Cryptococcus neoformans

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Cryptococcus neoformans
Scientific classification
Kingdom: Fungi
Phylum: Basidiomycota
Subphylum: Basidiomycotina
Order: Sporidiales
Family: Sporidiobolaceae
Genus: Filobasidiella (Cryptococcus)
Species: Filobasidiella neoformans
(Cryptococcus neoformans)

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This page is about microbiologic aspects of the organism(s).  For clinical aspects of the disease, see Cryptococcosis.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Cryptococcus neoformans is an encapsulated yeast-like fungus that can live in both plants and animals.This species, also known by its teleomorph name, Filobasidiella neoformans, belongs to the broad class of organisms called "club fungi" or Division Basidiomycota, which is one the five major types of fungi. C. neoformans usually grows as a yeast (unicellular) and replicates by budding. Under certain conditions, both in nature and in the laboratory, C. neoformans can grow as a filamentous fungus as pictured here: picture of the organism[1]. When grown as a yeast, C. neoformans has a prominent capsule composed mostly of polysaccharides. Microscopically, the India ink stain is used for easy visualization of the capsule. The particles of ink pigment do not enter the capsule that surrounds the spherical yeast cell, resulting in a zone of clearance or "halo" around the cells.

Cryptococcus neoformans seen in the lung of a patient with AIDS. The inner capsule of the organism stains red in this photomicrograph

The species C. neoformans is composed of three variants (v.): C. neoformans v. gattii, v. grubii, and v. neoformans. C. neoformans v. gattii is found mostly in the tropics, but has also been confirmed on southern Vancouver Island on the southwestern coast of Canada. Cryptococcus gattii has recently been shown to be different enough from other subspecies to be elevated to its own species level. C. neoformans v. grubii and v. neoformans have a worldwide distribution and are often found in soil which has been contaminated by bird excrement. The genome sequence of C. neoformans v. neoformans was published in 2005.[2] Recent studies made on Chernobyl Nuclear Power Plant have shown that colonies of Cryptococcus neoformans developed on the ruins of melted down reactor harvest energy of radiation (primary beta radiation from caesium-137) itself.[3]

Infection with C. neoformans is termed cryptococcosis.

Treatment

Cryptococcosis that does not affect the central nervous system can be treated with fluconazole alone.

Cryptococcal meningitis should be treated for two weeks with intravenous Amphotericin B 0.7–1.0 (mg/kg)/day and oral flucytosine 100 (mg/kg)/day (or intravenous flucytosine 75 (mg/kg)/day if the patient is unable to swallow). This should then be followed by oral fluconazole 200mg daily for ten weeks[4] and then 200 mg daily until the patient's CD4 count is above 100 for three months and his HIV viral load is undetectable.[5][6]

Intravenous Ambisome 4 (mg/kg)/day may be used but is not superior: its main use is in patients who do not tolerate Amphotericin B. The 200 (mg/kg)/day dose for flucytosine is not more effective, is associated with more side-effects and should not be used.

In Africa, oral fluconazole at a rate of 200 mg daily is used. However, this does not result in cure because it merely suppresses the fungus and does not kill it; viable fungus can continue to be grown from CSF of patients who have taken fluconazole for many months. An increased dose of 400 mg daily does not improve outcomes,[7] but preliminary data from Uganda shows that very high doses of 1200 mg or more per day may be effective. The duration of this treatment and the post-treatment maintenance dose is not known.


References

  1. Photomicrograph hosted by the Tree of Life project and specifically contributed by the Duke University Mycology Research Unit; the picture is part of the Hymenomycetes article. Retrieved 2005-03-15
  2. Loftus BJ; et al. "The genome of the basidiomycetous yeast and human pathogen Cryptococcus neoformans". Science. 307 (5713): 1321&ndash, 24. PMID 15653466.
  3. Dadachova E; et al. "Ionizing Radiation Changes the Electronic Properties of Melanin and Enhances the Growth of Melanized Fungi". PLoS One. 2(5). doi:10.1371/journal.pone.0000457. PMID 17520016.
  4. Saag MS, Graybill RJ, Larsen RA; et al. (2000). "Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America". Clin Infect Dis. 30 (4): 710&ndash, 8. PMID 10770733.
  5. Martínez E, García-Viejo MA, Marcos MA; et al. (2000). "Discontinuation of secondary prophylaxis for cryptococcal meningitis in HIV-infected patients responding to highly active antiretroviral therapy". AIDS. 14 (16): 2615&ndash, 26. PMID 11101078.
  6. Vibhagool A, Sungkanuparph S, Mootsikapun P; et al. (2003). "Discontinuation of secondary prophylaxis for Cryptococcal meningitis in Human Immunodeficiency Virus-infected patients treated with highly active antiretroviral therapy: a prospective, multicenter, randomized study". Clin Infect Dis. 36: 1329&ndash, 31. doi:10.1086/374849. PMID 12746781.
  7. CF Schaars, Meintjes GA, Morroni C; et al. (2006). "Outcome of AIDS-associated cryptococcal meningitis initially treated with 200 mg/day or 400 mg/day of fluconazole". BMC Infect Dis. 6: 118. doi:10.1186/1471-2334-6-118.

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