Objectives

Zika virus (ZIKV) infection during pregnancy may cause neurological abnormalities in the foetus, and therefore fast and accurate laboratory assays are critical for rapid diagnosis. ELISA based on ZIKV NS1 protein has been developed and shown to be sensitive and highly specific; however, its negative and positive predictive values have not been tested. In this study we evaluated the ability of the NS1-based ELISA to exclude ZIKV infection and serve as a first-line screening tool for travellers.

Methods

We tested samples obtained during the peak of ZIKV infection from 1188 symptomatic and asymptomatic Israeli travellers using NS1-based IgG and IgM ELISA, real-time RT-PCR analysis and ZIKV neutralization. The Kaplan–Maier method was used to evaluate the duration of ZIKV RNA in whole blood and urine samples.

Results

NS1-based ELISA identified 20 true-positive, five false-positive and four false-negative cases, resulting in sensitivity and specificity of 83.3% (95%CI: 62–94%) and 97.5% (95%CI: 94–99%) respectively, and positive and negative predictive values of 80% (95%CI: 59–92%) and 98% (95%CI: 95–99%) respectively. Based on 14 RT-PCR-positive cases, median time to detect ZIKV RNA in whole blood was 17.5 days (range 5–58 days) and in urine 10 days (range 5–26 days).

Conclusions

The NS1-based ELISA and RT-PCR in whole blood are highly reliable for identification of ZIKV-negative and -positive cases, respectively. Combination of both assays minimizes the risk of false-negative results, and thus allows the exclusion of ZIKV infection in travellers returning from ZIKV-endemic countries, including those who are pregnant or wish for preconception screening.

中文翻译：

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基于NS1的ELISA和qRT-PCR筛选和排除旅行者中的寨卡病毒感染

目标

怀孕期间感染寨卡病毒（ZIKV）可能会导致胎儿神经系统异常，因此快速准确的实验室检测对于快速诊断至关重要。已经开发了基于ZIKV NS1蛋白的ELISA方法，并显示出高灵敏度和高特异性。但是，尚未测试其阴性和阳性预测值。在这项研究中，我们评估了基于NS1的ELISA排除ZIKV感染的能力，并作为旅行者的一线筛查工具。

方法

我们使用基于NS1的IgG和IgM ELISA，实时RT-PCR分析和ZIKV中和，测试了1188名有症状和无症状以色列旅行者在ZIKV感染高峰期获得的样本。Kaplan–Maier方法用于评估全血和尿液样本中ZIKV RNA的持续时间。

结果

基于NS1的ELISA鉴定了20例真阳性，5例假阳性和4例假阴性的病例，其敏感性和特异性分别为83.3％（95％CI：62–94％）和97.5％（95％CI：94–99） ％），阳性和阴性预测值分别为80％（95％CI：59–92％）和98％（95％CI：95–99％）。基于14例RT-PCR阳性病例，检测全血中ZIKV RNA的中位时间为17.5天（5至58天），尿中10天（5至26天）。

结论

全血中基于NS1的ELISA和RT-PCR分别可高度可靠地鉴定ZIKV阴性和阳性病例。两种检测方法的组合可最大程度地降低假阴性结果的风险，因此可以将ZIKV感染排除在从ZIKV流行国家返回的旅行者中，包括那些怀孕或希望进行孕前筛查的旅行者。