Canine Protothecosis

Amanda M. Hall, DVM; Perry J. Bain, DVM, PhD; Kenneth S. Latimer, DVM, PhD; Bruce LeRoy, DVM, PhD; Pauline M. Rakich, DVM, PhD

Class of 2005 (Hall), Department of Pathology (Bain, Latimer, Leroy), and Athens Veterinary Diagnostic Laboratory (Rakich), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7388.

Introduction

Canine protothecosis is a rare disease caused by Prototheca, a saprophytic achlorophyllus alga. Protothecosis occurs in Europe, Asia, Africa, Oceania, and in North America. The organism affects both humans and animals including cats, dogs and cattle. The organism is ubiquitous in nature and is commonly found in sewage, slime flux of trees and in animal wastes. Despite the abundance of this organism in nature, the incidence of disease is rare.^{1, 2}

Infection

The two species of Protetheca that are known to cause disease in animals are P. zopfii and P. wickerhamii. Protothecosis is an opportunistic infection that occurs when the organism comes into contact with injured skin or mucosa. It is believed that those animals that have suppressed immune systems or are overwhelmed by a pre-existing disease are at greater risk of infection. It is postulated that weak cell mediated immunity is responsible for allowing the organism to gain entrance into the body. However, very few canine cases have undergone significant immune system assessment due to the rarity of this disease. It has also been theorized that the organism can become highly virulent and is able to evade the host’s immune response. It is believed that in the systemic form of the disease the organism is ingested, enters the body via the intestinal mucosa and spreads through out the body hematogenously or through the lymph system. In contrast, the cutaneous form of disease originates with punctures, cuts, or abrasions in the skin.

Incidence

Female dogs and Collies are over represented in most reports of disease. Most cases of protothecosis in the United States are restricted to the Southeast. ²

Clinical Findings

Protothecosis presents as one of two forms of disease. These have been designated systemic infection and cutaneous infection.

Systemic Infection

The systemic form of protothecosis is most often caused by P. zopfii. Organs commonly infected include the eyes, kidney, liver, heart, large intestines, skeletal muscle, myocardium, lymph nodes, thyroid, pancreas, peritoneum, diaphragm, and brain. Clinical signs depend on the organ systems involved and the severity of the lesions. White to tan granulomatous lesions can be seen within affected organs (Fig. 1). These lesions range from 0.5 to 2.0 mm in diameter. The inflammatory cell types seen on histopathologic evaluation are highly variable and may include plasma cells, macrophages, lymphocytes, and neutrophils. Plasma cells often predominate. ¹

Figure 1. Numerous small granulomas of the myocardium from a dog with disseminated protothecosis (courtesy of Dr. Rakich).

Gastrointestinal Signs

The most commonly reported clinical sign of disseminated protothecosis is intermittent bloody diarrhea presenting as hematochezia or melena. The colon is most often affected; however, lesions can be found throughout the intestinal tract. Grossly, colonic mucosal lesions can range from large white nodules to diffuse hyperemia to ulcerations that may or may not be hemorrhagic. These lesions may extend into the submucosa. ¹

Central Nervous System Signs

Clinical signs such as cervical pain, head tilt, depression, ataxia, circling, ataxia and paresis are seen in a large percentage of dogs with systemic protothecosis. At necropsy, the central nervous system may contain white to tan, granulamatous nodules. Microscopically, lesions in the brain and spinal cord can be highly disseminated and consist of regions of necrosis surrounded by mixed inflammatory cells. The number of organisms per lesion can vary from many to none. ¹

Ophthalmic Signs

In a retrospective study, 20 of 26 dogs with systemic protothecosis presented with or developed ophthalmic signs. These dogs generally presented with red, painful eyes and blindness. On ophthalmic examination, the pupil or cornea appeared cloudy. The most common histologic finding in affected eyes is choroditis characterized by exudative granulomatous inflammation and retinal detachment. ²

