Health in Ye Olde Mouldy House

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Health in Ye Olde Mouldy House

• Michael R. McGinnis. Ph.D.
• Department of Pathology
• University of Texas Medical Branch
• Galveston, TX 77555-0609
• michael.mcginnis_at_utmb.edu

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Evaluate Potential or Actual Mould-related
Health Issues

• Establish the cause-effect relationship
  between indoor amplification of fungi and the
  health problem of the building resident.

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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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Asthma Symptoms
1. difficult to breathe 2. wheezing 3. shortness
of breath 4. coughing 5. constriction of air
passages 6. Inflammation of air passages
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Allergic Symptoms
1. runny nose 2. eye irritation 3. cough 4.
congestion 5. aggravation of asthma
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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. a. bio-signal compounds b.
mycotoxin biosynthetic pathway molecules
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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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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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Aw Levels for Colonization

• Low (aw lt0.85), primary colonizer
• a. Aspergillus versicolor (25C)
• b. Eurotium spp.
• c. Penicillium aurantiogriseum
• d. P. brevicompactum
• e. P. chrysogenum
• f. Wallemia sebi

Flannigan et al. Microorganisms in Home and
Indoor Work Environments.Taylor Francis,
London, 2001.
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2. Intermediate (aw 0.85-0.90),
secondary colonizer a. Aspergillus
flavus b. A. nidulans c. A.
sydowii d. A. versicolor (12C)
e. Cladosporium cladosporioides f.
C. sphaerospermum
Flannigan et al. Microorganisms in Home and
Indoor Work Environments.Taylor Francis,
London, 2001.
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3. High (aw gt0.90), tertiary colonizer
a. Alternaria alternata
b. Aspergillus fumigatus c.
Chaetomium spp. d. Exophiala spp.
e. Fusarium spp. f.
Memnoniella echinata g.
Phialophora spp. h. Rhodotorula
spp. i. Stachybotrys chartarum
j. Trichoderma spp.
Flannigan et al. Microorganisms in Home and
Indoor Work Environments.Taylor Francis,
London, 2001.
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Risk of Developing Disease Following Mould
Exposure
1. Existing respiratory condition (allergies,
chemical sensitivities, or asthma) 2. Infants and
young children 3. Elderly 4. Impaired immune
system
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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

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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? 8. Are there surgical specimens a.
tissue sections b. gross description of
specimen
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Thought Process (continued)
c. fungal infectious disease d. ask about
family pets 4. What is the residents past
medical history for a. respiratory
disease b. allergic disease c. sinusitis
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Thought Process (continued)
9. Is there mold count data for the
outdoor air a. daily and seasonal data
(weather reports and summaries) b.
intensity of mold counts during
investigation 10. What are the levels of other
allergens such as pollen, mites?
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Proof of Cause-Effect Relationship Criteria
1. Fungus, secondary metabolites, or both present
at fungal growth site or in air. 2. Fungus,
secondary metabolites, or both cause disease in
animals. 3. Fungus, secondary metabolites, or
both cause disease in human tissue cell
cultures. 4. Demonstrate fungus in clinical
specimens.
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Proof of Cause-Effect Relationship Problems
1. When discussing fungi in general, criteria
easily met. 2. When discussing specific fungi,
all criteria usually not met. 3. Distinguish
normal background exposure from indoor
amplification. 4. Absence of case definitions.
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Fungal Components in Pathogenesis
1. ß-1,3-D-glucan 2. Hydrophobins 3.
Mycotoxins 4. Volatile organic compounds
(trichodiene) 5. Dihydroxynaphthalene (DHN)
Melanin
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Stachybotrys chartarum Pathogenesis
Conidia, spores, hyphae, melanin, stachylysin,
VOCs, mycotoxins

• Inhalation
• Dermal contact
• Ingestion

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Stachybotrys chartarum Conidium (spore)
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(No Transcript)
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Deoxynivalenol (DON)
Diacetoxyscirpenol (DAS) Nivalenol (NIV),
Roridin, Satratoxin, T-2, Verrucarin
Trichodiene synthase
FPP
DHN-melanin
Aflatoxin B1 B2 G1 G2 Alternariol,
Citrinin, Penicillic acid, Ochratoxin,
Sterigmatocystin zearalenone
PKSs
Acetyl-coenzyme A Malonyl-coenzyme A
FPP Farnesyl pyrophosphate DHN-melanin
1,8-dihydroxynaphthalene melanin PKSs polyketide
synthases
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Mycotoxins Detected in Crude Building Materials
Acetyl-T-2 toxin Satratoxin
G Citrinine
Sterigmatocystin DAS
T-2 toxin
DON T-2
tetraol HT-2 toxin
T-2 triol Nivalenol
Verrucarine A
Ochratoxin A Verrucarol
RDRA ____________  Tuomi et al.
Appl. Environ. Microbiol. 2000, 661899-1904
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Ecology of Mycotoxins

• Not all strains of a known mycotoxin producing
  species may produce mycotoxins.
• a. two chemotypes of Stachybotrys
• chartarum
• 2. The strain that produced the mycotoxin may
  not be present at the time of sampling.

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Trichothecene Biosynthetic Pathway
Mol. Gen. Genet. 257421-432, 1998.
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Mycotoxin Symptoms
1. fatigue 2. nausea 3. headaches 4. respiratory
irritation 5. eye irritation 6. discomfort 7.
inability to concentrate 8. dermatitis
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Mycotoxin Pulmonary Disease

• Exposure dose.
• Site of deposition.
• a. tracheobronchial tree
• b. alveoli
• 3. Time in pulmonary zone.
• 4. Sensitivity of individual.

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Mycotoxicosis Severity

• Type of mycotoxin.
• Exposure duration and dose.
• Age.
• Nutritional status and health of individual.
• Synergistic effect with other chemicals or
  mycotoxins.
• Primary target organs.
• liver, lungs, kidney, and nervous,
• endocrine, immune systems

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Mycotoxins and Secondary Metabolites
1. Stachybotrys chartarum a. trichothecenes
18 b. non-trichothecenes
28 2. Aspergillus versicolor a.
sterigmatocystin and other secondary
metabolites 51
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Dihydroxynaphthalene Melanin Biosynthetic Pathway
Wang Breuil. Mol. Genet. Genomics 267557-563,
2002
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Melanized Cells
Cryptococcus neoformans
Cryptococcus neoformans
Aspergillus niger
Rosas et al. J. Immunol. Meth. 24469-80, 2000.