\u201cThe rash and the fever, that\u2019s the tip of the iceberg,\u201d Michael J. Mina, MD, PhD, coauthor of two seminal studies in Science<\/a> on the effect of measles<\/a> on the immune system, told CIDRAP News. \u201cThe majority of the damage being done is under the surface.\u201d<\/p>\n 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\u2019s memory of earlier infections, measles causes a condition called \u201cimmune amnesia.\u201d<\/p>\n 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.<\/p>\n \u2018Thousands of additional medical clinic visits\u2019<\/p>\n Immune amnesia \u201chappens in 100% of measles-infected individuals to some degree,\u201d Mina said.<\/p>\n 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\u2019s age and underlying health, Mina said.<\/p>\n A child whose immune system forgets how to fight off the common cold, for example, may suffer the sniffles and sneezes of last year\u2019s respiratory viruses a second time.<\/p>\n But a baby who loses the protection provided by whooping cough (pertussis) vaccines could end up hospitalized.<\/p>\n A woman who loses her immunity against chickenpox, which causes much more severe disease in adults than in children, could develop pneumonia, Mina said.<\/p>\n With more than 6,000<\/a> measles infections in less than two years, immune amnesia could pose a real threat, Mina said.<\/p>\n \u201cWe will see thousands of additional medical clinic visits,\u201d said Mina, chief medical officer at Invivyd, a biotech company developing experimental treatments for measles. \u201cIf your child gets measles, you have to be looking over your shoulder\u201d for years.\u00a0<\/p>\n Children in poor health are especially vulnerable<\/p>\n 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.<\/p>\n Titanji treated many children affected by immune amnesia in Cameroon, which has one of the highest rates<\/a> of measles in the world. Those suffering from malnutrition were more likely to be hospitalized, she said.<\/p>\n \u201cAfter 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,\u201d Titanji said.\u00a0<\/p>\n In West Africa, children who survived measles were more likely to be later infected with malaria, Titanji noted. \u201cIn general, they were just more sickly children,\u201d she said.<\/p>\n The rash and the fever, that\u2019s the tip of the iceberg….The majority of damage being done is under the surface.<\/p>\n But immune amnesia isn\u2019t limited to developing nations.<\/p>\n Recent studies have found evidence of immune amnesia in wealthy countries with strong healthcare systems, including Germany<\/a>, Israel<\/a>, Switzerland<\/a> and the United Kingdom<\/a>. Children in these studies who had been infected with measles were more likely than others to need antibiotics or visit the doctor.<\/p>\n \u201cImmune amnesia is probably something that we’re going to encounter\u201d in the United States, said C. Mary Healy, MD, an associate professor of pediatrics and infectious disease specialist at Texas Children\u2019s Hospital. \u201cWe\u2019re on the cusp of finding out just how significant immune problems may be.\u201d<\/p>\n Pain seared into her memory<\/p>\n When Crystal Webster moved to Switzerland in 2008 at age 27, she wasn\u2019t aware that the country was experiencing its largest measles outbreak<\/a> in years.<\/p>\n 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%<\/a> of measles infections; two doses prevent 97%.<\/p>\n When Webster broke out all over in red pustules that looked \u201calmost like zits,\u201d 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.<\/p>\n The misery of measles is seared into Webster\u2019s memory. She felt a blaze of pain any time that one of the pustules came in contact with something else.<\/p>\n \u201cI remember lying on the wood floor, completely naked, spread eagled, because I didn\u2019t want any part of my body to touch any other part of my body,\u201d said Webster, now 44.\u00a0<\/p>\n The summer heat made Webster\u2019s skin feel even worse, especially since her home had no air conditioning.\u00a0<\/p>\n The following winter, Webster said, \u201cI felt like I always had a runny nose.\u201d But she chalked her constant colds up to living in a new environment with unfamiliar germs.\u00a0<\/p>\n While it\u2019s impossible for doctors to know for certain if Webster\u2019s symptoms were caused by immune amnesia, \u201cher increased respiratory infections in the year immediately following measles are certainly consistent with what we know about this phenomenon,\u201d Titanji said.<\/p>\n An unwelcome souvenir from her measles infection<\/p>\n 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.<\/p>\n Although chickenpox typically goes away after four to seven days<\/a>, the virus that causes the disease, called varicella-zoster, sticks around for decades, hiding in nerve cells<\/a> of the spinal cord. The virus can re-emerge as people age or if they become immune suppressed.<\/p>\n Shingles was just as painful as measles, Webster said. \u201cI wrapped my stomach in gauze so that my pants wouldn\u2019t rub up against the blisters,\u201d said Webster.<\/p>\n Webster\u2019s shingles infection also could have been caused by immune amnesia, Mina said.<\/p>\n \u201cIt\u2019s 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,\u201d Mina said.<\/p>\n Webster said she assumed her infections were due to bad luck.<\/p>\n \u201cI was pretty young to have all these things,\u201d Webster said. \u201cI thought I had done what I needed to do to be healthy.\u201d<\/p>\n Difficult diagnoses to make<\/p>\n Like Webster, many people with immune amnesia don\u2019t connect their illnesses back to measles, said Pia Pannaraj, MD, MPH, vice chair of the American Academy of Pediatrics\u2019 (AAP) Committee on Infectious Diseases.