Introduction
Ehrlichia canis is the causative agent of canine monocytic ehrlichiosis which is an important canine infectious disease in Africa, Asia, America, and Europe. Ehrlichia canis is transmitted by the three-host tick Rhipicephalus sanguineus. A recent study has shown that transmission of E. canis by R. sanguineus starts within 3 hours after the tick's attachment to the canine host. The pathogenesis of the disease involves an incubation period of 8–20 days, followed by three 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 assumed to be associated with individual susceptibility and breed predisposition. Ehrlichia canis can be transmitted by blood transfusion and it is recommended to screen for its presence in the blood of donor dogs.
Clinical Findings
The most frequently reported clinical signs of canine monocytic ehrlichiosis are 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 also been described in E. canis infection. The neurological abnormalities found in canine ehrlichiosis are associated with vasculitis, meningoencephalitis, and lymphocytic infiltration of the central and peripheral nervous system or hemorrhages. Ehrlichia canis infection has been termed the "silent killer" as its infection is often not apparent during the early and subclinical stages of infection, and 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 caused by bone marrow suppression 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 nonregenerative 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 and 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 have been demonstrated less than a week after experimental E. canis infection of dogs. Platelet aggregation abnormalities, anti-nuclear antibodies, RBC autoagglutination with positive Coombs' test, and circulating immune complexes have been described in infected dogs and are associated with the disease process.
The decrease in platelets during canine ehrlichiosis is 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 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 implicated as an additional factor contributing to lack of platelet functionality in canine monocytic ehrlichiosis.
Diagnosis
The laboratory diagnosis of canine monocytic ehrlichiosis includes evaluation of the hemogram and serum biochemistry panel. Specific diagnosis of infection includes:
1. PCR: Detection of the presence of E. canis DNA by PCR is highly sensitive and specific and has become the most useful diagnostic test for the confirmation of canine monocytic ehrlichiosis. Several conventional and real-time PCR protocols have been described for E. canis and the assay can be performed on blood or tissue including the spleen and bone.
2. Serology: Anti-E. canis antibodies 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. Furthermore, seropositive dogs with previous exposure to the pathogen may also present in the clinic due to other urgent disease conditions.
3. Cytology: E. canis morulae found in monocytes and macrophages are a "microcolony" of bacteria surrounded by a membranous vacuole. Morulae may contain 100 or more ehrlichial organisms. The detection of morulae in monocytes in stained blood smears is rare and cannot serve as a main diagnostic option.
Treatment and Prevention
Ehrlichia canis is susceptible to doxycycline which is highly efficient in clearing rickettsemia in acute cases of E. canis infection. Clinical recovery is noticed within 48–72 hours, yet treatment should be continued 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 totally eliminating E. canis. However, it is often used in combination with doxycycline when Babesia co-infection is suspected. The control of tick infestation by topical treatment with acaricidals and environmental eradication of ticks is recommended for the prevention of E. canis. No vaccines for the disease are currently available; however, a candidate attenuated-live vaccine has been recently evaluated for preventing the disease.
References
1. Baneth G, Harrus S, Ohnona FS, Schlesinger Y. Longitudinal quantification of Ehrlichia canis in experimental infection with comparison to natural infection. Vet Microbiol. 2009;136:321–325.
2. Cohn LA. Ehrlichiosis and related infections. Vet Clin North Am Small Anim Pract. 2003;33:863–884.
3. Frank JR, Breitschwerdt EB. A retrospective study of ehrlichiosis in 62 dogs from North Carolina and Virginia. J Vet Intern Med. 1999;13:194–201.
4. Gaunt S, Beall M, Stillman B, Lorentzen L, Diniz P, Chandrashekar R, Breitschwerdt E. Experimental infection and co-infection of dogs with Anaplasma platys and Ehrlichia canis: hematologic, serologic and molecular findings. Parasit Vectors. 2010;3:33.
5. Harrus S, Kass PH, Klement E, Waner T. Canine monocytic ehrlichiosis: a retrospective study of 100 cases, and an epidemiological investigation of prognostic indicators for the disease. Vet Rec. 1997;141:360–363.
6. Harrus S, Waner T. Diagnosis of canine monocytotropic ehrlichiosis (Ehrlichia canis): an overview. Vet J. 2011;187:292–296.
7. Little SE. Ehrlichiosis and anaplasmosis in dogs and cats. Vet Clin North Am Small Anim Pract. 2010;40:1121–1140.
8. Rudoler N, Baneth G, Eyal O, van Straten M, Harrus S. Evaluation of an attenuated strain of Ehrlichia canis as a vaccine for canine monocytic ehrlichiosis. Vaccine. 2012;31:226–233.