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: relevance to human disease Abba I. Terr, MD

Learning Objectives: Recent public concern about the danger of environmental dia, where it may compete poorly with fungi has focused attention on one particular , Stachybotrys. The purpose of other rapidly growing fungi. Micro- this review is to examine and critique the published literature on Stachybotrys for scopically, there are clusters of phi- objective scientific and clinical evidence of disease caused by the presence of this alides at the tips of conidiophores. The fungal organism in the environment. (conidia) are produced from the Data Sources: Data were obtained from all published research and reviews of tips of the phialides and collect in wet Stachyboirys indexed in MEDLINE since 1966. masses, dying promptly on release into Study Selection: The publications used for this review were those that contained the air. information about human health effects of this microorganism. The critique of these Stachybotrys is rarely recovered publications is the author's. from outdoor air samples. It is also Results: Stachybotrys is a minor component of the indoor mycoflora, found on difficult to find in undisturbed indoor certain building material surfaces in water-damaged buildings, but airborne spores air. Because of its affinity for cellu- are present in very low concentrations. Published reports fail to establish inhalation lose, it is found in nature on substrates of Stachybotrys spores as a cause of human disease even in water-damaged build- of plant origin, but under very wet ings. A possible exception may be -caused pulmonary hemorrhage/ conditions. As a strong decomposer of hemosiderosis in infants, although scientific evidence to date is suggestive but not cellulose, it favors decaying plant ma- conclusive. Based on old reports ingestion of food prepared from Stachybotrys- terials. with spores in chains contaminated grains may cause a toxic gastroenteropathy. No convincing cases of are referred to as Memnoniella. human allergic disease or infection from this mold have been published. Conclusions: The current public concern for adverse health effects from inhala- STACHYBOTRYS IN THE tion of Stachybotrys spores in water-damaged buildings is not supported by pub- NATURAL ENVIRONMENT lished reports in the medical literature. Outdoors Ann Allergy Asthma Immunol 2001;87(Suppl):57-63. Although Stachybotrys is rarely found in outdoor air (and when found, is INTRODUCTION These concerns have centered par- present in low quantities), it is poten- There are close to 100,000 recognized ticularly on one fungal , Stachy- tially an important contaminant of ag- species of fungi. They exist throughout botrys, which is increasingly being im- ricultural produce. The has the habitable world, and airborne plicated as a cause of human disease been cultured from soil2 and substrates spores of many species are present in and often called the "fatal fungus."1 rich in cellulose, such as hay and straw, cereal grains, plant debris, rice respirable air. Recognized human dis- STACHYBOTRYS eases of fungal origin occur through paddy grains, combine harvester wheat one of three mechanisms: infection, al- Nomenclature and sorghum dusts,3 and broad bean lergy, or toxicity (Table 1). In each Stachybotrys is a deuteromycete (Ta- (Vicia faba) seeds.4 In each case, case, a specific disease can be traced to ble 2). There are a number of species, Stachybotrys is accompanied by many a particular species of mold. but the one most commonly encoun- other genera of fungi, and it is usually Recently, there have been concerns tered is referred to as 5. atra, S. char- not the dominant one. Urea application tarum, or S. alternans. These are three as a source of nitrogen fertilization of expressed that the mere presence of synonyms for the same species. soil promotes the growth of numerous in indoor air may cause an illness fungi, including Stachybotrys.5 Characteristics of the Organism characterized by 1) multiple nonspecific Stachybotrys has also been cultured symptoms and/or generalized malaise Stachybotrys is a greenish-black, from the hair of large mammals, in- sooty-looking saprophytic mold that and fatigue, or 2) immunosuppression cluding cow, dog, donkey,6 and the grows on nonliving organic material, resulting in susceptibility to viral and skin surface of cynomolgus monkeys.7 bacterial respiratory infections. especially cellulose, under conditions As in the case of plant contamination, of high humidity and low nitrogen con- it is found on these animals along with tent, in common with Aspergillus fu- orner fungi, especially Cladosporium. migatus and niger, Cladosporium her- San Francisco, California. barum, Altemaria altemata, and Indoors Received for publication July 25, 2001. Accepted for publication in revised form Sep- others. It is a slow-growing organism, Stachybotrys spores may be recovered tember 25. 