Getting infected with measles is much more dangerous than scientists once suspected. In addition to the illness caused by the virus, a measles infection also takes a wrecking ball to the immune system. It destroys up to half of the existing antibodies that protect against other viruses and bacteria, according to research published Thursday.
That means people, especially children, who get measles become much more vulnerable to other germs that cause diseases such as pneumonia and influenza that they had previously been protected against.
The discoveries have enormous and immediate public health implications, researchers and clinicians said, and underscore more than ever the importance of measles vaccination. In recent years, anti-vaccine misinformation has been one reason vaccination rates have plummeted and global measles cases have surged. This year, the United States has had 1,250 cases of measles, the most since 1992.
Measles is not a harmless illness, as some anti-vaccine activists falsely claim, but one with deadly consequences. Most people, even doctors, have never seen the consequences of the disease because it became so rare thanks to vaccination and was declared eliminated in the United States in 2000.
"The big thing we show here is that even if a child gets through measles — and you have to be lucky to get through the measles infection — you're setting your kid up to be at increased risk to all these other infectious diseases that they could encounter on any given day," said Michael Mina, an infectious disease epidemiologist at Harvard's T.H. Chan School of Public Health and lead author of the first study, published in Science.
More than 7 million people are estimated to have been infected with measles in 2018, according to global health officials. Comprehensive coverage with measles, mumps, rubella vaccine would prevent more than 120,000 deaths directly attributed to measles this year, and it could also "avert potentially hundreds of thousands of additional deaths attributable to the last damage to the immune system," the authors wrote.
Mina and investigators from Harvard Medical School, Brigham and Women's Hospital, analyzed blood samples of 77 unvaccinated children before and two months after a measles outbreak in 2013 their Netherlands community, which is religiously conservative and opposed to vaccination. Using a tool that tracks antibodies, they found measles infection wiped out 11% to 73% of different antibodies that "remember" past encounters with germs and help the body avoid repeat bouts of influenza, herpes virus, pneumonia and skin infections.
No loss of antibodies was observed in children vaccinated against measles, mumps and rubella.
Mina and his colleagues found that those who survive measles gradually regain their previous immunity to other viruses and bacteria as they get re-exposed to them. But the process may take months to years. In the meantime, people remain susceptible to serious complications of those infections, he said.
A second study, in the journal Science Immunology, analyzed the antibodies collected from blood samples of 26 children from the same group of unvaccinated Dutch children. Researchers from the Wellcome Sanger Institute, University of Amsterdam and their collaborators sequenced their antibody genes and found that specific immune memory cells were no longer in the blood of two children after measles illness, leaving them vulnerable against infectious diseases they had previously been protected against.
Past studies suggested that measles virus wipes out a significant portion of essential immune memory cells that protect the body against infectious diseases, creating "immune amnesia." The findings by the two international teams of researchers are the first to measure how that damage occurs.
Doctors who treated children during New York City's measles outbreak this year are starting to see children getting subsequent severe infections that require hospitalization. New York's outbreak was centered in the ultra-Orthodox Jewish community that was targeted by anti-vaccine activists. Many parents were reluctant to get their children vaccinated against measles.
The two studies "break open and elucidate the pathway of how a child becomes immune-compromised after measles, and it's pretty devastating," said Jennifer Lighter, a pediatric infectious disease physician and epidemiologist who helped lead the measles response at NYU Langone Medical Center and was not involved in either study. Fifty children were treated at NYU Langone; about half were admitted. The measles, mumps and rubella vaccine, or MMR, "clearly has protection much greater than we previously recognized," she said.
At least three children who had measles developed subsequent severe infections, Lighter said. Clinicians are already pondering whether children who had measles should now get booster shots for other diseases, Lighter said.
The Harvard-led team's discovery happened by accident. Stephen Elledge, a genetics professor at Harvard Medical School and Brigham and Women's Hospital, was fine-tuning a tool he had developed that gives a snapshot of a person's entire history of antibodies to viruses and bacteria from a single drop of blood. Elledge's lab was having trouble detecting measles antibodies.
The researchers teamed up with Dutch scientists who had collected blood samples from the 77 unvaccinated children before and after the 2013 measles outbreak in an Orthodox Protestant community in the Netherlands.
When they measured the children's antibodies before and two months after measles infection, Elledge's team had no trouble seeing the measles antibodies. But they also noticed something remarkable. There was a striking drop in antibodies from other pathogens.
Depending on whether the measles infection was mild or severe, the children lost on average about 50% of their total antibodies acquired over a lifetime of fighting infections, Mina said. Some lost over 70% of their preexisting antibodies.
"This proved to be the first definitive evidence that measles affects the levels of protective antibodies themselves, that it's damaging your immune system and making you more susceptible to other infections later on," Elledge said.
The virus has unique capability to directly attack immune memory cells, mostly in the bone marrow, that produce almost all antibodies, Mina said.
Working with a team at Johns Hopkins Bloomberg School of Public Health, researchers repeated the experiment in four macaque monkeys. They collected blood samples before and up to five months after measles infection. The results were even more dramatic. The monkeys lost, on average, 40% to 60% of the antibodies that protect them from other pathogens.
Doctors say the findings have practical implications for immune-compromised children and adults who can't get the measles vaccine.
"This has huge implications not only for children, but for all the friends and family members of people who are undergoing cancer therapy or organ transplants with weakened immune systems," said Helen Boucher, an infectious disease expert at Tufts Medical Center. "Surviving cancer or surviving a heart transplant, they can tolerate. But for those at huge risk from measles, their immune system can't take it."