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DIAGNOSTIC PERFORMANCE OF ANTI-ZIKA VIRUS IGM, IGAM AND IGG ELISAS DURING CO-CIRCULATION OF ZIKA, DENGUE, AND CHIKUNGUNYA VIRUSES IN BRAZIL AND VENEZUELA
Enzyme-linked immunoassays
Dengue virus
Chikungunya virus
Antibodies
Immunoassays
Serology
Author
Morales, Ivonne
Rosenberger, Kerstin D.
Magalhaes, Tereza
Morais, Clarice N. L.
Braga, Cynthia
Marques, Ernesto T. A.
Calvet, Guilherme Amaral
Damasceno, Luana
Brasil, Patricia
Filippis, Ana Maria Bispo de
Tami, Adriana
Bethencourt, Sarah
Alvarez, Mayling
Martínez, Pedro A.
Guzman, Maria G.
Benevides, Bruno Souza
Caprara, Andrea
Quyen, Nguyen Than Ha
Simmons, Cameron P.
Wills, Bridget
Lamballerie, Xavier de
Drexler, Jan Felix
Jaenisch, Thomas
IDAMS Clinical Study Group
Rosenberger, Kerstin D.
Magalhaes, Tereza
Morais, Clarice N. L.
Braga, Cynthia
Marques, Ernesto T. A.
Calvet, Guilherme Amaral
Damasceno, Luana
Brasil, Patricia
Filippis, Ana Maria Bispo de
Tami, Adriana
Bethencourt, Sarah
Alvarez, Mayling
Martínez, Pedro A.
Guzman, Maria G.
Benevides, Bruno Souza
Caprara, Andrea
Quyen, Nguyen Than Ha
Simmons, Cameron P.
Wills, Bridget
Lamballerie, Xavier de
Drexler, Jan Felix
Jaenisch, Thomas
IDAMS Clinical Study Group
Affilliation
Heidelberg University Hospital. Department for Infectious Diseases. Section Clinical Tropical Medicine. Heidelberg, Germany / Associated partner Heidelberg University Hospital. German Centre for Infection Research. Heidelberg, Germany.
Heidelberg University Hospital. Department for Infectious Diseases. Section Clinical Tropical Medicine. Heidelberg, Germany / Associated partner Heidelberg University Hospital. German Centre for Infection Research. Heidelberg, Germany.
Colorado State University. Department of Microbiology, Immunology and Pathology. Center for Vector-Borne Infectious Diseases. Fort Collins, Colorado, United States of America.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia e Terapêutica Experimental. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Parasitologia. Recife, PE, Brasil / Instituto de Medicina Integral Professor Fernando Figueira. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia e Terapêutica Experimental. Recife, PE, Brasil / University of Pittsburgh. Graduate School of Public Health. Department of Infectious Diseases. Pittsburgh, Pennsylvania, United States of America.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivirus. Rio de Janeiro, RJ, Brasil.
University of Groningen. University Medical Center Groningen. Department of Medical Microbiology and Infection Prevention. Groningen, The Netherlands / Universidad de Carabobo. Facultad de Ciencias de la Salud. Valencia, Venezuela.
Universidad de Carabobo. Facultad de Ciencias de la Salud. Valencia, Venezuela.
Instituto de Medicina Tropical Pedro Kouri. La Habana, Cuba.
Instituto de Medicina Tropical Pedro Kouri. La Habana, Cuba.
Instituto de Medicina Tropical Pedro Kouri. La Habana, Cuba.
Universidade Estadual do Ceará. Fortaleza, CE, Brasil.
Universidade Estadual do Ceará. Fortaleza, CE, Brasil.
Oxford University Clinical Research Unit. Hospital for Tropical Diseases. Ho Chi Minh City, Vietnam.
Oxford University Clinical Research Unit. Hospital for Tropical Diseases. Ho Chi Minh City, Vietnam / Monash University. Institute for Vector-Borne Disease. Melbourne, Australia.
Oxford University Clinical Research Unit. Hospital for Tropical Diseases. Ho Chi Minh City, Vietnam / Oxford University. Nuffield Department of Clinical Medicine. Centre for Tropical Medicine and Global Health. Oxford, United Kingdom.
Unité des Virus Emergents. Marseille, France.
Humboldt-Universität zu Berlin. Charité-Universitätsmedizin Berlin. Institute of Virology. Berlin, Germany / Sechenov University. Martsinovsky Institute of Medical Parasitology. Tropical and Vector-Borne Diseases. Moscow, Russia / Universitätsmedizin Berlin. German Centre for Infection Research. Berlin, Germany.
