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Page 1 of 6 An Overview of Canine Babesiosis C. Wyatt Cleveland, DVM; David S. Peterson, DVM, PhD; and Kenneth S. Latimer, DVM, PhD Class of 2002 (Cleveland), Department of Medical Microbiology and Parasitology (Peterson), and Department of Pathology (Latimer), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7388 University of Georgia Veterinary Clinical pathology Clerkship Program http://www.vet.uga.edu/vpp/clerk/Cleveland/ Introduction Babesia sp. are protozoal organisms that parasitize erythrocytes, causing anemia in the host. Many different species exist with varying host specificity (5). B. canis and B. gibsoni are two organisms commonly known to infect dogs. Both organisms have Ixodid tick vectors and are found throughout Asia, Africa, Europe, the Middle East, and North America, with B. canis being more prevalent (11). Infection by B. gibsoni is increasing in frequency, particularly in North America, although no specific species of ticks in this region have been proven to transmit the disease. However, Rhipicephalus sanguineus and Dermacentor variabilis are believed to be potential vectors of disease (2). There also is evidence that some direct animal-to-animal transmission may occur, as when an infected dog with oral abrasions bites a naïve dog. Kennel settings with poor tick surveillance and control are at a higher risk for housed animals to develop babesiosis (2). Developments in genetic technology have contributed to the delineation between species and subspecies of Babesia organisms. Three subspecies of B. canis have been identified using RFLP (restriction fragment length polymorphism) analysis of PCR (polymerase chain reaction) amplified small subunit ribosomal RNA. These subspecies have been named Babesia canis canis, B. canis vogeli, and B. canis rossi (3). Analysis of the DNA from two organisms causing babesiosis in North America and Asia, once believed to be B. gibsoni, has shown that the two organisms belong to different species (12). An Overview of Canine Babesiosis University of Georgia Page 2 of 6 Life Cycle The typical life cycle of Babesia spp. is presented in Figure 3. Following attachment of an infected tick, Babesia spp. trophozoites are released into the blood, infecting erythrocytes. Within the erythrocytes, the parasite multiplies by binary fission, an asexual form of schizogony. Naïve ticks attach to the dog and become infected with Babesia spp. when they ingest a blood meal. Fig. 3. Typical life cycle of Babesia spp. (Gardiner CH, Fayer R, Dubey JP: An Atlas of Protozoan Parasites in Animal Tissues. Washington, DC: USDA/ARS, Agriculture Handbook #651, p. 70). Clinical Findings Cases of canine babesiosis may present with a wide variation of severity of clinical signs, ranging from a hyperacute, shock-associated, hemolytic crisis to an inapparent, subclinical infection (11). Dogs typically present with the acute form of babesiosis, which is characterized by general findings such as pyrexia, weakness, mucous membrane pallor, depression, lymphadenopathy, An Overview of Canine Babesiosis University of Georgia Page 3 of 6 splenomegaly, and general malaise (2). Laboratory studies may document anemia, thrombocytopenia, hypoalbuminemia, and bilirubinuria (5,2,11). Initially, the anemia is normocytic, normochromic, and nonregenerative, but later develops into a macrocytic, hypochromic, regenerative anemia with reticulocytosis (5,11). The anemia is hypochromic because the reticulocytes have not yet formed their adult concentrations of hemoglobin. Diagnosis Babesiosis has been classically diagnosed by demonstrating intraerythrocytic trophozoites on a blood smear. Giemsa, Romanowsky, Field's, and modified Wright's stains are suitable for this purpose. B. canis generally appears as a paired, piriform figure measuring 5 x 2-3 micrometers (Fig. 1). B. gibsoni is usually smaller (measuring 1.9 x 1.2 micrometers), singular, and signet ring shaped (Fig. 2). Sampling of blood from a capillary bed (from the ear, for instance) yields more diagnostic smears than sampling blood from a larger vein (8). Isolation of infected erythrocytes with a Percoll gradient can be used to enhance the recovery and identification of parasitized erythrocytes (4). The degree of parasitemia is very low with B. canis, but may range from 2% to 6% (or greater) of the erythrocyte population with B. gibsoni (7). Fig. 1. Blood smear, dog, Wright’s stain. Large, slightly irregular piroplasms of Babesia canis are present within erythrocytes. Fig. 2. Blood smear, dog, Wright’s stain. Inclusions of Babesia gibsoni are smaller, ring-shaped, and more numerous than those of B. canis. Other diagnostic tests are becoming increasingly available to diagnose babesiosis. These techniques include FA (fluorescent antibody) staining of the organism and commercially produced ELISA tests (for B. canis only) (2). Serologic testing in the diagnosis of babesiosis has limitations. A positive test result is dependent on an antibody response by the host, which may take up to An Overview of Canine Babesiosis University of Georgia Page 4 of 6 ten days to develop (4). Probing for genetic markers of