Search

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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., (© 2024 The Author(s). Mycoses published by Wiley‐VCH GmbH.)

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.

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

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., (© 2023 International Federation of Gynecology and Obstetrics.)

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.

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 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.

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

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.

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Blastomycosis is a fungal infectious disease prevalent in North America and rarely reported in Asia. Misdiagnosis of malignancy and other infectious diseases were reported., Case Presentation: A 24-years-old male patient presented with chronic non-productive cough of 4 months duration. He had been diagnosed with Mycobacterium tuberculosis infection and lung malignancy elsewhere and presented to us as the symptoms persisted. We offered him the biopsy under endobronchial ultrasound-guide sheath-transbronchial lung biopsy and sample specimen were sent for next generation sequencing analysis, returned as Blastomyces Dermatitidis infection. The patient was treated by itraconazole for 6 months, his symptoms decreased significantly and the CT scan showed resolution of the lesion., Conclusion: We shared a case of blastomycosis with delayed and difficult diagnosis and reviewed the knowledge regarding differential diagnosis and next generation sequencing technologies.

Published case fatality in blastomycosis patients ranges between 4% and 78%. This study aimed to assess mortality associated with blastomycosis and identify its associated risk factors. We conducted a systematic review of publications related to Blastomyces dermatitidis available in PubMed and Scopus databases. Studies that reported data on blastomycosis mortality and that were published from inception through February 2018 were assessed and included in the analysis. Using the R meta package, a random-effect model meta-analysis was used to calculate pooled and stratified estimates of case-fatality proportions and risk ratios. Of 1553 publications, we included 20 studies reporting on a total of 2820 cases of blastomycosis between 1970 and 2014 and three case series reports with 10, 21, and 36 patients. The mean or median ages ranged from 28 to 59 years. Mortality was defined as attributable mortality caused by blastomycosis in 13 studies. Among 14 studies with a standard error ≤0.05, the overall pooled mortality was 6.6% (95% confidence interval [CI], 4.9-8.2) with 57% heterogeneity. The mortality rate was 37% (95% CI, 23-51) in immunocompromised patients and 75% (95% CI, 53-96) in patients who developed an acute respiratory distress syndrome (ARDS) (n = 3 studies each). ARDS was the only identified risk factor in general patients (risk ratio = 10.2). The overall mortality was significantly higher in studies involving immunocompromised patients and ARDS patients. Our analysis showed considerable heterogeneity among studies. Inconsistent mortality definitions may have contributed to the observed heterogeneity. Further research is needed to assess potential risk factors for mortality., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

We report a case of a 41-year-old male who presented to our institution with a large groin mass. CT, MRI and PET imaging was performed and was concerning for a soft tissue abscess likely originating in the lumbar spine. Differential considerations included infection, with atypical infections such as tuberculosis strongly considered. Biopsy revealed fungal elements preliminarily reported as consistent with Cryptococcus neoformans but later revealed to be Blastomyces dermatitidis. The patient responded positively following the introduction of appropriate treatment. This case illustrates the imaging similarities between spinal blastomycosis, spinal tuberculosis, and other fungal infections as well as the need for biopsy to differentiate.

This review article focuses on the mechanisms underlying temperature adaptation and virulence of the etiologic agents of blastomycosis, Blastomyces dermatitidis , Blastomyces gilchristii , and Blastomyces percursus . In response to temperature, Blastomyces undergoes a reversible morphologic switch between hyphae and yeast known as the phase transition. The conversion to yeast for Blastomyces and related thermally dimorphic fungi is essential for virulence. In the yeast phase, Blastomyces upregulates the essential virulence factor, BAD1, which promotes attachment to host cells, impairs activation of immune cells, and blunts cytokine release. Blastomyces yeast also secrete dipeptidyl-peptidase IVA (DPPIVA), a serine protease that blunts the action of cytokines released from host immune cells. In vivo transcriptional profiling of Blastomyces yeast has uncovered genes such as PRA1 and ZRT1 involved in zinc scavenging that contribute to virulence during murine pulmonary infection. The discovery and characterization of genes important for virulence has led to advances at the bedside regarding novel diagnostics, vaccine development, and new targets for drug discovery.