2001. both in nature and on laboratory me- from indoor air samples, but generally

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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 1. Human Diseases Caused by board, gypsum board, carpets, jute, vi- Biosynthesis of these chemicals de- Fungi nyl and paper wall coverings, and pends upon, and therefore varies with, Infection other indoor building materials,"-'-1 es- the age of the hyphae, available nutri- Systemic pecially those containing wood or pa- ents, and the physical environment. Localized per materials. They have been recov- Each chemical can be termed a myco- Allergy ered from a variety of dust and lint toxin when it can be shown to have a Atopy (especially asthma) samples, and even from the tobacco in Hypersensitivity pneumonitis particular adverse physiologic effect cigarettes.14 In all cases, Stachybotrys Toxicity on another living organism (animal, Unverified claims of: is only a minor component of the my- plant, or other microorganism) under Nonspecific symptoms coflora, which usually features Peni- appropriate conditions of exposure. cillium, Aspergillus, and Trichoderma Susceptibility to respiratory viral and Chemistry bacterial infections by species, as well as Gram-negative bac- immunosuppression teria and even Mycoplasma. Numerous Stachybotrys Air samples from 48 US schools have been characterized and studied by contained similar fungal genera as in many laboratories over many years only where there is significant water outdoor air, with Cladosporium, Peni- (Table 3). There are more than 40 tet- damage and visible mold growth on cillium, Chrysosporium, Alternaria, racyclic sesquiterpenes, collectively building surfaces. Even under these and Aspergillus comprising 95% of the know as . The same or similar ones are also produced by conditions, its concentration is very total. In some schools Penicillium air low compared with the more common concentrations were higher indoors, Fusarium, Acremonium, Trichoderma, Penicillium and Aspergillus species. In and Stachybotrys was present on some Trichothecium, Myrothecium, and Cy- lindrocarpon species. Stachyhotrys one study8-9 it was found in the air of visibly wet and mold-contaminated also synthesizes spirocyclic lactones, 2.9% of homes in southern California, carpet and wall surfaces.15 cyclosporins, stachybotrylactams, and and the mean concentration was only both constitutive and induced enzymes 0.3 spores/m3. STACHYBOTRYS TOXINS with potential toxic properties. Various Evaluation and quantitation of in- Definition assays systems are used for their de- door molds can be done by several Toxicity refers to the pathologic effect methods on both surface and air sam- of a specific chemical on a living or- ples. Air sampling routinely uses either ganism.16 Any chemical, whether nat- Table 3. Stachybotrys Toxins the Rotorod Sampler (Sampling Tech- ural or synthetic, is potentially toxic or nologies, St. Louis Park, MN) or nontoxic, depending upon the recipient Macrocydic trichothecenes Andersen sampler (Andersen Sam- organism and the conditions of expo- 3-Acetyl-deoxynivalenol plers, Atlanta, GA). Microscopic ex- Citrinine sure, such as concentration, duration, Deoxynivalenol amination is used to identify and quan- and route. Toxicity is further defined titate spores by their characteristic Diacetoxyscirpenol by the method used to detect the patho- Isosatratoxin F, G, S, H morphology, or gross inspection and physiologic or anatomic effect. Kam panels counting of fungal colonies is per- Toxicity is thus not an absolute Nivalenol formed on culture plates.9 Recently, property of any chemical even if it is Phenylspirodrimanes (9) the polymerase chain reaction technol- referred to as a "toxin," but