Human Blastomycosis in South Africa Caused byBlastomyces percursusandBlastomyces emzantsisp. nov., 1967 to 2014

Abstract

We reevaluated 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 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 B. dermatitidis, Blastomyces gilchristii, and Blastomyces parvus. The first group (n = 12) corresponded to the recently described species 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 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 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 the diagnosis of blastomycosis in resource-limited countries.

Development of a duplex real-time PCR assay for the differentiation ofBlastomyces dermatitidisandB. gilchristiiand a retrospective study of blastomycosis in New York (2005-2019)

“…BAD1 gene and its promoter have been extensively used for the differentiation of Blastomyces species using restriction fragment length polymorphism (RFLP), PCR and real-time PCR assays (9, 19, 23). The polymorphism in BAD1 gene and markedly different sizes including 363-bp in B. dermatitidis , 663-bp in B. gilchrstii and absence of this gene in African isolates of Blastomyces (8, 9, 19, 20), proved this target as highly specific for the identification of B. dermatitidis , and B. gilchristii in the present investigation.…”

“…are thermally dimorphic fungi, exist as a mold form at ambient temperature in the environment but convert to the pathogenic yeast form in vitro at 37°C or when susceptible mammalian host inhales the conidia of the mold form. The yeast form of these pathogens can be microscopically differentiated with B. dermatitidis and B. gilchrtstii producing abundant large (8-20 mm) broad-based budding yeasts; B. percursus producing large yeast-like cells from fragmented swollen hyphal cells and B. helicus producing variably shaped yeast cells (4 to 5 μm) in short chain, while thin walled giant cells and occasional broad-based budding yeast like-cells are seen in B. parva and B. silverae (8). The distinct yeast morphology might be helpful in the species differentiation from the primary specimens; but this approach would require significant mycology expertise, which is not always available in diagnostic laboratories.…”

Epidemiology of fungal diseases in Africa: A review of diagnostic drivers

“…Blastomyces dermatitidis , B. percursus , and B. emzantsi are the causative agents of blastomycosis [ 71 ]. Extrapulmonary (skin or bone) disease, probably resulting from haematogenous spread from a primary lung infection, is the commonest presentation among the patients who were infected with these organisms.…”

Diagnosis of Pulmonary Infections Due to Endemic Fungi

“…mNGS has been used to diagnosis blastomycosis from a transbronchial biopsy and BAL fluid but diagnostic performance characteristics are unknown [ 89 ]. Whole genome sequencing may have a role for identification, but experience is limited at this time [ 90 ].…”