Chapter 75Spectrum of Mycoses

Classification of Mycoses

The clinical nomenclatures used for the mycoses are based on the (1) site of the infection, (2) route of acquisition of the pathogen, and (3) type of virulence exhibited by the fungus.

Classification Based on Site

Mycoses are classified as superficial, cutaneous, subcutaneous, or systemic (deep) infections depending on the type and degree of tissue involvement and the host response to the pathogen.

Classification Based on Route of Acquisition

Infecting fungi may be either exogenous or endogenous. Routes of entry for exogenous fungi include airborne, cutaneous or percutaneous. Endogenous infection involves colonization by a member of the normal flora or reactivation of a previous infection.

Classification Based on Virulence

Primary pathogens can establish infections in normal hosts. Opportunistic pathogens cause disease in individuals with compromised host defense mechanisms.

Epidemiology

The primary pathogens have relatively well-defined geographic ranges; the opportunistic fungi are ubiquitous.

Current magnitude and problems of mycoses

Fungal infections or mycoses cause a wide range of diseases in humans. Mycoses range in extent from superficial infections involving the outer layer of the stratum corneum of the skin to disseminated infection involving the brain, heart, lungs, liver, spleen, and kidneys. The range of patients at risk for invasive fungal infections continues to expand beyond the normal host to encompass patients with the acquired immunodeficiency syndrome; those immunosuppressed due to therapy for cancer and organ transplantation, and those undergoing major surgical procedures. Each of these patient populations has a high risk of developing invasive fungal infections. As the population at risk continues to expand so also does the spectrum of opportunistic fungal pathogens infecting these patients also continue to increase. Many of the deeply invasive mycoses are difficult to diagnose early and often difficult to treat effectively. The development of new approaches to diagnosis and treatment of invasive fungal infections is the subject of intensive research.

Concepts of classification

Fungal infections may be classified according to the site of infection, route of acquisition, and type of virulence. When classified according to the site of infection, fungal infections are designated as superficial, cutaneous, subcutaneous, and deep (Fig. 75-1). Superficial mycoses are limited to the stratum corneum and essentially elicit no inflammation. Cutaneous infections involve the integument and its appendages, including hair and nails. Infection may involve the stratum corneum or deeper layers of the epidermis. Inflammation of the skin is elicited by the organism or its products. Subcutaneous mycoses include a range of different infections characterized by infection of the subcutaneous tissues usually at the point of traumatic inoculation. An inflammatory response develops in the subcutaneous tissue frequently with extension into the epidermis. Deep mycoses involve the lungs, abdominal viscera, bones and or central nervous system. The most common portals of entry are the respiratory tract, gastrointestinal tract, and blood vessels (Fig. 75-2).

When classified according to the route of acquisition, a fungal infection may be designated as exogenous or endogenous in origin. If classified as exogenous, an infecting organism may be transmitted by airborne, cutaneous, or percutaneous routes. An endogenously-acquired fungal infection may be acquired from colonization or reactivation of a fungus from a latent infection. Fungi may be classified also according to virulence, as primary pathogens or as opportunistic pathogens. A primary pathogen may establish infection in an immunologically normal host; whereas, an opportunistic pathogen requires some compromise of host defenses in order for infection to become established.

General Concepts

Primary Mycoses

Most cases of primary deep mycoses are asymptomatic or clinically mild infections occurring in normal patients living or traveling in endemic areas. However, patients exposed to a high inoculum of organisms or those with altered host defenses may suffer life-threatening progression or reactivation of latent foci of infection.

The arthroconidia of C immitis are inhaled and convert in the lung to spherules. Most cases of coccidioidomycosis are clinically occult or mild infections in patients who inhale infective arthroconidia. However, some patients have progressive pulmonary infection and also may suffer dissemination to the brain, bone, and other sites. Coccidioides meningitis is a life-threatening infection requiring lifelong treatment.

Histoplasmosis is a primary pulmonary infection resulting from inhalation of conidia of Histoplasma capsulatum which convert in vivo into the blastoconidial (budding yeast) form. Dissemination to the hilar and mediastinal lymph nodes, spleen, liver, bone marrow, and brain may be life-threatening in infants and other immunocompromised patients. Histoplasmosis (like tuberculosis) is characterized by intracellular growth of the pathogen in macrophages and a granulomatous reaction in tissue. These granulomatous foci may reactivate and cause dissemination of fungi to other tissues. These patterns of primary infection and reactivation are similar to those of Mycobacterium tuberculosis (see Chapter 33). Histoplasmosis also may be associated with a chronic inflammatory process known as fibrosing mediastinitis, where scar tissue (formed in response to H capsulatum) encroaches on vital structures in the mediastinum.

Blastomycosis, similar to histoplasmosis, is a primary pulmonary infection resulting from inhalation of conidia from the mycelial phase of Blastomyces dermatitidis which convert in vivo to the parasitic yeast phase. Blastomycosis (due to B dermatitidis) in the blastoconidial phase also causes a primary pulmonary infection. The organism elicits a granulomatous reaction often associated with a marked fibrotic reaction. The clinical pattern of pulmonary blastomycosis is one of chronic pneumonia. Dissemination occurs most commonly to the skin, bone, and, in males, prostate.

Opportunistic Mycoses

Basic Concepts of Environmental Epidemiology

The epidemiology of dimorphic primary pathogens may be contrasted with that of the opportunistic fungal pathogens. The primary pathogens have a relatively well-defined geographic range of endemic infection in immunocompromised hosts. By comparison, the opportunistic fungi (e.g. Aspergillus spp.) are ubiquitously distributed with the frequency of infection being dependent upon a population of immunocompromised hosts. Penicillium marneffei, an opportunistic pathogen, appears to be geographically restricted to the East Asia, particularly Thailand and China.

Control and Treatment

Hospital-acquired fungal infections may be reduced by maintaining the lowest possible concentration of fungal spores in the ambient air of the institution. Ideally, a “spore-free” environment should be sought. Antifungal therapy, which is reviewed in depth elsewhere, is an area of intense investigation (See Chapter 76). New antifungal compounds will hopefully improve the efficacy and reduce toxicity of treatment of invasive fungal infections.