Serological Tests for Blastomycosis: Assessments During a Large Point-Source Outbreak in Wisconsin

Abstract

Enzyme immunoassay (EIA), immunodiffusion (ID), and complement fixation (CF) tests for antibody to the A antigen of Blastomyces dermatitidis were assessed in 47 patients in an epidemic of blastomycosis and in 89 control subjects with lower respiratory tract illness. Antibody was detected by EIA, ID, and CF in 77%, 28%, and 9% of the patients, respectively. EIA titers ranged from 1:8-1:512 (median titer, 1:128). Antibody detected by ID or CF was always detectable by EIA. Antibody was detected by EIA 13 days after illness onset, and the peak seroprevalence rate and geometric mean titer occurred 50-70 days after onset. Antifungal therapy produced a significant decline in antibody titer by approximately six months after onset. Seven (8%) control subjects had detectable antibody, six had EIA titers of 1:8, and one had a titer of 1:16. The specificities for EIA, ID, and CF were 92%, 100%, and 100%, respectively. The EIA provides a significant advance in serodiagnostic testing for blastomycosis and can be used in an outbreak setting as an epidemiological tool to identify acute B. dermatitidis infection; titers greater than or equal to 1:32 strongly support the diagnosis, whereas titers of 1:8 or 1:16 are suggestive.

Isolation, purification, and radiolabeling of a novel 120-kD surface protein on Blastomyces dermatitidis yeasts to detect antibody in infected patients.

“…Each serum specimen had been tested previously in two other studies for antibody to A antigen by enzyme immunoassay (8,13) and was tested in the present study only for antibody to WI-I by RIA. Of these sera evaluated sequentially by both tests, 82%…”

“…It was The RIA we describe offers a significant advance for serological studies of blastomycosis. When results of the RIA for detection of antibody to WI-1 are compared to those reported using an enzyme immunoassay for detection of antibody to A antigen (8,13), several observations can be made: (a) antibody to WI-1 can be detected earlier, occasionally even at the onset of acute pulmonary illness; (b) antibody titers to WI-l are far higher, the GMT is -2.5 logs greater; and (c) antibody to WI-I persists for a longer interval, although antibody to both antigens declines to low or undetectable levels by 6 mo after illness onset in patients with resolution or successful treatment of disease (8). We recognize that caution should be used in drawing conclusions about the relative sensitivities of the two tests for detection of antibody in blastomycosis, since the assays were not run in parallel in this study.…”

“…Both antigens are impure (5,6), they appear to be a mixture ofcell wall components, and tests employing them are not widely available. A further problem with serologic tests using A antigen has been diminished specificity as sensitivity is increased by enzyme immunoassay techniques (7)(8)(9). This problem results from A-antigen impurity and the extensive sharing of cell wall components between dimorphic fungi, particularly B. dermatitidis and Histoplasma capsulatum.…”

Development of a Highly Sensitive and Specific Blastomycosis Antibody Enzyme Immunoassay Using Blastomyces dermatitidis Surface Protein BAD-1

“…According to a recent review, an agar gel immunodiffusion (AGID) test showed a sensitivity of only 32%, and in previous studies less than half of blastomycosis cases were seropositive (6)(7)(8)(9)(10)(11). Complement fixation is less sensitive than AGID in patients with blastomycosis, is more difficult to perform, and offers no advantages over AGID (7)(8)(9).…”

“…The enzyme immunoassay (EIA) is more sensitive than the AGID test, but previous tests were falsely positive in one quarter of patients with histoplasmosis (7)(8)(9)(10)(11). In one study using a commercially available EIA, the sensitivity was 100%, but false positives in nonfungal controls were detected in 20% of cases (10).…”