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CALLISTO research project is funded by the European Union, 7th Framework Programme. 3

TABLE OF CONTENTS

EXECUTIVE SUMMARY 6

OVERVIEW OF THE CALLISTO PROJECT FIRST CYCLE 8

• MEMBERS OF CALLISTO 9 -- MEMBERS OF EAG I 9 -- MEMBERS OF EAG II 9 -- MEMBERS OF EAG III 10 -- MEMBERS OF EAG IV 10 -- MEMBERS OF EAG V 11 -- MEMBERS OF EAG VI 11 -- MEMBERS OF EAG VII 11

1. COMPANION : DEFINITIONS AND DEMOGRAPHICS 12

• 1.1 DEFINITION OF COMPANION ANIMALS AND THE SCOPE OF CALLISTO 12 • 1.2 SMALL COMPANION ANIMALS IN EUROPE 13 • 1.3 NEW COMPANION ANIMALS 14 • 1.4 HORSES 15 • 1.5 THE ECONOMIC SIGNIFICANCE OF THE COMPANION SECTOR 16 IN EUROPE

2. SOCIOLOGICAL AND WELFARE ASPECTS OF KEEPING 21 COMPANION ANIMALS

• 2.1 THE SOCIAL AND SOCIETAL REASONS FOR KEEPING COMPANION 21 ANIMALS AND THE BENEFIT TO HUMAN HEALTH AND WELLBEING THAT COMPANION ANIMALS CAN BRING • 2.2 THE SOCIETAL VALUE OF PETS BY HUMAN AGE GROUP 24 -- 2.2.1 BENEFITS OF PET KEEPING FOR CHILDREN 24 -- 2.2.2 BENEFITS OF PET KEEPING FOR ADOLESCENTS 25 -- 2.2.3 BENEFITS OF PET KEEPING FOR ADULTS 26 -- 2.2.4 BENEFITS OF PET KEEPING FOR THE ELDERLY 27 • 2.3 ZOONOTIC ASPECTS RELEVANT FOR HUMAN AND ANIMAL 27 WELFARE • 2.4 INFORMATION ALREADY AVAILABLE TO , AND HORSE 29 OWNERS ON RISK OF ZOONOSES

3. POLICY ACTIONS RELATED TO SPREAD OF ZOONOSES 34

• 3.1 INTRODUCTION 34 • 3.2 METHODS USED FOR DATA COLLECTION 35 • 3.3 GENERAL, NON-DISEASE SPECIFIC POLICY ACTIONS RELATED TO THE 36 SPREAD OF THROUGH COMPANION ANIMALS • 3.4 POLICY ACTIONS RELATED TO THE SPREAD OF PARASITIC DISEASES 38 THROUGH COMPANION ANIMALS TO PEOPLE AND FOOD PRODUCING ANIMALS 4

39 • 3.5 POLICY ACTIONS RELATED TO THE SPREAD OF BACTERIAL DISEASES THROUGH COMPANION ANIMALS TO PEOPLE AND FOOD PRODUCING ANIMALS 40 • 3.6 POLICY ACTIONS RELATED TO THE SPREAD OF VIRAL DISEASES THROUGH COMPANION ANIMALS TO PEOPLE AND FOOD PRODUCING ANIMALS 40 • 3.7 COMPLIANCE WITH POLICY ACTIONS RELATED TO THE SPREAD OF DISEASES THROUGH COMPANION ANIMALS TO PEOPLE AND FOOD PRODUCING ANIMALS

41 4. INTRODUCTION TO SPECIFIC ZOONOTIC

43 5. VIRAL INFECTIONS

43 • 5.1 APPROACH TO IDENTIFICATION OF SIGNIFICANT VIRAL ZOONOSES 47 • 5.2 OF PRIMARY CONCERN TO HUMAN HEALTH 47 -- 5.2.1 48 -- 5.2.2 WEST NILE VIRUS 50 -- 5.2.3 -BORNE VIRUS 52 -- 5.2.4 CRIMEAN-CONGO HAEMORRHAGIC VIRUS 53 -- 5.2.5 HANTAVIRUSES (INCLUDING DOBRAVA-BELGRADE VIRUS) 55 -- 5.2.6 TAHYNA VIRUS 56 -- 5.2.7 AICHI VIRUS 58 -- 5.2.8 EUROPEAN LYSSAVIRUS 59 -- 5.2.9 HEPATITIS E VIRUS 62 -- 5.2.10 COWPOX VIRUS 64 -- 5.2.11 G5 ROTAVIRUS 66 -- 5.2.12 A VIRUS 68 -- 5.2.13 LYMPHOCYTIC CHORIOMENINGITIS VIRUS 70 • 5.3 VIRUSES OF PRIMARY CONCERN TO FOOD ANIMAL HEALTH AND PRODUCTION 70 -- 5.3.1 BLUETONGUEVIRUS 72 -- 5.3.2 AFRICAN SWINE FEVER VIRUS 73 -- 5.3.3 FOOT-AND-MOUTH-DISEASE VIRUS 75 -- 5.3.4 RABBIT HAEMORRHAGIC DISEASE VIRUS 76 -- 5.3.5 LUMPY SKIN DISEASE VIRUS 77 • 5.4 VIRUSES OF PRIMARY CONCERN TO FOOD ANIMAL HEALTH AND PRODUCTION () 77 -- 5.4.1 CYPRINID HERPESVIRUS 3 (KOI HERPESVIRUS) 79 -- 5.4.2 VIRAL HAEMORRHAGIC SEPTICAEMIA VIRUS 80 -- 5.4.3 INFECTIOUS PANCREATIC NECROSIS VIRUS

82 6. BACTERIAL INFECTIONS

82 • 6.1 SPP. (CAT SCRATCH DISEASE) 86 • 6.2 BITE INFECTIONS 88 • 6.3 CAMPYLOBACTER SPP. (CAMPYLOBACTERIOSIS) 92 • 6.4 CHLAMYDOPHILA PSITTACI (PSITTACOSIS) 94 • 6.5 CLOSTRIDIUM DIFFICILE 5

• 6.6 COXIELLA BURNETII (Q FEVER) 98 • 6.7 DERMATOPHYTES (DERMATOPHYTOSIS/‘RINGWORM’) 102 • 6.8 EXTENDED-SPECTRUM Β-LACTAMASE (ESBL) PRODUCING 105 • 6.9 LEPTOSPIRA SPP. (LEPTOSPIROSIS) 109 • 6.10 METHICILLIN-RESISTANT AUREUS (MRSA) 115 • 6.11 METHICILLIN-RESISTANT STAPHYLOCOCCUS PSEUDINTERMEDIUS 120 (MRSP) • 6.12 SALMONELLA SPP. (SALMONELLOSIS) 124

7. PARASITIC INFECTIONS 129

• 7.1 CYSTIC AND ALVEOLAR ECHINOCOCCOSIS 129 • 7.2 DIROFILARIOSIS 134 • 7.3 TOXOCARA SPP. 136 • 7.4 HOOKWORMS 139 • 7.5 TOXOPLASMOSIS 142 • 7.6 LEISHMANIOSIS 145 • 7.7 NEOSPOROSIS 149 • 7.8 GIARDIOSIS 152

8. RISK ANALYSIS AND EPIDEMIOLOGY 155

• 8.1 INTRODUCTION TO RISK ANALYSIS AND DISEASE MODELLING 155 -- 8.1.1 STATE TRANSITION MODELS 158 -- 8.1.2 SCENARIO TREE 161 • 8.2 EPIDEMIOLOGICAL SIMILARITIES AND DIFFERENCES BETWEEN THE 167 PARADIGMATIC DISEASES SELECTED IN CHAPTERS 5–7 -- 8.2.1 DISEASES TRANSMITTED BY DIRECT CONTACT 170 -- 8.2.2 DISEASES TRANSMITTED BY VECTORS 170 • 8.3 REVIEW OF EXISTING PUBLISHED RISK ASSESSMENTS CONCERNING 175 THE TRANSMISSION OF DISEASES FROM COMPANION ANIMALS TO OR FARMED ANIMALS -- 8.3.1 IMPORT RISK ASSESSMENTS 175 -- 8.3.3 RISK ASSESSMENTS CONCERNING THE ‘PARADIGMATIC DISEASES’ 178 -- 8.3.4 TYPE OF INFORMATION REQUIRED FOR THE SPECIFIC RISK ASSESSMENT 179 OF EACH PARADIGMATIC DISEASE

9. CALLISTO WEB SITE 185

• 9.1 INTRODUCTION 185 • 9.2 MAIN SECTIONS AND FUNCTIONING 186 • 9.3 DATA CONCERNING WEBSITE VISITS 187 • 9.4 IMPROVEMENTS AND FORTHCOMING ACTIONS 188

GLOSSARY 190 6 EXECUTIVE SUMMARY

This document represents the first annual report of the EU Framework 7-funded project entitled CALLISTO (Companion Animal multisectoriaL interprofessionaL and interdisciplinary Strategic Think tank On zoonoses), which investigates zoonotic infectious diseases transmitted between companion animals and humans and food producing animals. The specific aim of the first year of the project was to develop a detailed overview of the role of companion animals as a source of infectious diseases for man and farmed animals, including available information on disease incidence and geographical distribution in these host categories. The present report is the compilation of the work of seven Expert Working Groups under five Work Packages during the calendar year 2012.

Companion animals are any domesticated, domestic-bred or wild- caught animals, permanently living in a community and kept by people for company, enjoyment, work (e.g. support for blind or deaf people, police or military ) or psychological support – including, but not limited to dogs, , horses, rabbits, ferrets, guinea pigs, , birds and ornamental fish.

The report describes the very large and growing number of companion animals estimated to be kept within EU countries and the major economic contribution made by the associated industry (e.g. breeding, sales, pet food, insurance, pharmaceutical and veterinary support). For example, there are an estimated 64 million cats and 60 million dogs in EU countries and the estimated annual spend on petcare products alone is €25.7 billion. It is also recognized that there are great challenges to obtaining accurrate data of this type.

Companion animals make crucial contributions to human society. In addition to working roles (e.g. dogs for visually or hearing impaired 7

people), companion animals afford profound benefit in areas as diverse as human healthcare and childhood development. The positive influence of owning a companion animal has further benefit by reducing human healthcare spend.

Despite these unquestionable benefits, there are risks that human owners may contract zoonotic infectious diseases directly or indirectly from companion animal species. Moreover, as traditional livestock species now increasingly serve a role as companions, there are disease transmission risks from these animals to farmed animals of the same species.

This report systematically defines the major bacterial, viral and parasitic zoonoses that fall into these categories and identifies the risks to the human and farmed animal populations. The current availability of surveillance systems for these infections and of governmental awareness and interest in these diseases is also explored. With few exceptions (e.g. canine rabies virus infection) there is little serious attempt to monitor the prevalence, emergence or re-emergence of zoonotic arising from companion animal species. With the exception of the EU Pet Travel scheme (again focussed on canine rabies) there is little legislative awareness of the scale or significance of companion animal zoonoses.

The monitoring and control of companion animal zoonoses is a prime example of where a ‘One Health’ (joint human and veterinary medical and ) approach is essential. In Years 2 and 3 of the CALLISTO project gaps in knowledge will be identified, and risks will be modelled in order to produce clear recommendations to stakeholders. 8 OVERVIEW OF THE CALLISTO PROJECT FIRST CYCLE

The aim of the first cycle of CALLISTO was to review the current knowledge of the role of companion animals as a source of infectious diseases in man and farmed animals in the EU. Accordingly, the first part of this cycle was used to collect and review existing data within each area represented by the seven expert advisory groups (EAG I to EAG VII). The work done by the seven EAGs has been gathered and merged into the present cross-EAG report. The report was planned during the first cycle of EAG meetings and cross-EAG meetings held in January 2012 in Brussels. Subsequently the various EAGs arranged ad hoc meetings and teleconferences for the implementation of the working plan, and a cross-EAG preparatory report was agreed by the partners to delineate the topics and scopes to be covered by each EAG, the results expected from each EAG, and the format of the report. This final synthesis report from the first year of the project follows from a CALLISTO conference held in Brussels in October 2012.

EAG I represents the user community. This group gathered data describing the composition of companion animal populations in Europe as well as the socioeconomic significance of companion animals. Examples of user communities and animal health organizations in Europe were also listed.

EAG II deals with policy actions and has conducted an e-mail questionnaire survey asking for actions aiming at the prevention of the spread of diseases by companion animals to people and food producing animals. Questionnaires were sent to national authorities, veterinary organisations and stakeholder organisations such as animal owner organisations and trade organisations.

EAGs III-V have expertise in companion animal zoonoses of viral, bacterial and parasitic origin, respectively. Each group started the first cycle by definining a broad list of companion animal zoonoses and pathogens, which may be transmitted to food animals. From this list, each group defined a shorter list of paradigmatic priority pathogens, which were further described with regards to route of transmission, occurrence and clinical impact in man and companion animals, link to agriculture and control measures. Apart from describing traditional zoonotic pathogens, EAG IV also focused on multidrug-resistant 9 bacteria that have recently emerged in companion animals and are currently regarded as potential threats to animal and/or public health.

The focus areas of EAG VI are risk analysis and data modeling. The work by this group has built on the lists of relevant pathogens provided by EAGs III-V. Pathogens were grouped according to epidemiological criteria such as pathway of spread, type of risk to people etc. Based on these criteria, a group of important diseases and pathogens were selected for risk analysis, and specific data requirements were listed for each selected disease. EAG VI also prepared a general introduction to risk analysis and disease modelling and reviewed existing published risk assessments concerning transmission of diseases from companion animals to humans or farm animals.

EAG VII handles sociology and welfare aspects concerning the relationship between companion animals and man. This group has described some of the social and societal reasons for keeping companion animals as well as human health aspects of contact with companion animals. The group also reviewed existing information available for owners of dogs, cats and horses on risk of zoonoses.

MEMBERS OF CALLISTO

MEMBERS OF EAG I

FECAVA (Federation of European Johan Van Tilburg (chair) Companion Animal Associations) Simon Orr FECAVA WSAVA (World Small Animal Jolle Kirpensteijn Association) Tjeerd Jorna WVA (World veterinary Association) ISCAID (international society for Jane Sykes companion animals infectious diseases) FEEVA (Federation of European Vivienne Duggan Equine Veterinary Associations) Michael Day WSAVA CPME (standing committee for Brian Kristensen European doctors) FEDIAF (the European Pet Food Thomas Meyer industry)

MEMBERS OF EAG II

EUROFACW-European Animal Laurens Hoedemakers Welfare Councils IFAH-Europe-Federation for Animal Declan O’Brien Health 10

Succeeded by Nicki Cross. Animal David Bayvel Welfare Directorate, Ministry for Primary Industries, New Zealand Sonja Van Tichelen Eurogroup for Animals Staci McLennan Eurogroup for Animals Nadège Leboucq OIE representative in Brussels Frank Boelaert European Food Safety Authority Alex Ploeg European Pet Organisation European Centre for Disease Céline Gossner Prevention and Control Federation of of Jan Vaarten (chair) Europe Federation of Veterinarians of Talina Sterneberg Europe

MEMBERS OF EAG III

Veterinary Laboratories Agency, Ian Brown United Kingdom Academic Medical Centre, The Menno de Jong Netherlands Erasmus Medical Centre, The Thijs Kuiken (chair) Netherlands Erasmus Medical Centre, The Ab Osterhaus Netherlands Aristotle University of Thessaloniki, Anna Papa Greece Erasmus Medical Centre, The Leslie Reperant (rapporteur) Netherlands Norwegian School of Veterinary Espen Rimstad Science, Norway Noël Tordo Institut Pasteur,

MEMBERS OF EAG IV

Luca Guardabassi (chair) University of Copenhagen, Denmark University of Utrecht, the Jaap Wagenaar Netherlands University of Utrecht, the Els Broens Netherlands Bruno Chomel University of , the USA

Lothar Wieler Free University of Berlin, Germany

Sebastian Güenther Free University of Berlin, Germany Frank Pasmans University of Gent, Belgium Peter Damborg University of Copenhagen, Denmark Scott Weese University of Guelph, Canada National Veterinary Institute, Ulrika Windahl Sweden 11

MEMBERS OF EAG V

Gad Baneth (chair) Hebrew University, Israel Domenico Otranto University of Bari, Italy

Stig Milan Thamsborg University of Copenhagen, Denmark

Ecole Nationale Vétérinaire d’Alfort, Jacques Guillot Maisons-Alfort, France Universitat Autònoma de Barcelona, Lala Solano Gallego Spain Peter Deplazes Vetsuisse Faculty, Switzerland

MEMBERS OF EAG VI

Istituto Zooprofilattico Sperimentale Armando Giovannini (chair) dell’Abruzzo e del Molise, Italy Institute of Zoology, Zoological Andrew Cunningham Society of London, UK

Sarah Cleaveland University of Glasgow, UK

Exotic Veterinary department - Neil Forbes Great Western Referrals, UK

Andrew Breed Veterinary Laboratories Agency UK

Animal Transportation Association, Jef Segers Belgium Ted Leighton University of Saskatchewan, Canada National School of Public Health, Vasileios Kontos Greece Stuart Reid University of Glasgow, UK National School of Public Health, E. I. Papadogiannakis Greece

MEMBERS OF EAG VII

IAHAIO (International Assocociation Dennis Turner (chair) of Human-Animal Interaction Organizations) Marie-Jose Enders-Slegers IAHAIO International Society for James Serpell Anthrozoology (ISAZ) Companion Animals at World Elly Hiby Society for the Protection of Animals, now at DogsTrust Istituto Zooprofilattico Sperimentale Barbara Alessandrini dell’Abruzzo e del Molise, Italy Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise, Italy Paolo Dalla Villa and Animal Welfare, European Commission Katinka DeBalogh FAO (Veterinary Public Health) EU representative of the Humane Jo Swabe Society International (HSI)

12 1. COMPANION ANIMALS: DEFINITIONS AND DEMOGRAPHICS

1.1 DEFINITION OF COMPANION ANIMALS AND THE SCOPE OF CALLISTO

Companion animals are any domesticated, domestic-bred or wild- caught animals, permanently living in a community and kept by people for company, enjoyment, work (e.g. support for blind or deaf people, police or military dogs) or psychological support – including, but not limited to dogs, cats, horses, rabbits, ferrets, guinea pigs, reptiles, birds and ornamental fish.

The Callisto definition of companion animals also encompasses backyard or hobby animals and animals in petting zoos, including sheep, goats, pigs and poultry, so the role of farm animal diseases as [re]emerging and zoonotic diseases is an important consideration in the Callisto project. Although the project primarily considers spread of disease from the commonly-owned companion animals to people and to farm animals, the potential for spread from backyard livstock to people and farmed animals will also be considered.

In all the countries of Europe, people keep backyard livestock. Data and numbers are difficult to find. In some countries the owners of backyard animals are organized (e.g. in the Netherlands there is the Nederlandse Belangenvereniging van Hobbydierhouders or Dutch Association of Backyard Animal Keepers). Petting zoos are more commonly located in cities (e.g. in Belgium there are about 900 and in the Netherlands about 450 of such establishments). 13

In the EU there are regulations and in many countries, manuals for disease control, to prevent transfer of zoonoses and emerging diseases to people and farm animals. The EU considers these animals again in the new Animal Health Law.

Keeping companion animals is also related to cultural diversity in the different member states of the EU. Belgium is the only country to use a POSITIVE LIST, which refers to the animals ( only) that can be kept as companion animals. The list is restricted but not limited.

1.2 SMALL COMPANION ANIMALS IN EUROPE

An estimated 70 million European households own at least one pet animal (excluding Russia). The estimated cat population of the EU is 64,448,500 and the total number of cats estimated in all of Europe is 84,705,500. Russia has the highest number of cats with an estimate of 18 million cats, followed by Italy with 7 million cats. The estimated percentage of households keeping pet cats ranges from 9% in Slovakia to 42% in Latvia and Romania.

The estimated number of dogs in the EU is 60,226,400 and the total number of dogs estimated in all of Europe is 84,705,500. Russia has the highest number of dogs with an estimate of 12.5 million followed by Italy with 7 million dogs. The estimated percentage of households keeping pet dogs ranges from 11% for Switzerland to 44% in Hungary.

The estimated number of ornamental birds in the EU is 39 million and the total number of such birds in all of Europe is 42.5 million. Italy has the greatest number of ornamental birds (23 million) and there are 6 million ornamental birds in France.

The estimated number of aquaria containing ornamental fish in the EU is 8,272,000 and in all of Europe there are an estimated 9,221,000 aquaria. The largest number of aquaria are in France, Germany and Italy.

The estimated number of small mammals kept as companion animals in the EU is 24.6 million and in all of Europe there are an estimated 30.6 million small pets. The largest numbers of small mammal pets are in Russia and Germany, followed by the UK and France.

[Report FEDIAF Facts and Figures 2010] 14

Figures in this report come from market research of Fediaf member associations, market research of pet food companies and estimations based thereupon when indicated. Data on the number of reptiles, , invertebrates and other mammals (exluding cats, dogs and “small mammals”) are unknown.

1.3 NEW COMPANION ANIMALS

In 2010, a report was commissioned by Eurogroup for Animals in cooperation with the Eurogroup for and Laboratory Animals (EWLA) to study the Health Risks of keeping ‘new companion animals’ (Praud A, Moutou F [2010] Health Risks from New Companion Animals. Eurogroup for Animals; http://eurogroupforanimals.org/files/ publications/downloads/Zoonotic-risk-report.pdf).

In recent years, there has been an unprecedented increase in the keeping of wild animals or new companion animals as pets. Many of these animals originate from other parts of the world and some are protected species. The increasing trend in keeping wild animals as pets raises concerns regarding human and animal health.

This boom raises the issue of zoonoses and animal diseases that imported wild animals may transmit to human and animal populations. Sixty percent of emerging infectious diseases are zoonotic with over 70% of those originating in wildlife, presenting an increasing and significant threat to global health. Some of these zoonoses are severe including rabies, , salmonellosis and Ebola virus infection.

Species are being introduced to new parts of the world at an unprecedented rate due to the increased volume of trade, transport and tourism. Transportation conditions can facilitate the spread of disease as species are mingled and transported under stress, which can compromise the immune system. The duration of transport may be shorter than the incubation period, so that the signs of disease may not be detected until after the animal arrives at the pet shop or in a home.

Primates represent one of the highest risk groups for zoonoses due to their close genetic relationship to man. Zoonoses presenting risks include rabies, herpes B virus, monkeypox, tuberculosis, enteric bacteria (e.g. Salmonella spp., Shigella spp.), zoonoses transmitted through bites () and various parasites (e.g. amoeba, whipworms and roundworms). 15

Rodents are the most widespread wild pet in Europe. Zoonotic risks include benign skin infections (dermatophytosis, scabies, , leptospirosis and contamination with enteric bacterial such as Salmonella spp.). More rarely, wild rodents can transmit severe diseases such as plague.

Carnivores are less frequently imported than monkeys or reptiles, but some wild are kept, including , and fennec foxes. The major risk associated with these species is rabies. There may also be a link to the wild reservoirs of the coronavirus that causes severe acute respiratory syndrome (SARS) in humans.

Some marsupials such as the sugar glider and the common brushtail possum have recently been sold in Europe as pets. The latter has become the reservoir for bovine tuberculosis caused by Mycobacterium bovis in New Zealand and may represent a risk to the establishment of a new tuberculosis strain in Europe.

Bats are known to function as a reservoir for rabies and other viruses. Fruit in Australia and Malaysia have been linked to severe zoonoses caused by Hendra virus and Nipah virus, respectively, with resulting human fatalities.

Salmonellosis is the main zoonosis transmitted by reptiles. It is estimated that 90% of captive reptiles are healthy carriers of Salmonella spp. Reptiles can also transmit tuberculosis (Mycobacterium marinum) and some parasites.

Most of the pathogenic agents causing these zoonoses can also be transmitted to other animals. This is the case with rabies (primates, carnivores and bats), tuberculosis (all mammals and reptiles), leptospirosis (rodents) and also Q-fever (reptiles and primates) and brucellosis (all mammals).

The probability of introducing a severe zoonosis via an exotic animal may be low but the danger that it poses to public health needs to be recognized.

1.4 HORSES

The European Horse Network estimates that there are over 6 million horses in Europe (European Horse Network, 2010). There are some regional economic clusters, including Basse–Normandie in France where there is 10% of the entire French horse population and 20% of 16

foals and Newmarket and Lambourn in the UK and the Curragh, Co. Kildare in Ireland.

The European thoroughbred breeders association figures in 2009 claim some 47,303 mares, 2,350 stallions and 26,581 foals. There are over 15,000 racehorses in training and an estimated 1 million horses and ponies in Great Britain. In Ireland there are an estimated 110,000 sport horses and 34,233 thoroughbred mares, stallions, foals and horses in training (Dukes Report, 2010). In Denmark there are about 170,000 horses (Danish National Council, 2011) and there are about 700,000 registered horses in Spain. In Hungary there are about 74,000 horses. These figures only cover registered horses. There are also draft horses, unregistered horses, wild pony breeds, donkeys and zebras for which there is little information.

In Europe the horse industries provide around 400,000 jobs. About 150,000 people are involved in racing and breeding and related sectors. The number of horse riders is growing at about 5% per year. In Great Britain racing provides 20,000 direct full time jobs (BHIC Briefing). The British Horse Industry Federation estimates that there are 4.3 million riders in Great Britain, with 2 million of these riding at least once a month (BHIC Briefing). There are an estimated 550,000 horse owners or primary carers. Sixty-five percent of owners own one horse, 15% own two, 12% own three to five, 4% own six to ten, and fewer than 2% own >20 horses.

There are an estimated 19,000 businesses active in the equestrian sector, including riding schools, farriers, livery yards and trainers, providing over 28,000 full time jobs. In Ireland there are 53,000 people regularly involved in the sport horse industry and total employment in the thoroughbred industry is around 17,000 people (Dukes Report, 2010). In Denmark there are about 18,000 people employed in the horse industry (Danish National Council, 2011). In Spain, the majority of horses are pleasure horses with only one owner.

In 2008, 14,386 horse movements took place from North and South America, Africa and Asia to Europe (TRACES data, 2008). In 2005, 99,087 slaughter horses moved into and moved between EU States.

Equine disease surveillance is passive in all countries and is geared around OIE List A diseases (FEEVA survey on equine disease). With the exception of Austria, governmental responsibility does not extend to endemic diseases. France and the UK have industry-led schemes for passive surveillance of endemic diseases, monitored via clinical sample submissions to participating laboratories (UK and France) and from data contributed by equine practitioners (France). The UK has a syndromic disease surveillance scheme for the horse owner population. Throughout Europe there is variable stakeholder consultation/involvement by government departments responsible 17 for equine disease surveillance and control: in some countries there is active stakeholder consultation (e.g. Belgium, Denmark and France), while in others there has been none to date (e.g. Germany and Spain).

Examples of equine disease notification in Europe include:

• BEVA/Blue Cross: national census days based on owner reporting of syndromes (such as cough, nasal discharge). Involves around 10,000 owners. • French Government network of sentinel practices scattered across France; group of trained practitioners that contribute disease information as a field force for the Animal Health Office. • In Hungary, all horses taking part in any competitions, shows or transported for breeding are tested each year for glanders. All horses in Hungary theoretically have to be tested for this disease every 3 years, even if horses are not transported anywhere from their own stables or farms. The results are checked by state official veterinarians. • Promed email alerts www.promedmail.org • OIE website www.oie.int • DEFRA/AHT/BEVA Equine Quarterly Disease Surveillance Reports www.aht.org.uk/cms-display/disease_surveillance.html • Gluck Equine Research Centre Equine Disease Quarterly www.ca.uky.edu/gluck/q_jan12.asp

Information on transmission of serious zoonotic diseases from horses is difficult to find. The transmission of disease between horses and man is believed to be limited, except more recently in Australia with Hendra virus, first described in Brisbane in 1994, for which a number of human fatalities in horse handlers have been ascribed. Transmission of zoonotic disease from horse carcases may occur infrequently in laboratory personnel handling post-mortem samples. It is believed that no major human disease outbreak has been attributed to transmission from horses (Timoney, 2008). However, there is known transmission of particular diseases such as glanders from infected horses to people, although the most recent case of this was in the USA in 1945. Rhodococcus equi, the cause of foal pneumonia, may be transmitted to immunocompromised people and result in disease. People may also be infected with brucellosis from exposure to horses. Tuberculosis, although rare in horses, could also be potentially transmitted to man. There are rare cases of equi subsp. zooepidemicus causing respiratory disease and meningitis in man. Trichinosis is an important food-borne zoonosis associated with consumption of raw or undercooked horse meat and there have been a number of cases in France. Enteric pathogens such as Salmonella spp., Clostridium difficile, Giardia, Cryptosporidium and Escherichia coli may also be transmitted to people from horses. Skin infections such as ringworm and meticillin- resistant Staphylococcus aureus (MRSA) can also be transmitted from horses to people (Weese, 2002). 18

REFERENCES

European Horse Network Key Figures 2010 (www.europeanhorsenetwork. eu). BHIC Briefing. Size and Scope of the Equine Sector. (www.bhic.co.uk). Hennessy and Quinn (2007) The Future of the Irish Sport Horse Industry. Dukes Report (2010) Analysis of the economic impact of the Irish Thoroughbred Horse Industry. (www.itba.info/PDFitbadown/ DukesReport2010_Update.pdf). Collins, J., Hanlon, A., More, S.J. and Duggan, V. 2008. The structure and regulation of the Irish equine industries: links to considerations of equine welfare. Irish. Vet. J., 61, 746–756. Danish National Council Covering Horses, 2011. Agriculture Ministry, Thoroughbred Breeders Association, Federacion Hípica, Spain (2011). Leadon, D.P., Herholz, C.P., 2009. Globalisation of trade and spread of infectious disease. Equine Vet. Educ. 8. Weese, J. S., 2002. A review of equine zoonotic diseases: risks in veterinary practice. AAEP Proceedings, Vol. 48. Centre for Food Security and Public Health. Iowa State: www.cfsph. iastate.edu Equine Species Working Group: Reviewing the Role of the National Animal Identification System (NAIS) within the Equine Industry www. equinespeciesworkinggroup.com Timoney. 2008. How significant are horses and other equids as a source of zoonotic diseases? Proceedings of the 10th International Congress of WEVA.

1.5 THE ECONOMIC SIGNIFICANCE OF THE COMPANION ANIMAL SECTOR IN EUROPE

The companion animal world is becoming increasingly important economically, and there is a substantial human health benefit in owning a companion animal with estimated associated reductions in spending on human healthcare. The economic importance of companion animals was highlighted in a 2007 FECAVA Report. Although this report is now 5 years old, it still gives a good indication of the economic importance of companion animals and the statistics given below are based on this report.

• Sale of animals - The data on population size and geographical distribution of major companion animal species give a measure of 19

the number of companion animals kept in Europe. While the dog and cat (and horse) remain the most popular companion animals, the market in smaller animals is growing significantly.

• Sale of pet food - According to the European Pet Food Association, pet food sales are 5 million tonnes per year to the value of Β 8.5 billion. The European Pet Food Association represents around 450 pet food companies across Europe. The European pet food industry employs around 21,000 people.

• Sale of equipment - Like the pet food market, the pet care product market is a large and increasing industry. The growth is largely due to the increasing tendency for owners to treat their pets as family members and spend more on accessories for them. This has led to a huge expansion of pet superstores.

• Sale of animal health services - The global dog and cat animal health market was valued at approximately $5,000 million in 2005 and accounted for nearly 40% of the global animal health market.

• Sale of insurance - Pet insurance is a large and a growing market. According to researchers (Packaged Facts), the pet insurance market in the US was expected to reach a value of $551 million by 2010. The total UK market for pet insurance was worth an estimated $245 million in 2002, growing 34.8% since 1998. The major factors contributing to the strong growth in the pet insurance market are increasingly sophisticated veterinary treatments, resulting in more conditions being detectable and treatable, and a general increase in the cost of veterinary treatment.

• Sale of veterinary services - Today there are more than 35,000 vets in Europe who work with companion animals. Most of them are general practitioners and many have additional qualifications (e.g. national specialization). At present, 50% of the veterinarians who graduate will work in companion animal practice.

• Advanced veterinary service demands better education and better equipment - Veterinarians invest in instruments, equipment and continuing professional development including course fees, congress fees, textbooks, journals, online education plus travel and accommodation.

• Activities (e.g. dog shows, competitions, etc.) generate money flow - Activities related to dogs and other companion animals are a large and important industry. In Norway the GNP of dog sport has been calculated to be greater than that of sheep farming (Norwegian Kennel Club). In addition to classical dog and cat shows, the dogs and their owners also compete in obedience, agility, hunting, sledge racing etc. 20

• Sale of animal transportation services - Populations are much more mobile than previously, travelling between countries with their companion animals both to live and work in a different country and also to go on holiday. Animal transportation companies have expanded to meet the needs of the migrant population

An up-to-date estimate of the retail value (in millions of Euros) of pet care products can be obtained from ©2012 Euromonitor International.

Pet care products include pet foods and pet products. Pet products include everything from cat litter to over-the-counter medications and treatments, but does NOT include the costs of veterinary care or prescription drugs:

Pet Care € Millions Austria 509.00.00 Belgium 617.10.00 Bulgaria 37.00.00 Czech Republic 295.10.00 Denmark 371.00.00 Finland 374.20.00 France 4,046.70 Germany 3,759.20 Greece 129.10.00 Hungary 286.30.00 Ireland 139.30.00 Italy 2,524.80 Netherlands 1,198.40 Norway 413.20.00 Poland 509.30.00 Portugal 353.20.00 Romania 152.00.00 Russia 2,267.60 Slovakia 88.20.00 Spain 1,321.30 Sweden 591.10.00 Switzerland 559.30.00 Turkey 295.10.00 Ukraine 243.20.00 United Kingdom 4,636.80 Total 25,712.70

Research Sources: Pet Care: Euromonitor from trade sources/national statistics ©2012 Euromonitor International. 21 2. SOCIOLOGICAL AND HUMAN WELFARE ASPECTS OF KEEPING COMPANION ANIMALS

The members of CALLISTO consider it of paramount importance that the project emphasizes the health and human welfare benefits of keeping companion animals, while still emphasizing the need for factual information about the dangers of zoonotic infection from such animals.

2.1 THE SOCIAL AND SOCIETAL REASONS FOR KEEPING COMPANION ANIMALS AND THE BENEFIT TO HUMAN HEALTH AND WELLBEING THAT COMPANION ANIMALS CAN BRING

Various reports indicate that up to 50% of households in countries of the western world keep at least one, and often more than one, companion animal. Pets are kept to varying degrees in every culture of the world and have been kept by people since the domestication of the first animal, the dog, at least 15,000 years ago (Messent and Serpell, 1981; Serpell, 1986). Three theories have been drawn upon to 22

explain the popularity of keeping pets and/or why they provide the benefits to our health and wellbeing discussed below: (1) attachment theory (Bowlby, 1969), first applied to the infant to mother relationship, later to the pet-human bond; (2) socio-emotional support theory (see Collis and McNicolas, 1998), claiming that in times of need companion animals provide us with emotional support helping us to cope; and (3) the ‘biophilia hypothesis’ (Wilson, 1984; Kellert and Wilson, 1993) claiming that we have an innate need to have contact with the natural world, including animals, plants and natural settings. There is indirect evidence to support this hypothesis.

Although few people, even some stakeholders, are aware that keeping pets, especially dogs and cats, might be accompanied by nett human health cost savings (Turner, 2004; Headey and Grabka, 2006) and more research in the direction of a financial cost-benefit analysis is needed, this might be an important societal factor to consider, even if not a reason for keeping a pet on the individual level. Although several studies have considered annual numbers of dog bites, only one (German) government commissioned study has considered the non- financial benefits of contact with companion animals relative to the ‘costs’ (Weber and Schwarzkopf, 2003).

This latter review came to the conclusion that the positive effects for people of keeping companion animals outweighed the potential dangers. Further, that the risk of transmission of viral, bacteriological, fungal or parasitic zoonotic agents from companion animals to people can be strongly reduced by following the rules of hygiene as well as veterinary control combined with vaccination of the animals. Lastly, that the risk of an allergic reaction to susceptible persons has to be considered and balanced against the potential increase in Quality of Life to that person of contact with such animals.

Two very recent reviews have summarized the proven benefits of contact and/or interactions with some species of companion animals on human health and wellbeing (Turner et al., in press; Julius et al., in press, respectively; Beetz et al., 2012). The former review first considers benefits (mostly) of dogs to the general public before considering the therapeutic effects of animal-assisted interventions on people of different ages with specific needs. The latter review considers the design (e.g. control group or not; cross-over), sample sizes and statistical analyses of the studies before being included in the review.

From Turner et al. (in press) the following effects in the general public have been established:

• Acquisition of a pet reduces complaints about minor health problems and improves measurable Quality of Life. • Pet ownership (as a main factor) predicts higher 1-year survival rates after hospitalization for acute myocardial infarction. 23

• Pet owners have lower levels of risk factors for cardiovascular disease. • Pet owners visit their primary physicians significantly less often over a 1-year period than non-owners. • Cat and dog (but not pocket-pet) owners spend a relatively lower proportion of their income on human health care expenses than non-pet owners. • Empathy toward people is increased by increasing empathy toward animals in children and the effect is long-lasting. • Pets act as social facilitators for increased social contact with other people and the effect is robust for children, adults (including the elderly), physically challenged persons and non-communicative persons. • Pets provide important emotional support to children.

Turner et al. (in press) list the following health conditions to which animal-assisted interventions have been successfully applied:

• Aphasic patients in psychotherapy • PVS, apallic syndrome • ADHD- and Conduct Disorder in children • Children with reading difficulties • Down’s Syndrome • Autism spectrum disorders • Alzheimer’s disease patients • Neurological/motor dysfunction • Physically challenged persons

Beetz et al. (2012), with strenuous inclusion criteria for that review, conclude the following, significant positive effects of human-animal interaction:

Effects on Social Interaction: • Increased positive social attention from others and stimulation of social behaviour • Effects on empathy • Reduction of aggression • Reduction of depression and promotion of positive mood

Anti-Stress Effects: • Effects on cortisol, epinephrine, and norepinephrine • Effects on blood pressure, heart rate, and heart rate variability

Effects on Anxiety and : • Reduction of fear and anxiety and promotion of calmness • Effects on perception of pain (reduction)

Effects on Learning (improvement) 24

Effects on Human Health and Restoration: • Cardiovascular disease (survival and prevention) • Immune system effects

2.2 THE SOCIETAL VALUE OF PETS BY HUMAN AGE GROUP

Companion animals are indeed companions to people. Cats and dogs are used for emotional support or have specific working roles (e.g. as guides for visually or hearing impaired people, rescue dogs, shepherding dogs, military dogs and dogs working to locate bombs or drugs).

The benefits are seen across the age groups from pre-school children through to the elderly. These effects have been reported in numerous original research studies and summarized in several book chapters. Most of the studies have been conducted using companion dogs, then cats, but there are also occassional studies reporting positive effects of farm animal species (mammals, but also chickens). Rarely do the studies employ exotic animals or reptiles/amphibians. Although horses have long been used in therapy (and hippotherapy is recognized by heath insurance companies) only fairly recently have studies on the effectiveness of therapeutic riding been published.

2.2.1 BENEFITS OF PET KEEPING FOR CHILDREN

• Being attached to a pet is related to positive emotional function. • Both social as well as cognitive development can be enhanced by owning a pet. • Positive self-esteem of children is enhanced by owning a pet. • Pets provide social support to children. • Presence of animals increases social contact between children. • Child-companion animal interaction generally facilitates childhood development. • Children with a strong pet bond have higher scores on empathy than children without pets. • Children perceive their pets as special friends, important family members and providers of social interactions, affection and emotional support. • Children state that their pets know when they are upset and that pets help them feel better. 25

For children with special needs, there is increased awareness of the benefits of pet-assisted therapy. Pets as facilitators in hospital situations are a challenge to the staff, but of benefit to the children:

• Animals help children overcome physical and emotional challenges. • The presence of animals in a stressful situation causes reduced heart rate and blood pressure in children. • Service dogs are valuable additions to parents raising a child with autism, especially in the areas of social acknowledgement, improved child safety and companionship.

For children in hospitals:

• Pet-assisted therapy relieves stress, normalizes the hospital milieu and improves patient and parent morale. • Pet-assisted therapy may be a useful adjunct to traditional pain management for children.

HEALTH IMPLICATIONS IN CHILDREN

Recent studies have shown that the risk of adverse health effects on children exposed to pets is minimal:

• Dog keeping in infancy may offer protection from allergy. • Pet keeping during the first year of life is not associated with an increased risk of atopy at 4 years. • Pet ownership is unrelated to an increased risk of childhood leukaemia. • Living with a pet was not associated with an increased risk of gastroenteritis in young children. The exception to this is the keeping of reptiles and amphibians, which is not recommended for households with children <5 years of age due to the possible risk of salmonellosis.

2.2.2 BENEFITS OF PET KEEPING FOR ADOLESCENTS

There is a surprising lack of controlled studies on the effect of pet- assisted companionship in adolescents. Anecdotal reports indicate a positive effect of human-animal interaction in this period, with production animals, horses and companion animals.

Adolescence is a difficult period, and coping may be difficult even for teenagers in well-functioning families with a good social network, and even more for adolescents with special needs. When leaving the child welfare system, adolescents meet challenges that those in normal family situations do not have to handle alone. The lack of a family network may further complicate situations, with feeling of loneliness 26

and lack of support. Studies have shown that former child welfare clients achieve lower education levels as adults than their peers in the general population. They have lower income and are more often unemployed. More of the former clients receive social security benefits. The benefit of pet-assisted companionship in this group of people should be further investigated.

Even young students experience the positive effects of companion animals. It has been found that students who live with a pet are less likely to report feeling lonely or depressed. They often rely on the animal to help them through stressful times.

2.2.3 BENEFITS OF PET KEEPING FOR ADULTS

The health benefits of pets can be considered in separate categories, although these factors overlap to some extent. These categories are:

• Therapeutic • Psychological • Physiological • Psychosocial

Compared with people without a pet, people who keep a pet have been reported to:

• Require fewer visits to the doctor. • Adapt more quickly to stress associated with bereavement and other adverse events. • Have stronger emotional stability and maintain a generally sounder state of health. • Have higher survival rates 1 year after hospital admission for coronary heart disease. • Have improved cardiovascular health. • Have reduced blood pressure when patting and talking to a pet dog or cat (for patients with hypertension who were under stress). • Have lower systolic blood pressure and lower levels of serum triglycerides (dog owners) compared with non-dog owners.

The direct economic impact regarding visits to the doctor can be outlined as follows:

• Annual national health expenditure in Australia would increase by $3.86 billion (7.19 %) if pet owners visited a doctor as often as non- pet owners. • In China, urban women aged 25–40 who are dog owners make fewer than half the number of visits to a doctor compared with non- owners, and average 2.92 fewer visits per year. 27

• Elderly people with dogs visit physicians 21% less often than do those without a dog. • When hospitalised, Canadian pet owners spend on average 38% less time in hospital (8 versus 13 days). • Expenditure for the Canadian insurance companies in order to cover health related expenses per person: -- Pet owners: €36, 000 -- Non-owners: €47, 500 • In a country like Norway, with a population of 4 million inhabitants, this means a net saving of €88 million annually for the ten largest hospitals (average cost/day estimated low: €625). • For Belgium with 10.5 million inhabitants, this equals €231 million annually.

2.2.4 BENEFITS OF PET KEEPING FOR THE ELDERLY

The direct health effects are similar to those for adults.

However, the social and, thus secondarily, the economic positive effect in healthcare for the elderly has received increasing awareness. Elderly people constitute a segment of the population at heightened risk for a variety of physical and emotional problems. The use of specially trained companion animals in institutions is increasing and the positive effect of this intervention has been documented.

REFERENCES

Bjerkås, E., 2007. The economic importance of companion animals. FECAVA (Federation of European Companion Animal Veterinary Associations). FECAVA, 2009. Health benefits (socioeconomic value) of companion animals - a review of the literature with focus on essential aspects.

2.3 ZOONOTIC DISEASE ASPECTS RELEVANT FOR HUMAN AND ANIMAL WELFARE

We reviewed information available on the link between animal health and public health, especially as it relates to companion animals, and conclude the following: Since most zoonotic diseases are not reportable nationally, information on pet-associated zoonotic disease burden is generally incomplete and not reliable, leading to categorizing 28

them as being of low priority. Therefore, pet zoonoses are generally inadequately identified and managed by public health agencies.

Information pertaining to pets or pet ownership is not collected routinely by health care practitioners. Health care practitioners and veterinarians should be part of a more integrated sentinel surveillance system for zoonotic disease. This information could in turn be used to educate the public on measures of how to prevent disease and promote health. Veterinarians should have some understanding of the health and well-being of a pet’s owner and family members, and should be in a position to discuss the possible risk of zoonotic infections, which could certainly contribute to prevention of zoonotic disease of pet owners or persons working closely with companion animals.

According to the former president of the European Association of Establishments for Veterinary Education (EAEVE), Marcel Wanner, Directive 2005/36/EC, Article 38 (3d) mandates that veterinary training include “adequate knowledge of… including a special knowledge of the diseases which may be transmitted to humans” (Wanner, pers. comm.). This may be taught in various disciplines (microbiology, veterinary public health, epidemiology, etc.) and is (only) controlled when a faculty is externally evaluated. The exact content of zoonotic knowledge, resp. which zoonoses are to be covered, is not specified, only that “knowledge about zoonoses” is provided.

Studies have also shown that pet owners and pet distributors have knowledge gaps and often do not understand the disease risks associated animals. Furthermore, there appears also to be an inadequate understanding among day-care staff, school teachers, and healthcare practitioners, pertaining to the screening and safe handling of pets and the risks of disease transmission. Human-animal interaction organizations, such as those gathered in IAHAIO, indeed warn about the need for proper veterinary care and immunization of companion animals used in school and therapeutic programs (IAHAIO, 2012); the International Society for Animal-Assisted Therapy requires that its members, which offer training to therapists and pedagogues, cover common zoonoses and hygiene plans in their courses (ISAZ, 2012).

Healthcare practitioners could also be encouraged to provide information and education to their patients, given the lack of public awareness of zoonoses associated with pets.

There is growing evidence of the link between three specific diseases in livestock and the presence of faeces from infected companion animals on grazing land. Among the wide range of diseases that could be transmitted from companion animals to livestock, the scientific literature focuses mainly on: • Neosporosis (which can cause abortions in cattle) • Toxoplasmosis (which can cause abortions in sheep and goats) 29

• Sarcocystosis (which can cause neurological disease and death in sheep)

More information is required on how these various zoonotic diseases affect the welfare of the companion animals themselves.

2.4 INFORMATION ALREADY AVAILABLE TO DOG, CAT AND HORSE OWNERS ON RISK OF ZOONOSES

We reviewed information already available to pet owners on risk of zoonoses from various sources (e.g. websites, brochures, etc.), considering the content, ease of access and “balance” of how that information was presented. Information was gathered using an Excel sheet matrix (example in Annex VII-I) form.

WHO, the US CDC, the European CDC, the OIE – the World Organization for Animal Health, the ESCCAP (parasites), Euromonitor International (on the pet population), FEDIAF– The European Pet Food Industry (and leading individual companies via FEDIAF, which did not reply), IFAH – the International Federation for Animal Health Europe and through IFAH, major veterinary pharmaceutical companies (but to no avail), the European Commission and Council of Europe (mostly on legislation and policy, not to be summarized here), the AVMA, and various NGOs as examples: In The Netherlands (Koninklijke Nederlandse Maatschappij voor Diergeneeskunde; Landelijk InformatieCentrum Gezelschapsdieren; Institute for Risk Assessment Sciences, University of Utrecht); France (Fondation A. et P. Sommer); Switzerland/Germany (IEMT, resp. Pets in Society); and in the UK (Dogs Trust and Cats Protection).

The World Health Organization (WHO) has four websites relevant to this this topic:

1. www.who.int/neglected_diseases/zoonoses/en/ 2. www.who.int/ith/diseases/rabies/en/ 3. www.who.int/tdr/news/2011/zoonoses-research/en/ 4. www.who.int/zoonoses/en/

First concerning the WHO websites: There is no mention of the role or value (health benefits) of companion animals on the four start pages 30

listed above, nor any of their first level sub-menu pages. However, in a web link to PAHO’s (a division of WHO) Perspectives in Health - The Magazine of the Pan American Health Organization, Volume 10, Number 1, 2005, many health benefits of companion animals, especially dogs and cats, are listed, and responsible pet ownership (RPO) is promoted, including a general warning that one should regularly vaccinate (especially for rabies) and de-worm dogs and cats. On this latter web link the balance is tipped in favor of companion animals with relatively little information on zoonotic diseases. Back to the WHO websites, there is information on zoonoses: On (4) above, one finds the definition of zoonoses and general information with examples of bacteria (including campylobacteriosis, leptospirosis, Q fever), parasites (including echinococcosis, toxoplasmosis), viruses (including rabies, avian influenza), fungi and unconventional agents (BSE). On (1) above, besides defining neglected zoonotic diseases (NZD), echinococcosis and rabies are listed and figures on impact - numbers and costs - are listed (55,000 rabies deaths annually mostly in Asia and Africa). Recommendations on zoonosis risk reduction are provided (only for rabies), whereas most EU countries are at low to at most moderate risk.

