Chapter 134: Cryptococcosis and the Endemic Mycoses

Introduction

Histoplasmosis and blastomycosis mostly afflict those living in the Mississippi and Ohio River Valleys, while coccidioidomycosis occurs primarily in the Southwestern desert of the United States (Fig. 134-1). Histoplasmosis and coccidioidomycosis also are endemic in parts of Mexico and Central and South America. Infection with Cryptococcus neoformans var. gatti is endemic to parts of British Columbia, the Pacific Northwest region of the United States and Australia while C. neoformans var. neoformans exhibits no geographical predilection. These mycoses are often mistakenly diagnosed and incorrectly treated as community-acquired pneumonia or sarcoidosis, resulting in serious morbidity or death in many cases.^1–3

These organisms are found in the soil, and infection occurs following inhalation of the infectious forms of these fungi when sites containing the organism are disturbed. In some endemic areas over one-half of residents have acquired these mycoses early in life. In healthy individuals the infections are usually asymptomatic or clinically self-limited. In others, especially those who are immunosuppressed, the course of infection may be progressive and fatal without treatment. While these mycoses are less often seen in patients with acquired immunodeficiency syndrome (AIDS) who have access to effective antiretroviral therapy, they are occurring more frequently in those with other immunosuppressive conditions, and continue to be pathogenic for individuals without underlying disease. The majority of those hospitalized due to infection with endemic mycoses in the United States in fact have no identifiable immunologic deficits. In a study of patients hospitalized with histoplasmosis, blastomycosis, or cocciodiodomycosis, only 13% of those infected were immunosuppressed. Hospital costs alone exceeded $250 million,⁴ providing an estimate of the impact of the endemic mycoses in the United States. Advances in diagnosis and treatment provide opportunities to improve the outcome of these mycoses.

Cryptococcal Infections

Cryptococcosis is caused by infection with the encapsulated fungus C. neoformans, an organism with a worldwide distribution. Inhalation of C. neoformans initiates the infection in the lung with hematogenous dissemination most often involving the meninges. Although pulmonary infection may be discovered in the presence or absence of disseminated infection, meningoencephalitis remains the most commonly diagnosed form of cryptococcal infection. The spectrum of disease ranges from asymptomatic pulmonary infection in the immunocompetent host to diffuse pulmonary disease associated with respiratory failure and widespread disseminated disease in the immunocompromised host. It is estimated that nearly 1 million cases of cryptococcal meningitis occur worldwide annually, with the majority of cases occurring in those with HIV infection.⁵ The incidence of cryptococcosis in patients with AIDS in the United States has declined since the introduction of potent antiretroviral therapy; most cases now occur in those with limited access to ...