JOURNAL OF CLINICAL MICROBIOLOGY, Aug. 1991, p. 1616-1619 Vol. 29, No.

8
0095-1137/91/081616-04$02.00/0
Copyright © 1991, American Society for Microbiology

Comparison of the PREMIER Cryptococcal Antigen Enzyme

Immunoassay and the Latex Agglutination Assay
for Detection of Cryptococcal Antigens
WAYNE GADE,1* SUZANNE W. HINNEFELD,l LAURA S. BABCOCK,' PETER GILLIGAN,2
WILLIAM KELLY,2 KIMBERLEY WAIT,2 DOTTIE GREER,3 MARCELLA PINILLA,3
AND RAYMOND L. KAPLAN3
Research and Development, Meridian Diagnostics, Inc., Cincinnati, Ohio 45244'; Clinical Microbiology and Immunology
Laboratories, North Carolina Memorial Hospital, Chapel Hill, North Carolina 275142; and
SmithKline Beecham Clinical Laboratories, Atlanta, Georgia 303403

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Received 4 March 1991/Accepted 23 May 1991

A new enzyme immunoassay (EIA), PREMIER Cryptococcal Antigen, was compared with latex agglutina-
tion (LA) for the detection and quantitation of circulating capsular polysaccharide antigen from Cryptococcus
neoformans. The clinical evaluation of PREMIER EIA as a screening assay, including 475 specimens with 120
LA and EIA positives, resulted in 99% sensitivity and 97% specificity. The clinical specimens included sera and
cerebrospinal fluids as well as 10 rheumatoid factor-positive and 20 anti-nuclear antibody-positive serum
samples. This monoclonal antibody-based assay detects serotypes A to D at 0.63, 0.63, 7.8, and 62 ng/ml,
respectively. With three different known positive specimens, the assay was found to yield coefficients of
variation of 2 to 12% for intra- and interassay comparisons of precision and reproducibility. The primary use
for semiquantitative values derived with the LA or EIA is to follow the course of disease and monitor drug
therapies. The present data suggest that the PREMIER EIA will be a valuable method for this purpose. We
conclude that the PREMIER Cryptococcal Antigen EIA provides a rapid, convenient, and reliable antigen
detection method for screening and semiquantitative determination of antigen levels.

Cryptococcus neoformans is an encapsulated yeast which
frequently causes subclinical pulmonary infections in the
immunocompetent host (10, 12, 13). Cryptococcal infections
are an increasingly important cause of meningeal complica-
tions in immunocompromised patients (12, 13). For example,
cryptococcosis is now the fourth most common opportunis-
tic infection in AIDS patients (12, 13). Although four major
serotypes (A to D) of cryptococcal capsular polysaccharide
antigen exist, serotypes A and B predominate (10). Interest-
ingly, cryptococcal isolates from AIDS patients have been
almost exclusively of serotype A, even in Southern Califor-
nia where the serotype pair B and C is isolated more
frequently from the general population (2).
Traditionally, diagnosis of cryptococcal meningitis de-
pends on culturing C. neoformans or the demonstration of
encapsulated yeasts in India ink preparations from cerebro-
spinal fluid (CSF) (5, 7). Detection of the capsular antigen in
either serum or CSF has been established as a reliable
additional means of diagnosis (1, 3, 5-7). When both serum
and CSF specimens are assayed for cryptococcal antigen,
the sensitivity is well above 90% (7, 10). Antigen detection is
most often performed by latex agglutination (LA) assays (1,
5, 10, 12, 13). The diagnostic and prognostic value of antigen
detection and quantitation are well documented (1, 3, 10, 12,
13).
An enzyme immunoassay (EIA), the PREMIER Crypto-
coccal Antigen assay, has been developed for the detection
of cryptococcal capsular polysaccharide antigen in either
serum or CSF specimens. The assay utilizes a polyclonal
capture system and a monoclonal detection system (4).
Performance characteristics of the screening assay proce-
*
Corresponding author.
1616
dure were evaluated at three locations, and the results are
reported here. The rapid screening procedure provides a
visual or numeric result in less than 45 min without pretreat-
ment of the specimen. This EIA appears to offer a sensitivity
advantage over LA for serotypes A and B. The data show
that the PREMIER EIA is a rapid, sensitive, and specific
assay for the detection of capsular polysaccharide in either
serum or CSF.
MATERIALS AND METHODS
Specimens. Serum and CSF specimens were submitted to
clinical laboratories for the detection of cryptococcal anti-
gen. These clinical specimens were supplemented by 30
additional serum samples which were negative for crypto-
coccal antigen (by LA). These 30 serum samples included 10
which contained rheumatoid factor and 20 which were
positive for anti-nuclear antibodies. Whenever possible, LA
and EIA were performed within 72 h of receipt of the
specimen. Specimens not tested within 72 h were stored
frozen.
Cryptococcal antigens. Purified preparations of the four
major serotypes of capsular polysaccharide antigens were
obtained from Thomas Kozel (University of Nevada, Reno)
(11). Isolates of C. neoformans serotypes A to D were
obtained from the American Type Culture Collection (sero-
type A, ATCC 24064; serotype B, ATCC 24065; serotype C,
ATCC 24066; and serotype D, ATCC 24067). The cells were
grown in yeast extract dialysate media and were formalin
killed prior to use. The polysaccharides were precipitated
from the medium by the addition of cold absolute ethanol.
The precipitated material was dried by washing with ethanol,
acetone, and diethyl ether. Precipitates were further purified
by cetyltrimethylammonium bromide precipitation (11).
VOL. 29, 1991 EVALUATION OF EIA FOR CRYPTOCOCCAL ANTIGEN 1617

