Tick-Borne Infectious Diseases of Dogs

74 Review TRENDS in Parasitology Vol.17 No.2 February 2001 Tick-borne infectious diseases of dogs

Susan E. Shaw, Michael J. Day, Richard J. Birtles and Edward B. Breitschwerdt

Tick-transmitted infections are an emerging problem in dogs. In addition to Mediterranean area4. In addition, during the same causing serious disease in traditional tropical and semi-tropical regions, they are period, both Ehrlichia canis infection and infestation now increasingly recognized as a cause of disease in dogs in temperate climates with Rhipicephalus sanguineus, the ehrlichiosis and urban environments. Furthermore, subclinically infected companion vector traditionally found in southern Europe, were animals could provide a reservoir for human tick-transmitted infectious agents, found in dogs that had never been outside Germany4. such as Ehrlichia chaffeensis, Ehrlichia ewingii, the Ehrlichia phagocytophila The zoogeographical range is also increasing because group and Rickettsia conorii. Here, we discuss the emergence of new canine tick- tick species are finding niches in different climatic transmitted diseases, which results from several factors, including the conditions. Since the 1980s, Ixodes ricinus has expansion of the tick range into urban and semi-urban areas worldwide, the extended its range in Sweden to include more movement of infected dogs into previously non-endemic areas, and the advent northern and western areas5 and Dermacentor of novel molecular techniques for diagnosis and pathogen identification. variabilis, the major vector of Rocky Mountain spotted fever (RMSF), has extended its range to Being haematophagous, ticks are well designed to include the northeastern USA6. transmit disease agents such as viruses, bacteria and protozoa. Historically, they have been considered Dogs as sentinels for human infection second only to mosquitoes in this ability1. Ticks attach The medical and veterinary importance of tick securely to their hosts, facilitating not only effective infestation in dogs lies in the transmission of a wide transmission of infectious agents, but also the spread variety of infectious agents (Table 1). The most of both ticks and microorganisms to different important tick-transmitted infectious diseases geographical habitats via travelling pets. Pathogens causing severe clinical illness in dogs are babesiosis, ingested by ticks can be spread trans-stadially and/or ehrlichiosis and, in the USA, RMSF and trans-ovarially. As female ticks are extremely fecund, hepatozoonosis. However, although Borrelia this allows effective dissemination of infectious burgdorferi and Rickettsia conorii infections agents in reservoir populations with which pets and commonly produce subclinical infection, as evidenced their owners interact. by seropositivity, their association with clinical Arthropods in general, and ticks in particular, disease in dogs is more difficult to evaluate7. Dogs have evolved as ectoparasites of wild animals1. Only a also appear to be susceptible to infection with minority of tick species, generally those with a wide Coxiella burnetii (Q fever) and tick-borne viral host range, transmit diseases to domestic animals encephalitides8, but reports of clinical illness are and humans. The increasing prevalence of tick- uncommon. Other canine tick-transmitted infections Susan E. Shaw transmitted diseases of pets and their owners has include haemobartonellosis, bartonellosis, Dept of Clinical Veterinary been associated with increased accessibility of tularaemia (Francisella tularensis) and, rarely, Sciences, University of traditional ‘wilderness’ environments and an increase louping ill (Flaviviridae). Bristol, Langford House, Langford, Bristol, UK in the reservoir of wild host species (deer, small Several of the tick-borne infections that affect dogs BS40 5DU mammals and foxes) that now have a closer can cause serious disease in humans, notably e-mail: association with human activity. In addition, there borreliosis, ehrlichiosis, RMSF, R. conorii infection [email protected] has been a rapid evolution of molecular-based and tick-borne encephalitis. However, the potential Michael J. Day techniques, which has allowed more sensitive and zoonotic threat posed by dogs is strongly influenced by Dept of Pathology and accurate detection of tick-borne pathogens. For the natural cycle of the specific agent with which the Microbiology, University of Bristol, Langford example, granulocytic ehrlichiosis in dogs, cats, dog is infected. Three general epidemiological House, Langford, Bristol, horses and humans is now considered to be a disease scenarios can be described. First, if transmission of an UK BS40 5DU. of major importance in Sweden2, the USA3, Scotland, infectious agent involves ticks with a broad host Richard J. Birtles Switzerland and Slovenia. range (such as I. ricinus), dogs can act directly as Dept of Pathology and Ticks and the diseases they transmit have a sentinels for infection of humans. Second, by acting Microbiology, School of zoogeographical range restricted by host movement as natural hosts for certain nidicolous ticks (such as Medical Sciences, University of Bristol, and, to some extent, climatic factors. However, the R. sanguineus and Ixodes canisuga), dogs Medical Walk, Bristol, UK increased mobility of pets has resulted in rapid significantly increase contact between these species BS8 1TD. extension of the zoogeographical ranges for many and humans, thereby increasing the risk of 9 Edward B. Breitschwerdt species. In the UK, this will be exacerbated by recent transmission . Finally, there is a limited risk of College of Veterinary alterations to the animal quarantine regulations (Box transmission by exposure to infected-tick contents Medicine, North Carolina 1). Between 1995 and 1998, 36% of cases of monocytic following damage to ticks during grooming of infested State University, 4700 Hillsborough St, Raleigh, ehrlichiosis reported in Germany occurred in dogs animals. This scenario has been reported for NC 27606, USA. that had travelled for short periods to the R. conorii10.

