Cryptococcus neoformans
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Direct answer
Cryptococcus neoformans is an encapsulated yeast that causes meningoencephalitis, most often in advanced HIV when CD4 counts fall below about 100 cells per microlitre. Its polysaccharide capsule appears as a clear halo on India ink, and the capsular antigen is detected in serum or CSF by lateral flow assay. Treatment is induction with amphotericin B and flucytosine, then fluconazole, with repeated lumbar puncture relieving raised pressure.
What you must remember
- Capsule: a polysaccharide capsule of glucuronoxylomannan that shows as a halo on India ink and stains with mucicarmine.
- Urease and seed agar: Cryptococcus is urease positive, and it forms brown colonies on Niger seed (caffeic acid) agar.
- Cryptococcal antigen test: a lateral flow assay on serum or CSF that is highly sensitive and useful for screening in advanced HIV.
- Raised intracranial pressure: common in cryptococcal meningitis, and managed with repeated therapeutic lumbar punctures and, if persistent, a lumbar drain or shunt.
- Induction therapy: liposomal amphotericin B with flucytosine, then fluconazole consolidation; WHO 2022 prefers one high dose of liposomal amphotericin B with 14 days of flucytosine and fluconazole.
- Cryptococcus gattii: a related species that infects immunocompetent people and is found in tropical and subtropical regions.
- Pigeon droppings: an environmental reservoir for Cryptococcus neoformans, linked to inhalation of dried droppings.
A headache in advanced HIV
A man with advanced HIV, with a CD4 count of 60 cells per microlitre, presents with three weeks of headache, low-grade fever and neck stiffness.
- Examine the CSF: India ink, the cryptococcal antigen lateral flow assay and culture on Sabouraud agar are sent, and the opening pressure is recorded.
- Act on raised pressure: elevated opening pressure needs urgent therapeutic lumbar puncture, since it is a leading cause of death in this infection.
- Start induction: liposomal amphotericin B with flucytosine is given for about two weeks, and where flucytosine is unavailable, amphotericin is combined with high-dose fluconazole.
- Consolidate and maintain: fluconazole continues for consolidation, followed by maintenance until immune recovery on antiretroviral therapy.
- Time antiretroviral therapy: treatment is started after induction and timed to limit the risk of immune reconstitution inflammatory syndrome, with the decision individualised.
Each step is tied to the CSF findings, so the lumbar puncture and the antigen result guide the rest of the management.
Where the exam tries to catch you
Cryptococcus questions test staining, antigen tests and the management of pressure.
- Trap: treating a yeast in CSF with antibiotics alone Correct: a yeast with a capsule on India ink needs antifungal therapy, and cryptococcal meningitis is not cleared by antibacterial drugs.
- Trap: taking normal-looking CSF as proof of no raised pressure Correct: raised pressure is common in cryptococcal meningitis, so it is measured directly and treated by lumbar drainage.
- Trap: using Gram stain to identify Cryptococcus Correct: the organism stains poorly on Gram stain, so India ink, the capsule stain and the antigen test are the practical tools.
Frequently asked questions
Why is India ink used to examine Cryptococcus neoformans?
India ink is a negative stain that outlines the polysaccharide capsule of Cryptococcus neoformans as a clear halo around the yeast. It is quick and inexpensive, although it is less sensitive than the capsular antigen test. The capsule is the feature to look for on the slide.
Which test screens for cryptococcal disease in advanced HIV?
The cryptococcal antigen lateral flow assay is the usual test, performed on serum or CSF. Its high sensitivity makes it useful for screening people with low CD4 counts before symptoms develop. A positive serum result is followed by CSF examination to exclude meningitis.
How is raised intracranial pressure managed in cryptococcal meningitis?
Raised intracranial pressure is managed with repeated therapeutic lumbar punctures that drain CSF and lower the pressure. A lumbar drain or shunt may be needed if pressure stays high. Controlling pressure is essential, because it is a leading cause of death in cryptococcal meningitis.
What is the induction treatment for cryptococcal meningitis?
Induction uses liposomal amphotericin B combined with flucytosine, given as the conventional two-week course or, in the WHO 2022 preferred regimen, as a single high dose with 14 days of flucytosine and fluconazole. Fluconazole then consolidates the response, followed by maintenance therapy.