Measles study raises questions about timing of vaccination

ORONTO – A second study from Quebec is calling into question the timing at which young children are vaccinated against measles.

by Helen Branswell

TORONTO – A second study from Quebec is calling into question the timing at which young children are vaccinated against measles.

The new research shows that teenagers who received the recommended two doses of measles vaccine but who got the first shot when they were 12 months old were six times more likely to go on to contract the disease than those who got their first dose at 15 months.

The work was done to try to puzzle out why a number of teenagers who would have been assumed to have been protected — because they got two doses of vaccine in childhood — nevertheless were infected during Quebec’s large measles outbreak in 2011.

More than 700 measles cases were reported in that outbreak.

Lead author Dr. Gaston De Serres of Quebec’s provincial public health agency presented the work Sunday at a major international infectious diseases conference in San Francisco. The study was a followup to an initial paper on the outbreak that he presented to the same conference last year.

While the situation bears watching, De Serres said Canadian policy on timing of measles vaccine delivery isn’t likely to change just yet.

“For Canada I would probably say that at this time we will not change the schedule,” De Serres said during a webcast press conference from ICAAC, the Interscience Conference on Antimicrobial Agents and Chemotherapy.

“We need to follow up with more studies.”

Prior to the introduction of the measles vaccine, most children contracted the disease and roughly two million a year died from it.

One of the most contagious diseases to afflict humans, measles has largely been quelled in the Americas and countries that use measles vaccine, though it remains endemic in a number of parts of the world.

Still, outbreaks do crop up in North America, triggered by cases imported from parts of the world where the virus still spreads.

Generally those outbreaks take place among children whose parents refused to vaccinate them for religious reasons or because the parents subscribe to anti-vaccination views. It is rare to see cases in vaccinated children.

While measles can be particularly dangerous for infants, they cannot be vaccinated. That’s because antibodies they get from their mothers while they were in the womb kill the virus in the vaccine before it has a chance to induce an immune response in the vaccinated child.

That phenomenon is called maternal antibody interference. Maternal antibodies protect an infant while its own immune system is just starting to develop. The effect of maternal antibodies wanes in the months after birth.

The World Health Organization recommends giving the first dose of measles vaccine at nine months, with the second dose to follow any time after 12 months.

Jane Seward, a measles expert with the U.S. Centers for Disease Control, said the goal is to vaccinate children as soon as the vaccine can take effect so as to minimize the risk of death and severe disease.

“It’s a balance between getting the first dose as early as possible to decrease deaths and as late as possible to get the best immune response,” she said.

In Canada, where an infant’s risk of encountering measles is lower than it would be in India or Africa, officials have pushed back the start of the immunization program to try to take advantage of the difference in the risk-benefit ratio.

Here the first dose of measles vaccine — it comes bundled in a vaccine that covers mumps, rubella and chickenpox as well — is generally given at 12 months of age. The second is given at 18 months or at four to six years of age, before the child starts school.

When De Serres and some of his colleagues saw twice-vaccinated teenagers among the measles cases in Quebec, they did a study in a high school trying to figure out why those cases had occurred.

That work, presented last year at ICAAC, showed that teenagers who got their first shot at 12 months were three times more likely to get measles than teenagers who had received their first shot at 15 months.

(It should be noted it is rare that twice-vaccinated children develop measles, regardless of when they got their first shot. De Serres’ study suggested the vaccine was 94 per cent effective in preventing measles in children who got two doses starting at 12 months, and over 97 per cent effective in children who got two doses starting at 15 months.)

To try to confirm their findings, the group did a second study. They found 61 cases of twice-vaccinated children — cases who weren’t in the original study — and compared them to 305 teens who did not contract measles. They found the risk for kids who received their first dose at 12 or 13 months was six times higher than those who were first vaccinated at 15 months.

De Serres said it isn’t clear whether this difference is all due to maternal antibody interference. It’s possible, he suggested, that waiting longer gives the immune system more time to mature and that results in a better response to the vaccine.

“We don’t know the contribution of maternal antibody and maturation of the immune system to what we’ve seen,” he said.

Figuring that out will be important, because experts expect to see changes in the pattern of maternal antibody interference in coming years.

That’s because the generations of women who had measles when they were children — and developed a strong antibody response to the disease — will be moving out of their childbearing years.

Vaccines are known to produce lower levels of antibodies than natural infection. So when women who never had measles, who got their measles protection from vaccine, pass on maternal antibodies to their fetuses, those antibodies may wane faster, Seward noted.

That would mean giving the first dose when it is currently given might not leave some children vulnerable in future, she said. “But we need to watch.”




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