Cryptococcal meningitis is a serious infection of the brain and spinal column that can occur in people living with HIV. It is caused by a fungus—Cryptococcus neoformans.

Cryptococcus neoformans is very common in the environment and can be found in soil and in bird droppings. If soil containing Cryptococcus neoformans is kicked up into the air, it can be inhaled and deposited in the lungs. From there, the fungus can travel through the blood to the spinal column and brain where it can cause disease.

While most adults and children have been exposed to this fungus at some point during their lives, they generally have immune systems that are healthy enough to prevent Cryptococcus neoformans from causing disease. At one time, between 5 and 8 percent of people with HIV developed cryptococcal meningitis. Since the introduction of potent combination antiretroviral (ARV) therapy, however, that number has dropped significantly. People with compromised immune systems, particularly HIV-positive people with CD4 cell counts below 50, are more likely to experience cryptococcal meningitis.

Cryptococcal meningitis results in inflammation and swelling of the brain. This can be extremely debilitating and/or painful and can cause damage to the brain. Cryptococcus neoformans can also cause disease in the lungs and, less commonly, in the kidneys, skin, urinary tract, and lymph nodes.

If it is not treated correctly, cryptococcal meningitis can be fatal. Thus, it is very important for HIV-positive people with compromised immune systems to monitor their health closely and report any symptoms to their health care provider.

What are the symptoms, and how is it diagnosed?

Many of the symptoms of cryptococcal meningitis are similar to those seen in other diseases. These include: fever, fatigue, stiff neck, body aches, headaches (often severe), nausea/vomiting, and skin lesions. Other important symptoms include confusion, muddled thinking, vision problems, and possibly seizures.

People diagnosed with cryptococcal meningitis often have symptoms of infection outside the brain. This includes coughing and shortness of breath, from infection in the lungs, and skin lesions that can look like another infection called molluscum contagiosum. It is always advisable for HIV-positive people to report any symptoms, now matter how mild, to their health care provider.

There are two ways to diagnose cryptococcal meningitis. The first involves looking for the fungus in the bloodstream. This is nothing more than a simple blood test. The second, most common way to diagnose cryptococcal meningitis involves the liquid—the cerebrospinal fluid (CSF)—that surrounds the brain and the spine. To collect this fluid, a doctor or a technician must perform a lumbar puncture, also called a spinal tap. Once a small amount of CSF has been removed from the spine, a laboratory can look for Cryptococcus neoformans in the fluid. A spinal tap is also done to check the amount of pressure in the brain. Because cryptococcal meningitis can cause the brain to swell, the pressure of the CSF can increase. Knowing the CSF pressure can help determine how severe the disease is. If the pressure is extremely high, additional CSF might be drained to ease symptoms and prevent damage to the brain.

This is what is involved in a spinal tap:

  1. Your lower spine, just above your hips, will be punctured with a hollow needle. Your lower back will be cleaned and a local anesthetic (e.g., Novocain) will be injected near the site of the puncture.
  2. You will lie on your side with your back to the person performing the test. You will be asked to bring your knees up to your abdomen and to bend your forehead toward your knees. Alternatively, you will be asked to sit up, with your knees tucked under your chin and your head dropped into your chest.
  3. The needle is inserted through your lower back into the spinal column. You may feel a “pop” but, generally speaking, it is not painful. It is very important that you take deep breaths to keep yourself relaxed and that you remain perfectly still.
  4. It takes approximately five minutes to remove enough CSF for analysis.
  5. To check the pressure of the CSF, the person conducting the spinal tap will attach a machine called a manometer to the needle.
  6. If you experience discomfort, you should communicate this to the person performing the test—without moving—so that he or she can reposition the needle.
  7. After the spinal tap is completed, you will be asked to lie on your back for 15 to 30 minutes. Less than 1% of people experience a severe headache due to the movement of the CSF during a spinal tap.

Some doctors also request brain scans using magnetic resonance imagining (MRI). This is usually done before a spinal tap to check for other diseases than can cause symptoms similar to cryptococcal meningitis.

How is it treated?