Cutaneous Infection

Cutaneous infection is associated with infection by P. wickerhamii. This form of protothecosis is less commonly observed. Skin lesions consist of nodules and draining ulcers with crusty exudates on the extremities, trunk and mucosal surfaces (Fig. 2). Hyperkeratosis may be present as well as secondary bacterial infections. Microscopically, masses of Prototheca cells may be found in the dermis, subcutis, and adjacent skeletal muscle. Occasionally, the organisms may spread to the regional lymph nodes. In some animals, the cutaneous form of disease may transform to systemic infection as organisms spread to other tissues and organ systems. ¹

Figure 2. Paw of a dog with draining ulcers associated with cutaneous protothecosis (courtesy of Dr. Rakich).

Clinical Laboratory Findings

The complete blood cell count, biochemical profile, and urinalysis are usually unremarkable unless the disease dog has become debilitated. Cerebrospinal fluid (CSF) may or may not be abnormal. If abnormalities are present, the CSF may have marked pleocytosis (>100 cells/µl) with a predominance of granulocytes and lymphocytes. There also is an increase in protein concentration.

Diagnosis

The most consistent clinical finding with systemic protothecosis is granulomatous retinal separation seen via ophthalmoscopy. Protothecal organisms can be identified on rectal or colonic scrapings if the large intestine is involved (Fig. 3). The protothecal cells are 1.3-16.1 µm in diameter with granular basophilic cytoplasm, and a thin hyaline cell wall. Some cells may be seen going through endosporulation, producing as many as twenty daughter cells. Tissue samples of the affected organs can be submitted and the organism can often be identified on histopathological evaluation (Fig. 4). Prototheca is easily cultured on a variety of laboratory media. Differentiation of P. zopfii and P. wickerhamii can be achieved by fluorescent antibody staining or sugar and alcohol assimilation tests of cultured organisms. If there is renal involvement, the organism may be seen on microscopic evaluation of the urine sediment.^{1, 2}

Figure 3. Rectal scraping from a dog with protothecosis. Organisms (arrows) are delineated by a thin cell wall, vary size, and have a granular internal structure. (Wright stain, courtesy of Dr. Latimer).	Figure 4. Section of pancreas of a dog with disseminated protothecosis. Normal exocrine tissue is present at left. Parenchyma at right has been replaced by proliferating protohecal cells (courtesy of Dr. Latimer).

Treatment

Protothecosis is a difficult disease to treat. Amphotericin B, tetracycline, ketoconazole, itraconazole, fluconazole and clorimazole have been used to attempt to treat this disease. Unfortunately, these drugs have shown little success in treating systemic protothecosis. Surgical excision has been used to correct a colonic stricture that resulted from the systemic form of disease. Cutaneous protothecosis has been successfully treated by surgical excision and drug therapy. Ketoconazole has been used successfully in two cases of cutaneous form that was cased by P. wickerhamii. ¹

Conclusion

Canine protothecosis is a very rare disease that should only be considered after other more common diseases have been excluded. Protothecosis is very difficult to treat and is often fatal. More research is needed to determine why the organism occasionally causes disease and to determine a successful treatment regimen.

References

1. Greene CE (ed): Infectious Disease of the Dog and Cat, 2nd ed. Philadelphia, WB Saunders, 1998, pp. 430-435.

2. Hollingsworth SR: Canine protothecosis. Vet Clin N Am Small Anim Pract 30:1091-1101, 2000.

3. Strunck E, Billups L, Avgeris S: Canine protothecosis. Compend Contin Educ Pract Vet 26:96-102, 2004.

4. Rallis TS, Tontis D, Adamama-Moraitou KK, Mylonakis ME, Papazoglou LG: Protothecal colitis in a German Shepherd Dog. Aust Vet J 80:406-408, 2002.

Acknowledgement

"Black Dog at Yotatiro, Mexico" by Robin Richmond is from her website and is used with permission.

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