Gonçalo Moniz Institute, Oswaldo Cruz Foundation-Bahia, Salvador, Brazil.
Fio-Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Am J Trop Med Hyg. 2018 Nov;99(5):1174-1179. doi: 10.4269/ajtmh.17-0727.
The existence of an imperfect reference standard presents complications when evaluating the unbiased performance of novel diagnostic techniques. This is especially true in the absence of a gold standard, as is the case in chronic Chagas disease (CD) diagnosis. To circumvent this constraint, we elected to use latent class analysis (LCA). Previously, our group demonstrated the high performance of four -chimeric proteins (Molecular Biology Institute of Paraná [IBMP]-8.1, -8.2, -8.3, and -8.4) for CD diagnosis using several distinct immunoassays. Although commercial tests had previously been established as a reference standard, the diagnostic performance of these chimeric antigens could present bias because these tests fail to produce 100% accurate results. Thus, we used LCA to assess the performance of these IBMP chimeric antigens in chronic CD diagnosis. Using the LCA model as a gold standard, sensitivity and specificity values ranged from 93.5% to 99.4% and 99.6% to 100%, respectively. The accuracy values were 96.2% for IBMP-8.2, approximately 98% for IBMP-8.1 and IBMP-8.3, and nearly 100% for IBMP-8.4. For IBMP-8.1 and IBMP-8.2, higher positive predictive values were associated with increases in hypothetical prevalence. Similarly, higher hypothetical prevalence resulted in lower negative predictive values for IBMP-8.1, IBMP-8.2, and IBMP-8.3. In addition, samples with serodiscordant results from commercial serological tests were analyzed using LCA. Molecular Biology Institute of Paraná -8.1 demonstrated potential for use in confirmatory testing with regard to samples with inconsistent results. Moreover, our findings further confirmed the remarkable performance of the IBMP-8.4 antigen to diagnose chronic CD in both endemic and non-endemic areas.
当评估新型诊断技术的无偏性能时,存在不完善参考标准会带来一些复杂情况。在缺乏金标准的情况下尤其如此,恰如慢性恰加斯病(CD)的诊断。为了规避这一限制,我们选择使用潜在类别分析(LCA)。此前,我们的团队使用几种不同的免疫测定法,证明了四个嵌合蛋白(分子生物学研究所的-8.1、-8.2、-8.3 和-8.4)在 CD 诊断中的高性能。尽管商业测试先前已被确立为参考标准,但这些嵌合抗原的诊断性能可能存在偏差,因为这些测试无法产生 100%准确的结果。因此,我们使用 LCA 评估这些 IBMP 嵌合抗原在慢性 CD 诊断中的性能。使用 LCA 模型作为金标准,敏感性和特异性值分别在 93.5%到 99.4%和 99.6%到 100%之间。IBMP-8.2 的准确率为 96.2%,IBMP-8.1 和 IBMP-8.3 的准确率约为 98%,IBMP-8.4 的准确率接近 100%。对于 IBMP-8.1 和 IBMP-8.2,随着假设患病率的增加,阳性预测值更高。同样,对于 IBMP-8.1、IBMP-8.2 和 IBMP-8.3,假设患病率的降低导致阴性预测值降低。此外,使用 LCA 分析了商业血清学测试结果不一致的样本。分子生物学研究所的-8.1 显示出在对结果不一致的样本进行确认性测试方面的应用潜力。此外,我们的研究结果进一步证实了 IBMP-8.4 抗原在诊断流行地区和非流行地区慢性 CD 方面的出色性能。