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Perinatal analyses of Zika- and dengue virus-specific neutralizing antibodies: A microcephaly case-control study in an area of high dengue endemicity in Brazil

Laboratory confirmation of Zika virus (ZIKV) infection during pregnancy is challenging due to cross-reactivity with dengue virus (DENV) and limited knowledge about the kinetics of anti-Zika antibody responses during pregnancy. We described ZIKV and DENV serological markers and the maternal-fetal tra...

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Autores principales: Castanha, Priscila M. S., Souza, Wayner V., Braga, Cynthia, de Araújo, Thalia Velho Barreto, Ximenes, Ricardo A. A., Albuquerque, Maria de Fátima P. M., Montarroyos, Ulisses R., Miranda-Filho, Demócrito B., Cordeiro, Marli T., Dhalia, Rafael, Marques, Ernesto T. A., Rodrigues, Laura C., Martelli, Celina M. T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428350/
https://www.ncbi.nlm.nih.gov/pubmed/30856223
http://dx.doi.org/10.1371/journal.pntd.0007246
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author Castanha, Priscila M. S.
Souza, Wayner V.
Braga, Cynthia
de Araújo, Thalia Velho Barreto
Ximenes, Ricardo A. A.
Albuquerque, Maria de Fátima P. M.
Montarroyos, Ulisses R.
Miranda-Filho, Demócrito B.
Cordeiro, Marli T.
Dhalia, Rafael
Marques, Ernesto T. A.
Rodrigues, Laura C.
Martelli, Celina M. T.
author_facet Castanha, Priscila M. S.
Souza, Wayner V.
Braga, Cynthia
de Araújo, Thalia Velho Barreto
Ximenes, Ricardo A. A.
Albuquerque, Maria de Fátima P. M.
Montarroyos, Ulisses R.
Miranda-Filho, Demócrito B.
Cordeiro, Marli T.
Dhalia, Rafael
Marques, Ernesto T. A.
Rodrigues, Laura C.
Martelli, Celina M. T.
author_sort Castanha, Priscila M. S.
collection PubMed
description Laboratory confirmation of Zika virus (ZIKV) infection during pregnancy is challenging due to cross-reactivity with dengue virus (DENV) and limited knowledge about the kinetics of anti-Zika antibody responses during pregnancy. We described ZIKV and DENV serological markers and the maternal-fetal transfer of antibodies among mothers and neonates after the ZIKV microcephaly outbreak in Northeast Brazil (2016). We included 89 microcephaly cases and 173 neonate controls at time of birth and their mothers. Microcephaly cases were defined as newborns with a particular head circumference (2 SD below the mean). Two controls without microcephaly were matched by the expected date of delivery and area of residence. We tested maternal serum for recent (ZIKV genome, IgM and IgG3 anti-NS1) and previous (ZIKV and DENV neutralizing antibodies [NAbs]) markers of infection. Multiple markers of recent or previous ZIKV and DENV infection in mothers were analyzed using principal component analysis (PCA). At delivery, 5.6% of microcephaly case mothers and 1.7% of control mothers were positive for ZIKV IgM. Positivity for ZIKV IgG3 anti-NS1 was 8.0% for case mothers and 3.5% for control mothers. ZIKV NAbs was slightly higher among mothers of cases (69.6%) than that of mothers of controls (57.2%; p = 0.054). DENV exposure was detected in 85.8% of all mothers. PCA discriminated two distinct components related to recent or previous ZIKV infection and DENV exposure. ZIKV NAbs were higher in newborns than in their corresponding mothers (p<0.001). We detected a high frequency of ZIKV exposure among mothers after the first wave of the ZIKV outbreak in Northeast Brazil. However, we found low sensitivity of the serological markers to recent infection (IgM and IgG3 anti-NS1) in perinatal samples of mothers of microcephaly cases. Since the neutralization test cannot precisely determine the time of infection, testing for ZIKV immune status should be performed as early as possible and throughout pregnancy to monitor acute Zika infection in endemic areas.
