Clinical Implications of Mycotoxins and Stachybotrys

There has been considerable interest and concern in recent years regarding the potential health effects of mycotoxins in the indoor environment. Although the existence of mycotoxins has been known for several decades, relatively little is known about their effects in humans. What is known comes almost exclusively from studies of ingestion as the route of exposure. This review summarizes what is known regarding health effects of mycotoxins in general and specifically examines the evidence for the role of indoor exposure to the fungi of the genus Stachybotrys as a cause of disease in humans. Much work remains to be done in the area of mycotoxin research. The risk of health effects from ingestion seems much more widespread than from indoor airborne exposure, although the latter has received considerably more media attention. Rigorously controlled studies are needed to clarify these issues. KEY INDEXING TERMS: Mycotoxin; Stachybotrys; Fungi; Environmental health; Mold. [Am J Med Sci 2003;325(5):262– 274. ] T are an estimated 100,000 described species of fungi, which probably represents less than half the total species that exist in nature.1 A small fraction ( 0.1%) routinely cause infection in humans, although several hundred have been reported as agents of disease in the literature. Fungi can be broadly classified as (1) yeasts, which are unicellular and reproduce by budding, (2) filamentous fungi or molds, which reproduce by spores and grow in a mycelium with hyphae, or (3) dimorphic fungi, which can exist as either yeasts or molds depending on their environmental conditions. Despite advances in molecular techniques for identifying most microorganisms, the standard for mold identification remains colony and microscopic examination. Spore characteristics, including size, shape, and type of sporulation, are critical for reliable identification to species level.1 Identification is generally done by experienced reference labs. Abnormal growth of mold has been recognized as unhealthy since ancient times. In the Old Testament (Leviticus 14:37–45), the Lord tells Moses: “If [the priest] finds greenish or reddish streaks of mildew in the walls of the house. he shall close up the house seven days, and return the seventh day to look. If the spots have spread in the wall, then the priest shall order the removal of the spotted section of the wall, and the material must be thrown in a defiled place without the city. If the spots appear again, the house is defiled [and] he shall order destruction of the house. ” Ergotism, the first widespread disease related to mycotoxin exposure, was commonly seen in the Middle Ages and probably much earlier but was not recognized for its fungal origin until the 1800s.2 It was not until 1960 that the formal study of mycotoxins really began, with the investigation of the deaths of more than 100,000 turkey poults in England, which were eventually linked to aflatoxin in the grains they were being fed.3 Mycotoxins are secondary metabolites of fungi, usually molds, that can cause injury to animals or humans.4 They are not required for growth of the fungus and are often formed after exponential growth has ceased. Secondary metabolites may be produced by the fungus to reduce competition for growth by other microorganisms. The species that synthesize these compounds are often able to detoxify them to protect themselves. Antibiotics such as penicillins, cephalosporins, and griseofulvin are also secondary metabolites of fungi but are not considered toxins. Toxigenic fungi have been considered a potential public health concern in the food industry for several decades but have not garnered much notice by the lay public. This has changed dramatically in just the past few years, with fears of ‘toxic black mold’ gripping news headlines and the public’s attention. The issue was initially brought into the public spotlight by the report from Cleveland, Ohio, of a cluster of infants with pulmonary hemorrhage and its association with toxigenic molds, specifically those of the genus Stachybotrys.5 Since then, ‘toxic mold’ has often been front-page news, with claims of health problems and building closures blamed on mold. Couples have burned their houses to the ground as the only way to get rid of mold growth, and a couple in California recently built a house entirely of stainless steel coated with silver impregnated ceramic material to prevent mold growth, at a cost of $3 million.6 In addition, public buildings are regularly closed because of indoor mold growth, and the occupants are allowed in only after remediation (cleaning and/or removal of affected areas) is complete. From the Dallas Veterans Affairs Medical Center, and the University of Texas Southwestern Medical Center at Dallas, Dal-