Galactomannan and Polymerase Chain Reaction-Based Screening for Invasive Aspergillosis Among High-Risk Hematology Patients: A Diagnostic Meta-analysis

Clin Infect Dis. 2015 Oct 15;61(8):1263-72. doi: 10.1093/cid/civ555. Epub 2015 Jul 8.

Abstract

Background: Screening of high-risk patients for invasive aspergillosis (IA) has the potential to decrease the use of empiric antifungal agents. However, the performance of different screening methods has not been studied.

Methods: We performed a meta-analysis of published studies to assess the diagnostic performance of galactomannan (GM) and polymerase chain reaction (PCR) as weekly screening tests in high-risk populations. The sensitivity and specificity of 6 approaches combining GM and PCR were estimated using the bivariate model.

Results: Thirteen studies with 1670 patients met our inclusion criteria. Single positive test results had modest sensitivity and specificity for screening (respectively, 92% and 90% for GM; 84% and 76% for PCR). The screening approach with the highest sensitivity was the one that used at least 1 GM- or PCR-positive result to define a positive episode, achieving a sensitivity of 99%, significantly higher than any single test (P = .0018 compared with GM and P < .0001 compared with PCR). Meanwhile, when both GM and PCR were positive for the same patient, the specificity increased to 98%, which was not significantly different compared to the specificity of at least 2 positive GM (95%, P = .56 for the comparison) or PCR results (93%, P = .07 for the comparison).

Conclusions: When screening high-risk patients for IA with GM and PCR tests, the absence of any positive test can obviate the need for antifungal agents with a negative predictive value of 100%, whereas the presence of at least 2 positive results is highly suggestive of an active infection with a positive predictive value of 88%.

Keywords: Aspergillus; PCR; diagnosis; fungal infection; galactomannan.

Publication types

  • Meta-Analysis

MeSH terms

  • Aspergillosis / diagnosis*
  • Aspergillosis / microbiology
  • Aspergillus / genetics
  • Aspergillus / isolation & purification*
  • DNA, Fungal / analysis
  • Enzyme-Linked Immunosorbent Assay / methods
  • Galactose / analogs & derivatives
  • Humans
  • Mannans / analysis*
  • Mass Screening / statistics & numerical data
  • Polymerase Chain Reaction
  • Risk Factors
  • Sensitivity and Specificity

Substances

  • DNA, Fungal
  • Mannans
  • galactomannan
  • Galactose