ACIP approves new live-attenuated influenza vaccine recommendations

December 2007

ATLANTA — The Advisory Committee on Immunization Practices voted at its October meeting to recommend that either the trivalent inactivated vaccine or the live-attenuated influenza vaccine could be used to vaccinate healthy people aged 2 to 49 years.

Additionally, Anthony Fiore, MD, MPH, presented the ACIP influenza vaccine work group’s suggested guidance for wheezing screening in young children and new information regarding the expansion of influenza vaccination recommendations to include all school-aged children.

“The current rationale for influenza vaccination recommendation in this country is to reduce influenza and influenza complications in groups with the highest rates of severe outcomes, including hospitalizations, medical or emergency room visits and mortality, and also to provide vaccination for everybody who wants it,” said Fiore, of the National Center for Immunization and Respiratory Diseases and member of the influenza vaccine work group.

With the number of influenza cases that occur each year, however, the need for a new approach may be at hand.

“Influenza causes an enormous burden of disease each year. In fact, one child in every 1,000 children aged younger than 5 years is admitted to the hospital with influenza each year, and as many as 20% of children in that age group visit their doctors during influenza outbreaks,” Kathryn M. Edwards, MD, director of the division of pediatric clinical research and professor of pediatrics at Vanderbilt University, told Infectious Diseases in Children.

“Thus widespread vaccination would reduce substantial disease in the population,” said Edwards, also a member of the Infectious Diseases in Children editorial board.

During its meetings, the work group discussed the safety and efficacy of the live-attenuated influenza vaccine (LAIV; FluMist, MedImmune) in younger children compared with that of TIV.

“Vaccination of 6- to 23-month-olds is a high priority because these infants and toddlers have rates of hospitalization for influenza that are similar to those observed in the elderly; however vaccination coverage in this age group remains unacceptably low,” Fiore said.

The work group found the efficacy of LAIV to be at least equivalent to that of TIV in children aged 6 months and older.

There was also good evidence for safety among children aged 24 months and older who did not have a history of asthma or wheezing; however, the work group said that additional safety information was needed for children aged 24 months and older with a history of asthma or wheezing, according to Fiore.

They also concluded that guidance for health care practitioners and immunization programs needed to better define the meaning of “recurrent wheezing” in patients aged 2 to 4 years.

When creating this guidance, the work group took certain points into consideration, such as the fact that “recurrent wheezing” is not defined in LAIV prescribing information.

As a result, the group establish- ed and presented a suggested guidance for screening for wheezing in young children.

The group also included a question for physicians to ask parents to identify children who might be at high risk for developing asthma: “In the past 12 months, has a health care provider ever told you that your child had wheezing or asthma?”

The difficulty in developing this guidance was trying to combine the thoroughness of a study with the practicality needed for everyday use, according to Kathleen Neuzil, MD, MPH.

“We were really striving for that balance between being as accurate and consistent with the trials as we could be, but also having to be simple and straightforward in clinical practice,” said Neuzil, chair of the influenza vaccine work group.

“[In a clinical trial], we obviously have the ability to spend a lot more time with each volunteer and their parents and ask a number of questions; we felt that a simple, single question was the way to go in practice.”

New recommendation

The work group also proposed the recommendation that either TIV or LAIV could be used for healthy people aged 2 to 49 years; “healthy” was defined as any person who did not have an underlying medical condition that would predispose him to influenza complications.

Following the conclusion of the work group’s initial presentation, the ACIP voted to approve this recommendation.

The recommendation follows a number of other positive safety and efficacy trials of LAIV in various age groups, including one by Robert B. Belshe, MD, and colleagues. The researchers found that in nearly 8,000 children aged between 6 and 59 months, there were 54.9% fewer cases of culture-confirmed influenza in those who received LAIV compared with those who received the inactivated vaccine (153 cases vs. 338 cases; P<.001).

Earlier this year, the FDA issued a warning letter to LAIV manufacturer MedImmune for deviations from current good manufacturing practice guidelines at its influenza vaccine manufacturing facility in the United Kingdom.

The issue was resolved in September, by which time MedImmune had received approval for LAIV’s expanded indication; however, the delay in production resulted in a simultaneous surge in supply and demand, according to Karen Lancaster, of MedImmune’s media relations department.

Expanding recommendations

According to Fiore, the work group previously presented a potential time frame for the modification of influenza vaccination recommendations, which began with the consideration of expanding recommendations to all school-aged children between 2007 and 2008.

This was to be followed by the consideration to include all household contacts and caregivers for school-aged children in 2010 to 2011 and then for the expansion to universal vaccination between 2012 and 2013.

“The discussion can be broken into six critical factors,” Fiore said. “[These include] vaccine supply; vaccine effectiveness; vaccine safety; disease burden; the feasibility of implementation, especially sustained implementation; and cost effectiveness.”

To help sort through these factors, the work group convened a group of about 70 consultants, including influenza researchers, epidemiologists and professional organization representatives.

Objectives of the consultation were to review the evidence base supporting expansion, to identify key evidence gaps and potential solutions to implementation challenges, and to discuss methods for assessing the effect.

The group concluded that school-aged children have the highest influenza attack rates, are a major source of community infection and respond well to the vaccine with few instances of adverse events.

They also concluded that full implementation with good coverage would be difficult to accomplish in traditional medical settings, and although it should reduce influenza illness among contacts, this would be difficult to definitively measure.

“Within the work group, there is strong support for moving toward universal influenza vaccination, but the best strategy to get there is still under some discussion,” Neuzil said. “Much of our work group discussion did center on the timing of recommendations.”

The work group found that although there were currently no critical data gaps and no clear indications that more data would be available anytime soon, waiting to make a new recommendation could be potentially helpful by allowing more time for education.

Due to the number of unanswered questions, the work group proposed further discussion at the February ACIP meeting and a continued effort to harmonize any potential recommendation timelines with those of provider, public health and immunization programs.

For more information:

• Fiore A. Influenza vaccine session.
• Fiore A. Expanding recommendations for routine influenza vaccination.
• Neuzil K. Summary of ACIP influenza working group discussions.
• All presented at: ACIP meeting; Oct. 24-25, 2007; Atlanta.