The WHO website (1) makes the following recommendation concerning Neglected Zoonotic Diseases (NZDs): Successful prevention and control of NZDs rests on three key requirements:

Assess the needs of communities and their livestock and pets affected by NZDs;

• Use integrated approaches to cure, prevent and control disease at the human-animal interface; and • Use evidence-based advocacy to leverage resources and commitment for control from the national and international community.

The WHO websites make no specific link between animal health and welfare and between animal and human health but there is a reference to cooperation between WHO-OIE-FAO (www.who.int/influenza/ resources/documents/tripartite_concept_note_hanoi_042011_ en.pdf).

As for many of the web-based information sources, there is no control of the effectiveness of information provided directly on the WHO websites, although in our opinion, the information provided on rabies is excellent, with WHO being the most important source of information on that zoonosis. Nevertheless, WHO provides excellent, downloadable pdfs on Neglected Zoonoses (WHO, 2010a); Neglected Tropical Diseases (WHO, 2010b); and Avian Influenza (WHO, 2007).

The US Centers for Disease Control (US CDC) provide easy to understand information on zoonoses for different groups (pet owners, people at 31 extra risk, as well as for health professionals). The website www.cdc. gov/healthypets/ can be browsed either by animalspecies (birds, cats, dogs, farm animals, fish, horses, reptiles, wildlife, pocket pets) or by disease (practically all) and is extremely well designed. Our evaluation of the website (see the attached CDC-Matrix, Annex VII-I) found it to be well balanced (including mention of the value and health benefits of companion animals), extremely informative and easy to use, with information on prevention and links to downloadable brochures.

When one browses by species (e.g. “dog”) and already knows the name of the zoonosis of interest, the US CDC website also contains easily understood measures on prevention and reducing risk. However, laypersons do not always know the name of a particular zoonotic disease in the long list of such (to ‘browse by disease’), emphasizing the need for information from health care specialists and veterinarians to the pet owners.

Interestingly, website of the European Center for Disease Prevention and Control www.ecdc.europa.eu is quite different from the US CDC site in that it is somewhat less user-friendly but leads to numerous, short reports (pdfs) on specific zoonotic diseases and their prevalence. In reports there is some mention of other categories of animals (wild, farm, exotic etc.), but on the website there is no mention of the value or health benefits of companion animals, therefore no balance between costs and benefits. Nor are preventive measures to reduce risk mentioned or other recommendations made. Nevertheless, the links between animal health and welfare and between animal and human health are well described. No controls on the effectiveness of information transfer are mentioned.

The European Scientific Counsel for Companion Animal Parasites (ESCCAP), an independent organisation, is dedicated to providing access to clear and constructive information for veterinarians and pet owners with the aim of strengthening the animal-human bond. Its pet owners’ website has been designed to bring expert and independent information on how best to protect pets and family from the parasitic threats found in the UK and abroad. www.esccapuk.org.uk/petowners. php?run=zoonoses.

The European website (www.esccap.eu in French and Dutch), as well as brochures provided us by the ESCCAP secretariat, include folders which cover mostly dogs and cats, health risks for children and pregnant women, and recommendations for risk reduction, but do not mention the value of companion animals or their health benefits. Access to information on the Internet is not easy to find.

From generally searching the Internet there are other websites providing scientific information on zoonotic risks. Another category of websites and blogs provide information on zoonotic diseases and 32

include preventive measures for pet owners: • www.squidoo.com/10-diseases-you-can-catch-from-pets • blogs.discovermagazine.com/80beats/2011/12/12/diseases-you- can-get-from-your-pets- plague-mrsa-meningitis/ • www.petplace.com/dogs/diseases-you-can-catch-from-your-dog/ page1.aspx • pets.webmd.com/diseases-you-can-get-from-your-pets • ncceh.ca/sites/default/files/Household_Pets_Zoonoses_Jan_2012. pdf • www.vetmed.ucdavis.edu/vetext/INF-DI/Pet-ZD-nat-disasters.pdf

Generally, but with exceptions, we have found that web sites primarily with information about zoonotic diseases neglect the fact that dogs, cats, other pets and horses, can also bring health benefits to their owners, and rarely mention preventive measures, while web sites promoting responsible pet ownership (RPO), especially those from the pet food industry, and national human-animal bond organisations, hardly mention zoonoses. However, a number of pet food industry- sponsored, school educational packages do at least mention that animals can carry diseases and that basic hygiene rules need to be followed after contact. A better balance of information should be aimed for to increase adherence. The veterinary pharmaceutical industry (individual companies) did not comply with our request for brochures on products to treat zoonotic infections, and we could therefore not assess the “balance” of product information. Further, hardly any websites or organizations control (or report on) the effectiveness of the information they provide, e.g. ‘number of hits per month’, comments by readers, numbers of pdfs ordered. These are all points to be considered when making recommendations for action later on.

REFERENCES

Beetz, A., Uvnäs-Moberg, K., Julius, H., Kotrschal, K., 2012. Psychosocial and psychophysiological effects of human-animal interactions: the possible role of oxytocin. Frontiers in Psychology 3, 1-15. DOI: 10.3389/ fpsyg.2012.00234 Bowlby, J., 1969. Attachment and Loss: Volume 1. Attachment. Penguin Books, London, 425 pp. Collis, G., McNicolas, J., 1998. A theoretical basis for health benefits of pet ownership: attachment vs. psychological support. In: Wilson, C.C., Turner, D.C. (Eds.) Companion Animals in Human Health, Sage Publications, Thousand Oaks, pp. 105 ‒ 122. Headey, B., Grabka, M.M., 2007. Pets and human health in Germany and Australia: National longitudinal results. Social Indicators Research 80, 297-311. DOI 10.1007/s11205-005-5072-z IAHAIO, International Association of Human-Animal Interaction 33

Organizations, Declarations. http://iahaio.org/pages/declarations/ declarations.php accessed September, 2012. ISAZ, International Society for Animal-Assisted Therapy. See “ISAAT Standards” for Institutions with Programmes of Continuing Education in Animal-Assisted Activities, Animal- Assisted Pedagogy and/or Animal- Assisted Therapy. http://www.aat-isaat.org accessed September, 2012. Julius, H., Beetz, A., Kotrschal, K., Turner, D., Uvnäs Moberg, K. (in press, 2012). Effects of human-animal interaction on health, social interaction, mood, autonomous nervous system and hormones, Chapter 3, Table 1. In: Julius, H. et al., Attachment to Pets. An integrative view of human- animal relationships with implications for therapeutic practice, Hogrefe Verlag, Goettingen. Kellert, S., Wilson, E.O. (Eds.), 1993. The Biophilia Hypothesis, Island Press, Washington, D.C., 484 pp. Messent, P., Serpell, J., 1981. A historical and biological view of the pet- owner bond. In: Fogle, B. (Ed.), Interrelations between People and Pets, Charles C Thomas Publisher, Springfield, Ill., pp. 5-22. Serpell, J., 1986. In the Company of Animals, Basil Blackwell, Oxford, 215 pp. Turner, D.C., 2004. Hundehaltung und Gesundheit, Gesundheitskosten. In: Kortrschal, K., Bromundt, V., Föger, B. (Eds.) Faktor Hund. Eine sozio- ökonomische Bestandesaufnahme der Hundehaltung in Österreich, Czernin Verlag, Vienna, pp. 45-46. Turner, D.C., Waiblinger, E., Meslin, F.-X. (in press, 2012). Benefits of the human-dog relationship. In: Macpherson, C.N.L., Meslin, F.-X., Wandeler, A.I. (Eds.), Dogs, Zoonoses and Public Health, CABI Publishers, Wallingford, UK. Weber, A., Schwarzkopf, A. 2003. Heimtierhaltung ‒ Chancen und Risiken für die Gesundheit. Gesundheitsberichterstattung des Bundes, Heft 19. Robert Koch-Institut, Germany. Wilson, E.O., 1984. Biophilia: The human bond with other species, Harvard University Press, Cambridge, 157 pp. World Health Organization, 2007. National Consultation on Avian Influenza, Jakarta, Indonesia, WHO, Geneva, 31 pp. World Health Organizaion, 2010a. The Control of Neglected Zoonotic Diseases, WHO, Geneva, 70 pp. World Health Organization, 2010b. Working to Overcome the Global Impact of Neglected Tropical Diseases, WHO, Geneva, 172 pp. 34 3. POLICY ACTIONS RELATED TO SPREAD OF ZOONOSES

3.1 INTRODUCTION

CALLISTO has investigated the current situation regarding policy actions aiming at the prevention of the spread of diseases by companion animals to food producing animals and people. As policy action we define any legal or non-legal initiatives to influence the way people interact with and take care of the health of their companion animals.

All kinds of companion animals can play a role in the transmission of a wide range of pathogens to food producing animals as well as to people. Depending on the , the companion animal acts as a mechanical vector or as a host animal, multiplying and spreading the pathogen.

Where the companion animal lives in close contact with people or farm animals, there is a particular risk of a constant exchange of (potentially) pathogenic micro-organisms. Since the companion animal itself may not necessarily show clinical signs of the infection/infestation the dissemination of the pathogen can remain undetected for a long time. Moreover for agents with a long incubation period or where no direct contact between the companion animal and the food producing animal or person is required, the link between the transmitter and the diseased can easily be overlooked.

To reduce the above mentioned risks, policy makers, such as competent authorities, NGOs and stakeholder organisations, at international, national and local level can take actions to raise awareness and to influence people’s behaviour towards these animals: either on a mandatory or voluntary basis. 35

3.2 METHODS USED FOR DATA COLLECTION

A questionnaire (Annex II-I) was developed asking for further information about general as well as disease specific policy actions. Questions included amongst others the origin, format and scope of the policy action.

The questionnaire was circulated by e-mail to national authorities, veterinary organisations, and a number of stakeholder organizations (e.g. animal owner organizations, trade organisations) both with and without a representation within the CALLISTO consortium (see list Annex II-III).

Furthermore addressees were invited to forward the questionnaire to their relevant contacts. It was also sent to international organisations such as the Council of Europe, World Veterinary Association (WVA), World Organisation for Animal Health (OIE), the World Health Organisation (WHO) and the United Nations Food and Agriculture Organisation (FAO).

In case the information received was not clear or where it appeared that questions were misinterpreted, respondents were contacted by mail or telephone and asked for further clarification. Responses were received from 21 European countries, 18 EU countries and 3 non-EU countries. Further responses were received from OIE and WHO. Relatively little information came back from countries that joined the EU in 2004 and 2007 and it is not clear whether little or no policy actions are taken in these countries or that they simply did not respond.

The largest group of respondents was formed by the group of veterinary associations, chambers and councils. Several of them have initiated own policy actions, others participate in actions taken by the authorities. On behalf of the Competent Authorities, responses were received from Ministries of Agriculture, Public Health, Chief Veterinary Officers, and food safety Authorities. Further responses were received from pet trade organisations, veterinary faculties, and animal owner and stakeholder organisations and NGOs. (see list Annex II-IV)

Policy actions reported by the respondents include mandatory and voluntary measures, varying from formal legislative measures to less formal guidance documents, support actions, awareness and communication campaigns, etc. They were all put together in a Microsoft Excel file and were categorized according to type of pathogen (viral, bacterial parasitic), disease specificity and country of origin (Annex II-II). 36

3.3 GENERAL, NON-DISEASE SPECIFIC POLICY ACTIONS RELATED TO THE SPREAD OF DISEASES THROUGH COMPANION ANIMALS

The number and character of non-disease specific policy actions varies widely from country to country. On one topic however – “non- commercial movements of companion animals” – the EU has established a harmonized approach based on EU Directive 998/2003. This regulation applies to the movement between Member States or from third countries into the EU of dogs, cats and ferrets. When being moved, these animals must be identified (microchipped) and accompanied by a passport issued by a certifying that a valid rabies vaccination was carried out and where necessary, preventative health measures regarding other diseases were carried out on the animal in question. This Directive also stated that Finland, Ireland, Malta, Sweden and the United Kingdom, as regards echinococcosis, and Ireland, Malta and the United Kingdom, as regards , were allowed to make the entry of pet animals into their territory subject to compliance with the special rules applicable on the date of entry into force of this Regulation until 31st December 2011. Regulation no 1152/2011 has prolonged these specific rules for echinococcosis-free countries until 2017.

Directive 998/2003 furthermore states that Member States shall provide the public with clear and easily accessible information concerning the health requirements that apply for the non-commercial movement of pets in Community territory and the conditions under which they may enter or re-enter such territory. They shall also ensure that personnel at entry points are fully informed of these rules and are able to implement them.

Identification and registration of companion animals, regardless if they travel abroad or stay within the country is mandatory in several EU countries. In some countries the relevant legislation is relatively new and currently introduced in a progressive way, starting with the newborn animals. This mainly applies to dogs, however cats, ferrets and horses have been mentioned as well(see Annex II-II).

Other, more general policy measures include (animal) disease notification which is based on the OIE listed diseases (see Annex II- II). Additionally, the OIE has published generic information on the prevention, detection and control of zoonotic diseases. 37

According to the European legislation, there are 52 (human) communicable diseases and conditions that must be reported within the EU (www.ecdc.europa.eu), of which over 20 are zoonotic.

The European Centre for Disease Prevention and Control (ECDC) together with the European Food Safety Authority (EFSA) produce summary reports on trends and sources of zoonoses, zoonotic agents and food-borne outbreaks annually. They also produce a summary report on antimicrobial resistance in zoonotic and indictor bacteria from humans, animals and food in the EU. Furthermore ECDC produces annual epidemiological reports on all diseases under surveillance, including epidemic intelligence (health threats) data. These reports do not focus on companion animal zoonoses, but include some of the diseases transmissible between companion animals and humans or food-producing animals.

ECDC and EFSA are also investigating the possibilities to set up a joint communication platform for risk assessment of non-foodborne zoonotic diseases at EU level.

Some countries have taken policy actions dealing with dog population management and responsible ownership in order to reduce the number of stray animals. According to CAROdog, stray animals are a problem in at least the following European countries: Bulgaria, Greece, Italy, Latvia (mainly cats), Lituania, the Netherlands (mainly cats), Portugal, Romania and Serbia. However this is not an exclusive list as for several countries no information is available.

While all EU Member States have animal welfare legislation, specific actions targeted at companion animals are generally limited in comparison to farm and research animals. Many countries have established restrictions on the types of animals which may or may not be kept as companion animals, usually based on safety concerns for poisonous or dangerous animals (though the welfare of the animal was a consideration for restrictions in Belgium on the keeping of mammals). No information was found for policy actions in welfare legislation related to transmission of pathogens to people or farm animals.

In the EU there is very little focus on “exotic” companion animals (encompassing all non - domesticated animals kept as companion animals or pets) from a health perspective. Although one can assume frequent contacts between companion animals and wildlife, for example cats catching birds, this has, as far as we know, not led to further policy actions. 38

3.4 POLICY ACTIONS RELATED TO THE SPREAD OF PARASITIC DISEASES THROUGH COMPANION ANIMALS TO PEOPLE AND FOOD PRODUCING ANIMALS

For policy actions relating to parasitic diseases spread by companion animals to people and food producing animals, there is wide diversity in actions: the level of activity varies from country to country as well from disease to disease. Again there is not much information about policy actions in countries that have joined the EU in the last decade.

Echinococcosis is an OIE-notifiable disease. Within the EU special measures have been taken for keeping countries free of Echinococcus multilocularis. EU Member States, able to demonstrate that they are free of these tapeworms (Finland, Ireland, UK and Malta) may require companion animals entering their country to be treated against the parasite. The treatment should take place within a certain time window before the scheduled entry into the Member State concerned.

The European Scientific Council on Companion Animal Parasites (ESCCAP) has developed a very informative and accessible website on a large number of relevant parasitic diseases. The website is available in different languages, including English, French, German, Polish, Italian, Spanish and Dutch. Diseases addressed by ESCCAP include worms (trematodes, cestodes, intestinal and non-intestinal nematodes), ticks and tick borne diseases, other vector borne diseases and protozoa.

Policy actions dealing with the protozoan blood parasite Leishmania, are mainly found in the southern part of Europe (Portugal, Spain and Italy), which is explained by the fact that the vector for the transmission of the parasite, blood-sucking flies of the genus Phlebotomus, are found there. Preventative measures focus on the vector although a canine vaccine has very recently been introduced in Europe.

In different countries we found policy actions targeting a specific disease or situation, such as specific campaigns and brochures.

Apart from the information on ESSCAP, relatively little information was found regarding do’s and don’ts related to the often discussed occurrence of toxoplasmosis in cats. 39

3.5 POLICY ACTIONS RELATED TO THE SPREAD OF BACTERIAL DISEASES THROUGH COMPANION ANIMALS TO PEOPLE AND FOOD

PRODUCING ANIMALS

The websites of the international organisations, OIE and WHO, provide information on a range of bacterial diseases and related issues (e.g. antimicrobial resistance). It should be noticed that although much information is available on these sites, a major part of it is aimed at professional users such as policy makers and veterinarians. For the general public, it might be difficult to find the information they seek, and when found the available information often is quite technical and difficult to understand for lay people. A positive exception is formed by the OIE General Disease Information Sheets which are specifically dedicated to the public at large.

At national level, the number of diseases on which we received information varies. A few that are reported to us more often were salmonellosis, leptospirosis, brucellosis and tularemia. Tularemia can be transmitted directly from cats to people, but also via vectors like ticks. This is why this disease is also covered by ESCCAP on their website.

We received several brochures produced by the Irish Health Service. They cover a wide range of diseases, hygiene measures and other practical tips to reduce the risks of transmission of infectious diseases in a clear and understandable way.

OIE and a number of countries have taken actions to reduce the selection and spread of antimicrobial resistant strains. Some countries have a broader range of notifiable diseases than others. 40

3.6 POLICY ACTIONS RELATED TO THE SPREAD OF VIRAL DISEASES THROUGH COMPANION ANIMALS TO PEOPLE AND FOOD PRODUCING ANIMALS

For several of the targeted diseases, such as influenza, rabies, , Rift Valley fever, sheep and goat pox, etc. the web site of the OIE provides reliable and detailed facts and information on diagnosis, prevention and treatment. The WHO website also provides information on diseases as influenza, SARS and monkey pox.

The disease with the most consistent approach is rabies. Information on policy actions against rabies was received from the majority of countries. In case such information was not received, it probably reflects a shortcoming in the response to the questionnaire rather than the absence of policy actions. Within the EU, all member countries are obliged to take measures to assure that companion animals imported from other EU countries or from third countries are free of rabies. Some countries (e.g. Austria and Finland) have put legal obligations in place that also require the vaccination of certain categories of companion animals (like hunting dogs) even if they do not travel.

West Nile Virus, transmitted by is addressed by ESCCAP guidelines.

3.7 COMPLIANCE WITH POLICY ACTIONS RELATED TO THE SPREAD OF DISEASES THROUGH COMPANION ANIMALS TO PEOPLE AND FOOD PRODUCING ANIMALS

Information received on the compliance with policy actions was scarce. In fact it was too little and too fragmented to draw any reliable conclusion. 41 4. INTRODUCTION TO SPECIFIC ZOONOTIC INFECTIONS

Some bacteria, parasites and viruses causing infection or carried by asymptomatic companion animal carriers are able to cross host barriers and pose risks to the health of humans, food animals or both. Because companion animals often live in close contact with humans and farmed animals, it is important to know which of the infectious agents present in companion animals could have significant effects on human health and food production in Europe. This depends on a number of factors such as the prevalence of the pathogen in the relevant companion animal population in Europe, its mode and frequency of transmission, and the severity of the disease caused in humans and farmed animals. The following three chapters review the main pathogens that can be transmitted from companion animals to humans and/or farmed animals.

The expert advisory groups focused on viral, bacterial and parastic zoonoses had two main tasks during the first year of the project: a. To generate a short list of paradigmatic priority pathogens/ diseases for which the risks and consequences of transmission from companion animals to humans and/or farmed animals are higher. b. To collect and review the data available for each paradigmatic priority pathogen/disease with respect to occurrence in the companion animal population, disease incidence and mortality in humans, current methods for prevention and control of the infection and relevant links to agriculture.

A common objective was to identify and characterize the most important infectious agents in companion animals that constitute a current or potential threat to human health and food producing animals in Europe. It should be noted that for several of the selected pathogens/diseases, very little is known about prevalence in companion animals and disease incidence in humans and therefore about the relative contribution from companion animals to human disease. For others, sporadic data are available in certain countries, but a complete overview for all European countries does not exist. As such, the present work has resulted in the identification of important data gaps that should be filled in the future. 42

A different approach was used to select the paradigmatic priority pathogens/diseases depending on the group of microorganisms (viruses, bacteria or parasites). For bacteria and parasites, the most relevant pathogens were prioritized from a broad list of pathogens (Annex IV-I and V-I) based on expert opinion on their zoonotic potential, mode of transmission and possible consequenses for humans and food animals. For viruses, a ranking system was developed based on a of the existing literature on host range, level of emergence in Europe, and frequency of human infection (Annex III: I-IV). This difference in the methodological approach was mainly due to the scarcity of scientific data on the host range and zoonotic potential of many viruses infecting companion animals, which required a more systematic approach in the collection and analysis of the data. 43 5. VIRAL INFECTIONS

5.1 APPROACH TO IDENTIFICATION OF SIGNIFICANT VIRAL ZOONOSES

The literature was reviewed to identify and list mammalian, avian and fish viruses that have proven ability to cross the species barrier from companion animals to humans and food producing animals. To this end, PubMed was searched for combinations of terms belonging to the following general categories: “virus” AND “companion animal” AND “food production animal” OR “human”. The specific terms in each category are detailed in Annex III-1a and 1b. Viruses of avian and mammalian food producing animals (without report of infection in companion animals) were also included, to account for the risk posed by viruses transmitted from ruminants, pigs and poultry kept as companion animals to humans and food producing animals. Viruses of the production fish species listed in Annex III-1b (without report of infection in ornamental fish) were also included, to record all virus species of importance in these species.

Based on a set of priority criteria, these viruses were ranked for importance, and viruses with highest ranks were chosen for the current report. The criteria used for this prioritization are detailed in Annex III-II. The rank was calculated based on the sum of all criteria, with the criteria of impact and disease in humans and food producing animals only taken into account if the virus is reported in Europe (see Annex III-III). The rank was calculated separately for viruses transmitted from companion animals to humans and for viruses transmitted from companion animals to food producing animals, as well as for vector- borne viruses and non-vector borne viruses. Priority viruses were chosen independently in these four different categories, with ranks equal or higher than 5 for zoonotic viruses and equal or higher than 7 for non-zoonotic viruses.

A total of 148 avian and mammalian viruses that have proven ability to cross the species barrier from companion animals to humans, from companion animals to food animals, or both, were identified by literature 44

search (Annex III-IV). Taking a cut-off > 5 for zoonotic viruses and a cut-off value > 7 for non-zoonotic viruses provided a list representing the top 10% in each category (Annex III-V).

The top-ranked viruses only or primarily of concern for human health were:

• Hantaviruses (Heyman et al., 2009), including Belgrade-Dobrava virus (Papa, 2012) • Tahyna virus (Hubalek, 2008) • Rabies virus (Capello et al., 2010) • West Nile virus (Campbell et al., 2002) • Tick-borne encephalitis virus (Gritsun et al., 2003) • Crimean-Congo haemorrhagic fever virus (Ergonul, 2006) • Aichi virus (Reuter et al., 2011) • European bat lyssavirus (Fooks et al., 2003) • Hepatitis E virus (Kamar et al., 2012) • Cowpox virus (Tack, 2011) • G5 rotavirus (Midgley et al., 2012) • Influenza A virus (Amman et al., 2007; Reperant et al., 2012) • Lymphocytic choriomeningitis virus (Amman et al., 2007) • Astroviruses (De Benedictis et al., 2011) • Noroviruses (Bank- et al., 2010) • Sapoviruses (Bank-Wolf et al., 2010) • Gyroviruses (Sauvage et al., 2011)

The top-ranked viruses only or primarily of concern for food animals were:

• Bluetongue virus (Mellor and Wittmann, 2002) • African swine fever virus (Costard et al., 2009) • Foot and mouth disease virus (Valarcher et al., 2008) • Rabbit haemorrhagic disease virus (Belz, 2004) • Lumpy skin disease virus (Tuppurainen and Oura, 2012) • African horse sickness virus (Maclachlan and Guthrie, 2010) • Rift Valley fever virus (Gerdes, 2004) • Schmallenberg virus (Beer et al., 2013) • Porcine circovirus (Li et al., 2010) • Classical swine fever virus (Edwards et al., 2000) • Equine herpesvirus 9 (Schrenzel et al., 2008) • Peste des Petits Ruminants (Banyard et al., 2010) • Equine infectious anaemia virus (Cappelli et al., 2011)

A total of 22 viruses that have ability to cross the species barrier from ornamental fish to food producing fish were identified by literature search (Annex III-VI). Three viruses, representing the top 10% of the list, were selected among the viruses with a ranking score >= 6. 45

The top-ranked viruses primarily of concern for production fish species were:

• cyprinid herpesvirus-3 (Koi herpesvirus) • viral haemorrhagic septicaemia virus • infectious pancreatic necrosis virus

These are described further below.

The above ranking only is to obtain a rough selection of the viruses of concern. A more detailed assessment of the risks involved with these viruses potentially originating from companion animals will take place in the second year of the CALLISTO project. A description of the 18 top-ranked viruses of concern for either human health or food animal health follows below.

REFERENCES

Amman, B.R., Pavlin, B.I., Albarino, C.G., Comer, J.A., Erickson, B.R., Oliver, J.B., Sealy, T.K., Vincent, M.J., Nichol, S.T., Paddock, C.D., Tumpey, A.J., Wagoner, K.D., Glauer, R.D., Smith, K.A., Winpisinger, K.A., Parsely, M.S., Wyrick, P., Hannafin, C.H., Bandy, U., Zaki, S., Rollin, P.E., Ksiazek, T.G., 2007, Pet rodents and fatal lymphocytic choriomeningitis in transplant patients. Emerg. Infect. Dis. 13, 719-725. Bank-Wolf, B.R., Konig, M., Thiel, H.J., 2010, Zoonotic aspects of infections with noroviruses and sapoviruses. Vet. Microbiol. 140, 204-212. Banyard, A.C., Parida, S., Batten, C., Oura, C., Kwiatek, O., Libeau, G., 2010, Global distribution of peste des petits ruminants virus and prospects for improved diagnosis and control. J. Gen. Virol. 91, 2885- 2897. Beer, M., Conraths, F.J., WH, V.D.P., 2013, ‘Schmallenberg virus’ - a novel orthobunyavirus emerging in Europe. Epidemiol. Infect. 141, 1-8. Belz, K., 2004, Rabbit hemorrhagic disease. Seminars in Avian and Exotic Pet Medicine 13, 100-104. Campbell, G.L., Marfin, A.A., Lanciotti, R.S., Gubler, D.J., 2002, West Nile virus. Lancet Infect. Dis. 2, 519-529. Capello, K., Mulatti, P., Comin, A., Gagliazzo, L., Guberti, V., Citterio, C., De Benedictis, P., Lorenzetto, M., Costanzi, C., Vio, P., Zambotto, P., Ferri, G., Mutinelli, F., Bonfanti, L., Marangon, S., 2010, Impact of emergency oral rabies vaccination of foxes in northeastern Italy, 28 December 2009-20 January 2010: preliminary evaluation. Euro. Surveill. 15. Cappelli, K., Capomaccio, S., Cook, F.R., Felicetti, M., Marenzoni, M.L., Coppola, G., Verini-Supplizi, A., Coletti, M., Passamonti, F., 2011, Molecular detection, epidemiology, and genetic characterization of novel European field isolates of equine infectious anemia virus. J. Clin. Microbiol. 49, 27-33. Costard, S., Wieland, B., de Glanville, W., Jori, F., Rowlands, R., Vosloo, W., Roger, F., Pfeiffer, D.U., Dixon, L.K., 2009, African swine fever: how 46

can global spread be prevented? Philos. Trans. R. Soc. Lond. B Biol. Sci. 364, 2683-2696. De Benedictis, P., Schultz-Cherry, S., Burnham, A., Cattoli, G., 2011, Astrovirus infections in humans and animals - molecular biology, genetic diversity, and interspecies transmissions. Infect. Genet. Evol. 11, 1529-1544. Edwards, S., Fukusho, A., Lefevre, P.C., Lipowski, A., Pejsak, Z., Roehe, P., Westergaard, J., 2000, Classical swine fever: the global situation. Vet. Microbiol. 73, 103-119. Ergonul, O., 2006, Crimean-Congo haemorrhagic fever. Lancet Infect. Dis. 6, 203-214. Fooks, A.R., Brookes, S.M., Johnson, N., McElhinney, L.M., Hutson, A.M., 2003, European bat lyssaviruses: an emerging zoonosis. Epidemiol. Infect. 131, 1029-1039. Gerdes, G.H., 2004, Rift Valley fever. Rev. Sci. Tech. 23, 613-623. Gritsun, T.S., Lashkevich, V.A., Gould, E.A., 2003, Tick-borne encephalitis. Antiviral Res. 57, 129-146. Heyman, P., Vaheri, A., Lundkvist, A., Avsic-Zupanc, T., 2009, Hantavirus infections in Europe: from virus carriers to a major public-health problem. Expert Rev. Anti. Infect. Ther. 7, 205-217. Hubalek, Z., 2008, -borne viruses in Europe. Parasitol. Res. 103 Suppl 1, S29-43. Kamar, N., Bendall, R., Legrand-Abravanel, F., Xia, N.S., Ijaz, S., Izopet, J., Dalton, H.R., 2012, Hepatitis E. Lancet 379, 2477-2488. Li, L., Kapoor, A., Slikas, B., Bamidele, O.S., Wang, C., Shaukat, S., Masroor, M.A., Wilson, M.L., Ndjango, J.B., Peeters, M., Gross-Camp, N.D., Muller, M.N., Hahn, B.H., Wolfe, N.D., Triki, H., Bartkus, J., Zaidi, S.Z., Delwart, E., 2010, Multiple diverse circoviruses infect farm animals and are commonly found in human and chimpanzee feces. J. Virol. 84, 1674- 1682. Maclachlan, N.J., Guthrie, A.J., 2010, Re-emergence of bluetongue, African horse sickness, and other orbivirus diseases. Vet. Res. 41, 35. Mellor, P.S., Wittmann, E.J., 2002, Bluetongue virus in the Mediterranean Basin 1998-2001. Vet. J. 164, 20-37. Midgley, S.E., Banyai, K., Buesa, J., Halaihel, N., Hjulsager, C.K., Jakab, F., Kaplon, J., Larsen, L.E., Monini, M., Poljsak-Prijatelj, M., Pothier, P., Ruggeri, F.M., Steyer, A., Koopmans, M., Bottiger, B., 2012, Diversity and zoonotic potential of rotaviruses in swine and cattle across Europe. Vet. Microbiol. 156, 238-245. Papa, A., 2012, Dobrava-Belgrade virus: phylogeny, epidemiology, disease. Antiviral Res. 95, 104-117. Reperant, L.A., Kuiken, T., Osterhaus, A.D., 2012, Influenza viruses: from birds to humans. Hum. Vaccin. Immunother. 8, 7-16. Reuter, G., Boros, A., Pankovics, P., 2011, Kobuviruses - a comprehensive review. Rev. Med. Virol. 21, 32-41. Sauvage, V., Cheval, J., Foulongne, V., Gouilh, M.A., Pariente, K., Manuguerra, J.C., Richardson, J., Dereure, O., Lecuit, M., Burguiere, A., Caro, V., Eloit, M., 2011, Identification of the first human gyrovirus, a virus related to chicken anemia virus. J. Virol. 85, 7948-7950. 47

Schrenzel, M.D., Tucker, T.A., Donovan, T.A., Busch, M.D., Wise, A.G., Maes, R.K., Kiupel, M., 2008, New hosts for equine herpesvirus 9. Emerg. Infect. Dis. 14, 1616-1619. Tack, D.M., 2011, Zoonotic poxviruses associated with companion animals. Animals 1, 377-395. Tuppurainen, E.S., Oura, C.A., 2012, Review: lumpy skin disease: an emerging threat to Europe, the Middle East and Asia. Transbound. Emerg. Dis. 59, 40-48. Valarcher, J.F., Leforban, Y., Rweyemamu, M., Roeder, P.L., Gerbier, G., Mackay, D.K., Sumption, K.J., Paton, D.J., Knowles, N.J., 2008, Incursions of foot-and-mouth disease virus into Europe between 1985 and 2006. Transbound. Emerg. Dis. 55, 14-34.

5.2 VIRUSES OF PRIMARY CONCERN TO HUMAN HEALTH

5.2.1 RABIES VIRUS

AETIOLOGY Rabies virus is a negative single-strand RNA virus in the genus Lyssavirus of the family Rhabdoviridae.

ANIMAL SPECIES INVOLVED Rabies virus infects a variety of wild and domestic animals, including, in Europe, red foxes, dogs, other wild terrestrial carnivores, cattle, sheep, goats, dogs and cats. In Europe, the red fox is the main reservoir host. Domestic animals, primarily domestic dogs and cats, forge the link between infected wildlife and humans (Rupprecht et al., 2001). Transmission principally occurs by the bites of infected carnivores (Rupprecht et al., 2001).

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES Rabies virus infection causes neurological disease and is nearly always fatal. The pathology is characterized by non-suppurative encephalomyelitis with eosinophilic intracytoplasmic inclusions in affected neurons (Rupprecht et al., 2001).

IMPACT ON HUMAN HEALTH Rabies is a major health risk for people in most developing countries. Annually, approximately 50,000–100,000 cases of human rabies may occur worldwide. There is no effective treatment for clinical rabies, but prompt post exposure prophylaxis will almost always prevent disease. 48

Many developed countries have successfully controlled domestic animal rabies. In these countries, the economic and emotional impact of evaluating exposure for rabies prophylaxis exacts a much greater toll than the disease itself. Even in the absence of direct mortality, rabies results in numerous expenditures, including expensive human vaccination, a complicated medical infrastructure and lost wages (Rupprecht et al., 2001).

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL Preventative measures in areas where rabies re-emerged in Italy included compulsory rabies vaccination of dogs and domestic at risk of infection (i.e. cows, horses, sheep and goats kept outdoors), prohibition of hunting with dogs, enhancement of surveillance in the wild animal population and implementation of oral rabies vaccination campaigns (De Benedictis et al., 2008).

LINK TO AGRICULTURE While livestock such as cattle, sheep and goats may be infected by rabid wildlife, the main concern about rabies is for human health.

REASONS FOR CONCERN Although rabies is largely under control in Europe through oral vaccination of red foxes, rabies virus re-emerged in Italy—which was classified as rabies-free since 1997—in 2008. In that year, two foxes were diagnosed with rabies in the Province of Udine, north-east Italy. One case of human exposure caused by a bite from one of the foxes occurred, but luckily was properly treated (De Benedictis et al., 2008). This outbreak shows that there is a risk of re-emergence of rabies in Europe, with potential involvement of domestic dogs and cats, and impact on human health.

REFERENCES De Benedictis, P., Gallo, T., Iob, A., Coassin, R., Squecco, G., Ferri, G., D’Ancona, F., Marangon, S., Capua, I., Mutinelli, F., 2008, Emergence of fox rabies in north-eastern Italy. Euro. Surveill. 13, pii: 19033. Rupprecht, C.E., Stöhr, K., Meredith, C., 2001, Rabies, In: Williams, E.S. (Ed.) Infectious diseases of wild mammals. Iowa State University Press, Ames, Iowa, pp. 3-36.

5.2.2 WEST NILE VIRUS

AETIOLOGY West Nile virus (WNV) is a member of the Japanese encephalitis antigenic complex of the genus Flavivirus, family Flaviviridae.

ANIMAL SPECIES INVOLVED Birds, mammals, reptiles and amphibians may be infected by WNV, but 49 wild birds are the main amplifying host species (Hubalek and Halouzka, 1999). Horses are affected severely by WNV infection, and natural infection also has been identified in domestic cats. Experimental studies suggest that horses are dead-end hosts for WNV, but this issue deserves further study (Campbell et al., 2002). Experimental infection of domestic dogs and cats indicated that neither species is likely to function as an epidemiologically important amplifying host, although the peak viraemia observed in cats may be high enough to infect mosquitoes at low efficiency (Austgen et al., 2004).

MODE/S OF TRANSMISSION WNV is mainly transmitted by bird-feeding mosquitoes, predominantly of the genus Culex. In Europe, WNV circulation is confined to two basic types of cycles and ecosystems: rural (sylvatic) cycle (wild, usually wetland birds and ornithophilic mosquitoes) and urban cycle (synanthropic or domestic birds and mosquitoes feeding on both birds and humans, mainly Cx. pipiens/molestus). The principal cycle is rural, but the urban cycle predominated in Bucharest during the 1996-97 outbreak (Hubalek and Halouzka, 1999).

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES WNV infection in horses can cause fever and encephalomyelitis, and may have a moderate to high case fatality rate. Infection of dogs and pigs is asymptomatic. Infection of sheep can lead to fever, abortion, and encephalitis (Hubalek and Halouzka, 1999). WNV was detected in seven captive psittacines (six rosellas and a Prince of Wales parakeet) that had died suddenly, some with neurological signs (Crespo et al., 2009).

IMPACT ON HUMAN HEALTH Most human WNV infections are subclinical but clinical infections can range in severity from uncomplicated fever to fatal meningoencephalitis; the incidence of severe neuroinvasive disease and death increase with age (Campbell et al., 2002). At autopsy, fatal WNV infection is characterized by a non-suppurative meningoencephalitis.

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL Preventive measures in humans focus on the use of mosquito repellents and limiting outdoor activity during peak mosquito periods. Mosquito control measures by large sprays of insecticides are not efficient, partly due to the large variety of mosquito populations involved in the cycle of transmission. There is no human vaccine available. Killed vaccines have been used in horses (Campbell et al., 2002; Zeller and Schuffenecker, 2004).

LINK TO AGRICULTURE The main concern of WNV is for companion animals (horses) and humans. 50

REASONS FOR CONCERN The occurrence of outbreaks of WNV infection in humans and horses in Europe and the Mediterranean basin remains unpredictable, as was most recently shown by human cases of WNV infection that were detected in several European and Mediterranean countries in 2010 (Danis et al., 2011). Many bird species, including pet birds, may be hosts for WNV, and so potentially either transport the virus to a new area, or act as a local amplifying host for the virus.

REFERENCES Austgen, L.E., Bowen, R.A., Bunning, M.L., Davis, B.S., Mitchell, C.J., Chang, G.J., 2004, Experimental infection of cats and dogs with West Nile virus. Emerg. Infect. Dis. 10, 82-86. Campbell, G.L., Marfin, A.A., Lanciotti, R.S., Gubler, D.J., 2002, West Nile virus. Lancet Infect. Dis. 2, 519-529. Crespo, R., Shivaprasad, H.L., Franca, M., Woolcock, P.R., 2009, Isolation and distribution of West Nile virus in embryonated chicken eggs. Avian Dis. 53, 608-612. Danis, K., Papa, A., Theocharopoulos, G., Dougas, G., Athanasiou, M., Detsis, M., Baka, A., Lytras, T., Mellou, K., Bonovas, S., Panagiotopoulos, T., 2011, Outbreak of West Nile virus infection in Greece, 2010. Emerg. Infect. Dis. 17, 1868-1872. Hubalek, Z., Halouzka, J., 1999, West Nile fever--a reemerging mosquito- borne viral disease in Europe. Emerg. Infect. Dis. 5, 643-650. Zeller, H.G., Schuffenecker, I., 2004, West Nile virus: an overview of its spread in Europe and the Mediterranean basin in contrast to its spread in the Americas. Eur. J. Clin. Microbiol. Infect. Dis. 23, 147-156.

5.2.3 TICK-BORNE ENCEPHALITIS VIRUS

AETIOLOGY Tick-borne encephalitis virus (TBEV) is a single-strand positive RNA virus in the genus Flavivirus of the family Flaviviridae.

ANIMAL SPECIES INVOLVED Many different mammalian species can act as hosts for the virus. However, in the natural environment, TBEV is maintained in a cycle involving ticks and wild hosts, mainly small wild rodent species (Gritsun et al., 2003).

MODE/S OF TRANSMISSION Under natural conditions humans walking through the dense vegetation in forests are most likely to become infected with TBEV following the bite of an infected tick. Another natural route of human TBEV infection is associated with the consumption of raw milk of goats, sheep or cows (Gritsun et al., 2003). 51

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES In endemic areas, high seroprevalence in domestic dogs indicates that they are highly susceptible to infection (Pfeffer and Dobler, 2011).

IMPACT ON HUMAN HEALTH Tick-borne encephalitis is the most important tick-borne viral disease of humans in Eurasia with an estimated annual number up to 10,000 cases in Russia and 3,000 cases in Europe. Clinical disease is often diphasic, with a non-specific flu-like illness, then an asymptomatic period followed by meningoencephalitic symptoms. Approximately, two-thirds of cases are asymptomatic or only show the first clinical stage before symptoms subside (Gover et al., 2011; Pfeffer and Dobler, 2011).

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL Prevention and control in humans include mapping and surveillance of natural foci of TBEV, pasteurization of milk, protection from tick exposure (e.g. clothing, repellents), vector tick control, and vaccination. A 5-to-10 fold decrease of TBE incidence has been reported in European countries after frequent vaccination of population (Hubalek and Rudolf, 2012).

LINK TO AGRICULTURE Although TBEV infection can affect multiple livestock species, including cattle, sheep and goats, the main concern about TBEV is for human health.

REASONS FOR CONCERN Being a dog owner in an endemic area increases the risk of being bitten by a tick, simply because of the increased time spent outdoors compared with people not regularly walking a dog. In addition, ticks attached to dogs (dogs are 50 to 100 times more likely to come in contact with disease-carrying ticks than people) are brought into the house, where they may infect humans, particularly children, who play with the dog indoors (Pfeffer and Dobler, 2011). In addition, travel of dogs from endemic areas may allow TBEV to be introduced and to become established in parts of Europe that are currently free, e.g. the U.K. (Gover et al., 2011).

REFERENCES Gover, L., Kirkbride, H., Morgan, D., 2011, Public health argument to retain current UK national controls for tick and tapeworms under the Pet Travel Scheme. Zoonoses Public Health 58, 32-35. Gritsun, T.S., Lashkevich, V.A., Gould, E.A., 2003, Tick-borne encephalitis. Antiviral Res 57, 129-146. Hubalek, Z., Rudolf, I., 2012, Tick-borne viruses in Europe. Parasitol. Res. 111, 9-36. 52

Pfeffer, M., Dobler, G., 2011, Tick-borne encephalitis virus in dogs--is this an issue? Parasit. Vectors 4, 59.

5.2.4 CRIMEAN-CONGO HAEMORRHAGIC FEVER VIRUS

AETIOLOGY Crimean-Congo haemorrhagic fever virus (CCHFV) is a negative single- strand RNA virus in the genus Nairovirus of the family Bunyaviridae.

ANIMAL SPECIES INVOLVED The virus has been isolated from numerous domestic and wild , including cattle, goats, sheep, hares, hedgehogs, a Mastomys spp. mouse and domestic dogs. Serum antibodies have been detected in several species of wild mammals, as well as domestic cattle, horses, donkeys, sheep, goats and pigs (Whitehouse, 2004). Ostriches also may be infected (Capua, 1998). Antibody was also found in the sera of 118/1,978 domestic dogs (Shepherd et al., 1987).

MODE/S OF TRANSMISSION CCHFV can be transmitted by ticks of several genera, predominantly Hyalomma spp. (Whitehouse, 2004).

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES In contrast to severe haemorrhagic disease in man, the infection is inapparent in most other vertebrate hosts (Whitehouse, 2004).

IMPACT ON HUMAN HEALTH The disease occurs sporadically throughout much of Africa, Asia and Europe. CCHFV infection is characterized by a sudden onset of high fever, chills, severe headache, dizziness, back and abdominal pain. Haemorrhagic manifestations develop in severe cases and result in an approximately 30% fatality rate (Whitehouse, 2004).

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL The best means of preventing disease is to avoid or minimize exposure to the virus. Acaricide treatment of livestock in CCHFV endemic areas is effective in reducing the population of infected ticks. Use of commercially available insect repellents, as well as prompt removal of ticks from skin and clothing, can give some protection against tick bites and infection. A suckling mouse brain, formalin-inactivated vaccine has been used in Bulgaria and other parts of Eastern Europe and the former Soviet Union (Whitehouse, 2004).

LINK TO AGRICULTURE The main concern for CCHFV is for human health. 53

REASONS FOR CONCERN Several recent outbreaks of CCHF have occurred in Turkey and clusters of cases have been observed recently in Balkan countries (Ergonul, 2006). CCHFV infection in companion animals such as domestic dogs and exotic rodents may be important, because the importation of CCHFV-infected animals (together with adult H. marginatum ticks) from endemic areas is one route by which the virus could be introduced into CCHFV-free countries. Additionally, having these companion animals increases the chance of contact with CCHFV-infected ticks, and thus the risk of disease from CCHFV infection.

REFERENCES Capua, I., 1998, Crimean-Congo haemorrhagic fever in ostriches: A public health risk for countries of the European Union? Avian Pathol. 27, 117-120. Ergonul, O., 2006, Crimean-Congo haemorrhagic fever. Lancet Infect. Dis. 6, 203-214. Shepherd, A.J., Swanepoel, R., Shepherd, S.P., McGillivray, G.M., Searle, L.A., 1987, Antibody to Crimean-Congo hemorrhagic fever virus in wild mammals from southern Africa. Am. J. Trop. Med. Hyg. 36, 133-142. Whitehouse, C.A., 2004, Crimean-Congo hemorrhagic fever. Antiviral Res. 64, 145-160.

5.2.5 HANTAVIRUSES (INCLUDING DOBRAVA-BELGRADE VIRUS)

AETIOLOGY Hantaviruses are negative single-strand RNA viruses in the genus Hantavirus of the family Bunyaviridae.

ANIMAL SPECIES INVOLVED Hantaviruses are carried by rodents and insectivores. In rodents, hantaviruses are found in the families Cricetidae and Muridae. In insectivores, hantaviruses are found in the family Soricidae. Host species carrying hantaviruses infecting humans in Europe are the bank vole (Myodes glareolus; carrier of Puumala virus), yellow-necked mouse (Apodemus flavicollis; carrier of Dobrava-Belgrade virus), striped field mouse (Apodemus agrarius; carrier of Saaremaa virus), brown (Rattus norvegicus) and black rat (R. rattus; carriers of Seoul virus; laboratory infections only in Europe), and field vole (Microtus arvalis; carrier of Tula virus) (Heyman et al., 2009). There is also evidence of hantavirus infection in mammals other than rodents or insectivores: hantavirus was isolated from bats, and antibodies against hantavirus were detected in domestic cats, domestic dogs and foxes (reviewed by (Dobly et al., 2012). 54

MODE/S OF TRANSMISSION Humans are thought to be infected from aerosolized rodent excreta when exposed to hay and crop during harvesting, cleaning cellars, sheds, stables or summer cottages in the autumn, handling wood (especially in dusty woodsheds), and trapping rodents (Heyman 2009). While most human infections are linked to free-living rodents, laboratory also may be a source of infection (Desmyter et al., 1983; Zhang et al., 2010).

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES There is no information on the prevalence of carriage of hantavirus in pet rodents. Seroprevalence of hantavirus infection in Belgium was 20% in domestic cats and 5% in domestic dogs (Dobly et al., 2012). Hantavirus infection occurs in laboratory rats and sporadically results in outbreaks in humans. In free-living rodents, the spatial as well as temporal variation in the occurrence of HFRS is linked to geographical differences in the population dynamics of the reservoir rodents in different biomes of Europe. While rodent abundance may follow mass seeding events in many parts of temperate Europe, in northern (N) Europe multiannual cycles in population density exist as the result of the interaction between rodent populations and specialist predator populations in a delayed density-dependent manner. In multiannually fluctuating populations of rodents, with population increases of great amplitude, one should expect a simultaneous build-up of recently hantavirus-infected (shedding) rodents. The increasing number of infectious, virus-shedding rodents leads to a rapid transmission of hantavirus across the rodent population, and to humans. No disease from hantavirus infection is reported in rodents, dogs or cats (Dobly et al., 2012; Olsson et al., 2010).

IMPACT ON HUMAN HEALTH Hantavirus infections cause two clinical syndromes in humans: haemorrhagic fever with renal syndrome (HFRS) in Asia and Europe, and hantavirus pulmonary (or cardiopulmonary) syndrome in the Americas, with fatality rates of up to 12% and 60%, respectively. The pathogenic hantaviruses in Europe are Puumala virus and Saaremaa virus, which have been known for several decades as a cause of mild HFRS in northern Europe, with very low case-fatality rate, and Dobrava-Belgrade virus, a more recently recognized agent in southeastern Europe, which exhibits a case-fatality rate up to 12%. The clinical manifestations of HFRS range from a mild or moderate febrile illness to fulminant haemorrhagic fever and death (Heyman et al., 2009; Papa, 2012).

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL Laboratory animals, particularly laboratory rats should be housed in adequate biocontainment facilities and regularly tested for antibodies against hantavirus antigens (Zhang et al., 2010). Recombinant vaccines are being developed in Europe and the USA. Until these become available, prevention relies mainly on reduced contact with excreta 55 from infected rodents (Heyman et al., 2009; Papa, 2012).

