Evaluation of eight commercial Zika virus IgM and IgG serology assays for diagnostics and research.

Swee Ling Low,Hwee Huang Tan,Judith Chui Ching Wong,Lee Ching Ng,Yee Ling Lai,Yee Sin Leo,Sally Lam,Li Kiang Tan,Kevin K Ariën

doi:10.1371/journal.pone.0244601

Abstract

Several commercial Zika virus (ZIKV) serology assays have been developed since the recognition of ZIKV outbreaks as a Public Health Emergency of International Concern in 2016. However, test interpretation for ZIKV serology can be challenging due to antibody cross-reactivity with other flaviviruses like dengue virus (DENV). Therefore, we sought to evaluate the performance of eight commercially available ZIKV IgM and IgG assays across three testing platforms, namely, immunochromatographic tests (ICT), ELISAs and immunofluorescence tests (IIFT). The test panel comprised of 278 samples, including acute and convalescent sera or plasma from ZIKV-confirmed, DENV-confirmed, non-ZIKV and non-DENV patients, and residual sera from healthy blood donors. The ZIKV IgM and IgG serology assays yielded higher test sensitivities of 23.5% - 97.1% among ZIKV convalescent samples as compared to 5.6% - 27.8% among ZIKV acute samples; the test specificities were 63.3% - 100% among acute and convalescent DENV, non-DENV samples. Among the ELISAs and IIFTs, the Diapro ZIKV IgM ELISA demonstrated high test sensitivity (96%) and specificity (80%) when tested on early convalescent samples, while the Euroimmun ZIKV IgG ELISA yielded the highest test specificity of 97% - 100% on samples from non-ZIKV patients and healthy blood donors. For rapid ICTs, the LumiQuick IgM rapid ICT yielded low test sensitivity, suggesting its limited utility. We showed that commercial ZIKV IgM and IgG serology assays have differing test performances, with some having moderate to high test sensitivities and specificities when used in a dengue endemic setting, although there were limitations in IgG serology.

Highlights

Zika virus (ZIKV) is a mosquito-borne virus that belongs to the family Flaviviridae, genus Flavivirus
When acute samples were tested (Set A, n = 78), ZIKV IgM test sensitivities for rapid immunochromatographic tests (ICT) and ELISA/IgM immunofluorescence Test (IIFT) tests ranged from 5.6% to 27.8% (Fig 1A), with the InBios ZIKV IgM ELISA yielding the highest ZIKV IgM test sensitivity of 27.8% and highest Area under Receiver Operating Characteristics Curve (AUROCC) value of 0.631 (Table 3)
Test specificities for the ZIKV IgM assays ranged from 86.7% to 100% (Fig 1A), with NovaLisa1 ZIKV IgM ELISA yielding the highest specificity

Summary

Introduction

Zika virus (ZIKV) is a mosquito-borne virus that belongs to the family Flaviviridae, genus Flavivirus. ZIKV infections received significant global public health attention when they were associated with severe neurological complications such as GuillainBarresyndrome (GBS) in adults and congenital Zika syndrome (includes microcephaly and other severe birth defects) in neonates, in epidemics in French Polynesia and Brazil, respectively [4,5,6,7,8]. ZIKV is primarily transmitted by infected Aedes species mosquitoes, mainly Aedes aegypti, which transmits dengue virus (DENV) Both viruses share similar geographical distribution, transmission cycles and symptoms of infection [14]. In a dengue endemic country like Singapore, where dengue seroprevalence is approximately 50% in the resident population [30, 31], it is important to evaluate the impact of cross-reactivity of DENV antibodies when using ZIKV serological assays in an endemic area. In this study, we evaluated the performance of eight ZIKV serology assays [one ZIKV IgM/IgG rapid immunochromatograhic tests (ICT), four ZIKV IgM ELISAs, one ZIKV IgM immunofluorescence Test (IIFT) and two ZIKV IgG ELISA assays] for their potential use

Materials and methods

Method

Results

Discussion