THE FUNGUS AMONG US

1. THE FUNGUS AMONG US Or How to break the medicolegal Mold dilemma Warren Silverman MD Medical Director Access Health Systems Latham, NY

2. How are we affected by Fungi? • ACTUAL INFECTIONS • ALLERGIC REACTIONS • FUNGAL TOXINS

3. Skin Infections

13. Enough GrossPictures Fungal infections can be bad, particularly in the immunosuppressed, but what about allergies?

14. Wheezing Coughing Runny Nose Itchy Nose Sinus congestion Eye tearing Eye itching Symptoms can be caused by dead fungi as well as live organisms. The reaction is to the antigens which make up parts of the organism. Symptoms of Allergic Reaction

15. Allergic Reactions • Usually require • Prior exposure • Reaction upon re-exposure • Allergic Bronchopulmonary Aspergillosis • Rarely: Organic Dust Toxic Exposure • Single exposure to a large amount of fungal containing dust • Flu-like Symptoms • Usually in an occupational setting (i.e.: fungal contamination of grain dust, saw dust, or fungal remediation work

16. Fungi can produce VOC’s causing the musty odor (2-octen-1-ol), but the health risk is not demonstrated Other environmental agents can cause identical symptoms (bacteria, avian proteins) Symptoms will go away when away from the environment and return upon re-exposure. There are no persistent manifestations. Allergic Reactions – Cont.

17. ASPERGILLOSIS • Over 100 species of Aspergillus • Most infection by A. fumigatus and A.niger, less by flavus and clavatus • 4 syndromes: • Allergic bronchopulmonary aspergillosis • Chronic necrotizing pneumonia • Aspergilloma • Invasive aspergillosis

18. Hypersensitivity Pneumonitis • Farmer’s lung • Maple Bark stripper’s lung • Chicken Plucker’s Lung • Humidifier Lung • Malt Worker’s Lung • Grain Handler’s Lung • Woodworker’s lung • Bagassosis • Bird Breeders Lung • Cheese worker’s Lung • Wheat Weevil Lung • Paprika Splitter’s Lung

19. Nasal Cultures :Normals • Acremonium 7% • Alternaria 50% • Aspergillus 42.9% • Candida 7.1% • Cladosporium 57.1% • Geotrichum 28.6% • Penicillium 21.4% • Pithomyces 7.1%

20. FUNGAL TOXINS • ALMOST ALL REAL EPISODES OF HUMAN ILLNESS DUE TO FUNGAL TOXINS OCCUR FOLLOWING INGESTION

22. ERGOTISM • Known for hundreds of years • Causes limb gangrene • Hallucinations • Death • Classical Case: Ingestion of Rye contaminated by Claviceps Purpurae producing ergot alkaloids

23. Why not by inhalation? • The toxins are produced in very low levels (in many cases, while they can be found on a culture plate, they may not be produced at all in an environmental setting) • Mycotoxins are large non-volatile molecules • Direct contact is required • Multiple fungi are usually present

24. Stachybotrys: Perils and Pitfalls • Stachybotrys chartarum (aka S. atra or S. alternans) known to produce mycotoxins called trichothecenes as well as a variety of other toxins. • Contaminated straw and grain caused epidemics in Ukraine in horses and other animals called stachybotryocosis

25. Hyperplastic dermatitis on a horse four days after feeding on straw infested with S. chartarum. Notice the scaly appearance of the upper lip area. Photograph reprinted from Sarkisov, A. Kh. 1954. Mikotoksikozi (Gribkovye otravleniia). Moscow. 216 pp. (click image for larger view). Straw contaminated with S. chartarum (top) compared to clean straw. Persons handling this heavily contaminated straw could develop stachybotryotoxicosis

27. The Human connection? • From 1/93 – 11/94 a number of infants in Cleveland died with a hemorrhagic lung disease first labeled acute idiopathic pulmonary hemosiderosis • A study reported that the majority lived in water damaged homes and these homes were more likely to contain S. chartarum than controls.

28. Beware the mold stachybotrys 'The average person will spread the mold' November 5, 1997Web posted at: 11:34 p.m. EST (0434 GMT) From Correspondent Joan MacFarlane WEST BLOOMFIELD, Michigan (CNN)-- Deloris Griffin's 14-month-old granddaughter, Mikala,

29. Inconsistencies • The symptoms were different than that seen in veterinary disease • Other infants heavily exposed to this fungus did not develop disease • Another cluster of these cases in Chicago did not have the fungal link

30. Conclusions • The original study and data were reviewed and a statistical connection could not be established • The CDC retracted the conclusions reached based upon the original study • No clear evidence of human disease based upon environmental inhalation exposure is established. • The amount of S. Chartarum required to produce human illness is estimated at 1000 times that measured in most environmental surveys.