Heidelberg University Hospital. Department for Infectious Diseases. Section Clinical Tropical Medicine. Heidelberg, Germany / Associated partner Heidelberg University Hospital. German Centre for Infection Research. Heidelberg, Germany.
Colorado State University. Department of Microbiology, Immunology and Pathology. Center for Vector-Borne Infectious Diseases. Fort Collins, Colorado, United States of America.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia e Terapêutica Experimental. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Parasitologia. Recife, PE, Brasil / Instituto de Medicina Integral Professor Fernando Figueira. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia e Terapêutica Experimental. Recife, PE, Brasil / University of Pittsburgh. Graduate School of Public Health. Department of Infectious Diseases. Pittsburgh, Pennsylvania, United States of America.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivirus. Rio de Janeiro, RJ, Brasil.
University of Groningen. University Medical Center Groningen. Department of Medical Microbiology and Infection Prevention. Groningen, The Netherlands / Universidad de Carabobo. Facultad de Ciencias de la Salud. Valencia, Venezuela.
Universidad de Carabobo. Facultad de Ciencias de la Salud. Valencia, Venezuela.
Instituto de Medicina Tropical Pedro Kouri. La Habana, Cuba.
Instituto de Medicina Tropical Pedro Kouri. La Habana, Cuba.
Instituto de Medicina Tropical Pedro Kouri. La Habana, Cuba.
Universidade Estadual do Ceará. Fortaleza, CE, Brasil.
Universidade Estadual do Ceará. Fortaleza, CE, Brasil.
Oxford University Clinical Research Unit. Hospital for Tropical Diseases. Ho Chi Minh City, Vietnam.
Oxford University Clinical Research Unit. Hospital for Tropical Diseases. Ho Chi Minh City, Vietnam / Monash University. Institute for Vector-Borne Disease. Melbourne, Australia.
Oxford University Clinical Research Unit. Hospital for Tropical Diseases. Ho Chi Minh City, Vietnam / Oxford University. Nuffield Department of Clinical Medicine. Centre for Tropical Medicine and Global Health. Oxford, United Kingdom.
Unité des Virus Emergents. Marseille, France.
Humboldt-Universität zu Berlin. Charité-Universitätsmedizin Berlin. Institute of Virology. Berlin, Germany / Sechenov University. Martsinovsky Institute of Medical Parasitology. Tropical and Vector-Borne Diseases. Moscow, Russia / Universitätsmedizin Berlin. German Centre for Infection Research. Berlin, Germany.
Abstract
Background: Serological diagnosis of Zika virus (ZIKV) infection is challenging because of the antibody cross-reactivity among flaviviruses. At the same time, the role of Nucleic Acid Testing (NAT) is limited by the low proportion of symptomatic infections and the low average viral load. Here, we compared the diagnostic performance of commercially available IgM, IgAM, and IgG ELISAs in sequential samples during the ZIKV and chikungunya (CHIKV) epidemics and co-circulation of dengue virus (DENV) in Brazil and Venezuela.
Methodology/principal findings: Acute (day of illness 1-5) and follow-up (day of illness ≥ 6) blood samples were collected from nine hundred and seven symptomatic patients enrolled in a prospective multicenter study between June 2012 and August 2016. Acute samples were tested by RT-PCR for ZIKV, DENV, and CHIKV. Acute and follow-up samples were tested for IgM, IgAM, and IgG antibodies to ZIKV using commercially available ELISAs. Among follow-up samples with a RT-PCR confirmed ZIKV infection, anti-ZIKV IgAM sensitivity was 93.5% (43/46), while IgM and IgG exhibited sensitivities of 30.3% (10/33) and 72% (18/25), respectively. An additional 24% (26/109) of ZIKV infections were detected via IgAM seroconversion in ZIKV/DENV/CHIKV RT-PCR negative patients. The specificity of anti-ZIKV IgM was estimated at 93% and that of IgAM at 85%.
Conclusions/significance: Our findings exemplify the challenges of the assessment of test performance for ZIKV serological tests in the real-world setting, during co-circulation of DENV, ZIKV, and CHIKV. However, we can also demonstrate that the IgAM immunoassay exhibits superior sensitivity to detect ZIKV RT-PCR confirmed infections compared to IgG and IgM immunoassays. The IgAM assay also proves to be promising for detection of anti-ZIKV seroconversions in sequential samples, both in ZIKV PCR-positive as well as PCR-negative patients, making this a candidate assay for serological monitoring of pregnant women in future ZIKV outbreaks.
Keywords
Zika virusEnzyme-linked immunoassays
Dengue virus
Chikungunya virus
Antibodies
Immunoassays
Serology
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