Abstract
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.
Highlights
Syphilis is an infectious disease caused by Treponema pallidum
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)
All samples were tested with Treponema pallidum particle agglutination (TP-PA) and, if negative or inconclusive, with a line immunoassay (LIA)
Summary
Syphilis is an infectious disease caused by Treponema pallidum. With only 3 cases reported in Quebec in 1998 (0.04 per 100,000 people), it was possible to hope that syphilis could be eradicated. The traditional algorithm of syphilis serodiagnosis starts with a subjective manual assay using a non treponemal test (NTT), the rapid plasma reagin (RPR). This NTT, which detects non-specific anticardiolipin antibodies, is followed, when reactive, by a treponemal test (TT) that detects anti-treponemal antibodies for confirmation [1,2]. In 2009, several laboratories in Quebec adopted a reverse screening algorithm (RSA) in which a TT (EIA or CIA), which can be automated, is first performed followed by a reflex RPR when positive [4]. 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
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