Cryptococcosis

Definition

Cryptococcosis is an infection caused by inhaling the fungus Cryptococcus neoformans. It is one of the diseases most often affecting AIDS patients. Cryptococcosis may be limited to the lungs, but frequently spreads throughout the body. Although almost any organ can be infected, the fungus is often fatal if it infects the nervous system where it causes an inflammation of the membranes covering the brain and spinal cord (meningitis).

Description

The fungus causing cryptococcus, C. neoformans, is found worldwide in soil contaminated with pigeon or other bird droppings. It has also been found on unwashed raw fruit. Cryptococcosis is a rare disease in healthy individuals, but is the most common fungal infection affecting people with AIDS.

People with Hodgkin's disease or who are taking large doses of drugs that suppress the functioning of the immune system (corticosteroids, chemotherapy drugs) are also more susceptible to cryptococcal infection. Cryptococcosis is also called cryptococcal meningitis (when the brain is infected), Busse-Buschke disease, European blastomycosis, torular meningitis, or torulosis.

Causes & symptoms

Once the cryptococcal fungus reaches the lungs, three things can happen. The immune system can heal the body without medical intervention, the disease can stay localized in the lungs, or it can spread throughout the body. In healthy people with normally functioning immune systems, the body usually heals itself, and the infected person notices no symptoms and has no complications (asymptomatic). The disease does not spread from one person to another.

Cryptococcosis is an opportunistic infection that puts people with immune system diseases at higher risk of developing more serious forms of the disease. In the United States, 6-10% of all patients with AIDS get cryptococcosis.

If the body does not heal itself, the fungus begins to grow in the lungs and form nodules that can be seen on chest x rays. In the early stages of infection, an individual usually only exhibits symptoms of a respiratory infection, such as a dry cough, so the disease is rarely diagnosed.

The fungus can remain dormant in the lungs and produce an active infection later if the immune system is weakened. If the disease becomes active, it can cause cryptococcal pneumonia in the lungs. Unfortunately, however, cryptococcal pneumonia has symptoms similar to other pneumonias (cough, chest pain, difficulty breathing), making it difficult to accurately diagnose. The infection can spread to other parts of the body, particularly the brain and central nervous system.

Most patients are not diagnosed as having cryptococcosis until they show signs of cryptococcal meningitis, or infection of the membranes surrounding the brain and spinal cord. Symptoms appear gradually over a period of two to four weeks. Fever and headache are the most common symptoms, occurring in about 85% of patients. Nausea, vomiting, unwanted weight loss, and fatigue are also common. Other symptoms seen in 25-30% of patients are blurred vision, stiff neck, aversion to light, and seizures. Since the symptoms of classic meningitis, such as stiff neck and aversion to light, do not occur in many patients, diagnosis is often delayed. In addition to meningitis, inflammation of the brain (encephalitis) and brain lesions called cryptococcomas or tortulomas can also develop.

In addition to the brain, the cryptococcal infection can spread to the kidneys, bone marrow, heart, adrenal glands, lymph nodes, urinary tract, blood, and skin. Often times preceding the development of cryptococcal meningitis, painless rashes and lesions that mimic other skin diseases, such as molluscum contagiosum, may develop. A small percentage of patients with brain infections show infections in other organs as well.

Diagnosis

Physicians who regularly work with AIDS patients have the most experience in diagnosing cryptococcosis. The preferred methods of diagnosis use simple and very accurate blood and cerebrospinal fluid (CSF) tests that detect the presence of an antigen produced by the fungus. The cerebrospinal fluid test is generally more sensitive to detecting the meningitis form of the infection. CSF is collected during a procedure called a lumbar puncture, during which an anesthetic is applied to a small area of the back near the spine and a needle is used to withdraw a sample of cerebrospinal fluid from the space between the vertebrae and the spinal cord. Once obtained, a small amount of ink (called India ink) is added to a sample of CSF or a sample prepared from skin lesions. If the fungus is present, it will become visible when the ink binds to the capsule or covering that surrounds the fungus. Faster results are obtained with the India ink test, but it is less accurate than the blood test (75-85% accuracy compared to 99% accuracy with the blood test) because some strains are not visible using this method. Antigen tests are routinely recommended for non-symptomatic patients with advanced AIDS.

Another way to diagnose cryptococcosis is to culture a sample of sputum, tissue from a lung biopsy, or CSF in the laboratory to isolate the fungus. Cultures are also done to assess the effectiveness of treatment.

Chest x rays are useful in assessing lung damage and may reveal a single mass or multiple distinct nodules, but the x ray alone does not lead to a definitive diagnosis of cryptococcosis.

