How to diagnose Coccidioidomycosis (Valley fever)?

From the Guidelines

Diagnosing coccidioidomycosis requires a combination of clinical evaluation, laboratory tests, and imaging studies, with the most definitive diagnosis coming from identifying the fungus Coccidioides in patient specimens through culture, microscopy, or molecular testing, as suggested by the 2019 American Thoracic Society clinical practice guideline 1. To diagnose coccidioidomycosis, the following steps can be taken:

• Clinical evaluation: Assess the patient's symptoms, medical history, and travel history to endemic areas.
• Laboratory tests: Use more than one diagnostic test, including:
  • Direct visualization and culture of sputum, bronchoalveolar lavage (BAL), or other biopsy material.
  • Urine and serum antigen testing.
  • Serology (serum antibody testing) to detect IgM and IgG antibodies against Coccidioides, such as enzyme immunoassay (EIA), immunodiffusion, and complement fixation 1.
• Imaging studies: Chest X-rays or CT scans to evaluate pulmonary disease, potentially showing nodules, cavities, or infiltrates. It is essential to note that serological testing for coccidioidomycosis can wane over time, and results might become negative after successful treatment of infection 1. Additionally, Coccidioides-specific antigen testing can result in false positives and false negatives, and a positive BDG test result can also occur in Coccidioides infection 1. The approach to diagnosis should be tailored based on the severity of illness, clinical context, and availability of tests, as recommended by the 2019 American Thoracic Society clinical practice guideline 1.

From the Research

Diagnosis of Coccidioidomycosis

To diagnose coccidioidomycosis, several methods can be employed, including:

• Serologic tests, such as enzyme immunoassay (EIA), immunodiffusion, and complement fixation, to detect antibodies against Coccidioides species 2, 3, 4, 5
• Detection of coccidioidal antigen in serum, cerebrospinal fluid, or other bodily fluids 4
• Culture or histopathological examination of tissue samples 5

Serologic Tests

Serologic tests are valuable in the management of patients with suspected or confirmed coccidioidomycosis, including:

• Qualitative tests, such as EIA, immunodiffusion, or latex particle agglutination, to detect IgM and IgG antibodies 4
• Quantitation of IgG antibody levels to aid in prognosis and diagnosis 4
• Use of humanized monoclonal antibodies as dilution controls in EIA kits to improve test accuracy 6

Enzyme Immunoassay (EIA)

EIA is a commonly used diagnostic test for coccidioidomycosis, with:

• Variable sensitivity and specificity depending on the test kit used 2, 3
• Improved sensitivity and specificity with the use of certain EIA kits, such as the MVista Coccidioides antibody detection EIA 2, 3
• Potential for false-positive results, particularly in asymptomatic patients 5

Interpretation of Test Results

Interpretation of serologic test results should be done in conjunction with clinical history, physical examination, and radiographic findings, considering:

• The reason for test performance, as false-positive results may occur in asymptomatic patients 5
• The presence of immunocompromising conditions, which may affect test accuracy 2, 3
• The need for confirmatory testing, such as culture or histopathology, to support diagnosis 5