Coccidioidesspp. afflicts ~100,000 patients per year in a nationwide distribution reflective of travel to the Southwest.¹ Culture is straightforward but negative results do not rule out disease; Papanicolaou staining of bronchial washings is useful.² Recent reviews of new treatments³ and serologic tests⁴ are available.

Development of sufficiently sensitive and specific EIAs has considerably improved the diagnostic value of C. immitis-specific antibody detection. EIA using a combination of coccidioidal antigens for differential detection of IgM and IgG antibodies is the method of choice for diagnosis of C. immitis infection, offers sensitivities >92% and 100% and specificities >98% and 96% for serum and CSF, respectively, and provides information about disease stage.^5,6  Maximal sensitivity for diagnosis of coccidioidomycosis is achieved by testing for both IgG and IgM antibodies by EIA; however, cross-reactions can occur with sera from patients with confirmed blastomycosis and noncoccidioidal disease.⁶ Serological diagnosis of C. immitis infection is frequently based on CF, immunodiffusion CF (IDCF), tube precipitin (TP) and/or immunodiffusion TP (IDTP) tests. CF and IDCF are routinely used to detect C. immitis-specific IgG; whereas, TP and IDTP tests are used to detect C. immitis-specific IgM (early acute infection). However, even purified TP antigen preparations can detect both IgM and IgG by EIA, indicating that there is also an IgG response to TP antigen.^4-6  EIA can detect antibody responses to C. immitis sooner after infection than can CF, TP, IDCF and IDTP assays;^4-6 this allows timely institution of antifungal therapy. Additionally, circulating coccidioidal antigen can be detected by inhibition EIA prior to development of specific antibodies.⁶ EIA-based IgG and IgM assays against TP and CF antigens of C. immitis are strangely correlated with traditional methods, (CF, LA and ID) with 96.7% agreement for both IgG and IgM. EIAs offer a specificity of 98.5% and sensitivity of 94.8% with the subjectivity involved in interpretation of traditional assays and anticomplement interference.⁵ CF tests can yield cross-reactions with sera from patients with other mycoses due to Aspergillus spp., B. dermatitidis, H. capsulatum, P. pedrosi, Candida spp., C. neoformans and T. glabrata and other diseases including tuberculosis and pneumonia due to Streptococcus and Mycoplasma pneumoniae;^7,8 such cross-reactions are minimal in an EIA format. Anticomplementary sera can also be reliably evaluated by EIA^2,3 in contrast to CF.^9,10 Detection of only specific IgM by EIA or LPA is uncommon and should be confirmed by ID testing.⁴

Qualitative IDCF is a useful screening test; concentration of serum or CSF increases the sensitivity relative to CF; IDCF, however, can yield false-positive results in patients with nonmeningitic coccidioidomycosis who have leaky blood-brain-barriers, especially with concentrated CSF.¹¹ Titers of quantitative IDCF approximate those of CF.¹² Serum CF titers parallel the severity of infection.^8,13 Low CF titers (<1:8) are found in pulmonary coccidioidomycosis, extrapulmonary disease affecting the CNS, bones and joints and skin and in patients with inactive disease. Higher CF titers (>1:16) are often associated with disseminated disease.^8,13 Serum CF titers of 1:2-1:8 should be further evaluated by ID or EIA. CF titers in CSF are usually lower than serum titers (by 1-2 dilutions).¹⁴ CSF CF titers >1:2 usually indicate meningitis, except in the case of juxtadural coccidioidal disease, which can be distinguished by normal CSF glucose concentration and cell count but increased CSF protein concentration. Approximately 95% of patients with coccidioidal meningitis have detectable levels of CF antibody in CSF.⁴  Rising CF titers in serum or CSF are associated with disease progression; falling titers parallel clinical improvement.¹⁴

C. immitis is probably the most common cause of eosinophilic meningitis in the U.S.¹³

The Spherulin skin test is preferable to that using coccidioidin; neither test elicits an antibody response.¹⁵ A positive skin test correlates with present or past coccidioidomycosis; conversion of a negative to a positive skin test suggests recent infection.¹⁵ In vitro lymphocyte transformation assays and evaluation of lymphokine production are potentially more useful than delayed dermal hypersensitivity reaction in individuals with progressive or disseminated coccidioidomycosis.¹⁶ The clinical utility of DNA probes for detection of C. immitis requires further evaluation,^17,18 as do PCR-based tests. Multilocus genotyping can identify sources of Coccidioides infections, including  C. immitis and C. posadasii.¹⁹