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Abstract：
BACKGROUND: 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).
METHODS: 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.
METHODS: 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.
摘要：
背景：国际指南建议使用检测螺旋体和非螺旋体抗体的测试，在关键人群和脆弱人群中常规筛查梅毒（病因：梅毒螺旋体亚种）。虽然密螺旋体测试具有很高的敏感性和特异性，它们在主观或客观解释上有所不同，吞吐量和工作负载。化学发光免疫测定(CLIA)是用于检测密螺旋体抗体的成本和时间有效的自动化方法。梅毒螺旋体颗粒凝集试验（TPPA）被认为是“金标准”螺旋体试验，然而,这包括一个高度手动的程序，低吞吐量和主观解释。本多国研究评估了ADVIACentaur®梅毒CLIA（SiemensHealthcare）测定与参考SERODIA-TP·PA®（FujirebioDiagnostics）比较，用于男男性行为者（MSM）的梅毒血清诊断。
方法：在英国布莱顿注册了1,485名MSM，马耳他,和维罗纳（意大利）作为更大规模的世卫组织多国和多站点ProSpeRo研究的一部分。获得了伦理上的认可。用ADVIACentaur®梅毒CLIA测定法和SERODIA-TP·PA®测试血清，根据制造商的说明，进行第一轮验证。对差异结果进行了第二轮验证，并使用Western印迹（WesternblotEUROIMMUN®）和免疫印迹（INNO-LIA，Fujirebio诊断）。灵敏度,特异性，阳性和阴性预测值(PPV和NPV)，似然比（正/负），并计算诊断赔率比(DOR)/检验前概率(Fagan列线图)。
结果：在第一阶段分析的1,485个合格样品中，SERODIA-TP·PA®确定了360例阳性和1,125例阴性。ADVIACentaur®梅毒CLIA检测(西门子)鉴定出366个阳性,对一个TPPA阳性样本分类错误。在第二阶段,ADVIACentaur®梅毒CLIA导致1例假阴性和4例假阳性。考虑到梅毒研究患病率为24%(95%CI:22-26.7)，ADVIACentaur®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面积值为0.996(95%CI:0.992-0.999),PPV和NPV值均高于98%(PPV98.1%，95%CI：96.1-99.2；净现值99.9%，95%CI：99.5-100）。
结论：与SERODIA-TP·PA®相比，ADVIACentaur®梅毒CLIA试验显示出相似的性能。考虑到这项研究是基于QUADAS原理和同质人群，结果也可能适用于MSM人群,但可能不适用于常规梅毒筛查的低患病率人群.自动CLIA密螺旋体测定被证实是准确的，适用于常规的初始梅毒筛查。即当应用反向测试算法时。
方法：在英国布莱顿注册了1,485名MSM，马耳他,和维罗纳（意大利）作为更大规模的世卫组织多国和多站点ProSpeRo研究的一部分。获得了伦理上的认可。用ADVIACentaur®梅毒CLIA测定法和SERODIA-TP·PA®测试血清，根据制造商的说明，进行第一轮验证。对差异结果进行了第二轮验证，并使用Western印迹（WesternblotEUROIMMUN®）和免疫印迹（INNO-LIA，Fujirebio诊断）。灵敏度,特异性，阳性和阴性预测值(PPV和NPV)，似然比（正/负），并计算诊断赔率比(DOR)/检验前概率(Fagan列线图)。
结果：在第一阶段分析的1,485个合格样品中，SERODIA-TP·PA®确定了360例阳性和1,125例阴性。ADVIACentaur®梅毒CLIA检测(西门子)鉴定出366个阳性,对一个TPPA阳性样本分类错误。在第二阶段,ADVIACentaur®梅毒CLIA导致1例假阴性和4例假阳性。考虑到梅毒研究患病率为24%(95%CI:22-26.7)，ADVIACentaur®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面积值为0.996(95%CI:0.992-0.999),PPV和NPV值均高于98%(PPV98.1%，95%CI：96.1-99.2；净现值99.9%，95%CI：99.5-100）。
结论：与SERODIA-TP·PA®相比，ADVIACentaur®梅毒CLIA试验显示出相似的性能。考虑到这项研究是基于QUADAS原理和同质人群，结果也可能适用于MSM人群,但可能不适用于常规梅毒筛查的低患病率人群.自动CLIA密螺旋体测定被证实是准确的，适用于常规的初始梅毒筛查。即当应用反向测试算法时。
