Giving first dose of measles vaccine too early has risks

By Megan Brooks

NEW YORK (Reuters Health) - Giving the first dose of the measles vaccine at 12 months may not provide optimal protection, a study from Canada shows.

Investigating a large 2011 measles outbreak at a high school in Quebec, researchers saw that adolescents who got their first dose of measles vaccine beginning at 12 months of age had a two- to four-fold greater risk of measles than those whose first dose was given at 15 months of age or later.

This "unexpected finding" prompted Dr. Gaston De Serres, medical epidemiologist at Quebec's Institute of Public Health, and colleagues to do an expanded case-control study in the whole province. This investigation confirmed what they saw in the outbreak school: there's a greater risk with first dose at 12 months.

The expanded investigation included all 102 measles cases occurring in twice-vaccinated school-age children aged 5 to 17 that were reported in Quebec in 2011. Each case was matched to five controls.

In line with their earlier observations, when the first dose of measles vaccine was given at 12 to 13 months of age, compared with at least 15 months of age, the risk of measles in participants outside the outbreak school was six times higher, and 5.2 times higher in the pooled estimate (participants from the outbreak school and outside that school).

The researchers say the pooled fivefold greater risk of measles "is concerning, especially in the context of measles elimination efforts that require high levels of immunity."

"The mechanism remains unknown, but the findings warrant additional evaluation in the context of measles elimination efforts," the researchers say.

"Currently, measles has been eliminated from the Americas, and global experience overwhelmingly supports durable immunity from two doses of measles vaccine," Dr. De Serres and colleagues pointed out in Pediatrics online October 21.

"However, the unexpected vulnerability we have identified in twice-vaccinated people during the epidemic in Quebec should be considered a signal warranting additional investigation. In particular, other locations with ongoing measles activity can explore the epidemiologic associations we have raised, and serosurveys of infants who received an early versus later first dose of MMR would be informative," they conclude.

In the U.S., the recommended age at first dose of measles vaccine is 12 to 15 months. In Canada, it's 12 months. Do the findings call for a change in policy in Canada?

Dr. De Serres told Reuters Health by email, "They will call for a change of age at first dose only if the negative effect of an early age at first dose is also present in infants who will be born after 2013."

"One of the alleged mechanisms to explain the negative effect of an early age at first dose is the interference of maternal antibodies that can inhibit/destroy the vaccine," Dr. De Serres said.

Maternal antibodies protect children against measles when they are very young but slowly disappear as the child ages, he said. "If the vaccine is injected when maternal antibodies are still present, the vaccine will not take. An older age at first dose means a smaller probability that maternal antibodies are still present," Dr. De Serres explained.

He pointed out that the children in this study were mostly born to mothers with a history of measles infection. "Mothers previously infected by measles have higher antibody levels than mothers who were vaccinated and therefore transmit more antibodies to their child. It is anticipated that the negative impact of vaccinating at an early age is less pronounced in children born to vaccinated mothers who constitute the vast majority of the 2013 newborns. We therefore need to assess the validity of this hypothesis before recommending a change in the age at first dose. We are currently doing studies to assess that."

In email to Reuters Health, Dr. Ali Rowhani-Rahbar, an epidemiologist at the University of Washington in Seattle who wasn't involved in the study, said it's important to note that "delaying the first dose beyond 15 months of age with the hope of providing a more sustained immunity later in life may expand the 'window of vulnerability' among very young children who are susceptible to this infection."

"It is true," he continued, "that the risk of exposure to measles in countries such as the U.S. and Canada might not be very high; however, there is always the risk of exposure to imported cases who come from other countries, or if young children travel to other countries."

He added, "The authors astutely point out that with the increasing number of vaccinated mothers in the U.S. and Canada, the effect of age at first dose on protection against infection may become less pronounced.

SOURCE: http://bit.ly/1cfKHMr

Pediatrics 2013.