Current Fungal Infection Reports

, Volume 4, Issue 3, pp 151–157 | Cite as

Cryptococcus gattii: Clinical Importance and Emergence in North America



Cryptococcus gattii is an emerging fungal pathogen in the Pacific Northwest of North America, where it has caused more than 50 human infections since its emergence in 2004. Among residents of British Columbia, where the disease emerged in 1999 on Vancouver Island, many infections have occurred in immunocompetent persons. The cause for the emergence is currently unknown. The pathogenic profile of Cryptococcus gattii in North American patients appears to be different from that seen previously for C. gattii and from the profile of infection among patients with Cryptococcus neoformans. Treatment duration and the need for patient follow-up may be different between patients infected with C. gattii and C. neoformans. For this reason, physicians treating atypical patients with Cryptococcal spp infection, particularly HIV-uninfected patients, should obtain a travel history and obtain a species identity for Cryptococcus isolates.


Cryptococcus Cryptococcus gattii Cryptococcus neoformans Fungal epidemiology Pacific Northwest Fungal infection Cryptococcoma 


Recently published papers of interest have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Kwon-Chung KJ, Bennett JE: Epidemiologic differences between the two varieties of Cryptococcus neoformans. Am J Epidemiol 1984, 120:123–130.PubMedGoogle Scholar
  2. 2.
    Speed B, Dunt D: Clinical and host differences between infections with the two varieties of Cryptococcus neoformans. Clin Infect Dis 1995, 21:28–34.PubMedGoogle Scholar
  3. 3.
    Mitchell DH, Sorrell TC, Allworth AM, et al.: Cryptococcal disease of the CNS in immunocompetent hosts: influence of cryptococcal variety on clinical manifestations and outcome. Clin Infect Dis 1995, 20:611–616.PubMedGoogle Scholar
  4. 4.
    Chen SCA, Sorrell TC, Nimmo G, et al.: Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Australasian Cryptococcal Study Group. Clin Infect Dis 2000, 31:499–508.CrossRefPubMedGoogle Scholar
  5. 5.
    Mirza SA, Phelan M, Rimland D, et al.: The changing epidemiology of cryptococcosis: an update from population-based active surveillance in 2 large metropolitan areas, 1992–2000. Clin Infect Dis 2003, 36:789–794.CrossRefPubMedGoogle Scholar
  6. 6.
    Dromer F, Mathoulin-Pélissier S, Fontanet A, et al.: Epidemiology of HIV-associated cryptococcosis in France (1985–2001): comparison of the pre- and post-HAART eras. AIDS 2004, 18:555–562.CrossRefPubMedGoogle Scholar
  7. 7.
    • Park BJ, Wannemuehler KA, Marston BJ, et al.: Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 2009, 23:525–530. This is the first report to try to estimate the global burden of cryptococcal disease.CrossRefPubMedGoogle Scholar
  8. 8.
    Morgan J, McCarthy KM, Gould S, et al.: Cryptococcus gattii infection: characteristics and epidemiology of cases identified in a South African province with high HIV seroprevalence, 2002–2004. Clin Infect Dis 2006, 43:1077–1080.CrossRefPubMedGoogle Scholar
  9. 9.
    •• Galanis E, MacDougall L: Epidemiology of Cryptococcus gattii, British Columbia, Canada, 1999–2007. Emerg Infect Dis 2010, 16:251–257. This report is the first comprehensive look at the epidemiology of C. gattii infection in BC.PubMedGoogle Scholar
  10. 10.
    MacDougall L, Kidd SE, Galanis E, et al.: Spread of Cryptococcus gattii in British Columbia, Canada, and detection in the Pacific Northwest, USA. Emerg Infect Dis 2007, 13:42–50.CrossRefPubMedGoogle Scholar
  11. 11.
    • Iqbal N, DeBess EE, Wohrle R, et al.: Correlation of genotype and in vitro susceptibilities of Cryptococcus gattii from the Pacific Northwest of the United States. J Clin Microbiol 2010, 48:539–544. This report is the first to show that susceptibilities to azole drugs in C. gattii vary by genotype. It also provided the first look at the genotype of a large number of US isolates.CrossRefPubMedGoogle Scholar
  12. 12.
