Cryptococcus deuterogattii VGIIa infection associated with travel to the Pacific Northwest outbreak region in an anti-GM-CSF autoantibody positive patient in the United States

Abstract

The Pacific Northwest (PNW), Vancouver Island, Oregon, and Washington have been the location of an ongoing Cryptococcus gattii outbreak since the 1990s, and there is evidence that the outbreak is expanding along the West Coast into California. Here we report a clinical case of a 69-year-old, HIV-negative man from North Carolina who was diagnosed with a fungal brain mass by magnetic resonance imaging (MRI) and pathology. He had traveled to Seattle and Vancouver three years earlier and Costa Rica four months prior to presentation. Phenotypic evidence shows the fungal mass isolated from the patient's brain is C. gattii. In agreement with the phenotypic results, MLST provides genotypic evidence that assigns the infecting organism within in the C. gattii species complex and belonging to the C. deuterogattii VGIIa clade. Whole genome sequencing revealed >99.99% identity to the C. deuterogattii reference strain R265, indicating that the infecting strain is derived from the highly clonal outbreak strains in the PNW. We conclude the patient acquired the C. gattii infection during his travel to region three years prior and the infection was dormant for an extended period of time before causing disease. The patient tested positive for anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies, supporting earlier reports that implicate these autoantibodies as a risk factor a risk factor associated with C. gattii infection.

Disseminated cryptococcosis and anti‐granulocyte‐macrophage colony‐stimulating factor autoantibodies: An underappreciated association

“…6 This intracellular yeast is a ubiquitous, well-recognised opportunistic pathogen for immunocompromised patients, including people living with advanced HIV infection 7 in patients with cryptococcosis to include idiopathic CD4 + lymphocytopenia, GATA 2 mutations, anti-IFNγ autoantibodies and anti-GM-CSF autoantibodies. 8 However, nearly 20% of individuals with this fungal disease do not have an identified immunodeficiency disorder. 9 Cytokines are indispensable proteins for host defence against intracellular pathogens.…”

“…Nowadays, reports of OIs in patients with confirmed anti-GM-CSF autoantibodies with or without PAP have been increasing. 8,15,18,[23][24][25][26][27][28][29][30] Since the first documented case of anti-GM-CSF autoantibodies associated with disseminated cryptococcosis, 15 a total of 27 cases have been reported in the literature (Table 1). The median age at the time of presentation was 41 years (range 20-73 years).…”

“…24 C neoformans is dispersed worldwide and primarily infects immunocompromised patients, whereas C gatti infects otherwise healthy individuals in a more restricted geographical niche, that is western Canada and United States plus tropical and subtropical regions of Oceania, Southeast Asia and South America, where most patients described herein have resided or travelled. 8,31 Therefore, it has been argued that because anti-GM-CSF autoantibodies are a risk factor for disseminated C gatti infection, patients without a known immunodeficiency should be tested for anti-GM-CSF neutralising autoantibodies. 8,24,27 In our review, more than half of the patients had a serum CrAg titre available, with a median titre of 1:192 (range 1:2 to >1:1,100,000).…”

“…8,31 Therefore, it has been argued that because anti-GM-CSF autoantibodies are a risk factor for disseminated C gatti infection, patients without a known immunodeficiency should be tested for anti-GM-CSF neutralising autoantibodies. 8,24,27 In our review, more than half of the patients had a serum CrAg titre available, with a median titre of 1:192 (range 1:2 to >1:1,100,000).…”

A case of Cryptococcus gattii infection in South Carolina: A possible challenge to known endemicity

“…C. neoformans has been shown to have a higher susceptibility to antifungal azole agents than C. gattii and C. neoformans . 4 C. deutergattii has been isolated in Australia, as well as Denmark, Germany, and Japan, with an increase in the number of cases reported after international travel [ 5 ]. Across the species complex, C. deutergattii possesses the largest cell size and the greatest tolerance to high-heat conditions [ 6 ].…”