The dark art of syphilis serology - an analysis of testing algorithms at a UK reference laboratory

Antonia Scobie; Colin S. Brown; Patrick French; Matthew Donati; Peter Muir; Kate Templeton; Stephen P. Higgins; Hemanti Patel; Sarah Alexander; Helen Fifer

doi:10.1099/jmm.0.001479

The dark art of syphilis serology - an analysis of testing algorithms at a UK reference laboratory

Antonia Scobie, Colin S. Brown, Patrick French, Matthew Donati, Peter Muir, Kate Templeton, Stephen P. Higgins, Hemanti Patel, Sarah Alexander, Helen Fifer

UK Health Security Agency

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Abstract

Introduction. Due to the complex nature of treponemal serology interpretation, testing algorithms vary across the UK.

Gap statement. There is currently no gold standard method for interpretation of discordant serology results.

Aim. To analyse serological response in early infection and to determine the best approach for discordant total antibody EIA and TPPA samples.

Methodology. National reference laboratory serology and PCR (genital ulcer swabs) results from 2010 to 2017 were extracted from an electronic laboratory database.

Results. A total of 24149 sera underwent analysis. Of syphilis PCR positive cases with contemporaneous sera, 33% (17/52) were IgM positive/equivocal, whilst all were EIA and TPPA positive. No sera with isolated IgM positivity (0/90) demonstrated seroconversion consistent with early treponemal infection, in contrast to 17% (2/12) of sera with isolated TPPA positivity. Isolated EIA positivity was observed in 6.2% (1499/24149) samples with the same result on repeat testing in 73% (154/211). In 100 samples with discordant EIA/TPPA results, IgG Immunoblot was more commonly positive (12/41, 29%) or equivocal (24/41, 59%), in those with a higher EIA antibody index, compared to those with a low antibody index, of which none tested positive and 2/3 (67 %) were equivocal.

Conclusion. Isolated IgM positivity was not helpful in identifying early infection; isolated total antibody EIA positivity is unlikely to be a significant finding. IgG immunoblot testing was unable to determine clear treponemal antibody status in nearly half of all EIA/TPPA discordant samples.

Original language	English
Article number	001479
Journal	Journal of Medical Microbiology
Volume	71
Issue number	4
Early online date	22 Apr 2022
DOIs	https://doi.org/10.1099/jmm.0.001479
Publication status	E-pub ahead of print - 22 Apr 2022

Bibliographical note

Funding Information: Public Health England.

Open Access: This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.

Publisher Copyright: © 2022 Crown Copyright is asserted

Citation: Scobie, Antonia, et al. "The dark art of syphilis serology-an analysis of testing algorithms at a UK reference laboratory." Journal of Medical Microbiology 71.4 (2022): 001479.

DOI: https://doi.org/10.1099/jmm.0.001479

Keywords

serology
syphilis
testing
treponema

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Scobie2022TheDarkArtOfSyphilisSerologyJMedMicrobiolFinal published version, 363 KBLicence: CC BY

Cite this

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title = "The dark art of syphilis serology - an analysis of testing algorithms at a UK reference laboratory",

abstract = "Introduction. Due to the complex nature of treponemal serology interpretation, testing algorithms vary across the UK.Gap statement. There is currently no gold standard method for interpretation of discordant serology results.Aim. To analyse serological response in early infection and to determine the best approach for discordant total antibody EIA and TPPA samples.Methodology. National reference laboratory serology and PCR (genital ulcer swabs) results from 2010 to 2017 were extracted from an electronic laboratory database.Results. A total of 24149 sera underwent analysis. Of syphilis PCR positive cases with contemporaneous sera, 33% (17/52) were IgM positive/equivocal, whilst all were EIA and TPPA positive. No sera with isolated IgM positivity (0/90) demonstrated seroconversion consistent with early treponemal infection, in contrast to 17% (2/12) of sera with isolated TPPA positivity. Isolated EIA positivity was observed in 6.2% (1499/24149) samples with the same result on repeat testing in 73% (154/211). In 100 samples with discordant EIA/TPPA results, IgG Immunoblot was more commonly positive (12/41, 29%) or equivocal (24/41, 59%), in those with a higher EIA antibody index, compared to those with a low antibody index, of which none tested positive and 2/3 (67 %) were equivocal.Conclusion. Isolated IgM positivity was not helpful in identifying early infection; isolated total antibody EIA positivity is unlikely to be a significant finding. IgG immunoblot testing was unable to determine clear treponemal antibody status in nearly half of all EIA/TPPA discordant samples.",

