Cryptococcus neoformans (abbreviated C. neoformans) is a fungus that lives in the environment throughout the world. People can become infected with C. neoformans after breathing in the microscopic fungus, although most people who are exposed to the fungus never get sick from it.

Infection with the fungus Cryptococcus (either C. neoformans or C. gattii) is called cryptococcosis. Cryptococcosis usually affects the lungs or the central nervous system (the brain and spinal cord), but it can also affect other parts of the body. Brain infections due to the fungus Cryptococcus are called cryptococcal meningitis.

C. neoformans infections are rare in people who are otherwise healthy. Most cases of C. neoformans infection occur in people who have weakened immune systems, particularly those who have advanced HIV/AIDS.

Who gets C. neoformans infections?

C. neoformans infections are rare among people who are otherwise healthy. Most cases of C. neoformans infection occur in people who have weakened immune systems, such as people who:

• Have advanced HIV/AIDS,
• Have had an organ transplant, or
• Are taking corticosteroids, medications to treat rheumatoid arthritis, or other medications that weaken the immune system.

Is C. neoformans infection contagious?

No. The infection can’t spread between people or between people and animals.

Can pets get C. neoformans infections?

Yes. Pets can get C. neoformans infections, but it is very rare, and the infection cannot spread between animals and people. If you’re concerned about your pet’s risk of getting a C. neoformans infection, or if you think that your pet has the infection, please talk to a veterinarian.

How can I prevent a C. neoformans infection?

It’s difficult to avoid breathing in C. neoformans because it’s thought to be common in the environment. Most people who breathe in C. neoformans never get sick from it. However, in people who have weakened immune systems, C. neoformans can stay hidden in the body and cause infection later when the immune system becomes too weak to fight it off. This leaves a window of time when the silent infection can be detected and treated early, before symptoms develop (see “Detecting silent cryptococcal infection in people who have HIV/AIDS”).

Detecting silent cryptococcal infections in people who have HIV/AIDS

One approach to prevent cryptococcal meningitis is called “targeted screening.” Research suggests that C. neoformans is able to live in the body undetected, especially when a person’s immune system is weaker than normal. In a targeted screening program, a simple blood test is used to detect cryptococcal antigen (an indicator of cryptococcal infection) in HIV-infected patients before they begin taking antiretroviral treatment (ART). A patient who tests positive for cryptococcal antigen can take fluconazole, an antifungal medication, to fight off the silent fungal infection and prevent it from developing into life-threatening meningitis.

What is CDC doing about C. neoformans?

CDC is assisting areas of the world where the prevalence of cryptococcal infections is high, such as sub-Saharan Africa and Southeast Asia, to prevent deaths from cryptococcal infections by helping implement targeted screening programs to detect early cryptococcal disease in HIV-infected persons. Because many of the countries in these areas of the world often don’t have the resources needed to detect Cryptococcus as the underlying cause of meningitis, CDC is also helping these countries build their laboratory capacity. Early identification of cryptococcal-infected patients in resource-limited settings may lead to more timely treatment, reduced mortality due to cryptococcal meningitis, and overall improved quality of life.

What is cryptococcal meningitis?

Cryptococcus neoformans is a fungus that lives in the environment throughout the world. Most people likely breathe in this microscopic fungus when they are children but never get sick from it, but in people with weakened immune systems such as those living with HIV/AIDS, Cryptococcus can stay hidden in the body and later become a serious (but not contagious) brain infection called cryptococcal meningitis.

Why is cryptococcal meningitis a problem?

Most cases of cryptococcal meningitis occur in people who have HIV/AIDS. The widespread availability of antiretroviral therapy (ART) in developed countries has helped improve the immune systems of many HIV patients so that they don’t become vulnerable to infection with Cryptococcus. However, cryptococcal meningitis is still a major problem in resource-limited countries where HIV prevalence is high and access to healthcare is limited. Worldwide, nearly 220,000 new cases of cryptococcal meningitis occur each year, resulting in 181,000 deaths. Most of the illnesses and deaths occur in sub-Saharan Africa.