instead, it Roridin A ogy has been used to uncover evidence is dependent upon the factors men- Satratoxin F, G, H of a particular fungus in biologic or tioned above. Further, a toxic potential T-2-Tetraol other material when the expected T-2 Toxin can be exploited therapeutically, as in Verrucarin A quantity is especially small.10 the case of the many currently used Stachybotrys spores are found Verrucarol antibiotics and immunosuppressant Vomitoxin worldwide in or on a variety of indoor drugs isolated from certain species of Enzymes items, especially organic substrates fungi. In fact, some Stachybotrys tox- 0-Glucanase rich in cellulose. These include urea- ins (satratoxins) inhibit bacteria, Acti- 1,3-Endoglucanases formaldehyde foam insulation, fiber- nomycetes, and other fungi,17 and Famesyl-protein transferase could in the future be potentially avail- Sesquiterpenes: K-76, K-76 COOH able as antimicrobial drugs. SMTP-3, -4, -5, -6 Table 2. Stachybotrys Classification Stachybocins A, B, and C Class: Oeuteromycete Mycotoxins Stachybotramide Order Moniliaceae All fungi produce and liberate an array Stachybotrin C Family: Dematiaceae of chemicals that are necessary for Staplabin Genus: Stachybotrys their survival, nourishment, and prop- Staplabin analogs: SMTP-7 and -8 Species: atra tphartarum, altemans) agation under a range of conditions. Triprenyl phenol metabolites

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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. tection,13 including chemical, physico- ation of EACl,4b,2a3b,5b from C5 and HUMAN DISEASES CAUSED BY chemical, and biologic methods. EACl,4b,2a,3b, and accelerating the STACHYBOTRYS Biologic Effects decay of EACI,4b,2a,3b,5b. They Infection also inhibit some of the reactions of The biologic effects of the many chem- To date, no case of a human systemic icals produced by S. chartarum (atrd) C2,C3,C6,C7, and C9 with (heir respec- tive preceding intermediates. Both com- or local infection caused by any spe- have been extensively studied. Most of pounds also strongly inhibit hemolysis cies of Stachybotrys has been reported, them vary among different strains of even in immunosuppressed patients. through the alternative pathway of com- the organism. Some of these activities plement activation by cobra venom fac- Allergy are summarized here. tor. They also reduce both natural killer Kozak et al' cited the case of a 4-year- Cytotoxicity. A number of macrocy- cell activity and antibody-dependent old asthmatic boy whose asthma im- clic trichothecenes (satratoxins), in- cell-mediated cytotoxicity, enhance re- proved when he was removed from his cluding isosatratoxin G and 5-isosatra- sponses to phytohemagglutinin A and home. Stachybotrys was found in a wa- toxin H, inhibit protein synthesis and lipopolysaccharide, inhibit the response ter-damaged bedrooom carpet, but not in cause direct cellular cytotoxicity in nu- to conconavalin A, and increase the air samples. Although Stachybotrys al- merous experimental systems in ani- numbers of circulating CD8+ T-lym- lergy was suspected as the cause of his mals and plants both in vitro and in phocytes. These and other immune- asthma, no allergy testing was reported. vivo. In some cases, this is mediated modulating properties can be found in There is no case of hypersensitivity through apoptosis by activation of pro- other fungi and bacteria isolated from pneumonitis caused by Stachybotrys in the published literature. Because of the tein kinases. indoor environments. Some fungal iso- unusually high levels of inhaled anti- Metabolic Effects. The activities of lates from indoor air are able to trigger enzymes of major metabolic pathways, gen required in its pathogenesis,18 histamine release by non-immunoglobu- Stachybotrys as the cause of this dis- glycolysis, the pentose phosphate path- lin (Ig)E-mediated mechanisms. way, and the tricarboxylic acid cycle, ease would be most unlikely, consid- Cytokine Effects. Satratoxins G, H, ering the extremely low airborne levels are altered by S. chartarum toxins in F, and other mycotoxins from Stachy- of Stachybotrys spores in homes or vitro. Enzymes that have been found to botrys affect interleukin 2 (IL-2) pro- buildings, even where there are obvi- be affected include aldolase, succinate duction and viability in mouse T cells. ous sources