The control of measles through vaccines is one of the most successful public health interventions in recent years. The vaccine has reduced childhood mortality by 30 to 50 percent in some countries; this reduction is even larger in the most impoverished populations, reaching up to 90 percent. Yet the vaccine appears to have additional benefits that are still poorly understood.

A measles infection is typically accompanied by a severe immunosuppression, often thought to be transient, which increases the host’s susceptibility to other illnesses. The World Health Organization recently concluded that the vaccine is associated with large reductions in childhood mortality, regardless of infectious agent. Thus, in addition to its intended target, the vaccine appears to prevent some opportunistic infections.

But rather than a transient benefit, research has demonstrated that the protective effects of the measles vaccine can lead to a reduction in infectious disease mortality of roughly five years—and even persist for life in some cases.

These surprising long-term benefits of the vaccine suggest that measles' immunosuppression may be long-term rather than transient. However, we didn't know of any immunological mechanisms that could explain the nonspecific vaccine benefits. Scientists have previously suggested one possible explanation: measles could cause the loss of immune memory cells, thus erasing previously acquired immunities.

Four predictions

To explore this idea, a team of scientists recently combed through epidemiological data collected from England, Wales, the US, and Denmark during periods where measles infections were common. They looked for evidence of host susceptibility to opportunistic diseases caused by exposure to the measles virus. The scientists tested four hypotheses to determine whether nonspecific benefits of the vaccine could be attributed to the prevention of the measles virus' assault on the immune system.

First, the scientists expected to find a mathematical relationship indicating that nonmeasles mortality is associated with measles incidence. They also expected that, when previous measles cases were also accounted for, the association between nonmeasles mortality and measles incidence would be stronger, providing evidence of an immunological memory loss.

In addition, the team suggested that the association between nonmeasles mortality and measles incidence would be greatest for cases where the time between measles exposure and nonmeasles mortality matched the time it takes to restore proper immune system function after exposure to the measles virus. Finally, they proposed that the time required to restore proper function of the immune system would be consistent with the evidence of increased risk of mortality after infection with the measles virus.

The scientists found that for Europe and the US, mass vaccination against the measles was followed by a reduction in the death of children due to nonmeasles infectious diseases. In all locations, measles incidence showed significant associations with mortality; however, the effect sizes varied, probably due to differences of reporting in the US and changes in health care practices.

Spotting trends

The team performed further mathematical analysis of the data to determine the underlying trends. They found that for England and Wales, the measles virus led to immunosuppression for an average of 28.3 months. This corresponded to a strengthened association between measles and infectious disease mortality from any pathogen.

The team then compared the average time required for the return of full immunity to what happens in children exposed before six months of age—before they had developed much in the way of immune memory. The rise of immune memory was registered by tracking the age at which mortality from bacterial diseases started to decline. This data was correlated with the ability of measles to increase mortality from bacterial infections.

Before vaccination, the average length of the immunosuppressive response caused by the measles virus closely matched the duration identified in the post-vaccine era as well.

Immunosuppression caused by the measles virus was also evaluated for different disease classes. The specific disease didn't matter much—individuals were predisposed to death for a period of 18 to 30 months in most cases.

To further test the immunosuppressive impact of measles, the team carried out a similar analysis on the vaccine-preventable disease pertussis, which is not known to be immunosuppressive. High quality population-level data regarding pertussis are available for England and Wales for the pre-measles-vaccine years. This analysis revealed no correlation even when the sum of previous pertussis cases was extended over two years.

The study revealed that when measles was common, measles infections may have contributed to as many as half of all childhood deaths from infectious diseases. The scientists found that the reduction in measles virus infections through vaccination was the largest factor in reducing overall childhood infectious disease mortality. The results of this study provide strong support for the idea that measles may reset our immune system's memory.

While both infection and vaccination can provide a robust herd immunity against subsequent epidemics, this study also reveals that measles virus infections could actually reduce a population's herd immunity against other infections.

Science, 2015. DOI: 10.1126/science.aaa3662 (About DOIs).