Abstract
Dengue virus (DENV) and Zika virus (ZIKV) are flaviviruses of public health relevance. Both viruses circulate in the same endemic settings and acute infections generally manifest similar symptoms. This highlights the importance of accurate diagnosis for clinical management and outbreak control. One of the commonly used acute diagnostic markers for flaviviruses is nonstructural protein 1 (NS1). However, false positives due to antigenic cross-reactivity have been reported between DENV and ZIKV infections when using DENV NS1 antigen (NS1 Ag) detection assays in acute cases. Therefore, we investigated the lowest detectable virus titres and cross-reactivity of three commercial dengue NS1 Ag rapid assays and two ELISAs for different flaviviruses. Our results showed that substantially high viral titres of ZIKV, Kunjin virus (KUNV) and yellow fever virus (YFV) are required to give false-positive results when using DENV NS1 rapid detection assays. Commercial DENV NS1 ELISAs did not react with ZIKV and YFV. In comparison, tested assays detected DENV at a significantly low virus titre. Given the relatively low viral loads reported in clinical samples, our findings suggest that commercially available dengue NS1 Ag detection assays are less likely to generate false-positive results among clinical samples in areas where multiple flaviviruses cocirculate.
Highlights
Zika virus (ZIKV) is an emerging mosquito-borne virus that is closely related to other flaviviruses of public health relevance, such as dengue virus (DENV) and yellow fever virus (YFV)
Our findings showed that nonstructural protein 1 (NS1) Ag assays designed for the diagnosis of dengue could generate false-positive results in ZIKV, Kunjin virus (KUNV) and YFV infections but at substantially higher virus titres than those reported in natural infections due to respective viruses
The virus titres in culture supernatants detected by DENV NS1 antigen (NS1 Ag) rapid assays and ELISAs for DENV-1–4 were compared with other flaviviruses
Summary
Zika virus (ZIKV) is an emerging mosquito-borne virus that is closely related to other flaviviruses of public health relevance, such as dengue virus (DENV) and yellow fever virus (YFV). ZIKV infections in various African countries and Southeast Asia from the 1950s to the 1990s were largely unnoticed until epidemics occurred in the Pacific Islands after 2007 and in Latin American countries in 2015 [1,2]. ZIKV and DENV coexist in tropical and subtropical regions, where there are favourable environmental conditions for their main vector, Aedes spp. mosquitoes. The accurate diagnosis of ZIKV infections is essential for proper clinical management and public health risk assessment. Uncomplicated acute infections of ZIKV and DENV are difficult to be clinically differentiated. Confirmatory diagnosis of ZIKV infections largely relies on the detection of viral RNA either in sera
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