LETTER TO THE EDITOR

crossm

Analytical Comparison of the Architect Syphilis TP and

Liaison Treponema Automated Chemiluminescent
Immunoassays and Their Performance in a Reverse Syphilis
Screening Algorithm
Alan M. Sanfilippo,a,b Kristie Freeman,a John L. Schmitza,b

a
McLendon Clinical Laboratories, University of North Carolina Hospitals, Chapel Hill, North Carolina, USA
b Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel
Hill, North Carolina, USA

KEYWORDS reverse algorithm, syphilis

T he incidence of syphilis has increased in the United States since 2000 (1, 2) and
remains a global public health concern (3, 4). A tiered serology-based testing
approach, historically starting with nontreponemal testing, is recommended by the
Centers for Disease Control and Prevention (CDC) (5). To increase throughput and
improve sensitivity for latent syphilis, laboratories are switching to a testing algorithm
that starts with an FDA-cleared automated treponeme-specific chemiluminescent im-
munoassay (CLIA), followed by confirmation with a nontreponemal test and/or a
different treponeme-specific test (6–11).
In this study, we compared the recently FDA-cleared Architect Syphilis TP (Architect;
Abbott Laboratories, Abbott Park, IL) CLIA to the Liaison Treponema (Liaison; DiaSorin,
Stillwater, MN) CLIA by testing 1,028 consecutive sera submitted for syphilis screening
to the University of North Carolina Hospitals (UNCH) Clinical Immunology Laboratory.
Serum was stored for no longer than 3 months at ⫺80°C. All specimens were remnant
specimens from UNCH patients over the age of 18, and approval was obtained from the
University of North Carolina Institutional Review Board. Initial screening identified 976
nonreactive and 47 reactive specimens that were concordant by both methods (Table
1). Of the five discordant specimens, four were Architect reactive and Liaison nonre-
active, while one specimen was Liaison reactive and Architect nonreactive, providing
positive, negative, and total percent agreements of 97.9%, 99.6%, and 99.5%, respec-
tively (kappa coefficient ⫽ 0.947; 95% confidence interval [95% CI], 0.901 to 0.993).
Comparing each assay’s screening results to reverse-algorithm-verified positive Accepted manuscript posted online 16 May
2018
results (see the materials and methods in the supplemental material), the Architect
Citation Sanfilippo AM, Freeman K, Schmitz JL.
Syphilis TP assay identified 45 of 45 verified positive results, while five specimens were 2018. Analytical comparison of the Architect
Architect reactive, ASI rapid plasma reagin (RPR) (Arlington Scientific, Inc., Springville, Syphilis TP and Liaison Treponema automated
chemiluminescent immunoassays and their
performance in a reverse syphilis screening
algorithm. J Clin Microbiol 56:e00215-18.
TABLE 1 Liaison and Architect result concordancea https://doi.org/10.1128/JCM.00215-18.
No. of specimens with Editor Geoffrey A. Land, Carter BloodCare and
Liaison result: Baylor University Medical Center
Copyright © 2018 American Society for
Architect result RX NR Total Microbiology. All Rights Reserved.
RX 47 4 51 Address correspondence to John L. Schmitz,
NR 1 976 977 John.Schmitz@unchealth.unc.edu.
Total 48 980 1,028 For a companion article on this topic, see
aNR, nonreactive; RX, reactive. The positive and negative percent agreements were 97.9% and 99.6%, https://doi.org/10.1128/JCM.00214-18.
respectively. The kappa coefficient was 0.947 (95% CI, 0.901 to 0.993).

August 2018 Volume 56 Issue 8 e00215-18 Journal of Clinical Microbiology jcm.asm.org 1

Letter to the Editor Journal of Clinical Microbiology

FIG 1 Reverse syphilis testing algorithm. RX, reactive; NR, nonreactive; RPR, rapid plasma reagin.

