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 amongst keypopulations and vulnerable populations using tests detecting treponemal and nontreponemalantibodies. Whilst treponemal tests have high sensitivities and specificities,they differ regarding subjective or objective interpretation, throughput and workload.CLIAs are cost- and time-effective automated methods for detecting treponemalantibodies. The TPPA has been considered the “gold standard” treponemal assay,however, this includes a highly manual procedure, low throughput and subjectiveinterpretation. The present multi-country study evaluated the ADVIA Centaur® SyphilisCLIA assay compared to the reference SERODIA-TP·PA® for the serodiagnosis ofsyphilis amongst MSM.Method:1,485 MSM were enrolled in Brighton (UK), Malta, and Verona (Italy) as part of a largerWHO multi-country and multi-site ProSPeRo study. Serum was tested with the CLIAassay and TP·PA, in accordance with the manufacturers’ instructions, for a first roundof validation. A second round of validation was carried out for discrepant results thatwere additionally tested with both Western Blot and an Immunoblot.Sensitivity, specificity, positive and negative predictive value (PPV and NPV), likelihoodratios (positive/negative), and the Diagnostic Odds Ratio (DOR)/pre-post-testprobability were calculated.Results:Out of 1,485 eligible samples analysed in the first phase, the SERODIATP·PA identified 360 positive and 1,125 negative cases. The CLIA assay identified 366positives, missclassifying one TPPA-positive sample. In the second phase, the CLIAresulted in 1 false negative and 4 false positive results. Considering the syphilis studyprevalence of 24% (95% CI: 22-26.7), The sensitivity of the ADVIA Centaur® SyphilisCLIA 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 PPVand NPV values were above 98%Conclusions:The CLIA assay showed similar performance compared to the SERODIA-TP·PA.Considering the study is based on QUADAS principles and with a homogeneouspopulation, results are also likely to be generalisable to MSM population but potentiallynot applicable to lower prevalence populations routinely screened for syphilis. Theautomated CLIA treponemal assay confirmed to be accurate and appropriate forroutine initial syphilis screening, i.e. when the reverse testing algorithm is applied