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

Hall, Jaimee M. DO, MA*,†; Havens, Peter L. MD, MS*; Mitchell, Errin A. MD*; De Vela, Gabriel N. MD*; Titus, Lauren L. MD*; Dasgupta, Mahua MS; Simpson, Pippa M. PhD; Kehl, Sue C. PhD, D(ABMM)§; Willoughby, Rodney E. MD*; Henrickson, Kelly J. MD*; Mitchell, Michelle L. MD*; Huppler, Anna R. MD*; Chusid, Michael J. MD*

Author Information
The Pediatric Infectious Disease Journal: September 2021 - Volume 40 - Issue 9 - p 802-807
doi: 10.1097/INF.0000000000003178

Abstract

Blastomyces species (spp.) are thermally dimorphic fungi found in soil in the Upper Great Lakes Region, Ohio and Mississippi River valleys, parts of the southeastern United States and an area of New York and Canada adjacent to the St. Lawrence Seaway.1–6 Infection occurs through inhalation of conidia of disrupted mycelia found in the environment with the transformation of the infectious agent to the pathogenic yeast form within mammalian tissues.1,7 Humans can develop asymptomatic or symptomatic pulmonary infection after inhalation of the agent or, less commonly, local infection at the site of direct inoculation.5,6,8 Disseminated disease involving infection of bone, genitourinary (GU) tract, skin or central nervous system (CNS) may occur, especially after prolonged infection.1,2,9 Unlike many deep fungal infections, blastomycosis occurs primarily in immunocompetent individuals.5,6,10

Children comprise approximately 10% of all cases of blastomycosis and some data have suggested more frequent dissemination in children.6,8,11 An overall blastomycosis mortality rate of 6–9% has been estimated, although on average pediatric mortality seems to be lower, ranging from 3% to 4% in larger studies.6,12–14

Sporadic cases within endemic areas are possible, although large outbreaks of blastomycosis occur following point source exposure.13,15 Environmental exposure to moist soil enriched with decaying vegetation, particularly in close proximity to bodies of water, is most commonly associated with disease acquisition.16 Reported blastomycosis outbreaks in northern and central Wisconsin and Minnesota were associated with environmental exposures to soil, yard waste, waterways and recreational activities including camping, hiking and fishing.9,16–18 However, only a small number of children were included in these studies.6,13,19,20

Several reports have suggested ethnic predisposition toward the acquisition and/or aggressiveness of invasive blastomycosis. A matched case–control study in northern Wisconsin found a higher incidence of infection rate among Asians than non-Asians between 2005 and 2010, later confirmed by retrospective pediatric review of blastomycosis in northern Wisconsin.1,20 High incidence rates of blastomycosis in non-Caucasian racial and ethnic groups have also been described in persons of aboriginal ethnicity in Canada and individuals who are black in the United States, and genetic causes are suggested for these associations.5,21–24 Higher mortality rates for both black children and adults affected by blastomycosis in Illinois have been suggested, although these studies included few children overall and few children of black race.12,25 In contrast to numerous adult studies, no pediatric blastomycosis studies to date are inclusive of enough black children to delineate a possible racial predisposition to the acquisition of infection and disease severity.

The goal of this retrospective analysis was to explore the risk factors for blastomycosis acquisition and disease severity in children. We identified a cohort of urban children with blastomycosis lacking a “classic” or “typical” environmental exposure history and a suggestion that black children may have more severe disease.

MATERIALS AND METHODS

We performed a retrospective chart review of children 0–18 years of age diagnosed with probable or confirmed blastomycosis infection at Children’s Wisconsin and associated clinics for the years 1998–2018. This tertiary care children’s hospital serves the local urban Milwaukee county population and acts as the referral site for children from many eastern Wisconsin counties, including the mostly urban Racine and Kenosha counties in the southeast, and more rural and wooded northeastern Wisconsin counties. Confirmed cases were defined as those with positive culture or identification of characteristic yeast on histopathology or cytopathology for Blastomyces spp. Blastomyces isolates were not differentiated to species level. Probable cases included those with positive Blastomyces antigen or antibody assays in blood or urine. Demographic, epidemiologic and clinical information was collected and patient anonymity maintained. The Children’s Wisconsin institutional review board approved the study.