UT) nonreactive, and Serodia Treponema pallidum particle agglutination (TP-PA) (Fu-
jirebio Inc., Malvern, PA) nonreactive, for a false-positivity rate of 0.5% (Fig. 1). No
verified-positive specimens were missed by Architect, providing a sensitivity, speci-
ficity, positive predictive value (PPV), and negative predictive value (NPV) of 100%
(95% CI, 92.1 to 100%), 99.5% (95% CI, 98.8 to 99.8%), 90.0% (95% CI, 78.2 to 96.7%),
and 100.0% (95% CI, 99.6 to 100.0%), respectively (Table 2). The Liaison Treponema
assay also identified 45 of 45 verified positives, while two specimens were positive
by the Liaison assay but RPR and TP-PA nonreactive, for a false-positivity rate of
0.2% (Fig. 1). The Liaison assay also had no false-negative specimens, for a sensi-
tivity, specificity, PPV, and NPV of 100.0% (95% CI, 92.1 to 100.0%), 99.8% (95% CI,
99.3 to 100.0%), 95.7% (95% CI, 85.5 to 99.5%), and 100.0% (95% CI, 99.6 to 100.0%),
respectively (Table 2). One specimen was falsely positive by both the Architect and
Liaison assays, while an additional specimen that was positive by both assays was
RPR nonreactive but TP-PA indeterminate (Table 3). The levels of inter- and intra-
assay precision of both assays were comparable, with the coefficients of variation of
all reactive TP-PA specimens being equal to or less than 3.5% (Table S1).

TABLE 2 Reverse-algorithm comparisona

No. (%) of indicated
positive specimens
that were verified
to be:
Test and Sensitivity Specificity PPV NPV
result RX NR Total (%) (%) (%) (%) (%)
Liaison
RX 45 (4.4) 2 (0.2) 47 (4.6)
NR 0 (0.0) 980 (95.4) 980 (95.4)

Totals 45 (4.4) 982 (95.6) 1,027 100.0 99.8 95.7 100.0

Architect
RX 45 (4.4) 5 (0.5) 50 (4.9)
NR 0 (0.0) 977 (95.1) 977 (95.1)

Totals 45 (4.4) 982 (95.6) 1,027 100.0 99.5 90.0 100.0

aRX, reactive; NR, nonreactive; PPV, positive predictive value; NPV, negative predictive value.

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Letter to the Editor Journal of Clinical Microbiology

TABLE 3 Discordant-specimen resultsa

Liaison Architect ASI RPR TP-PA
Specimen result result result result Interpretation
610 NR RX NR NR Architect false positive
948 NR RX NR NR Architect false positive
1002 NR RX NR NR Architect false positive
1025 RX RX NR NR Dually false positive
1128 NR RX NR NR Architect false positive
1282 RX NR NR NR Liaison false positive
1493 RX RX NR IND Undefined
aNR, nonreactive; RX, reactive; IND, indeterminate.

Considering that the reverse-testing algorithm involves one additional test com-
pared to the traditional algorithm, strategies to identify potential false positives and
reduce unnecessary tests have been employed by using chemiluminescent signal
strengths to set a cutoff for confirmatory testing (12–14). The optimal Architect
assay signal to cutoff (S/CO) and Liaison assay index values used to predict TP-PA
confirmatory testing results were determined using receiver operating characteris-
tic (ROC) curves. An S/CO value that provided 100% specificity was determined for
the Architect Syphilis TP assay, as all specimens with an S/CO value greater than 6.0
(40/40; P ⫽ 0.0001) were confirmed by TP-PA testing (Fig. 2A). For the Liaison
Treponema assay, an index value greater than 3.0 provided 100% specificity, as all
specimens testing higher than 3.0 (45/45) were confirmed by TP-PA testing (Fig. 2B)
(P ⫽ 0.005). Adopting a testing approach where subsequent testing is based on CLIA
signal strengths might significantly reduce costs for a laboratory (13); however, a larger
sample size which includes more CLIA-reactive but RPR- and TP-PA-nonreactive spec-
imens will be needed to determine reliable S/CO and index values to use clinically.
Similar studies performed outside the United States have evaluated the Architect
Syphilis TP assay, with reported sensitivities of 99.5 to 100.0% and specificities of 54.5
to 100.0%, depending on patient population (15, 16).
In conclusion, the Architect Syphilis TP assay exhibited sensitivity and specificity that
were as high as those of the Liaison Treponema assay and is suitable as a syphilis
screening assay in a clinical laboratory setting.

FIG 2 ROC analysis to predict truly positive (TP-PA-confirmed) specimens. Signal/cutoff (S/CO) and
index values providing 100% specificity were selected for the Architect Syphilis TP assay (manufac-
turer’s reactive S/CO, ⱖ1.00) (A) and Liaison Treponema assay (manufacturer’s equivocal index,
0.90 ⬍ 1.10, and positive index, ⱖ1.10) (B) for which all specimens with higher values resulted in
reactive TP-PA results. P was 0.0001 (A) and P was 0.005 (B) by Fisher’s exact test. AUC, area under
the curve.

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Letter to the Editor
SUPPLEMENTAL MATERIAL
Supplemental material for this article may be found at https://doi.org/10.1128/JCM
.00215-18.
SUPPLEMENTAL FILE 1, PDF file, 0.2 MB.
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