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cryptococcus meningitis for 10 mark question

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cryptococcal meningitis

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WHO cryptococcal disease guidelines meningitis amphotericin flucytosine 2022

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https://www.ncbi.nlm.nih.gov/books/NBK620076

Cryptococcal Meningitis

Definition: A subacute fungal meningitis caused mainly by the encapsulated yeasts Cryptococcus neoformans and C. gattii. It is an important opportunistic infection in advanced HIV/AIDS and may also occur in transplant recipients, patients on corticosteroids, and occasionally immunocompetent persons.

Etiology and pathogenesis

  • C. neoformans is ubiquitous and predominantly affects immunocompromised people, especially those with HIV and CD4 count <100 cells/mm³.
  • C. gattii can affect immunocompetent hosts.
  • Infection follows inhalation of fungal cells from the environment, with a primary pulmonary focus followed by hematogenous dissemination to the CNS.
  • The polysaccharide capsule is an important virulence factor. It causes chronic basilar meningitis, raised intracranial pressure (ICP), and sometimes cryptococcoma formation.

Clinical features

The onset is gradual, usually over days to weeks:
  • Headache, fever, malaise
  • Nausea, vomiting
  • Altered behavior, confusion, drowsiness, or coma
  • Neck stiffness and photophobia may be absent, particularly in AIDS
  • Cranial nerve palsies, seizures, focal deficits, or stroke due to meningovascular involvement
  • Raised ICP causes severe headache, vomiting, visual symptoms, and impaired consciousness.
In HIV-associated disease, about 70% may have increased ICP, and absence of meningism does not exclude the diagnosis. Cryptococcus is a leading cause of meningoencephalitis in AIDS. Symptom to Diagnosis, p. 97.

Diagnosis

  1. Lumbar puncture, after neuroimaging if focal neurological deficit, papilledema, seizures, or impaired consciousness:
    • Measure opening pressure, often elevated.
    • CSF may show lymphocytic pleocytosis, raised protein, and low glucose, but can be nearly normal in severe immunosuppression.
  2. CSF cryptococcal antigen (CrAg) by lateral-flow assay:
    • Rapid and highly sensitive diagnostic test.
  3. CSF fungal culture:
    • Gold standard, but takes time.
  4. India ink preparation:
    • May demonstrate round budding yeast with a clear capsular halo.
    • A negative result does not rule out disease.
  5. Serum CrAg and blood culture support diagnosis. CSF should be tested by CrAg, India ink, and culture. Frameworks for Internal Medicine, p. 539.
  6. CT/MRI brain may reveal hydrocephalus, dilated perivascular spaces, gelatinous pseudocysts, infarcts, or cryptococcoma. Bradley and Daroff's Neurology in Clinical Practice, p. 1637.

Treatment

Treatment has three phases:
PhaseRegimen
InductionPreferred WHO regimen for HIV-associated disease: single dose liposomal amphotericin B 10 mg/kg IV plus flucytosine 100 mg/kg/day in 4 divided doses plus fluconazole 1200 mg/day for 14 days
ConsolidationFluconazole 800 mg/day for 8 weeks
Maintenance / secondary prophylaxisFluconazole 200 mg/day until immune reconstitution, usually CD4 >200 cells/mm³ with virologic suppression on ART
Where liposomal amphotericin B is unavailable, alternative regimens include amphotericin B deoxycholate plus flucytosine-based treatment. Renal function, potassium, magnesium, hemoglobin, and blood counts require close monitoring during amphotericin B and flucytosine therapy. The WHO cryptococcal disease guidance provides these regimens.

Management of raised intracranial pressure

  • Measure CSF opening pressure at every lumbar puncture.
  • If symptomatic or markedly elevated, perform therapeutic lumbar punctures, removing CSF daily or repeatedly until pressure and symptoms improve.
  • Persistent hydrocephalus may require lumbar drain or ventriculoperitoneal shunt.
  • Mannitol, acetazolamide, and routine corticosteroids are not recommended solely for cryptococcal raised ICP.

ART timing and prognosis

  • In ART-naive HIV patients, defer ART for 4-6 weeks after starting effective antifungal therapy to reduce life-threatening immune reconstitution inflammatory syndrome (IRIS).
  • Untreated disease is fatal. Poor prognosis is associated with altered sensorium, high fungal burden, markedly raised ICP, and delayed diagnosis.
Key point: Early CrAg-based diagnosis, fungicidal induction therapy, repeated therapeutic LPs for raised ICP, and delayed ART initiation are the pillars of management.
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