Currently, diagnosis can be established using immunologic assays, culture, or histopathology of tissues involved (1). In mammalian tissues, coccidioidomycosis exists nearly exclusively as a characteristic spherule with endospores (Figure 1). Spherules are approximately 60 – 100 μm in diameter and can contain hundreds of variable sized daughter endospores, each capable of propagating infection. Rarely, hyphae and other atypical forms have been identified in tissues such as lung cavities or bone (2-5). In addition to histopathology, culture of the fungus isolated from a clinical specimen (i.e. bronchoalveolar lavage, CSF culture, tissue culture) confirms the diagnosis (1). Nucleic acid amplification is still being evaluated and developed for use in clinical diagnosis, with several centers using novel primers (6-10). Its potential ability to effectively detect organism in culture negative samples would be welcome, but is as yet unproven. Skin testing to identify the presence of cellular immunity to Coccidioides species is also being redeveloped after a multi-decade absence; the reader is referred to the excellent review by Wack et al (11). Its use is anticipated in both clinical and epidemiologic scenarios and for screening of at risk populations.

Currently, most clinical infections are diagnosed serologically in the setting of a compatible clinical syndrome. Immunodiffusion (ID) for the detection of IgG and IgM specific antibodies is a preferred test for detection of exposure to C. immitis, with high specificity. Complement fixation (CF) tests for IgG specific antibody are most useful in immunocompetent patients; both for diagnosis and long-term disease assessment (12). The CF titer can be useful in monitoring disease activity, and may revert to negative with long-term disease control. Complement fixation titers greater than 1:16 increase the possibility of disseminated disease. Very early in a patient’s infection, serologic results may be negative. Most frequently performed on blood samples, serology may also be performed on cerebrospinal fluid and other samples such as joint or pleural fluid.  Serologic assays are less reliable in immunosuppressed patients with 20-50% of patients testing negative with these methods. In forms of disease with a more benign clinical course, such as patients with isolated pulmonary nodules confirmed by culture or histopathology, serologic testing may often be negative.

Other assays such as latex agglutination and enzyme-linked immunosorbant assay (ELISA) have been used in the endemic region as well, though with mixed results, and often with a high false positive rate (13, 14). Coccidioides galactomannan antigen testing and serum (1→3)-β-D-glucan are available in some reference laboratories and undergoing further evaluation for their role in patient diagnosis or management (15). Identification may also be possible through the use of commercially available rRNA probes (16).



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