Profiling mumps' behavior

In 2016 and 2017, a spike of mumps cases at Boston-area universities baffled epidemiologists, virologists and physicians. The unusual viral activity prompted researchers at Harvard Medical School, the Broad Institute of MIT and Harvard, and the Harvard T.H. Chan School of Public Health to dig deeper.

Now, in a newly published report, the scientists involved in this effort share the insights gleaned from profiling the disease’s behavior as it spread across the state and across the country. The findings appeared Feb. 11 in PLOS Biology.

Collaborating with the Massachusetts Department of Public Health and local university health services, the researchers used genomic data and public health records to profile the behavior of the virus.

Analyzing viral genomes from an outbreak vastly augments epidemiologic surveillance data and can show how a virus is evolving and is being transmitted—information that can help public health officials slow and stop the spread of disease, the researchers said.

“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,” said co-senior author Pardis Sabeti, institute member at the Broad Institute, professor at Harvard University and Howard Hughes Medical Institute investigator. “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.”

In Massachusetts, the typical mumps rate is fewer than 10 cases per year. In 2016 and 2017 the numbers spiked—more than 250 cases were reported in 2016 and more than 170 in 2017, despite high rates of vaccination. Many of the cases were from 18 colleges and universities in the state, including Harvard University, University of Massachusetts Amherst and Boston University. Other outbreaks flared elsewhere in Boston and across the country around the same time.

These unusually high patterns were intriguing. To learn more, the research teams paired traditional epidemiologic data with mumps whole genome sequences from 201 infected individuals, focusing primarily on the Massachusetts university communities.

As the outbreaks unfolded, the teams analyzed mumps genomes collected from patients, revealing new links between cases that first appeared unrelated and other details about how the disease was spreading that weren’t apparent from the epidemiological investigation. The teams shared their sequencing data and findings in real-time during the outbreaks, with both each other and the broader scientific community.

Mumps insight

The genomic analyses revealed details about the Boston-area outbreaks that could not be reconstructed by relying solely on more traditional approaches. For example, the researchers found a clear link between cases at Harvard and an outbreak in East Boston, which were classified as distinct outbreaks during the initial public health investigation.

Public health officials first thought the cases in these two communities were unrelated based on several pieces of evidence: epidemiological data, the different demographic makeup of the two populations (older adults with no obvious university connection versus mostly college-aged students), and a long gap between the apparent end of the outbreak at Harvard and the cases in the local community.

However, the genomic data indicated that the mumps viruses in the East Boston cases were genetically related to those in the Harvard virus samples. This finding enabled the teams to identify contacts and transmission links between the university and the wider community.

“Even though the two outbreaks were occurring at different places and different times, we were able to show connections between these outbreaks that were operationally informative,” explained senior co-author Bronwyn MacInnis, associate director of malaria and viral genomics in the Infectious Disease and Microbiome Program and co-lead of the Global Health Initiative at Broad. “The public health teams could determine that they were essentially dealing with one problem, not two.”

Understanding such transmission routes can help guide the outbreak response –– for example, by determining whether efforts should be focused more on controlling transmission within a single community or between different ones.

“Whole-genome sequencing of patient samples helps us reconstruct the progression of an outbreak,” said co-first author Shirlee Wohl, formerly a Harvard graduate student in the Sabeti lab and now a postdoctoral fellow at Johns Hopkins Bloomberg School of Public Health. “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.”

The team emphasized that this study was made possible by the close partnerships it had with the Massachusetts Department of Health and the health services teams at several universities.

“I am proud to be part of the Massachusetts higher education community,” Sabeti added. “They worked together and demonstrated the necessity of transparency in outbreak response. This is not a story of mumps at these universities, but of outstanding mumps reporting.”

Mutating mumps?

Another question of particular interest to the researchers was whether a new mutation in the mumps virus—for example, one that allows it to evade the immune defenses of a vaccinated individual—might have sparked the outbreak. Of the infected individuals, 65 percent had received the recommended two doses of the MMR vaccine. However, given the available data, the researchers found no evidence that new genetic variants arising specifically during this outbreak contributed to the disease spread. This finding suggests that, in the Boston area, the virus wasn’t evolving into one that could dodge vaccine-induced immunity.

In addition to the findings related to the Boston-area outbreaks, the study’s broader geographic analysis suggested that the mumps virus has been circulating continuously at a low rate around the U.S., only rarely flaring up into notable outbreaks as in 2016 and 2017.

“This whole endeavor demonstrated the value of genetic data to the epidemiological health response, and of data-sharing among collaborating teams,” Sabeti said. “One of our goals is to build this capacity in many areas around the world so that public health officials can rapidly mobilize and do this type of analysis whenever they need to.”

Co-first authors on this study include Hayden Metsky (Broad, MIT) and Steve Schaffner (Broad, Harvard, Harvard Chan School). Co-senior authors on this study are Paul Rota (Centers for Disease Control and Prevention), Larry Madoff (Mass. Department of Public Health, UMass Medical School), Nathan Yozwiak (formerly Broad/Sabeti lab), Bronwyn MacInnis, Sandra Smole (Mass. Department of Public Health), Yonatan Grad (Broad, Harvard Chan School, HMS) and Pardis Sabeti (Broad, Harvard, HHMI).

This study was supported by the National Institute of Allergy and Infectious Diseases (grants U19AI110818 and U54GM088558), Howard Hughes Medical Institute, a Harvard University Burke Global Health Fellowship, Amazon Web Services Cloud Credits for Research, and the National Institute of General Medical Sciences (grant T32GM007753).

Adapted from a Broad news release.