1887
Research article Open Access
Like 0

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 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.

Loading

Article metrics loading...

/content/10.2807/1560-7917.ES.2016.21.50.30426
2016-12-15
2024-12-12
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2016.21.50.30426
Loading
Loading full text...

Full text loading...

/deliver/fulltext/eurosurveillance/21/50/eurosurv-21-30426-3.html?itemId=/content/10.2807/1560-7917.ES.2016.21.50.30426&mimeType=html&fmt=ahah

References

  1. European Centre for Disease Prevention and Control (ECDC). Rapid risk assessment: Zika virus epidemic in the Americas: potential association with microcephaly and Guillain-Barré syndrome. Stockholm: ECDC; 10 Dec 2015. Available from: http://ecdc.europa.eu/en/publications/Publications/zika-virus-americas-association-with-microcephaly-rapid-risk-assessment.pdf
  2. Fauci AS, Morens DM. Zika Virus in the Americas--Yet Another Arbovirus Threat. N Engl J Med. 2016;374(7):601-4.  https://doi.org/10.1056/NEJMp1600297  PMID: 26761185 
  3. European Centre for Disease Prevention and Control (ECDC). Zika virus outbreak in the America's and the pacific; epidemiological situation 20 may 2016. Stockholm: ECDC; 2016. Available from: http://ecdc.europa.eu/en/healthtopics/zika_virus_infection/zika-outbreak/Pages/epidemiological-situation.aspx
  4. Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med. 2009;360(24):2536-43.  https://doi.org/10.1056/NEJMoa0805715  PMID: 19516034 
  5. Gould EA, Solomon T. Pathogenic flaviviruses. Lancet. 2008;371(9611):500-9.  https://doi.org/10.1016/S0140-6736(08)60238-X  PMID: 18262042 
  6. Lanciotti RS, Kosoy OL, Laven JJ, Velez JO, Lambert AJ, Johnson AJ, et al. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis. 2008;14(8):1232-9.  https://doi.org/10.3201/eid1408.080287  PMID: 18680646 
  7. Cao-Lormeau VM, Blake A, Mons S, Lastère S, Roche C, Vanhomwegen J, et al. Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet. 2016;387(10027):1531-9.  https://doi.org/10.1016/S0140-6736(16)00562-6  PMID: 26948433 
  8. Martines RB, Bhatnagar J, Keating MK, Silva-Flannery L, Muehlenbachs A, Gary J, et al. Notes from the Field: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses--Brazil, 2015. MMWR Morb Mortal Wkly Rep. 2016;65(6):159-60.  https://doi.org/10.15585/mmwr.mm6506e1  PMID: 26890059 
  9. Mlakar J, Korva M, Tul N, Popović M, Poljšak-Prijatelj M, Mraz J, et al. Zika Virus Associated with Microcephaly. N Engl J Med. 2016;374(10):951-8.  https://doi.org/10.1056/NEJMoa1600651  PMID: 26862926 
  10. Johansson MA, Mier-y-Teran-Romero L, Reefhuis J, Gilboa SM, Hills SL. Zika and the Risk of Microcephaly. N Engl J Med. 2016;375(1):1-4.  https://doi.org/10.1056/NEJMp1605367  PMID: 27222919 
  11. Bingham AM, Cone M, Mock V, Heberlein-Larson L, Stanek D, Blackmore C, et al. Comparison of Test Results for Zika Virus RNA in Urine, Serum, and Saliva Specimens from Persons with Travel-Associated Zika Virus Disease - Florida, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(18):475-8.  https://doi.org/10.15585/mmwr.mm6518e2  PMID: 27171533 
  12. Reusken C, Pas S. GeurtsvanKessel C, Mögling R, van Kampen J, Langerak T, et al. Longitudinal follow-up of Zika virus RNA in semen of a traveller returning from Barbados to the Netherlands with Zika virus disease, March 2016. Euro Surveill. 2016;21(23):30251.  PMID: 27313200 
