What are the laboratory tests for diagnosing valley fever?

Laboratory Testing for Valley Fever (Coccidioidomycosis)

The primary laboratory test for diagnosing valley fever is coccidioidal serological testing, specifically enzyme immunoassay (EIA) with immunodiffusion (ID) confirmation for IgM and IgG antibodies, though these tests may not become positive until 1-3 weeks after symptom onset. 1

Initial Diagnostic Approach

Serological Testing (Primary Method)

• Enzyme immunoassay (EIA) is the recommended initial screening test, followed by immunodiffusion (ID) for confirmation of positive or equivocal results 2
• IgM antibodies (detected by tube precipitin/TP antigen) appear first and indicate early or acute infection, typically becoming detectable within 1-3 weeks of symptom onset 1, 2, 3
• IgG antibodies (detected by complement fixation/CF) develop later and can be used to monitor disease severity and treatment response through serial titers 1, 2
• Sensitivity of serological testing is 78.8-92.7% depending on the specific assay and timing of specimen collection 4, 3

Critical Timing Considerations

• Serological tests are often negative during the first 1-3 weeks of illness, which is precisely when most patients present for care 1, 2
• The false-negative rate can be as high as 50-70% in early disease, with approximately 5% of symptomatic patients never developing detectable antibody levels 5
• Diagnosis should not be ruled out based on a single negative serological test if clinical suspicion remains high 2

Fungal Culture and Direct Detection

Culture Methods

• Fungal cultures of respiratory specimens (sputum, bronchoalveolar lavage) or tissue samples can definitively diagnose coccidioidomycosis by isolating Coccidioides species 1, 6
• Culture is highly specific but requires biosafety level 3 precautions due to the infectious nature of the organism 3
• Culture results may take several weeks, making this method less useful for acute management decisions 1

Molecular Testing

• PCR-based assays are not commercially available in the United States but can be performed at reference laboratories such as the CDC 1
• Molecular testing can be performed on tissue specimens, including paraffin-fixed samples, allowing for retrospective diagnosis 1

Supporting Laboratory Tests

Complete Blood Count and Chemistry

• CBC typically shows normal or mildly elevated white blood cell count in uncomplicated primary pulmonary coccidioidomycosis 1
• Eosinophilia may be present in some patients with coccidioidomycosis 1
• Liver function tests and inflammatory markers (ESR, CRP) should be obtained to assess for disseminated disease 2

Special Populations and Circumstances

Immunocompromised Patients

• Serological testing may have reduced sensitivity in HIV/AIDS patients and solid organ transplant recipients, though this appears less problematic than with some other fungal infections 1
• Direct detection methods (culture, histopathology) should be prioritized in immunocompromised patients when feasible 1

Disseminated Disease

• Complement fixation titers ≥1:16 suggest disseminated or severe disease and warrant more aggressive management 1, 2
• Serial CF titers should be monitored to assess treatment response, with testing recommended for at least 2 years in treated patients 2

Newer Diagnostic Technologies

Rapid Lateral Flow Assays

• A rapid lateral flow assay detecting anti-CTS1 (chitinase 1) antibodies has been developed with 92.9% positive agreement and 97.7% negative agreement compared to ID/CF 4
• This 10-minute point-of-care test could improve efficiency of healthcare delivery, though it is not yet widely available 4

Immunosignature Technology

• Peptide microarray-based immunosignatures can detect valley fever with 98% accuracy and may identify false-negative patients with 100% sensitivity 5
• This technology remains investigational and is not currently available for routine clinical use 5

Common Pitfalls to Avoid

• Never rely on a single negative serological test to exclude valley fever, especially if obtained within the first 3 weeks of illness 1, 2
• Do not delay empiric antifungal therapy in high-risk patients (immunocompromised, pregnant, certain ethnicities) while awaiting serological confirmation 1, 2
• Avoid ordering only IgM or only IgG testing—both should be assessed as they provide complementary diagnostic information 2
• Remember that positive serology only indicates infection at some point, not necessarily active disease; clinical and radiographic correlation is essential 1

Monitoring During Treatment

• Serial complement fixation titers and chest radiography should be performed until patients stabilize and symptoms resolve 2
• In patients receiving antifungal therapy, CF titers should be followed for at least 2 years to detect relapse 2
• Rising CF titers during or after treatment suggest treatment failure or relapse and warrant reassessment 2