31. S. chartarum growing on the back side of water damaged gypsum wall board (i.e. sheetrock) behind a basement shower stall. A high water table caused flooding in the basement Heavy growth of S. chartarum and some other fungi on gypsum wall board in a flooded school basement. This growth occurred about one week after the flood. It was removed before remodeling

32. Some Mycotoxins we love • Many fungi are very useful to humans: • yeasts-- baking and brewing wine, beer • many organic acids are commercially produced with fungi- - e.g. citric acid in Coke is produced by an Aspergillus • steroids and hormones--- e.g. the pill • certain “stinky” cheeses-- e.g. blue cheese, Roquefort and Camembert • Antibiotics • Griseofulvin • Cyclosporins

33. Some of the rest • MycotoxinOrganismAcetoxyscirpenediolFusarium moniliforme, F. equiseti, F. oxysporum, F. culmorum, F. avenaceum, F. roseum, and F. nivaleAcetyldeoxynivalenolFusarium moniliforme, F. equiseti, F. oxysporum, F. culmorum, F. avenaceum, F. roseum, and F. nivaleAcetylneosolaniolFusarium moniliforme, F. equiseti, F. oxysporum, F. culmorum, F. avenaceum, F. roseum, and F. nivaleAcetyl T-2 toxin Fusarium moniliforme, F. equiseti, F. oxysporum, F. culmorum, F. avenaceum, F. roseum, and F. nivaleAflatoxinAspergillus flavus, A. parasiticusAflatrem Aspergillus flavusAltenuic acid Alternaria alternataAlternariolAlternaria alternataAustdiol  Aspergillus ustusAustamide Aspergillus ustusAustocystin Aspergillus ustusAvenacein +1Fusarium moniliforme, F. equiseti, F. oxysporum, F. culmorum, F. avenaceum, F. roseum, and F. nivaleBeauvericin +2 Fusarium moniliforme, F. equiseti, F. oxysporum, F. culmorum, F. avenaceum, F. roseum, and F. nivaleBentenolide Monographella nivalisBrevianamide Aspergillus ustusButenolideFusarium moniliforme, F. equiseti, F. oxysporum, F. culmorum, F. avenaceum, F. roseum, and F. nivaleCalonectrinFusarium moniliforme, F. equiseti, F. oxysporum, F. culmorum, F. avenaceum, F. roseum, and F. nivaleChaetoglobosinChaetomium globosumCitrinin  Aspergillus carneus, A. terreus, Penicillium citrinum, P. hirsutum, P. verrucosumCitreoviridin Aspergillus terreus, Penicillium citreovirideCochliodinol Chaetomium cochliodesCrotocin Acremonium crotocinigenumCytochalasin E Aspergillus clavatusCyclopiazonic acidAspergillus versicolorDeacetylcalonectrinFusarium moniliforme, F. equiseti, F. oxysporum, F. culmorum, F. avenaceum, F. roseum, and F. nivaleDeoxynivalenol diacetateFusarium moniliforme, and F. nivaleDeoxynivalenol monoacetateFusarium moniliforme, F. culmorum, F. avenaceum, F. roseum, and F. nivaleDiacetoxyscirpenolFusarium moniliforme, F. equisetiDestruxin B  Aspergillus ochraceusEnniatinsFusarium moniliforme,  F. avenaceum, F. roseum, F. solani, and F. nivaleFructigenin +1Fusarium moniliforme, F. culmorum, F. avenaceum, and F. roseumFumagilin Aspergillus fumigatusFumonisin B1Fusarium moniliforme, F. culmorum, F. avenaceum, and F. nivaleFusaric acidFusarium moniliformeFusarin  Fusarium moniliformeGliotoxinAlternaria, Aspergillus fumigatus, PenicilliumHT-2 toxinFusarium moniliforme, F. culmorum, F. avenaceum, and F. nivaleIpomeanineFusarium moniliforme, F. culmorum, F. avenaceum, and F. nivaleIslanditoxinPenicillium islandicumLateritin +1 Fusarium moniliforme, F. culmorum, F. avenaceum, and F. nivaleLycomarasmin +1 Fusarium moniliformeMalformin Aspergillus nigerMaltoryzine Aspergillus spp.Moniliformin Fusarium moniliforme, F. equiseti, F. oxysporum, F. culmorum, F. avenaceum, F. roseum, and F. nivaleMonoacetoxyscirpenolFusarium