Based on epidemiologic data during a blastomycosis outbreak, exposure within the home was suspected for two case patients that resided together. Soil and air samples were collected from the basement of their residence. Samples were tested for Blastomyces by culture and polymerase chain reaction (PCR) to compare with an available clinical isolate. An air sample from the basement of the residence was PCR positive for Blastomyces. Sequence data from the air sample and the outbreak clinical isolate were identified as different Blastomyces spp. Despite this, our findings suggest that the basement was suitable for the growth of Blastomyces and airborne organism was circulating., (© The Author(s) 2018. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Urinary tract blastomycosis is an uncommon manifestation of disseminated Blastomyces infection. Here, we report a 50-year-old male with common variable immunodeficiency who presented with urinary symptoms and a renal mass concerning for a kidney neoplasm. Urine cytology revealed typical broad-based budding yeasts with thick-walled refractile capsules, leading to diagnosis of urinary tract blastomycosis. In this case, urine cultures were negative, and urine cytology was the main method of diagnosis of blastomycosis. Thus, urine cytology represents a rapid and reliable method of diagnosing blastomycosis, which in the current case led to prompt treatment of this potentially life threatening infection., (© 2018 Wiley Periodicals, Inc.)

Background: Blastomycosis is an endemic mycosis in North America that is caused by the dimorphic fungus Blastomyces dermatitidis. The illness is a systemic disease with a wide variety of pulmonary and extra-pulmonary manifestations. The initial presentation of blastomycosis may easily be mistaken for other infectious or non-infectious etiologies., Case Presentation: We present the case of a 52-year-old African-American male and former smoker that presented to his primary care provider with a 2-week history of non-productive cough, night sweats and weight loss. Initially diagnosed with primary lung malignancy, the patient was subsequently found to have pulmonary blastomycosis mimicking lung cancer. The patient underwent a successful course of treatment with posaconazole., Conclusions: Chronic blastomycosis can present with clinical and radiographic features indistinguishable from thoracic malignancies. There is no clinical syndrome specific for blastomycosis, thus a high degree of suspicion is required for early diagnosis. In this case report, we review recent evidence in radiographic features, diagnostic considerations and treatment of the disease.

A 20-y-old female llama ( Lama glama) was euthanized after a history of chronic dyspnea and osteoarthritis. At autopsy, the lungs were covered by clear gelatinous material and expanded by firm, variably discrete, tan-white nodules up to 8 cm diameter containing tan-white, viscous material. The tracheobronchial lymph nodes were firm and enlarged up to 6 × 4 × 3 cm; the thoracic aorta and carotid arteries were lined by hard, tan-white, mineralized intimal plaques. Histologic examination of lung revealed numerous 10-20 μm diameter yeasts with clear 1-2 μm thick double-contoured walls, central basophilic nuclei, and frequent broad-based budding, consistent with Blastomyces dermatitidis. DNA sequencing confirmed the diagnosis. B. dermatitidis should be considered in the differential diagnosis of pulmonary disease in llamas.

Endemic mycoses represent a growing public health challenge in North America. We describe the epidemiology of 1,392 microbiology laboratory-confirmed cases of blastomycosis, histoplasmosis, and coccidioidomycosis in Ontario during 1990-2015. Blastomycosis was the most common infection (1,092 cases; incidence of 0.41 cases/100,000 population), followed by histoplasmosis (211 cases) and coccidioidomycosis (89 cases). Incidence of blastomycosis increased from 1995 to 2001 and has remained elevated, especially in the northwest region, incorporating several localized hotspots where disease incidence (10.9 cases/100,000 population) is 12.6 times greater than in any other region of the province. This retrospective study substantially increases the number of known endemic fungal infections reported in Canada, confirms Ontario as an important region of endemicity for blastomycosis and histoplasmosis, and provides an epidemiologic baseline for future disease surveillance. Clinicians should include blastomycosis and histoplasmosis in the differential diagnosis of antibiotic-refractory pneumonia in patients traveling to or residing in Ontario.

