Pathogenesis

The Zygomycetes represent relatively uncommon isolates in the clinical laboratory, reflecting either environmental contaminants, or, less commonly, a clinical disease called Zygomycosis. There are two orders of Zygomycetes-containing organisms that cause human disease, the Entomophthorales and the Mucorales.

The Entomophthorales derive their name from the Greek word "entomon," meaning insect, reflecting their original identification as pathogens or parasites infecting insects. The Entomophthorales cause distinctive clinical syndromes, which are usually clearly separable from those produced by the agents causing mucormycosis. Entomophthoromy-cosis is the currently accepted general term used to describe the disease caused by these fungi. Extremely rare in North America, they are usually found in Africa, Southeast Asia, Indonesia, and South America (7). Entomophthoramycosis is a tropical infection of the subcutaneous tissue or paranasal sinuses, caused by species of Basidiobolus and Conidiobolus, respectively.

The majority of human illness is caused by the Mucorales. These organisms are ubiquitous saprophytic fungi and are abundant in nature. They have been recovered from bread, fruits, vegetables, soil, and manure. The spores from these molds are transmitted by inhalation, via a variety of percutaneous routes, or by ingestion of spores. Human zygomycosis caused by the Mucorales generally occurs in immunocompromised hosts as opportunistic infections. Zygomycosis occurs only rarely in immunocompetent hosts. The disease manifestations reflect the mode of transmission, with rhinocerebral and pulmonary diseases being the most common manifestations. Cutaneous, GI, and allergic diseases are also seen. The Mucorales are associated with angioinvasive disease, often leading to thrombosis, infarction of involved tissues, and tissue destruction mediated by a number of fungal proteases, lipases, and mycotoxins (7).

Traditionally, the Mucorales are divided into six families of significance in causing human or animal disease: Mucoraceae, Cunninghamellaceae, Saksenaea, Thamnidiaceae, Syncephalastraceae, and Mortierellaceae (8). Under this classification system, the vast majority of human zygomycotic disease is caused by the members of the family Mucoraceae. The taxonomy of these fungi is based on a morphologic analysis of the fungus, in addition to carbohydrate assimilation and maximal temperature compatible with growth. These organisms typically grow in two to five days on most media. However, cycloheximide inhibits the growth of these fungi, and media that contain this compound, such as mycosel and mycobiotic agar, should not be used.

Routine stains, such as potassium hydroxide and hematoxylin and eosin (H&E), help visualize mucor hyphae, while Grocott methenamine stains (GMS) and periodic acid-Schiff stains help demarcate fungal elements in tissue (8). The Rhizopus species are mucoraceous Zygomycetes, which produce wide ribbon-like aseptate hyphae in tissues stained with GMS. Another useful stain is Cresyl violet, which stains Mucor fungi walls brick red, while other fungi are stained purple or blue. There is a great deal of variation of hyphal width, ranging from 6 to 50 |m (typically 6-15 |m) (7). Branching occurs at wide angles nearing 90°. The organisms are inexplicably difficult to grow from infected tissue. When growth does take place, it is rapid and profuse on most media at room temperature. Identification is based on the gross and microscopic appearance of the mold.

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