Treatment

Once cryptococcosis is diagnosed, treatment begins with amphotericin B (Fungizone), sometimes in combination with 5-flucytosine (Ancobon). Amphotericin B is a powerful fungistatic drug with potentially toxic side effects, such as kidney toxicity and lower concentrations of an important blood component called hemoglobin. This medication can also cause fever, chills, nausea and vomiting, diarrhea, headache, and muscle aches. Treatment is generally given intravenously during a hospital stay and continues until the patient is stable or improving (no more than two to three weeks). 5-flucytosine is given orally. Patients may also receive other medication to minimize the side effects from these drugs.

Amphotericin B, with or without 5-flucytosine, is given for several weeks until the patient is stable, after which the patient receives oral fluconazole (Diflucan). Fluconazole is a broad-spectrum antifungal drug with few serious side effects. Patient with AIDS must continue taking fluconazole for the rest of their lives to prevent a relapse of cryptococcosis. Sometimes fluconazole is given to patients with advanced AIDS as a preventative (prophylactic) measure.

Because of the high cost of fluconazole, the manufacturer of the drug, Pfizer, has established a financial assistance plan to make the drug available at lower cost to those who meet certain criteria. Patients needing this drug should ask their doctors about this program.

Prognosis

Untreated cryptococcosis is always fatal. The acute mortality rate for patients with AIDS is 10-25%. Most deaths are attributable to cryptococcal meningitis and occur within two weeks after diagnosis. For AIDS patients who do not receive continued suppressive therapy (fluconazole), the relapse rate is 50-60% within six months and a shortened life expectancy. Once the cryptococcosis infection has been successfully treated, individuals may be left with a variety of neurologic symptoms, such as weakness, headache, and hearing or visual loss. In addition, fluid may accumulate around the brain (hydrocephalus).

Prevention

The best way to prevent cryptococcosis is to stay free of HIV infection. People with suppressed immune systems should try to stay away from areas contaminated with pigeon or other bird droppings, such as the attics of old buildings, barns, and areas under bridges where pigeons roost.

Key Terms

Adrenal gland

A pair of organs located above the kidneys. The outer tissue of the gland produces the hormones epinephrine (adrenaline) and norepinephrine, while the inner tissue produces several steroid hormones.

Amphotericin B (Fengizone)

An antifungal medication, prescribed for topical or systemic use in treating fungal infections.

Antibody

A specific protein produced by the immune system in response to a specific foreign protein or particle called an antigen.

Antigen

A foreign protein or particle capable of eliciting an immune response.

Asymptomatic

Persons who carry a disease but who do not exhibit symptoms of the disease are said to be asymptomatic.

Biopsy

The removal of a tissue sample for diagnostic purposes.

Cerebrospinal fluid (CSF)

The clear fluid that surrounds the spinal cord and brain and acts as a shock absorber.

Corticosteroids

A group of hormones produced naturally by the adrenal gland or manufactured synthetically. They are often used to treat inflammation. Examples include cortisone and prednisone.

Encephalitis

Inflammation of the brain.

Hodgkin's disease

A disease that causes chronic inflammation of the lymph nodes, spleen, liver and kidneys. It is also called malignant lymphoma.

Hydrocephalus

Build-up of fluid around the brain.

Immunocompromised

A state in which the immune system is suppressed or not functioning properly.

India ink test

A diagnostic test used to detect the cyptococcal organism . A dye, called India ink, is added to a sample of CSF fluid, and if the fungi is present, they will become visible as the dye binds to the capsule surrounding the fungus.

Lumbar puncture

Also called a spinal tap, a procedure in which a thin needle is used to withdraw a sample of cerebrospinal fluid for diagnostic purposes from the area surrounding the spine.

Meningitis

Inflammation of the membranes covering the brain and spinal cord called the meninges.

Molluscum contagiosum

A disease of the skin and mucuous membranes, caused by a poxvirus and found all over the world.

Opportunistic infection

An infection that is normally mild in a healthy individual, but which takes advantage of an ill person's weakened immune system to move into the body, grow, spread, and cause serious illness.

Pneumonia

Inflammation of the lungs, typically caused by a virus, bacteria, or other organism.

Further Reading

For Your Information

Organizations

• Centers for Disease Control and Prevention. 1600 Clifton Road NE, Atlanta, Georgia 30333. 404-639-3534. http://www.cdc.gov.
• National Aids Clearinghouse. 800-458-5231.
• National Aids Hotline. 800-342-AIDS.
• Project Inform. 205 13th Street #2001, San Francisco, CA 94103. 800-822-7422 or 415-558-9051. www.projinf.org.

  Other

• Powderly, William G. "Cryptococcosis." Journal of the International Association of Physicians in AIDS Care (July 1996) http://www.iapac.org/diseases/fungi/cocc.html.
• "Project Inform Cryptococcal Infections Fact Sheet." (21 May 1996). http://www.projinf.org/fs/crypto.html.

Gale Encyclopedia of Medicine. Gale Research, 1999.