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.
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.
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.
World Health Organization, 2009. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. Geneva, Switzerland: WHO Press.
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.
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.
Katzelnick LC et al. 2020. Zika virus infection enhances future risk of severe dengue disease. Science 369: 1123–1128.
Salje H et al. 2018. Reconstruction of antibody dynamics and infection histories to evaluate dengue risk. Nature 557: 719–723.
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.
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.
Roehrig JT, Hombach J, Barrett ADT, 2008. Guidelines for plaque-reduction neutralization testing of human antibodies to dengue viruses. Viral Immunol 21: 123–132.
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.
Zhang B et al. 2017. Diagnosis of Zika virus infection on a nanotechnology platform. Nat Med 23: 548–550.
Rojas A et al. 2019. Characterization of dengue cases among patients with an acute illness, Central Department, Paraguay. PeerJ 7: e7852.
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.
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.
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.
Cardozo F et al. 2018. Alphaviruses: serological evidence of human infection in Paraguay (2012–2013). Vector Borne Zoonotic Dis 75: 710–715.
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.
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.
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.
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.
Ministerio de Salud Publica y Bienestar Social, 2017. Boletín Epidemiológico República Del Paraguay. Asunción, Paraguay: Dirección General de Vigilancia de la Salud.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 | |
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Abstract Views | 873 | 231 | 19 |
Full Text Views | 352 | 164 | 1 |
PDF Downloads | 243 | 102 | 1 |
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.
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.
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.
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.
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.
World Health Organization, 2009. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. Geneva, Switzerland: WHO Press.
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.
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.
Katzelnick LC et al. 2020. Zika virus infection enhances future risk of severe dengue disease. Science 369: 1123–1128.
Salje H et al. 2018. Reconstruction of antibody dynamics and infection histories to evaluate dengue risk. Nature 557: 719–723.
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.
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.
Roehrig JT, Hombach J, Barrett ADT, 2008. Guidelines for plaque-reduction neutralization testing of human antibodies to dengue viruses. Viral Immunol 21: 123–132.
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.
Zhang B et al. 2017. Diagnosis of Zika virus infection on a nanotechnology platform. Nat Med 23: 548–550.
Rojas A et al. 2019. Characterization of dengue cases among patients with an acute illness, Central Department, Paraguay. PeerJ 7: e7852.
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.
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.
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.
Cardozo F et al. 2018. Alphaviruses: serological evidence of human infection in Paraguay (2012–2013). Vector Borne Zoonotic Dis 75: 710–715.
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.
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.
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.
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.
Ministerio de Salud Publica y Bienestar Social, 2017. Boletín Epidemiológico República Del Paraguay. Asunción, Paraguay: Dirección General de Vigilancia de la Salud.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 |