Overview 

Fungal meningitis is a rare and serious condition characterised by the inflammation of the three protective membranes - dura mater, arachnoid, and pia mater - surrounding the brain and spinal cord (meninges), resulting from a fungal infection.¹ This condition is different from bacterial or viral meningitis which are common types of meningitis that develop suddenly and acutely, fungal meningitis has a more gradual onset and may be subacute or chronic.²  

Causes and symptoms 

Risk factors

Fungal meningitis is not contagious, and can only occur when one of the several fungi pathogens enter the central nervous system.  This can happen through direct injection, such as during surgery or trauma, or hematogenous spread from a primary infection site elsewhere in the body.¹ While anyone can get fungal meningitis, certain risk factors can increase a person's risk of having fungal meningitis.  These risk factors can include:

• Weakened immune systems: conditions that weaken the immune system, such as HIV/AIDS, organ transplantation, cancer chemotherapy, or immunosuppressive medications, increase susceptibility to fungal infections, including fungal meningitis^3,4
• Medications: certain medications that suppress the immune system, such as corticosteroids or immunosuppressants, can predispose individuals to fungal infections by compromising the body's ability to fight off pathogens^3,4 
• Premature birth: premature babies with very low birth weight are at increased risk of fungal infections, including fungal meningitis, due to their immature immune systems and prolonged hospitalisations^3,4
• Geographic locations: living in certain regions with higher levels of environmental fungi, such as certain parts of the United States or other countries, may increase the risk of exposure to fungal pathogens and subsequent fungal infections^3,4

Fungi that cause fungal meningitis 

Fungal meningitis can be caused by the following types of fungi:

• Cryptococcus: are the most common pathogen to cause fungal meningitis in people with weakened immune systems and are found throughout the environment, particularly in soil contaminated with bird droppings³ 
• Candida: Candida species, commonly found in the gastrointestinal tract and on the skin, can sometimes invade the bloodstream and spread to the central nervous system, leading to fungal meningitis³
• Histoplasma: Histoplasma capsulatum is a dimorphic fungus found in soil enriched with bird or bat droppings. Inhalation of fungal spores can lead to pulmonary histoplasmosis, and in some cases, dissemination to the central nervous system can occur, causing fungal meningitis³
• Blastomyces: Blastomyces dermatitidis is another dimorphic fungus found in soil, particularly in regions with humid climates. It can cause blastomycosis, a systemic fungal infection that may involve the central nervous system, leading to fungal meningitis in severe cases
• Aspergillus: Aspergillus species, commonly found in soil, decaying organic matter, and indoor environments, can cause invasive aspergillosis, a severe fungal infection that may affect various organs, leading to fungal meningitis⁴

Symptoms 

Fungal meningitis has similar symptoms to other forms of meningitis but it develops slowly, with general symptoms, such as fatigue and a persistent headache, which can last for some time before specific symptoms of fungal meningitis appear. Other symptoms of fungal meningitis can include:¹

• Fever 
• Confusion
• Stiff neck
• Nausea 
• Vomiting
• Sensitivity to bright lights

Diagnosis and treatment 

Diagnosis 

Diagnosing fungal meningitis involves a combination of clinical, laboratory, and imaging tests.⁵

Clinical evaluation

If meningitis is suspected, a doctor may perform specific physical examination techniques to assess for signs of meningitis, including Brudzinski's sign and Kernig's sign:¹

• Brudzinski's sign: the doctor will gently flex the patient's neck forward. If there's involuntary flexion of the hips and knees, it suggests irritation of the meninges
• Kernig's sign: the doctor will gently flex the patient's hip and knee at 90-degree angles, then attempt to straighten the knee. Pain in the back of the thigh and resistance to straightening the knee may indicate irritation of the meninges

While these signs can raise suspicion of meningitis, they are not specific to any particular cause (e.g., bacterial, viral, or fungal).¹ 

Laboratory tests 

To identify the underlying cause of meningitis, the following tests may be conducted:⁵

• Cerebrospinal fluid (CSF): analysis of CSF obtained via lumbar puncture can reveal abnormalities such as elevated white blood cell count, increased protein levels, and decreased glucose levels
• Blood cultures: culturing blood samples can help identify the presence of bacteria or fungi in the bloodstream

Imaging tests

Imaging studies such as computed tomography (CT) or magnetic resonance imaging (MRI) may be performed to searchfor signs of inflammation or complications such as brain abscesses or hydrocephalus.

