What is the diagnosis for coccidioidomycosis (Valley fever)?

From the Guidelines

Diagnosing coccidioidomycosis requires a combination of clinical evaluation, laboratory tests, and imaging studies, with the most recent and highest quality study recommending serological testing of blood and microscopic examination of specimens for the presence of Coccidioides spp 1. The diagnosis begins with recognizing risk factors such as travel or residence in endemic areas (southwestern United States, parts of Mexico, and Central and South America) and considering symptoms like fever, cough, fatigue, chest pain, and rash.

• Laboratory testing includes serologic tests for Coccidioides antibodies (IgM and IgG), which are the most common diagnostic tools.
• The enzyme immunoassay (EIA) is typically used first, followed by confirmation with immunodiffusion or complement fixation tests.
• Direct detection methods include fungal culture from respiratory specimens, body fluids, or tissue, though cultures can take up to 3 weeks and pose infection risks to laboratory personnel.
• Microscopic examination of specimens may reveal characteristic spherules with endospores.
• Molecular tests like PCR can provide rapid results but aren't widely available.
• Chest imaging (X-ray or CT) often shows infiltrates, nodules, or cavities. In cases of suspected disseminated disease, additional testing may include lumbar puncture for meningitis, bone scans, or biopsies of affected tissues.
• A definitive diagnosis requires either isolation of Coccidioides from cultures, identification of spherules in tissue or body fluids, or positive serologic tests in the appropriate clinical context 1. It is essential to note that the diagnosis of coccidioidomycosis is proven by culture of Coccidioides spp from any clinical site, and histopathology can show spherules or endospores 1.
• The recommended approach includes serological testing of blood in all patients with suspected coccidioidomycosis, with repeat quantitative serological testing (CF) approximately every 12 weeks during care to evaluate a response to therapy 1.

From the FDA Drug Label

Amphotericin B for Injection USP is specifically intended to treat potentially life-threatening fungal infections: ... coccidioido-mycosis... The diagnosis of coccidioidomycosis can be suspected in patients with progressive, potentially life-threatening fungal infections.

• Key symptoms are not explicitly mentioned in the label, but treatment with amphotericin B may be indicated for this condition 2. Definitive diagnosis would require additional testing and clinical evaluation, as the label does not provide direct diagnostic criteria.

From the Research

Diagnosis of Coccidioidomycosis

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

• Serologic tests to detect antibodies against the fungus, such as immunoglobulin M (IgM) and immunoglobulin G (IgG) 3, 4, 5
• Direct microscopy using stains like Grocott methenamine silver (GMS) and calcofluor white (CFW) to visualize the fungus 5
• Culture of the fungus on suitable media, requiring biological safety level 2 or 3 5
• Nucleic acid amplification tests (NAATs) to detect Coccidioides spp. in specimens, although not yet commercially available 5, 6
• Enzyme immunoassays (EIA) and immunodiffusion methods to detect IgM and IgG antibodies 5
• Sequential complement fixation (CF) studies for IgG class of antibody to monitor disease progression 5

Serologic Testing

Serologic tests are useful for diagnosing coccidioidomycosis, particularly in immunocompetent individuals 3, 4. However, immunosuppressed persons may have lower rates of seropositivity, requiring multiple testing methods to improve detection 4. The combination of different serologic tests can increase the sensitivity of diagnosis 4.

Laboratory Aspects

Laboratory diagnosis of coccidioidomycosis requires specialized techniques and precautions, including biological safety level 2 or 3 for culture isolation 5. Molecular probes can be used to confirm the identity of Coccidioides spp. 5. However, species separation into C. immitis and C. posadasii requires specialized molecular techniques not typically available in routine clinical laboratories 5.

Current Diagnostic Landscape

The current diagnostic landscape for coccidioidomycosis is limited by the lack of specificity and sensitivity of available tests 7. New diagnostic directions, including polymerase chain reaction assays and commercially available tests for coccidioidal galactomannan antigenuria, are being explored to improve diagnosis, particularly in immunocompromised hosts 6.