Felipedia

It is unknown how clinically ill, naturally exposed cats are infected with an Ehrlichia canis-like organism. Ixodes spp ticks have been associated with several cases with Anaplasma phagocytophilum (previously Anaplasma equi) infection. Exposure to arthropods has been reported in about 30% of the cases in the literature.

The Ehrlichiae are a group of small, gram-negative, pleomorphic, obligate intracellular cocci that infect different blood cells in various animal species and in humans. There has recently been a reclassification of the family Anaplasmataceae to which the Ehrlichiae belong. According to this new classification there are two leukotrophic diseases in dogs that are caused by bacteria in the genus Ehrlichia, namely, Canine Monocytic Ehrlichiosis (caused mainly by Ehrlichia canis) and Canine Granulocytic Ehrlichiosis (caused by Ehrlichia ewingii). It should be noted that cross-reactivity and co-infection is common among the ehrlichiae. Classically, canine ehrlichiosis presents as a rather non-specific multisystemic disorder with the primary complaints being depression, lethargy, mild weight loss, vomiting, diarrhoea, and anorexia, with or without hemorrhagic tendencies. Furthermore, patients may present with uveitis and/or retinal petechiae, polymyositis, polyarthritis, and central nervous system signs. Hematologic abnormalities most commonly associated with canine ehrlichiosis include nonregenerative anemia and thrombocytopenia. Serum chemistry commonly reveals hyperglobulinemia (monoclonal or polyclonal gammopathy), hypoalbuminemia, and low albumin-globulin ratio.

Pathogenesis is unknown, but it is likely similar to dogs based on clinical and laboratory findings.

Infection occurs through salivary secretions of the tick at the attachment site during ingestion of a blood meal or through blood transfusions. If the adult Rhipicephalus sanguineus engorges on the dog during the acute stage, it can transmit the disease to other dogs for at least 155 days following detachment. Transmission by Rhipicephalus sanguineus is transstadial: the tick acquires the bacteria by feeding on an infected dog in either the larvae or nymph form and the tick transmits the disease to another dog as either the nymph or adult form. The life cycle of Ehrlichia is not yet completely understood but it is thought that it occurs in three intracellular forms. The initial bodies are small spherical structures (1-2 micrometers in diameter) which are believed to develop into larger multiple membrane-bound units known as morulae. The morulae are inclusions within the cytoplasm of the leukocyte as seen in the figures below. This morula is thought to then dissociate into small granules called elementary bodies.

After an incubation period of 8-20 days, the acute phase of infection occurs which lasts 2-4 weeks. At this time, the organism multiplies within circulating mononuclear cells and the mononuclear phagocytes within the liver, spleen, and lymph nodes. The infected cells are then transported in circulation to the rest of the body, with a predilection for the the lungs, kidneys and meninges. Cells infected with Ehrlichia spp adhere to the vascular endothelium and induce a vasculitis and subendothelial tissue infection. This subsequently leads to platelet consumption, sequestration, and destruction that results in the thrombocytopenia seen during this acute phase. Variable leukocyte counts and anemia may also develop progressively during this stage. After 6-9 weeks, dogs will either eliminate the parasite (if immunocompetent) or develop a parasitemia in which clinical signs absent to mild to severe. This stage is also characterized by variable persistence of thrombocytopenia, leukopenia, and anemia. Dogs that cannot mount an effective immune response will become chronically infected. In dogs, infection may result in either a regenerative or non-regenerative anaemia. Early in infection, acute aplastic anaemia occurs because of destruction of progenitor and proliferative cells in the bone marrow. The resulting anaemia is usually mild or absent because of the long erythrocyte lifespan. Secondary immune-mediated anaemia may occur. In the chronic phase of the disease, hemopoietic stem cell injury results in moderate to severe non-regenerative anaemia. Cats experimentally infected with Neorickettsia ristticii develop morulae in mononuclear cells and occasionally develop fever, depression, lymphadenopathy, anorexia and diarrhoea. Cats experimentally infected with Anaplasma phagocytophilum develop morulae in neutrophils and eosinophils.

Ehrlichia-like morula have been detected in mononuclear cells or neutrophils of naturally exposed cats in the USA, Kenya, France, Sweden, Brazil and Thailand.

Other cases have been diagnosed based on combination of positive Ehrlichia canis or Anaplasma phagocytophilum serology, clinical or laboratory findings consistent with ehrlichial infection, exclusion of other causes, and response to an anti-rickettsial drug. However, it is unknown whether these cats were ill from the Ehrlichia spp infection.


Ehrlichia spp infection in blood

Diff-Quick stain of Ehrlichia spp	Ehrlichia canis seen in a membrane-bound inclusions (morulae) within the cytoplasm of a monocyte (buffy coat smear, Wright stain).

Cats are usually young and both males and females have been infected. Cats infected with Anaplasma phagocytophilum have only been diagnosed in areas with Ixodes ticks.

Fever, inappetence, lethargy, weight loss, hyperesthesia or joint pain, and pale mucous membranes are the most common abnormalities. Splenomegaly, dyspnoea, uveitis, diarrhoea and lymphadenopathy are also detected in some. Concurrent diseases are rarely reported but included hemotropic Mycoplasma haemofelis infection and lymphosarcoma. Anaemia was reported for some cats; most are non-regenerative and both cats with known regenerative anaemia were infected with a hemotropic Mycoplasma spp.

Leukopenia, leukocytosis characterised neutrophilia, lymphocytosis, monocytosis, and intermittent thrombocytopenia can occur. Thrombocytopenia is the most common abnormality in cats infected with Anaplasma phagocytophilum.

Hyperglobulinemia was reported for some cats; protein electrophoresis documented polyclonal gammopathy in the cat assayed.

Epidemiologic associations have been made with ocular discharge, monoclonal gammopathy or polyarthritis in Ehrlichia canis-seropositive cats and with outdoor exposure and vomiting in Neorickettsia risticii seropositive cats.

Morulae appear as clusters of short rods in the cytoplasm of leukocytes. Determination of species by PCR or culture and electron microscopy.

Presumptive diagnosis based on the combination of disease consistent with Ehrlichia infection, exclusion of other causes of the disease syndrome, and response to antirickettsial drugs.

Some cats with suspected clinical ehrlichiosis had antibodies against E. canis and N. risticii and some had antibodies to only one of the two. Positive serological tests occur in healthy cats as well as clinically ill cats, and so a diagnosis of clinical ehrlichiosis should not be based on serological tests alone. Some cats with PCR-positive E. canis infection were negative on antibody testing. All cats proven by PCR assay to be infected by A. phagocytophilum have also been seropositive.

Clinical improvement after therapy with tetracycline, doxycycline or imidocarb dipropionate was reported for most cats.