title: Serodiagnosis of Zika virus (ZIKV) infections by a novel NS1-based ELISA devoid of cross-reactivity with dengue virus antibodies: a multicohort study of assay performance, 2015 to 2016.
abstract: Serological diagnosis of Zika virus (ZIKV) infections is challenging due to high cross-reactivity between flaviviruses. We evaluated the diagnostic performance of a novel anti-ZIKV ELISA based on recombinant ZIKV non-structural protein 1 (NS1). Assay sensitivity was examined using sera from 27 patients with reverse transcription (RT)-PCR-confirmed and 85 with suspected ZIKV infection. Specificity was analysed using sera from 1,015 healthy individuals. Samples from 252 patients with dengue virus (n = 93), West Nile virus (n = 34), Japanese encephalitis virus (n = 25), chikungunya virus (n = 19) or Plasmodium spp. (n = 69) infections and from 12 yellow fever-vaccinated individuals were also examined. In confirmed ZIKV specimens collected ≥ 6 days after symptom onset, ELISA sensitivity was 58.8% (95% confidence interval (CI): 36.0-78.4) for IgM, 88.2% (95% CI: 64.4-98.0) for IgG, and 100% (95% CI: 78.4-100) for IgM/IgG, at 99.8% (95% CI: 99.2-100) specificity. Cross-reactivity with high-level dengue virus antibodies was not detected. Among patients with potentially cross-reactive antibodies anti-ZIKV positive rates were 0.8% (95% CI: 0-3.0) and 0.4% (95% CI: 0-2.4) for IgM and IgG, respectively. Providing high specificity and low cross-reactivity, the NS1-based ELISA has the potential to aid in counselling patients, pregnant women and travellers after returning from ZIKV-endemic areas.
authors.affiliation: Institute for Experimental Immunology, EUROIMMUN AG, Lübeck, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Steinhagen
authors.affiliation: Institute for Experimental Immunology, EUROIMMUN AG, Lübeck, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Probst
authors.affiliation: Institute for Experimental Immunology, EUROIMMUN AG, Lübeck, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Radzimski
authors.affiliation: WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research, Bernhard-Nocht Institute for Tropical Medicine, Hamburg, Germany.|German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel, Hamburg, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Schmidt-Chanasit
authors.affiliation: WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research, Bernhard-Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Emmerich
authors.affiliation: National Reference Center for Arboviruses, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Marjan
authors.initials: M
authors.lastname: van Esbroeck
authors.affiliation: Department of Medical Microbiology, Section of Clinical Virology, Academic Medical Center, Public Health Service, Amsterdam, the Netherlands.
authors.forename: Janke
authors.initials: J
authors.lastname: Schinkel
authors.affiliation: Center for Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Grobusch
authors.affiliation: Center for Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Abraham
authors.initials: A
authors.lastname: Goorhuis
authors.affiliation: Institute for Experimental Immunology, EUROIMMUN AG, Lübeck, Germany.
authors.forename: Jens M
authors.initials: JM
authors.lastname: Warnecke
authors.affiliation: Institute for Experimental Immunology, EUROIMMUN AG, Lübeck, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Lattwein
authors.affiliation: Institute for Experimental Immunology, EUROIMMUN AG, Lübeck, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Komorowski
authors.affiliation: Institute for Experimental Immunology, EUROIMMUN AG, Lübeck, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Deerberg
authors.affiliation: Institute for Experimental Immunology, EUROIMMUN AG, Lübeck, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Saschenbrecker
authors.affiliation: Institute for Experimental Immunology, EUROIMMUN AG, Lübeck, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Stöcker
authors.affiliation: Institute for Experimental Immunology, EUROIMMUN AG, Lübeck, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schlumberger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood*; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012698:Serologic Tests / Q000379:methods*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology; D055815:Young Adult; D000071244:Zika Virus / Q000276:immunology / Q000302:isolation & purification*; D000071243:Zika Virus Infection / Q000097:blood / Q000175:diagnosis* / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D017361:Viral Nonstructural Proteins
keywords: ELISA; NS1; Zika virus; antibody; infection; non-structural protein 1