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Fig. 6.1 A-E Fungal infections present in many different ways. A A localized verrucous lesion on the thumb due to sporotrichosis: other fungi, particularly chromoblastomycosis, may have a similar appearance. B Diffuse nodular thickening of the left ear due to lobomycosis. The majority of keloids are not due to fungus, which may make the recognition of a fungal infection more difficult. C A small lesion may be the first sign of a fungus which may spread with devastating effect. This is a vegetating lesion of the conjunctiva due to rhinosporidiosis. D-E A fungal infection may start subcutaneously and spread to underlying tissue or spread outwards from mucosa to form gross deformities. In both these patients entomophthoromycosis (zygomycosis) was responsible. Many varieties of fungi disseminate through the lungs and many other parts of the body. F It is not always possible to identify the causal fungus. This African girl from Kenya suffered from an unidentified infection which caused marked thickening of the frontal bones and the base of her skull anteriorly. Using blood cultures to identify a fungus is of little clinical value. Only about 1% will identify the organism. When they are available, more information will be obtained from microscopy, cultures, and serology. (A-E from Bittencourt and Londero 1995)

 

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True and False Fungi

Included in this chapter are diseases caused by filamentous bacteria which bear a superficial resemblance to fungi and which have traditionally been described in medical mycology. They clinically and radiologically closely resemble true fungi: they form grains in the tissues and cause swelling and draining sinus tracts. These bacteria are prokaryotic, with cells and other properties which are very different from those of the true fungi: they include members of the genera Actinomyces, Nocardia, and Streptomyces.

True fungi are eukaryotic organisms which have no chlorophyll, but their cells resemble those of eukaryotes, including those of mammals which may be infected by fungi. When they invade body tissues, they grow as budding, round, or oval cells, or as filaments, hyphae, or mycelia (molds). Many of the medically important fungi are Fungi Imperfecti, meaning that their sexual phase has not been recognized. Others are "perfect fungi", i.e., they have a specific sexual phase which classifies them as Ascomycetes, Basidiomycetes, or Zygomycetes: they can reproduce by forming sexual spores of asexual conidia. In nature they are biodegraders and make an essential contribution to the natural balance. They require an exogenous carbon source (heterotrophic). In vivo they can release enzymes to break down tissues to obtain their nourishment.

There are two distinct clinical types of fungal infection: (1) the superficial mycoses, in which the fungi live in nonliving keratin-containing parts of skin, hair, or nails and (2) the intermediate and deep mycoses, where fungi invade deep tissues from the skin. The superficial mycoses, including the socalled dermatophytes, will not be discussed in detail. Only the more significant fungi that cause deep and systemic, often life-threatening disease in humans, are described in this chapter. Each can only be summarized, because there is immense variety and no two are alike (Fig. 6.1). There are many very complex alternatives, for example, the vegetative phase may last a few days or several decades, but always precedes the reproductive phase. Some invade human tissues as hyphae (filaments), some as yeast forms, and some as both; these are called biphasic fungi and sometimes the two phases are morphologically identical. Most fungi that cause disease are saprophytic, degrading vegetation in soil and water, and only appear to infect humans and other animal species accidentally. The reproductive structures are disseminated by movement of air and only infrequently are the fungi spread from one animal directly to another. Two pathogenic species, Histoplasma capsulatum and Cryptococcus neoformans, are found in bird droppings or on soil which the droppings have contaminated.

Fungi can be grouped as primary pathogens, which can establish an infection in the immuno-normal host, usually by inhalation or by implantation of their spores, or as opportunistic, fungi which can cause disease when the natural defenses of the host are lowered or absent. This division is not absolute, as some of the fungi which are primary pathogens may also affect immunodeficient hosts. The pathogenic fungi can adapt to the higher temperature of tissues (thermotolerance) or the lower oxidation-reduction potential of tissue (Eh tolerance) and then overcome host defenses by a combination of increased multiplication and relative insensitivity to phagocytosis. Several systemic pathogens exhibit thermal dimorphism. The infectious conidia or spores of the mold (mycelial) phase invade human tissues when inhaled or implanted, and, under the influence of body temperature and other effects, change to the yeast phase. This dimorphism permits a morphological form to change to a yeast form and commonly takes place when tissue invasion occurs: the reverse can be seen during culture. At the same time other changes occur, including the composition of the cell wall. This process is also reversible. Histoplasmosis, blastomycosis, coccidioidomycosis, and paracoccidioidomycosis are diseases caused by fungi that exhibit dimorphism. Candidiasis is caused by yeasts which also can change their morphology although this is not really dimorphism. Cryptococcus neoformans is usually monomorphic, i. e., yeast-like, in the infected host and in culture.

The opportunistic fungi are probably the commonest cause of human infections and can result in both superficial and systemic disease. They are usually less virulent than viruses or bacteria, and may coexist peacefully in most people, causing no harm until there is a change in their immune status. Examples are Aspergillus, Candida, Cryptococcus, and the genera causing mucormycosis. These fungi cannot exhibit thermal dimorphism and thus remain either in a mycelial hyphae stage (e. g., Aspergillus) or in the yeast stage (e. g., Cryptococcus neoformans), invading tissues in hosts with an abnormal immune system.

 

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