title: High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases.
abstract: 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.
authors.affiliation: National Center for Immunization and Respiratory Diseases, Division of Viral Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA sib9@cdc.gov.
authors.forename: Sun B
authors.initials: SB
authors.lastname: Sowers
authors.affiliation: National Center for Immunization and Respiratory Diseases, Division of Viral Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Rota
authors.affiliation: National Center for Immunization and Respiratory Diseases, Division of Viral Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
authors.forename: Carole J
authors.initials: CJ
authors.lastname: Hickman
authors.affiliation: National Center for Immunization and Respiratory Diseases, Division of Viral Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Mercader
authors.affiliation: National Center for Immunization and Respiratory Diseases, Division of Viral Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Redd
authors.affiliation: National Center for Immunization and Respiratory Diseases, Division of Viral Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: McNall
authors.affiliation: National Center for Immunization and Respiratory Diseases, Division of Viral Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
authors.forename: Nobia
authors.initials: N
authors.lastname: Williams
authors.affiliation: National Center for Immunization and Respiratory Diseases, Division of Viral Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
authors.forename: Marcia
authors.initials: M
authors.lastname: McGrew
authors.affiliation: National Center for Immunization and Respiratory Diseases, Division of Viral Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
authors.forename: M Laura
authors.initials: ML
authors.lastname: Walls
authors.affiliation: National Center for Immunization and Respiratory Diseases, Division of Viral Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Rota
authors.affiliation: National Center for Immunization and Respiratory Diseases, Division of Viral Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Bellini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood; D000915:Antibody Affinity; D002648:Child; D002675:Child, Preschool; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008457:Measles / Q000175:diagnosis* / Q000276:immunology; D008459:Measles virus / Q000276:immunology*; D008875:Middle Aged; D009500:Neutralization Tests / Q000379:methods*; D012008:Recurrence; D012680:Sensitivity and Specificity; D014481:United States; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G