infection has been reproduced experimentally for Box 1. The UK Pet Travel Scheme vaccine development11. Since February 2000, the pilot Pet Travel Scheme (PETS) has provided an Recent work using laboratory animals suggests alternative to the mandatory six-month period of quarantine for dogs and that tick salivary components or intestinal secretions cats entering the UK. Such animals can now travel freely from particular EU introduced during feeding produce profound changes countries providing they satisfy the requirements of the scheme (microchip in the immunological activity of the surrounding skin identification, rabies vaccination confirmed by serology and ecto- and and draining lymph nodes12. Direct suppressive endoparasiticidal treatment 24–48 h before re-entry to the UK). The scheme effects of I. ricinus and Dermacentor andersoni saliva is to be extended in April 2001. More than 9000 dogs and cats travelled on the host immune system have been reported, under the scheme between February and October 2000. including inhibition of T-cell responses to concanavalin A. Immunoglobulin-binding and high- affinity histamine-binding proteins have been Pathogenesis of tick-borne infectious diseases isolated from the saliva of several tick species Although the cutaneous pathology induced by tick (Rhipicephalus appendiculatus, Amblyomma bites has been described, there have been a limited veriegatum, I. hexagonus); both of these proteins number of studies on the process of transmission of might reduce tick rejection and facilitate disease infectious agents by ticks to dogs, and even fewer transmission. There is strong evidence in studies on factors that determine vector competency. R. sanguineus infestation for a switch from the Most recent studies relate to canine borreliosis, where normal protective T helper 1 (Th1) cytokine profile

Table 1. Emerging tick-transmitted diseases of dogs Disease agent Geographical distribution Tick vectors Refs

Babesiosis Babesia canis canis Tropical/semitropical worldwide Rhipicephalus sanguineus, 16,19,21–26,45 Dermacentor reticulatus, Dermacentor marginatus B. canis vogeli Tropical/semitropical worldwide R. sanguineus B. canis rossi Southern Africa Haemaphysalis leachi B. gibsoni Africa, Asia, USA, southern Europe, Haemaphysalis bispinosa, Middle East R. sanguineus Hepatozoonosis Hepatozoon canis Southern Europe, Middle East, Far East, R. sanguineus, 27–29,31–35,38 Africa Amblyomma maculatum, Haemaphysalis longicornis H. americanum Southern USA Amblyomma americanum Ehrlichia canis genogroup E. canis Southern USA, southern Europe, R. sanguineus 4,17–20,31–35,38 Africa, Middle East, eastern Asia E. chaffeensis USA A. americanum, Dermacentor variabilis E. ewingii USA Unconfirmed E. phagocytophila genogroup E. phagocytophila Northwestern Europe 3,36,37 E. equi USA Ixodes speciesa Human granulocytic Midwestern and northeastern USA, ehrlichiosis agent northwestern Europe E. platys USA, southern Europe, Middle East Unconfirmed Borreliosis (Lyme disease) Borrelia burgdorferi 7,11,15,20,39–42, sensu lato 46, 47 Genogroups: B. burgdorferi sensu stricto North America, Europe, Middle East B. garinii Europe, Asia Ixodes speciesa B. afzelii Europe, Asia B. japonica Japan Spotted fever group Rickettsia conorii Southern Europe, Middle East, Africa R. sanguineus 9,17,19,30,43 (Boutonneuse fever) Rickettsia rickettsii USA Dermacentor andersoni, (Rocky Mountain D. variabilis spotted fever) aSpecies dependent on geographical location, unconfirmed for B. japonica.