  13. Gourinat AC, O’Connor O, Calvez E, Goarant C, Dupont-Rouzeyrol M. Detection of Zika virus in urine. Emerg Infect Dis. 2015;21(1):84-6.  https://doi.org/10.3201/eid2101.140894  PMID: 25530324 
  14. Corbett KS, Katzelnick L, Tissera H, Amerasinghe A, de Silva AD, de Silva AM. Preexisting neutralizing antibody responses distinguish clinically inapparent and apparent dengue virus infections in a Sri Lankan pediatric cohort. J Infect Dis. 2015;211(4):590-9.  https://doi.org/10.1093/infdis/jiu481  PMID: 25336728 
  15. Puschnik A, Lau L, Cromwell EA, Balmaseda A, Zompi S, Harris E. Correlation between dengue-specific neutralizing antibodies and serum avidity in primary and secondary dengue virus 3 natural infections in humans. PLoS Negl Trop Dis. 2013;7(6):e2274.  https://doi.org/10.1371/journal.pntd.0002274  PMID: 23785536 
  16. Lindenbach BD, Rice CM. Molecular biology of flaviviruses. Adv Virus Res. 2003;59:23-61.  https://doi.org/10.1016/S0065-3527(03)59002-9  PMID: 14696326 
  17. Muller DA, Young PR. The flavivirus NS1 protein: molecular and structural biology, immunology, role in pathogenesis and application as a diagnostic biomarker. Antiviral Res. 2013;98(2):192-208.  https://doi.org/10.1016/j.antiviral.2013.03.008  PMID: 23523765 
  18. MacKenzie JM, Jones MK, Young PR. Immunolocalization of the dengue virus nonstructural glycoprotein NS1 suggests a role in viral RNA replication. Virology. 1996;220(1):232-40.  https://doi.org/10.1006/viro.1996.0307  PMID: 8659120 
  19. Winkler G, Randolph VB, Cleaves GR, Ryan TE, Stollar V. Evidence that the mature form of the flavivirus nonstructural protein NS1 is a dimer. Virology. 1988;162(1):187-96.  https://doi.org/10.1016/0042-6822(88)90408-4  PMID: 2827377 
  20. Flamand M, Megret F, Mathieu M, Lepault J, Rey FA, Deubel V. Dengue virus type 1 nonstructural glycoprotein NS1 is secreted from mammalian cells as a soluble hexamer in a glycosylation-dependent fashion. J Virol. 1999;73(7):6104-10. PMID: 10364366 
  21. Brown WC, Akey DL, Konwerski JR, Tarrasch JT, Skiniotis G, Kuhn RJ, et al. Extended surface for membrane association in Zika virus NS1 structure. Nat Struct Mol Biol. 2016;23(9):865-7.  https://doi.org/10.1038/nsmb.3268  PMID: 27455458 
  22. Lee JM, Crooks AJ, Stephenson JR. The synthesis and maturation of a non-structural extracellular antigen from tick-borne encephalitis virus and its relationship to the intracellular NS1 protein. J Gen Virol. 1989;70(Pt 2):335-43.  https://doi.org/10.1099/0022-1317-70-2-335  PMID: 2471787 
  23. Alcon S, Talarmin A, Debruyne M, Falconar A, Deubel V, Flamand M. Enzyme-linked immunosorbent assay specific to Dengue virus type 1 nonstructural protein NS1 reveals circulation of the antigen in the blood during the acute phase of disease in patients experiencing primary or secondary infections. J Clin Microbiol. 2002;40(2):376-81.  https://doi.org/10.1128/JCM.40.02.376-381.2002  PMID: 11825945 
  24. Macdonald J, Tonry J, Hall RA, Williams B, Palacios G, Ashok MS, et al. NS1 protein secretion during the acute phase of West Nile virus infection. J Virol. 2005;79(22):13924-33.  https://doi.org/10.1128/JVI.79.22.13924-13933.2005  PMID: 16254328 
  25. Matheus S, Boukhari R, Labeau B, Ernault V, Bremand L, Kazanji M, et al. Specificity of Dengue NS1 Antigen in Differential Diagnosis of Dengue and Zika Virus Infection. Emerg Infect Dis. 2016;22(9):1691-3.  https://doi.org/10.3201/eid2209.160725  PMID: 27347853 
