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    Discovery’s Edge: Mayo experts on the measles outbreak

The recent measles outbreak in Minnesota reached an unfortunate milestone (and extensive national news coverage) on June 1, 2017 when it exceeded the total number of cases reported in the entire United States last year. The disease is particularly tricky to control because it can linger in the air for hours, waiting to be inhaled.

“You can't predict when you’ll be exposed to measles,” says Gregory Poland, M.D., a Mayo Clinic vaccine researcher. “If you get on an airplane, visit Disneyland, go to a mall, or frequent any place where there are other people, you're at risk.”

Once contracted, a measles infection is not trivial. The virus causes fevers over 104°F, a hacking cough, runny nose, enflamed eyes, and a full-body rash. It can trigger severe complications, such as pneumonia, brain swelling, and blindness. For every 1,000 children infected, three will die. And every new infection creates another opportunity for the potentially fatal virus to spread. Essentially anyone who is not nonimmune and is exposed to an infected measles patient will end up getting the measles themselves.

Roberto Cattaneo, Ph.D., is an international expert on the measles virus and is credited with discovering why it is extremely contagious.

Roberto Cattaneo, Ph.D., a Mayo Clinic molecular biologist who has been studying the virus that causes measles for three decades, is the scientist who discovered what makes it so contagious (Nature, 2011). Unlike other respiratory viruses that settle in the lungs, measles replicates in the windpipe, which it uses like a trampoline to bounce millions of infectious particles into the air.

"The measles virus has developed a strategy of diabolic elegance," said Dr. Cattaneo. Once inhaled, the virus hijacks immune cells patrolling the lungs to get into the host’s system. Then it multiplies in lymph nodes and in the organs producing new circulating immune cells. Those circulating immune cells deliver the infection to cells lining the trachea. There, the virus multiplies again before inducing spasms of coughing to launch itself out of the patient and possibly onto its next victim.

Dr. Cattaneo is now investigating how the virus, known to inhabit the immune and respiratory systems, also manages to find its way into the brain to cause a rare and deadly brain disorder called subacute sclerosing panencephalitis (SSPE) that appears years after infection.

“It is another unsolved mystery of measles virus spread, but I think we have the answer,” said Dr. Cattaneo. “We’re still working out the details now, but it appears to get into the brain by a completely different mechanism than it uses to get into immune cells and out of the host.” Understanding how the measles infiltrates different organ systems could lead to new ways to prevent its most dangerous complications.

Of course, there is already a pretty effective way to prevent those complications: vaccination.

And getting vaccinated is more important than ever. The disease still kills more than 100,000 people a year, most under the age of five. To be protected from the virus, people need two doses of the MMR vaccine. The first dose is given to infants after their first birthday, and a booster is given between four and six years of age. Those two doses are about 97 percent effective against infection.

Impressive, but not perfect.

To protect the remaining three percent – as well as babies or people with compromised immune systems who are also not immune to the virus – requires something known as herd immunity. When a critical proportion of the community is immunized against the disease, then most members will be protected because there is little opportunity for an outbreak.

Vaccine expert Gregory Poland, M.D., looks forward to new vaccines individualized for each patient.

The more contagious the disease, the more people that need to be vaccinated to protect the herd. Dr. Poland says that for measles, that threshold is 95 percent. According to the Centers for Disease Control, only 91.5 percent of children received the MMR vaccine in 2014, the last date such data was available.

As head of Mayo Clinic’s Vaccine Research Group, Dr. Poland is studying why the vaccine works better in some people than in others in the hopes of building a better vaccine. In an approach he calls “vaccinomics,” He and his team are searching for genetic signatures of people who have abundant, luxuriant protective responses to the current vaccine and will use that data to reverse engineer novel vaccine candidates.

The ultimate goal is to design a vaccine that is more effective, easily administered, biodegradable, cheap, and storable indefinitely. Poland says vaccinomics could also be used to develop types of vaccines that are tailored to each individual’s genetic profile. For example, an individualized genetic screen might identify who is at risk for a serious adverse side effect, who might need multiple doses, as well as those who are already immune to the disease and therefore can skip the shot altogether.

For now, two doses of the MMR vaccine remain the best shot at avoiding a measles infection. Convincing parents to make that decision requires an entirely different kind of personalized medicine – one that takes into account each individual’s biases and belief systems.

“I have come to believe that a wise clinician understands where the patient is coming from in their decision-making process and then adapts their education method to the cognitive style of that patient,” said Dr. Poland. “I find there are very, very few people that I ever see as a clinician who don't end up getting their vaccines. Maybe not at the first meeting or the second, but eventually they do.”

- Marla Vacek Broadfoot, June 2017

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