Article Category:
Research Article

Comparison of Anti-Dengue and Anti-Zika IgG on a Plasmonic Gold Platform with Neutralization Testing

Alejandra Rojas Departamento de Producción, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, San Lorenzo, Paraguay;

Search for other papers by Alejandra Rojas in
Current site
Google Scholar
PubMed Close
,
Muktha S. Natrajan Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia;

Search for other papers by Muktha S. Natrajan in
Current site
Google Scholar
PubMed Close
,
Jenna Weber Department of Pathology, Stanford University School of Medicine, Palo Alto, California;

Search for other papers by Jenna Weber in
Current site
Google Scholar
PubMed Close
,
Fátima Cardozo Departamento de Salud Pública, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, San Lorenzo, Paraguay;

Search for other papers by Fátima Cardozo in
Current site
Google Scholar
PubMed Close
,
César Cantero Departamento de Producción, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, San Lorenzo, Paraguay;

Search for other papers by César Cantero in
Current site
Google Scholar
PubMed Close
,
Jeyarama S. Ananta Nirmidas Biotech Inc., Palo Alto, California;

Search for other papers by Jeyarama S. Ananta in
Current site
Google Scholar
PubMed Close
,
Jessica Kost Nirmidas Biotech Inc., Palo Alto, California;

Search for other papers by Jessica Kost in
Current site
Google Scholar
PubMed Close
,
Meijie Tang Nirmidas Biotech Inc., Palo Alto, California;

Search for other papers by Meijie Tang in
Current site
Google Scholar
PubMed Close
,
Sanny López Departamento de Producción, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, San Lorenzo, Paraguay;

Search for other papers by Sanny López in
Current site
Google Scholar
PubMed Close
,
Cynthia Bernal Departamento de Producción, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, San Lorenzo, Paraguay;

Search for other papers by Cynthia Bernal in
Current site
Google Scholar
PubMed Close
,
Yvalena Guillén Departamento de Producción, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, San Lorenzo, Paraguay;

Search for other papers by Yvalena Guillén in
Current site
Google Scholar
PubMed Close
,
Laura Mendoza Departamento de Salud Pública, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, San Lorenzo, Paraguay;

Search for other papers by Laura Mendoza in
Current site
Google Scholar
PubMed Close
,
Malvina Páez Departamento de Salud Pública, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, San Lorenzo, Paraguay;

Search for other papers by Malvina Páez in
Current site
Google Scholar
PubMed Close
,
Benjamin A. Pinsky Department of Pathology, Stanford University School of Medicine, Palo Alto, California;
Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California;

Search for other papers by Benjamin A. Pinsky in
Current site
Google Scholar
PubMed Close
, and
Jesse J. Waggoner Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia;
Department of Global Health, Rollins School of Public Health, Atlanta, Georgia

Search for other papers by Jesse J. Waggoner in
Current site
Google Scholar
PubMed Close
DOI:
https://doi.org/10.4269/ajtmh.20-1449
Volume/Issue:
Volume 104: Issue 5
Page(s):
1729–1733
Restricted access
Get Permissions

ABSTRACT

Antibody cross-reactivity confounds testing for dengue virus (DENV) and Zika virus (ZIKV). We evaluated anti-DENV and anti-ZIKV IgG detection using a multiplex serological platform (the pGOLD assay, Nirmidas, Palo Alto, CA) in patients from the Asunción metropolitan area in Paraguay, which experiences annual DENV outbreaks but has reported few autochthonous ZIKV infections. Acute-phase sera were tested from 77 patients who presented with a suspected arboviral illness from January to May 2018. Samples were tested for DENV and ZIKV RNA by real-time reverse transcription-PCR, and for DENV nonstructural protein 1 with a lateral-flow immunochromatographic test. Forty-one patients (51.2%) had acute dengue; no acute ZIKV infections were detected. Sixty-five patients (84.4%) had anti–DENV-neutralizing antibodies by focus reduction neutralization testing (FRNT50). Qualitative detection with the pGOLD assay demonstrated good agreement with FRNT50 (kappa = 0.74), and quantitative results were highly correlated between methods (P < 0.001). Only three patients had anti–ZIKV-neutralizing antibodies at titers of 1:55–1:80, and all three had corresponding DENV-neutralizing titers > 1:4,000. Hospitalized dengue cases had significantly higher anti-DENV IgG levels (P < 0.001). Anti-DENV IgG results from the pGOLD assay correlate well with FRNT, and quantitative results may inform patient risk stratification.

