Cryptococcosis is a systemic fungal infection of worldwide significance that initially infects the nasal cavity, paranasal tissues, or lungs. It can then spread, most commonly to the skin, eyes, or central nervous system. The disease occurs in a wide variety of mammalian species. Among domestic animals, it occurs most commonly in the cat, in which it is the most common of the systemic fungal infections. It is often seen in the southeastern and southwestern United States, southern California, the western part of British Columbia, and the east coast of Australia.
Cryptococcosis is caused primarily by Cryptococcus neoformans and Cryptococcus gattii, encapsulated basidiomycetous yeast. Several sources of this yeast exist, including bird excreta, soil, and fruits. Cryptococcus species can survive in feces for up to two years. The infection does not spread via direct contact but instead is transmitted by inhalation of the organism from the soil or feces. Cryptococcus neoformans var. gattii is primarily found in tropical and subtropical areas due to its very specific habitat of Eucalyptus trees.
The four groups of organs affected are the respiratory tract, central nervous system, eyes, and skin. The clinical signs, therefore, depend on the system(s) affected. Respiratory infections (seen in over 80% of cases) are characterized by sneezing, nasal discharge (pus-filled, bloody, or clear), swelling underneath the skin in the nasal area, mouth lesions, and swelling of the lymph nodes. Neurological signs vary with the location of the lesion and can include depression, poor movement coordination, seizures, partial paralysis, and blindness. Eye abnormalities predominately affect the retina, choroid, and optic nerve. Clinical signs can range from dilated, unresponsive pupils and blindness to chorioretinitis, anterior uveitis, and retinal damage. While the prognosis for survival with the ocular form of cryptococcosis is fair to good using triazole antifungals, the prognosis for return of vision is guarded to poor due to retinal damage.
Skin lesions are seen in approximately 45% of infected animals and often occur with additional organs simultaneously being affected. The skin lesions are more likely caused by previous spreading of the infection to the skin. A more rare presentation of cryptococcosis may include bone destruction, chronic cough, and kidney failure.
Dogs are infected by C. neoformans much less frequently than cats which are 7-10 times more likely to be infected. The average age of infected dogs is 3.5 years and, unlike cats, there is no gender predisposition. Overrepresented dog breeds include American Cocker Spaniel and Labrador Retriever in North America, and Doberman Pinscher and Great Dane in Australia. Cryptococcosis affects the same four organ systems as with cats, but the CNS and eyes are more commonly involved in dogs than in cats. The clinical signs are similar to those found in cats except that fever (103-105° F) is seen more often in affected dogs (25% of cases).
Diagnosis & Treatment
Cryptococcosis is a challenging disease to treat in cats and dogs and it typically requires protracted therapy and long-term follow-up. The most rapid and practical means of diagnosing Cryptococcus neoformans is by laboratory test (examination or nasal discharge and urine analysis). Amphotericin B (AMB), alone or in combination with other antifungal drugs, has been previously used to treat cryptococcosis. However, this drug is usually reserved for life-threatening and previously unresponsive cases due to its toxicity. Several disadvantages of AMB make it less desirable than other drugs. Intravenous treatment is difficult and causes many adverse reactions, AMB has side-effects including nephrotoxicity and severe azotemia, it has poor efficacy in dogs, and is ineffective with cryptococcal meningitis because AMB does not cross the blood-brain barrier.
Ketoconazole (KTZ) is another treatment option for cryptococcosis. Itraconazole (ITZ) is a triazole antifungal drug similar to KTZ but with fewer adverse side-effects. Fluconazole (FCZ) is another triazole agent that does have the ability to cross the blood-brain barrier and has fewer side effects than the aforementioned antifungal compounds. FCZ has been reported to have the highest success rates in cats, including those with advanced, longstanding, or disseminated disease.
Outcomes of treatment of cryptococcosis are quite varied. Drug therapy is long-term (average of 8.5 months) and relapses occur frequently. Patients with the CNS form of cryptococcosis will require lifelong treatment maintenance. The prognosis is much worse if the patient has the neurological form of disease or is immunocompromised by FeLV or FIV infections. Since Cryptococcus neoformans is ubiquitous, the best means of prevention is to decrease contact with areas containing a high concentration of organisms (pigeon droppings, damp buildings or basements).
A case reported described Cryptococcus gattii (the second most important cause of cryptococcosis) infection causing spinal cord compression in a dog. Neurologically, the dog was paralyzed in both hind limbs. Following surgery, the dog had improved neurologically and was demonstrating some early evidence of mild motor function in the hind limbs. The owners reported improvement in motor function at home over the next several weeks.
The number of C. gattii infections is not only increasing in the endemic areas in South and Central America but also in the USA, where it is now a major cause of human and animal disease, with increasing cases reported from the Southeastern parts, especially California.4
- Cecily A. Reynolds, DVM; Perry J. Bain, DVM, PhD; and Kenneth S. Latimer, DVM, PhD
Department of Pathology (Bain, Latimer), College of Veterinary Medicine, The University of Georgia. Canine and Feline Cryptococcosis
- Stephen J. Ettinger, DVM, DACVIM and Edward C. Feldman, DVM, DACVIM. Textbook of Veterinary Internal Medicine
- Acute hind limb paralysis secondary to an extradural spinal cord Cryptococcus gattii lesion in a dog
- MLST and Whole-Genome-Based Population Analysis of Cryptococcus gattii VGIII Links Clinical, Veterinary and Environmental Strains, and Reveals Divergent Serotype Specific Sub-populations and Distant Ancestors. PLoS Negl Trop Disv.10(8); 2016 Aug PMC4975453