Cryoptococcal meningitis

January 2010    View PDF    En español    Email a question

Cryptococcal meningitis (crip-toe-CAWK-kull men-in-JYE-tis) is an inflammation and swelling of the brain and spinal cord tissues, caused by a fungus called Cryptococcus neoformans. This inflammation is dangerous and leads to death in nearly all people who are not treated. However, treatments do exist and are quite effective.

Cryptococcal meningitis is not very common. It is rare in people with CD4 counts above 100, more often occurring when CD4 counts falls below 50. It does also occur, though rarely, in people who are otherwise healthy and not living with HIV. While a diagnosis of this disease can be a serious and life-changing event, it is both treatable and survivable.

The fungus that causes cryptococcal disease is common in dirt and dust, especially that contains bird droppings. People are usually infected when they breathe in the fungus, but in healthy individuals, this infection is usually contained in the lungs and never causes disease. Scientists believe that most disease is caused by a reactivation of previous infection rather than a new infection.

Cryptococcal disease in the lungs can lead to pneumonia. Outside the lungs, it can infect the kidneys, bone marrow, urinary tract, lymph nodes and the skin which most often appears as skin lesions.

Symptoms of cryptococcal meningitis

Many symptoms of cryptococcal meningitis are the same as other common infections, though sometimes it may present as nothing more than the worst headache of a person’s life. Because these symptoms may appear slowly and gradually, it can be difficult for a person living with HIV to know for certain if they are ill with cryptococcal disease or something else. If you are experiencing confusion, disorientation, severe headache or seizures, you should contact a health provider immediately and/or go to an emergency room. Contact your doctor if you experience any of the following for 3 or more days in a row:

•     Moderate to high fever (over 100°)
•     Nausea
•     Vomiting
•     Fatigue
•     Severe body aches, especially stiff neck
•     Irritation to the eyes from bright light
•     Skin lesions
•     Coughing, shortness of breath

How is cryptococcal meningitis diagnosed?

Your doctor will usually diagnose cryptococcal meningitis through either a simple blood test or spinal tap. Although a spinal tap may sound frightening, it’s a common procedure. A local anesthetic will be given and some people lie down for a couple of hours directly after the procedure to ease possible headaches.

The blood or spinal fluid is then tested to find the fungus. This test, called a CRAG test, can detect about 95% of people who are ill with cryptococcal disease. Your doctor may treat you with antibiotics immediately while waiting for the CRAG test results since because bacterial meningitis is deadly and progresses rapidly without antibiotics.

How to treat it?

Your doctor will prescribe treatment based on the severity of your illness and based on previous meds you’ve used.

Treating mild cryptococcal meningitis
For very mild cases with no mental status problems and normal cerebral spinal fluid  pressure, Diflucan (fluconazole) is normally prescribed. A dose of 400–800mg a day in pill form is generally prescribed for 10–12 weeks. For people with CD4 counts below 50, a doctor may recommend you continue to take fluconazole at a maintenance dose of 200mg a day to keep it from recurring.

Treating moderate to severe meningitis
Dosing:
AmB (IV amphotericin B) + flucytosine (Ancobon) for 2 weeks,
Then ...                                                                      
Fluconazole at 400mg/day for 8 weeks,
Then ...
Fluconazole at 200mg/day for life.

For those who become resistant to fluconazole, it may be possible to substitute Sporanox (itraconazole). As with the treatment mentioned above, mild meningitis may be treated with itraconazole at a dose of 200mg three times a day for 3 days. On the fourth day, the dose is lowered to 200mg twice a day for 6–10 weeks. For more severe meningitis, AmB + flucytosine is used as prescribed and then itraconazole is recommended at a dose of 200mg twice a day for life.

One of the most dangerous complications in severe cases of cryptococcal disease is extreme swelling in the skull. Therefore, your doctor should closely monitor the pressure on your brain.

Other treatments
AmB can often cause severe side effects, so other forms of it are also approved to treat cryptococcal disease. The newer formulations are inserted into a liposome, or a fat bubble, to slows down the process by which the body breaks down and used the active drug. This can result in fewer side effects. Those liposomal drugs include Amphotec, Ambisome and Abelcet.

Ambisome may cause fewer side effects than standard AmB, as reported from several of its studies. Ambisome is recommended for patients with kidney problems or who can not tolerate amphotericin B.

However, many doctors who regularly treat cryptococcal disease do not find that any of the liposomal drugs are significantly more effective or less toxic than standard AmB. They do believe Ambisome to be superior to Abelcet or Amphotec, and they do recommend using Ambisome when patients have kidney problems or cannot tolerate AmB, which is consistent with the Federal Guidelines.

Fluconazole resistance

Some health providers discourage using fluconazole to prevent fungal diseases since can easily become resistant to fluconazole. Should you become resistant while taking fluconazole to prevent an infection, you couldn’t use it to treat that infection later. Because fluconazole is considered the most effective treatment for these fungal infections, you may be better off to save this drug for primary treatment. Moreover, fungus resistant fluconazole may also have some degree of resistance to itraconazole.

Stopping maintenance therapy

Using potent combinations of HIV drugs has reduced the overall number of people who get sick with opportunistic infections, including cryptococcal meningitis.  But whether or not to continue with life-long fluconazole maintenance therapy is a challenging question faced by most people who start on a new potent regimen. Fluconazole may be stopped if the CD4 count stays above 200 for at least 6 months. The Federal Guidelines for the Prevention and Treatment of Opportunistic Infections recommends that people take maintenance therapy even with successful HIV therapy.

Special considerations for pregnant women

AmB alone is recommended as primary therapy for women who become ill with cryptococcal meningitis while pregnant since treating with any of the azole drugs including fluconazole may cause severe birth defects.

Pregnant women should be checked closely for a reccurrence of the infection. Also, because potent HIV therapy helps control other types of infections, pregnant women who become ill with cryptococcal disease may want to strongly consider HIV therapy. If you were treated for cryptococcal disease during pregnancy, you should discuss maintenance therapy after giving birth.

Special considerations for children or infants

Cryptococcal meningitis occurs in less than 1% of all children living with HIV. Fever was the most common symptom. Federal guidelines suggest using fluconazole as primary treatment for cryptococcal disease only in extreme situations,. An alternative treatment is itraconazole.

Drug access information

Prescriptions are available from pharmacies and some states may cover these drugs through their AIDS Drug Assistance Programs (ADAP). The liposomal formulas of amphotericin B, although approved, may be more difficult to access.