Exome Sequencing of a Blastomycosis Case-Control Cohort From Manitoba and Northwestern Ontario, Canada.

BACKGROUND: Blastomycosis is a pulmonary disease caused by Blastomyces spp., a group of pathogenic dimorphic fungi endemic to a number of geographic regions, specifically Manitoba and northwestern Ontario, Canada. Immunosuppression is a major risk factor affecting disease susceptibility, yet host immunity is not well understood. Genetic immunodeficiencies can also influence disease, with variants in IL6, GATA2 and VDBP shown to influence susceptibility. Additional genetic factors in disease susceptibility and severity remain undetected. Our study seeks to identify potential genetic risk factors in a blastomycosis case-control cohort from Manitoba and northwestern Ontario, Canada. METHODS: Exomes from 18 blastomycosis cases and 9 controls were sequenced, variants were identified and filtered for accuracy and quality. We performed candidate gene prioritisation and variant aggregation to identify genetic associations and explored the full exome dataset. RESULTS: Ninety-nine genetic variants in 42 candidate genes were identified in the exome dataset. No variants associated with susceptibility were identified in a single-variant analysis although two non-synonymous variants in TYK2 were enriched among cases suggesting a possible role in susceptibility. Gene-based association analysis found variants in TLR1 enriched in controls (p = 0.024) suggesting a possible protective effect. Gene cluster analysis identified genetic variants in genes of chromatin remodelling, proteasome and intraflagellar transport significantly enriched in cases (false discovery rates < 14%). CONCLUSIONS: The findings in this study show novel associations with blastomycosis susceptibility. A better understanding of host immunity and genetic predisposition to Blastomyces infection can help to inform clinical practice for improved outcomes.

Genomic Epidemiology of Large Blastomycosis Outbreak, Ontario, Canada, 2021.

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.

Effectors and environment modulating rice blast disease: from understanding to effective control.

Rice blast is a highly destructive crop disease that requires the interplay of three essential factors: the virulent blast fungus, the susceptible rice plant, and favorable environmental conditions. Although previous studies have focused mainly on the pathogen and rice, recent research has shed light on the molecular mechanisms by which the blast fungus and environmental conditions regulate host resistance and contribute to blast disease outbreaks. This review summarizes significant achievements in understanding the sophisticated modulation of blast resistance by Magnaporthe oryzae effectors and the dual regulatory mechanisms by which environmental conditions influence rice resistance and virulence of the blast fungus. Furthermore, it emphasizes potential strategies for developing blast-resistant rice varieties to effectively control blast disease.

Detection of Blastomyces gilchristii via metagenomic sequencing in outbreak-associated soils.

Cases of blastomycosis, a serious fungal disease globally rare but endemic to North America, can appear both sporadically and in outbreaks. Tracing these outbreaks to their environment has traditionally used culturing and polymerase chain reaction. Here, we present our method for metagenomic detection of Blastomyces in a 2015 outbreak soil sample from central Wisconsin. By sequencing this sample to multiple depths, we simulated the minimum required depth to detect Blastomyces in this outbreak. Our methods and recommendations can be used to identify the sources of blastomycosis during outbreaks and to learn about the ecology of Blastomyces.

A case series and literature review of blastomycosis during pregnancy amidst the COVID-19 crisis.

Blastomycosis dermatitidis is a rare fungus known for is classic mimicry of pneumonia, lung cancer, and mycobacterial infections. Whilst it is known best for affecting those in the Ohio and Mississippi River basins, several cases have erupted in the Midwest region. Few case reports have focused on blastomycosis and its sequalae in pregnancy. We present a case series of blastomycosis diagnosed during the second and third trimesters in two women amidst the COVID-19 pandemic. Given immunosuppression, complications and treatment can be challenging for clinicians. This case series and discussion hopes to provide future clinicians with the presentation, diagnosis, management, and treatment of this uncommon infection.

Disseminated Blastomycosis in an African American immunocompetent pediatric patient: Lessons learned.

Disseminated blastomycosis can be challenging to diagnose given possible involvement of nearly any extrapulmonary organ system and the limitations of fungal diagnostic testing. Certain racial groups are at increased risk of disseminated fungal infections, even in immunocompetent patients. We describe a case of disseminated blastomycosis with cutaneous involvement in an African American adolescent with delayed diagnosis. Dermatologists can play an important role in the timely diagnosis of this disease entity by performing appropriate cutaneous biopsy techniques and should be involved early in these cases.

Classical Presentation of Disseminated Blastomycosis in a 44-Year-Old Healthy Man 3 Months After Diagnosis of COVID-19.