Selected variables including age, sex, race, environmental exposure, time to diagnosis, region of residence at diagnosis, affected infection sites and quarter year of diagnosis were categorized for analysis. Race was categorized as black or other races. The classic environmental exposure was defined as significant exposure to any of the northern or northeastern regions of Wisconsin and/or rivers, forests or bodies of water. Symptom onset to time of diagnosis was reported as median days. Regions of residence at time of diagnosis were characterized as Milwaukee, Racine or Kenosha counties (MRK) versus other Wisconsin regions. MRK counties are southeastern Wisconsin counties that are more urban and typically lack opportunities for classic environmental exposure activities. The number of disease sites was categorized as one versus greater than one. Disseminated blastomycosis was defined as the presence of extrapulmonary disease. Cranial dissemination was defined as any clinical disease of the skull and brain; however, clinically CNS dissemination was defined as meningeal and/or parenchymal involvement. Quarters of the year at time of admission were divided into quarter one (January/February/March) as winter season, quarter two (April/May/June) as spring season, quarter three (July/August/September) as summer season and quarter four (October/November/December) as fall season. Disease severity categories included mild 1 (ambulatory only), mild 2 (hospitalization without complications), moderate (hospitalization with supplemental oxygen requirement or readmission) and severe (pediatric intensive care unit admission, intensive care interventions or death). Intensive care interventions were defined as mechanical ventilation, vasopressor support, tracheostomy, extracorporeal membrane oxygenation or hemodialysis.

Categorical variables are reported as N (%), continuous as median (interquartile range). Analyses were performed using Mann-Whitney, χ2 and Fisher’s Exact tests as appropriate. Significance was defined as P value of <0.05 using two-tailed tests.

RESULTS

Demographics

A total of 64 children were identified with confirmed (N = 47, 73%) or probable (N = 17, 27%) blastomycosis. Mean age at diagnosis was 12.9 years ± 3.8 years, range 2–18 years. Forty-six (72%) were male and 17 (27%) were black. Typical environmental exposure before disease acquisition was noted in 32 (50%) children. At the time of illness diagnosis, 24 (38%) children were living in southeastern Wisconsin. A large majority (78%) of children were hospitalized for their infection. The most common season of presentation was quarter one (36%), the winter (Table 1). Median time from symptom onset to diagnosis was 38.5 days (18.0, 65.0), range 3–358 days.

TABLE 1. - Demographics of Children with Blastomycosis
Attribute Patients (n = 64)
Age at illness diagnosis (years) (mean ± SD) 12.9 ± 3.8
Symptom onset to diagnosis* (days) (median [IQR]) 38.5 (18.0, 65.0)
Sex (n [%])
 Male 46 (72%)
 Female 18 (28%)
Race (n [%])
 White 31 (48%)
 Black 17 (27%)
 Other 16 (25%)
Environmental exposure (n [%])
 Northern or northeastern Wisconsin 13 (20%)
 River/Forest/Lake 29 (45%)
 None 31 (48%)
 Unknown 1 (2%)
Region of residence (n [%])
 Milwaukee–Racine–Kenosha (MRK) 24 (38%)
 Other 40 (63%)
Care setting (n [%])
 Ambulatory 14 (22%)
 Inpatient 50 (78%)
Quarter of year at admission (n [%])
 Quarter 1: January–February–March 23 (36%)
 Quarter 2: April–May–June 10 (16%)
 Quarter 3: July–August–September 13 (20%)
 Quarter 4: October–November–December 18 (28%)
*Date of illness onset missing for 6 patients.
†Northern or northeastern Wisconsin exposure was exclusive of exposure to river/forest/lake.
‡First admission.
IQR, interquartile range.

Three children were immunosuppressed: one receiving high-dose steroids, another transplant immunosuppression and third immunomodulation. Comorbid health conditions were found in 26 children (33%), in descending order: atopy (N = 10; asthma, environmental, eczema), neurologic (N = 4; chronic headache, migraine, Tourette syndrome, tic disorder), immunocompromising conditions (N = 3) and psychiatric (N = 2; anxiety, depression and attention-deficit/hyperactivity disorder).

