Autopsy-Controlled Prospective Evaluation of Serial Screening for Circulating Galactomannan by a Sandwich Enzyme-Linked Immunosorbent Assay for Hematological Patients at Risk for Invasive Aspergillosis

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Journal of Clinical Microbiology, October 1999, p. 3223-3228, Vol. 37, No. 10
0095-1137/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Autopsy-Controlled Prospective Evaluation of Serial Screening for Circulating Galactomannan by a Sandwich Enzyme-Linked Immunosorbent Assay for Hematological Patients at Risk for Invasive Aspergillosis

Johan Maertens,¹ Jan Verhaegen,² Hilde Demuynck,¹ Penelope Brock,³ Gregor Verhoef,¹ Peter Vandenberghe,¹ Johan Van Eldere,² Ludo Verbist,² and Marc Boogaerts¹^,^*

Departments of Haematology,¹ Paediatrics,³ and Microbiology,² University Hospital Gasthuisberg, Leuven, Belgium

Received 12 April 1999/Returned for modification 1 June 1999/Accepted 28 June 1999

Efforts to improve the diagnosis of invasive aspergillosis (IA) have been directed towards the detection of fungal antigens,including galactomannan (GM). However, previous evaluations ofGM detection have been hampered by a lack of proven cases of IAand by a nonserial study design. This prospective study assessedthe diagnostic value of serial screening for circulating GM byusing a recently developed sandwich enzyme-linked immunosorbentassay (ELISA) for prolonged-neutropenic and/or steroid-treatedpatients with hematological disorders. Serum GM levels were monitoredtwice weekly for 186 consecutive patients at increased risk forIA. The patients were stratified according to the likelihood ofIA (proven, probable, possible, and no evidence of IA) by usingstringent criteria. Proven IA was defined by characteristic histopathologicalfindings together with a positive culture for Aspergillus species.Autopsy and culture from autopsy specimens was used to verifyboth positive and negative test results. A total of 2,172 serumsamples were tested from 243 episodes (mean, 9 samples/episode).Based on the analysis of 71 patients with confirmed disease status(culture and histology), the sensitivity and specificity of serialGM monitoring were 92.6 and 95.4%, respectively. The positivepredictive value was almost 93%, the negative predictive valuewas 95%, and the efficacy was 94%. False-positive reactions occurredat a rate of nearly 8%, although this figure might have been overestimated.Less than 1% of all tested sera were considered inconclusive.In more than half of the cases, antigenemia was detected beforeclinical suspicion of IA (median, 6 days before). Serial determinationof serum GM by the sandwich ELISA technique is a sensitive toolfor the diagnosis of IA in hematological patients at risk. Thisapproach may substantially influence clinical management withregard to preemptive and empirical antifungaltherapy.

^* Corresponding author. Mailing address: Department of Haematology, University Hospital Gasthuisberg, Herestraat 49, B-3000Leuven, Belgium. Phone: 32 16 346880. Fax: 32 16 346881. E-mail:marc.boogaerts{at}uz.kuleuven.ac.be.

Journal of Clinical Microbiology, October 1999, p. 3223-3228, Vol. 37, No. 10
0095-1137/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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