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Fungi are widely distributed in the environment and are uncommon respiratory pathogens in children or adolescents. Fungi causing infection can be viewed as 2 main groups: those that cause endemic mycoses (eg, Histoplasma and Blastomyces species), which can lead to disease in both immunocompetent and immunocompromised hosts; and those considered opportunistic fungal pathogens (eg, Aspergillus and Mucor species), which primarily cause disease in immunocompromised hosts (Fig. 237-1). Although the endemic mycoses can be severe in otherwise healthy hosts, especially when exposed to a large infectious inoculum, infection is more often mild and self-limiting or even subclinical. In contrast, the endemic mycoses and opportunistic fungal pathogens can cause life-threatening pulmonary infections in patients with primary or secondary immunodeficiency. Early diagnosis of respiratory fungal infection is a challenge in both immunocompetent and immunocompromised patients. The initial clinical findings are nonspecific and are similar to other more common bacterial and viral infections. Critical to an early diagnosis is a clinician’s index of suspicion, which is influenced by recognition of the host’s immune status and vulnerability to fungal infections.

Figure 237-1

Classification of fungal respiratory pathogens.


The endemic mycoses are diseases caused by fungi with shared characteristics, including thermal dimorphism (mycelial form in the environment and yeast in tissue), the ability to cause clinically significant disease in otherwise well hosts, and specific geographic distributions.


The respiratory tract serves as the most common primary site of infection and portal of systemic entry for many of the endemic mycoses, including Histoplasma capsulatum, Blastomyces species, Coccidioides species, and Paracoccidioides species. Exposure typically occurs as a result of inhalation of infectious conidia aerosolized from soil disrupted due to wind or human activity. Although Blastomyces species may cause primary cutaneous infection by direct inoculation in children, it most frequently causes primary pulmonary infection. Organisms within the Sporothrix schenckii complex predominantly cause a cutaneous infection acquired through traumatic inoculation and only rarely cause primary respiratory tract disease. The mechanism by which humans become infected with Talaromyces marneffei is incompletely understood, but epidemiologic studies suggest that, similar to these other organisms, inhalation of infectious conidia from disrupted soil is a likely route of acquisition.

After inhalation of conidia, intact cell-mediated immunity appears to be of critical importance for control of infection. Underlying deficiencies in cell-mediated immune function predispose to severe or disseminated disease and to reactivation of latent infection. Examples of medications and conditions that increase risk of severe disease include the acquired immunodeficiency syndrome (AIDS), anticancer chemotherapy, solid organ or hematopoietic stem cell transplantation, chemotherapy, and immunomodulatory medications (including systemic corticosteroids) used for the treatment of rheumatologic and other conditions.

Although cases are documented in patients with apparently normal immunologic function, disseminated histoplasmosis and penicilliosis are considered AIDS-defining ...

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