Clinical Presentation and Laboratory Findings

Pulmonary involvement was seen in most (92%) children, with 33 (52%) having pulmonary disease exclusively. Of the 31 children with disseminated infection, affected sites included bone (N = 16), skin (N = 13), cranium (N = 7), soft tissue (N = 5), GU (N = 1) and other sites of involvement (N = 4) (Table 2). Of 7 children with abnormal head imaging, 4 had true CNS dissemination with meningeal and/or parenchymal disease and 3 had osteomyelitis and/or soft tissue involvement. Of the 4 with meningeal and/or parenchymal disease, 3 had symptoms of CNS disease and abnormal CSF WBC and/or protein. In 13 patients with CSF evaluation, fungal stains were negative and cultures were sterile. Four patients with abnormal head imaging had normal CSF evaluation.

TABLE 2. - Clinical Presentation of Children with Blastomycosis
Attribute Patients (n = 64)
Disease severity* (n [%])
 1 (Mild 1) 14 (22%)
 2 (Mild 2) 31 (48%)
 3 (Moderate) 12 (19%)
 4 (Severe) 7 (11%)
Sites of infection (n [%])
 Pulmonary 59 (92%)
 Skin 13 (20%)
 Bone 16 (25%)
 Cranium 7 (11%)
 Genitourinary (GU) 1 (2%)
 Soft-tissue abscess 5 (8%)
 Other 4 (6%)
Number of disease sites (n [%])
 One 37 (58%)
 >One 27 (42%)
Disseminated disease (n [%])
 Exclusive pulmonary 33 (52%)
 Extrapulmonary 31 (48%)
*Mild 1, ambulatory only; Mild 2, hospitalization without complications; Moderate, supplemental oxygen requirement and/or readmission (any one of these); Severe, pediatric intensive care unit, ventilator, vasopressor, tracheostomy, extracorporeal membrane oxygenation, hemodialysis and/or death (any one of these).

Diagnostic Imaging

Chest radiographs and chest computed tomography (CT) images each yielded 95% positivity. Of the 56 chest radiographs performed, 37 identified single lobe and 13 identified multiple lobe involvement. Other findings on chest radiographs included pleural effusions (N = 9), mediastinal lymphadenopathy (N = 5), nodules (N = 4) and masses (N = 1). Of the 43 chest CT studies performed, 9 identified pleural effusions and 2 revealed pericardial effusions. Other chest CT findings included lobar consolidation (N = 36), mediastinal lymphadenopathy (N = 21), pulmonary nodules (N = 10) and pulmonary masses (N = 2).

Bone scan and/or total body magnetic resonance imaging (MRI) images overall yielded 41% positivity. Of the 16 children with osseous disease revealed on imaging, 7 were not exhibiting bony symptoms at the time of clinical presentation (Table 3).

TABLE 3. - Diagnostic Imaging in Children With Blastomycosis
Imaging Modality N positive/N patients with test performed (% positive) Comment
Chest radiographs 53/56 (95%) 37 single lobe; 13 multiple lobes; 1 mass; 4 nodules; 5 mediastinal adenopathy; 9 pleural effusions
Chest CT 41/43 (95%) 2 mass; 10 nodules; 36 lobar consolidations; 21 mediastinal lymphadenopathy; 9 pleural effusions; 2 pericardial effusions
Bone imaging* 16/39 (41%) 7 single site; 9 multiple sites
 Asymptomatic, positive  bone imaging 7/16 (44%)
Head imaging 7/54 (13%) 0 mass; 1 meningitis; 4 parenchymal; 3 osteomyelitis; 1 soft-tissue lesion
 Asymptomatic, positive  head imaging 3/7 (43%)
Echocardiogram 4/7 (57%) 2 pericardial effusions; 2 ventricular dilations; 2 ventricular hypertrophy; 3 diminished ventricular functions; 1 pulmonary hypertension; 1 valvular insufficiency
*Bone imaging: bone scan or total body magnetic resonance imaging.
†Head imaging: computed tomography of head or brain magnetic resonance imaging.
CT, computed tomography; MRI, magnetic resonance imaging.

Head imaging (head CT or brain MRI) overall yielded 13% positivity. Of the 7 children with the positive cranial disease on imaging, 3 were not exhibiting localizing cranial symptoms at the time of clinical presentation, including one with parenchymal disease. Of the 54 head images performed, 1 revealed meningitis, 4 parenchymal brain lesions, 3 cranial osteomyelitis and 1 a soft tissue lesion.

