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Viruses 2018, 10(7), 379; https://doi.org/10.3390/v10070379

Comparative Evaluation of Indirect Immunofluorescence and NS-1-Based ELISA to Determine Zika Virus-Specific IgM

1
Laboratorio de Serología y Arbovirus, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda 28220, Spain
2
Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid 28029, Spain
3
Hospital Universitario La Paz, Madrid 28046, Spain
4
Hospital Vall d’Hebron, Barcelona 08035, Spain
5
Hospital Clínic, Barcelona 08036, Spain
6
Hospital Universitari Germans Trias i Pujol, Badalona 08916, Spain
7
Hospital Severo Ochoa, Leganés 28911, Spain
Working Group for the Study of Zika Virus Infections (WGSZVI): Elena Sáez, BR Salud, Hospital Infanta Sofía, San Sebastián de los Reyes; Mercedes Rodríguez Pérez, Hospital Universitario Central de Asturias; Carlos Gustavo Cilla, Hospital de Donostia; José Cobos Dorado, Megalab, Madrid; Jorge Cabrera, Hospital do Meixoeiro, Vigo; Marta Domínguez Gil-González, Hospital Universitario Del Río Hortega, Valladolid; Juan Carlos Galán, Hospital Ramón y Cajal, Madrid; María Nieves Gutiérrez Zufiaurre, Hospital Clínico, Salamanca; María José Goyanes, Hospital General Universitario Gregorio Marañón, Madrid; Carolina Campelo, Fundación Hospital Alcorcón; Mirian Blasco Alberdi, Hospital San Pedro, Logroño; Bartolomé Carrilero Fernández, Hospital Universitario Virgen de la Arrixaca, Murcia; Rodolfo Copado Carretero, Hospital General de Lanzarote; María Teresa Durán Valle, Hospital de Móstoles; Ricardo Fernández Roblas, Fundación Jiménez Díaz, Madrid; Isabel García Bermejo, Hospital de Getafe; José Ignacio García Cía, Unilabs, Madrid; Araceli Hernández Betancor, Hospital Universitario Insular de Gran Canaria, Las Palmas; Isabel Cristina López Mestanza, Hospital Santa Bárbara, Soria; Lourdes Roc Alfaro, Hospital Universitario Miguel Servet, Zaragoza; Giovani Fedele; Centro Nacional de Microbiología; Luis Antonio Arroyo Pedrero, Hospital Rafael Méndez, Lorca; Rafael Benito Ruesca, Hospital Clínico Universitario Lozano Blesa, Zaragoza; Buenaventura Buendía, Hospital de la Princesa, Madrid; Alejandro González Praetorius, Hospital Universitario de Guadalajara; Miriam Hernández Porto, Hospital Universitario de Canarias, La Laguna; Adoración Hurtado Hernández, Hospital Can Misses, Ibiza; Marta Lalana Garcés, Hospital de Barbastro; Ana Isabel López López, Labco General Lab, Pozuelo de Alarcón; Paloma Martín Cordero, Hospital Infanta Cristina, Badajoz; Rosario Millán Pérez, Hospital Puerta de Hierro, Majadahonda; Laura Molina Esteban, Hospital de Fuenlabrada; Francisco Javier Ramos Germán, Hospital Obispo Polanco, Teruel; Montserrat Ruiz García, Hospital General Universitario de Elche; Pino del Carmen Suárez, Hospital General de Fuerteventura; César Gómez Hernando, Hospital Virgen de la Salud, Toledo; Mariano Andreu López, Hospital General Universitario, Alicante; Noelia Arenal Andrés, Hospital Santos Reyes, Aranda de Duero; Francisco José Arjona Zaragozi, Hospital de la Marina Baixa, Villajoyosa; Elvira Baos Muñoz, Hospital Clínico San Carlos, Madrid; Xavier Casal Martínez, Hospital Nostra Senyora de Meritxell, Andorra; Amparo Coira Nieto, Complejo Hospitalario Xeral-Calde, Lugo; David Navalpotro, Consorcio Hospital General Universitario, Valencia; Alfredo Esteban Martín, Hospital de León; Mónica Gozalo Margüello, Hospital Universitario Marqués de Valdecilla, Santander; Susana Hernando Real, Hospital General de Segovia; María Jesús Lezaun Bugui, Hospital Galdakao-Usansolo; Elisa Martínez Alfaro y Juan Carlos Segura Luque, Complejo Hospitalario Universitario de Albacete; María Mateo Maestre, Hospital Central de la Defensa, Madrid; Ana MíguezSantiyán, Centro de Salud Pública de Valencia; Alfredo Pérez Rivilla, Hospital 12 de Octubre, Madrid; Mercedes Pérez Ruiz, Hospital Universitario Virgen de las Nieves; Isabel Polo Vigas, Complejo Hospitalario de Navarra; Carmen Raya Fernández, Hospital El Bierzo, Ponferrada; Rafael Sánchez Arroyo, Hospital Nuestra Señora de Sonsoles; María Reyes Sánchez Flórez, Complejo Hospitalario Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife; Matilde Trigo Daporta, Complejo Hospitalario de Pontevedra; Emilio David Valverde Romero, Hospital de León; Silvia Rojo Rello, Hospital Clínico Universitario, Valladolid; María José Rodríguez Escudero, Hospital General Virgen de la Luz, Cuenca; Francisco Salva, Hospital Universitario Son Espases, Palma de Mallorca; Juan Carlos Sanz, Laboratorio de Salud Pública, Comunidad de Madrid, and Teodora Minguito, Francisca Molero, Jesús María de la Fuente, Laura Herrera, Pilar
*
Author to whom correspondence should be addressed.
Received: 23 May 2018 / Revised: 27 June 2018 / Accepted: 30 June 2018 / Published: 19 July 2018
(This article belongs to the Special Issue New Advances on Zika Virus Research)
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Abstract

