The association between
environment and fungal disease
Malcolm Richardson
University Hospital of South Manchester, and
The University of Manchester, UK
Fungi are in the air
Public concern
”Exorcising a mold monster”
”Attack on the killer mold”
”It’s 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”
Public concern: Europe
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Smaller scale than US
High public awareness
Regional
Limited research
Limited funding:
– EU: MOULDARRAY: Co-Operative Award:
Holland, Finland, UK, Denmark, Sweden
Patients live in mouldy houses:
exposure to Aspergillus and more......
Exposure in the garden
The tsunami and Sakseniae vasiformis
42 days LAMB
Snell & Yavakoli 2007; 119: 448-449
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
Aw < 0.80, ERH <80%
Aw < 0.80-0.90, ERH <80-90%
Aw >0.90, ERH >90%
water
Evaluate Potential or Actual Mouldrelated 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.
Indoor Events
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.
1.
Indoor Events
(continued)
Coordination of conidiogenesis or ascocarp
formation, melanin biosynthesis, mycotoxin
production.
9. Release of Volatile Organic Compounds.
8.
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.
Relationship Between Health
and Indoor Moulds
exposure from mould
growth indoors
indoors
outdoors
background exposure from all
sources and agents
individual’s health and genetics
Baseline health status
Final health status
Effect of indoor exposure
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.
Exposure and Disease (continued)
2. Disease
a. Allergic
• alveolitis, anaphylaxis, asthma,
conjunctivitis, dermatitis, hypersensitivity
pneumonitis, rhinitis, rhinosinusitis, sinusitis
b. irritant
Exposure and Disease (continued)
c. Mycotoxicosis
1). fungal volatile organic compounds
• mycotoxin biosynthetic pathway
2). mycotoxins and other secondary
metabolites
• inhalation, ingestion, skin contact
Exposure and Disease (continued)
d. Invasive
1). exceptionally rare
2). immunocompromised patients
3). aspergillosis
4). invasive sinusitis
Thought Process
1. Is there amplification of the fungus indoors?
2. What species has been identified growing within the
structure?
3. 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?
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?
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?
Hospital demolition
Hansen et al. JHI 2008; 70: 259-264.
Heavy excavation!
Nihtinen et al. 2007 BMT
Benet et al. CID 2007; 45: 682-686.
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”
Six links in the nosocomial infection chain
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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
Source of Aspergillus
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
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.
Toxic mould in the hospital
setting
Growth: 1-2 mm per hour!
ASPERGILLOSIS
Invasive aspergillosis
Aspergillus: Time to diagnosis of
aspergillosis after BMT
20
Neutropenia
Graft versus host disease
18
Wald et al. J Infect Dis
1997;175:1459
16
Cases
14
12
10
8
6
4
2
0
10
20
30
40
50
60
70
80
90 100
110 120 130
Days after transplant
140 150 160 170
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
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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