Hepatozoonosis

Canine hepatozoonosis is a tick-borne disease caused by protozoa of the genus Apicomplexa. Two different species of Hepatozoon have been identified, H. canis responsible for the disease in Europe and in South America and H. americanum which is spread in the south of the United States. In Italy, H. canis has been reported in the central-southern regions of the country (Fig. 1).

Unlike other tick-borne diseases in which the parasite is inoculated during the blood meal in the wound caused by the tick, Hepatozoon parasitosis is the result of the dog ingesting the tick, or parts of it, containing Hepatozoon oocysts. The sporozoites released by the oocysts cross the intestinal wall, colonise monocytes and spread in the blood stream inside granulocytes or via the lymphatic system.

A merogonic stage takes place in the tissues of the dog, followed by gametogony in leucocytes. The tick, which is the definitive host, is infected by feeding on the blood of a dog carrying the parasite. The gamonts of Hepatozoon in the intestine of the tick undergo gametogenesis followed by fertilisation and sporogony in the haemocoel.

The main vector of Hepatozoon is Rhipicephalus sanguineus, although in some regions of the United States Amblyomma maculatum can also act as a vector for H. americanum.  In both species of tick, transmission of Hepatozoon is trans-stadial from nymph to tick. H. canis predominantly affects the blood-lymphatic system and the organs involved in haematopoiesis (in particular, bone marrow, spleen and lymph nodes). Its pathogenic power is limited and it is usually found incidentally. Overtly manifested clinical forms are often found in association with other tick-borne diseases. The severity of the symptoms seems to be associated with the parasitic load in the blood. Asymptomatic or pauci-symptomatic subjects usually have a low percentage of affected neutrophils (1-5%). When almost 100% of the neutrophils are affected, the most frequent clinical signs are fever, lethargy, weight loss, anaemia, leucocytosis and hypergammaglobulinaemia. Some subjects may develop hepatitis, pneumonia or glomerulonephritis. The most severe clinical forms are those that occur in animals with other concomitant infections such as Parvovirus, Ehrlichia canis and Leishmania infantum or which are manifested as a consequence of immunosuppressive treatment.

Differently from H. canis, H. americanum (which has been reported in Texas, where it was originally isolated, Louisiana, Alabama, Oklahoma, Georgia, Tennessee, and Florida) is responsible for a severe disease with an often fatal outcome. Most infected dogs have a violent myositis, with fever, pain, lameness and difficulty in walking followed by atrophy of the muscles. The most frequent blood-chemistry findings are pronounced leucocytosis, raised levels of alkaline phosphatase and hypoalbuminaemia. Periosteal proliferations are often evident on X-rays.

The diagnosis of H. canis is based on finding the gamonts within the neutrophils of a peripheral blood smear (Figs. 2 and 3), while, for the diagnosis of H. americanum a muscle biopsy is necessary to show the parasite inside cysts or granulomas, given the low level of parasitaemia (> 0.1%).

The treatment of H. canis is based on the administration of imidocarb dipropionate subcutaneously or intramuscularly at a dose of 5-6 mg/kg every 14 days until the gamonts disappear from the peripheral blood. It is advisable to give doxycycline at a dose of 10 mg/kg per os as well for the first 21 days. The average duration of treatment is 8 weeks.

The suggested treatment for H. Americanum infection is the contemporaneous administration of trimethoprim/sulphadiazine (15 mg/kg every 12 hours), pyrimethamine (0.25 mg/kg every 24 hours) and clindamycin (10 mg/kg every 8 hours). The remission of clinical signs can be prolonged by the administration of decoquinate (10-20 mg/kg in food every 12 hours). Anti-inflammatory treatment with a non-steroidal anti-inflammatory drug or corticosteroids helps to relieve the symptoms. Recurrences are extremely common.

The only valid prophylaxis is planned, periodic treatments against the tick vector.