LA assays. All LA assays were performed with CALAS TABLE 1. Clinical comparison of EIA and LA for detection
(Meridian Diagnostics, Inc., Cincinnati, Ohio) according to of cryptococcal antigen
the instructions on the package insert. All serum samples No. of samples (EIA/LA)': Sensi- Speci-
were pronase treated (15 min at 56°C and then boiled for 5 Site tivity ficity
min), and CSF specimens were boiled (5 min) prior to +/+ -/- +/- -+ Ind/- Ind/+ (%) (%)
testing.
PREMIER Cryptococcal Antigen EIA. The PREMIER 1 32 185 6b lb 1 0 97 97
2 41 91 0 0 0 0 100 100
Cryptococcal Antigen EIA was obtained from Meridian 3 47 68 2b 0 0 1c 100 96
Diagnostics, Inc., and assays were performed as indicated
on the package insert. All EIA screening assays were Total 120 344 8 1 1 1 99 97
performed without specimen pretreatment. The EIA proce- a +, positive result; -, negative result; Ind, indeterminant.
dure involves the addition of 50 ,u1 of serum, CSF, or control b
These nine discrepant samples are identified in Table 2.
and 50 ,ul of peroxidase-conjugated monoclonal antibody to c
Insufficient quantities precluded retesting of the two indeterminant spec-
the antibody-coated microwells. After a 30-min simulta- imens.
neous incubation of samples with the capture and detection

