Measles outbreaks could leave thousands vulnerable to infectious diseases for years
Liz Szabo, MAToday at 1:00 p.m.
Measles infections make people miserable for up to two long weeks, commonly causing dangerously high fevers, a painful sensitivity to light and, of course, a tell-tale red rash.
Sufferers who escape without developing pneumonia, brain swelling, or other serious complications may believe the worst is over.
Yet the measles virus has only gotten started.
The virus also damages the immune system, leaving people vulnerable to other infections for up to five years.
“The rash and the fever, that’s the tip of the iceberg,” Michael J. Mina, MD, PhD, coauthor of two seminal studies in Science on the effect of measles on the immune system, told CIDRAP News. “The majority of the damage being done is under the surface.”
The measles virus hijacks the immune system, using specialized memory cells to make copies of itself before blowing them up, Mina said. By deleting the body’s memory of earlier infections, measles causes a condition called “immune amnesia.”
Without those memory cells, the body essentially forgets how to fight off infections it defeated before. That leaves people newly vulnerable to bacteria and viruses against which they were once protected, either through infection or vaccination.
‘Thousands of additional medical clinic visits’
Immune amnesia “happens in 100% of measles-infected individuals to some degree,” Mina said.The condition causes more harm in some people than others, depending on how much immune memory is deleted, which immune cells are destroyed, and a person’s age and underlying health, Mina said.
A child whose immune system forgets how to fight off the common cold, for example, may suffer the sniffles and sneezes of last year’s respiratory viruses a second time.
But a baby who loses the protection provided by whooping cough (pertussis) vaccines could end up hospitalized.
A woman who loses her immunity against chickenpox, which causes much more severe disease in adults than in children, could develop pneumonia, Mina said.
With more than 6,000 measles infections in less than two years, immune amnesia could pose a real threat, Mina said.
“We will see thousands of additional medical clinic visits,” said Mina, chief medical officer at Invivyd, a biotech company developing experimental treatments for measles. “If your child gets measles, you have to be looking over your shoulder” for years.
Children in poor health are especially vulnerable
Children who are sick or malnourished before contracting measles are especially vulnerable to additional infectious diseases, said Boghuma Titanji, MD, PhD, an infectious disease specialist and assistant professor of medicine at the Emory University School of Medicine.Titanji treated many children affected by immune amnesia in Cameroon, which has one of the highest rates of measles in the world. Those suffering from malnutrition were more likely to be hospitalized, she said.
“After a child is admitted to the hospital for measles, they're more likely in the year or two that follows to be readmitted multiple times for a variety of viral, bacterial, or parasitic infections,” Titanji said.
In West Africa, children who survived measles were more likely to be later infected with malaria, Titanji noted. “In general, they were just more sickly children,” she said.
But immune amnesia isn’t limited to developing nations.
Recent studies have found evidence of immune amnesia in wealthy countries with strong healthcare systems, including Germany, Israel, Switzerland and the United Kingdom. Children in these studies who had been infected with measles were more likely than others to need antibiotics or visit the doctor.
“Immune amnesia is probably something that we're going to encounter” in the United States, said C. Mary Healy, MD, an associate professor of pediatrics and infectious disease specialist at Texas Children’s Hospital. “We’re on the cusp of finding out just how significant immune problems may be.”
Pain seared into her memory
When Crystal Webster moved to Switzerland in 2008 at age 27, she wasn’t aware that the country was experiencing its largest measles outbreak in years.Like most children born in the 1980s, Webster received a single dose of measles-containing vaccine as a baby, which was standard practice at the time. One dose of the measles, mumps, and rubella vaccine prevents 93% of measles infections; two doses prevent 97%.
When Webster broke out all over in red pustules that looked “almost like zits,” she looked up her symptoms online. She learned that her itchy rash, fatigue, cough, runny nose, and pink eye were all classic symptoms of measles.
The misery of measles is seared into Webster’s memory. She felt a blaze of pain any time that one of the pustules came in contact with something else.
“I remember lying on the wood floor, completely naked, spread eagled, because I didn’t want any part of my body to touch any other part of my body,” said Webster, now 44.
The summer heat made Webster’s skin feel even worse, especially since her home had no air conditioning.
The following winter, Webster said, “I felt like I always had a runny nose.” But she chalked her constant colds up to living in a new environment with unfamiliar germs.
While it’s impossible for doctors to know for certain if Webster’s symptoms were caused by immune amnesia, “her increased respiratory infections in the year immediately following measles are certainly consistent with what we know about this phenomenon,” Titanji said.
An unwelcome souvenir from her measles infection
A few years later, after Webster had returned to the United States, she broke out in a red, painful rash around her waistline. A doctor at an urgent care clinic confirmed Webster had shingles, which can afflict adults who, like Webster, had chickenpox as a child.Although chickenpox typically goes away after four to seven days, the virus that causes the disease, called varicella-zoster, sticks around for decades, hiding in nerve cells of the spinal cord. The virus can re-emerge as people age or if they become immune suppressed.
Shingles was just as painful as measles, Webster said. “I wrapped my stomach in gauze so that my pants wouldn’t rub up against the blisters,” said Webster.
Webster’s shingles infection also could have been caused by immune amnesia, Mina said.
“It’s very likely her measles infection would have deleted or drained a portion of her antibodies against varicella, driving her to have increased susceptibility to [shingles] rearing its head early,” Mina said.
Webster said she assumed her infections were due to bad luck.
“I was pretty young to have all these things,” Webster said. “I thought I had done what I needed to do to be healthy.”
