Major Parasitic Zoonoses Associated with Dogs and Cats in Europe

Baneth, G.; Thamsborg, S M; Otranto, D; Guillot, J.; Blaga, R; Deplazes, P; Solano-Gallego, L

Published in: Journal of Comparative Pathology

DOI: 10.1016/j.jcpa.2015.10.179

Publication date: 2016

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Citation for published version (APA): Baneth, G., Thamsborg, S. M., Otranto, D., Guillot, J., Blaga, R., Deplazes, P., & Solano-Gallego, L. (2016). Major Parasitic Zoonoses Associated with Dogs and Cats in Europe. Journal of Comparative Pathology, 1(S1), s54-s74. https://doi.org/10.1016/j.jcpa.2015.10.179

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Major Parasitic Zoonoses Associated with Dogs and Cats in Europe

x x G. Baneth*, S. M. Thamsborg†, D. Otranto‡, J. Guillot , R. Blaga , k { P. Deplazes and L. Solano-Gallego *Koret School of Veterinary Medicine, Hebrew University, Rehovot, Israel, † University of Copenhagen, Department of Veterinary Disease Biology, Veterinary Parasitology Research Group, Frederiksberg C, Denmark, ‡ Dipartimento di Medicina x Veterinaria, Universita degli Studi di Bari, Valenzano, Bari, Italy, Ecole Nationale Veterinaire d’Alfort, Department of k Parasitology, BioPole d’Alfort, UPE, Maisons-Alfort, France, Institute of Parasitology, University of Zurich, Zurich, { Switzerland and Departament de Medicina i Cirurgia Animals, Universitat Autonoma de Barcelona, Cerdanyola del Valles, Spain

Summary Some of the most important zoonotic infectious diseases are associated with parasites transmitted from companion animals to man. This review describes the main parasitic zoonoses in Europe related to dogs and cats, with particular emphasis on their current epidemiology. Toxoplasmosis, leishmaniosis, giardiosis, echinococcosis, dirofilariosis and toxocariosis are described from the animal, as well as from the human host perspectives, with an emphasis on parasite life cycle, transmission, pathogenicity, prevention and identification of knowledge gaps. In addition, priorities for research and intervention in order to decrease the risks and burden of these diseases are presented. Preventing zoonotic parasitic infections requires an integrated multidisciplinary ‘One Health’ approach involving collaboration between veterinary and medical scientists, policy makers and public health officials.

Ó 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Keywords: companion animal; Europe; parasite; zoonotic disease

Contents

Introduction ...... S55 Toxoplasmosis ...... S55 Aetiology ...... S55 Hosts and Life Cycle ...... S56 Epidemiology ...... S56 Diagnosis of Infection in Man and Animals ...... S56 Prevention of Infection in Man and Animals ...... S56 Gaps in Knowledge and Recommendations for Further Research ...... S57 Leishmaniosis ...... S57 Aetiology ...... S57 Hosts and Life Cycle ...... S57 Epidemiology ...... S58 Diagnosis of Infection in Man and Animals ...... S58 Prevention of Infection in Man and Animals ...... S58

Correspondence to: G. Baneth (e-mail: [email protected]).

0021-9975/$ - see front matter Ó 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the http://dx.doi.org/10.1016/j.jcpa.2015.10.179 CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Parasitic Zoonoses of Dogs and Cats in Europe S55

Gaps in Knowledge and Recommendations for Further Research ...... S59 Giardiosis ...... S59 Aetiology ...... S59 Hosts and Life Cycle ...... S59 Epidemiology ...... S59 Diagnosis of Infection in Man and Animals ...... S60 Prevention of Infection in Man and Animals ...... S60 Gaps in Knowledge and Recommendations for Further Research ...... S60 Echinococcosis ...... S60 Aetiology ...... S60 Hosts and Life Cycle ...... S60 Epidemiology ...... S61 Diagnosis of Infection in Animals ...... S63 Prevention of Infection in Man and Animals ...... S63 Gaps in Knowledge and Recommendations for Further Research ...... S63 Vector-borne Helminths ...... S63 Aetiology ...... S63 Hosts and Life Cycle ...... S63 Epidemiology ...... S64 Diagnosis of Infection in Man and Animals ...... S65 Prevention of Infection in Man and Animals ...... S66 Gaps in Knowledge and Recommendations for Further Research ...... S66 Toxocariosis ...... S66 Aetiology ...... S66 Hosts and Life Cycle ...... S66 Epidemiology ...... S67 Diagnosis of Infection in Man and Animals ...... S68 Prevention of Infection in Man and Animals ...... S68 Gaps in Knowledge and Recommendations for Further Research ...... S69 Conclusions ...... S69 Acknowledgments ...... S69 Conflict of Interest Statement ...... S69 References ...... S69