of the fungus identified on dehydrogenase, and gIucose-6-phos- IL-2 concentrations increase at low water-damaged surfaces, phate dehydrogenase. concentrations and are depressed at Toxicity Hemotysis. Some 5. chartanon conidia higher concentrations of satratoxins. Human stachybotryotoxicosis has been display hemolytic activity at 37° C when Effects on Cholesterol. Several tri- the subject of clinical investigation and cultured on sheep's blood agar. prenyl phenol metabolites isolated Plasmin Effects. A triprenyl phenol speculation for many years. The sus- from cultures of Stachybotrys were pected routes of exposure are ingestion, from Stachybotrys, designated sta- found to be inhibitors of pancreatic plabin, stimulates plasminogen activa- inhalation, and skin contact. cholesterol esterase, reducing choles- By Ingestion. The possibility of hu- tion, the binding of plasminogen to terol absorption and serum total cho- fibrin, and fibrinolysis. man toxic effects from ingestion of lesterol when fed to rats, without Stachybotrys arises because of a rec- Effects on the Lung. S. chartarum causing a significant change in the conidia and a , isosatra- ognized toxic disease in animals and high-density lipoprotein cholesterol because of the observed effects of in- toxin F, depress choline incorporation level. This may be the same com- gestion of Fitfar/um-contaminated into fetal rabbit alveolar type II cells. pound previously reported as a nema- grains in Japan and former USSR, re- Intratracheal exposure of mice to the tocidal agent. One fungal metabolite, ferred to as "alimentary toxic aleukia." trichothecene increases newly secreted stachybotramide, modulates the ac- In Siberia in the 1930s, horses fed alveolar surfactant and accumulates tivity of cholesteryl ester transfer barley, corn, and wheat stored under used forms of surfactant. protein to stimulate the transfer of winter snow developed gastrointestinal Immunologic Effects. Stachybotrys high-density lipoprotein to low-den- hemorrhages and ulcerations, accom- mycotoxins have been extensively sity lipoprotein. panied by agranulocytosis, ulcers studied for evidence of humoral and Neurologic Effects. Stachybotrin C around the mouth, inflammation of the cell-mediated immune suppression and induces significant neurite outgrowth respiratory tract, fever, and failure of prolonged allograft survival. and enhances cell survival in primary blood clotting. Many animals died K-76, a sesquiterpene, and its oxidation culture of cerebral cortical neurons. within days to weeks after the onset of product, K-76 OOOH, a monocarboxylic Other Effects. Stachybocins A, B, illness. The disease was traced to acid derivative, inhibit complement activ- and C are endothelin receptor antago- Stachybotrys infestation of the fodder, ity, mainly on C5, by inhibiting the gener- nists and inhibit HIV-1 protease. and later the condition was reproduced

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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. experimentally by feeding horses S. atra, Aspergillus, Penicillium, and A geographic cluster of 10 cases of Stachybotrys organisms added to fresh Cladosporium was performed, as were acute pulmonary hemorrhage/hemo- hay or by feeding them a pure culture several immunologic tests. The inves- siderosis occurred among infants be- of the fungus. It has affected other tigators concluded that some workers tween 1 and 8 months of age living in large farm animals, such as sheep, had experienced an allergic or immu- a localized inner-city area of Cleve- cows, swine, deer, and calves as well. notoxic disease from "toxigenic" 5. land, Ohio, between January 1993 and The condition in animals typically atra or other "atypical" fungi.27 December 1994. The disease was suc- follows a heavy rainfall and is often A two-building complex comprising cessfully treated in the hospital but re- characterized by hemorrhage in other a county courthouse in Florida sus- curred in five of the infants shortly visceral organs in addition to the al- tained considerable water damage. after they returned home. One infant imentary tract."'24 Fungi, including Stachybotrys, were died. Based on epidemiologic evidence At the time of the original observa- recovered on bulk samples of water- of severe water damage resulting in tions by veterinarians and later,23 a