Cryptococcosis in Dogs

Dogs

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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.

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

In affected dogs, 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

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.

    • Cytology from a cutaneous nodule. Specimen was stained with a special stain (mucicarmine) to identify the capsule of the organism (stained in purple/red).

    • Cat diagnosed with crytococcosis. Note the cutaneous nodules on his face.

    • Close up of an ulcerated nodule on the same cat. Exudate was found to be rich in organisms.


    Treatment

    Treatment for cryptococcosis may include

  • Surgery to de-bulk lesions in the nasal cavity. The prognosis for recovery is poor when infected dogs 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.

  • 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.

    Cryptococcus neoformans has a worldwide distribution and is the most common systemic fungal infection of cats, although it also affects dogs. Doberman pinschers and Great Danes appear to be at increased risk in Australia, whereas cocker spaniels seem to be at higher risk in North America. However, dogs of any breed, as well as mixed breed dogs, can develop cryptococcosis. Young dogs less than four years of age seem to be predisposed. No gender predilection has been recognized.

    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. Immunosuppressed animals, such as animals suffering from malnutrition or receiving treatment with cortisone-like drugs are most susceptible.

    Clinical Symptoms

  • Non-specific symptoms of systemic disease such as fever, lethargy, loss of appetite, and weight loss

  • Skin nodules in 40 percent of affected animals, in which the organism may be detected by microscopic examination of the exudate

  • Neurologic symptoms in 15 percent of affected animals, which include incoordination, seizures, lethargy, circling, head-pressing, head tilt, back-and-forth eye movements called nystagmus, paralysis of the facial nerve and blindness.

  • Eye abnormalities in 15 percent of affected animals, which include dilated, unresponsive pupils. Inflammation of both the front (anterior uveitis) and back (granulomatous chorioretinitis) of the eyes may be detected. Small hemorrhages may be detected in the back of the eye (retinal hemorrhages).

    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

  • Veterinary care should include diagnostic tests and subsequent treatment recommendations. Diagnostic tests are needed to identify cryptococcosis and exclude other diseases that may cause similar symptoms. Tests may include:

  • A complete medical history and physical examination including neurologic and ophthalmologic (eye) examinations

  • A complete blood count (CBC or hemogram)

  • A serum biochemical profile

  • Bile acid determinations to evaluate liver function

  • Urinalysis

  • Fecal examination

    The need for additional diagnostic tests will be determined based on the results of the medical history, physical examination and initial laboratory tests:

  • Blood lead determination if lead poisoning is suspected

  • Cerebrospinal fluid analysis

  • Computerized tomography (CT), which is a radiographic imaging test to evaluate the nervous system tissues

  • Magnetic resonance imaging (MRI), which is a sophisticated computer process that produces highly detailed images of cross-sections of the body without radiation exposure

    Your veterinarian may recommend additional diagnostic tests based on the results of initial examinations. These tests may help diagnose other concurrent medical problems or allow your veterinarian to understand the impact of the underlying disease on your pet. Such tests insure optimal medical care and are selected on a case-by-case basis.

  • Latex agglutination test may be performed either on serum or cerebrospinal fluid to detect the capsule antigen of Cryptococcus neoformans. False negative results may occur due to localized infection and false positive results may occur due to contamination of the specimen with talc from latex gloves used during cerebrospinal fluid collection. The latex agglutination test is correlated with disease severity. Animals with disseminated skin or lymph node involvement have higher titers than those that do not. Generally, the titer decreases by two- to four-fold per month during successful therapy.

  • Antibodies against Cryptococcus neoformans also can be measured. Most affected animals (over 80 percent) have high antibody titers at the time of diagnosis. Antibody titers in these patients remain high or decrease slowly after treatment.

  • Microscopic examination of exudates from the nasal cavity or skin nodules often allows identification of the organism.

  • Microscopic examination of a biopsy specimen by a veterinary pathologist also allows identification of the organism and the characteristic "pyogranulomatous" inflammation. Organisms usually are present in large numbers.

  • The organism can be isolated and identified in culture using exudate or tissue samples. The cultures are not hazardous because the cultured organisms do not aerosolize.

    Treatment In-depth

    Various anti-fungal drugs can be used for the treatment of cryptococcosis but most affected pets require prolonged therapy, often six months or more depending on the severity and extent of the disease. Treatments include:

  • Ketoconazole. The response with ketoconazole is not as good as with some of the other anti-fungal drugs. Ketoconazole also may result in liver damage which may be identified by monitoring blood tests of liver function.

  • Itraconazole. The solution form of this drug appears to result in better absorption and availability to the tissues than does the capsule form. The adverse effects of itraconazole are similar to those of ketoconazole and include vomiting, diarrhea and liver damage.

  • Fluconazole has the advantage of providing excellent penetration into the brain and eyes (common sites of cryptococcal infection). Also, fluconazole has better availability to the tissues than does itraconazole. Also, fluconazole produces fewer adverse effects than does either ketoconazole or itraconazole. Fluconazole is not metabolized in the liver, and thus is safe in when there is concern about liver function. It is eliminated primarily by the kidneys, and its dosage should be adjusted if kidney failure is present.

  • Amphotericin B usually is by intravenous infusion after dilution in 5 percent dextrose in water. It must be given 3 times weekly until an effective cumulative dose has been reached. An alternative protocol involving subcutaneous administration of amphotericin B also has been developed. Amphotericin B is very toxic to the kidneys and kidney function must be monitored closely during treatment with amphotericin B.

  • Flucytosine is an anti-fungal drug that may be administered alone or in combination with amphotericin B. When used alone, the organism usually develops resistance to the drug.

    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 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.

    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.

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