Echocardiograms performed in 7 children were positive in 4 and showed pericardial effusion, ventricular dilation, ventricular hypertrophy or diminished ventricular function.

Associations With Disease Severity

About 70% of children were considered to have a mild infection, either not requiring admission or if admitted had no complications during admission (Table 2). A significant association was found between increased severity of infection and absence of typical environmental exposure as 48% of infected children without typical exposure and 9% with typical exposure developed moderate or severe blastomycosis disease (P = 0.008) (Table 4). An association was also found between exclusive pulmonary infection and mild disease as 82% of children with exclusive pulmonary infection had mild disease and 18% had moderate or severe disease (P = 0.04) (Table 4). Of 17 black children, 7 (42%) had moderate/severe disease. Among 47 children of other races, only 12 (26%) had moderate/severe disease (P = 0.23). No significant relationship between disease severity groups and age at illness diagnosis, sex, race, median time from symptom onset to diagnosis or season of the first admission was found. There were 2 (3%) patient deaths in our study cohort, both with intractable cardiorespiratory failure.

TABLE 4. - Associations with Disease Severity
Attribute Total Patients (n) P
Combined disease severity categories (n [%]) Milds 1 and 2 Moderate and severe
 Cumulative disease severity 64 45 (70%) 19 (30%)
Age (at illness diagnosis) [median (Q1, Q3)] 13.0 (10.2, 15.4) 14.2 (11.6, 17.6) >0.10
Sex (n [%]) 0.83
 Female 18 13 (72%) 5 (28%)
 Male 46 32 (70%) 14 (30%)
Race (n [%]) 0.23
 Black 17 10 (59%) 7 (41%)
 Other 47 35 (74%) 12 (26%)
Environmental exposure* (n [%]) 0.008
 Northern or northeastern Wisconsin/river/forest/lake 32 29 (91%) 3 (9%)
 None 31 16 (52%) 15 (48%)
Region of residence (n [%]) 0.10
 Milwaukee/Racine/Kenosha 24 14 (58%) 10 (42%)
 Other 40 31 (78%) 9 (22%)
Number of disease sites (n [%]) 0.10
 One 37 29 (78%) 8 (22%)
 >One 27 16 (59%) 11 (41%)
Disseminated disease (n [%]) 0.04
  Exclusive pulmonary 33 27 (82%) 6 (18%)
  Extrapulmonary 31 18 (58%) 13 (42%)
Quarter of the year (n [%]) 0.33
 Quarter 1: January–February–March 23 17 (74%) 6 (26%)
 Quarter 2: April–May–June 10 5 (50%) 5 (50%)
 Quarter 3: July–August–September 13 11 (85%) 2 (15%)
 Quarter 4: October–November–December 18 12 (67%) 6 (33%)
*Environmental exposure was unknown for one patient.
†First admission.
Percentages represent row proportionalities not column proportionalities.

Associations With Region of Residence at Diagnosis

Significantly more children diagnosed with blastomycosis and living in the urban MRK region were black (63%) compared with children from other regions (5%; P < 0.0001) (Table 5). According to MRK census data, the mean percentage of African American individuals in those counties is approximately 22%, suggesting an over-representation of black children in this cohort with blastomycosis.26 Typical exposure history was identified in 7/24 (29%) children living in MRK, compared with 25/40 (63%) living in other regions of the state (Table 5). Disseminated blastomycosis was more common in children residing in MRK region (P = 0.006). The season of presentation for urban children with blastomycosis was similar to nonurban children (see Table, Supplemental Digital Content 1; https://links.lww.com/INF/E390).