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thrombocytopenia, leukopenia or non-erosive polyarthropathy11,16,17. Infected tick Coinfection Coinfection Infection with multiple tick-transmitted pathogens, Joints or with multiple genotypes of the same pathogenic Immune Tick salivary Antigens species, can occur in an individual animal following complex Uvea molecules heavy exposure to ticks18,19. The same tick species can Babesia deposition Kidney with be a vector for several pathogens (Table 1) and Ehrlichia Skin vasculitis coinfection of individual ticks can occur20. Infection CNS with tick-borne pathogens can also be complicated by Th1 Cross-reactive Non-protective Disease other arthropod-borne diseases that share the tick immunity antibodies biohabitat, such as leishmaniosis. In dogs, coinfection Th2 Antibodies Hypergammaglobulinaemia with combinations of Ehrlichia, Bartonella, Babesia, Hepatozoon, Leishmania and Rickettsia species Cytokines Autoantibodies Red blood cells occurs in endemic areas. The role of such coinfection B Platelets is being clarified by PCR19. Coinfection could partially explain variations in clinical presentation, Acute disease Chronic disease pathogenicity and response to therapy. TRENDS in Parasitology Protozoan diseases transmitted by ticks Fig. 1. A hypothetical model for the immunopathogenesis of tick-transmitted disease in non-immune Babesiosis dogs. The bite of an infected tick transmits microorganisms to the host. Tick salivary proteins are able Canine babesiosis is caused by the intraerythrocytic to subvert the skin-associated immune system from the normally protective T helper 1 (Th1) protozoan parasite Babesia canis, and increasingly by immunity to a Th2 response, which permits establishment of systemic infection. This non-protective immune response is dominated by antibody production, and these antibodies can be significant Babesia gibsoni, which is extending its range in the mediators of the chronic clinical symptoms of disease, via: (1) the vascular effects of USA21 and Europe. Molecular studies have recently hypergammaglobulinaemia; (2) the formation of autoantibodies or antibodies that cross-react with identified novel Babesia spp. that infect dogs22. self tissue; and (3) the formation of immune complexes that deposit in predisposed capillary beds and initiate tissue damage. Abbreviation: CNS, central nervous system. Although the pathogenicity of B. gibsoni is uniformly high, pathogenicity varies among strains of Babesia canis: Babesia canis rossi, the prevalent strain in associated with resistance to tick-borne disease to an South Africa, causes severe clinical disease; aberrant Th2 cytokine profile13. In addition, a B. canis canis in Europe is moderately pathogenic; component of the I. ricinus salivary gland that and Babesia canis vogeli infection causes relatively inhibits the antiviral effect of interferon has recently mild disease worldwide23. The relative importance of been isolated. These local immunomodulatory tick species in the transmission of canine babesiosis changes enhance transmission of infectious varies with geographical location. organisms by I. ricinus not only to the host but also to The clinico-pathogenesis of babesiosis caused by co-feeding ticks14. B. c. canis and B. gibsoni involves progressive After successful transmission, tick-transmitted haemolytic anaemia. By contrast, the more severe pathogens can induce profound immunological disease caused by B. c. rossi can involve hypoxic, abnormalities (Fig. 1). In fully susceptible dogs, hypotensive shock with disseminated intravascular infection can produce clinical syndromes easily coagulation (DIC), systemic inflammatory response recognized in endemic areas. However, despite syndrome and multiple organ dysfunction therapy, animals with an incomplete protective syndrome24 (Table 2). The severity of disease also immune response commonly develop persistent varies with the species of vector, and the age, breed subclinical infection which can recrudesce with stress and immune status of the dog23. Erythrocyte-bound or concurrent disease15. In these cases, low numbers autoantibodies are involved in the haemolytic form of of organisms and cryptic infections make diagnosis the disease16. There can be erythrocyte difficult using routine methods. It is likely that autoagglutination and many dogs with babesiosis tick-transmitted pathogens contribute significantly give a positive Coombs’ test. Methaemoglobinaemia to the considerable numbers of dogs with ‘pyrexia of and methaemoglobinuria occur secondary to unknown origin’, lymphadenopathy, chronic cyclic oxidative damage in parasitized red blood cells25. As a anaemia and thrombocytopenia, polyarthropathy, consequence of the methaemoglobinaemia, there is uveitis or vasculitis. Continued antigenaemia can enhanced damage by anti-erythrocyte antibodies and lead to the induction of polysystemic immune- erythrophagocytosis. Persistent infection with mediated disease. Infected animals commonly have B. canis or B. gibsoni is common in endemic areas26. high serum globulin levels, with monoclonal or Although these animals appear healthy unless polyclonal gammopathies and immune-complex subjected to stress, they provide a reservoir of formation. Immunological mechanisms can result in infection for susceptible animals and have suboptimal Coombs’ positive haemolytic anaemia, athletic performance26.

