Abstract
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.
References
Recently published papers of interest have been highlighted as: • Of importance •• Of major importance
Kwon-Chung KJ, Bennett JE: Epidemiologic differences between the two varieties of Cryptococcus neoformans. Am J Epidemiol 1984, 120:123–130.
Speed B, Dunt D: Clinical and host differences between infections with the two varieties of Cryptococcus neoformans. Clin Infect Dis 1995, 21:28–34.
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.
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.
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.
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.
• 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.
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.
•• 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.
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.
• 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.
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.
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.
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.
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.
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.
Ellis DH, Pfeiffer TJ: Natural habitat of Cryptococcus neoformans var. gattii. J Clin Microbiol 1990, 28:1642–1644.
BC Centre for Disease Control: BC Cryptococcus gattii surveillance summary, 1999–2006. 2007. Available from http://www.llbc.leg.bc.ca/public/pubdocs/bcdocs/424022/c.gattii_surveillance_summary_bc_1999–2006.pdf.
• 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.
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.
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.
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.
Kidd SE, Bach PJ, Hingston AO, et al.: Cryptococcus gattii dispersal mechanisms, British Columbia, Canada. Emerg Infect Dis 2007, 13:51–57.
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.
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.
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.
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.
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.
Boekhout T, Theelen B, Diaz M, et al.: Hybrid genotypes in the pathogenic yeast Cryptococcus neoformans. Microbiology 2001, 147:891–907.
•• 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.
Meyer W, Castañeda A, Jackson S, et al.: Molecular typing of IberoAmerican Cryptococcus neoformans isolates. Emerg Infect Dis 2003, 9:189–195.
• 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.
Lindberg J, Hagen F, Laursen A, et al.: Cryptococcus gattii risk for tourists visiting Vancouver Island, Canada. Emerg Infect Dis 2007, 13:178–179.
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.
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.
Georgi A, Schneemann M, Tintelnot K, et al.: Cryptococcus gattii meningoencephalitis in an immunocompetent person 13 months after exposure. Infection 2009, 37:370–373.
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.
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.
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.
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.
• 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.
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.
Brouwer AE, Siddiqui AA, Kester MI, et al.: Immune dysfunction in HIV-seronegative, Cryptococcus gattii meningitis. J Infect 2007, 54:e165–e168.
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.
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.
Acknowledgments
The findings and conclusions of this article are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.
The authors wish to thank members of the C. gattii Public Health Working Group (Emilio E. DeBess and Dawn Daly, Oregon Department of Human Services; Ron Wohrle, Nicola Marsden-Haug, Marcia Goldoft, and Cyndi Free, Washington State Department of Health; Ben Sun and Duc Vugia, California Department of Public Health; Tom Chiller, Naureen Iqbal, and Joyce Peterson, Centers for Disease Control and Prevention; Linda Hoang and Muhammad Morshed, BC Centers for Disease Control; and Karen Bartlett, University of British Columbia) for thoughtful discussions, and Mary Brandt and Tom Chiller for critical reading of the manuscript.
Disclosure
No potential conflicts of interest relevant to this article were reported.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lockhart, S.R., Harris, J. Cryptococcus gattii: Clinical Importance and Emergence in North America. Curr Fungal Infect Rep 4, 151–157 (2010). https://doi.org/10.1007/s12281-010-0021-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12281-010-0021-y