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Understanding Mold Related Illnesses

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Title: Understanding Mold Related Illnesses


1
Understanding Mold Related Illnesses
  • University of North Texas Health Science Center
    in Fort Worth
  • Stevan Cordas DO MPH
  • Occupational, Allergic and Environmental Medicine.

2
Molds! An Overview
  • Molds are non chlorophyll containing filamentous,
    spore producing organisms containing chitin in
    cell walls instead of cellulose and lignin and
    ergosterol instead of cholesterol.
  • Of over 100,000 types, about 300 are pathogenic
    to man.
  • Four types of disease Hypersensitivity,
    mycotoxicosis, mycetismus and infection.

3
Mycotoxicoses
  • The big scary thing
  • Example Ergotism
  • Claviceps purpurea
  • Infects rye
  • Produces sclerotia
  • Ergot is released
  • Huge outbreaks
  • Salem witch trials?
  • Image from www.TomVolkFungi.Net

4
Classification of Pathogenic Molds
  • Actinomycetes Nocardiosis, Streptomycetes
    mycetoma, Lumpy jaw- These are really bacteria.
  • Yeasts Candidiasis, Cryptococcosis.
  • Superficial mycosis Tinea.
  • Filamentous fungi- Aspergillosis,
    Chromoblastomycosis.
  • Dimorphic fungi Histoplasmosis,
    Coccidiomycosis, Blastomycosis.

5
Lumpy Jaw from Actinomycetes isreali
6
Diagnosis
  • Skin scrapings KOH.
  • Skin testing except for allergy testing not
    commonly used - i.e. Histo and Coccidio testing.
  • Serology Latex agglutination IgM, double
    immunodiffusion and Complement fixation, ELISA-
    IgG.
  • Direct fluorescent microscopy.

7
Diagnosis
  • Biopsy and histopathology Gomori methenamine
    silver stain.
  • Culture Sabouraud dextrose agar pH 5.6. two
    samples cultured at 37 C and 25 C to check for
    dimorphism.
  • Immunological and other methods to examine
    mycologic byproducts endotoxins, mycotoxins
    just emerging.

8
The Known and the Unknown
  • Many molds appear not to be human pathogens. Some
    are beneficial PCN and other antibiotics, ergot,
    cyclosporin etc.
  • Some mold problems are clearly defined and well
    understood.
  • These include various manifestations of
    Aspergillosis and Candidiasis.
  • No review of mold pathogens would be complete
    without at least some overview of these pathogens.

9
Candida From a Skin Lesion
10
Candida Species
  • Most common form of mycotic disease in man. About
    200 species. Do not call them Moniliasis.
    Torulopsis species are now added to the genus
    Candida.
  • They are differentiated mainly by fermentation
    characteristics and morphology in the laboratory .

11
Candida Species
  • These are asexual imperfect yeasts (Division
    Fungi Imperfecti).
  • May produce budding (blastoconidia), pseudohypae
    or actual mycelium. The latter is usually
    affiliated with invasiveness.
  • Some forms are drug resistant.
  • Ex C. glabrata, tropicalis, krusei, lusitaniae.
  • Infections can be superficial, local, or
    systemic.
  • Recurring yeast infections defective CMI.

12
Candida Species
  • Candida is the leading cause of opportunistic
    infections. Candida albicans is the most common
    pathogenic species.
  • They can affect nipples when breastfeeding, mouth
    (thrush), vagina, skin and nails (onchomycosis),
    brain (abscess and meningitis), gastrointestinal
    tract esophageal, pharyngeal, intestinal,
    cystitis and pyelonephritis, endocarditis, liver,
    spleen and lung including fungus ball.

13
Penile Candida
14
Cutaneous Candida
15
Cerebral Candidiasis
16
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17
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18
Aspergillosis
  • 900 species of Aspergillus. 75 of human
    infection caused by A. fumigatus. A. flavus next
    most common and more likely to disseminate.
    Usually these molds found in neutropenic or
    immunocompromised hosts (esp. HIV).
  • Even large amounts normally wont bother a
    normal person.
  • May cause 3 types of problems. Allergic
    Localized - Invasive.

19
A. Flavus Conidia
20
Different Types of Allergic Patterns to
Aspergillus
  • The conidia of Aspergillus can precipitate
    bronchial asthma.
  • Allergic rhinitis.
  • Allergic sinusitis.

