Institute for Experimental Immunology, Euroimmun AG, Seekamp 31, D-23560, Lübeck, Germany.
Institute for Experimental Immunology, Euroimmun AG, Seekamp 31, D-23560, Lübeck, Germany.
J Virol Methods. 2019 May;267:8-15. doi: 10.1016/j.jviromet.2019.02.005. Epub 2019 Feb 16.
Zika virus (ZIKV) is a mosquito-borne flavivirus posing a public health threat due to its association with neurological complications in newborns and adults. In flavivirus-endemic areas, coming mosquito seasons will require the differentiation of primary versus secondary and acute versus past ZIKV/flavivirus infections. This is complicated by two major difficulties: [i] secondary infections often present with low or undetectable titres of specific IgM and with early-positive IgG, [ii] previous flavivirus infection(s) or vaccinations cause elevated cross-reactivities. Here, we analysed the anti-ZIKV IgA, IgG, and IgM responses at different stages of infection in an endemic setting, scrutinising the diagnostic relevance of specific IgA. Anti-ZIKV antibodies were measured by ELISA based on ZIKV non-structural protein 1 (NS1) in paired sera from 31 patients with suspected primary or (flavivirus-primed) secondary ZIKV infection. The control panel comprised samples from 136 DENV-infected patients. Among ZIKV samples collected 8-16 days after symptom onset, ELISA sensitivities for detecting anti-ZIKV NS1 IgA, IgG, and IgM were 93.5%, 100%, and 48.4%, respectively. The proportion of cases with negative IgM but positive IgA was higher in suspected secondary (61.9%) than in primary (30.0%) ZIKV infections. Combined IgA/IgM detection yielded a sensitivity of 100% at a specificity of 97.1%. In conclusion, at time points after PCR can detect the virus, the determination of anti-ZIKV NS1 IgA may improve the accuracy in diagnosing acute ZIKV infection in flavivirus-endemic regions in the context of both primary and secondary infection, especially when IgM is undetectable.
Zika 病毒（ZIKV）是一种通过蚊子传播的黄病毒，由于其与新生儿和成年人的神经并发症有关，因此对公共卫生构成威胁。在黄病毒流行地区，即将到来的蚊子季节将需要区分原发性、继发性和急性、过去的 ZIKV/黄病毒感染。这是由两个主要困难造成的：[i] 二次感染通常表现为特异性 IgM 滴度低或无法检测，且 IgG 早期呈阳性，[ii] 先前的黄病毒感染（或疫苗接种）会导致交叉反应升高。在这里，我们在流行地区分析了感染不同阶段的抗 ZIKV IgA、IgG 和 IgM 反应，仔细研究了特异性 IgA 的诊断相关性。通过 ELISA 基于 ZIKV 非结构蛋白 1（NS1）测量抗 ZIKV 抗体，该 ELISA 基于来自 31 名疑似原发性或（黄病毒引发的）继发性 ZIKV 感染患者的配对血清。对照组包括 136 名登革热感染患者的样本。在症状出现后 8-16 天采集的 ZIKV 样本中，检测抗 ZIKV NS1 IgA、IgG 和 IgM 的 ELISA 敏感性分别为 93.5%、100%和 48.4%。在疑似继发性（61.9%）ZIKV 感染中，IgM 阴性但 IgA 阳性的病例比例高于原发性（30.0%）ZIKV 感染。IgA/IgM 联合检测的敏感性为 100%，特异性为 97.1%。总之，在 PCR 可以检测到病毒的时间点之后，测定抗 ZIKV NS1 IgA 可能会提高在黄病毒流行地区诊断急性 ZIKV 感染的准确性，尤其是在 IgM 无法检测到的情况下。