Introduction gaps in knowledge of these infections and recommendations for further research. Parasites are responsible for some of the most important and well recognized zoonotic infectious diseases transmitted from companion animals to man globally. Toxoplasmosis The CALLISTO (Companion Animal multisectoriaL Aetiology interprofessionaL and interdisciplinary Strategic Think tank On zoonoses) project, an EU Framework Toxoplasma gondii is a tissue cyst-forming coccidium 7-funded project, was established to discuss and inves- (Protozoa, Apicomplexa) with a complex life cycle. tigate infectious diseases transmitted between com- The asexual phase of T. gondii development takes panion animals, man and food producing animals, place in various tissues of herbivorous or omnivorous aiming to focus on these diseases in Europe. Expert intermediate hosts and is linked to a sexual phase of Advisory Group (EAG) V in the CALLISTO project development in the intestine of felids, the definitive discussed the most important parasitic zoonoses in Eu- hosts. There are three infectious stages in the life cycle rope, describing their epidemiology and identifying of the parasite: tachyzoites, bradyzoites contained in priorities for research and intervention to decrease tissue cysts and sporozoites contained in sporulated the burden of these infections. This review by the oocysts. The parasite can invade the gut, become sys- members of EAG V includes descriptions of the para- temic and localize in vital organs such as muscle and sitic diseases considered as most relevant for the nervous system. In most cases infection is subclin- CALLISTO, with further insights into their epidemi- ical, but devastating disease can occur (Cenci-Goga ology, diagnosis and prevention, with identification of et al., 2011). The virulence of T. gondii strains is highly variable and dependent on the genotype of the S56 G. Baneth et al. parasite. Many atypical genotypes exist besides the on surveillance and control methods for toxoplasmosis ‘commonest’ genotypes (genotypes I, II and III) first for man, animals and food. described from Europe and the USA (Shwab et al., 2014). Diagnosis of Infection in Man and Animals A diagnosis of infection by T. gondii can be established Hosts and Life Cycle by the isolation of the parasite from various tissues, Felids are the definitive hosts for T. gondii, but all detection of specific DNA by polymerase chain reac- warm-blooded vertebrates including man may serve tion (PCR) or by carrying out serological tests. as intermediate hosts and potentially be infected by Currently, routine diagnosis of toxoplasmosis relies bradyzoites in meat, by sporulated oocysts or by in- mainly on the use of serological assays that are avail- trauterine tachyzoites (Dabritz and Conrad, 2010; able for both man and animals such as the Elmore et al., 2010). T. gondii has become adapted SabineFeldman dye test, indirect fluorescent anti- to exploit multiple routes of transmission through a body test (IFAT), enzyme-linked immunosorbent sexual cycle in the definitive host and asexually, assay (ELISA) or various agglutination tests. Most through carnivorous behaviour and by vertical clinical laboratories use an ELISA for the routine transmission. These different routes may operate screening of specific immunoglobulin (Ig) G and synergistically to enhance transmission, but they IgM, while other techniques are mostly reserved for might also provide a vehicle for selection leading to reference laboratories (Robert-Gangneux and partitioning of strains in the environment. Human Darde, 2012). infections are acquired from eating undercooked or Isolation of the parasite by mouse bioassay is a raw meat, such as pork and lamb. However, the laborious and time-consuming technique, and rep- prevalence of T. gondii infection in human resents the ‘gold standard’ for the detection of T. gon- populations that do not consume meat or eat it well- dii in meat for human consumption (Villena et al., cooked, suggests that the acquisition of infection 2012). It is still used for diagnosis in people with from the environment, via oocysts in soil, water or immunosuppression (Robert-Gangneux and Darde, on uncooked vegetables, may also play an important 2012). role in transmission. Only a small proportion Over the past two decades, PCR-based tests have (<0.1%) of infected people acquire infection congen- been developed to detect parasite DNA in human itally (Lindsay and Dubey, 2011). and animal tissues. Nevertheless, this molecular diagnosis remains unsatisfactory due to a low sensitivity compared with the mouse bioassay, lack of Epidemiology standardization and a considerable diversity among Latent infections with T. gondii are common in do- DNA extraction methods, amplification systems and mestic cats throughout the world. Antibodies to T. DNA primers (Sterkers et al., 2010). In an attempt gondii may be detected in up to 74% of adult cats, de- to increase the sensitivity of detection, a method based pending on the type of feeding and whether cats are on sequence-specific magnetic capture of T. gondii kept indoors or outdoors (Tenter et al., 2000). After DNA followed by DNA amplification has been devel- primary infection, cats spread Toxoplasma oocysts in oped (Opsteegh et al., 2010). their faeces within 3e10 days and shedding continues for approximately 7e21 days (median 8 days), with Prevention of Infection in Man and Animals up to hundreds of millions of oocysts shed in the faeces of a single infected cat (Dubey, 2001). Afterwards, the Control measures should be aimed at the prevention direct risk for cat owners is limited. of oocyst shedding in order to reduce infection of peo- T. gondii infects up to a third of the human popula- ple with T. gondii (Tenter et al., 2000). The risk for tion of the world. In Europe, European Commission exposure to T. gondii parasites is greatest in cats that (EC) Directive 2003/99 stipulates that member coun- prey on wildlife and live outdoors or in farms. Kittens tries report human seroprevalence results every year are very susceptible to infection and shed greater or every other year, according to their epidemiolog- quantities of oocysts. Efforts to develop a T. gondii ical status (http://eur-lex.europa.eu/LexUriServ/ vaccine for cats should be renewed, which will lead LexUriServ.do?uri¼OJ:L:2003:325:0031:0040:EN: to better protection of people (Robert-Gangneux PDF). Despite this directive, accurate information is and Darde, 2012). Responsible cat ownership should incomplete and the EC has applied to the European also be encouraged. This includes measures such as Food Safety Authority (EFSA) for recommendations collecting faeces in litter trays for ultimate disposal Parasitic Zoonoses of Dogs and Cats in Europe S57 in rubbish destined for landfills, which are designed to advancement in the field of vaccination, with the prevent waste materials leaking into groundwater. In objective of significantly reducing oocyst excretion, addition, cat faeces should not be disposed of in toi- since felids represent the major source of environ- lets. mental contamination. Human infection can be acquired either by ingestion of infected raw or undercooked meat or by inges- Leishmaniosis tion of sporulated oocysts from the contaminated environment. As a consequence, it is highly recom- Aetiology mended (especially for high-risk individuals, e.g. pre- Leishmaniosis (or leishmaniasis) is a complex of viously unexposed pregnant women) that meat is mammalian diseases caused by diphasic protozoans consumed only after thorough cooking or freezing of the genus Leishmania (Kinetoplasta, Trypanosoma- and personal hygiene in handling meat is mandatory. tidae). The Leishmania species endemic in Europe is The control of human toxoplasmosis also relies on the Leishmania infantum and its most common zymodeme avoidance of direct or indirect exposure to cat faeces. is MON-1. However, other zymodemes are also found Proper faecal handling, litter tray management, in Europe. In addition, it is important to highlight removal of faeces from public areas and yards and that because multilocus enzyme electrophoresis, the hand hygiene are critical. Litter trays should be thor- classical reference method for Leishmania typing oughly cleaned every day so that any potential oocysts (Rioux et al., 1990), is laborious and expensive, molec- do not have time to sporulate (i.e. in about 48 h) ular typing methods of L. infantum isolates have been (Dubey et al., 2011). People, particularly those developed such as multilocus microsatellite typing vulnerable to infection, such as pregnant women (Gouzelou et al., 2013) or multilocus sequence anal- and the immunosuppressed, should avoid this task. ysis, PCR with restriction fragment length polymor- Similarly, drinking unfiltered surface water or acci- phism (RFLP) and whole genome sequencing. dental ingestion of soil must be avoided. Hosts and Life Cycle Gaps in Knowledge and Recommendations for Further Research The leishmanioses affect man and domestic and wild A major gap in knowledge is the relationship between animals worldwide. Most transmission cycles are zoo- seropositivity in the main livestock species and pres- notic, involving reservoir hosts such as rodents, mar- ence of T. gondii in meat. There is a straightforward supials, edentates, monkeys, domestic dogs and wild relationship between the level of antibodies detected canids. Only a few Leishmania species are strictly in serum and the likelihood of isolating a viable para- anthroponotic (i.e. transmitted directly from person site in pigs and sheep, but this relationship appears to person via sand flies) (Quinnell and Courtenay, not to be clear for horses and cattle (Opsteegh et al., 2009). Dogs are the major reservoir for canine and hu- 2011) and needs further investigation. man L. infantum infection, in an area that stretches Another gap resides in the identification of the from Portugal to China and across South, different sources of infection in various human popu- Central and parts of North America, with the excep- lations. While multicentre studies pointed out the tion of Oceania. In Europe, the domestic dog is the consumption of undercooked lamb, beef or game, only reservoir host of major veterinary and human contact with soil and travel outside Europe and North importance (Solano-Gallego et al., 2009). Infection America as strong risk factors for acquiring infection in cats (Martin-Sanchez et al., 2007), wild canids with T. gondii, little is known about the relative (Sobrino et al., 2008; Millan et al., 2011) and horses importance of transmissions via tissue cysts versus oo- (Fernandez-Bellon et al., 2006) has also been reported cysts in a given human population (Cook et al., 2000; in areas where disease is common in dogs, but the role Jones et al., 2009). The discovery of a sporozoite- of these species as reservoirs remains unclear. specific protein, which elicited differential antibody Natural transmission of L. infantum between ani- production in experimentally infected pigs and mals and from animals to man occurs usually by the mice, may contribute to filling this gap in knowledge bite of a phlebotomine sand fly species (Diptera, Psy- (Hill et al., 2011). chodidae, Phlebotominae) of the genera Phlebotomus Further studies need to be undertaken in the field of (Old World) and Lutzomyia (New World). Sand flies molecular biology for standardization of PCR are the only arthropod vectors that are adapted for methods to be applied both in man and animals, the transmission of Leishmania species. Leishmania com- while improvements need to be made in the sensitivity pletes its life cycle in the sand fly, which harbours the of these techniques for detecting viable parasites. flagellated extracellular promastigote form and in a Concerning the definitive host, there is need for mammal where the intracellular amastigote form S58 G. Baneth et al. develops. A female sand fly ingests Leishmania while which involves internal organs and is fatal if blood feeding and then transmits the infective stages untreated, and the cutaneous (CL) and mucocuta- (metacyclic promastigotes) during a subsequent neous forms, which affect the skin or mucocutaneous blood meal. The infective promastigotes inoculated junctions and may heal spontaneously, leaving disfig- by the sand fly are phagocytosed in the mammalian uring scars (Murray et al., 2005). This group of infec- host by macrophages and other phagocytic cells, in tions is the third most important vector-borne disease which they transform to amastigotes. after