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systems, the solutions are removed by inverting the micro-
wells. The microwells are washed (four times) with a propri-
etary wash buffer. The tetramethylbenzidine-urea peroxide mens. The other three EIA+/LA- specimens were consid-
substrate system is incubated for 10 min and stopped with 2 ered false positives, since there was no other evidence of
N H2SO4. The results were scored visually and read at 450 cryptococcal infection (Table 2). Two of the 11 discordant
and 630 nm with a dual-wavelength EIA reader. The positive results were indeterminant by the EIA; one was negative and
cutoff value for dual-wavelength EIA readers was 0.10, and one was positive by LA (insufficient specimen prevented
the negative cutoff value was 0.07. Values between 0.07 and retesting of these indeterminants). One of the 11 specimens
0.10 were considered indeterminants and were repeated if was weakly positive with LA and negative with EIA. Clini-
possible. cal information was not available for this patient.
The semiquantitative assay protocol requires that all re- The EIA yielded negative results with all rheumatoid
agents be dispensed with pipetters and that the two-vial factor and anti-nuclear antibody serum samples. Following
substrate system be premixed immediately prior to the pronase treatment, all LA assays were also negative.
substrate incubation. Dilution of the specimen prior to When specimen type is used as the basis for comparison,
assaying is required. Recommended dilutions include 100 ,ul the screening assay results for 169 CSF and 304 serum
of specimen and 100 ,ul of sample diluent, followed by a samples are very similar. The sensitivity of the EIA screen-
series of fivefold dilutions (50 p.l in 200 ,ul) in sample diluent. ing assay with serum was 100% (95 of 95 LA positives),
The impact of interassay differences due to slight varia- while the specificity was 97% (203 of 209 LA negatives). The
tions in protocol (e.g., incubation temperatures, incubation sensitivity of the EIA with CSF was 96% (25 of 26 LA
times, etc.) are minimized through the use of the control positives), and the specificity was 99% (141 of 143 LA
factor. The value of the control factor is calculated from the negatives). The two indeterminant specimens were sera and
average of two positive control absorbance values.
are not included in the sensitivity and specificity calcula-
Calculation of the EIA titer utilizes the following formula: tions. The overall agreement between LA and the EIA was
absorbance x dilution factor x control factor = EIA titer. 98% with both sera and CSF.
Cross-reactivity. The PREMIER EIA was tested with Limits of detection of serotypes A to D. The limits of
suspensions of microorganisms and fungal antigen prepara- detection of the four major serotypes were determined for
tions that may cause similar clinical symptoms or represent both LA and EIA. A series of twofold dilutions (in the
contaminants frequently found in specimens tested for cryp- respective sample diluents) was made from purified prepa-
tococcal antigen. Stock cultures of the microorganisms and rations of each serotype (11). The limits of detection for the
commercially available fungal antigen preparations were EIA were 0.63, 0.63, 15, and 62 ng/ml for serotypes A to D,
prepared by Meridian Diagnostics, Inc. Suspensions of the respectively. This was compared with 7.6, 7.6, 15, and 61
bacteria and yeast (106 to 1010 cells per ml in sample diluent) ng/ml for serotypes A to D, respectively, for the LA assay.
and viral suspensions (approximately 107 particles per ml) Thus, the EIA has a 12-fold sensitivity advantage over the
were substituted for the patient specimen in the assay
procedure. The suspensions and fungal antigen preparations
were also mixed with a known quantity of cryptococcal TABLE 2. Clinical diagnosis of discrepant specimensa
antigen and tested to evaluate whether there were significant
changes in absorbance compared with that in cryptococcal Site and Specimen Reactivity with: Clinical
antigen alone. patient type LA EIA diagnosis
Site 1
A Serum - +
RESULTS A Serum - +
B CSF - + +
Comparison of the screening assays. A total of 475 speci- B Serum - + +
mens were tested by both the LA assay and the PREMIER C CSF - + +
EIA. Both assays identified 120 of these specimens as D Serum - +
positive and 344 as negative (Table 1). Eight of 11 discordant E CSF + - NA
results were identified as positive by the EIA and negative Site 3
F Serum - + +
by LA (EIA+/LA-). Of these eight specimens, five came G Serum - + +
from patients who were diagnosed as having cryptococcosis
after positive LA results were obtained on additional speci- a
-, negative; +, positive; NA, not available.
1618 GADE ET AL. J. CLIN. MICROBIOL.

0-0 Latex TABLE 3. Cross-reactivity data for microorganisms

0-* EIA and antigen preparations
40 Absorbance with organism:
to
D Microorganism or With
30- antigen preparation In Diluent cryptococcus
_ antigen
0
lY
0
0.
20 4 Bacteria
Escherichia coli Kl 0.011 0.719
ex 10o F Icc 0 Haemophilus influenzae 0.012 0.695
C~~~~~~~~~~~~~~~~
Neisseria meningitidis 301 0.009 0.361
Neisseria meningitidis 362 0.007 0.464
Pseudomonas aeruginosa 0.009 0.470
0 20 40 60 80 100 120 Staphylococcus aureus 0.011 0.369
Time (Days) Staphylococcus aureus 0.013 0.668

