Measles was once seen as a childhood disease. Increasingly, adults are susceptible, too

Simon Matthews made three trips this spring to the emergency room of his local hospital in Eastbourne, on England’s southeast coast, before doctors managed to figure out what was making him so ill.

He had a fever of 104 Fahrenheit, uncommonly high for an adult. On his first foray to the hospital — in an ambulance — it was feared he had meningitis. Cleared of that, Matthews, 62, was sent home with a vague diagnosis; doctors believed he had an unidentified viral infection.

But in addition to the fever, Matthews had the beginnings of what quickly turned into an itchy, full-body red rash — a type that a few decades ago all parents dreaded, and all doctors recognized.

Not so these days. It would take two more visits and a pair of Nigerian physicians, who had experience diagnosing this rash, before he would learn that he was suffering from measles.

“The fever was pretty brutal,” Matthews told STAT. “The rash is incredibly itchy. Drove me nuts.”

In fact, he was one of a number of adults in Eastbourne who contracted measles this spring, he was told. The infection was once a rarity in adults. But the reality of measles as a disease that strikes almost uniquely in childhood is changing. The shift is driven in part by the fact that the first wave of children whose parents shunned vaccination in the late 1990s and early 2000s — in response to a fallacious, since-retracted study in the Lancet that linked measles vaccine to autism — are now in young adulthood.

A recent report from the United Kingdom’s Health Security Agency suggested the growing pool of non-immune adults — known as susceptibles in the lexicon of epidemiology — could fuel future measles outbreaks.

There is also a growing body of adults in this country who have no immunity against measles, experts say. In fact, since the year 2000, about 40% of measles cases in the U.S. have been in adults, with about one-quarter in people aged 20 to 29.

The growing susceptibility of adults worries infectious disease experts who know how difficult this infection can be when it is experienced in adulthood. To be clear, measles is hardest on babies. But after that very vulnerable demographic, those most likely to be hospitalized for measles infections are adults over the age of 25.

Many adults, like Matthews, come through it just fine, albeit with very unpleasant memories. But in some adults, measles triggers a dangerous brain inflammation called post-infectious encephalomyelitis. In some, it sets off a hard-to-treat lung condition called acute respiratory distress syndrome, or ARDS, which can lead to a need for mechanical ventilation. Both conditions can be fatal, and people who survive encephalomyelitis may sustain lifelong neurological damage. Measles can also induce hepatitis, an inflammation of the liver, a 2020 study of adult measles cases in Greece reported.

“It’s not a trivial illness. And I think people need to realize that,” said Walter Orenstein, a professor of infectious diseases at the Emory University School of Medicine.

It’s not super surprising doctors didn’t think of measles when Matthews sought care. In many high-income countries, most doctors have never seen a case of measles, so effective have been the vaccines that were introduced in the U.S. in 1963 and in the U.K. in 1968.

Even before the vaccines were rolled out, measles infections in adults were uncommon. That’s because the virus transmits so efficiently that in the pre-vaccine days, almost no one escaped childhood without having contracted measles.

“Basically everybody got it by school age. Everybody got it in first grade if they hadn’t gotten it before, because it is so infectious,” said Diane Griffin, a professor of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health.

Family lore is that Matthews and his three siblings all had measles before measles vaccination began in the U.K. The family doctor didn’t offer to vaccinate them, on the assumption they were already immune. Measles is generally considered a one-and-done type infection; though there are reports of second infections in the medical literature, they are rare. Whether Matthews is one of those rare cases is a question that probably can’t be answered.

His case this spring was uncomplicated, as adult measles cases go. But it was absolutely no fun.

At a point he woke up to find his arm bleeding, he had scratched it so persistently in his sleep. “Once the fever had gone, it was just the rash and just feeling really weak and exhausted,” he said.

Matthews was in bed for 11 straight days, and it took about a month, he estimated, before his energy levels were back to pre-illness levels.

His wife, Jennifer — a few years younger, and vaccinated — didn’t catch measles.

The Health Security Agency report used mathematical modeling to estimate how likely it is that the U.K. could experience large outbreaks of measles. It concludes that the risk does not exist across the entire country at this point, but that London, with its massive population and pockets of communities with very low vaccination rates, could see outbreaks involving between 40,000 and 160,000 cases — an extraordinary prospect given the efficacy of the measles vaccine.

While outbreaks would span a range of ages, the report identifies young adults as helping to fuel the risk, because vaccination rates in that age group are lower than what is needed to keep measles transmission from taking off, if the virus is introduced into the population.

“Accumulation of susceptibles in older age groups over time will increase the risk of epidemics in the longer term,” the report stated.

The risk of an explosive outbreak along the lines of what the Health Security Agency predicts for London is likely lower in the United States, said Orenstein, who suggested the school entry immunization requirements that the U.S. has had — requirements the U.K. did not impose — have kept vaccination rates higher in this country than in Britain. (A number of states have taken aim at school vaccination mandates in the wake of the Covid-19 pandemic.)

“In our population, I think because of our [school entry] mandates and all, we generally have reasonable levels in most communities of immunity to measles,” he said. “I think the big concern is in subpopulations, such as the Orthodox Jewish community, where we almost lost our measles elimination status in 2019.”

