Cryptococcosis in Cats

Overview of Cryptococcosis in Cats

Cryptococcosis is an infectious disease caused by the fungus Cryptococcosis neoformans. The disease affects human beings and animals and is contracted by inhaling infectious spores. The excrement of birds, especially pigeons, is the main environmental reservoir for the spores, although birds rarely become infected with this organism due to the higher body temperature, which does not allow the growth of the organism. After the spores are inhaled, the organism spreads to other organs. Cryptococcus has a tendency to invade the nervous system.

Below is an overview of Cryptococcosis in Cats followed by detailed information on the diagnosis and treatment of this serious infection.

Immunosuppressed humans and animals are at increased risk for developing cryptococcosis. Cryptococcosis has a worldwide distribution.

In affected cats, non-specific symptoms of systemic illness are most common, such as weight loss and lethargy. Central nervous system problems may also occur such as head tilt, back-and-forth eye movements called nystagmus, paralysis of the facial nerve leading to inability to blink, incoordination, circling and seizures. Eye problems, such as hemorrhage in the retina and inflammatory disorders of the eye called chorioretinitis and anterior uveitis, also are common.

Contact with infected animals is not a concern because the yeast form of the organism grows in infected tissues and does not become aerosolized.

Diagnosis of Cryptococcosis in Cats

Diagnostic tests are needed to recognize cryptococcosis and confirm the diagnosis. Tests may include:

• A complete medical history and physical examination. The diagnosis of cryptococcosis is based on history, clinical symptoms, microscopic examination of exudates, serologic tests and biopsy if necessary.
• Serology. Blood samples or samples of cerebrospinal fluid in animals with nervous system symptoms may be tested for antibodies. The most commonly used serology test is the latex agglutination test, designed to detect antigens from the capsule of the fungus. The test is very specific and sensitive. False negative results may occur in localized infections and false positive results may result from contamination of the specimen by talc from latex gloves worn during fluid collection.
• Microscopic examination of exudate from cutaneous nodules or the nose. The organism also can be identified by microscopic examination of tissue biopsy specimens (histopathology). Special stains may be needed.

Treatment of Cryptococcosis in Cats

Treatment for cryptococcosis may include:

• Surgery to de-bulk lesions in the nasal cavity. The prognosis for recovery is poor when infected cats have widespread nervous system involvement.
• Anti-fungal drugs such as amphotericin B, flucytosine, ketoconazole, itraconazole, and fluconazole.

Home Care and Prevention

Administer as directed any medications prescribed by your veterinarian and follow recommendations for dietary modification. Long term treatment up to 6 months or more may be required. Observe your pet’s general condition: Watch for worsening of symptoms and bring any changes to the attention of your veterinarian.

Some anti-fungal medications (e.g. ketoconazole, itraconazole) have the potential to cause liver damage. The animal should have periodic blood tests performed to evaluate for the presence of liver damage. These medications should be administered with food and they may cause vomiting or diarrhea.
Amphotericin B has the potential to cause kidney damage and must be given by intravenous infusion after being diluted in a 5 percent dextrose solution. The animal should have periodic blood tests performed to evaluate for the presence of kidney damage.

The possible sources of infection for affected animals should be evaluated because these areas represent potential sources of exposure and infection for human beings as well, especially children, immunosuppressed patients, and the elderly.

Restrict animals from areas that contain large amounts of pigeon droppings, especially shady, damp buildings. Areas where pigeons reside should be cleaned with hydrated lime diluted in water and sodium hydroxide solution.

In-depth Information on Feline Cryptococcosis

Cryptococcosis is a systemic fungal disease caused by Cryptococcus neoformans. Cryptococcus is a yeast-like fungus found most often in association with pigeon droppings. Cryptococcus does not cause disease in pigeons due to the high body temperature of these birds (107.6 degrees Fahrenheit or 42 degrees Celsius), which inhibits growth of the organism. Optimal growth occurs at 98.6 degrees F (37 C), which is the average temperature of mammals. It has worldwide distribution. It is the most common systemic mycosis in cats.

