Chapter 70 Protothecosis is an uncommon cutaneous or systemic disease caused by Prototheca species, which are unicellular algae. Prototheca spp. lack chlorophyll, and as a result they are dependent on a saprophytic lifestyle. Although ubiquitous in nature, they are especially prevalent in warm, humid climates (e.g., southern and southeastern United States, northeastern Australia, southern continental Europe, Japan) in aqueous environments where decaying organic matter is present. They have been isolated from tree slime, sewage, fresh and saltwater sources, fish tanks, soil, animal excrement, and foodstuffs. Routine water chlorination may not inactivate Prototheca.2 Prototheca spp. also colonize the skin and gastrointestinal and respiratory tracts of humans.3 The algae are round to oval, 5 to 30 µm in diameter, have a thick cell wall, and reproduce asexually by endosporulation (internal division), which results in a sporangium that contains up to multiple sporangiospores. Rupture of the sporangium releases sporangia into tissues, and the cycle continues. Although the classification of Prototheca species is still in flux, six species are currently recognized: Prototheca zopfii, Prototheca wickerhamii, Prototheca blaschkeae, Prototheca stagnora, Prototheca ulmea, and Prototheca cutis (Table 70-1).4 Only P. zopfii and P. wickerhamii have been identified as causes of disease in dogs and cats. Two genotypes of P. zopfii are recognized. P. zopfii genotype 1 is a weakly pathogenic variant and has been isolated from a minority of protothecal mastitis cases in dairy cows.4,5 In contrast, P. zopfii genotype 2 may be the most virulent Prototheca variant. It causes the vast majority of bovine Prototheca mastitis cases worldwide and most protothecosis in dogs.4 P. wickerhamii is often associated with cutaneous disease and has to date been isolated from all affected cats, some dogs, and almost all human patients (see Table 70-1). In dogs, disease caused by P. wickerhamii may follow a less aggressive clinical course than that caused by P. zopfii genotype 2.6 TABLE 70-1 Major Species (and Genotypes) of Prototheca and Their Clinical Relevance Protothecosis is an uncommon and sporadic disease of dogs and is rare in cats. In dogs, protothecosis is usually a serious disseminated disease, but localized cutaneous disease occurs occasionally. Most affected dogs do not have a history of immunosuppressive drug therapy or illness. Boxer dogs and collies may be predisposed,6 possibly secondary to an underlying genetic immunodeficiency, although a variety of other small- and large-breed dogs also can be affected. Occasionally protothecosis occurs in dogs in conjunction with infection by other opportunistic pathogens such as Neospora,7 which supports the likelihood that underlying immune deficiency is present. At the author’s hospital, disseminated protothecosis was diagnosed in a canine renal transplant recipient that was treated with cyclosporine, and lymphocutaneous P. wickerhamii infection was diagnosed in a dog treated with chemotherapy for lymphoma.7 The median age of affected dogs in one series of 17 dogs was 4 years (range, 18 months to 11 years), and approximately 70% of the affected dogs were female.6 Cats with protothecosis have single or multiple nodular skin lesions; disseminated disease has not been reported. Affected cats are typically FIV and FeLV negative, are otherwise in good health, and have ranged in age from 3 to 16 years.8–13 The pathogenesis of protothecosis is not fully understood. Infection may occur secondary to cutaneous inoculation of organisms, which may be followed by development of localized cutaneous nodules or dissemination through lymphatic or hematogenous spread. It is also possible that systemic invasion by organisms that are ingested or colonize the gastrointestinal tract occurs. An incubation period of 10 days to several weeks has been suggested for human protothecosis, based on recollection of penetrating injuries before onset of disease.2 In dogs, Prototheca can disseminate to a variety of tissues, but especially the colon, eyes, brain and meninges, kidneys, and long bones. This results in clinical signs of inappetence and weight loss; acute or chronic large bowel diarrhea (often with hematochezia and tenesmus); blindness; neurologic signs such as obtundation, seizures, or ataxia; polyuria and polydipsia; and sometimes lameness due to osteomyelitis.6,13–16 Deafness is often reported