malaria and lymphatic filariosis. It is endemic in Non-sand fly modes of transmission have also been many tropical and subtropical regions of the Old and described, but their role in the natural history and New World. Leishmaniosis is endemic in 88 countries, epidemiology of L. infantum infection remains unclear. with more than 350 million people at risk. The esti- Proven modes of non-sand fly transmission in dogs mated incidence is 2 million new cases per year: 0.5 include infection through transfused blood products million VL and 1.5 million CL cases (Desjeux, 2004). (Owens et al., 2011) from blood donors that are car- There are only two transmission cycles with riers of infection (de Freitas et al., 2006; Tabar et al., proven long-term endemicity in Europe: (1) visceral, 2008), vertical (Rosypal et al., 2005; Pangrazio et al., cutaneous and mucocutaneous human leishmaniosis 2009; Boggiatto et al., 2011) and venereal caused by L. infantum throughout the Mediterranean transmission (Silva et al., 2009). region and (2) anthroponotic cutaneous human leishmaniosis caused by L. tropica, which occurs sporadically in Greece. In Europe, about 1,000 peo- Epidemiology ple are estimated to be affected by clinical disease Based on seroprevalence studies from Spain, France, due to L. infantum annually (Dujardin et al., 2008), Italy and Portugal, it has been estimated that 2.5 although asymptomatic or subclinical infections are million dogs in these countries are infected with L. more frequent (Michel et al., 2011). The high preva- infantum and infection is spreading north in Europe, lence (2e40%) of asymptomatic human carriers of reaching the foothills of the Alps (Maroli et al., L. infantum in some areas of southern Europe suggests 2008), Pyrenees (Chamaille et al., 2010) and north- that this parasite is a latent public health threat. western Spain (Amusategui et al., 2004). The Asymptomatic infections are estimated to have a numbers of dogs travelling to southern Europe or im- prevalence ratio of >100 asymptomatic:1 clinical ported as companion animals from areas where case (Michel et al.,2011). canine leishmaniosis is endemic have increased, as Mediterranean VL primarily affects children as have the numbers of clinical cases reported in non- well as an increasing number of immunocompro- endemic countries such as the UK (Shaw et al., mised and immunosuppressed adult individuals, 2009) and Germany (Menn et al., 2010). such as people who are positive for the human immu- The seroprevalence in dogs in the Mediterranean nodeficiency virus (HIV) and people under immuno- basin ranges from 5% to 30% depending on the re- suppressive therapy. Mortality rates due to gion (Solano-Gallego et al., 2009). Surveys employing leishmaniosis in LeishmaniaeHIV co-infected patients other detection methods to estimate the prevalence of can reach over 56% (Lopez-Velez et al., 1998; Leishmania infection by amplification of Leishmania Pasquau et al.,2005). Therefore, risk factors for DNA from different tissues or by detection of specific human infection include age, poor socioeconomic anti-Leishmania cellular immunity have revealed even conditions, malnutrition and immunosuppressive higher infection rates, approaching 70% in some foci. conditions (Alvar et al.,2006). Most dogs in these areas appear to have chronic infection that may be lifelong, but only a small proportion Diagnosis of Infection in Man and Animals of dogs develop severe disease (Baneth et al., 2008). In cats, serological and PCR surveys in southern The most common techniques used for disease detec- Europe indicate that Leishmania infection is more tion in man and animals include microscopical obser- widespread than clinical disease. Epidemiological vation (i.e. cytology, biopsy or immunohisto- studies have described rates ranging from 0.4% to chemistry) and serological and molecular techniques 30% based on serological and molecular techniques (Solano-Gallego et al., 2009; Elmahallawy et al., (Martin-Sanchez et al., 2007; Solano-Gallego et al., 2014). 2007; Maia et al., 2008; Millan et al., 2011; Sherry et al., 2011). Prevention of Infection in Man and Animals Human leishmaniosis, caused by several species of Leishmania, comprises a heterogeneous group of dis- Control measures for man and dogs are available eases. These include visceral leishmaniosis (VL), and include medical treatment, individual use of Parasitic Zoonoses of Dogs and Cats in Europe S59 sand fly repellents in dogs, canine vaccines and immu- blage F from cats and assemblage G from rodents nomodulating drugs (Otranto and Dantas-Torres, (Caccio et al., 2005; Thompson et al., 2008; Tysnes 2013; Wylie et al., 2014a,b). et al., 2014). Treatment for people and dogs in Europe is different, thus limiting the likelihood of developing Hosts and Life Cycle resistance. People are commonly treated with a short course of amphotericin B (Murray et al., 2005), while Giardia is a very common enteric protozoal parasite of moderately to severely sick dogs are usually treated domestic animals, including livestock, dogs, cats and with a combination of a 1-month course of meglumine wildlife. G. duodenalis causes giardiosis in man and in antimoniate or miltefosine and a long-term course of most mammals. The life cycle of Giardia is allopurinol. Generally, treatment in dogs leads to a direct and the infective stage of the parasite, the clinical cure and decreased parasite load. However, cyst, is immediately infectious when released into complete parasitological cure in the majority of dogs the faeces. Cysts remain infectious for months in appears to be unlikely (Solano-Gallego et al., 2009). cool, damp areas and accumulate in the environment. When ingested by the host, cysts excyst in the duo- Gaps in Knowledge and Recommendations for Further Research denum, releasing the trophozoites. The latter undergo repeated mitotic division in the gut lumen There are numerous gaps in knowledge regarding and form environmentally resistant cysts. Cysts pass Leishmania infection. These include: (1) a better un- through the intestine in faeces and are spread by derstanding of the immunopathogenesis of the dis- contaminated water, food and fomites and by direct ease in man and dogs and how clinical disease physical contact (Feng and Xiao, 2011). appears versus subclinical infection, (2) knowledge of the immune mechanisms that control infection and how to develop efficacious vaccines for man Epidemiology and dogs, (3) understanding the role of domestic or It has been estimated that about 200 million people in wild mammals other than the dog as reservoirs of L. Asia, Africa and Latin America have symptomatic infantum infection and (4) understanding the risk fac- infection with Giardia (Feng and Xiao, 2011). Once tors associated with human and animal infection in infected, Giardia causes a generally self-limited clinical Europe. illness characterized by diarrhoea, abdominal cramps, bloating, weight loss and malabsorption. Giardiosis However, asymptomatic giardiosis occurs frequently, especially in developing countries. In Germany, on Aetiology average, 3,806 notified giardiosis cases (range The genus Giardia (Diplomonadida, Hexamitidae) in- 3,101e4,626) were reported between 2001 and cludes intestinal protozoan parasites that infect 2007, which corresponded to an average incidence numerous hosts, ranging from mammals to amphib- of 4.6 cases/100,000 population (Sagebiel et al., ians and birds. Currently, six Giardia species are 2009). Much higher incidence rates were reported accepted: Giardia agilis, Giardia ardeae, Giardia muris, for some other countries. In the Netherlands, there Giardia microti and Giardia psittaci infecting various spe- were 11,600 cases in 2004, corresponding to 69.9 cies of animals, while Giardia duodenalis infects man cases/100,000 population (Vijgen et al., 2007). and many other mammals. Giardia species differ The relationship between human and animal Giar- significantly in host range, with G. duodenalis (syn. dia infection is not clear. Although people share the Giardia lamblia and Giardia intestinalis) having the same G. duodenalis assemblages with animals with broadest host range and greatest public health signif- which they have close contact, such as household icance (Feng and Xiao, 2011). dogs, it is not known how frequently infection is actu- Although G. duodenalis is found in man and other ally acquired from household animal contact or mammals, including pets and livestock, it is now whether both people and pets acquire it from a com- considered a multispecies complex. Historically, allo- mon source, such as contaminated water. Undoubt- zyme analyses placed all isolates from man into two edly, people also commonly infect each other. genetic assemblages (assemblages A and B). Multi- Infection rates with Giardia in dogs were 24.8% in a genic sequence analyses confirmed this assemblage large study in Europe (Epe et al., 2010), 22.7% in separation and identified additional lineages of G. du- Belgium (Claerebout et al., 2009) and 21.0% in the odenalis from animals including assemblages A and B UK (Upjohn et al., 2010). Infection rates in cats in man and other animals, assemblages C and D were 20.3% in a multicountry study in Europe (Epe from dogs, assemblage E from artiodactyls, assem- et al., 2010). Giardiosis in animals is often subclinical, S60 G. Baneth et al. but has been associated with the occurrence of diar- Gaps in Knowledge and Recommendations for Further Research rhoea and illness in puppies and kittens (Thompson, Gaps in knowledge of giardiosis include the need to 2004). clarify if there are animal reservoirs for human giar- Giardia infections are common in pigs, cattle, sheep, diosis and to what extent, if at all, human giardiosis goats, elks and deer and other ruminants (Feng and can be caused by contamination from an animal Xiao, 2011). Although it is believed that infection source. In that respect, it would also be important with Giardia is associated with economic losses to find out whether animals may be infected by their through the occurrence of diarrhoea, poor owners and suffer from clinical giardiosis. A vaccine growth and even death in farm animals (Geurden for giardiosis would be beneficial for people and also et al., 2005), only a few studies have been conducted for domestic animals. to assess the effect of giardiosis on livestock production or growth rates. In bottle-fed specific-pathogen-free lambs infected experimentally with Giardia cysts, Echinococcosis infection was associated with delay in reaching Aetiology slaughter weight and decreased carcass weight (O’Handley and Olson, 2006). The genus Echinococcus includes several species and genotypes of zoonotic cestodes (tapeworms). The adult stages occur in the intestines of canids and felids Diagnosis of Infection in Man and Animals without clinical relevance. The larval stages develop Giardia infection can be diagnosed by stool examina- in tissues of various organs of a variety of mammalian tion to identify cyst and trophozite stages in direct intermediate hosts, including man, as aberrant hosts. fresh stool smears or by flotation for cysts. Rapid Cystic echinococcosis (CE) is caused by species of the detection of Giardia antigen can be made using immu- Echinococcus granulosus sensu lato (s. l.) complex. In Eu- nochromatographic kits, by immunofluorescence, rope, E. granulosus sensu stricto (s. s.) (‘sheep strain’) ELISA or PCR in a suitably equipped parasitology and Echinococcus canadensis (Echinococcus intermedius, laboratory (Feng and Xiao, 2011). ‘pig strain’) are of major zoonotic significance (Table 1). The controversially discussed taxonomy Prevention of Infection in Man and Animals and the molecular epidemiology of the E. granulosus complex has been reviewed recently (Romig et al., The prevention of giardiosis in man is closely associ- 2015). Alveolar echinococcosis (AE) caused by Echi- ated with the provision of clean fresh water and nococcus multilocularis is one of the most pathogenic zoo- adequate sewage systems. Boiling or filtering water noses in Europe and leads to death of people in 10e15 from the environment before drinking it is essential years if untreated (Eckert et al., 2011). and removal of infected faeces from infected animals or people followed by proper disinfection is necessary. Hosts and Life Cycle Adherence to personal hygiene habits such as washing hands and cleaning fresh food is important in limiting E. granulosus s.s. is mainly transmitted within a infection. dogesheep cycle in pastoral regions (Table 1);

