A multi-country comparative study of two treponemal tests for the serodiagnosis of syphilis amongst men who have sex with men (MSM): Chemo-luminescent assay vs Treponema pallidum particle agglutination assay
Abstract Introduction International guidelines recommend routine screening for syphilis (aetiological agent: Treponema pallidum subspecies pallidum) amongst key populations and vulnerable populations using tests detecting treponemal and non-treponemal antibodies. Whilst treponemal tests have high se...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | BMC Infectious Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12879-024-09100-x |
| _version_ | 1797259534423556096 |
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| author | Lorenzo Gios Massimo Mirandola Maddalena Cordioli Antonella Zorzi Nigel Sherriff Jaime Vera Dominika Wlazly Mohammed Osman Hassan-Ibrahim Valeska Padovese Anabel Darmanin Rosanna W. Peeling Magnus Unemo Karel Blondeel Igor Toskin |
| author_facet | Lorenzo Gios Massimo Mirandola Maddalena Cordioli Antonella Zorzi Nigel Sherriff Jaime Vera Dominika Wlazly Mohammed Osman Hassan-Ibrahim Valeska Padovese Anabel Darmanin Rosanna W. Peeling Magnus Unemo Karel Blondeel Igor Toskin |
| author_sort | Lorenzo Gios |
| collection | DOAJ |
| description | Abstract Introduction International guidelines recommend routine screening for syphilis (aetiological agent: Treponema pallidum subspecies pallidum) amongst key populations and vulnerable populations using tests detecting treponemal and non-treponemal antibodies. Whilst treponemal tests have high sensitivities and specificities, they differ regarding subjective or objective interpretation, throughput and workload. Chemiluminescence immunoassays (CLIAs) are cost- and time-effective automated methods for detecting treponemal antibodies. The Treponema pallidum particle agglutination assay (TPPA) has been considered the “gold standard” treponemal assay, however, this includes a highly manual procedure, low throughput and subjective interpretation. The present multi-country study evaluated the ADVIA Centaur® Syphilis CLIA (Siemens Healthcare) assay compared to the reference SERODIA-TP·PA® (Fujirebio Diagnostics) for the serodiagnosis of syphilis amongst men who have sex with men (MSM). Method 1,485 MSM were enrolled in Brighton (UK), Malta, and Verona (Italy) as part of a larger WHO multi-country and multi-site ProSPeRo study. Ethical approval was obtained. Serum was tested with the ADVIA Centaur® Syphilis CLIA assay and SERODIA-TP·PA®, in accordance with the manufacturers’ instructions, for a first round of validation. A second round of validation was carried out for discrepant results that were additionally tested with both Western Blot (Westernblot EUROIMMUN®) and an Immunoblot (INNO-LIA, Fujirebio Diagnostics). Sensitivity, specificity, positive and negative predictive value (PPV and NPV), likelihood ratios (positive/negative), and the Diagnostic Odds Ratio (DOR)/pre-post-test probability (Fagan's nomogram) were calculated. Results Out of 1,485 eligible samples analysed in the first phase, the SERODIA-TP·PA® identified 360 positive and 1,125 negative cases. The ADVIA Centaur® Syphilis CLIA assay (Siemens) identified 366 positives, missclassifying one TPPA-positive sample. In the second phase, the ADVIA Centaur® Syphilis CLIA resulted in 1 false negative and 4 false positive results. Considering the syphilis study prevalence of 24% (95% CI: 22–26.7), The sensitivity of the ADVIA Centaur® Syphilis CLIA assay was 99.7% (95% CI: 98.5–100), and the specificity was 99.4% (95% CI: 98.7–99.7). The ROC area values were 0.996 (95% CI: 0.992–0.999), and both the PPV and NPV values were above 98% (PPV 98.1%, 95% CI: 96.1–99.2; NPV 99.9%, 95% CI: 99.5–100). Conclusions The ADVIA Centaur® Syphilis CLIA assay showed similar performance compared to the SERODIA-TP·PA®. Considering the study is based on QUADAS principles and with a homogeneous population, results are also likely to be generalisable to MSM population but potentially not applicable to lower prevalence populations routinely screened for syphilis. The automated CLIA treponemal assay confirmed to be accurate and appropriate for routine initial syphilis screening, i.e. when the reverse testing algorithm is applied. |
