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Reporter Virus Neutralization Test Evaluation for Dengue and Zika Virus Diagnosis in Flavivirus Endemic Area - PubMed

  • ️Fri Jan 01 2021

Reporter Virus Neutralization Test Evaluation for Dengue and Zika Virus Diagnosis in Flavivirus Endemic Area

Jannyce G C Nunes et al. Pathogens. 2021.

Abstract

Reporter virus neutralization test (RVNT) has been used as an alternative to the more laborious and time-demanding conventional PRNT assay for both DENV and ZIKV. However, few studies have investigated how these techniques would perform in epidemic areas with the circulation of multiple flavivirus. Here, we evaluate the performance of ZIKV and DENV Rluc RVNT and ZIKV mCh RVNT assays in comparison to the conventional PRNT assay against patient sera collected before and during ZIKV outbreak in Brazil. These samples were categorized into groups based on (1) acute and convalescent samples according to the time of disease, and (2) laboratorial diagnostic results (DENV and ZIKV RT-PCR and IgM-capture ELISA). Our results showed that DENV Rluc assay presented 100% and 78.3% sensitivity and specificity, respectively, with 93.3% accuracy, a similar performance to the traditional PRNT. ZIKV RVNT90, on the other hand, showed much better ZIKV antibody detection performance (around nine-fold higher) when compared to PRNT, with 88% clinical sensitivity. Specificity values were on average 76.8%. Even with these results, however, ZIKV RVNT90 alone was not able to reach a final diagnostic conclusion for secondary infection in human samples due to flavivirus cross reaction. As such, in regions where the flavivirus differential diagnosis represents a challenge, we suggest the establishment of a RVNT panel including other flaviviruses circulating in the region, associated with the other serological techniques such as IgM ELISA and the investigation of seroconversion, in order to help define an accurate diagnostic conclusion using serology.

Keywords: Dengue; ZIKV; diagnosis; flavivirus; neutralization test; reporter virus.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1

ROC curves comparing the performance of the DENV and ZIKV RVNT assays with the conventional PRNT. (A) DENV RVNT Rluc versus PRNT; (B) ZIKV RVNT Rluc versus PRNT; (C) ZIKV RVNT mCherry versus PRNT. (D) Comparison between ZIKV RVNT assays and the ZIKV PRNT using ZIKV diagnostic results (IgM-ELISA) as query.

Figure 2
Figure 2

Neutralizing antibodies titers comparison. (A) DENV RVNT Rluc versus PRNT; (B) ZIKV RVNT Rluc and mCherry versus PRNT.

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