Table 1 Echinococcus spp. in Europe and their deﬁnitive and intermediate hosts

Echinococcus species Echinococcus strains or E. Deﬁnitive hosts Intermediate hosts Zoonotic signiﬁcance granulosus s. l. genotypes (G)

E. granulosus sensu stricto Sheep strain (G1, 2, 3) Dog (fox*) Sheep, cattle†, pig and +++ (s. s.) other herbivores† E. ortleppi Cattle strain (G5) Dog Cattle + E. canadensis Cervid strain (G8, 10) Wolf (dog) Cervids + E. canadensis, (proposed Pig strain (G7) Dog (wolf) Pig, other herbivores† ++ E. intermedius) E. equinus Horse strain (G4) Dog Equids E. multilocularis European strain Fox, dog, raccoon dog, Arvicolids and other +++ (cat*) rodents

Zoonotic significance is graded as: , none; +, mild; ++, moderate; or +++, marked. *Mostly low worm numbers with very low egg production. †Mostly with strongly reduced protoscolex formation in the cysts often resulting in infertile cysts. Parasitic Zoonoses of Dogs and Cats in Europe S61 however, other potential intermediate hosts can be concerning definitive hosts are scarce, especially for involved. Interestingly, the development of protosco- pet dogs. Prevalence rates of 0e31% are reported leces in the cysts can be markedly reduced in cattle as from farm and shepherd dogs in Italy and compared with sheep. The E. canadensis (pig strain, G Spain and 14.2% from farm village dogs in Lithuania 7) cycle is characterized in the Baltic states and (Bruzinskaite et al., 2009; Carmena and Cardona, Poland by a small scale transmission pattern between 2013). farm dogs and pigs in family farms with the practice of E. multilocularis occurs in the northern hemisphere, traditional home slaughter (Bruzinskaite et al., 2009), with large endemic areas in Europe including parts of but possible wild or semi-wild animal cycles have the western continent (e.g. France, Benelux States) been observed, including wolves in Portugal or wild and all countries of central Europe including North- boars in Corsica (Umhang et al., 2014). Echinococcus or- ern Italy, Slovenia, Romania and the Baltic States. tleppi was prevalent in cattle all over central Europe, Furthermore, foci also exist in Denmark, Sweden but has nearly disappeared without specific control and on Svalbard Island (Gottstein et al., 2015) programmes. (Fig. 1). E. multilocularis is perpetuated in a wildlife cycle Based on recently improved diagnostic strategies, mainly by foxes as definitive hosts and small mammals several studies have investigated the prevalence of as intermediate hosts. Definitive hosts with high E. multilocularis in pet dog populations. Low preva- reproductive potential of E. multilocularis are predom- lence rates of <0.5% were recorded in the privately inantly the red fox, the raccoon dog, the wolf and the owned dog populations in France, Germany, domestic dog. After a prepatency of around 1 month, Switzerland and Denmark, but a higher prevalence eggs are shed over a few months, but 95% of the total (3e8%) was found in dogs with predatory habits egg excretion occurs within the first month of patency and those able to roam more widely (Deplazes et al., (Kapel et al., 2006). Wild felines and domestic cats 2011). In Switzerland, 0.3% of randomly selected pri- have occasionally been found to harbour intestinal vately owned dogs were found to be infected with this stages. Although cats are more likely to be infected tapeworm. Based on this prevalence, the individual with E. multilocularis than dogs, their zoonotic signifi- probability of being infected at least once during 10 cance is estimated to be small, based on the low level years can be estimated at 8.7%. Large population of egg excretion. Dogs, on the other hand, may play a studies in Germany revealed that 0.13% of dogs in very important role in the transmission to man, but northern and 0.35% in southern Germany excreted they probably do not contribute significantly to the E. multilocularis eggs in their faeces. Considering the contamination of rodent habitats as compared with total dog population in Germany (approximately foxes (Deplazes et al., 2011; Hegglin and Deplazes, 5.4 106 dogs), around 13,000 are estimated to be 2013). infected. Echinococcosis is not a food-borne zoonosis in the The prevalence of E. multilocularis in cat popula- classical sense. Eggs are typically excreted fully devel- tions, as determined at necropsy examination, ranged oped and infectious (containing an oncosphere larva) between 0% and 5.5% in various endemic areas. Cat by defecation in the environment. In addition, these infections are characterized by low worm burdens eggs are highly resistant: E. multilocularis eggs survive and strongly reduced worm development, resulting in the environment for up to 8 months; however, in lower egg production compared with foxes or they are sensitive to desiccation. Eggs can be dispersed dogs. Therefore, the epidemiological role of the cat from the deposition sites either by being washed away in spreading this infection is estimated to be low or carried by flies and other vectors (Eckert et al., (Hegglin and Deplazes, 2013). 2011). Echinococcus eggs may also adhere to tyres, shoes In the human population, CE is one of the five most or animal paws, resulting in more widespread frequently diagnosed zoonoses in the Mediterranean dispersal and contamination of the environment, region and is re-emerging in South Eastern Europe including human dwellings. (Jenkins et al., 2005). Incidence rates for CE of 1.1e3.3/100,000 were recorded in Spain, up to 3.5 in Sardinia in Italy and 3.3 in Greece, Bulgaria and Epidemiology Romania (Torgerson et al., 2011). Economic loss In Europe, the endemic area of E. granulosus s. s. attributable to human CE was estimated for Spain covers southern and south-eastern Europe; E. canaden- at V133 million (Benner et al., 2010). sis G7 is prevalent in the Baltic countries, Poland and Human AE is one of the most pathogenic helmin- southwards to Romania. For E. granulosus s. l., most thic zoonoses and causes a high burden of disease in prevalence data are based on slaughterhouse investi- Europe (Torgerson et al., 2008). Recent studies sup- gations of intermediate hosts, while prevalence data port the hypothesis that the infection pressure caused S62 G. Baneth et al.