Strategies to prevent deaths

Although it’s not possible to prevent the initial exposure to Cryptococcus, diagnosing and treating early cryptococcal infections in people at high risk for developing cryptococcal meningitis can prevent associated deaths. Therefore, CDC is working to improve diagnosis and treatment of cryptococcal meningitis in countries with large populations of people living with HIV/AIDS. In these areas, CDC is helping implement targeted cryptococcal screening programs and build laboratory capacity to detect cryptococcal infections early. This allows for more timely treatment, reduced mortality due to cryptococcal meningitis, and overall improved quality of life.

• Targeted screening for early cryptococcal infection
  Cryptococcal antigen, a chemical marker for cryptococcal infection, can be detected in the body weeks to months before symptoms of meningitis appear. In a targeted screening program, people who have advanced HIV infection are tested for cryptococcal antigen before starting ART. A patient who tests positive for cryptococcal antigen can take antifungal medication to help the body fight the early stage of the infection, which has been shown to prevent deaths due to cryptococcal meningitis.
• Improved access to diagnostics
  In order to screen people living with HIV for early cryptococcal infection and to diagnose other patients with cryptococcal meningitis, healthcare facilities and laboratories must have access to the right diagnostic tests. Currently, these tests are unavailable in many district and provincial laboratories in sub-Saharan Africa. Equipping these facilities with the ability to perform these tests is an important step in reducing deaths from cryptococcal meningitis.

  A new lateral flow assay for detecting cryptococcal antigen is simple to use on a small sample of blood or spinal fluid. The test accurately detects both early and advanced cryptococcal infections more than 95% of the time. In addition, the test is inexpensive, rapid, and doesn’t require costly laboratory equipment and expertise, making it ideal for resource-limited settings. CD4 testing is also needed to help stratify HIV patients by their immune and clinical status and their related risk for cryptococcal meningitis. Many countries currently do not have adequate CD4 testing capacity to conduct cryptococcal antigen testing when it is needed.

• Improved access to antifungal medications
  Essential medications for the treatment of cryptococcal infections are often unavailable in areas of the world that are most in need. Amphotericin B and flucytosine are two antifungal medications that have been shown to improve survival in patients with cryptococcal meningitis. Although these drugs are the standard-of-care in developed countries, they are widely unavailable in sub-Saharan Africa and Asia.

Preventing deaths from cryptococcal meningitis: resources for countries

CDC’s training materials can be used to educate physicians, nurses, HIV/AIDS counselors, pharmacists, and patients about the diagnosis, management, and prevention of cryptococcal disease. These materials are intended to help healthcare providers, particularly those in resource-limited settings, implement a screen-and-treat strategy for cryptococcal disease among people living with HIV/AIDS. CDC can help provide customized resources on training and case studies for cryptococcal screening. Please email cryptococcus@cdc.gov for more information.

Where does C. neoformans live?

C. neoformans lives in the environment throughout the world. The fungus is typically found in soil, on decaying wood, in tree hollows, or in bird droppings.

How does someone get a C. neoformans infection?

C. neoformans infections are not contagious. Humans and animals can get the infection after inhaling the microscopic fungus from the environment. Some research suggests that people may be exposed to C. neoformans in the environment when they are children. Most people who breathe in C. neoformans never get sick from it. However, in people who have weakened immune systems, C. neoformans can stay hidden in the body and cause infection later when the immune system becomes too weak to fight it off.

C. neoformans usually infects the lungs or the central nervous system (the brain and spinal cord), but it can also affect other parts of the body. The symptoms of the infection depend on the parts of the body that are affected.

In the lungs

A C. neoformans infection in the lungs can cause a pneumonia-like illness. The symptoms are often similar to those of many other illnesses, and can include:

• Cough
• Shortness of breath
• Chest pain
• Fever

In the brain (cryptococcal meningitis)

Headache, fever, and neck pain are common symptoms of cryptococcal meningitis.

Cryptococcal meningitis is an infection caused by the fungus Cryptococcus after it spreads from the lungs to the brain. The symptoms of cryptococcal meningitis include:

• Headache
• Fever
• Neck pain
• Nausea and vomiting
• Sensitivity to light
• Confusion or changes in behavior

If you have symptoms that you think may be due to a C. neoformans infection, please contact your healthcare provider.

