Reviewed on 2/17/2022

What Facts Should I Know about Cryptococcosis?

What Is the Medical Definition of Cryptococcosis?

  • 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. The disease was first termed "Busse-Buschke disease" after the two individuals who first identified the fungus in 1894-1895.

What Causes Cryptococcosis?

  • Cryptococcosis is found worldwide; the predominant way the disease is spread is through inhalation of fungus that is associated with many bird species, especially old pigeon feces and bat guano.
  • Cryptococcus spp. is found in bird feces (mainly C. neoformans) throughout the world, but usually, the birds themselves are not infected or sick. Humans and animals usually get the infection from inhaling dust contaminated with bird feces, but humans do not transmit cryptococcosis to other humans or animals. However, C. gattii is a type of Cryptococcus that is acquired by inhalation of airborne plant material (propagules or reproductive plant parts like a seed or spore).
  • Until a few years ago, almost all C. gattii infections were associated with plants found in tropical and subtropical climates. This has changed since an outbreak has occurred in the Pacific Northwest (Vancouver Island, Washington, and Oregon).
  • The vast majority of cryptococcosis infections are caused by C. neoformans and C. gattii. Although there are over 50 Cryptococcus species, only a few other species rarely infect humans.
  • In general, the people infected with C. neoformans usually have some defect in cell-mediated immunity (especially HIV/AIDS patients). However, C. gattii usually infects immunocompetent individuals (most occur in "normal" individuals) but can infect immunocompromised people. Cryptococcosis is rarely transmitted directly into the skin (by laboratory accidents) and by organ transplants.

What Are the Causes and Risk Factors Cryptococcosis?

The major causes of cryptococcosis are infection by C. neoformans and C. gattii. These two species have several types (serotypes) of different capsular polysaccharides that cause the majority of human cryptococcosis (A, D, and AD for C. neoformans; B and C for C. gattii). The three strains of C. gattii that are most frequently found causing cryptococcosis are designated VGlla, VGllb, and VGllc.

Cryptococcus spp. was thought to occur only as a yeast form until 1976 when Dr. Kyung Joo Kwon-Chung described the mycelial form (taking the form of branching, threadlike structures) of C. neoformans (termed Filobasidiella neoformans). C. gattii also has a mycelial form. The polysaccharide capsule covering the yeast forms renders Cryptococcus species resistant to human and animal immune defenses. The fungi do not usually cause major problems during the initial infection, but they slowly multiply. The organ damage begins to occur when the slowly replicating fungi develop fungal masses (termed cryptococcomas) that start to compress or distort the involved organ (usually the lung or brain) and its vasculature. Some of these fungi can separate from a lung fungal mass or infected pulmonary nodule and then be carried by cells or swept into the bloodstream to then lodge and grow in other organs, especially the brain. Many patients may show no symptoms related to the lung infection during this process. Because there is little or no inflammatory response to these organisms, symptoms do not develop in humans and animals until late in the disease process when the fungal mass begins to alter the organ where it is located. This is why some individuals show brain changes as their first symptoms of having cryptococcosis.

Risk factors for cryptococcosis caused by C. 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 C. gattii are different from C. neoformans. In general, C. 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. However, C. gattii seems capable of inhabiting other areas; in 1999, there were cases of C. gattii noted in animals (cats, dogs, ferrets, marine animals) and a few individuals in Vancouver Island, Canada. In 2006, an outbreak of cases (over 100) occurred with at least six deaths attributed to C. gattii on Vancouver Island. Since that time, other cases have been found in Washington and Oregon in the U.S. Currently, C. gattii has been sporadically isolated from plant debris, dust, and air samples, and usually near stands of trees or logging areas in the Pacific Northwest. Some authors suggest C. gattii was imported with semitropical vegetation, inadvertently released into the environment, and has begun to adapt and grow in the northwest states. Consequently, a risk factor occurs when people encounter airborne propagules or "dust," especially around logging operations and sawmills. Other investigators suggest that C. gattii has been around for a long time and only recently we have developed tests that distinguish C. gattii from C. neoformans and that many infections previously attributed to C. neoformans were caused by C. gattii. Others speculate that more virulent strains of C. gattii have evolved and are now being noticed by the medical community.

What Are the Signs and Symptoms Cryptococcosis?

Several researchers suggest that the first sign that cryptococcosis is in an area is the increased diagnosis of the disease in animals, especially domestic pets. Although the animals do not pass the disease to humans, their disease indicates a likely chance of exposure of humans to Cryptococcus. People with lung or CNS (brain or central nervous system) problems who have visited or inhabited areas where animals have acquired the infection should be tested for the disease.

The majority of symptoms of cryptococcosis occur in the lungs, the brain, or both. The following is a list of the major symptoms:

Some people may develop skin changes (rash, pustules, nodules, ulcers).

When to Seek Medical Care for Cryptococcosis

When symptoms occur (listed above) and have no clear source (for example, cold, viral syndrome, bacterial infection), a medical caregiver should be consulted, especially if the individual lives in or has visited areas where animals and humans have been diagnosed with cryptococcosis. People who are immunocompromised (for example, those with HIV, cancer patients, chemotherapy patients) are at higher risk for complications (meningitis, coma, death) from cryptococcosis so they should seek care immediately if symptoms develop.

How Is Cryptococcosis Diagnosed?

The medical caregiver should be informed of the possible exposure to Cryptococcus if the individual knows they have been in risk areas like logging sites, tropical regions, or the Pacific Northwest (Vancouver Island, Washington, or Oregon) or know their domestic pets or people who live in or visited the same regions as the patient have been diagnosed with cryptococcosis. This medical history will help the medical caregiver order additional tests as the initial physical exam often yields few if any diagnostic features.