Fig. 1. Approximate distribution of Echinococcus multilocularis in Europe shown in dark orange colour (with permission from the Institute of Parasitology, University of Zurich, Switzerland). by E. multilocularis eggs has increased across certain of contaminated water, food or soil. Adherent eggs large European regions. In Switzerland, a representa- and even proglottids of Echinococcus have been tive endemic area for central Europe, the annual inci- observed on infected dogs in individual cases. Direct dence rates of new human AE cases varied between exposure to these eggs is influenced by occupation 0.10 and 0.16/100,000 individuals over a 45-year and behaviour, especially a close humaneanimal period, suggesting a high degree of epidemiological bond. stability. However, approximately 10e15 years (cor- Domestic transmission of E. granulosus eggs from responding to the incubation time of AE) after a pet, stray and working dogs is particularly important distinct increase in the fox populations (with E. multi- in areas with inadequate educational standards and locularis prevalences of 30e60%), a higher incidence veterinary control. Risk factors for infection of inter- rate of 0.25/100,000 was recorded (Deplazes et al., mediate and definitive animal hosts with E. granulosus 2011). Similar trends of increasing incidence have s. l. have been recently reviewed (Otero-Abad and been observed in Austria, France and Lithuania. Torgerson, 2013; Craig et al., 2015). Indeed, the The overall incidence of AE is variable (0.03e0.26) number of owned dogs and the frequency of contact in Central Europe, but estimated to be 200 new cases with dogs were identified as risk factors for human per year (Deplazes, personal communication). AE in studies from China (Craig et al., 2015), while Humans are exposed to eggs of Echinococcus spp. via in a Spanish study, cohabitation with dogs and different ways. The most important sources of infec- feeding of uncooked viscera were defined as risk fac- tion are handling of definitive hosts and oral uptake tors for CE (Campos-Bueno et al., 2000). As home Parasitic Zoonoses of Dogs and Cats in Europe S63 slaughter of sheep in parts of Southern Europe and of prescribed strict deworming regime of all dogs pigs in parts of Poland and the Baltic states is still entering these countries. widespread, local family dogs may be infected by feeding of infected offal. Gaps in Knowledge and Recommendations for Further Research Recommendations for further research and actions Diagnosis of Infection in Animals against echinococcosis include: (1) establishment of Intestinal infections with E. granulosus or E. multilocula- a One Health concept for systematic, specific and ris are typically subclinical in definitive hosts. The standardized surveillance of AE and CE in man and diagnosis of the infection in dogs or cats has been of Echinococcus infection in animals, (2) definition of considerably improved in recent years by egg isolation minimal standards and harmonized approaches for methods, coproantigen ELISAs and PCR tests for E. the monitoring of the epidemiological state of these in- granulosus s. l. and for E. multilocularis (Craig et al., fections in Europe and (3) further development of 2015; Conraths and Deplazes, 2015). These control strategies adapted to the local and socio- techniques can also be used for the examination of cultural epidemiological situation to prevent both faecal samples collected in the environment. AE and CE in man.