moniliforme, F. equiseti, F. oxysporum, F. culmorum, F. avenaceum, F. roseum, and F. nivaleNeosolaniol Fusarium moniliforme, F. solani, F. culmorum, F. avenaceum, and F. roseumNivalenolFusarium moniliforme, F. equiseti, F. oxysporum, F. culmorum, F. avenaceum, F. roseum, and F. nivaleNT-1 toxinFusarium moniliforme, F. equiseti, F. oxysporum, F. culmorum, F. avenaceum, F. roseum, and F. nivaleNT-2 toxinFusarium moniliforme, F. equiseti, F. oxysporum, F. culmorum, F., F. solani, avenaceum, F. roseum, and F. nivaleOchratoxinAspergillus ochraceus, Penicillium viridictumOxalic acidAspergillus nigerPatulinAspergillus clavatus, Penicillium expansum, Botrytis,P. roquefortii, P. claviforme, P. griseofulvumPenicillic acidAspergillus ochraceusPenitremPenicillium crustosumRoridin EMyrothecium roridum, M. verrucaria, Dendrodochium spp., Cylindrocarpon spp., Stachybotrys spp.RubratoxinPenicillium rubrumRubroskyrinPenicillium spp.RubrosulphinPenicillium viridicatumRugulosinPenicillium brunneum, P. kloeckeri, P. rugulosumSambucynin +1 Fusarium moniliforme, F. equiseti, F. oxysporum, F. culmorum, F. solani, F. avenaceum, F. roseum, and F. nivaleSatratoxins, F,G,HStachybotrys chartarum, Trichoderma viridiScirpentriolFusarium moniliforme, F. equiseti, F. oxysporum, F. culmorum, F. solani, F. avenaceum, F. roseum, and F. nivaleSlaframineRhizoctonia leguminicolaSterigmatocystinAspergillus flavus, A. nidulans, A. versicolor, Penicillium rugulosumT-1 toxin Fusarium moniliforme, F. equiseti,  F. culmorum, F. solani, F. avenaceum, F. roseum, and F. nivaleT-2 toxin Fusarium moniliforme, F. equiseti,  F. culmorum, F. solani, F. avenaceum, F. roseum, and F. nivaleTriacetoxyscirpendiolFusarium moniliforme, F. equiseti,  F. avenaceum, F. roseum, and F. nivaleTrichoderminTrichoderma virideTrichothecinTrichothecium roseumTrichoverrinsStachybotrys chartarumTrichoverrolsStachybotrys chartarumTryptoquivaleneAspergillus clavatusVerrucarinMyrothecium verrucaria, Dendrodochium spp., Stachybotrys chartarumVerruculogenAspergillus fumigatus, Stachybotrys chartarumViopurpurinTrichophyton spp., Penicillium viridicatumViomelleinAspergillus spp., Penicillium aurantiogriseum, P. crustosum, P. viridicatumViriditoxinAspergillus fumigatusXanthocillinEurotium chevalieriYavanicin  +1 Fusarium culmorum, F. graminearum, F. oxysporum, F. roseum,  F. moniliforme, F. avenaceum, F. equiseti, and F. nivaleZearalenoneFusarium culmorum, F. graminearum, F. oxysporum, F. roseum,  F. moniliforme, F. avenaceum, F. equiseti, and F. nivale 

35. Sick Building Building Factors Mechanical ventilation Relative humidity < 30% Fresh air ventilation rates < 10 liters/second/person Specific Environmental Factors & Pollutants Volatile organic compounds (VOCs): formaldehyde, solvents, etc. Carbon monoxide: Stoves, heaters, and furnaces Dust &amp; fibres: asbestosis, fibreglass, dirt Bioaerosols: Bacteria, moulds, viruses, pollen, dust mites, animal danders, animal excreta Trapped outdoor pollutants: vehicle or industrial exhausts Physical factors: Lighting, vibration, noise, temperature, crowding, photoduplication Personal Factors Female sex History of being allergic (atopic) Job-related tensions Job dissatisfaction

36. Dampness and Odors • Dampness Index • Odor • Condensation on windows • Humidity in Bathrooms • Water leakage Eye /Nasal/Throat/Facial-Skin Headache/Tiredness

37. What are safe levels of Fungi? ?

39. How to clean the site? You are done when: • There is no visible mold • There are no mold odors • You have fixed all of the moisture/water problems