damaged materials. A "trace" of fungal indoor growth in the homes of similar disease occurred in some of the Stachybotrys spores was found in 1 of the patients, the illness was believed to local farmers in contact with mold- 24 quiescent air samples, but none in be caused by mycotoxin from inhaled contaminated hay or straw. Since the two aggressively stirred air samples. Stachybotrys. Between 1993 and 1998, 1940s, however, no additional human Indoor total airborne mold concentra- a total of 37 infants had been diag- case reports or epidemics have been tions were only 50% of those in the nosed with idiopathic pulmonary hem- published, although it remains a threat outdoor air, with Aspergillus versi- orrhage in metropolitan Cleveland, to farm animals. color predominant at the time the build- with 12 deaths, including 7 originally By Inhalation. In the last few years ing was occupied. After the building was diagnosed as sudden infant death syn- there has been great concern about wa- vacated, A. versicolor and Aspergillus drome. Thirty of them lived in a lim- ter-damaged building-related illnesses glaucus predominated. Stachybotrys was ited area of older housing, water dam- caused by Stachybotrys mycotoxins. recovered from surface sampling of age, and household exposure to S. These concerns center on two possible books in the law library but not in the chartarum and other fungi. These in- clinical presentations: 1) multiple sub- room air. All fungal recoveries (includ- vestigators felt that the rapidly grow- jective "health complaints" and 2} acute ing Stachybotrys) were higher after ing lungs of young infants were vul- pulmonary hemorrhage in infants. building remediation. An epidemiologic nerable to the toxigenic molds because A publication in 198626 reported that study used subjects selected by volun- adults in the household were unaf- five members of a family and their teering and not by random selection. "In- fected. S. chartarum and the closely maid "were subject to a variety of re- terstitial lung disease" was diagnosed related fungus Memnoniella echinata curring maladies," although repeated solely by the patient's history, if 2 of 3 recovered from these homes were be- examinations were negative. S. atra symptoms (fevers, myalgias, chest lieved to be responsible for these cases was cultured from an aqueous suspen- symptoms) were reported. Spirometry because of their similar and highly sion of 6,000 L air, and an undescribed but no physical examinations were per- toxic trichothecene mycotoxins.30"^ "crude test" was said to show the pres- formed. The presence of IgG and IgE More than 100 additional cases of ence of trichothecene. An ethanol ex- RAST to molds did not relate to either acute idiopathic pulmonary hemor- tract of S. atra containing debris from symptoms or "diagnosis." The report rhage with or without hemosiderosis in an air duct was fatal when injected into nonetheless concluded that this was a which Stachybotrys was present in the weanling rats and adult mice, but there building-associated disease from expo- home have been reported in infants were no appropriate controls. The au- sure to S. chartarum and A. versicolor.^ throughout the United States over the thors concluded, nevertheless, that the Multiple-symptom health com- past 5 years after the publications on family illness was caused by airborne plaints, especially "neurobehavioral the cluster of cases in Cleveland. In trichothecenes from Stachybotrys. and upper respiratory tract" were elic- several cases, the organism was also An epidemiologic study was re- ited in a survey of workers in a water- recovered from the patient's lung.3-W7 ported in 1996 of workers in an office damaged office building.29 Symptoms Although the Cleveland experience building in which 5. atra was cultured improved after the workers were re- has been widely disseminated and is from water-contaminated surface sam- moved from the environment. Fungal responsible for an intense search for ples. Subjects were limited to those contamination with S. atra was found Stachybotrys-associated disease else- seen in an occupational health clinic in 1 of 5 surface samples, and S. atra where, two expert panels commis- and were not randomly selected. Their spores in 1 of 19 air samples. Although sioned by the United States Centers for medical histories were obtained from a Stachybotrys mycotoxin was the sus- Disease Control and Prevention re- health complaint questionnaire which pected cause of the symptoms, the au- cently found serious flaws in the stud- elicited numerous specific and nonspe- thors concluded that the limitations of ies and concluded that the evidence for cific symptoms, but physical examina- epidemiologic methods made this dif- Stachybotrys as the cause of pulmo- tions were not reported. IgE RAST to ficult to investigate and confirm. nary hemorrhage in the infants was not

