What are the causes of fungal meningitis?

Causes of Fungal Meningitis

Fungal meningitis is caused by two distinct categories of pathogens: primary fungal pathogens that infect immunocompetent hosts (Cryptococcus, Coccidioides, Histoplasma, Blastomyces) and opportunistic fungi that predominantly infect immunocompromised patients (Candida, Aspergillus, Zygomycetes). 1, 2

Primary Fungal Pathogens (Infect Normal Hosts)

Cryptococcus species are the most common cause of fungal meningitis worldwide and represent the single most important fungal pathogen affecting the CNS. 1, 3

• Cryptococcus neoformans and Cryptococcus gattii cause the majority of cases, with C. neoformans having broader geographic distribution while C. gattii was historically limited to tropical environments but now occurs in temperate regions. 1
• Cryptococcus is considered a true neurotropic fungus with specific affinity for CNS tissue. 3
• These organisms can infect both immunocompetent and immunocompromised hosts, though disease is more severe in the latter. 2

Endemic dimorphic fungi cause meningitis primarily through hematogenous spread from pulmonary infection:

• Coccidioides immitis is geographically restricted and causes coccidioidal meningitis, particularly in endemic areas. 1, 3
• Histoplasma capsulatum causes CNS infection through hematogenous dissemination. 1, 3
• Blastomyces dermatitidis can produce meningitis as part of disseminated disease. 2
• Sporothrix schenckii rarely causes meningeal sporotrichosis, which has poor prognosis and limited treatment options. 1, 4

Opportunistic Fungal Pathogens (Primarily Immunocompromised Hosts)

These fungi cause secondary CNS infections in patients with impaired immunity:

Candida species, particularly Candida albicans, cause meningitis in specific high-risk populations: 1, 3

• Patients receiving hyperalimentation, corticosteroids, or cytotoxic drugs 5
• Transplant recipients and those with hematologic malignancies 5
• Patients with indwelling neurosurgical devices or following neurosurgical procedures 1

Aspergillus species cause CNS infection through hematogenous spread or direct extension from colonized sinuses: 3, 2

• More commonly cause brain abscesses than meningitis 3
• Occur in severely immunocompromised patients 4

Zygomycetes (Mucorales) cause rhino-cerebral syndrome with potential meningeal involvement: 3, 4

• Direct extension from colonized sinuses or ear canal 3
• Associated with diabetes mellitus and immunosuppression 4

Rare melanized (dematiaceous) fungi with neurotropic properties: 3

• Cladophialophora bantiana, Exophiala dermatitidis, Ramichloridium mackenziei, Ochroconis gallopava are considered true neurotropic fungi 3
• These organisms have specific affinity for CNS tissue even in immunocompetent hosts 3

Trichosporon species cause opportunistic infections in immunocompromised patients. 4

Routes of CNS Infection

Fungal pathogens reach the CNS through three primary mechanisms: 3

• Hematogenous spread from distant sites (most common route for Cryptococcus, Candida, endemic fungi) 3
• Direct extension from colonized paranasal sinuses or ear canal (Aspergillus, Zygomycetes) 3
• Direct inoculation during neurosurgical procedures or trauma (Candida, Aspergillus) 1, 3

High-Risk Populations

The following patient populations are at substantially increased risk for fungal meningitis: 5

• HIV/AIDS patients (particularly for Cryptococcus) 1, 3
• Hematologic malignancy patients 5
• Solid organ and hematopoietic stem cell transplant recipients 5
• Patients receiving corticosteroids or cytotoxic chemotherapy 3, 5
• Injection drug users 5
• Post-neurosurgical patients 1
• Patients with COVID-19 requiring immunosuppressive therapy 6

Critical Clinical Context

Fungal meningitis typically presents as chronic meningitis with symptoms persisting ≥4 weeks, distinguishing it from acute bacterial meningitis. 1, 7

• The incidence has increased dramatically since the 1970s due to widespread use of immunosuppressive medications and the HIV/AIDS epidemic. 3, 5
• Even immunocompetent hosts can develop CNS fungal infections, particularly with primary fungal pathogens. 3, 4
• Geographic exposure history is critical for diagnosing endemic fungal causes (Coccidioides, Histoplasma, Blastomyces). 2