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Table 2.Clinical features and chemotherapy of canine tick-transmitted diseases Disease Major clinical syndrome Therapya Refs Babesiosis Uncomplicated disease 16,21–26 Intravascular haemolytic anaemia Imidocarb diproprionate Diminazene aceturate Complicated disease Hypotensive shock Phenamidine isethionate Multiple organ dysfunction syndrome Pentamidine isethionate Hepatozoonosis Myositis with muscle atrophy and paresis Imidocarb diproprionate 27–29 Doxycycline Polysystemic immune complex disease Minocycline Oxytetracycline Tetracycline Sulfonamide/pyrimethamine/ clindamycin in combination Ehrlichiosis Ehrlichia canis Thrombocytopenia causing bleeding diathesis Doxycycline 18,19,32–35 genogroup Minocycline Irreversible bone marrow destruction Oxytetracycline (chronic disease) Tetracycline Polysystemic immune complex disease Chloramphenicol Rifampin Fluquinolones Imidocarb diproprionate E. phagocytophila Severe lethargy and weakness Doxycycline 37 genogroup Polyarthritis Minocycline Central nervous signs Oxytetracycline Tetracycline Borreliosis Non-erosive polyarthropathy Doxycycline 5,7,11,15,39–42 Central and peripheral neurological signs Amoxicillin Azithromycin Penicillin Ceftriaxone Cefotaxime Chloramphenicol Rocky Mountain Subcutaneous oedema owing Doxycycline Spotted Fever to necrotising vasculitis Oxytetracycline 9,17,43 Central and peripheral neurological signs Chloramphenicol Enrofloxacin aTherapeutic agents are listed in order of decreasing efficacy, with drug of choice listed first.

