Two species of Hepatozoon organisms have been reported to infect domestic dogs worldwide.
Two species of Hepatozoon organisms have been reported to infect domestic dogs worldwide. The first species described was Hepatozoon canis, initially reported in India in 1905. Since then, H. canis has been reported in dogs from Japan, Africa, Israel, Spain, France, Italy, Portugal, Greece, and the Philippines.
In 1978, hepatozoonosis was first reported in dogs in the USA along the Texas Gulf Coast region. Initially, the causative agent was thought to be Hepatozoon canis, but differences in clinical features of disease, parasite stages, parasite location, and gametocyte structure resulted in the designation of a new species, Hepatozoon Americanum. H. Americanum now appears to be a serious emerging tick-borne disease in the USA.
The definitive host of H. canis is the brown dog tick, Rhipicephalus sanguineus. Ticks become infected by ingesting circulating gametocytes from the bloodstream of a dog. The gametocytes fuse in the tick to form an ookinete. Each ookinete becomes an oocyst which contains numerous sporocysts. Within each sporocyst are 12-24 sporozoites. In order to become infected, a dog must ingest the tick. Following ingestion, sporozoites are released and penetrate the dog's intestinal tract to be carried by blood or lymph to mononuclear phagocytic cells in various organs (spleen, lymph nodes, liver, lung, pancreas, and bone marrow). Asexual reproduction of the organism occurs through schizogony. Merozoites are formed within the schizont and released to either become circulating gametocytes in white blood cells, or to become additional tissue schizonts. A single tick can contain hundreds to thousands of infective organisms.
The life cycle of Hepatozoon americanum is essentially the same, except that the definitive tick host is Amblyoma maculatum, the Gulf Coast Tick. The gametocyte is identical in appearance, but parastemia generally affects < 0.1% of leukocytes. In contrast, parasitemia is a common finding in dogs with H. canis, and 1-90% of leukocytes can be infected. Another difference in the H. americanum life cycle is the presence of a cystic tissue stage that is not seen in H. canis infections.
Hepatozoon canis infection is associated with the occurrence of schizonts in the spleen, liver, lymph nodes, kidney, pancreas, lungs, and bone marrow. Schizonts have a characteristic "wheel-spoke" pattern and are not associated with tissue inflammation.
The most common tissue stage of H. americanum is a large "onion-skin" cyst found most often in skeletal muscle. At the center of the "cyst" is the host cell with the intracellular parasite. The infected cell is surrounded by lamellar muco-polysaccharide secretions, resulting in the characteristic "onion-skin" appearance. Schizogony occurs and merozoites are released resulting in an intense pyogronulommatous inflammatory reaction. Cysts can be found in skeletal muscle, cardiac muscle, pancreas, kidneys, lymph nodes, and spleen.
The pathogenicity of H. canis has been questioned because most dogs with circulating gametocytes are asymptomatic. With severe parasitemia or concurrent infection, however, dogs may exhibit fever, cachexia, splenomegaly, anemia, and lethargy.
H. americanum infection commonly results in severe disease characterized by fever, muscle pain, stiffness, ocular discharge, and weight loss. Gait abnormalities range from stiffness to total recumbency. The disease has a chronic course, and clinical signs often wax and wane. Death usually occurs within 12 months. Chronic infection may result in amyloid deposition, vasculitis, and glomerulonephritis with protein-losing nephropathy.
H. canis is most commonly diagnosed by finding circulating gametocytes on the CBC or buffy coat. H. americanum is most commonly diagnosed by finding cysts or pyogranulomas on a muscle biopsy specimen. The gametocyte appearance in WBC's is similar, but can affect 20-60% of the cells in dogs with H. canis and is rarely found in more than 0.1% of WBC's in dogs with H. americanum.
The most common findings in dogs with H. canis are mild anemia and mild thrombocytopenia. Dogs with marked parasitemia may have elevated CPK, elevated SAP, hypoalbuminemia, and leukocytosis, but dogs with low parasitemia are usually subclinical.
H. americanum infection generally causes severe disease and is associated with marked leukocytosis (typically in the range of 25,000-150,000/uL), non-regenerative anemia, elevated SAP, hypoalbuminemia, low BUN, and hypoglycemia. The anemia is generally associated with chronic disease. The elevation in SAP is thought to be secondary to periosteal inflammation associated with myositis. Hypoalbuminemia and low BUN are often the result of altered protein metabolism associated with the production of acute phase proteins and macroglobulins as a consequence of inflammation. Hypoglycamia may be spurious because of the increased white blood cell count. The clinicopathologic findings of H. americanum are so consistent that, when they are noted, they should prompt consideration of a muscle biopsy for definitive diagnosis. Radiography frequently demonstrates periosteal proliferation at sites of muscle attachment as a result of pyogranulomatous myositis and is also considered a good "screening test" for the disease.
For H. canis, the recommended treatment is imidocarb dipropionate, 5 mg/kg SC or IM every 14 days until parasitemia clears. One or two injections are usually sufficient. Dogs with concurrent tick borne infections should receive doxycycline, and heavily parasitized dogs may require supportive care.
Treatment of H. americanum has been frustrating because no therapy is effective in eliminating the tissue stage of the organism. Palliative therapy with NSAIDs is often helpful in controlling fever and muscle pain, but definitive treatment requires anti-protozoal therapy. Beneficial response has been obtained with a 14 day course of trimethoprim sulfa (15 mg/kg q 12 h), clindamycin (10-15 mg/kg q 8 h), and pyrimethamine (0.25 mg/kg q 24 h). Unfortunately, relapse will occur within 1-6 months as merozoites are released from tissue schizonts. At Auburn University, decoquinate, a quinolone anticoccidial agent, has been used to prevent continued development of tissue stages of the organism. Doses of 10-20 mg/kg (¼ - ½ teaspoon per 10 pounds) mixed in the food twice daily have been effective in preventing relapse and extending survival time in infected dogs. Long term treatment of 18 months to 2 years is recommended as well as aggressive tick control measures to prevent re-infection of susceptible dogs.
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