Advances in Diagnosis of Progressive Pulmonary and Disseminated Coccidioidomycosis

Abstract

Background Antibody detection is the main method for diagnosis of coccidioidomycosis, but it has limitations. The Coccidioides antigen enzyme immunoassay is recommended for testing cerebrospinal fluid in suspected meningitis. Reports on urine and serum antigen detection evaluated small numbers of patients who were mostly immunocompromised. The purpose of this study was to assess the accuracy of combined antibody and antigen detection for diagnosis. Methods A retrospective study, including all patients in whom Coccidioides antigen detection in serum was performed between January 2013 and May 2017, was conducted at Valleywise Health Medical Center (formerly Maricopa Integrated Health System). Sensitivity and specificity of antigen and antibody were evaluated in 158 cases and 487 controls. Results The sensitivity of antibody detection by immunodiffusion (ID) was 84.2%. The sensitivity of antigen detection was 57.0% if both urine and serum were tested and 36.7% if urine alone was tested. The sensitivity of combining antigen and ID antibody detection was 93.0%. The sensitivity of urine and serum antigen detection was 55.4% in proven and 58.7% in probable cases, 79.1% in disseminated and 41.6% in pulmonary cases, and 74.7% in immunocompromised and 40.0% in immunocompetent patients. Specificity was 99.4% for antigen detection and 96.5% for ID antibody detection. Diagnostic accuracy was 95.4% for ID antibody and antigen detection, 93.6% for ID antibody alone, and 89.1% for pathology or culture. Conclusions These findings support combined antibody and antigen detection for diagnosis of progressive coccidioidomycosis. The diagnosis may have been missed if antigen detection was not performed.

Comparative Study of Newer and Established Methods of Diagnosing Coccidioidal Meningitis

“…Previous studies with the classical CF antibody test on CSF have reported false negative results that range from 17–41% [ 14 , 15 , 16 ]. A recent study [ 17 ] found CSF CF antibody testing to be 70% sensitive and 100% specific, virtually identical to what we found ( Table 4 a) with our specimens and assays.…”

“…We did not have information on the level of CSF inflammation (CSF leukocytes, protein, glucose) in almost all specimens, to correlate with our test results. To date, testing sera in coccidioidal antibody and antigen assays [ 16 , 22 ] has suggested only histoplasmosis presents a significant cross-reaction problem, but meningitis in histoplasmosis is a rare event; more data about performance of the tests studied here in other CNS mycotic infections would still be of interest. Data-gathering addressed to these shortcomings can be derived in future studies, and inform them.…”

Lifecycle dominates the volatilome character of the dimorphic fungusCoccidioidesspp

“…Multiple serological tests are available for IgM, IgG, or complement-fixing antibodies, as well as an enzyme-linked immunoassay that uses proprietary coccidioidal antigens. However, these tests lack sensitivity for coccidioidomycosis (5,6). Due to the difficulty in diagnosing Valley fever, it is often mistaken for bacterial pneumonia and inappropriately treated with antibiotics (7)(8)(9)(10).…”

Life Cycle Dominates the Volatilome Character of Dimorphic Fungus Coccidioides spp.

“…Multiple serological tests are available for IgM, IgG, or complement-fixing antibodies, as is an enzymelinked immunoassay that uses proprietary coccidioidal antigens. However, these tests lack sensitivity for coccidioidomycosis (5,6). Due to the difficulty in diagnosing Valley fever, it is often mistaken for bacterial pneumonia and inappropriately treated with antibiotics (7)(8)(9)(10), and the lack of a suitable diagnostic strongly contributes to an unacceptably long 23-day median time to diagnosis (2).…”