Infectious Division of Infectious Diseases, Department of Medicine, Verona University Hospital, Verona, Italy.
WHO Collaborating Centre for Sexual Health and Vulnerable Populations - Epidemiology Unit - Division of Infectious Diseases, Department of Medicine, Verona University Hospital, Verona, Italy.
BMC Infect Dis. 2024 Mar 14;24(Suppl 1):313. 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 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.
国际指南建议使用检测梅毒螺旋体和非梅毒螺旋体抗体的试验，对关键人群和弱势群体进行梅毒（病原体：苍白密螺旋体亚种苍白密螺旋体）的常规筛查。虽然梅毒螺旋体试验具有较高的灵敏度和特异性，但它们在主观或客观解释、吞吐量和工作量方面存在差异。化学发光免疫分析（CLIA）是一种具有成本效益和时间效益的自动检测梅毒螺旋体抗体的方法。梅毒螺旋体颗粒凝集试验（TPPA）一直被认为是梅毒螺旋体检测的“金标准”，然而，该方法包括一个高度手动的过程，吞吐量低且需要主观解释。本多中心研究评估了 ADVIA Centaur®梅毒 CLIA（西门子医疗）检测与参考 SERODIA-TP·PA®（富士瑞必欧诊断）在男男性行为者（MSM）梅毒血清学诊断中的应用。
1485 名 MSM 参与了英国布莱顿、马耳他和意大利维罗纳的一项更大规模的世卫组织多国家和多地点 ProSPeRo 研究。本研究获得了伦理批准。血清根据制造商的说明，先用 ADVIA Centaur®梅毒 CLIA 检测和 SERODIA-TP·PA®进行第一轮验证。对出现差异的结果进行第二轮验证，这些结果还需要用 Western blot（EUROIMMUN®Western blot）和免疫印迹（INNO-LIA，富士瑞必欧诊断）进行进一步检测。计算了灵敏度、特异性、阳性和阴性预测值（PPV 和 NPV）、似然比（阳性/阴性）、诊断比值比（DOR）/前后测试概率（Fagan 的Nomogram）。
在第一阶段分析的 1485 份合格样本中，SERODIA-TP·PA®鉴定出 360 例阳性和 1125 例阴性病例。ADVIA Centaur®梅毒 CLIA 检测（西门子）鉴定出 366 例阳性，漏检了 1 例 TPPA 阳性样本。在第二阶段，ADVIA Centaur®梅毒 CLIA 检测导致 1 例假阴性和 4 例假阳性结果。考虑到梅毒研究的流行率为 24%（95%CI：22-26.7），ADVIA Centaur®梅毒 CLIA 检测的灵敏度为 99.7%（95%CI：98.5-100），特异性为 99.4%（95%CI：98.7-99.7）。ROC 曲线下面积值为 0.996（95%CI：0.992-0.999），PPV 和 NPV 值均高于 98%（PPV 98.1%，95%CI：96.1-99.2；NPV 99.9%，95%CI：99.5-100）。
ADVIA Centaur®梅毒 CLIA 检测与 SERODIA-TP·PA®的性能相似。考虑到本研究基于 QUADAS 原则且人群具有同质性，结果也可能适用于 MSM 人群，但可能不适用于常规筛查梅毒的低流行率人群。自动 CLIA 梅毒螺旋体检测被证实准确且适用于常规初始梅毒筛查，即在应用反向检测算法时。
