Measles and Immunosuppression—When Getting Well Means You Can Still Get Sick

Posted on by Kelly Grooms
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In 2000 measles was officially declared eliminated in the United States (1), meaning there had been no disease transmission for over 12 months. Unfortunately it was not gone for good. So far in 2024 there have been 8 outbreaks and 131 cases. Ninety of these case (69%) are associated with an outbreak and seventy (53%) have resulted in hospitalization (as of May 2, 2024; 2).  

Help in Limiting a Dangerous Childhood Disease

Before the development of a vaccine in the 1960s, measles was practically a childhood rite of passage. This common childhood disease is not without teeth however. One out of every 20 children with measles develops pneumonia, 1 out of every 1,000 develops encephalitis (swelling of the brain), and 1 to 3 of every 1,000 dies from respiratory and neurological complications (3). Between the years of 1958 and 1962, the US averaged 503,282 reported cases of measles (4). The first measles vaccine was licensed in the U.S. by John Enders in 1963, and not surprisingly, after the measles vaccine became widely used, the number of cases of measles plummeted. By 1970, there were under 1,000 cases (2).

Decreased Childhood Mortality from Other Infectious Diseases—An Unexpected Benefit

What was surprising was that with the disappearance of this childhood disease, the number of childhood deaths from all infectious diseases dropped dramatically. As vaccination programs were instituted in England and parts of Europe, the same phenomenon was observed. Reduction or elimination of measles-related illness and death alone can’t explain the size of the decrease in childhood mortality. Although measles infection is associated with suppression of the immune system that will make the host vulnerable to other infections, these side effects were assumed to be short lived. In reality, the drop in mortality from infectious diseases following vaccination for measles lasted for years, not months (5).

Proposed mechanisms for this phenomena included the possibility that the measles vaccine stimulates a cross-reactive T-cell response or that it might cause an expanded immunity response. In 2014 the WHO released a report that acknowledged the observed association between the reduction in infectious disease-related childhood mortality and measles vaccine but concluded that there was no conclusive mechanistic evidence of an immunological cause for the nonspecific vaccine benefits (6).

A recent hypothesis proposes a different mechanism to explain these long-term benefits. This hypothesis suggests that infection with the measles virus essentially resets previously acquired immunity by destroying immunity memory cells (7,8). Simply put, infection with measles gives your immune system amnesia, and it may take reinfection to stimulate a new immune response. So it is not the vaccine itself that confers protection from other infectious agents, it is the lack of infection by the measles virus (a result of vaccination) that allows the host to maintain already developed immunity to other pathogens.

In a study published in Science in May of 2015 (5), a group of researchers suggested that epidemiological data collected when measles was common should have evidence of this loss of acquired immunity following measles infection if it exists.  Where previous population studies had focused on low resource areas and populations, the authors maintained that if this “immune amnesia” existed, it should also be detectable in high-resource populations. For their study they used national data from the U.S., Denmark, Wales and England beginning in the 1940s and extending through 2010.

They identified four parameters to test the hypothesis that the there is a loss of immunological memory following infection with measles:

  1. The non-measles mortality could be correlated with the number of measles cases.
  2. If measles infection results in the loss of immune memory for up to three years, then the number of individuals susceptible to other infections should be a reflection of the number of measles cases over the last three years. They called this the “measles shadow”.
  3. The greatest association between measles and childhood mortality would be the strongest when the mean duration over which the cases are accumulation matches the mean duration it takes to restore immunological memory.
  4. The estimated length of immunosuppression following measles infection should agree with the evidence of increased childhood mortality after measles infection compared to uninfected children and this evidence of immunosuppression should correlate with the time required to build (or in this case, rebuild) immunity in early life.

Casting a Deadly Shadow

The analysis of the population data found that they met all these criteria. The incidence of measles infection was significantly (P<0.001) associated with mortality, and further supported the presence of a measles shadow. Using a mean value of 28.3 months for duration of measles-induced immunosuppression tightened the association between measles infection and all-caused infectious disease mortality. Finally, the elevated relative risk of mortality after measles exposure declined at the expected rate to correspond with immunity redevelopment.

The Promise Is About More Than Preventing One Childhood Disease

When measles was prevalent, the population data suggest that measles infection can be implicated in nearly half of all childhood deaths (2). The introduction of a vaccine is credited for dramatically dropping childhood mortality numbers. However, it appears that the measles vaccine isn’t a super protective wonder vaccine, but instead, measles is just a super sneaky, immune suppressing virus. And sometimes successfully slaying one infectious giant means you neutralize an army of smaller giants without even trying.

References

  1. Center for Disease Control and Prevention. Measles History: Measles elimination. Accessed May 7, 2024.
  2. Center for Disease Control and Prevention. Measles Cases and Outbreaks. Accessed May 7. 2024.
  3. Center for Disease Control and Prevention. Complications of Measles. Accessed May 7, 2024.
  4. NVIC. What is the History of Measles in America and Other Countries? (https://www.nvic.org/disease-vaccine/measles/history-in-america) Accessed March 2015.
  5. Mina, M.J. et al. (2015) Science 348, 694–9.
  6. WHO. Meeting of the Strategic Advisory Group of Experts on immunization, March 2014, Systematic Review of the Nonspecific Effects of BCG, DTP and Measles Containing Vaccines,
    https://terrance.who.int/mediacentre/data/sage/SAGE_Docs_Ppt_Apr2014/9_session_non-specific_vaccine_effects/Apr2014_session9_epidemiologic_review.pdf
  7. de Vries, R.D. et al. (2012) PLoS Pathogens 8, e1002885.
  8. de Vries, R.D. et al. (2015) PLoS Pathogens 10, e1004482.
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Kelly Grooms

Kelly Grooms

Scientific Communications Specialist at Promega Corporation
Kelly earned her B.S. in Genetics from Iowa State University in Ames, IA. Prior to coming to Promega, she worked for biotech companies in San Diego and Madison. Kelly lives just outside Madison with her husband, son and daughter. Kelly collects hobbies including jewelry artistry, reading, writing and knitting. A black belt, she enjoys practicing karate with her daughter as well as hiking, biking and camping.

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