    • Supplemental Materials (DOCX 76.08 KB)

Author Notes

Address correspondence to Jesse J. Waggoner, Emory University Department of Medicine, Division of Infectious Diseases, 1760 Haygood Dr. NE, Rm. E-132, Atlanta, GA 30322. E-mail: jjwaggo@emory.edu

Disclosure: Three authors were employees of Nirmidas Biotech (JSA, JK, and MT) and were involved in sample testing. All data were available to all authors for analysis.

Financial support: Research was supported by NIH grants R21 AI131689 (B. A. P. and J. S. A.) and K08 AI110528 (J. J. W.). In addition, the development of this collaboration was supported by funding from the Consejo Nacional de Ciencia y Tecnología (CONACYT) in Paraguay (A. R.: PVCT16-66 and J. J. W.: PVCT17-65).

Authors’ addresses: Alejandra Rojas, César Cantero, Sanny López, Cynthia Bernal, and Yvalena Guillén, Departamento de Producción, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, San Lorenzo, Paraguay, E-mails: arojass@iics.una.py, cesarcantero24@gmail.com, sannylo2894@gmail.com, bernalcynthiaq@gmail.com, and ivalenaguillen@yahoo.com. Muktha S. Natrajan, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, CDC, Atlanta, GA, and Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, GA, E-mail: qdz9@cdc.gov. Jenna Weber, Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, E-mail: jmicweber@gmail.com. Fátima Cardozo, Laura Mendoza, and Malvina Páez, Departamento de Salud Pública, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, San Lorenzo, Paraguay, E-mails: fati.cardozo@hotmail.com, lauramendozatorres@gmail.com and paezmalvina@yahoo.es. Jeyarama S. Ananta, Jessica Kost, and Meijie Tang, Research and Development, Nirmidas Biotech Inc., Palo Alto, CA, E-mail: viskid@gmail.com, jessica.kost@nirmidas.com, and meijie.tang@nirmidas.com. Benjamin A. Pinsky, Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, E-mail: bpinsky@stanford.edu. Jesse J. Waggoner, Department of Infectious Disease, Emory University, Atlanta, GA, E-mail: jesse.waggoner@emoryhealthcare.org.

Copyright:
© The American Society of Tropical Medicine and Hygiene 2021
Received:
10 Nov 2020
|
Accepted:
02 Feb 2021
|
Published Online:
29 Mar 2021
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
Online ISSN:
1476-1645
  • 1.

    Waggoner JJ et al. 2016. Viremia and clinical presentation in Nicaraguan patients infected with Zika virus, chikungunya virus, and dengue virus. Clin Infect Dis 63: 1584–1590.

    • Search Google Scholar
    • Export Citation
  • 2.

    Brasil P et al. 2016. Zika virus outbreak in Rio de Janeiro, Brazil: clinical characterization, epidemiological and virological aspects. PLoS Negl Trop Dis 10: e0004636.

    • Search Google Scholar
    • Export Citation
  • 3.

    Silva MMO et al. 2019. Concomitant transmission of dengue, chikungunya, and Zika viruses in Brazil: clinical and epidemiological findings from surveillance for acute febrile illness. Clin Infect Dis 69: 1353–1359.

    • Search Google Scholar
    • Export Citation
  • 4.

    World Health Organization, 2009. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. Geneva, Switzerland: WHO Press.

  • 5.

    Balmaseda A et al. 2018. Comparison of four serological methods and two reverse transcription-PCR assays for diagnosis and surveillance of Zika virus infection. J Clin Microbiol 56: e01785–e01817.

    • Search Google Scholar
    • Export Citation
  • 6.

    Waggoner JJ, Katzelnick LC, Burger-Calderon R, Gallini J, Moore RH, Kuan G, Balmaseda A, Pinsky BA, Harris E, 2020. Antibody-dependent enhancement of severe disease is mediated by serum viral load in pediatric dengue virus infections. J Infect Dis 221: 1846–1854.

    • Search Google Scholar
    • Export Citation
  • 7.

    Katzelnick LC et al. 2020. Zika virus infection enhances future risk of severe dengue disease. Science 369: 1123–1128.

  • 8.

