Iin the Netherlands, more than 2,600 people were infected with measles in 2013 in an orthodox-Protestant community that refuses immunization. Even before the outbreak, doctors had taken blood samples from dozens of children between the ages of four and 13. About two months after their recovery, they were again taken for blood. Since then, researchers have used specimens to study measles infections and their effects. Because the effects of measles infection on the immune system are still poorly understood.
To many, highly contagious measles is still considered a harmless childhood illness, experts say. Although infection, which includes colds, fever, conjunctivitis, white spots in the mouth and skin rashes, it does not cause major acute problems in most children. But sometimes there can be deadly complications.
Measles weaken the immune system – not only during the disease, but after it. This, according to a study by the Robert Koch Institute (RKI), could increase susceptibility to bacterial superinfections. These include, for example, bronchitis, middle ear and lung infections, and especially frightening post-infectious encephalitis. According to RKI, this brain inflammation occurs in about 0.1 percent of cases, and in ten to 20 percent of patients, it ends fatal.
Now, two international research teams are reporting that the long-term effects of the infection are even more serious. "Symptoms of measles may just be the tip of the iceberg," says Michael Mina of the Howard Hughes Institute of Medicine in Boston.
Already four years ago, Mina, then still at Princeton University, caused confusion in a study published in Science. A team of researchers based on infant mortality data before and after the introduction of measles vaccine in England, Wales, Denmark and the United States has calculated that measles disease can weaken the immune system by up to three years – thus increasing the number of deaths in children.
A new study by Mine and colleagues, republished in "Science," deepens the context. They analyzed blood samples from 77 children in the Netherlands before and after measles infection, among others. Researchers examined the blood for antibodies to viruses and bacteria, which formed the immune system after prior contact with appropriate pathogens, such as influenza, shrimp or pneumonia. Result: Depending on the severity of the disease, between eleven and 73 percent of the antibody repertoire disappeared after the disease. In contrast, the measles vaccine had no immunodeficiency effect.
"Think of pathogen immunity as a book with photos of criminals punched in someone's holes," Mina illustrates. "If you saw a criminal, it would be much harder to identify him, especially if holes affect important facial features like eyes or mouth."
In a second step, the researchers analyzed the development of antibodies in rhesus monkeys that had contracted the measles virus. In the five months after infection, monkeys lost an average of 40 to 60 percent of protective antibodies against other pathogens.
Another piece of the puzzle is provided by another team study led by Velislav Petrova of the Wellcome Sanger Institute, Cambridge, UK, in Science Immunology. These researchers analyzed B cells of the immune system responsible for the detection of pathogens in 26 Dutch children. After the infection has disappeared, accordingly, the diversity of these memory cells responsible for antibody production. "This study is a direct human test for immune amnesia, where the immune system forgets how to respond to previous infections," says Petrova. The possible consequences were investigated by a team of ferrets who were vaccinated against the flu. Following infection with the CDV pathogen CDV (canine virus virus), influenza antibodies are lost in animals. The flakes were again susceptible to infection despite vaccination. "It shows that measles could help protect against other infectious diseases," concludes co-author Paul Kellam, an infectious biologist at Imperial College in London.
"Both studies come to the same conclusion in very different methods," says Klaus Überla, director of the Institute of Virology at the University of Erlangen. "This is very convincing." The reason for the weakening of the immune memory is probably simple: Viruses infect the host cells via a surface protein that occurs in cells B and T of the immune system. Destruction of these cell types by the virus causes loss of immune memory.
"It has been clear so far that measles infection leads to short-term immunosuppression," said Überla, who was not involved in the studies. The number of immune cells regenerates within a few weeks. "However, it has been clinically noticeable that children then have an increased risk of infection in the long run. So far, this has not been explained on the basis of laboratory values." The effects on the immune memory presented in the studies now provide a reason for this.
Commenting on Science Immunology, Harvard Medical School immunologist Duane Wesemann points out the peculiarities of the measles virus: "Humans are its only host, cause aggressive disease with extreme contagion, and cause years of immunosuppression." Paradoxically, leave it with the lifelong immunity against measles itself. Experts may speculate that destroyed cells of the immune system can be replaced again, but newly formed heirs lack specific memory.
It is during these years that measles disease is increasing again all over the world. From 2000 to 2016, according to the World Health Organization (WHO), the death toll decreased by 84 percent – from over 550,000 to 88,000. Most measles deaths occur in countries with poor health systems.
In fact, WHO has set a goal of eliminating the world's disease by 2020. But now things are going in the opposite direction: According to the WHO, in the first six months of 2019, three times as many cases were reported worldwide compared to the same period last year – this was the highest level since 2006. In August, WHO regretted the development in Europe. For the first time since 2012, four countries lost their "laser-free" status: Albania, the Czech Republic, Greece and the United Kingdom. The United States, with only 86 cases registered in 2000, recorded about 1,250 diseases between 2019 and early October.
In Germany, the rate for two measles vaccines among beginners in schools increased from 89 percent in 2008 to 92.9 percent in 2016. In 2017, that figure was 92.8 percent. That's not enough, as 95% of the herd would be required to protect the herd, according to the WHO.
"A normal child may become ill with a depression in the immune system and his body may be able to cope with it," says Harvard geneticist Stephen Elledge, head of the study, currently published in Science. "But children at the border – such as those with a serious measles infection or those who are weakened or malnourished – will have serious problems." He adds, "The virus is much more harmful than we thought. This makes the vaccine even more valuable."