Page 1535 - Small Animal Internal Medicine, 6th Edition

CHAPTER 97 Polysystemic Mycotic Infections 1507

antigen was measured in samples from 60 dogs with anti- CRYPTOCOCCOSIS
body titers 1 : 16 or greater, the sensitivity was low for both Etiology and Epidemiology
VetBooks.ir serum (19%) and urine (3.5%), suggesting this assay should Cryptococcus neoformans is a 3.5- to 7.0-µm yeast-like
not be used in dogs (Kirsch et al., 2012).
Treatment organism with worldwide distribution. It has a thick polysac-
charide capsule and reproduces by narrow-based budding
Ketoconazole is inexpensive and a drug of choice for (see Table 97.1). Cryptococcus gattii is also common in some
treatment of coccidioidomycosis in dogs (see Table 97.1). regions and is associated with disease. Clinical findings with
However, this drug commonly leads to inappetence, vom- either infection are similar. Many cases have been described
iting, diarrhea, weight loss, and increases in liver enzyme in California, British Columbia, and both coasts of Aus-
activities in some dogs and cats. In dogs, long-term use of tralia. An outbreak of Cryptococcus spp. infections recently
ketoconazole can suppress testosterone and cortisol produc- occurred in people, dogs, cats, ferrets, and a bird in British
tion and has been associated with cataracts. Amphotericin Columbia (Lester et al., 2004; MacDougall et al., 2007).
B should be used if life-threatening disease is present or if Most cases were on Vancouver Island and were caused by
response to ketoconazole is poor. Itraconazole can be used C. gattii. The organisms are acquired from the environment;
in animals with toxicity from ketoconazole. Fluconazole risk factors significantly associated with infection in animals
should be considered for animals with meningoencephali- in the British Columbia outbreak included living near a site
tis. Posaconazole has fungistatic activity against Coccidioi- of soil disturbance such as logging sites, having an above-
des spp. and has been used successfully in management of average level of activity, hunting, and having owners who
human cases with refractory respiratory disease. Pharma- hiked or visited a botanic garden (Duncan et al., 2006b).
cokinetic information is now available for this drug in cats There may be breed predispositions; in one study in Cali-
(Mawby et al., 2016). fornia, American Cocker Spaniels were more likely to have
Cats and dogs should be treated for 60 to 90 days or until cryptococcosis than other breeds (Trivedi et al., 2011a). In
clinical illness has been resolved for at least 1 month. Bone the same study, most cats were infected by C. gattii and
infections are often incurable; therefore repeated treatments most dogs were infected by C. neoformans. Whether disease
are often required. When treated with ketoconazole, itra- occurs is dependent on both host and organism factors (Ma
conazole, or fluconazole, 32 of 44 cats with coccidioidomy- and May, 2009).
cosis were asymptomatic during or after treatment; relapse The route of transmission for Cryptococcus spp. is believed
occurred in 11 cats during or after treatment (Greene et al., to be inhalation. Nasal and pulmonary disease manifesta-
1995). Voriconazole is a newer fluconazole derivative that tions are common; however, on the basis of culture and
achieves high concentrations in the CNS and so could be serologic studies of healthy animals, an inapparent carrier
considered for dogs with CNS involvement. Neurologic state also occurs. The organism probably spreads to extra-
adverse effects appear to be common in cats but have not pulmonary sites hematogenously; the CNS may also be
been well defined in dogs (Quimby et al., 2010). infected by direct extension across the cribriform plate from
Daily administration of lufenuron, a chitin synthesis the nasal cavity. Immunity is cell mediated; individuals with
inhibitor, has been evaluated in a limited number of dogs incomplete responses do not completely remove the organ-
with coccidioidomycosis. Nikkomycin Z (NikZ) is another ism, thus resulting in granulomatous lesions. The polysac-
chitin synthase inhibitor that was used to treat 12 dogs charide capsule of the organism inhibits plasma cell function,
with Coccidioides spp.-associated respiratory disease for an phagocytosis, leukocyte migration, and opsonization, poten-
average of 3 months (Shubitz, 2013). Seven of the nine dogs tiating infection.
that completed the protocol had clinical and laboratory evi- Cryptococcus spp. can be primary pathogens. However,
dence of improvement. Pharmacologic studies with terbin- preexisting immunosuppressive conditions are documented
afine have been completed (Sakai et al., 2011), and it could in approximately 50% of people with cryptococcosis. Sero-
be considered as another option for the treatment of coc- logic evidence of co-infection with feline immunodeficiency
cidioidomycosis (30-35 mg/kg, orally [PO], daily). virus or feline leukemia virus occurs in some cats with cryp-
tococcosis. Potentially immunosuppressive conditions such
Zoonotic Aspects and Prevention as administration of corticosteroids, ehrlichiosis, heartworm
One study showed an association between the location of disease, and neoplasia are identified in a small percentage of
canine and human coccidioidomycosis in California sug- dogs with cryptococcosis.
gesting dogs could be used as sentinels for infection in
people (Grayzel et al., 2017). People exposed to C. immitis Clinical Features
develop asymptomatic infection or mild, transient respira- Cryptococcosis is the most common systemic fungal infec-
tory signs. The organism is not transmitted from infected tion of cats and should be considered a differential diagnosis
animals to people. However, the mycelial phase occurs for cats with clinical evidence of upper or lower respiratory
outside the vertebrate host, so fomites such as bandage mate- tract disease, subcutaneous nodules, lymphadenopathy,
rial and cultures should be handled carefully. Avoiding intraocular inflammation, fever, or CNS disease. Lower
endemic areas is the only way to prevent the disease. urinary tract disease has also been described. All ages of cats