Diagnostic performance of commercial IgM and IgG enzyme-linked immunoassays (ELISAs) for diagnosis of Zika virus infection

Abstract

BackgroundSerologic detection of Zika virus (ZIKV) infections is challenging because of antigenic similarities among flaviviruses.ObjectiveTo evaluate the sensitivity and specificity of commercial ZIKV IgM and IgG enzyme-linked immunoassay (ELISA) kits.MethodsWe used sera from febrile patients with RT-PCR-confirmed ZIKV infection to determine sensitivity and sera from RT-PCR-confirmed dengue cases and blood donors, both of which were collected before ZIKV epidemics in Brazil (2009–2011 and 2013, respectively) to determine specificity.ResultsThe ZIKV IgM-ELISA positivity among RT-PCR ZIKV confirmed cases was 0.0% (0/14) and 12.5% (1/8) for acute- and convalescent-phase sera, respectively, while its specificity was 100.0% (58/58) and 98.3% (58/59) for acute- and convalescent-phase sera of dengue patients, and 100.0% (23/23) for blood donors. The ZIKV IgG-ELISA sensitivity was 100.0% (6/6) on convalescent-phase sera from RT-PCR confirmed ZIKV patients, while its specificity was 27.3% (15/55) on convalescent-phase sera from dengue patients and 45.0% (9/20) on blood donors’ sera. The ZIKV IgG-ELISA specificity among dengue confirmed cases was much greater among patients with primary dengue (92.3%; 12/13), compared to secondary dengue (7.1%; 3/42).ConclusionsIn a setting of endemic dengue transmission, the ZIKV IgM-ELISA had high specificity, but poor sensitivity. In contrast, the ZIKV IgG-ELISA showed low specificity, particularly for patients previously exposed to dengue infections. This suggests that this ZIKV IgM-ELISA is not useful in confirming a diagnosis of ZIKV infection in suspected patients, whereas the IgG-ELISA is more suitable for ZIKV diagnosis among travelers, who reside in areas free of flavivirus transmission, rather than for serosurveys in dengue-endemic areas.

Concomitant Transmission of Dengue, Chikungunya, and Zika Viruses in Brazil: Clinical and Epidemiological Findings From Surveillance for Acute Febrile Illness

“…This may be explained by our limited capacity for detecting ZIKV infections among the general patient population seeking medical care at the health unit because our inclusion criteria required the presence of fever, which is less common in ZIKV infections [19]. In addition, the sensitivity of ZIKV molecular diagnosis is limited [20], hampering case detection during the viremic phase of the infection, and we did not employ ZIKV serological tests due to their low accuracy [13,14]. Finally, some patients diagnosed with an acute FLAV infection based on DENV IgM-ELISA seroconversion might actually have reflected a ZIKV infection that cross-reacted with DENV.…”

Optimization and scale-up production of Zika virus ΔNS1 in Escherichia coli: application of Response Surface Methodology

“…Since the ZIKV outbreak in the Northeast of Brazil, there was a major effort towards the development of a reliable serological test. For other flavivirus, particularly DENV, the laboratory diagnostic was mostly based on the detection of antibodies against the non-structural protein 1, NS1 (Kikuti et al 2018;Stettler et al 2016). Previous work indicated that serological assays based on NS1 can be used to discriminate ZIKV and DENV infections (Balmaseda et al 2017;Bosch et al 2017;Stettler et al 2016).…”

“…However, ZIKV and DENV proteins share high sequence identity resulting in the cross-reactivity of antibodies generated after the infection (Balmaseda et al 2017;Fernanda Estofolete et al 2016;Granger et al 2017;Priyamvada et al 2017). In spite of significant progress made in the last years in our understanding of ZIKV, the improvement of diagnostic assays is still needed (Kikuti et al 2018;Theel and Hata 2018).…”

Neurological complications associated with emerging viruses in Brazil

“…To this extent, we can only report that patients had some type of arbovirus, but cannot determine whether it was chikungunya, dengue, or Zika virus. Differential diagnosis of Flavivirus species is complicated because commercial tests for dengue virus cross‐react to Zika virus antibodies and vice versa …”