Using phylogenomic analysis, we provide genomic epidemiology analysis of a large blastomycosis outbreak in Ontario, Canada, caused by Blastomyces gilchristii. The outbreak occurred in a locale where blastomycosis is rarely diagnosed, signaling a possible shift in geographically associated incidence patterns. Results elucidated fungal population genetic structure, enhancing understanding of the outbreak.

Blastomycoses dermatitidis is a dimorphic fungus that can cause disseminated blastomycosis with varying clinical manifestations and multiorgan involvement. While blastomycosis commonly causes pulmonary disease, extrapulmonary spread can result in skin, bone, and central nervous system involvement. Cutaneous blastomycosis can present as pustular lesions that evolve into ulcerative or verrucous plaques. We present a case of disseminated blastomycosis in an immunocompetent patient with both pulmonary and cutaneous features. The patient developed hypoxic respiratory failure and was subsequently diagnosed with disseminated blastomycosis after undergoing bronchoscopy with bronchial washing. He was found to have ulcerative nasal lesions as part of his disseminated disease. He was successfully treated with amphotericin B and ultimately discharged from the hospital.

We describe a recent case of Coccidioides bioprosthetic aortic valve infective endocarditis successfully managed at our institution. This led us to perform a literature review of endemic fungal infective endocarditis in the United States caused by Coccidioides, Blastomyces, and Histoplasma. Symptoms preceded infective endocarditis diagnosis by several months. Patients with Coccidioides and Blastomyces infective endocarditis were younger with fewer comorbid conditions. Valvular involvement was relatively uncommon in Blastomyces infective endocarditis (27%). Fungemia was noted in patients with infective endocarditis due to Histoplasma (30%) and Coccidioides (18%). Mortality rates for infective endocarditis were high (Histoplasma, 46%; Coccidioides, 58%; Blastomyces, 80%); infective endocarditis was commonly diagnosed post-mortem (Coccidioides, 58%; Blastomyces, 89%). Most surviving patients with infective endocarditis (Histoplasma, 79%; Coccidioides, 80%) underwent valve surgery along with prolonged antifungal therapy. The two surviving patients with Blastomyces infective endocarditis received antifungal therapy without surgery.

Objective: To determine if host genetics may be a risk factor for severe blastomycosis.Design: A cohort of patients who had contracted blastomycosis underwent targeted SNP (single nucleotide polymorphism) genotyping. The genetics of these patients were compared to a set of age and gender-matched controls and between patients with severe versus mild to moderate blastomycosis.Setting: The Marshfield Clinic Health System in central and northern WisconsinParticipants: Patients with a diagnosis of blastomycosis prior to 2017 were contacted for enrollment in this study. A phone hotline was also set up to allow interested participants from outside the Marshfield Clinic Health System to request enrollment.Methods: SNP frequency was assessed for significant differences between the patient cohort and controls and between patients with severe versus mild to moderate blastomycosis. We also tested the effect of Blastomyces species identified in clinical isolates on disease symptoms and severity.Results: No significant differences were found in SNP frequency between cases and controls or between those with severe or mild to moderate blastomycosis. We did detect significant differences in symptom frequency and disease severity by Blastomyces species.Conclusions: Our study did not identify any genetic risk factors for blastomycosis. Instead, the species of Blastomyces causing the infection had a significant effect on disease severity.

UNASSIGNED: Geographically endemic fungi can cause significant disease among solid organ transplant (SOT) recipients. We provide an update on the epidemiology, clinical presentation, and outcomes of 5 endemic mycoses in SOT recipients.
UNASSIGNED: Multiple databases were reviewed from inception through May 2023 using key words for endemic fungi (eg, coccidioidomycosis or Coccidioides, histoplasmosis or Histoplasma, etc). We included adult SOT recipients and publications in English or with English translation.
UNASSIGNED: Among 16 cohort studies that reported on blastomycosis (n = 3), coccidioidomycosis (n = 5), histoplasmosis (n = 4), and various endemic mycoses (n = 4), the incidence rates varied, as follows: coccidioidomycosis, 1.2%-5.8%; blastomycosis, 0.14%-0.99%; and histoplasmosis, 0.4%-1.1%. There were 204 reports describing 268 unique cases of endemic mycoses, including 172 histoplasmosis, 31 blastomycosis, 34 coccidioidomycosis, 6 paracoccidioidomycosis, and 25 talaromycosis cases. The majority of patients were male (176 of 261 [67.4%]). Transplanted allografts were mostly kidney (192 of 268 [71.6%]), followed by liver (n = 39 [14.6%]), heart (n = 18 [6.7%]), lung (n = 13 [4.9%]), and combined kidney-liver and kidney-pancreas (n = 6 [2.7%]). In all 5 endemic mycoses, most patients presented with fever (162 of 232 [69.8%]) and disseminated disease (179 of 268 [66.8%]). Cytopenias were frequently reported for histoplasmosis (71 of 91 [78.0%]), coccidioidomycosis (8 of 11 [72.7%]) and talaromycosis (7 of 8 [87.5%]). Graft loss was reported in 12 of 136 patients (8.8%). Death from all-causes was reported in 71 of 267 (26.6%); half of the deaths (n = 34 [50%]) were related to the underlying mycoses.
UNASSIGNED: Endemic mycoses commonly present with fever, cytopenias and disseminated disease in SOT recipients. There is a relatively high all-cause mortality rate, including many deaths that were attributed to endemic mycoses.