\u00a0<\/p>\n Measles amnesia \u201coften goes undiagnosed,\u201d said Pannaraj, who has treated measles patients in the United States, Asia, and Africa. \u201cPeople get measles, and then afterwards they will have recurrent ear infections or pneumonia, but they don\u2019t tie it back to measles. They think, \u2018Oh, this is just bad luck that I happen to have this ear infection or that I got pneumonia.\u2019\u201d<\/p>\n 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.<\/p>\n 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,<\/a> response, and education.<\/p>\n \u201cThe people who are getting measles now tend to be those that are unvaccinated and may not interact with the medical system very often,\u201d she said.<\/p>\n A childhood of illness<\/p>\n Before vaccines became available, virtually all children contracted measles.<\/p>\n Suzanne, 71, became severely ill with measles when she was 6 years old, two years before the measles vaccine was released.<\/p>\n \u201cIt\u2019s been over 60 years, and I can still picture how sick I was,\u201d 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\u2019s account of her illness was confirmed by her older sister.<\/p>\n Suzanne said she remembers lying in bed, with \u201cbig sheet around me<\/a> like a tent\u201d to protect her eyes, which measles had made very sensitive to light.\u00a0<\/p>\n \u201cMy mother put cold, damp clothes on my head, and everyone was standing around like, \u2018Is she going to die?\u2019\u201d Suzanne recalled. \u201cMy parents said I was on the verge of being hospitalized when my fever broke.\u201d<\/p>\n 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.<\/p>\n \u201cI was very sickly as a child after that,\u201d Suzanne said. \u201cI seemed to get everything. I got every cold that went around. I was prone to like urinary infections, kidney infections, respiratory infections.\u201d<\/p>\n 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.<\/p>\n Suzanne said she learned about immune amnesia from her sister, a nursing professor. She wonders if her sickly childhood\u2014and continuing immune problems as an adult\u2014were caused by immune amnesia.<\/p>\n \u2018A shadow of death\u2019<\/p>\n Doctors have known for hundreds of years<\/a> that measles can lead to later waves of disease.<\/p>\n After a measles outbreak, \u201cthere would be a shadow of death that would linger for months,\u201d Mina said. \u201cMeasles outbreaks were extraordinarily predictive of the amount of death that would happen from all other infectious diseases in a community.\u201d<\/p>\n Yet doctors also reported sporadic cases in which measles survivors benefitted from a less aggressive immune system, Mina said.<\/p>\n In the pre-vaccine days, doctors wrote letters to the editors of medical journals about children with autoimmune disorders\u2014which result from a hyperactive immune system\u2014whose disease went away after a measles infection, Mina said.\u00a0\u00a0<\/p>\n Scientists have only recently begun to understand how measles causes immune amnesia.<\/p>\n In 2012, animal studies showed the measles virus destroys immune cells<\/a> 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,<\/a> coined the term immune amnesia.<\/p>\n We\u2019re on the cusp of finding out just how significant immune problems may be.<\/p>\n Even then, scientists believed that measles suppressed the immune system only for weeks or months.<\/p>\n In 2015, Mina was part of a team of researchers who discovered that children take two to three years<\/a> to recover antibodies lost to measles. Authors of a 2018 study based on a British medical database found increased rates<\/a> of infections in measles survivors for up to five years.<\/p>\n In 2019, Mina and his colleagues showed that measles survivors lose 11% to 73%<\/a> of the antibodies they had before getting sick. It\u2019s not possible to predict who will suffer the greatest harm.<\/p>\n Rebuilding the immune system<\/p>\n 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.<\/p>\n In Mina\u2019s 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.<\/p>\n \u201cIt turns out that what we were witnessing in real time was people rebuilding their immune repertoire,\u201d Mina said. The children with increasing RSV antibodies were all in the same classroom at school. \u201cWe saw a silent RSV virus going through the class.\u201d<\/p>\n No universal recommendations<\/p>\n 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.\u00a0<\/p>\n Doctors can\u2019t easily predict \u201cwhich parts of the immune system have been wiped out by the measles infection,\u201d Titanji said<\/p>\n Doctors may weigh the benefits of booster shots for children who develop multiple infections after a case of measles, Titanji said. \u201cIt\u2019s really on a case-by-case basis; a provider would have to make that call.\u201d<\/p>\n There\u2019s no universal recommendation about revaccinating people after a measles infection, Pannaraj said.<\/p>\n \u201cIt\u2019s a question we\u2019ve been thinking about, but there\u2019s not yet enough data\u201d to issue recommendations, Pannaraj said. \u201cTo be honest, we haven\u2019t had to think about it much until now.\u201d<\/p>\n One shot that protects against multiple diseases<\/p>\n Understanding immune amnesia helps explain why measles epidemics are so deadly\u2014both during an outbreak and years later\u2014and why maintaining high levels of protection against measles saves so many lives, Mina said.<\/p>\n What we were witnessing in real time was people rebuilding their immune repertoire.<\/p>\n Before measles vaccines were available, measles immune amnesia caused about half of all child deaths<\/a> from infectious diseases.<\/p>\n In recent decades, campaigns to protect children through measles vaccination have reduced overall child mortality<\/a> by 30% to 50% in countries with limited resources, and up to 90% in the poorest nations.\u00a0<\/p>\n
\nMichael Mina
Photo courtesy of Invivyd<\/p>\n
\nCrystal Webster
Photo courtesy of Crystal Webster<\/p>\n