American Canine Hepatozoonosis

Synopsis

CAPC Recommends

• Consider a diagnosis of hepatozoonosis in dogs with high neutrophil counts, myalgia, unexplained weight loss, and exposure to ticks or vertebrate prey, and confirm with PCR of whole blood or microscopic examination of muscle biopsy samples.
• Reduce risk of infection through year-round tick control, avoiding areas with ticks, and limiting opportunities for predation or scavenging.
• Treatment of American canine hepatozoonosis entails acute antiprotozoal therapy using either TCP (see Treatment guidelines) or ponazuril followed by two years or more of long-term maintenance with decoquinate.

Species

Hepatozoon americanum

Overview of Life Cycle

Hepatozoon americanum undergoes sexual development and sporogony in the tick Amblyomma maculatum.


Merogony and gametogony occur in canid hosts.



Cystozoites are present in the tissues of paratenic hosts.

• The tick ingests gametocytes contained in neutrophils or monocytes in the dog’s peripheral blood.
• Within the tick’s gut, gametocytes fuse to form an ookinete.
• The ookinete penetrates the gut epithelium and becomes a nonsporulated oocyst.
• Numerous sporocysts form within developing oocysts.
• Each mature sporocyst contains between 12 and 24 sporozoites.
• Sporulated oocysts enter and remain in the hemocoelom of the tick; they do not migrate to the tick’s salivary glands or mouthparts.
• Dogs acquire infection by ingesting a tick containing sporulated oocysts.
  • Dogs may also acquire infection by the ingestion of paratenic hosts that have ingested a tick containing sporocysts. In these paratenic hosts, the sporozoites enter the host tissues, enlarge, and become dormant stages called cystozoites.
• Sporozoites are released; penetrate the intestinal epithelium of the dog; enter leukocytes in the lamina propria, regional lymph nodes, or liver; and are transported to body tissues where merogony occurs.
• Merozoites form within a meront and are then released to invade another cell. After multiple cycles of merogony, some merozoites invade leukocytes and develop into gametocytes.

Gamont within a circulating white blood cell from a dog with American canine hepatozoonosis

Stages

Sexual stages (tick)

• Ookinete

• Oocyst

• Sporocyst

• Sporozoite

Asexual stages (dog)

• Merozoites in “onion-skin” cysts

• Merozoites in mononuclear cells within well-vascularized pyogranulomas

• Gametocytes in white blood cells

Muscle cyst (often described as an “Onion-skin cyst”) containing merozoite of Hepatozoon americanum

Pyogranuloma containing merozoites of Hepatozoon americanum

Disease

• Disease is debilitating and often fatal.
• Disease is characterized by periodic or persistent fever, weakness, muscle atrophy, generalized pain or hyperesthesia, reluctance to move, mucopurulent ocular discharge, and gradual deterioration of body condition.
• Laboratory findings include neutrophilic leukocytosis (leukocyte counts can exceed 200,000/µL), mild to moderate nonregenerative anemia, mild elevation in serum alkaline phosphatase, decreased BUN and albumin, and occasional hyperglobulinemia. Some dogs may be hypoglycemic due to high glucose utilization by elevated leukocyte numbers.
  • Despite myositis being a hallmark clinical sign, CK is typically normal
• Radiography may demonstrate periosteal proliferation of various bones, including the ilium, humerus, radius, ulna, femur, tibia, fibula, scapulae, flat bones of the skull, and vertebrae. These lesions occur most often in younger dogs.
• Dogs may continue to eat and drink while losing weight due to increased caloric demands associated with the chronic inflammation
• Glomerulonephritis has been described in chronic cases due to prolonged inflammation
• Without treatment, chronic wasting commonly leads to death within several months.

Radiograph showing periosteal bone proliferation associated with American canine hepatozoonosis

Incidence and Prevalence

• American canine hepatozoonosis has been described from the southern United States including Alabama, Florida, Georgia, Louisiana, Mississippi, Oklahoma, Tennessee, and Texas. Hepatozoon americanum is likely to be a potential risk wherever the vector, Amblyomma maculatum, is found.
• Until a reliable serologic test is developed, the true prevalence of infection will be difficult to ascertain.
• It is unlikely that genetic predisposition, breed, and age are important factors in transmission or manifestation of the disease.
• However, certain management styles, such as allowing dogs to hunt, scavenge, or consume prey, could increase exposure risk via ingestion of cystozoites in tissues of prey or ticks attached to prey.
• Canids residing in areas where A. maculatum is endemic are at risk of infection; dogs allowed to hunt, scavenge, or consume prey are at increased risk.

Host Associations and Transmission Between Hosts

• American canine hepatozoonosis is acquired by ingestion of ticks (A. maculatum) containing sporozoites within sporulated oocysts, ingestion of paratenic hosts with cystozoites, or ingestion while the dog is grooming itself or feeding on prey infested with parasitized ticks. Transfer of H. americanum in tick saliva has not been described.
• Vertical transmission may occur by placental passage of merozoites from the bitch to the pup, but this has not been conclusively demonstrated.