Difficult diagnoses to make
Like Webster, many people with immune amnesia don’t connect their illnesses back to measles, said Pia Pannaraj, MD, MPH, vice chair of the American Academy of Pediatrics’ (AAP) Committee on Infectious Diseases.Measles amnesia “often goes undiagnosed,” said Pannaraj, who has treated measles patients in the United States, Asia, and Africa. “People get measles, and then afterwards they will have recurrent ear infections or pneumonia, but they don’t tie it back to measles. They think, ‘Oh, this is just bad luck that I happen to have this ear infection or that I got pneumonia.’”
Even doctors may be unfamiliar with immune amnesia, which scientists have only truly begun to understand in the past 15 years, Pannaraj said. Most doctors learned little about the condition during medical school or residency.
Pannaraj is a member of the Measles Collaborative, a newly formed coalition of healthcare providers and public health experts that aims to strengthen measles prevention, response, and education.
“The people who are getting measles now tend to be those that are unvaccinated and may not interact with the medical system very often,” she said.
A childhood of illness
Before vaccines became available, virtually all children contracted measles.Suzanne, 71, became severely ill with measles when she was 6 years old, two years before the measles vaccine was released.
“It’s been over 60 years, and I can still picture how sick I was,” said Suzanne, a human resources consultant who lives in Fort Myers, Florida, and asked to be identified only by her first name to protect her privacy. Suzanne’s account of her illness was confirmed by her older sister.
Suzanne said she remembers lying in bed, with “big sheet around me like a tent” to protect her eyes, which measles had made very sensitive to light.
“My mother put cold, damp clothes on my head, and everyone was standing around like, ‘Is she going to die?’” Suzanne recalled. “My parents said I was on the verge of being hospitalized when my fever broke.”
Although Suzanne remembers being healthy before contracting measles, she said the virus left her very weak. She was too sick to return to school for weeks.
“I was very sickly as a child after that,” Suzanne said. “I seemed to get everything. I got every cold that went around. I was prone to like urinary infections, kidney infections, respiratory infections.”
Six years after her measles infection, Suzanne and her two siblings contracted chickenpox. Suzanne suffered the most, and still has scars on her face from the blisters.
Suzanne said she learned about immune amnesia from her sister, a nursing professor. She wonders if her sickly childhood—and continuing immune problems as an adult—were caused by immune amnesia.
‘A shadow of death’
Doctors have known for hundreds of years that measles can lead to later waves of disease.After a measles outbreak, “there would be a shadow of death that would linger for months,” Mina said. “Measles outbreaks were extraordinarily predictive of the amount of death that would happen from all other infectious diseases in a community.”
Yet doctors also reported sporadic cases in which measles survivors benefitted from a less aggressive immune system, Mina said.
In the pre-vaccine days, doctors wrote letters to the editors of medical journals about children with autoimmune disorders—which result from a hyperactive immune system—whose disease went away after a measles infection, Mina said.
Scientists have only recently begun to understand how measles causes immune amnesia.
In 2012, animal studies showed the measles virus destroys immune cells called memory T cells and memory B cells, which help the body recognize other infections. Without memory cells to make antibodies, the immune system has no targeted defense against diseases the body has seen before. The authors of the study, published in PLOS Pathogens, coined the term immune amnesia.
Even then, scientists believed that measles suppressed the immune system only for weeks or months.
In 2015, Mina was part of a team of researchers who discovered that children take two to three years to recover antibodies lost to measles. Authors of a 2018 study based on a British medical database found increased rates of infections in measles survivors for up to five years.
In 2019, Mina and his colleagues showed that measles survivors lose 11% to 73% of the antibodies they had before getting sick. It’s not possible to predict who will suffer the greatest harm.
Rebuilding the immune system
The good news is that people rebuild their immune systems over time, as they are exposed to viruses and bacteria, Mina said. Those exposures can act like a booster shot to children who keep some immunity to a disease.In Mina’s study, for example, blood tests revealed that some children were accumulating antibodies against respiratory syncytial virus (RSV). That virus, which circulates in fall and winter, can cause severe disease in newborns but symptoms similar to the common cold in older children and adults.
“It turns out that what we were witnessing in real time was people rebuilding their immune repertoire,” Mina said. The children with increasing RSV antibodies were all in the same classroom at school. “We saw a silent RSV virus going through the class.”
No universal recommendations
Doctors still have many questions about immune amnesia, such as whether children should be revaccinated after having measles, said Healy, also a member of the Measles Collaborative.Doctors can’t easily predict “which parts of the immune system have been wiped out by the measles infection,” Titanji said
Doctors may weigh the benefits of booster shots for children who develop multiple infections after a case of measles, Titanji said. “It’s really on a case-by-case basis; a provider would have to make that call.”
There’s no universal recommendation about revaccinating people after a measles infection, Pannaraj said.
“It’s a question we’ve been thinking about, but there’s not yet enough data” to issue recommendations, Pannaraj said. “To be honest, we haven’t had to think about it much until now.”
One shot that protects against multiple diseases
Understanding immune amnesia helps explain why measles epidemics are so deadly—both during an outbreak and years later—and why maintaining high levels of protection against measles saves so many lives, Mina said.Before measles vaccines were available, measles immune amnesia caused about half of all child deaths from infectious diseases.
In recent decades, campaigns to protect children through measles vaccination have reduced overall child mortality by 30% to 50% in countries with limited resources, and up to 90% in the poorest nations.
Comprehensive vaccination could prevent the 95,000 annual deaths from measles, as well as hundreds of thousands of additional deaths caused by lasting damage to the immune system, Mina said.
“This is why,” he said, “it’s so important to protect against measles.”