Researchers have long known that measles inhibits the immune system, but they generally thought this effect wore off after a few months at the most. However, studies of children in developing countries, where most cases occur, found that measles vaccination reduces the overall death rate from infections for up to 5 years, suggesting that preventing the disease somehow provides protection against other illnesses.
One possible explanation for this benefit is that the measles vaccine somehow spurs the immune system to produce defenses against these other diseases. But work on monkeys recovering from measles spawned an alternative hypothesis. In 2012, Rik de Swart of Erasmus MC in Rotterdam, Netherlands, and colleagues revealed that the measles virus kills large numbers of memory cells, white blood cells that prevent subsequent infections by the same pathogen. Thus, the measles virus might cause what the scientists termed immunological amnesia, impairing the immune system’s ability to remember and quickly eliminate other microbes it has already beaten. As a result, “you are vulnerable to diseases you shouldn’t be vulnerable to,” says Michael Mina, lead author of the new paper and a medical student at Emory University School of Medicine in Atlanta.
To test this explanation, a team that included De Swart and Mina, then a postdoc at Princeton University, obtained data on the numbers of measles cases and deaths from other infectious diseases in the United States, Denmark, and part of the United Kingdom. Measles vaccination started in the 1960s in the United Kingdom and United States and in the 1980s in Denmark, and the researchers had statistics from before and after its introduction.
The team’s mathematical analysis tried to determine whether there was a relationship between the number of measles cases and the number of kids who died from other diseases. If the virus inhibits immunity for only a short time, for example, the number of deaths from other infections in a specific year might correlate to the number of measles cases in that year. But if the virus triggers a prolonged immune amnesia, the number of deaths in a particular year might correlate to the total number of cases in that year and the previous year or two.
Using this approach, the researchers calculated that children who survive measles remain vulnerable to other diseases for an average of 2.5 years. The value was almost the same for all three countries, the team reports online today in Science. “Our results suggest that the adverse effects of measles are much more lasting,” Mina says.
To check that the immune impairment resulted from measles, the researchers analyzed statistics for whooping cough, which doesn’t suppress the immune system. They found no link between the number of whooping cough cases and mortality from other infectious diseases.
Mina and his colleagues also determined that the length of susceptible period didn’t change in any of the three countries after introduction of vaccination. That finding supports the idea that the measles vaccine benefits children not just because it prevents them from getting measles, but also because it provides protection against the other diseases. In the days before vaccination, measles was responsible for about half of childhood deaths from other illnesses, the team says. With that many dead children, why didn’t researchers detect this connection before? Many assumed that measles’ impact on the immune system quickly faded, Mina says. “So when a kid gets pneumonia 6 months later, nobody would link that to measles.” Other studies of children in West Africa didn’t show a lasting “measles shadow.” Mina and colleagues note that half of the kids in these studies died from other diseases within 2 months after they had measles, which would have made it difficult to detect a long-term effect.
“That there could be a prolonged immunosuppression is possible,” says vaccine immunologist Katie Flanagan of Monash University in Melbourne, Australia. But the study “is a long way from really proving it.” For example, researchers need to show that the kids who had measles are the ones dying from other illnesses, she says.
“It is indirect evidence,” says William Moss, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. But he says that the results are “highly suggestive” that measles is contributing to this longer period of immune suppression. And if the researchers are right, he says, “the benefits of measles vaccination are far greater than simply the reduction in measles deaths.”