Clinical and Therapeutic Aspects of Canine Ehrlichiosis
Angel Sainz, DVM, PhD
College of Veterinary Medicine, Complutense University of Madrid
Many changes have occurred in the last several years regarding knowledge about Ehrlichia spp. infections in man and animals. Advanced molecular biology techniques have provided evidence of the existence of new species of Ehrlichia and of other similar genus (Anaplasma or Neorickettsia). Furthermore, until very recently, each species of Ehrlichia was considered to be localized geographically and to infect only one specie of animal (or man). This idea has been altered with the existence of the same species of Ehrlichia in widely divergent latitudes and capable of infecting not only man but also distinct animal species.
ETIOLOGY AND EPIDEMIOLOGY
Canine ehrlichiosis is a rickettsial tick-borne disease, which is caused by different species of the genus Ehrlichia. A reorganization of the taxonomy of the genus Ehrlichia and closely related genus has recently been suggested. Currently, the genus Ehrlichia is considered to include only E.canis, E.chaffeensis, E.ewingii, and E.muris. Additionally, the previously named Cowdria ruminantum is now considered a member of the genus Ehrlichia. The species E.platys, E.equi, E.phagocytophila, as well as the human granulocytic ehrlichiosis (HGE) agent are considered to be members of the genus Anaplasma while E.risticii has been integrated into the genus Neorickettsia.
Therefore, strictly speaking, the species of Ehrlichia that are currently able to infect dogs are E.canis, E.chaffeesis (both of which cause monocytic ehrlichiosis) and E.ewingii (which infects granulocytic cells). E.canis is considered to be the most important Ehrlichia spp. able to infect dogs.
When considering transmission, in the case of E. canis, there exists only one known vector: Rhipicephalus sanguineus. Amblyomma americanum is the known vector for E. chaffeensis as well as E. ewingii.
Blood transfusions coming from dogs infected with Ehrlichia spp. could potentially cause the disease in receptor dogs.
Three stages are classically distinguished: acute, subclinical, and chronic. In clinical practice, these stages are not always clearly differentiated.
During the acute phase, which coincides with the spread of the causal agent, typical signs include: apathy, anorexia, fever, weight loss, hemorrhages, hepatomegalia, splenomegalia, and lymphadenopathy. If the disease is not diagnosed in the acute phase, it then progresses to the subclinical phase in which asymptomatic dogs are discovered only through variations in laboratory tests.
As the illness continues, it can progress to the chronic stage which may range from a slightly affected state of health to a very severe clinical picture. Clinical signs caused by the different Ehrlichia spp. are very similar. These same signs are also similar to those described in human ehrlichiosis.
Generally, the most frequent clinical signs are quite nonspecific: fever, weight loss, lethargy, and anorexia. In our experience, approximately 40% of the cases are affected with lymphadenopathy. Hepatomegalia and splenomegalia can also be observed in some cases.
Hemorrhages are also frequently detected in dogs with ehrlichiosis. Epistaxis is the most frequent type of hemorrhage observed.
Many ocular signs are found in dogs infected by Ehrlichia spp. Anterior uveitis, which is usually bilateral, is the most typical ocular sign, and can be accompanied by glaucoma. Different retinal pathologies can be present: chorioretinitis, retinal detachment, retinal hemorrhage.
Polyarthritis and polymiositis can be present, probably as a result of an immune-mediated response. Polyarthritis seems to be particularly frequent in dogs infected by E.ewingii.
There are many neurological signs related to ehrlichiosis, most of them due to meningoencephalitis/vasculitis. Thus, canine ehrlichiosis should be ruled out in patients with both neurological and systemic signs.
With a lesser frequency, renal failure (due to immune-mediated glomerulonephritis) as well as reproductive disorders (infertility and abortions) is detected.
A wide variety of cutaneous signs are associated with ehrlichiosis, although its pathogenesis is still unknown. Deep pyoderma in the German shepherd has been suggested to be associated with ehrlichiosis.