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Cowan's strain 1
Staphylococcus epidermidis 0.011 0.722
4500 I,
\-o Latex Streptococcus agalactiae 0.011 0.714
4000 0 0 * EIA Streptococcus pneumoniae 0.013 0.670
3500 Yeast
0
ID 3000- Candida albicans 0.007 0.461
Rhodotorula rubra 0.011 0.413
0
2500- Torulopsis glabrata 0.011 0.416
i 2000-- 0 0-0o Trichosporon beigelii 0.732 1.572
0
°- 1500-
0. Fungal antigen preparation
a
r
10000 '0-0- 0 Aspergillus flavus 0.009 0.411
500- Aspergillus fumigatus 0.009 0.407
Aspergillus niger 0.010 0.398
0 25 50 75 100 125 150 175 200 225
Blastomyces dermatitidis 0.035 0.530
Coccidioides immitis 0.010 0.314
Time (Days) Histoplasma capsulatum 0.010 0.413
FIG. 1. Comparison of EIA and LA titers. Sequential serum Virus
samples from two patients undergoing therapy for cryptococcal Coxsackie virus A-16 0.011 0.472
disease were assayed by both assays on the same day. Coxsackie virus B-5 0.010 0.378
Echovirus 11 0.011 0.378
Poliovirus 1 0.012 0.376
Poliovirus II 0.013 0.387
LA for serotypes A and B and equivalent sensitivities for Poliovirus III 0.012 0.396
serotypes C and D. Controls
EIA precision. The precision of the PREMIER EIA was Diluent 0.011
determined by comparing the results of 16 replicates for Cryptococcus antigen 0.458
three known positive samples. The coefficients of variation
within the first run were 8.6, 2.1, and 2.2%. Interassay
variation was determined by repeat assays of three samples
(16 replicates of each sample, two operators, and two runs).
The interassay variations were 7.2, 11.5, and 11.8%. cryptococcus. All five pairs contained detectable serum
Comparison of semiquantitative results. Semiquantitative antigen by both assays. However, antigen was detected in
EIA and LA results from sequential specimens obtained only four of these five CSF specimens by EIA and two of the
from several patients were compared to determine if PRE- five by LA. In three specimen pairs from an individual
MIER EIA titers could be utilized to follow the course of patient, the mean serum titers were 2,000 and 87,000 for LA
disease and monitor drug therapies. Figure 1 shows data and EIA, respectively. The corresponding mean CSF titers
from two patients who were undergoing therapy for crypto- were 2 and 16 for LA and EIA, respectively.
coccal disease. Each serum sample was tested with both Specificity of the EIA. The EIA was tested with suspen-
assays on the same date. All sera had been frozen between sions of 20 different microorganisms and 6 fungal antigen
the date drawn and the date of testing. The results obtained preparations, representing 26 organisms that may cause
from both LA and EIA of sequential specimens showed similar clinical symptoms or that may be found as contami-
similar decreases in titer for patients A and B. nants in serum or CSF specimens. Table 3 illustrates the
Comparison of serum and CSF antigen concentrations. results when antigen preparations or suspensions of organ-
When both serum and CSF were obtained from an individual isms were (i) substituted for the patient specimen and tested
on the same day, antigen levels were higher in the serum and (ii) mixed with a known quantity of cryptococcal antigen
than the CSF. During the clinical trial, 10 such serum-CSF and tested. Only Trichosporon beigelii caused a false-posi-
pairs were tested by both LA and EIA. Five pairs did not tive reaction with the EIA, and this organism also causes
contain detectable antigen in either serum or CSF and were false positives with the LA assay (8). None of the other
diagnosed as negative for cryptococcal disease. The other organisms or antigen preparations caused significant inter-
five paired specimens were obtained from four patients, all ference with the assay when mixed with a known quantity of
of whom had previously had positive CSF cultures for cryptococcal antigen.
VOL. 29, 1991 EVALUATION OF EIA FOR CRYPTOCOCCAL ANTIGEN
DISCUSSION
The data presented here indicate that the PREMIER
Cryptococcal Antigen EIA screening assay yields results
which are equivalent to those from the LA (98% overall
agreement). Both assays detected cryptococcal antigen in
120 specimens, with a total of 11 discordant results between
the two tests. Eight discordant results were cases of positive
EIA results and negative LA tests. In five of these eight
cases, additional testing of other specimens supported the
presence of cryptococcal disease. Three EIA positive spec-
imens were never confirmed to contain cryptococcal antigen
and were considered false positives (clinical diagnosis was
negative).
The limits of antigen detected by each assay and the
clinical data indicate that the EIA is somewhat more sensi-
tive than the LA assay. With serotypes A and B, the EIA