LINK TO AGRICULTURE The main concern for hantavirus is for human health.

REASONS FOR CONCERN The number of human cases is increasing in almost all European countries, with a record number of cases in Finland, Sweden, Germany and Belgium in the last 5 years (Heyman et al., 2009). Although there are no reported human cases from pet rodents, the increase both in having pet rodents and the associated pet rodent trade is of concern for incursion of hantavirus into pet rodent populations and subsequent transmission to humans.

REFERENCES Desmyter, J., LeDuc, J.W., Johnson, K.M., Brasseur, F., Deckers, C., van Ypersele de Strihou, C., 1983, Laboratory rat associated outbreak of haemorrhagic fever with renal syndrome due to Hantaan-like virus in Belgium. Lancet 2, 1445-1448. Dobly, A., Cochez, C., Goossens, E., De Bosschere, H., Hansen, P., Roels, S., Heyman, P., 2012, Sero-epidemiological study of the presence of hantaviruses in domestic dogs and cats from Belgium. Res. Vet. Sci. 92, 221-224. Heyman, P., Vaheri, A., Lundkvist, A., Avsic-Zupanc, T., 2009, Hantavirus infections in Europe: from virus carriers to a major public-health problem. Expert Rev. Anti. Infect. Ther. 7, 205-217. Olsson, G.E., Leirs, H., Henttonen, H., 2010, Hantaviruses and their hosts in Europe: reservoirs here and there, but not everywhere? Vector Borne Zoonotic Dis. 10, 549-561. Papa, A., 2012, Dobrava-Belgrade virus: phylogeny, epidemiology, disease. Antiviral Res. 95, 104-117. Zhang, Y., Zhang, H., Dong, X., Yuan, J., Yang, X., Zhou, P., Ge, X., Li, Y., Wang, L.F., Shi, Z., 2010, Hantavirus outbreak associated with laboratory rats in Yunnan, China. Infect. Genet. Evol. 10, 638-644.

5.2.6 TAHYNA VIRUS

AETIOLOGY Tahyna virus is a negative single-strand RNA virus in the genus Orthobunyavirus of the family Bunyaviridae.

ANIMAL SPECIES INVOLVED Principal vertebrate hosts are the brown hare, rabbit, hedgehog and rodent species (Hubalek, 2008).

MODE/S OF TRANSMISSION Transmission occurs by bites of culicine mosquitoes (Hubalek, 2008). 56

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES Natural foci of infection occur in inundated lowland habitats in diverse biomes, such as floodplains of forests or in periurban areas (Hubalek, 2008). Disease in animal hosts is unknown.

IMPACT ON HUMAN HEALTH Human disease caused by Tahyna virus is termed Valtice fever. It is an influenza-like illness occurring in summer and early autumn, mainly in children. It is characterized by fever, headache, malaise, conjunctivitis, pharyngitis, myalgia, nausea, gastrointestinal disorders, anorexia, arthralgia, meningitis and sometimes bronchopneumonia. Mortality has not been reported. More than 200 cases have been documented in the Czech Republic and Slovakia since 1963, and it has been diagnosed in other European countries, including France, as well as outside Europe. In endemic foci, the seroprevalence in elderly people is 60– 80% (Hubalek, 2008).

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL Control measures include surveillance of mosquitoes and humans for virus infection, as well as integrated mosquito control (Hubalek et al., 2005). Individual prevention relies on personal protection measures against insects. There is no vaccine against Tahyna virus.

LINK TO AGRICULTURE The main risk of Tahyna virus infection is to human health. Animal disease is unknown (Hubalek, 2008).

REASONS FOR CONCERN The concern for Tahyna virus infection is due to several reasons: it probably occurs more frequently than is reported because of lack of awareness by the public and the medical community; outbreaks may occur due to changes in environmental conditions, such as flooding from heavy rains or restoration of wetlands; and infection may cause clinical disease, Valtice fever, in people (Hubalek, 2008).

REFERENCES Hubalek, Z., 2008, Mosquito-borne viruses in Europe. Parasitol. Res. 103 Suppl 1, S29-43. Hubalek, Z., Zeman, P., Halouzka, J., Juricova, Z., Stovickova, E., Balkova, H., Sikutova, S., Rudolf, I., 2005, Mosquitoborne viruses, Czech Republic, 2002. Emerg. Infect. Dis. 11, 116-118.

5.2.7 AICHI VIRUS

AETIOLOGY Human Aichi virus is a positive single-strand RNA virus in the genus 57

Kobuvirus of the family Picornaviridae. Other viruses recently discovered are bovine kobuvirus, porcine kobuvirus, salivirus/klassevirus from human and bat faeces, canine kobuvirus (Li et al., 2011) and mouse kobuvirus (Phan et al., 2011). By phylogenetic analysis, human Aichi virus clusters most closely to mouse kobuvirus and canine kobuvirus.

ANIMAL SPECIES INVOLVED Canine kobuvirus was detected in the faeces of both healthy domestic dogs and dogs with bloody diarrhoea in California (Li et al., 2011). Mouse kobuvirus was detected in the faeces of Canyon mice (Peromyscus crinitus) and deer mice (P. maniculatus) from California (Phan et al., 2011). The close relationship between human, mouse and canine kobuviruses suggests past zoonotic transmission of kobuviruses between these hosts or their recent ancestors, followed by independent evolution leading to the close but distinct species seen today (Phan et al., 2011).

MODE/S OF TRANSMISSION Known mode of transmission of human Aichi virus infection is ingestion of raw shellfish, including oysters, from sewage-polluted seawater (Le Guyader et al., 2008; Reuter et al., 2011). Antibody to Aichi virus has not been detected in sera of monkeys, horses, dogs, cats or rats (Reuter et al., 2011). It is not known whether animal kobuviruses are transmitted to humans.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES Mouse kobuvirus was found in two of seven Canyon mice and two of 20 deer mice, in the absence of reported clinical signs (Phan et al., 2011). Out of 18 domestic dogs, canine kobuvirus was found in three, two of which had bloody diarrhoea (Li et al., 2011).

IMPACT ON HUMAN HEALTH Serological studies in various countries show that 80–95% of the population have antibody to Aichi virus by the age of 30–40 years. This suggests that subclinical infections may be more common than clinically manifest disease. Aichi virus infection is associated with acute gastroenteritis, resulting in diarrhoea, abdominal pain, nausea, vomiting and fever (Reuter et al., 2011).

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL Shellfish harvesting areas may be closed when heavy rains increase sewage contamination. Short-term depuration, which is used to meet recommended bacterial regulatory requirements, may not be sufficient to remove contaminating viral pathogens such as Aichi virus (Le Guyader et al., 2008).

LINK TO AGRICULTURE The main concern for Aichi virus is for human health. 58

REASONS FOR CONCERN Human Aichi virus, canine kobuvirus and mouse kobuvirus are recently discovered viruses, two of which are associated with digestive tract disease in their hosts. There is currently insufficient information to know whether animal kobuviruses may be transmitted to humans, but based on their close genetic relationship this cannot be ruled out.

REFERENCES Le Guyader, F.S., Le Saux, J.C., Ambert-Balay, K., Krol, J., Serais, O., Parnaudeau, S., Giraudon, H., Delmas, G., Pommepuy, M., Pothier, P., Atmar, R.L., 2008, Aichi virus, norovirus, astrovirus, enterovirus, and rotavirus involved in clinical cases from a French oyster-related gastroenteritis outbreak. J. Clin. Microbiol. 46, 4011-4017. Li, L., Pesavento, P.A., Shan, T., Leutenegger, C.M., Wang, C., Delwart, E., 2011, Viruses in diarrhoeic dogs include novel kobuviruses and sapoviruses. J. Gen. Virol. 92, 2534-2541. Phan, T.G., Kapusinszky, B., Wang, C., Rose, R.K., Lipton, H.L., Delwart, E.L., 2011, The fecal viral flora of wild rodents. PLoS Pathog. 7, e1002218. Reuter, G., Boros, A., Pankovics, P., 2011, Kobuviruses - a comprehensive review. Rev. Med. Virol. 21, 32-41.

5.2.8 EUROPEAN BAT LYSSAVIRUS

AETIOLOGY European bat lyssavirus, types 1 and 2 (EBLV-1 and EBLV-2), are negative single-strand RNA viruses in the genus Lyssavirus of the family Rhabdoviridae.

ANIMAL SPECIES INVOLVED Most commonly infected bat species are the serotine bat (Eptesicus serotinus), for EBLV-1, and Daubenton’s bat (Myotis daubentonii) and pond bat (M. dasycneme), for EBLV-2 (van der Poel et al., 2006).

MODE/S OF TRANSMISSION Transmission principally occurs by the bites of an infected animal.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES More than 600 bats infected with EBLV have been detected since its discovery in 1954. Most cases have been detected in Denmark and the Netherlands, although this is likely to reflect more extensive surveillance rather than major differences in epidemiology in these countries (van der Poel et al., 2006).

IMPACT ON HUMAN HEALTH Five human deaths from EBLV infection have been reported. The overall rarity of EBLV-associated death in terrestrial animals may be because the transmission from bats to other mammals is infrequent, 59 the virulence of EBLV is relatively low, or because cases go undetected (van der Poel et al., 2006).

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL People with occupational exposure to bats should be prophylactically vaccinated against rabies (Fooks et al., 2003). People bitten by bats or dogs, cats or other carnivores should wash with water and soap and seek medical attention (Dacheux et al., 2009).

LINK TO AGRICULTURE While there is a report of five sheep infected by EBLV-1, the main concern about EBLV is for human health (van der Poel et al., 2006).

REASONS FOR CONCERN EBLV-1 infection was diagnosed in two domestic cats in France. Since cats often predate on bats, and a rabid bat with a highly homologous EBLV-1 was found at the location of one of the cats, it is highly likely that the cats were directed infected by bats. More than 1,500 other cats suspected of having rabies and tested for EBLV were negative; suggesting bat-to-cat transmission of EBLV is rare. Furthermore, terrestrial mammals seem to represent dead-end hosts for EBLV infection, based on experimental infections. Therefore, it is unlikely for EBLV-infected cats to actively transmit to a new host, including humans (Dacheux et al., 2009).

REFERENCES Dacheux, L., Larrous, F., Mailles, A., Boisseleau, D., Delmas, O., Biron, C., Bouchier, C., Capek, I., Muller, M., Ilari, F., Lefranc, T., Raffi, F., Goudal, M., Bourhy, H., 2009, European bat Lyssavirus transmission among cats, Europe. Emerg. Infect. Dis. 15, 280-284. Fooks, A.R., Brookes, S.M., Johnson, N., McElhinney, L.M., Hutson, A.M., 2003, European bat lyssaviruses: an emerging zoonosis. Epidemiol. Infect. 131, 1029-1039. van der Poel, W.H., Lina, P.H., Kramps, J.A., 2006, Public health awareness of emerging zoonotic viruses of bats: a European perspective. Vector Borne Zoonotic Dis. 6, 315-324.

5.2.9 HEPATITIS E VIRUS

AETIOLOGY Hepatitis E virus (HEV) is a positive single-strand RNA virus in the genus Hepevirus of the family Hepeviridae (Kamar et al., 2012). HEV genomes vary substantially and consist of at least four mammalian genotypes and one avian HEV. Genotypes 1 and 2 are restricted to humans and are mainly associated with large waterborne epidemics in endemic regions. Genotypes 3 and 4 are found in humans and other mammalian hosts, and are mainly responsible for sporadic cases of hepatitis E (Pavio et al., 2010). 60

ANIMAL SPECIES INVOLVED Domestic pigs and are the main animal reservoirs for genotypes 3 and 4 of HEV. In addition, HEV antibody also has been detected in other animal species including deer, rats, dogs, cats, mongoose, cows, sheep, goats, birds, rabbits and horses, suggesting that these host species are exposed to HEV or a closely related virus. While genotype 3 and/or 4 HEV strains have been identified in domestic pigs, wild boar, deer, mongoose and rabbit, the source of seropositivity in other animals, with the exception of chickens and rats, remains to be determined (Pavio et al., 2010).

MODE/S OF TRANSMISSION Transmission of genotypes 3 and 4 of HEV in Europe is likely faecal- oral via direct contact or ingestion of products from reservoir species, mainly domestic pigs and wild boar. However, multiple other routes of transmission are likely to exist (Lewis et al., 2010).

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES In domestic pigs, HEV infection is widespread in swine farms worldwide in both developing and industrialized countries. Infection generally occurs at 2–3 months of age, and shedding via faeces lasts about 3–7 weeks. Most adult domestic pigs that are seropositive do not shed virus (Meng, 2010). The prevalence of genotype 3 HEV infection in wild boar and roe deer in several European countries also is high (de Deus et al., 2008; Rutjes et al., 2010; Schielke et al., 2009). HEV antibodies were detected in 27% of tested dog serum samples in Vietnam and 7% of animals in Brazil. Among 135 domestic cats tested in Japan, HEV antibodies were detected in 44 (33%) of them (Vasickova et al., 2007).

IMPACT ON HUMAN HEALTH HEV infection has been found in every developed country in which it has been sought, with the possible exception of Finland. Seroprevalence rates of less than 5% are reported in developed countries, but may be much higher due to low sensitivity of the assays used. Acute infection with genotypes 3 and 4 of HEV is usually a self-limiting illness that lasts 3–4 weeks. Clinical signs include jaundice, malaise, anorexia, nausea, abdominal pain, fever and arthralgia. Most infections, however, seem to be asymptomatic (Kamar et al., 2012).

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL Prevention in developed countries is complex because several possible routes of infection exist. Approaches include ensuring meat products are thoroughly cooked, taking appropriate measures when handling uncooked meat, and ensuring proper disposal of pig faeces. Two candidate vaccines for humans are currently being tested in clinical trials. Treatment of acute HEV infection is usually not required, but patients with severe disease have been treated successfully with ribavirin. Ribavirin also is used in transplant recipients and other immunosuppressed patients (Kamar et al., 2012). 61

LINK TO AGRICULTURE Pigs naturally infected with HEV are asymptomatic. In chickens, the morbidity and mortality associated with HEC infection is very low, although subclinical infections of avian HEV are common (Kuno et al., 2003; Meng, 2010).

REASONS FOR CONCERN Although farmed domestic pigs and farmed or free-living wild boar seem to be important sources of human infection with genotypes 3 and/or 4 of HEV, companion animals should not be neglected. First, domestic pigs kept as companion animals may be a source of infection. This is illustrated by a patient from France who developed hepatitis E 8 weeks after acquiring a pet Vietnamese pig. The clinical history of the patient, together with the isolation of a genotype 3 HEV from the pet pig that was closely related to the HEV isolate from the patient, suggests that he was most likely infected by his pet pig (Renou et al., 2007). Secondly, based on serological prevalence of HEV infection, multiple other species (including those kept as companion animals such as dogs, cats and rats) may be sources of human infection. This is illustrated by the possible transmission of hepatitis E from a pet cat to its human owner. The only discovered source of infection was the owner’s cat, which was positive for HEV antibody (Kuno et al., 2003).

REFERENCES de Deus, N., Peralta, B., Pina, S., Allepuz, A., Mateu, E., Vidal, D., Ruiz-Fons, F., Martin, M., Gortazar, C., Segales, J., 2008, Epidemiological study of hepatitis E virus infection in European wild boars (Sus scrofa) in Spain. Vet. Microbiol. 129, 163-170. Kamar, N., Bendall, R., Legrand-Abravanel, F., Xia, N.S., Ijaz, S., Izopet, J., Dalton, H.R., 2012, Hepatitis E. Lancet 379, 2477-2488. Kuno, A., Ido, K., Isoda, N., Satoh, Y., Ono, K., Satoh, S., Inamori, H., Sugano, K., Kanai, N., Nishizawa, T., Okamoto, H., 2003, Sporadic acute hepatitis E of a 47-year-old man whose pet cat was positive for antibody to hepatitis E virus. Hepatol. Res. 26, 237-242. Lewis, H.C., Wichmann, O., Duizer, E., 2010, Transmission routes and risk factors for autochthonous hepatitis E virus infection in Europe: a systematic review. Epidemiol. Infect. 138, 145-166. Meng, X.J., 2010, Hepatitis E virus: animal reservoirs and zoonotic risk. Vet. Microbiol. 140, 256-265. Pavio, N., Meng, X.J., Renou, C., 2010, Zoonotic hepatitis E: animal reservoirs and emerging risks. Vet. Res. 41, 46. Renou, C., Cadranel, J.F., Bourliere, M., Halfon, P., Ouzan, D., Rifflet, H., Carenco, P., Harafa, A., Bertrand, J.J., Boutrouille, A., Muller, P., Igual, J.P., Decoppet, A., Eloit, M., Pavio, N., 2007, Possible zoonotic transmission of hepatitis E from pet pig to its owner. Emerg. Infect. Dis. 13, 1094-1096. Rutjes, S.A., Lodder-Verschoor, F., Lodder, W.J., van der Giessen, J., Reesink, H., Bouwknegt, M., de Roda Husman, A.M., 2010, Seroprevalence and molecular detection of hepatitis E virus in wild boar and red deer 62

in The Netherlands. J. Virol. Methods 168, 197-206. Schielke, A., Sachs, K., Lierz, M., Appel, B., Jansen, A., Johne, R., 2009, Detection of hepatitis E virus in wild boars of rural and urban regions in Germany and whole genome characterization of an endemic strain. Virol. J. 6, 58. Vasickova, P., Psikal, I., Kralik, P., Widen, F., Hubalek, Z., Pavlik, I., 2007, Hepatitis E virus: a review. Vet. Med-Czech. 52, 365-384.

5.2.10 COWPOX VIRUS

AETIOLOGY Cowpox virus is a double-strand DNA virus in the genus Orthopoxvirus of the family Poxviridae.

ANIMAL SPECIES INVOLVED Wild rodents are considered the reservoir of cowpoxvirus, although the exact species are unknown. Cowpox virus is known to infect a broad range of other animal species throughout Europe and Western Asia, including domestic cats, pet rats and domestic dogs (Tack, 2011).

MODE/S OF TRANSMISSION Transmission to humans likely occurs via direct contact with an affected animal, resulting in implantation of the virus into non-intact skin or mucous membranes (Baxby et al., 1994).

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES Nowadays, human infection is predominantly associated with domestic cats, although pet rats and other animal species such as monkeys and elephants also have been associated with human infection. Cowpox infection in domestic cats usually occurs during the autumn, when the size and activity of wild rodent populations peak. Domestic cats are thought to become infected while hunting rodents, either through bites, scratches, or possibly ingestion. About 20% of domestic cats develop oral lesions and 20% show mild respiratory tract and ocular disease. Fatal outcome in domestic cats is mainly associated with underlying disease (Pfeffer et al., 2002; Tack, 2011). Clinical signs in pet rats are primarily upper respiratory signs and death, although skin lesions, particularly on the paws, have been reported (Wolfs et al., 2002). Clinical signs in domestic dogs are single ulcers (von Bomhard et al., 2011).

IMPACT ON HUMAN HEALTH Children and those involved in veterinary care or husbandry of animals appear to be at most risk (Baxby and Bennett, 1997). Most people show single pustular lesions in the skin and have influenza-like signs. Generalized infections, some of which are fatal, only occur in people with predisposing disease such as eczema, atopic and 63

Darier’s disease. In the European Union, pet rats purchased in pet stores were responsible for more than 30 human cases of cowpox, but the disease is undoubtedly under-reported so that the true impact is unknown (Tack, 2011).

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL Behaviours that reduce the risk of infection include hand washing after handling an animal, applying quarantine when introducing new animals into a group, wearing gloves when manipulating an animal’s oral cavity or when a cut is present on the hand and seeking veterinary care for an ill pet. Smallpox vaccine is used in laboratory personnel working with orthopoxviruses, and is used to protect elephants against cowpox. In general, cowpox infections are self-limiting and antibacterial therapy only is given when secondary infection is present (Tack, 2011).

LINK TO AGRICULTURE Cowpox virus is of minor concern to agriculture. Cowpox virus infection in cattle in Europe occurs rarely. It involves typical poxvirus lesions on the teats and udder of milk cows, and on the muzzle of suckling calves.

REASONS FOR CONCERN Pet rats and other rodents have become more popular as companion animals, resulting in cowpox virus and other poxviruses occurring in areas outside their normal geographical range and affecting people who are not aware of these pathogens. Cowpox virus infections in humans, domestic cats and pet rodents are rarely initially suspected by the patient, owner or clinician. Delays in diagnosing infections in animals may lead to inadvertent human exposures, and delays in diagnosing infections in humans may result in inappropriate treatment or delayed recovery (Tack, 2011).

REFERENCES Baxby, D., Bennett, M., 1997, Cowpox: a re-evaluation of the risks of human cowpox based on new epidemiological information. Arch. Virol. Suppl 13, 1-12. Baxby, D., Bennett, M., Getty, B., 1994, Human cowpox 1969-93: a review based on 54 cases. Br. J. Dermatol. 131, 598-607. Pfeffer, M., Pfleghaar, S., von, B.D., Kaaden, O.R., Meyer, H., 2002, Retrospective investigation of feline cowpox in Germany. Vet. Rec. 150, 50-51. Tack, D.M., 2011, Zoonotic poxviruses associated with companion animals. Animals 1, 377-395. von Bomhard, W., Mauldin, E.A., Breuer, W., Pfleghaar, S., Nitsche, A., 2011, Localized cowpox infection in a 5-month-old Rottweiler. Vet. Dermatol. 22, 111-114. Wolfs, T.F., Wagenaar, J.A., Niesters, H.G., Osterhaus, A.D., 2002, Rat- to-human transmission of Cowpox infection. Emerg. Infect. Dis. 8, 1495- 1496. 64

5.2.11 G5 ROTAVIRUS

AETIOLOGY Rotavirus is a double-strand RNA virus in the genus Rotavirus of the family Reoviridae. Rotaviruses are classified into seven groups, A to G. Rotaviruses are further divided based on their G serotype and P serotype (Santos and Hoshino, 2005). Most common G serotypes in humans are G1 to G4. However, other serotypes, including G5, are emerging.

ANIMAL SPECIES INVOLVED Type G5 rotavirus is an important and commonly detected pathogen of domestic swine. Phylogenetic analysis of the VP7 protein of human and domestic swine isolates have shown that the viruses found in children with diarrhoea in Brazil and Cameroon are likely to be reassortants between human and swine strains (Santos and Hoshino, 2005). Type G5 rotavirus may also be found in cattle and horses (Esona et al., 2004; Santos and Hoshino, 2005).

MODE/S OF TRANSMISSION Transmission likely occurs by the faecal-oral route.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES Rotaviruses were detected in 43% of cattle samples and 14% of domestic pig samples from six European countries between 2003 and 2007. When compared at the nucleotide level, the identified porcine rotavirus strains and contemporary human strains grouped together phylogenetically, while bovine rotavirus strains formed separate clades. These data suggest that domestic animals, particularly domestic swine, may serve as potential reservoirs of rotavirus for humans (Midgley et al., 2012).

IMPACT ON HUMAN HEALTH Group A rotaviruses are the single most important cause of severe acute gastroenteritis in infants and young children in both developed and developing countries and are estimated to cause each year, 111 million episodes of diarrhoea requiring only home care, 25 million clinic visits, 2 million hospitalisations, and 325,000 to 592,000 deaths (median 440,000) deaths in children under 5 years of age (Santos and Hoshino, 2005). G5 strains have been detected in Brazil, Argentina, Paraguay, Cameroon, Vietnam and Bulgaria. Particularly, in Brazil, a surprising prevalence rate of 26% has been reported for G5 strains (Ahmed et al., 2007; Duan et al., 2007; Mladenova et al., 2012). From over 36,000 human rotavirus strains typed in Europe, about 2% were characterized as a potential zoonotic rotavirus genotype, or a possible human-animal hybrid rotavirus genotype (Midgley et al., 2012). 65

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL Hygienic measures are important to limit faecal-oral transmission. Two rotavirus vaccines have been available worldwide since 2006 (Mladenova et al., 2012).

LINK TO AGRICULTURE Rotaviruses infect and cause gastroenteritis in a broad range of animal species, and result in substantial economic losses in food animals, particularly neonates of domestic pigs and cattle (Midgley et al., 2012).

REASONS FOR CONCERN Although transmission of animal rotavirus to humans appears to be a very rare event, the introduction of certain animal rotavirus genes into human rotaviruses through genetic reassortment appears to be common. Some of such possible animal-human rotavirus reassortants are well established in various human populations as in the case of P[11]G10 rotavirus strains in India, P[8]G5 strains in Brazil and the P[6] G8 strains in Africa (Santos and Hoshino, 2005). It is thought that the immunity to rotavirus infection is predominantly homotypic initially and broadens after subsequent infections. Because the development of rotavirus vaccine formulations have been targeted at the most commonly circulating human rotavirus strains, G1 to G4, the occurrence of other G types may compromise the efficacy of such vaccines. The close contact between people and pet pigs may promote the interspecies transmission of rotaviruses and reassortment of human and porcine rotaviruses. The recent identification of a type G5 rotavirus in human specimens indicates that such pig-to-human transmission events also may occur in Europe. This virus shared no neutralization antigens with rotavirus vaccines used for routine immunization in children (Mladenova et al., 2012).

REFERENCES Ahmed, K., Anh, D.D., Nakagomi, O., 2007, Rotavirus G5P[6] in child with diarrhea, Vietnam. Emerg. Infect. Dis. 13, 1232-1235. Duan, Z.J., Li, D.D., Zhang, Q., Liu, N., Huang, C.P., Jiang, X., Jiang, B., Glass, R., Steele, D., Tang, J.Y., Wang, Z.S., Fang, Z.Y., 2007, Novel human rotavirus of genotype G5P[6] identified in a stool specimen from a Chinese girl with diarrhea. J. Clin. Microbiol. 45, 1614-1617. Esona, M.D., Armah, G.E., Geyer, A., Steele, A.D., 2004, Detection of an unusual human rotavirus strain with G5P[8] specificity in a Cameroonian child with diarrhea. J. Clin. Microbiol. 42, 441-444. Midgley, S.E., Banyai, K., Buesa, J., Halaihel, N., Hjulsager, C.K., Jakab, F., Kaplon, J., Larsen, L.E., Monini, M., Poljsak-Prijatelj, M., Pothier, P., Ruggeri, F.M., Steyer, A., Koopmans, M., Bottiger, B., 2012, Diversity and zoonotic potential of rotaviruses in swine and cattle across Europe. Vet. Microbiol. 156, 238-245. Mladenova, Z., Papp, H., Lengyel, G., Kisfali, P., Steyer, A., Steyer, A.F., Esona, M.D., Iturriza-Gomara, M., Banyai, K., 2012, Detection of rare 66

reassortant G5P[6] rotavirus, Bulgaria. Infect. Genet. Evol. 12, 1676-1684. Santos, N., Hoshino, Y., 2005, Global distribution of rotavirus serotypes/ genotypes and its implication for the development and implementation of an effective rotavirus vaccine. Rev. Med. Virol. 15, 29-56.

5.2.12 INFLUENZA A VIRUS

AETIOLOGY Influenza A virus is a negative single-strand RNA virus in the genus Influenza A virus of the family Orthomyxoviridae. They are categorized into different subtypes based on their haemagglutinin (H) and neuraminidase (N) surface glycoproteins. Currently, there are 17 known H subtypes and 9 known N subtypes.

ANIMAL SPECIES INVOLVED Influenza A viruses occur in a wide range of animal species, both wild and domestic. The original reservoir of all influenza A viruses are wild birds, particularly wild waterbirds of the orders Anseriformes (mainly ducks, geese, and swans) and Charadriiformes (mainly gulls and waders); these viruses are termed avian influenza viruses. From the wild bird reservoir, influenza A viruses may spread to other species, where adapted variants occasionally become established. In this way, influenza A viruses have become established in humans (human influenza viruses). They have also become established in different species of poultry, domestic pigs (swine influenza virus), horses (equine influenza virus) and domestic dogs (canine influenza virus). Most cases of animal-to-human transmission of influenza A viruses involve poultry or domestic pigs (Reperant et al., 2012).

MODE/S OF TRANSMISSION Transmission of influenza A viruses in wild birds is considered to be mainly faecal-oral, while in mammals, including humans, it is considered to be mainly respiratory. Activities associated with bird- to-human transmission of avian influenza viruses include care giving, managing avian influenza outbreaks, visiting bird markets, de- feathering, butchering, meat processing and consumption of poultry products. Activities associated with pig-to-human transmission of swine influenza viruses include care giving, visiting animal markets or county fairs, contact with a patient with swine influenza virus infection and butchering (Reperant et al., 2012).

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES Different species of poultry may be endemically infected with low pathogenic avian influenza viruses. In addition, high pathogenic avian influenza virus of the subtype H5N1 is endemic in poultry in a number of Asian and African countries. Equine influenza virus infections are established in horse populations. Influenza A virus of the subtype 67

H3N8 is established in domestic dog populations in . This virus originated from an equine influenza virus, presumably after consumption of infected horse meat by racing greyhounds. Domestic cats are not endemically infected by influenza A virus, but infections with avian and human influenza viruses are increasingly reported (Reperant et al., 2012). Pandemic H1N1 influenza virus also has been reported in pet ferrets (Swenson et al., 2010).

IMPACT ON HUMAN HEALTH There are more than ten reports of poultry-to-human transmission of avian influenza virus (Peiris, 2009) and 30 reports of pig-to-human transmission of swine influenza virus (Myers et al., 2007; Peiris, 2009; Reperant et al., 2012). The severity of disease in these cases is highly dependent on the virulence of the virus, and may vary from subclinical infection to rapid death. An important consideration regarding impact on human health is the risk that introduction of a novel influenza A virus, or parts of its genome, into the human population may result in an influenza A virus that transmits efficiently in the human population and to which the human population has little or no herd immunity. Typically, this results in an influenza pandemic with more extensive epidemic waves and more severe disease (Reperant et al., 2012).

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL Control of infection in poultry and domestic pig populations includes stamping-out policies and vaccination. Prevention of infection in domestic cats, ferrets and domestic dogs includes preventing access to infected birds (Thiry et al., 2007); vaccination against some influenza virus subtypes is available (Harder and Vahlenkamp, 2010). Prevention of transmission of zoonotic influenza virus to humans includes appropriate hygienic measures when handling animals and animal products, particularly of poultry and domestic pigs. Human risk groups are vaccinated against seasonal human influenza viruses, but vaccination against zoonotic influenza virus is rarely performed. Therapeutic measures include the use of neuraminidase inhibitors.

LINK TO AGRICULTURE Outbreaks of avian influenza in commercial poultry have major impacts on the poultry industry and international agricultural trade. For example, highly pathogenic avian influenza outbreaks in Southeast Asia between 2003 and 2005 cost about $10 billion (Chmielewski 2011). Although rarely fatal, influenza in domestic pigs can be of substantial economic impact because of costs for veterinary prevention and care and up to a 2-week delay in reaching market weight (Olsen, 2000).

REASONS FOR CONCERN So far, no transmission of equine or canine influenza viruses to humans has been reported. However, transmission of avian and human influenza viruses to domestic dogs and cats, as well as pet ferrets, is increasingly reported. Domestic dogs and cats may therefore represent new 68

“bridge species” for transfer of zoonotic influenza viruses from animals to humans. In particular, the continued presence of highly pathogenic avian H5N1 influenza virus in poultry of several Asian and African countries poses an ongoing risk of transfer to humans and food animals in Europe, including through companion animals (Reperant et al., 2012).

REFERENCES Harder, T.C., Vahlenkamp, T.W., 2010, Influenza virus infections in dogs and cats. Vet. Immunol. Immunopathol. 134, 54-60. Myers, K.P., Olsen, C.W., Gray, G.C., 2007, Cases of swine influenza in humans: A review of the literature. Clin. Infect. Dis. 44, 1084-1088. Olsen, C.W., 2000, DNA vaccination against influenza viruses: a review with emphasis on equine and swine influenza. Vet. Microbiol. 74, 149- 164. Peiris, J.S.M., 2009, Avian influenza viruses in humans. Rev. Sci. Tech. OIE 28, 161-173. Reperant, L.A., Kuiken, T., Osterhaus, A.D., 2012, Adaptive pathways of zoonotic influenza viruses: from exposure to establishment in humans. Vaccine 30, 4419-4434. Swenson, S.L., Koster, L.G., Jenkins-Moore, M., Killian, M.L., DeBess, E.E., Baker, R.J., Mulrooney, D., Weiss, R., Galeota, J., Bredthauer, A., 2010, Natural cases of 2009 pandemic H1N1 Influenza A virus in pet ferrets. J. Vet. Diag. Invest. 22, 784-788. Thiry, E., Zicola, A., Addie, D., Egberink, H., Hartmann, K., Lutz, H., Poulet, H., Horzinek, M.C., 2007, Highly pathogenic avian influenza H5N1 virus in cats and other carnivores. Vet. Microbiol. 122, 25-31.

5.2.13 LYMPHOCYTIC CHORIOMENINGITIS VIRUS

AETIOLOGY Lymphocytic choriomeningitis virus (LCMV) is a negative single-strand RNA virus in the genus Arenavirus of the family Arenaviridae.

ANIMAL SPECIES INVOLVED LCMV is endemic in free-living house mice worldwide (Amman et al., 2007); however, other rodent species can be incidentally infected.

MODE/S OF TRANSMISSION Human infection occurs most commonly through exposure (by direct contact or inhalation of infectious aerosol) to secretions or excretions of infected animals (Amman et al., 2007).

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES Several rodent species sold as pets, including hamsters, mice and guinea pigs, can be incidental hosts of LCMV. These species become infected through contact with infected wild house mice and can pass the infection to humans (Amman et al., 2007). 69

IMPACT ON HUMAN HEALTH LCMV infection in immunocompetent people usually is asymptomatic or mild; aseptic meningitis also can occur but the infection is rarely fatal. In immunocompromised people, LCMV infection may result in severe systemic disease and death (Amman et al., 2007). LCMV infection in pregnant women may cause abortion or severe birth defects, including hydrocephalus, chorioretinitis, blindness or mental retardation. Since 1993, 29 infants were diagnosed with congenital LCMV infection, but it is likely that congenital LCMV infection is greatly underreported (Barton and Mets, 2001). While most human LCMV infections are associated with exposure to wild house mice, several outbreaks have been attributed to laboratory and pet rodents (Amman et al., 2007). One example was the 1974 outbreak associated with pet hamsters sold by a single distributor. A total of 181 symptomatic cases (46 requiring hospitalization) in persons with hamster contact were identified; no deaths occurred (Gregg, 1975). Another was the occurrence of four cases of acute meningitis in France occurring after close contact with pet Syrian hamsters (Rousseau et al., 1997).

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL LCMV already is actively excluded from laboratory rodent populations, but economic considerations may prohibit such rigorous biosecurity measures in the pet rodent industry. Nevertheless, LCMV surveillance should be a primary concern in the pet rodent industry by excluding wild house mice. Immunocompromised people and pregnant women should avoid close contact with pet rodents (Amman et al., 2007).

LINK TO AGRICULTURE LCMV is not considered a problem for food animal production or health.

REASONS FOR CONCERN In 2005 in the USA, a person infected with LCMV from a pet hamster donated his organs to four transplant patients, of whom three died from the infection. This was the first documented case of fatal LCMV infection involving a pet animal (Amman et al., 2007). The main reasons for concern are the risk of LCMV infection of pet rodents by contact with wild house mice, and the relative lack of awareness, both of the general public and the medical profession, of the risks of severe disease for immunocompromised people and pregnant women.

REFERENCES Amman, B.R., Pavlin, B.I., Albarino, C.G., Comer, J.A., Erickson, B.R., Oliver, J.B., Sealy, T.K., Vincent, M.J., Nichol, S.T., Paddock, C.D., Tumpey, A.J., Wagoner, K.D., Glauer, R.D., Smith, K.A., Winpisinger, K.A., Parsely, M.S., Wyrick, P., Hannafin, C.H., Bandy, U., Zaki, S., Rollin, P.E., Ksiazek, T.G., 2007, Pet rodents and fatal lymphocytic choriomeningitis in transplant patients. Emerg. Infect. Dis. 13, 719-725. Barton, L.L., Mets, M.B., 2001, Congenital lymphocytic choriomeningitis 70

virus infection: decade of rediscovery. Clin. Infect. Dis. 33, 370-374. Gregg, M.B., 1975, Recent outbreaks of lymphocytic choriomeningitis in the of America. Bull. World Health Organ. 52, 549-553. Rousseau, M.C., Saron, M.F., Brouqui, P., Bourgeade, A., 1997, Lymphocytic choriomeningitis virus in southern France: four case reports and a review of the literature. Eur. J. Epidemiol. 13, 817-823.

5.3 VIRUSES OF PRIMARY CONCERN TO FOOD ANIMAL HEALTH AND PRODUCTION

5.3.1 BLUETONGUEVIRUS

AETIOLOGY Bluetongue virus (BTV) is a double-stranded RNA virus within the genus Orbivirus of the family Reoviridae.

ANIMAL SPECIES INVOLVED BTV can infect most species of domestic and wild ruminants (Mellor and Wittmann, 2002). There also is serological evidence of BTV infection in multiple species of carnivores, including domestic dogs and domestic cats from Kenya (Alexander et al., 1994).

MODE/S OF TRANSMISSION BTV is transmitted almost exclusively by the bites of Culicoides midges. Occasionally, it has been shown to be transmitted directly from vertebrate to vertebrate, in semen, and transplacentally (Mellor and Wittmann, 2002). Infection of carnivores is not known, but could be by vector transmission or by the oral route (i.e. by eating contaminated meat)(Alexander et al., 1994). Oura and El Harrak (2011) showed that a high percentage of domestic dogs in Morocco (21%) were seropositive for BTV. Because these dogs were fed tinned commercial food only and had no access to other meat products, they suggested the most likely source of infection was through Culicoides midges.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES Alexander et al. (1994) found antibodies against BTV in 18% (46/254) of domestic dogs and 21% (7/34) of domestic cats in Kenya. Although there are no recorded cases of natural BTV infection in domestic dogs, injection of BTV-contaminated canine distemper virus vaccine caused abortion and death in domestic dogs (Akita et al., 1994). Experimental 71 inoculation of this virus caused abortion and death of pregnant dogs, but no clinical signs in non-pregnant dogs (Brown et al., 1996).

IMPACT ON HUMAN HEALTH BTV is not considered to be a zoonosis.

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL BTV is spread mainly by the bites of infected vector species of Culicoides or rarely, by the direct transfer of blood or germ plasms from an infected to a susceptible animal. Current control measures consist of introducing animal movement restrictions to prevent infected animals initiating new foci of infection, banning the movement or use of germ plasms to prevent virus spread via this route, slaughter of viraemic animals to prevent them acting as a source of virus for vector insects, husbandry modification, vector control and vaccination (Mellor and Wittmann, 2002).

LINK TO AGRICULTURE Although BTV is thought to infect all known species of ruminant, severe disease usually occurs only in certain breeds of sheep, particularly the fine-wool and mutton breeds and some species of deer, most notably the North American white-tailed deer. Clinical signs may include fever, depression, excessive salivation, nasal discharge, facial oedema, hyperaemia and ulceration of the oral mucosa, coronitis, lameness, muscle weakness and death. The mortality rate and the severity of the clinical signs seem to vary with the breed and age of the infected animal, the type and strain of the virus and interactions with the environment (Mellor and Wittmann, 2002).

REASONS FOR CONCERN Many thousands of dogs and cats are transported annually into the EU from BTV-endemic countries in Africa and Asia without any pre- or postimport movement testing for BTV. If these dogs were capable of being infected with BTV and became viraemic for a significant period of time, it is possible that they could carry BTV with them when transported from endemic to non-endemic countries. If the climatic conditions were favourable upon arrival it is possible that Culicoides midges in the country of destination could feed off these viraemic imported dogs or cats and in turn pass on the virus to the domestic ruminant population (Oura and El Harrak, 2011).

REFERENCES Akita, G.Y., Ianconescu, M., MacLachlan, N.J., Osburn, B.I., 1994, Bluetongue disease in dogs associated with contaminated vaccine. Vet. Rec. 134, 283-284. Alexander, K.A., MacLachlan, N.J., Kat, P.W., House, C., O’Brien, S.J., Lerche, N.W., Sawyer, M., Frank, L.G., Holekamp, K., Smale, L., et al., 1994, Evidence of natural bluetongue virus infection among African carnivores. Am. J. Trop. Med. Hyg. 51, 568-576. 72

Brown, C.C., Rhyan, J.C., Grubman, M.J., Wilbur, L.A., 1996, Distribution of bluetongue virus in tissues of experimentally infected pregnant dogs as determined by in situ hybridization. Vet. Pathol. 33, 337-340. Mellor, P.S., Wittmann, E.J., 2002, Bluetongue virus in the Mediterranean Basin 1998-2001. Vet. J. 164, 20-37. Oura, C.A., El Harrak, M., 2011, Midge-transmitted bluetongue in domestic dogs. Epidemiol. Infect. 139, 1396-1400.

5.3.2 AFRICAN SWINE FEVER VIRUS

AETIOLOGY African swine fever virus (ASFV) is a double-stranded DNA virus in the genus Asfivirus of the family Asfarviridae.

ANIMAL SPECIES INVOLVED A range of wild pigs, as well as domestic pigs, can be infected by ASFV (Costard et al., 2009).

MODE/S OF TRANSMISSION In warthogs in East and southern Africa, transmission of ASFV is dependent on a sylvatic cycle involving soft ticks of the Ornithodoros spp., and horizontal or vertical transmission is not thought to occur. In other areas of Africa, and for other wild pig species, the epidemiology is poorly known. In domestic pigs, virus may be transmitted directly between pigs, indirectly through ingestion of infected pork products, or by fomites such as clothing, equipment and vehicles (Costard et al., 2009).

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES Most ASFV isolates cause acute haemorrhagic fever in domestic pigs, with mortality approaching 100% (Costard et al., 2009).

IMPACT ON HUMAN HEALTH ASFV is not considered to be zoonotic.

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL There is currently no vaccine available against ASFV infection. To prevent the spread of ASFV through movement of livestock, countries are advised to follow international standards as outlined by the World Organization for Animal Health. Strict regulations regarding animal by-products have proven effective in many developed countries and are critical given the high tenacity of the virus in meat products and in the environment (Costard et al., 2009).

LINK TO AGRICULTURE Besides causing high mortality in domestic pigs, ASFV infection causes loss of status for international trade as well as drastic and expensive control strategies to eradicate the virus (Costard et al., 2009). 73

REASONS FOR CONCERN Originally limited to Africa, ASFV has caused outbreaks elsewhere in the world, including several European countries. It was eradicated from all European countries except Italy, where the virus has remained endemic on the island of Sardinia since it was introduced in 1982. In 2007, further spread of ASFV occurred to Georgia in the Caucasus region, with further distribution to neighbouring countries including Armenia, Azerbaijan and Russia. Besides domestic pigs, the virus also has been reported in wild boar in these areas (Costard et al., 2009). Within the European Union, illegal or uncontrolled imports of pig meat products, either accidentally by tourists returning from endemic countries or, more importantly, intentionally by smuggling meat products for personal or commercial use, presents a continuous threat (Costard et al., 2009). From this viewpoint, the ever-increasing popularity of owning pet pigs (especially miniature pigs like Vietnamese potbellied pigs) is of concern (Marshall et al., 2007; Sipos et al., 2007), because biosecurity measures are difficult to enforce and owners are not always aware of the legislation and regulations that affect pig ownership. Outdoor units may be at risk from passers-by throwing pork or pork products into them, if they are near roads or campsites. Owners of pet pigs in particular should be aware of this risk. Therefore, pet pigs may form a weak spot in the defences against incursion of ASFV into the European Union.

REFERENCES Costard, S., Wieland, B., de Glanville, W., Jori, F., Rowlands, R., Vosloo, W., Roger, F., Pfeiffer, D.U., Dixon, L.K., 2009, African swine fever: how can global spread be prevented? Philos. Trans. R. Soc. Lond. B Biol. Sci. 364, 2683-2696. Marshall, E.S., Carpenter, T.E., Thurmond, M.C., 2007, Results of a survey of owners of miniature swine to characterize husbandry practices affecting risks of foreign animal disease. J. Am. Vet. Med. Assoc. 230, 702-707. Sipos, W., Schmoll, F., Stumpf, I., 2007, Minipigs and potbellied pigs as pets in the veterinary practice – a retrospective study. J. Vet. Med. A Physiol. Pathol. Clin. Med. 54, 504-511.

5.3.3 FOOT-AND-MOUTH-DISEASE VIRUS

AETIOLOGY Foot-and mouth-disease virus (FMDV) is a virus in the genus Aphthovirus of the family Picornaviridae.

ANIMAL SPECIES INVOLVED Cloven-hoofed animals, both domestic (cattle, pigs, sheep, goats and buffalo) and wild (deer, antelope, wild boar, giraffe and camelids) are susceptible to FMDV infection. 74

MODE/S OF TRANSMISSION These include direct contact between animals, indirect contact with fomites, consumption (mainly by pigs) of untreated infected meat products, consumption of infected milk, artificial insemination with infected semen, inhalation of infectious aerosols and airborne transmission.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES FMDV infection typically causes vesicles on the oral mucosa, nasal mucosa, coronary bands and mammary skin. Signs can range from inapparent to severe, morbidity may approach 100%, and mortality is generally low in adult animals but higher in young animals.

IMPACT ON HUMAN HEALTH FMDV is not considered to be a zoonotic agent.

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL These consist of a combination of several measures: protection of free zones by border animal movement control and surveillance; quarantine measures; slaughter of infected, recovered, and FMDV-susceptible contact animals; cleaning and disinfection of premises and all infected material, such as implements, cars and clothes; disposal of carcasses, bedding and contaminated animal products in the infected area; and use of inactivated vaccines (www.oie.int/fileadmin/Home/eng/Animal_ Health_in_the_World/docs/pdf/FOOT_AND_MOUTH_DISEASE_FINAL. pdf).

LINK TO AGRICULTURE FMDV is economically the most important pathogen of livestock. The non-vaccination policy of the EU renders its livestock fully susceptible to infection with this virus.

REASONS FOR CONCERN FMDV remains close to the borders of Europe and regularly makes incursions into the EU. In the last 22 years (1985–2006), FMD has occurred 37 times in 14 European countries (Valarcher et al., 2008). The main routes through which FMDV is likely to be introduced in the EU is legal or illegal importation of infected live animals (cattle, goats, sheep and pigs) and legal or illegal importation of infected meat, meat products or other animal products (such as casings). Feeding contaminated swill, such as catering or other waste, to pigs is by far the most efficient means of establishing disease (Anonymous, 2006; Marshall et al., 2007). Potentially, cattle, goats, sheep, and pigs kept as companion animals or backyard livestock can be involved. For example, in a recent survey, more than 40% of owners fed food waste to miniature swine kept as pets (Marshall et al., 2007). 75

REFERENCES Anonymous, 2006, Assessing the risk of foot-and-mouth disease introduction into the EU from developing countries. European Food Safety Agency J 313, 1-34. Marshall, E.S., Carpenter, T.E., Thurmond, M.C., 2007, Results of a survey of owners of miniature swine to characterize husbandry practices affecting risks of foreign animal disease. J. Am. Vet. Med. Assoc. 230, 702-707. Valarcher, J.F., Leforban, Y., Rweyemamu, M., Roeder, P.L., Gerbier, G., Mackay, D.K., Sumption, K.J., Paton, D.J., Knowles, N.J., 2008, Incursions of foot-and-mouth disease virus into Europe between 1985 and 2006. Transbound. Emerg. Dis. 55, 14-34.

5.3.4 RABBIT HAEMORRHAGIC DISEASE VIRUS

AETIOLOGY Rabbit haemorrhagic disease virus (RHDV) is a positive single-stranded RNA virus in the genus Lagovirus of the family Caliciviridae.

ANIMAL SPECIES INVOLVED RHDV is a calicivirus specific to the European rabbit (Oryctolagus cuniculus), either wild or domesticated (Lenghaus et al., 2001).

MODE/S OF TRANSMISSION The main route of transmission is direct contact, although it also may take place through fomites or via insects such as mosquitoes and flies (Lenghaus et al., 2001).

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES RHDV infection often causes peracute disease, with adult rabbits dying within a day of developing inappetence, depression and fever. In contrast, rabbits younger than about 6 weeks may become infected without apparent disease. Pathologically, RHDV infection is characterized by disseminated intravascular coagulation, haemorrhages in multiple organs, and marked necrosis in liver and spleen (Lenghaus et al., 2001).

IMPACT ON HUMAN HEALTH RHDV infection is not considered to be zoonotic.

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL Eradication is currently considered the best response to this disease when it is introduced to a country that does not have RHDV infection. When infected rabbits are identified, all in contact rabbits are destroyed and their housing is decontaminated. Vaccines against RHD are available in countries with enzootic RHD (Belz, 2004). 76

LINK TO AGRICULTURE RHD is a disease with a potentially devastating impact on the rabbit industry in countries where this disease has previously been excluded (Belz, 2004).

REASONS FOR CONCERN Although there are no reported examples of transmission of RHDV from pet rabbits to commercial rabbit farms, it is a potential risk, and such an event would have dramatic consequences for the commercial rabbit production in the affected country.

