Community-Acquired Pneumonia (CAP): Clinical Testing Algorithm for Coccidioidomycosis

This clinical testing algorithm was made in collaboration with the Mycoses Study Group Education & Research Consortium and the Coccidioidomycosis Study Group.

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In the United States, coccidioidomycosis is endemic to the Southwest and parts of the Pacific. Globally, it is endemic in parts of South and Central America. These maps are approximations. Coccidioides is not distributed evenly and may not be present everywhere within the shaded areas. It may also be present outside of the areas indicated.

map of continental US showing places where patients live or having traveled to a coccidiodomycosis endemic area - mostly west of the Mississippi

dark orange: areas Coccidioides is more likely to live; orange stripes: potential range of Coccidioides

Global map showing where patients live in or have traveled to a coccidiodomycosis endemic area - western U.S., Brazil, and Argentina

If a patient lives in or has traveled to a disease-endemic area and has:

Community-Acquired Pneumonia flowchart to determine if it's Coccidioidomycosis

1a. CAP of unknown etiology not responding to a course of empiric antibiotics

1b. Initial presentation of CAP (or erythema nodosum in the setting of recent respiratory symptoms) if people have:

Lived in or traveled to highly endemic desert regions of Arizona (i.e. South-Central Arizona) or the San Joaquin Valley of California) OR
Link to a known coccidioidomycosis outbreak

2. Consider serologic testing by enzyme immunoassay (EIA) with immunodiffusion (ID) and complement fixation (CF)

Note: initial testing with EIA or ID and CF may depend on availability and performance characteristics of test at facility
IgM (+) or IgG (+): pulmonary coccidioidomycosis
1. If an EIA test is positive, clinicians can consider follow-up testing with ID and CF to further establish the diagnosis. If ID and CF are negative after a positive EIA test, clinicians can consider repeat ID and CF 2-4 weeks later to confirm diagnosis. Patients with positive EIA results in highly endemic areas or with highly suggestive clinical findings (e.g., erythema nodosa), clinicians might start management for pulmonary coccidioidomycosis while awaiting results from ID or CF.
IgM (-) and IgG (-): no infection OR immunosuppressed OR false negative
1. False-negative results are possible. If clinical suspicion for coccidioidomycosis continues and if the patient is immunosuppressed or clinical illness is progressing rapidly, consider microscopy and culture of respiratory specimens from a bronchoscopy. Polymerase chain reaction (PCR) and antigen detection can also be helpful but are done less frequently.
2. Consider alternative diagnosis
3. If high degree of suspicion remains, progression of illness, or recent symptom onset
  1. Repeat serology 2-6 weeks later
    1. Positive
      1. Pulmonary coccidiomycosis
  2. Consider consulting infectious diseases or pulmonology

Information About Coccidioidomycosis

See Clinical Infectious Diseases publication, Clinician Outreach and Communications Activity Call, and Medscape Article covering the coccidioidomycosis algorithm.

About Coccidioidomycosis

Coccidioidomycosis is an invasive fungal disease that often presents as community-acquired pneumonia in primary and urgent care settings. Coccidioidomycosis cannot be reliably distinguished from other causes of respiratory illness by signs or symptoms alone. Thus, the disease is commonly misdiagnosed and inappropriately treated with antibiotics—up to 70% of patients may receive inappropriate antibacterial drugs.¹ In highlyendemic regions for coccidioidomycosis, erythema nodosum is commonly the presenting symptom.² Climate change may be impacting the distribution in the United States, and travel-associated disease is common, particularly in people who have recently been to highly endemic areas like Arizona and California.^1,2

When to Consider Testing for Coccidioidomycosis

Clinicians may consider testing for coccidioidomycosis in patients on an initial presentation of CAP (or erythema nodosum in the setting of recent respiratory symptoms) in patients who have lived in or have traveled to the highly endemic desert regions of Arizona (i.e., South-Central Arizona) or the San Joaquin Valley of California or a link to a known coccidiomycosis outbreak.

Clinicians may also consider testing for coccidioidomycosis in patients with CAP who have symptoms that did not improve following empiric antibiotics and have lived in or have traveled to generally endemic areas (Arizona, California, Nevada, New Mexico, Texas, Utah, and Washington State, and Central and South America).^4,5

How to Test for Coccidioidomycosis

We recommend ordering an enzyme immunoassay (EIA) antibody with immunodiffusion (ID) or complement fixation (CF) antibody test initially for coccidioidomycosis diagnosis. Initial testing with EIA or ID and CF may depend on availability and performance characteristics of test at facility. EIAs have a quicker turnaround time than ID and CF antibody testing. If the EIA is positive, clinicians may consider follow-up testing with ID and CF to rule out false positives and confirm the diagnosis. For patients in highly endemic areas or with highly suggestive clinical findings (e.g., erythema nodosa), clinicians might start management for pulmonary coccidioidomycosis while awaiting results from ID and CF. If the follow-up testing with ID or CF is negative, consider repeat ID or CF to rule out false negatives.

If the initial EIA test is negative, clinicians should consider alternative diagnoses. If a high degree of suspicion remains, progression of illness occurs, or if symptom onset was recent, repeat serology may be considered 2 to 6 weeks after the initial EIA test, or you may consult a specialist in infectious diseases or a pulmonologist. Note that antibody testing may be negative early in the illness course.

Antigen testing is available; however, it has primarily been studied in immunocompromised patients with moderately severe or disseminated disease or in meningitis.⁶ PCR and LFA can be helpful in diagnosing patients, but it is not readily available in many clinical settings.

Clinicians should refer to the Infectious Diseases Society of America’s coccidioidomycosis treatment guidelines or consult a specialist in infectious diseases when selecting therapy after a positive result.⁶

tests for coccidioidomycosis
Test	Sensitivity	Specificity	Population studied
Antibody tests
EIA (IgM & IgG) antibody^7–9	59%–88%	68%–96% (Cross reacts with other dimorphic fungi)	General patient population, immunocompromised population, patients with disseminated disease
Complement fixation (CF) antibody^7,10,11	65%–83%	High	General patient population, immunocompromised population, patients with disseminated disease
Immunodiffusion (ID) antibody⁷	60%	99%	General patient population, immunocompromised population, patients with disseminated disease
Lateral flow assay (LFA) antibody¹²	31%	92%	General patient population
Antigen tests
EIA urine antigen^15,16	37%–71%	High (but does cross-react with other dimorphic fungi)	General patient population, immunocompromised population, patients with disseminated disease
EIA serum antigen^16,17	51%–73%	High (but does cross-react with other dimorphic fungi)	General patient population, immunocompromised population, patients with disseminated disease
Other tests
Histopathology⁵	23%–84%	High	General patient population, patients with diabetes, patients with disseminated disease
Cytology⁵	15%–75%	High	General patient population, patients with diabetes, patients with disseminated disease
PCR^13,14	56%–75%	99%–100%	General patient population