The association between environment and fungal disease

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The association between environment and fungal
disease

• Malcolm Richardson
• University Hospital of South Manchester, and
• The University of Manchester, UK

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Fungi are in the air
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Public concern

• Exorcising a mold monster
• Attack on the killer mold
• Its everywhere. Tales about rampant toxic mold
  get plenty of attention, but science tells a less
  dramatic story
• The mold rush
• One in four homes in the UK is infested with
  toxic mould

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Public concern Europe

• Smaller scale than US
• High public awareness
• Regional
• Limited research
• Limited funding
• EU MOULDARRAY Co-Operative Award Holland,
  Finland, UK, Denmark, Sweden

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Patients live in mouldy housesexposure to
Aspergillus and more......
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Exposure in the garden
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The tsunami and Sakseniae vasiformis
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42 days LAMB
Snell Yavakoli 2007 119 448-449
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Key issues

1. Air as a source of human infection
2. Water as a source of human infection
3. Other environmental sources of human infection
4. Hospital versus community acquisition of
   infection
5. Molecular strain typing of Aspergillus species

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Aw lt 0.80, ERH lt80
Aw lt 0.80-0.90, ERH lt80-90
Aw gt0.90, ERH gt90
water
Aw Minimum water activity level at 25C ERH
Equilibrium relative humidity
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Evaluate Potential or Actual Mould-related
Health Issues

• We have to establish the cause-effect
  relationship between indoor amplification of
  fungi and the health problem of the building
  resident or hospital patient.

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Indoor Events
1.  Intrusion and condensation of water. 2. 
Impact of conidium or spore from air.
3.  Germination of conidium or spore.
4.  Penetration of substrate. 5.  Development
of vegetative hyphae. 6. Translocation of
nutrients. 7. Development of aerial hyphae.  
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Indoor Events(continued)
8. Coordination of conidiogenesis or ascocarp
formation, melanin biosynthesis, mycotoxin
production. 9. Release of Volatile Organic
Compounds.
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Indoor Events (continued)
10. Liberation and air dispersal of conidia,
spores, hyphal fragments, cell wall pieces,
melanin particles. 11. Inhalation, skin
contact 12. Absorption of mycotoxins. 13. Antigen
challenge.
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Relationship Between Health and Indoor Moulds
exposure from mould growth indoors
indoors
background exposure from all sources and
agents
outdoors
individuals health and genetics
Baseline health status
Final health status
Effect of indoor exposure
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Exposure and Disease
1. exposure a. inhalation of conidia,
spores, hyphae, cell wall components,
mycotoxins, MVOCs.     b. contact by conidia,
spores, hyphae, cell wall components,
mycotoxins, MVOCs.     c. ingestion of conidia,
spores, hyphae, mycotoxins.
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Exposure and Disease (continued)
2. Disease a. Allergic
alveolitis, anaphylaxis, asthma,
conjunctivitis, dermatitis, hypersensitivity
pneumonitis, rhinitis, rhinosinusitis,
sinusitis b. irritant
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Exposure and Disease (continued)
c. Mycotoxicosis 1). fungal volatile organic
compounds mycotoxin biosynthetic
pathway 2). mycotoxins and other secondary
metabolites inhalation,
ingestion, skin contact
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Exposure and Disease (continued)
d. Invasive 1). exceptionally
rare 2). immunocompromised patients
3). aspergillosis 4). invasive
sinusitis
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Thought Process

• Is there amplification of the fungus indoors?
• What species has been identified growing within
  the structure?
• Are there signs and symptoms compatible with
• a. allergic fungal disease?
• b. fungal toxicosis?
• 4. What is the residents past medical
• history for
• a. respiratory disease?
• b. allergic disease?
• c. sinusitis?

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Thought Process (continued)
5. Have mycotoxins been detected in a.
building materials? b. air samples? 6. Is
serology an option? 7. Is skin testing an option?
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Thought Process (continued)
9. Is there mould count data for the
outdoor air a. daily and seasonal data
(weather reports and summaries) b.
intensity of mould counts during
investigation 10. What are the levels of other
allergens such as pollen, mites?
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Hospital demolition
Hansen et al. JHI 2008 70 259-264.
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Heavy excavation!
Nihtinen et al. 2007 BMT
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Benet et al. CID 2007 45 682-686.
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Key statements

• a significant relationship between environmental
  fungal contamination in haematology wards and the
  incidence of IPA
• a straightforward association between
  environmental modification and decreased IA
  incidence

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• Six links in the nosocomial infection chain
• The causative agent environmental moulds
• Mode of transmission air, water, food
• Susceptible host high risk patients
• Portal of entry respiratory tract, skin
• Portal of exit person to person transmission
• Reservoir air, water

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Source of Aspergillus
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Air as a source of human infection

• Inhalation most common portal of entry
• Temporal association between hospital-based
  outbreaks and construction
• Very little data on base-line concentrations
• Longitudinal studies show no correlation between
  sporadic cases of IA and changes in spore count

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Concentrations of airborne Aspergillus compared
to the incidence of invasive aspergillosis lack
of correlation

• 54-week air sampling period
• A. fumigatus and A. flavus mean 1.83 cfu m-3
• Individual samples maximum 11.6 cfu m-3
• No correlation with season or ward
• 6 cases of IPA during sampling period
• No association with fluctuations in air count
• Conclusion the available data do not provide a
  firm link between hospital exposure and an
  increased incidence of aspergillosis
• Hospenthal et al., Medical Mycology 1998.

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Toxic mould in the hospital setting
Growth 1-2 mm per hour!
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ASPERGILLOSIS
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Invasive aspergillosis
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Aspergillus Time to diagnosis of aspergillosis
after BMT
Graft versus host disease
20 18 16 14 12 10 8 6 4 2 0
Neutropenia
Wald et al. J Infect Dis 19971751459
Cases
10 20 30 40 50 60 70 80 90 100 110 120 130 140 150
160 170
Days after transplant
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Nosocomially vs. community-acquired IA

• Nosocomial
• Due to break in, or contamination of hospital
  water system
• Due to break in HEPA filtration system
• Due to construction or demolition work in the
  hospital

• Community-acquired
• Due to housing quality
• Due to occupational activities
• Due to leisure activities
• Due to exposure to Aspergillus spores (minimum
  effective dose not known)

Praz-Christinaz et al. Transplant Infect Dis
2007 9 175-181
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