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Histoplasmosis duboisii

Histoplasma capsulatum var. duboisii

cal, as are many biochemical reactions. Consequently, drugs that will kill a fungus will have a toxic effect on human cells at normal doses.

A slight difference exists in the cell membranes. Lipid bi-layers by themselves are unstable and would be unable to hold their shape and support their functions. Sterols are embedded in the bilayers to act as stiffening agents. The 3-hy-droxyl group represents the polar "head" group, and the nonpolar sterol skeleton and side chain align perfectly with the nonpolar chains of the bilayer. In human cells, the sterol in the membrane is cholesterol (Fig. 6.1). In fungi, the sterol is er-gosterol (Fig. 6.2). This difference amounts to the only source of selectivity that we have in treating fungal infections. New antifungal drug development has focused on this difference as a way to achieve selectivity, creating highly potent antifungal drugs that are much less toxic to the human host.

Subcutaneous Fungal Infections22

Subcutaneous mycosis refers to a group of fungal diseases in which both the skin and subcutaneous tissue are involved but typically no dissemination to the internal organs occurs.

The causative agents are classified among several unrelated genera. They have the following characteristics in common: (a) they are primarily soil saprophytes of very low-grade virulence and invasive ability; and (b) in most human and animal infections, they gain access as a result of a trauma to the tissue. Many, if not all, organisms have the potential to establish local infections under certain circumstances, depending on their adaptability and the response of the host. The tissue reaction in most cases varies with the agent in question but usually remains a localized lesion similar to that elicited by a foreign body. The major disease types are chromomycosis, sporotrichosis, mycetoma, lobomycosis, and entomophthoromycosis. A type of dimorphism accompanies infection by agents of some of these groups. The organisms undergo a morphogenesis from their saprophytic form into a tissue or parasitic stage.

Tissue Reactions of Fungal Disease23

The tissue response of the host to the infecting fungus varies widely and depends somewhat on various invasive organisms. In dermatophyte infections, erythema is gener

ally produced and is a result of the irritation of the tissues by the organism. Sometimes, severe inflammation, followed by scar tissue and keloid formation, occurs. This results from an exaggerated inflammatory response and an allergic reaction to the organism and its products.

With organisms that invade living tissue, such as those responsible for subcutaneous and systemic disease, there is generally a uniform acute pyogenic reaction that gives way to various chronic disease outcomes. Granuloma with caseation and fibrocaseous pulmonary granuloma are potential outcomes of infection with Histoplasma capsulatum, and thrombotic arteritis, a thrombosis characterized by a purulent coagulative necrosis and invasion of blood vessels, may be caused during aspergillosis and mucormycosis. The large numbers of fungal species of many morphotypes, their disease etiology, and the diversity of outcomes make medical mycology a complex field.

Topical Agents for Dermatophytoses

Collectively, the dermatophytoses are called tinea, or ringworm. Since these infections tend to be topical, their treatment has been directed to surface areas of the skin. The skin is a formidable barrier to drug penetration, and many of the topical agents work best if an adjuvant is added that opens the barrier function of the skin. Keratolytic agents such as salicylic acid or other ^-hydroxy compounds perform this function reasonably well.

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