Evaluation of ViroTrack Sero Zika IgG/IgM, a New Rapid and Quantitative Zika Serological Diagnostic Assay

Abstract

Dengue virus (DENV) and Zika virus (ZIKV) belong to the flavivirus genus and are antigenically closely related. They also share the same mosquito vector and can cause similar symptoms upon infection. However, DENV and ZIKV infections lead to different clinical sequelae and treatments; therefore, clinicians need rapid and accurate diagnostics capable of distinguishing between the two diseases.

Methods: We employed the immuno-magnetic assay technology on a microfluidic cartridge (ViroTrack Sero Zika IgG/IgM) for diagnosis of ZIKV infection based on the aggregation of magnetic nanoparticles. We carried out three serological studies including samples from the Dominican Republic, USA, and Nicaragua, aimed at detecting ZIKV-specific IgG and IgM using the ViroTrack Sero Zika IgG/IgM test.

Results: The seroconversion results were comparable with ZIKV IgG and IgM reactivity measured by the commercial ZIKV ELISA kit. The sensitivity and specificity for both ZIKV IgG and IgM tested by the ViroTrack Sero Zika IgG/IgM was approximately 98% and 93%, respectively.

Conclusion: Serological detection of ZIKV infection by the new ViroTrack Sero Zika IgG/IgM test shows promising performance and limited cross-reactivity with DENV.

Keywords: ViroTrack Sero Zika IgG/IgM; Zika virus; dengue virus; diagnosis; immuno-magnetic assay.

Figure 1

Blubox and ViroTrack Sero Zika IgG/IgM.

Figure 2

Serological study 1: ViroTrack Sero Zika IgG/IgM serological evidence study. (a) ZIKV IgM measured by ViroTrack Sero Zika IgG/IgM. (b) ZIKV IgM measured by DIA.PRO ZIKV ELISA kit. (c) ZIKV IgG measured by ViroTrack Sero Zika IgG/IgM. (d) ZIKV IgG measured by DIA.PRO ZIKV ELISA kit. ZIKV IgM and IgG values were measured by ViroTrack Sero Zika IgG/IgM for serial draw samples collected on different days from illness for 3 different ZIKV RT-PCR positive patients from the Dominican Republic. The expected seroconversion pattern is clearly measurable, and it is comparable with the ZIKV IgG and IgM patterns measured by commercial ZIKV ELISA kits.

Figure 3

Serological study 2: ViroTrack Sero Zika IgG/IgM sensitivity and specificity. (a) ROC curve analysis by R for differentiation of 91 ZIKV-infected samples from 10 healthy control samples, based on ViroTrack Zika IgG measurement; and (b) ROC curve analysis by R for differentiation of 122 ZIKV-infected samples from 10 healthy control samples, based on ViroTrack Zika IgM measurement.

Figure 4

Serological study 3: Zika and dengue differential study. (a) ROC curve analysis by R for differentiation of ZIKV- from DENV-infected samples based on ZIKV IgG measurements: four groups of samples were analyzed, they are 25 pZIKV-infected samples, 25 DENVpZIKV-infected samples, 25 pDENV-infected samples and 25 sDENV samples; and (b) ROC curve analysis by R for differentiation of ZIKV- from DENV-infected samples based on ZIKV IgM measurements: four groups of samples were analyzed, they are 25 pZIKV-infected samples, 25 DENVpZIKV-infected samples, 25 pDENV-infected samples and 25 sDENV samples. (c) Violin plot of ViroTrack Sero Zika IgG/IgM measurements on ZIKV IgG and (d) IgM level from serum samples from four groups of samples as described in (a). (e) Violin plot of ViroTrack Sero Zika IgG/IgM measurements on ZIKV IgG level to compare primary and secondary DENV-infected samples from 25 serum samples with primary DENV infection collected at convalescent phase (around 20 days post-onset of illness), 25 serum samples with secondary infection collected at convalescent phase (around 20 days post-onset of illness), 20 serum samples with primary DENV infection (pDENV_>3MPO, sample collected 3 months post-onset of illness) and 20 serum samples with secondary DENV infection (sDENV_>3MPO, sample collected 3 months post-onset of illness). (f) Both sDENV samples from different stages of illness onset show significantly higher IgG levels than both groups of pDENV samples. ** p ≤ 0.05, **** p ≤ 0.0001.