We all have regular contact with fungi. They are so widely distributed in our environment that thousands of fungal spores are inhaled or ingested every day. Some species are so well adapted to humans that they are common members of the microbiota. Despite this ubiquity, clinically apparent systemic fungal infections are uncommon, even among persons living within the geographic habitat of the more pathogenic species. However, progressive systemic fungal infections pose some of the most difficult diagnostic and therapeutic problems in infectious disease, particularly among immunocompromised patients to whom they are a major threat. The purpose of this chapter is to provide an overview of the pathogenesis and immunology of fungal infections. Details relating to specific fungi are provided in Chapters 45, 46, and 47.
GENERAL ASPECTS OF FUNGAL DISEASE EPIDEMIOLOGY
Fungal infections are acquired from the environment or may be endogenous in the few instances where they are members of the resident flora (Figure 43–1). Inhalation of infectious conidia generated from molds growing in the environment is a common mechanism. Some of these molds are ubiquitous, whereas others are restricted to geographic areas whose climate favors their growth. In the latter case, disease can be acquired only in the endemic area. Some environmental fungi produce disease after they are accidentally injected past the skin barrier. The pathogenic fungi represent only a small percentage of those found in the environment. Endogenous infections are restricted to a few yeasts, primarily Candida albicans. These yeasts have the ability to colonize by adhering to host cells and, given the opportunity, invade deeper structures.
Fungi system view. Localized disease (left) is caused by local trauma or the superficial invasion of flora resident on the oropharyngeal (thrush), gastrointestinal, or vaginal mucosa. Systemic disease (right) begins with inhalation of conidia followed by dissemination to other sites.
Environmental conidia are inhaled or injected
Endogenous yeasts may invade
Compared with bacterial, viral, and parasitic disease, less is known about the pathogenic mechanisms and virulence factors involved in fungal infections. Analogies to bacterial diseases come the closest because of the apparent importance of adherence to mucosal surfaces, invasiveness, extracellular products, and interaction with phagocytes (Figure 43–2). In general, the principles discussed in Chapter 22 apply to fungal infections. Most fungi are opportunists, causing serious disease only in individuals with impaired host defense systems. Only a few fungi are able to cause disease in previously healthy persons.
Immunity to fungal infections. A. Pathogenic fungi are able to survive and multiply slowly in nonactivated macrophages. B. When macrophages are activated by cytokines from T-cells the growth is restricted and the fungi digested.