Orenstein was referring to measles outbreaks in and near New York City that began in 2018 and spread through unvaccinated members of Orthodox Jewish communities. It took nearly a year to extinguish the outbreaks, putting the U.S.’s position as a measles-free country in jeopardy.

Griffin agreed with Orenstein that the risk of big outbreaks is probably higher in the United Kingdom. But she said the possibility of increasing cases in adults is something that worries her.

“We know that certain complications of measles are more common in older individuals. … And neurologic complications are one of those. The post-infectious encephalomyelitis is a complication that’s not usually seen in young children but is more likely in children and adults,” Griffin said. “That complication, which is more common in older individuals, I think is a real concern for measles occurring in that age group.”

Griffin noted that about 20% of people who develop post-infectious encephalomyelitis die.

Measles also presents a substantial threat to pregnant people, with complications not only for the pregnant individual but any infants who catch measles at or after birth.

Sonja Rasmussen, a professor of pediatrics at Johns Hopkins School of Medicine, co-authored a review of the medical literature on measles in pregnancy for an article published in 2015 in the journal Obstetrics and Gynecology. The good news, she and her co-author wrote, is that there is no evidence that measles infection during pregnancy causes congenital defects in babies, in the way rubella infection does.

But they went on to say that there is evidence that measles infection is bad news. “Pregnant women infected with measles are more likely to be hospitalized, develop pneumonia, and die than nonpregnant women. Adverse pregnancy outcomes, including pregnancy loss, preterm birth, and low birth weight, are associated with maternal measles,” they wrote.

If the mother gets infected near the time of her delivery, there is also a risk the baby could have measles at birth. “Babies can be very, very sick with measles,” Rasmussen told STAT.

The expanding pool of vulnerable adults isn’t simply made up of people whose parents believed that the measles vaccine causes autism. It’s actually bigger than that. There are people, like Matthews, who perhaps should have been vaccinated when the measles vaccine first became available, but were not. Even now, there is a presumption that anyone born before 1957 has measles immunity, because they were probably infected in childhood.

There are, of course, exceptions to every rule. Griffin recalls that a number of years ago, a friend told her she thought she was vulnerable to measles, because she hadn’t had it when she was a child. Her doctor wouldn’t vaccinate her, citing the “born before” guideline. Griffin tested her friend’s blood for measles antibodies, found she had none, and promptly vaccinated her.

The adult pool of susceptibles also includes people who were vaccinated, but were not protected. The measles vaccine is highly effective; two doses protects 97% of people. But that leaves 3% who remain vulnerable. One dose of measles-containing vaccine — which was the recommendation in the U.S. until 1989, and in the U.K. until 1996 — protected on average 93 out of 100 people vaccinated.

There’s even evidence that waning immunity could increase the pool of adults who are susceptible to measles, said Michael Mina, a former Harvard University epidemiologist who has studied the disease extensively.

All the data on how well the measles vaccine protects people was generated at a time when the measles virus was still circulating broadly. That meant many people who were vaccinated were having their immunity naturally boosted, by sporadic exposure to the virus. This phenomenon, called anamnestic boosting, is no longer happening, Mina said.

“I would not be surprised if in the next 10 years, we end up with a whole lot of people who are now in their 60s … who have never seen the virus, whose immunity starts to wane, just as it does, who then actually fall below protective [antibody] thresholds,” he said.

One could actually chart this by looking at measles antibody data from hospitals, which require employees to be tested every few years to ensure they’re still protected. Mina, whose measles immunity is derived from vaccination, tested his own antibody titers a few years back and discovered they were low. “So I got a booster.”

Another possible implication of measles infections in adults is something Mina has studied in children, a condition called “immune amnesia.”

In a paper published in Science in 2019, he and colleagues reported that measles infection wipes out a swath of children’s existing antibodies, leaving them more vulnerable to all sorts of other infections in the years that follow their bout with measles. In a 2018 paper, using health data from the U.K., Mina and co-authors compared hospitalization and drug prescription patterns of children who had had measles to those who had not. They found the children who had had measles were three times more likely to receive an antibiotic in the first month after having the infection and between 15% and 24% more likely to receive anti-infective drugs over the next five years.

Whether measles triggers immune amnesia in adults is not known; it hasn’t been studied. Getting a definitive answer would be a complicated task, Mina said.

“When you’re talking about immune amnesia, you’re really talking about following people for years to understand: Are they dying at higher rates? Are they getting sick at higher rates? Having infections that they shouldn’t otherwise really be getting infected with? And that’s a really hard study to do,” he said.

Griffin, whose lab has researched measles-induced immune amnesia in primates, and who was a co-author on the 2019 Science paper, believes it likely does happen. “I don’t know any reason why it would be different in adults, frankly,” she said.

The fact that adults have built up a broader array of antibodies might make the impact of measles-induced immune amnesia less profound in adults. “Every time we see a virus we develop yet another B cell clone to give us protection or another T cell clone,” Mina said. “So we do have redundancy in a way that the youngest of children don’t have. So maybe that ends up protecting us a little bit.”

But he thinks there is an immunity toll to pay for having measles infection, regardless of the age at which a person contracts it.

“The impact of measles is like having to live the next few years of your life always looking over your shoulder, wondering if you’re at increased risk to some pathogen you’ve never even thought about,” Mina said. “And in general, that’s what the data suggests and shows that you are. It destroys memory cells that are meant to protect you for very long periods.”