Treatment 

The treatment of fungal meningitis typically involves antifungal medications and supportive care.⁶  

Antifungal medications 

The duration of antifungal therapy can vary depending on the type of fungal infection, the severity of the infection, and the individual patient's response to treatment. Treatment may continue for several weeks to months.  Close monitoring of symptoms, laboratory parameters, and imaging studies is essential to assess treatment response and determine the appropriate duration of therapy.⁶

Some antifungal medications can include:⁴

• Amphotericin B: this is often the initial drug of choice for treating fungal meningitis. It can be administered intravenously
• Flucytosine: this is sometimes used in combination with amphotericin B, flucytosine can enhance its effectiveness
• Azole Antifungals: drugs such as fluconazole, voriconazole, and itraconazole may be used as maintenance therapy following initial treatment with amphotericin B

Supportive care

Supportive measures may include intravenous fluids, electrolyte management, and management of intracranial pressure if elevated.  Pain management and anti-inflammatory medications may also be prescribed to alleviate symptoms such as headaches.  Additionally, Identifying, and addressing any underlying conditions or factors, that predispose the patient to fungal infections is crucial. This may include optimizing immune function in immunocompromised individuals or treating concurrent medical conditions.  Patients with fungal meningitis require close follow-up and monitoring, to evaluate treatment response, manage potential side effects of antifungal medications, and prevent disease recurrence.^1,4

Prevention strategies 

Unlike viral or bacterial meningitis, there are no vaccines available to prevent fungal meningitis.   Fungal meningitis is rare, and there is no need for most people to take precautionary measures.  However, people with compromised immune systems, orwho reside in an area where there is a higher rate of fungal infection, should take precautionary measures to prevent fungal meningitis.  Therefore, early diagnosis and prompt and appropriate treatment are crucial for improving outcomes in patients.^4,6 

Prevention strategies can include:⁶

• Avoiding exposure to environments with fungi: people at risk should minimise exposure to environments where fungal pathogens thrive, such as areas with high humidity, moisture, or organic debris
• Avoiding bird and bat droppings: bird and bat droppings can harbour fungal spores, so individuals should take precautions to avoid exposure to these sources, especially in enclosed spaces like attics or caves
• Wearing protective masks: when working in dusty environments or areas where fungal spores may be present, such as construction sites or areas with mould growth, wearing a properly fitted N95 mask can help reduce inhalation of fungal spores
• Minimise soil digging: direct contact with soil, particularly in areas with known fungal contamination, should be minimised to reduce the risk of exposure to fungal pathogens
• Indoor air filtration system: installing indoor air filtration systems can help remove airborne fungal spores and improve indoor air quality, reducing the risk of respiratory exposure to fungal pathogens
• Practising good hygiene: maintaining good personal hygiene, including regular hand washing and proper wound care, can help prevent fungal infections from gaining entry into the body

Summary 

In summary, fungal meningitis is characterised by inflammation of the meninges of the brain and spinal cord.  Although rare, fungal meningitis develops gradually and can be chronic, requiring prolonged therapeutic intervention.  Certain risk factors, such as weakened immune systems, certain medications, premature birth, and specific geographic locations can increase a person’s risk of having fungal meningitis. Prevention strategies, particularly for those at increased risk, include minimising exposure to fungal environments, avoiding contact with bird and bat droppings, using protective masks in high-risk areas, and maintaining good hygiene practices. While there are no vaccines for fungal meningitis, early recognition and intervention remain key to improving patient outcomes.