Pathogenesis and electron microscopic changes of spherulogenesis of Coccidioides immitis (valley fever)

Pathogenesis and electron microscopic changes of spherulogenesis of Coccidioides immitis were determined. The organism showed a strong affinity for lung tissue, with granuloma developing in 100% (n = 40) of animals after subcutaneous and intraperitoneal inoculation. Intranasal instillation of the arthrospores resulted in moderate granuloma, with a markedly low frequency rate of infection in 11 animals (55%). Intradermal inoculation and skin scarification did not induce systemic infection. Unlike other routes used to induce infection, only 30% of the mice showed cutaneous changes, whereas in the group infected by skin scarification, 25% of the animals revealed pathologic changes. Indurated tiny nodular lesions developed in the skin at the site of the inoculation. The lesions did not ulcerate, and complete resolution was observed in 4 to 6 weeks. Electron microscopy of the spherulogenesis showed that the tissue form of the fungus replicated in the host tissues by segmentation of the innermost stratum of the wall of the spherule. The layer appeared to function as a germinating center, and as many as 8 spores of irregular size and shape were produced within a kidney-shaped segment. Many segments were in each spherule. The spores were separated, pushed more centrally, and became rounded to become the endospores. When the endospores were freed, each developed into a spherule.