Hepatozoonosis Bacterial diseases transmitted by ticks Canine hepatozoonosis is a tick-transmitted, Ehrlichiosis protozoan disease caused by species of the Canine ehrlichiosis is caused by tick-transmitted intraleukocytic parasite Hepatozoon. Unlike most intracellular bacteria of the genus Ehrlichia, which, other tick-borne diseases, Hepatozoon is transmitted in dogs, have been identified parasitizing monocytes, by ingestion of an infected tick, rather than tick bites. granulocytes and platelets. Three genogroups of Hepatozoon canis commonly infects dogs in Africa, ehrlichiae have now been identified by 16S rRNA30 southern Europe, the Middle East and Asia, phylogenetic analysis (Table 1). Genogroup III reflecting the geographical distribution of its major includes E. canis, which is responsible for widespread vector, R. sanguineus. However, unique clinical disease in tropical and temperate areas of the world. features suggest that a separate species The geographical distribution of E. canis has (Hepatozoon americanum) transmitted by the tick expanded with the distribution of R. sanguineus. Amblyomma maculatum causes disease in dogs in More recently, other genogroup III species, the southern USA and that this disease is E. chaffeensis and Ehrlichia ewingii, have been spreading27,28. The clinical spectrum of H. canis identified by PCR in naturally infected dogs, with or infection ranges from subclinical to severe life- without ehrlichiosis symptoms18,19. These species threatening disease28,29. Hepatozoon canis is have more restricted geographical distributions but a commonly associated with coinfection with other potentially wider range of tick vectors than E. canis. diseases, in particular ehrlichiosis and leishmaniosis A subspecies of Ehrlichia risticii (Genogroup I) has in endemic areas, and clinical presentations are also been reported to cause an atypical syndrome of variable (Table 2). monocytic ehrlichiosis in dogs in the USA31. http://parasites.trends.com 78 Review TRENDS in Parasitology Vol.17 No.2 February 2001

Disease manifestations caused by members of the ticks of the genus Ixodes (Table 1). At least four E. canis genogroup (genogroup III) infecting dogs can genospecies, with geographical distributions be indistinguishable18 (Table 2), and there can be primarily in the northern hemisphere, cause disease strain variation in pathogenicity32. At present, in humans39 (Table 1). In northern Europe, the information on the pathogenesis of experimental distribution of borreliosis is expanding, and infected monocytic ehrlichiosis relates primarily to E. canis. I. ricinus ticks are now commonly found in urban Immunological destruction of platelets occurs in acute areas5,40. Much of the published borreliosis research disease and anti-platelet antibodies have been found relates to the Genogroup I species, B. burgdorferi in naturally occurring and experimental cases33. sensu stricto, which is the primary isolate in humans Autoantibodies decrease platelet life-span, and and dogs in the USA. There is considerable genetic interfere with platelet membrane glycoproteins, heterogeneity between North American and causing inhibition of aggregation. Other factors such European isolates of B. burgdorferi 41. In Europe, as splenic sequestration and the production of a human borreliosis is also caused by Borrelia garinii cytokine, platelet migration-inhibition factor, are also and Borrelia afzelii. and in Japan, by Borrelia involved in the pathogenesis of thrombocytopenia. japonica, a separate genospecies. The degree to which Hyperviscosity owing to hyperproteinaemia adds B. garinii, B. afzelii and B. japonica contribute to further to platelet dysfunction and can result in ocular canine infection and disease is currently unclear. and central nervous system (CNS) abnormalities. However, infection with these Borrelia spp. could Subclinical persistent infection owing to splenic explain the disparity in pathogenicity and clinical sequestration of organisms is common34. Severe life- syndromes described42. threatening chronic ehrlichiosis can develop following Although a high proportion of dogs are seropositive persistent infection and can be associated with in endemic areas, relatively few develop clinical irreversible bone marrow destruction. Factors that signs7 (Table 2). Several mechanisms have been predispose to myelofibrosis are not understood. incriminated in causing joint damage. The production Ehrlichiosis is more severe in certain breeds (e.g. of the inflammatory mediator nitric oxide is German shepherd) and in younger animals. However, upregulated, as is interleukin 8, a cytokine that coinfection, immune status and strain variation could recruits neutrophils into infected synovial all play a role35. membranes11. Neurological abnormalities occur in Genogroup II Ehrlichiae of pathogenic significance some cases of borreliosis, most particularly in Japan42 include the Ehrlichia phagocytophila group and (Table 2). Immunological cross-reactions to bacterial Ehrlichia platys. Strains (currently species) within and self-antigens are important in human the E. phagocytophila genogroup (Ehrlichia equi, neuroborreliosis (Fig. 1), and antibodies to flagellin, human granulocytic ehrlichiosis agent and one of the most immunogenic Borrelia antigens, have E. phagocytophila) are transmitted by Ixodes spp. been shown to cross-react with neuroaxonal proteins. ticks, and are the major causative agents of canine In canine borreliosis, cutaneous and cardiac disease ehrlichiosis in the northern and western USA3 and in are rare. northern and central Europe2,36. Persistent infection with Borrelia even after Infection with species of the E. phagocytophila antibiotic therapy is reportedly common in dogs15. group is generally associated with less severe clinical The organism is sequestered in the skin, connective signs than ehrlichiosis caused by E. canis (Table 2). tissue, joints and CNS. Reactivation of infection with Persistent sub-clinical infection has recently been recrudescence of disease can occur in identified with the granulocytic Ehrlichia species in immunocompromised individuals or in coinfection. dogs in Sweden37. However, the severe chronic disease seen with E. canis in susceptible dogs has not The spotted fever group been reported. As granulocytic ehrlichiosis is RMSF is a potentially fatal rickettsial disease of dogs transmitted by Ixodes spp. ticks, coinfection with and humans caused by the intracellular bacterium Borrelia in dogs is probable, as reported in humans. Rickettsia rickettsii. It has been reported throughout Canine cyclic thrombocytopenia (Table 2), caused the USA, Central and South America, and is by E. platys, was first reported in the USA and transmitted by ticks of the Dermacentor, appears to be an emerging problem in several Rhipicephalus and Amblyomma genera, respectively southern European countries, Israel, Taiwan and (Table 1). Rickettsia conorii, the agent of boutonneuse Venezuela38. Although it is assumed to be fever in humans in southern Europe, the Middle East transmitted by R. sanguineus, its natural mode of and southern Africa (Table 1), is reported to infect transmission is uncertain. Pathogenicity is generally dogs9, but clinical signs of disease have not been low but E. platys infection might play a role in reported. coinfection with other arthropod-borne diseases. The major pathogenic mechanism involved in canine RMSF is rickettsial invasion of, and damage to, Borreliosis endothelial cells of small arteries and venules (Table Canine borreliosis is caused by a spirochete, 2). Although platelet consumption is considered the B. burgdorferi sensu lato, which is transmitted by primary cause of the thrombocytopenia in clinical