REFERENCES Belz, K., 2004, Rabbit hemorrhagic disease. Seminars in Avian and Exotic Pet Medicine 13, 100-104. Lenghaus, C., Studdert, M.J., Gavier-Widen, D., 2001, Calicivirus infections, In: Williams, E.S., Barker, I.K. (Eds.) Infectious diseases of wild mammals. Iowa State University Press, Ames, Iowa, pp. 280-291. 5.3.5 Lumpy Skin Disease Virus

5.3.5 LUMPY SKIN DISEASE VIRUS

AETIOLOGY Lumpy skin disease virus (LSDV) is a double-stranded DNA virus in the genus Capripoxvirus of the family Poxviridae (Tuppurainen and Oura, 2012) .

ANIMAL SPECIES INVOLVED Cattle are the main species involved. Wild ruminant species, such as giraffe and impala, have been reported with clinical disease, but it has not been confirmed whether these cases were due to LSDV or another capripoxvirus (Tuppurainen and Oura, 2012).

MODE/S OF TRANSMISSION The transmission of LSDV is believed to occur mainly by blood-feeding (Tuppurainen and Oura, 2012).

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES Infection is currently endemic in the continent of Africa, including Madagascar. In 2006, the infection emerged in Egypt, and also has been reported in the 2000s in United Arab Emirates, Bahrain, Israel and Oman (Tuppurainen and Oura, 2012).

IMPACT ON HUMAN HEALTH LSDV infection is not considered to be zoonotic.

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL Only live attenuated vaccines against lumpy skin disease are available. 77

Because of antigenic homology between sheep pox virus, goat pox virus and LSDV, any of these viruses can be used as a vaccine strain to protect cattle against lumpy skin disease (Tuppurainen and Oura, 2012). LINK TO AGRICULTURE The OIE categorizes African horse sickness as a notifiable disease because of the substantial economic impact of an outbreak: decreased milk yield, temporary or permanent infertility, decreased growth rate, decreased hide value. In addition, restrictions to global trade of live animals and animal products, and costly control measures cause substantial financial losses at a national level (Tuppurainen and Oura, 2012). LSDV infection is an occasionally fatal infection of cattle with morbidity averaging 10% and mortality 1% in affected herds, although mortality rates over 75% have been recorded (Babiuk et al., 2008).

REASONS FOR CONCERN The main concern is that LSDV infection will spread from the Middle East to neighbouring countries in Europe and Asia, including Turkey. There are several factors involved: growing importation of cattle and beef into the Middle East, lack of strict quarantine, suitability of the region for blood-feeding arthropods, maintenance of dense cattle populations, communal grazing and nomadism and relative lack of diagnostic and control capacities (Tuppurainen and Oura, 2012).

REFERENCES Babiuk, S., Bowden, T.R., Boyle, D.B., Wallace, D.B., Kitching, R.P., 2008, Capripoxviruses: an emerging worldwide threat to sheep, goats and cattle. Transbound. Emerg. Dis. 55, 263-272. Tuppurainen, E.S., Oura, C.A., 2012, Review: lumpy skin disease: an emerging threat to Europe, the Middle East and Asia. Transbound. Emerg. Dis. 59, 40-48.

5.4 VIRUSES OF PRIMARY CONCERN TO FOOD ANIMAL HEALTH AND PRODUCTION (FISH)

5.4.1 CYPRINID HERPESVIRUS 3 (KOI HERPESVIRUS)

AETIOLOGY Cyprinid herpesvirus 3 (Koi herpesvirus) is a double-stranded DNA virus in the genus Cyprinivirus of the family Alloherpesviridae of the order Herpesvirales. 78

ANIMAL SPECIES INVOLVED Natural infection has only been detected in common carp (Cyprinius carpio) and different varieties of common carp, such as Koi carp. Hybrids between goldfish (C. auratus) and common carp are of intermediate susceptibility (Haenen and Hedrick, 2006).

MODE/S OF TRANSMISSION Koi herpesvirus is transmitted through water and direct contact between fish. Egg-associated transmission (vertical transmission) cannot be excluded. The optimal temperature range for replication of the virus is 15–25°C. Survivor fish may be persistently infected.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES Koi herpesvirus was originally reported from Israel (Hedrick et al 2000), but has been spread across the globe through trade of Koi carp.

IMPACT ON HUMAN HEALTH There is no indication that Koi herpesvirus is a threat to human health.

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL Aquaculture facilities should avoid the supply of contaminated water and the introduction of infected fish. Spring or borehole influx water is considered safe. Koi herpesvirus-free broodstock fish and iodophor disinfection of fertilized eggs should be used. An attenuated virus vaccine has been developed (Perelberg et al., 2008).

LINK TO AGRICULTURE/AQUACULTURE Koi herpesvirus can cause mass mortality in carp in both cultured fish and wild environments. Trade of ornamental carp is complex and difficult to control. No transmission has been shown to commonly cultivated fish species such as tilapia, silver perch, goldfish, silver carp and black carp.

REASONS FOR CONCERN The virus is able to cause an epizootic among farmed as well as wild common carp and varieties of common carp. The mortality rate of affected population of carp can be as high as 80–100%. The mortality level is related to water temperature.

REFERENCES Haenen, O., Hedrick, R., 2006. Koi herpesvirus workshop. Bulletin of the European Association of Fish Pathologists 26, 26-37. Hedrick, R. P., Gilad, O., Yun, S., Spangenberg, J. V., Marty, G. D., Nordhausen, R. W., Kebus, M. J., Bercovier, H., Eldar, A., 2000. A herpesvirus associated with mass mortality of juvenile and adult koi, a strain of common carp. J. Aquat. An. Health 12, 44-57. Perelberg, A., Ilouze, M., Kotler, M., Steinitz, M., 2008. Antibody response 79 and resistance of Cyprinus carpio immunized with cyprinid herpes virus 3 (CyHV-3). Vaccine 26, 3750-3756.

5.4.2 VIRAL HAEMORRHAGIC SEPTICAEMIA VIRUS

AETIOLOGY Viral haemorrhagic septicaemia virus (VHSV) is a negative single- stranded RNA virus in the genus Novirhabdovirus of the family Rhabdoviridae.

ANIMAL SPECIES INVOLVED Many different fish species from many different fish families can act as hosts for VHSV. Skall et al. (2005) listed 53 species of marine and freshwater fish species found as natural hosts and 11 others as experimentally susceptible.

MODE/S OF TRANSMISSION VHSV is a highly transmissible virus and experimentally the virus can be transmitted by cohabitation, bathing and injection. VHSV is thought to enter the body through the gills or possibly through wounds. VHSV is a cold water virus with an optimum growth at 9–12°C. Temperatures above 18°C are considered inhibitory to viral growth.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES There is no information of VHSV prevalence in ornamental fish. VHSV affects rainbow trout and other freshwater species in continental Europe and Japan. VHSV has also been isolated from a variety of wild marine fish in North Atlantic, the Baltic Sea and the North American part of the Pacific and Atlantic Oceans.

IMPACT ON HUMAN HEALTH There is no indication that VHSV is a threat to human health.

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL Current control methods include fish health surveillance programs and measures such as eradication and fallowing. These procedures have eliminated viral VHS from parts of Europe. VHSV can survive for long periods in the bottom of farm ponds if the ponds are not dried and disinfected (Smail and Snow 2011).

LINK TO AGRICULTURE/AQUACULTURE Besides causing high mortality in farmed rainbow trout, salmon, turbot and others, VHSV infection causes loss of status for international trade as well as drastic and expensive control strategies to eradicate the virus. 80

REASONS FOR CONCERN The morbidity and mortality rates vary with the environmental conditions as well as the species of fish, strain of virus and route of infection. The virus is able to infect a large number of fish species and cause epizootics among farmed as well as wild fish. The mortality rate can be as high as 80–100% in farmed rainbow trout fry.

REFERENCES Skall, H. F., Olesen, N. J., Mellergaard, S., 2005. Viral haemorrhagic septicaemia virus in marine fish and its implications for fish farming - a review. J. Fish Dis. 28, 509-529. Smail DA, Snow M: Viral hemorrhagic septicaemia. In: Woo PTK, Bruno DW, editors. Fish diseases and Disorders, 2nd ed. Wallingford, UK. CAB International, 2011; p. 166-244.

5.4.3 INFECTIOUS PANCREATIC NECROSIS VIRUS

AETIOLOGY Infectious pancreatic necrosis virus (IPNV) is a double-stranded RNA virus within the genus Aquabirnavirus of the family Birnaviridae (Dobos, 1995).

ANIMAL SPECIES INVOLVED IPNV has been isolated from numerous fresh water and marine fish species and from molluscs and crustaceans (Munro & Midtlyng 2011).

MODE/S OF TRANSMISSION Both water-borne transmission as well as vertical transmission (i.e. egg-associated transmission) occurs. Infected fish may become carriers of the virus. Carriers may shed IPNV intermittently. Survival of IPNV infectivity in untreated fresh, estuarine and seawater is long- lasting, with an inactivation profile of approximately10-fold reduction per week at 15°C. At lower temperatures the infectivity of the virus may be considerably longer. The virus may still be infective after oral passage in birds or mammals.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES There is no information of IPNV prevalence in ornamental fish. The virus has been found in aquatic animal species from all continents.

IMPACT ON HUMAN HEALTH There is no indication that IPNV is a threat to human health.

CURRENT MEASURES FOR DISEASE PREVENTION AND CONTROL Different fish health surveillance programs and measures are used. Testing of broodstock fish for presence of virus and iodophor disinfection of fertilized eggs are used to control vertical transmission. This control 81 is not completely efficient. Fallowing and disinfection of premises are used to control horizontal transmission. Vaccination of farmed salmonid fish is used. The currently available vaccines do not induce satisfactory protection. Breeding for IPN resistance is considered as promising and is widely used.

LINK TO AGRICULTURE/AQUACULTURE IPNV causes high mortality in farmed salmonid and marine fish species. Epizootics in wild stocks have been observed.

REASONS FOR CONCERN The virus is able to infect a large number of fish species and cause epizootic among farmed as well as wild fish. The mortality rate can be as high as 80–100% in fry of several species.

REFERENCES Dobos, P., 1995. The molecular biology of infectious pancreatic necrosis virus. Ann. Rev. Fish Dis. 5, 25-54. Munro ES, Midtlyng PJ: Infectious pancreatic necrosis and associated aquatic birnaviruses; In : Woo PTK, Bruno DW, editors. Fish diseases and Disorders, 2nd ed. Wallingford, UK. CAB International, 2011. p. 1-65. 82 6. BACTERIAL INFECTIONS

6.1 BARTONELLA SPP. (CAT SCRATCH DISEASE)

AETIOLOGY Cat scratch disease (CSD) is caused by members of the genus Bartonella; a diverse group of blood-borne, vector-transmitted Gram-negative bacteria. The agent of CSD, was discovered in the early 1990s and the previous hypothetical agent, Afipia felis, was shown to be a bacterial contaminant, not the aetiological agent of CSD. It is still not clear if B. clarridgeiae is also involved in human cases of CSD.

ANIMAL SPECIES INVOLVED Domestic cats are the natural reservoir of B. henselae. Humans, dogs and horses are more likely to be accidental hosts. A few cases of B. henselae infection have also been detected in wildlife including sea mammals such as belugas, loggerhead turtles, porpoises, sea otters and seals.

MODE/S OF TRANSMISSION Bartonella henselae is commonly transmitted from cat-to-cat by the cat , mainly by intradermal inoculation of flea faeces. Horizontal or vertical transmission between cats has not been documented. Zoonotic transmission from cats to humans is likely acquired by scratching when the claws of a cat are contaminated with infected flea faeces or indirectly through exposure to faeces of that have fed on infected cats. Transmission through bites has also been suggested both for cats and dogs.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES The prevalence of Bartonella carriage can be measured in different ways, the most common being seroprevalence and bacteraemia prevalence. In Europe, the bacteraemia prevalence amongst pet cats varies from 0–68%, while the seroprevalence varies from 1–71% between 83 countries (Table 6.1). Pet cats in Scandinavian countries are generally infected less frequently compared with the rest of Europe. Bartonella infection is most frequent in stray cats, cats in shelters/catteries and young cats infested with fleas (Boulouis et al., 2005; Chomel et al., 2009; Breitschwerdt et al., 2010). For these populations, prevalence rates of two to five times the prevalence in pet cats may be seen (Boulouis et al., 2005). Prevalences are generally higher in warm and humid environments.from companion animals to food animals, or both, were identified by literature.

TableTable 6.1 Prevalence of Bartonella spp. in pet cats based on seropositivity (S) or presence of bacteremia (B)

Number of animals Prevalence Country Survey Reference studied (%) Boulouis et al., Austria S 96 33 2005 Boulouis et al., B 535 15 2005 France Boulouis et al., S 436 41 2005 Boulouis et al., S 713 15 2005 Germany Boulouis et al., B 100 13 2005 Juvet et al., Ireland S 83 27 2010 Boulouis et al., B 248 10 2005 Italy Boulouis et al., S 254 16 2005 Boulouis et al., B 100 0 2005 Norway Boulouis et al., S 100 1 2005 Podsiadly et al., Poland S 131 45 2007 Alves et al., B 29 68 2009 Portugal Boulouis et al., S 14 7 2005 Pons et al., 2005; Solano- Spain S 680 24–71 Gallego et al., 2006a; Ayllón et al., 2012 Boulouis et al., S 292 1 2005 Sweden Boulouis et al., B 91 2 2005 Boulouis et al., Switzerland S 728 8 2005 84

Number of animals Prevalence Country Survey Reference studied (%) Boulouis et al., B 711 10 2005 United Kingdom Boulouis et al., S 69 41 2005

Bartonella in pet dogs in Europe is quite rare compared with cats. This is illustrated by a B. henselae seroprevalence of only 3% in dogs in the UK (Barnes et al., 2000). Somewhat higher prevalence rates have been reported from Southern Europe. One study in Spain reported that 17% of dogs were seropositive for B. henselae (Solano-Gallego et al., 2006b). Cats with Bartonella bacteraemia generally display no clinical signs although some studies suggest that B. henselae may cause signs following experimental infection and in cats infected with feline virus (FIV). B. henselae has not been associated with disease in dogs.

IMPACT ON HUMAN HEALTH CSD usually occurs 3–10 days after being scratched by a cat and often results in mild, non-specific symptoms such as lymphadenopathy, fever or headaches in immunocompetent people. However, more severe diseases such as endocarditis, encephalitis or angiomatosis may occur as sequelae and are much more common in immunocompromised patients. The incidence of CSD has been estimated in few European countries. In France and the Netherlands, 7.6 and 11.9 cases occur per 100,000 inhabitants each year, respectively. This is comparable to the estimated 9.3 cases per 100,000 inhabitants in North America. These numbers are based on the number of reported cases and are likely to be underestimates of the actual incidences (personal communication, Bruno Chomel). Bartonella spp. are thought to account for between 0% (Norway, Sweden) and 4.5% (France) of cases of human endocarditis in Europe.

CONTROL MEASURES IN COMPANION ANIMALS As Bartonella bacteria are mainly vector borne, flea and tick control is the most logical way of preventing transfer of Bartonella spp. between animals and to humans. No vaccine is available to prevent infection in cats and dogs.

PREVENTION OF ZOONOTIC INFECTION There are two main aspects to control of zoonotic infection. One is reducing exposure, which is achieved mainly through flea control. Proper flea control practices can eliminate the vector and have a profound effect on the likelihood of transmission from cats to humans. The other aspect is preventing scratches and bites. This mainly involves proper training of people and animals. The role of care after bites or scratches is unclear, but prompt and proper bite/scratch management, particularly lavage of wounds, may also be beneficial. 85

LINK TO AGRICULTURE Livestock are generally infected with Bartonella species other than those detected in companion animals, hence there are no reasons to suspect transmission.

REASONS FOR CONCERN The high prevalence of Bartonella in some cat populations combined with the fact that domestic cats represent the largest population of pets in Europe (see Section 1) implies a potentially high risk of transmission of CSD. Although the incidence of CSD is not known, the potential for serious disease, and the potential for misdiagnosis of human infection highlights concerns regarding this disease.

REFERENCES Alves, A.S., Milhano, N., Santos-Silva, M., et al., 2009. Evidence of Bartonella spp., Rickettsia spp. and Anaplasma phagocytophilum in domestic, shelter and stray cat blood and fleas, Portugal. Clin. Microbiol. Infect. 15 Suppl 2, 1-3. Ayllón, T., Diniz, P.P., Breitschwerdt, E.B., et al., 2012. Vector-borne diseases in client-owned and stray cats from Madrid, Spain. Vector Borne Zoonotic Dis. 12, 143-150. Barnes, A., Bell, S.C., Isherwood, D.R., et al., Evidence of Bartonella henselae infection in cats and dogs in the United Kingdom. Vet. Rec. 147, 673-677. Boulouis, H.J., Chang, C.C., Henn, J.B., et al., 2005 Factors associated with the rapid emergence of zoonotic Bartonella infections. Vet. Res. 36, 383-410. Breitschwerdt, E.B., Maggi, R.G., Chomel, B.B., et al., 2010. Bartonellosis: an emerging infectious disease of zoonotic importance to animals and human beings. J. Vet. Emerg. Crit. Care. 20, 8-30. Chomel, B.B., Boulouis, H.J., Breitschwerdt, E.B., et al., 2009. Ecological fitness and strategies of adaptation of Bartonella species to their hosts and vectors. Vet. Res. 40, 29. Juvet, F., Lappin, M.R., Brennan, S., et al., 2010. Prevalence of selected infectious agents in cats in Ireland. J. Feline Med. Surg. 12, 476-482. Podsiadly, E., Chmielewski, T., Marczak, R., et al., 2007. Bartonella henselae in the human environment in Poland. Scand. J. Infect. Dis. 39, 956-962. Pons, I., Sanfeliu, I., Quesada, M., et al. 2005. Prevalence of Bartonella henselae in cats in Catalonia, Spain. Am. J. Trop. Med. Hyg. 72, 453-457. Solano-Gallego, L., Hegarty, B., Espada, Y., et al., 2006a. Serological and molecular evidence of exposure to -borne organisms in cats from northeastern Spain. Vet. Microbiol. 118, 274-277. Solano-Gallego, L., Llull, J., Osso, M., et al., 2006b. A serological study of exposure to arthropod-borne pathogens in dogs from northeastern Spain. Vet. Res. 37, 231–244. 86

6.2 BITE INFECTIONS

AETIOLOGY Apart from Rabies virus that is mainly transmitted by the bite of mammals, a wide range of bacteria can be transmitted by dog and cat bites. Additionally, bite infections can be associated with inoculation of bacteria from the skin of the bite victim. Pasteurellosis is the most common bacterial bite infection, more frequently acquired after a (20–50%) than a (3–20%). In terms of frequency, the most common bacteria transmitted by bites from dogs and cats are: spp., Streptococcus spp., Staphylococcus spp., Moraxella spp., Neisseria spp., Bergeyella (Weeksella) zoohelcum, Capnocytophaga canimorsus and Capnocytophaga cynodegmi. Bites by rodents can cause rat bite fever, which is due to infection with either Streptobacillus moniliformis, or less frequently Spirillum minus. There is increasing recognition that dogs are also common carriers of S. moniliformis and dog bite-associated infections can occur

ANIMAL SPECIES INVOLVED All domestic animal species pose a risk for bite infections. The oral cavity of domestic dogs and cats, rodents and other pocket pets is the natural reservoir for many of these bacteria and these are the most common animals that cause bites. Bites by wildlife can also lead to infections caused by similar infectious agents.

MODE OF TRANSMISSION Bites, especially if deep and narrow, as occurs with cat bites.

IMPACT ON HUMAN HEALTH Dog and cat bites comprise approximately 1% of admissions to emergency rooms in both the USA and in Europe (Modrau et al., 2001; Oehler et al., 2009). In the Netherlands, between 50,000 to 100, 000 people are bitten by a pet animal each year (Gaastra and Lipman, 2010), corresponding to 0.3–0.6% of the total population. Dogs account for 80–90% of bites and cats about 20%. About 10–20% of bites will become infected (Patronek and Slavinski, 2009). Underlying these numbers are large differences, since 20–80% of cat bites may become infected, while infection rates for dog bites are as low as 3–18% (Talan et al., 1999). Pasteurella spp. were detected in samples from 50% of 50 dog bites and from 75% of 57 cat bites in one study (Talan et al., 1999). Pasteurella multocida is the species most often found in cat bite wounds, and Pasteurella canis is predominant in dog bite wounds. Since its first description in 1976, approximately 200 human cases of C. canimorsus infection have been reported worldwide (Gaastra and Lipman, 2010). Infections caused by C. canimorsus can lead to a variety of symptoms and systemic diseases such as septicaemia, 87 meningitis and disseminated intravascular coagulation. These severe clinical presentations are particularly common in immunocompromised individuals (especially splenectomized individuals), and can have a mortality rate about 30%.

CONTROL MEASURES IN COMPANION ANIMALS Not relevant as transmission between animals is not considered in this context.

PREVENTION OF ZOONOTIC INFECTION The main method to prevent bite-associated infections is to prevent bites, through various activities, particularly education of people about proper interactions with dogs. Close monitoring and supervision of children around animals is very important. When bites occur, basic first aid measures are indicated to reduce the infectious burden and determine the appropriate response. The approach to antimicrobial prophylaxis following bites is variable, but there are situations where antimicrobial prophylaxis is indicated, including bites that appear to be minor, but are located at sites of special concern (e.g. bites over joints, tendon sheaths and the face).

LINK TO AGRICULTURE None.

REASONS FOR CONCERN Dog and cat bites are frequent events among pet owners and their relatives, as well as among certain professions (e.g. veterinarians, postmen, rescue personnel and people capturing stray animals). Several million bites occur annually in many European countries and are certainly one of the first sources of human infections caused by zoonotic bacteria related to pet ownership. With an ageing population and a larger number of immunocompromised people, these zoonotic infections may be responsible for severe outcomes in these highly susceptible individuals.

REFERENCES Oehler, R.L., Velez, A.P., Mizrachi, M., et al., 2009. Bite-related and septic syndromes caused by cats and dogs. Lancet Infect. Dis. 9, 439-447. Modrau, I.S., Jakobsen, J., Schønheyder, H.C., 2001. Bidsår og infektionsprofylakse. Ugeskrift for læger. 38 (in Danish). Gaastra, W., Lipman, L.J., 2010. Capnocytophaga canimorsus. Vet. Microbiol. 140, 339-346. Patronek, G.J., Slavinski, S.A., 2009. Animal bites. J Am. Vet. Med. Assoc. 234, 336-345. Talan, D.A., Citron, D.M., Abrahamian, F.M., et al., 1999. Bacteriologic analysis of infected dog and cat bites. Infection Study Group. N. Engl. J. Med. 340, 85–92. 88

6.3 CAMPYLOBACTERSPP. (CAMPYLOBACTERIOSIS)

AETIOLOGY Campylobacter is a Gram-negative, spiral-shaped bacterium, which generally grows under microaerobic conditions. Campylobacter can survive for up to several months in moist environments, but is sensitive to desiccation and heat. Campylobacter species have a varying degree of host range. C. jejuni is the most common Campylobacter species in many domestic animals and the most important for human infections. Other species appear to be more host specific, for example C. upsaliensis and C. helveticus, which have been isolated almost entirely from dogs, cats and humans.

ANIMAL SPECIES INVOLVED Campylobacter has a very broad host range including a wide range of companion animals such as dogs, cats, horses, rodents, reptiles and pet birds.

MODE/S OF TRANSMISSION All Campylobacter species of zoonotic risk are transmitted by the faecal-oral route. Transmission can occur by direct contact or indirectly via fomites such as food and water or via arthropod vectors.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES Both dogs and cats are well-known carriers of Campylobacter. Species distribution and prevalence in these animals vary widely between studies, probably due to different study populations, isolation techniques and geographical variation. Campylobacter carriage rates may reach figures around 50% in both dog and cat populations, and C. upsaliensis appears to be the most common species followed by C. jejuni. The highest rates generally occur in stray animals and in densely populated communities such as kennels (Bruce et al., 1980; Burnie et al., 1983, Baker et al., 1999). The pathogenicity in dogs and cats appears to be low although young individuals (< 1 year of age) may be affected by Campylobacter-associated diarrhoea (Fox et al., 1983; Burnens et al., 1992; Wieland et al., 2005). Many other companion animals are potential carriers of Campylobacter, but they have not been studied systematically when it comes to prevalence. Horses appear to be rarely colonized by Campylobacter, but case reports have documented a possible role in foal diarrhoea (Gardner and Young, 1987; Hurcombe et al., 2009). Rodents and reptiles such as turtles may also be colonized by Campylobacter, but these animals are rarely affected clinically (Harvey and Greenwood, 1985; Skirrow, 1994; 89

López et al., 2002). Except for sporadic fertility problems in ruminants and diarrhoea in tropical pet birds, other animal species are often asymptomatic carriers of Campylobacter.

IMPACT ON HUMAN HEALTH Campylobacteriosis is the leading cause of gastroenteritis in most developed countries and it has been estimated that approximately 10% of the population in Western Europe will be affected by this disease every year (Humphrey et al., 2007). Symptoms are usually mild to profuse diarrhoea, which rarely develops into more severe disease such as septicaemia. Sequelae associated with Campylobacter infections in humans are the Guillain-Barré syndrome, irritable bowel syndrome and reactive arthritis. Severity of disease depends on both the patient and Campylobacter species involved. C. jejuni can affect most age groups, unlike C. upsaliensis, which is less common and mainly causes mild symptoms in children and immunocompromised persons (Jenkin and Tee, 1998; Jimenez et al., 1999). In industrialized countries, Campylobacter is rarely isolated from humans without diarrhoea. In developing countries, there is not difference in prevalence in people with and without diarrhoea from about 1 year of age. Although the role of companion animals in human infections is not clear, various epidemiological studies have identified contact with pets as a risk factor for human campylobacteriosis (Adak et al., 1995; Neimann et al., 2003; Friedman et al., 2004; Carrique-Mas et al., 2005). Some studies have identified the same clone in humans and dogs living together (Wolfs et al., 2001; Damborg et al., 2004), but often the direction of transmission is not clear and a common source of infection cannot be ruled out. One study from Australia estimated that approximately 3% of cases of human campylobacteriosis could be attributed to ownership of puppies (Stafford et al., 2008). A Swiss study, incorporating data on Campylobacter prevalence in dogs and cats, estimated that 8% of cases of human campylobacteriosis might be due to contact with these animals (Buettner et al., 2010). The predominance of C. upsaliensis in dogs in many regions requires consideration, as the human health risk of this species is currently unclear. While it is uncommonly reported, human infections have been described and there is concern that standard methods used to diagnose campylobacteriosis in humans, which focus on C. jejuni and C. coli, may not be effective for isolation of C. upsaliensis.

CONTROL MEASURES IN COMPANION ANIMALS Although there is no scientific evidence, general hygiene and infection control measures will likely limit transmission of this bacterium between animals. This seems particularly relevant in densely populated places like kennels. However, the widespread presence and limited clinical relevance (e.g. in adult dogs) raises the question of whether preventive treatment is necessary. 90

PREVENTION OF ZOONOTIC INFECTION As a faecal-oral pathogen, control of campylobacteriosis relies on avoidance of direct or indirect exposure to animal faeces. Factors such as proper faecal handling, litterbox management, removal of faeces from public areas and yards and hand hygiene are likely critical.

LINK TO AGRICULTURE Transmission between livestock and companion animals is a very likely scenario, but the direction of transmission is difficult to identify in such circumstances. Studies have shown that shedding of Campylobacter by poultry is significantly associated with the presence of other animals on the farm (van de Giessen et al., 1996) and shedding of Campylobacter by other animals on the same farm (Ellis-Iversen et al., 2012).

REASONS FOR CONCERN Campylobacter is an important and common human enteric pathogen and a clear link to pet contact has been established. Even if transmission from companion animals accounts for only a few per cent of human cases, these animals may constitute a major source of infection. While typically a self-limiting disease, campylobacteriosis can be serious in some individuals with serious complications such as Guillain-Barre syndrome occurring occasionally.

REFERENCES Adak, G.K., Cowden, J.M., Nicholas, S., et al., 1995. The Public Health Laboratory Service national case-control study of primary indigenous sporadic cases of Campylobacter infection. Epidemiol. Infect. 115, 15-22. Baker, J., Barton, M.D., Lanser, J. 1999. Campylobacter species in cats and dogs in South Australia. Aust. Vet. J. 77, 662-666. Bruce, D., Zochowski, W., Fleming, G.A., 1980. Campylobacter infections in cats and dogs. Vet. Rec. 107, 200-201. Buettner, S., Wieland, B., Staerk, K.D., et al., 2010. Risk attribution of Campylobacter infection by age group using exposure modelling. Epidemiol. Infect. 138, 1748-1761. Burnens, A.P., Angèloz-Wick, B., Nicolet, J. 1992. Comparison of Campylobacter carriage rates in diarrheic and healthy pet animals. J. Vet. Med. 39, 175-180. Burnie, A.G., Simpson, J.W., Lindsay, D., et al. 1983. The excretion of Campylobacter, Salmonella and Giardia lamblia in the faeces of stray dogs. Vet. Res. Comm. 6, 133-138. Carrique-Mas, J., Andersson, Y., Hjertqvist, M., et al., 2005. Risk factors for domestic sporadic campylobacteriosis among young children in Sweden. Scand. J. Infect. Dis. 37, 101-110. Damborg, P., Olsen, K.E., Møller Nielsen, E., et al., 2004. Occurrence of Campylobacter jejuni in pets living with human patients infected with C. jejuni. J. Clin. Microbiol. 42, 1363-1364. Ellis-Iversen, J., Ridley, A., Morris, V., et al., 2012. Persistent environmental reservoirs on farms as risk factors for Campylobacter in commercial 91 poultry. Epidemiol. Infect. 140, 916-924. Fox, J.G., Moore, R., Ackerman, J.I., 1983. Campylobacter jejuni associated diarrhea in dogs. J. Am. Vet. Med. Assoc. 183, 1430-1433. Friedman, C.R., Hoekstra, R.M., Samuel, M., et al., 2004. Risk factors for sporadic Campylobacter infection in the United States: A case-control study in FoodNet sites. Clin. Infect. Dis. 15, 38 Suppl 3, S285-296. Gardner, D.E., Young, G.W. 1987. Campylobacter in foals. N. Z. Vet. J. 35, 116-117. Harvey, S., Greenwood, J.R. 1985. Isolation of Campylobacter fetus from a pet turtle. J. Clin. Microbiol. 21, 260-261. Humphrey, T., O’Brien, S., Madsen, M., 2007. Campylobacters as zoonotic pathogens: a food production perspective. Int. J. Food Microbiol. 117, 237-257. Hurcombe, S.D., Fox, J.G., Kohn, C.W. 2009. Isolation of Campylobacter fetus subspecies fetus in a two-year-old quarterhorse with chronic diarrhea of an undetermined etiology. J. Vet. Diagn. Invest. 21, 266-269. Jenkin, G.A., Tee, W. 1998. Campylobacter upsaliensis-associated diarrhea in human immunodeficiency virus-infected patients. Clin. Infect. Dis. 27, 816-821. Jimenez, S.G., Heine, R.G., Ward, P.B., et al., 1999. Campylobacter upsaliensis gastroenteritis in childhood. Pediatr. Infect Dis. J. 18, 988- 992. López, C.M., Giacoboni, G., Agostini, A., et al., 2002. Thermotolerant Campylobacters in domestic animals in a defined population in Buenos Aires, Argentina. Prev. Vet. Med. 55, 193-200. Neimann, J., Engberg, J., Mølbak, K., et al., 2003. A case-control study of risk factors for sporadic Campylobacter infections in Denmark. Epidemiol. Infect. 130, 353-366. Skirrow, M.B. 1994. Diseases due to Campylobacter, Helicobacter and related bacteria. J. Comp. Pathol. 111, 113-149. Stafford, R.J., Schluter, P.J., Wilson, A.J., et al., 2008. Population- attributable risk estimates for risk factors associated with Campylobacter infection, Australia. Emerg. Infect. Dis. 14, 895-901. van de Giessen, A.W., Bloemberg, B.P., Ritmeester, W.S., et al., 1996. Epidemiological study on risk factors and risk reducing measures for Campylobacter infections in Dutch broiler flocks. Epidemiol. Infect. 117, 245-250. Wieland, B., Regula, G., Danuser, J., et al., 2005. Campylobacter spp. in dogs and cats in Switzerland: risk factor analysis and molecular characterization with AFLP. J. Vet. Med. B. Infect. Dis. Vet. Public. Health. 52, 183-189. Wolfs, T.F., Duim, B., Geelen, S.P., et al., 2001. Neonatal sepsis by jejuni: Genetically proven transmission from a household puppy. Clin. Inf. Dis. 32, e97-e99. 92

6.4 CHLAMYDOPHILA PSITTACI (PSITTACOSIS)

AETIOLOGY Ornithosis in birds is mainly caused by seven ompA-based genotypes of Chlamydophila (Chlamydia) psittaci, which is a Gram-negative, coccoid, obligate intracellular bacterium. Most genotypes show some degree of host specificity: genotype A is mainly associated with psittacines, B with pigeons, C and E/B with anseriforms, D with galliforms and F with psittacines and turkeys. Genotype E may have a broader host range. C. psittaci may exist in an infectious extracellular form (elementary bodies), which can survive in the environment for months.

ANIMAL SPECIES INVOLVED C. psittaci is widely distributed in avian taxa, which are the main reservoirs. At least 465 avian species have been found to be infected. Among pet birds, psittacines and pigeons are most frequently infected. Previous reports of C. psittaci in poikilothermic animals may at least in part be attributed to other Chlamydiaceae.

MODE/S OF TRANSMISSION C. psittaci is excreted from the respiratory and gastrointestinal tracts. Birds are mainly infected after inhalation of C. psittaci-containing aerosols or dust; however, infection also occurs by vertical transmission, ingestion and via blood-sucking parasites. Humans are mostly infected after inhalation of C. psittaci-infected aerosols or dust, after petting infected companion birds, after handling infected avian tissues or being exposed to C. psittaci in secretions (e.g. from cage bedding). Most human cases are associated with exposure to psittacine birds. Human-to-human transfer is considered to be rare.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES C. psittaci is highly prevalent in psittacine birds (16–81%) and pigeons (seroprevalence of 12.5–95%). Colonized birds are most often healthy carriers, which intermittently shed C. psittaci and constitute an important source of infection for other birds and humans. C. psittaci- associated disease (ornithosis) is mainly observed in psittacine birds, in which it is one of the most prevalent infectious diseases. Clinically- infected psittacines mostly show severe respiratory distress, both of the upper and lower respiratory tract, and signs of general illness (e.g. anorexia, lethargy and ruffled feathers). Death frequently occurs. Chronic ornithosis in these birds often results in hepatic disorders. In turkeys and anseriforms, ornithosis may result in severe respiratory and systemic clinical signs and elevated mortality. In many avian species, 93 including pigeons and most passerine birds, the clinical significance of ornithosis is not clear. The non-specific nature of the disease may result in failure to suspect ornithosis clinically, with subsequent failure to submit proper diagnostic specimens.

IMPACT ON HUMAN HEALTH Populations most at risk include bird owners, pet shop employees and veterinarians. An example of such an occupational risk was evident during an outbreak in Germany involving more than 1,000 birds from poultry farms. Twenty-four persons in contact with infected birds developed psittacosis, and the same C. psittaci genotype was detected in affected birds and humans (Gaede et al., 2008). The course of C. psittaci infections in humans (‘psittacosis’ or ‘parrot fever’) may vary from asymptomatic to a flu-like syndrome and involvement of the respiratory tract. Most infected people show mild symptoms, while immunocompromised people are at highest risk of developing clinical signs. Severe complications such as myocarditis, endocarditis, pericarditis, encephalitis, hepatitis, reactive arthritis, multiorgan failure, renal insufficiency, premature birth or fetal death are rare. Psittacosis, if left untreated may rarely result in death. In many European countries the disease is notifiable. An overview of the number of reported human cases in Europe was provided by Beeckman and Vanrompay (2009). Typically, from 2001 onwards, less than 400 cases were reported annually in Europe, mortality being 0–2 people per year. However, these numbers are likely a severe underestimation of the true prevalence, due to incorrectly or unreported cases.

CONTROL MEASURES IN COMPANION ANIMALS Prevention of chlamydiosis among birds involves good husbandry practices such as regular cleaning of cages, avoiding spread of feathers, dust and litter between cages, and quarantine of diseased birds. Care should be taken not to buy birds with signs of psittacosis. Entry control for chlamydiosis in any newly acquired psittacine bird is highly recommended.

PREVENTION OF ZOONOTIC INFECTION People handling sick psittacines or pigeons or their cages should wear protective clothing such as gloves, eyewear, surgical caps and respirators with N95 or higher rating. Cleaning of cages should be done in a way to prevent dust from aerosolizing. Birds with frequent public contact (e.g. in zoos, schools etc.) should be screened for chlamydiosis regularly.

LINK TO AGRICULTURE Companion birds may constitute a reservoir for C. psittaci strains that are highly virulent to industrial poultry.

REASONS FOR CONCERN While the incidence of psittacosis appears to be quite low, this can 94

be a life-threatening infection and control measures are complicated by potential misdiagnosis of human infection. Several avian species such as cockatiels (Nymphicus hollandicus), considered domesticated at present, are kept widely in households in the EU and are notoriously infected by C. psittaci. An extensive C. psittaci reservoir is thus present in pet birds in European households. Restrictions on the importation of wildcaught birds in the EU will thus probably be of little influence on zoonotic transfer of Chlamydiales from companion birds to humans.

REFERENCES Beeckman, D.S.A., Vanrompay, D., 2009. Zoonotic Chlamydophila psittaci infections from a clinical perspective. Clin. Microbiol. Infect. 15, 11-17. Evans, E.E. 2011. Zoonotic diseases of common pet birds: psittacine, passerine, and columbiform species. Vet. Clin. North Am. Exot. Anim. Pract. 14, 457-476. Gaede, W., Reckling, K.F., Dresenkamp, B., et al., 2008. Chlamydophila psittaci infections in humans during an outbreak of psittacosis from poultry in Germany. Zoonoses Public Health. 55, 184-188. West, A. 2011. A brief review of Chlamydophila psittaci in birds and humans. J. Exot. Pet. Med. 20, 18-20.

6.5 CLOSTRIDIUM DIFFICILE

AETIOLOGY Clostridium difficile is a Gram-positive, spore-forming, anaerobic bacterium. The bacterium may produce one or more of the following toxins: toxin A (an enterotoxin), toxin B (a cytotoxin) or C. difficile toxin (CDT, an ADP-ribosyltransferase). Toxins A and B are thought to play an important role in the development of disease, especially in humans, horses and piglets for which most evidence on C. difficile-associated disease exists.

ANIMAL SPECIES INVOLVED As research progresses, it is becoming apparent that there is a very broad distribution of C. difficile. Most work involving companion animals has been with dogs and cats, where the organism can be found in both healthy and diseased animals. The bacterium is uncommonly detected in healthy horses, but may be enriched and cause disease in horses under certain conditions such as antimicrobial treatment or in young animals.

MODE/S OF TRANSMISSION C. difficile is transmitted by the faecal-oral route, either directly or 95 indirectly through contaminated fomites such as food and water. Clostridia are saprophytes and are ubiquitous in the environment. C. difficile may thus be ingested by foraging, without any shedding animals nearby.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES Prevalence data are variable, likely reflecting differences in study populations (e.g. age, hospitalization and disease status) as well as differences in methodology. In most studies of healthy adult dogs and cats, the prevalence of C. difficile shedding is low (0–10%) (Lefebvre et al., 2009; McKenzie et al., 2009; Weese et al., 2010). Geographical differences may occur, but cannot be distinguished based on the limited number of studies and different study designs. In general, higher rates of shedding can be found in young animals, hospitalized individuals, animals with antimicrobial exposure and dogs that participate in hospital visitation programs. Living with an immunocompromised person and antimicrobial treatment of a human in the house have also been identified as a risk factor for C. difficile shedding, highlighting the potential for intrahousehold transmission (Lefebvre et al., 2009; Weese et al., 2010). The incidence of C. difficile infection (CDI) in dogs and cats is poorly described. Some studies have reported CDI as a common cause of community-associated diarrhoea in dogs (Weese et al., 2001; Cave et al., 2002), but difficulties in diagnosing CDI in dogs (Marks et al., 2011) complicate this assessment. As opposed to the situation in humans, CDI in dogs and cats is predominantly a community- associated disease. While veterinary hospital-associated colonization and infection can occur (Weese and Armstrong, 2003), these probably account for a minority of cases. The pathogenic role of C. difficile is much clearer in horses. In fact, CDI in horses resembles the disease in humans, since it often appears as a nosocomial infection following antimicrobial treatment.

IMPACT ON HUMAN HEALTH C. difficile is the most commonly diagnosed cause of antimicrobial- and hospital-associated diarrhoea in humans. CDI is a critically important disease, particularly in elderly individuals and in people with various risk factors (e.g. antimicrobial treatment, chemotherapy or hospitalization). The incidence and severity of CDI have been increasing in recent years in many countries, in part because of the emergence of the hypervirulent ribotype 027. Mortality rates have increased, as have relapse rates, and recurrent CDI can be a debilitating disorder (McDonald et al., 2005; Mulvey et al., 2010). More recently, it has become apparent that community-associated (CA) CDI is an emerging or previously underdiagnosed problem. This includes disease in people that would otherwise be considered at low risk (e.g. young, minimal or no antimicrobial exposure) (Benson et al., 2007; Kuijper and van Dissel, 2008) and has raised many questions about sources of exposure and the epidemiology of disease. The role of animals in human CDI is unclear, 96

although the disproportionate involvement of ribotype 078 in CA-CDI in some regions has led to concerns that food animals may play a role, through direct contact, food contamination or environmental exposure (Rupnik, 2007). Companion animals may also be a source of human infection. Typically, indistinguishable strains are found in humans and companion animals living in the same area (Weese et al., 2010; Koene et al., 2012), but within-household transmission between humans and companion animals has not yet been shown. Given limited risk factor studies as well as typing data, there is certainly circumstantial evidence that C. difficile can be transmitted between humans and companion animals, at least in certain settings; however, the true human health risk is unknown.

CONTROL MEASURES IN COMPANION ANIMALS General infection control and hygiene measures will limit the spread of C. difficile between animals. Keeping the above-mentioned risk factors for shedding in mind, particular attention should be paid to hospital environment hygiene and prudent use.

PREVENTION OF ZOONOTIC INFECTION While the role of animals in human CDI is unclear, the importance of this pathogen and the fact that identical strains are found in humans and animals indicates a need for prudence. Avoidance of direct or indirect faecal-oral exposure is the most important measure.

LINK TO AGRICULTURE C. difficile can be found in various food animals, including pigs, cattle and poultry (Debast et al., 2009; Harvey et al., 2011; Costa et al., 2012). Ribotype 078 tends to predominate in most food animals and is an emerging pathogen in humans in some regions (Keel et al., 2007; Goorhuis et al., 2008; Debast et al., 2009), a fact that has raised concerns about the potential for zoonotic transmission. The link between companion animals and food animals is unclear as it has received very little study. Since the same strains can be found in food animals and companion animals, some risk may be present, yet the predominant food animal strain appears to be very rare in companion animals. The risk posed by companion animals for transmission of C. difficile between food animals, or from food animals to humans, is likely very low.

REASONS FOR CONCERN The apparent emergence of community-associated C. difficile infection in the absence of a clear reservoir, the potential severity of disease, the indistinguishable nature of strains from humans and pets, and the increases in morbidity, treatment failure and mortality that have been noted in the past 10 years raise concerns (currently unsubstantiated) that pets may serve as a reservoir for this critical pathogen. 97

REFERENCES Benson, L., Song, X., Campos, J., et al., 2007. Changing epidemiology of Clostridium difficile-associated disease in children. Infect. Control Hosp. Epidemiol. 28, 1233-1235. Cave, N.J., Marks, S.L., Kass, P.H., et al., 2002. Evaluation of a routine diagnostic fecal panel for dogs with diarrhea. J. Am. Vet. Med. Assoc. 221, 52-59. Costa, M.C., Reid-Smith, R., Gow, S., et al., 2012. Prevalence and molecular characterization of Clostridium difficile isolated from feedlot beef cattle upon arrival and mid-feeding period. BMC Vet. Res. 8, 38. Debast, S.B., van Leengoed, L.A., Goorhuis, A., et al., 2009. Clostridium difficile PCR ribotype 078 toxinotype V found in diarrhoeal pigs identical to isolates from affected humans. Environ. Microbiol. 11, 505-511. Goorhuis, A., Debast, S.B., van Leengoed, L.A., et al., 2008. Clostridium difficile PCR ribotype 078: an emerging strain in humans and in pigs? J. Clin. Microbiol. 46, 1157. Harvey, R.B., Norman, K.N., Andrews, K., et al., Clostridium difficile in Poultry and Poultry Meat. Foodborne Pathog. Dis. 8, 1321-1323. Keel, K., Brazier, J.S., Post, K.W., et al., Prevalence of PCR ribotypes among Clostridium difficile isolates from pigs, calves, and other species. J. Clin. Microbiol. 45:1963-1964. Koene, M.G.J., Mevius, D., Wagenaar, J.A., et al., 2012. Clostridium difficile in Dutch animals: their presence, characteristics and similarities with human isolates. Clin. Microbiol. Infect. 18, 778-784. Kuijper, E.J., van Dissel, J.T. 2008. Spectrum of Clostridium difficile infections outside health care facilities. CMAJ. 179, 747-748. Lefebvre, S.L., Reid-Smith, R.J., Waltner-Toews, D., et al., 2009. Incidence of acquisition of methicillin-resistant Staphylococcus aureus, Clostridium difficile, and other health-care-associated pathogens by dogs that participate in animal-assisted interventions. J. Am. Vet. Med. Assoc. 234, 1404-1417. Marks, S.L., Rankin, S.C., Byrne, B.A., et al., 2011. Enteropathogenic bacteria in dogs and cats: diagnosis, epidemiology, treatment, and control. J. Vet. Intern. Med. 25, 1195-1208. McDonald, L.C., Killgore, G.E., Thompson, A., et al., 2005. An epidemic, toxin gene-variant strain of Clostridium difficile. N. Engl. J. Med. 353, 2433-2441. McKenzie, E., Riehl, J., Banse, H., et al., 2010. Prevalence of diarrhea and enteropathogens in racing sled dogs. J. Vet. Intern. Med. 24, 97-103. Mulvey, M.R., Boyd, D.A., Gravel, D., et al., Hypervirulent Clostridium difficile strains in hospitalized patients, Canada. Emerg. Infect. Dis. 16, 678-681. Riley, T.V., Adams, J.E., O’Neill, G.L., et al., 1991. Gastrointestinal carriage of Clostridium difficile in cats and dogs attending veterinary clinics. Epidemiol. Infect. 107, 659-665. Rupnik, M., 2007. Is Clostridium difficile-associated infection a potentially zoonotic and foodborne disease? Clin. Microbiol. Infect. 13, 457-459. 98

Weese, J., Armstrong, J., 2003. Outbreak of Clostridium difficile- associated disease in a small animal veterinary teaching hospital. J. Vet. Intern. Med. 17, 813-816. Weese, J., Finley, R., Reid-Smith, R., et al., 2010. Evaluation of Clostridium difficile in dogs and the household environment. Epidemiol. Infect. 138, 1100-1104. Weese, J., Staempfli, H., Prescott, J.F., et al., 2001. The roles of Clostridium difficile and enterotoxigenic Clostridium perfringens in diarrhea in dogs. J. Vet. Int. Med. 15, 374-378.

6.6 COXIELLA BURNETII (Q FEVER)

AETIOLOGY Coxiella burnetii is an obligate intracellular Gram-negative bacterium, which is closely related to Legionella, Francisella and Rickettsiella. The bacterium can exist in a pathogenic and a non-pathogenic phase. The former is present in infected animals and in nature, while the latter can appear during passage in the laboratory. C. burnetii can form spore- like structures, which are resistant to environmental conditions and to a range of physical and chemical agents.

ANIMAL SPECIES INVOLVED C. burnetii can infect a wide range of animals, although small ruminants and cattle are considered the reservoir hosts and the main source of human infection. C. burnetii has also been identified in wildlife and can be identified in healthy cats and dogs.

MODE/S OF TRANSMISSION C. burnetii is highly infectious with an infectious dose of only a few organisms. Infected animals can shed C. burnetii in faeces, urine and milk, but highest levels are in placental tissue, and uterine secretions are most commonly implicated in transmission. Zoonotic infections are most often related to inhalation of infectious aerosols from a periparturient animal (because of the large number of organisms that are in placenta and fetal fluids), although direct contact and ingestion can also be involved (Hartzell et al., 2008). C. burnetii can also be found in ticks (Mantovani and Benazzi, 1953; Loftis et al., 2006), and while ticks are potentially important for facilitating a sylvan cycle in reservoir species, the role of ticks in human or domestic animal transmission is likely minimal.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES Seroprevalence data in cats from Canada, Japan and South Africa range 99 from 2–42% with higher rates in stray cats (Marrie et al., 1985; Higgins and Marie, 1990; Morita et al., 1995; Matthewman et al., 1997; Komiya et al., 2003). Lower prevalences (1.4–8.5%) have been identified when using PCR to detect the actual organism (Komiya et al., 2003; Cairns et al., 2007), although a shedding rate of 31% was identified in vaginal swabs from cats in a Japanese study (Nagaoka et al., 1998). There are fewer studies in dogs. Most have reported seroprevalence rates of 0–12%, with one American study reporting antibodies against C. burnetii in 48% of hospitalized dogs and 66% of stray dogs (Willeberg et al., 1980). Very few European studies on C. burnetii in companion animals exist. One Italian study reported that only 0.9% of dogs in the Bologna region were seropositive (Baldelli et al., 1992), while a study from the Netherlands showed a seroprevalence of 13.2% in dogs and 10.4% in cats (Houwers et al., 1992). The incidence of Q fever in dogs and cats is not known and is presumably very rare since most infections are subclinical. When infection develops, clinical signs are either non-specific or related to the reproductive organs. Abortion, stillbirth, endometritis or infertility are possible consequences of Q fever in companion animals.

