No.7 December 2010 CVBD® DIGEST www.cvbd.org Canine Ehrlichiosis – from Acute Infection to Chronic Disease Cutting-edge information brought to you by the CVBD® World Forum ® No.7 December 2010 CVBD DIGEST Canine Ehrlichiosis – from Acute Infection to Chronic Disease Quick Digest Wide Distribution • Canine monocytic ehrlichiosis (CME) is caused by Ehrlichia canis. • It has been reported in all continents from tropical and subtropical regions and is probably the most widely distributed CVBD (canine vector-borne disease). • Distribution is driven by the global abundance of its main vector, the Brown Dog tick, Rhipicephalus sanguineus. And … Increasing • With global warming and expanding tick habitats the spread of disease to former non-endemic areas is of great concern. • Ehrlichia vectors and infections should also be considered in non-endemic areas due to increasing international pet travel and dog importation. Zoonotic Potential • E. chaffeensis (monocytic ehrlichiosis) and E. ewingii (granulocytic ehrlichiosis) also cause canine ehrlichiosis and both can affect humans. • To date, canine infections with E. chaffeensis and E. ewingii have only been diagnosed in the United States. Diagnostic Challenge • Multiple clinical and subclinical presentations make diagnosis challenging. • Acute and chronic phases as well as co-infection with other tick-borne pathogens may further complicate therapy. Silent Infections • Often, the pathogen cannot be completely eliminated, despite antibiotic treatment and resolution of clinical signs. Prevention • A vaccine for ehrlichiosis is not currently available. • Treatment with an ectoparasiticide product with repelling and killing activity against ticks presents the best option for prevention. ® No.7 December 2010 3 Canine Ehrlichiosis – from Acute Infection to Chronic Disease CVBD DIGEST Cutting-edge information brought to you by the CVBD World Forum Canine Ehrlichiosis – from Acute Infection to Chronic Disease Author: Juliane Straube Three different Ehrlichia species can cause canine Institute for Animal Hygiene and Veterinary Public Health, ehrlichiosis: E. canis, E. chaffeensis and E. ewingii University of Leipzig, Germany (see Tab. 1). The term “ehrlichiosis” may still some- times be used to describe infections by organisms Ehrlichiosis is a globally distributed canine vector- belonging to the former Ehrlichiae tribe. However, borne disease (CVBD) transmitted by ticks. Caused with reclassification into the genera Anaplasma, by the rickettsial bacteria Ehrlichia spp., ehrlichiosis Ehrlichia and Neorickettsia the term now refers affects dogs and humans as well as other domestic specifically to infections by species within the newly and wild animal species. With global warming, ex- reorganized genera (see Fig. 2 and Info Box 1). panding tick habitats and increasing international travel the spread of disease to former non-endemic E. canis causes canine monocytic ehrlichiosis (CME). areas is of great concern. This disease, also known as tropical canine pancy- topenia, canine rickettsiosis or canine hemorrhagic Ehrlichiosis can have multiple clinical and subclinical fever, was first described in Algeria in 1935 by Dona- presentations making diagnosis challenging. Acute tien and Lestoquard.1 CME has since been reported and chronic phases as well as co-infection with in many parts of the world, mainly in the tropical other tick-borne pathogens may further complicate and subtropical regions. However, the geo graphical therapy. Often, the pathogen cannot be completely distribution of E. canis is expanding alongside that eliminated, despite antibiotic treatment and resolu- of its main tick vector, the Brown Dog tick, Rhipi- tion of clinical signs. A vaccine for ehrlichiosis is not cephalus sanguineus. currently available, so treatment with an ectopara- siticide product with repelling and killing activity E. canis form microcolonies within a membrane- against ticks presents the best option for preven- lined intracellular vacuole (so-called morula), primar- tion. ily in monocytes and macrophages of mammalian hosts. The pathogen replicates only in the cytoplasm of monocytic cells, and the formation of morulae is Pathogen/Taxonomy a defining characteristic that can be used for diag- nosis (see Fig. 1). Ehrlichia spp. are gram-negative obligate intracellu- lar bacteriae with tropism for hematopoietic cells. Canine ehrlichiosis is also caused by the species E. chaffeensis (monocytic ehrlichiosis) and E. ewingii (granulocytic ehrlichiosis). Both species can also affect humans. Clinical signs of both related diseases in dogs are indistinguishable from those seen with CME. Discriminating the pathogens by serological testing may be difficult due to a substantial cross- reactivity, mainly between