title: Multicountry prospective clinical evaluation of two enzyme-linked immunosorbent assays and two rapid diagnostic tests for diagnosing dengue fever.
abstract: We evaluated four dengue diagnostic devices from Alere, including the SD Bioline Dengue Duo (nonstructural [NS] 1 Ag and IgG/IgM), the Panbio Dengue Duo Cassette (IgM/IgG) rapid diagnostic tests (RDTs), and the Panbio dengue IgM and IgG capture enzyme-linked immunosorbent assays (ELISAs) in a prospective, controlled, multicenter study in Peru, Venezuela, Cambodia, and the United States, using samples from 1,021 febrile individuals. Archived, well-characterized samples from an additional 135 febrile individuals from Thailand were also used. Reference testing was performed on all samples using an algorithm involving virus isolation, in-house IgM and IgG capture ELISAs, and plaque reduction neutralization tests (PRNT) to determine the infection status of the individual. The primary endpoints were the clinical sensitivities and specificities of these devices. The SD Bioline Dengue Duo had an overall sensitivity of 87.3% (95% confidence interval [CI], 84.1 to 90.2%) and specificity of 86.8% (95% CI, 83.9 to 89.3%) during the first 14 days post-symptom onset (p.s.o.). The Panbio Dengue Duo Cassette demonstrated a sensitivity of 92.1% (87.8 to 95.2%) and specificity of 62.2% (54.5 to 69.5%) during days 4 to 14 p.s.o. The Panbio IgM capture ELISA had a sensitivity of 87.6% (82.7 to 91.4%) and specificity of 88.1% (82.2 to 92.6%) during days 4 to 14 p.s.o. Finally, the Panbio IgG capture ELISA had a sensitivity of 69.6% (62.1 to 76.4%) and a specificity of 88.4% (82.6 to 92.8%) during days 4 to 14 p.s.o. for identification of secondary dengue infections. This multicountry prospective study resulted in reliable real-world performance data that will facilitate data-driven laboratory test choices for managing patient care during dengue outbreaks.
authors.affiliation: Naval Medical Research Center, Silver Spring, Maryland, USA subhamoy.pal.ctr@mail.mil.
authors.forename: Subhamoy
authors.identifier: http://orcid.org/0000-0003-0133-8444
authors.initials: S
authors.lastname: Pal
authors.affiliation: Naval Medical Research Center, Silver Spring, Maryland, USA.
authors.forename: Allison L
authors.initials: AL
authors.lastname: Dauner
authors.affiliation: Alere, Brisbane, Australia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Valks
authors.affiliation: U.S. Naval Medical Research Unit No. 6, Lima, Peru.
authors.forename: Brett M
authors.initials: BM
authors.lastname: Forshey
authors.affiliation: U.S. Naval Medical Research Unit No. 6, Lima, Peru University of California, Davis, California, USA.
authors.forename: Kanya C
authors.initials: KC
authors.lastname: Long
authors.affiliation: Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Butsaya
authors.initials: B
authors.lastname: Thaisomboonsuk
authors.affiliation: Laboratorio Regional de Diagnostico e Investigación del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomédicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela.
authors.forename: Gloria
authors.initials: G
authors.lastname: Sierra
authors.affiliation: Laboratorio Regional de Diagnostico e Investigación del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomédicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela.
authors.forename: Victor
authors.initials: V
authors.lastname: Picos
authors.affiliation: University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Talmage
authors.affiliation: U.S. Naval Medical Research Unit No. 6, Lima, Peru University of California, Davis, California, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Morrison
authors.affiliation: U.S. Naval Medical Research Unit No. 6, Lima, Peru.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Halsey
authors.affiliation: Laboratorio Regional de Diagnostico e Investigación del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomédicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Comach
authors.affiliation: U.S. Naval Medical Research Unit-2, Phnom Penh, Cambodia.
authors.forename: Chadwick
authors.initials: C
authors.lastname: Yasuda
authors.affiliation: University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Loeffelholz
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Jarman
authors.affiliation: Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Stefan
authors.initials: S
authors.lastname: Fernandez
authors.affiliation: National Institute of Public Health, Phnom Penh, Cambodia.
authors.forename: Ung Sam
authors.initials: US
authors.lastname: An
authors.affiliation: Naval Medical Research Center, Silver Spring, Maryland, USA.
authors.forename: Tadeusz J
authors.initials: TJ
authors.lastname: Kochel
authors.affiliation: U.S. Army Medical Materiel Development Activity, Frederick, Maryland, USA.
authors.forename: Louis E
authors.initials: LE
authors.lastname: Jasper
authors.affiliation: Naval Medical Research Center, Silver Spring, Maryland, USA.
authors.forename: Shuenn-Jue L
authors.initials: SJ
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology; D003716:Dengue Virus / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007223:Infant; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011933:Reagent Kits, Diagnostic / Q000821:virology*; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011933:Reagent Kits, Diagnostic