Systemic Mycoses

These infections result from inhalation of the spores of dimorphic fungi that have their saprophytic old forms in the soil. Within the lungs, the spores differentiate into yeasts or other specialized forms. Most lung infections are asymptomatic and self‑limited. However, some persons develop diseminated disease in which the organisms grow in other organs, cause destructive lesions, and may result in death. Infected persons do not communicate these diseases to others.

 COCCIDIOIDES

 Disease Coccidioides immitis causes coccidioidomycosis.

 Properties C immitis is a dimorphic fungus that exists as a mold in soil and as a spherule in tissue (Fig 49‑1).

 Transmission & Epidemiology The fungus is endemic in and regions of the southwestern United States and Latin America. In soil, it forms hyphae with alternating arthrospores and empty cells. Arthrospores are very light and are carried by the wind. They can be inhaled and infect the lungs.

 Pathogenesis In the lungs, arthrospores form spherules that are large (30 gm in diameter), have a thick, doubly refractive wall, and are filled with endospores. Upon rupture of the wall, endospores are released and differentiate to form new spherules. The organism can spread within a person by direct extension or via the bloodstream. Granulomatous lesions can occur in virtually any organ but are found primarily in bones and the central nervous system (meningitis). Dissemination indicates some defect in cell‑mediated immunity. Most persons who develop a positive skin test to infection develop immunity to spread and to reinfection. However, if their cellular immunity is suppressed by drugs or disease, dissemination can occur at any time. 

Clinical Findings Infection of the lungs is often asymptomatic and is evident only by a positive skin test and the presence of antibodies. Some infected persons have an influenzalike illness with fever and cough. About 50% have changes in the lungs as seen in x‑rays, and 10% develop erythema. nodosurn (see below) or arthralgias. This syndrome is called "valley fever" (in the San Joaquin Valley of California) or "desert rheumatism" (in Arizona); it tends to subside spontaneously. 

Disseminated disease can occur in almost any organ; the messiness, bone, and skin are important sites, The overall incidence of dissemination in persons infected with C immitis is 1%, although the incidence in Filipinos and African Americans is 10 times higher. Pregnant women in the third trimester also have a markedly increased incidence of dissemination.  

Erythema nodosum (EN) manifests as red, tender nodules on extensor surfaces such as the shins. It is a delayed (cell‑mediated) hypersensitivity response to fungal antigens and thus is an indicator of a good prognosis. There are no organisms in these lesions; they are not a sign of disseminated disease. EN is not specific for coccidioidomycosis; it occurs in other granulomatous diseases, eg, histoplasmosis, tuberculosis, and leprosy.

 Laboratory Diagnosis In tissue specimens, spherules are seen microscopically. Cultures on Sabouraud's agar incubated at 25 PC show hyphae with arthrospores. (Caution: Cultures are highly infectious; precautions against inhaling  must be taken.) In infected persons, skin tests with fungal extracts (coccidioidin or spherulin) cause at least a 5‑mm induration 48 hours after injection (delayed hypersensitivity reaction). Skin tests become positive within 2‑4 weeks of infection and remain so for years but are often negative (anergy) in patients with disseminated disease. In serologic tests, IgM and IgG precipitins appear within 2‑4 weeks of infection and then decline in subsequent months. Complement fixing antibodies occur at low titer initially, but the titer rises greatly if dissemination occurs.

Treatment and Prevention No treatment is needed in asymptomatic or mild primary infection. Amphotericin B (Fungizone) is used for persisting lung lesions or disseminated disease. Ketoconazole is a also effective in lung disease. If meningitis occurs, fluconazole is the drug of choice. Intrathecal amphotericin B may be required  and may induce remission, but long term results are often poor. There are no means of prevention except avoiding travel to endemic areas.