Professor of Veterinary Medicine, School of Veterinary Medicine, Hebrew University, Rehovot, Israel
Ehrlichial organisms are obligatory intracellular bacteria of the order Rickettsiales. Recently, the nomenclature of organisms in this order was revised. Ehrlichioses are caused by organisms of the genera Ehrlichia, Anaplasma and Neorickettsia. Ehrlichia canis and E. chaffeensis infect monocytes, Anaplasma phagocytophilum and E. ewingii infect granulocytes, and A. platys infects platelets. The significance of the ehrlichioses has been highlighted since the discovery and emergence of the human ehrlichioses caused by E. chaffeensis, E. ewingii, and A. phagocytophilum. Most ehrlichioses are tick borne diseases.
Etiology of Canine Monocytic Ehrlichiosis
Ehrlichia canis, the etiologic agent of canine monocytic ehrlichiosis, has been recognized worldwide as an important canine infectious agent. Ehrlihcia canis infection has been reported from Africa, Asia, America, and Europe. Autochtonous (non-imported) cases of Ehrlichia canis in Europe have been reported mostly from Spain, Portugal, Southern France, Corsica, Italy including Sardinia, and Greece.
Ehrlichia canis morulae found in monocytes and macrophages are a "microcolony" of bacteria surrounded by a membranous vacuole. Morulae may contain 100 or more ehrlichiae resembling elementary bodies of chlamydiae. E. canis is transmitted by the three-host tick Rhipicephalus sanguineus. The pathogenesis of the disease involves an incubation period of 8-20 days, followed by 3 consecutive phases: an acute phase which lasts 1-4 weeks, a subclinical phase which may last from months to years, and a chronic phase. Not all infected dogs develop the chronic severe form of the disease and the conditions that lead to the development of this stage are unknown.
The clinical presentation of the disease caused by E. canis may vary, and the clinical signs most frequently reported are depression, lethargy, anorexia, fever, lymphadenomegaly, splenomegaly and hemorrhages (mainly petechiae, ecchymoses and epistaxis). Ocular manifestations of canine ehrlichiosis include anterior uveitis, keratoconjunctivitis, hyphema, glaucoma, chorioretinitis and retinal detachment.
Polyarthritis and polymyositis have been described in E. canis infection. The neurological abnormalities found in canine ehrlichiosis are associated with vasculitis, meningoencephalitis, lymphocytic infiltration of the central and peripheral nervous system or hemorrhages. Renal pathology has been associated with canine ehrlichiosis due to immune-complex glomerulonephritis.
Ehrlichia canis infection has been termed by some clinicians as the "silent killer". It is often inapparent during the early and sub-clinical stages of infection. When the disease is diagnosed in the chronic stage, it may be too late to save the canine patient as treatment may not be helpful in reversing the severe pancytopenia and immune mediated phenomena associated with this disease.
Laboratory abnormalities in canine monocytic ehrlichiosis include hematologic and serum biochemistry changes. Thrombocytopenia is the most frequent hematological abnormality occurring in more than 90% of cases. Anemia, usually non-regenerative normocytic and normochromic, is another common finding in this disease. In addition, mild to severe leucopenia is a frequent abnormality. Hyperglobulinemia, hypoalbuminemia and mild elevation of alkaline phosphatase (ALP) and alanine aminotransferase (ALT) activities are frequently reported in ehrlichiosis. Dogs in the chronic severe stage of the disease may develop severe pancytopenia as their bone marrow becomes hypocellular. The prognosis of these chronically ill dogs is grave.
Immune-mediated responses play a major role in the pathogenesis of E. canis infection. Anti-platelets antibodies (APA) have been demonstrated less than a week after experimental E. canis infection of dogs. Platelet aggregation abnormalities, anti-nuclear antibodies (ANA), RBC autoagglutination with positive Coombs' test, and circulating immune-complexes have been shown in infected dogs and are associated with the disease process.
The decrease in platelets during canine ehrlichiosis is probably a result of several mechanisms. These mechanisms include increased consumption with vascular endothelial changes, platelet sequestration and pooling in the spleen, thrombophagocytosis with immunological destruction, a decrease in the half life time of circulating platelets possibly due to opsonization with antibodies, and production impairment due to bone marrow destruction and hypocellularity. In addition to the decrease in circulating platelet number, platelets dysfunction (thrombocytopathy) has also been implicating as an additional factor contributing to lack of platelet functionality in canine monocytic ehrlichiosis.
Co-infections with hemoparasites or other infectious agents are often detected in conjunction with canine ehrlichiosis. Hepatozoon canis and Babesia canis vogeli are transmitted by the same vector tick, R. sanguineus. In addition, Leishmania infantum is another common co-infecting protozoal pathogen whose vector, phlebotomine sand flies are often found in the same sub-tropical climate conditions and ecological niches, as R. sanguineus ticks transmitting E. canis infection.
The laboratory diagnosis of E. canis infection includes evaluation of the hemogram and serum biochemistry panel. The detection of morulae in monocytes in stained blood smears is rare and can not serve as a main diagnostic option.
Anti-E. canis antibodies can be detected in dogs infected with this pathogen and persist long after recovery from the disease. Serum antibodies are thought not to be protective or play an important role in eliminating this intracellular infection. Serology is indicative of exposure to E. canis and may often be helpful in ruling out progressive infection. Antibodies may not be detectable during the early stage of infection. However, seropositive dogs with previous exposure to the pathogen may also present due to other urgent disease conditions. Several commercial "in house" test kits are available for E. canis infection in addition to the laboratory indirect fluorescent antibody test (IFAT) which is often considered the golden standard for serology. Some serologic cross-reactivity between different Ehrlichia species may occur. Anti-E. canis antibodies have been reported to cross-react with E. chaffeensis, A. phagocytophilum & E. ewingii but not with A. platys.
Detection of the presence of E. canis DNA by the polymerase chain reaction (PCR) is highly sensitive and specific and has become a popular assay in research of this disease as well as in its clinical diagnosis.
Treatment and Prevention
Ehrlichial organisms are susceptible to tetracyclines, and doxycycline is most widely used for treatment of infection. Doxycycline is very efficient in clearing rickettsemia in acute cases of E. canis infection. Clinical recovery is noticed within 48-72 hours, yet treatment should be commenced for 3 weeks, as some dogs may remain carriers when shorter treatments are applied.
Treatment with the injectable drug imidocarb dipropionate has been shown to be ineffective in eliminating E. canis in some cases. However, it is often used in combination with doxycyline when Babesia co-infection is suspected.
The control of tick infestation by topical treatment with acaricidas and environmental eradication of ticks is recommended for the prevention of E. canis infection.
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