TABLE 5. - Associations With Region of Residence at Diagnosis
Attribute Total Patients (n) P
Region of residence MRK* Other
Overall (n [%]) 64 24 (38%) 40 (62%)
Age at illness diagnosis (median [Q1, Q3]) 14.3 (12.0–17.0) 12.6 (9.7–15.4) 0.12
Sex (n [%]) 0.88
 Female 18 11 (61%) 7 (39%)
 Male 46 29 (63%) 17 (37%)
Race (n [%]) <0.0001
 Black 17 15 (88%) 2 (12%)
 Other 47 9 (19%) 38 (81%)
Environmental exposure (n [%]) 0.007
 Northern or northeastern Wisconsin/river/forest/lake 32 7 (22%) 25 (78%)
 None 31 17 (55%) 14 (45%)
Disseminated disease (n [%]) 0.006
 Exclusive pulmonary 33 7 (21%) 26 (79%)
 Extrapulmonary 31 17 (55%) 14 (45%)
Number of disease sites (n [%]) 0.13
 One 37 11 (30%) 26 (70%)
 >One 27 13 (48%) 14 (52%)
*MRK, Milwaukee–Kenosha–Racine counties.
†Environmental exposure was unknown for one patient.
Percentages represent row proportionalities not column proportionalities.

Associations With Time to Diagnosis

Of 57 children with data on typical environmental exposure and date of symptom onset, those with no typical environmental exposure (25/57; 44%), had longer median delay in diagnosis (50; interquartile range [IQR] 27–95 days) compared with median of 33 (IQR 17–52) days in children with typical exposure (P = 0.02). There was no significant difference when comparing time from symptom onset to diagnosis by gender, race, disease severity or clinical outcome (life versus death).

DISCUSSION

This is the first pediatric study to show blastomycosis risk for children that live in urban areas within endemic regions, despite a lack of classic or typical, exposure history. Additionally, we present data to suggest black race is a potential risk factor for more severe blastomycosis disease in children. Blastomycosis affects children across a wide spectrum of ages and races. An association between being black and Blastomyces risk has been previously suggested, but prior pediatric studies have generally been conducted in locations with low populations of black children.1,6,12,23,25 Our study included more black children than previous pediatric studies, and our data suggest children of black race may be at higher risk for more severe disease and extrapulmonary dissemination, although our study was underpowered to find a statistically significant difference.1,6,12

Our findings confirm a male predisposition for Blastomyces spp. infection was seen in other pediatric and adult studies, which has been previously attributed to a proposed higher frequency of outdoor occupational and recreational habits.1,24 Well-recognized environmental or regional exposure history to the infectious agent was reported in only half of our patients with no difference based on sex, although a uniform approach to the documentation of exposure history was not utilized and therefore may be unknown in some members of our cohort. Our data might be interpreted as suggesting a male predominance of infection independent of a male predisposition to outdoor activities.

Most children in our study developed mild disease requiring ambulatory management or short hospitalization without complications. Low mortality in this cohort was similar to other pediatric studies.1,6,12 Hospitalizations occurred most commonly in the first quarter of the year, similar to findings noted by Anderson et al, perhaps suggesting a delay in diagnosis assuming initial infection acquisition occurs in summer and fall.12

Blastomycosis can mimic other conditions including tuberculosis, neoplasms and bacterial pneumonia, which also can delay diagnosis and lead to suboptimal clinical outcomes; therefore, early consideration in endemic areas is essential.5,6,8,11 Similar to previous studies, most children who developed blastomycosis were previously healthy and initially developed pulmonary infection, with dissemination occurring in almost half of children.6,8,12 Our findings suggest dissemination in pediatric blastomycosis involves, in descending order, bone, skin, cranium, soft tissue and GU systems, respectively. A high rate of soft tissue dissemination was noted in a recent large adult study.18 This site of dissemination, not previously noted within pediatric studies, was also noted in our patient cohort.

Our data suggest that head imaging may be necessary to identify brain or cranial dissemination since 3 of 7 patients with abnormal head imaging did not show clinical signs of disease or abnormal CSF. The microbiologic diagnosis of blastomycosis never came from CSF sampling (stain or culture). Dedicated CNS imaging occasionally identified skull osteomyelitis lesions not found with other imaging modalities.

Blastomycosis was common in children residing in urban southeastern Wisconsin and the infectious source remains unclear in this setting. One prior report proposed urban waterways in southeastern Wisconsin as a potential source of infection acquisition.27 In our study, children living in southeastern Wisconsin were less likely than those from other regions to have typical travel or exposure history and no urban water source exposure was consistently reported. However, in Wisconsin, it is common to live by a river or lake overall, even within the urban setting. Possible explanations for unexpected blastomycosis infections in urban children include alternative, unsuspected sources of infection such as nearby construction or increased inherent vulnerability of the minority population to this fungal pathogen.

