Hepatozoonosis and American Canine Hepatozoonosis

Etiology, Epidemiology, and Transmission

Etiology, Epidemiology, and Transmission:

Hepatozoonosis is a tickborne disease of wild and domestic carnivores caused by the protozoal agent, Hepatozoon canis . It is unclear whether or not infections in wild and domestic Felidae are caused by H canis , or by another species of Hepatozoon . This organism is transmitted by the brown dog tick, Rhipicephalus sanguineus , but its mode of transmission is not typical in the classical sense of a tickborne disease; although the tick ingests the organism from the mammalian host during a blood meal, and oocysts develop in the tick, the dog (or cat) actually obtains the disease from an infected tick by ingesting the tick, and not from being bitten by the tick. Unique features of the clinical presentation in North American dogs have suggested that a different strain or species of Hepatozoon may be responsible for the disease in North America as compared to other parts of the world; in 1997, this was confirmed. It is now known that the disease in North America is caused by the protozoal agent H americanum , which is transmitted by the Gulf Coast tick, Amblyomma maculatum , instead of by the brown dog tick. The disease in North America is now referred to as a separate entity, American canine hepatozoonosis.

In much of the world (India, Africa, southeast Asia, the Middle East, southern Europe, and islands in the Pacific and Indian Oceans), most dogs with hepatozoonosis generally have subclinical infections or only mild clinical signs, and immunosuppression caused by concurrent disease or other factors appears to play an important role in the manifestation of significant clinical signs. In the USA, immunosuppression or concurrent disease does not appear necessary to induce the more severe clinical signs typically seen. Most cases in the USA have been diagnosed in Texas (primarily along the Gulf Coast), Oklahoma, and Louisiana, but cases have also been reported as far east as Tennessee, Alabama, Georgia, and Florida. This 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 parallels the distribution of the Gulf Coast tick. H americanum may also be found in Central and South America.

Experimentally, dogs >4-6 mo old are resistant to infection with H canis . However, H americanum causes severe clinical signs, even in adult dogs. Because disease caused by H americanum is much more clinically significant than that caused by H canis , the descriptions in the remainder of this chapter refer primarily to American canine hepatozoonosis.

Clinical Findings:

The tissue phases of the hepatozoonosis organism induce pyogranulomatous inflammation, which results in clinical signs. These signs, which may be intermittent, include fever, depression, weight loss, poor body condition, muscle atrophy and weakness, mucopurulent ocular discharge, and bloody diarrhea. Surprisingly, many dogs maintain a normal appetite. Severe hyperesthesia or pain over the paraspinal region is a common finding on physical examination; cervical, joint, or generalized pain are also seen. Hyperesthesia manifests as stiffness and reluctance to move, as well as cervical and/or truncal rigidity. Fever, which may fluctuate with the waxing and waning of clinical signs, may range from 102.7-106.0°F (39.3-41.0°C) and is unresponsive to antibiotics. Longterm sequelae include glomerulonephritis and amyloidosis.

Diagnosis:

The most consistent laboratory abnormality is a neutrophilic leukocytosis, with counts ranging from 20,000-200,000 cells/µL. This is typically a mature neutrophilia, although a left shift may be present. A mild to moderate normocytic, normochromic, nonregenerative anemia is another common finding. The platelet count is typically normal to elevated. Mildly increased alkaline phosphatase, hypoalbuminemia, and increased CK may also be seen. Although profound hypoglycemia has been reported, this is thought to be an in vitro sampling artifact caused by increased metabolism of glucose due to the high number of leukocytes. On radiographs, periosteal reactions may be seen involving any bone (except the skull), particularly the long bones; these periosteal reactions are most likely related to an inflammatory response to tissue phases of the organism in adjacent muscle.

The definitive diagnosis of hepatozoonosis is made by finding gamonts in neutrophils or monocytes (using Romanowsky-type stains); identifying the typical cysts, meronts, or pyogranulomas in muscle biopsies; or detecting serum antibodies against H americanum sporozoites. In some dogs, multiple or sequential muscle biopsies may be necessary to detect the organism. The relatively new serologic method of diagnosis (an ELISA that detects antibodies to H americanum sporozoites) appears to be both highly sensitive and specific.

Treatment:

Hepatozoonosis is a life-long infection in dogs. No known therapeutic regimen completely clears the body of the organism. In the past, treatment has been frustrating because most dogs showed only temporary improvement, with frequent relapses within 3-6 mo and death within 2 yr of diagnosis. Remission of clinical signs can usually be achieved through combination therapy, referred to as TCP, which includes 3 drugs: trimethoprim-sulfadiazine (15 mg/kg, PO, bid), clindamycin (10 mg/kg, PO, tid), and pyrimethamine (0.25 mg/kg, PO, sid); these drugs should be administered for 14 days. Unfortunately, remission with this therapy has often been short-lived, and dogs frequently relapse within 2-6 mo. However, a relatively new adjunctive treatment using decoquinate (a large animal anticoccidial drug) has been described; decoquinate does not resolve active clinical disease but may prevent clinical relapses; it is given after resolution of clinical signs as an adjunct to TCP therapy. The recommended dose for decoquinate is 10-20 mg/kg, PO, bid continuously for 2 yr. The advent of TCP combination therapy followed by daily decoquinate therapy has resulted in a marked improvement in the prognosis for dogs with hepatozoonosis.

Other treatments include imidocarb dipropionate (5 mg/kg, SC, given once), a combination of imidocarb dipropionate (6 mg/kg, SC, every 14 days) with tetracycline (22 mg/kg, PO, tid for 14 days) or the coccidiostat toltrazuril (5-10 mg/kg, SC or PO, sid for 3-5 days or 5 mg/kg, PO, bid for 4 days). The effect of imidocarb therapy has been inconsistent and may be dependent on the severity of signs and geographic location. Similarly, although excellent initial clinical response to toltrazuril has been reported, relapses occurred, and there was no evidence of clearing of the cyst forms from the muscle tissue.

NSAID may be the best treatment for control of fever and pain, especially during the first few days of TCP therapy. Glucocorticoid administration should be avoided, because although steroids may provide temporary relief, longterm use can exacerbate the disease.

Prevention of access to ticks is the most effective form of control for hepatozoonosis. There is no known zoonotic risk with this disease; whether the lack of reports in humans is due to the minimal risk of ingesting infected ticks or to natural resistance is unknown.