Prevention of Infection in Man and Animals Vector-borne Helminths Comprehensive control programmes have so far only Aetiology been applied for CE, with varying degrees of success Filaroids are roundworms that belong to the family (Craig and Larrieu, 2006) including control of stray Onchocercidae. Filaroid species are prevalent in dogs, slaughter supervision and public education Europe and some of them are of increasing concern campaigns, routine anthelmintic treatment of dogs due to the significant level of disease they cause in and vaccination of sheep. More detailed control op- dogs and man (Genchi et al., 2011; Otranto and tions for CE have been reviewed by Lightowlers Eberhard, 2011; Morchon et al., 2012). The species (2013) and Barnes et al. (2012). Dirofilaria immitis and Dirofilaria repens (Spirurida, A treatment schedule individually designed for pets Onchocercidae) are the best known filaroids affecting based on infection risks (e.g. free roaming, uncon- dogs. They present different pathogenic potentials for trolled access to rodents or offal) can improve treat- man and animals; while D. immitis threatens dogs and ment efficiency against cestodes. Uniform guidelines cats, causing a severe and often fatal cardiocirculatory for the control and treatment of parasites in pet ani- disease referred to as ‘heartworm disease’, D. repens in- mals were developed and published by the European duces a non-pathogenic subcutaneous infestation in Scientific Council on Companion Animal Parasites dogs, but is a more prevalent zoonotic pathogen in (ESCCAP) in Europe (www.esccap.org). The cur- man (Dantas-Torres and Otranto, 2013). Mosquitoes rent recommendation is to treat dogs with access to transmit these Dirofilaria species to dogs, cats and Echinococcus metacestodes monthly with praziquantel other wild carnivores. About 45% of the total human in order to reduce environmental contamination and pet population are exposed to the risk of vector- with eggs. However, even strict compliance of the borne helminths (VBHs) in Europe (Petric et al., pet owners will not reduce the environmental 2012). Although Dirofilaria spp. represent the most contamination with eggs of E. granulosus caused by prevalent VBHs, other helminths of dogs and cats, stray dogs or of E. multilocularis caused by foxes. The such as the Thelazia callipaeda eyeworm (Spirurida, growing fox populations in Central Europe, especially Thelaziidae), are emergent zoonotic agents in several in urban areas, with a prevalence of E. multilocularis European regions (Otranto et al., 2013a). Finally, the infection above 30% is causing a high infection pres- recent finding of the zoonotic potential of a little sure and maintaining the parasite cycle without the known filaroid of dogs, Onchocerca lupi (Spirurida, On- pet population. Therefore, a promising approach is chocercidae), rendered the puzzle of human VBH in- to reduce the infection pressure by the delivery of fections in Europe even more complicated. anthelmintic baits for foxes (Hegglin and Deplazes, 2013). Hosts and Life Cycle To prevent the introduction of E. multilocularis into Great Britain, Ireland and as of yet non-endemic Dirofilarioses are transmitted by bloodsucking Scandinavian countries, where, due to the presence mosquitoes, primarily to dogs, although cases of infec- of suitable intermediate hosts, the establishment of tion in man are reported increasingly (Otranto and the parasite would be possible, the Pet Travel Scheme Eberhard, 2011). Soon after mosquitoes inoculate S64 G. Baneth et al. infective third-stage larvae (L3) to dogs and cats, This was the case for the introduction of the invasive developing larvae migrate to the definitive site of mosquito species Stegomyia albopicta (Aedes albopictus) parasitism, the pulmonary arteries and right cham- into Italy (Romi and Majori, 2008), which most likely bers of the heart for D. immitis and the subcutaneous contributed to the spread of D. immitis from endemic tissues for D. repens. In these locations, following their areas of the Po river valley in northern Italy to south- development into adult worms (in 120e180 and ern Italy (Otranto et al., 2009). However, several mos- 189e259 days for D. immitis and D. repens, respec- quito species of the genus Anopheles, Aedimorphus, tively), females release microfilariae into the blood Armigeres, Ochlerotatus, Stegomyia, Culex, Coquillettidia of the definitive host (Genchi et al., 2009), which are and Mansonia may act as intermediate hosts, although thereafter ingested by mosquitoes during their blood Aedimorphus vexans (Aedes vexans), Culex pipiens pipiens intake. Microfilariae of Dirofilaria spp. develop in and S. albopicta are also implicated as the most impor- the intermediate mosquito vectors from embryos to tant natural vectors of these worms in Europe. Since infective L3 larvae in a variable period of time at a both D. repens and D. immitis grow under laboratory minimum threshold of 14C and the requirement of conditions in the same mosquito species with similar a minimum of 130 days for larvae to reach infectivity developmental times, these infections are often sym- (Genchi et al., 2009). patric in animal populations (Genchi et al., 2009). T. callipaeda nematodes live in the orbital cavities The relationship between the prevalence of D. repens and associated host tissues, causing ocular disease in in dogs and the occurrence of human cases of dirofi- carnivores and representing a potential public health lariosis, based on a review of the historical literature, concern due to the zoonotic impact. Adults live in the was evident in some provinces of Sicily (Otranto et al., conjunctival sacs of animals under the nictitating 2011a). Indeed, while D. immitis is recognized as the membrane and the mature females release first- main agent of human dirofilariosis in the Americas stage larvae (L1) into the lachrymal secretions, and was described in a few cases in Italy, Greece which are ingested subsequently by the zoophilic and Spain (Miliaras et al., 2010; Morchon et al., fruit fly Phortica variegate (Diptera, Drosophilidae), 2010; Avellis et al., 2011), D. repens is the most the known vector of this spirurid in Europe prevalent species infesting people in Europe (Otranto et al.,2005). In the intermediate host, L1s (Pampiglione et al., 1995, 2009). Human cases of undergo development to L3s approximately 14e21 dirofilariosis are increasing in Europe, most likely days after infestation (in laboratory conditions) and paralleling the spreading of infection in dogs in may also survive in overwintering flies for 6 months central and north-eastern European countries (Otranto et al., 2004, 2005). Finally, mature L3s including Poland, Switzerland, the Czech Republic, migrate through the arthropod coeloma to the Hungary, Romania, Serbia and the Slovak Republic labella to be then transmitted to a receptive host as (Genchi et al., 2014)(Fig. 2). soon as the drosophilid feeds on the lachrymal Over the last 20 years, T. callipaeda has been repeat- secretions (Otranto et al.,2005). edly reported to infest the eyes of domestic (dogs and Scant information is available on O. lupi, which lo- cats) and wild carnivores (foxes, wolves, beech mar- calizes in nodular lesions under the sclera and perioc- tens and wild cats). Countries considered as endemic ular tissues of dogs and cats or in the retrobulbar eye for this worm in Europe include Italy, France, (Otranto et al., 2013b). The biology of this filaroid in Switzerland, Spain and Portugal (Malacrida et al., the definitive host is almost unknown and the vector 2008; Miro et al., 2011; Vieira et al., 2012; Otranto of this infestation is not well characterized (Otranto et al., 2013b). The same areas where the infection et al., 2012a). was recently diagnosed were predicted by a model published about 10 years before, which was based on the ecology and the seasonal occurrence of the Epidemiology drosophilid fly in a highly endemic area of southern The interaction between helminths, vectors and ani- Italy (Otranto et al., 2006). Indeed, that model antic- mals is the consequence of a complex range of biolog- ipated that large areas of Europe were likely to repre- ical (e.g. vectorial capacity, biting rates) and sent suitable habitats for Phortica variegata and, environmental (e.g. climate, population movements therefore, for the expansion of thelaziosis. Conse- and trade) factors, which ultimately affect the epide- quently, the first cases of human thelaziosis in Europe miology of VBH infections. This picture is compli- have been diagnosed in north-western Italy, south- cated further by the fact that new potential vectors eastern France (Otranto and Dutto, 2008) and Spain are introduced into previously non-endemic areas, (Fuentes et al., 2012). therefore increasing the risk for establishing new O. lupi has been found to infect dogs in southern transmission cycles in populations of susceptible hosts. (Greece, Portugal) and Central Europe (Germany, Parasitic Zoonoses of Dogs and Cats in Europe S65

Fig. 2. Distributions of Diroﬁlaria immitis and Diroﬁlaria repens infections in Europe (with permission from the Institute of Parasitology, Uni- versity of Zurich, Switzerland).