Prepatent Period and Environmental Factors

• Following experimental transmission of H. americanum, dogs demonstrate elevations in body temperature and neutrophilic leukocytosis about 4 to 10 weeks after ingestion of infected ticks; myasthenia, bone pain, and ocular discharge are observed shortly thereafter.
• Cysts in muscle and gametocytes in the blood are observed about 5 to 10 weeks after infection.
• Dogs can be long-term carriers of H. americanum and thus are potential reservoir hosts. It is suspected that other vertebrates also may serve as reservoirs.

Site of Infection and Pathogenesis

• Meronts infect striated muscle and produce mucopolysaccharide layers, which aid in protecting the parasite from the immune system
• A severe inflammatory response occurs at tissue sites where merozoites are released from mature meronts in cysts, causing intense myositis.
• Once cysts rupture, localized pyogranulomas form in areas where intact cysts were
• Periosteal proliferation of the long bones may be due to the chronic inflammatory state
• Muscle and periosteal pain is responsible for inability or reluctance to rise, stiffness of gait, and hyperesthesia.
• Muscle atrophy is evident in chronic cases. Muscle atrophy can cause severe weakness.
• Decreased tear production may cause mucopurulent ocular discharge.

Diagnosis

• Diagnosis is based on finding meronts in muscle biopsy samples or gamonts in peripheral blood smears. Muscle lesions consist of large cysts (“onion-skin” cysts) and pyogranulomas. Because of the infrequency with which gamonts are observed in blood smears, a muscle biopsy is the most consistently reliable method of obtaining a definitive diagnosis.
• Diagnostic polymerase chain reaction (PCR) is also available and may aid diagnosis in some cases. Due to the low number of circulating gamonts in both the early course of infection and in the chronic phase of disease, PCR on whole blood is less sensitive during those times. Therefore a negative PCR should not rule out hepatozoonosis. A muscle biopsy would be recommended if H. americanum was still suspected.
• An indirect enzyme-linked immunosorbent assay using sporozoites as antigens has been developed but is not commercially available.

Treatment

• No treatment is effective in eliminating H. americanum in infected dogs. Treatment can increase survival time, improve the quality of life, and decrease the number and severity of clinical relapses. Supportive care can ensure hydration, and nonsteroidal anti-inflammatory drugs assist with pain control.
• Either of two acute parasiticidal treatments may be administered:
  • Ponazuril at a dose of 10 mg/kg PO q12h for 14 days.
  • OR a triple-combination therapy, referred to as TCP, consisting of trimethoprim-sulfadiazine (15 mg/kg PO q12h for 14 days), clindamycin (10 mg/kg PO q8h for 14 days), and pyrimethamine (0.25 mg/kg PO q24h for 14 days)

• Regardless of the choice of initial parasiticide treatment protocol, prolonged therapy with a quinolone anticoccidial agent is recommended to aid in the control of relapses. The regimen consists of the following:
  • Decoquinate (Deccox®, Alpharma Inc., Fort Lee, NJ) administered at a dose of 10 to 20 mg/kg mixed in the food twice daily. This is equivalent to 0.5 to 1.0 teaspoon/10kg (22 lb) of formulated decoquinate administered twice daily. It is recommended that the regimen be continued for 2 years.
• If relapse occurs, either ponazuril or TCP should be administered again for 14 days followed by long-term decoquinate therapy.

Control and Prevention

• Routine application of effective acaricides is essential for preventing infection and disease due to H. americanum.
• Attached ticks found on pets should be removed promptly to prevent ingestion by the dog during grooming and to prevent transmission of any pathogens the ticks may harbor.
• Dogs should be prevented from roaming and should not be allowed to engage in predatory or scavenging behavior to prevent ingestion of ticks on prey species.

Public Health Considerations

• American canine hepatozoonosis is not a zoonotic disease.

Selected References

• Allen KE, et al., 2011. Hepatozoon spp. infection in the United States. Vet Clin NA Small Animal Pract 41:1221-1238.
• Baneth G an Allen KE. 2022. Hepatozoonosis of Dogs and Cats. Vet Clin Small Anim 52: 1341 – 1358.
• Holman PJ, Snowden KF. 2009. Canine Hepatozoonosis and babesiosis, and feline cytauxzoonosis. Vet Clin Small Anim 39: 1035-1053.
• Johnson EM, et al., 2010. Alternate pathway of infection with Hepatozoon americanum and the epidemiologic importance of predation. JVIM 23:1315-1318.
• Little SE, et al., 2009. New developments in canine hepatozoonosis in North America: a review. Parasites & Vectors 2(Supp 1):S5 doi:10.1 186/1756-3305-2-S1-S5