title: Clinical Performance of Aspergillus PCR for Testing Serum and Plasma: a Study by the European Aspergillus PCR Initiative.
abstract: Aspergillus PCR testing of serum provides technical simplicity but with potentially reduced sensitivity compared to whole-blood testing. With diseases for which screening to exclude disease represents an optimal strategy, sensitivity is paramount. The associated analytical study confirmed that DNA concentrations were greater in plasma than those in serum. The aim of the current investigation was to confirm analytical findings by comparing the performance of Aspergillus PCR testing of plasma and serum in the clinical setting. Standardized Aspergillus PCR was performed on plasma and serum samples concurrently obtained from hematology patients in a multicenter retrospective anonymous case-control study, with cases diagnosed according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) consensus definitions (19 proven/probable cases and 42 controls). Clinical performance and clinical utility (time to positivity) were calculated for both kinds of samples. The sensitivity and specificity for Aspergillus PCR when testing serum were 68.4% and 76.2%, respectively, and for plasma, they were 94.7% and 83.3%, respectively. Eighty-five percent of serum and plasma PCR results were concordant. On average, plasma PCR was positive 16.8 days before diagnosis and was the earliest indicator of infection in 13 cases, combined with other biomarkers in five cases. On average, serum PCR was positive 10.8 days before diagnosis and was the earliest indicator of infection in six cases, combined with other biomarkers in three cases. These results confirm the analytical finding that the sensitivity of Aspergillus PCR using plasma is superior to that using serum. PCR positivity occurs earlier when testing plasma and provides sufficient sensitivity for the screening of invasive aspergillosis while maintaining methodological simplicity.
authors.affiliation: Public Health Wales Microbiology Cardiff, Cardiff, United Kingdom lewis.white@wales.nhs.uk.
authors.forename: P Lewis
authors.initials: PL
authors.lastname: White
authors.affiliation: Cardiff University, UHW, Cardiff, United Kingdom.
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Barnes
authors.affiliation: University of Würzburg Medical Center, Würzburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Springer
authors.affiliation: Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Klingspor
authors.affiliation: Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Cuenca-Estrella
authors.affiliation: University of Western Sydney, Sydney, NSW, Australia.
authors.forename: C Oliver
authors.initials: CO
authors.lastname: Morton
authors.affiliation: National Reference Centre for Mycosis, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Lagrou
authors.affiliation: Department of Microbiology and Immunology, Paris Diderot University, Saint Louis Hospital-APHP, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bretagne
authors.affiliation: Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Willem J G
authors.initials: WJ
authors.lastname: Melchers
authors.affiliation: University of Padua, Padua, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Mengoli
authors.affiliation: Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: J Peter
authors.initials: JP
authors.lastname: Donnelly
authors.affiliation: University of Würzburg Medical Center, Würzburg, Germany.
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Heinz
authors.affiliation: University of Würzburg Medical Center, Würzburg, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Loeffler
mesh_terms: D000328:Adult; D000368:Aged; D001228:Aspergillosis / Q000175:diagnosis* / Q000382:microbiology; D001230:Aspergillus / Q000235:genetics / Q000302:isolation & purification*; D016022:Case-Control Studies; D004271:DNA, Fungal / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D010949:Plasma / Q000382:microbiology*; D016133:Polymerase Chain Reaction / Q000379:methods*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013048:Specimen Handling / Q000379:methods*; D013997:Time Factors; D055815:Young Adult
chemical_list: D004271:DNA, Fungal