Hungary and Switzerland) (Szell et al., 2001; tected in skin biopsy samples from the interscapular Komnenou et al., 2002; Hermosilla et al., 2005; region and the head (Otranto et al., 2013a). While Faısca et al., 2010; Otranto et al., 2013a) and in the the morphological discrimination of microfilariae USA (Orihel et al., 1991; Eberhard et al., 2000; might be challenging and lack in sensitivity, as other Zarfoss et al., 2005) where it was recently found also filaroids may infect dogs (e.g. Acanthocheilonema recondi- in cats (Labelle et al., 2011). Since the first report of tum, Acanthocheilonema dracunculoides), an alternative human ocular infestation (Otranto et al., 2011b), O. method for diagnosing D. immitis infection in dogs is lupi has been recognized as a zoonotic agent in pa- the use of commercial kits for the detection of antigens tients from Turkey (Otranto et al., 2012b; Ilhan released into the blood by adult females. The acid et al., 2013), Tunisia (Otranto et al., 2012b), Iran phosphatase histochemical staining method can be (Mowlavi et al., 2013) and the USA (Eberhard useful for differentiating microfilariae of D. immitis, et al., 2013). D. repens and A. reconditum based on species-typical staining patterns of their anatomical structures, although this method presents limitations for the Diagnosis of Infection in Man and Animals identification of microfilariae and major disadvan- Diagnosis of VBH infections is achieved through tages due to the short shelf-life of its reagents detection of circulating microfilariae (e.g. D. immitis (Peribanez~ et al., 2001). Recent molecular-based as- and D. repens) in the bloodstream of infected animals says have enabled identification of filaroids, irrespec- by microscopical techniques, with the Knott’s tive of their life cycle stage (Latrofa et al., 2012). method as the gold standard (McCall et al., 2008). In man, Dirofilaria spp. localize predominantly in In contrast, dermal microfilariae of O. lupi can be de- the subcutaneous tissues and lungs, but also in the S66 G. Baneth et al. central nervous system, causing a range of clinical on the occurrence of these pathogens and to prevent manifestations ranging from asymptomatic infection the spread of filaroids into non-endemic areas, there- to fatal syndromes (Otranto and Eberhard, 2011). fore limiting the outbreaks of zoonotic filariosis. Diagnosis in human patients is usually only possible after surgery and extraction of the worm from the tis- Toxocariosis sues for Dirofilaria spp. and O. lupi and often requires the assistance of a specialist with an appreciation of Aetiology the microscopical features of helminth histology Toxocariosis is caused by Toxocara canis and Toxocara (Otranto and Eberhard, 2011). Molecular character- cati (syn. Toxocara mystax), which are ubiquitous, pro- ization of samples also assists in achieving a diagnosis lific nematodes with a complicated life cycle. Other from the tissue biopsies. ascarids that may potentially be of clinical importance in man include Baylisascaris procyonis of raccoons Prevention of Infection in Man and Animals and Ascaris suum of pigs. In contrast to the other nematodes, the latter is expected to complete its migration The prevention and the treatment of VBH infections and may reach patency in man (Nejsum et al., 2012). in endemic areas is challenging, due to the many com- ponents involved in the epidemiology and biology of Hosts and Life Cycle these infections in man and animals. In dogs, dirofilariosis can be prevented with a number of macrocy- The definitive host of T. canis are canids, including clic lactones administered in different formulations dogs and foxes, while T. cati has cats and other felids (e.g. tablets, chewable, spot on and injectable) with as definitive hosts. Invertebrates (e.g. earthworms), different protocols, from daily administration up to rodents, foxes, birds and livestock (e.g. sheep, pigs slow release products with effects lasting for 6 months, and poultry) can serve as paratenic hosts (Taira which kill D. immitis or D. repens larvae before they et al., 2004; Schnieder et al., 2011). Dogs are infected develop into adults. The injectable long-lasting with T. canis by ingestion of embryonated eggs or formulation containing moxidectin is effective in con- hypobiotic (arrested) L3 in paratenic hosts; even trolling D. immitis and D. repens infestations for a older immune dogs may acquire new patent period of 6 months after a single administration infections if exposed to low numbers of eggs (Genchi et al., 2002, 2010). Current guidelines on (Fahrion et al., 2008). Pups are infected vertically, management of D. immitis infection in dogs formed either prenatally in the last trimester of gestation or by ESCCAP and by the American Heartworm by larvae in milk from the bitch. Transplacental Society suggest extending preventive treatment to transmission accounts for many more infections than 7e8 months or even year round. No data are the lactational route (Burke and Roberson, 1985) available on the efficacy of macrocyclic lactones as and represents either recent infection of the pregnant chemoprophylactic agents against O. lupi, while bitch or reactivated hypobiotic larvae after somatic preventing contact with the fly intermediate host of migration in the immune bitch (Schnieder et al., T. callipaeda by use of bed nets is currently the only 2011). Occasionally, bitches are reinfected by eating strategy to prevent this infection. intestinal larvae (L4) from faeces of pups. T. cati is primarily transmitted to kittens by ingestion of larvae in milk following acute infection of the queen, while pre- Gaps in Knowledge and Recommendations for Further Research natal infection apparently does not take place (Coati While the scientific knowledge of the biology, epide- et al., 2004). The lack of reactivation indicates miology, control and treatment of D. immitis and D. different characteristics of hypobiotic larvae in cats repens has increased considerably over past decades, compared with dogs. Other infection routes in cats for other filaroids such as O. lupi there are still gaps are intake of embryonated eggs from soil or larvae in knowledge that impair a realistic appreciation of within paratenic hosts (e.g. rodents). their impact in veterinary and human medicine. In The life cycle is typically migratory: after ingestion addition, the reasons why human cases of VBH infec- of eggs in a fully susceptible host, hatched larvae tions have increased in Europe are not fully known, migrate through the liver and lungs while moulting but this most likely reflects the spread of arthropod from L3 to L4, are coughed up through the trachea vector species and lack of economic means for their (L4 to L5) to finally develop into adults that reside control in the environment. Large epidemiological in the small intestine of the definitive hosts. Eventu- studies to estimate the occurrence of filaroid infections ally, eggs in large number (thousands per day) are in animals, coupled with entomological surveillance voided in the faeces. In the immune host, the larvae programmes, are essential for providing information do not perform tracheal migration, but re-enter the Parasitic Zoonoses of Dogs and Cats in Europe S67 circulation for somatic migration (i.e. L3 relocate to as in other tissues, but continue migration for a pro- skeletal muscles, kidneys, mammary gland, CNS longed period of time (Kazacos, 2001). and other organs) (Schnieder et al., 2011). For T. canis, the prepatent period thus varies with the route Epidemiology of infection; eggs can be found in puppies 2e3 weeks of age after prenatal infection, while prepatency is The heaviest infections and highest morbidity are 4e5 weeks after ingestion of eggs followed by tracheal seen in pups and kittens. Heavy prenatal infections migration (Overgaauw, 1997). Eggs are usually in pups may lead to severe disease with alternating excreted for 4 months. The prepatent period for T. diarrhoea and constipation, vomiting, typical ‘pot cati is also variable, but is usually 6e8 weeks after belly’, reduced growth with cachexia, poor hair ingestion of eggs. Patency lasts 4e6 months. Eggs un- coat and in some cases death (Schnieder et al., dergo development outside the host for at least 2e4 2011). Dogs older than 6 months are usually less weeks to reach the infective stage (L3), which remains severely or not affected. Clinical signs of T. cati infec- inside the egg and shows extreme persistence in the tion in young cats are similar, but generally less se- environment for months to years, although it is gener- vere; respiratory tract signs are also reported. The ally sensitive to ultraviolet light, desiccation and high prevalence of T. canis in dogs, based on faecal exami- temperature. nation, varies considerably in EU countries Human infections are predominantly acquired (1.4e30.5%) (Schnieder et al., 2011) and depends from ingestion of embryonated eggs by geophagia in on the composition of the host population, animal sandpits, parks or other places where cats, dogs or density (definitive and paratenic hosts), seasonality, wildlife have defecated. Toxocara spp. eggs have region and methods employed. The prevalence of T. been recovered worldwide from sand or soil in play- cati is generally higher due to the low level of resis- grounds and public parks (Overgaauw, 1997). tance to reinfection in older cats, around 8e76% Embryonated eggs have also been found in the hair (Overgaauw, 1997), with large variation between do- coat of dogs, mainly puppies (Amaral et al., mestic cats with or without access to the outdoors, 2010) and foxes, but the relative importance of this stray cats or those in shelters. In foxes, T. canis has for human transmission remains unknown. Food- been reported with mean prevalence rates up to borne infections may also take place, for example by 49e87%, depending on age group (Saeed et al., drinking water or eating vegetables