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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. proven. Specifically, case and control tibodies to 5. atra were detected.41 In disease in the workers. Physical exam- homes differed and sampling methods another study, S. chartarum was grown inations to uncover further objective were not standardized; there was no in aluminum dishes in closed exposure evidence of pathology are notably ab- case definition of the disease; results of chambers corresponding to 2.8 times sent from these reports. Concluding some of the data were skewed by ex- the calculated loading dose that would that their complaints or symptoms are tremely high outlying values; and the cover all surfaces in a normal room caused by inhalation of Stachybotrys disease was not felt to be consistent with mold. Despite airflow that was and/or its toxin is usually based on with idiopathic pulmonary hemosider- 4-fold greater than found in normal finding the organism on building sur- osis because of the acute onset, limited homes, there was almost no sensory face samples and absent or low levels age range, and absence of iron defi- irritation, bronchoconstriction, or pul- of spores in the air. Based on the ex- ciency. There were concerns about monary irritation effects using a sensi- tremely low levels of airborne Stachy- quantitation of water damage and the tive mouse bioassay in which the airway botrys spores in all reported cases, clinical significance (vs contamina- reactions were measured plethysmo- however, it remains extremely doubt- tion) of the exposure measurements of graphically.42 ful that there would be sufficient ex- Stachybotrys or its toxins. It was con- posure to cause an effect, even if the cluded that "a possible association be- DISCUSSION recovered fungus is able to produce a tween acute pulmonary hemorrhage There is a clear discrepancy today be- relevant mycotoxin. Self-reported but ... and [mold] exposure ... was not tween the public perception and the objectively unsubstantiated improve- proven."-18 current available scientific and clinical ment on removal of the worker from By Contact. There is one report of evidence concerning the toxic health the building is cited in some of these fingertip skin inflammation in three effects of Stachybotrys, especially as it studies as confirmation of a mycotoxic women handling moldy horticulture affects occupants of buildings that disease. This presumptive illness, pots made of recycled paper that had have sustained water damage from therefore, does not qualify as a "build- visible black masses of Stachybotrys leakage or groundwater intrusion. ing-related illness" with defined clini- conidia, as well as Chaetomium peri- Human stachybotryotoxicosis from cal and pathophysiologic features.43 It thecia and other fungi. The illness, de- ingestion of the fungus was first re- is more reminiscent of the idiopathic scribed as painful, inflamed efflores- ported as an epidemic in the 1930s in environmental intolerance phenome- cences at the fingertips, followed by Soviet farmers who were in close con- non ("multiple chemical sensitivi- scaling, was attributed to the effect of a tact with contaminated barley straw. ties"), in which nonspecific ill health mycotoxin. However, no tests were re- Since then, reports of possible human or subjective symptomatology are at- ported to determine the etiologic agent disease have been largely restricted to tributed to normal indoor environmen- or the mechanism (allergic or irritant a variety of illnesses believed to be tal chemicals.44 contact dermatitis, toxicity, or infec- caused by water-damaged buildings. Stachybotrys, like any other fungus, tion). Interestingly, handling these pots These reports fall into two distinct cat- has the capacity to generate