American Hepatozoonosis

Species

Hepatozoon americanum

Hepatozoon americanum undergoes sexual development and sporogony in the tick Amblyomma maculatum and merogony and gametogony in the domestic dog.

The tick ingests gametocytes contained 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.
Sporocysts form within developing oocysts (sporulated oocyst).
Each mature sporocyst contains between 12 and 24 sporozoites.
Sporozoites 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. 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. Schizonts form merozoites, which are released to invade another cell. After multiple cycles of merogony, some merozoites invade leukocytes and produce gametocytes.

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, and occasional hyperglobulinemia.
Radiography may demonstrate periosteal proliferation of various bones, including the ilium, humerus, radius, ulna, femur, tibia, fibula, and vertebrae.
Dogs may continue to eat and drink.
Without treatment, chronic wasting commonly leads to death within several months.

American hepatozoonosis has been described from the southern United States including Alabama, Florida, Georgia, Louisiana, Mississippi, Oklahoma, Tennessee, and Texas.
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.

Canine hepatozoonosis is acquired by ingestion of ticks (A. maculatum) containing oocysts (sporozoites). Infection could occur while the dog is grooming itself or feeding on prey infested with parasitized ticks. Transfer of H. americanum in salivary secretions 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.

Following experimental transmission of H. americanum, dogs demonstrate elevations in body temperature and neutrophilic leukocytosis about 4 to10 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.
Rural dogs residing in areas where A. maculatum is endemic are at risk of 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.

A severe inflammatory response occurs at tissue sites where merozoites are released from mature meronts in muscles, causing intense myositis.
Muscle and periosteal pain is responsible for inability or reluctance to rise, stiffness of gait, and hyperaesthesia.
Muscle atrophy is evident in chronic cases. Muscle atrophy can cause severe weakness.
Decreased tear production may cause mucopurulent ocular discharge.

Diagnosis is based on finding meronts in muscle biopsy samples (Link to Image) or gametocytes in peripheral blood smears (Link to Image). Muscle lesions consist of large cysts (“onion-skin” cysts) and pyogranulomata. 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. An indirect enzyme-lined immunosorbent assay using sporozoites as antigens has been developed but is not commercially available.

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 and nonsteroidal anti-inflammatory drugs can ensure hydration and assist with pain control. Either of two acute parasiticidal treatments may be administered:

A triple-combination therapy consists of trimethoprim-sulfadiazine (15 mg/kg PO q12h for 14 days), pyrimethamine (0.25 mg/kg PO q24h for 14 days), and clindamycin (10 mg/kg PO q8h for 14 days).
OR
Ponazuril may be administered at a dose of 10 mg/kg PO q12h 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) may be 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.

Stringent adherence to 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.