Diagnosis Coccidioidomycosis

Question

I suspect coccidioidomycosis in a patient. Symptoms include a painful and swollen shoulder, fever, weight loss, cough for the past month and shortness of breath for the past week. Chest x-ray shows diffuse pulmonary infiltrates and shoulder radiographs (not shown) show a primarily lytic bone lesion.

I asked an infectious disease consultant if antigen testing should be performed. I was advised that antigen detection is not as sensitive a method for diagnosing coccidioidomycosis and that antibody detection is the method of choice. What diagnostic tests would you recommend to most accurately diagnose coccidioidomycosis?

Background

Antibody detection is the most common method for diagnosis of coccidioidomycosis, and the enzyme immunoassay (EIA) is the most sensitive method for antibody detection [1]. Antigen detection is less sensitive than antibody detection and is most useful for diagnosis of progressive coccidioidomycosis [2]. Combined antigen and immunodiffusion (ID) antibody detection are more sensitive than ID alone in immunocompromised patients, table 1 [2]. Antibody detection measures immune response which can be reduced with immunocompromise, while antigen detection measures fungal burden.

Figure 1

Image 1: chest x-ray showing diffuse infiltrate Image 2: picture showing swollen erythematous left shoulder
Chest X-Ray Swollen Erythematous Left Shoulder

 

Evidence

Antigen is detected in both immunocompromised and non-immunocompromised patients although the sensitivity is higher with immunocompromised (79.5%) as compared with those who are not (38.3%), table 1 [2]. Measurement of urine and serum antigen is more sensitive than either alone in immunocompromised patients. Likewise, combined antigen and ID antibody detection is more sensitive than either alone.

The most sensitive method for antibody detection is IgG and IgM EIA, table 2, with the MiraVista EIA being more sensitive (88.3%) than two commercial EIAs, 59.2% and 71.8%, table 3 [3].

Recommendation

Combined antigen and antibody detection offers the most sensitive method for diagnosing progressive coccidioidomycosis [2], but more information is needed in non-progressive coccidioidomycosis. IgG and IgM antibody detection is most sensitive using the MiraVista EIA. The role of antigen and antibody detection for assessing response to treatment is unknown.

Table 1 Diagnostic sensitivity of antigen and antibody detection for coccidioidomycosis in immunocompromised and non-immunocompromised patients [2].

Test Immunocompromised1 (N= 75) Non-immunocompromised (N=83)
Antigen - Serum 49/75 (65.3%) 32/83 (38.6%)2
Antigen - Urine 40/70 (57.1%) 11/69 (15.9%)2
Antigen - Serum or Urine 56/75 (74.7%) 34/83 (41.0%)2 2
ID-IgG 49/69 (71.0%) 64/76 (84.2%)
ID-IgM 12/69 (17.4%) 26/76 (34.2%)2
ID-IgG or IgM 52/71 (73.2%) 71/76 (93.4%)2
CF 39/55 (70.9%) 47/72 (65.3%)
ID or CF 55/73 (75.3%) 74/79 (93.7%)2
Antigen or ID 70/75 (93.3%) 77/83 (92.8%)

1 HIV/AIDS-66, autoimmune-7, hematologic malignancy-3, organ transplant-1
2 Statistically significant

 

Table 2 MiraVista EIA, ID, and CF [4].

Classification MiraVista IgG N=103 MiraVista IgM N=103 ID N=102 CF N=62
Positive 87.4% 61.2% 60.2%1 53.2%1
Indeterminant 9.7% 4.9% Not applicable Not applicable
Negative 2.8% 34.0% 39.8% 46.8%

1P <0.001

 

Table 3 MiraVista and commercial antibody EIAs [3].

  MVD IMMY Meridian
Sensitivity
IgG 87.4%1 46.6% 70.9%
IgM 61.2%1 22.3% 29.1%
IgG/IgM 88.3%1 59.2% 71.8%
Specificity
IgG 89.3% 94.6% 96.4%
IgM 94.6% 98.2% 99.1%
IgG/IgM 87.5% 93.7% 95.5%

1Statistically significant

Reference List:

  1. Blair JE, Ampel NM. Coccidioidomycosis. 2021.
  2. Kassis C, Durkin M, Holbrook E, Myers R, Wheat L. Advances in Diagnosis of Progressive Pulmonary and Disseminated Coccidioidomycosis. Clin Infect Dis 2021 Mar 15; 72(6):968-75.
  3. Malo J, Holbrook E, Zangeneh T, et al. Comparison of three anti-coccidioides antibody enzyme immunoassay kits for the diagnosis of coccidioidomycosis. Med Mycol 2020 Apr 11.
  4. Malo J, Holbrook E, Zangeneh T, et al. Enhanced Antibody Detection and Diagnosis of Coccidioidomycosis with the MiraVista IgG and IgM Detection Enzyme Immunoassay. J Clin Microbiol 2017 Mar; 55(3):893-901.