IMPACT ON HUMAN HEALTH Humans are the only species that regularly develop disease following C. burnetii exposure (Marrie and Raoult, 2005). The incidence of Q fever in humans is highly variable and relates to the nature of C. burnetii in domestic ruminant populations in the region. It is a rare disease in many regions, but a significant problem in others where the disease is highly endemic. Many (if not most) people that are exposed simply seroconvert, with no clinical signs. However, Q fever can produce very serious disease, with severity dictated in large part by the amount of exposure. The classical presentation is flu-like illness with fever, headache, sweats, cough, myalgia and arthralgia (Marrie and Raoult, 2005; Hartzell et al., 2008). The triad of fever, hepatitis and atypical pneumonia is strongly suggestive of Q fever, but virtually any body system can be affected, complicating diagnosis and surveillance. The acute Q fever mortality rate is estimated to be approximately 1% (Kampschreur et al., 2001). Infection in pregnant women can result in spontaneous abortion, premature birth and low birth-weight. Chronic Q fever develops in a small percentage of cases, most often pregnant women, immunosuppressed individuals and people with heart valve lesions or vascular abnormalities (Hartzell et al., 2008). Endocarditis is the most common form of chronic disease (Schimmer et al., 2011). Companion animals have been implicated in Q fever in humans (Kosatsky, 1984; Embil et al., 1990) with cats posing the greatest risk. It has been suggested that cats may be the most important reservoir in urban areas (Morita et al., 1994). As with ruminants, most infections are associated with contact with periparturient pets (Kosatsky, 1984; Embil et al., 1990). Simply being in the same house or room with an infected animal shedding large number of C. burnetii may be adequate to infect humans. Dog-associated Q fever appears to be very rare, but can 100

occur from contact with periparturient dogs (Buhariwalla et al., 1996). A case of Q fever in a person was also linked to a dog obtained from a sheep research facility with an ongoing Q fever outbreak (Rauch et al., 1987), something that should be considered if pet dogs are obtained from farms where Q fever is endemic in ruminants.

CONTROL MEASURES IN COMPANION ANIMALS The highest numbers of C. burnetii are shed during parturition. Accordingly, good hygiene should be practiced when handling the placenta and secretions from the uterus. Prophylactic antibiotic treatment prior to parturition is another measure, which could be practiced in endemic areas.

PREVENTION OF ZOONOTIC INFECTION Periparturient cats are the highest risk, although periparturient dogs cannot be ignored. High risk personnel (e.g. young, elderly, pregnant, immunocompromised, people with cardiac valvular disease) should be especially careful, and ideally avoid contact with periparturitent animals, newborns, uterine secretions, placentas and surfaces or bedding potentially contaminated by those. People who do have contact with those sources should wear gloves and avoid contamination of clothing. Aerosol transmission is also a concern, so high risk individuals should stay away from enclosed areas where animals are giving birth. Another potential concern is companion animals that live on (or are obtained from) farms where Q fever is endemic. The true risk of this is unclear, but it cannot be dismissed. Control measures have not been evaluated but good hygiene practices should be used with new animals.

LINK TO AGRICULTURE There is concern that companion animals could play a role in transmission of C. burnetii in areas where Q fever is endemic or hyperendemic. The presence of dogs or cats has been associated with increased risk of goat herd seropositivity in the Netherlands (Schimmer et al., 2011). Dogs that have contact with sheep may also have a higher seroprevalence (Boni et al., 1998). Therefore, concern has been expressed about the potential for dogs and cats to either introduce C. burnetii or facilitate its spread within a farm, although clear data are currently lacking.

REASONS FOR CONCERN The high infectivity and potential for serious disease highlight the concerns around this pathogen, despite the peripheral role that pets play in human infection. As a potential bioterrorism agent, pet surveillance is an important public health tool.

REFERENCES Baldelli, R., Cimmino, C., Pasquinelli, M., 1992. Dog-transmitted zoonoses: a serological survey in the province of Bologna. Ann. Ist Super Sanita. 28, 493-496. Boni, M., Davoust, B., Tissot-Dupont, H., et al., 1998. Survey of 101 seroprevalence of Q fever in dogs in the southeast of France, French Guyana, Martinique, Senegal and the Ivory Coast. Vet. Microbiol. 64, 1-5. Buhariwalla, F., Cann, B., Marrie, T.J., 1996. A dog-related outbreak of Q fever. Clin. Infect. Dis. 23, 753-755. Cairns, K., Brewer, M., Lappin, M.R., 2007. Prevalence of Coxiella burnetii DNA in vaginal and uterine samples from healthy cats of north-central Colorado. J. Feline Med. Surg. 9, 196-201. Embil, J., Williams, J.C., Marrie, T.J., 1990. The immune response in a cat-related outbreak of Q fever as measured by the indirect immunofluorescence test and the enzyme-linked immunosorbent assay. Can. J. Microbiol. 36, 292-296. Hartzell, J.D., Wood-Morris, R.N., Martinez, L.J., et al., 2008. Q fever: epidemiology, diagnosis, and treatment. Mayo Clin. Proc. 83, 574-579. Higgins, D., Marrie, T.J., 1990. Seroepidemiology of Q fever among cats in New Brunswick and Prince Edward Island. Ann. N. Y. Acad. Sci. 590, 271-274. Houwers, D.J., van der Meer, M., van Dijk, A.A., et al., 1992. Prevalence of infections with C. burnetii in dogs and cats in the Netherlands and the central region of the Netherlands, 1991-1992. Research report 91-102. Utrecht. Kampschreur, L.M., Wegdam-Blans, M.C.A., Thijsen, S.F.T., et al., 2010. Acute Q fever related in-hospital mortality in the Netherlands. Neth. J. Med. 68, 408-413. Komiya, T., Sadamasu, K., Kang, M.I., et al., 2003. Seroprevalence of Coxiella burnetii infections among cats in different living environments. J. Vet. Med. Sci. 65, 1047-1048. Kosatsky, T., 1984. Household outbreak of Q-fever pneumonia related to a parturient cat. Lancet. 2, 1447-1449. Loftis, A.D., Reeves, W.K., Szumlas, D.E., et al., 2006. Rickettsial agents in Egyptian ticks collected from domestic animals. Exp. Appl. Acarol. 40, 67-81. Mantovani, A., Benazzi, P., 1953. The isolation of Coxiella burnetii from Rhipicephalus sanguineus on naturally infected dogs. J. Am. Vet. Med. Ass. 122, 117-118. Marrie, T.J., Van Buren, J., Fraser, J., et al., 1985. Seroepidemiology of Q fever among domestic animals in . Am. J. Public Health. 75, 763-766. Marrie, T.J., Raoult, D., 2005. Coxiella burnetii (Q fever). In: Mandell, G.L., Bennett, J.E., Dolin, R., (Eds.), Principles and practice of infectious diseases. Elsevier, Philadelphia, pp. 2296-2303. Matthewman, L., Kelly, P., Hayter, D., et al., 1997. Exposure of cats in southern Africa to Coxiella burnetii, the agent of Q fever. Eur. J. Epidemiol. 13, 477-479. Morita, C., Katsuyama, J., Yanase, T., et al., 1994. Seroepidemiological survey of Coxiella burnetii in domestic cats in Japan. Microbiol. Immunol. 38, 1001-1003. Nagaoka, H., Sugieda, M., Akiyama, M., et al., 1998. Isolation of Coxiella burnetii from the vagina of feline clients at veterinary clinics. J. Vet. 102

Med. Sci. 60, 251-252. Rauch, A.M., Tanner, M., Pacer, R.E., et al., 1987. Sheep-associated outbreak of Q fever, Idaho. Arch. Intern. Med. 147, 341-344. Schimmer, B., Luttikholt, S., Hautvast, J.L.A., et al., 2011. Seroprevalence and risk factors of Q fever in goats on commercial dairy goat farms in the Netherlands, 2009-2010. BMC Vet. Res. 7, 81. Willeberg, P., Ruppanner, R., Behymer, D.E., et al., 1980. Environmental exposure to Coxiella burnetii: a sero-epidemiologic survey among domestic animals. Am. J. Epidemiol. 111, 437-443.

6.7 DERMATOPHYTES (DERMATOPHYTOSIS/ ‘RINGWORM’)

AETIOLOGY Dermatophytosis, more commonly referred to as ringworm, is a fungal skin infection caused by a variety of fungal pathogens. There are three general groups of dermatophytes: (i) zoophilic species are normally found on animals and many can also infect people; (ii) anthropophilic species are normally found on humans and may occasionally infect animals; (iii) geophilic species are soil-inhabiting saprophytes. The zoophilic species Microsporum canis, Trichophyton mentagrophytes and M. gypseum are the main zoonotic species associated with dogs and cats. T. equinum is most common in horses and is also zoonotic.

ANIMAL SPECIES INVOLVED Dermatophytes can infect most, if not all, companion mammals, as well as psittacine birds. Cats are the most commonly implicated companion animal source of human infections.

MODE/S OF TRANSMISSION Dermatophytes are highly transmissible and infection of other animals and people is common when an infected pet is identified (Pepin and Oxenham, 1986). Transmission is through direct contact with an infected animal or contact with dermatophyte arthrospores in the environment or on fomites. Arthrospores can also be disseminated through the air over short distances. Fleas may also carry arthrospores between individuals.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES While diseased animals probably pose the greatest risk to humans, healthy animals (particularly cats) can be carriers and sources of 103 human infection. Variable carriage rates have been reported, but the data available are too limited to suggest any geographical differences. Studies show that 3–36% of healthy dogs and 0–54% of healthy cats may be carriers (Moriello and DeBoer, 1991a; Moriello and DeBoer, 1991b; Cabañes et al., 1997; Guzman-Chavez et al., 2000; Brilhante et al., 2003; Cafarchia et al., 2006; Iorio et al., 2007; Mancianti et al., 2009). Higher rates, up to 100%, can be found in certain groups such as stray cats, cats from multicat facilities and cats <1 year of age (Iorio et al., 2007; Mancianti et al., 2009). Long-haired animals may be predisposed, although there are conflicting data on this point (Mancianti et al., 2002; Moriello and DeBoer, 1991b). Dogs are less commonly affected than cats and carriage is most common amongst puppies. Other household pet species that have been reported to carry or transmit dermatophytes include guinea pigs (Drouot et al., 2009), hamsters and psittacine birds (Cabañes et al., 1997). The incidence of disease in animals is unclear and highly variable between populations. Outbreaks with high attack rates can occur, particularly in cats in shelters, but otherwise it tends to be a sporadic disease. Symptoms are often typical ringworm lesions, which appear as scaly, focal hairless areas surrounded by erythema. Mortality rates are very low.

IMPACT ON HUMAN HEALTH The mild nature of disease in humans means that there is little surveillance and reporting of cases, so the overall burden of disease is hard to assess. Dermatophytosis has been suggested to be one of the most common zoonotic diseases. Contact with animals is one of the risk factors for human infection with M. canis (Iorio et al., 2007). Transmission between pets and humans is also suggested by the fact that cats and dogs are more likely to be carriers of M. canis when living together with a human with dermatophytosis (Cafarchia et al., 2006). Human infections are typically mild and either self-limiting or responsive to topical therapy. Symptoms are generally similar to those encountered in animals. Invasive or disseminated disease is rare and mainly occurs in highly immunocompromised individuals (Lowinger- Seoane et al., 1992; Porro et al., 1997).

CONTROL MEASURES IN COMPANION ANIMALS General infection control and hygiene measures apply to prevent the occurrence of dermatophytoses. This should include isolating infected animals on arrival in shelters, veterinary hospitals and other settings with more animals.

PREVENTION OF ZOONOTIC INFECTION Prompt recognition of ringworm in animals with clinical disease is important to allow for use of enhanced infection control measures (i.e. hand hygiene, avoiding contact with infected sites), to start treatment and to allow for environmental cleaning and disinfection. People in contact with high-risk animals (e.g. strays) may be regularly exposed to dermatophytes so good attention to hand hygiene and use of personal 104

protective equipment (e.g. protective clothing) is important.

LINK TO AGRICULTURE There is no clear link between companion animals and livestock, although the nature of dermatophytes means that transmission between those species groups (in both directions) is certainly possible. Given the endemic nature of different dermatophyte species in both groups, it is unlikely that interspecies transmission is an important problem.

REASONS FOR CONCERN While typically a self-limiting disease, dermatophytosis is one of the most common pet-associated zoonotic infections and can be highly problematic because of its highly transmissible nature and the intensity of measures that can be required to eliminate the pathogen in an infected household.

REFERENCES Brilhante, R.S., Cavalcante, C.S., Soares-Junior, F.A., et al. High rate of Microsporum canis feline and canine dermatophytoses in Northeast Brazil: epidemiological and diagnostic features. Mycopathologia. 156, 303-308. Cabañes, F.J., Abarca, M.L., Bragulat, M.R. 1997. Dermatophytes isolated from domestic animals in Barcelona, Spain. Mycopathologia. 137, 107- 113. Cafarchia, C., Romito, D., Capelli, G., et al., 2006. Isolation of Microsporum canis from the hair coat of pet dogs and cats belonging to owners diagnosed with M. canis tinea corporis. Vet. Dermatol. 17, 327-331. Drouot, S., Mignon, B., Fratti, M., et al., 2009. Pets as the main source of two zoonotic species of the Trichophyton mentagrophytes complex in Switzerland, Arthroderma vanbreuseghemii and Arthroderma benhamiae. Vet. Dermatol. 20, 13-18. Guzman-Chavez, R.E., Segundo-Zaragoza, C., Cervantes-Olivares, R.A., et al., 2000. Presence of keratinophilic fungi with special reference to dermatophytes on the haircoat of dogs and cats in México and Nezahualcoyotl cities. Rev. Latinoam. Microbiol. 42, 41-44. Hermoso de Mendoza, M., Hermoso de Mendoza, J., Alonso, J.M., et al., 2010. A zoonotic ringworm outbreak caused by a dysgonic strain of Microsporum canis from stray cats. Rev. Iberoam. Micol. 27, 62-65. Iorio, R., Cafarchia, C., Capelli, G., et al., 2007. Dermatophytoses in cats and humans in central Italy: epidemiological aspects. Mycoses. 50, 491- 495. Lowinger-Seoane, M., Torres-Rodríguez, J.M., Madrenys-Brunet, N., et al., 1992. Extensive dermatophytoses caused by Trichophyton mentagrophytes and Microsporum canis in a patient with AIDS. Mycopathologia. 120, 143-146. Mancianti, F., Nardoni, S., Cecchi, S., et al., 2002. Dermatophytes isolated from symptomatic dogs and cats in Tuscany, Italy during a 15-year-period. Mycopathologia. 156, 13-18. Moriello, K.A., DeBoer, D.J. 1991. Fungal flora of the coat of pet cats. Am. 105

J. Vet. Res. 52, 602-606. Moriello, K.A., DeBoer, D.J. 1991. Fungal flora of the haircoat of cats with and without dermatophytosis. J. Med. Vet. Mycol. 29, 285-292. Pepin, G.A., Oxenham, M. 1986. Zoonotic dermatophytosis (ringworm). Vet. Rec. 118, 110-111. Porro, A.M., Yoshioka, M.C., Kaminski, S.K., et al., 1997. Disseminated dermatophytosis caused by Microsporum gypseum in two patients with the acquired immunodeficiency syndrome. Mycopathologia. 137, 9-12.

6.8 EXTENDED-SPECTRUM β-LACTAMASE (ESBL) PRODUCING BACTERIA

AETIOLOGY ESBL stands for extended-spectrum β-lactamase, which is an enzyme produced by Gram-negative bacteria that inactivates a wide range of β-lactam including most broad-spectrum penicillins and cephalosporins. In companion animals, it is primarily associated with Escherichia coli, but can also occur in other pathogenic Enterobacteriaceae such as Proteus, Salmonella and Klebsiella. There are over 200 types of ESBL classified into three major classes: CTX-M, SHV and TEM. ESBL-encoding genes are often located on plasmids, which can harbour other resistance genes and be transmitted between bacteria. Therefore, ESBL isolates are frequently co-resistant to a range of non-β-lactam antibiotics, for example sulphonamides and aminoglycosides. AmpC is another type of β-lactamase. AmpC genes are located on the chromosome of many Enterobacteriaceae, and overexpression due to mutations can confer broad-spectrum β-lactam resistance. Some plasmids have acquired AmpC genes leading to the risk of horizontal spread between bacteria. The most common plasmid- mediated AmpC is CMY, in particular CMY-2. There are other types of extended-spectrum cephalosporinases (e.g. carbapenemases), which have an even broader spectrum of antimicrobial resistance. These enzymes certainly have the potential to spread across host barriers, but very few case reports have reported the occurrence of these enzymes in companion animals so far. Therefore, they will not be considered further.

ANIMAL SPECIES INVOLVED ESBL- and AmpC-producing bacteria have been isolated from a wide range of companion animals, food animals and wildlife species all over the world. Among companion animals, ESBLs and AmpCs are most often described in dogs, cats and horses, while their prevalence in 106

other companion animals remains to be elucidated (Ewers et al., 2012).

MODE(S) OF TRANSMISSION As for other intestinal bacteria, ESBL-and AmpC-producers are spread by the faecal-oral route. Transmission may happen either by direct contact or by contaminated fomites such as food and water.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES ESBL-producing Enterobacteriaceae have been described in companion animals since the late 1990s. Some early studies reported the presence of mainly TEM and SHV genes in clinical isolates from dogs in Spain, Portugal and Italy (Teshager et al., 2000; Féria et al., 2002). Similar to the situation in humans, a shift towards CTX-M-genes seems to have occurred in companion animals over the last decade. CTX-M-genes have been detected in 2.6–5.6% of all reported clinical and commensal Enterobacteriaceae, and overall this gene type accounts for 25–76% of all broad spectrum β-lactamases detected in companion animals (Ewers et al., 2011). CTX-M is particularly common in isolates originating in Europe, while isolates from companion animals in other continents such as America, Australia and Asia seem to have a broader variety of ESBLs and AmpCs (Ewers et al., 2012). For example, CMY-2 was detected as the only β-lactamase in two studies involving more than 200 isolates from dogs in the USA and Canada (Sanchez et al., 2002; Murphy et al., 2009). The most frequent CTX-M types reported in companion animals are CTX-M-15 and CTX-M-1 (Ewers et al., 2010; Doljeska et al., 2011; Schink et al., 2011; Damborg et al., 2012; Dierikx et al., 2012), but other types have been described as the most prevalent in specific geographical regions (e.g. CTX-M-27 in Japan) (Harada et al., 2012). Risk factors for ESBL and AmpC carriage in companion animals have not been studied to the same extent as for MRSA and MRSP. However, some studies have shown that hospitalization and antimicrobial treatment - in particular with cephalosporins - appears to select for ESBL and AmpC carriage in horses and dogs (Damborg et al., 2011; Dolejska et al., 2011; Maddox et al., 2011; Damborg et al., 2012). This is particularly concerning, since cephalosporins are one of the most common antimicrobial classes used in companion animals. ESBL and AmpC-producing bacteria are often commensals in healthy individuals, but may also represent primary or secondary pathogens in a wide range of diseases. Some of the most common clinical presentations are urinary tract infections and wound infections.

IMPACT ON HUMAN HEALTH ESBL- and AmpC-producing Enterobacteriaceae occur in hospital as well as community settings, and are an emerging threat to human health across the world. ESBLs have been associated with longer duration of hospital stays, increased treatment cost and higher mortality compared with infections with the same bacteria not producing ESBL. Some of the most commonly described risk factors associated with ESBL 107 infections are international travel, previous antimicrobial treatment and previous hospitalization (Pitout, 2010). CTX-M-15 is spread globally and predominates in most European countries (Livermore et al., 2007). This ESBL-type is generally associated with a multidrug-resistant and virulent E. coli lineage known as B2-O25b:H4-ST131. Various recent studies have reported this lineage in association with CTX-M-15 among E. coli isolates from dogs, cats and horses worldwide (Ewers et al., 2010; Timofte et al., 2011; Albrechtova et al., 2012). This illustrates that not only ESBL and AmpC genes, but also important lineages possessing these genes, may be shared between humans and companion animals. It therefore appears that transmission of this recently evolved clone has happened between humans and companion animals, either directly or indirectly. CTX-M-15 has also been reported in other Enterobacteriaceae isolated from companion animals such as K. pneumoniae (Haenni et al., 2012). A recent study showed contact with pets to be a risk factor for ESBL- carriage in healthy humans (meyer et al , 2012). Another study showed the presence of the same E. coli clone harbouring CTX-M-1 in a human and horses at the same riding centre (Dolejska et al., 2011); Apart from these studies, limited evidence of transmission between closely related humans and companion animals exists. Nevertheless, a large reservoir of both ESBL and AmpC genes exists in companion animals. Research is needed to assess and prevent the human health risk associated with this reservoir, especially in consideration of the frequent use of cephalosporins in companion animals.

CONTROL MEASURES IN COMPANION ANIMALS Considering the main risk factors for infection (antibiotic use and hospitalization), general infection control measures and rational antibiotic use appear to be important steps to prevent spread of cephalosporin-resistant bacteria among animals.

PREVENTION OF ZOONOTIC INFECTION Two main aspects must be considered. One is reducing the likelihood that companion animals are carriers. While data are lacking, this presumably largely involves prudent antimicrobial use and probably also good general infection control in veterinary hospitals. The other is reduction of exposure of humans to infected or colonized animals. Standard faecal avoidance practices and good general hygiene measures are critical to avoid faecal-oral transmission and to avoid direct contact of wounds with animal faeces.

LINK TO AGRICULTURE The alarmingly high rates of ESBL-producing E. coli from livestock, especially poultry and pigs, are an important issue all over the world. At least seven clones of E. coli possessing ESBL genes have been reported in both companion animals and livestock (Ewers et al., 2012). This indicates a potential for transmission of these bacteria and their resistance determinants across the host barrier. Nevertheless, there is currently no evidence that companion animals are an important source 108

of ESBL for livestock, but the situation is dynamic and further study is required.

REASONS FOR CONCERN While the role of pets in human infection is currently unknown, establishment of ESBLs in a vast commensal population of Enterobacteriaceae in pets could create a significant community reservoir for subsequent human colonization and infection.

REFERENCES Albrechtova, K., Dolejska, M., Cizek, A., et al., 2012. Dogs of nomadic pastoralists in northern Kenya are reservoirs of plasmid-mediated cephalosporin- and quinolone-resistant Escherichia coli, including pandemic clone B2-O25-ST131. Antimicrob. Agents Chemother. 56, 4013- 4017. Damborg, P., Gaustad, I.B., Olsen, J.E., et al., 2011. Selection of CMY- 2 producing Escherichia coli in the faecal flora of dogs treated with cephalexin. Vet. Microbiol. 151, 404-408. Damborg, P., Marskar, P., Baptiste, K.E., et al., 2012. Faecal shedding of CTX-M-producing Escherichia coli in horses receiving broad-spectrum antimicrobial prophylaxis after hospital admission. Vet. Microbiol. 154, 298-304. Dierikx, C.M., van Duijkeren, E., Schoormans, A.H., et al., 2012. Occurrence and characteristics of extended-spectrum-β-lactamase- and AmpC- producing clinical isolates derived from companion animals and horses. J. Antimicrob. Chemother. 67, 1368-1374. Dolejska, M., Duskova, E., Rybarikova, J., et al., 2011. Plasmids carrying blaCTX-M-1 and qnr genes in Escherichia coli isolates from an equine clinic and a horseback riding centre. J. Antimicrob. Chemother. 66, 757- 764. Ewers, C., Grobbel, M., Stamm, I., et al., 2010. Emergence of human pandemic O25:H4-ST131 CTX-M-15 extended-spectrum beta-lactamase- producing Escherichia coli among companion animals. J. Antimicrob. Chemother. 65, 651-660. Ewers, C., Grobbel, M. Bethe, et al., 2011. Extended-spectrum beta- lactamases-producing gram-negative bacteria in companion animals: action is clearly warranted! Berl. Munch. Tierarztl. Wochenschr. 124, 10- 17. Ewers, C., Bethe, A., Semmler, T., et al., 2012. Extended-spectrum β-lactamase-producing and AmpC-producing Escherichia coli from livestock and companion animals, and their putative impact on public health: a global perspective. Clin. Microbiol. Infect. 18, 646-655. Féria, C., Ferreira, E., Correia, J.D., et al., 2002. Patterns and mechanisms of resistance to beta-lactams and beta-lactamase inhibitors in uropathogenic Escherichia coli isolated from dogs in Portugal. J. Antimicrob. Chemother. 49, 77-85. Haenni, M., Ponsin, C., Métayer, V., et al. 2012. Veterinary hospital- acquired infections in pets with a ciprofloxacin-resistant CTX-M-15- producing Klebsiella pneumoniae ST15 clone. J. Antimicrob. Chemother. 109

67, 770-771. Harada, K., Nakai, Y., Kataoka, Y., 2012. Mechanisms of resistance to cephalosporin and emergence of O25b-ST131 clone harboring CTX-M-27 β-lactamase in extraintestinal pathogenic Escherichia coli from dogs and cats in Japan. Microbiol Immunol. 56, 480-485. Livermore, D.M., Canton, R., Gniadkowski, M., et al., 2007. CTX-M: changing the face of ESBLs in Europe. J. Antimicrob. Chemother. 59, 165-174. Maddox, T.W., Pinchbeck, G.L., Clegg, P.D., et al., 2011. Cross-sectional study of antimicrobial-resistant bacteria in horses. Part 2: Risk factors for faecal carriage of antimicrobial-resistant Escherichia coli in horses. Equine Vet. J. 44, 297–303. Meyer, E, Gastmeyer, P., Kola, A., Schwab, F. 2012. Pet animals and foreign travel are risk factors for colonization with extended-spectrum b-lactamase-producing Escherichia coli. Infection. 40, 685-687. Murphy, C., Reid-Smith, R.J., Prescott, J.F., et al., 2009. Occurrence of antimicrobial resistant bacteria in healthy dogs and cats presented to private veterinary hospitals in southern : A preliminary study. Can. Vet. J. 50, 1047-1053. Pitout, J.D.D., 2010. Infections with Extended-Spectrum β-Lactamase- Producing Enterobacteriaceae. Changing Epidemiology and Drug Treatment Choices. Drugs. 70, 313-333. Sanchez, S., McCrackin Stevenson, M.A., Hudson, C.R., et al., 2002. Characterization of multidrug-resistant Escherichia coli isolates associated with nosocomial infections in dogs. J. Clin. Microbiol. 40, 3586-3595. Schink, A.K., Kadlec, K., Schwarz, S., 2011. Analysis of bla(CTX-M)- carrying plasmids from Escherichia coli isolates collected in the BfT- GermVet study. Appl. Environ. Microbiol. 77, 7142-7146. Teshager, T., Dominguez, L., Moreno, M.A., et al., 2000. Isolation of an SHV-12 beta-lactamase-producing Escherichia coli strain from a dog with recurrent urinary tract infections. Antimicrob. Agents Chemother. 44, 3483-3484. Timofte, D., Dandrieux, J., Wattret, A., et al., 2011. Detection of extended- spectrum-beta-lactamase-positive Escherichia coli in bile isolates from two dogs with bacterial cholangiohepatitis. J. Clin. Microbiol. 49, 3411- 341

6.9 LEPTOSPIRA SPP. (LEPTOSPIROSIS)

AETIOLOGY Leptospirosis is caused by members of the genus Leptospira, a diverse 110

group of spiral-shaped Gram-negative bacteria. Classification and nomenclature contribute to confusion, and while there are hundreds of different serovars, a limited number are responsible for the majority of human and domestic animal infections. Leptospires can survive for long periods of time in warm, wet environments (Langston and Heuter, 2003).

ANIMAL SPECIES INVOLVED Virtually any domestic animal species can be infected, but certain serovars predominate in different animal species (Table 6.2). Each serovar has one or more reservoir hosts, and these hosts tend to be able to shed large numbers of leptospires in urine in the absence of clinical disease. These are, therefore, the main sources of environmental contamination, and human and animal exposure.

Table 6. 2 Common serovars of L. interrogans sensu lato in dogs and humans (Weese and Fulford, 2011)

Other incidental domestic Serovar Primary reservoir host animal hosts Bratislava Rat, pig, horse? Cow, horse Autumnalis Mouse Cow Cow, horse, pig, cat, guinea Icterohemorrhagiae Rat pig Horse, sheep, goat, rabbit, Pomona Cow, pig, , possum cat, guinea pig Canicola Dog Cow, horse, pig, cat, raccoon Bataviae Dog, rat, mouse Cow, cat Hardjo Cow Pig, horse, sheep Vole, raccoon, skunk, Cow, pig, sheep, goat, rabbit, Gryppotyphosa possum gerbil, guinea pig

MODE/S OF TRANSMISSION Ingestion of leptospires or contact of leptospires with mucous membranes or broken skin can result in infection (Levett, 2001 and 2007). Infected individuals shed leptospires in their urine, and most infections are from urine-contaminated environmental sources, particularly water.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES Prevalence data are variable and typically focus on seroprevalence, with no indication of actual urine shedding of leptospires. Seroprevalence rates vary in healthy pet dogs across Europe. Rates of <12% have been seen in surveys in Denmark, Greece and Italy (Scanziani et al., 2002; Burriel et al., 2003; Thorsen, 2008), while rates of 22–36% were detected in dogs from Spain, Poland and Scotland (van den Broek et al., 1991; Krawczyk, 2005; Millán et al., 2009). In general, higher rates (up to 84%) are often present in stray dogs and kennelled dogs (Scanziani et al., 2002; Jittapalapong et al., 2009), and predominant serovars vary 111 by animal species and region. It should be noted that seroprevalence rates must be interpreted with caution, since titres often vary between studies. Risk factors for seropositivity or disease in dogs include factors that would increase the risk of exposure to areas contaminated by livestock or wildlife urine: livestock exposure, wildlife exposure, exercise outside of fenced yards, being a working, herding or hound dog, living in periurban regions and living in urban versus rural regions (Ward et al., 2002; Ward et al., 2004; Stokes et al., 2007; Alton et al., 2009). While much less common, leptospirosis can occur in cats, particularly stray cats (Bolin, 1996; Millán et al., 2009). Leptospirosis can also occur in a variety of other companion animals and less common pets such as rats, which may be reservoir hosts of important serovars. Such animals may actually pose a much higher relative risk compared with dogs and cats (Gaudie et al., 2008; Guerra et al., 2008). Leptospirosis is considered a re-emerging disease in companion animals in North America, as rates of infection have greatly increased (Moore et al., 2006; Alton et al., 2009). Possible reasons for this change in incidence include a change in the predominant serovars, increased numbers of raccoons and other urban wildlife, increased infection of urban wildlife and perhaps climate changes that favour survival of the organism in the environment (Glickman et al., 2006; Prescott, 2008; Alton et al., 2009). A gradual change in serovars is also apparent in Europe, but available data is too limited to conclude whether infections rates are increasing in companion animals. Animals are often asymptomatic carriers of leptospires, but mild to severe disease may develop. Clinical signs can be non-specific, but are often related to the urinary tract.

IMPACT ON HUMAN HEALTH The incidence of human infection in most regions is low, such as the 0.06/100,000 people incidence rate reported in Germany (Jansen et al., 2005). Most infections are mild or asymptomatic, but leptospirosis may develop into more serious disease. Symptoms are generally non- specific and can range from rash, headache and lymphadenopathy to systemic symptoms with signs of multiorgan failure. Leptospirosis is considered to be one of the most common zoonotic pathogens internationally, yet the vast majority of infections are from wildlife and food producing animals. Companion animals can be sources of infection, yet their overall contribution to the burden of disease in humans is thought to be very limited. Zoonotic transmission from dogs is poorly documented and largely involves anecdotal reports. Two case reports have documented leptospirosis in dog owners following contact with urine from infected dogs (Allard and Bedard, 2006; Vincent et al., 2007), although it is difficult to exclude common source exposure of both the dog and person. However, while the limitations of anecdotes and single case reports must be remembered, it appears clear that there is a risk of transmission of leptospirosis from dogs to people, particularly people caring for dogs with acute disease. The risk is likely greatest to veterinary personnel that handle acutely ill animals and are at greatest risk of encountering urine or urine-soaked items. Given the 112

potential severity of disease, especially in pregnant women and people with compromised immune systems, this disease is of concern. Apart from veterinary personnel and owners of infected dogs, rat owners may be the main risk group for companion animal-associated disease, including disease from contact with apparently healthy rats (Gaudie et al., 2008; Guerra et al., 2008).

CONTROL MEASURES IN COMPANION ANIMALS Vaccinating dogs against leptospirosis prevents disease, but not all vaccines prevent infection or shedding of leptospires. Vaccination has also been associated with side effects, particularly in puppies <12 weeks of age and in small/toy dog breeds. Accordingly, vaccination is mainly recommended for dogs subjected to the above-mentioned risk factors for seropositivity (e.g. exposure to wildlife). Most vaccines against leptospirosis are killed or attenuated bacterins protecting against the serovars canicola and icterohemorrhagiae. However, a quadrivalent, subunit-based vaccine providing additional protection against the serovars grippotyphosa and pomona has been introduced in North America recently after a change in the serovars observed among dogs. Although less is known about the situation in Europe, a similar change in serovars also seems to occur in European countries suggesting that currently available vaccines may not always provide sufficient protection. Leptospirosis suspects should be housed in isolation, if possible, and direct or indirect contact with other animals or personnel should be avoided. Infected dogs should not be allowed to urinate outside in areas where other animals may visit and ideally not in the vicinity of water sources. Antimicrobial treatment should be initiated promptly when leptospirosis is suspected. It is assumed that dogs stop shedding leptospires within 24–72h of initiation of proper antimicrobial therapy, yet dog-specific data are limited. A reasonable approach used by some facilities is to consider cases non-infectious after 48–72 h of appropriate therapy. Some facilities also require a bath and hot air drying on the basis that this would help eliminate any leptospires on the hair coat. Optimal practices are not known, but this is a reasonable and practical approach. Zoonotic infection from rats is another concern, and one that is heightened by the potential for long term leptospire shedding by clinically normal rats. Routine testing is impractical or has unknown sensitivity, so measures to reduce the risk of rats becoming infected and to reduce human exposure are indicated. While rats should not be adopted as pets, pet rats should not be allowed to have contact with wild rodents, and pet rat owners should be particularly diligent to ensure that there are no wild rodent infestations in their household.

PREVENTION OF ZOONOTIC INFECTION In dogs, the risk of infection is greatest during the initial phase of disease, when leptospiruria may be present, when there may be abundant handling of the animal for diagnosis and treatment, and when leptospirosis may not yet be suspected. Prevention involves avoiding 113 contact with urine from infected animals. This involves pet owners and veterinary personnel. A key aspect is prompt recognition of the potential for leptospirosis so that treatment can be started promptly. For pet owners prior to (or in the absence of) veterinary care, good general hygiene practices, particularly hand hygiene associated with handling of animals or contact with urine (e.g. cleaning rat cages), is critical. Veterinary personnel may be at particular risk when handling infected animals prior to treatment, especially as the vague nature of disease may result is leptospirosis not being considered initially. Contact with rat urine should be avoided. Care should be taken when handling rats or cleaning their cages. Good handwashing practices are probably adequate in most situations, but individuals with skin lesions should wear gloves when contact with urine may occur (e.g. cage cleaning). High-risk individuals (i.e. <5 yrs of age, elderly, immunocompromised or pregnant) should limit or avoid contact with rats, and at a minimum avoid cleaning rat cages and ensure good hand hygiene practices.

LINK TO AGRICULTURE There is little concern that companion animals are a realistic source of food animal leptospirosis. Leptospirosis is a concern in food producing animals, yet there are much more likely sources of exposure than urine from companion animals.

REASONS FOR CONCERN As a re-emerging pathogen in many areas that is well established in wildlife (including urban wildlife) populations, the risk of pet infections may be increasing. Increasing rates of leptospirosis in pets create risk to in-contact humans, with the potential for severe disease. Further, the often vague nature of human disease can complicate diagnosis, leading to suboptimal treatment.

REFERENCES Allard, R., Bedard, L., 2006. Explanatory notes on statistics for reportable disease and other infectious diseases under surveillance, period 3, year 2006 (weeks 9-12) [26 February 2006 to 25 March 2006]) , Quebec: Montreal Public Health Department. Alton, G.D., Berke, O., Reid-Smith, R., et al., 2009. Increase in seroprevalence of canine leptospirosis and its risk factors, Ontario 1998-2006. Can. J. Vet. Res. 73, 167-175. Bolin, C.A., 1996. Diagnosis of leptospirosis: a reemerging disease of companion animals. Semin. Vet. Med. Surg. Small Anim. 11, 166-171. Burriel, A.R., Dalley, C., Woodward, M.J., 2003. Prevalence of leptospira species among farmed and domestic animals in Greece. Vet. Rec. 153, 146-148. Gaudie, C.M., Featherstone, C.A., Phillips, W.S., et al., 2008. Human Leptospira interrogans serogroup icterohaemorrhagiae infection (Weil’s disease) acquired from pet rats. Vet. Rec. 163, 599-601. Glickman, L., Moore, G., Glickman, N., et al., 2006. Purdue University- Banfield National Companion Animal Surveillance Program for emerging 114

and zoonotic diseases. Vector Borne Zoonotic Dis. 6, 14-23. Guerra, B., Schneider, T., Luge, E., et al., 2008. Detection and characterization of Leptospira interrogans isolates from pet rats belonging to a human immunodeficiency virus-positive patient with leptospirosis. J. Med. Microbiol. 57, 133-135. Jansen, A., Schöneberg, I., Frank, C., et al., 2005. Leptospirosis in Germany, 1962-2003. Emerging Infect. Dis. 11, 1048-1054. Jittapalapong, S., Sittisan, P., Sakpuaram, T., et al., 2009. Coinfection of Leptospira spp and Toxoplasma gondii among stray dogs in Bangkok, Thailand. Southeast Asian J. Trop. Med. Public Health. 40, 247-252. Krawczyk, M. 2005. Serological evidence of leptospirosis in animals in northern Poland. Vet. Rec. 156, 88-89. Langston, C.E., Heuter, K.J., 2003. Leptospirosis. A re-emerging zoonotic disease. Vet. Clin. North Am. Small Anim. Pract. 33, 791-807. Levett, P.N., 2001. Leptospirosis. Clin. Microbiol. Rev. 14, 296-326. Levett, P.N., 2007. Leptospira. In: Murray, P.R., Baron, E.J., Jorgensen, J.H., et al., (Eds.), Manual of clinical microbiology. 9th ed., ASM Press, Washington, DC, pp. 963-970. Millán, J., Candela, M.G., López-Bao, J.V., et al., 2009. Leptospirosis in wild and domestic carnivores in natural areas in Andalusia, Spain. Vector Borne Zoonotic Dis. 9, 549-554. Moore, G.E., Guptill, L.F., Glickman, N.W., et al., 2006. Canine leptospirosis, United States, 2002-2004. Emerging Infect. Dis. 12, 501-503. Prescott, J., 2008. Canine leptospirosis in Canada: a veterinarian’s perspective. CMAJ. 178, 397-398. Scanziani, E., Origgi, F., Giusti, A.M., et al., 2002. Serological survey of leptospiral infection in kennelled dogs in Italy. J. Small Anim. Pract. 43, 154-157. Stokes, J.E., Kaneene, J.B., Schall, W.D., et al., 2007. Prevalence of serum antibodies against six Leptospira serovars in healthy dogs. J. Am. Vet. Med. Ass. 230, 1657-1664. Thorsen, M., 2008. Leptospirose. Dansk Veterinær Tidsskrift. 7, 20-24 (in Danish). Van den Broek, A.H.M., Thrusfield, M.V., Dobbie, G.R., et al., 1991. A serological and bacteriological survey of leptospiral infection in dogs in Edinburgh and Glasgow. J. Small Anim. Pract. 32, 118-124. Vincent, C., Munger, C., Labrecque, O., 2007. La leptospirose: Cas de transmission d’un chien a un humain. Quebec City, QC: Reseau d’Alerte et d’Information Zoosanitaire (RAIZO) Bulletin Zoosanitaire [no. 51]. Ward, M.P., Glickman, L.T., Guptill, L.E., 2002. Prevalence of and risk factors for leptospirosis among dogs in the United States and Canada: 677 cases (1970-1998). J. Am. Vet. Med. Ass. 220, 53-58. Ward, M.P., Guptill, L.F., Wu, C.C., 2004. Evaluation of environmental risk factors for leptospirosis in dogs: 36 cases (1997-2002). J. Am. Vet. Med. Ass. 225, 72-77. Weese, J.S., Fulford, M.B., 2011. Bacterial diseases In: Weese, J.S., Fulford, M.B., (Eds.), Companion Animal Zoonoses, Wiley-Blackwell, Ames, Iowa. 115

6.10 METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)

AETIOLOGY Staphylococcus aureus is a coagulase-positive Staphylococcus species and an important cause of opportunistic infections in humans and various animal species. MRSA is S. aureus that has acquired mecA, a gene that confers resistance to virtually all β-lactam antimicrobials. MRSA isolates often are also resistant to various other antimicrobial classes.

ANIMAL SPECIES INVOLVED MRSA can be identified in many companion animal, food animal, exotic and wildlife species. Among companion animals, MRSA can be found not uncommonly in dogs, cats and horses.

MODE/S OF TRANSMISSION MRSA is spread primarily through direct contact with an infected or colonized animal. Infection from contaminated environmental sources or fomites cannot be ruled out, but presumably is of much less concern. While MRSA can be transmitted within veterinary hospitals (Weese et al., 2006 and 2007), most MRSA cases appear to originate in the community.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES MRSA occurs sporadically in companion animals and geographical differences in prevalence appear to follow local prevalence rates in humans. Reported colonization rates are variable but tend to be 0–3.3% in healthy dogs and 0–6% in healthy cats (Abraham et al., 2007; Hanselman et al., 2009; Kottler et al., 2009; Loeffler et al., 2010). Higher rates can be encountered periodically in animals in veterinary facilities (Loeffler et al., 2005; Weese et al., 2007) as well as specific dog populations such as households where another pet has an MRSA infection (Faires et al., 2009), or during outbreaks in breeding or rescue kennels (Loeffler et al., 2009; Floras et al., 2010). Being owned by a human healthcare worker, participation in hospital visitation programs, contact with children and antimicrobial exposure have been identified as risk factors for MRSA colonization in dogs (Boost et al., 2007; Lefebvre et al., 2009; Faires et al., 2010; Soares Magalhaes et al., 2010). Virtually all MRSA isolates from dogs and cats are recognized human epidemic clones, and the strain distribution in dogs and cats tends to mirror the human strain distribution in the area (Lefebvre et al., 2009; Loeffler et 116

al., 2009). In Europe, this can be exemplified by the situation in the UK, where the local human epidemic clones EMRSA-15 and EMRSA-16 predominate in dogs and cats (Loeffler et al., 2005; Moodley et al., 2006). This fact, along with some of the reported risk factor data strongly suggests that MRSA in companion animals is largely driven by MRSA in the corresponding human population. It is unclear whether there is truly a self-propagating MRSA population in dogs and cats, or whether canine and feline prevalence data simply reflect the degree of exposure from humans. MRSA colonization in cats and dogs seems to be transient (Lefebvre et al., 2009; Loeffler et al., 2009) further supporting the need for close contact with humans for maintenance of MRSA in pet populations. MRSA appears to be endemic in the horse population in many areas, with prevalence rates of up to 11% in surveillance studies (Weese et al., 2005a; Loeffler et al., 2010). Higher rates (50% or more) can be found on individual farms (Weese et al., 2005a). As opposed to dogs and cats, where MRSA strains mimic those that predominate in their human contacts, two main clones are found in horses internationally. These are a sequence type (ST) 8 clone that is presumably of human origin and the livestock-associated ST398. The majority of animals that harbour MRSA do not have clinical infections. The incidence of MRSA infection in dogs and cats is therefore low and subject to geographical variation. MRSA infections most commonly involve skin, ears, wounds and surgical sites (Moodley et al., 2006; Faires et al., 2010) as would be expected for an opportunistic pathogen like S. aureus. In horses, wound, surgical site and joint infections tend to predominate (Weese et al., 2005b).

IMPACT ON HUMAN HEALTH MRSA is a critically important pathogen in humans causing both nosocomial and community-associated (CA) infections. It has been estimated that annually approximately 150,000 people within the EU are affected by MRSA, and such infections are associated with higher morbidity, mortality and healthcare costs compared with infections caused by methicillin-susceptible S. aureus (MSSA). Some of the common risk factors for acquisition of healthcare-associated MRSA include previous antibiotic treatment, hospital care and presence of indwelling devices, while poor hygiene and living in crowded facilities are amongst the risk factors for CA-MRSA (Köck et al., 2011). Besides these well-established risk factors for infection, animal contact appears to be a risk factor for MRSA colonization. Numerous studies of MRSA colonization in veterinary personnel have been performed, generally reporting high (up to 18%) colonization rates (Loeffler et al., 2005; Burstiner et al., 2009). It cannot be determined with certainty that these colonization rates reflect acquisition of MRSA from animals; however, identification of higher rates than present in the general population (Gorwitz et al., 2008) and the similarity between human and animal strains provide support of occupational origin. Similarly, horse owners have been identified as having high MRSA colonization rates (Weese et al., 2005a). Therefore, MRSA is a recognized occupational 117 risk for veterinary staff, farm workers, animal caretakers and other professionals working in contact with animals. Such a risk is particularly high for farmers and veterinary staff exposed to livestock due to the recent spread of zoonotic MRSA ST398 in humans (Garcia-Graells et al., 2012). The role of companion animals in human infection is poorly understood. While it is clear that people and companion animals can share the same MRSA strains (Weese et al., 2005b; Boost et al., 2007), direction of transmission has not been elucidated. Regardless, while information from most studies should be considered preliminary and circumstantial, it is very likely that interspecies transmission can occur in households and in veterinary clinics and that MRSA, while human in origin, is a relevant zoonotic pathogen.

CONTROL MEASURES IN COMPANION ANIMALS Risk factors for MRSA infections in dogs and cats include veterinary treatment, number of antimicrobial treatments, number of days admitted to veterinary hospitals, and having surgical implants (Loeffler et al., 2010; Soares-Magalhaes et al., 2010). This shows that prevention of MRSA is particularly important in veterinary hospitals where focus should be on general infection control measures as well as prudent antibiotic use.

PREVENTION OF ZOONOTIC INFECTION Two different concepts must be considered. One is limiting MRSA carriage in companion animals. This can be accomplished by prudent use of antimicrobials, good hygiene practices when working with animals, restriction of contact between people with MRSA infection or colonization and animals, and improvement in infection control in veterinary hospitals. The second concept is reducing the risk of transmission of MRSA from companion animals to people when infection or colonization does develop. One component of this is ensuring prompt and correct diagnosis of MRSA infection. Another is the use of routine hygiene and infection control practices to reduce the risk of transmission from animals of unknown MRSA status. The final is the use of enhanced hygiene practices as well as isolation of animals when dealing with known infected or colonized animals.

LINK TO AGRICULTURE Livestock-associated MRSA is an important issue in some regions, particularly northern Europe. However, this almost exclusively involves MRSA ST398. This livestock-associated MRSA lineage has been reported in dogs and horses (Van den Eede et al., 2008; Floras et al., 2010) and may be increasing in prevalence, particularly in horses. Indeed, several outbreaks of MRSA ST398 have been reported in equine hospitals in Europe (van Duijkeren et al., 2010; Bergström et al., 2012). There is no evidence that companion animals are a potentially important source of MRSA transmission to or between food animals, but the situation is dynamic and research is required. The main concern is the potential for companion animals on farms to act as a vector of MRSA from livestock 118

to human household members. There are also serious animal health concerns associated with the emergence of livestock-associated MRSA ST398 in equine hospitals.

REASONS FOR CONCERN As a critically important human pathogen that is increasingly a cause of community-associated disease, there is much public and regulatory concern about MRSA in animals. While the role of pets in human disease is unclear, it is clear that MRSA can be transmitted between humans and animals, and that there is the potential for pets to act as important reservoirs of MRSA in the community (typically after exposure to an infected person). As MRSA continues to increase in people in the community, the risk to, and from, pets will presumably increase correspondingly. Recent identification of livestock-associated MRSA strains in pets also creates the potential that pets could be an additional source of this emerging pathogen.