Cryptococcus has a thick capsule surrounding it, which contributes to its virulence and resistance to treatment. Infection occurs after inhalation of the organism, when cryptococcus produces a thick capsule that interferes with the ability of the immune system to eliminate it.

Animals that are compromised immunologically, such as by feline immunodeficiency virus, feline leukemia virus, corticosteroid therapy or malnutrition are most susceptible.

Spreading of infection depends on the host’s immunity however not all affected animals have concurrent immunosuppressive disease to justify the development of cryptococcosis. Cell-mediated immunity is vital to recover from Cryptococcosis. More specifically, it seems that T helper type 1 cells (the ones producing interleukin-12 and gamma interferon) are the ones involved in the defense mechanisms against this type of infection.

Clinical Symptoms of Cryptococcosis in Cats

• Respiratory disease is present in most cases (70 percent). The nasal cavity is affected in 80 percent of cats. Sneezing and nasal discharge are common clinical symptoms.
• Involvement of the nasopharynx is common. Symptoms such as snoring and breathing difficulty are seen.
• Superficial skin nodules are found in 40 percent of animals. They include papules, nodules and draining tracts. Organisms are frequently detected in the draining material.
• Neurological signs are variable depending on the location of the infection. They are present in 15 percent of cases and include ataxia, seizures, depression, circling, head-pressing, head tilt, nystagmus, facial paralysis, and blindness.
• Ocular signs are present in 15 percent of cases and include dilated, unresponsive pupils, infection of the retina, retinal hemorrhage and inflammation of the front chamber of the eye are not uncommon.

Other diseases of the nasal cavity and nervous system may produce similar signs and must be eliminated as diagnostic possibilities:

• Nasal cavity tumors
• Foreign bodies in the nasal cavity
• Other fungal infections (aspergillosis)
• Tooth root abscess
• Chronic bacterial sinusitis
• Nervous system diseases
• Other infectious diseases such as distemper and toxoplasmosis
• Cancer of the nervous system like lymphosarcoma
• Granulomatous meningoencephalitis
• Epilepsy
• Certain metabolic diseases like hepatic encephalopathy
• Drug or chemical toxicity

Diagnosis In-depth

• Diagnosis is based on history, clinical signs, serology, cytology, biopsy for histopathology and culture.
• Serology (latex-agglutination test) to detect capsular antigen is highly specific and sensitive. False negative could be due to localized infection. False positive may be due to contamination of the specimen with talc from latex gloves used during the collection.

Latex antigen titer is positively correlated with disease severity. Patients with disseminated skin or lymph node involvement have significantly higher titers than those that do not.

The presence of neurological signs, the species of the patient, concurrent viral disease in cats and the biotype of the isolate have no significant association with the latex agglutination titer.

Cats that die of active cryptococcosis despite treatment do not always have significantly higher titers than the ones that respond to treatment. Generally, the antigen titer declines by two- to four-fold per month during successful therapy. It has been recommended that antifungal therapy be continued until the latex agglutination test titer declines to less than one, or therapy be discontinued after a 32-fold or greater reduction in titer, with periodic monitoring of the serum antigen titer.

Treatment of serum samples with pronase substantially increased the sensitivity of the latex agglutination test.

• Antibodies against the organism can also be measured. Over 80 percent of animals have elevated antibody levels at the time of diagnosis, during or after successful therapy. Antibody levels in these patients remain elevated or decline slowly after treatment. The persistence of increased anti-cryptococcal antibody levels in over half of the feline cases following active infection suggest the use of antibody determinations as a seroepidemiologic marker of previous infection.
• Cytology of nasal and skin exudate is often positive. New methylene blue and Gram’s stain are suitable stains to detect the organism.
• Histopathology. Special stains should be used to detect cryptococcus. For example, Mayer mucicarmine can detect the capsule of the fungus, or Periodic Acid Shiff, Gomori methenamine silver. Organisms are usually numerous.
• Fungal culture. Isolation of the organism can be done from the exudate, or from tissue samples. Sabouraud agar is a suitable media. Organism is sensitive to cyclohexamide. Organism will grow in 2 to 42 days depending on the dose.
• Cultures are not a hazard, as the organisms do not aerosolize from cultures.

