A Large NonRural Point Source Outbreak of Blastomycosis Occurring Near a Wisconsin Yard Waste Materi

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A Large Non-Rural Point Source Outbreak of
Blastomycosis Occurring Near a Wisconsin Yard
Waste Material Collection Site

• John R. Pfister, M.S., John R. Archer, M.S.,
  Shelly Hersil, B.S., C.H.E.S., Tammi Boers, R.S.,
  Kurt D. Reed, M.D., M.GIS, Jennifer K. Meece,
  Ph.D., Jennifer L. Anderson, B.S., Joshua W.
  Burgess, Ph.D., Thomas D. Sullivan, Ph.D., Bruce
  S. Klein, M.D., L. Joseph Wheat, M.D., Jeffrey
  P. Davis, M.D.

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Blastomycosis

• Fungal infection of humans and lower animals,
  especially dogs
• Caused by inhalation of conidia (spores) of the
  thermal dimorphic fungus Blastomyces dermatitidis
  
• Dimporphic grows as a mycelial form at room
  temperature, and a yeast form at 37C
• Uncommon but potentially serious

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Spectrum of Clinical Disease

• Clinical presentations are highly variable
• Symptoms of acute illness are non-specific
• fever, cough, chills, weight loss, malaise, and
  fatigue
• Pulmonary, cutaneous, and disseminated forms have
  all been described the pulmonary form
  predominates
• Asymptomatic self-limited infections occur
• May mimic many other disease processes
• bacterial community-acquired pneumnia, TB,
  carcinoma

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Blastomycosis Incidence Rates (Cases per
100,000) 1999-2005
Statewide Incidence 1.9 per 100,000
gt 20.0 Cases / 100K 6.0 to 20.0 Cases /
100K 2.0 to 5.9 Cases / 100K lt2.0 Case /
100K No Cases
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Recognition of 2006 Blastomycosis Outbreak

• LCHD notified on 2/15/2006 of 6 patients with
  blastomycosis DPH notified by LCHD
• E-mail health alert sent to medical providers
• News releases to local media
• Community educational meetings held
• Active surveillance identified 27 cases from Jan
  through April 2006
• Series of investigations conducted

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Investigations

• Epidemiologic
• Epi Curve Spot Map
• Comparisons with Historical Cases
• Case-Control Study
• Environmental
• Site Visits/Inspections/Interviews
• Climatologic/Meteorologic
• Laboratory
• Environmental Samples
• Clinical Specimens

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Epidemic Curve of Blastomycosis Study Cases
Enrolled (n21) and Excluded (n6) Case ID
Number (I)Irma, (T)Tomahawk, All Others
Merrill
Spring 2005
Week of Disease Onset
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Merrill Blastomycosis Case Patients,1999-2005
versus 2006
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Merrill Blastomycosis Case Patients, 1999-2005
versus 2006
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Case-Control Study

• Case definition
• Recruitment of controls
• random digit dialing
• matching of cases controls on age group sex
• Standardized questionnaire
• Telephone interview
• Defined estimated exposure period

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Estimated Exposure Period for Blastomycosis Case
Patients included in the Merrill Case-Control
Study (n21)(Exposure Period is 21 to 84 days
prior to onset of symptoms median45 days)
12/22/05 (75ile)
12/5/05 (Median)
11/18/05 (25ile)
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Case-Control Study Results
No association between illness and

• Time outdoors in woods, fields, or undeveloped
  areas
• Hunting, fishing or trapping
• Walking, jogging or biking near waterways or
  exposed shorelines
• Exposure to beaver dams
• Underlying medical conditions
• Immunosupressive medications
• Cigarette smoking

• Employment status
• Outdoor occupational exposures
• Fireplace wood use or indoor storage
• Dog ownership
• Water frontage or wetlands
• Distance from waterways
• Landscaping, brush cutting
• Gardening
• Yard waste collection or transport
• Exposure to rotten wood or vegetation

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Case-Control Study Results
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Aerial View of Merrill, WI
0.25 mi
0
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Merrill City Garage Yard Waste Collection Site
(Picture Taken April 11, 2006)
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Pine Needle Pile (Picture Taken April 11, 2006)
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Cumulative weekly precipitation departures from
normal, and drought index, Merrill, WI,
2005with estimated exposure period for
blastomycosis case patients.
Median Estimated Exposure Period
Palmer Drought Severity Index ------------------
-----------------Normal---------------------------
--------------Moderate----SevereModerate------
---Normal-------------
Data from the National Weather Service
cooperative observer, Merrill Wastewater
Treatment Plant provided by the Wisconsin State
Climatology Office, Atmospheric and Oceanic
Sciences Department, UW-Madison
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Daily Precipitation and High and Low Temperatures
(11/18/05-12/4/05), and Wind Speed and Direction
(11/27/05-12/4/05) - Merrill, Wisconsin
Data from the National Weather Service
cooperative observer, Merrill WI Wastewater
Treatment Plant provided by the Wisconsin State
Climatology Office, Atmospheric and Oceanic
Sciences Department, UW-Madison
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Laboratory Findings

• Environmental Samples
• Only 1 of 19 (5) positive by PCR
• All negative by mouse inoculation and culture
• Clinical Specimens
• All urine specs negative for Bd Ag
• 5 of 9 (56) case patient sera pos for Bd Ab
• Clinical Isolates
• 14 Outbreak isolates compared with 40
  non-outbreak isolates 13/14 (93) RFLP-Type A

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Presumed Point Source Outbreak

• Area of high endemicity for B. dermatitidis
• Spatial and temporal clustering of cases
• Age and sex distribution unlike sporadic, endemic
  cases
• No usual risk factors associated with illness
  among cases
• Favorable climatologic conditions for growth of
  organism
• Presence of large amounts of decaying organic
  debris capable of supporting growth in proximity
  to cases
• Debris material disturbed during estimated
  exposure period
• Favorable meteorologic conditions for airborne
  dispersal of spores during estimated exposure
  period
• Consistent bioaerosol studies with Aspergillus
  fumigatus
• Genetic similarities of outbreak isolates
• Failure to isolate organism is not unusual

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Conclusions

• The increase in the number of cases of
  blastomycosis in the Merrill area during early
  2006 most likely is related to
• favorable environmental, climatologic and
  meteorologic conditions, and
• unintentional practices, that
• facilitated the growth, spore formation, and
  dispersal of Blastomyces dermatitidis
• in close proximity to a residential neighborhood
• within this endemic area.

