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FUNGI AND HUMAN HEALTH EFFECTS - Part 1 of 3
It is estimated that the number of fungal species is now in excess of 100,000, with
approximately 1500 new species described each year. It has been reported that populations
allergic to moulds vary from 2-18%. Approximately 80% of asthmatics have been reported to
be allergic to moulds. Many patients with chronic rhinosinusitis have a high incidence of
positive fungal cultures and chronic rhinosinusitis is often associated with allergic
fungal sinusitis (1). All fungi may be allergenic depending on exposure time and dose
(concentration). The predominant route of exposure is inhalation. However, typical for
allergic reactions is that once an individual develops an allergy to specific fungi, even
small concentrations may trigger an allergic reaction or asthma attack. Fungi (moulds)
affect human health by three different processes: 1) Infection; 2) Allergy; and 3)
Toxicity.
Infection: Infections caused by fungi
(moulds) are called mycoses. At present, more than 200 species of fungi have been reported
to cause disease in humans.
- 1) Superficial fungal infections - dermatophytoses (tinea or
ringworm): infections of the skin, hair and nails are common in the normal host. These
fungal infections are named according to the anatomic location involved: tinea pedis
(feet), tinea unguium (nails), tinea manuum (palms), tinea capitis (scalp, eyebrows and
moustache), tinea cruris (groin, perineal, and perianal areas). Some of the fungi involved
include Trichophyton, Epidermophyton and Microsporum spp.
2) Serious fungal infections may be divided into
two categories, namely: nosocomical (hospital acquired) and community acquired.
Almost all nosocomial fungal infections may be considered opportunistic mycoses since the
fungi are usually nonpathogenic, harmless saprobes that may cause life-threatening disease
in the seriously debilitated and/or immunocompromised patients. Although a host of fungal
pathogens known to cause nosocomial infection is extremely diverse, most of these
infections are due to Candida spp. Candida spp. accounted for 88% of all
nosocomial fungal infections in the United States between 1980 and 1990.
Although of major concern as a cause of serious, often
fatal, nosocomial infection, Aspergillus spp. accounted for only 1% of all
nosocomial fungal infections. Aspergillus species are ubiquitous fungi that are
isolated from a variety of environmental sources, including bird and bat guano, soil,
grain, leaves, grass, air, insulation, water damaged materials and organic rich substrates
in buildings. Reservoirs in hospitals from which aspergilli have been cultured include
unfiltered air, HVAC systems, dust produced from construction in and around hospitals,
carpeting, food, and soil/surfaces of ornamental plants.
Although several hundred species of Aspergillus have been described, relatively few
(approx. 12 species) are known to cause human disease. Aspergillus fumigatus is
still the most common cause of aspergillosis, followed by A.flavus, A. terreus, A.
niger, A. glaucus group, and A. nidulans. The aspergilli are most frequently
encountered as respiratory pathogens, but infections of almost every body tissue has been
described.
The hyaline (transparent) hyphomycetes constitute a large
array of fungal pathogens that are ubiquitous in the environment. As many as 20 different
genera have been reported as causative agents of hyalohyphomycosis, including such diverse
opportunistic pathogens as Acremonium, Chrysosporium, Fusarium, Paecilomyes,
Penicillium, Scopulariopsis, and Sepedonium species.
Although infections caused by these fungi are relatively
uncommon, they appear to be increasing in incidence. Acquisition of the infection is
generally thought to be by inhalation or by the progression of previously localized
cutaneous lesions. The most important of these agents as a cause of nosocomial fungal
infection is Fusarium spp.
Phaeohyphomycosis is defined as tissue infection caused
by dematiaceous (pigmented) hyphae or yeasts. The dematiaceous fungi that have been
documented to cause human infection comprise a large number of different species; however,
most infections have been caused by Alternaria, Bipolaris, Curvularia, Cladosporium,
and Exserohilum species. The reservoir for these fungi is the environment and
transmission can occur by inhalation or primary (percutaneous) inoculation.
