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J Clin Microbiol. 2019 Jan 30;57(2). pii: e01464-18. doi: 10.1128/JCM.01464-18. Print 2019 Feb.

Combination of Nonstructural Protein 1-Based Enzyme-Linked Immunosorbent Assays Can Detect and Distinguish Various Dengue Virus and Zika Virus Infections.

Author information

1
Department of Tropical Medicine Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.
2
Tropical Medicine Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
3
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
4
Center for Dengue Fever Control and Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
5
School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
6
LAPI-Laboratório de Pesquisa em Infectologia School of Medicine, Federal University of Bahia, Salvador, Brazil.
7
Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
8
Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany.
9
German Centre for Infection Research, Munich, Germany.
10
American Red Cross Scientific Support Office, Gaithersburg, Maryland, USA.
11
National Virology Laboratory, National Center for Diagnosis and Reference, Ministry of Health, Managua, Nicaragua.
12
Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, California, USA.
13
Department of Tropical Medicine Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA wangwk@hawaii.edu.

Abstract

The recent outbreaks of Zika virus (ZIKV) and associated birth defects in regions of dengue virus (DENV) endemicity emphasize the need for sensitive and specific serodiagnostic tests. We reported previously that enzyme-linked immunosorbent assays (ELISAs) based on the nonstructural protein 1 (NS1) of DENV serotype 1 (DENV1) and ZIKV can distinguish primary DENV1, secondary DENV, and ZIKV infections. Whether ELISAs based on NS1 proteins of other DENV serotypes can discriminate various DENV and ZIKV infections remains unknown. We herein developed DENV2, DENV3, and DENV4 NS1 IgG ELISAs to test convalescent- and postconvalescent-phase samples from reverse transcription-PCR-confirmed cases, including 25 primary DENV1, 24 primary DENV2, 10 primary DENV3, 67 secondary DENV, 36 primary West Nile virus, 38 primary ZIKV, and 35 ZIKV with previous DENV infections as well as 55 flavivirus-naive samples. Each ELISA detected primary DENV infection with a sensitivity of 100% for the same serotype and 23.8% to 100% for different serotypes. IgG ELISA using a mixture of DENV1-4 NS1 proteins detected different primary and secondary DENV infections with a sensitivity of 95.6% and specificity of 89.5%. The ZIKV NS1 IgG ELISA detected ZIKV infection with a sensitivity of 100% and specificity of 82.9%. On the basis of the relative optical density ratio, the combination of DENV1-4 and ZIKV NS1 IgG ELISAs distinguished ZIKV with previous DENV and secondary DENV infections with a sensitivity of 91.7% to 94.1% and specificity of 87.0% to 95.0%. These findings have important applications to serodiagnosis, serosurveillance, and monitoring of both DENV and ZIKV infections in regions of endemicity.

KEYWORDS:

Zika virus; dengue virus; nonstructural protein 1; serodiagnosis

PMID:
30429254
PMCID:
PMC6355536
[Available on 2019-07-30]
DOI:
10.1128/JCM.01464-18

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