Even if the patient has some visible findings such as skin lesions, or even pulmonary or bone lesions seen on X-rays, many other diseases (for example, histoplasmosis, toxoplasmosis, tuberculosis) may also have these findings. A CT scan or MRI of the brain may show focal areas of possible infection in the brain, but again many diseases may show similar findings.

However, serological testing of spinal fluid obtained by spinal puncture and blood may provide presumptive evidence of cryptococcosis if the person has symptoms of cryptococcosis.

Definitive diagnosis of cryptococcosis depends on isolating the fungus from an infected patient's tissue or bodily fluids or identifying the organisms in tissue biopsy samples. Further immunological testing such as a PCR test for the genetic material of the fungus can identify if the infection is caused by either C. neoformans or C. gattii.

What Are the Treatment and Medications for Cryptococcosis?

The treatment and medications depend on the patient's overall condition (for example, HIV/AIDS, immunocompetent, having brain lesions or only pulmonary lesions) and the extent of the cryptococcal infection (single organ or multiple organ involvement). Most experts suggest that an infectious disease specialist should help guide the often long-term treatment with multiple antifungal medications. A few patients may require surgery to reduce or remove a fungal mass (cryptococcoma). The goal of treatment is to eliminate the fungi; however, for some patients, this is not possible, so these patients may require lifelong medication to suppress fungal growth or reactivation. Treatments for C. neoformans and C. gattii are similar.

Patients who are not immunocompromised usually are treated with amphotericin B alone (about six to 10 weeks) or combined with flucytosine (about two weeks). These treatments are then followed by fluconazole treatment for at least 10 additional weeks. This treatment is used for brain and severe lung infections. Antifungal therapy is usually extended until spinal fluid is negative in patients with brain infections, and lung lesions should show a size decrease in response to therapy. Mild infections in the lung may resolve without treatment but must be monitored to be sure reactivation or slow advancement of the infection does not occur.

Immunocompromised patients are treated as above but usually with only intravenously administered (IV) drugs at the start of treatment, and the length of treatment may range from about one to two years to a lifetime of suppressive therapy, usually with fluconazole. Regular medical checkups to determine if cryptococcosis is reactivated or lesions increase in size.

Consultation with an expert in infectious diseases is recommended to provide the individual with optimal treatment; in addition, these consultants are usually aware of any new treatment protocol changes that may develop with ongoing research that may benefit the patient.

Self-Care at Home for Cryptococcosis

People, especially immunocompromised individuals, should avoid going to areas that may have high concentrations of the fungi (see risk factors and prevention). People who are on long-term medication protocols for cryptococcosis need to take their home medications regularly and keep all follow-up appointments to avoid disease progression or reactivation.

What Is the Follow-up for Cryptococcosis?

Follow-up is very important for all patients diagnosed with cryptococcosis. Patients who do not follow up with their medical-care providers leave themselves open to reactivation of the fungal infection, and in some cases, progression to dire outcomes. Follow-up allows the caregivers to adjust medications to fit the ongoing condition of the individual and discover if treatments are effective and if the disease is progressing or, at some point, eliminated. This information allows caregivers to modify treatment protocols to best serve the patient.

How Do You Prevent Cryptococcosis?

The best way to prevent cryptococcosis is to not inhale the fungus. This is difficult to do if you live in areas where the fungus resides, although some researchers say that some masks (ones that filter particles that are as small as 3 micrometers) may help prevent inhalation. One of the main sources of C. neoformans is dried pigeon feces, so avoiding areas that contain it may help prevent the disease. Avoiding dust that contains any type of bird feces may also help prevent infections.

Because C. gattii is spread by plant debris and propagules, it is hard to avoid inhalation if a person is in an area that C. gattii inhabits. Higher concentrations occur in the air when trees like eucalyptus and gum trees release propagules, but they are also found in the dust around these trees. However, since these trees are usually found in semitropical and tropical regions, avoiding areas where these trees are producing propagules (flowering) may help prevent the disease. Unfortunately, with C. gattii now occurring in the Pacific Northwest, researchers suggest that C. gattii is adapting to survive in this region. Avoiding dust inhalation, especially in dense forests and around logging operations may help reduce exposure to C. gattii in the Pacific Northwest.

There is no commercially available vaccine to prevent cryptococcosis.

What Is the Prognosis for Cryptococcosis?

With early diagnosis and treatment, most people with cryptococcosis will have a good or excellent prognosis because the infection will be stopped. Those who are diagnosed late in the infectious process or who are immunosuppressed have a fair to poor prognosis and may have a mortality (death) rate as high as 30%. Those who survive have a relapse or reactivation rate as high as 25% while others often have long-term (years) or lifelong requirements for suppression treatment with antifungal drugs.

Cryptococcosis Research

The U.S. Centers for Disease Control and Prevention (CDC) considers cryptococcosis, especially when caused by C. gattii, as an emerging infectious disease because of the recently increased occurrence in the Pacific Northwest. Consequently, to prepare for better ways to identify and treat this disease, ongoing research is increasing. To date, there is no vaccine available for humans. However, researchers have developed an experimental vaccine from the fungal carbohydrate capsule that can protect mice from infection, so a vaccine for humans may be developed in the near future. Several laboratories are trying to develop quick, easy, and accurate methods to distinguish the various subtypes of C. neoformans and C. gattii. Other environmental scientists are trying to determine the extent of the spread of C. gattii in the U.S. and other countries to determine if environmental changes are influencing (increasing) the areas where Cryptococcus can survive and become endemic. A few researchers are examining the virulence of various strains as some strains (C. gattii, VGllc) may cause more serious infections and deaths than other strains.

Reviewed on 2/17/2022
Medically reviewed by Joanne Getsy, MD; Board Certification in Internal Medicine with Subspecialities in Pulmonary Disease and Sleep Medicine


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