Community acquired infections may comprise not only
opportunistic mycoses but also endemic mycoses, in which susceptibility to the infection
is acquired by living in a geographic area constituting the natural habitat of the
pathogenic fungus. The agents of community-acquired mycoses include the geographically
delimited endemic dimorphic fungi and an increasing number of opportunistic yeasts and
moulds. The infectious unit present in the environment as either a single cell yeast or a
filamentous hyphal element (mould) enters the human by inhalation, ingestion, or traumatic
implantation and a localized infection is initiated in the lung, paranasal sinus, or
tissues.
Infections caused by the endemic, dimorphic pathogens Histoplasma
capsulatum, Blastomyces dermatitidis, Coccidioides immitis, Paracoccidioides brasiliensis,
and Penicillium marneffei are acquired in specific geographic regions of the world.
Although these fungi may affect immunocompromised as well immune competent individuals.
severe, life-threatening infection with H. capsulatum, C. immitis and P.
marneffei, in particular, is more common among individuals with AIDS and recipients of
organ transplantation.
Among the community-acquired opportunistic fungal
pathogens, perhaps the most important and certainly the single most common agent of serous
infection is Cryptococcus neoformans. A rare disease before the emergence of the
HIV endemic, cryptococcosis is one of the most common life-threatening infections in AIDS
patients
As noted, the array of opportunistic fungal pathogens is
almost unlimited. Given the degree of immunosuppression that is generated iatrogencially
(medical treatment) or secondary to HIV infection, virtually any fungus present in the
environment may cause localized or invasive infection when introduced into the appropriate
host.
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Fungi and Human Health Effects - Part 2 of 3
Bioaerosol-induced hypersensitivity diseases:
A. Allergic Diseases: Allergic respiratory diseases are
caused by an immediate hypersensitivity response to inhaled particles containing
microorganisms and their components such as spores, enzymes, proteins and cell wall
fragments (hyphae). Many times there is an absent of positive laboratory findings.
Residential or office fungal exposures may be a substantial factor in an individual's
allergic airway disease depending on the subject's profile of allergic sensitivity and the
levels of indoor exposures. Persons with this type of mould allergy are considered
"atopic" individuals, i.e., have allergic asthma, allergic rhinitis, or atopic
dermatitis and manifest allergic (IgE) antibodies to a wide range of environmental
proteins among which moulds are only one entity. These persons will also be alleric to a
variety of allergens such as animal dander, dust mites, and weed, tree and grass pollens.
Several recent epidemiological studies have shown that
long-duration indoor exposure to certain fungi can result in hypersensitivity reactions
and chronic diseases. However, as mould levels in the indoor environment increase due to
recurrent water leaks, home dampness, and high humidity, the prevalence of allergy and
respiratory problems also arise.
Dampness and mould have been shown in many epidemiological
studies to be associated with cough and asthma. Damp buildings materials, particularly
cellulose-containing substrates, are prone to fungal multiplication. Fungi commonly found
are species of Penicillium, Aspergillus, Chaetomium, Ulocladium, Stachybotrys, and Cladosporium.
Three types of allergic immune reactions according to the
Coomb-Gell classification (1975) are listed below:
Type and Diseases
I - Immediate hypersensitivity: Asthma, Rhinitis, hay
fever, Allergic bronchopulmonary aspergillosis, Allergic fungal sinusitis
III - Immune complex mediated: Hypersensitivity pneumonitis
(allergic alveolitis)
IV - Delayed hypersensitivity: Allergic contact dermatitis,
pneumonitis
1).Allergic rhinoconjunctivitis: known as allergic
rhinitis, or its recurrent form - hay fever. Symptoms inlude sneezing, nasal blockage,
runny nose, ocular tearing,and pruritus (itching) of the eyes, nose and throat.
Occasionally, constitutional symptoms of fatigue and feeling lousy maybe present,
especially with loss of sleep or poor sleep from nasal congestion.
2).Allergic asthma: characterized by cough,
shortness of breath, wheezing, malaise and dyspnea or chest tightness, most typically
episodic, but often continuous in severity. Among the fungi, the most important indoor
allergenic moulds are Penicillium and Aspergillus species.
