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Old World Hepatozoonosis and American Canine Hepatozoonosis

By

Kelly E. Allen

, PhD, Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University

Medically Reviewed Mar 2022 | Modified Oct 2022
Topic Resources

Disease associated with Hepatozoon canis infection, or Old World Hepatozoonosis, ranges from subclinical and chronic to severe and life-threatening. Clinical signs include fever, lethargy, anorexia, and anemia. H americanum is the causative agent of American canine hepatozoonosis (ACH), a condition which is most commonly severe to fatal, with salient clinical features including fever, mucopurulent ocular discharge, muscle atrophy, muscle and bone pain, lameness, and recumbency. H canis is typically diagnosed by observation of parasites within leukocytes or by PCR. Infections are most commonly treated with imidocarb dipropionate for 2–3 months. ACH infections may be diagnosed by clinical signs, PCR, observation of parasites or associated lesions in muscle biopsies, and radiographs. Treatment is with antibiotics and NSAIDs for 2 weeks, followed by daily decoquinate for at least 2 years.

Etiology, Epidemiology, and Transmission of Hepatozoonosis in Dogs

Old World hepatozoonosis is a tick-borne disease of wild and domestic canids caused by the protozoal agent Hepatozoon canis. The organism is transmitted by the brown dog tick, Rhipicephalus sanguineus. In North America, Hepatozoon americanum, causative agent of American canine hepatozoonosis (ACH) is transmitted by the Gulf Coast tick, Amblyomma maculatum, rather than by the brown dog tick. H canis and H americanum, although closely related, result in clinically distinct syndromes in infected dogs, and genetic and antigenic differences between the organisms further support their classification as distinct species.

H canis is reported in many regions of the world, including Asia, Africa, the Caribbean islands, Europe, and South America. Before 2008, H canis was not thought to infect canids in North America, despite the presence of R sanguineus, but molecular evidence has since emerged that suggests otherwise. Still, ACH remains the more common and severe form of canine hepatozoonosis in the United States. American canine hepatozoonosis is an emerging disease that has primarily spread north and east from the Gulf coast of Texas, where it was originally detected in 1978. The distribution of this parasite chiefly parallels the distribution of the Gulf coast tick, although sporadic cases have been reported from disparate geographic locations presumably due to travel history. The associated table States in which H canis and H americanum infections in domestic dogs have been documented States in which <i >H canis</i> and <i >H americanum</i> infections in domestic dogs have been documented indicates states in which H canis, H americanum, and concomitant H canis and H americanum infections have been reported in domestic dogs.

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The mode of transmission of hepatozoonosis is not typical in the classical sense of a tickborne disease; like other species in the genus, H canis and H americanum infections occur when infected ticks, the definitive host, are ingested by canine hosts. Sporozoites released from the mature oocysts in the ticks' hemocoel enter canine hosts via the gut. Dogs can also develop ACH after eating paratenic (transport) hosts that contain cystozoites, a resting stage of H americanum encysted within tissues.

In general, immunocompetent dogs appear to tolerate infection with H canis very well. Although life-threatening infections have been reported, clinical signs associated with H canis infection are most often subclinical to mild. H americanum, however, causes severe clinical signs in most infected dogs, with death often occurring within 1–2 years without supportive therapies; immunosuppression or concurrent disease does not appear necessary to induce the severe syndrome.

Clinical Findings of Hepatozoonosis in Dogs

H canis tissue stages reside within bone marrow, lymph nodes, and spleen, and unlike ACH patients, dogs infected with the Old World parasite do not appear to be in pain at presentation; in dogs with overt disease, nonspecific clinical signs including fever, lethargy, depression, and anemia may be observed.

The tissue phases of H americanum induce pyogranulomatous inflammation, which results in clinical signs including fever, depression, weight loss, poor body condition, muscle atrophy, pain, and weakness; mucopurulent ocular discharge is common, and bloody diarrhea occurs occasionally. Fever, which may fluctuate with the waxing and waning of clinical signs, ranges from 102.7°–106°F (39.3°–41°C) and is unresponsive to antibiotics. Surprisingly, many dogs maintain a normal appetite if food is placed directly in front of them, but they often will not move to eat, apparently because of intense pain. Hyperesthesia, presumably due to severe inflammation within muscle and sometimes along bone, manifests as stiffness and reluctance to move, as well as cervical and/or truncal rigidity. Longterm sequelae include glomerulonephritis and amyloidosis.

Diagnosis of Hepatozoonosis in Dogs

  • Clinical evaluation and patient history

  • CBC and biochemistry panel

  • Cytology

  • PCR

  • Muscle biopsy and histologic evaluation

  • Bone radiography

Patient history of tick exposure, travel, and, in suspected ACH cases, predation on rodents or rabbits, are important factors to consider when forming a potential diagnosis of canine hepatozoonosis, in conjunction with clinical examination and laboratory testing. The most common abnormality on blood work in dogs infected with H canis is anemia. Serum chemistry abnormalities may include increased CK and alkaline phosphatase (AP) activities as well as hypoproteinemia with polyclonal hyperglobulinemia and hypoalbuminemia. Parasitemia in dogs with clinical H canis infection is often quite high, and a diagnosis can readily be achieved by microscopic examination of Romanowsky-type stained blood films to visualize parasite-containing leukocytes or by PCR to detect parasite DNA in peripheral blood. Hepatitis, pneumonia, and glomerulonephritis associated with H canis tissue stages have been reported postmortem in some animals with extremely high parasitemia.

