Human Blastomycosis in South Africa Caused by<i>Blastomyces percursus</i>and<i>Blastomyces emzantsi</i>sp. nov., 1967 to 2014

Abstract

We reevaluated 20 cases of blastomycosis diagnosed in South Africa between 1967 and 2014, with <i>Blastomyces dermatitidis</i> considered to be the etiological agent, in light of newly described species and the use of more advanced technologies. In addition to histopathological and/or culture-based methods, all 20 isolates were phenotypically and genotypically characterized, including multilocus typing of five genes and whole-genome sequencing. Antifungal susceptibility testing was performed as outlined by Clinical and Laboratory Standards Institute documents 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 <i>B. dermatitidis</i>, <i>Blastomyces gilchristii</i>, and <i>Blastomyces parvus</i> The first group (<i>n</i> = 12) corresponded to the recently described species <i>Blastomyces percursus</i>, and the other (<i>n</i> = 8) is described here as <i>Blastomyces emzantsi</i> sp. nov. Both species exhibited incomplete conversion to the yeast phase at 37°C and were heterothallic for mating types. All eight <i>B. emzantsi</i> 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 <i>BAD-1</i> gene. Extrapulmonary (skin or bone) disease, probably resulting from hematogenous spread from a primary lung infection, was more common than pulmonary disease alone. Voriconazole, posaconazole, itraconazole, amphotericin B, and micafungin had the most potent <i>in vitro</i> activity. Over the 5 decades, South African cases of blastomycosis were caused by species that are distinct from <i>B. dermatitidis</i> Increasing clinical awareness and access to simple rapid diagnostics may improve the diagnosis of blastomycosis in resource-limited countries.