What laboratory tests are used to diagnose valley fever?

Laboratory Testing for Valley Fever (Coccidioidomycosis)

The primary laboratory test for diagnosing valley fever is serologic testing using enzyme immunoassay (EIA) with immunodiffusion (ID) confirmation for IgM and IgG antibodies against Coccidioides antigens. 1, 2

Initial Serologic Testing Approach

• Order coccidioidal antibody testing via EIA with ID confirmation as the first-line diagnostic test, which detects both IgM (early infection marker) and IgG (later infection and disease severity marker) antibodies 1, 2
• IgM antibodies typically become detectable within 1-3 weeks after symptom onset and indicate acute or early infection 2, 3
• IgG antibodies develop later and can be monitored through serial titers to assess disease severity and treatment response 2
• Critical pitfall: Serologic tests may remain negative for 1-3 weeks after symptom onset, so a single negative test does NOT exclude valley fever 2, 3

Alternative Serologic Methods

The CDC recommends several acceptable serologic approaches: 1

• Detection of coccidioidal IgM by immunodiffusion, enzyme immunoassay, latex agglutination, or tube precipitin 1
• Detection of rising titer of coccidioidal IgG by immunodiffusion, EIA, or complement fixation 1
• Complement fixation testing can be used to monitor disease progression and treatment response 3

Important limitation: Standard serologic testing has a false-negative rate as high as 50-70%, with 5% of symptomatic patients never developing detectable antibody levels 4

Definitive Diagnostic Testing

When serologic testing is negative but clinical suspicion remains high: 1

• Obtain fungal cultures from respiratory specimens (sputum, bronchoalveolar lavage) or tissue samples to isolate Coccidioides species 1, 2
• Submit tissue specimens for histopathologic examination to identify spherules 1
• Consider PCR-based molecular assays on tissue specimens, including paraffin-fixed samples for retrospective diagnosis 2

Major caveat: Culture results may take several weeks, making this less useful for acute management decisions 2

Repeat Testing Algorithm

If initial serology is negative but clinical suspicion persists: 1

1. Repeat serologic testing in 2-3 weeks to allow time for antibody development 1
2. Simultaneously obtain appropriate specimens (respiratory samples, tissue biopsies) for culture and histopathology 1
3. For suspected disseminated disease, obtain specimens from affected sites (skin lesions, bone, CSF) for culture and histopathology 1

Supporting Laboratory Tests

• Complete blood count typically shows normal or mildly elevated white blood cell count in uncomplicated cases 2
• Eosinophilia may be present and can provide a diagnostic clue 5, 2
• Chest radiography should be performed to assess pulmonary involvement 3

Special Populations Requiring Modified Approach

Immunocompromised patients (HIV/AIDS, solid organ transplant recipients): 2

• Serologic testing may have reduced sensitivity in these populations 2
• Prioritize direct detection methods (culture, histopathology) over serology when feasible 2
• Do not delay empiric antifungal therapy while awaiting serological confirmation 2

High-risk patients (pregnant women, certain ethnicities including African Americans and Filipinos): 2

• Do not delay empiric antifungal therapy in these populations while awaiting diagnostic confirmation 2

Skin Testing (Historical)

• Coccidioidal skin-test conversion from negative to positive after symptom onset can support diagnosis 1
• This test is rarely used in current clinical practice

Monitoring During Treatment

• Follow complement fixation titers and chest radiography until patients stabilize and symptoms resolve 3
• In patients treated with antifungals, monitor complement fixation titers for at least 2 years 3