641. Lessons From the Cryptococcus Outbreak in the Pacific Northwest: Emergence, Expansion, and Virulence Attributes of Highly Virulent C. gattii Genotypes
Session: Abstracts: Mycology
Friday, October 22, 2010
Background: Cryptococcus gattii causes life-threatening disease in otherwise healthy hosts in addition to immunocompromised patients. This pathogen resides in the environment where humans and other animals acquire infections via inhalation. One of the highest incidence rates for this disease is in the North American Pacific Northwest, where an outbreak that began in 1999 has now expanded throughout British Columbia, Washington, and Oregon. This outbreak is caused predominantly by C. gattii molecular type VGII, specifically the VGIIa/major genotype. In addition, a novel genotype, VGIIc, has emerged in Oregon and is now a major source of human and mammalian illness in the region.

Methods: Analysis was completed through multilocus sequence typing, clustering analyses, haplotype mapping, recombination studies, murine challenges, and macrophage assays.

Results: We show that the VGIIc group is clonal and hypothesize it arose recently. The VGIIa/IIc outbreak lineages are sexually fertile and our studies support ongoing recombination in the global VGII population, with recent studies of VGII mating under laboratory condition and analysis of the resulting recombinant progeny. This illustrates two hallmarks of emerging outbreaks: high clonality and the emergence of novel genotypes via recombination. In macrophage and murine infections, the novel VGIIc genotype and VGIIa/major isolates from the United States are highly virulent compared to similar non-outbreak VGIIa/major-related isolates. Our analyses distinguish clonal expansion of the VGIIa/major outbreak genotype from related but distinguishable less-virulent genotypes isolated from other geographic regions. Current efforts are focused on the analysis of recent isolates from patients, animals, and the environment, as well as the development of a true inhalation model for infection.

Conclusion: Our evidence documents emerging hypervirulent genotypes in the United States that may expand further, and provides insight into the possible molecular and geographic origins of the outbreak. This unprecedented fungal outbreak in a temperate climate raises concern regarding microbial pathogens emerging in novel geographic locales.


Subject Category: M. Mycology including clinical and basic studies of fungal infections

Speakers:
Edmond J. Byrnes III, B.S. , Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC
Wenjun Li, M.D., Ph.D. , Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC
Yonathan Lewit, B.S. , Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC
Kerstin Voelz , Department of Molecular Pathobiology, University of Birmingham, Birmingham, United Kingdom
Hansong Ma , Department of Molecular Pathobiology, University of Birmingham, Birmingham, United Kingdom
Ping Ren, Ph.D. , Wadsworth Center, Albany, NY
Kieren A. Marr, M.D. , Medicine & Oncology, The Johns Hopkins Hospital, Baltimore, MD
Dee A. Carter, Ph.D. , The University of Sydney, Sydney, Australia
Vishnu Chaturvedi, Ph.D. , Wadsworth Center, Albany, NY
Robert J. Bildfell, DVM , Oregon State University, Corvallis, OR
Robin C. May, Ph.D. , Department of Molecular Pathobiology, University of Birmingham, Birmingham, United Kingdom
Joseph Heitman, MD, PhD , Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC

Disclosures:

E. J. Byrnes III, None

W. Li, None

Y. Lewit, None

K. Voelz, None

H. Ma, None

P. Ren, None

K. A. Marr, Yes
Astellas: Consultant and Grant Investigator,
Merck: Consultant and Grant Investigator,
Pfizer: Consultant and Investigator,

D. A. Carter, None

V. Chaturvedi, None

R. J. Bildfell, None

R. C. May, None

J. Heitman, None

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