a very released up to 7,500 conidia per cubic egories of illness: 1) a presumed ex- large number and variety of chemicals meter of air, although there was no cess numbers of "health complaints," with toxic potential to humans, pro- report of respiratory or systemic dis- rather than a specific disease and 2) vided that the exposure is sufficient. ease under these conditions!39 a specific disease-acute pulmonary The range of toxic effects demon- hemorrhage/hemosiderosis in very strated in laboratory animals and in ANIMAL DISEASE MODELS young infants. vitro cellular systems makes it difficult Experimental Stachybotrys mycotoxi- There are several publications de- to predict a particular profile of pathol- cosis in mice is limited to only a few scribing epidemiologic investigations ogy that one might expect in humans published reports. In one study, intra- of workers in office buildings in which under conditions of heavy exposure. nasal exposure to spores of S. atra a mixed fungal growth, including However, the effect of unintentional containing satratoxins caused severe Stachybotrys, is recovered after rain or ingestion of Stachybotrys-contami- intraalveolar, bronchiolar, and intersti- groundwater damage. Typically, the nated feed by large animals recognized tial inflammation with hemorrhagic workers respond to a health question- by veterinarians and even confirmed in exudation in the alveolar and bronchio- naire with numerous health com- deliberate challenge studies can serve lar lumen. The spores without satratox- plaints, especially neuropsychologic as a guide to at least one possible con- ins induced a similar but milder in- and upper respiratory symptoms, many sequence of human ingestion of the flammation.40 The injection of spores of which are also reported by workers mycotoxin. Although these reports and into mice resulted in decreased platelet in unaffected buildings. Some of these studies are now quite old and lack counts but an increase in leukocytes, investigations include a range of labo- modern scientific sophistication, these erythrocytes, and red cell indices. ratory tests that are of a screening na- horses and other animals suffered a There was no pathology in the spleen, ture, rather than those designed to con- specific condition characterized pri- thymus, or intestines, and no IgG an- firm objective evidence of a specific marily by gastrointestinal hemorrhage.

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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. The same clinical presentation oc- the current published reports of possi- Gillman SA. Currently available meth- curred in farmers who also acciden- ble human disease from inhalation of ods for home mold surveys. II. Exam- tally consumed Stachybotrys-contumi- Stachybotrys spores does not yet estab- ples of problem homes surveyed. Ann nated food, and this is consistent with lish a clear-cut cause and effect rela- Allergy 1980;45:167-176. at least one recognized toxic property tionship to warrant the degree of con- 10. Rowan NJ. Johnstone CM, McLean of this fungus. cern now expressed by such terms as RC, et al. Prediction of toxigenic fun- gal growth in buildings by using a The report from Cleveland of pul- "fatal fungus."1 The endemic cases of novel modelling system. Appl Environ monary hemorrhage from presumed pulmonary hemorrhage with or with- Microbiol 1999;65:4814-4821. inhalation of airborne Stachybotrys out hemosiderosis in Cleveland are the 11. Bissett J. Fungi associated with urea- spores occurring as a cluster of cases in most suggestive because some of the formaldehyde foam insulation in Can- which the epidemiology revealed that established in vitro properties of satra- ada. Mycopathologia 1987;99:47-56. water damage from flooding of old, toxins could be consistent with the 12. Bagy MM, Gohar YM. Mycoflora of poorly maintained inner-city homes clinical disease, although the epidemi- air-conditioners dust from Riyadh, was a significant risk factor for the ologic data have been called into ques- Saudi Arabia. J Basic Microbiol 1988; disease is certainly consistent in prin- tion. However, reports of building-as- 28:571-577. cipal with the cases associated with sociated subjective illnesses attributed 13. Andersson MA, Nikulin M, Koljalg U, ingestion of Stachybotrys. The fact that to Stachybotrys