Performance of 2 Commercial Serologic Tests for Diagnosing Zika Virus Infection

Séverine Matheus; Cheikh Talla; Bhety Labeau; Franck de Laval; Sébastien Briolant; Lena Berthelot; Muriel Vray; Dominique Rousset

Disclosures

Emerging Infectious Diseases. 2019;25(6):1153-1160. 

In This Article

Abstract and Introduction

Abstract

Reliable serologic tests are needed for diagnosis and surveillance of Zika virus infection. We evaluated the Euroimmun and Dia.Pro serologic tests for detection of Zika virus IgM and IgG by using a panel of 199 samples from a region endemic for flaviviruses. Kinetics of Zika virus antibodies were monitored from 300 sequential specimens sampled over a period of 10 months after infection. We observed suboptimal performance; sensitivity for Zika virus IgM was low, especially in the Euroimmun assay (49%), whereas IgM could be detected for months with the Dia.pro assay. The specificity of the Zika virus IgG assays was also low, especially that of Dia.Pro (62%); findings were strongly influenced by the epidemiologic context. These results highlight the complexity of serologic diagnosis of Zika virus infection in regions endemic for flaviviruses. Accurate analysis of the performance of assays is required to adapt and interpret algorithms.

Introduction

Zika virus belongs to the Flaviviridae family, genus Flavivirus, and is an arbovirus transmitted mainly by mosquitoes of the genus Aedes(Stegomyia). Initially isolated in 1947 from a sentinel monkey during yellow fever surveillance in Uganda, Zika virus was reported as causing only sporadic human infections, associated with asymptomatic or mild, self-limiting illness, until 2007.[1,2] In 2007, Zika virus spread first to Pacific islands and then throughout the Americas, resulting in large outbreaks in several regions of the world. Zika virus infection is estimated to be symptomatic in 18%–73% of cases;[3–5] severe complications have been reported, including neurologic disorders, such as Guillain-Barré syndrome, and congenital Zika virus syndrome, which is characterized by severe microcephaly, brain and ocular anomalies, congenital contractures, and neurologic impairment in the fetuses and newborns of mothers infected during pregnancy.[3,4,6]

The mild signs and symptoms of Zika virus infection include fever, rash, joint pain, conjunctivitis, headache, and myalgia.[7] These manifestations are difficult to distinguish clinically from those caused by other arboviral infections, such as dengue or chikungunya, which are often observed in the same geographic areas. Therefore, specific, reliable diagnostic tools are needed.

Several commercial kits are available for direct viral detection by nucleic acid–based testing, which enable diagnosis during the acute phase of the disease:[8,9] up to 7 days after symptom onset in serum samples, up to 20 days in urine, and even longer in semen.[10–13] This virologic window, combined with the high proportion of asymptomatic forms, makes the monitoring of Zika virus infection difficult, especially in pregnant women. Therefore, serologic tools for diagnosis of Zika virus infection are urgently needed. This challenge remains because of cross-reactivity among flaviviruses, especially in a context of secondary flavivirus infection or previous immunization.

The first objective of this study was to evaluate the performance of two commercial serologic kits for the detection of Zika virus–specific IgM and IgG in serum samples from patients with an arboviral-like syndrome in a region where other arboviruses are known to circulate, including dengue and chikungunya viruses. The 2 commercial kits (4 assays) studied were the Euroimmun Zika virus IgM and IgG ELISAs (https://www.euroimmun.com) and Dia.Pro Zika virus IgM and IgG ELISAs (Diagnostic Bioprobes Srl, https://www.diapro.it). The second objective was to determine the kinetics of Zika virus IgM and IgG induced after infection, as defined by these kits.

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