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Recommendations

• Community yard materials management activities
  should be located away from occupied properties.
• Employees engaged in mechanical agitation of
  decayed and rotting vegetation and organic debris
  should use appropriate respiratory protective
  equipment.
• Residents, especially people with impaired immune
  systems, should be aware of the risks associated
  with soil-disturbing activities (e.g., gardening
  or landscaping) and consider the use of
  HEPA-filter or dust masks when participating in
  such activities.

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Recommendations continued

• Persons with prolonged exposures, particularly
  the elderly or immune compromised, should be
  aware of signs and symptoms of blastomycosis and
  immediately contact their health care providers
  if they have an illness consistent with
  blastomycosis.
• Clinicians should suspect blastomycosis in anyone
  presenting with pneumonia-like illness who does
  not respond to conventional management in a
  timely fashion.
• In states where blastomycosis is endemic there is
  public health value in prompt reporting of
  confirmed or suspected cases of blastomycosis to
  the patients local health department for
  epidemiologic investigation.

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Blastomycosis

• Two clinical presentations
• A primary cutaneous infection which usually
  remains localized to one area of the body
• May indicate systemic disease
• Primary pulmonary with possible secondary
  dissemination.
• 30-45 day incubation
• Mimics flu progressing to cough, weight loss,
  chest pain, low grade fever
• Asymptomatic in gt50 of those infected

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Systemic Disease

• Common sites of infection in systemic disease
• Bones---long bones, ribs, vertebrae
• Joints
• Genitourinary tract----prostate, epididymis
• CNS-----common in AIDS (40), uncommon in
  immunocompetent (lt5)

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Laboratory Diagnosis

• Histology/Cytology
• Direct Microscopic Examination
• Culture
• Antigen Detection
• Serology

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Specimens

• Sputum
• Bronchial washings
• Bronchial alveolar lavages (BALs)
• Post-bronchoscopy sputum
• Tissues
• Pleural fluid
• CSF
• Urine

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Histology/Cytology

• Body fluids or tissue specimens
• Look for the characteristic yeast form
• Large (8-15um) and thick walled
• Single daughter cell (bud) with a broad-based
  buds
• Stains
• Gomori methenamine-silver (GMS)
• Periodic acid-Schiff
• Papanicolaou

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Histology/Cytology

• Sensitivity
• 56 of all cases
• 72 of pulmonary

PAS Stain
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Hematoxylin and Eosin
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Gomori Methenamine-Silver
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Direct Microscopy in the Micro Lab

• KOH Prep or Wet Mount
• 36 sensitivity for a single specimen
• 46 sensitivity for multiple
• Calcofluor white
• Requires a fluorescence microscope
• Particularly useful when organisms are sparse
• Gram stain
• Gram negative
• Bizarre morphology

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KOH Wet Mount
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Calcofluor White
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Blastomyces Gram Stain 400X
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Blastomyces Gram Stain 1000X
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Culture Media

• Non-selective
• Sabouraud dextrose
• Potato flake agar
• Enriched
• SABHI Agar
• Yeast-extract phosphate agar
• BHI w/wo blood
• Selective
• Mycosel---dermatophytes
• BHI w/wo blood plus antibiotics
• Inhibitory mold agar

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Culture Sensitivity

• Sputum
• 75 with single specimen
• 86 with multiple
• Bronchoscopy
• 92 of patients

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Blastomyces dermatitidis---30C Incubation
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Blastomyces dermatitidis---30C Incubation
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Mold Phase
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Mold Phase---LPCB Stain
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Culture Identification

• The characteristic morphology of the mold form of
  B. dermatitidis is shared with several other
  potential pathogens and saprophytes
• Chrysosporium sp
• Scedosporium apiospermum

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Culture Identification

• Confirmation of identification
• Conversion to yeast phase
• Cotton seed agar or BHI blood agar
• 37C Incubation
• Exoantigen test
• Nucleic acid probes
• Gen-Probe

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Blastomyces----Yeast Phase
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Lactophenol Cotton Blue
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Serology

• Complement fixation
• Neither sensitive nor specific
• Immunodiffusion---most useful
• Using A antigen, 52-80 sensitive
• Virtually no cross reactivity with other fungi
• Higher sensitivity in disseminated disease (88)
  vs localized (33)
• Kits
• Gibson Laboratories, Immuno-Mycologics, and
  Meridian Diagnostics

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Serology

• Radioimmunoassay
• Cell wall protein antigen WI-1---Klein et al
• 85 sensitivity
• Enzyme immunoassay
• Purified A antigen
• 77 sensitive in a common-source outbreak
• Peak seroprevalence and titers at 50-70 days post
  onset

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Antigen Detection

• MiraVista Diagnostics
• Urine, serum, CSF, other body fluids
• Sensitivity greatest in urine
• 70-80 sensitivity in disseminated disease
• Close to 100 in pulmonary cases
• Serum approximately 50 sensitive
• Cross-reactivity
• Histoplasma, Paracoccidiodes, Penicillium

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