    Stephen C, Lester S, Black W, et al.: Multispecies outbreak of cryptococcosis on southern Vancouver Island, British Columbia. Can Vet J 2002, 43:792–794.PubMedGoogle Scholar
  13. 13.
    Kidd SE, Hagen F, Tscharke RL, et al.: A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada). Proc Natl Acad Sci U S A 2004, 101:17258–17263.CrossRefPubMedGoogle Scholar
  14. 14.
    Fyfe M, MacDougall L, Romney M, et al.: Cryptococcus gattii infections on Vancouver Island, British Columbia, Canada: emergence of a tropical fungus in a temperate environment. Can Commun Dis Rep 2008, 34:1–12.PubMedGoogle Scholar
  15. 15.
    Kidd SE, Guo H, Bartlett KH, et al.: Comparative gene genealogies indicate that two clonal lineages of Cryptococcus gattii in British Columbia resemble strains from other geographical areas. Eukaryot Cell, 2005 4:1629–1638.CrossRefPubMedGoogle Scholar
  16. 16.
    Fraser JA, Giles SS, Wenink EC, et al.: Same-sex mating and the origin of the Vancouver Island Cryptococcus gattii outbreak. Nature 2005, 437:1360–1364.CrossRefPubMedGoogle Scholar
  17. 17.
    Ellis DH, Pfeiffer TJ: Natural habitat of Cryptococcus neoformans var. gattii. J Clin Microbiol 1990, 28:1642–1644.PubMedGoogle Scholar
  18. 18.
    BC Centre for Disease Control: BC Cryptococcus gattii surveillance summary, 1999–2006. 2007. Available from–2006.pdf.
  19. 19.
    • Byrnes EJ, Bildfell RJ, Frank SA, et al.: Molecular evidence that the range of the Vancouver Island outbreak of Cryptococcus gattii infection has expanded into the Pacific Northwest in the United States. J Infect Dis 2009, 199:1081–1086. This report was the first to show that a third clonal genotype of C. gattii, VGIIc, was emerging in the USPNW.CrossRefPubMedGoogle Scholar
  20. 20.
    Upton A, Fraser JA, Kidd SE, et al.: First contemporary case of human infection with Cryptococcus gattii in Puget Sound: evidence for spread of the Vancouver Island outbreak. J Clin Microbiol 2007, 45:3086–3088.CrossRefPubMedGoogle Scholar
  21. 21.
    Lester SJ, Kowalewich NJ, Bartlett KH, et al.: Clinicopathologic features of an unusual outbreak of cryptococcosis in dogs, cats, ferrets, and a bird: 38 cases (January to July 2003). J Am Vet Med Assoc, 225:1716–1722.CrossRefGoogle Scholar
  22. 22.
    Duncan C, Stephen C, Campbell J: Clinical characteristics and predictors of mortality for Cryptococcus gattii infection in dogs and cats of southwestern British Columbia. Can Vet J 2006, 47:993–998.PubMedGoogle Scholar
  23. 23.
    Kidd SE, Bach PJ, Hingston AO, et al.: Cryptococcus gattii dispersal mechanisms, British Columbia, Canada. Emerg Infect Dis 2007, 13:51–57.CrossRefPubMedGoogle Scholar
  24. 24.
    Kidd SE, Chow Y, Mak S, et al.: Characterization of environmental sources of the human and animal pathogen Cryptococcus gattii in British Columbia, Canada, and the Pacific Northwest of the United States. Appl Environ Microbiol 2007, 73:1433–1443.CrossRefPubMedGoogle Scholar
  25. 25.
    MacDougall L, Fyfe M: Emergence of Cryptococcus gattii in a novel environment provides clues to its incubation period. J Clin Microbiol 2006, 44:1851–1852.CrossRefPubMedGoogle Scholar
  26. 26.
    Lizarazo J, Linares M, de Bedout C, et al.: [Results of nine years of the clinical and epidemiological survey on cryptococcosis in Colombia, 1997–2005] [Article in Spanish]. Biomedica 2007, 27:94–109.PubMedGoogle Scholar
  27. 27.
    Kwon-Chung KJ, Polacheck I, Bennett JE: Improved diagnostic medium for separation of Cryptococcus neoformans var. neoformans (serotypes A and D) and Cryptococcus neoformans var. gattii (serotypes B and C). J Clin Microbiol 1982, 15:535–537.PubMedGoogle Scholar
  28. 28.
    Klein KR, Hall L, Deml SM, et al.: Identification of Cryptococcus gattii by use of L-canavanine glycine bromothymol blue medium and DNA sequencing. J Clin Microbiol 2009, 47:3669–3672.CrossRefPubMedGoogle Scholar
  29. 29.
    Boekhout T, Theelen B, Diaz M, et al.: Hybrid genotypes in the pathogenic yeast Cryptococcus neoformans. Microbiology 2001, 147:891–907.PubMedGoogle Scholar
