Importance of operational factors in the reproducibility of Aspergillus galactomannan enzyme immune assay

PLoS One. 2015 Apr 10;10(4):e0124044. doi: 10.1371/journal.pone.0124044. eCollection 2015.

Abstract

Background: The Platelia Aspergillus Ag assay (Bio-Rad) is designed for detecting Aspergillus galactomannan (GM) and is widely used for diagnosing invasive aspergillosis but is hampered by variable occurrences of unreproducible positive results. Frequency and origin of these unreproducible results have not been formally studied.

Methods: Different technicians simultaneously performed four tests on 550 consecutive sera from adult patients (Test#1-Test#2 for extraction#1 and Test#3-Test#4 for extraction#2). The samples were classified as confirmed negative [all tests with GM optical density index (GM-ODI) <0.5], confirmed positive (all tests with GM-ODI ≥0.5), extraction unreproducible positive (Test#1 and Test#2 ODIs ≥0.5, and Test#3 and Test#4 GM-ODIs <0.5, or conversely), and ELISA unreproducible positive (only one test with GM-ODI ≥0.5). The samples with positive and negative GM-ODIs within the assay coefficient of variation values were classified as non-conclusive. Four similar additional tests were performed after ≤72h storage at 4 °C and a new GM test after 8 months at -20 °C.

Results: Five-hundred-twenty sera (94.5%) were confirmed negative, 15 (2.7%) confirmed positive, 4 (0.7%) extraction unreproducible positive, 6 (1.1%) ELISA unreproducible positive, and 5 (0.9%) non-conclusive. Upon retesting, the unreproducible positive results turned negative except for one which turned non-conclusive. The confirmed positive and non-conclusive had similar GM-ODIs (p>0.4) upon retesting after storage ≤72h at 4 °C (n = 20) or eight months at -20 °C (n = 17).

Conclusions: Operational unreproducible positives represent 33% of the GM-positive results and a second sample evaluation appears mandatory to avoid useless investigations or treatments. When operational artifacts are excluded, GM remains stable at standard storage conditions.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Antigens, Fungal / blood
  • Aspergillosis / diagnosis*
  • Aspergillosis / microbiology
  • Aspergillus / chemistry*
  • Aspergillus / immunology
  • Enzyme-Linked Immunosorbent Assay / methods
  • False Positive Reactions
  • Galactose / analogs & derivatives
  • Humans
  • Mannans / blood*
  • Mannans / immunology
  • Reproducibility of Results

Substances

  • Antigens, Fungal
  • Mannans
  • galactomannan
  • Galactose

Grants and funding

Bio-rad provided Samuel Lardeux with the extra kits for the tests not included in the routine procedure. The routine tests were performed as part of the authors' routine laboratory procedure. Besides this, there was no other relationships or activities that could appear to have influenced the submitted work. Other than the named authors, no one played a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.