E. canis and E. chaffeen- sis, but also to a lesser degree to E. ewingii. To date, infections with E. chaffeensis and E. ewingii have only been diagnosed in dogs in the United States. Fig. 1 Intracytoplasmic gram-negative E. canis in monocytes forming morulae. (With kind permission of D. Otranto, Bari, Italy) ® 4 No.7 December 2010 CVBD DIGEST Canine Ehrlichiosis – from Acute Infection to Chronic Disease Common Cells most Common Primary Species name of commonly Distribution natural host(s) vector(s) disease(s) infected Worldwide, Dogs and other Primarily mono - Rhipicephalus Canine mono- primarily tropi- members of the nuclear cells sanguineus, E. canis cytic ehrlichio- cal, subtropical, family Canidae, (monocytes and Dermacentor sis (CME) and temperate cats, humans lymphocytes) variabilis climates Amblyomma USA, Europe, Human mono- Humans, deer, Monocytes, americanum, Africa, South E. chaffeensis cytic ehrlichio- horses, rodents macrophages Dermacentor and Central sis (HME) variabilis America, Korea Canine Amblyomma granulocytic Primarily ehrlichiosis americanum, USA, Africa, E. ewingii Dogs, humans neutrophils and (CGE), human Otobius Korea eosinophils granulocytic megnini ehrlichiosis (HGE) Not currently Rodents, Mononuclear Haemaphy- E. muris associated with Japan humans cells salis spp. disease Heartwater Endothelial Amblyomma Africa, E. ruminantium Ruminants disease cells spp. Caribbean Tab. 1 Summary of ehrlichial diseases and their related Ehrlichia pathogens. Co-infections of Ehrlichia with Anaplasma, Ricket t- Note: The failure of canids to completely clear sia, Babesia or Bartonella spp. occur frequently as E. canis is one important mechanism of this dogs are naturally exposed to multiple tick-borne ongoing persistence. pathogens. Little is known about the clinical out- ! come of concurrent infections with different pa- A natural reservoir of infection is maintained in both thogens. A recently reported study looked at dogs wild and domestic canids, including but not limited that were simultaneously and sequentially co-in- to, dogs, wolves, coyotes, and foxes. The failure of fected with E. canis and A. platys. Lower platelet canids to completely clear E. canis is one important counts and hematocrit were seen in co-infected an- mechanism of this ongoing persistence and should imals, along with an enhanced humoral immune re- be considered when selecting canine blood donors sponse to A. platys and a slower clearance of that from endemic regions. pathogen.2 The awareness of co-infections is impor- tant in clinical practice, as diagnosis may be compli- cated by the presence of multiple pathogens. Zoonotic Potential Transmission/Vector A few decades ago, ehrlichioses were considered to only have veterinary relevance. The first human infection with E. chaffeensis was diagnosed in 1986 Ehrlichiae have a complex life cycle involving a tick raising the awareness of Ehrlichia spp. as zoonotic vector and a mammalian host. Typically, tick nymphs pathogens.8 or larvae are infected with E. canis after feeding on a persistently infected dog. Transstadial transmission occurs to subsequent stages of the tick vector. A new Note: Nowadays E. canis, E. chaffeensis,and host is infected via salivary gland secretions during E. ewingii are all known to cause ehrlichiosis blood feeding. Transmission of the disease has also !in humans. been reported via blood transfusion. 7 ® No.7 December 2010 5 Canine Ehrlichiosis – from Acute Infection to Chronic Disease CVBD DIGEST INFO BOX 1 ANAPLASMA SPECIES The genus Ehrlichia is closely related to that of anaplasmosis in dogs and humans. Vectors of Anaplasma, both of which reside intracellularly. this pathogen are ticks of the species Ixodes. Clinical manifestation of the two resulting dis - Their reservoir consists of small wild mammals, eases is similar; however, there are notable zoo- deer and possibly birds. notic and epidemiological differences between them. A second example is Anaplasma platys (formerly Ehrlichia platys), which infects platelets. The The best-known Anaplasma species is A. phago- probable vector for A. platys is also the Brown cytophilum, formerly referred to as human Dog tick R. sanguineus, meaning the distribution granulocytic ehrlichiosis (HGE) factor, E. phago - is similar to that of E. canis, and co-infection cytophila or E. equi. It causes granulocytic with the two organisms has been reported.3,4,5,6 Anaplasma phagocytophilum (AY055469) 0.02 Anaplasma platys (AF303476) Anaplasma bovis (AB211163) Ehrlichia ruminantium (X61659) Ehrlichia chaffeensis (AF416764) Ehrlichia muris (U15527) Ehrlichia ewingii (U96436) Ehrlichia canis (CP000107) Neorickettsia sennetsu (M73225) Neorickettsia risticii (AF037211) Neorickettsia helminthoeca (U12457) Wolbachia sp. (AF088187) Fig.