BACKGROUND During the COVID-19 pandemic, the incidence of opportunistic infections, including fungal infections, has increased. Blastomycosis is caused by inhalation of an environmental fungus, Blastomyces dermatides, which is endemic in parts of the USA and Canada. This case report is of a 44-year-old man from the American Midwest who presented with disseminated blastomycosis infection 3 months following a diagnosis of COVID-19. CASE REPORT Our patient initially presented to an outpatient clinic with mild upper-respiratory symptoms. He tested positive for SARS-CoV-2 via polymerase chain reaction (PCR). Three months later, he presented to our emergency department due to some unresolved COVID-19 symptoms and the development of a widely disseminated, painful rash of 1-week duration. A positive Blastomyces urine enzyme immunoassay was the first indication of his diagnosis, which was followed by the identification of the pathogen via fungal culture from bronchoscopy samples and pathology from lung and skin biopsies. Given the evidence of dissemination, the patient was treated with an intravenous and oral antifungal regimen. He recovered well after completing treatment. CONCLUSIONS The immunocompetent status of patients should not exclude disseminated fungal infections as a differential diagnosis, despite the less frequent manifestations. This is especially important when there is a history of COVID-19, as this may predispose once-healthy individuals to more serious disease processes. This case supports the recent recommendations made by the U.S. Centers for Disease Control and Prevention (CDC) for increased vigilance regarding fungal infections in patients with a history of COVID-19.

Blastomyces dermatitidis Septic Arthritis in a Renal Transplant Patient.

Blastomycosis is a rare endemic fungal infection caused by the dimorphic fungus Blastomyces dermatitidis. It is more likely to occur in persons living in areas of the United States and Canada, which border the Ohio and Mississippi River Valleys and the Great Lakes region. Most infections are localized to the lungs, often presenting as acute or chronic pneumonia. Occasionally, patients progress to develop disseminated disease and extrapulmonary infections. Blastomycosis tends to be misdiagnosed initially at clinical evaluation as it is rare and may resemble other common conditions. We present a case of a 78-year-old immunosuppressed renal transplant patient who was suspected of having gout but eventually was diagnosed with an unusual presentation of septic arthritis of the ankle secondary to blastomycosis.

Disseminated Blastomycosis Mimicking Metastatic Head and Neck Cancer in a 70-year-Old Man.

Blastomycosis is a fungal infection known to mimic many disease processes, including malignancy. A 70-year-old man presented with an enlarging neck mass and, incidentally found on preliminary imaging, a lung mass. The initial biopsy of the neck mass demonstrating cytologic atypia and mitotic figures was suggestive of malignancy. Whole body positron emission tomography (PET)/CT revealed hypermetabolic lesions in multiple sites, including the neck, lung, and soft tissue, raising concern for metastatic disease. Repeat sampling from multiple lesions, however, demonstrated granuloma. Microbiological studies were collected, and Blastomyces dermatitidis was isolated in culture. The diagnosis of disseminated blastomycosis was made, and the patient received antifungal therapy with good response. A high degree of suspicion for blastomycosis in endemic areas is required to ensure patients receive appropriate and timely treatment. Laryngoscope, 133:2237-2239, 2023.

Scrotal abscess as an unusual presentation of blastomycosis.

Blastomyces dermatitidis is an environmental fungus endemic to parts of Eastern North America that notably causes pulmonary infection in humans and other animals with the potential for extrapulmonary spread, particularly in immunocompromised hosts. However, it rarely presents with genitourinary (GU) tract involvement. Herein, we present a unique case of a 37-year-old immunocompetent male with genitourinary blastomycosis with the initial presentation of a scrotal abscess.

Diagnostic delay in pulmonary blastomycosis: a case series reflecting a referral center experience.

PURPOSE: The diagnosis of pulmonary blastomycosis is usually delayed because of its non-specific presentation. We aimed to assess the extent of diagnostic delay in hospitalized patients and detect the step in the diagnostic process that requires the most improvement. METHODS: Adult patients diagnosed with pulmonary blastomycosis during a hospital admission between January 2010 through November 2021 were eligible for inclusion. Patients who did not have pulmonary involvement and who were diagnosed before admission were excluded. Demographics and comorbid conditions, specifics of disease presentation, and interventions were evaluated. The timing of the diagnosis, antifungal treatment, and patient outcomes were noted. Descriptive analytical tests were performed. RESULTS: A total of 43 patients were diagnosed with pulmonary blastomycosis during their admissions. The median age was 47 years, with 13 (30%) females. Of all patients, 29 (67%) had isolated pulmonary infection, while 14 (33%) had disseminated disease, affecting mostly skin and musculoskeletal system. The median duration between the initial symptoms and health care encounters was 4 days, and the time to hospital admission was 9 days. The median duration from the initial symptoms to the diagnosis was 20 days. Forty patients (93%) were treated with empirical antibacterials before a definitive diagnosis was made. In addition, corticosteroid treatment was empirically administered to 15 patients (35%) before the diagnosis, with indications such as suspicion of inflammatory processes or symptom relief. In 38 patients (88%), the first performed fungal diagnostic test was positive. Nineteen patients (44%) required admission to the intensive care unit, and 11 patients (26%) died during their hospital stay. CONCLUSION: There was a delay in diagnosis of patients with pulmonary blastomycosis, largely attributable to the lack of consideration of the etiological agent. Novel approaches to assist providers in recognizing the illness earlier and trigger evaluation are needed.