contaminated 2006; Morgan et al., 2013). Similar infection levels with eggs and by eating raw liver or other viscera of of B. procyonis (39e80%) have been reported in paratenic hosts, including livestock, as experimentally raccoons in some areas of Germany (Bauer, 2011). demonstrated for pigs or chickens (Taira et al., 2004). Seroprevalence of Toxocara spp. infections in man is It is possible that food-borne infections may be rela- around 3e19% in many European countries, varying tively common in certain cultural settings, for by diagnostic methods, age profile (highest in young instance in Japan where raw liver is eaten (Akao people) and cultural habits (Overgaauw and and Ohta, 2007), but the relative importance of this Knapen, 2013). A certain level of cross-reaction means of transmission in the European context is pres- with other nematode infections cannot be ruled out; ently unknown. for example, A. suum from pigs may cause patent (or Raccoons are the major definitive hosts of B. procyo- aborted) infections in man, particularly in young in- nis, but infection also reaches patency in dogs; the dividuals (Nejsum et al., 2012). Risk factors related latter has been observed in many cases in the USA to seropositivity include young age, playing in sand- (Lee et al., 2010), usually with low intensity infections. pits, dog ownership, poor sanitation, rural popula- However, no data for dogs in Europe have been re- tions and low socioeconomic status, while the effect ported. A wide range of animals (>90 species of mam- of gender is variable (Magnaval et al., 2001; mals and birds) may serve as intermediate hosts, as it Rubinsky-Elefant et al., 2010). The vast majority of is believed that the L2 stage is in the ingested infective human Toxocara spp. infections are asymptomatic. egg and it develops to L3 in the intermediate host However, T. canis and, probably less commonly, T. (Kazacos, 2001). In raccoons, there is no migration, cati, may cause clinical syndromes in man described while there is extensive somatic migration in the inter- as visceral larvae migrans (VLM), ocular larvae mediate hosts. A proportion of larvae has propensity migrans (OLM), covert toxocariosis and more for migration in the CNS (neural larvae migrans, rarely NLM. VLM and OLM are most often NLM). This is particularly harmful as development observed in children (VLM at 1e5 years of age from L2 to L3 is accompanied by a four- to five-fold predominantly; OLM at 5e10 years), while the less increase in length (up to 1,300e1,900 mm) and larvae well-defined covert toxocariosis is found in both chil- do not readily encapsulate in eosinophilic granulomas dren and adults (Smith et al., 2009). The incidence in S68 G. Baneth et al. the EU is largely unknown, but presumably very low CNS involvement) and serology. In cases of (Smith et al., 2009), and the relative contribution of OLM and perhaps NLM, extirpation by biopsy and the two species is unknown (Fisher, 2003; Rubinsky- subsequent histopathology can be performed and Elefant et al., 2010). Signs of VLM depend on the parasite material can be speciated by PCR. Detection infective dose and are non-specific, including abdom- of IgG antibodies to T. canis excretory/secretory anti- inal pain, fever, anorexia, respiratory signs, head- gens (TES) by indirect ELISA, followed by western ache, skin lesions and occasionally neurological blot to limit cross-reactivity, is central to the diagnosis symptoms, accompanied by hepatomegaly and eosin- (Fillaux and Magnaval, 2013). However, antibody ti- ophilia. OLM indicates the location of a Toxocara tres do not necessarily correlate with active versus larva in an eye or optic nerve and is often painless, non-active infection and false-positive outcomes exist but leads to visual disturbances and unilateral blind- (Smith et al., 2009). These assays cross-react with T. ness. It is increasingly seen also in adults (Akao and cati and can be used for evaluating toxocariosis as Ohta, 2007). Specific antibody levels in OLM are such; none of the currently available tests are capable often low because the larvae evade the immune sys- of discriminating between T. canis and T. cati infec- tem or their number is low. There are some indica- tions in man or any other paratenic host. tions that T. canis and T. cati larvae have different tissue preferences during somatic migration in the Prevention of Infection in Man and Animals same paratenic host or at least different time courses (Strube et al., 2013). T. cati larvae predominantly A cornerstone in prevention is minimizing the envi- locate in skeletal muscles while T. canis more rapidly ronmental contamination with (infective) eggs by migrate to the CNS in addition to the muscle, indi- rigorous removal of faeces and by treatment of in- cating perhaps a higher degree of neuroaffinity. fected dogs and cats. Faeces should be removed and B. procyonis eggs are particularly abundant in destroyed when dropped in public areas, streets, ken- latrine areas of raccoons and people contract infec- nels and also in private gardens. Intestinal stages of tion mainly by geophagia (Bauer, 2013). As Toxocara spp. are susceptible to the most commonly mentioned, B. procyonis causes severe OLM and used anthelmintics, while hypobiotic stages in tissues NLM (acute eosinophilic meningoencephalitis) in are impossible to treat effectively, thus posing a prob- intermediate hosts, including man. The NLM syn- lem of clearing breeding bitches of infection drome is often fatal or causes permanent neurolog- (Othman, 2012). Although some hypobiotic larvae ical disease to the intermediate host, as observed in may become susceptible to anthelmintics on reactiva- almost all reported human cases in the USA (Lee tion, it is not advisable to treat pregnant animals to et al., 2010). Only single cases in people have been reduce perinatal transmission (Overgaauw and reported from Europe (Bauer, 2013). Knapen, 2013). Repeated application of anthelmintics is therefore recommended for puppies and kittens (and their mothers) during lactation and early life in Diagnosis of Infection in Man and Animals order to avoid pathogenic infections and limit Patent infections in dogs and cats can be diagnosed by contamination (Fisher et al., 1993). Older dogs and standard faecal flotation. A study combining PCR cats can either be treated on a routine basis or exam- analysis and egg morphology showed that T. cati ined for eggs regularly followed by treatment of pat- eggs are distinctly smaller than T. canis eggs, but ent cases. Guidelines for the control and treatment also revealed that up to 30% of eggs found in dogs of parasites in pet animals were developed and pub- could be T. cati (Fahrion et al., 2011). This is most lished by ESCCAP in Europe (www.esccap.org). likely due to coprophagia, as these species seem to Other preventive measures include avoiding trans- be host specific. Ingestion of fox faeces by dogs may mission by feeding of raw liver or offal and also lead to false-positive observations. B. procyonis coprophagy in dogs. The relative contribution of T. eggs can easily be mistaken for T. canis eggs based canis from foxes to environmental contamination is on size; however, the latter have a regular pitted sur- difficult to assess in an urban context and equally face while B. procyonis eggs have a fine granular surface difficult to control. An attempt to quantify the contri- (Kazacos, 2001; Lee et al., 2010). This may, however, butions of dogs, cats and foxes in the Bristol area be difficult to ascertain by routine microscopy and (UK) indicated that the main contributor was dogs, baylisascariosis needs in most cases to be confirmed although obviously modified by the degree of removal by PCR on eggs. of faeces and dog access to public spaces (Morgan Human toxocariosis is diagnosed by clinical mani- et al., 2013). festations, ophthalmology (OLM), clinical pathol- Prevention of human infections should be based on ogy, including eosinophilia, bioimaging (typically in appropriate control of infections in pets, removal of Parasitic Zoonoses of Dogs and Cats in Europe S69 faeces from surroundings, limiting access of pets to Conclusions children’s play areas, good hygiene and lastly, educa- Parasitic zoonoses constitute some of the most impor- tion. The environmental efforts include fencing of tant and common infections threatening human pop- playgrounds, covering of sandpits, regular applica- ulations in Europe as well as other continents. This tion of new sand, exclusion of dogs from parks and rec- review has presented the major diseases in this cate- reational areas, provision of information (signs) and gory associated with companion animals, describing bags for faeces and management of stray animals. the current status of infections in man and animals Furthermore, general good hand hygiene, rinsing of in an effort to highlight gaps in knowledge and poten- fresh produce from gardens and prevention of geo- tial interventions to prevent or limit their spread. phagia in children are essential. Combating parasitic zoonoses requires an integrated Treatment of larvae migrans in people includes multidisciplinary approach involving collaboration anti-inflammatory and anthelmintic treatments between veterinary and medical scientists and policy with moderate reduction in clinical symptoms makers. (Strube et al., 2013) and in the case of OLM, possible extirpation. Anthelmintics may have limited effect in OLM. Acknowledgments B. procyonis infections in dogs are treated with The authors thank the EU seventh framework CALL- commonly available anthelmintics, such as benz- SITO programme for funding the meetings and dis- imidazoles, macrocyclic lactones or tetrahydropyr- cussions, which provided the basis for composing imidines. Raccoon populations should be this manuscript, and for funding its publication. controlled as well as any animal considered infected. 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