21
Different Types of Allergic Patterns to
Aspergillus
  • Allergic bronchopulmonary aspergillosis (ABA)
    Transient atelectatic lines on x ray, fever,
    eosinophilia sputum, blood. More persistent
    bronchial obstruction.
  • Extrinisic allergic bronchiolitis (EAB) - A.
    clavatus 4 hours after breathing malt or grain.
    Repeated bouts can lead to pulmonary fibrosis.

22
Invasive Aspergillosis in HIV
23
Granulomatous Response and Mycelia of A.
Fumigatus.
24
Aspergillus of the Skin
25
Aspergillus in the Human Mouth
26
Treatment of Various Aspergillus Infections.
  • ABA Corticosteroids.
  • EAB Same avoid moldy grains.
  • Invasive liposomal Amphotericin B, regular
    Amphotericin B or itraconazole.
  • Aspergilloma Removal if massive hemoptysis
    occurs only.
  • Resection with Sino naso orbital type is
    required. Usually A. flavus.

27
Molds and Indoor Contamination
  • Black molds are causing the closing of schools,
    businesses, firehouses, apartments and entire
    buildings.
  • Some toxigenic molds are not black.
  • Some black molds are not Stachybotrys.
  • Much hysteria.
  • Some fact.

28
Molds
  • Separate kingdom Neither plant or animal.
  • Indoor molds include Cladosporium,Penicillium,
    Aspergillus, Alternaria, Wallenia, Chaetomium,
    Acremonium and less commonly Stachybotrys
    chartarum (the famous black mold).

29
Products From Molds
  • Allergens
  • Endotoxins,
  • 1-3 B-D- Glucans
  • Mycotoxins
  • Ergosterols
  • Extracellular Polysaccharides
  • VOC
  • Enzymes

30
Exposures From Work or Schools
  • Of 131.2 Million workers in the US, 70 Million
    work indoors. OSHA reported that 30 of those
    indoors are subjected to poor air quality.
  • NIOSH reported that of 104 buildings
    investigated, 42 had water damage.
  • 1/2 of our 115,000 schools in the US have a
    problem with indoor air quality. 55 million
    children affected. (EPA).

31
EPA
  • The Indoor Air Quality (IAQ) Tools for Schools
    Kit (Kit) shows schools how to carry out a
    practical plan of action to improve indoor air
    problems at little or no cost using
    straightforward activities and in-house staff. 
    Indoor Air Quality Tools for Schools is
    co-sponsored by the National PTA, National
    Education Association, Council for American
    Private Education, Association of School Business
    Officials, American Federation of Teachers, and
    the American Lung Association.

32
Exposure From Homes
  • US Census 1998 indicates that 13 or 10.9 million
    US homes had water damage from inside.
  • 16.9 million or 21 of US homes had leakage from
    outside.

33
Potential Indoor Agents
  • Fungal products
  • Bacteria and their endotoxins
  • Viruses
  • Volatile Organic Compounds
  • Other Materials outgassing
  • Heavy metals (mercury)

34
Clinical Observations
  • The presence of mold as observed or bulk sampling
    does not correlate with clinical symptoms well.
    There must be the presence of spores, fragments
    or metabolites in the air or direct contact or
    ingestion of the material to make problems.
  • Problems develop and vary with atopic status,
    age, state of health and concurrent exposures.
    COPD and allergic individuals more prone.

35
Allergic Statistics
  • 50 Million allergic rhinitis cases in US.
  • 17.3 Million asthmatics in the US (CDC).
  • Expected to double by 2020.
  • 15 of asthmatics are reported to be from
    occupational causes.
  • 450 Substances in the workplace that can cause
    occupational asthma.
  • Molds are the second most common allergy in the
    US after dust mites.

36
Molds Known to Cause Allergies
  • Absidia
  • Agaricus
  • Alternaria
  • Amillaria
  • Aspergillus
  • Aureobasidium
  • Botrytis
  • Candida
  • Cantharelius
  • Chaetomium
  • Chlorophyllum
  • Cladosporium
  • Claviceps
  • Coniosporium
  • Coprinus
  • Curvularia

37
Molds Known to Cause Allergies
  • Dacrymyces
  • Daldinia
  • Epicoccum
  • Epidermophyton
  • Erysiphe
  • Eurotum
  • Fuligo
  • Fusarium
  • Ganoderma
  • Gliocladium
  • Helminthosporiu
  • Hypholoma
  • Lycogala
  • Monilia
  • Mucor
  • Nigrospora

