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Distinguishing Secondary Dengue Virus Infection From Zika Virus Infection With Previous Dengue by a Combination of 3 Simple Serological Tests.

Abstract

Background

The explosive spread of Zika virus (ZIKV) and associated microcephaly present an urgent need for sensitive and specific serodiagnostic tests, particularly for pregnant women in dengue virus (DENV)-endemic regions. Recent reports of enhanced ZIKV replication by dengue-immune sera have raised concerns about the role of previous DENV infection on the risk and severity of microcephaly and other ZIKV complications.

Methods

Enzyme-linked immunosorbent assays (ELISAs) based on ZIKV and DENV nonstructural protein 1 (NS1) were established to test acute, convalescent phase, and post-convalescent phase serum/plasma samples from reverse-transcription polymerase chain reaction-confirmed cases including 20 primary ZIKV, 25 ZIKV with previous DENV, 58 secondary DENV, and 16 primary DENV1 infections.

Results

ZIKV-NS1 immunoglobulin M (IgM) and immunoglobulin G (IgG) ELISAs combined can detect ZIKV infection with a sensitivity of 95% and specificity of 66.7%. The ZIKV-NS1 IgG cross-reactivity by samples from secondary DENV infection cases ranged from 66.7% to 28.1% (within 1 month to 1-2 years post-illness, respectively). Addition of DENV1-NS1 IgG ELISA can distinguish primary ZIKV infection; the ratio of absorbance of ZIKV-NS1 to DENV1-NS1 IgG ELISA can distinguish ZIKV with previous DENV and secondary DENV infections with a sensitivity of 87.5% and specificity of 81.3%. These findings were supported by analysis of sequential samples.

Conclusions

An algorithm for ZIKV serodiagnosis based on 3 simple ELISAs is proposed to distinguish primary ZIKV, ZIKV with previous DENV, and secondary DENV infections; this could be applied to serodiagnosis for ZIKV, serosurveillance, and monitoring ZIKV infection during pregnancy to understand the epidemiology, pathogenesis, and complications of ZIKV in dengue-endemic regions.

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  • Authors+Show Affiliations

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    Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu.

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    Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu.

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    Laboratory of Infection Research, School of Medicine, Federal University of Bahia, Salvador, Brazil.

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    Divison of Infectious Diseases. Department of Internal Medicine and Tropical Medicine Center, Kaohsiung Medical University Hospital. Department of Medicine, College of Medicine. Center for Dengue Fever Control and Research, Kaohsiung Medical University, Taiwan.

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    Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu.

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    Laboratory of Infection Research, School of Medicine, Federal University of Bahia, Salvador, Brazil.

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    University of Bonn Medical Centre, Institute of Virology. German Centre for Infection Research, Bonn-Cologne, Germany.

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    Blood Systems Research Institute.

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    Blood Systems Research Institute. University of California, San Francisco.

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    Blood Systems Research Institute. University of California, San Francisco.

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    Blood Systems Research Institute. University of California, San Francisco.

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    American Red Cross Scientific Support Office, Gaithersburg, Maryland.

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    National Virology Laboratory, National Center for Diagnosis and Reference, Ministry of Health, Managua, Nicaragua.

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    Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley.

    Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu.

    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    29020159