Cryptococcal meningitis is a fungal infection causing inflammation of the meninges, the protective membranes surrounding the brain and spinal cord. This condition is caused by a fungus from the Cryptococcus genus. While uncommon in individuals with healthy immune systems, it poses a significant threat to those with compromised immunity. The infection develops after fungal spores are inhaled, leading to a lung infection that can spread to the central nervous system.
The Fungal Cause and Transmission
The primary causes of cryptococcal meningitis are two species of fungi: Cryptococcus neoformans and Cryptococcus gattii. C. neoformans is responsible for most cases and is found globally in soil contaminated with bird droppings, particularly from pigeons. The other species, C. gattii, is not associated with birds but is found in and around various trees, such as eucalyptus, where it grows in debris near the tree’s base.
Infection occurs when a person inhales microscopic, airborne spores from a contaminated source. These spores travel into the lungs, where they can establish an initial infection that may not produce symptoms. From the lungs, the fungal cells can enter the bloodstream and spread throughout the body. If they cross the blood-brain barrier and reach the central nervous system, they cause meningitis. Cryptococcal meningitis is not contagious and cannot be spread from person to person.
Populations at High Risk
The risk of developing cryptococcal meningitis is not evenly distributed; it is overwhelmingly higher in individuals with weakened immune systems. The most significant risk factor is advanced HIV/AIDS, especially when an individual’s CD4 cell count falls below 100 cells/mm³. This group accounts for a substantial majority of cases worldwide.
Other conditions and treatments that suppress the immune system also increase vulnerability. These include:
- Organ transplant recipients who take immunosuppressive drugs to prevent organ rejection.
- Cancer patients undergoing chemotherapy.
- Individuals on long-term corticosteroid therapy for autoimmune diseases.
- People with underlying conditions such as liver cirrhosis or diabetes.
Although much less common, C. gattii can cause the illness in people with seemingly normal immune systems.
Signs and Symptoms
The clinical presentation of cryptococcal meningitis often develops slowly, with symptoms appearing over several days to a few weeks. This gradual onset can sometimes delay diagnosis. The most common initial symptoms are similar to other forms of meningitis and include a persistent headache, low-grade fever, and a stiff neck. Nausea and vomiting are also frequently reported.
As the infection progresses, more specific neurological signs may emerge. Patients often experience changes in their mental state, such as confusion, drowsiness, or memory loss. Sensitivity to bright light (photophobia) and blurred or double vision are common visual complaints. If the pressure inside the skull becomes significantly elevated, it can lead to more severe symptoms like hearing loss, seizures, and coma if the condition is not treated.
Diagnosis and Medical Treatment
A definitive diagnosis of cryptococcal meningitis requires a lumbar puncture, also known as a spinal tap. This procedure involves inserting a needle into the lower back to collect a sample of cerebrospinal fluid (CSF). The collected CSF is analyzed for several indicators.
Its opening pressure is measured, and the fluid is tested for the Cryptococcus fungus using a rapid cryptococcal antigen (CrAg) test. The CSF is also cultured to grow the fungus, confirming the diagnosis. It is also examined for elevated white blood cell counts and protein levels, and low glucose levels.
Blood tests to detect the cryptococcal antigen are also performed and can be positive before meningitis develops. Imaging studies, such as a CT or MRI scan of the brain, may be conducted before the lumbar puncture to check for high intracranial pressure or fungal masses called cryptococcomas. Managing elevated intracranial pressure is a major part of treatment, often requiring repeated lumbar punctures to drain excess CSF.
Treatment for the infection is a lengthy process involving antifungal medications administered in three phases. The initial “induction” phase uses a combination of intravenous amphotericin B and oral flucytosine for at least two weeks to clear the fungus. This is followed by a “consolidation” phase with high-dose oral fluconazole for at least eight weeks, and a lower-dose “maintenance” phase of fluconazole for a year or longer to prevent relapse.
Prognosis and Recovery
The outcome for a patient with cryptococcal meningitis depends on their underlying immune status and how quickly diagnosis is made and treatment begins. For individuals with compromised immune systems, such as those with advanced HIV, the condition can be fatal if left untreated or if treatment is delayed. Mortality rates remain high, especially in resource-limited regions where access to diagnostic tools and antifungal medications is scarce. One-year mortality can range from 13% to as high as 78%.
For those who survive, the recovery process can be long, and permanent neurological damage is a concern. Potential long-term consequences include persistent headaches, memory problems, cognitive deficits, and hearing or vision loss. Even after completing the intensive treatment phases, many patients require long-term suppressive therapy with antifungal medication to prevent a relapse, particularly if their immune system remains compromised.