Blastomycosis

We describe a case of blastomycosis in an 8-year-old boy with Blastomyces-associated osteomyelitis and possible pulmonary involvement. We also identify 309 cases of blastomycosis in Ontario that were seen during a 10-year period, 57% of which occurred from 2001 to 2003. The overall incidence during the study period was 0.30 cases per 100,000 population. Most patients were from north Ontario (n = 188), where the incidence was 2.44 cases per 100,000. The incidence in the Toronto region was 0.29 per 100,000. Thirteen percent of cases occurred in children <19 years of age. These findings substantially increase the number of known cases in Ontario and Canada. Clinicians may encounter persons infected with Blastomyces dermatitidis and must be familiar with its signs and symptoms and be aware of locations, such as northwestern Ontario, where disease is endemic or hyperendemic. We advocate resuming blastomycosis as a reportable disease in Ontario to facilitate tracking cases.

Neutrophils are classically defined as terminally differentiated, short-lived cells; however, neutrophils can be long-lived with phenotypic plasticity. During inflammation, a subset of neutrophils transdifferentiate into a population called neutrophil-DC hybrids (PMN-DCs) having properties of both neutrophils and dendritic cells. While these cells ubiquitously appear during inflammation, the role of PMN-DCs in disease remains poorly understood. We observed the differentiation of PMN-DCs in pre-clinical murine models of fungal infection: blastomycosis, aspergillosis and candidiasis. Using reporter strains of fungal viability, we found that PMN-DCs associate with fungal cells and kill them more efficiently than undifferentiated canonical neutrophils. During pulmonary blastomycosis, PMN-DCs comprised less than 1% of leukocytes yet contributed up to 15% of the fungal killing. PMN-DCs displayed higher expression of pattern recognition receptors, greater phagocytosis, and heightened production of reactive oxygen species compared to canonical neutrophils. PMN-DCs also displayed prominent NETosis. To further study PMN-DC function, we exploited a granulocyte/macrophage progenitor (GMP) cell line, generated PMN-DCs to over 90% purity, and used them for adoptive transfer and antigen presentation studies. Adoptively transferred PMN-DCs from the GMP line enhanced protection against systemic infection in vivo. PMN-DCs pulsed with antigen activated fungal calnexin-specific transgenic T cells in vitro and in vivo, promoting the production of interferon-γ and interleukin-17 in these CD4+ T cells. Through direct fungal killing and induction of adaptive immunity, PMN-DCs are potent effectors of antifungal immunity and thereby represent innovative cell therapeutic targets in treating life-threatening fungal infections.

Blastomycosis is a potentially fatal fungal infection endemic to parts of North America. We used national multiple-cause-of-death data and census population estimates for 1990-2010 to calculate age-adjusted mortality rates and rate ratios (RRs). We modeled trends over time using Poisson regression. Death occurred more often among older persons (RR 2.11, 95% confidence limit [CL] 1.76, 2.53 for those 75-84 years of age vs. 55-64 years), men (RR 2.43, 95% CL 2.19, 2.70), Native Americans (RR 4.13, 95% CL 3.86, 4.42 vs. whites), and blacks (RR 1.86, 95% CL 1.73, 2.01 vs. whites), in notably younger persons of Asian origin (mean = 41.6 years vs. 64.2 years for whites); and in the South (RR 18.15, 95% CL 11.63, 28.34 vs. West) and Midwest (RR 23.10, 95% CL14.78, 36.12 vs. West). In regions where blastomycosis is endemic, we recommend that the diagnosis be considered in patients with pulmonary disease and that it be a reportable disease.

ImportanceLaboratory testing is necessary to distinguish blastomycosis, coccidioidomycosis, or histoplasmosis from other causes of community-acquired pneumonia (CAP). Robust data about testing for and diagnosis of these fungal diseases among patients with CAP throughout the US are lacking.ObjectiveTo examine proportions and characteristics of (1) adult outpatients with CAP who underwent diagnostic testing for blastomycosis, coccidioidomycosis, or histoplasmosis; and (2) tested patients who received diagnoses of these diseases.Design, setting, and participantsThis retrospective cohort study used 2017 to 2023 commercial health insurance claims data from the Merative MarketScan Commercial/Medicare Database. Adult outpatients with diagnosis codes for unspecified CAP were included.Main outcomes and measuresThe primary outcome was the proportion of patients who underwent fungal diagnostic testing. The secondary outcomes were the proportions of tested patients who received diagnoses of blastomycosis, coccidioidomycosis, or histoplasmosis. Multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) for characteristics independently associated with receiving a diagnosis of coccidioidomycosis or histoplasmosis.ResultsAmong 573 994 patients (318 152 female [55%]; median [IQR] age, 54 [41-63] years) with unspecified CAP, 25 822 (5%) underwent fungal diagnostic testing, which occurred a median (IQR) of 3 (1-6) health care visits after the initial CAP diagnosis. Among tested patients, 755 (3%) received a blastomycosis, coccidioidomycosis, or histoplasmosis diagnosis code. Rash (aOR, 3.24; 95% CI, 2.27-4.63), lymphadenopathy (aOR, 1.74; 95% CI, 1.15-2.63), myalgia (aOR, 1.66; 95% CI, 1.11-2.49), chest pain (aOR, 1.65; 95% CI, 1.35-2.02), and receipt of antibiotics from multiple classes (aOR, 1.40; 95% CI, 1.17-1.67) were independently associated with increased odds of receiving a coccidioidomycosis diagnosis. Autoimmune inflammatory disease (aOR, 3.00; 95% CI, 1.72-5.21), chest pain (aOR, 1.84; 95% CI, 1.20-2.82), and abnormal weight loss (aOR, 5.15; 95% CI, 2.71-9.79) were associated with increased odds of receiving a histoplasmosis diagnosis.Conclusions and relevanceIn this cohort study of patients with unspecified CAP, testing rates for blastomycosis, coccidioidomycosis, and histoplasmosis were low in many locations. Increased awareness of these fungal infections may help increase timely testing for fungal diseases among patients with CAP, decrease health care utilization and inappropriate antibiotic use, and improve patient outcomes.