http://parasites.trends.com Review TRENDS in Parasitology Vol.17 No.2 February 2001 79 cases, anti-platelet antibodies have also been consequently, drug efficacy. Therapy with a single identified in infected dogs17. A tendency towards more chemotherapeutic agent might not be sufficient to fulminant disease has been reported in Springer eliminate infection. There are species variations in spaniels with phosphofructokinase deficiency43 and in response to therapy; for example, B. gibsoni is German shepherds. relatively unresponsive to the drugs used to treat B. canis. In addition, some drugs have Diagnosis of tick-borne diseases toxic side-effects. Poor or partial responses to single- Diagnosis of tick-transmitted diseases requires a agent chemotherapy might also reflect the presence of combination of compatible clinical and laboratory coinfection. findings, direct microscopic visualization or immunodetection of infective organisms in blood or Vaccination infected tissue, microbial culture, serological testing, Although vaccination is a potentially important immunoblotting and PCR. Although in endemic means of control, there are inherent problems in areas, direct visualization (using light microscopy) of designing effective vaccines against organisms that Babesia, Ehrlichia and Hepatozoon spp. is valuable, can evade host immunity effectively and that have the tendency for chronic and/or subclinical disease to species or strain variability. Moreover, relatively be associated with cryptic infection reduces its little is known of what constitutes a protective sensitivity and does not allow intraspecies immune response to these agents in dogs, and such differentiation. However, the use of direct endogenous immune responses can be subverted by immunohistochemical or immunocytochemical tick-derived soluble factors, as discussed. Despite methods can increase sensitivity. Cultivation of tick- this, commercially produced vaccines are available for borne bacteria is generally difficult as these are canine babesiosis and borreliosis. fastidious organisms, and eukaryotic cell co-culture The canine babesiosis vaccine is based on systems are often required. exoantigens of B. canis obtained from cell culture, and Serological testing is the most commonly used is available in Europe45. The vaccine does not prevent diagnostic methodology, and the indirect fluorescent infection, but reduces parasitaemia and limits the antibody and ELISA tests are most widely used. severity of anaemia and splenomegaly. Moreover, the However, serological testing is limited by reduced vaccine is capable of protection only from homologous ability to identify acute infection, difficulty in strains of B. canis45. By contrast, inactivated differentiating infection from prior exposure or bacterins and a recombinant vaccine based on the vaccinal titres, and species cross-reactivity. Western outer surface protein OspA (Ref. 46) are commercially immunoblotting has been used to characterize and available for canine borreliosis. OspA is expressed by distinguish different species involved. However, PCR Borrelia in unfed ticks, and, following transmission to assays and are becoming increasingly practicable for the host, is replaced by OspC expression. Anti-OspA all tick-borne infections already described. The antibodies induced by vaccination and ingested by sensitivity of PCR makes it particularly appropriate feeding ticks halt the growth and migration of for diagnosis of this group of diseases, although this Borrelia to the salivary gland. A combined technique does not distinguish between acute OspA–OspB subunit vaccine has also been evaluated infection and a carrier state. experimentally in the dog47. In experimental challenge studies, these vaccines Strategies for control appear to protect from spirochetaemia and clinical Vector control signs (polyarthritis) relative to unvaccinated control Tick control using an effective long-acting acaricide, dogs. The vaccines are recommended for use in for example fipronil44, permethrin or amitraz in spot- endemic areas but, as they are based on on, spray or collar formulation according to B. burgdorferi sensu stricto, they might not manufacturers instructions, remains the most crossprotect against other Borrelia species. Although effective preventative measure for this group of not commercially available, experimental vaccines for diseases. This is particularly the case where canine monocytic ehrlichiosis (E. canis) have also unexposed dogs are travelling into endemic areas or been reported. Antigen extracts from cell-cultured where they are involved in activities where exposure E. canis, administered with adjuvant, induced to ticks can be high, such as hunting and herding. antibody-mediated but not protective immunity, Tick eradication is impossible in most situations whereas a vaccine based on inactivated whole because of maintenance of the tick life cycle on E. canis organisms was able to protect dogs from reservoir hosts. experimental challenge35.

