Prepared for the Aspergillus website by:
Elena
Piecková,
Institute of Preventive and Clinical Medicine,
Limbová 14,
SK-833 01 Bratislava,
Slovakia. Email:pieckova@upkm.sk
According to his/her life style, a person can commonly spend 75 - 90 % of their time in an indoor environment. That is one reason why the effects of different indoor factors on human health are studied very carefully. Indoor bacteria or fungi can cause allergic, infectious, toxic or inflammatory diseases i. e. building-related illnesses. A complex of health troubles, bad feelings and general discomfort due to a stay in certain buildings is known as sick building syndrome (Kroeling, 1998).
Problems connected with the presence of microscopic fungi in the working environment and their effects on the health status of employees have been studied in many papers. It has been found that the health of people working with moldy materials can be seriously affected. The air of working environments may contain as much as 109 viable germs or particles (not only spores, also hyphal fragments etc.) of microscopic filamentous fungi and yeasts per m3 and a large amount of various mycotoxins. Regarding the character of manufactured substrates, irritation of eye, nose and mouth mucous membranes were found, as well as serious acute and chronic damage of respiratory organs, i.e. bronchitis, allergic alveolitis "farmer´s lung", lung mycotoxicoses and similar disorders. Some mycotoxins can also possess carcinogenic properties affecting lung tissue (Dutkiewicz, 1997, Dutkiewicz et al., 1994, Jesenská, 1993, Sorenson et al., 1991).
While the work with moldy materials is mostly sporadic and the possible adverse effects of the microscopic fungi and their toxins can be foreseen and thus the exposed persons can be protected using respiratory filters, families including infants living in homes with moldy walls are exposed to these noxae for a long periods of time. The amount of fungal colony forming units (cfu)/m3 can vary from a standard of 500 - 1000 to 6000 - 450000 cfu/m3 in "moldy" houses (Nevalainen et al., 1991). Spores are liberated into the air in places with higher turbulence e.g. during home maintenance, cleaning, dusting, vacuum cleaning, vegetable peeling, when door is opened, when pets enter or leave etc. These activities can cause an increase in air spore amount up to 3000-fold (Lehtonen and Reponen, 1993). Many species of micromycetes (according to Hunter et al. (1988) up to 56) have been isolated from miscellaneous objects and walls in residences.
Allergies of inhabitants have been studied very extensively in connection with moldy dwellings. Cytoplasmic glycoproteins of fungal spores are important aeroallergens in genetically pre-determined humans (Linas et al., 1998). In dwellings occupied by children suffering from asthma, significantly greater spore counts of Cladosporium sp. and Penicillium sp. were found (Li et al., 1995).In some case studies, explicit relations between the presence of the fungus in dwellings and allergic reactions of their occupants were found. After cleaning the contaminated sites, or when the occupants moved into a new home, the symptoms disappeared (Senkpiel et al., 1996).
It was found that allergic alveolitis (hypersensitivity pneumonia) was caused by Penicillium expansum (Park et al., 1994) and Rhodotorula rubra (Siersted and Gravesen, 1993). Kanny et al. (1996) found the cause of an eczema and respiratory disorder in a 25-years-old female student was her hypersensitivity against the antigens of micromycetes growing on walls of her home, i.e. Fusarium sp., Cladosporium sp., Pullularia sp., Rhizopus sp. and Penicillium sp. An explicit relation between summer hypersensitivity pneumonia and the presence of Trichosporon sp. in homes of the patients was found in Japan (Ando et al., 1991, Lehtonen and Reponen, 1993, Rylander, 1997, Sumi et al., 1994, Summerbell et al., 1992). Kauffman et al. (1995) found that atopic humans suffered from acute symptoms of fungal asthma when they inspired a great number of spores. An adverse situation appears when mucous membrane of the epithelium of respiratory tract of sensitive person is systematically colonized with fungi whose cells possess the ability to penetrate into the deeper parts of lung tissue and produce protease in a depository niche. These authors also found that sensitization with fungal antigens is dependent on the person´s age, as most humans with positive skin tests to the antigens of micromycetes are persons in younger age categories. An increasing mortality among asthmatic patients was observed during the period when a statistically significant higher number of fungal spores was found in the air (Targonski et al., 1995). According to Garrett et al. (1998), the high incidence of Penicillium sp. in dwellings was a significant risk factor for asthma, while spores of Aspergilli potentiated atopic reactions of inhabitants. Based on long-term epidemiological studies in USA, Australia, New Zealand and the European Nordic Countries, the statistic significance of higher outbreak of respiratory allergies (asthma, allergic rhinitis, hypersensitivity pneumonia) in children from damp and wet dwellings with a high concentration of fungal, namely Alternaria sp. spores in the air, was apparent (Huang and Kimbrough, 1997, Page and Trout, 1998, Peat et al., 1998).