3).Allergic bronchopulmonary aspergillosis (ABPA):
an allergic (IgE-mediated) disease in which the fungus will colonize and grow within the
patient's airway. This condition occurs in allergic individuals who generally have airway
damage from previous illnesses leading to bronchial abnormalities that impair normal
drainage. Bronchial disease and old cavitary lung disease are predisposing factors
contributing to fungal colonization and the formation of mycetomas. The most important
fungus causing this disease is Aspergillus fumigatus and additional fungal genera
may rarely cause a similar problem.
4).Allergic fungal sinusitis (AFS): a more recently
appreciated condition whereby individuals who have underlying allergic disease and in
whom, because of poor drainage, a fungus colonizes the sinus cavity. Aspergillus
and Curvularia have been the most common fungi reported in AFS. Recently invasive
fungal sinusitis has increasingly been recognized as a cause of morbidity and mortality in
the immunocompromised patient. Moulds again are the most frequently detected, with Aspergillus
flavus and Aspergillus fumigatus being most widely isolated. Invasive fungal
sinusitis caused by other species of fungi include Psuedallescheria boydii, Rhizopus
arrhizus, Fusarium spp. and Alternaria spp.
B. Hypersensitivity Pneumonitis (HP): also termed
"allergic alveolitis" results from an increase of IgG mediated immune response
to inhaled foreign (fungal or other) proteins. The disease is characterized by: 1) high
serum levels of specific IgG proteins (classically precipitins detected in immunodiffusion
tests); and 2) inhalation exposure of large numbers of bacterial/fungal proteins. The
resulting interaction between the inhaled bacterial/fungal particles and cell mediated and
humoral (antibody) immune reactivity leads to an intense local immune reaction. Most cases
of hypersensitivity pneumonitis result from occupational exposures (e.g., farm workers and
other outdoor occupations), although cases have also been attributed to pet birds,
humidifiers and HVAC systems. The predominant organisms in most cases of HP are
thermophilic actinomyces, which are not moulds, but are filamentous bacteria that grow at
elevated temperatures.
Once a diagnosis of HP is made in a clinical setting and
with appropriate laboratory evidence, it is important to consider potential sources of
exposure. If evaluation of the occupational environment fails to detect the source of
antigens (proteins), exposures in home, school, or office should be investigated.
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FUNGI AND HUMAN HEALTH EFFECTS - Part 3 of 3
Toxicity:
Mycotoxins: fungi produce secondary metabolites
called mycotoxins that when ingested, inhaled, or come in contact with the skin can
be harmful to humans and animals. In addition, fungi produce toxic chemicals such as
poisonous compounds found in certain mushrooms that cause an illness known as mycotoxicosis.
This review will only deal with the effects of mycotoxins on human health and not on
mushroom poisoning.
General Aspects of Mycotoxins
1). Mycotoxins may be detected in all parts of the fungal
colony, including the hyphae, mycelium, spores (conidia) and the substrate on which the
fungus is growing. There are more than 200 mycotoxins produced by a variety of common
fungi according to the WHO Environmental Health Criteria 105 on mycotoxins.
2). Mycotoxins are generally low volatile, low-molecular
weight secondary metabolic products of fungi, that is to say these products are not
required for growth and survival of the fungus. The function of fungal toxins has not been
clearly established, however, they probably play a role in competitive inhibition with
other microorganisms.
3). From a public health standpoint, the most important
toxigenic fungi include Aspergillus species, Penicillium species, Fusarium
species, Stachybotrys chartarum, Paecilomyces species and Trichoderma
species. These fungi have been associated with adverse health effects in humans and
animals resulting in typical tissue damage and illness. In several outbreaks of illness,
human and animal deaths have been linked to exposure to toxigenic fungi, usually through
ingestion.
4). Historically mycotoxin exposure has been associated
with the agricultural and food industries with most of the knowledge of the health effects
derived from the agricultural literature. Most exposure to toxic moulds occurs from
materials of the agricultural industry such as: stored grain, wood chips and municipal
compost and from industrial substrates such as delignified cellulose (e.g., paper).