was approximately 12-fold more sensitive than LA, while the
assays were equivalent in detection of serotypes C and D. In
this investigation the PREMIER EIA detected cryptococcal
antigen at an earlier stage of disease in two CSF specimens
and one serum sample. The presence of serum antigen was
also demonstrated by EIA (but not LA) from a patient at the
end of successful treatment. In all of these cases, the EIA
appeared to be more sensitive than LA.
Both the EIA and the LA (8) cross-react with T. beigelii.
The existence of cross-reactive circulating antigen was re-
cently demonstrated in an experimental model of dissemi-
nated trichosporonosis (9). However, this organism is an
uncommon pathogen and is unlikely to cause frequent mis-
diagnoses with either assay (8).
The use of EIA data for monitoring disease status and drug
therapy was evaluated through the use of sequential serum
samples from six individual patients. Data from two patients,
illustrated in Fig. 1, show similar trends in the amount of
antigen detected with both assays. Both patients appear to
be responding to therapy. Although more extensive evalua-
tion of the EIA's value in monitoring sequential specimens is
needed, the preliminary comparisons are encouraging.
It is noteworthy that the LA and PREMIER EIA titers are
not numerically equivalent. In general, the EIA titers are
slightly higher than LA titers for specimens with relatively
low antigen concentrations. At higher antigen concentra-
tions the EIA titers are frequently 20- to 100-fold higher than
LA titers. Therefore, it is not advisable to convert EIA titers
into LA titers. The data from sequential specimens from a
single patient suggest that a similar trend will be observed
with both assays, even though the actual numbers may be
quite different.
We conclude that the PREMIER Cryptococcal Antigen
1619
EIA provides for direct specimen detection (without pronase
or other pretreatment) in less than 45 min. PREMIER
appears to have a 12-fold sensitivity advantage over LA for
the two most common serotypes (A and B). The EIA is a
simple, rapid, and reliable screening assay for the early
detection of cryptococcal antigen in either serum or CSF.
Preliminary data indicate that the semiquantitative assay
may be a useful method of monitoring the efficacies of drug
therapies. Prospective evaluation of the utility of the EIA for
monitoring sequential specimens is ongoing.
REFERENCES
1. Bennett, J. E., H. F. Hasenclever, and B. S. Tynes. 1964.
Detection of cryptococcal polysaccharide in serum and spinal
fluid: value in diagnosis and prognosis. Trans. Assoc. Am.
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Physicians 77:145-150.
2. Bottone, E. J., I. F. Salkin, N. J. Hurd, and G. P. Wormser.
1987. Serogroup distribution of Cryptococcus neoformans in
patients with AIDS. J. Infect. Dis. 156:242.
3. Diamond, D., and E. Bennett. 1974. Prognostic factors in cryp-
tococcal meningitis. Ann. Int. Med. 80:176-181.
4. Eckert, T. F., and T. R. Kozel. 1987. Production and character-
ization of monoclonal antibodies specific for Cryptococcus
neoformans capsular polysaccharide. Infect. Immun. 55:1895-
1899.
5. Goodman, J. S., L. Kaufman, and M. G. Koenig. 1971. Diagno-
sis of cryptococcal meningitis: value of immunologic detection
of cryptococcal antigen. N. Engl. J. Med. 285:434-436.
6. Gray, L. D., and G. D. Roberts. 1988. Experience with the use
of pronase to eliminate interference factors in the latex aggluti-
nation test for cryptococcal antigen. J. Clin. Microbiol. 26:2450-
2451.
7. Kaufman, L., and S. Blumer. 1977. Cryptococcosis: the awak-
ening giant. Pan Am. Health Organ. Sci. Publ. 356:176-182.
8. McManus, E. J., and J. M. Jones. 1985. Detection of a Tricho-
sporon beigelli antigen cross-reactive with Cryptococcus neo-
formans capsular polysaccharide in serum from a patient with
disseminated Trichosporon infection. J. Clin. Microbiol. 21:
681-685.
9. Melcher, G. P., K. D. Reed, M. G. Rinaldi, J. W. Lee, P. A.
Pizzo, and T. J. Walsh. 1991. Demonstration of a cell wall
antigen cross-reacting with cryptococcal polysaccharide in ex-
perimental disseminated trichosporonosis. J. Clin. Microbiol.
29:192-196.
10. Murphy, J. M. 1989. Immunology of the fungal diseases, p.
93-138. CRC Press, Inc., Boca Raton, Fla.
11. Murphy, J. W., R. L. Mosley, R. Cherniak, G. H. Reyes, T. R.
Kozel, and E. Reiss. 1988. Serological, electroporetic, and
biological properties of Cryptococcus neoformans antigens.
Infect. Immun. 56:424-431.
12. Patterson, T. F., and V. T. Andriole. 1989. Current concepts in
cryptococcosis. Eur. J. Clin. Microbiol. Infect. Dis. 8:457-465.
13. Perfect, J. R. 1989. Cryptococcosis. Infect. Dis. Clin. N. Am.
3:77-102.
JOURNAL OF CLINICAL MICROBIOLOGY, Sept. 1992, p. 2521-2522