There is a close relationship between the presence of spores of microscopic fungi in the indoor air of dwellings and allergic symptoms in some patients. Nevertheless, most of the patients suffer from "multiallergy", with allergic reaction also against other environmental components. The relationship between the fungal antigens and the allergic patients is considerably influenced by the personality of the patient. This probably causes in some groups of atopic humans an apparently clear relation between the spore count in the air and the patient´s reaction, but this could not be proved (Dill and Niggemann, 1996, Jarvis et al., 1996). For the mycologists, there is a great challenge in preparing a high quality antigen test sets to prove patient´s allergy.
Currently, a general approach to the study of the mechanism of fungal effects on human beings is becoming more urgent. Such an approach includes the immunosuppressive influence of beta-glucans from fungal cell wall as well as toxic and irritative effects of secondary metabolites - mycotoxins and/or volatile organic compounds (Larsen et al., 1998). Low molecular organic compounds, namely alcohols, aldehydes, ketones, aromatic compounds, amines, terpenes, chlorinated hydrocarbons and sulphuric compounds, cause typical "moldy" odor but also an inflammation of airways of sensitive people. Aspergillus sp., A. versicolor, Cladosporium sp. and Penicillium sp. are strong producers of these compounds. Such effects are associated with invisible moulds growing under wallpaper, carpets or mattresses (Korpi et al., 1997). In some well-known toxinogenic strains, a direct correlation was found between the mycotoxin production and production of volatile products, e.g. ketones (Pasanen et al., 1996).
Some authors have revealed that in occupants of "moldy" dwellings there is a higher incidence of bronchitis, sore throat, concentration difficulties, back-aches, irritation of eyes and mouth cavity, feeling of weekness etc. (Pirhonen et al., 1996, Summerbell et al., 1992). Ill health symptoms were also associated with increased amounts of Epicoccum sp., Aureobasidium sp. and yeasts in dwellings (Su et al., 1992). Chronic intoxication is also suffered by the occupants of a house where the air conditioning system and wet ceiling were contaminated with Stachybotrys chartarum, and in indoor air there were found spores of that species (Bjurman and Kristensson, 1992). A study was carried out on an unusual incidence of acute lung hemosideroses in infants aged six weeks to six months in Cleveland, Ohio, USA. One child died, and the only common sign was that all those families lived in dwellings contaminated with S. chartarum. Among others, Memnoniella echinata strains were also isolated from the environment, and it was found that their metabolites were highly cytotoxic. It was also proved that the M. echinata strains produce trichothecenous mycotoxins trichodermol and trichodermin. Jarvis et al. (1996) reported that this species can sometimes grow together with S. chartarum. Massive incidence of spores of S. chartarum was also found in the indoor work environment which had been flooded accidentally. The staff (53 persons) suffered from symptoms of toxic damage of the lower part of lung tissue, skin and eyes irritations and chronic weakness. Statistically significant damage to the immune system, especially of T-lymphocytes was found too (Johanning et al., 1996). S. chartarum strains produce toxic trichothecenes, e.g. satratoxins, verrucarins, roridins and others. The toxic metabolites stachybotryotoxins-trichothecenes are concentrated in the cells of the fungus, they are produced in phialides, conidia, conidiophores but also diffuse into growth medium (Pasanen et al., 1993).