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spelling pubmed-64283502019-04-01 Perinatal analyses of Zika- and dengue virus-specific neutralizing antibodies: A microcephaly case-control study in an area of high dengue endemicity in Brazil Castanha, Priscila M. S. Souza, Wayner V. Braga, Cynthia de Araújo, Thalia Velho Barreto Ximenes, Ricardo A. A. Albuquerque, Maria de Fátima P. M. Montarroyos, Ulisses R. Miranda-Filho, Demócrito B. Cordeiro, Marli T. Dhalia, Rafael Marques, Ernesto T. A. Rodrigues, Laura C. Martelli, Celina M. T. PLoS Negl Trop Dis Research Article Laboratory confirmation of Zika virus (ZIKV) infection during pregnancy is challenging due to cross-reactivity with dengue virus (DENV) and limited knowledge about the kinetics of anti-Zika antibody responses during pregnancy. We described ZIKV and DENV serological markers and the maternal-fetal transfer of antibodies among mothers and neonates after the ZIKV microcephaly outbreak in Northeast Brazil (2016). We included 89 microcephaly cases and 173 neonate controls at time of birth and their mothers. Microcephaly cases were defined as newborns with a particular head circumference (2 SD below the mean). Two controls without microcephaly were matched by the expected date of delivery and area of residence. We tested maternal serum for recent (ZIKV genome, IgM and IgG3 anti-NS1) and previous (ZIKV and DENV neutralizing antibodies [NAbs]) markers of infection. Multiple markers of recent or previous ZIKV and DENV infection in mothers were analyzed using principal component analysis (PCA). At delivery, 5.6% of microcephaly case mothers and 1.7% of control mothers were positive for ZIKV IgM. Positivity for ZIKV IgG3 anti-NS1 was 8.0% for case mothers and 3.5% for control mothers. ZIKV NAbs was slightly higher among mothers of cases (69.6%) than that of mothers of controls (57.2%; p = 0.054). DENV exposure was detected in 85.8% of all mothers. PCA discriminated two distinct components related to recent or previous ZIKV infection and DENV exposure. ZIKV NAbs were higher in newborns than in their corresponding mothers (p<0.001). We detected a high frequency of ZIKV exposure among mothers after the first wave of the ZIKV outbreak in Northeast Brazil. However, we found low sensitivity of the serological markers to recent infection (IgM and IgG3 anti-NS1) in perinatal samples of mothers of microcephaly cases. Since the neutralization test cannot precisely determine the time of infection, testing for ZIKV immune status should be performed as early as possible and throughout pregnancy to monitor acute Zika infection in endemic areas. Public Library of Science 2019-03-11 /pmc/articles/PMC6428350/ /pubmed/30856223 http://dx.doi.org/10.1371/journal.pntd.0007246 Text en © 2019 Castanha et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Castanha, Priscila M. S.
Souza, Wayner V.
Braga, Cynthia
de Araújo, Thalia Velho Barreto
Ximenes, Ricardo A. A.
Albuquerque, Maria de Fátima P. M.
Montarroyos, Ulisses R.
Miranda-Filho, Demócrito B.
Cordeiro, Marli T.
Dhalia, Rafael
Marques, Ernesto T. A.
Rodrigues, Laura C.
Martelli, Celina M. T.
Perinatal analyses of Zika- and dengue virus-specific neutralizing antibodies: A microcephaly case-control study in an area of high dengue endemicity in Brazil
title Perinatal analyses of Zika- and dengue virus-specific neutralizing antibodies: A microcephaly case-control study in an area of high dengue endemicity in Brazil
title_full Perinatal analyses of Zika- and dengue virus-specific neutralizing antibodies: A microcephaly case-control study in an area of high dengue endemicity in Brazil
title_fullStr Perinatal analyses of Zika- and dengue virus-specific neutralizing antibodies: A microcephaly case-control study in an area of high dengue endemicity in Brazil
title_full_unstemmed Perinatal analyses of Zika- and dengue virus-specific neutralizing antibodies: A microcephaly case-control study in an area of high dengue endemicity in Brazil
title_short Perinatal analyses of Zika- and dengue virus-specific neutralizing antibodies: A microcephaly case-control study in an area of high dengue endemicity in Brazil
title_sort perinatal analyses of zika- and dengue virus-specific neutralizing antibodies: a microcephaly case-control study in an area of high dengue endemicity in brazil
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428350/
https://www.ncbi.nlm.nih.gov/pubmed/30856223
http://dx.doi.org/10.1371/journal.pntd.0007246
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