Blastomyces Induced Otomastoiditis With Local Soft Tissue Invasion: A Case Report.

The aim of this report is to document a very rare case of Blastomycosis dermatitidis mastoiditis with extension into the retromastoid soft tissue and surrounding muscle. Blastomycosis dermatitidis is a dimorphic fungus of endemic areas which classically infiltrates the lungs; however, dissemination presenting as otomastoiditis is exceedingly rare. The patient was an immunocompetent 27-year-old male with no significant preexisting health conditions. He had significant work exposure to dust and soil and was referred to our department for evaluation of otalgia with headaches, hearing loss, and intermittent facial paralysis. Initially, the extent of the infection was unknown. Based on extensive disease on magnetic resonance imaging, the patient was scheduled for urgent tympanoplasty and mastoidectomy. Postoperative treatment with itraconazole resolved any further manifestations and halted further soft tissue invasion. It is important to consider uncommon fungal infections in the workup of persistent otalgia, especially when presenting with facial paralysis and a history of environmental exposure to soil and dust. This type of infection should be considered regardless of immunodeficiency status. Early detection may prevent hearing loss and local invasion into surrounding structures.

Pulmonary Blastomycosis: A Rare Cause of Acute Chest Syndrome and Prolonged Fevers in a Pediatric Patient With Sickle Cell Disease.

Blastomyces is a fungus found in the soil of regions of North America including the Mississippi and Ohio River Valleys. It can be inhaled into the lungs and cause pneumonia and disseminated disease. Although blastomycosis is not widely reported in the sickle cell literature, sickle cell patients may be at increased risk of complications from blastomycosis pneumonia due to their immune compromise and risk of developing acute chest syndrome. We describe the case of a 13-year-old female with homozygous sickle cell disease who presented with pneumonia and acute chest syndrome and was found to have pulmonary blastomycosis.

Blastomycosis in 64 Wisconsin Children: Unanticipated Infection Risk and Severity in Urban Residents.

BACKGROUND: Blastomycosis, an endemic mycosis of immunocompetent individuals, is typically seen after exposure to waterways within rural wooded regions. It is not considered a disease of urban environments. Infection can be solely pneumonic or disseminate to skin, bone or central nervous system. Unknown factors influence disease acquisition and severity in children. METHODS: We analyzed acquisition risks and disease characteristics of blastomycosis in children seen at a tertiary care center from 1998 to 2018 to identify potential exposure sources, measure disease severity and assess the effect of race upon disease severity. RESULTS: Of 64 infected children, mean age was 12.9 years, with median time to diagnosis 38.5 days. About 72% were male, 38% resided in urban counties and 50% had typical environmental exposure. Isolated pulmonary infection occurred in 33 (52%). The remainder had evidence of dissemination to skin (N = 13), bone (N = 16; 7 clinically silent) and cranium (N = 7; 3 clinically silent). Infection was moderate/severe in 19 (30%). Two children (3%) died. About 79% of children with moderate/severe disease (P = 0.008) and 71% of urban children (P = 0.007) lacked typical environmental exposure. Comparing children from urban counties to other residences, 63% versus 5% were black (P < 0.001) and 71% versus 35% developed extrapulmonary dissemination (P = 0.006). Moderate/severe disease was seen in 7/17 (42%) black children but only 12/47 (26%) children of other races (P = 0.23). CONCLUSIONS: Blastomycosis, can be endemic in urban children in the absence of typical exposure history, have frequent, sometimes clinically silent, extrapulmonary dissemination and possibly produces more severe disease in black children.

Blastomycosis in the Capital District of New York State: A Newly Identified Emerging Endemic Area.

BACKGROUND: The Centers for Disease Control and Prevention and New York State Department of Health recently identified the Capital District of New York (CDNY) as an emerging endemic area for blastomycosis. However, no clinical or epidemiological description of blastomycosis in the CDNY has been published. METHODS: We performed a retrospective analysis of blastomycosis cases at Albany Medical Center (AMC) and Albany Stratton Veterans Affairs Medical Center (VAMC) from January 1, 2000, through June 1, 2019. Patients were identified via an institution-approved informatics system at the hospital's microbiology laboratory. RESULTS: We identified 20 patients diagnosed with blastomycosis over the past 2 decades. There was a nearly 9-fold increase in the annual number of cases in 2016-2019 compared with 2000-2015. The majority of patients resided in the CDNY (90%), and 65% lived within the Mohawk River valley. Most cases (85%) were assumed to be malignancies or non-mycotic infections prior to diagnosis, with median time between presentation and diagnosis of 53 days. CONCLUSIONS: Our data support recent reports that blastomycosis is an emerging disease in the CDNY. Most patients were misdiagnosed as malignancy or non-mycotic infection, which led to treatment delays.