Invasive fungal infections are a feared complication in kidney transplant recipients (KTRs). Here we present the University of Wisconsin experience with 5 invasive fungal infections-aspergillosis, cryptococcosis, histoplasmosis, blastomycosis, and coccidioidomycosis-in KTRs transplanted between 01/01/1994 and 06/30/2014. During this period, there were 128 cases of fungal infections; aspergillosis was the most common (72), followed by cryptococcosis (29), histoplasmosis (14), blastomycosis (10), and coccidioidomycosis (3). The mean interval from transplant to fungal infection was 3.19 ± 3.58 years (range 5 days-15.8 years). By 6 months postinfection, there were 53 (41%) graft failures and 24 (19%) deaths. Graft failure occurred in 46%, 38%, 21%, 40%, and 67% of patients with aspergillosis, cryptococcosis, histoplasmosis, blastomycosis, and coccidioidomycosis, respectively. Anti-thymocyte globulin (ATG) induction (HR, 1.49; 95% CI, 1.03-2.16; P = .04), diabetes (HR, 1.53; 95% CI, 1.05-2.21; P = .03), and age (HR, 1.47; 95% CI, 1.27-1.70; P ≤ .001) were associated with an increased risk for infection in univariate analysis. Multivariate adjustment retained ATG induction and older age. A large proportion of kidney transplant recipients with invasive fungal infections suffer graft failure within 3 years. Preventive, therapeutic, and monitoring strategies are needed to improve graft and patient outcomes., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Blastomyces dermatitidis is a human fungal pathogen of the lung that can lead to disseminated disease in healthy and immunocompromised individuals. Genetic analysis of this fungus is hampered by the relative inefficiency of traditional recombination-based gene-targeting approaches. Here, we demonstrate the feasibility of applying CRISPR/Cas9-mediated gene editing to Blastomyces , including to simultaneously target multiple genes. We created targeting plasmid vectors expressing Cas9 and either one or two single guide RNAs and introduced these plasmids into Blastomyces via Agrobacterium gene transfer. We succeeded in disrupting several fungal genes, including PRA1 and ZRT1 , which are involved in scavenging and uptake of zinc from the extracellular environment. Single-gene-targeting efficiencies varied by locus (median, 60% across four loci) but were approximately 100-fold greater than traditional methods of Blastomyces gene disruption. Simultaneous dual-gene targeting proceeded with efficiencies similar to those of single-gene-targeting frequencies for the respective targets. CRISPR/Cas9 disruption of PRA1 or ZRT1 had a variable impact on growth under zinc-limiting conditions, showing reduced growth at early time points in low-passage-number cultures and growth similar to wild-type levels by later passage. Individual impairment of PRA1 or ZRT1 resulted in a reduction of the fungal burden in a mouse model of Blastomyces infection by a factor of ~1 log (range, up to 3 logs), and combined disruption of both genes had no additional impact on the fungal burden. These results underscore the utility of CRISPR/Cas9 for efficient gene disruption in dimorphic fungi and reveal a role for zinc metabolism in Blastomyces fitness in vivo IMPORTANCE Blastomyces is a human fungal pathogen that can cause serious, even fatal, lung infections. Genetic analysis of this fungus is possible but inefficient. We applied a recently developed gene editing technology, CRISPR/Cas9, to dramatically improve the efficiency with which gene disruptions are introduced into Blastomyces We used this system to disrupt genes involved in zinc uptake and found that this reduced the fitness of the fungus upon infection., (Copyright © 2018 Kujoth et al.)

Blastomyces dermatitidis is a thermally dimorphic fungus that is capable of causing pulmonary and extra-pulmonary disease, including infections of the central nervous system (CNS). Diagnosis of CNS blastomycosis with non-invasive testing can be difficult, and a surgical biopsy may ultimately be required for microbiological and/or histopathological confirmation. A case of B. dermatitidis meningitis is presented where the diagnosis was made by testing cerebrospinal fluid (CSF) using the MVista® Blastomyces Quantitative Antigen Enzyme Immunoassay test. The utility of performing this test on CSF for diagnosis of CNS mass lesions/abscesses caused by B. dermatitidis in the absence of associated meningitis remains unclear. Cross reaction of the Blastomyces antigen test with other dimorphic fungi is a concern, necessitating that positive test results are interpreted in the context of the patient's exposure and travel history., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Blastomycosis elicits a pyogranulomatous inflammatory response that involves a prominent recruitment of neutrophils to the site of infection. Although neutrophils are efficiently recruited to the site of infection, this event is paradoxically coupled with the host's inability to control infection by Blastomyces dermatitidis, the causative agent. The mechanisms underlying this characteristic pyogranulomatous response and inability of neutrophils to kill the yeast are poorly understood. We recently reported that the fungal protease dipeptidyl peptidase IVA (DppIVA) promotes B. dermatitidis virulence by cleaving a dipeptide from the N-terminus of C-C chemokines and granulocyte/macrophage-colony stimulating factor, thereby inactivating them. Herein, we present evidence that DppIVA can also truncate the N-terminus of members of the ELR + CXC chemokine family, which are known to modulate neutrophil function. We show that the DppIVA cleaved form of human (h) CXCL-2, for example, hCXCL-2 (3-73), is a more potent neutrophil chemoattractant than its intact counterpart, but hCXCL-2 (3-73) is conversely impaired in its ability to prime the reactive oxygen species response of neutrophils. Thus, DppIVA action on ELR + CXC chemokines may promote the pyogranulomatous response that is typical of blastomycosis, while also explaining the inability of neutrophils to control infection., (© 2017 John Wiley & Sons Ltd.)

