fungal meningitis
Summary
Fungal meningitis is a subacute-to-chronic infection of the meninges most commonly caused by Cryptococcus neoformans, particularly in immunocompromised patients (e.g., HIV/AIDS with CD4 <100). It presents with headache, fever, and altered mental status over days to weeks, distinguishing it from the acute presentation of bacterial meningitis. Diagnosis relies on CSF analysis with cryptococcal antigen testing and India ink staining.
Detail
Fungal meningitis is most frequently caused by Cryptococcus neoformans, especially in immunocompromised hosts such as those with AIDS (CD4 count <100 cells/µL), transplant recipients, or patients on chronic corticosteroids. Other causative fungi include Coccidioides immitis (endemic to Southwest US), Histoplasma capsulatum (Ohio/Mississippi River valleys), and Candida species (especially in neonates or after neurosurgery/CNS shunts). Aspergillus can cause meningitis via direct extension or hematogenous spread in severely immunocompromised patients.
Pathophysiology: Cryptococcus is acquired via inhalation of spores from soil contaminated with bird droppings, disseminating hematogenously to the CNS where its polysaccharide capsule impairs phagocytosis and immune clearance. The organism has tropism for the CNS, possibly due to lack of complement in CSF and utilization of host catecholamines via laccase enzyme.
Clinical presentation: Subacute onset (over days to weeks) of headache, fever, neck stiffness, photophobia, nausea/vomiting, and altered mental status. Papilledema and cranial nerve palsies can occur due to elevated intracranial pressure, which is a hallmark complication requiring serial lumbar punctures or CSF shunting.
Diagnosis: Lumbar puncture with CSF analysis showing lymphocytic pleocytosis, elevated protein, and low-to-normal glucose (unlike the very low glucose seen in bacterial meningitis). Cryptococcal antigen (CrAg) testing in serum and CSF is highly sensitive and specific. India ink staining reveals encapsulated yeast with a characteristic halo (narrow-based budding). Fungal cultures confirm diagnosis but take time. Opening pressure is often markedly elevated in cryptococcal meningitis.
Treatment: Induction therapy with amphotericin B plus flucytosine, followed by consolidation and maintenance therapy with fluconazole. Management of elevated intracranial pressure via therapeutic lumbar punctures is critical to reducing mortality. In HIV patients, antiretroviral therapy should be delayed 2-10 weeks after starting antifungal treatment to avoid immune reconstitution inflammatory syndrome (IRIS).
Key associations for boards: Cryptococcus neoformans + HIV/AIDS + soil/pigeon droppings + India ink stain + narrow-based budding yeast + mucicarmine stain (stains capsule red) + latex agglutination test for capsular antigen.
Sources
- First Aid for the USMLE Step 1
- Sabiston Textbook of Surgery (Microbiology sections)
- Harrison's Principles of Internal Medicine
- Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases
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