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

26062330-March-7-Kelly-600x900-WEBBefore the development of a vaccine in the 1960s, the measles were practically a childhood rite of passage. This common childhood disease was not without teeth however. Between the years of 1958 and 1962 (the first measles vaccine was licensed in the U.S. by John Enders in 1963), the US averaged 503,282 reported cases of measles (1). Not surprisingly, after the measles vaccine became widely used, the number of cases of measles plummeted.

What was surprising was that the number of childhood deaths from all infectious diseases dropped dramatically as well.
The same phenomenon was observed in England and parts of Europe as vaccination programs were instituted in those places. Reduction or elimination of measles-related illness and death alone can’t explain the size of the decrease in childhood mortality. Although measles infection was associated with suppression of the immune system making the host vulnerable to other infections, these side effects, and the concurrent vulnerability to other infections, were assumed to be short lived. However, the post-vaccination numbers showing the drop in mortality from infectious diseases following vaccination for measles suggested that the effects of measles induced immunosupression might last for years, not months (2).

Proposed mechanisms for this phenomenon 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 (3).

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 (4, 5). Simply put, infection with measles gives your immune system amnesia, and it may take reinfection to stimulate a new immune response. With this hypothesis, 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 last year (2), 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 United States, 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.

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.

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. NVIC. What is the History of Measles in America and Other Countries? (http://www.nvic.org/vaccines-and-diseases/measles/measles-history-in-america.aspx) Accessed March 2015.
  2. Mina, M.J. et al. (2015) Science 348, 694–9.
  3. 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,
    http://www.who.int/immunization/sage/meetings/2014/april/3_NSE_Epidemiology_review_Report_to_SAGE_14_Mar_FINAL.pdf.
  4. de Vries, R.D. et al. (2012) PLoS Pathogens 8, e1002885.
  5. de Vries, R.D. et al. (2015) PLoS Pathogens 10, e1004482.

 

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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, photography and knitting. She would like to be an avid runner, as evidenced by her growing collection of running gear and her single half-marathon finishers t-shirt.

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