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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 of GM detection have been hampered by a lack of proven cases of IA and by a nonserial study design. This prospective study assessed the diagnostic value of serial screening for circulating GM by using a recently developed sandwich enzyme-linked immunosorbent assay (ELISA) for prolonged-neutropenic and/or steroid-treated patients with hematological disorders. Serum GM levels were monitored twice weekly for 186 consecutive patients at increased risk for IA. The patients were stratified according to the likelihood of IA (proven, probable, possible, and no evidence of IA) by using stringent criteria. Proven IA was defined by characteristic histopathological findings together with a positive culture for Aspergillus species. Autopsy and culture from autopsy specimens was used to verify both positive and negative test results. A total of 2,172 serum samples 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 serial GM monitoring were 92.6 and 95.4%, respectively. The positive predictive value was almost 93%, the negative predictive value was 95%, and the efficacy was 94%. False-positive reactions occurred at 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 before clinical suspicion of IA (median, 6 days before). Serial determination of serum GM by the sandwich ELISA technique is a sensitive tool for the diagnosis of IA in hematological patients at risk. This approach may substantially influence clinical management with regard to preemptive and empirical antifungal therapy.


* Corresponding author. Mailing address: Department of Haematology, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, 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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