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

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.

Investigation of a mumps outbreak among university students with two measles-mumps-rubella (MMR) vaccinations, Virginia, September-December 2006.

Following the clinical diagnosis of the first case of mumps on September 22, 2006 at the University of Virginia (UVA), 52 suspected cases were identified through active surveillance for mumps by the end of December 2006. Samples were collected from 47 students who presented with parotitis despite a documented history of two doses of measles, mumps, and rubella (MMR) vaccine. Six of 47 serum samples (13%) were positive for mumps IgM, and 46/47 specimens were positive for mumps IgG. Endpoint titration of acute phase serum samples from laboratory-confirmed cases did not provide evidence that elevated serum IgG is a consistent marker for infection among cases due to secondary vaccine failure. Buccal swab samples from 39 of the 47 students were tested by real-time reverse transcription-polymerase chain reaction (RT-PCR) and/or viral culture. Mumps virus or mumps RNA was detected in 12 of 39 buccal samples (31%). Genetic analysis of the virus from the outbreak at UVA indicated that the outbreak was not linked to the large mumps outbreak in the Midwestern US that occurred earlier in 2006. Our findings support the use of viral detection to improve laboratory diagnosis of mumps among persons who have received two doses of MMR.