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Viral Genomes Trace Spread of Mumps in Vaccinated Population

NEW YORK – By combining genomic and epidemiological data, researchers were able to trace how the mumps spread in Massachusetts and elsewhere in the US during the 2016 to 2017 outbreak.

There are usually fewer than 10 cases of mumps every year in Massachusetts, but in 2016 there were more than 250 reported mumps cases and more than 170 cases in 2017, even among a highly vaccinated population.

A Broad Institute-led team of researchers sequenced mumps virus samples from more than 200 cases — many of which were from universities in the state — and paired that sequencing data with epidemiology data. As they reported Tuesday in PLOS Biology, the researchers found mumps has been circulating continuously both locally and nationally undetected and that one lineage has dominated infections since 2006.

"High-resolution genomic data about a virus, gathered from patient samples, allows us to reconstruct parts of an outbreak that aren't evident at first," co-senior author Pardis Sabeti from the Broad and Harvard University said in a statement. "The better we understand transmission chains in situations like this, the better we can inform efforts to control outbreaks and devise strategies to predict and stop them in the future."

The researchers generated 201 mumps virus genomes from buccal swabs obtained from patients who were positive for the virus on a PCR-based test. Of these samples, 158 were collected in Massachusetts during the 2016 to 2017 outbreak and 92 of them were from the Harvard, Boston University, or University of Massachusetts Amherst communities in particular. Forty-three samples were from other states.

Nearly all of these viral genomes belong to the same mumps genotype, mumps virus genotype G. A phylogenetic analysis of these new mumps genomes and 25 other publicly available genotype G genomes further revealed that they all belonged to a single lineage within genotype G, even though the samples hailed from all over the US. As this lineage descends from a 2006 US mumps outbreak, it suggests there has been ongoing transmission of this lineage since then and that unreported infections may be common.

But many of these infected individuals had been vaccinated, as about 65 percent of the infected individuals received the two recommended doses of the MMR vaccines. This increase in cases among vaccinated individuals led to speculation that the virus may have evolved a way around vaccine-induced immunity. 

However, the researchers found no evidence of positive selection at any gene or site in their mumps genomes, suggesting the virus wasn't turning into one that was outmaneuvering vaccine-induced immunity. 

This genomic data also enabled the researchers to examine how the virus spread. The analysis uncovered a connection between the mumps cases at Harvard and the local non-academic community, indicating a spillover event from the university into the community. The initial epidemiological investigation had not uncovered this connection, the researchers noted.

"Whole-genome sequencing of patient samples helps us reconstruct the progression of an outbreak," co-first author Shirlee Wohl, who was a grad student in the Sabeti lab and is now a postdoc at Johns Hopkins University, said in a statement. "Traditional outbreak surveillance efforts can help identify possible sources of infection, but whole-genome sequencing can confirm these links and even suggest new, unexplored connections."