in association with disseminated protothecosis and may occur as a result of central nervous system (CNS) or inner ear involvement.13,16,17 Ocular lesions include granulomatous chorioretinitis, uveitis, and panophthalmitis. Other affected organs include the liver, skeletal muscle, thyroid gland, lymph nodes, spleen, pancreas, stomach, small intestine, omentum, myocardium, aorta, spinal cord, and/or lungs.16–19 Involvement of these organs may lead to other signs such as vomiting, small bowel diarrhea, and/or melena. Sudden death has also been reported, possibly secondary to myocardial involvement.6,20,21 Cutaneous lesions in dogs are nodular and may ulcerate. They often involve the footpads or distal limbs and associated draining lymph nodes, but involvement of other sites such as the trunk and planum nasale can also occur. In cats, single or multiple firm and sometimes ulcerated cutaneous nodules may be present. Lesions may be located on the head, footpads, and distal limbs and tailbase8–10 and can resemble those caused by Cryptococcus or Sporothrix. Dogs with disseminated disease may be obtunded and/or dehydrated and can have a thin body condition. Some dogs are febrile, but rectal temperature may also be normal. Ocular involvement may be manifested by blindness or evidence of conjunctivitis, hyphema, uveitis, cataract formation, panophthalmitis, or granulomatous chorioretinitis, often with retinal detachment. Arrhythmias with pulse deficits may be present in dogs with protothecal myocarditis.7 Neurologic signs include obtundation, blindness, deafness, ataxia, abnormal placing reactions, circling, head tilt, nystagmus, strabismus, and abnormalities of cranial nerve function such as absent or decreased facial sensation, palpebral, menace, or gag reflexes.6,14,22–25 Dried fecal material or blood may be present around the anus, and rectal examination may reveal the presence of hematochezia, increased fecal mucus, or melena. The CBC in dogs with disseminated protothecosis is often normal. Occasionally it reveals nonregenerative anemia and/or leukocytosis due to a neutrophilia and sometimes monocytosis.15,16,18 Mild bandemia and/or eosinophilia may be present in some dogs. The serum biochemistry panel may also be normal or reveal hyperglobulinemia due to a polyclonal gammopathy. Mild to moderate azotemia may be evident in dogs with renal involvement.15,18 Hypoalbuminemia and hypocholesterolemia may occur with severe bowel involvement.6 The urinalysis in dogs with disseminated protothecosis may be unremarkable or reveal isosthenuria, hematuria, pyuria, proteinuria, and the presence of Prototheca organisms in the sediment.15 Urinalysis and urine culture should be performed in all dogs suspected to have protothecosis, because more than half of affected dogs shed algae into the urine. CSF analysis in dogs with CNS protothecosis may be normal or reveal markedly increased total nucleated cell count (sometimes >1000 cells/µL) and increased CSF protein concentration (often >500 mg/dL).18,22,23 Eosinophilic pleocytosis has been described in some dogs,22,25 but eosinophils are not always present.23 Prototheca algae may also be found in the CSF.22,23 Thoracic radiographs in dogs with disseminated protothecosis are usually unremarkable.15,18,19,21 Radiographs of affected long bones may reveal periosteal proliferative and/or osteolytic lesions due to osteomyelitis.6 Findings on abdominal ultrasound examination in dogs with disseminated protothecosis include hyperechogenicity of the renal cortices,15 a thickened colonic wall with loss of normal bowel wall layering,6 and abdominal lymphadenopathy. Some dogs have no abdominal sonographic abnormalities despite the presence of disseminated disease with colonic and renal involvement.7
Protothecosis
Etiology and Epidemiology
Species
Host Species Infected
Clinical Manifestations
P. zopfii genotype 1
Cattle
Mastitis (low pathogenicity)
P. zopfii genotype 2
Dogs, humans, cattle, other
Mastitis (cattle), disseminated infections (dogs)
P. wickerhamii
Dogs, cats
Cutaneous disease
P. blaschkeae
Cattle, humans
Mastitis (cattle), cutaneous disease (humans)
P. stagnora
Nonpathogenic
NA
P. ulmea
Nonpathogenic
NA
P. cutis
Humans
Cutaneous disease
Clinical Features
Physical Examination Findings
Diagnosis
Complete Blood Count and Serum Biochemical Tests
Urinalysis
Cerebrospinal Fluid Cytology
Diagnostic Imaging
Sonographic Findings
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