38
Molds Known to Cause Allergies
  • Paecilomyces
  • Penicillium
  • Phoma
  • Pleurotus
  • Podaxis
  • Polyporus
  • Puccinia
  • Rhizopus
  • Rhodotorula
  • Saccharomyces
  • Serpula
  • Sporobolomyces
  • Sporotricium
  • Stachylidius
  • Stemonitis
  • Stemphylitis

39
Molds Known to Cause Allergies
  • Stereum
  • Tillelia
  • Trichoderm
  • Trichothec
  • Urocystis
  • Usilago
  • Xylaria

40
Fungal Sinusitis
  • Allergic fungal sinusitis
  • Chronic invasive fungal sinusitis
  • Indolent granulomatous fungal sinusitis
  • Fungal ball (mycetoma)
  • Acute invasive fungal sinusitis

41
Bipolaris Spicifera
42
Clinical Observations
  • A number of investigators are observing patients
    that are not allergic but have similar symptoms -
    Irritative and neurologic.
  • In most cases, the symptoms persist as long as
    they are in the moldy environment and get better
    eventually if they leave it.
  • We are interested in investigating and helping
    those cases that dont seem to improve on their
    own.

43
Animal Mycotoxicosis
  • Well known to vets and grain handlers.
  • Causes corn poisoning in horses
    (leukoencephalopahty) fumonisin. FDA guidance.
  • Deoxynivalenol (DON) is a vomitotoxin in man and
    animals. Cold wet Pigs affected most wheat
    contamination. Common.
  • Zearalenone produces feminization of animals and
    interferes with reproduction.

44
Mycotoxins
  • Over 400 now identified.
  • 5 types Ochratoxins (nephrotoxic), Rubratoxins,
    Fumonisins (produce many harmful types),
    Aflatoxins (the most carcinogenic natural
    substance known), and trichothecenes (3 classes).
  • One fumonisin was weaponized T2.
  • Orenberg, Siberia 1943 Alimentary toxic aleukia
    (ATA).

45
Main Mycotoxin generating molds
Aspergillus flavus, Emericella (Aspergillus)
nidulans, Penicillium expansum, Aspergillus
fumigatus, Paecilomyces variotii, Penicillium
italicum, Aspergillus niger, Penicillium
aurantiogriseum, Penicillium roqueforti,
Aspergillus ochraceus ,Penicillium
brevicompactum, Penicillium viridicatum,
Aspergillus parasiticus, Penicillium chrysogenum,
Stachybotrys chartarum, Aspergillus ustus,
Penicillium citrinum, Trichoderma harzianum,
Aspergillus versicolor, Penicillium corylophilum
,Trichoderma viride, Chaetomium globosum,
Penicillium digitatum, various Fusarium.
46
T2
47
T2 As a Weapon
  • Only biological agent that can kill through
    intact skin.
  • Some evidence that it killed villagers in
    Afghanistan, Laos and Kampuchea.
  • Produces intense burning and skin necrosis,
    pulmonary edema, multisystem disease resembling
    radiation poisoning.
  • Sadam, aflatoxin and the Scud missiles. The
    future?

48
Clinical Observations -Controversy
  • The role of mycotoxins creating illness, other
    than allergies, from those molds found in homes
    and schools is controversial.

49
Clinical Observations -Controversy
  • Case reports and cross sectional studies
    primarily. Case controls starting to appear. CDC
    1993 Cleveland cohort. Can not conclusively prove
    causation.
  • Ann Allergy Asthma Immunol 2001 Dec87(6 Suppl
    3)57-63. There is a failure to establish, after
    a review of the literature, that human disease
    can be attributable to Stachybotrys even in water
    damaged buildings. An exception may be pulmonary
    hemosiderosis/hemorrhage in children.

50
CDC
  • Cluster of infants in Cleveland with Pulmonary
    hemorrhage and hemorrhage. 47 cases 6 deaths
    1993-1996. First 10 cases studied 1993 by CDC.
    Stachy found in some homes and also in homes of
    controls without symptoms. Tobacco smoke
    incriminated. Was Stachy a cofactor?
  • June 17 1999 Update report by CDC- No
    conclusion that it was.

51
Some References Supporting Toxigenic Molds and
Illness.
  • Sudakin DL. AJIM 1998 August 34(2)184-190
  • Etzel RA. JAMA 2002 Jan 23-30 287(4) 425-7 (Good
    review)
  • Johanning E, Landsbergis P. Clinical findings
    related to indoor fungal exposure review of
    clinical data of a specialty clinic in
    Bioaerosols, Fungi and Mycotoxins Health
    Effects, Assessment, Prevention and Control.
    Johanning E. ed. Mount Sinai School of Medicine,
    Department of Community Medicine, Fungal Research
    Group (2001) Fungal Research Group

52
World Health Organization
  • The World Health Organization states, the
    mycotoxins described in their treatise, are
    acutely toxic, carcinogenic, immunosuppressive
    and oestrogenic and have been the cause of
    serious human and/or animal diseases. The
    potential immunosuppressive role of mycotoxins in
    the aetiology of human disease is an especially
    important issue, which requires further careful
    study.