Children with a history of “classic” or “typical” environmental exposures were diagnosed with blastomycosis significantly more quickly than those without such history. Known environmental exposures within blastomycosis endemic areas potentially heightens the index of suspicion for this diagnosis. Although no significant difference was noted when comparing time from symptom onset to diagnosis by gender, race, disease severity or clinical outcome (life versus death), we believe our study was unpowered. We hypothesize; however, that with additional subjects, median time to diagnosis of black children may be longer than in children of other races and that this may be related to the lack of classic exposure history and contribute to more severe disease in black children. We also hypothesize that with additional subjects, time to diagnosis of mild disease compared with moderate/severe disease may be longer due to an amplified clinical urgency to identify diagnosis in higher acuity patients.

Children with a classic exposure history had less severe disease than their urban counterparts lacking classic exposure history. Possible explanations for variations in disease severity include varying Blastomyces spp. pathogenicity, variable geographic distribution of Blastomyces spp. within endemic regions, delay in seeking care, delay in diagnosis, delay in targeted antimicrobial use, misdiagnosis, missed diagnosis and varying host immune response by race. Blastomyces speciation was not delineated in this study. However, it has been suggested an increased risk of disseminated disease is associated with Blastomyces dermatitidis whereas focal pulmonary infection is more commonly seen with Blastomyces gilchristii.28 Furthermore, one Wisconsin study found a predilection for B. dermatitidis infection in non-Hispanic whites and for B. gilchristii in Hispanic whites, American Indian or Alaskan Native, or Asian patients.29 Host genetics and immune response to blastomycosis infection is not well understood, especially in the pediatric population. A recent study and subsequent review suggest genetically based less robust blastomycosis immune response by Hmong individuals.21,22 The genetics of fungal immune response in black children is yet to be reported.

Limitations of this study include insufficient power for some subgroup analyses. The retrospective and single-center design renders this study susceptible to recall bias and limited generalizability, respectively. Clinical findings described were limited to children living in and around Wisconsin and to those children ill enough to require specialty care at our tertiary referral center or associated clinics and for these reasons, the data is prone to selection bias.

CONCLUSIONS

Blastomycosis is endemic in black children in urban southeastern Wisconsin, with high rates of disseminated disease. Urban children may lack classic exposure history. Bone and head imaging should be considered in all children with blastomycosis infection as sites of dissemination may be clinically silent. Future studies are needed to further delineate possible explanations for observed infection risk and disease severity observed in urban southeastern Wisconsin children. Within Blastomyces endemic areas, high index of suspicion for blastomycosis should be maintained for urban children.

ACKNOWLEDGMENTS

A special thank you to Kim Gajewski, BA, who is a database analyst and a member of the department of Qualitative Health Sciences at Medical College of Wisconsin who assisted in formulating the RedCap database.

