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Cryptococcosis in Cats

By: Dr. Rosanna Marsalla

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Diagnosis

  • 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 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.

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