REFERENCES Abraham, J., Morris, D., Griffeth, G., et al., 2007. Surveillance of healthy cats and cats with inflammatory skin disease for colonization of the skin by methicillin-resistant coagulase-positive staphylococci and Staphylococcus schleiferi ssp. schleiferi. Vet. Dermatol. 18, 252-259. Bergström, K., Nyman, G., Widgren, S., et al., 2012. Infection prevention and control interventions in the first outbreak of methicillin-resistant Staphylococcus aureus infections in an equine hospital in Sweden. Acta Vet. Scand. 54, 14. Boost, M., O’donoghue, M., Siu, K., 2007. Characterisation of methicillin- resistant Staphylococcus aureus isolates from dogs and their owners. Clin. Microbiol. Infect. 13, 731-733. Burstiner, L., Faires, M., Weese, J.S., 2009. Methicillin-resistant Staphylococcus aureus colonization of veterinary personnel at a surgical conference. ASM-ESCMID conference on methicillin-resistant staphylococci in animals, London, UK. Faires, M.C., Tater, K.C., Weese, J.S., 2009. An investigation of methicillin- resistant Staphylococcus aureus colonization in people and pets in the same household with an infected person or infected pet. J. Am. Vet. Med. Assoc. 235, 540-543. Faires, M.C., Traverse, M., Tater, K.C., et al., 2010. Methicillin-resistant and -susceptible Staphylococcus aureus infections in dogs. Emerg. Infect. Dis. 16, 69-75. Floras, A., Lawn, K., Slavic, D., et al., 2010. Sequence type 398 meticillin- resistant Staphylococcus aureus infection and colonisation in dogs. Vet. Rec. 166, 826-827. Garcia-Graells, C., Antoine, J., Larsen, J., et al., 2012. Livestock veterinarians at high risk of acquiring methicillin-resistant Staphylococcus aureus ST398. Epidemiol. Infect. 140, 383-389. Gorwitz, R.J., Kruszon-Moran, D., McAllister, S.K., et al., 2008. Changes in the prevalence of nasal colonization with Staphylococcus aureus in the United States, 2001-2004. J. Infect. Dis. 197, 1226-1234. 119

Hanselman, B.A., Kruth, S.A., Rousseau, J., et al., 2009. Coagulase positive staphylococcal colonization of humans and their household pets. Can. Vet. J. 50, 954-958. Köck, R., Becker, K., Cookson, B., et al., 2011. Methicillin-resistant Staphylococcus aureus (MRSA): burden of disease and control challenges in Europe. Clin. Microbiol. Infect. 17, 1507-1513. Kottler, S., Middleton, J.R., Perry, J., et al., 2009. Prevalence of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus carriage in three populations. J. Vet. Intern. Med. 24, 132-139. Lefebvre, S.L., Reid-Smith, R.J., Waltner-Toews, D., et al., 2009. Incidence of acquisition of methicillin-resistant Staphylococcus aureus, Clostridium difficile, and other health-care-associated pathogens by dogs that participate in animal-assisted interventions. J. Am. Vet. Med. Assoc. 234, 1404-1417. Loeffler, A., Boag, A., Sung, J., et al., 2005. Prevalence of methicillin- resistant Staphylococcus aureus among staff and pets in a small animal referral hospital in the UK. J. Antimicrob. Chemother. 56, 692-697. Loeffler, A., Pfeiffer, D.U., Lindsay, J.A., et al., 2010. Prevalence of and risk factors for MRSA carriage in companion animals: a survey of dogs, cats and horses. Epidemiol Infect. 14, 1-10. Loeffler, A., Pfeiffer, D., Lindsay, J., et al., 2009. Lack of transmission of methicillin-resistant Staphylococcus aureus (MRSA) between apparently healthy dogs in a rescue kennel. Vet. Microbiol. 141, 178-181. Moodley, A., Stegger, M., Bagcigil, A.F., et al., 2006. spa typing of methicillin-resistant Staphylococcus aureus isolated from domestic animals and veterinary staff in the UK and Ireland. J. Antimicrob. Chemother. 58, 1118-1123. Soares Magalhães, R.J., Loeffler, A., Lindsay, J., et al., 2010. Risk factors for methicillin-resistant Staphylococcus aureus (MRSA) infection in dogs and cats: a case-control study. Vet. Res. 41, 55. van den Eede, A., Martens, A., Lipinska, U., et al. High occurrence of methicillin-resistant Staphylococcus aureus ST398 in equine nasal samples. Vet. Microbiol. 133, 138-144. van Duijkeren, E., Moleman, M., Sloet van Oldruitenborgh-Oosterbaan, M.M., et al., 2010. Methicillin-resistant Staphylococcus aureus in horses and horse personnel: an investigation of several outbreaks. Vet. Microbiol. 141, 96-102. Weese, J.S., Rousseau, J., Traub-Dargatz, J.L., et al., 2005a. Community- associated methicillin-resistant Staphylococcus aureus in horses and humans who work with horses. J. Am. Vet. Med. Assoc. 226, 580-583. Weese, J.S., Archambault, M., Willey, B.M., et al., 2005b. Methicillin- resistant Staphylococcus aureus in horses and horse personnel, 2000- 2002. Emerg. Infect. Dis. 11, 430-435. Weese, J.S., Rousseau, J., Willey, B.M., et al., 2006. Methicillin-resistant Staphylococcus aureus in horses at a veterinary teaching hospital: frequency, characterization, and association with clinical disease. J. Vet. Intern. Med. 20, 182-186. Weese, J.S., Faires, M., Rousseau, J., et al., 2007. Cluster of methicillin- resistant Staphylococcus aureus colonization in a small animal intensive care unit. J. Am. Vet. Med. Assoc. 231, 1361-1364. 120

6.11 METHICILLIN-RESISTANT STAPHYLOCOCCUS PSEUDINTERMEDIUS (MRSP)

AETIOLOGY Staphylococcus pseudintermedius is a coagulase-positive Staphylo- coccus species that is a common commensal and opportunistic path- ogen in dogs and to a lesser degree cats. Some strains (MRSP) have acquired mecA, a gene that confers resistance to β-lactam antimicro- bials. These have often acquired various other resistance genes, and MRSP are commonly resistant to a wide range of antimicrobials. Most individuals harbouring MRSP are carriers, with no sign of clinical dis- ease, but serious infections can develop. Previously, S. intermedius was considered the main canine coagulase-positive Staphylococcus spe- cies; however, it is apparent that this was due to misidentification and that canine ‘S. intermedius’ isolates should be regarded as S. pseud- intermedius in the absence of genotypic identification (Devriese et al., 2005).

ANIMAL SPECIES INVOLVED Dogs are the main host of S. pseudintermedius and correspondingly MRSP, while MRSP is less common in cats and has been sporadically identified in horses (Wettstein et al., 2008; Ruscher et al., 2009; Perreten et al., 2010; Beck et al., 2012).

MODE/S OF TRANSMISSION Transmission is primarily through direct contact with an infected or colonized individual. Transmission may also occur via contaminated fomites or hospital environments.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES MRSP has emerged globally in dogs and to a lesser extent in cats since 2006. MRSP prevalence data vary between studies, reflecting differences in study populations. Surveillance studies of mainly healthy individuals from America, Asia and Europe have reported prevalence of 2.1–17% in dogs and 1.2–2.3% in cats (Vengust et al., 2006; Hanselman et al., 2007; Griffeth et al., 2008; Epstein et al., 2009; Hanselman et al., 2009; Nienhoff et al., 2011) with higher rates identified in groups such as animals that have been treated for pyoderma (Beck et al., 2012). In Europe, the extent of MRSP amongst clinical isolates varies widely between countries. In Denmark and Sweden, 2–3% of clinical S. pseudintermedius were MRSP in 2010 (Damborg and Guardabassi, 2012; Bengesson et al., 2012), while the corresponding number for 121 recent studies in the Netherlands, Italy and Switzerland were 9% (Duim et al., 2011), 21% (De Lucia et al., 2011) and 46% (Huber et al., 2011), respectively. MRSP can be found occasionally in healthy or diseased horses but proper prevalence data are lacking.

MRSP has emerged as a critically important canine pathogen. In many regions, it is a leading cause of pyoderma and otitis, and a common cause of wound and surgical site infections, along with a range of other opportunistic infections (Wettstein et al., 2008; Perreten et al., 2010; Beck et al., 2012). Veterinary hospital-associated transmission can occur, yet MRSP is primarily a community-associated pathogen. Reasons for the rapid international emergence of highly drug-resistant MRSP are unclear. The potential for long-term carriage of MRSP (mainly at mucosal sites) (Laarhoven et al., 2011), the impact of antimicrobial therapy on MRSP acquisition (Nienhoff et al., 2011b; Beck et al., 2012) and biofilm production (Osland et al., 2012) may play a role, along with other unknown factors. MRSP spreads clonally and the most prevalent MRSP clone in Europe is by far ST71 (Perreten et al., 2010).

IMPACT ON HUMAN HEALTH S. pseudintermedius infections are reported sporadically in humans (Chuang et al., 2010; Durdik et al., 2010), including MRSP infections (Stegmann et al., 2010). MRSP carriage in healthy people is more common, especially amongst owners of dogs with MRSP infections and veterinary personnel. MRSP carriage rates of ≤8.8% have been observed in these presumed risk groups (Ishihara et al., 2011; Laarhoven et al., 2011; Paul et al., 2011; Walther et al., 2012). The sporadic reports of S. pseudintermedius infection in humans must be considered in the context of what must be very frequent exposure of dog (and to a lesser degree cat) owners to S. pseudintermedius. Since most dogs harbour S. pseudintermedius and a large percentage of the population has contact with dogs on a daily basis, the rarity of human infections belies the rather low pathogenicity of this organism in people. Since MRSP is no more inherently pathogenic than methicillin-susceptible S. pseudintermedius, the risk should be correspondingly low for people in contact with companion animals harbouring MRSP. However, while the risk may be low, the multidrug-resistant nature of MRSP and the potential for S. pseudintermedius to cause serious disease in humans should not be dismissed.

CONTROL MEASURES IN COMPANION ANIMALS Risk factors for MRSP carriage include former hospitalization and prior antibiotic treatment (Nienhoff et al. 2011a). Therefore, preventing emergence and spread of these bacteria is centered on rational antibiotic use and general infection control measures.

PREVENTION OF ZOONOTIC INFECTION While the risk of zoonotic infection is quite low, basic practices are indicated because of the potential for disease and the highly drug- 122

resistant nature of most MRSP. Basic hygiene practices (especially hand hygiene), limiting contact with colonization sites (i.e. nose, perineum and mouth), keeping infected sites covered whenever possible and avoiding contact with high-risk individuals likely lessen the already low risk. LINK TO AGRICULTURE There is currently no evidence of a realistic risk to food animals. While S. pseudintermedius can infect a range of species, including cattle, the overall impact is likely to be negligible.

REASONS FOR CONCERN The dramatic increase in prevalence of MRSP and the highly drug- resistant nature of most MRSP strains highlight concerns. As MRSP increases in the pet population, human exposure will inevitably increase. While MRSP appears to be a rare infection in humans, surveillance is required to ensure that this is not an emerging (or misdiagnosed) human health problem.

REFERENCES Beck, K.M., Waisglass, S.E., Dick, H.L.N., et al., 2012. Prevalence of meticillin-resistant Staphylococcus pseudintermedius (MRSP) from skin and carriage sites of dogs after treatment of their meticillin-resistant or meticillin-sensitive staphylococcal pyoderma. Vet. Dermatol. 23, 369-375. Bengesson, B., Unnerstad, H.E., Greko, C., et al., 2011. SVARM (Swedish Veterinary Antimicrobial Resistance Monitoring). Report available at www.sva.se. Chuang, C.Y., Yang, Y.L., Hsueh, P.R., et al., 2010. Catheter-related bacteremia caused by Staphylococcus pseudintermedius refractory to antibiotic-lock therapy in a hemophilic child with dog exposure. J. Clin. Microbiol. 48, 1497-1498. Damborg, P., Guardabassi, L., 2012. Resistance report on clinical bacterial isolates of veterinary origin, University of Copenhagen (in Danish). De Lucia, M., Moodley, A., Latronico, F., et al., 2011. Prevalence of canine methicillin resistant Staphylococcus pseudintermedius in a veterinary diagnostic laboratory in Italy. Res. Vet. Sci. 91, 346-348. Devriese, L.A., Vancanneyt, M., Baele, M., et al., 2005. Staphylococcus pseudintermedius sp. nov., a coagulase-positive species from animals. Int. J. Syst. Evol. Microbiol. 55, 1569-1573. Duim, B., Laarhoven, M., van Duijkeren, E., et al., 2011. Occurrence and clonal spread of methicillin-resistant Staphylococcus pseudintermedius in dogs in the Netherlands. Abstract presented at the 2nd ASM- ESCMID conference on methicillin-resistant staphylococci in animals, Washington, DC. Durdik, P., Fedor, M., Jesenak, M., et al., 2010. Staphylococcus intermedius- rare pathogen of acute meningitis. Int. J. Infect. Dis. Suppl 3, e236-e238. Epstein, C.R., Yam, W.C., Peiris, J.S., et al., 2009. Methicillin-resistant commensal staphylococci in healthy dogs as a potential zoonotic 123 reservoir for community-acquired antibiotic resistance. Infect. Genet. Evol. 9, 283-285. Griffeth, G.C., Morris, D.O., Abraham, J.L., et al., 2008. Screening for skin carriage of methicillin-resistant coagulase-positive staphylococci and Staphylococcus schleiferi in dogs with healthy and inflamed skin. Vet. Dermatol. 19, 142-149. Hanselman, B.A., Kruth, S., Weese, J.S., 2007. Methicillin-resistant staphylococcal colonization in dogs entering a veterinary teaching hospital. Vet. Microbiol. 126, 277-281. Hanselman, B.A., Kruth, S.A., Rousseau, J., et al., 2009. Coagulase positive staphylococcal colonization of people and their household pets. Can. Vet. J. 50, 954-958. Huber, H., Ziegler, D., Wittenbrink, M., et al., 2011. Methicillin-resistant Staphylococcus pseudintermedius in Swiss dogs from 2007 to 2011. Abstract presented at the 2nd ASM-ESCMID conference on methicillin- resistant staphylococci in animals, Washington, DC. Ishihara, K., Shimokubo, N., Sakagami, A., et al., 2010. Occurrence and molecular characteristics of methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus pseudintermedius in an academic veterinary hospital. Appl. Environ. Microbiol. 76, 5165-5174. Laarhoven, L.M., de Heus, P., van Luijn, J., et al., 2011. Longitudinal Study on methicillin-resistant Staphylococcus pseudintermedius in households. PLoS ONE. 6, e27788. Nienhoff, U., Kadlec, K., Chaberny, I.F., et al., 2011a. Methicillin-resistant Staphylococcus pseudintermedius among dogs admitted to a small animal hospital. Vet. Microbiol. 150, 191-197. Nienhoff, U., Kadlec, K., Chaberny, I.F. 2011b. Methicillin-resistant Staphylococcus pseudintermedius among cats admitted to a veterinary teaching hospital. Vet. Microbiol. 153, 414–416. Osland, A.M., Vestby, L.K., Fanuelsen, H., et al., 2012. Clonal diversity and biofilm-forming ability of methicillin-resistant Staphylococcus pseudintermedius. J. Antimicrob. Chemother. 67, 841-848. Paul, N.C., Moodley, A., Ghibaudo, G., et al., 2011. Carriage of Methicillin-resistant Staphylococcus pseudintermedius in small animal veterinarians: indirect evidence of zoonotic transmission. Zoonoses Public Health. 58, 533-539. Perreten, V., Kadlec, K., Schwarz, S., et al., 2010. Clonal spread of methicillin-resistant Staphylococcus pseudintermedius in Europe and North America: an international multicentre study. J. Antimicrob. Chemother. 65, 1145-1154. Ruscher, C., Lübke-Becker, A., Wleklinski, C., et al., 2009. Prevalence of methicillin-resistant Staphylococcus pseudintermedius isolated from clinical samples of companion animals and equidaes. Vet. Microbiol. 136, 197-201. Stegmann, R., Burnens, A., Maranta, C.A., et al., 2010. Human infection associated with methicillin-resistant Staphylococcus pseudintermedius ST71. J. Antimicrob. Chemother. 65, 2047-2048. Vengust, M., Anderson, M., Rousseau, J., et al., 2006. Methicillin-resistant staphylococcal colonization in clinically normal dogs and horses in the 124

community. Lett. Appl. Microbiol. 43, 602-606. Walther, B., Hermes, J., Cuny, C., et al., 2012. Sharing more than friendship — nasal colonization with coagulase-positive staphylococci (CPS) and co-habitation aspects of dogs and their owners. PLoS ONE. 7, e35197. Wettstein, K., Descloux, S., Rossano, A., et al., 2008. Emergence of methicillin-resistant Staphylococcus pseudintermedius in Switzerland: three cases of urinary tract infections in cats. Schweiz Arch. Tierheilkd. 150, 339-343.

6.12 SALMONELLA SPP. (SALMONELLOSIS)

AETIOLOGY Salmonella is a Gram-negative, facultative anaerobic rod belonging to the family Enterobacteriaceae. There are only two species (S. enterica and S. bongori), but more than 2,500 serovars have been distinguished based on variation in the lipopolysaccharide (O), capsular (Vi) and flagellar (H) antigens. Salmonella can survive for relatively long periods (weeks to months) in the environment, in particular in warm and moist places. Although most Salmonella serovars could be considered pathogenic to humans, some, such as pigeon-adapted Salmonella Typhimurium strains, are probably not.

ANIMAL SPECIES INVOLVED Reptiles belonging to all extant reptilian orders (i.e. crocodylians, lizards and , chelonians) are involved, with the possible exception of tuataras. Reptiles constitute the most important Salmonella reservoir in pet animals. Besides reptiles, Salmonella can infect all other classes of vertebrate animals and pet birds, fish and mammals including dogs and cats.

MODE(S) OF TRANSMISSION Although there is some evidence that Salmonella might be transferred vertically in reptiles (Chiodini, 1982; Schröter et al., 2006), faecal- oral transmission is probably most common. Coprophagia, which is a natural phenomenon in many herbivorous reptiles, enables direct transfer of Salmonella. Turtle eggs are frequently infected shortly after egg laying. D’Aoust et al. (1990) found 21% of turtle eggs exported from the USA to be infected with Salmonella. Dogs and cats generally become infected through ingestion of contaminated and undercooked treats or food, including food intended for human use. Other sources are contaminated water, contact with infected faecal material and 125 ingestion of infected wild birds. Sources of infection for humans are: contact with animals, their faeces or contaminated water and objects such as aquaria and feeding bowls (Ackman et al., 1995). Consumption of undercooked meat may also result in human salmonellosis (Magnino et al., 2009).

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COMPANION ANIMAL SPECIES Both Salmonella enterica and Salmonella bongori, their subspecies and serovars can be found in reptiles (Zwart et al., 1970; Bäumler et al., 1998; Mitchell and Shane, 2001; Pedersen et al., 2009). Moreover, reptiles can be infected by multiple serovars at the same time. Known host-adapted and host-restricted serovars (e.g. Salmonella Dublin) are rarely reported from reptiles. It is well-established that a high carriage rate of Salmonella exists among reptiles. In fact, each reptile should be considered a Salmonella carrier until the contrary is proven, since cumulative prevalence studies often show rates approaching 100%. The longer reptiles stay in captivity, the higher the probability that they are colonized with Salmonella (Pfleger et al., 2003). Salmonella occurs as a natural component of the intestinal microflora in reptiles. A primary role of Salmonella in the development of disease in reptiles has still to be demonstrated. Clinical salmonellosis is rare in reptiles, but might present as salpingitis, coelomitis, dermatitis, abscessation, osteomyelitis, arthritis, septicaemia or granulomatous disease (Pasmans et al., 2008). Its role in enteric disease in reptiles is not clear. Data on the occurrence of Salmonella in other companion animals are generally sparse. Prevalences ranging from 0–8.6% and 0–3.5% have been reported in dogs and cats, respectively (Marks et al., 2011). Much higher prevalences may, however, occur in stray or shelter cats/dogs as well as dogs fed raw food diets (Joffe et al., 2002; Marks et al., 2011). Dogs, cats and other non-reptile species are generally asymptomatically infected, with the exception of companion birds (including pigeons) and rabbits, where salmonellosis often is a fatal condition. However, clinical salmonellosis occasionally occurs in carnivores and rodents. In fish and amphibians, there is currently no evidence for clinical disease after exposure to Salmonella.

IMPACT ON HUMAN HEALTH Reptilian Salmonella isolates should be considered pathogenic to humans (Pasmans et al., 2005). Human salmonellosis and Salmonella infections in chelonians (turtles and tortoises) were linked for the first time in 1962 (Communicable Disease Center, 1963). Since then, an increasing number of cases of reptile-associated salmonellosis have been reported. In the 1970s, the sources of infection of 11–22% of all registered cases of human salmonellosis were chelonians (Lamm et al., 1972; Cohen et al., 1980). In 1975, the sale of turtles with a carapace length <4 cm was prohibited, which resulted in an estimated annual reduction of 100,000 Salmonella infections in US children between 1 and 9 years old (Cohen et al., 1980). A more recent study estimated that 126

6% of all sporadic Salmonella infections in the USA can be attributed to reptiles (Mermin et al., 2004). Of the top 20 increasing serovars isolated from 1987 until 1997 in the USA, seven were common reptile- associated Salmonella serovars (Olsen et al., 2001). Reptiles have become increasingly popular companion animals in Europe. However, recent and reliable estimates of reptile-associated salmonellosis in humans in Europe are lacking. Children <5 years of age are particularly at risk of infection, probably due to the combination of their higher susceptibility to infection and limited hygienic conscience (Mermin et al., 2004; Jones et al., 2006; Aiken et al., 2010). Reptile-associated Salmonella infections generally cause gastroenteritis in humans. However, depending on age or immune status of the patient and the serovar involved, generalization may occur, leading to septicaemia, abortion and even death (Woodward et al., 1997). Immune deficiencies, for instance caused by leukaemia, systemic lupus erythematosus or HIV infections predispose to a very severe clinical course (Ackman et al., 1995; Woodward et al., 1997). The impact of Salmonella infections of other animal species on human health is much lower. In their review, Hoelzer et al. (2011) mention 11 published cases of confirmed transfer from cats or dogs to humans (five in the EU), four from rodents, one from a parakeet, one (confirmed) from amphibians, five from aquarium fish (three in the EU) and five from non-traditional mammalian pets (e.g. hedgehogs; none from the EU). Despite few case reports, cat exposure as well as reptile contact was shown to be a risk factor for childhood salmonellosis (Younus et al., 2010), thus the risk of contact with non-reptile companion animals should not be neglected. Pet food may be a source of salmonellosis as well, although no cases have been published from the EU.

CONTROL MEASURES IN COMPANION ANIMALS Since all reptiles should be assumed to be Salmonella carriers and eradication by antimicrobial treatment is very difficult, little can be done to prevent the spread amongst reptiles in captivity. Furthermore, shedding can be intermittent, and a negative culture is not proof of lack of Salmonella carriage status. Accordingly, focus should be on prevention of zoonotic exposure. In other animal species, hygiene measures to limit direct or indirect contact with animal faeces seem most appropriate. Feeding raw diets to carnivores should be limited as they are associated with significantly higher prevalences of Salmonella compared with other diets (Hoelzer et al., 2011).

PREVENTION OF ZOONOTIC INFECTION High-risk groups (i.e. children <5 yrs of age, elderly individuals, pregnant women, immunocompromised individuals) should avoid both direct and indirect contact with reptiles. Reptile owners and people in contact with reptiles must focus on good hygiene measures, particularly hand hygiene. Reptiles should not be allowed to have access to the kitchen or bathroom, and roaming in the house should be discouraged. Reptiles and items from the reptile’s environment should not be handled in the 127 kitchen or bathroom. More basic and less stringent hygiene measures (e.g. hand washing) can probably be used to prevent transmission from other companion animals, since these animals are less commonly associated with infections in humans.

LINK TO AGRICULTURE Salmonella infections are of special concern in food animal production, both because of their impact on animal health (clinical salmonellosis) and public health through the food chain. The risk posed by companion animals for transmission of Salmonella between food animals, or from food animals to humans, is likely very low.

REASONS FOR CONCERN The potential severity of disease, particularly in young children (who may have the greatest contact with reptiles), the increasing keeping of reptiles as pets, the potential for contact of people with reptiles outside of the household (e.g. animal shows, school exhibits, petting zoos), the endemic nature of Salmonella in reptiles and unlikely ability to eradicate Salmonella colonization in reptiles highlight concerns. Zoonotic transmission from other companion animals is certainly possible, but of less concern compared with reptiles.

REFERENCES Ackman, D.M., Drabkin, P., Birkhead, G., et al., 1995. Reptile-associated salmonellosis in State. Pediatr. Infect. Disease. J. 14, 955-959. Aiken, A.M., Lane, C., Adak, G.K., 2010. Risk of Salmonella infection with exposure to reptiles in England, 2004-2007. Euro Surveill. 15, 11-18. Bäumler, A.J., Tsolis, R.M., Ficht, T.A., et al., 1998. Evolution of host adaptation in Salmonella enterica. Infect. Immun. 66, 4579-4587. Chiodini, R.J., 1982. Transovarian passage, visceral distribution, and pathogenicity of Salmonella in snakes. Infect. Immun. 36, 710-713. Cohen, M.L., Potter, M., Pollard, R., et al., 1980. Turtle-associated salmonellosis in the United States: effect of Public Health Action, 1970 to 1976. J. Am. Med. Ass. 243, 1247-1249. Communicable Disease Center. 1963. Salmonella surveillance report. 10, 22-24. D’Aoust, J.Y., Daley, E., Crozier, M., et al., 1990. Pet turtles: a continuing international threat to public health. Am. J. Epidemiol. 132, 233-238. Hoelzer, K., Moreno Switt, A.I., Wiedmann, M., 2011. Animal contact as a source of human non-typhoidal salmonellosis. Vet. Res. 42, 34. Joffe, D.J., Schlesinger, D.P., 2002. Preliminary assessment of the risk of Salmonella infection in dogs fed raw chicken diets. Can. Vet. J. 43, 441–442. Jones, T.F., Ingram, L.A., Fullerton, K.E., et al., 2006. A case-control study of the epidemiology of sporadic Salmonella infection in infants. . 118, 2380-2387. Lamm, S.H., Taylor, A., Gangarosa, E.J., et al., 1972. Turtle-associated salmonellosis. An estimation of the magnitude of the problem in the United States. Am. J. Epidemiol. 95, 511-517. 128

Magnino, S., Colin, P., Dei-Cas, E., et al., 2009. Biological risks associated with consumption of reptile products. Int. J. Food Microbiol. 134, 163-175. Marks, S.L., Rankin, S.C., Byrne, B.A., et al., 2011. Enteropathogenic bacteria in dogs and cats: diagnosis, epidemiology, treatment, and control. J. Vet. Intern. Med. 25, 1195-208. Mermin, J., Hutwagner, L., Vugia, D., et al., 2004. Reptiles, amphibians, and human Salmonella infection: a population-based, case-control study. Clin. Infect. Dis. 38, 253-261. Mitchell, M.A., Shane, S.M., 2001. Salmonella in reptiles. Sem. Avian Exot. Pet Med. 10, 25-35. Olsen, S.J., Bishop, R., Brenner, F.W., et al., 2001. The changing epidemiology of Salmonella: trends in serotypes isolated from humans in the United States, 1987 – 1997. J. Infect. Dis. 183, 753-761. Pasmans, F., Martel, A., Boyen, F., et al., 2005. Characterization of Salmonella isolates from captive lizards. Vet. Microbiol. 110, 285-291. Pasmans, F., Blahak, S., Martel, A., et al., 2008. Introducing reptiles into a captive collection: the role of the veterinarian. Vet. J. 175, 53-68. Pedersen, K., Lassen-Nielsen, A.M., Nordentoft, S., et al., 2009. Serovars of Salmonella from captive reptiles. Zoonoses Public Health. 56, 238- 242. Pfleger, S., Benyr, G., Sommer, R., et al., 2003. Pattern of Salmonella excretion in amphibians and reptiles in a vivarium. Int. J. Hyg. Environ. Health. 206, 53-59. Schröter, M., Speicher, A., Hofmann, J., et al., 2006. Analysis of the transmission of Salmonella spp. through generations of pet snakes. Environ. Microbiol. 8, 556-559. Woodward, D.L., Khakhria, R., Johnson, W.M., 1997. Human salmonellosis associated with exotic pets. J. Clin. Microbiol. 35, 2786-2790. Younus M., Wilkins M., Davies H., et al., 2010. Case-control study of disease determinants for nontyphoidal Salmonella infections among Michigan children. BMC Res. Notes 3:105. Zwart, P., Poelma, F.G., Strik, W.J., 1970. The distribution of various types of salmonellae and arizonas in reptiles. Zentralblatt für Bakteriologie, Parasitenkunde Infektionskrankheiten und Hygiene Abteilung. 213, 201- 212. 129 7. PARASITIC INFECTIONS

7.1 CYSTIC AND ALVEOLAR ECHINOCOCCOSIS

AETIOLOGY The genus Echinococcus includes several species and strains/geno- types of zoonotic cestodes (tapeworms) of which the adult stages oc- cur in the intestines of canids and felids, and the larval stages in var- ious organs of other mammalian hosts, including humans as aberrant hosts (Table 7.1).

Table 7.1 Echinococcus spp. in Europe and their definitive and intermediate hosts

Intermediate hosts [former] E. gra- Echinococcus (zoonotic signifi- nulosus strains or Definitive hosts species cance: high Z, low genotypes (G) z) sheep, cattle**, pig E. granulosus sheep strain (G1, dog (fox*) and other herbivo- sensu stricto 2, 3) res**, Z [pig/camel strain; pig, other herbivo- E. intermedius Dog G7, 9] res**, Z E. ortleppi [cattle strain; G5] Dog cattle, z [cervid strain; G8, E. canadensis wolf, dog cervids, z 10] E. equinus [horse strain; G4] Dog Equines fox, dog, raccoon arvicolids and E. multi-locularis n.a. dog, (cat*) other rodents, Z

*mostly low worm numbers with very low egg production, **mostly with strong- ly reduced protoscolex formation in the cysts often resulting in infertile cysts, n.a. not applicable.

Cystic echinococcosis (CE) is caused by species of the E. granulo- sus complex; however, in Europe, E. granulosus sensu stricto (‘sheep strain’) and E. intermedius (‘pig strain’) are of major zoonotic signifi- 130

cance. Alveolar echinococcosis (AE) caused by E. multilocularis is one of the most lethal zoonoses in Europe and leads to death in 10–15 years if untreated.

ANIMAL SPECIES INVOLVED Echinococcus granulosus sensu stricto is mainly transmitted within a dog-sheep cycle in pastoral regions. The E. intermedius epidemiology is characterised by a small scale transmission pattern between farm dogs and pigs in family farms with traditional home slaughter practice. Echinococcus ortleppi was prevalent in cattle all over central Europe, but has nearly disappeared without the implementation of specific control programmes. Echinococcus multilocularis is perpetuated in a wildlife cycle with foxes as definitive and small mammals as intermedi- ate hosts. Definitive hosts with high reproductive potential of E. multi- locularis are predominantly the red fox, raccoon dog, wolf and domes- tic dog. Wild felines and domestic cats have occasionally been found to harbour intestinal stages. Although cats are likely to be infected with E. multilocularis more often than dogs, their zoonotic significance is es- timated to be very low based on the low excretion of eggs. Dogs on the other hand may play a very important role in the transmission to hu- mans, but they probably do not contribute significantly to the contam- ination of rodent habitats as compared to foxes (Deplazes et al., 2011).

MODE/S OF TRANSMISSION Echinococcosis is not a foodborne disease in the classical sense. Eggs and proglottids typically are fully developed and infectious when ex- creted by defecation into the environment. In addition, these eggs are highly tenacious: E. multilocularis eggs in the environment survive up to 8 months; however, they are sensitive to desiccation. Eggs can be dispersed from the deposition sites either by being washed away or carried by flies and other vectors. Also, eggs of Echinococcus may adhere to tyres, shoes or animal paws leading to widespread dispersal and contamination of the environment, including human dwellings. Hu- mans are exposed to eggs of Echinococcus spp. through different ways. The most important are handling of definitive hosts and oral uptake of contaminated water, food or soil. Adhering eggs and even proglottids of Echinococcus have been observed on infected dogs in single cases. Direct exposure to these eggs is influenced by occupation and behav- iour, especially a close human-animal bond. Indeed, the number of owned dogs and the frequency of contact with dogs were identified as risk factors for human AE in a study from China, while cohabitation with dogs and feeding of uncooked viscera were defined as risk factors for CE in a Spanish study. Domestic transmission of E. granulosus eggs from pet, stray and working dogs is particularly important in areas with inadequate educational standards or veterinary control. As home slaughter of sheep in parts of Southern Europe and of pigs in parts of Poland and the Baltic states is still widespread, local dogs may be in- fected by feeding infected offal. PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT 131

COMPANION ANIMAL SPECIES Intestinal infections with E. granulosus or E. multilocularis are typical- ly asymptomatic in definitive hosts. The diagnosis of the infection in living dogs or cats has considerably been improved in recent years by coproantigen ELISAs and PCR tests. These techniques can also be used for the examination of faecal samples collected in the environment. E. granulosus: The endemic area of E. granulosus sensu stricto in Europe covers southern and south-eastern Europe; E. intermedius is prevalent in the Baltic countries, Poland and southwards to Romania. For E. gran- ulosus ‘sensu lato’, most prevalence data are based on slaughterhouse investigations of intermediate hosts, while prevalence data concerning definitive hosts are scarce, especially for pet dogs. Prevalence rates of 0–31% have been reported from farm and shepherd dogs in Italy and Spain, and 14.2% from farm village dogs in Lithuania. E. multilocularis occurs in the northern hemisphere, with endemic ar- eas in Europe, and has been reported, as of the end of 2010, in 44 countries (Eckert et al., 2011). In Europe, the endemic area of E. multi- locularis covers parts of the western continent (France, Benelux States) and all countries of central Europe (including Northern Italy, Slovenia, Romania and the Baltic States). Furthermore, foci exist in Denmark and Sweden. Based on recently improved diagnostic strategies, the preva- lence of E. multilocularis in pet dog populations has been investigated in several studies. Low prevalence rates <0.5% were recorded in the privately owned dog populations in France, Germany, Switzerland and Denmark, but prevalences were higher (3–8%) in dogs with predatory habits and those with the possibility to move around freely (Deplazes et al., 2011). In Switzerland, 0.3% of randomly selected privately owned dogs were found to be infected with this tapeworm. Based on this prev- alence, the individual probability of being infected at least once during 10 years can be estimated at 8.7%. Large population studies in Germa- ny revealed that 0.13% of dogs in northern and 0.35% in southern Ger- many excreted E. multilocularis eggs. Considering the total dog popu- lation in Germany (approximately 5.4 x 106 dogs), around 13,000 dogs are expected to be infected. The prevalence of E.multilocularis in cat populations, as determined at necropsy examination, ranged between 0–5.5% in various endemic areas. Cat infections are characterized by low infection intensity.

IMPACT ON HUMAN HEALTH Human CE belongs to one of the five most frequently diagnosed zo- onoses in the Mediterranean and is re-emerging in the endemic are- as of south-eastern Europe (Jenkins et al., 2005). Incidences of CE of 1.1–3.3/100,000 were recorded for Spain, and up to 3.5 for Sardinia in Italy, and 3.3 for Greece, Bulgaria and Romania (Torgerson et al., 2011). Economic losses attributable to human CE were estimated for Spain at €133,416,600 (Benner et al., 2010). Human AE is one of the most lethal zoonoses in Europe, and leads to death in 10–15 years if untreated, caus- ing a high burden of disease (Torgerson et al., 2008). Recent studies 132

support the hypothesis that the infection pressure with E. multilocularis eggs has increased in large areas of Europe. In Switzerland, a repre- sentative endemic area for Central Europe, the mean annual incidence rates of new human AE cases varied between 0.10–0.16/100,000 indi- viduals during at least 45 years, suggesting a high degree of epidemi- ological stability. However, approximately 10–15 years (corresponding to the incubation time of AE) after a distinct increase of the fox popula- tions (with E. multilocularis prevalences of 30–60%), a higher incidence rate of 0.25/100,000 was recorded (Deplazes et al., 2011). Overall inci- dences are variable (0.03–0.26) in Central Europe, but around 110 new cases per year have been estimated.

LINK TO AGRICULTURE Echinococcus granulosus infection in livestock can lead to significant losses of production due to liver condemnation, decreased milk, meat and wool production or lower fertility in animals (Torgerson et al., 2011). For Spain, the overall economic loss attributable to CE in animals was estimated at €15,532,242 for 2005 (Benner et al., 2010). Echinococcus multilocularis has no impact on food animal health. Liver infections in pigs are of no epidemiological significance as no protoscoleces are produced, but they result in condemnation of livers during meat in- spection. Comprehensive control programmes involving the decrease of risk of transmission from pets have so far only been applied for CE including: (1) long lasting routine anthelminthic treatment of dogs, (2) control and reduction of stray dog populations, (3) supervision of live- stock slaughter and subsequent disposal of offal and (4) education of the public (Torgerson et al. (2011). A treatment schedule individually designed for pets based on infection risks (e.g. free roaming, uncon- trolled access to rodents or offal) can improve treatment efficiency. Uniform guidelines for the control and treatment of parasites in pet animals were developed and published by ESCCAP in Europe (www. esccap.org). However, even strict compliance of the pet owners will not reduce the environmental contamination with E. multilocularis or Toxocara canis eggs shed by foxes. Therefore, the growing fox pop- ulations, especially in urban areas with prevalence of E. multilocularis above 30%, cause a high infection pressure and maintain parasite cy- cles independently from the pet populations. Therefore, a promising approach for reducing the infection pressure is the delivery of anthel- minthic baits for foxes. To prevent the introduction of E. multilocularis into e.g. Great Britain, Ireland and the currently non-endemic Scandi- navian countries, where due to the presence of suitable intermediate hosts the establishment of the parasite would be possible, the Pet Trav- el Scheme prescribes a strict deworming regime for all dogs entering these countries. This form of prevention may be helpful in decreasing the likelihood of introduction of E. multilocularis into non-endemic re- gions in Europe and is therefore recommended for implementation in additional countries. REASONS FOR CONCERN The endemic area of E. multilocularis is still expanding and new endem- 133 ic areas have recently been identified in Northern Italy, the Nether- lands, Denmark, Sweden and Romania. Due to the long incubation time of AE, new cases can be expected to appear in these areas within the next 10 years (Takumi et al. 2012). The significant increase of annual incidence of AE in humans in Switzerland and Lithuania, a trend to more AE cases in many countries of the well known endemic area, as well as first AE cases on the border of the endemic area in Western and East- ern Europe, are strongly indicative of emergence of this zoonosis. The reasons for this development are a general increase of fox populations especially in urbanized areas and the urbanization of the E. multilocu- laris life cycle causing an increased probability that dogs become in- fected with the parasite after ingestion of infected voles. Echinococcus granulosus s.l. still persists in Southern and Eastern Europe. In some of these areas, uncontrolled stray dog populations are responsible for a high environmental E. granulosus egg contamination. Furthermore, home slaughter practices are a major risk for infections in farm and family dogs.

REFERENCES Benner, C., Carabin, H., Sánchez-Serrano, L.P., Budke, C.M., Carmena, D., 2010. Analysis of the economic impact of cystic echinococcosis in Spain. Bull World Health Organ. 88, 49-57. Erratum in: Bull. World Health Organ. 88, 236. Deplazes, P., van Knapen, F., Schweiger, A., Overgaauw, P.A.M., 2011. Role of pet dogs and cats in the transmission of helminthic zoonoses in Europe, with a focus on echinococcosis and toxocarosis. Vet. Parasitol. 182, 41 – 53. Eckert, J., Deplazes, P., Kern, P., 2011. Alveolar echinococcosis (Echino- coccus multilocularis) and neotropical forms of echinococcosis (Echi- nococcus vogeli and Echinococcus oligarthrus). In: Brown, D., Palmer, S., Torgerson, P. R., Soulsby, E. J. L. (Eds.), Zoonoses 2nd Edition. Oxford University Press, Oxford, pp. 669-699. Jenkins, D.J., Romig, T., Thompson, R.C.A., 2005.Emergence/re-emer- gence of Echinococcus spp.-a global update. Int. J. Parasitol. 35, 1205- 1219. Takumi, K, Hegglin, D, Deplazes, P, Gottstein, B, Teunis, P, van der Gies- sen, J. 2012. Mapping the increasing risk of human alveolar echinococ- cosis in Limburg, The Netherlands. Epidemiol Infect.140, 867-71. Torgerson P.R., MacPherson C.N.L. Vuitton D.A., 2011. Cystic Echinococ- cosis. In: Brown, D., Palmer, S., Torgerson, P. R., Soulsby, E. J. L. (Eds.), Zoonoses 2nd Edition. Oxford University Press, Oxford, pp. 650-668. 134

7. 2 DIROFILARIOSIS

AETIOLOGY Dirofilariosis is a widespread helminthic disease caused by filarioid nematodes (Spirurida, Onchocercidae) of the genus Dirofilaria, which are transmitted by several mosquito species (family Culicidae). Zo- onotic filarioids are transmitted at a larval stage by bloodsucking in- sects from infested animals to humans. Dirofilaria immitis, the agent of cardiopulmonary disease in dogs, is considered the main agent of human dirofilariosis in the Americas. Dirofilaria repens, which is usual- ly localized in the subcutaneous tissue of dogs, is the main causative agent of human dirofilariosis in the Old Word (McCall et al., 2008).

ANIMAL SPECIES INVOLVED Dirofilaria immitis and D. repens infect mainly dogs and cats, but also other hosts such as wild carnivores and humans. Adult D. immitis worms occur in the pulmonary arteries and right heart chambers, causing a se- vere condition known as canine and feline heartworm disease, while D. repens is found mainly in subcutaneous tissues, causing subcutaneous dirofilariosis. Aberrant migration with ectopic localization (e.g. body cavities, central nervous system, eye etc.) has also been described for both Dirofilaria species (Otranto and Eberhard, 2011).

MODE/S OF TRANSMISSION Dirofilaria spp. are transmitted by bites of mosquitoes. These hel- minths develop throughout five larval stages within the intermediate vector mosquito host (from embryo to infective L3 larva), and in the de- finitive vertebrate host (from L3 to the adult stage). The adult females of D. immitis and D. repens develop in 120–180 days and 189–259 days, respectively, and release microfilariae into the blood of the definitive host (Genchi et al., 2009). The intermediate hosts are mosquitoes of the family Culicidae (e.g. Culex, Aedes, Ochlerotatus, Anopheles, Ar- migeres and Mansonia), although Aedes vexans, Culex pipiens and Ae- des albopictus are mainly implicated as the natural vectors of these worms in Europe. Dirofilaria repens is able to grow under laboratory conditions in the same mosquito species as D. immitis and at the same temperature and humidity as D. immitis and has the same developmen- tal time from the microfilarial stage to the infective larva. Prevalence of carriage and/or disease in the relevant companion animal species Climate change has affected mosquito abundance and their seasonal survival in many areas of Europe, greatly impacting on the spread of filarial infestation. While D. immitis infestation has a world- wide distribution and is endemic in many countries, D. repens is mostly found in the Old World and has not yet been reported in the Americas. Over the last decades, the distribution of Dirofilaria infections in dogs 135 and cats has been greatly reduced in some hyper-endemic areas (e.g. along the Po River Valley in northern Italy) by preventative drugs able to stop the development of patent infections. More recently, canine cases of diorofilarioses have been increasingly reported in dogs living in areas previously considered non-endemic. Currently, autochthonous infections are found in several northern and north-eastern European countries including Austria, Germany, southern Switzerland, the Neth- erlands, Croatia, northern Serbia, Hungary, Czech Republic, Poland and southern Russia (Morchón et al., 2012). An updated distribution map of dirofilariosis in Europe can be found at www.esccap.org.

IMPACT ON HUMAN HEALTH Dirofilaria spp. infections in humans are detected predominantly in the subcutaneous tissues and pulmonary vessels, and also in the central nervous system, causing a range of clinical manifestations from asymp- tomatic to fatal syndromes. A recent re-examination of 28 cases of human dirofilariosis reported in the last 30 years in the Old Word and erroneously attributed to D. immitis or Dirofilaria spp. other than D. re- pens indicated that D. repens was, indeed, the most prevalent species causing human infestation. In the United States, human dirofilariosis is also caused by Dirofilaria tenuis, a common parasite of raccoons. Other Dirofilaria spp. such as Dirofilaria ursi of , Dirofilaria subdermata of porcupines and Dirofilaria striata of wild cats, have been reported occasionally from humans. To decrease the risk of human dirofilari- osis by D. repens and D. immitis in endemic areas, animals should be monitored for microfilariae and adulticide compounds be used for the treatment of canine heartworm. In addition, microfilaricidal treatment is required as a chemoprophylaxis measure against larvae transmitted by mosquitoes. Finally, a novel approach for the treatment of dirofilar- iosis is targeting the Wolbachia rickettsial endosymbionts.

LINK TO AGRICULTURE There does not appear to be a significant impact of dirofilariosis on food animal production in Europe.

REASONS FOR CONCERN Dirofilaria immitis and D. repens represent the vector-borne species of helminths most frequently reported in human infestation where they are detected predominantly in the subcutaneous tissues, pulmonary vessels, testicles and also in the central nervous system, causing a range of clinical manifestations from asymptomatic to, more rarely, fa- tal syndromes. In addition, human infestations by Dirofilaria spp. often induce nodular lesions, which may me erroneously diagnosed as can- cer, hence representing a further challenge to physicians. Although D. immitis is the main agent of human dirofilariosis in the Americas and D. repens in Europe, cases of human dirofilariosis by D. immitis have been recently described in Italy, Greece and Spain and this trend is at an increase in Europe, most likely paralleling the spread of infestation in dogs in central and north-eastern countries of Europe (e.g. south of 136

Switzerland, Czech Republic, Hungary, Serbia and Slovak Republic).

REFERENCES Genchi, C., Rinaldi, L., Mortarino, M., Genchi, M., Cringoli, G., 2009. Cli- mate and Dirofilaria infection in Europe. Vet. Parasitol. 163, 286-292. McCall, J.W., Genchi, C., Kramer, L.H., Guerrero, J., Venco, L., 2008. Heartworm disease in animals and humans. Adv. Parasitol. 66, 193-285. Morchón, R., Carretón, E., González-Miguel, J., Mellado-Hernández, I., 2012. Heartworm disease (Dirofilaria immitis) and their vectors in Eu- rope - new distribution trends. Front. Physiol. 3:196. Otranto, D., Eberhard, M.L., 2011 Zoonotic helminths affecting the hu- man eye. Parasit. Vectors. 23, 4:41.

7. 3 TOXOCARA SPP. INFECTION

AETIOLOGY Toxocara canis and T. cati (syn. T. mystax) are ubiquitous, prolific round- worms (nematodes) with a direct life cycle. The life cycle is typically migratory after infection with eggs. Mating only takes place in the small intestine of the primary hosts and eggs in large numbers are void in the faeces (millions per day). For T. canis, the prepatent period (time from infection to egg shedding) varies with the route of infection, but is not less than 2–3 weeks. Eggs are usually excreted for 4 months. The prepatent period for T. cati is also variable, but is usually 6–8 weeks after ingestion of eggs. Patency lasts 4–6 months. Other ascarids that may potentially be of differential diagnostic importance in humans in- clude Baylisascaris procyonis and Ascaris suum.

ANIMAL SPECIES INVOLVED The definitive hosts of Toxocara canis are canids, including dogs and foxes, while T. cati has cats and other felids as definitive hosts. Inver- tebrates (e.g. earthworms), rodents and birds but also livestock (e.g. pigs, sheep and poultry) may serve as paratenic hosts. B. procyonis has racoons as definitive host, but also reaches patency in dogs.

MODE/S OF TRANSMISSION Eggs undergo development outside the host for at least a month to reach the infective larval stage (L3), which remains inside the egg and shows extreme persistence in the environment for months to years. Dogs, in general, are infected with T. canis by ingestion of embryonat- ed eggs or larvae in paratenic hosts; even older immune dogs may ac- quire new patent infections if exposed to low numbers of eggs (Fahrion et al., 2008). Pups are infected vertically either prenatally in the last trimester or by larvae passed in milk from the bitch. The intrauterine 137 transmission of larvae is of major importance and represents either recent infection or reactivated hypobiotic larvae after somatic migra- tion in the immune bitch. Occasionally bitches get reinfected by eating larvae (L4) from the faeces of pups. T. cati is transmitted by ingestion of larvae in milk (considered most important), embryonated eggs from soil, or paratenic hosts whereas prenatal infection does not take place. Human infections are predominantly acquired from ingestion of em- bryonated eggs by geophagia (e.g. in sand pits, parks or other places where dogs, cats or wildlife have defecated). Toxocara spp. eggs have been recovered worldwide from sand or soil in playgrounds and public parks. Embryonated eggs have also been found in the hair coats of dogs and foxes, but the relative importance of this for human transmis- sion is unknown. Baylisascaris procyonis eggs are particularly abun- dant in latrine areas of raccoons (Bauer, 2011). Food-borne infections also take place (e.g. by eating raw liver or other viscera of paratenic hosts like chicken, pigs or sheep) (Taira et al., 2004), or by using water or vegetables contaminated with eggs).

