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PRIORITY PRESS - 28th International Congress of Pediatrics (IPA 2016)

Vancouver, BC / August 17-22, 2016

Vancouver - Uptake of the seasonal influenza vaccine is far from optimal in pediatric practice and physicians have an important role to play in helping parents understand why influenza vaccination is critical for infants and young children. The availability of the first effective influenza pediatric vaccine now makes it possible for physicians to recommend an influenza vaccine that is more immunogenic and effective for children between 6 and 24 months of age and when they do so convincingly, most parents are willing to accept vaccination for their child. The same vaccine is also effective in high-risk children with underlying medical conditions who are at greater risk for complications from influenza. Vaccinating children and adolescents against influenza also extends immunity to adults, widening the circle of effectiveness through herd immunity.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

A brief discussion about the efficacy, safety and necessity of vaccinating young infants against influenza could make a dramatic difference in vaccine uptake and help protect this vulnerable group of children against what can be a potentially lethal infection, speakers here agreed.

“It is widely believed that influenza is a trivial, non-serious disease state,” William Fisher, PhD, Professor of Psychology, University of Western Ontario, London, Ontario, told delegates here at the 2016 meeting of the International Congress of Pediatrics. “But in a brief communication, we can highlight the significance of the morbidity threat influenza has in infants and it’s very simple to say: There is a new vaccine. It’s safe. It’s effective and I recommend it. It takes 90 seconds and it’s well worth your time.”

Indeed, when Dr. Fisher studied a group of over 200 parents to determine whether they would vaccinate their infant when an effective pediatric influenza vaccine became available, 73% of them indicated they would do so. Most also indicated they would accept the vaccine during a routine visit for scheduled childhood vaccination. Dr. Fisher also found that 89% of parents who intended to vaccinate their child thought pediatric influenza vaccination was “very” or “moderately” important and about the same percentage thought the vaccine would work and was safe.

“This is a profile of the kinds of beliefs that drive uptake and decline of vaccine and for clinicians, it is critical to remember that these beliefs are amenable to change,” Dr. Fisher emphasized.

Why It’s Necessary

If a positive recommendation to vaccinate can do much to cement parental decision to do so, the epidemiology of influenza provides a compelling rationale as well. “Children have the highest influenza attack rates, especially young children,” Dr. Carol Baker, Professor of Pediatrics and Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas noted. They also carry very high viral titres when infected; shed the virus longer than older children and are subject to behaviours like cuddling that effectively promote the spread of the virus, particularly to grandparents, among whom mortality rates from influenza are high.

“Most people don’t think of healthy children dying of influenza,” Dr. Baker added, “but between 45 to 50% of deaths from influenza each year are in completely healthy children.” So why is uptake of the seasonal influenza vaccine in the pediatric population so alarmingly low? Until recently, no really effective vaccine strategy has been available for young infants, especially for infants between the ages of 6 to 24 months.

Older vaccines such as the inactivated trivalent influenza vaccine (TIV) can offer between 45 to 50% protection against influenza in older children but these vaccines are less effective in infants because young infants are unable to mount an adequate immune response to unadjuvanted vaccines to achieve seroprotective levels. The arrival of the MF59-adjuvanted trivalent influenza vaccine (aTIV, FLUAD) has now changed that paradigm and is especially well suited for younger children.

As explained by Dr. Terry Nolan, Head, Melbourne School of Population and Global Health, University of Melbourne, Australia, MF59 is an oil-in-water emulsion composed of squalene, a natural metabolite of cholesterol. Many millions of adults have received the MF59-adjuvanted influenza vaccine since the 1990s, when it was first licensed for use in adults, as he observed. Now, that same vaccine has consistently been shown to offer superior protection against influenza for children between 6 and <72 months of age.

