Human Blastomycosis Surveillance in Minnesota, Carrie Klumb 1,2, Kirk Smith 1, Joni Scheftel 1 1 Minnesota Department of Health 2 CSTE/CDC Applied Epidemiology Fellowship

Background Blastomycosis is caused by the dimorphic fungus Blastomyces dermatitidis Growth dependent on weather and environmental factors (e.g., recent rainfall, soil acidity) –Fastidious organism –Extremely difficult to isolate from the environment

Background (cont.) Infection occurs through inhalation of airborne spores from disturbed soil Approximately 50% of infections asymptomatic or resolve spontaneously

Background (cont.) Median incubation period is 45 (range, 21 to 106 days) Acute infections present with sudden fever, cough, and pulmonary symptoms of varying severity National case fatality rate is approximately 5%

Blastomycosis Endemic Regions of North America (in brown) Fang et al. Radiographics 2007;27:

Study Objective Review surveillance data from 1999 to 2010 to better describe the burden and epidemiology of blastomycosis in Minnesota

Methods Human blastomycosis cases are reportable in Minnesota Passive surveillance using standard report form Each case interviewed by MDH staff regarding health history, symptoms, and potential exposures during 3 months prior to onset –Likely county of exposure determined from interview

Methods - Case Definition A Minnesota resident with either: a) B. dermititidis cultured or visualized from tissue or bodily fluids OR b) A positive urine antigen test for B. dermititidis and compatible clinical symptoms Case inclusion criteria: cases with a diagnosis date between January 1, 1999 and December 31, 2010

Methods (cont.) Fatal blastomycosis cases compared to hospitalized non-fatal cases to examine possibility of delayed diagnosis Descriptive analyses were performed using SAS, version 9.2 ArcMap version used to identify highly endemic counties in Minnesota

389 cases of blastomycosis diagnosed and reported to MDH from 1999 to 2010 –Incidence: 0.58 cases/100,000 person-yrs 371 (95%) cases sporadic –71% (n=265) male –Median age: 44 yrs (range, 3 to 93 yrs) –31% (90/289) underlying conditions –67% (n=247) hospitalized –11% (n=39) fatal Results

Demographic Characteristics of Human Blastomycosis Cases, Minnesota, (n=371) Age Group (yrs)No. (%) 0-95 ( 1) (11) (12) (18) (20) (18) ( 7) ≥7043 (12) 56%

Demographic Characteristics of Human Blastomycosis Cases, Minnesota, Race (n=305)No. (%) % MN Population White 256 (84)85 American Indian 23 ( 8) 1 Black 12 ( 4) 5 Asian 12 ( 4) 4 Other 2 (0.7) 2 Ethnicity (n=201) No. (%) % MN Population Non-Hispanic 190 (95)95 Hispanic 11 ( 6) 5

Symptoms Reported by Cases, Minnesota, (n=371) SymptomNo. (%) Cough258 (70) Fatigue229 (62) Fever210 (57) Weight Loss175 (47) Night Sweats161 (43) Chest Pain157 (42) Headache113 (30) Skin Sores91 (25) Cough with Blood68 (18)

Clinical Characteristics of Human Blastomycosis Cases, Minnesota, CharacteristicNo. (%) Disease Locationn=339 Pulmonary229 (68) Disseminated 81 (24) Extra-pulmonary* 29 ( 9) *Typically a soft tissue infection following a wound

Clinical Characteristics of Human Blastomycosis Cases, Minnesota, CharacteristicNo. (%) Diagnosis Method n=371 Culture 304 (82) Smear 142 (38) Histopathology 54 (18) Urine Antigen 19 ( 5)

Clinical Characteristics of Human Blastomycosis Cases, Minnesota, Treatment Typen=314 Antifungals Itraconazole221 (79) Amphotericin B51 (18) Fluconazole11 ( 4) Voriconazole5 ( 2) Other Antifungals 7 ( 5) Antibiotics Only14 ( 5) Surgical Removal 2 ( 1)

Hospitalized Cases Fatal Cases n=39 Non-fatal Cases n=205p-value No. Underlying Conditions (%) 15 (38)52 (25)0.09 Days hospitalized, median (range) 9 (3 to 48) 7 (1 to 137) 0.03 Days admission to testing, median (range) 4 (0 to 32) 1 (0 to 60) 0.02

Number of Blastomycosis Cases in Minnesota by Year of Diagnosis, (n=371) Year of Diagnosis No. of Cases

Human Blastomycosis Cases by Month of Onset, Minnesota, (n=324) No. of Cases Month of Onset

Human Blastomycosis cases by Season of Onset, Minnesota, (n=324) No. of Cases Season of Onset Mar-May Jun-Aug Sept-Nov Dec-Feb

237 (64%) cases had probable county of exposure in Minnesota –176 (74%) of those cases exposed in county of residence 33 (9%) cases likely exposed outside of Minnesota 101 (27%) cases had unknown county of exposure Results (cont.)

Human Blastomycosis Cases by Probable County of Exposure, (n=237) Itasca St. Louis Chisago Washington Beltrami Cass Number of Cases

Human Blastomycosis Incidence, Cases that were Exposed in County of Residence (n=176) Incidence per 100,000 person-years Cook Big Stone Lake of the Woods Itasca

Minnesota Biomes Coniferous and Mixed Forest Tallgrass Aspen Parkland Prairie Grassland Deciduous Forest Minneapolis-St. Paul Metropolitan Area Modified from Minnesota DNR,

Exposure Frequency Among Cases (n = 273*) Exposure/Activity% Woodcutting38 Gardening31 Fishing31 Excavation30 Hiking27 Cabin26 Hunting19 Camping15 *Median number of cases with one or more exposures

Statewide incidence of 0.58 cases per 100,000 person-years –Ranges from 0 to 4.6 cases per 100,000 person-years Northeast and North central part of the state most endemic –Coniferous and Mixed Forest Biome Recently more cases along St. Croix River bordering Wisconsin Discussion

Minnesota Biomes Coniferous and Mixed Forest Tallgrass Aspen Parkland Prairie Grassland Deciduous Forest Chisago and Washington Counties Modified from Minnesota DNR,

Majority of cases are male and between 30 and 59 years of age –Possibly due to gender-specific activities American Indians affected by blastomycosis more than other minority groups. However, higher populations in endemic region Case-control study necessary to better answer these questions and determine specific risk factors –Recent IRB approval Discussion

Time from admission to diagnostic testing significantly longer in fatal cases –delayed diagnosis Data suggest early detection is critical in preventing fatal outcome Discussion

Blastomycosis difficult to diagnosis –Rare –Symptoms begin as non-specific respiratory illness –Often confused with bacterial pneumonia –Most common diagnosis method is culture but takes 3 to 4 weeks –Contributes to delay in diagnosis Discussion

Smears give same day results; Blastomyces is pathognomonic Discussion

Conclusion The association between delayed diagnosis and case fatality indicate that increased awareness among clinicians and the public could lead to earlier detection and treatment, and reduced mortality due to blastomycosis

Acknowledgments Minnesota Department of Health Brittani Schmidt Linda Gabriel Foodborne, Vectorborne, and Zoonotic Disease Unit Reporting Health Care Facilities