A challenging case: A dog with intermittent pain and fever - Veterinary Medicine
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A challenging case: A dog with intermittent pain and fever
This dog was repeatedly evaluated because of waxing and waning pain. A key radiographic sign in determining the diagnosis did not appear until much later.


For definitive diagnosis of canine hepatozoonosis, the parasites must be detected on cytologic or histologic examination. Examination of blood smears may reveal the gametocytes within the cytoplasm of leukocytes as 11-x-5-μm oblong inclusion bodies with clear or pale-blue capsules.3 Recent studies have identified both merozoites and gamonts in circulating macrophages.4 But often only a few white blood cells (about 0.1%) are infected. In addition, the parasites' nuclei stain poorly, and the parasites may leave the cells once the blood sample is collected, so only empty capsules remain. Thus, skeletal muscle biopsy is often indicated for definitive diagnosis, and histologic examination reveals meront cysts, merozoites, or pyogranulomas among the muscle cells.3

Hepatozoon americanum infection in dogs is most common where A. maculatum, resides—primarily the Gulf Coast states. Hepatozoon americanum needs two hosts to complete its life cycle, and A. maculatum is thought to be the definitive host. Dogs are the intermediate host; there have been reports of the disease in dogs in Texas, Oklahoma, Louisiana, Mississippi, Alabama, Georgia, and Florida.1,2 When the ticks feed on infected dogs, they ingest gametocytes. In the tick, these gametocytes fuse into an ookinete. The ookinete becomes an oocyst consisting of many sporocysts, each of which contains 12 to 24 sporozoites.3 Dogs become infected by ingesting the ticks, likely through grooming, rather than by being bitten by the tick.1 Hundreds of sporozoites can then penetrate the dog's gastrointestinal tract and circulate through the blood or lymphatic system.1,3

To continue their life cycle, the sporozoites enter macrophages4 where they are protected and intracellular merogony (asexual reproduction) may occur.1 When a meront ruptures and the cyst wall disintegrates, the area becomes inflamed and angiogenesis occurs.1 Zoites that have been phagocytized enter the bloodstream through these vessel walls and may either circulate as gamonts, which ticks can ingest while feeding on the dog, or become merozoites, which repeat the asexual reproduction life cycle within the dog. Thus, a dog that ingests a single infected tick can have a prolonged waxing and waning illness associated with the repeated asexual reproduction cycles of the organism.1

Cysts are the stage most likely to be seen in dogs. The 250- to 500-μm-diameter, round-to-ovoid cysts have pale-blue laminar membranes and resemble an onion skin.3 These cysts are usually found in cardiac and skeletal muscle, lymph nodes, the spleen, and the pancreas.3 Long-term complications may include vascular thrombosis; interstitial nephritis; glomerulonephritis; nephrotic syndrome; amyloid deposits in the spleen, lymph nodes, small intestines, liver, and kidneys; and hypercoagulability.2,3

Initially, treatment is empirical depending on the presenting signs. Often, doxycycline (5 mg/kg once a day for 14 days) is initiated to treat for other possible concomitant tick-borne diseases. No definitive treatment reliably eliminates H. americanum in dogs. Initially, the signs may subside with a two-week course of trimethoprim-sulfadiazine1,2 or trimethoprim-sulfamethoxazole (15 mg/kg orally b.i.d.), pyrimethamine (0.25 mg/kg orally once a day), and clindamycin (10 mg/kg orally t.i.d.) along with nonsteroidal anti-inflammatory drugs for fever and pain. Many dogs relapse within six months, possibly because of cyst rupture and release of merozoites with resulting secondary pyogranulomatous inflammation.

Administering decoquinate (10 to 20 mg/kg orally b.i.d.) for at least two years may extend remission.1-3 Optimally, any patient that relapses should be treated with a two-week course of trimethoprim-sulfadiazine1 or trimethoprim-sulfamethoxazole, pyrimethamine, and clindamycin, and the dosage of decoquinate should be increased simultaneously to the upper dosage limits.


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