Although uncommon in children, fungal infections of the central nervous system can be devastating and difficult to treat. A better understanding of basic mycologic, immunologic, and pharmacologic processes has led to important advances in the diagnosis and management of these diseases, but their mortality rates remain unacceptably high. In this focused review, we examine the epidemiology and clinical features of the most common fungal pathogens of the central nervous system in children and explore recent advances in diagnosis and antifungal therapy., (© The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Fungal infections have an important role in organ transplant recipients, and in some cases can be lethal. Blastomycosis is rare in kidney transplantation. We present a case of cutaneous blastomycosis in a kidney transplant recipient in Tunisia, a country outside the known endemic countries. This case, with the very uncommon and unexpected diagnosis of blastomycosis, demonstrates the diversity of infections in transplant recipients and reflects the importance of histologic and serologic tests in the immunocompromised patient., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Our understanding of persistence and plasticity of IL-17A+ memory T cells is clouded by conflicting results in models analyzing T helper 17 cells. We studied memory IL-17A+ CD8+ T-cell (Tc17) homeostasis, persistence and plasticity during fungal vaccine immunity. We report that vaccine-induced memory Tc17 cells persist with high fidelity to the type 17 phenotype. Tc17 cells persisted durably for a year as functional IL-17A+ memory cells without converting to IFNγ+ (Tc1) cells, although they produced multiple type I cytokines in the absence of residual vaccine antigen. Memory Tc17 cells were canonical CD8+ T cells with phenotypic features distinct from Tc1 cells, and were Ror(γ)thi, TCF-1hi, T-betlo and EOMESlo. In investigating the bases of Tc17 persistence, we observed that memory Tc17 cells had much higher levels of basal homeostatic proliferation than did Tc1 cells. Conversely, memory Tc17 cells displayed lower levels of anti-apoptotic molecules Bcl-2 and Bcl-xL than Tc1 cells, yet were resistant to apoptosis. Tc1 cells required Bcl-2 for their survival, but Bcl-2 was dispensable for the maintenance of Tc17 cells. Tc17 and Tc1 cells displayed different requirements for HIF-1α during effector differentiation and sustenance and memory persistence. Thus, antifungal vaccination induces durable and stable memory Tc17 cells with distinct requirements for long-term persistence that distinguish them from memory Tc1 cells.

Background: Blastomyces spp. are endemic in regions of the United States and result in blastomycosis, a serious and potentially fatal infection. Little is known about the presentation, clinic course, epidemiology, and genetics of blastomycosis in children., Methods: A retrospective review of children with blastomycosis confirmed by culture or cytopathology between 1999 and 2014 was completed. Blastomyces sp. isolates were genotyped by using microsatellite typing, and species were typed by sequencing of internal transcribed spacer 2 (its2)., Results: Of the 114 children with blastomycosis identified, 79% had isolated pulmonary involvement and 21% had extrapulmonary disease. There were more systemic findings, including fever (P = .01), poor intake (P = .01), elevated white blood cell count (P < .01), and elevated C-reactive protein level (P < .01), in children with isolated pulmonary disease than in children with extrapulmonary disease. Children with extrapulmonary disease had more surgeries (P = .01) and delays in diagnosis (P < .01) than those with isolated pulmonary infection. Of 52 samples genotyped, 48 (92%) were Blastomyces gilchristii and 4 (8%) were Blastomyces dermatitidis., Conclusion: This is the first large-scale study of the clinical, epidemiologic, and genetic features of blastomycosis in children. The majority of the children had isolated pulmonary disease with systemic findings. Patients with extrapulmonary disease were less likely to have systemic symptoms or additional laboratory evidence of infection, which made delays in diagnosis more common. More than 90% of the pediatric cases were caused by B gilchristii., (© The Author 2015. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Dimorphic fungi cause several endemic mycoses which range from subclinical respiratory infections to life-threatening systemic disease. Pathogenic-phase cells of Histoplasma, Blastomyces, Paracoccidioides and Coccidioides escape elimination by the innate immune response with control ultimately requiring activation of cell-mediated immunity. Clinical management of disease relies primarily on antifungal compounds; however, dimorphic fungal pathogens create a number of challenges for antifungal drug therapy. In addition to the drug toxicity issues known for current antifungals, barriers to efficient drug treatment of dimorphic fungal infections include natural resistance to the echinocandins, residence of fungal cells within immune cells, the requirement for systemic delivery of drugs, prolonged treatment times, potential for latent infections, and lack of optimized standardized methodology for in vitro testing of drug susceptibilities. This review will highlight recent advances, current therapeutic options, and new compounds on the horizon for treating infections by dimorphic fungal pathogens.

