Symptoms, transmission, and current treatments for cryptococcal meningitis
What is cryptococcal meningitis?
Cryptococcal meningitis is a fungal infection caused by Cryptococcus neoformans, which is often found in bird droppings. If breathed in, the spores can multiply and spread from the lungs to the membranes that cover the brain or spinal cord, causing meningitis.
Cryptococcal meningitis is rare in healthy people, but it is a major cause of illness and death in people with advanced HIV disease, whose impaired immune system makes them more likely to get this infection.
Symptoms include fever, headache, stiff neck, nausea and vomiting, increased sensitivity to light, and confusion. If left untreated, cryptococcal meningitis usually leads to more serious symptoms and ultimately death.
Antiretroviral therapy helps improve the immune systems of HIV patients, reducing the risk of cryptococcal meningitis, but the infection remains a serious problem in areas where HIV is very common. Adhering to antiretroviral therapy for many years also brings challenges. Cryptococcal meningitis is far less common among children with advanced HIV disease.
What is the impact of cryptococcal meningitis?
- Causes about 15% of all AIDS-related deaths globally, most of them in Africa
- 223,100 cases of cryptococcal meningitis resulted in 181,100 deaths of people living with HIV, in 2014
- Deadly without treatment
- Can be treated effectively with a combination of drugs, but one of the key drugs (flucytosine) is unregistered in most African countries, and availability is very limited
What are current treatments for cryptococcal meningitis?
The World Health Organization recommends that cryptococcal meningitis is treated with:
- 1 mg/kg/day amphotericin B and 100 mg/kg/day flucytosine divided into four doses per day for one week
- followed by fluconazole at 1200 mg/day for one week
- followed by fluconazole at 800 mg/day for eight weeks
- followed by, finally, fluconazole at 200 mg/day for at least a year
Depending on drug availability, the initial two weeks of treatment may be replaced by either two weeks of 1200 mg/day fluconazole and 100 mg/kg/day flucytosine divided into four doses per day, or two weeks of 1 mg/kg/day amphotericin B deoxycholate and 1200 mg/day fluconazole.
In practice, however, treatment is often just fluconazole, which is ineffective.
Amphotericin B can be toxic to the kidneys and is delivered intravenously, making it impractical to administer in many settings. Flucytosine must be taken 4 times per day. For certain patients the tablets are crushed and delivered through a nasogastric tube. Flucytosine is only registered in a few African countries.
While some projects are providing flucytosine in a few selected countries, most patients do not have access to this critical drug for the treatment of cryptococcal meningitis.
What new treatments for cryptococcal meningitis are needed?
Effective treatments exist to drastically reduce deaths from cryptococcal meningitis, but they are often not used because of cost, lack of availability, and other access issues. The Global AIDS Strategy (2021–2026) aims to end AIDS as a public health threat by 2030. That goal can only be achieved if the main causes of AIDS deaths, such as cryptococcal meningitis, are addressed.
Cryptococcal meningitis treatment could be further improved with access to the less toxic liposomal version of amphotericin B and the development of a flucytosine formulation that could be administered less often. It would also help if the treatment could be administered through a nasogastric tube when needed, since some cryptococcal meningitis patients have difficulty swallowing or may not be fully conscious.
What cryptococcal meningitis treatments are we working on?
We aim to deliver an affordable, sustained release formulation of flucytosine to be taken only twice a day either orally or through a nasogastric tube. We also aim to address the difficulty in accessing existing and future formulations of flucytosine. To do that, we are working with partners to improve access to life-saving treatments in low- and middle-income countries in Africa.
Find out about our work developing treatments for cryptococcal meningitis
How do you get cryptococcal meningitis?
- People become infected with cryptococcal meningitis when they breathe in fungal spores from the environment, often from bird droppings
- Cryptococcal meningitis does not spread between people
- People with weakened immune systems are at increased risk, e.g. people living with unsuppressed HIV infection, cancer, or taking immunosuppressant medications
What are the symptoms of cryptococcal meningitis?
Within a few days to a few weeks of infection, the following symptoms may develop:
- Stiff neck
- Nausea and vomiting
- Sensitivity to light
- Altered mental states, such as confusion
Untreated, more serious symptoms may develop, including:
- Brain damage
- Hearing loss
- Hydrocephalus (water on the brain)
If not treated, cryptococcal meningitis is ultimately fatal.
How is cryptococcal meningitis diagnosed?
To diagnose cryptococcal meningitis, a sample of cerebrospinal fluid is taken by lumbar puncture, which is then tested using a rapid antigen test, or an India ink test if a rapid antigen test is not available. If a lumbar puncture is not possible, a sample of blood is taken for testing.
Last updated: September 2021
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