Hepatozoon Canis Infection in Dogs: A Brief Review

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Hepatozoon canis is a protozoan from the phylum Apicomplexa, detected for the first time in the blood of dogs in India and determined as Leukocytozoon canis (James, 1905). All Hepatozoon species have the same life cycle: gametogony and sporogony in the definitive host (a bloodsucking invertebrate) and schizogony followed by formation of gametes in the intermediate host (a vertebrate). The definitive host of Hepatozoon canis is the brown dog tick
Rhipicephalus sanguineus, and the intermediate hosts are dogs and wild canids. Because of the long time interval between becoming infected and developing illness, this disease is not just seen during the tick season, but all year-round. This parasite infects dogs, coyotes, and fox.
Hepatozoon infection in the dog, caused by Hepatozoon canis is widely spread in South Europe (Kontos et al., 1991), Africa (Ezekolli et al., 1983), Аsia (Murata et al., 1991), and South Аmerica (O’ Dwyer et al., 2001).

Life Cycle of H. canis
The vector tick Rhipicephalus sanguineus becomes infected in the nymph stage by ingesting blood of a dog, possessing Hepatozoon canis gamonts located within Leukocytes. The dog becomes infected with Hepatozoon canis by eating ticks or parts of tick body containing oocysts Craig (1990). H. canis is freed and migrates through the dog’s intestine to the liver, spleen, lymph nodes, heart, and muscles. When a tick bites the dog, the tick takes in the white
blood cells. H. canis reproduces in the tick, and when eaten, the tick will infect another dog. Inside the cells of these organs, the parasite reproduces by dividing and eventually ruptures the cell. The parasite then moves into different cells to continue the process of maturing and rupturing cells. The damage caused by the rupturing of these cells causes the severe muscle pain. Eventually, the more mature forms enter particular white blood cells. Numerous studies
have demonstrated that the primary site for schizogony, merozoite penetration in leukocytes and their development to gamonts is the bone marrow (Baneth, 2006). Schizonts are detected in the lungs, heart, skeletal muscles, liver, spleen, lymph nodes.

Clinical Signs
The infections with Hepatozoon canis in dogs could occur in three forms: subclinical – probably the commonest one; acute developing about one week before the death and chronic – with phases of clinical expression and remission (Barton et al., 1985). The most frequently observed clinical signs were anaemia, emaciation and intermittent fever on many occasions, cachexia, depression, muscle hyperaesthesia, purulent conjunctivitis and rhinitis. Less frequently, diarrhoea (often bloody), anorexia, paraparesis and paraparalysis were observed.

Clinico-pathologic Features
Generally mature neutrophilia is a consistent feature of Hepatozoonosis. Serum alkaline phosphatase levels increase with concurrent decrease in serum protein and albumin levels (Vincent et al., 1997). Radiographs reveal extensive periosteal bone proliferation (Drost et al., 2003). Lesions occur more frequently and more severely on the proximal bones of the limbs.

Pathological Findings
Muscle atrophy is most frequent and most visible in the temporal region, anaemia, mildly icteric mucous coats and slightly enlarged spleen and liver are also observed. Congestive changes in the lungs and the gastric mucous coat, lymphadenopathy and pale kidneys are also observed. Histologically, schizonts are observed in the skeletal and cardiac muscles, lymph nodes, the spleen, liver, kidneys etc. (Gevrey, 1993 and Baneth et al., 1995). In muscles, they form clusters of neutrophils that are probably the cause for the pain, fever and periosteal proliferations. These proliferations are localized at the sites of attachment of muscles to the vertebra, pelvis, radius, ulna, humerus, femur, fibula and tibia. Bone lesions are not present in all affected animals, but are more common in young dogs (less than 1 year of age) (Craig, 1990).

Diagnosis
A diagnosis of H. canis infection is made by microscopically examining the blood and finding the parasite in particular white blood cells such as neutrophils. Gamonts are with an oval shape, dimensions of 8-12/3-6 μm (Baneth et al., 1995) and are detected in the cytoplasm of neutrophils and rarely in that of monocytes. Finding the parasite in a muscle biopsy is a very reliable method of diagnosing this disease. Usually, it is normocytic, normochromic, regenerative type of anaemia is observed. Touch impression preparations from lymph nodes, spleen, and bone marrow reveals schizonts.
Serological Test
Indirect immunofluorescent antibody test (IFAT) and ELISA are applied. Previously prepared antigen of Hepatozoon canis gamonts is used (Heerden et al., 1995 and Baneth et al., 2002).