    Salje H et al. 2018. Reconstruction of antibody dynamics and infection histories to evaluate dengue risk. Nature 557: 719–723.

  • 9.

    Katzelnick LC, Gresh L, Halloran ME, Mercado JC, Kuan G, Gordon A, Balmaseda A, Harris E, 2017. Antibody-dependent enhancement of severe dengue disease in humans. Science 358: 929–932.

    • Search Google Scholar
    • Export Citation
  • 10.

    Lanciotti RS, Kosoy OL, Laven JJ, Velez JO, Lambert AJ, Johnson AJ, Stanfield SM, Duffy MR, 2008. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis 14: 1232–1239.

    • Search Google Scholar
    • Export Citation
  • 11.

    Roehrig JT, Hombach J, Barrett ADT, 2008. Guidelines for plaque-reduction neutralization testing of human antibodies to dengue viruses. Viral Immunol 21: 123–132.

    • Search Google Scholar
    • Export Citation
  • 12.

    Rabe IB, Staples JE, Villanueva J, Hummel KB, Johnson JA, Rose L, Mts Hills S, Wasley A, Fischer M, Powers AM, 2016. Interim guidance for interpretation of Zika virus antibody test results. MMWR Morb Mortal Wkly Rep 65: 543–546.

    • Search Google Scholar
    • Export Citation
  • 13.

    Zhang B et al. 2017. Diagnosis of Zika virus infection on a nanotechnology platform. Nat Med 23: 548–550.

  • 14.

    Rojas A et al. 2019. Characterization of dengue cases among patients with an acute illness, Central Department, Paraguay. PeerJ 7: e7852.

  • 15.

    Pan American Health Organization, 2020. Dengue. Available at: https://www.paho.org/hq/index.php?option=com_topics&view=article&id=1&Itemid=40734&lang=en. Accessed May 15, 2020.

    • Search Google Scholar
    • Export Citation
  • 16.

    Aquino JD, Tang WF, Ishii R, Ono T, Eshita Y, Aono H, Makino Y, 2008. Molecular epidemiology of dengue virus serotypes 2 and 3 in Paraguay during 2001-2006: the association of viral clade introductions with shifting serotype dominance. Virus Res 137: 266–270.

    • Search Google Scholar
    • Export Citation
  • 17.

    Aquino VH et al. 2006. Molecular epidemiology of dengue type 3 virus in Brazil and Paraguay, 2002–2004. Am J Trop Med Hyg 75: 710–715.

  • 18.

    Cardozo F et al. 2018. Alphaviruses: serological evidence of human infection in Paraguay (2012–2013). Vector Borne Zoonotic Dis 75: 710–715.

    • Search Google Scholar
    • Export Citation
  • 19.

    Lovera D, Araya S, Mesquita MJ, Avalos C, Ledesma S, Arbo A, 2014. Prospective applicability study of the new dengue classification system for clinical management in children. Pediatr Infect Dis J 33: 933–935.

    • Search Google Scholar
    • Export Citation
  • 20.

    Lovera D, Martinez de Cuellar C, Araya S, Amarilla S, Gonzalez N, Aguiar C, Acuna J, Arbo A, 2016. Clinical characteristics and risk factors of dengue shock syndrome in children. Pediatr Infect Dis J 35: 1294–1299.

    • Search Google Scholar
    • Export Citation
  • 21.

    Rojas A, Aria L, de Guillen YA, Acosta ME, Infanzón B, Diaz V, López L, Meza T, Riveros O, 2016. Perfil clínico, hematológico y serológico en pacientes con sospecha de dengue del IICS-UNA, 2009–2013. Mem Inst Investig Cienc Salud 14: 68–74.

    • Search Google Scholar
    • Export Citation
  • 22.

    Dirección General de Vigilancia de la Salud, Ministerio de Salud Pública y Bienestar Social, 2016. Boletín Epidemiológico: Semana Epidemiológica. Asunción, Paraguay: Ministerio de Salud Pública y Bienestar Social, 52.

    • Search Google Scholar
    • Export Citation
  • 23.

    Ministerio de Salud Publica y Bienestar Social, 2017. Boletín Epidemiológico República Del Paraguay. Asunción, Paraguay: Dirección General de Vigilancia de la Salud.

    • Search Google Scholar
    • Export Citation
  • 24.

