Title : Breaking the paradigm of opportunism: A case study of cryptococcus neoformans invasion in the HIV-negative host
Abstract:
Background: Cryptococcal meningitis (CM) is traditionally categorized as a sentinel opportunistic infection of advanced HIV/AIDS, typically occurring when CD4 counts fall below 100 cells/µL. However, this clinical paradigm often leads to significant diagnostic delays in HIV-negative or apparently immunocompetent patients, where the disease may follow a more insidious and varied course. Literature indicates that while diagnosis in immunocompromised patients takes an average of 34 days, it extends to 81 days in "normal" hosts, contributing to higher mortality and late-onset morbidity. This case highlights the challenges of diagnosing CM when it masquerades as common neurological conditions in a non-HIV host.
Case Presentation: A 56-year-old Filipino male general contractor with a history of hypertension presented with acute agitation, disorientation, and an inability to recognize family members. The patient had a six-month history of intermittent, throbbing right temporal headaches (PS 10/10). Notably, neuroimaging performed four months and one month prior to admission suggested a subacute subarachnoid hemorrhage or parenchymal hematoma, which initially directed clinical suspicion toward a vascular etiology rather than an infectious one.
Diagnostics: Upon admission, the patient exhibited nuchal rigidity and positive Kernig’s and Brudzinski’s signs. A lumbar puncture revealed a significantly elevated opening pressure of >34 cmH2O, which later peaked at 47 cmH2O. CSF analysis showed elevated protein (109 mg/dL) and a positive Cryptococcal Antigen (CALAS) test at a titer of 1:8. HIV serostatus and other common sources of immunosuppression (e.g., diabetes, malignancy) were negative.
Management and Outcome: The patient underwent induction therapy with Amphotericin B deoxycholate and high-dose Fluconazole (800mg). Management of severe intracranial hypertension required aggressive intervention with Mannitol and therapeutic lumbar punctures. Although the patient developed drug-induced hypokalemia and a late-onset Klebsiella pneumoniae hospital-acquired pneumonia, his sensorium improved following 14 doses of Amphotericin B. He was discharged in stable condition to continue maintenance therapy.
Conclusion: This case demonstrates that Cryptococcus neoformans can act as a primary invader in the absence of traditional opportunistic risk factors. The pathogen’s ability to mimic vascular events on initial imaging underscores the necessity of early CSF analysis in cases of chronic, refractory headache. Breaking the paradigm that CM only affects the severely immunocompromised is critical to reducing diagnostic delays, managing lifethreatening intracranial hypertension, and preventing permanent neurological damage in the HIV-negative population.
