The effect of measles vaccination was studied using population-level data before and after the introduction of measles vaccination approximately 50 years ago in England and Wales, the United States, and Denmark. There was a strong association of measles vaccination in these countries with declines in mortality from other childhood infectious diseases; for example, the association (after transformation of the pre-vaccine data) for the United States was R2 = 0.87. The nonspecific impact of measles vaccination was generalized and prolonged, with a duration of two to three years, with robust results across all ages studied from 1-14 years of age. The effect of immunomodulation after measles infection aligned with the risk of bacterial invasive disease in children younger than 5 years of age, with both declining along the same gamma curve (R2 = 0.97 and 0.99, respectively). Furthermore, and confirming previous findings, there was consistently stronger association of immunomodulation for females than for males. Similar results of the adverse impact of measles on immunomodulation were found in both pre- and post-vaccine eras.
The results showed that when measles was common, it was indirectly responsible for as much as half of all childhood deaths from infectious diseases, accounting for nearly all of the interannual fluctuations in childhood infectious disease deaths. The main factor in the overall reduction of childhood mortality from infectious diseases in these countries was attributable to the implementation of measles vaccination programs. Fluctuations in childhood mortality in the United Kingdom, the United States, and Denmark were able to be explained by a simple weighted integral that described the prevalence of measles immune memory loss, capturing the generalized impact of measles infection on immune depletion.
COMMENTARY
Measles infection is accompanied by a transient general immunosuppression lasting a few weeks to a few months. Beyond the immediate benefits of prevention of mortality from measles directly, the World Health Organization recently concluded that measles vaccination is associated with significant reductions in overall childhood mortality from all causes.
Recent studies showed that measles infection results in rapid expansion of predominantly measles-specific B and T lymphocytes, essentially replacing the memory cell population. This has been postulated to result in “immune amnesia” to non-measles pathogens.
This study supports this hypothesis that measles infection results in loss of immunological memory cells by demonstrating that this effect on the mortality associated with other childhood infectious diseases is demonstrable. Measles vaccination had demonstrable impact to reduce overall childhood mortality and improve childhood survival. This was shown in high-resource settings where mortality from opportunistic infections associated with acute measles infections is low. It would be expected that studies of morbidity would also show the generalized adverse impact of measles infections. Measles vaccination may also contribute to preserving effective herd or community immunity to non-measles pathogens.
Vaccinations are the most important measure in reducing mortality from infectious diseases. These results underscore the reach of measles vaccine beyond reducing the morbidity and mortality directly attributable to measles illness, to a generalized and significant adverse effect on immune function that has far-reaching impact not previously appreciated.
Population-level studies in high-resource countries demonstrated that fluctuations in childhood mortality from all infectious diseases are strongly associated with measles infection. The effect is likely attributable to generalized immunomodulation that follows measles infection, with a duration of two to three years.
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