In dogs with ACH, the most consistent laboratory abnormality is a neutrophilic leukocytosis, with counts ranging from 20,000–200,000 cells/μL. This is typically a pronounced, mature neutrophilia, although a left shift may be present. A mild to moderate anemia is also common. The platelet count is typically normal to high. Serum chemistry abnormalities in ACH patients are similar to those occasionally observed in H canis patients. Definitive diagnosis of ACH in suspicious patients is made by finding rare gamonts in peripheral blood leukocytes, by occasional PCR detection of circulating parasite, or by identifying pathognomonic "onion skin" cysts or pyogranulomas in stained sections of biopsied muscle.

Although invasive, muscle biopsy is considered the gold standard for diagnosing ACH, because parasites and associated lesions are often extensively distributed throughout muscle tissue (especially in areas with observable atrophy); multiple or sequential biopsies may be necessary in some animals.

Radiographs in ACH patients may show periosteal reactions involving any bone, including the skull and vertebrae. The lesions resemble those of hypertrophic osteopathy except that they tend to be proximal rather than distal, and often markedly obvious in long bones; the physiologic basis for bony proliferation animals with H americanum infection is unknown.

No commercially available serologic assays have been developed to detect canine hepatozoonosis infection. PCR methods detecting circulating Hepatozoon spp are available through several academic institutions, although the assays may lack sensitivity in diagnosing H americanum infections because of the typically low levels of parasitemia in ACH patients. Use of these molecular tests has revealed that hepatazoonosis caused by H canis is more common in North America than previously known.

Treatment of Hepatozoonosis in Dogs

  • Antiprotozoal therapy

  • Supportive care

  • Tick control products

  • Preventing predation

Hepatozoonosis is generally considered a lifelong infection in dogs. No known therapeutic regimen completely clears animals of the organisms. H canis infections are treated with imidocarb dipropionate, twice monthly, at 5–6 mg/kg, SC, until the parasite is no longer evident in blood smears for 2–3 consecutive months. Prognosis often depends on the degree of parasitemia; dogs with low parasitemia typically respond well to treatment, whereas those with high parasitemia may not, especially if afflicted by concurrent illness.

Remission of clinical signs associated with H americanum infection can usually be achieved through a 14-day course of combination therapy, referred to as TCP, which consists of trimethoprim-sulfadiazine (15 mg/kg PO twice daily), clindamycin (10 mg/kg PO three times daily), and pyrimethamine (0.25 mg/kg PO daily), or ponazuril (10 mg/kg PO twice daily). Remission with these therapies alone is often temporary, with many dogs relapsing within 2–6 months. Decoquinate mixed in food at a dose of 10−20 mg/kg is given twice daily as an adjunct therapy to initial TCP or ponazuril treatment for at least 2 years to help prevent relapse. NSAIDs may be the best treatment for control of fever and pain, especially during the first few days of TCP or ponazuril therapy. Glucocorticoid administration should be avoided because, although steroids may provide temporary relief, longterm use can exacerbate disease.

Preventing access to ticks and discouraging predation are the most effective forms of control for hepatozoonosis. Predation presents a dual risk for acquiring ACH: prey captured or eaten by dogs could have infected ticks on their coats that would provide a source of sporozoites; additionally, the prey could contain cystozoites (at least in the case of H americanum) that are also infectious. Additionally, dogs diagnosed with hepatozoonosis should not be bred because transplacental transmission of H canis has been documented. Although vertical transmission of H americanum has not been reported, it may be possible.

There is no known zoonotic risk with hepatozoonosis.

Key Points

  • Canine hepatozoonosis is caused by H canis and H americanum, which are tick-borne protozoan parasites causing distinct clinical manifestations in canine patients after infected ticks are ingested.

  • H canis infection often leads to mild to moderate clinical disease, with anemia in some cases, whereas H americanum infection often results in a severe clinical syndrome known as American canine hepatozoonosis (ACH), with patients commonly exhibiting fever, mucopurulent ocular discharge, intense pain, muscle atrophy, and elevated neutrophil counts.

  • Diagnosis of canine hepatozoonosis is often based on patient history, clinical signs, blood work and cytology, PCR of peripheral blood, and in the case of ACH, characteristic histopathologic lesions evident in biopsied muscle tissue.

  • H canis infections are treated with imidocarb dipropionate (5−6 mg/kg SC) 2 times monthly for 2−3 consecutive months, whereas H americanum infections are treated with a 14-day combination antibiotic therapy (trimethoprim-sulfadiazine 15 mg/kg PO twice daily, clindamycin 10 mg/kg PO three times daily, and pyrimethamine 0.25 mg/kg PO daily) or ponazuril (10 mg/kg PO twice daily) followed by long-term decoquinate administration (10−20 mg/kg PO twice daily, mixed in food); tick control products are recommended to help prevent infection.

  • Treatment regimens recommended for canine hepatozoonosis are not curative, and prognoses are considered guarded, especially for ACH patients. Clinical signs often abate with treatment and animals return to having a good quality of life.

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