Correlation of Treponemal Immunoassay Signal Strength Values with Reactivity of Confirmatory Treponemal Testing

Fakile, Yetunde; Jost, Heather; Hoover, Karen W.; Gustafson, Kathleen J.; Novak-Weekley, Susan; Schapiro, Jeffrey M.; Tran, Anthony; Chow, Joan M.; Park, Ina U.

doi:10.1128/jcm.01165-17

Cited by 18 publications

(17 citation statements)

References 11 publications

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“…All four proteins showed AUC and accuracy values above 99% and 91%, respectively (Fig 3). Similar results were described in other studies [31][32][33]. In fact, studies using the BioPlex 2200 syphilis IgG assay revealed a sensitivity from 95.8% to 100% and specificity from 89.7% to 99.4% for the proteins TpN15, TpN17 and TpN47 assayed together [31][32][33].…”

Section: Discussionsupporting

confidence: 89%

Performance of Treponema pallidum recombinant proteins in the serological diagnosis of syphilis

et al. 2020

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Syphilis serodiagnosis is challenging because distinct clinical forms of the infection may influence serological performance and discordant results between tests make clinical decisions difficult. Several recombinant Treponema pallidum-proteins have already been tested for syphilis diagnosis and they are critical to achieve high accuracy in serological testing. Our aim was to assess the varied from performance of T. pallidum-recombinant proteins TmpA, TpN17 and TpN47 for syphilis serodiagnosis. The proteins were evaluated using sera of 338 T. pallidum-negative, 173 T. pallidum-positive individuals and 209 sera from individuals infected with unrelated diseases. The diagnostic potential was validated by analysis of ROC curves. In the liquid microarray analyses, the ROC curve varied from 99.0% for TmpA and TpN17 to 100% for TpN47. The sensitivity score yielded values of up to 90% for TpN17, 100% for TpN47 and 80.0% for TmpA. The lowest and highest specificity values were presented by TpN47 (91.9%) and TmpA antigens (100%), respectively. TpN47 showed the highest accuracy score (95.5%) among all the recombinant proteins assayed. For the ELISA, the ROC curve was 97.2%, 91.8% and 81.6% for TpN17, TmpA and TpN47, respectively. TpN17 and TmpA yielded a sensitivity of 69.9%, while TpN47 obtained a value of 53.8%. Specificity was almost 100% for all three proteins. No cross-reaction was observed for TpN17 in the serum samples from non-bacterial infections. Regarding leptospirosis-positive samples, cross-reactivity score was varied from 8.6 to 34.6%. This is most probably due to conservation of the epitopes in these proteins across bacteria. The use of recombinant proteins in immunoassays for syphilis diagnosis was showed provide greater reliability to results of the treponemal assays. Despite the low sensitivity, the proteins showed high diagnostic capacity due to the AUC values found. However, an improvement in sensitivity could be achieved when antigenic mixtures are evaluated.

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Section: Discussionsupporting

confidence: 89%

Performance of Treponema pallidum recombinant proteins in the serological diagnosis of syphilis

et al. 2020

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“…Indeed, Fakile et al . [ 15 ] obtained a S/CO ratio of 4.4 that correlated at 100% with a positive TP-PA reactivity suggesting that a second TT may not be necessary. In a more recent study, Berry and Loeffelholz [ 7 ] concluded that TP-PA testing is unnecessary on specimens with S/CO ≥8 using BioPlex IgG kit.…”

Section: Discussionmentioning

confidence: 99%

“…Based on TP-PA confirmatory assay, specimens with S/CO > 5.6 were considered positive and do not require further confirmation testing as compared to the higher S/CO threshold of 16.4 predicted in our study. Such a difference can be explained by the sample size (668 versus 178 samples) in addition to the S/CO range [ 1 – 15 ] used in each study as well as by the fact that only specimens with a low Architect value were included in Jonckheere et al . study.…”

Section: Discussionmentioning

confidence: 99%

Improvement of reverse sequence algorithm for syphilis diagnosis using optimal treponemal screening assay signal-to-cutoff ratio