The standard recommended treatment for all forms of cryptococcal meningitis involves two drugs. The first, amphotericin B (Fungizone), is given every day through an IV line. The second, flucytosine (Ancobon), is taken orally.

Amphotericin B can cause side effects, some of them serious. Side effects include nausea, fever, chills, muscle pain, low potassium levels, damage to the bone marrow and its ability to produce red blood cells and white blood cells, and kidney damage. Tip: Take a regular dose of acetaminophen (e.g., Tylenol), ibuprofen (e.g., Advil), naproxen (e.g., Aleve), or diphenhydramine (e.g., Benadryl) approximately half an hour before receiving amphotericin B—this can help prevent/reduce some side effects during and after receiving the infusion.

Liposomal amphotericin B—a drug involving microscopic spheres of lipids (fats) that contain amphotericin B—may be prescribed for patients who become very ill while taking Fungizone or develop kidney problems. If liposomal amphotericin B is used, experts recommend a dose between 4 and 6 milligrams per kilogram of body weight per day.

After two weeks of taking amphotericin B and flucytosine, you will need to have another blood test and/or spinal tap to check for Cryptococcus neoformans. If the test is positive, combination treatment will be continued. If the tests are negative, both drugs are stopped and another drug, fluconazole (Diflucan), is immediately started. This is necessary to help prevent the cryptococcal meningitis from recurring. Fluconazole is taken by mouth, every day, at a dose of 400 mg.

Fluconazole treatment may be stopped if the patient sees his or her CD4 cell count increase to levels above 200 for at least six months in response to ARV drug treatment. However, some specialists recommend a spinal tap before discontinuing fluconazole treatment, to make sure that there is no detectable Cryptococcus neoformans infection in the CSF. Fluconazole treatment should be restarted if the CD4 cell count falls below 200 again.

Because cryptococcal meningitis can cause the brain to swell, which can lead to debilitating symptoms and brain damage, it is often necessary to drain CSF from the spinal column to reduce the amount of pressure in the brain. These spinal taps may need to be repeated daily during the first few weeks of treatment to keep CSF pressure low.

A syndrome—called immune reconstitution inflammatory syndrome (IRIS)—where initiating antiretroviral treatment can actually exacerbate the symptoms of an opportunistic infection due to a strengthened immune response, has been reported in up to 30 percent of people diagnosed with cryptococcal meningitis. For this reason, some experts recommend waiting to start ARV therapy until people have been on treatment for cryptococcal meningitis for two weeks.

How is it prevented?

Because Cryptococcus neoformans can be found in many parts of the environment, it is very difficult to prevent coming into contact with the fungus. Moreover, Cryptococcus neoformans can live in a person’s body for many months or possibly years before it causes disease, depending on the health of the person’s immune system.

Since Cryptococcus neoformans will most likely lead to cryptococcal meningitis in people with damaged immune systems, the best possible way to prevent this disease is to keep the immune system healthy. This includes starting ARV therapy before the immune system becomes impaired.

For people who do have compromised immune systems (less than 50 CD4 cells), it is possible to take fluconazole (Diflucan), an oral pill (200 mg) taken once a day, to help prevent cryptococcal meningitis and other serious fungal infections. However, most experts don’t recommend using fluconazole to prevent this disease. This is because cryptococcal meningitis is quite rare. As explained in the first section of this lesson, only 5 to 8 percent of HIV-positive people with severely suppressed immune systems experience this disease. Because fluconazole can cause side effects and may cause Cryptococcus neoformans or other fungi to become resistant to the drug—which would prevent fluconazole from being effective when it is most needed—many experts are concerned that the risks of using this drug on a long-term basis might outweigh the its potential benefits.

Are there any experimental treatments?

If you would like to find out if you are eligible for any clinical trials involving new treatments for cryptococcal meningitis, visit, a site run by the U.S. National Institutes of Health. The site has information about all HIV-related clinical studies in the United States. For more info, you can call their toll-free number at 1-800-HIV-0440 (1-800-448-0440) or email

Last Reviewed: January 18, 2016