An occupant of a "moldy" dwelling is exposed in that environment not only to microscopic fungi but also to a number of volatile compounds released from furniture, carpets, various paints and other materials. The mechanism of the potential pathological effects of microscopic fungi and their toxins on lung tissue in healthy humans has not yet been made sufficiently clear.
For estimating the micromycete effects in the indoor home environments it is necessary to consider the results of the experiments conducted in vitro or on laboratory animals. Thus, it was found that 47 % of the examined strains isolated from the dwellings were cytotoxic against human embryonal diploid fibroblasts from lung tissue (Smith et al., 1992). The pure known toxic metabolites of microscopic fungi, e.g. trichothecenes and sterigmatocystin, and extracts from some strains isolated from house walls cause cilia of tracheal mucous membranes to stop moving in organ cultures from one-day-old chickens and affect the self-cleaning ability of these membranes (Jesenská and Bernát, 1994, Piecková and Jesenská, 1995, 1996, 1997a, b, 1998). Intranasal application of 1x106 spores of the satratoxin-producing S. chartarum strain caused inflammatory reactions in the lung tissue of experimental mice together with exudative processes in alveoli and bronchi. These disorders could be classified as lung mycotoxicosis (Nikulin et al., 1996).
Regarding the health conditions of the occupants whose dwellings have moldy walls, it is important to pay special attention to the species of Aspergillus clavatus, A. fumigatus, species from the group of A. niger, and A. versicolor, rarely to other fungi of this genus.
Indoor air in dwellings. In the USA, the Aspergillus sp. fungus was found in 9 - 29 % and in Scotland in 74 % of the examined homes. In Ontario, Canada, their concentration in the air of dwellings was 22 cfu/m3. In Slovakia, Aspergillus sp. strains were isolated from 9 %, A. flavus from 30 % ( 5 % of strains were able to produce alflatoxins B1, B2, G1 and G2 in vitro), Aspergilli from the group of A. glaucus from 2 %, A. ochraceus from 12 %, Aspergilli from the group of A. restrictus from 2 % and A. ustus from 5 % of examined "moldy" dwellings. Microscopic pictures of scrapings from walls and wooden window frames of some houses are presented (Fig. 1-4) (Piecková et al., 1999).
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Fig 1. Scraping from a wall in a nursery - a fragment of a fruiting body of A. versicolor type (magn. 1000x). |
Fig 2. Scraping from a wall in a fitness room - a fruiting body of Aspergillus sp. type (magn. 200x). |
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Fig 3. Home dust - a fruiting body of A. versicolor (magn. 400x). |
Fig 4. Scraping from the window frame in a fitness room - a fruiting body of Aspergillus sp. type (magn. 400x). |
During the evaluation of dwellings in Belgium, the following Aspergilli were isolated: A. fumigatus from kitchens and bathrooms, A. versicolor and A. repens from mattresses and carpets, A. versicolor and A. fumigatus from cellars, A. fumigatus, A. niger and A. flavus from flower pot soil, A. versicolor andA. fumigatus from various pad materials (Summerbell et al., 1992). In Denmark, Aspergillus sp. strains were isolated from 56 % of evaluated moldy indoor samples (Gravesen et al., 1999).
Damp materials with an aw value ranging from 0.90 to 0.95 are usually colonized by strains of A. fumigatus, materials with aw values ranging from 0.90 to 0.85 by strains of A. versicolor, materials with aw values of 0.85 and a little less, by strains of A. versicolor, Eurotium sp. (Samson et al., 1994).
In general, it is thought that the amount of Aspergillus sp. germs is higher in indoor air than outdoors at any given time. In the home, the amount of spores in the air is markedly increased when the cleaning is carried out mechanically, for example, when carpets are vacuum cleaned.