  30. 30.
    •• Meyer W, Aanensen DM, Boekhout T, et al.: Consensus multi-locus sequence typing scheme for Cryptococcus neoformans and Cryptococcus gattii. Med Mycol 2009, 47:561–570. This report describes the consensus MLST genotyping scheme for both C. gattii and C. neoformans.CrossRefPubMedGoogle Scholar
  31. 31.
    Meyer W, Castañeda A, Jackson S, et al.: Molecular typing of IberoAmerican Cryptococcus neoformans isolates. Emerg Infect Dis 2003, 9:189–195.PubMedGoogle Scholar
  32. 32.
    • Perfect JR, Dismukes WE, Dromer F, et al.: Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2010, 50:291–322. This report contains the IDSA-recommended guidelines for the treatment of all Cryptococcus disease.CrossRefPubMedGoogle Scholar
  33. 33.
    Lindberg J, Hagen F, Laursen A, et al.: Cryptococcus gattii risk for tourists visiting Vancouver Island, Canada. Emerg Infect Dis 2007, 13:178–179.CrossRefPubMedGoogle Scholar
  34. 34.
    Levy R, Pitout J, Long P, Gill MJ.: Late presentation of Cryptococcus gattii meningitis in a traveller to Vancouver Island: a case report. Can J Infect Dis Med Microbiol 2007, 18:197–199.PubMedGoogle Scholar
  35. 35.
    Chambers C, MacDougall L, Li M, et al.: Tourism and specific risk areas for Cryptococcus gattii, Vancouver Island, Canada. Emerg Infect Dis 2008, 14:1781–1783.CrossRefPubMedGoogle Scholar
  36. 36.
    Georgi A, Schneemann M, Tintelnot K, et al.: Cryptococcus gattii meningoencephalitis in an immunocompetent person 13 months after exposure. Infection 2009, 37:370–373.CrossRefPubMedGoogle Scholar
  37. 37.
    Byrnes EJ 3 rd, Li W, Lewit Y, et al.: First reported case of Cryptococcus gattii in the Southeastern USA: implications for travel-associated acquisition of an emerging pathogen. PLoS One 2009, 4:e5851.CrossRefPubMedGoogle Scholar
  38. 38.
    Hagen F, van Assen S, Luijckx GJ, et al.: Activated dormant Cryptococcus gattii infection in a Dutch tourist who visited Vancouver Island (Canada): a molecular epidemiological approach. Med Mycol 2010, 48:528–531.CrossRefPubMedGoogle Scholar
  39. 39.
    Dong ZM, Murphy JW: Effects of the two varieties of Cryptococcus neoformans cells and culture filtrate antigens on neutrophil locomotion. Infect Immun 1995, 63:2632–2644.PubMedGoogle Scholar
  40. 40.
    Wright L, Bubb W, Davidson J, et al.: Metabolites released by Cryptococcus neoformans var. neoformans and var. gattii differentially affect human neutrophil function. Microbes Infect 2002, 4:1427–1438.CrossRefPubMedGoogle Scholar
  41. 41.
    • Cheng PY, Sham A, Kronstad JW: Cryptococcus gattii isolates from the British Columbia cryptococcosis outbreak induce less protective inflammation in a murine model of infection than Cryptococcus neoformans. Infect Immun 2009, 77:4284–4294. This report describes one hypothesis about why C. gattii is more successful than C. neoformans in infecting immunocompetent hosts.CrossRefPubMedGoogle Scholar
  42. 42.
    Einsiedel L, Gordon DL, Dyer JR: Paradoxical inflammatory reaction during treatment of Cryptococcus neoformans var. gattii meningitis in an HIV-seronegative woman. Clin Infect Dis 2004, 39:e78–e82.Google Scholar
  43. 43.
    Brouwer AE, Siddiqui AA, Kester MI, et al.: Immune dysfunction in HIV-seronegative, Cryptococcus gattii meningitis. J Infect 2007, 54:e165–e168.CrossRefPubMedGoogle Scholar
  44. 44.
    Young BJ, Kozel TR.: Effects of strain variation, serotype, and structural modification on kinetics for activation and binding of C3 to Cryptococcus neoformans. Infect Immun 1993, 61:2966–2972.PubMedGoogle Scholar
  45. 45.
    Ma H, Hagen F, Stekel DJ, et al.: The fatal fungal outbreak on Vancouver Island is characterized by enhanced intracellular parasitism driven by mitochondrial regulation. Proc Natl Acad Sci U S A 2009, 106:12980–12985.CrossRefPubMedGoogle Scholar

Copyright information

© US Government 2010

Authors and Affiliations

  1. 1.Mycotic Disease BranchCenters for Disease Control and PreventionAtlantaUSA

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