Sharing local mumps genomes with the world

New mumps genomes and related sample information are being made freely available to the scientific community to help understand the virus’s rebound.

CDC
Credit: CDC

After decades of decline, several outbreaks of the mumps virus have flared up across the United States in recent years, especially among close-knit communities such as schools and universities. Notably, in 2016, the Massachusetts Department of Public Health (MA DPH) reported 252 mumps cases in the commonwealth, mostly associated with several Boston-area colleges. And the U.S. Centers for Disease Control and Prevention (CDC) reported more than 6,300 nationally — the most in a decade.

The recent spikes in mumps cases have researchers and public health officials asking several questions: Why is mumps spreading among vaccinated individuals? Has the virus mutated so that the vaccine is less effective? Is immunity from the childhood mumps vaccine waning in early adulthood?

To promote investigation of these questions, our team in the Broad Viral Genomics group (including Shirlee Wohl and Pardis Sabeti) — in partnership with Sandy Smole and colleagues at MA DPH, Yonatan Grad at the Harvard T.H. Chan School of Public Health, and Paul Rota and colleagues at the CDC — have released the genome sequences of 123 mumps virus isolates collected from patients in Massachusetts in 2016.

These data — available openly to the global scientific community via NCBI GenBank, along with corresponding sample data — more than doubles the mumps clinical sequence data available to the public. In the coming weeks, we plan to generate and share additional mumps genomes from Massachusetts patients diagnosed in 2017, and from patients in additional states.

Historically a common childhood illness, the number of reported mumps cases dropped more than 98 percent over the last 50 years thanks to routine vaccination. Since 2006, however, the US has experienced some large mumps outbreaks in highly vaccinated populations. Our team and partners will use sequences from recent outbreaks, along with patient vaccination histories and outbreak contact data to better understand why these outbreaks are occurring.

US mumps cases reported to the CDC since 2000. The case counts for 2016 and 2017 are considered preliminary. 2017 case count as of October 7, 2017. (Credit: CDC)

 

At a local/regional level, we also plan to use these new and additional future data to study the origin and spread of the recent Massachusetts outbreak across institutions and individuals. Mumps can be hard to trace because many patients never show symptoms, and those that do can spread it before those symptoms appear. But we can use the genetic changes mumps accumulates as it moves from place to place over time to draw a more detailed map and timeline of an outbreak. Ultimately, the better we understand mumps transmission chains, the better we can devise strategies to predict and stop future outbreaks.

The 123 genomes (114 of which are near-complete) also represent a shift in molecular epidemiological studies of this virus. Studies of mumps genetics have largely focused on one viral gene, the short hydrophobic (SH) gene. Comparing SH sequences is useful for tracking mumps circulation globally, but does not provide the resolution needed to follow transmission locally.

Thanks to sample processing innovations and reduced sequencing costs, complete genome sequencing of mumps is now widely possible. As a result, with our CDC and MA DPH partners, we aim to bolster mumps surveillance nationwide by making full-length sequencing a routine component of future mumps outbreak investigations.

This mumps sequencing effort builds on our group’s past experiences working together with long-term collaborators and forming partnerships with new ones to quickly generate and share virus genome data during major outbreaks, especially the 2014-15 Ebola outbreak in West Africa and the 2015-16 Zika outbreak in the Americas. The common thread linking these investigations is our desire to create a barrier-free, open exchange of genomic data for use among the wider science community.

We thank the National Institute of Allergy and Infectious Diseases and the Howard Hughes Medical Institute for their support of this work.

Nathan Yozwiak is the associate director of viral genomics in the Broad Institute's Infectious Disease and Microbiome Program.