cultured from surfaces et al. Bacteria, molds, and toxins in older children and adults living in the where water damage occurred in the water-damaged building materials. Appl Environ Microbiol 1997;63: same homes with the affected infants building are not compelling. A recent 387-393. failed to get sick suggests that the in- extensive literature review reached a 14. el-Maghraby OM, Abdel-Sater MA. fant's immature lungs lack some similar conclusion.45 Mycoflora and natural occurrence of chemical, physiologic, or anatomic mycotoxins in tobacco from cigarettes protection yet to be discovered. Al- REFERENCES in Egypt. Zentralbl Mikrobiol 1993; though the criticisms of the study of 1. Environmental Health Issues Forum. 148:253-264. these infants are valid and require cau- Fatal fungus [news]. Environ Health 15. Cooley JD, Wong WC, Jumper CA, tion in interpreting the findings, the Perspect 1998; 106: A11—A12. Straus DC. Correlation between the association of this specific illness with 2. Shaban GM. Further studies on Egyp- prevalence of certain fungi and sick inhalation of Stachybotrys spores tian soil fungi: succession of sugar and building syndrome. Occup Environ osmophilic fungi in soil amended with Med 1998;55:579-584. and/or its toxin (in contrast to nonspe- 16. Doull J, Bruce MC. Origin and scope cific health complaints in adults) is five organic substrates. Mycopatholo- gia 1996; 136:33-40. of toxicology. In: Klaasen LJ, editor. biologically reasonable. Further, acute 3. Abdel-Hafez SI, Moubasher AH, Sho- Casarett and Doull's Toxicology, 3rd pulmonary hemorrhage can be readily reit AA, Ismail MA. Fungal flora as- ed. New York, Macmillan, 1986:9. diagnosed by objective findings, and is sociated with combine harvester wheat 17. Butt ZL, Ghaffar A. Inhibition of serious and potentially fatal. and sorghum dusts from Egypt. J Basic fungi, actinomycetes and bacteria by Microbiol 1990;30:467-479. Stachvhotrys atra. Mycopathol My col CONCLUSION 4. el-Kady 1A, el-Maraghy SS, Zohri AA. Appl 1972;47:241-251. Fungi are a major component of the Mycotoxin production on different 18. Fink JN, Zacharisen MC. Hypersensi- biosphere. They adapt especially well cultivars and lines of broad bean (Vicia tivity pneumonitis. In: Middleton E Jr, Reed CE, Ellis EF, et al, editors. to varying environmental conditions faba L.) seeds in Egypt. Mycopatholo- gia 1991;113:165-169. Allergy: Principles and Practice. 5th by synthesizing chemical products 5. Omar SA, Ismail MA. Microbial pop- ed. St. Louis: Mosby, 1998;996. with biologic activities that are called ulations, ammonification and nitrifica- 19. Tantaoui-Elaraki A, Mekouar SL, el mycotoxins. These have the potential tion in soil treated with urea and inor- Hamidi M, Senhaji M. Toxigenic for adverse effects on the health of ganic salts. Folia Microbiol 1999;44: strains of Stachybotrys atra associated humans and other animals. Despite 205-212. with poisonous straw in Morocco. Vet present popular concerns, Stachybotrys 6. Bagy MM. Fungi on the hair of large Hum Toxicol 1994;36:93-96. is not unique in this regard. It is a mammals in Egypt. Mycopathologia 20. Le Bars J, Gerard JP, Michel C. Dem- minor part of the indoor mycoflora, 1986:93:73-75. onstration of stachybotryotoxicosis in growing well on cellulose and there- 7. Kawai S, Takatori K, Shimozawa K, France: a case of acute intoxication in Imai K. Mycological examination on deer [in French]. Ann Nutr Aliment fore found on certain building material skin surface of cynomolgus monkeys 1977:31:509-517. surfaces in water-damaged buildings. (Macaco fascicularis)[in Japanese]. 21. Aizenman BE, Kudlai DG. History of Even under these conditions, airborne Jikken Dobutsu 1991;40:549-551. the discovery of the causative agent of spores are usually absent or present in 8. Kozak PP, Gallup J, Cummins LH, Slachvbotrys toxicosis [in Russian]. extremely low concentrations. Gillman SA. Factors of importance in Mikrobiol Zh 1978:40:264-270. The potential adverse health effects determining the prevalence of indoor 22. Schneider DJ, Marasas WF, Dale Kuys of Stachybolrys toxins will remain a molds. Ann Allergy 1979;43:88-94. JC, et al. A field outbreak of suspected concern. However, a critical review of 9. Kozak PP Jr, Gallup J, Cummins LH, stachybotryotoxicosis in sheep. J S Afr

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