REFERENCES

1. Frost HM, Anderson J, Ivacic L, et al. Blastomycosis in children: an analysis of clinical, epidemiologic, and genetic features. J Pediatric Infect Dis Soc. 2017;6:49–56.
2. Chapman SW, Dismukes WE, Proia LA, et al.; Infectious Diseases Society of America. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:1801–1812.
3. Saccente M, Woods GL. Clinical and laboratory update on blastomycosis. Clin Microbiol Rev. 2010;23:367–381.
4. Schutze GE, Hickerson SL, Fortin EM, et al. Blastomycosis in children. Clin Infect Dis. 1996;22:496–502.
5. Crampton TL, Light RB, Berg GM, et al. Epidemiology and clinical spectrum of blastomycosis diagnosed at Manitoba hospitals. Clin Infect Dis. 2002;34:1310–1316.
6. Fanella S, Skinner S, Trepman E, et al. Blastomycosis in children and adolescents: a 30-year experience from Manitoba. Med Mycol. 2011;49:627–632.
7. Medoff G, Painter A, Kobayashi GS. Mycelial- to yeast-phase transitions of the dimorphic fungi Blastomyces dermatitidis and Paracoccidioides brasiliensis. J Bacteriol. 1987;169:4055–4060.
8. Laskey WK, Sarosi GA. Blastomycosis in children. Pediatrics. 1980;65:111–114.
9. Klein BS, Vergeront JM, Weeks RJ, et al. Isolation of Blastomyces dermatitidis in soil associated with a large outbreak of blastomycosis in Wisconsin. N Engl J Med. 1986;314:529–534.
10. Rao GR, Narayan BL, Durga Prasad BK, et al. Disseminated blastomycosis in a child with a brief review of the Indian literature. Indian J Dermatol Venereol Leprol. 2013;79:92–96.
11. Steele RW, Abernathy RS. Systemic blastomycosis in children. Pediatr Infect Dis. 1983;2:304–307.
12. Anderson EJ, Ahn PB, Yogev R, et al. Blastomycosis in children: a study of 14 cases. J Pediatric Infect Dis Soc. 2013;2:386–390.
13. Pfister JR, Archer JR, Hersil S, et al. Non-rural point source blastomycosis outbreak near a yard waste collection site. Clin Med Res. 2011;9:57–65.
14. McDonough ES, Kuzma JF. Epidemiological studies on blastomycosis in the state of Wisconsin. Sabouraudia. 1980;18:173–183.
15. Bradsher RW Jr. The endemic mimic: blastomycosis an illness often misdiagnosed. Trans Am Clin Climatol Assoc. 2014;125:188–202; discussion 202.
16. Klein BS, Vergeront JM, DiSalvo AF, et al. Two outbreaks of blastomycosis along rivers in Wisconsin. Isolation of Blastomyces dermatitidis from riverbank soil and evidence of its transmission along waterways. Am Rev Respir Dis. 1987;136:1333–1338.
17. Cockerill FR III, Roberts GD, Rosenblatt JE, et al. Epidemic of pulmonary blastomycosis (Namekagon fever) in Wisconsin canoeists. Chest. 1984;86:688–692.
18. Ireland M, Klumb C, Smith K, et al. Blastomycosis in Minnesota, USA, 1999-2018. Emerg Infect Dis. 2020;26:866–875.
19. Choptiany M, Wiebe L, Limerick B, et al. Risk factors for acquisition of endemic blastomycosis. Can J Infect Dis Med Microbiol. 2009;20:117–121.
20. Roy M, Benedict K, Deak E, et al. A large community outbreak of blastomycosis in Wisconsin with geographic and ethnic clustering. Clin Infect Dis. 2013;57:655–662.
21. Merkhofer RM Jr, O’Neill MB, Xiong D, et al. Investigation of genetic susceptibility to blastomycosis reveals interleukin-6 as a potential susceptibility locus. mBio. 2019;10:e01224–e01219.
22. Merkhofer RM, Klein BS. Advances in understanding human genetic variations that influence innate immunity to fungi. Front Cell Infect Microbiol. 2020;10:69.
23. Lowry PW, Kelso KY, McFarland LM. Blastomycosis in Washington Parish, Louisiana, 1976-1985. Am J Epidemiol. 1989;130:151–159.
24. Khuu D, Shafir S, Bristow B, et al. Blastomycosis mortality rates, United States, 1990-2010. Emerg Infect Dis. 2014;20:1789–1794.
25. Dworkin MS, Duckro AN, Proia L, et al. The epidemiology of blastomycosis in Illinois and factors associated with death. Clin Infect Dis. 2005;41:e107–e111.
26. Bureau USC. QuickFacts United States 2019. 2020. Available at: https://www.census.gov/quickfacts/fact/map/US/PST045219. Accessed June 06, 2020.
27. Lemke MA, Baumgardner DJ, Brummitt CF, et al. Blastomycosis in urban southeastern Wisconsin. WMJ. 2009;108:407–410.
28. Meece JK, Anderson JL, Gruszka S, et al. Variation in clinical phenotype of human infection among genetic groups of Blastomyces dermatitidis. J Infect Dis. 2013;207:814–822.
29. Anderson JL, Frost HM, King JP, et al. Racial differences in clinical phenotype and hospitalization of blastomycosis patients. Open Forum Infect Dis. 2019;6:ofz438.
Keywords:

blastomycosis; pediatric; urban; African American; dissemination

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