Molecular evidence that the range of the Vancouver Island outbreak of Cryptococcus gattii infection has expanded into the Pacific Northwest in the United States

Abstract

Cryptococcus neoformans frequently causes fungal meningitis in immunocompromised patients, whereas the related species C. gattii is restricted to tropical and subtropical regions,where it usually infects immunocompetent individuals.An outbreak of C. gattii infection that began in 1999 on Vancouver Island has resulted in endemic C. gattii infection and caused numerous human and veterinary infections; the outbreak's range has spread to mainland British Columbia. The outbreak-related isolates have been molecular type VGIIa, the major genotype, or VGIIb, the minor genotype. Since 2006, human and veterinary cases of C. gattii infection have emerged in Washington and Oregon. Multilocus sequence typing demonstrates the spread of C. gattii VGIIa and VGIIb from Vancouver Island to the Pacific Northwest. Clinical strains recovered in Oregon represent a unique VGIIc genotype.

Figure 1

A) C. gattii cases in animals and humans in Washington and Oregon during 2006–2008. All cases represented have been confirmed using phenotypic analysis and Multilocus Sequence Typing (MLST) genotypic profiling. There are a total of 22 cases, including thirteen in Washington State and nine in Oregon, United States. Of the 22 cases fourteen are human clinical isolates, and eight are isolates from deceased wild and companion animals. B) MLST reveals VGIIa major, VGIIb minor, and VGIIc isolates in Washington and Oregon. Multilocus Sequence Typing (MLST) was performed for eight unlinked loci. Numbers and color-coding represent different alleles designated by genetic sequence variation. The lone VGIII isolate was an identical match to only Australian isolates, indicating its possible origin. C) Expanded Multilocus Sequence Typing (MLST) analysis for selected VGII isolates, including VGIIc isolates. Six of the eight additional alleles were novel among the VGIIc isolates tested. Isolates WA861 and ICB184 were examined as other closely related VGII isolates to the VGIIc group, with MLST analysis providing further evidence that the VGIIc group is not closely related to these isolates.

Figure 2

Origin of an outbreak. Left panel) The arrival of minor and novel recombinant genotypes. Right panel) The dispersal of the VGIIa major, and VGIIb minor genotypes from Vancouver Island to the British Columbia mainland (1), from the British Columbia mainland to the United States (2), from Vancouver Island to the United States (3), and from Washington to Oregon (4).