Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Nov:112:21-24.
doi: 10.1016/j.ijid.2021.09.004. Epub 2021 Sep 8.

Classification of measles breakthrough cases in an elimination setting using a comprehensive algorithm of laboratory results: why sensitive and specific IgM assays are important

S Mercader  1 , A Dominguez  2 , N Torner  3 , J Costa  4 , S B Sowers  5 , A Martinez  6 , W J Bellini  7 , C J Hickman  5
Affiliations

Classification of measles breakthrough cases in an elimination setting using a comprehensive algorithm of laboratory results: why sensitive and specific IgM assays are important

S Mercader et al. Int J Infect Dis. 2021 Nov.

Abstract

Objective: In 2006, a measles outbreak occurred in Catalonia (Spain), six years after endemic measles was declared eliminated. This study aimed to classify 19 confirmed measles breakthrough cases (BC) using a high-performance avidity assay developed in 2010.

Methods: Serum specimens were tested by indirect IgG, indirect IgM, capture IgM enzyme immunoassay, an endpoint-titer IgG avidity assay, and a plaque reduction neutralization assay. Serology and RNA detection results were combined in an algorithm for measles confirmation and classification of breakthrough cases and analyzed with clinical and epidemiological data.

Results: Of 19 samples, thirteen (68%) were conclusive with the classification of BCs, and six (32%) had false-positive IgM results on an indirect-format assay; they were classified as rash and fever illness of undetermined etiology. BCs were primary vaccine failures (seven or 54%), secondary vaccine failures (four or 31%), and two (15%) could not be classified.

Conclusions: In measles elimination settings, high-performing assays and a comprehensive algorithm of laboratory results (IgG, IgM, and RNA detection), including IgG avidity and PRN results when necessary, can assist in accurate laboratory confirmation and classification of suspected measles cases for surveillance. Highly specific IgM assays are required to minimize the number of false-positive results.

Keywords: Measles; avidity assay; breakthrough case; case classification; elimination; vaccine failure.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References

    1. Cohen BJ, Audet S, Andrews N, Beeler J. test WHOwgomprn. Plaque reduction neutralization test for measles antibodies: Description of a standardized laboratory method for use in immunogenicity studies of aerosol vaccination. Vaccine 2007;26:59–66. doi: 10.1016/j.vaccine.2007.10.046. - DOI - PubMed
    1. Dominguez A, Torner N, Barrabeig I, Rovira A, Rius C, Cayla J, et al. Large outbreak of measles in a community with high vaccination coverage: implications for the vaccination schedule. Clin Infect Dis 2008;47:1143–9. doi: 10.1086/592258. - DOI - PubMed
    1. Hummel KB, Erdman DD, Heath J, Bellini WJ. Baculovirus expression of the nucleoprotein gene of measles virus and utility of the recombinant protein in diagnostic enzyme immunoassays. J Clin Microbiol 1992;30:2874–80. doi: 10.1128/jcm.30.11.2874-2880.1992. - DOI - PMC - PubMed
    1. Latner DR, Sowers SB, Anthony K, Colley H, Badeau C, Coates J, et al. Qualitative Variation among Commercial Immunoassays for Detection of Measles-Specific IgG. J Clin Microbiol 2020;58. doi: 10.1128/JCM.00265-20. - DOI - PMC - PubMed
    1. Mercader S, Garcia P, Bellini WJ. Measles virus IgG avidity assay for use in classification of measles vaccine failure in measles elimination settings. Clin Vaccine Immunol 2012;19:1810–17. doi: 10.1128/CVI.00406-12. - DOI - PMC - PubMed