High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases

In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR as...

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Main Authors:	Sowers, Sun B., Rota, Jennifer S., Hickman, Carole J., Mercader, Sara, Redd, Susan, McNall, Rebecca J., Williams, Nobia, McGrew, Marcia, Walls, M. Laura, Rota, Paul A., Bellini, William J.
Format:	Online
Language:	English
Published:	American Society for Microbiology 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979181/

id	pubmed-4979181
recordtype	oai_dc
spelling	pubmed-49791812016-08-17 High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases Sowers, Sun B. Rota, Jennifer S. Hickman, Carole J. Mercader, Sara Redd, Susan McNall, Rebecca J. Williams, Nobia McGrew, Marcia Walls, M. Laura Rota, Paul A. Bellini, William J. Diagnostic Laboratory Immunology In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml. American Society for Microbiology 2016-08-05 /pmc/articles/PMC4979181/ /pubmed/27335386 http://dx.doi.org/10.1128/CVI.00268-16 Text en Copyright © 2016 Sowers et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) .
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Sowers, Sun B. Rota, Jennifer S. Hickman, Carole J. Mercader, Sara Redd, Susan McNall, Rebecca J. Williams, Nobia McGrew, Marcia Walls, M. Laura Rota, Paul A. Bellini, William J.
spellingShingle	Sowers, Sun B. Rota, Jennifer S. Hickman, Carole J. Mercader, Sara Redd, Susan McNall, Rebecca J. Williams, Nobia McGrew, Marcia Walls, M. Laura Rota, Paul A. Bellini, William J. High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases
author_facet	Sowers, Sun B. Rota, Jennifer S. Hickman, Carole J. Mercader, Sara Redd, Susan McNall, Rebecca J. Williams, Nobia McGrew, Marcia Walls, M. Laura Rota, Paul A. Bellini, William J.
author_sort	Sowers, Sun B.
title	High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases
title_short	High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases
title_full	High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases
title_fullStr	High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases
title_full_unstemmed	High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases
title_sort	high concentrations of measles neutralizing antibodies and high-avidity measles igg accurately identify measles reinfection cases
description	In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml.
publisher	American Society for Microbiology
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979181/
_version_	1613624658649677824

High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases

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