53
World Health Organization Contd.
  • Every effort must be made to minimize the
    occurrence of mycotoxins in food and feed grains.
    Undoubtedly, the implementation of improved
    handling and quality control procedures will have
    a significant effect on the incidence of
    mycotoxins in important foods and feeds
    throughout the world.

54
Other Reviews Different Opinions.
  • Health Implications of Fungi in Indoor
    Environments. RA Samson, B. Flannigan, et al eds.
    Elsevier Science BV, Amsterdam, the Netherlands,
    1994.
  • We have known for years that aflatoxin, a
    mycotoxin produced by Aspergillus flavus, is a
    Class 1 carcinogen. Aflatoxin in association with
    Hepatitis B is responsible for many thousands of
    deaths per year., This probably also includes
    Hepatitis C.

55
Other Reviews Different Opinions
  • Other suspected carcinogenic mycotoxins include
    Ochratoxin A (urinary tract cancers and kidney
    disorders in Eastern and Northern Europe),
    zearalenone, which produce estrogenic effects in
    man and animals, fumonisins which appear to be
    associated with esophageal cancer in parts of
    China and Africa Fumonisins have been implicated
    in cases of anencephaly along the Rio Grande in
    Texas. They block folate.

56
Other Reviews Different Opinions
  • Trichothecenes of various types are generally
    immunosupressives and may have neurotoxic or
    hemolysin properties. Fungal byproducts are also
    teratogenic, and mutagenic and can influence the
    reproductive cycle of animals and possibly man.
    Much research in this area is still required.
    Other illnesses related to molds are mold related
    sinusitis, Farmers lung, organic toxic dust
    syndrome, hypersensitivity pneumonitis,
    occupational rhinitis and asthma, and building
    related illness. .

57
Clinical Observations
  • Evidence leans toward mycotic byproducts being
    contributory to human illness in some cases with
    high exposure or genetic susceptibility.
  • Many fungi can make mycotoxins including
    Tricoderma, Menmoniella, Aspergillus, Fusarium,
    and Penicillium in addition to S. chartarum.

58
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59
Stachybotrys Chartarum
  • Uses cellulose as its carbon source (wall board,
    sheet rock (gypsum), paper, ceiling tile).
  • Not very allergenic.
  • Implicated in infant Hemosiderosis and hemorrhage
    (CDC).
  • 15 strains not all produce mycotoxins.
  • Depends on the strain and moisture.
  • Can infest grains that are moist, barns.
  • Causes Stachybotrytoxicosis.

60
Mycotoxins
  • Stachybotrys produces a number of trichothecene
    mycotoxins that inhibit DNA and other protein
    metabolism, Reduce immune responses and cause
    cell apoptosis. There are 15 species of this
    mold.
  • The mycotoxins are Satratoxins, Roridin,
    lactams, Isosatratoxin, Verrucarin, Epiisororidin
    and Trichoverrol B.

61
Cognitive Impairment Associated With Exposure to
Toxigenic Fungi
  • Gordan et al at Mt Sinai School of Medicine have
    shown that 13 out of 20 subjects tested with
    neuropsychological batteries, who were exposed to
    Stachybotrus, have cognitive impairment. This was
    especially in verbal learning, attention/concentra
    tion, set shifting. Also this group had a higher
    number of physical and behavioral symptoms.

62
Encephalopathy
  • Auger and his team report several cases of toxic
    encephalopathy apparently from neurotoxins from
    indoor molds.
  • Auger PL, Gordeau P et al 1. 1998 AJIM 25(1)
    41-42.

63
Other Molds of Concern and Their Mycotoxins.
  • Aspergillus flavus Kojic acid, 3-nitoproprionic
    acid, aflatoxin B-1, aspergillic acid.
  • Alternaria tenuazonic acid, alternariol,
    altertoxins.
  • Aspergillus niger naphtha-pyrones, malformins.
  • Also can make Orchratoxins and Sterigmatoeystin
    toxins.