The severity of clinical signs seems to be related to the virulence of the strain and to the immune response of the dog during the course of the disease. The humoral immune response is usually very important but incapable of eliminating the causal agent and thus, can be responsible of the development of certain lesions, such as glomerulonephritis or polyarthritis. On the other hand, a good cellular response can result in the clearance of the infection without treatment. These differences in the immune response may be related to the breed; in fact, some breeds, such as the German shepherd, present severe clinical signs more frequently than other breeds.
Thrombocytopenia is the most typical laboratory finding detected in dogs with ehrlichiosis, occurring in approximately 80% of the animals. Anemia (generally non regenerative), and, with less frequency, leukopenia can be present.
Hyperproteinemia (usually polyclonal) due to the increase of the beta and gamma globulins is a very common laboratory finding. Furthermore, hypoalbuminemia associated with proteinuria may be observed. Occasionally, blood analysis may show alterations caused by renal and/or hepatic failure.
There are still some limitations for the clinician to reach an exact diagnosis of ehrlichiosis. Detection of inclusion bodies compatible with Ehrlichia in blood smears is difficult. It is for that reason that the IFA test and other serological diagnostic tools are nowadays the techniques routinely used. When interpreting antibody titers for ehrlichiosis diagnosis, cross-reactions between E.canis and other Ehrlichia spp. (such as E.chafffensis and E.ewingii) should be considered. In addition, antibody titers may remain high during long periods of time after treatment.
Western-blot or PCR are other techniques particularly useful in doubtful cases and to distinguish between infections of different species of Ehrlichia.
Many diseases must be ruled out, given the variety of clinical signs of ehrlichiosis. Many of these clinical signs (epistaxis, uveitis, weight loss, lymphadenopathy, hepatomegalia, splenomegalia) and the laboratory findings, especially hyperproteinemia, may also be present in canine leishmaniosis. In dogs with such clinical sings living in endemic areas, differential diagnosis may include at least both diseases.
Nevertheless, the frequent concurrence of ehrlichiosis with other tick-borne diseases, such as babesiosis or hepatozoonosis, and with certain parasitic diseases, such as leishmaniosis, must be beard in mind.
Doxycycline is the drug of choice in the treatment of ehrlichiosis. There are many different therapeutic protocols described in the literature. Our protocol is 10 mg/kg/day of doxycycline for 28 days. In our experience, using shorter protocols may relieve the signs initially, but later, they may relapse. In one study in which doxycycline was administered for seven days, E.canis was isolated after treatment. Whether the treatments completely clear the infection needs to be clarified. This is specially taking into account the persistence of antibody titers for long periods after treatment.
Imidocarb dipropionate seems to be effective at the dose of 5 mg/kg SQ (in a single injection or two injections 15 days apart), even though some in vitro studies have shown that E.canis may be resistant to this drug. Imidocarb dipropionate is specially indicated in dogs coinfected with Babesia spp. as well as in puppies.
In clinical practice, doxycycline and imidocarb are often used in combination for particularly severe cases. In our experience, the only significant differences when comparing the therapeutic efficacy when using either of the two drugs solely, or combined, was that in dogs treated only with imidocarb, the normalization of platelets count and of the proteinemia was slower.
It has also been proposed the use of enrofloxacine for the treatment of canine ehrlichiosis, at a dose of 5 mg/kg every 24 hours during 15 days. Nevertheless, different studies have showed the lack of response of dogs with ehrlichiosis to this drug.
It is usually possible to obtain a good treatment response with specific therapy without any further supportive therapy. However, blood transfusions are indicated in cases with severe anemia. Clinically, it is often difficult to differentiate an autoimmune thrombocytopenia from ehrlichiosis. For this reason, and also due to the immune-mediated aspect of the thrombcytopenia in ehrlichiosis, in acute cases, the combination of doxycycline and corticoids may be considered.
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Angel Sainz, DVM, PhD