How is a C. neoformans infection diagnosed?

Healthcare providers rely on your medical history, symptoms, physical examinations, and laboratory tests to diagnose a C. neoformans infection.

Your healthcare provider will take a sample of tissue or body fluid (such as blood, cerebrospinal fluid, or sputum) and send the sample to a laboratory to be examined under a microscope, tested with an antigen test, or cultured. Your healthcare provider may also perform tests such as a chest x-ray or CT scan of your lungs, brain, or other parts of the body.

How are C. neoformans infections treated?

People who have C. neoformans infection need to take prescription antifungal medication for at least 6 months, often longer. The type of treatment usually depends on the severity of the infection and the parts of the body that are affected.

• For people who have asymptomatic infections (e.g., diagnosed via targeted screening) or mild-to-moderate pulmonary infections, the treatment is usually fluconazole.
• For people who have severe lung infections or infections in the central nervous system (brain and spinal cord), the recommended initial treatment is amphotericin B in combination with flucytosine. After that, patients usually need to take fluconazole for an extended time to clear the infection.

The type, dose, and duration of antifungal treatment may differ for certain groups of people, such as pregnant women, children, and people in resource-limited settings. Some people may also need surgery to remove fungal growths (cryptococcomas).

The World Health Organization has also developed guidelines for the diagnosis, prevention, and management of cryptococcal disease in HIV-infected adults, adolescents, and children, with a focus on resource-limited settings.

How common are C. neoformans infections?

C. neoformans infections are rare among people who have healthy immune systems; however, C. neoformans is a major cause of illness in people living with HIV/AIDS, with an estimated 220,000 cases of cryptococcal meningitis occurring worldwide each year.

C. neoformans infections in the United States

Before antiretroviral therapy was discovered, fungal and other opportunistic infections were a major problem for people with advanced HIV/AIDS. Since then, the numbers of fungal infections and deaths due to fungal infections in people with advanced HIV/AIDS have decreased substantially in the US and other developed countries. For example, one study showed that the incidence of cryptococcosis in AIDS patients in the US decreased by approximately 90% in the 1990s. The decrease in opportunistic infections is primarily because earlier diagnosis of HIV and initiation of antiretroviral therapy (ART) helps keep people with HIV from reaching the stage where their immune systems leave them most vulnerable to fungal infections and other infections. However, fungal diseases, particularly cryptococcosis, are still a concern for people living with HIV/AIDS in the US.

Nationally representative estimates for the incidence of cryptococcosis are difficult to establish because cryptococcosis is only reportable in a few states. Results from active, population-based surveillance in two US locations in the year 2000 indicated that the annual incidence of cryptococcosis among persons with AIDS was between 2 and 7 cases per 1,000, and the overall incidence was 0.4 to 1.3 cases per 100,000 population; the case-fatality ratio was approximately 12%. More recently, an analysis of stored serum samples from HIV-infected persons with low CD4 counts enrolled in studies in the US during 1986–2012 found the prevalence of cryptococcal antigenemia to be 2.9%, indicating that the prevalence of cryptococcal infection among HIV patients in the US may be high enough to consider targeted screening.

C. neoformans infections worldwide

Although the widespread availability of antiretroviral therapy (ART) in developed countries has helped improve the immune systems of many HIV patients so that they don’t become vulnerable to infection with Cryptococcus, cryptococcal meningitis is still a major problem in resource-limited countries where HIV prevalence is high and access to healthcare is limited. An estimated 220,000 cases of cryptococcal meningitis occur among people with HIV/AIDS worldwide each year, resulting in nearly 181,000 deaths. Most cryptococcal meningitis cases occur in sub-Saharan Africa (Figure 1). Throughout much of sub-Saharan Africa, Cryptococcus is now the most common cause of meningitis in adults. Cryptococcal meningitis is therefore one of the leading causes of death in HIV/AIDS patients in sub-Saharan Africa, where it may kill more people each year than tuberculosis.