Cryptococcal meningitis
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 (AHD), 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 19% of all AIDS-related deaths globally, most of them in Africa
- An estimated 194,000 cases of cryptococcal meningitis result in 147,000 deaths each year
- 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:
- A single high dose of 10 mg/kg liposomal amphotericin B and 100 mg/kg/day flucytosine divided into four doses per day for two weeks
- fluconazole at 1200 mg/day for two weeks
- followed by fluconazole at 800 mg/day for eight weeks
- followed by 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 if liposomal amphotericin B is not available 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.
Flucytosine is registered in only a few African countries, and most patients do not have access to this critical drug.
What new treatments for cryptococcal meningitis are needed?
Effective treatments exist to drastically reduce deaths from cryptococcal meningitis, but they are often too expensive, unavailable, or not accessible at health facilities in areas where people are most affected. 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.
Treatment for cryptococcal meningitis – and outcomes for patients – could be drastically improved by increasing access to the less toxic liposomal form of amphotericin B, as well as better formulations of flucytosine that require fewer daily doses and are easier to administer, especially for severely ill patients who are not fully conscious and cannot swallow.
What cryptococcal meningitis treatments are we working on?
We aim to deliver an affordable, sustained release formulation of flucytosine that can be administered twice a day either orally or through a nasogastric tube. We are also working with partners to improve access to optimal treatments for cryptococcal meningitis among patients with advanced HIV disease – including flucytosine and liposomal amphotericin B – 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 advanced HIV disease, cancer, or other conditions that cause immune suppression
What are the symptoms of cryptococcal meningitis?
Within a few days to a few weeks of infection, the following symptoms may develop:
- Fever
- Headache
- Stiff neck
- Nausea and vomiting
- Sensitivity to light
- Altered mental states, such as confusion
If left untreated, more serious symptoms may develop, including:
- Brain damage
- Coma
- Hearing loss
- Hydrocephalus (water on the brain)
Without prompt treatment, cryptococcal meningitis is fatal.
How is cryptococcal meningitis diagnosed?
For people living with HIV suspected of having a first episode of cryptococcal meningitis, prompt lumbar puncture with measurement of cerebrospinal fluid opening pressure and rapid cryptococcal antigen assay is recommended as the preferred diagnostic approach.
More information
Last updated: September 2025
Making medical history for neglected patients
We develop urgently needed treatments for neglected patients and ensure they’re affordable, available, and adapted to the communities who need them
Stay connected
Get our latest news, personal stories, research articles, and job opportunities.