keywords = "serology, syphilis, testing, treponema",

author = "Antonia Scobie and Brown, {Colin S.} and Patrick French and Matthew Donati and Peter Muir and Kate Templeton and Higgins, {Stephen P.} and Hemanti Patel and Sarah Alexander and Helen Fifer",

note = "Funding Information: Public Health England. Open Access: This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author{\textquoteright}s institution. Publisher Copyright: {\textcopyright} 2022 Crown Copyright is asserted Citation: Scobie, Antonia, et al. {"}The dark art of syphilis serology-an analysis of testing algorithms at a UK reference laboratory.{"} Journal of Medical Microbiology 71.4 (2022): 001479. DOI: https://doi.org/10.1099/jmm.0.001479 ",

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AU - Scobie, Antonia

AU - Brown, Colin S.

AU - French, Patrick

AU - Donati, Matthew

AU - Muir, Peter

AU - Templeton, Kate

AU - Higgins, Stephen P.

AU - Patel, Hemanti

AU - Alexander, Sarah

AU - Fifer, Helen

N1 - Funding Information: Public Health England. Open Access: This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution. Publisher Copyright: © 2022 Crown Copyright is asserted Citation: Scobie, Antonia, et al. "The dark art of syphilis serology-an analysis of testing algorithms at a UK reference laboratory." Journal of Medical Microbiology 71.4 (2022): 001479. DOI: https://doi.org/10.1099/jmm.0.001479

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N2 - Introduction. Due to the complex nature of treponemal serology interpretation, testing algorithms vary across the UK.Gap statement. There is currently no gold standard method for interpretation of discordant serology results.Aim. To analyse serological response in early infection and to determine the best approach for discordant total antibody EIA and TPPA samples.Methodology. National reference laboratory serology and PCR (genital ulcer swabs) results from 2010 to 2017 were extracted from an electronic laboratory database.Results. A total of 24149 sera underwent analysis. Of syphilis PCR positive cases with contemporaneous sera, 33% (17/52) were IgM positive/equivocal, whilst all were EIA and TPPA positive. No sera with isolated IgM positivity (0/90) demonstrated seroconversion consistent with early treponemal infection, in contrast to 17% (2/12) of sera with isolated TPPA positivity. Isolated EIA positivity was observed in 6.2% (1499/24149) samples with the same result on repeat testing in 73% (154/211). In 100 samples with discordant EIA/TPPA results, IgG Immunoblot was more commonly positive (12/41, 29%) or equivocal (24/41, 59%), in those with a higher EIA antibody index, compared to those with a low antibody index, of which none tested positive and 2/3 (67 %) were equivocal.Conclusion. Isolated IgM positivity was not helpful in identifying early infection; isolated total antibody EIA positivity is unlikely to be a significant finding. IgG immunoblot testing was unable to determine clear treponemal antibody status in nearly half of all EIA/TPPA discordant samples.

AB - Introduction. Due to the complex nature of treponemal serology interpretation, testing algorithms vary across the UK.Gap statement. There is currently no gold standard method for interpretation of discordant serology results.Aim. To analyse serological response in early infection and to determine the best approach for discordant total antibody EIA and TPPA samples.Methodology. National reference laboratory serology and PCR (genital ulcer swabs) results from 2010 to 2017 were extracted from an electronic laboratory database.Results. A total of 24149 sera underwent analysis. Of syphilis PCR positive cases with contemporaneous sera, 33% (17/52) were IgM positive/equivocal, whilst all were EIA and TPPA positive. No sera with isolated IgM positivity (0/90) demonstrated seroconversion consistent with early treponemal infection, in contrast to 17% (2/12) of sera with isolated TPPA positivity. Isolated EIA positivity was observed in 6.2% (1499/24149) samples with the same result on repeat testing in 73% (154/211). In 100 samples with discordant EIA/TPPA results, IgG Immunoblot was more commonly positive (12/41, 29%) or equivocal (24/41, 59%), in those with a higher EIA antibody index, compared to those with a low antibody index, of which none tested positive and 2/3 (67 %) were equivocal.Conclusion. Isolated IgM positivity was not helpful in identifying early infection; isolated total antibody EIA positivity is unlikely to be a significant finding. IgG immunoblot testing was unable to determine clear treponemal antibody status in nearly half of all EIA/TPPA discordant samples.

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The dark art of syphilis serology - an analysis of testing algorithms at a UK reference laboratory

Abstract

Bibliographical note

Keywords

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