0095-1137/92/092521-02$02.00/0
Letters to the Editor
Detection of Circulating Capsular Polysaccharide Antigen
from Cryptococcus neoformans
In their paper entitled "Comparison of the PREMIER
Cryptococcal Antigen Enzyme Immunoassay and the Latex
Agglutination Assay for Detection of Cryptococcal Antigens"
(1), Gade et al. compare a new enzyme immunoassay (EIA)
for the detection and quantification of circulating capsular
polysaccharide antigen from Cryptococcus neoformans with
the latex agglutination (LA) test performed with a commer-
cially available kit, the CALAS LA test (Meridian Diagnos-
tics). In the Discussion, the authors conclude that "PRE-
MIER appears to have a 12-fold sensitivity advantage over
LA," which is indeed supported by their experimental data.
In our opinion, this sentence should be modified to read as
follows: "PREMIER appears to have a 12-fold sensitivity
advantage over the CALAS LA test," since it is well known
that the sensitivity of the LA test varies from one kit to
another.
In their comparative study, the authors have chosen a latex
kit which, in our experience, is much less sensitive than, e.g.,
the IMMY kit from Immuno-Mycologics. In our laboratory,
the IMMY has been used for years on several hundreds of
specimens. It is also our standard for the evaluation of the
value of other antigen detection kits. We would like to suggest
that they compare their new ETA kit, which possibly is better
than any latex kit, with a more sensitive LA test, such as the
IMMY kit from Immuno-Mycologics.
REFERENCE
1. Gade, W., S. W. Hinnefeld, L. S. Babcock, P. Gilligan, W. Kelly,
K. Wait, D. Greer, M. Pinilla, and R. L. Kaplan. 1991. Compar-
ison of the PREMIER Cryptococcal Antigen immunoassay and
the latex agglutination assay for detection of cryptococcal anti-
gens. J. Clin. Microbiol. 29:1616-1619.
Danielle Swinne
Charles De Vroey
Institute of Tropical Medicine
Laboratory for Mycology
Nationalestraat 155
B-2000Antwerpen I
Belgium
Author's Reply
We agree that the performance characteristics (i.e., sen-
sitivity and specificity) of the commercially available kits
vary between manufacturers. The conclusions expressed in
our manuscript (1) followed a direct comparison of the
PREMIER ETA with the CALAS latex agglutination kit
(both kits by Meridian Diagnostics, Cincinnati, Ohio). The
term LA was used throughout the article and was clearly
defined as referring to the CALAS test in the Materials and
2521
Vol. 30, No. 9
Methods section. As the market leader with over 60% of the
market shares, the CALAS kit seems an appropriate choice
for comparisons with any new cryptococcal antigen product.
A more complete and independent study comparing the EIA
with several latex products would certainly be even more
informative.
The sensitivity issue raised by Swinne and De Vroey
concerns whether the EIA is approximately 12-fold more
sensitive than latex assays in general or only the CALAS kit.
We did not directly compare the analytical or clinical sensi-
tivities of other latex kits, since the manuscript was intended
to describe the new EIA. Thus, it is quite possible that
another kit is more sensitive than the CALAS kit. The
IMMY package insert (Immuno-Mycologics, Inc.) claims a
range of detection limits of 5 ng/ml to 25 p,g/ml, which is
slightly more sensitive than the 7.6 ng/ml for CALAS stated
in the manuscript.
Only one comparison of several latex products and the
EIA has been published (2). In this study, the CALAS,
IMMY, and PREMIER EIA kits all detected antigen in 21 of
21 (100%) true positives. Two other commercial latex kits
missed two positives each. The specificity of the EIA (99%)
was superior to those of all latex kits, and the CALAS kit
(92%) was more specific than the IMMY kit (89%). In this
investigation, 17 of 155 negative specimens were incorrectly
detected as positives by the IMMY kit, compared with 12
false positives for the CALAS and only 2 for the EIA.
Thus, any evaluation of various diagnostic kits should
compare all of the performance characteristics. Although
Meridian plans no additional clinical evaluations of this prod-
uct, we would certainly encourage a thorough evaluation of
both the EIA and CALAS LA test by independent investiga-
tors.
REFERENCES
1. Gade, W., S. W. Hinnefeld, L. S. Babcock, P. Gilligan, W. Kelly,
K. Wait, D. Greer, M. Pinilla, and R. L. Kaplan. 1991. Compar-
ison of the PREMIER Cryptococcal Antigen immunoassay and
the latex agglutination assay for detection of cryptococcal anti-
gens. J. Clin. Microbiol. 29:1616-1619.
2. Tanner, D., M. P. Weinstein, B. Fedorciw, K. Joho, J. Thorpe,
and L. B. Reller. 1991. Program Abstr. 31st Intersci. Conf.
Antimicrob. Agents Chemother., abstr. 478.
Wayne Gade
Meridian Diagnostics
3471 River Hills Dr.
Cincinnati, Ohio 45244