Blastomyces helicus, an emerging systemic pathogen in western Canada and United States

Ilan S. Schwartz1, Nathan P. Wiederhold1,2, Martin Rofael3, Thomas F. Patterson1,4 & Lynne Sigler5 1San Antonio Center for Medical Mycology, UT Health San Antonio, San Antonio, TX; 2UT Health San Antonio Testing Laboratory, San Antonio, TX; 3Alameda County Medical Center, Oakland, CA; 4South Texas Veterans Health Care System, San Antonio, TX; 5University of Alberta Microfungus Collection and Herbarium, Edmonton, AB, Canada

Introduction Mycology Clinical Pathology Conclusions Blastomyces helicus is a dimorphic fungus first isolated from a Table 1. Clinical details of patients with disease caused by B. helicus infection Blastomyces helicus is an emerging pathogen that causes 1 Medical pulmonary and systemic disease in humans and companion man who died of encephalitis in Alberta, Canada . The patient Case Sample Treatment Outcome Ref was diagnosed with blastomycosis based on histopathology History animals. It differs from B. dermatitidis in the following ways: Alcoholism, • The fungus remains sterile in culture, producing neither and serology results; however, the fungus failed to sporulate 1 CSF, blood None Fatal 1 diabetes conidia or sexual spores. and was atypical for B. dermatitidis. Sigler described the A B C Chronic leukemia, BM, blood, fungus as Emmonsia helica2 since Blastomyces was then 2 *** Fatal • Areas of endemicity appear thus far to include western steroids liver, sputum illegitimate3. Phylogenetic analyses have demonstrated close provinces and states of Canada and the US, respectively 3 Lupus Blood FLUà AMB Survival relatedness to B. dermatitidis4, and taxonomic revision to • Most persons who develop disease are immunocompromised 4 *** Blood, BAL *** *** Blastomyces is anticipated5. • Systemic disease frequently involves fungemia and/or brain Orthotopic liver Blood, pleural 5 VORàAMB Fatal 7 disease and carries a high case-fatality rate D E F transplant fluid • Histopathological findings may include small or variably-sized Here we describe the mycology, and geographic range, 6 None CSF FLU Survival epidemiology and clinical features of disease caused by B. Figure 1. Colonial and microscopic features of B. helicus yeast-like cells; multiple budding; and/or buds in short chains. A. Mold to yeast transition of colonies on potato agar after 13 days at 35oC. 7 HIV BAL FLUàMICAàAMB Fatal 8 helicus infection. B-C. Yeast-like phase at 35°C showing pleomorphic cells in short, branched BAL, pleural chains. D. Mycelial phase at 25°C showing typical helically-coiled hyphae & 8 *** *** *** fluid absence of conidia. E-F. Rudimentary infertile ascocarp with coiled hyphal References appendages and peridial hyphae suggestive of a sexual phase. Abbreviations: AMB: amphotericin B; BAL: bronchoalveolar lavage; BM: bone marrow; CSF: cerebrospinal fluid; FLU: fluconazole; MICA: micafungin; VOR: voriconazole; 1. Sekhon AS, et al. Blastomycosis: report of the first case from Alberta Canada *** indicates data missing Mycopathologia. 1982;79(2):65–9. Methods 2. Sigler L. Emmonsia helica Sigler sp. nov. Index Fungorum. 2015;237(1). We reviewed clinical (human) and veterinary isolates of Geography 3. de Hoog GS, et al. Proposals to conserve Blastomyces Gilchrist & W.R. Stokes against Blastomyces Costantin & Rolland and Ajellomycetaceae against Paracoccidioidaceae Blastomyces and Emmonsia at the University of Alberta (: ). Taxon. 2017;65:1167–9. Microfungus Collection and Herbarium and the UT Health San 4. Schwartz IS, et al. 50 Years of Emmonsia Disease in Humans: The Dramatic Emergence of a Cluster of Novel Fungal Pathogens. PLoS Pathogens. 2015;11(11). Antonio Fungus Testing Laboratory. Isolates were selected for 5. Jiang Y, et al. Phylogeny, ecology and of systemic pathogens in further study based on low B. dermatitidis DNA probe values Ajellomycetaceae (Onygenales): Adiaspiromyces, Blastomyces, Emergomyces, and (Accuprobe, Hologic, Inc.) and/or atypical morphology. Internal A B C D Emmonsiellopsis. Stud Mycol (in review) 6. CDC. Sources of Blastomycosis. transcribed spacer and D1/D2 rRNA regions were sequenced Figure 3. Radiographic findings of an HIV-infected patient (case 7) with B. helicus https://www.cdc.gov/fungal/diseases/blastomycosis/causes.html and analyzed. Epidemiological and clinical data were also infection. A-C. Chest x-ray and CT showing apical cavitation and diffuse micronodules. 7. Kappagoda S, et al. Fatal Emmonsia sp. infection and fungemia after orthotopic liver D. MRI of brain showing a 6-mm ring-enhancing right cerebellar lesion (arrow). transplantation. Emerg Infect Dis. 2017 Feb;23(2):346–9. reviewed. 8. Rofael M, et al. HIV-associated Emmonsia infection in California. Emerg Infect Dis (Accepted)

Results Acknowledgements [email protected] We identified 8 clinical and 5 veterinary isolates of B. helicus. ISS was supported by the Royal College of Physicians and Surgeons of Canada Detweiler Traveling Fellowship. Pertinent mycological features are shown in Fig 1. The geographic origins of isolates are shown in Fig 2. All veterinary A B C [email protected] isolates were from lung tissue. Clinical features of human Figure 4. Pathological findings in disease caused by B. helicus infection. Contact patients are shown in Table 1; selected radiographic and Figure 2. Geographic origin of B. helicus isolates in contrast to the classic endemic A. Yeast-like cells (arrow) in feline lung tissue (courtesy of Dr. N. Haley). [email protected] range of B. dermatitidis (modified from6). Data missing for 1 dog. B-C. Human lung biopsy (case 7) with non-necrotizing granulomas (B, H&E), and yeast- pathological findings are in Fig 3 and 4, respectively. like cells with multiple broad-based buds, some forming chains (arrows) (C, GMS).