Based on evidence from both randomized clinical trials and cumulative clinical experience, results indicate that there are “very substantial” increased seroresponses to each of the antigens contained in the vaccine because of the boosting effect that the adjuvant has on the infants’ immune response to it. For example, a pivotal trial involving over 6000 children between the ages of 6 and <72 months of age (Vaccine. 2014; 32:6146-56) found that the aTIV has a faster onset, greater peak and longer duration of immunogenicity than a non-adjuvanted vaccine.  Absolute vaccine efficacy against influenza infection was 86% with the aTIV versus 43% for the comparator unadjuvanted TIV vaccine, as Dr. Nolan reported.

Among infants between the ages of 6 and 24 months in the same study, the absolute efficacy of the aTIV was 77% compared to only 11% for the non-adjuvanted TIV vaccine. The MF59-TIV vaccine also had a relative vaccine efficacy of 75% compared with the non-adjuvanted vaccine—“very impressive results,” as Dr. Nolan observed. Injection site reactions were slightly more pronounced with the adjuvanted vaccine but the difference in adverse events between the two vaccines was not significant.

Even young children with underlying medical conditions who are at greater risk for influenza-related complications respond well to the MF59-adjuvanted vaccine. In an integrated analysis of six randomized studies, geometric mean titres were two-to-three fold higher following vaccination with the aTIV compared with control vaccines and seroconversion rates were higher at between 79% and 96% following aTIV immunization compared to between 83% and 89% for control vaccines.

Importantly, as Dr. Nolan also pointed out, a hemagglutination inhibition (HI) titre of 1:40 corresponds to a 50% protection rate against influenza in adults. “In children, you need to get to a HI titre of 1:110 to achieve at least a 50% probability of being protected against influenza,” Dr. Nolan said.

As he demonstrated, the proportion of children who achieve this protective threshold is “very substantially” different for the adjuvanted TIV compared with non-adjuvanted control vaccines.

Another Good Reason

Vaccination of infants against influenza makes good sense for the protection of children themselves but it also has a positive “spill-over” effect in the form of herd immunity among adults. “The herd effect is what you get if you immunize more and more children in order to induce protection in people who’ve never gotten the vaccine,” Dr. Mark Loeb, Michael G. DeGroote Chair in Infectious Diseases, McMaster University, Hamilton, Ontario explained. In a study on herd immunity carried out in 49 Hutterite colonies in Saskatchewan (JAMA 2010;303:943-950), Dr. Loeb and colleagues inoculated 947 children and adolescents with an inactivated TIV. The hepatitis A vaccine was used as a control.

“The bottom line is that we found the indirect effect of immunizing children and adolescents led to a protective effectiveness of approximately 60% against influenza infection among adults so they achieved the same level of protection as they would have if they got the vaccine themselves,” Dr. Loeb reported. In a more recent study again carried out in Hutterite colonies, Dr. Loeb compared the effectiveness of the live-attenuated influenza virus “nasal” spray vaccine (LAIV or FLUMIST) to that of TIV at preventing PCR-confirmed influenza illness among study participants. Having vaccinated both comparator groups across three successive influenza seasons, investigators found absolutely no difference between the incidence of confirmed influenza between the two groups at 5.3% overall for the LAIV vaccine group and 5.2% for the TIV vaccine group.

“The key message for physicians is that they need to give some type of vaccine because so few parents are vaccinating their young children against influenza and that’s not good,” Dr. Loeb said. “So whatever you use, use something but again in the younger age group, the adjuvanted influenza vaccine elicits a better response.”

Final Thoughts

As is true for most new vaccines, the aTIV vaccine has not yet been folded into the publically funded vaccination program and the fact that it is not yet publically funded very strongly influences how parents think about it: namely, if the aTIV vaccine was really safe, effective, and important, public health would fund it. To counter this negative thinking, physicians need to develop a brief script that will allow them to discuss the potential morbidity associated with influenza, to address parental vaccine hesitancy if present and to recommend the vaccine as a safe and effective new option for infants and young children. It should take 90 seconds or less and yes, it is well worth the effort.