Therapy and Prevention
Imodocarb dipropionate at a dose rate of 5-6 mg/kg, subcutaneously or intramuscularly at 14- day intervals until the disappearance of gamonts in blood, but in severe infections, an 8-week or longer treatment could be necessitated (Baneth et al., 1997). Imidocarb dipropionate is combined with Doxycycline at daily oral doses of 10 mg/kg for 21 days. The prevention of Hepatozoon canis infection is based upon the effective control of ticks on dogs and in the
environment. This is done by application of various acaricides.

References
Barton CL, Russo EA, Craig TM, Green RW. 1985. Canine hepatozoonosis: a retrospective study of 15 naturally occurring cases. Journal of the American Animal Association, 21: 125-134.
Baneth G, Gonen L, Strauss-Ayali D, Shkap V. 2002. ELISA for Hepatozoon canis antibodies -evaluation of experimentally and naturally infected dogs. Veterinary Clinical Pathology. 31: 202.
Van Heerden J, Mills MG, Van Vuuren MJ, Kelly PJ, Dreyer M J. 1995. An investigation into the health status and diseases of wild dogs (Lycaon pictus) in the Kruger National Park. Journal of the South African Veterinary Association, 66: 18-27.
Baneth G, Weigler B. 1997. Retrospective case-control study of hepatozoonosis in dogs in Israel. Journal of Veterinary Internal Medicine, 11: 365-370.
Baneth G. 2006. Hepatozoonosis. In: Infectious diseases of the dog and cat. 3nd ed., C. E. Greene (ed.) W. B. Saunders, Philadelphia, Pensylvania, pp. 698-705.
Drost W T, Cummings CA, Mathew JS, Panciera RJ, Ko JCH. 2003. Determination of time of onset and location of early skeletal lesions in young dogs experimentally infected with Hepatozoon americanum using bone scintigraphy. Vet. Radiol. Ultrasound 44:86–91.
Gevrey J. 1993. Hepatozoonose canine. Recueil de Medecine Veterinaire. 169: 451- 455.
James SP. On parasite found in the white corpuscules of the blood of dogs. 1905. Scientific Memoirs by the Officers of the Medical and Sanitary Departments of the Government of India. 14: 1-12.
Kontos V and Koutinas A. 1991. Canine hepatozoonosis: a review of 11 naturally occurring cases. European Journal of Companion Animal Practice. 2:26-30.
Ezekolli CD, Ogunkoya AB, Abdullahi R, Tekedec LB, Sannusi A, Ilemobade AA. 1983. Clinical and epidemiological studies on canine hepatozoonosis in Zaria, Nigeria. Journal of Small Animal Practice. 24: 455-460.
Murata T, Shiramizu K, Hara Y, Shimoda K, Nakama S. 1991. First case of Hepatozoon canis infection in a dog in Japan. Journal of Veterinary Medical Science, 53: 1097-1099.
O’Dwyer LH, Massard CL, Pereira de Souza JC. 2001. Hepatozoon canis infection associated with dog ticks of rural areas of Rio de Janeiro State, Brazil. Veterinary Parasitology.94: 143-150. Craig TM. 1990. Hepatozoonosis. In: Infectious diseases of the dog and cat. First ed., C. E. Greene (ed.) W. B.Saunders, Philadelphia, Pensylvania, 778- 785.
Vincent-Johnson NA, MacIntire DK, Baneth G. 1997. Canine hepatozoonosis: pathophysiology, diagnosis and treatment. Compend. Cont.Ed. Pract. Vet. 19: 51–65.

Contributors

K.R. Anjan Kumar1*, B.R. Naveen2, Mohankumar Shettar2, H.R.Azeemulla2, G.R. Praveen
Kumar3

Neha Veterinary Clinic and Consultancy Services, Yelahanka New Town, Bangalore-560064
1 Consulting Pathologist, Neha Veterinary Clinic, Yelahanka New Town, Bangalore-560064
2 Veterinary Clinician, Neha Veterinary Clinic, Yelahanka New town, Bangalore-560064
3 M.V.Sc Scholar, Veterinary College, Hebbal, Bangalore-24

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