Measles vaccines protect against more than just measles. Here's how.

Without vaccination, the highly contagious virus can allow other diseases to flourish in unsuspecting populations for more than two years after an infection.Monday, 8 April 2019

By Maya Wei-Haas
<p>A doctor's assistant prepares 11-month-old Tijana for a vaccine against measles, rubella, mumps, and chicken pox in Berlin, Germany, in 2015.</p>

Measles is spiking worldwide, UNICEF announced on March 1, with 98 countries reporting more cases in 2018 than in the prior year. Spread through the air, measles is highly contagious, and the virus can linger in a room for up to two hours after an infected person has left.

But danger lurks even for those who survive an outbreak. Measles not only weakens your immune system in the short term, bouts with the virus seem to wipe your immune system's memory, causing the body to forget how to fight off things that you may have already conquered. For some people, this “immune amnesia” may linger for more than two years.

Before the introduction of the measles vaccine in 1963, it was nearly guaranteed that every child would catch it, and an estimated 2.6 million died from the disease each year. Luckily, the measles vaccine is incredibly effective, with two doses imparting nearly 97-percent protection. So why can't we get rid of the disease?

In some parts of the world, infrastructure issues and civil strife have been interfering with vaccination campaigns and are partly behind the recent spike in cases. But that's not the only issue: complacency about vaccination is also a factor, according to UNICEF.

“The benefit of the vaccines has actually been kind of its own downfall,” says Yvonne Maldonado, an epidemiologist at Stanford Medical School. “People just don’t see this as a relevant intervention.”

However, the data show that’s not the case: Not only did cases of measles plummet once vaccine use became widespread, but cases of other diseases dropped as well—pneumococcus, diarrhea, and more. In resource-poor regions, the decline was as dramatic as 50 percent; in impoverished regions, it dropped by as much as 90 percent.

“We actually saw the whole overall baseline for childhood mortality drop precipitously,” says Harvard's Michael Mina, an author on a 2015 study analyzing the decline. In essence, the measles vaccine seems to not only protect populations against measles, it seems to be keeping a slew of other infections at bay. And one way it may be doing this is through prevention of immune amnesia.

Anatomy of the infection

Over the years, scientists had accumulated clues to measles' mysterious mechanism, including the viruses' seeming proclivity for attacking the immune cells. But the puzzle remained incomplete. So Rik de Swart, a virologist at Erasmus University Medical Center, and his colleagues set out to find the missing pieces.

The team exploited one viral necessity: To multiply and spread, a virus has to invade a cell, hijacking the machinery to copy itself. So they inserted a gene in the measles virus that encodes for a fluorescent protein and introduced the modified virus into macaques. As the modified virus invades the cells to make copies, its host will light up, letting the scientists track its movement at various stages of the disease.

Health officers prepare a measles and rubella vaccine before immunization at an integrated health service post in Wanasari Village, West Java, on September 8, 2017.

Everywhere the monkey has lymphoid tissues—which house immune cells—glowing green speckles appeared, twinkling like stars in the night sky. These winks of light revealed that the virus favors what's known as immune memory cells. These cells record and catalog your lifetime of infections, helping you efficiently battle future invaders on repeat encounters. Later in the infection, the virus also settles into the surface lining of the lungs and nose, which help it launch into the air with each cough.

Once the immune system kicked in to clear the infection, this viral constellation vanished. The sudden darkness highlighted an important step of immune amnesia: By infecting memory cells, the virus not only wiped out some of the body's immune recollections, it essentially turned the system against itself by forcing healthy immune cells to kill off their infected comrades.

“If the virus didn’t kill those memory cells already, the immune system would finish the job off,” de Swart says. “We could literally see it happening under our hands.”

The team later confirmed that a similar mechanism is likely at play in humans. But it's unclear exactly how much immune memory vanished; that probably varies from person to person, de Swart notes. Still, the process emphasizes why secondary disease is so common with measles: Not only does the virus assault the immune system's first line of defense and damage your skin, respiratory, and gastrointestinal tract, it also erases your other hard-won resistances.

Health workers in northern Laos inoculate children in 1991 as part of a UNICEF-sponsored health drive against polio, measles, tetanus, and other potential ailments.
A nurse prepares a measles vaccine in a school in Lapaivka village, near the western Ukrainian city of Lviv, on February 21, 2019. Ukraine had the highest incidence of measles in 2018, with more than 30,000 confirmed cases. Since the start of 2019, more than 20,000 people in Ukraine have been infected.

Lingering effects

For Mina, the monkey's glowing innards raised a nagging question: “If measles is essentially chewing up all of our immune cells, does that have a long-term impact on our immune memory?”

To tackle this question, Mina and his colleagues turned to massive data sets from the United States, Denmark, England, and Wales from before and after widespread vaccination began in the 1960s. The analysis revealed that declines in childhood disease were stark. In general, when measles was flourishing in unvaccinated populations, up to half of all childhood deaths from infectious disease could be explained by non-measles infection that occur following illness with measles.

What's more, the effects lingered. At any given time, the best predictor of non-measles deaths was the total number of measles cases during the prior three years, Mina explains. This suggests that kids with measles still had a higher risk of death from infections three years later. But these temporal relationships can only tell the scientists so much.

“At the end of the day, that's all epidemiological associations,” Mina notes. “You have to drill into the biology.”

Here, too, scientists have started to make a dent. In one study, the researchers found that U.K. children who had measles also had an increase in infections and doctor's visits in the years after infection. Mina's team also developed tests to catalog antibodies—or invader-neutralizing proteins formed by one type of memory cell—in a blood sample. Instead of looking at just one type of antibody at a time, as most tests require, he's created tiny biological sensors that can flag hundreds of thousands in one go. By testing before and after a measles infection, scientists can actually quantify which and how many antibodies someone has lost after an infection.

Global spread

So could secondary infections affect people who currently have measles in the United States?

“I absolutely think so,” Mina says, though he emphasizes that the U.S. healthcare system is strong enough to treat these infections and prevent most of them from turning deadly.

That isn't the case in many developing regions, where something as seemingly mild as diarrhea can kill. And because the virus attacks the immune system, the severity of infections depends on the general health of the population. In essence, measles acts like an infection amplifier, turning up the volume of background disease. This means that in resource-limited areas, the virus will cause higher overall death rates.

“In lots of developing countries still today, we see one in 50 or one in a hundred kids still dying from measles, primarily due to these sort of immune effects,” Mina says. To make matters worse, measles is contagious long before those infected even know it, making it easy for the virus to tag along if its unwitting hosts take to traveling.

“This is a virus that doesn’t stop at borders,” de Swart says, referencing a famous saying: “You cannot stop measles anywhere if you don’t stop it everywhere.”

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