Canine Hepatozoonosis

Definition/Overview

• Tick-borne disease of wild and domestic canids.

• Caused by protozoal agent genus Hepatozoon.

• Two main species cause clinically distinct syndromes in dogs: H. canis and H. americanum.

• Generally considered a lifelong infection in dogs.

• No known therapeutic regimen completely clears the organisms.

• No known zoonotic risk.

Causative Agents

• Hepatozoon canis (Old World Hepatozoonosis)

  • Disease ranges from subclinical and chronic to severe and life-threatening.

  • Infections in immunocompetent dogs are most often subclinical to mild.

  • Reported in many regions of the world, including Asia, Africa, the Caribbean islands, Europe, South America, and North America.

  • More common in North America than previously known based on molecular evidence.

• Hepatozoon americanum (American Canine Hepatozoonosis - ACH)

  • Condition is most commonly severe to fatal.

  • Causes severe clinical signs in most infected dogs.

  • Death often occurs within 1–2 years without supportive therapies.

  • Emerging disease in the United States.

  • Primarily spread north and east from the Gulf coast of Texas.

  • Distribution chiefly parallels the distribution of the Gulf coast tick.

  • Sporadic cases reported from disparate geographic locations presumably due to travel history.

Etiology, Epidemiology, and Transmission

• Mode of Transmission: Not typical tick-borne.

  • Infection occurs when infected ticks (definitive host) are ingested by canine hosts.

  • Sporozoites released from mature oocysts in ticks' hemocoel enter canine hosts via the gut.

  • Dogs can also develop ACH after eating paratenic (transport) hosts that contain cystozoites.

• Vectors (Ticks - Definitive Hosts):

  • H. canis: Brown dog tick (Rhipicephalus sanguineus).

  • H. americanum: Gulf Coast tick (Amblyomma maculatum).

• Paratenic Hosts (H. americanum): Prey captured or eaten by dogs containing cystozoites.

• Geographic Distribution in US (Documented States):

  • H. canis: AL, GA, LA, MS, NJ, VA.

  • H. americanum: AL, CA, FL, GA, KY, LA, MS, NE, NC, TN, TX, VT, VA, WA.

  • Co-infections (H. canis and H. americanum): AL, LA, MS.

• Predisposing Factors: Immunosuppression does not appear necessary to induce the severe H. americanum syndrome. Immunocompetent dogs appear to tolerate H. canis very well.

• Vertical Transmission: Transplacental transmission of H. canis has been documented. Vertical transmission of H. americanum has not been reported but may be possible.

Clinical Findings

• General: Severity varies widely from subclinical to severe/fatal.

• H. canis:

  • Most often subclinical to mild.

  • Dogs do not appear to be in pain at presentation (unlike ACH patients).

  • Overt signs: fever, lethargy, depression, and anemia.

  • Tissue stages reside within bone marrow, lymph nodes, and spleen.

  • Hepatitis, pneumonia, and glomerulonephritis reported postmortem in some animals with extremely high parasitemia.

• H. americanum (ACH):

  • Severe clinical signs in most infected dogs.

  • Tissue phases induce pyogranulomatous inflammation.

  • Salient features: fever (102.7°–106°F), depression, weight loss, poor body condition, muscle atrophy, muscle and bone pain, weakness, lameness, recumbency.

  • Mucopurulent ocular discharge is common.

  • Bloody diarrhea occurs occasionally.

  • Fever may fluctuate, unresponsive to antibiotics.

  • Often will not move to eat apparently because of intense pain, despite maintaining normal appetite.

  • Hyperesthesia (stiffness, reluctance to move, cervical/truncal rigidity) manifests presumably due to severe inflammation within muscle and sometimes along bone.

  • Longterm sequelae include glomerulonephritis and amyloidosis.

Diagnosis

• Based on clinical signs, patient history (tick exposure, travel, predation), and laboratory testing.

• Methods: Clinical evaluation, CBC, biochemistry panel, cytology, PCR, muscle biopsy and histologic evaluation, bone radiography.

• H. canis:

  • Most common abnormality on blood work: anemia.

  • Serum chemistry abnormalities: increased CK and alkaline phosphatase (AP) activities, hypoproteinemia with polyclonal hyperglobulinemia and hypoalbuminemia.

  • Diagnosis readily achieved by: Microscopic examination of Romanowsky-type stained blood films to visualize parasite-containing leukocytes or PCR to detect parasite DNA in peripheral blood.

  • Parasitemia is often quite high in dogs with clinical H. canis.

• H. americanum (ACH):

  • Most consistent laboratory abnormality: neutrophilic leukocytosis (20,000–200,000 cells/μL).

  • Mild to moderate anemia is also common.

  • Platelet count typically normal to high.

  • Serum chemistry abnormalities similar to H. canis occasionally observed.

  • Definitive diagnosis made by: Finding rare gamonts in peripheral blood leukocytes, occasional PCR detection of circulating parasite, or identifying pathognomonic "onion skin" cysts or pyogranulomas in stained sections of biopsied muscle.

  • Muscle biopsy: Considered the gold standard for diagnosing ACH. Parasites and associated lesions often extensively distributed throughout muscle tissue. Multiple or sequential biopsies may be necessary.

  • Radiographs: May show periosteal reactions involving any bone (skull, vertebrae, long bones). Resemble hypertrophic osteopathy but tend to be proximal and markedly obvious in long bones.

• Serology: No commercially available serologic assays.

• PCR: Available through academic institutions. Assays may lack sensitivity in diagnosing H. americanum due to typically low levels of parasitemia. Useful for detecting H. canis in North America.

Treatment and Control

• Goal: Remission of clinical signs. Not curative.

• H. canis Treatment:

  • Imidocarb dipropionate (5–6 mg/kg, SC).

  • Administer twice monthly.

  • Continue until parasite is no longer evident in blood smears for 2–3 consecutive months.

  • Prognosis depends on the degree of parasitemia.

• H. americanum (ACH) Treatment:

  • Initial therapy (14-day course) for remission:

    • Combination therapy (TCP): trimethoprim-sulfadiazine (15 mg/kg PO q12h) + clindamycin (10 mg/kg PO q8h) + pyrimethamine (0.25 mg/kg PO q24h).

    • OR Ponazuril (10 mg/kg PO q12h).

  • Adjunct therapy (long-term) to prevent relapse:

    • Decoquinate (10−20 mg/kg PO q12h, mixed in food).

    • Administer for at least 2 years.

  • Remission with initial therapy alone is often temporary (many dogs relapse within 2–6 months).

• Supportive Care:

  • NSAIDs may be the best treatment for control of fever and pain, especially during the first few days of initial therapy.

  • Glucocorticoid administration should be avoided as longterm use can exacerbate disease.

• Control Measures:

  • Most effective forms: Preventing access to ticks and discouraging predation.

  • Tick control products are recommended to help prevent infection.

  • Avoiding predation addresses dual risk: infected ticks on prey or cystozoites in prey tissues.

  • Dogs diagnosed with hepatozoonosis should not be bred because of documented or possible vertical transmission.

Prognosis

• Considered guarded, especially for ACH patients.

• Clinical signs often abate with treatment, and animals return to having a good quality of life.