PMID- 30212544
OWN - NLM
STAT- MEDLINE
DCOM- 20190306
LR  - 20190306
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 9
DP  - 2018
TI  - Improvement of reverse sequence algorithm for syphilis diagnosis using optimal
      treponemal screening assay signal-to-cutoff ratio.
PG  - e0204001
LID - 10.1371/journal.pone.0204001 [doi]
AB  - BACKGROUND: Although 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. OBJECTIVES: To 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.
      METHODS: Serum 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. RESULTS: Of 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. CONCLUSION: Signal-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.
FAU - Serhir, Bouchra
AU  - Serhir B
AUID- ORCID: 0000-0003-0735-0452
AD  - Laboratoire de sante publique du Quebec/Institut national de sante publique du
      Quebec, Sainte-Anne-de-Bellevue, Quebec, Canada.
FAU - Labbe, Annie-Claude
AU  - Labbe AC
AD  - CIUSSS de l'Est-de-l'Ile-de-Montreal, Hopital Maisonneuve-Rosemont, Service de
      Maladies infectieuses et microbiologie medicale, Montreal, Canada.
FAU - Doualla-Bell, Florence
AU  - Doualla-Bell F
AD  - Laboratoire de sante publique du Quebec/Institut national de sante publique du
      Quebec, Sainte-Anne-de-Bellevue, Quebec, Canada.
FAU - Simard, Marc
AU  - Simard M
AD  - Unite de surveillance des maladies chroniques et de leur determinants/Institut
      national de sante publique du Quebec, Quebec, Quebec, Canada.
FAU - Lambert, Gilles
AU  - Lambert G
AD  - Unite des infections transmissibles sexuellement et par le sang/Institut national
      de sante publique du Quebec, Montreal, Quebec, Canada.
FAU - Trudelle, Annick
AU  - Trudelle A
AD  - Laboratoire de sante publique du Quebec/Institut national de sante publique du
      Quebec, Sainte-Anne-de-Bellevue, Quebec, Canada.
FAU - Longtin, Jean
AU  - Longtin J
AD  - Laboratoire de sante publique du Quebec/Institut national de sante publique du
      Quebec, Sainte-Anne-de-Bellevue, Quebec, Canada.
FAU - Tremblay, Cecile
AU  - Tremblay C
AD  - Centre hospitalier de l'Universite de Montreal, Departement de microbiologie
      medicale et infectiologie, Montreal, Quebec, Canada.
FAU - Fortin, Claude
AU  - Fortin C
AD  - Centre hospitalier de l'Universite de Montreal, Departement de microbiologie
      medicale et infectiologie, Montreal, Quebec, Canada.
LA  - eng
PT  - Journal Article
PT  - Validation Studies
DEP - 20180913
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Algorithms
MH  - Diagnostic Errors
MH  - Humans
MH  - Immunoenzyme Techniques/methods/statistics & numerical data
MH  - Mass Screening/methods/statistics & numerical data
MH  - Quebec
MH  - Signal-To-Noise Ratio
MH  - Syphilis/*diagnosis
MH  - Syphilis Serodiagnosis/*methods/statistics & numerical data
MH  - Treponema Immobilization Test/statistics & numerical data
PMC - PMC6136794
COIS- The authors have declared that no competing interests exist.
EDAT- 2018/09/14 06:00
MHDA- 2019/03/07 06:00
CRDT- 2018/09/14 06:00
PHST- 2017/11/01 00:00 [received]
PHST- 2018/08/31 00:00 [accepted]
PHST- 2018/09/14 06:00 [entrez]
PHST- 2018/09/14 06:00 [pubmed]
PHST- 2019/03/07 06:00 [medline]
AID - 10.1371/journal.pone.0204001 [doi]
AID - PONE-D-17-37857 [pii]
PST - epublish
SO  - PLoS One. 2018 Sep 13;13(9):e0204001. doi: 10.1371/journal.pone.0204001.
      eCollection 2018.