Each of the four primary systemic mycoses—coccidioidomycosis, histoplasmosis, blastomycosis, and paracoccidioidomycosis—is geographically restricted to specific areas of endemicity. The fungi that cause coccidioidomycosis and histoplasmosis exist in nature in dry soil or in soil mixed with guano, respectively. The agents of blastomycosis and paracoccidioidomycosis are presumed to reside in nature, but their habitats have not been clearly defined. Each of these four mycoses is caused by a thermally dimorphic fungus, and the infections are initiated in the lungs following inhalation of the respective conidia. Most infections are asymptomatic or mild and resolve without treatment. However, a small but significant number of patients develop pulmonary disease, which may involve dissemination from the lungs to other organs. With rare exceptions, these mycoses are not transmissible among humans or other animals. Table 1 summarizes and contrasts some of the fundamental features of these systemic or deep mycoses.
Table1. Summary of Endemic Mycoses a
For all of these infections, the initial host defenses are provided by the alveolar macrophages, which are usually capable of inactivating the conidia and inducing a robust immune response. This process typically leads to granulomatous inflammation and the production of both antibodies and cell-mediated immunity. The induction of Th1 cytokines (eg, interleukin-12, interferon-γ, and tumor necrosis factor α) will amplify the cellular defenses, activating macrophages, and enhancing their fungicidal capacity. In an immunocompetent host, these responses lead to resolution of the inflammatory lesions. However, residual granulomata may retain dormant organisms with the potential for subsequent reactivation, constituting a latent form of the disease. Within the endemic areas for these fungi, most infections occur in immunocompetent individuals, but persons with impaired cellular immunity, such as patients with HIV/AIDS, have a greatly increased risk of serious infection. Strains of most pathogenic fungi exhibit large variations in laboratory assays of pathogenicity. For the agents of these endemic mycoses, virulence is associated with α-glucan in their cell walls, perhaps by masking pathogen-associated molecular patterns that trigger protective immune responses.
In recent years, two additional thermally dimorphic endemic molds have emerged in patients with HIV/AIDS— T. marneffei and Emergomyces africanus. Because T. marneffei and E. africanus were originally identified as members of different genera, Penicillium and Emmonsia, respectively, their infections are often called penicilliosis and emmonsiosis. These infections are described in the section on Opportunistic Mycoses. Figure 1 shows the areas of endemicity of these fungi. Sporotrichosis is included on the map because the etiology, S. schenckii, like the others and as described above, evinces thermal dimorphism, growing as a saprobic mold in nature at temperatures of 25-30°C, and switching to the yeast form (or spherules in Coccidioides) at mammalian body temperature. However, S. schenckii is found worldwide.
Fig1. Global distribution of endemic mycoses. Each is caused by a dimorphic environmental mold and undergoes morphogenesis within the host. (Reproduced with permission from Lee PP, Lau Y-L: Cellular and molecular defects underlying invasive fungal infections—revelations from endemic mycoses. Front Immunol 2017;8:375.)
