As if family physicians needed another reason to remind patients about the importance of measles vaccination, findings from a pair of recent studies strongly suggest that contracting measles can dramatically reduce a person's resistance to other diseases -- despite having been immunized against them.
This 3D illustration shows the structure of measles virus, with surface glycoprotein spikes hemagglutinin-neuraminidase and fusion proteins.
The studies, published in the Nov. 1 issue of Science(science.sciencemag.org) and the November issue of Science Immunology,(immunology.sciencemag.org) lend credence to a theory known as immune amnesia. The theory argues that measles infection impairs the body's immune system for months or even years, while vaccination against measles prevents loss of immune memory and helps maintain resistance to other infectious pathogens.
"This is the best evidence yet that immune amnesia exists and impacts our bona fide long-term immune memory," said Michael Mina, M.D., Ph.D., first author of the Science study, in a news release.(hms.harvard.edu) Mina, an epidemiologist at the Harvard T.H. Chan School of Public Health, first described the epidemiological effects of measles on long-term childhood mortality in a 2015 study.(science.sciencemag.org)
Study Details and Findings
In the Science study, researchers used a tool called VirScan that detects serum antibodies produced in response to current or past exposures to hundreds of viruses, thus creating a snapshot of the immune system's antibody repertoire.
- Findings from two new studies show that measles infection can dramatically lower a person's resistance to other diseases -- a phenomenon known as immune amnesia.
- One study found that in children, measles infection significantly reduced the number and type of serum antibodies to other diseases.
- The same study also found that receiving the measles, mumps and rubella vaccine did not produce the same negative immunological effects.
Specifically, the researchers used VirScan to analyze blood samples from 77 unvaccinated children who contracted measles during a 2013 outbreak in the Netherlands. Samples were obtained before and about two months after laboratory-confirmed measles infection, and the antibody repertoires of these children also were compared to those of four control groups totaling 119 children (including 33 children vaccinated against measles) and adults.
The authors found "substantial reductions" in the total number of unique pathogen epitopes in children infected with measles. The analysis showed a mean reduction of about 20% in the size or diversity of the antibody repertoire after measles infection.
The analysis also showed a link between severity of measles infection and damage to the immune system. Overall, measles infection eliminated between 11% and 73% of the antibody repertoire. Children with mild cases lost a median of 33% of their preexisting pathogen-specific antibody repertoire; those with more severe cases lost a median of 40%. The most-affected quintile of children lost more than one-half of the pathogen-specific antibodies for most pathogens, with some losing up to 70% of the antibodies for specific pathogens.
In contrast, antibody repertoire retention was about 90% in two age-matched control cohorts, despite differences in sampling interval between the two groups (i.e., about three months versus about one year between samples).
Notably, the MMR vaccine did not produce the same negative effects on the immune system as natural measles virus. The study authors noted a marked increase in antibody repertoire diversity among people in the control group who received the MMR vaccine, although they acknowledged that the antibody repertoire in young children -- who comprised the MMR-vaccinated cohort in this study -- continues to add diversity over time, which could conceivably mask small impairments from measles vaccine. Still, VirScan analysis of these individuals found no overall change in antibody titers after MMR vaccination.
"This analysis supports decades of observations that MMR vaccines do not increase susceptibility to subsequent infections," the authors wrote.
The authors of the Science Immunology study, meanwhile, used blood samples from 26 unvaccinated children in the Science study group who contracted measles to determine whether exposure to the virus altered the makeup of B cells.
The researchers conducted B cell receptor sequencing before and about 40 days after infection, identifying two distinct immunological sequelae. First, they found signs of immunological immaturity of the B naïve cell repertoire after measles infection, limiting the immune system's ability to respond to new infections and boosting the risk for secondary diseases. They also discovered that serum levels of B memory cells that had been built up to protect against other diseases were severely depleted after measles infection.
The researchers then further tested the immune amnesia theory in two groups of ferrets by vaccinating them with live-attenuated influenza vaccine, then infecting one group with a variant of canine distemper virus (which is closely related to measles). Ferrets infected with CDV had lower levels of influenza-neutralizing antibodies and experienced more severe flu symptoms after subsequently being infected with flu virus.
"This study is a direct demonstration in humans of immunological amnesia, where the immune system forgets how to respond to infections encountered before," said Velislava Petrova, Ph.D.(www.sanger.ac.uk), a postdoctoral fellow at the Wellcome Sanger Institute in Cambridge, U.K., and the study's lead author. "We show that measles directly causes the loss of protection to other infectious diseases."
FP Expert Perspective
Pamela Rockwell, D.O., of Ann Arbor, Mich., the AAFP's liaison to the CDC's Advisory Committee on Immunization Practices, discussed the implications of the research with AAFP News.
"I think it is so exciting to see science affirming even more than what was previously held to be true regarding the benefits of measles vaccination," Rockwell said. "We now know that not only does the MMR vaccine protect against the potentially devastating disease known as measles, but it also potentially helps prevent serious harm (or) death to those who contract measles when later exposed to other pathogens, truly debunking the false assumption that 'natural immunity' is superior to vaccines.
"With herd immunity against measles challenged at this time in the United States, and with the risk of contracting measles growing for those unvaccinated, not only does the MMR vaccine protect against three highly communicable infections, but it offers additional immune protection against other future potential infections in years to come," she added.
Rockwell also offered guidance on encouraging patients to get all of their necessary vaccines.
"Family physicians should stress the safety of vaccines as a proven health benefit, and if parents/patients are concerned about safety and side effects, assure patients vaccines offer much more benefit than potential risk of side effect," she said. "With the threat of the United Sates losing its status in maintaining herd immunity against measles, with more frequent measles outbreaks seen, it is now more important than ever to keep your children up to date on the MMR vaccine."
For patients or parents who remain hesitant, Rockwell said it often helps if FPs can personalize the process of receiving vaccines -- describing their own and their family's experiences.
"In addition, providing a strong recommendation to vaccinate without hesitation is helpful, as is addressing any concerns that a patient may have with the use of science, data and facts, including about any potential minor side effects a patient may experience. Explain that vaccines not only protect the individual who receives the vaccine, but also protect their loved ones and others in the community from disease. I often tell parents that antivaccine social media posts and online resources, though they appear to be legitimate, are not. They are often misleading and do not offer true or science-based facts," she said.
Rockwell recommended several vaccine-related resources for family physicians. These include
- the Shots Immunizations app created by the AAFP and the Society of Teachers of Family Medicine;
- the CDC's Standards for Practice: Vaccine Recommendation;(www.cdc.gov) and
- materials provided by the Immunization Action Coalition,(www.immunize.org) a nonprofit organization that offers information on immunizations for health care professionals and their patients.
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