Capacity of a Multiplex IgM Antibody Capture ELISA to Differentiate Zika and Dengue Virus Infections in Areas of Concurrent Endemic Transmission.

Gabriela Paz-Bailey,Aravinda de Silva,Luisa I. Alvarado,Freddy A. Medina,Frances Vila,Lakshmanane Premkumar,Steve Waterman,Olga Lorenzi,Jorge Muñoz-Jordán,Vanessa Rivera-Amill

doi:10.4269/ajtmh.20-1651

Abstract

ABSTRACT.Serological cross-reactivity has proved to be a challenge to diagnose Zika virus (ZIKV) infections in dengue virus (DENV) endemic countries. Confirmatory testing of ZIKV IgM positive results by plaque reduction neutralization tests (PRNTs) provides clarification in only a minority of cases because most individuals infected with ZIKV were previously exposed to DENV. The goal of this study was to evaluate the performance of a ZIKV/DENV DUO IgM antibody capture ELISA (MAC-ELISA) for discriminating between DENV and ZIKV infections in endemic regions. Our performance evaluation included acute and convalescent specimens from patients with real-time reverse transcription polymerase chain reaction (RT-PCR)-confirmed DENV or ZIKV from the Sentinel Enhanced Dengue Surveillance System in Ponce, Puerto Rico. The ZIKV/DENV DUO MAC-ELISA specificity was 100% for DENV (N = 127) and 98.4% for ZIKV (N = 275) when specimens were tested during the optimal testing window (days post-onset of illness [DPO] 6–120). The ZIKV/DENV DUO MAC-ELISA sensitivity of RT-PCR confirmed specimens reached 100% for DENV by DPO 6 and for ZIKV by DPO 9. Our new ZIKV/DENV DUO MAC-ELISA was also able to distinguish ZIKV and DENV regardless of previous DENV exposure. We conclude this novel serologic diagnostic assay can accurately discriminate ZIKV and DENV infections. This can potentially be useful considering that the more labor-intensive and expensive PRNT assay may not be an option for confirmatory diagnosis in areas that lack PRNT capacity, but experience circulation of both DENV and ZIKV.

Highlights

Zika virus (ZIKV) and dengue virus (DENV) are flaviviruses that are transmitted through mosquito bites.[1]
Our results demonstrate that the ZIKV/DENV DUO MAC-ELISA reaches a sensitivity of 100% for ZIKV or DENV compared with reverse transcription polymerase chain reaction (RT-PCR) in the acute phase and approximately 90% compared with the CDC ZIKV MACELISA and 96% compared with the InBios DENV Detect IgM Capture ELISA when tested in the days post-onset of illness (DPO) 6–120 window
The ZIKV/ DENV DUO ELISA was developed based upon the hypothesis that confirmation and discrimination of recent infections is more likely to occur by the detection of IgM, an isotype that is detectable early in infection and wanes over time, than by the detection of neutralizing antibodies that are more likely to be reflective of both recent and remote infections

Summary

Introduction

Zika virus (ZIKV) and dengue virus (DENV) are flaviviruses that are transmitted through mosquito bites.[1] Transmission mainly occurs through Aedes aegypti and to a smaller degree through A. albopictus. This results in these viruses coinciding in geographical areas within tropical and subtropical regions of the world.[2]. Despite serologic evidence of prior circulation of ZIKV in Africa and Asia, only a small number of cases with mild clinical symptoms were described.[4,5,6] Zika virus emerged as a new American subclade from the Asian lineage in the Americas and the Caribbean. The lack of immunity throughout the population facilitated its dissemination.[7]

Objectives

Methods

Results

Conclusion