Treatment In-depth

• Various antifungal drugs can be used for the treatment of cryptococcosis.
• Treatment outcome is influenced by FeLV and FIV status; cats seropositive for FeLV or FIV have a higher likelihood of treatment failure.
• Treatment outcome is not influenced by gender, location of the infection, or magnitude of pretreatment serum antigen titer.
• The cryptococcal antigen titers of cats successfully treated decreases over time during treatment.
• For cats in which treatment is successful, antigen titers usually decrease significantly from pretreatment values at 2 months after initiation of treatment. By 10 months after initiating treatment, titers decrease by at least 2 orders of magnitude in cats successfully treated.
• Most patients require prolonged therapy. The average case requires treatment for 6 to 10 months depending on the severity and extent of the disease.

Treatments for Cryptococcosis in Cats may include:

• Ketoconazole (Nizoral®) at 10 to 20 mg/kg twice daily with food for 6 to 10 months. Response is not as good as it is with other drugs (e.g. itraconazole). In addition ketoconazole is not well tolerated by cats and frequently causes vomiting and diarrhea. It has the potential to cause hepatitis (liver inflammation).
• Itraconazole is given orally at 10 mg/kg twice daily for 6 to 10 months. It comes in 100 mg capsules (Sporonox®) and in 10 mg/ml solution. The solution appears to have better absorption and bioavailability than the capsules. Adverse effects include vomiting, diarrhea and liver disease.
• Fluconazole (Diflucan®) orally at 5 to 15 mg/kg once to twice daily for 6 to 10 months. Fluconazole has excellent penetration in the brain and in the eyes. It has better bioavailability than itraconazole. Fewer adverse effects than both ketoconazole and itraconazole. It is not metabolized in the liver, thus it is safe in patients where there is concern regarding liver function. It is eliminated mostly unchanged in the urine. Dose may need to be adjusted in decreased kidney function exists.
• Amphotericin B in cats at 0.1 to 0.5 mg/kg IV 3 times weekly until total cumulative dose of 4 to 10 mg/kg is reached. Kidney toxicity is the main adverse effect.

Good prognosis is associated with decrease of serum antigen titers.

• If amphotericin B is used it is recommended to monitor kidney function. If ketoconazole or itraconazole are used then monitoring of liver enzymes is suggested.
• A simple, practical and inexpensive method of administering amphotericin B as a subcutaneous infusion has been developed. The calculated dose of amphotericin B (0.5 to 0.8 mg/kg) is added to 400 mL of 0.45 percent saline containing 2.5 percent dextrose. These amounts are given subcutaneously 2 or 3 times weekly over several months, to a total cumulative dose of 8 to 26 mg/kg of body weight. Subcutaneous infusions are well tolerated by the animals, although concentrations of amphotericin B in excess of 20 mg/L may result in local irritation.
• This protocol enables the administration of larger, and thus more effective, quantities of amphotericin B without producing marked kidney impairment.

Follow-up Care for Cats with Cryptococcosis

Optimal treatment for your pet requires a combination of home and professional veterinary care. Treatment may be necessary for 6 months to one year. Follow-up may include frequent re-evaluation will be necessary until the pet’s condition stabilizes.

A decrease in the cryptococcal titer over time suggests effective treatment and a hopeful prognosis. Affected animals should be treated for one month after resolution of clinical signs and preferably until their cryptococcal titer becomes undetectable.

Treated animals should be monitored closely for drug toxicity. Periodic liver function tests should be performed in pets treated with ketoconazole or itraconazole and kidney function tests should be monitored in pets treated with amphotericin B.

Cats with cryptococcosis that also are positive for feline immunodeficiency virus (FIV) or feline leukemia virus (FeLV) usually have a poor treatment outcome. Thus, determination of an affected cat’s FIV and FeLV status may allow the veterinarian to provide a more accurate prognosis for treatment.

The animal should be monitored closely for recurrence of symptoms after a decision has been made to stop treatment as a result of apparent recovery.

Therapy can be monitored repeating antigen titers. A decrease in the titers is indication of a positive response to the therapy. No vaccine is available. Contact with pigeon droppings should be avoided.