PCR amplified products from the parasite’s nucleic acid is both sensitive and specific for disease diagnosis; however, this technique is not yet currently available for routine testing (2). Pathophysiology Research studies have shown that the initial phase of infection with Babesia sp. causes systemic hypotension. A compensatory fluid shift from the interstitial to the intravascular compartment is responsible for the immediate decline in hematocrit and increase in plasma volume (9,10). Systemic hypotension also favors interaction of parasitized erythrocytes with endothelial cell membranes, allowing local areas of proliferation of the organism (9). In addition, the acute phase response stimulated within the host upregulates ligands on the surface of endothelial cells, thereby enhancing aggregation of red blood cells. A consumptive coagulopathy, attributed to a soluble plasma antigen (SPA) produced by Babesia spp., is triggered in foci of erythrocyte aggregation and organism proliferation. Vaccination of naïve individuals with SPA will inhibit development of clinical signs upon challenge with Babesia spp., but it will not affect the development of parasitemia (9,10). The major mechanism of tissue injury caused by Babesia spp. is ischemia (hypoxic damage) (6). Erythrocytes are retained and destroyed in massive quantities in the splenic sinusoids (10). Quantities of these parasitized erythrocytes can be found in other capillary beds throughout the body. Serious hepatic, renal, pulmonary, cardiac, splenic, and intracranial pathology can ensue (5,11). Treatment and Prevention Current chemotherapeutic agents used to treat canine babesiosis are incapable of completely eliminating the disease; they only are capable of limiting mortality and the severity of clinical signs (2). Two injections of Imidocarb diproprionate at 5.0 to 6.6 mg/kg given subcutaneously or intramuscularly at an interval of 2 to 3 weeks are reputed to be effective (8). Another possible treatment is a single intramuscular injection of Dimenazene aceturate at a dosage of 5 mg/kg (2). For a more exhaustive list of potential antiparasitic drugs, consult table 77-3 in Greene's Infectious Diseases of the Dog and Cat (11). Supportive therapy such as intravenous fluids and blood transfusions should be employed when necessary. Owners should be aware that animals that have survived babesiosis remain subclinically infected. These dogs may suffer a relapse of disease in the future or serve as point sources for the further spread of disease in a given area (2). In addition, dogs that have recovered from babesiosis should never be used as donors for blood transfusions because the recipients may develop the disease. An Overview of Canine Babesiosis University of Georgia Page 5 of 6 Currently, an effective vaccine is not commercially available to protect dogs against babesiosis. The previously mentioned vaccine against the soluble plasma antigen produced by Babesia organisms limits the clinical signs of disease, but does not affect the development of parasitemia. This vaccine is not available in the United States (11). Refrences 1. Ano H, Makimura S, Harasawa R. 2001. Detection of Babesia species from infected dog blood by polymerase chain reaction. J Vet Med Sci 63:111-113. 2. Birkenheuer AJ, Levy MG, Savary KC, et al.1999. Babesia gibsoni infections in dogs from North Carolina. J Am Anim Hosp Assoc 35:125-128. 3. Carret C, Walas F, Garcy B, et al. 1999. Babesia canis canis, Babesia canis vogeli, Babesia canis rossi: Differentiation of the three subspecies by a restriction fragment length polymorphism analysis on amplified small subunit ribosomal RNA genes. J Eukaryot Microbiol 46:298-303. 4. Comazzi S, Paltrinieri S, Manfredi MT, Agnes F. 1999. Diagnosis of canine Babesiosis by Percoll gradient separation of parasitized erythrocytes. J Vet Diagn Invest 11:102-104. 5. Gardiner CH, Fayer R, Dubey JP. 1988. An Atlas of Protozoan Parasites in Animal Tissues. U. S. Department of Agriculture, Agriculture Handbook No. 651, pp 70-71. 6. Leisewitz AL, Jacobson LS, de Morais HS, Reyers F. 2001. The mixed acidbase disturbances of severe canine Babesiosis. J Vet Intern Med 14:445-452. 7. Meinkoth JH, Kocan AA, Loud SD, Lorenz MD. 2002. Clinical and hematologic effects of experimental infection of dogs with recently identified Babesia gibsonilike isolates from Oklahoma. J Am Vet Med Assoc 220:185-189. 8. Perkins SC. 2000. Babesia and the pet travel scheme. Vet Rec 147:460. 9. Schetters TP, Kleuskens J, Scholtes N, Gorenflot A. 1998. Parasite localization and dissemination in the Babesia-infected host. Ann Trop Med Parasitol 92:513-519. 10. Schetters TP, Kleuskens J, Scholtes, et al. 1997. Vaccination of dogs against Babesia canis infection. Vet 11. Parasitol 73 :35-41. 11. Taboada J. 1998. Babesiosis. In: Greene CE (ed), Infectious Diseases of the Dog and Cat. WB Saunders, Philadelphia, PA, pp 473-481. An Overview of Canine Babesiosis University of Georgia Page 6 of 6 12. Zahler M, Rinder H, Zweygarth E, et al. 2000. Babesia gibsoni of dogs from North America and Asia belong to different species. Parasitology 120:365-369. An Overview of Canine Babesiosis University of Georgia