Chemotherapy and chemoprophylaxis Conclusions The treatment of tick-transmitted diseases is a The tick-transmitted infectious diseases of dogs that challenge for a variety of reasons (Table 2). Many of are described in this review have recently become a the target organisms are intracellular and major focus of interest in areas of the world in which sequestration limits drug penetration and, they have traditionally been considered non-endemic. http://parasites.trends.com 80 Review TRENDS in Parasitology Vol.17 No.2 February 2001

This relates to both their significance to canine enables rapid screening of blood samples for multiple health, and to the possible reservoir status of the dog tick-transmitted pathogens, and large-scale

Acknowledgements for potentially zoonotic disease. The concern that epidemiological surveys of disease prevalence. There We apologize to all the these diseases might become established in new is an urgent need for the provision of baseline data on authors whose primary geographical locations arises from the increased the prevalence of these diseases in dogs (and ticks) in contributions we were international mobility of pet dogs and increased traditionally non-endemic areas (e.g. northern unable to reference because of editorial contact of these animals with non-urban Europe), so future trends can be monitored. Further limitations on reference environments and wildlife disease reservoirs. These research is required to understand fully the numbers, and hope that factors, coupled with the trend for global climatic immunopathogenesis of these diseases in dogs, to original citations will be accessible through the change, create real risks for animal and human develop more effective chemotherapy and review papers. health. These changes come at a time when PCR now prophylactic vaccines.

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