5). Newer research has shown that water-damaged building
materials are often contaminated with fungi that produce detectable levels of mycotoxins
which may become airborne and contribute to indoor air quality problems. Mycotoxins have
low volatility; therefore, inhalation of mycotoxins is not likely. Instead, the toxins are
an integral part of the fungus (e.g., spores, hyphae). Spores are considered the most
common vehicle for mycotoxin inhalation and may contain significant toxin concentrations.
6). It has been suggested that inhalation exposure to
mycotoxin-containing fungal spores is significant in the reported cases of
building-related problems and illnesses. One of the more important toxigenic fungus
frequently detected in "water-damaged" buildings is Stachybotrys chartarum,
which produces more than 50 derivatives of the trichothecene mycotoxins (e.g., T-2,
satratoxin H & G, spirolactone).
7). It has been reported that spore viability, in addition
to mycotoxins contribute to the pathophysiology of mould inhalation in rats. These results
have shown that viable Stachybotrys chartarum spores have a much higher impact on
the lungs of young rats than the non-viable spores of S. chartarum. Croft et al.
identified several cases of mycotoxicosis caused by airborne exposure to the toxigenic
fungus Stachybotrys chartarum in a residential building. Additional cases of office
building-associated Stachbotrys mycotoxicosis have been reported by Johanning and
Johanning et al. Satratoxin H was detected in the fungus isolated from the contaminated
building. Characteristic symptoms and antibody tests for (IgE and IgG) specific to S.
chartarum and some other moulds strongly suggested exposure to the indoor fungi.
8). Stachybotrys chartarum, along with other moulds
and environmental tobacco smoke was reported to cause pulmonary hemosiderosis in a number
of infants in the eastern suburbs of Cleveland, OH. While Stachybotrys was found
more frequently in the homes of case infants compared to controls, exposure of case
infants to mycotoxins in the homes could not be determined. At the time of this
investigation, no field test for airborne mycotoxins was available, therefore it was not
possible to determine if mycotoxins were actually present in the living space of the case
infants.
Fungal Volatile Organic Conpounds (VOCs):
1). Actively growing fungi produce VOCs which can be
noticed by their musty, mouldy odor.
2). Indoor VOCs levels are usually low, therefore possible
health risks are unknown.
3). Measurement of VOCs may be an indicator of excessive
indoor fungal growth.
4). Some VOCs have unpleasant odors, while other fungi
(such as mushrooms) produce pleasant odors and flavors. Most of the fungal VOCs are
derivatives of alcohols, ketones, hydrocarbons, and aromatics.
5). A number of VOCs have been identified from fungi common
in indoor contamination. Most of the published information regarding fungal VOCs concerns Penicillium
spp. and Aspergillus spp.
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References
1. Anaissie EJ, McGinnis MR, Pfaller, MA:
Clinical Mycology, 2003.
2. Murray PR, Baron EJ, Jorgensen JH, Pfaller MA,
Yolken, RH: Manual of Clinical Microbiology 8th ed. (vol. 2), Chap 116-118,
American Society for Microbiology, Washington DC, 2003.
3. Hurst CJ, Crawford RL, et al (eds): Manual of
Environmental Microbiology 2nd ed. American Society for Microbiology,
Washington DC, 2002.
4. Macher, J, et al (eds): Bioaerosols: Assessment
and Control, Fungal Toxins and B-(1-3)-D-Glucans, American Conference of Governmental
Industrial Hygienists, 1999.
5. American College of Occupational and
Environmental Medicine: Position Statements/Guidelines, Adverse Human Health Effects
Associated with Molds in the Indoor Environment, 2002.
6. Manual of Environmental Microbiology, 2nd
ed. ASM Press, Washington, DC, 2002.
7. Croft WA, Jarvis BB, Yatawara CS.
"Airborne outbreak of Trichothecene Toxicosis: Atmospheric Environment. 1986, 20
(3):549-552.
8. CDC. "Update: pulmonary
hemorrhage/hemodiderosis among infants, Cleveland, OH, 1993-1996" MMWR 1997,
46:33-35.
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