Competing Interests: Competing interests: None declared.

Blastomyces dermatitidis is a thermally dimorphic fungus endemic to the North American soil near the Mississippi, Ohio, and St. Lawrence river valleys, as well as the Great Lakes Basin. It is responsible for blastomycosis, a systemic pyogranulomatous disease. Blastomycosis of the head and neck is decidedly uncommon and often mistaken for cancer. There are only 3 previous case reports of blastomycosis presenting as an intranasal lesion. We report the unusual case of a 24-year-old man with blastomycosis presenting with a 4-week history of a progressively enlarging intranasal mass who had complete resolution of symptoms after treatment with itraconazole and surgical excision of the lesion.

Background: Invasive fungal diseases (IFD) caused by Cryptococcus and dimorphic fungi are associated with significant morbidity and mortality. Isavuconazole (ISAV) is a novel, broad-spectrum, triazole antifungal agent (IV and by mouth [PO]) developed for the treatment of IFD. It displays potent activity in vitro against these pathogens and in this report we examine outcomes of patients with cryptococcosis or dimorphic fungal infections treated with ISAV., Methods: The VITAL study was an open-label nonrandomized phase 3 trial conducted to evaluate the efficacy and safety of ISAV treatment in management of rare IFD. Patients received ISAV 200 mg 3 times daily for 2 days followed by 200 mg once-daily (IV or PO). Proven IFD and overall response at end of treatment (EOT) were determined by an independent, data-review committee. Mortality and safety were also assessed., Results: Thirty-eight patients received ISAV for IFD caused by Cryptococcus spp. (n = 9), Paracoccidioides spp. (n = 10), Coccidioides spp. (n = 9), Histoplasma spp. (n = 7) and Blastomyces spp. (n = 3). The median length of therapy was 180 days (range 2-331 days). At EOT 24/38 (63%) patients exhibited a successful overall response. Furthermore, 8 of 38 (21%) had stable IFD at the end of therapy without progression of disease, and 6 (16%) patients had progressive IFD despite this antifungal therapy. Thirty-three (87%) patients experienced adverse events., Conclusions: ISAV was well tolerated and demonstrated clinical activity against these endemic fungi with a safety profile similar to that observed in larger studies, validating its broad-spectrum in vitro activity and suggesting it may be a valuable alternative to currently available agents., Clinical Trials Registration: NCT00634049., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)

Blastomyces dermatitidis and Blastomyces gilchristii are dimorphic fungal pathogens that cause serious pulmonary and systemic infections in humans. Although their natural habitat is in the environment, little is known about their specific ecologic niche(s). Here, we analyzed 25 microsatellite loci from 169 strains collected from various regions throughout their known endemic range in North America, representing the largest and most geographically diverse collection of isolates studied to date. Genetic analysis of multilocus microsatellite data divided the strains into four populations of B. dermatitidis and four populations of B. gilchristii. B. dermatitidis isolates were recovered from areas throughout North America, while the B. gilchristii strains were restricted to Canada and some northern US states. Furthermore, the populations of both species were associated with major freshwater drainage basins. The four B. dermatitidis populations were partitioned among (1) the Nelson River drainage basin, (2) the St. Lawrence River and northeast Atlantic Ocean Seaboard drainage basins, (3) the Mississippi River System drainage basin, and (4) the Gulf of Mexico Seaboard and southeast Atlantic Ocean Seaboard drainage basins. A similar partitioning of the B. gilchristii populations was observed among the more northerly drainage basins only. These associations suggest that the ecologic niche where the sexual reproduction, growth, and dispersal of B. dermatitidis and B. gilchristii occur is intimately linked to freshwater systems. For most populations, sexual reproduction was rare enough to produce significant linkage disequilibrium among loci but frequent enough that mating-type idiomorphic ratios were not skewed from 1:1. Furthermore, the evolutionary divergence of B. dermatitidis and B. gilchristii was estimated at 1.9 MYA during the Pleistocene epoch. We suggest that repeated glaciations during the Pleistocene period and resulting biotic refugia may have provided the impetus for speciation as theorized for other species associated with temperate freshwater systems.