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after infection. The appearance of these manifestations coincides with the development of delayed hypersensitivity to proteins of the infecting fungus, which is a characteristic feature of this disease.

Progressive, disseminated disease occurs in a very small percentage of infected persons, and almost any tissue or organ may be involved. Disseminated disease and chronic progressive pulmonary disease probably develop more readily in patients undergoing immunosuppressive therapy or in those with an underlying condition that lowers their immune competence, but these conditions also occur in individuals without such recognized conditions.

Pathogen Description

Coccidioides immitis is a dimorphic fungus of the subdivision Deuteromycotina (Huppert and Sun, 1980). The resistance engendered by vaccine prepared from a single strain protects in several animal species against challenge with a wide variety of strains of diverse morphological characteristics. C. immitis can be cultured easily as a mycelial fungus on dextrose-peptone agar; most strains grow more rapidly than other fungi that cause systemic disease (Huppert and Sun, 1980). The fungus also can be cultured on liquid media, under aerobic conditions. In infected hosts, C. immitis maintains a spherule endospore cycle that can be reproduced in vitro only under special physiochemical conditions. Protective antigens have not been identified. Growth and development of the spherule is associated with increased immunogenicity and the principal immunogens appear to reside in the spherule wall.

Host Immune Response

Infection with C. immitis induces both cell-mediated and humoral immune responses. Epidemiological studies indicate that recovery from primary, non-disseminated infection with C. immitis, whether symptomatic or asymptomatic, virtually always produces resistance to exogenous reinfection (Smith et al., 1948); although rare, documented reinfections have occurred in laboratory workers (Overholt and Hornick, 1964; Sorensen and Cheu, 1964).

Coccidioidin, a crude filtrate of a mycelial culture, is used in skin tests, precipitin reactions, and complement-fixation (CF) assays (Kobayashi, 1980). A positive coccidioidin skin test indicates that coccidioidal infection has occurred in the past. The close correlation between the intensity of the skin test response and immunologic competence permits the coccidioidin skin test to be used as a direct immunologic index of clinical prognosis in patients known to have coccidioidomycosis. Spherulin, a new antigenic extract from the spherule phase of the organism, appears to detect about one-third more skin test reactors than coccidioidin (Pappagianis, 1980).

In vitro parameters of cell-mediated immunity also correlate with disease activity. The macrophage inhibitory factor (MIF) is negative



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