Enhanced Antibody Detection and Diagnosis of Coccidioidomycosis with the MiraVista IgG and IgM Detection Enzyme Immunoassay

Abstract

Coccidioidomycosis is a common cause of community-acquired pneumonia in areas of the southwestern United States in which the disease is endemic. Clinical presentations range from self-limited disease to severe disseminated disease. Therefore, early and accurate diagnosis is essential to ensure appropriate treatment and monitoring. Currently available diagnostic tests have variable accuracy, particularly in certain patient populations, and new tests may offer improved accuracy for the diagnosis of coccidioidomycosis. Serum samples from 103 cases of coccidioidomycosis and 373 controls were tested for IgG and IgM antibodies using the MVista anti-Coccidioides antibody enzyme immunoassay. Serum specimens from 170 controls from areas in which the disease is endemic and 44 cases were tested by immunodiffusion at MiraVista Diagnostics. The sensitivity of the MVista antibody assay was 88.3%, and the specificity was 90%. The sensitivity was maintained in the presence of immunocompromising conditions or immunosuppressive therapies. The sensitivity of immunodiffusion was 60.2%, and the specificity was 98.8%. The sensitivity of complement fixation (62 cases) was 66.1%, but the specificity could not be determined. The MVista anti-Coccidioides antibody enzyme immunoassay offers improved sensitivity, compared with immunodiffusion and complement fixation, is not impaired in immunocompromised patients, and permits highly reproducible semiquantification.

Cryptococcal meningitis is a cause for cross‐reactivity in cerebrospinal fluid assays for anti‐Histoplasma, anti‐Coccidioides and anti‐Blastomyces antibodies

“…CSF from the 23 subjects with cryptococcal meningitis and elevated levels of anti‐cryptococcal antibodies were tested for antibodies in IgG antibody EIAs to Histoplasma , Blastomyces and Coccidioides . Of these 23 subjects, cross‐reactions for anti‐ Histoplasma antibodies were detected in eight (34.8%), anti‐ Coccidioides antibodies in six (26.1%) and anti‐ Blastomyces antibodies in one (4.3%) (Table ).…”

“…Additional controls included CSF specimens from 51 subjects at Indiana University Medical Center in whom fungal meningitis was not suspected clinically and in whom Histoplasma antigen testing was not performed from an IRB‐approved study . Additional CSF specimens were included from 10 subjects with Histoplasma meningitis and 10 subjects with Coccidioides meningitis with high levels of Histoplasma and Coccidioides antigen and anti‐ Histoplasma or anti‐ Coccidioides antibodies by EIA . Cryptococcal meningitis was excluded by CSF fungal culture and/or CSF cryptococcal antigen testing via latex agglutination (ImmunoMyologics or Meridian Biosciences) in these subjects.…”

“…and Coccidioides. 12 Of these 23 subjects, cross-reactions for anti-Histoplasma antibodies were detected in eight (34.8%), anti-Coccidioides antibodies in six (26.1%) and anti-Blastomyces antibodies in one (4.3%) ( Table 1). Individual cases are shown in Figure 2.…”

“…11 Additional CSF specimens were included from 10 subjects with Histoplasma meningitis and 10 subjects with Coccidioides meningitis with high levels of Histoplasma and Coccidioides antigen and anti-Histoplasma or anti-Coccidioides antibodies by EIA. 2,12 Cryptococcal meningitis was excluded by CSF fungal culture and/or CSF cryptococcal antigen testing via latex agglutination (ImmunoMyologics or Meridian Biosciences) in these subjects.…”

“…CSF specimens from subjects with cryptococcal meningitis were also tested via previously reported MiraVista enzyme immunoassays for anti-Blastomyces antibodies, 13 anti-Histoplasma antibodies 2 and anti-Coccidioides antibodies. 12 Unlike the anti-cryptococcal antibody EIA, these assays have been validated for clinical use and contain standard curves, from which results are calculated, and reported semi-quantitatively as units. The cut-off for a positive result is 10 units in each case, and the highest standard used in the assays is 80 units.…”