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COM- PANION ANIMAL SPECIES Heavy prenatal infections in pups may lead to severe disease with alter- nating diarrhoea and constipation, vomiting, typical potbelly, reduced growth/cachexia, poor haircoat and in some cases death (Schnieder et al., 2011). Dogs older than 6 months are usually less severely or not affected. Clinical signs of T. cati infection in young cats are sim- ilar, but generally less severe; respiratory tract signs also reported. The prevalence of T. canis in dogs, based on coprological examination, varies considerably in EU countries (1.4–30.5%) (Schnieder et al., 2011) and depends on the composition of the host population, animal den- sity (definitive and paratenic hosts), seasonality, region and methods employed. The prevalence of T. cati is generally higher due to lack of resistance to reinfection in older cats, (i.e. often 5–50% in domestic cats with access to the outdoor and 20–80% in stray and shelter cats by fecal examination) (Overgaauw, 1997). In foxes, T. canis has been reported with prevalence rates up to 75% and similar infection levels of B. procyonis have been reported in raccoons.

TREATMENT OF ANIMALS AND PREVENTION Toxocara spp. are susceptible to the most commonly used anthelminth- ics, while hypobiotic stages in tissues are more difficult to treat effica- ciously. Repeated applications of anthelminthics are therefore recom- mended in most countries for puppies and (and their mothers) during lactation and early life. Older dogs and cats can either be treated on a routine basis or examined for eggs regularly, followed by treatment of positive cases. Treatment of pregnant animals may also reduce perinatal transmission. As mentioned earlier, guidelines for the control and treatment of parasites in pet animals were developed and published by ESCCAP in Europe (www.esccap.org). Other preventive measures include picking up dog faeces immediately after deposition 138

and avoiding transmission by feeding raw liver or offal. Environmental contamination by foxes is difficult to control. Prevention of infections in humans includes appropriate control of infections in pets, fencing of playgrounds, exclusion of dogs from parks and recreational areas, management of stray animals, and covering of sandpits. Furthermore, general good hand hygiene and prevention of geophagia are essential. In smaller, heavily contaminated areas the top soil may be removed, pens can be flamed and sandpits steam sterilized or new sand applied. Baylisascaris procyonis infections in dogs are treated with commonly available anthelminthics (e.g. benzimidazoles or macrocyclic lactones). Raccoon populations should be controlled, as well as any animal con- sidered infected. Racoons in contact with the public should be regu- larly treated.

IMPACT ON HUMAN HEALTH Serological evidence of Toxocara spp. infections are found in 2–10% of humans in many EU countries, varying by diagnostic methods, age profile and cultural habits. A certain level of cross-reaction with other nematode infections cannot be ruled out; for example A. suum from pigs may cause patent (or aborted) infections in man, particularly in young individuals. Seropositivity may be higher among dog owners, males, rural inhabitants and people of low socioeconomic status. The majority of human Toxocara spp. infections are asymptomatic. Howev- er, both Toxocara canis and T. cati may less commonly cause clinical syndromes in humans described as visceral larvae migrans (VLM) or ocular larvae migrans (OLM). Both syndromes are most often observed in children (VLM 1–5 years of age predominantly; OLM 5–10 years of age) and seldom in adults. The incidence in the EU is largely unknown, but presumably is very low. Signs of VLM depend on the infective dose and are non-specific: abdominal pain, fever, anorexia, respiratory signs, headache, skin lesions and occasionally neurological symptoms, accompanied by hepatomegaly and eosinophilia. OLM indicates the location of a Toxocara larva in the eye and is often painless, but leads to visual disturbances and unilateral blindness. Specific antibody lev- els in OLM are often low because the larvae evade the immune sys- tem or the dose is low. There are some indications that T. canis and T. cati have different tissue preferences for the hypobiotic larvae in the paratenic host, like man. T. cati larvae predominantly locate in musculature, while T. canis also relocate to the musculature, but more commonly in the CNS and kidneys. This may reflect different migratory patterns of the two species. B. procyonis seems to have a higher affin- ity for the CNS and causes severe OLM and a syndrome described as neural larvae migrans (NLM) in intermediate hosts (acute eosinophilic meningoencephalitis). Few cases have been reported in man; the ma- jority in the USA, but a high proportion of NLM has had a fatal outcome. Treatment of larvae migrans in humans includes anti-inflammatory and anthelminthic treatments, and in the case of OLM, possible extirpation. 139

LINK TO AGRICULTURE Toxocara canis and T. cati spp. may infect food animals (e.g. pigs, sheep and poultry) and consumption of fresh or poorly prepared prod- ucts from such animals may lead to human infections. The importance of food-borne transmission in comparison to other transmission routes is not known. Clinical toxacarosis is presumably not of importance in food animals.

REASONS FOR CONCERN Although the occurrence of clinical disease associated with Toxocara infections is probably considerably lower than the seroprevalence, larvae migrans is widespread in the human population. The relative contribution of Toxocara from dogs, foxes and cats to environmental contamination is not known, but it is possible that an increasing urban fox population and increasing numbers of pets may increase the risk of larvae migrans in humans. Furthermore, B. procyonis, causing se- vere disease in humans and other paratenic hosts, is spreading with expanding populations of racoons in Europe. This infection may be difficult to detect because eggs look like Toxocara eggs. Early diag- nosis of disease and prompt treatment are important in order to avoid irreversible lesions or fatal outcome.

REFERENCES Bauer, C., 2011. Baylisascariose (Baylisascaris procyonis) – eine seltene parasitäre Zoonose in Europa. Berl. Münch.Tierärtz. Wochenschrift, 124, 465-472 Fahrion, A.S., Staebler, S., Deplazes, P., 2008. Patent Toxocara canis in- fections in previously exposed and in helminth-free dogs after infection with low numbers of embryonated eggs. Vet. Parasitol. 152, 108-115. Overgaauw, P.A., 1997. Prevalence of intestinal nematodes of dogs and cats in the Netherlands. Vet. Q. 19, 14-17. Schnieder, T., Laabs, E-M., Welz, C., 2011.Larval development of Toxo- cara canis in dogs. Vet. Parasitol. 175, 193-206. Taira, K., Saeed, I., Permin, A., Kapel, C.M.O., 2004. Zoonotic risk of Toxocara canis through consumption of pig or poultry viscera. Vet. Par- asitol. 121, 115-124.

7. 4

HOOKWORMS

AETIOLOGY The hookworms are nematodes (5–20 mm) of the small intestine with a direct life cycle and a high fecundity. Ancylostoma caninum has been reported in dogs in southern England, central Germany and Denmark, but the northern limit of A. caninum is not known. Ancylostoma tubae- 140

formes is found in cats in the EU except in the UK. Uncinaria stenoceph- ala (the northern hookworm) has been identified throughout Europe. Outside Europe, in tropical areas, A. ceylanicum and A. braziliense are common infections of dogs and cats and of considerable zoonotic importance. The pre-patent period of A. caninum and A. tubaeformes is 2–3 weeks and the worms are very fecund. Eggs develop to infec- tive larvae (L3) outside the host within 1–2 weeks and survive best in moist areas (e.g. grass or sandy areas) for up to 3–4 months. Uncinaria stenocephala has a prepatent period of 2–3 weeks and remains patent for several months.

ANIMAL SPECIES INVOLVED The definitive hosts of A. caninum are canids (e.g. dogs, the fox and wolf); A. tubaeformes infects cats and U. stenocephala infects dogs, foxes and seldomly cats. A range of mammals, including rodents, can serve as paratenic hosts for all three hookworms.

MODE/S OF TRANSMISSION Dogs are infected with A. caninum by ingestion of L3 from the envi- ronment, L3 in the dam’s milk or L3 in paratenic hosts (e.g. rodents). Lactogenic transmission is related to reactivation of hypobiotic larvae in somatic tissues post- partum. L3 can also penetrate the skin. Hu- man infections of A. caninum (like A. braziliensis and A. ceylanicum in the tropics) are acquired percutaneously when walking or lying on soil, sand or under houses (plumber’s ) contaminated with faeces from dogs. Ancylostoma tubaeformes infects by oral or less often by per- cutaneous uptake of L3. Although capable of skin penetration, patent infections of U. stenocephala are established after ingestion of L3 from contaminated environment.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COM- PANION ANIMAL SPECIES Ancylostoma caninum is haematophagous, and the clinical disease is related to acute or chronic haemorrhagic anaemia. Pups after lacto- genic infection and young dogs <1 year are most severely affected. An- cylostoma tubaeformes in cats is also haematophagous, but less path- ogenic. Uncinaria stenocephala feeds on the intestinal mucosa and causes less severe anaemia and disease as compared to A. caninum. Infections of are usually found at prevalence rates of less than 10–20% in dogs (Sager et al., 2006) and cats of households, while higher prev- alence rates are found in stray and shelter animals. Treatment of animals and prevention Hookworm infections can be treated with most of the commonly used anthelminthics, either applied regularly or after faecal examination. Young animals are usually covered by the treatment regime outlined for Toxocara spp. and similar preventive measures apply. Special at- tention is needed in high risk areas (e.g. dog kennels) in which having dry and clean floors, bedding and concrete yards are important to re- duce transmission. 141

IMPACT ON HUMAN HEALTH The clinical syndrome, cutaneous larvae migrans (CLM) may result when A. caninum tunnels through the skin about 2 weeks after infection. CLM in humans is characterized by serpinginous eruptions, erythema and intense pruritus, usually located in the skin of feet, legs, and hands (Saliba et al., 2002). CLM is commonly self-limiting; lasting normally for 4–8 weeks, but long term infections (1 year) are also seen. The Mediterranean basin and Middle East are endemic areas, and cases in northern Europe in humans who have not travelled are rare. Uncinaria stenocephala has been described in humans only in very few cases and is generally not considered zoonotic. The relative importance of A. tubaeformes in CLM is not known. In brief, most reports of CLM in man are from travellers in tropical endemic areas like the Caribbean (Moor and McCarthy 2006), while no centralized data exist from Europe. The prevalence is believed to be very low. The larvae usually die within 5–6 weeks. If treatment is initiated, anthelmintics (e.g. albendazole or iver- mectin) are recommended. Cryotherapy is not recommended. Humans should avoid walking barefooted in areas where dogs or cats are likely to have defaecated.

LINK TO AGRICULTURE Food producing animals are not involved.

REASONS FOR CONCERN The incidence of human disease is largely unknown and more evi- dence-based surveys and information are strongly needed. However, it is stated that CLM is the most common dermatological problem to affect Westerners after travel to tropical countries (Moor and McCar- thy 2006).

REFERENCES Moore, T.A., McCarthy, J.S., 2006.Toxocariasis and larvae migrans syndromes. In: Tropical infectious diseases: Principles, pathogens and practice (Eds. Guerrant, R.L., Walker, D.H. and Weller, P.F.). Elsevier, 1721 pp. Sager, H., Moret, C.S., Grimm, F., Deplazes, P., Doherr, M.G., Gottstein, B., 2006. Coprological study on intestinal helminths in Swiss dogs: tempo- ral aspects of anthelmintic treatment. Parasitol. Res. 98, 333-338 Saliba, E.K., Oumeish, Y.O., Oumeish, I., 2002. Epidemiology of common skin parasitic infections of the skin in infants and children. Clin. Derma- tol. 20, 36-43. 142

7. 5 TOXOPLASMOSIS

AETIOLOGY Toxoplasma gondii is a tissue cyst-forming coccidium (protozoan, api- complexa) with a complex life cycle. The asexual phase of T. gondii de- velopment takes place in various tissues of herbivorous or omnivorous intermediate hosts and is linked to a sexual phase of development in the intestine of felids, the definitive hosts. There are three infectious stages in the life cycle of the parasite: tachyzoites, bradyzoites con- tained in tissue cysts, and sporozoites contained in sporulated oocysts. The parasite can invade the gut, become systemic and localize in vital organs such as muscles and nervous system tissues. In most cases in- fection is asymptomatic, but devastating disease can occur (Cenci-Go- ga et al., 2011).

ANIMAL SPECIES INVOLVED Felids are definitive hosts for T. gondii, but all warm-blooded verte- brates (including humans) may behave as intermediate hosts and po- tentially be infected by bradyzoites in meat, by sporulated oocysts, or by tachyzoites intrauterinly (Dabritz and Conrad, 2010; Elmore et al., 2010).

MODE/S OF TRANSMISSION The parasite T. gondii has become adapted to exploit multiple routes of transmission through a sexual cycle in the definitive hosts (felids) and asexually, through carnivorous behavior, and by vertical transmission. These alternative routes may operate synergistically to enhance trans- mission, but they might also provide a vehicle for selection leading to partitioning of strains in the environment. Many human infections are believed to be acquired from eating undercooked or raw meat, such as pork and lamb. However, the prevalence of T. gondii infection in human populations that do not consume meat or eat it well-cooked suggests that the acquisition of infection from the environment, via oocysts in soil, water or on uncooked vegetables, may also be important. Only a small proportion (less than 0.1%) of people acquires infection congeni- tally (Lindsay and Dubey, 2011).

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COM- PANION ANIMAL SPECIES Latent infections with T. gondii are common in domestic cats through- out the world. Antibodies to T. gondii may be detected in up to 74% of adult cat populations, depending on the type of feeding and whether cats are kept indoors or outdoors. Cats only spread Toxoplasma oo- cysts in their faeces for a few weeks following infection. Afterwards, direct risk for cat-owners is supposed to be limited. Other companion 143 animals (e.g. dogs, rodents etc) may behave as intermediate hosts with- out any risk of transmission to humans. Cats with clinical disease can be treated with clindamycin (for several weeks). However, treatment of cats after infection has not been shown to prevent oocyst excretion. Control measures aim to prevent oocyst shedding in order to reduce the infection of humans with T. gondii. The risk for exposure to T. gon- dii parasites is greatest in cats that prey on wildlife and live outdoors or on farms. Kittens may also be highly susceptible to infection and shed greater quantities of oocysts. To protect the public health, efforts to develop a T. gondii vaccine for cats should be renewed. Responsi- ble cat ownership should also be encouraged. This includes measures such as keeping cats indoors and collecting faeces in litter boxes for ultimate disposal in garbage destined for landfills, which are designed to prevent waste materials leaking into groundwater. In addition, cat faeces should not be disposed of in toilets.

IMPACT ON HUMAN HEALTH Toxoplasma gondii infects up to a third of the world’s population. How- ever, the system for routine monitoring and reporting is inadequate in most countries and the incidence of human disease is undoubtedly underestimated. In Europe, the 2003/99 EC Directive stipulates that member countries report seroprevalence results in humans, every year or every other year, according to their epidemiological status. Despite this directive, accurate information is incomplete and the European Commission applied to the European Food Safety Authority (EFSA) for recommendations on the surveillance and control methods for humans, animals and food. Toxoplasmosis can induce clinical disease not only in immunocompromised patients or through congenital infections, but also in healthy patients. Prenatal exposure to toxoplasmosis and re- lated inflammatory responses may be associated with risk of neuro- logical or severe ocular conditions. The virulence of T. gondii strains is highly variable and dependent upon the genotype of the parasite. It is now apparent that many atypical genotypes exist besides the typical three genotypes (I, II and III) first described from samples from Europe and the United States. These genotypes can differ in pathogenicity and transmissibility from the typical genotypes. In humans, the infection can be acquired either by ingestion of infected raw or undercooked meat or by ingestion of sporulated oocysts from the contaminated en- vironment. As a consequence, it is highly recommended (especially for high-risk individuals, e.g. previously unexposed pregnant women) that meat is consumed only after thorough cooking or freezing and person- al hygiene in handling meat is mandatory. The control of human tox- oplasmosis also relies on the avoidance of direct or indirect exposure to cat faeces. Proper faecal handling, litter box management, removal of faeces from public areas and yards and hand hygiene are critical. Similarly, drinking unfiltered surface water or accidental ingestion of soil must be avoided. Within a household, cats themselves are not a risk factor for transmission to family members. A litter tray should be thoroughly cleaned every day so that any potential oocysts do not 144

have time to sporulate.

LINK TO AGRICULTURE The prevalence of T. gondii in adult sheep and lambs is high and the parasite is recognized as a major cause of abortion and neonatal mor- bidity in sheep. To control congenital toxoplasmosis in sheep, a live vaccine is available in most European countries. In cattle, many cas- es of abortion were attributed to T. gondii before the discovery that Neospora caninum can provoke abortions in cattle. Clinical signs of toxoplasmosis are rare in pigs, but it can cause premature births and pneumonia. Monitoring infection in animals destined for human con- sumption is a great challenge for toxoplasmosis control (Tenter et al., 2000).

REASONS FOR CONCERN Toxoplasmosis remains one of the most prevalent zoonoses worldwide. While healthy adults have a low risk of developing severe toxoplasmo- sis after infection, immunocompromised individuals or children infect- ed in utero can suffer from severe or even fatal, local or generalized toxoplasmosis. In developed countries, the seroprevalence of T. gondii appears to be declining in humans. As a consequence, the proportion of individuals at risk (i.e. previously unexposed pregnant women) is in- creasing. In the absence of an effective vaccine in humans, prevention of transmission remains the best way to approach the problem of hu- man toxoplasmosis, and must be done by limiting exposure to oocysts or tissue cysts.

REFERENCES Cenci-Goga, B.T., Rossitto, P.V., Sechi, P., McCrindle, C.M., Cullor, J.S., 2011. Toxoplasma in animals, food, and humans: an old parasite of new concern. Foodborne Pathog. Dis. 8, 751-762. Dabritz, H.A., Conrad, P.A., 2010. Cats and Toxoplasma: implications for public health. Zoonoses Public Health. 57, 34-52. Elmore, S.A., Jones, J.L., Conrad, P.A., Patton, S., Lindsay, D.S., Dubey, J.P., 2010. Toxoplasma gondii: epidemiology, feline clinical aspects, and prevention. Trends Parasitol. 26, 190-196. Lindsay, D.S., Dubey, J.P., 2011. Toxoplasma gondii: the changing para- digm of congenital toxoplasmosis. Parasitol. 9, 1-3. Tenter, A.M., Heckeroth, A.R., Weiss, L.M., 2000. Toxoplasma gondii: from animals to humans. Int. J. Parasitol. 30, 1217-1258. 145

7. 6 LEISHMANIOSIS

AETIOLOGY Leishmaniosis (or ‘leishmaniasis’) is a complex of mammalian diseases caused by diphasic protozoans of the genus Leishmania in the class Kinetoplasta and family Trypanosomatidae. Leishmania completes its life cycle in two hosts, a phlebotomine sandfly vector, which harbors the flagellated extracellular promastigote form and a mammal where the intracellular amastigote form develops. A female sandfly ingests Leishmania while blood feeding and then transmits the infective stages during a subsequent blood meal. The infective promastigotes inocu- lated by the sandfly are phagocytosed in the mammalian host by mac- rophages and related cells, in which they transform to amastigotes. The Leishmania species that is endemic in Europe is Leishmania infan- tum and the most common zymodeme is MON-1.

ANIMAL SPECIES INVOLVED The leishmaniases are a group of infectious diseases that affect hu- mans and domestic and wild animals worldwide. Most transmission cy- cles are zoonotic, involving reservoir hosts such as rodents, marsupials, edentates, monkeys, domestic dogs and wild canids. Most Leishmania spp. that infect humans are zoonotic, and only a few are strictly an- throponotic (i.e. transmitted directly from human to human via sand- flies). Dogs are the major reservoir for canine and human L. infantum infection, in an area that stretches from Portugal to China and across South, Central and parts of North America. In Europe, the domestic dog is the only reservoir host of major veterinary and human impor- tance (Solano-Gallego et al., 2009). Infection in cats (Martin-Sanchez et al., 2007), wild canids (Millan et al., 2011), horses (Fernandez-Bellon et al., 2006) and hares (Molina et al., in press) has also been reported in areas where disease is common in dogs, but their role as reservoir remains unclear.

MODE/S OF TRANSMISSION Natural transmission may be zoonotic or anthroponotic and it is usually by the bite of a phlebotomine sandfly species. Sandflies are the only arthropods that are adapted for biological transmission of Leishmania. Non-sandfly modes of transmission have also been described, but their role in the natural history and epidemiology of leishmaniosis remains unclear. Proven modes of non-sandfly transmission include infection through transfused blood products (Owens et al., 2001) from blood do- nors which are carriers of infection (de Freitas et al., 2006), vertical (Boggiatto et al., 2011) and venereal transmission (Silva et al., 2009). Prevalence of carriage and/or disease in the relevant companion an- imal species Based on seroprevalence studies from Spain, France, It- 146

aly, and Portugal, it has been estimated that 2.5 million dogs in these countries are infected with L. infantum, and infection is spreading north in Europe, reaching the foothills of the Alps (Maroli et al., 2008), Pyre- nees (Chamaille et al., 2010) and northwestern Spain (Amusategui et al., 2004). The large numbers of dogs travelling to southern Europe or imported as companion animals from areas where canine leishmani- osis is endemic have increased the number of clinical cases report- ed in non-endemic countries such as the UK (Shaw et al., 2009) and Germany (Menn et al., 2010). The seroprevalence reported in dogs in the Mediterranean basin ranges from 5–30% depending on the region (Solano-Gallego et al., 2009). Surveys employing other detection methods to estimate the prevalence of infection by amplification of Leishmania DNA from different tissues or by detection of specific an- ti-Leishmania cellular immunity have revealed even higher infection rates approaching 70% in some foci. Most dogs in these areas appear to have chronic infection that may be life long, but only a low proportion of dogs develop severe disease (Baneth et al., 2008). In cats, serologi- cal and PCR surveys in southern Europe indicate that Leishmania infec- tion is more widespread than clinical disease. Epidemiological studies have described rates ranging from 0.4–30% based on serological and molecular techniques (Solano-Gallego et al., 2007; Sherry et al., 2011).

IMPACT ON HUMAN HEALTH Human leishmaniasis, caused by several species of Leishmania, com- prises a heterogenous group of diseases. These include visceral leish- maniasis (VL), which involves internal organs and is fatal if untreated, and the cutaneous and mucocutaneous forms (CL), which affect the skin or mucocutaneous junctions and may heal spontaneously, leaving disfiguring scars. This group of infections is the third most important vector-borne disease after and lymphatic filariasis. It is en- demic in many tropical and sub-tropical regions of the Old and New World. Leishmaniasis is endemic in 88 countries, with more than 350 million people at risk. The estimated incidence is 2 million new cas- es per year, 0.5 million VL and 1.5 million CL (Desjeux, 2004). There are only two transmission cycles with proven long-term endemism in Europe: (1) visceral and cutaneous human leishmaniasis caused by L. infantum throughout the Mediterranean region and (2) anthroponotic cutaneous human leishmaniasis caused by L. tropica reported sporad- ically in Greece. In Europe and Mediterranean countries, about 1,000 people are estimated to be affected by clinical disease annually (Du- jardin et al., 2008) although asymptomatic or sub-clinical cases are by far more frequent (Michel et al., 2011). The high prevalence (2–40%) of asymptomatic human carriers of L. infantum in southern Europe (Michel et al., 2011) suggests that this parasite is a latent public health threat. Asymptomatic cases are also estimated at a ratio of >100 asymptomat- ic: 1 clinical case (Michel et al., 2011). Mediterranean VL primarily affects children as well as an increasing number of immunocompromised and immunosuppressed adult individuals, such as HIV-infected people and patients undergoing immunosuppressive therapies. Mortality rates in 147

HIV-infected patients can reach over 56% (Pasquau et al., 2005). Treat- ment of L. infantum infections in humans and dogs in Europe is mostly different, thus limiting the potential for drug resistance. Humans are commonly treated with a short course of amphotericin B while moder- ately to severely sick dogs are commonly treated with a combination of a month course of meglumine antimoniate or miltefosine and long course of allopurinol. Generally, treatment in dogs leads to a clinical cure and a decreased of parasite load. However, complete parasitolog- ical cure in the majority of dogs appears to be unlikely (Solano-Gallego et al., 2009). Control measures for both humans and dogs are available and include treatment of humans, individual use of sandfly repellents in dogs and recently introduced canine vaccines.

LINK TO AGRICULTURE There does not appear to be a significant impact of leishmaniosis on food animal production in Europe.

REASON FOR CONCERN The spread of L. infantum infection in dogs in northern European coun- tries is of concern due to climate changes (establishment of compe- sandfly vectors in those areas), increased pet travel movement between countries and the evidence of non-sandfly modes of trans- mission. Furthermore, there is risk of introduction of new species of Leishmania such as L. tropica into additonal areas of Europe, apart from Greece where it has been reported. In addition, increased poor socioeconomic and sanitary conditions in humans might induce a high- er incidence of clinical cases throughout Europe compared to the cur- rent situation.

REFERENCES Amusategui, I., Sainz, A., Aguirre, E., Tesouro, M.A., 2004. Seropreva- lence of Leishmania infantum in northwestern Spain, an area tradition- ally considered free of leishmaniasis. Ann N Y Acad Sci1026, 154-157. Baneth, G., Koutinas, A.F., Solano-Gallego, L., Bourdeau, P., Ferrer, L., 2008. Canine leishmaniosis - new concepts and insights on an expand- ing zoonosis: part one. Trends Parasitol24, 324-330. Boggiatto, P.M., Gibson-Corley, K.N., Metz, K., Gallup, J.M., Hostetter, J.M., Mullin, K., Petersen, C.A., 2011.Transplacental Transmission of Leishmania infantum as a Means for Continued Disease Incidence in North America.PLoSNegl Trop Dis5. Chamaille, L., Tran, A., Meunier, A., Bourdoiseau, G., Ready, P., Dedet, J.P., 2010. Environmental risk mapping of canine leishmaniasis in France. Parasit, Vectors 3, 31. deFreitas, E., Melo, M.N., da Costa-Val, A.P., Michalick, M.S., 2006. Trans- mission of Leishmania infantum via blood transfusion in dogs: potential for infection and importance of clinical factors. Vet Parasitol. 137, 159- 167. Desjeux, P., 2004. Leishmaniasis: current situation and new perspec- tives. Comp, Immunol. Microbiol. Infect. Dis. 27, 305-318. 148

Dujardin, J.C., Campino, L., Canavate, C., Dedet, J.P., Gradoni, L., So- teriadou, K., Mazeris, A., Ozbel, Y., Boelaert, M., 2008. Spread of vec- tor-borne diseases and neglect of Leishmaniasis, Europe. Emerg. Infect. Dis. 14, 1013-1018. Fernandez-Bellon, H., Solano-Gallego, L., Bardagi, M., Alberola, J., Ramis, A., Ferrer, L., 2006. Immune response to Leishmania infantum in healthy horses in Spain. Vet. Parasitol. 135, 181-185. Maroli, M., Rossi, L., Baldelli, R., Capelli, G., Ferroglio, E., Genchi, C., Gramiccia, M., Mortarino, M., Pietrobelli, M., Gradoni, L., 2008. The northward spread of leishmaniasis in Italy: evidence from retrospective and ongoing studies on the canine reservoir and phlebotomine vectors. Trop. Med. Int. Health 13, 256-264. Menn, B., Lorentz, S., Naucke, T.J., 2010. Imported and travelling dogs as carriers of canine vector-borne pathogens in Germany. Parasit. Vec- tors 3, 34. Michel, G., Pomares, C., Ferrua, B., Marty, P., 2011. Importance of world- wide asymptomatic carriers of Leishmania infantum (L. chagasi) in hu- mans. Acta Trop. 119, 69-75. Molina, R., Jiménez, M.I., Cruz, I., Iriso, A., Martín-Martín, I., Sevillano, O., Melero, S., Bernal, J., The hare (Lepus granatensis) as potential sylvatic reservoir of Leishmania infantum in Spain. Vet. Parasitol. Epub ahead of print 2012. Owens, S.D., Oakley, D.A., Marryott, K., Hatchett, W., Walton, R., Nolan, T.J., Newton, A., Steurer, F., Schantz, P., Giger, U., 2001. Transmission of visceral leishmaniasis through blood transfusions from infected English foxhounds to anemic dogs. J. Am. Vet. Med. Assoc. 219, 1076-1083. Pasquau, F., Ena, J., Sanchez, R., Cuadrado, J.M., Amador, C., Flores, J., Benito, C., Redondo, C., Lacruz, J., Abril, V., Onofre, J., 2005. Leishma- niasis as an opportunistic infection in HIV-infected patients: determi- nants of relapse and mortality in a collaborative study of 228 episodes in a Mediterranean region. Eur. J. Clin. Microbiol. Infect. Dis. 24, 411-418. Shaw, S.E., Langton, D.A., Hillman, T.J., 2009. Canine leishmaniosis in the United Kingdom: A zoonotic disease waiting for a vector? Vet .Par- asitol. 163, 281-285. Sherry, K., Miro, G., Trotta, M., Miranda, C., Montoya, A., Espinosa, C., Ribas, F., Furlanello, T., Solano-Gallego, L., 2011.A serological and mo- lecular study of Leishmania infantum infection in cats from the Island of Ibiza (Spain).Vector Borne Zoonotic Dis. 11, 239-245. Silva, F.L., Oliveira, R.G., Silva, T.M., Xavier, M.N., Nascimento, E.F., San- tos, R.L., 2009. Venereal transmission of canine visceral leishmaniasis. Vet. Parasitol. 160, 55-59. Solano-Gallego, L., Koutinas, A., Miro, G., Cardoso, L., Pennisi, M.G., Fer- rer, L., Bourdeau, P., Oliva, G., Baneth, G., 2009. Directions for the diag- nosis, clinical staging, treatment and prevention of canine leishmanio- sis. Vet. Parasitol. 165, 1-18. Solano-Gallego, L., Rodriguez-Cortes, A., Iniesta, L., Quintana, J., Pas- tor, J., Espada, Y., Portus, M., Alberola, J., 2007. Cross-sectional sero- survey of feline leishmaniasis in ecoregions around the Northwestern Mediterranean. Am. J. Trop. Med. Hyg. 76, 676-680. 149

7.7 NEOSPOROSIS

AETIOLOGY Neospora caninum is a coccidian parasite which is an important cause of abortion in livestock. Neospora caninum has a heteroxenous life cycle, with the sexually reproductive stage occurring in the intestine of a canine definitive host. Oocysts passed in the faeces of the definitive canine host are ingested by an intermediate host, such as cattle. These become permanently infected, and form tissue cysts. Pregnancy acti- vates these cysts, and active infection often causes spontaneous abor- tion. Non-suppurative is the main lesion in aborted fetal tissues. Congenitally infected calves may be born weak or with neuro- logical deficits. However, most congenital infections are subclinical. If the aborted fetus and membranes are then ingested by the definitive host, they cause further infection and the cycle is complete. In dogs, N. caninum can cause neurological disease, especially in congenitally infected puppies, where it can form cysts in the central nervous sys- tem. Adult dogs may have encephalomyelitis, focal cutaneous nodules or ulcers, pneumonia, peritonitis, or myocarditis. A second Neospora species, N. hughesi, is a cause of myelitis in horses. The life cycle of N. hughesi is currently unknown.

ANIMAL SPECIES INVOLVED Many domestic (e.g. dogs, cattle, sheep, goats, horses and chickens) and wild animals (e.g. deer, rodents, rabbits, , and foxes) can be infected with N. caninum. Neospora abortion is a major prob- lem in cattle, although it also occurs in sheep, goats, water buffalo and South American camelids, these being less susceptible than cattle. Un- til recently, the only known definitive host was the domestic dog (McAl- lister et al., 1998). New research has determined that coyotes (Canis latrans), grey wolves (Canis lupus) and Australian dingoes (Canis lupus ) are also definitive hosts (Gondim et al., 2004; King et al., 2010; Dubey et al., 2011). Neospora caninum has recently been found to infect domestic chickens and house sparrows (Passer domesticus), which may become infected after ingesting parasite oocysts from the soil. Spar- rows, which are common in urban and rural areas, may serve as a food source for wild and domestic carnivores. N. caninum has also been de- tected in common buzzards (Buteobuteo) and magpies. The presence of birds in cattle pastures has been correlated to higher infection rates in cattle. Birds may be an important link in the transmission of N. can- inum to other animals (Mineo et al., 2011; Darwich et al., 2012).

MODE/S OF TRANSMISSION Transplacental transmission (passage from mother to offspring during pregnancy) has been shown to occur in dogs, cats, sheep and cattle. In 150

cattle, N. caninum can be transmitted transplacentally from an infected cow to the developing fetus, an event that may occur in multiple preg- nancies of the same cow. Because the majority of congenital infections are subclinical, congenitally infected heifer calves may remain in the breeding herd and in turn may pass infections transplacentally to their own offspring. This endogenous transplacental transmission enables transgenerational maintenance of the parasite even if the herd does not have frequent transmission from dogs. Horizontal transmission of infection utilizing the two-host life cycle whereby the cow is infected from ingestion of the oocyst stage shed by the canine definitive host is possible, but considered as a less frequent cause of bovine disease when compared to tranplacental transmission.

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COM- PANION ANIMAL SPECIES The seroprevalence of N. caninum in dogs varies in different countries and dog populations. A recent study from Spain indicated that specific antibodies were detected in 43.6% of dog sera tested (Regidor-Cerrillo et al., 2010). However, only low prevalence rates of N. caninum shed- ding has been detected in most dog faecal surveys (Schares et al., 2005). Impact on human health Neospora caninum does not appear to be in- fectious to humans.

LINK TO AGRICULTURE Neospora caninum is a major cause of bovine abortion worldwide. It is the most frequently diagnosed cause of bovine abortion in the UK where it estimated to cause 13% of all bovine abortions (Davison et al., 1999) and in the USA it is estimated that 20% of all abortions are asso- ciated with this parasite (Dubey, 2003). In a recent study from Spain, N. caninum infection was detected by PCR in 6.8% of sheep aborted fetuses and in 11.5% of aborted goat fetuses (Moreno et al., 2012). The economic importance of this infection in Europe is great, due to its im- pact on the fertility of domestic ruminants and the economic losses due to this disease are probably underestimated. Strategies for the control of N. caninum infection and resultant abortion in cattle include a test- and-cull approach for seropositive cattle and treatment with coccidio- static drugs. However, there are no proven effective drugs to eliminate the bradyzoite tissue stage of the parasite and although a vaccine has been marketed in the USA and New Zealand, its efficacy is equivocal (Williams et al., 2009).

REASONS FOR CONCERN Abortions are a major cause of economic loss to both the dairy and beef industries, and to the caprine and ovine farmers in Europe and worldwide. Neospora caninum is a major infective cause of abortion which has not been controlled yet by vaccination or effective preventa- tive treatment. 151

REFERENCES Darwich, L., Cabezón, O., Echeverria, I., Pabón, M., Marco, I., Moli- na-López, R., Alarcia-Alejos, O., López-Gatius, F., Lavín, S., Almería, S., 2012. Presence of Toxoplasma gondii and Neospora caninum DNA in the brain of wild birds. Vet. Parasitol. 183, 377–381. Davison HC, Otter A, Trees AJ. Significance of Neospora caninum in British dairy cattle determined by estimation of seroprevalence in normally calving cattle and aborting cattle. Int J Parasitol. 1999 Aug; 29(8):1189-94. Dubey, J.P., 2003. Neosporosis in cattle. J. Parasitol. 89, S42-S56, Dubey, J,P., Jenkins, M.C., Rajendran, C., Miska, K., Ferreira, L.R., Mar- tins, J., Kwok, O.C.H., Choudhary, S., 2011. Gray Wolf (Canis lupus) is a natural definitive host for Neospora caninum. Vet. Parasitol. 181, 382– 387. Gondim, L.F.P., McAllister, M.M., Pitt, W.C., Zemlicka, D.E., 2004. Coyotes (Canis latrans) are definitive hosts of Neospora caniinum. Int. J. Para- sitol. 34, 159–161. King, J.S., Slapeta, J., Jenkins, D.J., Al-Qassab, S.E., Ellis, J.T., Windsor, P.A., 2010. Australian dingoes are definitive hosts of Neospora caninum. Int. J. Parasitol. 40, 945-950. McAllister, M.M., Dubey, J.P., Lindsay, D.S., Jolley, W.R., Wills, R.A., McGuire, A.M., 1998. Dogs are definitive hosts of Neospora caninum. Int. J. Parasitol. 28, 1473–1478. Mineo, T.W.P., Carrasco, A.O.T., Raso, T.F., Werther, K., Pinto, A.A., Macha- do, R.Z., 2011. Survey for natural Neospora caninum infection in wild and captive birds. Vet. Parasitol. 182, 352–355. Moreno, B., Collantes-Fernández, E., Villa, A., Navarro, A., Regidor-Cer- rillo, J., Ortega-Mora, L.M., 2012. Occurrence of Neospora caninum and Toxoplasma gondii infections in ovine and caprine abortions. Vet. Par- asitol. 187, 312-318. Regidor-Cerrillo, J., Pedraza-Diaz, S., Rojo-Montejo, S., Vazquez-More- no, E., Arnaiz, I., Gomez-Bautista, M., Jimenez-Palacios, S., Ortega-Mo- ra, L.M., Collantes-Fernandez, E., 2010. Neospora caninum infection in stray and farm dogs: seroepidemiological study and oocyst shedding. Vet, Parasitol. 174, 332-335. Schares. G., Pantchev, N., Barutzki, D., Heydorn, A.O., Bauer, C., Con- raths, F.J., 2005. Oocysts of Neospora caninum, Hammondia heydorni, Toxoplasma gondii and Hammondia hammondi in faeces collected from dogs in Germany. Int. J. Parasitol. 35, 1525-1537. Williams, D.J., Hartley, C.S., Björkman, C., Trees, A.J., 2009. Endoge- nous and exogenous transplacental transmission of Neospora caninum - how the route of transmission impacts on epidemiology and control of disease. Parasitology. 136, 1895-1900. 152

7. 8 GIARDIOSIS

AETIOLOGY Giardia spp. are intestinal protozoan parasites that infect numerous hosts, ranging from mammals to amphibians and birds. Currently, six Giardia species are accepted by most researchers. Among them, G. agilis, G. ardeae, G. muris, G. microti and G. psittaci infect various ani- mals, while G. duodenalis infects humans and many mammals. Giardia species differ significantly in host range, with G. duodenalis (syn. Gi- ardia lamblia and Giardia intestinalis), having the broadest host range and greatest public health significance (Feng and Xiao, 2011). Although G. duodenalis is the only species found in humans and many other mammals, including pets and livestock, it is now considered a multispecies complex. Historically, allozyme analyses placed all iso- lates from humans into two genetic assemblages (assemblages A and B). Multigeneic sequence analyses confirmed this assemblage separa- tion and identified additional lineages of G. duodenalis from animals: assemblages C and D from dogs, assemblage E from artiodactyls, as- semblage F from cats, assemblage G from rodents and assemblage H from marine vertebrates (Caccio et al., 2005; Thompson et al., 2008).

ANIMAL SPECIES INVOLVED Giardia is a very common enteric protozoal parasite of domestic ani- mals, including livestock, dogs, and cats and wildlife. One species with- in this genus, Giardia duodenalis causes infection in humans and most mammals.

MODE/S OF TRANSMISSION The life cycle of Giardia is direct, and the infective stage of the para- site, the cyst, is encysted when released into the faeces and is imme- diately infectious. Cysts remain infectious for months in cool, damp areas and accumulate in the environment. When ingested by the host, cysts excyst in the duodenum, releasing the trophozoites. The latter undergo repeated mitotic division and form environmentally-resistant cysts. Cysts pass through the intestine in faeces and are spread by contaminated water, food and fomites and by direct physical contact (Feng and Xiao, 2011).

PREVALENCE OF CARRIAGE AND/OR DISEASE IN THE RELEVANT COM- PANION ANIMAL SPECIES Infection rates in dogs were 24.8% in a large study in Europe (Epe et al., 2010), 22.7% in Belgium (Claerebout et al., 2009) and 21.0% in the UK (Upjohn et al., 2010). Infection rates in cats were 20.3% in a multi- country study in Europe (Epe et al., 2010). Giardia infection in animals is often asymptomatic, but has been associated with the occurrence of 153 diarrhoea and ill-thrift in puppies and kittens (Thompson, 2004). Infec- tions of dogs and cats can be treated with fenbendazole or other drugs. Cleaning and drying of the environment, the use of clean utensils for feed and water, bathing to remove adhering faeces or cysts and proper disposal of faeces are important to avoid transmission from animals. A commercial vaccine has been licensed for use in dogs and cats in the United States. It has been shown to decrease clinical signs of infection and reduce the total number of cysts shed in the feces in puppies and, to a lesser extent, in kittens.

IMPACT ON HUMAN HEALTH About 200 million people in Asia, Africa and Latin America have symp- tomatic infections (Feng and Xiao, 2011). Once infected, Giardia caus- es a generally self-limited clinical illness characterized by diarrhoea, abdominal cramps, bloating, weight loss and malabsorption. However, asymptomatic giardiasis occurs frequently, especially in developing countries. In Britain, there are approximately 3,500 cases per year according to a report of Health Protection Scotland (www.hps.scot.nhs. uk/giz/giardia.aspx), with an incidence of giardiasis in the UK of 5.5 cases per 100,000 population in 2005. In Germany, on average, 3,806 notified giardiasis cases (range 3,101 to 4,626) were reported between 2001 and 2007, which corresponded to an average incidence of 4.6 cas- es/100,000 population (Sagebiel et al., 2006). Much higher incidence rates were reported for some other countries. In the Netherlands, there were 11,600 cases in 2004, corresponding to 69.9 cases/100,000 pop- ulation (Vigjen et al., 2007). The molecular characterization of Giardia isolates from different species of mammalian hosts throughout the world has confirmed the existence of Giardia species with broad host ranges and which are clearly zoonotic (Thompson and Smith, 2011).

LINK TO AGRICULTURE Giardia infections are common in pigs, cattle, sheep, goats, elks and deer and other ruminants (Feng and Xiao, 2011). Although it is com- monly believed that infection with Giardia is associated with econom- ic losses through the occurrence of diarrhoea, poor growth and even death in farm animals (Geurden et al., 2005), only a few studies have been conducted to assess the effect of giardiasis on the production or growth rates in livestock. In bottle-fed specific pathogen-free lambs experimentally infected with Giardia cysts, the infection was associat- ed with delays in lambs reaching slaughter weight and decreased car- cass weight (O’Handley and Olson, 2006). Other studies demonstrat- ing the beneficial effect of treatment against giardiasis with similar results (reviewed in Feng and Xiao, 2011).

REASONS FOR CONCERN There is evidence that human contact with farm and companion an- imals, living in community settings with other animals, high environ- mental faecal contamination, and overcrowding with animal reservoirs of infection are risk factors for human infection. 154

REFERENCES Caccio, S. M., R. C. Thompson, J. McLauchlin, and H. V. Smith. 2005. Un- ravelling Cryptosporidium and Giardia epidemiology. Trends Parasitol. 21, 430-437. Claerebout, E., S. Casaert, A. C. Dalemans, N. De Wilde, B. Levecke, J. Vercruysse, and T. Geurden. 2009. Giardia and other intestinal para- sites in different dog populations in Northern Belgium. Vet. Parasitol. 161, 41-46. Epe, C., G. Rehkter, T. Schnieder, L. Lorentzen, and L. Kreienbrock. 2010. Giardia in symptomatic dogs and cats in Europe—results of a European study. Vet. Parasitol. 173, 32-38. Feng Y, Xiao L. 2011. Zoonotic potential and molecular epidemiology of Giardia species and giardiasis. Clin. Microbiol. Rev. 24, 110-140. Geurden, T., E. Claerebout, and J. Vercruysse. 2005. Protozoan infection causes diarrhea in calves. Tijdschr. Diergeneeskd. 130, 734-737. O’Handley, R. M., and M. E. Olson. 2006. Giardiasis and cryptosporid- iosis in ruminants. Vet. Clin. North Am. Food Anim. Pract. 22, 623-643. Sagebiel, D., T. Weitzel, K. Stark, and K. Leitmeyer. 2009. Giardiasis in kindergartens: prevalence study in Berlin, Germany, 2006. Parasitol. Res. 105, 681-687. Thompson, R. C., 2004. The zoonotic significance and molecular epide- miology of Giardia and giardiasis. Vet. Parasitol. 126, 15-35. Thompson, R. C., Palmer, C.S., O’Handley, R., 2008. The public health and clinical significance of Giardia and Cryptosporidium in domestic animals. Vet. J. 177:18-25. Thompson, R.C.A., Smith, A., 2011. Zoonotic enteric protozoa. Vet. Para- sitol. 182, 70–78. Upjohn, M., C. Cobb, J. Monger, T. Geurden, E. Claerebout, and M. Fox. 2010. Prevalence, molecular typing and risk factor analysis for Giardia duodenalis infections in dogs in a central London rescue shelter. Vet. Parasitol. 172, 341-346. Vijgen, S., M. Mangen, L. Kortbeek, Y. van Duijnhoven, and A. Havelaar. 2007. Disease burden and related costs of cryptosporidiosis and giardi- asis in the Netherlands. RIVM report 330081001/2007. RIVM, Bilthoven, Netherlands. 155 8. RISK ANALYSIS AND EPIDEMIOLOGY

8.1 INTRODUCTION TO RISK ANALYSIS AND DISEASE MODELLING

Risk and uncertainty are key features of most policy problems (includ- ing health policies) and need to be understood in order for rational decisions to be taken. Risk analysis has been used widely in a number of areas and has resulted in a variety of terms and definitions. It might be useful, therefore, to specify the meaning of the various terms for the purpose of this document. This does not imply that the following defi- nitions are in any way inherently better than others adopted elsewhere, rather they are given for the sake of standardization and clarity.

Most of the approaches to risk analysis, subdivide the subject into the following four components:

• Hazard identification: the process of identifying pathogenic agents that could potentially be responsible for damage to human or ani- mal health • Risk assessment: the component of the analysis which estimates the risks associated with a hazard. Risk assessment may be qualitative or quantitative. • Risk management: the process of deciding upon and implementing measures to achieve the appropriate level of protection • Risk communication: the process by which information and opinions regarding hazards and risks are gathered from potentially affected and interested parties during the risk analysis and by which the results of the risk assessment and the proposed risk management measures are communicated to decision makers and interested parties.

Of the many approaches to risk analysis, two are those mainly used in the veterinary field: the National Academy of Science–National Re- 156

search Council (NAS–NRC) model (National Research Council, 1983) and the Covello and Merkhofer model (Covello and Merkhofer, 1993).

The NAS–NRC model was developed in response to the need to set maximum limits of chemical substances (e.g. in the environment or in food). Risk assessments undertaken under this system were designed to answer the question: ‘what is the maximum amount of a hazard (i.e. a potentially harmful substance, a pathogen etc.) to which a person can be allowed to be exposed from a particular source?’ The framework used in this model is therefore designed mainly as a regulatory tool for setting acceptable or tolerable levels of contaminants and pathogens in food, or in the environment or in any source to which human beings are exposed.

The NAS–NRC system (Fig. 8.1) divides risk analysis into three compo- nents (hazard identification is included as a part of the risk assessment components):

• Risk assessment • Risk management • Risk communication

Fig. 8.1 Structure of the risk analysis process according to the NAS–NRC.

Risk assessment Risk management Hazart identification Risk evaluation Hazard characterisation Option assessment Exposure assessment Monitoring and review Risk characterisation

Risk communication 157

In the NAS–NRC framework, risk assessment is divided into the follow- ing phases:

• Hazard identification: the identification of biological, chemical and physical agents capable of causing adverse health effects and which may be present in a particular source. • Hazard characterization: the quantitative and/or qualitative eval- uation of the nature of adverse effects associated with biological, chemical or physical agents, which may be present in a given source (for chemical agents, a dose-response should be performed; for bi- ological or physical agents, a dose-response assessment should be performed if the data can be obtained). • Exposure assessment: the qualitative and/or quantitative evalua- tion of the likelihood of exposure to the possible sources of a hazard. • Risk characterization: the qualitative and/or quantitative estima- tion, including attendant uncertainties, of the probability of occur- rence and severity of known or potential adverse health effects in a given population, based on hazard identification, hazard character- ization and exposure assessment.

This scheme may be applied for both qualitative and quantitative risk assessments, but it is more suitable for a quantitative approach.

The components of risk management in the NAS–NRC model are as follows:

• Risk evaluation: the identification of a potential health problem, es- tablishment of a risk profile and ranking of hazards for risk assess- ment and risk management priority. • Option assessment: the identification of available management op- tions and selection of the preferred management option, including consideration of an appropriate safety standard (this steps includes weighing various health risks along with economic, political and so- cial factors). • Monitoring and review: the assessment of effectiveness of meas- ures taken and a review of risk management and/or assessment as necessary.

Another framework for risk analysis is the Covello and Merkhofer mod- el. This model was designed to assess the magnitude of risk for speci- fied consequences in a given situation. It can be used to decide which sanitary measures are required to reduce the risk to an acceptable lev- el (including the ‘do nothing’ option in case the level of risk is already acceptable).

Risk assessments using this system are designed to answer the ques- tion: ‘what is the likelihood of specified consequences (i.e. specified human/animal health or economic or environmental effects) occurring as a result of exposure to a particular substance/pathogen that came 158

from a defined release source?’ This approach is very versatile, it is the standard approach used for import risk analysis and it has also been used for the design and re-planning of control or surveillance programs and for the selection of mitigation measures to be applied in case of animal movements. This approach is also the most frequently used (together with disease spread modelling) in the field of aquatic animals (Peeler et al., 2007). In summary, it is the system of choice for many risk assessors (Murray et al., 2004).

