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

• Published in: BMC infectious diseases 2024-03, Vol.24 (Suppl 1), p.313-313, Article 313
• Main Authors: Gios, Lorenzo, Mirandola, Massimo, Cordioli, Maddalena, Zorzi, Antonella, Sherriff, Nigel, Vera, Jaime, Wlazly, Dominika, Hassan-Ibrahim, Mohammed Osman, Padovese, Valeska, Anabel Darmanin, Peeling, Rosanna W, Unemo, Magnus, Blondeel, Karel, Toskin, Igor
• Format: Article
• Language: English
• Subjects: Agglutination; Algorithms; Antibodies; Antigens; Assaying; At risk populations; Automation; Chemiluminescence; Chemo-luminescent assay; Comparative analysis; Comparative studies; Consent; Demographic aspects; Diagnosis; Diagnostic reagents; HIV; Human immunodeficiency virus; Immunoassay; Immunoassays; Infections; Laboratories; Likelihood ratio; Medical examination; MSM; MSM (Men who have sex with men); Nomograms; Point of care testing; Populations; Reproductive health; Sample size; Sensitivity; Serology; Sexually transmitted diseases; STD; Syphilis; Treponema pallidum; Treponema pallidum particle agglutination
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-024-09100-x

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). 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. 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). The ADVIA Centaur® Syphilis CLIA assay showed sim