title: Galactomannan detection for invasive aspergillosis in immunocompromised patients.
abstract: BACKGROUND
  Invasive aspergillosis is the most common life-threatening opportunistic invasive mycosis in immunocompromised patients. A test for invasive aspergillosis should neither be too invasive nor too great a burden for the already weakened patient. The serum galactomannan enzyme-linked immunosorbent assay (ELISA) seems to have the potential to meet both requirements.
  
  
  OBJECTIVE
  To obtain summary estimates of the diagnostic accuracy of galactomannan detection in serum for the diagnosis of invasive aspergillosis.
  
  
  METHODS
  We searched MEDLINE, EMBASE and Web of Science with both MeSH terms and text words for both aspergillosis and the sandwich ELISA. We checked the reference lists of included studies and review articles for additional studies. We conducted the searches in February 2014.
  
  
  METHODS
  We included cross-sectional studies, case-control designs and consecutive series of patients assessing the diagnostic accuracy of galactomannan detection for the diagnosis of invasive aspergillosis in patients with neutropenia or patients whose neutrophils are functionally compromised. The reference standard was composed of the criteria given by the European Organization for Research and Treatment of Cancer (EORTC) and the Mycoses Study Group (MSG).
  
  
  METHODS
  Two review authors independently assessed quality and extracted data. We carried out meta-analysis using the bivariate method. We investigated sources of heterogeneity by adding potential sources of heterogeneity to the model as covariates.
  
  
  RESULTS
  We included 54 studies in the review (50 in the meta-analyses), containing 5660 patients, of whom 586 had proven or probable invasive aspergillosis. When using an optical density index (ODI) of 0.5 as a cut-off value, the sensitivity of the test was 82% (73% to 90%) and the specificity was 81% (72% to 90%). At a cut-off value of 1.0 ODI, the sensitivity was 72% (65% to 80%) and the specificity was 88% (84% to 92%). At a cut-off value of 1.5 ODI, the sensitivity was 61% (47% to 75%) and the specificity was 93% (89% to 97%). None of the potential sources of heterogeneity had a statistically significant effect on either sensitivity or specificity.
  
  
  CONCLUSIONS
  If we used the test at a cut-off value of 0.5 ODI in a population of 100 patients with a disease prevalence of 9% (overall median prevalence), two patients who have invasive aspergillosis would be missed (sensitivity 82%, 18% false negatives), and 17 patients would be treated unnecessarily or referred unnecessarily for further testing (specificity 81%, 19% false negatives). If we used the test at a cut-off value of 1.5 in the same population, that would mean that four invasive aspergillosis patients would be missed (sensitivity 61%, 39% false negatives), and six patients would be treated or referred for further testing unnecessarily (specificity 93%, 7% false negatives). These numbers should, however, be interpreted with caution because the results were very heterogeneous.
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, P.O. Box 22700, Amsterdam, Netherlands, 1100 DE.
authors.forename: Mariska M G
authors.initials: MM
authors.lastname: Leeflang
authors.forename: Yvette J
authors.initials: YJ
authors.lastname: Debets-Ossenkopp
authors.forename: Junfeng
authors.initials: J
authors.lastname: Wang
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Visser
authors.forename: Rob J P M
authors.initials: RJ
authors.lastname: Scholten
authors.forename: Lotty
authors.initials: L
authors.lastname: Hooft
authors.forename: Henk A
authors.initials: HA
authors.lastname: Bijlmer
authors.forename: Johannes B
authors.initials: JB
authors.lastname: Reitsma
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhang
authors.forename: Patrick M M
authors.initials: PM
authors.lastname: Bossuyt
authors.forename: Christina M
authors.initials: CM
authors.lastname: Vandenbroucke-Grauls
mesh_terms: D001228:Aspergillosis / Q000175:diagnosis* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D005690:Galactose / Q000031:analogs & derivatives; D006801:Humans; D016867:Immunocompromised Host; D008351:Mannans / Q000097:blood*; D009894:Opportunistic Infections / Q000175:diagnosis* / Q000276:immunology; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D008351:Mannans; C012990:galactomannan; D005690:Galactose