Differential diagnosis of the Zika virus (ZIKV) is hampered by cross-reactivity with other flaviviruses, mainly dengue viruses. The aim of this study was to compare two commercial methods for detecting ZIKV immunoglobulin M (IgM), an indirect immunofluorescence (IIF) and an enzyme immunoassay (ELISA), using the non-structural (NS) 1 protein as an antigen, both from EuroImmun, Germany. In total, 255 serum samples were analyzed, 203 of which showed laboratory markers of ZIKV infections (PCR-positive in serum and/or in urine and/or positive or indeterminate specific IgM). When tested with IIF, 163 samples were IgM-positive, while 13 samples were indeterminate and 78 were negative. When IIF-positive samples were tested using ELISA, we found 61 positive results, 14 indeterminate results, and 88 negative results. Among the indeterminate cases tested with IIF, ELISA analysis found two positive, two indeterminate, and nine negative results. Finally, 74 of the 78 IIF-negative samples proved also to be negative using ELISA. For the calculations, all indeterminate results were considered to be positive. The agreement, sensitivity, and specificity between ELISA and IIF were 60.2%, 44.9%, and 94.9%, respectively. Overall, 101 samples showed discrepant results; these samples were finally classified on the basis of other ZIKV diagnostic approaches (PCR-positive in serum and/or in urine, IgG determinations using IIF or ELISA, and ZIKV Plaque Reduction Neutralization test—positive), when available. A final classification of 228 samples was possible; 126 of them were positive and 102 were negative. The corresponding values of agreement, sensitivity, and specificity of IIF were 86.0%, 96.8%, and 72.5%, respectively. The corresponding figures for ELISA were 81.1%, 65.9%, and 100%, respectively. The ELISA and IIF methods are both adequate approaches for detecting ZIKV-specific IgM. However, considering their respective weaknesses (low sensitivity in ELISA and low specificity in IIF), serological results must be considered jointly with other laboratory results. View Full-Text
Keywords: Zika virus; dengue viruses; flavivirus; ELISA; indirect immunofluorescence; plaque reduction neutralization test; polymerase chain reaction; cross-reactions Zika virus; dengue viruses; flavivirus; ELISA; indirect immunofluorescence; plaque reduction neutralization test; polymerase chain reaction; cross-reactions
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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De Ory, F.; Sánchez-Seco, M.P.; Vázquez, A.; Montero, M.D.; Sulleiro, E.; Martínez, M.J.; Matas, L.; Merino, F.J.; Working Group for the Study of Zika Virus Infections. Comparative Evaluation of Indirect Immunofluorescence and NS-1-Based ELISA to Determine Zika Virus-Specific IgM. Viruses 2018, 10, 379.

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