et al. 2018

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BackgroundAlthough reverse sequence algorithms (RSA) for syphilis screening are performing well, they still have to rely on treponemal confirmatory tests at least for sera reactive by enzyme immunoassay/chemiluminescence immunoassay (EIA/CIA) and unreactive by rapid plasma reagin (RPR). Quebec’s laboratory network previously showed that 3.3% of EIA/CIA reactive and weakly-reactive RPR samples (RPR titer of 1 to 4) would have been misclassified as syphilis cases if a treponemal confirmatory test had not been performed.ObjectivesTo correlate the magnitude of signal-to-cutoff (S/CO) ratios of the 4 most used commercial first-line EIA/CIA kits in Quebec with syphilis confirmation results and establish a S/CO value above which treponemal confirmation would not be required.MethodsSerum samples from previously undiagnosed individuals (n = 7 404) obtained between January 2014 and February 2017 that were reactive by EIA/CIA and either negative by RPR or reactive with a low titer (1 to 4) were included in the study. All samples were tested with Treponema pallidum particle agglutination (TP-PA) and, if negative or inconclusive, with a line immunoassay (LIA). Syphilis infection confirmation was defined by a reactive TP-PA or LIA. Logistic regression analysis was used to determine S/CO values (95% CI lower bound = 0.98) above which confirmation would not be required. The four kits studied were Architect TP, BioPlex IgG, Syphilis EIA II, and Trep-Sure.ResultsOf 2609 reactive EIA/CIA specimens tested for the determination of S/CO values, 1730 (66%) were confirmed as true syphilis cases. Confirmation rate was significantly higher in samples with low-titer positive RPR (92%) than with negative RPR samples (54%); p<0.01. A linear probability model (95% CI lower bound = 0.98) predicted the S/CO value above which a confirmation would no longer be needed for the Architect TP (16.4), Bioplex IgG (7.4) and Trep-Sure (24.6). No linearity was observed between the S/CO value of Syphilis EIA II and the confirmation rate. The validity of the predicted S/CO values was investigated using 4 795 specimens. The use of an S/CO value of 16.4 with the Architect TP kit and of 24.6 for the Trep-Sure kit would obviate the need for confirmation of 18.5% and 13.2% of sera from the all RPR subgroup, respectively. For the BioPlex IgG kit, 81.1% of sera would not require confirmation when using the S/CO value of 7.4 in the low titer RPR subgroup.ConclusionSignal-to-cut-off values could be used to identify sera that do not require extra treponemal confirmation for 3 of the 4 most used first-line EIA/CIA kits in Quebec. Using these values in our current reverse screening algorithm (RSA) would avoid the need for confirmatory tests in 14 to 20% of sera, a proportion that could reach 75% among low-titer RPR.

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“…The article by Fakile et al in this issue describes a comparison of four automated treponemal immunoassays used for syphilis screening as well as three manual assays (5). The authors demonstrated the capability of signal strength ratio cutoffs for automated immunoassays to predict the outcome of repeat treponemal testing.…”

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confidence: 99%

Using Treponemal Assay Signal Strength Cutoff Ratios To Predict Syphilis Infection

Bristow

Klausner

2018

J Clin Microbiol

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Syphilis screening with the reverse algorithm, a treponemal test for screening followed by a nontreponemal test if reactive, is increasingly being used. That algorithm has several advantages, including use of an automated screening test, saving on laboratory time and costs, as well as detection of very early syphilis infection. However, under that algorithm, in situations where the treponemal result is positive and the nontreponemal result is nonreactive a second treponemal test must be performed, which may actually lead to inefficiencies in the laboratory. In this issue of the Journal of Clinical Microbiology, Y. F. Fakile et al. (J Clin Microbiol 56:e01165-17, 2017, https://doi.org/10.1128/ JCM.01165-17) report the results of their study, which demonstrates the capability of signal strength ratio cutoffs for automated treponemal immunoassays to predict the outcome of repeat treponemal testing. Their findings suggest that anti-treponemal signal strength ratio values above a cutoff value can be used in lieu of repeat treponemal tests.KEYWORDS syphilis, diagnostics, treponemal testing S yphilis is on the increase in the United States. Reported rates of primary and secondary syphilis are the highest that they have been in more than 20 years and are increasing each year across the country and among almost every race/ethnicity and age group (1). There is an urgent need for new paradigms for the use of existing syphilis diagnostic tests.The reverse algorithm for syphilis screening is being used in many settings. (2). That algorithm allows for use of an automated or semiautomated screening test, which can reduce labor requirements and may have particular advantage in high-throughput laboratory settings. An additional advantage is that that algorithm may identify early syphilis infection in which nontreponemal antibodies are not yet detectable (3) or latent syphilis cases when nontreponemal antibodies are no longer detectable. Those early and latent cases would be undetected under the standard algorithm where RPR (or other nontreponemal tests) is used as the screening test. However, using the reverse algorithm, to address the potential of false-positive treponemal test results in cases where the nontreponemal tests are used as confirmatory tests and are nonreactive, the Centers for Disease Control and Prevention (CDC) recommends use of a second treponemal test to confirm the first reactive treponemal result (4). That need for a third assay increases cost and laboratory time and importantly may delay time to result. In an era of increasing syphilis, we want to decrease time to result and subsequent treatment delays as much as possible. Accepted manuscript posted online 18 October 2017Citation Bristow CC, Klausner JD. 2018. Using treponemal assay signal strength cutoff ratios to predict syphilis infection. J Clin Microbiol

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Correlation of Treponemal Immunoassay Signal Strength Values with Reactivity of Confirmatory Treponemal Testing

Cited by 18 publications

References 11 publications

Performance of Treponema pallidum recombinant proteins in the serological diagnosis of syphilis

Performance of Treponema pallidum recombinant proteins in the serological diagnosis of syphilis

Improvement of reverse sequence algorithm for syphilis diagnosis using optimal treponemal screening assay signal-to-cutoff ratio

Using Treponemal Assay Signal Strength Cutoff Ratios To Predict Syphilis Infection

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