A. clavatus is often associated with allergic alveolitis (hypersensitivity pneumonia) in workers of malthouses (Reynolds, 1991) . >Minimum awvalue for its growth is 0.85.
A. fumigatus is the most important and well known potential pathogen for humans with affected immunity.
Allergic diseases. As much as 10.8 % of asthma patients had positive reactions to the extract from A. fumigatus strains. Nevertheless, A. fumigatus possesses similar biochemical structure and antigenic properties to Penicillium glabrum, P. verrucosum var. verrucosum and A. versicolor. A. fumigatus spores have the ability to be bound on lung epithelium in asthma patients, causing complications in the health status of the patients (Bromley and Donaldson, 1996). In that case, the course of the patient‘s disease assumes a very destructive character (Kauffman et al., 1995).
Aspergillus Sp. were found in indoor air of dwellings, e.g. in South California in 2.9 % and in the Netherlands in 4.5 % of examined dwellings. In wallpapers of a hotel in Singapore, its incidence was as high as 18 - 88 %. In an air conditioning system in Saudi Arabia, it formed 11 % of all fungal isolates and its concentration was 15 700 cfu/g of dust.
When examining materials from the indoor work environment, it was found that about 70 % of A. fumigatus spores were able - due to their size - to penetrate into the trachea and primary bronchi and less than 1 % into alveoli (Millner et al., 1980).
The best known toxic metabolites of A. fumigatus are mainly fumigaclavin A, B, C, and D, spinulosin and tremorgenous toxins, e.g. verruculogen. Some rarely isolated strains produce kojic acid, sterigmatocystin and various unknown toxins affecting Artemia salina and Bacillus megatherium NRRL 1366, chicken embryos and other organisms. From 106 spores of the A. fumigatus SRRC 2006 strain, an amount of 9.89 ng of fumigaclavin A was isolated. In five out of eight A. fumigatus strains isolated from the indoor work environment in a sawmill, fumigaclavin C and verruculogen were found (Land et al., 1987). The investigation was carried out in connection with the assumed lung mycosis in workers. In the filtrate from mycelium and medium the presence of the hemolytic toxin was demonstrated, containing large protein amount and traces of saccharides (Yokota et al., 1977).
Minimum temperature for mycelium growth is 10 - 12oC, optimum 37 - 43oC, minimum relative air humidity 85 %, optimum 98 % and for conidia formation minimum 90 %, optimum 98 - 99 %. Minimum aw value for A. fumigatus growth is 0.94 and for sporulation 0.95. No spore germination was observed at 4 - 8oC, optimum germination temperature is 25oC and optimum aw value is 0.94. Optimum pH value of the environment for A. fumigatus ranges from 3.0-8.0.
A. niger. Aspergilli, characteristic with their striking black pigmentation of the colonies, are classified within a large A.niger group. In most papers describing the isolation of such strains, they are presented simply as A. niger. However, in that case it is difficult to differentiate which species were involved in the activity described below in the indoor environment and in the pathologic process.
Indoor air in the dwellings. A. niger isolates were described in homes in London and Central Scotland, in Plzeň (Czech Republic) (0.71 - 1.88 % of all isolates) and in Egypt (15 % of all isolates). They were found in Saudi Arabia in the dust from an air conditioning system (10 600 cfu/g and 7.93 % of all isolates) and in dust from dwellings (8 600 cfu and 4 % from all isolates), in homes in California (in 19 % of homes, on the average 2.9 cfu/m3, maximum 59 cfu/m3), in Canada (in 6 % of homes), in Ontario, Canada, (on the average 7 cfu/m3). Results presented in another paper describe the presence of A. niger in the dust from Canadian homes in 50 % of all examined samples in the amount of 0.7x104 cfu/g. In the Netherlands, it was found in 4.5 % of homes, in Slovakia, in 5 % of "moldy" dwellings.