Suggested reading

1. Baneth, G.(2001) Hepatozoonosis, canine. In Encyclopedia of Arthropod-transmitted Infections of Man and Domesticated Animals, Ed M.W. Service. Oxon, CAB International. pp 215-220
2. Baneth, G. & Weigler, B. (1997) Retrospective case-control study of hepatozoonosis in dogs in Israel. Journal of Veterinary Internal Medicine 11, 365-370
3. Baneth, G., Shkap, V., Presentey, B-Z. & Pipano, E. (1996) Hepatozoon canis: the prevalence of antibodies and gametocytes in dogs in Israel. Veterinary Research Communications 20, 41-46
4. Baneth. G., Samish, M., Aroch, I., Alekseev, Y. & Shkap, V. (2001) Transmission of Hepatozoon canis to dogs by naturally fed or percutaneously injected Rhipicephalus sanguineus ticks. Journal of Parasitology 87, 606-611
5. Baneth, G., Mathew, J.S., Shkap, V., Macintire, D.K., Barta, J.R., Ewing, S.A. (2003) Canine hepatozoonosis: two disease syndromes caused by separate Hepatozoon species. Trends in Parasitology 19, 27-31
6. Craig, T.M., Smallwood, J.E., Knauer, K.W. & McGrath, J.P. (1978) Hepatozoon canis infection in dogs: clinical, radiographic and hematological findings. Journal of the American Veterinary Medical Association 173, 967-72
7. Ewing, S. A., DuBois, J. G., Mathew, J.S. & Panciera, R.J. (2002) Larval Gulf Coast ticks (Amblyomma maculatum) [Acari: Ixodidae] as host for Hepatozoon americanum [Apicomplexa: Adeleorina]. Veterinary Parasitology 103, 43-51
8. Ewing, S.A., Panciera, R.J. (2003) American canine hepatozoonosis. Clinical Microbiology Reviews 16, 688-697
9. Inokuma, H., Ohno, K. & Yamamoto, S. (1999). Serosurvey of Ehrlichia canis and Hepatozoon canis infection in dogs in Yamaguchi Perfecture, Japan. Journal of Veterinary Medical Science 61, 1153-1155
10. Macintire, D.K., Vincent-Johnson, N., Dillon, A.R., Blagburn, B.L., Lindsay, D.S., Whitley, E.M. & Banfield, C. (1997) Hepatozoonosis in dogs: 22 cases (1989-1994). Journal of American Veterinary Medical Association 210, 916-922
11. Macintire, D.K., Vincent-Johnson, N.A., Kane, C.W., Lindsay, D.S., Blagburn, B.L. & Dillon, A.R. (2001) Treatment of dogs infected with Hepatozoon americanum: 53 cases (1989-1998). Journal of American Veterinary Medical Association 218, 77-82
12. Mathew, J.S., Ewing, S.A., Panciera, R.J. & Woods, J.P. (1998) Experimental transmission of Hepatozoon americanum (Vincent-Johnson et al., 1997) to dogs by the Gulf Coast tick, Amblyomma maculatum Koch. Veterinary Parasitology 80, 1-14
13. Mathew, J.S., Saliki J.T., Ewing, S.A., Lehenbauer, T.W., Panciera, R.J., Malayer, J.R., Cummings, C.A. & Kocan, A.A. (2001) An indirect enzyme-linked immunosorbent assay for diagnosis of American canine hepatozoonosis. Journal of Veterinary Diagnostic Investigation 13, 17-21
14. O'Dwyer, L.H., Massard, C.L. & Pereira de Souza, J.C. (2001) Hepatozoon canis infection associated with dog ticks of rural areas of Rio de Janeiro State, Brazil. Veterinary Parasitology 94, 143-150
15. Panciera, R.J. Ewing, S.A. & Mathew, J.S. (1999) Canine hepatozoonosis: comparison of lesions and parasites in skeletal muscle of dogs experimentally or naturally infected with Hepatozoon americanum. Veterinary Parasitology 82, 261-272
16. Shkap, V., Baneth, G. & Pipano, E. (1994). Circulating antibodies to Hepatozoon canis demonstrated by immunofluorescence. Journal of Veterinary Diagnostic Investigation. 6, 121-123
17. Smith, T.G. (1996) The genus Hepatozoon (Apicomplexa: Adeleina). Journal of Parasitology 82, 565-585
18. Vincent-Johnson, N. A., Macintire, D.K., Lindsay, D.S., Lenz, S.D., Baneth, G., Shkap, V. & Blagburn, B.L. (1997) A new Hepatozoon species from dogs: description of the causative agent of canine hepatozoonosis in North America. Journal of Parasitology 83, 1165-1172