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 called Cryptococcus neoformans.

This fungus is very common in the environment and can be found in soil and in bird droppings. If that soil is kicked up into the air, it can be inhaled into 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 the disease. At one time, 5–8 percent of people living with HIV developed cryptococcal meningitis. However, that number has dropped significantly since the availability of potent HIV treatment. People with CD4 counts below 100 are more at risk for cryptococcal meningitis.

Cryptococcal meningitis results in inflammation and swelling of the brain. This can be extremely debilitating and/or painful and can damage the brain. The fungus 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 people living with HIV at lower CD4 counts to monitor their health closely and report any symptoms to their health provider.

What are the symptoms, and how is it diagnosed?

Many of the symptoms are similar to those seen in other diseases. These include fever, tiredness, stiff neck, body aches, headaches (often severe), nausea/vomiting and skin lesions. Other 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 people living with HIV to report any symptoms, no matter how mild, to their health provider.

There are two ways to diagnose cryptococcal meningitis. The first involves looking for the fungus in the bloodstream through a simple blood test. The second, most common way is to test the cerebrospinal fluid (CSF). In this case, a lumbar puncture (spinal tap) must be done. A spinal tap can also check the amount of pressure in the brain because cryptococcal meningitis can cause the brain to swell, which increases pressure there.

The process for a spinal tap involves:

  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 will be given 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 doing 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 15–30 minutes. Less than one percent 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 recommended treatment involves two drugs: amphotericin B (Fungizone) given daily by IV and flucytosine (Ancobon), which is taken by mouth. There are three stages: induction (at least 2 weeks until substantial reduction of symptoms with negative spinal tap), consolidation (at least 8 weeks) and maintenance (up to one year and CD4 count stays above 100).

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

Liposomal amphotericin B may be prescribed for those who become very ill while taking the non-liposomal form or who develop kidney problems.

After two weeks of amphotericin B and flucytosine, you will need to have another spinal tap to check for the fungus. If the test is positive, combination treatment will continue. If the test is negative, both drugs are stopped and another drug, fluconazole (Diflucan), is immediately started. This is necessary to help prevent cryptococcal meningitis from recurring. Fluconazole is taken by mouth every day at a dose of 400 mg for at least 8 weeks.

Fluconazole treatment may be stopped after a year of total treatment and if the CD4 count increases to above 100 for at least three months with undetectable viral load in response to HIV treatment. However, some specialists recommend a spinal tap before stopping fluconazole to make sure that there is no detectable fungal infection in the CSF. Fluconazole should be restarted if the CD4 count falls below 100 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.

IRIS (immune reconstitution inflammatory syndrome) has been reported in up to 30 percent of people with cryptococcal meningitis—a condition that causes increased symptoms of an opportunistic infection to happen after starting or switching HIV treatment. For this reason, some experts recommend waiting to start HIV treatment until after two weeks and perhaps up to 10 weeks from starting treatment for cryptococcal meningitis.

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 it. Moreover, the fungus 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 the fungus will most likely lead to cryptococcal meningitis in people with low CD4 counts, the best possible way to prevent this disease is to keep the immune system as healthy as possible. This includes starting HIV treatment before the immune system weakens.

For people with CD4 counts below 100, it is possible to take fluconazole once a day to help prevent cryptococcal meningitis and other serious fungal infections. However, most experts don’t recommend this because cryptococcal meningitis is quite rare. Because Cryptococcus neoformans and other fungi can become resistant to long-term use of fluconazole, this would prevent its use when treatment is most needed.

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 ClinicalTrials.gov, 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 contactus@aidsinfo.nih.gov.

Last Reviewed: January 24, 2019