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Journal of Clinical Microbiology, July 1999, p. 2387-2387, Vol. 37, No. 7
0095-1137/99/$04.00+0
LETTERS TO THE EDITOR
Histoplasma capsulatum Antigen Detection: Comparison
of the Performance Characteristics of a New Inhibition Immunoassay to
Those of an Established Antibody Sandwich Immunoassay
 |
LETTER |
Dr. Beatriz L. Gomez and colleagues described a new inhibition
immunoassay for the diagnosis of histoplasmosis (1). My laboratory developed and extensively evaluated an antibody sandwich immunoassay for this purpose. It is important to contrast the two
methods, as their performance characteristics differ.
The characteristics of the assay developed in my laboratory are high
sensitivity in disseminated histoplasmosis but less sensitivity in
pulmonary and chronic pulmonary histoplasmosis, with greater sensitivity in urine, cross-reactions with Blastomyces
dermatitidis, Paracoccidioides brasiliensis, and
Penicillium marneffei, but not with Aspergillus
spp., Cryptococcus spp., and Mycobacterium tuberculosis (2). The report by Gomez et al.
demonstrated cross-reactivity in their inhibition assay with
Aspergillus spp. (20.00%), Cryptococcus spp.
(10.00%), and M. tuberculosis (22.22%)
(1).
Results obtained by using the inhibition immunoassay reported by Gomez
et al. differ from ours in several respects. Detection in serum
is more sensitive than in urine, and significant cross-reactivity is noted with Aspergillus spp.,
Cryptococcus spp., and M. tuberculosis. Furthermore, 2.27% of the normal human sera tested false positive for
Histoplasma capsulatum. Also, the sensitivity in cases of acute pulmonary histoplasmosis (88.88%) was greater than in cases of
disseminated histoplasmosis (non-AIDS, 62.50%; AIDS, 72.72%). In our
experience the sensitivity is higher for disseminated disease (urine
92%, serum 82%) than for acute pulmonary disease (44%) (3).
In conclusion, the detection characteristics of the inhibition
immunoassay differ considerably from those of the antibody sandwich
immunoassay, raising concern about the accuracy and usefulness of the
inhibition immunoassay.
| |
REFERENCES |
| 1.
|
Gomez, B. L.,
J. I. Figueroa,
A. J. Hamilton,
B. L. Ortiz,
M. A. Robledo,
A. Restrepo, and R. J. Hay.
1997.
Development of a novel antigen detection test for histoplasmosis.
J. Clin. Microbiol.
35:2618-2622[Abstract].
|
| 2.
|
Wheat, J.,
H. Wheat,
P. Connolly,
M. Kleiman,
K. Supparatpinyo,
K. Nelson,
R. Bradsher, and A. Restrepo.
1997.
Cross-antigen in Histoplasma capsulatum variety capsulatum antigen assays of urine samples from patients with endemic mycoses.
Clin. Infect. Dis.
24:1169-1171[Medline].
|
| 3.
|
Wheat, L. J.,
R. B. Kohler, and R. P. Tewari.
1986.
Diagnosis of disseminated histoplasmosis by detection of Histoplasma capsulatum antigen in serum and urine specimens.
N. Engl. J. Med.
314:83-88[Abstract].
|
| | | | |
Joe Wheat
Department of Medicine
Indiana University
Indianapolis, Indiana
|
| |
AUTHORS' REPLY |
We would like to take the opportunity to respond to Dr. Wheat's
comments regarding the recent publication (1) in which we
describe a novel test for the detection of Histoplasma
capsulatum antigen in sera. Dr. Wheat has highlighted three
variations in the inhibition immunoassay we describe compared to the
antibody sandwich immunoassay developed in his laboratory. These are
(i) differences in the spectrum of cross-reactivity, (ii) differences in the sensitivity in serum relative to that in urine, and (iii) differences in the sensitivity of the tests as applied to distinct patient groups.
We are somewhat perplexed to find that he uses these differences to
conclude that the inhibition immunoassay is of questionable accuracy
and usefulness. It seems to us that Dr. Wheat is overlooking the
profound differences in the nature of the diagnostic test we described
compared to his own assay. The inhibition assay we describe uses a
murine monoclonal antibody to detect a 70-kDa protein. This novel
antigen is currently being characterized. Dr. Wheat's test uses a
polyclonal serum in a radioimmunoassay to detect polysaccharide antigen.
As the two antigens being detected, the reagents being used, and the
methodologies adopted are all vastly different, is it not surprising
that there should be differences between the test results? This being
the case, is it not disingenuous to then use such differences to
conclude that one test is of questionable value? We have now followed
up our original observations with a second paper describing the use of
this inhibition assay (2), which to us, at least, confirms
that there is some merit in the test. We have always believed that
there are advantages in developing different approaches to the same
clinical problem and feel that our inhibition enzyme-linked
immunosorbent assay, while by no means a perfect assay, has something
to contribute to the diagnosis of histoplasmosis.
| |
REFERENCES |
| 1.
|
Gomez, B. L.,
J. I. Figueroa,
A. J. Hamilton,
B. L. Ortiz,
M. A. Robledo,
A. Restrepo, and R. J. Hay.
1997.
Development of a novel antigen detection test for histoplasmosis.
J. Clin. Microbiol.
35:2618-2622.
|
| 2.
|
Gómez, B. L.,
J. I. Figueroa,
A. J. Hamilton,
S. Diez,
M. Rojas,
A. Tobón,
A. Restrepo, and R. J. Hay.
1999.
Detection of the 70-kilodalton Histoplasma capsulatum antigen in serum of histoplasmosis patients: correlation between antigenemia and therapy during follow-up.
J. Clin. Microbiol.
37:675-680[Abstract/Free Full Text].
|
| | | | |
B. Gómez
A. Restrepo
Corporación para Investigaciones Biológicas
Medellín, Colombia
|
| | | | |
A. J. Hamilton
J. I. Figueroa
R. J. Hay
St. John's Institute of Dermatology
Guy's King's and St. Thomas's Medical School
King's College, University of London
London, United Kingdom
|
Journal of Clinical Microbiology, July 1999, p. 2387-2387, Vol. 37, No. 7
0095-1137/99/$04.00+0
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