64
Other Molds of Concern and Their Mycotoxins.
  • Cladosporium herbarum cladosporic acid.
  • There are over 400 more mycotoxins.
  • Cryptosporidia transient flu in normal patients.
    Can kill a immunocompromised patient. May respond
    to Diflucan.
  • Histoplasmosis Capsulatum. Coccidiomycosis,
    Blastomycosis. Dont forget these.

65
Coccidiomycosis spherule with endospores
66
Coccidiomycosis Prevalence in the US
67
Paracoccidiomycosis with Buds and Giant Cell
Formation.
68
Some Known Clinical Responses to Fungi.
  • Organic toxic dust syndrome Can come from a
    single exposure. Flu-like, not immune mediated.
  • Hypersensitivity pneumonitis- Repeated exposures,
    immune mediated. Can lead to interstitial
    fibrosis in rare cases.
  • Fungal sinusitis.
  • Activation or aggravation of bronchial asthma or
    other allergic manifestations.

69
Common Symptoms Found in Indoor Mold Exposures.
  • Generally non-specific.
  • Skin itching, rashes, periorbital swelling.
  • GI - Anorexia, diarrhea.
  • Muscular pains. Flu-like.
  • Low grade fever.

70
Common Symptoms Found in Indoor Mold Exposures.
  • Respiratory symptoms rhinitis, sinusitis,
    asthma, SOB, chest discomfort, epistaxis.
  • Neurologic concentration, memory, fatigue,
    headaches, unsteadiness.

71
Diagnosis
  • Reasonable suspicion on the part of the health
    care provider or the patient.
  • Screening or IAQ testing showing presence of
    toxigenic mold.
  • Rule out confounding variables.
  • Consider toxigenic and allergic testing to
    confirm correlation.

72
Testing
  • Blood mycotoxins. PCR, IgE, IgA and IgG fungal
    tests. Precipitins.
  • Blood allergy or skin allergy testing.
  • General tests to rule out other causes of these
    symptoms. HIV, ANA.
  • Pulmonary function testing.
  • Imaging studies of sinuses, chest etc. as
    appropriate. Immune studies.
  • May test for autoantibodies to glial and neuronal
    tissue.

73
Treatment for Indoor Mold Related Symptoms
  • Remove source of water or humidity. Keep it below
    55.
  • Remove the subject from the environment. In most
    cases it is reversible.
  • Remediate using professional assistance.

74
Treatment (Ctd)
  • Recheck IAQ afterwards.
  • Palliative therapy, antihistamines, dietary,
    nutritional, emotional, immunotherapy.
  • Trial of itraconazole or fluconazole?
  • Trial of mold yeast free diet?
  • Natural anti fungals - caprylic acid, Pau d
    Arco?

75
Experimental Therapies.
  • Xolair and Anti IgE RhumAb.
  • Valinomycin is produced by a bacterium
    (Streptomyces griseus) living closely associated
    with the fungus Stachybotrys is a poison in sick
    buildings that is being investigated.
  • Anidulafungin (Versicor).
  • Voriconazole (Pfizer).

76
Natural or Alternative Approaches That Have
Reportedly Helped Animal Models
  • Quinolones found in Taheebo bark (Pau DArco).
    Other herbs curanderos.
  • Dietary modification and improving nutritional
    status with vitamins.
  • Immunostimulants Astragalus, etc.
  • Cognitive therapy.
  • Homeopathy?.

77
Preventing Mold Buildup.
  • Use air conditioner or dehumidifier during humid
    months.
  • Be sure home has adequate ventilation, including
    exhaust fans in kitchen and bathroom.
  • Use mold inhibitors in paints.

78
Preventing Mold Buildup.
  • Clean bathroom with mold killing products.
  • Do not carpet bathroom.
  • Remove and replace flooded carpets.
  • Clean small areas with bleach while wearing
    protective mask.
  • Seek services of a certified industrial hygienist
    if larger areas are involved.

79
Recent Conference on Mycotoxins
  • Bioaerosols, Fungi and Mycotoxins Health
    Effects, Assessment, Prevention and Control.
    Edited by Eckhardt Johanning MD 2001, Mount Sinai
    School of Medicine, Department of Community
    Medicine, Fungal Research Group.
  • This publication is from the Third International
    Conference on Fungi, Mycotoxins and Bioaerosols
    held Sept 23-25 1998.

80
Summary
  • Most cases of mold related illness get better
    once the problem is remediated.
  • For those remaining, it is useful to determine
    extent of problems objectively and treat in a
    holistic manner (mind and body). It is important
    to separate those who are allergic, those who are
    probably toxic and those who are frightened or
    have any combination of these three.
  • Education is very important.
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