolle von Dosis-Wirkungsmodellen im Rahmen von quantitativen mikrobiologischen Risikobewertungen am Beispiel des Erregers Campylobacter. Dept. of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany. Stern, N.J., Hiett, K.L., Alfredsson, G.A., Kristinsson, K.G., Reiersen, J., Hardardottir, H., Briem, H., Gunnarsson, E., Georgsson, F., Lowman, R., Berndtson, E., Lammerding, A.M., Paoli, G.M., Musgrove, M.T., 2003. Campylobacter spp. in Icelandic poultry operations and human disease. Epidemiol. Infect. 130, 23–32. Strachan, N.J., Watson, R.O., Novik, V., Hofreuter, D., Ogden, I.D., Galan, J.E., 2008. Sexual dimorphism in campylobacteriosis. Epidemiol. Infect. 136, 1492–1495. Strachan, N.J., Gormley, F.J., Rotariu, O., Ogden, I.D., Miller, G., Dunn, G.M., Sheppard, S.K., Dallas, J.F., Reid, T.M., Howie, H., Maiden, M.C., Forbes, K.J., 2009. Attribution of Campylobacter infections in northeast Scotland to specific sources by use of multilocus sequence typing. J. Infect. Dis. 199, 1205–1208. Swart, A.N., Mangen, M.J., Havelaar, A.H., 2013. Microbiological Criteria as a Decision Tool for Controlling Campylobacter in the Broiler Meat Chain. RIVM Letter report 330331008/2013. van Doorn, L.J., Verschuuren-Van Haperen, A., van Belkum, A., Endtz, H.P., Vliegenthart, J.S., Vandamme, P., Quint, W.G., 1998. Rapid identification of diverse Campylobacter lari strains isolated from mussels and oysters using a reverse hybridization line probe assay. J. Appl. Microbiol. 84, 545–550. von Altrock, A., Louis, A.L., Rösler, U., Alter, T., Beyerbach, M., Kreienbrock, L., Waldmann, K.H., 2006. The bacteriological and serological prevalence of Campylobacter spp. and Yersinia enterocolitica in fattening pig herds in Lower Saxony. Berl. Munch. Tierarztl. Wochenschr. 119, 391–399. Wagenaar, J.A., Mevius, D.J., Havelaar, A.H., 2006. Campylobacter in primary animal production and control strategies to reduce the burden of human campylobacteriosis. Rev. Sci. Tech. 25, 581–594. Wagenaar, J.A., French, N.P., Havelaar, A.H., 2013. Preventing Campylobacter at the source: why is it so difficult? Clin. Infect. Dis. 57, 1600–1606. Wassenaar, T.M., 2011. Following an imaginary Campylobacter population from farm to fork and beyond: a bacterial perspective. Lett. Appl. Microbiol. 53, 253–263. Weijtens, M.J., Reinders, R.D., Urlings, H.A., van der Plas., J., 1999. Campylobacter infections in fattening pigs; excretion pattern and genetic diversity. J. Appl. Microbiol. 86, 63–70. WHO, 2011. Campylobacter. Fact Sheet, No. 255, http://www.who.int/mediacentre/ factsheets/fs255/en/ Wieland, B., Wittwer, M., Regula, G., Wassenaar, T.M., Burnens, A.P., Keller, J., Stark, K.D., 2006. Phenon cluster analysis as a method to investigate epidemiological relatedness between sources of Campylobacter jejuni. J. Appl. Microbiol. 100, 316–324.