Abstract
Dengue virus (DENV) and Zika virus (ZIKV) belong to the Flaviviridae family of viruses spread by Aedes aegypti mosquitoes in tropical and subtropical areas. Accurate diagnostic tests to differentiate the 2 infections are necessary for patient management and disease control. Using characterized ZIKV and DENV patient plasma in a blind manner, we validated an ELISA and a rapid immunochromatographic test for ZIKV detection. We engineered the ZIKV nonstructural protein 1 (NS1) for sensitive serologic detection with low cross reactivity against dengue and developed monoclonal antibodies specific for the ZIKV NS1 antigen. As expected, the serologic assays performed better with convalescent than acute plasma samples; the sensitivity ranged from 71% to 88%, depending on the performance of individual tests (IgM/IgG/NS1). Although serologic tests were generally less sensitive with acute samples, our ZIKV NS1 antibodies were able to complement the serologic tests to achieve greater sensitivity for detecting early infections.
Highlights
Dengue virus (DENV) and Zika virus (ZIKV) belong to the Flaviviridae family of viruses spread by Aedes aegypti mosquitoes in tropical and subtropical areas
This study included plasma samples obtained from 94 patients with ZIKV who were admitted to the Communicable Disease Centre at Tan Tock Seng Hospital (TTSH) during August 27, 2016–August 14, 2017, and 70 DENV patients admitted during April 29, 2016–March 28, 2017
Among the DENV samples from the SeraCare commercial panel 0845_0051 that were available at the time (DSC-7, DSC-12, and DSC-20), we found that DSC-7 showed cross reactivity to the ZIKV WT
Summary
Dengue virus (DENV) and Zika virus (ZIKV) belong to the Flaviviridae family of viruses spread by Aedes aegypti mosquitoes in tropical and subtropical areas. Nucleic acid testing has shown good specificity in general, but high variations in assay sensitivity have been reported (15) This variability can be the result of complicated experimental setups, genetic variability in different virus strains, or narrow detection window because of low viremia load in ZIKV-infected patients (16,17). In nucleic acid test–negative cases, complementary assays based on serology testing, such as Zika IgM antibody capture ELISA (MAC-ELISA) and plaque-reduction neutralization test (PRNT), are required to validate the results (18,19). Those secondary tests are not specific because of high cross reactivity with other flaviviruses, further complicating the interpretation of test results (20,21). We further assessed assay performance by testing plasma samples collected from patients during acute and convalescent phases of infection
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