The fungus is acidophilic, the mimimum pH value of 1.5 is suitable for mycelium growth, optimum pH is 4.4 - 7.5, maximum 9.8. Minimum temperature 6 - 8°C, optimum 35 - 37°C, maximum 45 - 47°C. Minimum air humidity is 88 - 89 %, optimum 96 - 98 %, and minimum aw value is 0.85. Minimum humidity for conidia formation is 92 - 95 %, optimum 96 - 98 %. Conidia germinate only in temperatures exceeding 10°C.
A. niger strains are known to be producers of many enzymes and other metabolites . To the well known toxic metabolites belong the malformins A1, A2, B1, B2, C and oxalic acid. In the spores of the A. niger strain SRRC 2005, aurasporon C was detected. However, the papers describing the incidence of toxic strains are full of contradictions that may be due to the imprecise identification of the isolates, as mentioned above.
A. versicolor has an antigen structure similar to that of P. glabrum. After an inhalation of A. versicolor spores, laboratory rats showed granulomatous lesions in lung tissue, localized mainly near to the bronchi, after one month exposure (Sumi et al., 1994).
Indoor air in the dwellings. A. versicolor was found in indoor air of homes in London, in Central Scotland, and in the Netherlands (in 9 of 11 examined homes, in 32 % of all examined homes, and in 50 % of examined schools). It formed 16 - 27% of isolates in homes in Torino, Italy, and 11.5 % of isolates from moldy wallpapers. A. versicolor was found also in dust in dwellings in Saudi Arabia (15 000 cfu/g and 7.66 % of all isolates). In Slovakia, it was isolated from 33 % of examined "moldy" dwellings. This fungus is placed among the primary wall colonizers at 25°C in dwellings and was also found in dust from mattresses.
A.versicolor spores germinate in 12 - 20 days in dependence on the temperature and the pH values of substrates and at the aw values ranging from 0.75 to 0.81. The aw values reported for this species are within the range 0.78 - 0.98, minimum growth temperature 6 - 9°C, and optimum temperature is 25 - 27°C. An A. versicolor isolate from moldy house wall was able to survive incubation onto six different types of plaster at 25°C in an atmosphere saturated with moisture for three months (Piecková and Jesenská, 2000).
Most of the relevant papers deal with the production of toxic and carcinogenic strigmatocystin by A. versicolor. The amount of toxinogenic strains is rather high, about 74% out of strains tested produced this toxin under various laboratory conditions. Strains of A. versicolor isolated from damp houses in USA, with occupants suffering from pulmonary disease, were able to produce this mycotoxin in vitro, too (Hodgson et al., 1998). A. versicolor isolates from "moldy" dwellings cultivated on plasterboard at 25°C in an atmosphere saturated with moisture for 46 - 77 days produced chloroform-extractable endo- and exometabolites able to stop the movement of cilia of chicken tracheal epithelium, similar to the effect of sterigmatocystin (Piecková et al., 1999).
Monitoring of exposure to the indoor fungi is rather complicated due to lack of standard and exact practical methods to evaluate how indoor microclimate (temperature, relative humidity, dust, ventilation, constructing materials and furnishings), outdoor ambient, and microscopic fungi affect each other.
To determine a causal relationship between mycotoxins in the indoor environment and particular human health disorders it is necessary to quantify mycotoxin concentration in damp and "healthy" buildings, to estimate minimal concentration of mycotoxin able to cause clinical symptoms in comparison with in vitro models, to choose optimal animal or other biological models for studying of mycotoxin pathogenicity and pathophysiology and to characterize short- and long-term health damages (not only biomarkers) in people under such an influence (Garrett et al., 1998).
Fungal contamination of the indoor environment of buildings has to be solved at the level of building, maintenance, and style of life and health of the occupants. This contamination is an indicator of unsuitable architecture, building construction and/or using of building. To reduce the concentration of microscopic fungi in the indoor environment, reduction of dampness, effective ventilation and right regime of temperature and hygiene is recommended. In particular cases, it is useful to consult industrial hygiene experts.
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