| first_indexed | 2024-04-24T23:10:57Z |
| format | Article |
| id | doaj.art-e129cb0fc0a24485b0f156ef3862979f |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-04-24T23:10:57Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-e129cb0fc0a24485b0f156ef3862979f2024-03-17T12:16:56ZengBMCBMC Infectious Diseases1471-23342024-03-0124S111410.1186/s12879-024-09100-xA multi-country comparative study of two treponemal tests for the serodiagnosis of syphilis amongst men who have sex with men (MSM): Chemo-luminescent assay vs Treponema pallidum particle agglutination assayLorenzo Gios0Massimo Mirandola1Maddalena Cordioli2Antonella Zorzi3Nigel Sherriff4Jaime Vera5Dominika Wlazly6Mohammed Osman Hassan-Ibrahim7Valeska Padovese8Anabel Darmanin9Rosanna W. Peeling10Magnus Unemo11Karel Blondeel12Igor Toskin13Infectious Division of Infectious Diseases, Department of Medicine, Verona University HospitalInfectious Division of Infectious Diseases, Department of Medicine, Verona University HospitalInfectious Division of Infectious Diseases, Department of Medicine, Verona University HospitalWHO Collaborating Centre for Sexual Health and Vulnerable Populations - Epidemiology Unit - Division of Infectious Diseases, Department of Medicine, Verona University HospitalSchool of Sport and Health Sciences, University of BrightonBrighton & Sussex Medical School, University of Sussex and University of BrightonBrighton & Sussex Medical School, University of Sussex and University of BrightonDepartment of Microbiology & Infection, Royal Sussex County Hospital, University Hospitals Sussex NHS Foundation Trust (Brighton & Haywards Heath Sites)Genitourinary Clinic, Department of Dermatology and Venereology, Mater Dei Hospital, Msida, MaltaGenitourinary Clinic, Department of Dermatology and Venereology, Mater Dei Hospital, Msida, MaltaClinical Research Department, London School of Hygiene & Tropical MedicineWHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Örebro UniversityDepartment of Sexual and Reproductive Health and Research (includes the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction [HRP]), World Health OrganizationDepartment of Sexual and Reproductive Health and Research (includes the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction [HRP]), World Health OrganizationAbstract Introduction International guidelines recommend routine screening for syphilis (aetiological agent: Treponema pallidum subspecies pallidum) amongst key populations and vulnerable populations using tests detecting treponemal and non-treponemal antibodies. Whilst treponemal tests have high sensitivities and specificities, they differ regarding subjective or objective interpretation, throughput and workload. Chemiluminescence immunoassays (CLIAs) are cost- and time-effective automated methods for detecting treponemal antibodies. The Treponema pallidum particle agglutination assay (TPPA) has been considered the “gold standard” treponemal assay, however, this includes a highly manual procedure, low throughput and subjective interpretation. The present multi-country study evaluated the ADVIA Centaur® Syphilis CLIA (Siemens Healthcare) assay compared to the reference SERODIA-TP·PA® (Fujirebio Diagnostics) for the serodiagnosis of syphilis amongst men who have sex with men (MSM). Method 1,485 MSM were enrolled in Brighton (UK), Malta, and Verona (Italy) as part of a larger WHO multi-country and multi-site ProSPeRo study. Ethical approval was obtained. Serum was tested with the ADVIA Centaur® Syphilis CLIA assay and SERODIA-TP·PA®, in accordance with the manufacturers’ instructions, for a first round of validation. A second round of validation was carried out for discrepant results that were additionally tested with both Western Blot (Westernblot EUROIMMUN®) and an Immunoblot (INNO-LIA, Fujirebio Diagnostics). Sensitivity, specificity, positive and negative predictive value (PPV and NPV), likelihood ratios (positive/negative), and the Diagnostic Odds Ratio (DOR)/pre-post-test probability (Fagan's nomogram) were calculated. Results Out of 1,485 eligible samples analysed in the first phase, the SERODIA-TP·PA® identified 360 positive and 1,125 negative cases. The ADVIA Centaur® Syphilis CLIA assay (Siemens) identified 366 positives, missclassifying one TPPA-positive sample. In the second phase, the ADVIA Centaur® Syphilis CLIA resulted in 1 false negative and 4 false positive results. Considering the syphilis study prevalence of 24% (95% CI: 22–26.7), The sensitivity of the ADVIA Centaur® Syphilis CLIA assay was 99.7% (95% CI: 98.5–100), and the specificity was 99.4% (95% CI: 98.7–99.7). The ROC area values were 0.996 (95% CI: 0.992–0.999), and both the PPV and NPV values were above 98% (PPV 98.1%, 95% CI: 96.1–99.2; NPV 99.9%, 95% CI: 99.5–100). Conclusions The ADVIA Centaur® Syphilis CLIA assay showed similar performance compared to the SERODIA-TP·PA®. Considering the study is based on QUADAS principles and with a homogeneous population, results are also likely to be generalisable to MSM population but potentially not applicable to lower prevalence populations routinely screened for syphilis. The automated CLIA treponemal assay confirmed to be accurate and appropriate for routine initial syphilis screening, i.e. when the reverse testing algorithm is applied.https://doi.org/10.1186/s12879-024-09100-xSyphilisChemo-luminescent assayTreponema pallidum particle agglutinationMSM |
| spellingShingle | Lorenzo Gios Massimo Mirandola Maddalena Cordioli Antonella Zorzi Nigel Sherriff Jaime Vera Dominika Wlazly Mohammed Osman Hassan-Ibrahim Valeska Padovese Anabel Darmanin Rosanna W. Peeling Magnus Unemo Karel Blondeel Igor Toskin A multi-country comparative study of two treponemal tests for the serodiagnosis of syphilis amongst men who have sex with men (MSM): Chemo-luminescent assay vs Treponema pallidum particle agglutination assay BMC Infectious Diseases Syphilis Chemo-luminescent assay Treponema pallidum particle agglutination MSM |
| title | A multi-country comparative study of two treponemal tests for the serodiagnosis of syphilis amongst men who have sex with men (MSM): Chemo-luminescent assay vs Treponema pallidum particle agglutination assay |
| title_full | A multi-country comparative study of two treponemal tests for the serodiagnosis of syphilis amongst men who have sex with men (MSM): Chemo-luminescent assay vs Treponema pallidum particle agglutination assay |
| title_fullStr | A multi-country comparative study of two treponemal tests for the serodiagnosis of syphilis amongst men who have sex with men (MSM): Chemo-luminescent assay vs Treponema pallidum particle agglutination assay |
| title_full_unstemmed | A multi-country comparative study of two treponemal tests for the serodiagnosis of syphilis amongst men who have sex with men (MSM): Chemo-luminescent assay vs Treponema pallidum particle agglutination assay |
| title_short | A multi-country comparative study of two treponemal tests for the serodiagnosis of syphilis amongst men who have sex with men (MSM): Chemo-luminescent assay vs Treponema pallidum particle agglutination assay |
| title_sort | multi country comparative study of two treponemal tests for the serodiagnosis of syphilis amongst men who have sex with men msm chemo luminescent assay vs treponema pallidum particle agglutination assay |
| topic | Syphilis Chemo-luminescent assay Treponema pallidum particle agglutination MSM |
| url | https://doi.org/10.1186/s12879-024-09100-x |
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