Galactomannan in Nonserum Specimens • CID 2004:39 (15 November) • 1467
R E V I E W A R T I C L E
Utility of Aspergillus Antigen Detection in Specimens
Other than Serum Specimens
Rocus R. Klont, Monique A. S. H. Mennink-Kersten, and Paul E. Verweij
Department of Medical Microbiology, University Medical Center St. Radboud, Nijmegen University Center for Infectious Diseases, Nijmegen,
The detection of circulating galactomannan in serum is an important tool for the early diagnosis of invasive
aspergillosis. A commercial enzyme-linked immunosorbent assay (Platelia Aspergillus; BioRad) was shown to
be both highly sensitive and specific for detection of galactomannan in serum samples. Despite the fact that
this assay is validated for serum samples, specimens of other body fluids are increasingly used for detection
of galactomannan, including urine, bronchoalveolar lavage fluid, and cerebrospinal fluid. Review of the lit-
erature shows that galactomannan can be detected in each of these samples from patients with invasive
aspergillosis with higher sensitivity than is the case with culture, as well as early in the course of infection.
However, the evidence thus far is based on case reports—predominantly retrospective studies—that often
include heterogeneous patient populations and limited numbers of cases of proven infection. Clearly, well-
designed prospective studies with systematic sampling and use of consensus case definitions are needed to
compare the performance of antigen detection in samples other than serum specimens with that in serum
Invasive aspergillosis is the most common opportun-
istic invasive mycosis . This disease is mainly caused
by Aspergillus fumigatus . Invasive aspergillosis pre-
dominantly affects patients with neutropenia or whose
neutrophils are functionally compromised. The inci-
dence of invasive aspergillosis has increased because of
the increased number of patients undergoing hema-
topoietic stem cell transplantation or receiving courses
of corticosteroid therapy for a prolonged time . In
addition, invasive aspergillosis may affect solid organ
transplant recipients . Despite the development and
registration of new antifungal drugs, such as caspofun-
gin and voriconazole, the overall survival rate remains
low (30%–50%) [5, 6]. This is partly because of the
difficulty in establishing the diagnosis in an early stage
of the infection. Early diagnosis and subsequent early
Received 25 April 2004; accepted 23 July 2004; electronically published 26
Reprints or correspondence: Dr. R. R. Klont, Dept. of Medical Microbiology,
University Medical Center St Radboud, PO Box 9101, 6500 HB Nijmegen, The
Clinical Infectious Diseases 2004;39:1467–74
? 2004 by the Infectious Diseases Society of America. All rights reserved.
initiation of therapy improves outcome [5, 7, 8]. How-
ever, clinical signs and symptoms are generally non-
specific, and characteristic lesions are frequently absent
from chest radiographs of neutropenic patients. The
use of high-resolution CT with high-risk patients could
result in earlier diagnosis, but characteristic lesions,
such as the halo sign and the crescent sign, are not
specific for Aspergillus species. The reference standard
for diagnosis, histopathologic examination and subse-
quent culture of the tissue samples, is often not done
because the patient’s status prohibits invasive proce-
dures (e.g., the patient has thrombocytopenia or poor
clinical condition). Furthermore, cultures for fungi and
cytopathological examination of respiratory specimens
often yield negative results and lack sensitivity for de-
tecting the fungus in an early stage of the infection .
Because of the limitations of the aforementioned di-
agnostic methods, a nonculture method, based on the
detection of the Aspergillus antigen galactomannan,has
Galactomannan is a cell wall polysaccharide that is
released by Aspergillus species during growth. A com-
mercially available sandwichELISA(PlateliaAspergillus;
BioRad) detects galactomannan by use of a rat mono-
1474 • CID 2004:39 (15 November) • Klont et al.
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