Which laboratory tests should be ordered for suspected valley fever (coccidioidomycosis)?

Laboratory Testing for Valley Fever (Coccidioidomycosis)

Order multiple tests simultaneously—serum antibody testing (IgM and IgG), urine and serum antigen testing, and respiratory culture/direct visualization—because no single test has adequate sensitivity when used alone. 1

Primary Serologic Testing (First-Line)

• Start with enzyme immunoassay (EIA) for both IgM and IgG antibodies as your initial serologic test, which offers rapid turnaround (hours vs. days) and higher sensitivity compared to older methods 1
• IgM antibodies appear 1-3 weeks after symptom onset and indicate acute infection 2
• IgG antibodies develop 4-8 weeks later and persist longer, useful for chronic disease 2
• EIA sensitivity is 87% in immunocompetent patients but drops to 67% in immunosuppressed patients 1
• Follow positive or equivocal EIA results with confirmatory immunodiffusion (ID) or complement fixation (CF) testing for increased specificity 1

Critical Serologic Pitfalls

• Serology may be negative early in infection (first 1-3 weeks) despite active disease 2
• Immunocompromised patients show reduced sensitivity (84% vs. 95% in healthy hosts), particularly those with HIV and CD4+ counts <250 cells/µL 2, 3
• Cross-reactivity occurs with histoplasmosis and blastomycosis in approximately 10% of cases 1, 3
• Antibody titers can wane over time and become negative after successful treatment 1, 3

Antigen Testing (Complementary)

• Order both urine AND serum Coccidioides antigen testing because they are complementary—some samples are positive in one specimen type but not the other 1, 2, 3
• Antigen testing has highest value in immunocompromised patients with severe or disseminated disease 1, 2
• Sensitivity is approximately 70-73% with specificity of 97.8% 1, 2
• Expect approximately 10% cross-reactivity with other endemic fungi (histoplasmosis, blastomycosis) 1, 2, 3
• Available only at reference laboratories, not point-of-care 1

Culture and Direct Visualization

• Obtain sputum, bronchoalveolar lavage (BAL), or tissue biopsy for culture and direct microscopy when respiratory specimens are accessible 1
• Culture is highly specific but has low sensitivity, so negative culture does not exclude disease 1, 2
• Coccidioides can grow as early as 48 hours but may require 2-5 weeks 3
• Direct visualization of spherules on histopathology proves the diagnosis even without positive culture 2
• Alert the laboratory that Coccidioides is suspected—the organism is highly infectious and requires biosafety level 3 precautions 1

Algorithmic Approach by Clinical Context

For Immunocompetent Patients with Suspected Pneumonia

• Order serum EIA (IgM and IgG) immediately 1
• Order urine and serum antigen testing simultaneously 1
• Obtain sputum or BAL for culture and direct visualization if respiratory specimens available 1
• If EIA positive, confirm with ID or CF 1

For Immunocompromised Patients (HIV, transplant, immunosuppressive therapy)

• Prioritize antigen testing (both urine and serum) over serology due to reduced antibody response 1, 2
• Still order serology but recognize 16% false-negative rate 2, 3
• Strongly pursue tissue diagnosis with culture and histopathology given higher risk of disseminated disease 1, 2
• Consider repeat testing if initial results negative but clinical suspicion remains high 2

For Suspected Disseminated Disease

• Order all tests: serology, antigen (urine and serum), and culture from affected sites 1
• CF titers correlate with disease severity and can guide prognosis 4
• Obtain tissue biopsy from accessible sites (skin lesions, lymph nodes) for definitive diagnosis 2

Geographic and Risk Factor Documentation

• Confirm exposure to endemic areas: southwestern US (Arizona, California, Nevada, New Mexico, Utah, Texas), parts of Mexico, Central and South America 5
• Assess risk factors: African or Filipino ancestry, pregnancy, diabetes, cardiopulmonary disease, immunosuppression 2, 5

Interpretation Strategy When Results Conflict

• When antigen positive but organism identity uncertain due to cross-reactivity, prioritize culture and direct visualization as definitive tests 2, 3
• Correlate all laboratory results with clinical presentation, radiographic findings, and epidemiologic exposure 1, 2
• If serology negative but clinical suspicion high, repeat testing in 2-4 weeks to capture seroconversion 1, 2
• Consider beta-D-glucan testing may be positive but is nonspecific 1