Comparison of the Sensitivity of Laboratory Diagnostic Methods from a Well-Characterized Outbreak of Mumps in New York City in 2009

Abstract

A mumps outbreak in upstate New York in 2009 at a summer camp for Orthodox Jewish boys spread into Orthodox Jewish communities in the Northeast, including New York City. The availability of epidemiologic information, including vaccination records and parotitis onset dates, allowed an enhanced analysis of laboratory methods for mumps testing. Serum and buccal swab samples were collected from 296 confirmed cases with onsets from September through December 2009. All samples were tested using the Centers for Disease Control and Prevention (CDC) capture IgM enzyme immunoassay (EIA) and a real-time reverse transcription-PCR (rRT-PCR) that targets the short hydrophobic gene. A subset of the samples (n ‫؍‬ 205) was used to evaluate 3 commercial mumps IgM assays and to assess the sensitivity of using an alternative target gene (nucleoprotein) in the rRT-PCR protocol. Among 115 cases of mumps with 2 documented doses of measles, mumps, and rubella (MMR) vaccine, the CDC capture IgM EIA detected IgM in 51% of serum samples compared to 9% to 24% using three commercial IgM assays. The rRT-PCR that targeted the nucleoprotein gene increased RNA detection by 14% compared to that obtained with the original protocol. The ability to detect IgM improved when serum was collected 3 days or more after symptom onset, whereas sensitivity of RNA detection by rRT-PCR declined when buccal swabs were collected later than 2 days after onset. Selection of testing methods and timing of sample collection are important factors in the ability to confirm infection among vaccinated persons. These results reinforce the need to use virus detection assays in addition to serologic tests.

Releasing the Genomic RNA Sequestered in the Mumps Virus Nucleocapsid

“…The Ebola virus outbreak in West Africa in 2014 (1) and the pandemic influenza A virus H1N1 outbreak in 2009 (2) are two recent examples. Some pathogens appear to reemerge in spite of available vaccines, such as mumps virus and measles virus (3)(4)(5). Effective controls are needed to combat these pathogens.…”

Challenges in Interpretation of Diagnostic Test Results in a Mumps Outbreak in a Highly Vaccinated Population

“…This is especially so where an enzyme immunoassay (EIA) is used as the diagnostic serology test, as this does not enable accurate quantification of antibody responses (18). Detection of IgM also presents diagnostic difficulties in vaccinated individuals, as a demonstrable increase in IgM levels following infection is often delayed or altogether absent in such individuals, even among those with positive RT-PCR results (16,18,22). The fact that the three IgM-positive serology specimens (see Table S3 [footnote]) had all been collected at Ն8 days after the onset of symptoms may be an indication of the need for delayed specimen collection when using IgM detection as a diagnostic test for mumps virus infection in vaccinated individuals.…”

“…With respect to serology, interpretation of results depends in part on the immunization history of the individual and the local prevalence of mumps, with most IgM-positive results in low-prevalence populations being false positives. Results of serological tests for IgM are often negative in individuals with acute wild-type mumps virus infections who have previously been vaccinated (16,19). In general, IgM analysis is considered acceptable as a diagnostic confirmatory test only if used in a patient who has been to a country where mumps is endemic or who is a contact of a patient with a confirmed case.…”

“…Of these two tests, RT-PCR is considered the more sensitive and specific; however, virus is most likely to be detected in specimens taken from day 7 before to day 9 after the onset of symptoms, with one study reporting that the likelihood of detection of RNA, despite the use of a relatively sensitive technique, declined for specimens collected from a highly vaccinated outbreak population more than 2 days after symptom onset (3,15,16). The recommended collection time window for testing buccal and throat swabs in Ontario provincial guidelines is Յ9 days after symptom onset and, for urine, Յ14 days after onset (17).…”

Epidemiology and the economic assessment of a mumps outbreak in a highly vaccinated population, Orange County, New York, 2009–2010

“…In a previously vaccinated case the timing of serum collection and the choice of the assay are both important as these individuals may not produce adequate levels of detectable mumps-specific IgM. 36 During this outbreak, of the 183 case-patients with documented 2 doses of MMR vaccine, 27 (15%) were found to be mumps IgM antibody positive while among the 17 case-patients with documented 1 dose of MMR vaccine, 2 (12%) were found to be mumps IgM antibody positive. PCR testing was conducted initially but with the confirmation of the outbreak, it was stopped.…”