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A SYSTEMATIC EVALUATION OF IGM AND IGG ANTIBODY ASSAY ACCURACY IN DIAGNOSING ACUTE ZIKA VIRUS INFECTION IN BRAZIL: LESSONS RELEVANT TO EMERGING INFECTIONS
Zika virus
Diagnosis
Immunoassays
Plaque reduction neutralization tests (PRNTs)
Serology
Serology evaluation
Author
Affilliation
National Institute for Health Research. Health Protection Research Unit in Emerging and Zoonotic Infections. Liverpool, UK / University of Liverpool. Institute of Infection and Global Health. Liverpool, UK.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Referência de Flavivírus. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, Brasil / Universidade de Pernambuco. Faculdade de Ciências Médicas. Instituto de Ciências Biológicas. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Referência de Flavivírus. 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 Nacional de Referência de Hepatite Viral. Rio de Janeiro, RJ, Brasil.
National Institute for Health Research. Health Protection Research Unit in Emerging and Zoonotic Infections. Liverpool, UK / University of Liverpool. Institute of Infection and Global Health. Liverpool, UK / Royal Liverpool University Hospital. Tropical & Infectious Disease Unit. Liverpool, UK.
National Institute for Health Research. Health Protection Research Unit in Emerging and Zoonotic Infections. Liverpool, UK / University of Liverpool. Institute of Infection and Global Health. Liverpool, UK / The Walton Centre NHS Foundation Trust. Liverpool, UK.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Referência de Flavivírus. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Referência de Flavivírus. Rio de Janeiro, RJ, Brasil / Public Health England. London, UK.
National Institute for Health Research. Health Protection Research Unit in Emerging and Zoonotic Infections. Liverpool, UK / University of Liverpool. Institute of Infection and Global Health. Liverpool, UK / Alder Hey Children's NHS Foundation Trust. Liverpool, UK.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Referência de Flavivírus. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, Brasil / Universidade de Pernambuco. Faculdade de Ciências Médicas. Instituto de Ciências Biológicas. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Referência de Flavivírus. 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 Nacional de Referência de Hepatite Viral. Rio de Janeiro, RJ, Brasil.
National Institute for Health Research. Health Protection Research Unit in Emerging and Zoonotic Infections. Liverpool, UK / University of Liverpool. Institute of Infection and Global Health. Liverpool, UK / Royal Liverpool University Hospital. Tropical & Infectious Disease Unit. Liverpool, UK.
National Institute for Health Research. Health Protection Research Unit in Emerging and Zoonotic Infections. Liverpool, UK / University of Liverpool. Institute of Infection and Global Health. Liverpool, UK / The Walton Centre NHS Foundation Trust. Liverpool, UK.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Referência de Flavivírus. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Referência de Flavivírus. Rio de Janeiro, RJ, Brasil / Public Health England. London, UK.
National Institute for Health Research. Health Protection Research Unit in Emerging and Zoonotic Infections. Liverpool, UK / University of Liverpool. Institute of Infection and Global Health. Liverpool, UK / Alder Hey Children's NHS Foundation Trust. Liverpool, UK.
Abstract
Accurate diagnostics underpin effective public health responses to emerging viruses. For viruses, such as Zika virus (ZIKV), where the viremia clears quickly, antibody-based (IgM or IgG) diagnostics are recommended for patients who present 7 days after symptom onset. However, cross-reactive antibody responses can complicate test interpretation among populations where closely related viruses circulate. We examined the accuracy (proportion of samples correctly categorized as Zika positive or negative) for antibody-based diagnostics among Brazilian residents (Rio de Janeiro) during the ZIKV outbreak. Four ZIKV enzyme-linked immunosorbent assays (ELISAs; IgM and IgG Euroimmun, IgM Novagnost, and CDC MAC), two dengue ELISAs (IgM and IgG Panbio), and the ZIKV plaque reduction neutralization test (PRNT) were evaluated. Positive samples were ZIKV PCR confirmed clinical cases collected in 2015-2016 (n = 169); negative samples (n = 236) were collected before ZIKV was present in Brazil (≤2013). Among serum samples collected ≥7 days from symptom onset, PRNT exhibited the highest accuracy (93.7%), followed by the Euroimmun IgG ELISA (77.9%). All IgM assays exhibited lower accuracy (<75%). IgG was detected more consistently than IgM among ZIKV cases using Euroimmun ELISAs (68% versus 22%). Anti-dengue virus IgM ELISA was positive in 41.1% of confirmed ZIKV samples tested. The Euroimmun IgG assay, although misdiagnosing 22% of samples, provided the most accurate ELISA. Anti-ZIKV IgG was detected more reliably than IgM among ZIKV patients, suggesting a secondary antibody response to assay antigens following ZIKV infection. Antibody ELISAs need careful evaluation in their target population to optimize use and minimize misdiagnosis, prior to widespread deployment, particularly where related viruses cocirculate.
Keywords
Zika antibody assaysZika virus
Diagnosis
Immunoassays
Plaque reduction neutralization tests (PRNTs)
Serology
Serology evaluation
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