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. However, systemic fungal infections pose some of the most difficult diagnostic and therapeutic problems in infectious disease, particularly among immunocompromised patients. 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 to 47.
GENERAL ASPECTS OF FUNGAL DISEASE EPIDEMIOLOGY
Fungal infections are most often acquired from the external environment. One common mechanism of infection is by the inhalation of conidia generated from environmental molds. Some of these fungi are ubiquitous, whereas others are restricted to specific endemic areas, geographic regions whose climate favors their growth. Many fungi produce disease only after they are accidentally injected past the skin/mucosal barrier, especially in immunocompromised patients. Other pathogenic fungi have more sophisticated means of tissue penetration and invasion. Infection can result from systemic invasion by a fungal species that is typically an endogenous member of the resident flora, such as that seen with systemic candidiasis (Figure 43–1).
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 fungal disease (right) most often begins with inhalation of conidia followed by dissemination to other sites.
Environmental conidia inhaled
❋ Certain fungi endemic to geographic regions
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 closest because of similarities in microbial adherence to mucosal surfaces, invasion into deeper tissue layers, production of extracellular compounds, and interaction with phagocytes (Figure 43–2). In general, the principles discussed in Chapter 22 also 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.
Fungi have mechanisms for adherence and invasion
Most fungi opportunists
Several fungal species, particularly the ...