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Sci Transl Med. 2017 Sep 27;9(409). pii: eaan1589. doi: 10.1126/scitranslmed.aan1589.

Rapid antigen tests for dengue virus serotypes and Zika virus in patient serum.

Author information

1
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2
Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
3
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
4
Institut Químic de Sarrià, Universitat Ramon Llull, Barcelona, Spain.
5
Programa de Medicina, Facultad de Salud, Universidad Surcolombiana, Neiva, Colombia.
6
Program in Virology, Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA.
7
Universidad Industrial de Santander and AEDES Program (Alianza para el desarrollo de estrategias que disminuyan el impacto de enfermedades transmitidas por Aedes como resultado del estudio de sus endemias y epidemias), Bucaramanga, Santander, Colombia.
8
HiMedia Laboratories Pvt. Ltd., Mumbai, India.
9
Immunopharmacology Group, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte, Brazil.
10
Departamento de Medicina Interna e Patologia, Hospital Universitário/Empresa Brasileira de Serviços Hospitalares (EBSERH), Universidade Federal de Sergipe, Aracaju, Brazil.
11
Laboratorio Central de Epidemiología, Instituto Mexicano del Seguro Social, Avenida Jacarandas S/N, Esquina Circuito Interior, Colonia La Raza Del Azcapotzalco, Código Postal 02990 México D.F., México.
12
Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Ciudad de México, México.
13
Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, Brazil.
14
Immunopharmacology Laboratory, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
15
National Institute of Infectious Disease Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brazil.
16
D'Or Institute of Research and Education (IDOR), Rio de Janeiro, Brazil.
17
National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), FIOCRUZ, Rio de Janeiro, Brazil.
18
Toxinology Laboratory and Center for Technological Development in Health (CDTS), FIOCRUZ, Rio de Janeiro, Brazil.
19
Flavivirus Laboratory, FIOCRUZ, Rio de Janeiro, Brazil.
20
Aggeu Magalhães Research Center, FIOCRUZ, Pernambuco, Recife, Brazil.
21
Department of Infectious Disease and Microbiology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
22
Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
23
Immunovirology Group, School of Medicine, University of Antioquia, Medellín, Colombia.
24
Instituto Colombiano de Medicina Tropical (ICMT), Universidad CES, Sabaneta, Antioquia, Colombia.
25
Universidad de Córdoba, Montería, Córdoba, Colombia.
26
Division of Infectious Diseases, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
27
Division of Infectious Diseases, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
28
Department of Paediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
29
Translational Health Science and Technology Institute, Faridabad, India.
30
Universidad Central de Venezuela, Caracas, Venezuela.
31
Winchester Engineering Analytical Center (WEAC), Winchester, MA 01890, USA.
32
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. kim.hamad@umb.edu lgehrke@mit.edu.
33
Department of Engineering, University of Massachusetts Boston, Boston, MA 02125, USA.
34
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. kim.hamad@umb.edu lgehrke@mit.edu.
35
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.

Abstract

The recent Zika virus (ZIKV) outbreak demonstrates that cost-effective clinical diagnostics are urgently needed to detect and distinguish viral infections to improve patient care. Unlike dengue virus (DENV), ZIKV infections during pregnancy correlate with severe birth defects, including microcephaly and neurological disorders. Because ZIKV and DENV are related flaviviruses, their homologous proteins and nucleic acids can cause cross-reactions and false-positive results in molecular, antigenic, and serologic diagnostics. We report the characterization of monoclonal antibody pairs that have been translated into rapid immunochromatography tests to specifically detect the viral nonstructural 1 (NS1) protein antigen and distinguish the four DENV serotypes (DENV1-4) and ZIKV without cross-reaction. To complement visual test analysis and remove user subjectivity in reading test results, we used image processing and data analysis for data capture and test result quantification. Using a 30-μl serum sample, the sensitivity and specificity values of the DENV1-4 tests and the pan-DENV test, which detects all four dengue serotypes, ranged from 0.76 to 1.00. Sensitivity/specificity for the ZIKV rapid test was 0.81/0.86, respectively, using a 150-μl serum input. Serum ZIKV NS1 protein concentrations were about 10-fold lower than corresponding DENV NS1 concentrations in infected patients; moreover, ZIKV NS1 protein was not detected in polymerase chain reaction-positive patient urine samples. Our rapid immunochromatography approach and reagents have immediate application in differential clinical diagnosis of acute ZIKV and DENV cases, and the platform can be applied toward developing rapid antigen diagnostics for emerging viruses.

PMID:
28954927
PMCID:
PMC6612058
DOI:
10.1126/scitranslmed.aan1589
[Indexed for MEDLINE]
Free PMC Article

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