Assessment of the Clinical Relevance of Fungal Genotype in Blastomycosis Infections

Abstract

While blastomycosis is a relatively rare disease throughout the United States at an annual incidence of 1-2/100,000 in humans, it is hyperendemic to Wisconsin. Some counties have reported an annual incidence as high as 41/100,000 in humans and 1,420/100,000 in dogs. The Midwestern region of the United States also has among the highest mortality rates associated with the disease in the country at 43.8% as opposed to 1.7% mortality in the Northeast region where it was initially discovered. Blastomycosis is caused by inhalation of conidia which are produced by soil-inhabiting fungi of the genus Blastomyces. Since 1896, it was believed that all cases of blastomycosis were caused by inhalation or inoculation with the species Blastomyces dermatitidis. However, in 2013, multi-locus sequence typing revealed another species was involved in these infections named “Blastomyces gilchristii.”

The research question of this thesis was to assess whether there was any clinical relevance to this recent species distinction. I collaborated with the Marshfield Clinic Research Institute and the University of Wisconsin Madison to establish a database of 141 patients from Wisconsin from 2008-2016 for which a clinical isolate was available to be species typed through a single-nucleotide polymorphism in the ITS2 region of the fungal genome. Species data were then compared to clinical features associated with blastomycosis abstracted from medical records to determine if a new diagnostic assay would be valuable for clinicians.

Significant differences in distributions were discovered among age groups (p<0.01), clinical presentation (p<0.001), and physician specialty seen (p<0.001) between patients infected B. gilchristii and B. dermatitidis. No significant differences were found in the non-invasive diagnostic test’s ability to detect either pathogen. Additionally, evidence was illuminated to support the use of therapeutic drug monitoring throughout the course of treatment for patients infected with either pathogen. These data may help inform new Infectious Diseases Society of America guidelines for the treatment and diagnosis of blastomycosis, which have not been updated since the recent species distinction.