Amsterdam UMC, University of Amsterdam, Center for Experimental and Molecular Medicine, Amsterdam Infection & Immunity, Meibergdreef 9, Amsterdam, 1105 AZ, the Netherlands.
Certe Laboratory of Infectious Diseases, Groningen, the Netherlands.
Eur J Clin Microbiol Infect Dis. 2020 Nov;39(11):2143-2152. doi: 10.1007/s10096-020-03946-0. Epub 2020 Jul 6.
Modified two-tier testing (MTTT) for Lyme borreliosis (i.e. confirmation with an EIA instead of an immunoblot) has been shown to have improved sensitivity compared with standard two-tier testing (STTT) in samples from American patients, without losing specificity. The current study assesses the sensitivity and specificity of various algorithms of MTTT in European patients with erythema migrans (EM) as a model disease for early Lyme borreliosis, and in appropriate controls. Four different immunoassays were used in the first tier, followed by either an immunoblot or the C6-EIA, or were used as standalone single-tier test. These tests were performed on consecutively collected sera of 228 Dutch patients with physician-diagnosed EM in the setting of general practice, 231 controls from the general population, and 50 controls with potentially cross-reactive antibodies. All the variants of MTTT that were studied had significantly higher sensitivity compared with their equivalent STTT, while retaining comparable specificity. Within the MTTT algorithms, classifying equivocal results as positive yielded better diagnostic parameters than classifying equivocal results as negative. The best diagnostic parameters were found using the Enzygnost-2 assay in the first tier, followed by a C6-ELISA in the second tier (sensitivity 77.6%, 95% CI 71.7-82.9; specificity 96.1%, 95% CI 92.7-98.2). This algorithm performed significantly better than the equivalent STTT algorithm in terms of sensitivity (p < 0.001), while maintaining comparable specificity (population controls p = 0.617). Our results show that MTTT can be a useful tool for the serodiagnosis of European patients with early Lyme borreliosis.
改良两阶段检测（MTTT）用于莱姆病（即使用 EIA 而非免疫印迹进行确认）已被证明在来自美国患者的样本中与标准两阶段检测（STTT）相比具有更高的敏感性，而特异性不变。本研究评估了 MTTT 在作为早期莱姆病模型疾病的游走性红斑（EM）欧洲患者中的敏感性和特异性，以及在适当对照中的敏感性和特异性。在第一阶段使用了四种不同的免疫测定法，然后是免疫印迹或 C6-EIA，或作为独立的单阶段测试使用。在普通实践中对 228 例荷兰医生诊断为 EM 的患者连续采集血清、231 例普通人群对照和 50 例可能具有交叉反应性抗体的对照进行了这些检测。与等效的 STTT 相比，所研究的 MTTT 的所有变体均具有显著更高的敏感性，同时保留了可比的特异性。在 MTTT 算法中，将不确定结果分类为阳性比将不确定结果分类为阴性可获得更好的诊断参数。在第一阶段使用 Enzygnost-2 检测，然后在第二阶段使用 C6-ELISA 时，发现了最佳的诊断参数（敏感性 77.6%，95%CI 71.7-82.9；特异性 96.1%，95%CI 92.7-98.2）。该算法在敏感性方面明显优于等效的 STTT 算法（p<0.001），同时保持了可比的特异性（人群对照 p=0.617）。我们的结果表明，MTTT 可作为欧洲早期莱姆病患者血清学诊断的有用工具。
