Cryptococcosis – Causes, Symptoms, and Treatment.

Definition

Cryptococcosis is a disease caused by fungi from the genus Cryptococcus that infect humans and animals, usually by inhalation of the fungus, which results in lung infection that may spread to the brain, causing meningoencephalitis.

Cryptococcosis

History

In 1894 in Italy, Francesco Sanfelice was the first to isolate Cryptococcus neoformans from peach juice.  At almost the same time, two German physicians, Abraham Buschke and Otto Busee isolated the same fungus from a sarcoma-like lesion in an orthopedic patient.  One year later in France, a pathologist named Fredinand Curtis, described a “vegetable parasite” belonging to the yeast species that caused skin and soft tissue tumors.  In 1901, the French mycologist Jean-Paul Vullemin reclassified the same yeast. Vullemin classified the yeast in the Genus Cryptococcus, which is Greek for “hidden”, which indicates the absence of endospores.

Epidemiology

Cryptococcus neoformans has a worldwide distribution and, similar to in the United States, preferentially infects immunosuppressed individuals, especially those with AIDS. Cryptococcal meningitis associated with HIV infection is responsible for more than 600,000 deaths per year worldwide. In sub-Saharan Africa, 15%-30% of all patients with AIDS develop cryptococcal disease. However, in some areas, such as Zimbabwe, 88% of patients with AIDS have cryptococcal infection as their AIDS-defining illness. Most case reports of C. gattii have been from Australia, with a few case reports from the southern California coast and tropical regions of Central and South America. As mentioned above, some recent cases have been reported from Vancouver, British Columbia, Canada and the states of Washington and Oregon, United States.

An outbreak of a hypervirulent strain of C. gattii has been linked to climate changes in the northwestern United States and British Columbia.

Types

It is classified based on the type of fungus:

1. In humans, neoformans causes three types of infections:

• Wound or cutaneous cryptococcosis
• Pulmonary cryptococcosis
• Cryptococcal meningitis.

Cryptococcal meningitis (infection of the meninges, the tissue covering the brain) is believed to result from dissemination of the fungus from either an observed or unappreciated pulmonary infection. Often there is also silent dissemination throughout the brain when meningitis is present.

2. Cryptococcus gattii causes infections in immunocompetent people (fully functioning immune system),

Risk factors of Cryptococcosis

• Risk factors for cryptococcosis caused by neoformans are inhalation of fungi that are associated with various bird droppings or guano, especially from pigeons.
• People who are immunocompromised, especially those with HIV/AIDS, are the most susceptible people to acquire infection. Risk factors for cryptococcosis caused by gattii are different from C. neoformans.
• In general, gattii infections were mainly associated with tropical or semitropical climates around the world and most frequently associated with inhalation of plant propagules, especially those from eucalyptus, red river gum, and forest red gum trees.

Causes

Cryptococcus neoformans and C. gattii are the fungi that cause this disease. Infection with C. neoformans is seen worldwide. Infection with C. gattii is mainly seen in the U.S. Pacific Northwest, British Columbia in Canada, Southeast Asia, and Australia. It is the more common fungus that causes the infection.

Causes of Cryptococcosis

Both types of fungi are found in soil. If you breathe the fungus in, it infects your lungs. The infection may go away on its own, remain in the lungs only, or spread throughout the body (disseminate). Cryptococcosis is most often seen in people with a weak immune system, such as those who:

• Are infected with HIV/AIDS
• Take high doses of corticosteroid medicines
• Cancer
• Are on chemotherapy medicines for cancer
• Have Hodgkin disease
• Have had an organ transplant

1. gattiimay affect people with normal immune system.
2. neoformansis the most common life-threatening cause of fungal infection in people with HIV/AIDS.

People between 20 to 40 years of age have this infection.

Symptoms of Cryptococcosis

The infection may spread to the brain in people who have a weakened immune system. Neurological (brain) symptoms start slowly. Most people have swelling and irritation of the brain and spinal cord when they are diagnosed. Symptoms of brain infection may include:

• Fever and headache
• Neck stiffness
• Nausea and vomiting
• Blurred vision or double vision
• Confusion

The infection can also affect the lungs and other organs. Lung symptoms may include:

• Difficulty in breathing
• Cough
• Chest pain

Other symptoms may include:

• Bone pain or tenderness of the breastbone
• Fatigue
• Skin rash, including pinpoint red spots (petechiae), ulcers, or other skin lesions
• Sweating — unusual, excessive at night
• Swollen glands
• Unintentional weight loss

People with a healthy immune system may have no symptoms at all.

Diagnosis and test

The health care provider will perform a physical exam and ask about symptoms and travel history. The physical exam may reveal:

• Abnormal breath sounds
• Fast heart rate
• Fever
• Mental status changes
• Stiff neck

Tests that may be done include:

• Blood culture to differentiate between the two fungi
• CT scan of the head
• Sputum culture and stain
• Lung biopsy
• Bronchoscopy and bronchoalveolar lavage
• Spinal tap to obtain a sample of cerebrospinal fluid (CSF)
• Cerebrospinal fluid (CSF) culture and other tests to check for signs of infection
• Chest x-ray
• Cryptococcal antigen test (looks for a certain molecule that is shed from the cell wall of the Cryptococcus neoformans fungus into the bloodstream)

Treatment and medications

Some infections require no treatment. Even so, there should be regular checkups for a full year to make sure the infection has not spread. If there are lung lesions or the disease spreads, your provider will prescribe you antifungal medicines. These medicines may need to be taken for a long time.

Medicines include:

• Amphotericin B (can have severe side effects)
• Flucytosine
• Fluconazole

Prevention of Cryptococcosis

C. neoformans is commonly spread by bird droppings, especially pigeon droppings. People who have weakened immune systems should avoid areas contaminated by bird droppings, and should avoid contact with birds. There are no formal recommendations for the prevention of C. gattii infection.