Blastomyces dermatitidis is a dimorphic fungus that can range from mild to severe disease presentation, including the acute respiratory distress syndrome (ARDS) based on the individual\'s immunity. Acute respiratory distress syndrome is an uncommon presentation having an incidence of about 10% to 15% but has a high mortality exceeding 90%. This is a case of a 50-year-old female with past medical history of asthma and type 2 diabetes mellitus who presented to the pulmonology clinic with worsening dyspnea for the last 2 months. She also had a lesion in the left lower back, which was draining purulent fluid. Chest radiographs showed bilateral infiltrates and was started empirically on vancomycin and piperacillin-tazobactam. Bronchoalveolar lavage was done and the cultures grew B dermatitidis. The patient was moved to a higher level of care and given amphotericin B. Unfortunately, the patient experienced septic shock, which later deteriorated into cardiac arrest, ultimately leading to their passing. The importance of early diagnosis of blastomycosis and timely treatment has been emphasized in this case report.

The epidemiology of blastomycosis in Vermont, USA, is poorly understood. Using insurance claims data, we estimated the mean annual blastomycosis incidence was 1.8 patients/100,000 persons during 2011-2020. Incidence and disease severity were highest in north-central counties. Our findings highlight a need for improved clinical awareness and expanded surveillance.

Histoplasma and Blastomyces antigen detection assays are commonly used diagnostic tools. However, a high level of cross-reactivity between these antigens prevents definitive pathogen identification by these assays alone. Retrospective analysis of 3,529 patients with Histoplasma and Blastomyces antigen testing performed on the same serum sample yielded an overall percent agreement of 99.3% (3,506 of 3,529; kappa: 0.859) between the two assays, suggesting that use of a single assay to detect both antigens may be an alternative diagnostic approach. We assessed performance of the Gotham BioTech Blastomyces antigen (GBA) enzyme immunoassay (EIA) (Portland, Maine) for detection of Blastomyces and Histoplasma antigens in serum. Comparison to the MiraVista Diagnostics Blastomyces (MVB) EIA showed 100% positive (24 of 24), negative (57 of 57), and overall (81 of 81) percent agreement. Additionally, 171 sera were used to compare the GBA EIA to the MiraVista Diagnostics Histoplasma (MVH) EIA, which showed 91.3% (63 of 69), 98% (100 of 102), and 95.3% (163 of 171) positive, negative, and overall percent agreement, respectively. Among eight patients with discordant GBA/MVH EIA results, seven had additional fungal testing performed, and results suggested that the MVH and GBA results were inaccurate for two and five samples, respectively. Overall, this study suggests that the GBA EIA has a high level of agreement with both of the commonly used, individual Blastomyces and Histoplasma antigen EIAs. By taking advantage of the high level of cross-reactivity between Blastomyces and Histoplasma antigen EIAs, utilization of a single antigen detection assay for these fungi provides an opportunity to optimize test utilization and decrease patient cost while maintaining a high level of diagnostic accuracy.

We performed in vitro antifungal susceptibility testing of manogepix against the yeast phase of 78 Emergomyces africanus, 2 Emergomyces pasteurianus, and 5 Blastomyces emzantsi isolates using a reference broth microdilution method following Clinical and Laboratory Standards Institute recommendations. All three pathogens had low minimum inhibitory concentrations ranging from <0.0005 to 0.008 mg/L. Manogepix should be investigated in animal models and potentially in future human clinical trials for endemic mycoses.

Human lung mycobiome studies typically sample bronchoalveolar lavage or sputum, potentially overlooking fungi embedded in tissues. Employing ultra-frozen lung tissues from biorepositories, we obtained fungal ribosomal RNA ITS2 sequences from 199 small mammals across 39 species. We documented diverse fungi, including common environmental fungi such as Penicillium and Aspergillus, associates of the human mycobiome such as Malassezia and Candida, and others specifically adapted for lungs (Coccidioides, Blastomyces, and Pneumocystis). Pneumocystis sequences were detected in 83% of the samples and generally exhibited phylogenetic congruence with hosts. Among sequences from diverse opportunistic pathogens in the Onygenales, species of Coccidioides occurred in 12% of samples and species of Blastomyces in 85% of samples. Coccidioides sequences occurred in 14 mammalian species. The presence of neither Coccidioides nor Aspergillus fumigatus correlated with substantial shifts in the overall mycobiome, although there was some indication that fungal communities might be influenced by high levels of A. fumigatus. Although members of the Onygenales were common in lung samples (92%), they are not common in environmental surveys. Our results indicate that Pneumocystis and certain Onygenales are common commensal members of the lung mycobiome. These results provide new insights into the biology of lung-inhabiting fungi and flag small mammals as potential reservoirs for emerging fungal pathogens.