    Vazquez C, de la Fuente AG, Villalba S, Torales J, Gamarra ML, Ortego MJ, Dunjo P, Chamorro G, Mendez J, Almiron M, 2019. Retrospective detection of Zika virus transmission in Paraguay – January to December 2016. Weekly Epidem Rec 94: 161–168.

    • Search Google Scholar
    • Export Citation
  • 25.

    Waggoner JJ et al. 2013. Comparison of the FDA-approved CDC DENV-1-4 real-time reverse transcription-PCR with a laboratory-developed assay for dengue virus detection and serotyping. J Clin Microbiol 51: 3418–3420.

    • Search Google Scholar
    • Export Citation
  • 26.

    Waggoner JJ et al. 2013. Single-reaction, multiplex, real-time rt-PCR for the detection, quantitation, and serotyping of dengue viruses. PLoS Negl Trop Dis 7: e2116.

    • Search Google Scholar
    • Export Citation
  • 27.

    Waggoner JJ, Gresh L, Mohamed-Hadley A, Ballesteros G, Davila MJ, Tellez Y, Sahoo MK, Balmaseda A, Harris E, Pinsky BA, 2016. Single-Reaction multiplex reverse transcription PCR for detection of Zika, chikungunya, and dengue viruses. Emerg Infect Dis 22: 1295–1297.

    • Search Google Scholar
    • Export Citation
  • 28.

    Cantero C et al. 2020. Implementation of a multiplex rRT-PCR for Zika, chikungunya, and dengue viruses: improving arboviral detection in an endemic region. Am J Trop Med Hyg 102: 625–628.

    • Search Google Scholar
    • Export Citation
  • 29.

    Lai L et al. Emory Zika Patient Study T, 2018. Innate, T-, and B-cell responses in acute human Zika patients. Clin Infect Dis 66: 1–10.

  • 30.

    Priyamvada L et al. 2016. Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus. Proc Natl Acad Sci U S A 113: 7852–7857.

    • Search Google Scholar
    • Export Citation
  • 31.

    El Sahly HM et al. 2019. Clinical, virologic, and immunologic characteristics of Zika virus infection in a cohort of US patients: prolonged RNA detection in whole blood. Open Forum Infect Dis 6: ofy352.

    • Search Google Scholar
    • Export Citation
  • 32.

    Collins MH, McGowan E, Jadi R, Young E, Lopez CA, Baric RS, Lazear HM, de Silva AM, 2017. Lack of durable cross-neutralizing antibodies against Zika virus from dengue virus infection. Emerg Infect Dis 23: 773–781.

    • Search Google Scholar
    • Export Citation
  • 33.

    Tesla B, Demakovsky LR, Mordecai EA, Ryan SJ, Bonds MH, Ngonghala CN, Brindley MA, Murdock CC, 2018. Temperature drives Zika virus transmission: evidence from empirical and mathematical models. Proc Biol Sci 285: 20180795.

    • Search Google Scholar
    • Export Citation
  • 34.

    Guzman MG, Harris E, 2015. Dengue. Lancet 385: 453–465.

  • 35.

    Glasner DR, Puerta-Guardo H, Beatty PR, Harris E, 2018. The good, the bad, and the shocking: the multiple roles of dengue virus nonstructural protein 1 in protection and pathogenesis. Annu Rev Virol 5: 227–253.

    • Search Google Scholar
    • Export Citation
  • 36.

    Shu PY, Chen LK, Chang SF, Yueh YY, Chow L, Chien LJ, Chin C, Lin TH, Huang JH, 2000. Dengue NS1-specific antibody responses: isotype distribution and serotyping in patients with dengue fever and dengue hemorrhagic fever. J Med Virol 62: 224–232.

    • Search Google Scholar
    • Export Citation
  • 37.

    Nascimento EJM, Huleatt JW, Cordeiro MT, Castanha PMS, George JK, Grebe E, Welte A, Brown M, Burke DS, Marques ETA, 2018. Development of antibody biomarkers of long term and recent dengue virus infections. J Virol Methods 257: 62–68.

    • Search Google Scholar
    • Export Citation
  • 38.

    Jayathilaka D et al. 2018. Role of NS1 antibodies in the pathogenesis of acute secondary dengue infection. Nat Commun 9: 5242.

Past two years Past Year Past 30 Days
Abstract Views 873 231 19
Full Text Views 352 164 1
PDF Downloads 243 102 1
 
Membership Banner
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save