Human blastomycosis in South Africa caused by Blastomyces percursus and Blastomyces africanus sp. nov., 1967 – 2014

We re-evaluated 20 cases of blastomycosis diagnosed in South Africa between 1967 and 2014, with Blastomyces dermatitidis considered to be the etiological agent, in light of newly-described species and use of more advanced technologies. In addition to histopathological and/or culture-based methods, all 20 isolates were phenotypically and genotypically characterised, including multilocus typing of five genes and whole genome sequencing. Antifungal susceptibility testing was performed as outlined in Clinical and Laboratory Standards Institute M27-A3 and M38-A2. We merged laboratory and corresponding clinical case data, where available. Morphological characteristics and phylogenetic analyses of five-gene and whole-genome sequences revealed two groups, both of which were closely related to but distinct from B. dermatitidis, Blastomyces gilchristii and Blastomyces parvus. The first group (n=12) corresponded to the recently-described Blastomyces percursus and the other (n=8) is described here as Blastomyces emzantsi sp. nov. Both species exhibited incomplete conversion to the yeast phase at 37°C and were heterothallic for mating types. All eight B. emzantsi isolates belonged to the α mating type. Whole genome sequencing confirmed distinct species identities, as well as the absence of a full orthologue of the BAD-1 gene. Extrapulmonary (skin or bone) disease, probably resulting from hematogeous spread from a primary lung infection, was more common than pulmonary disease alone. Voriconazole, posaconazole, itraconazole, amphotericin B and micafungin had the most potent in vitro activity. Over the 5 decades, South African cases of blastomycosis were caused by species that are distinct from B. dermatitidis. Increasing clinical awareness and access to simple rapid diagnostics may improve diagnosis of blastomycosis in resource-limited countries.