What laboratory tests are recommended for diagnosing valley fever?

Laboratory Tests for Valley Fever Diagnosis

The optimal laboratory approach for diagnosing valley fever (coccidioidomycosis) includes serologic testing for Coccidioides antibodies through immunodiffusion and complement fixation, along with culture and histopathology of appropriate specimens when indicated.

Serologic Testing

• Serologic testing is the cornerstone of valley fever diagnosis, with detection of IgM and IgG antibodies against coccidioidal antigens via immunodiffusion being the standard approach 1, 2

• The most common serologic tests include:

  • Enzyme immunoassay (EIA) with immunodiffusion confirmation - these tests may not be positive until 1-3 weeks after disease onset 2
  • 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 titers should be monitored until patients stabilize and symptoms resolve, and for at least two years in patients treated with antifungals 2

Culture and Histopathology

• Cultural, histopathologic, or molecular evidence of Coccidioides immitis can provide definitive diagnosis 1
• Tissue specimens, respiratory samples, or other appropriate clinical specimens may be submitted for culture and histopathology 1, 3
• Histopathologic examination can detect Coccidioides in formalin-fixed specimens 3

Molecular Testing

• Nucleic acid amplification tests (NAATs) may be used to detect Coccidioides DNA in clinical specimens, though these are not as widely available as serologic tests 3
• Molecular diagnostic techniques have shown promise in detecting valley fever in cases where serologic tests may be negative 4
• Immunosignature testing (pattern of antibody binding to random-sequence peptides) has demonstrated 100% sensitivity in diagnosing valley fever in patients with false-negative immunodiffusion results 4

Skin Testing

• Coccidioidal skin-test conversion from negative to positive after onset of clinical signs and symptoms can support diagnosis 1

Diagnostic Algorithm

1. Initial testing: Obtain serum for coccidioidal antibody testing (EIA with immunodiffusion confirmation) 2, 3
2. If initial serology is negative but clinical suspicion remains high:
   • Repeat serologic testing in 2-3 weeks (antibodies may take 1-3 weeks to develop) 2
   • Consider obtaining appropriate specimens for culture and histopathology 1, 3
3. For suspected disseminated disease:
   • Obtain specimens from affected sites for culture and histopathology 3
   • Monitor complement fixation titers to assess disease progression 2

Special Considerations

• False-negative rates for standard serologic tests can be as high as 50-70%, with approximately 5% of symptomatic patients never showing detectable antibody levels 4
• Diagnosis requires astute clinical suspicion based on compatible symptoms and exposure history (residence or travel to endemic areas) 2, 3
• Radiographic findings, particularly chest radiography, should be incorporated into the diagnostic evaluation 2
• Immunocompromised patients may have delayed or diminished antibody responses, potentially leading to false-negative serologic results 3

Common Pitfalls

• Relying solely on serologic testing early in the course of illness when antibodies may not yet be detectable 2
• Failing to consider valley fever in patients with community-acquired pneumonia who have resided in or traveled to endemic areas 2, 3
• Not repeating serologic testing when initial tests are negative but clinical suspicion remains high 2
• Overlooking the possibility of valley fever in patients outside traditional endemic areas, as the geographic distribution is expanding 3