  26. Cleton NB, Godeke GJ, Reimerink J, Beersma MF, Doorn HR, Franco L, et al. Spot the difference-development of a syndrome based protein microarray for specific serological detection of multiple flavivirus infections in travelers. PLoS Negl Trop Dis. 2015;9(3):e0003580.  https://doi.org/10.1371/journal.pntd.0003580  PMID: 25767876 
  27. Huzly D, Hanselmann I, Schmidt-Chanasit J, Panning M. High specificity of a novel Zika virus ELISA in European patients after exposure to different flaviviruses. Euro Surveill. 2016;21(16):30203.  https://doi.org/10.2807/1560-7917.ES.2016.21.16.30203  PMID: 27126052 
  28. Pan American Health Organization, World Health Organization (WHO). Zika virus (ZIKV) Surveillance in the Americas: Interim guidance for laboratory detection and diagnosis. 2015. Available from: http://iris.paho.org/xmlui/bitstream/handle/123456789/18602/zikavirusinterim_jan2015.pdf?sequence=1&isAllowed=y
  29. Zentrale Ethikkommission bei der Bundesärztekammer. Die (Weiter-) Verwendung von menschlichen Körpermaterialien für Zwecke der medizinischen Forschung (2003) [The (further) use of human body samples for the purpose of medical research (2003)]: Berlin: Zentrale Ethikkommussion bei der Bundesärztekammer. Available from: http://www.zentrale-ethikkommission.de/downloads/Koerpermat.pdf
  30. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, et al. STARD Group. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ. 2015;351:h5527.  https://doi.org/10.1136/bmj.h5527  PMID: 26511519 
  31. Gyurech D, Schilling J, Schmidt-Chanasit J, Cassinotti P, Kaeppeli F, Dobec M. False positive dengue NS1 antigen test in a traveller with an acute Zika virus infection imported into Switzerland. Swiss Med Wkly. 2016;146:w14296. PMID: 26859285 
  32. Rubin EJ, Greene MF, Baden LR. Zika Virus and Microcephaly. N Engl J Med. 2016;374(10):984-5.  https://doi.org/10.1056/NEJMe1601862  PMID: 26862812 
  33. Scholzen A, Sauerwein RW. How malaria modulates memory: activation and dysregulation of B cells in Plasmodium infection. Trends Parasitol. 2013;29(5):252-62.  https://doi.org/10.1016/j.pt.2013.03.002  PMID: 23562778 
  34. Van Esbroeck M, Meersman K, Michiels J, Arien KK, Van den Bossche D. Letter to the editor: Specificity of Zika virus ELISA: interference with malaria. Euro Surveill. 2016;21(21). http://dx.doi.org/ https://doi.org/10.2807/1560-7917.ES.2016.21.21.30237 
  35. Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, et al. Dengue in the early febrile phase: viremia and antibody responses. J Infect Dis. 1997;176(2):322-30.  https://doi.org/10.1086/514048  PMID: 9237696 
  36. Sa-Ngasang A, Anantapreecha S. A-Nuegoonpipat A, Chanama S, Wibulwattanakij S, Pattanakul K, et al. Specific IgM and IgG responses in primary and secondary dengue virus infections determined by enzyme-linked immunosorbent assay. Epidemiol Infect. 2006;134(4):820-5.  PMID: 16371180 
  37. World Health Organization (WHO). Zika virus–Fact sheet. Updated 6 September 2016. Geneva: WHO. [Accessed 9 Dec 2016]. Available from: http://www.who.int/mediacentre/factsheets/zika/en/
/content/10.2807/1560-7917.ES.2016.21.50.30426
Loading

Data & Media loading...

Submit comment
Close
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error