In the Covello and Merkhofer system (Fig. 8.2), risk assessment follows hazard identification, which is considered a separate step and is com- pleted first. This is followed by the four components of the risk assess- ment process (release assessment, exposure assessment, consequence assessment and risk estimation). Release assessment and exposure assessment are both included under the exposure assessment in the NAS–NRC model. The other difference between the two systems is the terminology to name the assessment of the consequences, called ‘haz- ard characterization’ in the NAS–NRC framework and ‘consequence as- sessment’ in the Covello and Merkhofer framework.

Since the Covello and Merkhofer system is the most frequently used in the field of animal health, this document will refer exclusively to this system, unless otherwise specified.

Fig. 8.2 Structure of the risk analysis process according to Covello and Merkhofer.

Risk assessment Risk management Release assessment Risk evaluation Hazard Exposure assessment Option assessment identification Consequence assessment Implementation Risk estimation Monitoring and review

Risk communication

8.1.1 STATE TRANSITION MODELS

Another approach to simulate the behaviour and the transmission of diseases in one or more populations of host is the use of state transition models.

State transition models, distinct from the above-described approach, are usually deterministic; i.e. a fixed law (system of equations) de- scribes the evolution of the system from a set of fixed values of the variables (instead of a set of probability distributions for the variables) 159 and are regulated by fixed parameters, for which uncertainty is not ac- counted. Nonetheless, recently state transition models have also been developed using a probabilistic approach.

The typical state transition models subdivide the host population into a set of compartments (the states), which usually are identified as ‘sus- ceptible’, ‘exposed’, ‘infectious’, ‘removed’ or ‘recovered’ (Fig. 8.3). In the most complete description of the system, all four states are consid- ered, but also simplified forms exist where only susceptible, infectious and recovered are considered, or even only susceptible and infectious. For chronic diseases or for diseases that are invariably lethal, the re- moved compartment is not considered. A system of differential equa- tions describes the passage through the various states.

Fig. 8.3 Schematic representation of a typical SEIR state transition model.

Susceptible Exposed Infectious Recovered

Susceptible (S): the fraction of the population including all animals sus- ceptible to the infection of interest, either naïve animals or (for some diseases) animals that have recovered after the complete disappear- ance of immunity.

Exposed (E): the fraction of the population including all animals that are infected, but are not yet able to infect other susceptible animals. This phase is roughly coincident with the incubation period. In many diseases, however, the infectious stage begins before the appearance of clinical signs, therefore still during the incubation period.

Infectious (I): the fraction of the population that is infected and able to transmit the infection to susceptible animals.

Recovered (R): the fraction of animals recovered from the infection that have developed immunity and are, therefore, resistant (or at least significantly less likely) to get the infection again.

This biological system is described by a system of differential equa- tions that describe the transition along time from one state to the next: 160

• dS/dt is the variation of the number of susceptible animals from time t to time t+1 • β is the transmission parameter, proportional to the probability of transmission of the infection following the contact between a sus- ceptible and an infectious animal • St is the number of susceptible animals at the time t • It is the number of infectious animals at the time t • N is the total number of animals in the population (N = S+E+I+R). In this specific system of equation N is constant over time. Mod- els with constant population are called meta-population models. In more detailed cases, natality and mortality are also considered and are linked to the carrying capacity, a parameter expressing the ef- fect of environmental factors and conditions. • dE/dt is the variation of the number of exposed animals from time t to time t+1 • Et is the number of exposed animals at time t • α is the probability of passage from the state E to the state I in the unitary time period (α=1/duration of the state E) • dI/dt is the variation of the number of infectious animals from time t to time t+1 • r is the probability of recovery in the unitary time period (r=1/dura- tion of the state I) • dR/dt is the variation of the number of recovered animals from time t to time t+1

This system of differential equations is strictly deterministic and does not consider the individual variability and the consequent variable out- comes and behaviours of the biological systems. To take into consider- ation this variability, a stochastic state transition model can be devel- oped, in which the unique values of the variables (S, E, I and R and their variation over time) are substituted by probability distributions. 161

The level of detail provided by state transition models is only required in some very specific cases, therefore the risk assessment approach is the most frequently used.

8.1.2 SCENARIO TREE

A tool frequently used in risk assessment (used both in the Covello and Merkhofer and in the NAS-NRC frameworks) is the scenario tree.

A scenario tree is a graphical depiction of the biological pathways by which a hazard might be introduced into an importing country or trans- mitted between different populations or subpopulations, and provides a useful conceptual framework. A scenario tree assists in conveying the range and types of pathways considered in a simple, transparent and meaningful fashion (Fig. 8.4). Scenario trees are an appropriate and effective way of depicting biological pathways (Murray et al., 2004).

Fig. 8.4 Generalized scheme for a scenario tree.

Endpoint: the outcome of interest DOES occur

An example of a scenario tree (Figs. 8.5 and 8.6) is that describing the transmission to humans of feline bartonellosis (cat scratch disease), that will be used for the part of this project concerning diseases trans- mitted by direct contact.

The following scenario tree is fairly exhaustive and may be simplified in case of lack of relevant information. Furthermore, part of the infor- mation used (possibly a small part of the information used) may not be ‘hard data’ from field or experimental work, but can be elicitated as expert opinion. 162

Fig. 8.5 Scenario tree for the transmission of cat scratch disease: release assessment and exposure assessment. Release assessment components are shown in blue; exposure assessment components are in orange.

S1=Binomial A (Na, P1sa) Scratched

Adults

Not FD 1-S1 Endpoint Scratched Family Infected members

Not FD 1-S2 Endpoint P1 Scratched

Children Owned cat

S2=Binomial Scratched B (Nc, P1sc) 1-P1

Non-infected Endpoint

S3=Binomial C (Tna, P2sa) Scratched

Adults

Not Tna 1-S3 Endpoint Scratched Human Infected population

Not 1-S4 Endpoint Isc=Binomial Tnc Scratched (Nsc, Ps1)

Children Stray cats

S4=Binomial Scratched D Nsc-Isc (Tnc, P2sc)

Non-infected Endpoint

• P1 = Prevalence of infection by Bartonella in owned cats. Since it is active infection, isolation or PCR data are representative of the real situation, although underestimated in relation to the sensitivity of the tests. Serological (ELISA) data are overestimated and must be corrected by a factor proportional to the ratio (duration of active infection)/(duration of immunity). • FD = Empirical frequency distribution of the family composition from census data • S1 = Number of adult family members scratched by the family cat • Na = Number of adults in the family • P1sa = Probability of an adult being scratched by the family cat • S2 = Number of child family members scratched by the family cat 163

• Nc = Number of children in the family • P1sc = Probability of a child being scratched by the family cat • Isc = Number of infected stray cats • Nsc = Total number of stray cats • Psi = Prevalence of infection in stray cats. Since it is active infec- tion, isolation or PCR data are representative of the real situation, although underestimated in relation to the sensitivity of the tests. Serological (ELISA) data are overestimated and must be corrected by a factor proportional to the ratio (duration of active infection)/ (duration of immunity). • Tna = Total number of adults in the human population • P2sa = Probability of an adult being scratched by a stray cat • S3 = Total number of adults in the population scratched by a stray cat • Tnc = Total number of children in the human population • P2sc = Probability of a child being scratched by a stray cat • S4 = Total number of children in the population scratched by a stray cat

Since stray cats are shy animals and avoid contact with human beings, the values for P2sa and P2sc are very low and might be considered negligible. In this case, the second part of the scenario tree may be omitted.

Fig. 8.6 Scenario tree for the transmission of Cat scratch disease: consequence as- sessment.

nai=Binomial TCai=nai x cai (S1+S3,fai)

All possible consequences of cat scratch disease in adults [Ci] with their relative Total number of cases Total costs of each frequency [fai]: for all possible possible consequences - signs at site of consequences of Cat A and C of Cat scratch disease in - general signs (fatigue, scratch disease in headache, adults [Tcai] adults [nai] swelling, etc.) - fever and loss of working days - ...

nci=Binomial TCci=nci x cci (S1+S3,fci)

All possible consequences of cat scratch disease in children [Ci] with their Total number of cases Total costs of each relative frequency [fci]: for all possible possible consequences - signs at site of injury consequences of Cat B and D of Cat scratch disease in - general signs (fatigue, scratch disease in headache, lymph node adults [Tcci] adults [nci] swelling, etc.) - fever and loss of working days - ... 164

• ci = each possible consequence of cat scratch disease • fai = relative frequency in adults of each possible consequence of cat scratch disease • nai = total number of cases in adults for each possible consequence of cat scratch disease • cai = unitary cost for each case of each possible consequence of cat scratch disease in adults • Tcai = total cost for each possible consequence of cat scratch dis- ease in adults • fci = relative frequency in children of each possible consequence of cat scratch disease • nci = total number of cases in children for each possible conse- quence of cat scratch disease • cci = unitary cost for each case of each possible consequence of cat scratch disease in children • Tcci = total cost for each possible consequence of cat scratch dis- ease in children

The scenario tree in Figs. 8.5 and 8.6 is not the only possible representa- tion of the pathway leading to the human infection by Bartonella. Many alternatives are possible, each of which may be aimed at a different objective and/or may require different types of data.

For example, in case the assessment was to include, from the risk man- agement component, the evaluation of antiparasitic treatment as a risk mitigation measure, the release assessment component would have to be changed as in Fig. 8.7.

Fig. 8.7 Scenario tree for the transmission of cat scratch disease: option evaluation of the effectiveness of cat anti-flea treatment to prevent human bartonellosis.

Effective Cat not Endpoint prophylaxis infected E1

Anti-flea prophylaxis P1 Infected As in Fig. 4 1-E1 Ineffective prophylaxis T1

1-P1 Non-infected Endpoint Stray cats

1-T1

Infected As in Fig. 4 P1

Not treated

1-P1 Non-infected Endpoint 165

• T1 = expected proportion of households adopting the flea prophy- laxis • E1 = probability that the prophylaxis prevents the flea infestation of the cat

The scenario tree has been also widely used in import risk assess- ments. Two different approaches to prevent the introduction of rabies into the UK are shown in form of the respective scenario trees in Figs. 8.8 and 8.9. In the two figures, the scenario trees have been simplified by not showing the branches leading to a safe import (i.e. no import of rabies)

Fig. 8.8 Pathway for rabies entry into the UK via a dog/cat movement through the 6-month quarantine system. 166

Fig. 8.9 Pathway for rabies entry into the UK via a dog/cat movement through EU pre-movement prophylaxis. Red italics denote illegal pathways.

Given that scenario trees are extremely flexible in order to accommo- date the various possible objectives of a risk assessment, the various possible pathways and the potential lack of information, it is impossible in this phase of the project to anticipate a set of scenario trees, one for each paradigmatic disease considered.

Scenario trees for each paradigmatic disease will be produced as part of the second cycle of the project.

Modified scenario trees to accommodate the various options consid- ered for the mitigation of the risks presented by the various paradig- matic diseases, will be produced in the third cycle of the project. 167

8.2 EPIDEMIOLOGICAL SIMILARITIES AND DIFFERENCES BETWEEN THE PARADIGMATIC DISEASES

SELECTED IN CHAPTERS 5–7

The diseases have been grouped according to Table 8.1.

Table 8.1 Classification of the diseases and risks to be assessed for each group of dis- eases

TYPE OF RISK TO BE ASSESSED The pathway of spread and trasmission Type of risk Vector-borne posed by the Direct and Vector-borne diseases Type of disease, for indirect diseases without relevance of which risk transmission with direct direct the desease assessment without transmission transmission could be vectors chains chains necessary. transmission transmission companion companion animals animals -- ->human ->human beings beings Zoonoses transmission transmission endemic in companion companion companion -- animals animals animals in ->vectors ->vectors the EU transmission transmission companion companion -- vectors vectors ->human ->human beings beings transmission transmission Public health companion companion relevance animals animals -- primarly ->human ->human Emerging and beings beings re-emerging transmission transmission zoonoses, companion companion -- already ->animals ->animals present in the vectors vectors EU (*) transmission transmission companion companion -- vectors vectors ->human ->human beings beings Zoonoses that may Import Risk Import Risk Import Risk become a assessment assessment assessment risk in the EU 168

TYPE OF RISK TO BE ASSESSED The pathway of spread and trasmission transmission transmission companion companion animals animals -- ->human ->human beings beings transmission transmission farmed farmed animals animals -- ->companion ->companion animals animals transmission transmission companion companion animals animals -- ->farmed ->farmed Diseases animals animals endemic in the EU and transmission transmission farmed farmed common -- to humans, ->animals ->animals companion vectors vectors animals transmission transmission and farmed companion companion -- animals ->animals ->animals vectors vectors transmission transmission vectors vectors -- ->human ->human beings beings Public transmission transmission health and vectors vectors -- economic ->companion ->companion relevance animals animals transmission transmission vectors vectors -- ->farmed ->farmed animals animals transmission companion animals -- ->human beings transmission farmed animals -- ->companion Emerging and animals re-emerging transmission diseases companion already animals -- present in the ->farmed EU (*) animals transmission transmission farmed farmed ->animals ->animals vectors vectors transmission transmission companion companion ->animals ->animals vectors vectors 169

TYPE OF RISK TO BE ASSESSED The pathway of spread and trasmission transmission transmission vectors vectors ->human ->human Emerging and beings beings Public re-emerging transmission transmission health and diseases vectors vectors economic already ->companion ->companion relevance present in the animals animals EU (*) transmission transmission vectors vectors ->farmed ->farmed animals animals (*) for these diseases, it is likely that the information available is too scanty to perform a risk assessment, therefore the research needs and knowledge gaps will be analysed

The grouping of the paradigmatic diseases selected according to their epidemiological similarities is shown in Table 8.2.

Table 8. 2 Grouping of the paradigmatic diseases according to their epidemiological characteristics

DISEASES TO BE CONSIDERED The pathway of spread and trasmission Type of risk Vector-borne posed by the Direct and Vector-borne diseases Type of disease, for indirect diseases without relevance of which risk transmission with direct direct the desease assessment without transmission transmission could be vectors chains chains necessary. Cat & Dog Zoonoses bites Cat West Nile endemic in scratch dis- Fever companion ease Psitta- (in some animals in cosis Salmo- countries) the EU nellosis Toxocarosis (ocular and Emerging and visceral Public health re-emerging larvae relevance diseases migrans) Rickettsiosis primarly already Cutaneous Borreliosis present in the larvae Leishmaniasis EU (*) migrans (hookworm disease) Zoonoses West Nile

that may Rift Valley Fever Rabies become a Fever (in some Influenza risk in the EU countries) 170

DISEASES TO BE CONSIDERED The pathway of spread and trasmission Diseases endemic in the EU and common West Nile Echinococcosis to humans, Disease in Toxoplasmosis companion farmed birds Public animals health and and farmed economic animals relevance Emerging and re-emerging Leptospirosis diseases (from dogs/ already pigs) present in the EU (*) (*) for these diseases, it is likely that the information available is too scanty to perform a risk assessment, therefore the research needs and knowledge gaps will be analysed

In Table 8.2, antibiotic resistance is not considered because the spread of antibiotic-resistant bacteria in the host populations follows the same rules followed by the non-resistant bacteria of the same species, while the means of spread of the resistance traits between bacteria of differ- ent strains or species follows rules described in specific models. The task in the field of antibiotic resistance will be to put together the two sets of models and assessments in order to obtain an overall model for the spread of resistance in the pet animal populations.

8.2.1 DISEASES TRANSMITTED BY DIRECT CONTACT

The epidemiological characteristics relevant for the modelling of dis- eases transmitted by direct contact have already been described in detail in the section on scenario trees, therefore they will not examined in more detail here.

8.2.2 DISEASES TRANSMITTED BY VECTORS

For vector-borne infections, a further component is added, the effect and the relevant characteristics of the vector. The important charac- teristics of the vector that must be taken into consideration in model- ling the risk for human health posed by vector-borne diseases are the following:

• The ability of the vector of obtaining and transmitting the infection is a crucial component of the epidemiology of vector-borne diseas- es. • The environmental requirements of the vector, which determine the geographical distribution of the vector itself, are another impor- 171

tant component. When the infection has an obligate vector-borne transmission (i.e. there is no possibility of transmission by direct contact), the geographical distribution of the vector determines a dichotomy in the areas where the risk of infection may be present and areas where the risk of infection is zero. For these diseases, for example, the OIE Terrestrial Animal Health Code states that the im- portation of an infected animal to a country where competent vec- tors for that specific infection are not present, has no consequences on the free health status of the importing country because there is no possibility of further spread of the disease. • Given the usually short life of insects and ticks, the population dy- namics of the vector and its life expectancy, given a set of envi- ronmental conditions, are a further important characteristic to be taken into consideration for many types of models for vector-borne infections. In vertebrate hosts, the disease-induced modifications in population dynamics may have importance, but in the absence of a high lethality, the population dynamics and the life expectancy of the host are not influential on the behaviour and the spread of the infection.

The variety of epidemiological factors relevant for vector-borne dis- eases have led to a wider variety of approaches in the study of these diseases than in the case of contagious diseases.

In some cases, a similar approach to that for contagious diseases has been followed, just more complex to account for the vector component. Napp et al. (2011), concerning bluetongue (not one of our paradigmat- ic diseases) considered two further pathways to describe the vector component of the epidemiology of bluetongue (Fig. 8.10).

Fig. 8.10 Pathways for vector-to-mammalian host bluetongue transmission at different times of the year.

Pathway I

CULICOIDES EFFECTIVE CULICOIDES SURVIVEA TRANSMISSION RISK INFECTED EIP+TNBM TO HOST

Pathway II & III

CULICOIDES EFFECTIVE CULICOIDES VIRAEMIA SURVIVEA TRANSMISSION RISK INFECTED EXCEEDS PLVA EIP+TNBM TO HOST 172

• EIP = extrinsic incubation period (i.e. the period before an infected vector becomes infectious for the vertebrate host) • TNBM = time to the next blood meal • PLVA = period of low vector activity

The pathways described for bluetongue by Napp et al. (2011) may be adapted to other diseases of pet animals of zoonotic relevance.

Data on the vector component of the infection pathway required to follow this approach are the duration of the various phases (EIP, TNBM, PLVA, duration of viraemia in the vertebrate host, life expectance of the vector at different environmental temperatures) and the probability of being in or of entering the various phases in the pathway.

The most widely followed approach to model the behaviour and the spread of vector-borne infections and to evaluate the effectiveness of control options is the use of state transition models. Some models have been developed for general purpose and may be used or adapted for any pathogens (Szymanski and Caraco, 1994; Wei et al., 2008; Lashari and Zaman, 2011; Ji et al., 2011; Jovanovic and Krstic, 2012), while others have been developed specifically to describe the spread of a specific pathogen (Ngwa and Shu, 1999; Rascalou et al., 2012, which has been used, among other diseases, for visceral leishmaniosis in humans with- out taking into consideration the dog infection). Additionally, possible control options are taken into account in some models (Hosack et al., 2008; Blayneh et al., 2009; Luz et al., 2010; Rodrigues et al., 2012).

The model described in Lashari and Zaman (2011) will be summarized here to give an example of the approach (Fig. 8.11). This models consid- ers both the transmission mediated by vectors (β2ShIv in Fig. 8.11 and solid line from the vector to the human population side) and the direct horizontal transmission between vertebrates (β1ShIh and the dotted line from the Ih to the Sh compartments in the human side of Fig. 8.11) of the pathogen, therefore its adaptation to those host–parasite sys- tems for which the transmission is exclusively due to vector is straight- forward. Moreover, this model considers real populations rather than metapopulations and it alos includes mortality parameters (μh and μv for the non-disease-induced mortality in the human and vector popu- lations, respectively; and δh and δv for the disease-induced mortality in the human and vector populations, respectively). 173

Fig. 8.11 Flow chart of the interactions and transitions in the model.

The system of differential equations in the model is the following:

The meaning of the symbols used is the same as already defined in the previous section on state transition models plus the new subscripts h and v for human and vector populations respectively and the mortality parameters μ and δ.

A simplification of this approach is to make reference to the basic re- 174

production number (or basic reproductive rate, R0). The basic repro- duction number is the number of further cases that one case gener- ates on average over the course of its infectious period. R0 is useful because it helps determine whether or not an infectious disease can spread through a population. When R0 <1 the infection will die out in the long run, but if R0 >1 the infection will be able to spread in a pop- ulation. R0 can be calculated from mathematical models, particularly from the differential equations of a state transition model. From the parameters of the model described in Lashari and Zaman, 2011, R0 can be estimated as:

Another important parameter, similar to R0, to be considered in the case of vector-borne diseases is the vectorial capacity, which is an expression of the number of infections that the population of a given vector would distribute per case, per day, at a given place and time (Garrett-Jones, 1964):

where:

• m = number of vectors per host • a = number of blood meals taken by a vector per host, per day [ma = biting rate] • V = vector competence (the proportion of vectors capable of agent transmission) • p = daily survival probability of the vector • n = extrinsic incubation period in days

A third approach frequently used for vector-borne diseases is the mod- elling of the geographical distribution and abundance of the vectors. To do this, a number of environmental characteristics relevant for the vector presence are measured, locally or through remote sensing, and are used to evaluate the suitability of the various habitats in a geo- graphical area for the specific vectors. The results are maps of fore- cast presence or maps of forecast abundance of the vectors.

Variables taken into consideration are dependent on the biology of the various vector species, but in general they include climatic and me- teorological variables (Brownstein et al., 2003; Conte et al., 2003; Fis- cher et al., 2011), or environmental variables such as land cover, remote sensing data on vegetation, aridity index, slope and slope orientation, soil composition, texture and water contents, together with climatic data (Baylis et al., 2001; Baylis et al., 2004; Conte et al., 2004; Purse et al., 2004; Conte et al., 2007a; Conte et al., 2007b). 175

A number of different spatial statistics are used to analyze the spatial data and create the distribution forecast maps (Rogers, 2006; Winters et al., 2010).

8.3 REVIEW OF EXISTING PUBLISHED RISK ASSESSMENTS CONCERNING THE TRANSMISSION OF DISEASES FROM COMPANION ANIMALS TO HUMANS OR FARMED ANIMALS

Similar to the case of farmed animals, most published risk assessments concerning diseases of companion animals are import risk assess- ments.

Among the paradigmatic diseases chosen for the CALLISTO project, the two with the greatest number of published risk assessments are salmonellosis and toxoplasmosis, but in both cases the assessments concern food safety risks for consumers. In the case of toxoplasmosis, a number of risk assessments concerning vertical transmission in hu- man beings are also published. Such assessments might constitute the second phase of assessments starting from the transmission from pets to human beings. They will be useful to evaluate the consequences of human infection and their likelihood.

A number of published papers, however, provide very useful data for the development of risk assessments and are worthy of analysis. The three groups of published papers will be considered separately.

8.3.1 IMPORT RISK ASSESSMENTS

The disease most frequently submitted to import risk assessments is rabies.

Among recent assessments, a qualitative risk assessment for the im- portation of rabies into the United Kingdom was performed in 2006 by the School of Agriculture, Policy and Development at The University of Reading (Wilsmore et al., 2006). The objectives of the assessment were to: 176

• Find out whether UK rabies controls relating to the import of ra- bies-susceptible mammals were proportionate and sustainable, and that their primary purpose was to protect public health • Inform the UK’s response to the EU review of some requirements of the EU pet movement regulation • Assess, using the best available current scientific evidence, the risk of introduction of rabies into the UK under current rabies polices and under alternative policies.

The final result of the assessment was a table with the classification of each country from which pets can be imported to the UK into three broad risk classes: countries posing low, medium and high risk to the UK and this level of risk was compared with the set of measures pro- vided by the legislation for the importation from that specific country. The measures foreseen by the legislation were generally well com- measured to the level of risk. Only in very few cases the measures and the level of risk appeared not consistent.

In 2004, the EU introduced a companion animal movement and impor- tation policy to protect against rabies introduction via cats and dogs and ferrets (the EU Pet Movement Policy - EUPMP). The UK had der- ogation from the EU policy of companion animal movement controls, which expired in December 2011. In anticipation of the expiry of this derogation, in 2010 the UK performed a quantitative assessment of the impact of adopting the EUPMP on the risk of rabies entering the UK due to the movement of companion animals (Goddard et al., 2010; Det Norske Veritas, 2011).

The questions to which this new risk assessment had to give answers were:

• How would the risk of rabies introduction to the UK via travelling pets from EU Member States and listed third countries change were the UK to apply the current harmonised EU rules for the non-com- mercial movement of pets? • How would risk of rabies introduction from all countries (EU Member States, listed third and unlisted third countries) change if rules were followed with 100% compliance or if rules were followed with vary- ing degrees of <100% compliance?

A stochastic QRA was developed using the software package @Risk. Only uncertainty was included in the model. The model estimated the probability of one or more infected dogs/cats entering the UK and the number of years between rabies entry for both the UK movement pol- icy current at the time (PETS/Quarantine) and EUPMP. The model only considered companion animals entering the UK from abroad; returning UK animals were not included in the assessment due to data limita- tions. 177

The results of the QRA, assuming 100% compliance with all regulations, suggested that under EUPMP the annual risk of rabies introduction from non-UK cats/dogs would increase from 7.79 x 10-5 (5.90 x 10-5–1.06 x 10-4) to 4.79 x 10-3 (4.05 x 10-3–5.65 x 10-3). This is a 60-fold increase in the mean risk; however, within the different country classifications (EU MSs, listed/unlisted third countries) different trends were observed.

Still concerning the importation of pets, a number of import risk as- sessments have been performed for ornamental fish, evaluating the risks posed to farmed fish (Kahn et al., 1999; Whittington and Chong, 2007; Biosecurity Australia, 2009) and to the environment (Biosecurity Australia, 2009; Bomford and Glover, 2004).

The 1999 IRA on ornamental fish (Kahn et al., 1999) was made following a request from Canada in 1997. The World Trade Organization (WTO) Dispute Settlement Panel and Appellate Body concluded that there were arbitrary or unjustifiable distinctions in the level of protection ap- plied by Australia in relation to salmon and other fish, and these dis- tinctions resulted in a disguised restriction on international trade and gave Australia until 6 July 1999 to address its obligations.

Australia, therefore, performed an IRA on qualitative basis on the risks to Australian animals and the environment associated with the impor- tation to Australia of live ornamental finfish belonging to a specific list. This risk analysis evaluated the risks associated with individual diseas- es and disease agents and identified measures appropriate to the risks presented by the importation of live ornamental finfish. Based on this evaluation, risk management measures for these fish were proposed, including the means for verifying the health certification provided by exporting countries. The IRA is ‘generic’ and addresses all relevant pests and diseases, to facilitate assessment of individual access re- quests according to the health status of the source country.

Subsequently, in 2007 this IRA was revised and updated (Whittington and Chong, 2007). The revision of the IRA on ornamental fish conclud- ed that ornamental finfish represent a special case in live animal trade. Due to the high numbers of exotic ornamental species traded interna- tionally, the plethora of exotic pathogens and parasites recorded and not yet recorded in these species, poorly defined epidemiological and pathogenic data for many of the diseases and parasites, the current risk analysis procedures applied to mammalian and other animal spe- cies for which the prevalence, geographical distribution and biologi- cal characteristics of hazards are well described are inappropriate for ornamental fish species. The authors proposed that the international community consider a new model for risk analysis for ornamental fin- fish, inclusive of potential and unidentified hazards.

Another assessment concerned the potential impacts of exotic finfish on the environment and on the native fish populations and biocenoses 178

(Bomford and Glover, 2004). This is a very interesting topic, but is out- side the scope of the CALLISTO project, which considers the impact on the health of human beings and farmed animals.

Concerning the transboundary spread of other paradigmatic diseases, some risk assessment exist that consider the main potential ways of diffusion, which generally are not the international movement or trade of companion animals.

Concerning Rift Valley Fever, four interesting assessment were per- formed. Two studies considered the risk of spread with the trade of susceptible domestic ruminants and the development of an epidemic, in one case at the Haj in Mecca (Davies, 2006), the other from the Horn of Africa to Yemen, considering the year round and evaluating the dif- ferences at the time of festivals (Abdo-Salem et al., 2011).

The third study concerned the risk of introduction to Tunisia of the Rift Valley fever virus by the mosquito Culex pipiens (Krida et al., 2011). This study is particularly relevant for Europe in consideration of the likely introduction of bluetongue in southern Europe through wind-borne in- fected midges (Calistri et al., 2004).

Finally, there is a very comprehensive risk assessment performed by EFSA on the introduction of Rift Valley fever to the EU by legal and illegal movement of animals, animal products and by transboundary movement of vectors and human beings (EFSA, 2005).

Finally, in the field of transboundary spread of diseases to areas of the EU not yet infected, there is a very recent assessment on the introduc- tion of West Nile virus to the UK (Roberts and Crabb, 2012), which con- siders the risk posed by migratory wild birds, legal movements of live equidae, equine germplasm, biologicals and research samples, poultry and captive birds and other animal species (e.g. exotic ungulates, rep- tiles), as well as by illegal movements and wind-borne or accidental introduction of infected vectors.

8.3.3 RISK ASSESSMENTS CONCERNING THE ‘PARADIGMATIC DISEASES’

Concerning the other paradigmatic diseases, those endemic or pres- ent in EU countries, most risk assessments concern salmonellosis and toxoplasmosis, but they are out of the scope of CALLISTO project since they are food safety risk assessments (e.g.: Lammerding and Paoli, 1997; Dubey et al., 2005; Mie et al., 2008; Opsteegh et al., 2011; Bayarri et al., 2012).

In the case of Toxoplasma gondii, however, a number of assessments on the risk of vertical transmission in humans have been published 179

(Vimercati et al., 2000; Mombrò et al., 2003; Bamba et al., 2012; Flatt and Shetty, 2012). Since the vertical transmission in humans is the most severe consequence of toxoplasmosis in man, these risk assess- ments can constitute the final part of a possible assessment of the risks posed by pets to human health.

Concerning the risk of human infection due to salmonellae transmitted by reptiles, a risk assessment has been published in England for the years 2004-2007 (Aiken et al., 2010), while a few other publications may provide useful data for a quantitative risk assessment (Mermin et al., 2004; Bertrand et al., 2008).

Echinococcosis has been the subject of some import risk assessments (Bødker et al., 2006; EFSA, 2006; Torgerson and Craig, 2009; Defra, 2010; Defra, 2012).

No assessment has been published for human health in countries where echinococcosis is endemic. Some useful data for a quantitative risk as- sessment in endemic rural areas may be found in Varcasia et al. (2011), which reports on echinococcosis in Sardinia.

Concerning bites, besides the risk related to rabies infection (e.g. Me- nachem et al., 2008), some detailed studies exist, which could pro- vide useful data for a quantitative risk assessment (Kato et al., 2003; Cornelissen and Hopster, 2010; Dixon et al., 2012; Messam et al., 2012; Quirck, 2012).

8.3.4 TYPE OF INFORMATION REQUIRED FOR THE SPECIFIC RISK ASSESSMENT OF EACH PARADIGMATIC DISEASE

Detailed examples of the information required for the specific risk as- sessments of each transmission and spread pathway (i.e. direct con- tact, vector-borne with or without direct transmission within the ver- tebrate host populations, specific information required for import risk assessment) are given in the previous sections where the pathways are described and where the existing published assessment were de- scribed.

A summary of the types of information necessary is also given in Annex VI-I, where the paradigmatic diseases are considered individually.

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9.1 INTRODUCTION

The website (www.callistoproject.eu) is the main communication tool of CALLISTO. The CALLISTO project started in January 2012 with the aim of developing an overview of the current situation, with regard to the role of companion animals as a source of infectious diseases for people and livestock, identifying knowledge and technology gaps for the most important zoonoses associated with keeping companion animals, and according to these propose targeted actions to prevent and reduce the health risks for both humans and animals.

Project partners agreed the importance of implementing a communi- cation and dissemination strategy to promote awareness of the objec- tives and activities of the think tank. The website was considered as the core of internal and external communication activities: it can facil- itate exchange of information and documents among experts involved in CALLISTO and promote constant interaction with the general public and relevant stakeholders. This interaction stimulates debates on the scientific topics and increases awareness and support for combating zoonosis outbreaks and spread at a European and National level.

Istituto G. Caporale Teramo (ICT) is the leader of the Work Package responsible for communication and dissemination of CALLISTO. The ICT team designed www.callistoproject.eu in co-operation with the FVE as project lead partner. The web site was launched on 31st March 2012 with a coordinated press release on 4th April 2012.

In order to address communication needs expressed by project part- ners and implement effective tools for knowledge sharing, the website was structured to have two main areas: (1) a public area, largely dedi- cated to the publication of relevant information on the initiative and for interaction between CALLISTO experts (Expert Advisory Group mem- bers) and the general public and (2) a restricted area for communica- tion, knowledge sharing and coordination among experts and internal users of the website. Moreover, multimedia tools (e.g. texts, videos etc.) are used in order to improve communication activities. A specific You- tube channel was opened for videos published by CALLISTO. 186

9.2 MAIN SECTIONS AND FUNCTIONING

The CALLISTO website has seven main sections.

The home page is an introductory page containing links to CALLISTO publications, the CALLISTO channel in YouTube, latest news and posts in the CALLISTO blog. There is a ‘Search’ function, quick links to web- site pages and other useful links. The home page describes the CAL- LISTO mission, main objectives and components of the initiative.

The EAG page gives access to a detailed description of each Expert Ad- visory Group, including its members and activities. Videos introducing the scope and actions of each EAG are also available.

The blog provides themes of public discussion and stimulates interac- tion among experts and other users.

News and events is a page for publication of news and events concern- ing CALLISTO and/or its area of activity.

The press area contains articles, publications and proceedings related to CALLISTO thematic issues.

‘Contacts’ is a specific page to enable contact with the CALLISTO sec- retariat to ask for more information and details.

The CALLISTO restricted area is set for CALLISTO partners and EAG members. Users registered in this area may have access to relevant documents produced by each EAG and general material used during the project (e.g. powerpoint presentation templates, reports etc). Au- thorized users (CALLISTO EAG experts registered in the log-in area) can create contents for the CALLISTO blog and participate in the virtu- al debate promoted through this tool.

General public users are also invited to register; external users are au- thorized only to post comments on the blog articles. 187

9.3 DATA CONCERNING WEBSITE VISITS

According to the website analytical tools, in the first nine months of activity and until 31st December 2012, www.callistoproject.eu received 2,995 visits. The percentage of new and returning visitors is depicted in the pie chart below:

The geographical origin of visitors to the website is depicted in the map shown below. 188

The highest number of visitors come from the following ten countries:

9.4 IMPROVEMENTS AND FORTHCOMING ACTIONS

The CALLISTO website is dedicated to communication and dissemina- tion activities. During the first months the website was presented on different occasions and by using various communication means.

Initially, www.callistoproject.eu was launched by all project partners’ websites and in publications including the FVE Newsletter, the ICT Newsletter on Animal Welfare and various articles on specialised web- sites and in online scientific magazines. Moreover, the CALLISTO web- site was shown during international conferences with the aim of pro- moting the initiative and increasing its audience.

In particular, CALLISTO intiative and, when possible, its website, were presented during the following events:

Animal Health Advisory Committee, Working Group of the Advisory Group on the Food Chain, Animal Health and Plant Health, in Brussels, on February 17th, 2012; • The 8th European Pet Night, Brussels, on February 29th, 2012, under the patronage of Members of the European Parliament; 189

• 1st FAO Global Multistakeholders Forum on Animal Welfare, organ- ized by FAO in Brussels on 1-2 March, 2012; • Workshop “Animal Welfare in the Western Balkans and Turkey” or- ganized by RSPCA International and Istituto Zooprofilattico Speri- mentale dell’Abruzzo e del Molise G. Caporale in Teramo (Italy) on 3-4 April, 2012; • OIE General Session, on May, 2012; • The “Animal Welfare Conference” organized by the Eurogroup for Animals in Brussels on 19-20 June, 2012 ; • The OIE “Animal Welfare Conference” organized by the Collaborat- ing Centre for Chile and Uruguay, held in Montevideo on July 2012.

As concerns the promotion of the website, forthcoming actions are:

• to update www.callistoproject.eu with First Conference proceed- ings and relevant news; • to prepare a press release on the First CALLISTO Conference out- comes and results to be circulated among partners for further com- munication; • to send informative emails concerning the CALLISTO website to project partner contacts. • With reference to internal communication purposes, it is necessary to promote the use of the reserved area for exchanging documents and publishing articles, since the number of registered users is still quite low. The reserved area should host approved EAG reports and Cross EAG reports; moreover it is especially devoted to the publica- tion of articles for the blog and interchange of comments.

Forthcoming actions to improve the use of the reserved area are:

• to publish some internal documents, useful for producing the con- clusions of the first CALLISTO Conference and developing further documents inviting participants to register and consult them • to stimulate EAG members to act as bloggers. 190 GLOSSARY

A

ACCIDENTAL HOST One that accidentally harbours an organism that is not ordinarily par- asitic in that particular species

ADAPTED VARIANTS Are variants of the pathogen that are adapted to different circumstanc- es (for example a different host)

ADULTICIDE COMPOUND A pesticide used against the adult stage of a parasite

AMPLIFYING HOST A host in which the level of pathogen can become high enough that a vector such as a mosquito that feeds on it will probably become infec- tious

ANAEROBIC ORGANISM An organism that does not require oxygen for growth. It could possibly react negatively and may even die if oxygen is present

ANTHELMINTHICS Drugs that expel parasitic worms (helminths) from the body, by either stunning or killing them. They may also be called vermifuges (stunning) or vermicides (killing)

ANTHROPOPHILIC SPECIES Parasites or dermatophytes that prefer humans over other animals

ANTIGENIC HOMOLOGY An antigen is a substance that evokes the production of one or more antibodies. Each antibody binds to a specific antigen by way of an in- teraction similar to the fit between a lock and a key. When two antigens are very similar they can evoke the production of similar antibodies.

ASYMPTOMATIC A disease is considered asymptomatic if a patient is a carrier for a dis- ease or infection, but experiences no symptoms

AUTOCHTHONOUS INFECTION An infection that is indigenous or endemic to a region 191

B

BACTERAEMIA PREVALENCE The proportion of a population found to have a bacterial infection of the blood

BRIDGE SPECIES A species transmitting a pathogen between an infected population and a naïve population

C

CHEMOPROPHYLAXIS the administration of a medication for the purpose of preventing dis- ease or infection

CLADES An approach to classification in which items are grouped together based on whether or not they have one or more shared unique char- acteristics that come from the group’s common ancestor and are not present in more distant ancestors. Therefore, members of the same group are thought to share a common history and are considered to be more closely related

CLINICAL INFECTION The invasion of host tissues by disease-causing organisms, their mul- tiplication, and the reaction of host tissues to these organisms and the toxins they produce

COMMUNITY-ASSOCIATED Acquired in the community

COMPANION ANIMAL Any domesticated, domestic-bred or wild-caught animal, permanent- ly living in a community and kept by people for company, enjoyment, work (e.g. support for blind or deaf people, police or military dogs) or psychological support – including, but not limited to dogs, cats, horses, rabbits, ferrets, guinea pigs, reptiles, birds and ornamental fish.

COPROANTIGEN Antigens found in faeces. Methods have been developed to detect co- proantigens in order to diagnose intestinal diseases, including hel- minth, protozoan, bacterial and viral infections 192

CROSS-REACTION Cross-reactivity is the reaction between an antibody and an antigen that differs from the immunogen that stimulated production of the an- tibody.

D

DEAD-END HOST OR INCIDENTAL HOST An intermediate host that does generally not allow transmission to the definitive host, thereby preventing the parasite from completing its de- velopment. For example, humans are dead-end hosts for Echinococcus canine tapeworms. As infected humans are not usually eaten by dogs, foxes etc., the immature Echinococcus is unable to infect the primary host and mature

E

ELISA Enzyme-linked immunosorbent assay (ELISA) is an immunological test that detects either antigens from an infectious agent or antibodies generated to that agent in an infected animal

ENDEMIC In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs.

ENDEMICALLY INFECTED See endemic

ENDOSYMBIONT Any organism that lives within the body or cells of another organism, i.e. forming an endosymbiosis

EPIZOOTIC A disease that appears as new cases in a given animal population, dur- ing a given period, at a rate that substantially exceeds what is “expect- ed” based on recent experience (i.e. a sharp elevation in the incidence rate). Epidemic is the analogous term applied to human populations

“EXOTIC” COMPANION ANIMALS Encompassing all non-domesticated animals kept as companion ani- mals or pets 193

EXTIRPATION Or local extinction, is the condition of a species (or other taxon) which ceases to exist in the chosen geographical area of study, though it still exists elsewhere. Local extinctions are contrasted with global extinc- tions

F

FAECAL-ORAL ROUTE A route of transmission of diseases, in which pathogens in faecal par- ticles from one host are introduced into the oral cavity of another po- tential host

FERAL ANIMAL An animal which has changed from being domesticated to being wild, natural, or untamed. Feral animals are born in the wild as opposed to stray animals that are abandoned or lost domesticated animals

FOMITES Any inanimate object or substance capable of carrying infectious or- ganisms

Food producing animal Any animal that produces food for humans

G

GENETIC ASSEMBLAGES Groups of organisms within a genus defined by their genetic similarity

GENOTYPE The genetic makeup of a cell, an organism, or an individual

GEOPHAGIA The practice of eating earth or soil-like substances such as clay, and chalk

GEOPHILIC SPECIES Soil loving or preferring the soil 194

H

HAEMATOPHAGOUS Feeding on blood

HERD IMMUNITY Vaccination of a significant portion of a population (or herd) provides a measure of protection for individuals who have not developed immu- nity

HETEROXENOUS LIFE CYCLE More than one obligatory host is necessary to complete the life cycle.

HOMOTYPIC The same type

HORIZONTAL TRANSMISSION The transmission of an infectious agent between members of the same species that are not in a parent-child relationship.

HOST-ADAPTED AND HOST-RESTRICTED SEROVARS Distinct variations within a species of bacteria or viruses or among im- mune cells of different individuals

HYPERENDEMIC A disease that is constantly present at a high incidence and/or preva- lence rate and affects all age groups equally

HYPER-ENDEMIC AREAS Geographical areas with a particularly high prevalence of a disease

HYPOBIOTIC LARVAE Arrested stage of development, as of nematode larvae in the gut muco- sa of the definitive host

I

IMMUNOCOMPETENT An individual that is able to produce a normal immune response follow- ing exposure to an antigen

IMMUNOCOMPROMISED An individual with compromised or entirely absent immune function 195

INCIDENTAL HOSTS See dead-end host

INCUBATION PERIOD The time between exposure to a pathogenic organism and when clini- cal signs are first apparent

INFECTION PRESSURE Infection pressure is high when there are many diseased animals or carriers of an infectious agent within a population

INFECTIOUS DOSE The amount of pathogen (measured in number of microorganisms) re- quired to cause an infection in the host. It varies according to the path- ogenic agent and the host’s age and overall health

L

LIVE ATTENUATED VACCINES A vaccine created by reducing the virulence of a pathogen. The organ- ism remains viable and infectious, but is unable to cause disease.

M

MECHANICAL VECTOR A carrier that picks up an infectious agent on the outside of its body and transmits it in a passive manner

MICROFILARICIDAL TREATMENT Chemotherapy directed against the microfilarial form of a parasite

MORBIDITY A diseased state, disability, or poor health due to any cause. The term ‘morbidity rate’ can refer to either the incidence rate, or the prevalence of a disease or medical condition.

MORTALITY RATE A measure of the number of deaths (in general, or due to a specific cause) in a population, scaled to the size of that population, per unit of time 196

MULTIDRUG-RESISTANCE A condition where a disease-causing organism can resist distinct drugs or chemicals of a wide variety of structures and functions targeted at eradicating the organism

N

NECROPSY EXAMINATION Post-mortem examination to determine the cause of death

NOSOCOMIAL INFECTION Hospital-acquired infection, also known as a HAI or in medical litera- ture as a nosocomial infection, is an infection whose development is favoured by a hospital environment, such as one acquired by a patient during a hospital visit or one developing among hospital staff

O

OCULAR LARVA MIGRANS The ocular form of the larva migrans syndrome that occurs when Tox- ocara canis larvae invade the eye

P

PANDEMIC An epidemic of infectious disease that has spread through human pop- ulations across a large region; for instance multiple continents, or even worldwide

PARATENIC HOSTS A host which is not needed for the development of the parasite, but nonetheless serves to maintain the life cycle of the parasite

PASSIVE SURVEILLANCE The routine reporting of the cases of diseases reaching health care fa- cilities for treatment or service. No special effort is made to find unsus- pected disease incidents. Passive surveillance will usually only detect disease in those who get sick, meaning that healthy carriers and long incubation periods combined with passive surveillance can maintain a reservoir of undiscovered disease carrying agents. 197

PATENT INFECTIONS Invasion by and multiplication of pathogenic microorganisms in a tis- sue, which then produces tissue injury and progresses to overt disease through a variety of cellular or toxic mechanisms

PATHOGENIC Capable of producing disease

PATHOGEN Infectious agent that causes disease in its host

PCR TESTS The polymerase chain reaction (PCR) is a technique widely used in mo- lecular biology. It derives its name from one of its key components, a DNA polymerase used to amplify a piece of DNA by in vitro enzymatic replication. PCR testing demonstrates the presence of genetic material from a pathogen in a sample (e.g. blood, faeces or tissue) as evidence of infection.

PERACUTE DISEASE Very severe and of very short duration, generally proving quickly fatal

PHYLOGENETICS The study of evolutionary relationships among groups of organisms (e.g. species, populations), which are discovered through molecular se- quencing data and morphological data matrices

PLASMIDS A small DNA molecule that is physically separate from, and can repli- cate independently of, chromosomal DNA within a bacterial cell

POCKET PETS A small mammal commonly kept as a household pet

PREDISPOSING DISEASE Disease that makes someone more susceptible or liable to a second disease

PREVALENCE The proportion of a population found to have a condition

PROGLOTTIDS One of the segments of a tapeworm, containing both male and female reproductive organs

PROTOSCOLECES Infective stages of echinococcus granulosis 198

PUBMED www.ncbi.nlm.nih.gov/pubmed

R

REASSORTANTS A new reassortant strain created after genetic reassortment that will share properties of both of its parental lineages.

REASSORTMENT Is the mixing of the genetic material of a species into new combinations in different individuals

RESERVOIR The long-term host of a pathogen causing an infectious disease. The reservoir host is infected and potentially infectious, but may not show clinical signs of disease.

RESERVOIR SPECIES A species that is infected by a pathogen, and which serves as a source of infection for another species

RISK ANALYSIS A process consisting of three components: risk assessment, risk man- agement and risk communication.

S

SEROCONVERSION Development of detectable specific antibodies to microorganisms in the blood serum as a result of infection or immunization

SEROPOSITIVITY An individual is seropositive when antibodies can be detected in blood serum

SEROPREVALENCE The number of persons in a population who test positive for a specific disease based on serology (blood serum)

SMALL MAMMALS Rodents and lagomorphs (rabbits are considered lagomorphs and not rodents) 199

SOMATIC MIGRATION Migration in the host by a parasite. For example, migration through the lungs into the systemic circulation with subsequent distribution throughout the body and encystment in tissues

STAMPING-OUT POLICIES Carrying out, under the authority of the Veterinary Authority, on con- firmation of a disease, the killing of the animals which are affected and those suspected of being affected in the herd and, where appro- priate, those in other herds which have been exposed to infection by direct animal-to-animal contact, or by indirect contact of a kind likely to cause the transmission of the causal pathogen. All susceptible ani- mals, vaccinated or unvaccinated, on an infected premises should be killed and their carcasses destroyed by burning or burial, or by any other method, which will eliminate the spread of infection through the carcasses or products of the animals killed.

STRAY ANIMAL A lost or abandoned companion animal that has been socialized to hu- mans before taking to the free-ranging life

SUBCLINICAL INFECTION The asymptomatic (without apparent clinical signs) carrying of an in- fection by an individual of an agent that usually is a pathogen causing illness, at least in some individuals

SYLVAN CYCLE A portion of the natural transmission cycle of a pathogen.

SYLVATIC CYCLE The fraction of the pathogen population’s lifespan spent cycling be- tween wild animals and vectors

SYNDROMIC SURVEILLANCE The analysis of medical data to detect or anticipate disease outbreaks. It applies to surveillance using health-related data that precede di- agnosis and signal a sufficient probability of a case or an outbreak to warrant further public health response

V

VECTOR-BORNE An infectious agent that is transmitted by an arthropod from one indi- vidual to another 200

VERTICAL INFECTION See vertical transmission

VERTICAL TRANSMISSION The transmission of an infection or other disease from the female of the species to the offspring

VIRAEMIA The presence of virus particles within the bloodstream

VIRULENCE The degree of pathogenicity of a pathogen as indicated by case fatal- ity rates and/or the ability of the organism to invade the tissues of the host.

VISCERAL LARVA MIGRANS Migration through body tissues of the larvae of certain nematodes

Z

ZOONOSES An infectious disease that is transmitted (sometimes by a vector) from animals to humans. A ‘reverse zoonosis’ is transmitted from humans to animals.

ZOOPHILIC SPECIES Zoophilic organisms are found primarily in animals

ZYMODEME A group of parasites defined by production of the same isoenzymes β-lactam antibiotics a broad class of antibiotics, consisting of all antibi- otic agents that contains a β-lactam ring in their molecular structures 201

The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant n° 289316 202