Seasonal influenza vaccines may not be as effective as we think — including among children and the elderly, two key groups that the vaccines have traditionally targeted — according to a comprehensive new study led by researchers at the University of Minnesota’s Center for Infectious Disease Research and Policy (CIDRAP).
The study — a meta-analysis of past studies — found that although vaccines provide adults aged 18 to 65 “modest protection” against influenza during most flu seasons, the evidence for protection in adults aged 65 or older is lacking.
The study also found that while there’s good evidence that the “live” nasal-spray flu vaccine is significantly effective in young children (those aged 6 months to 7 years), there is no such evidence in support of inactivated “jab-in-the-arm” vaccines. Yet most young children receive the inactivated version.
The authors of this study are not saying, however, that individuals should forgo getting vaccinated this flu season. They are arguing, instead, that we’ve become too complacent about our current vaccines and that there are gaps in our knowledge about their efficacy.
“While the [influenza] vaccine does work and we still recommend its use, we need a much better one,” said Michael Osterholm, the director of CIDRAP and the study’s lead author, in a phone interview. “What’s holding us back is this perception that what we have now is good enough.”
Only studies with solid endpoints
For the study, which was published online Tuesday in The Lancet Infectious Diseases, Osterholm and colleagues from CIDRAP, the Marshfield Clinic Research Foundation and Johns Hopkins University screened more than 5,700 studies published between 1967 and early 2011 that had investigated the efficacy and effectiveness of the influenza vaccine.
From that pool of studies, the researchers selected only those that used laboratory-confirmed influenza as their endpoints — in other words, only those studies that could be sure that the people who were diagnosed with the influenza virus actually had the illness. Such studies are also more likely to find cases of influenza that occur among their participants. Osterhom and his colleagues rejected studies that used other endpoints, such as a rise in blood levels of influenza antibodies. Antibody levels are not always reliable for confirming illness. That’s because the vaccine itself can interfere with antibody levels in a way that can cause a false-negative diagnosis of influenza, which, in turn, can lead to an overestimation of the vaccine’s effectiveness.
Using this and other stringent selection criteria, Osterholm and his colleagues ended up with 31 eligible studies: 17 randomized controlled trials (considered the gold standard of research) and 14 observational studies. After analyzing the data in these studies in detail (which involved more than 54,000 people and 24 flu seasons), they made the following observations:
- According to 10 of the randomized controlled trials, trivalent inactivated vaccines (TIV) helped prevent influenza in 8 of 12 flu seasons. The combined efficacy observed in those trials was 59 percent for adults aged 18 to 64 years.
To put it in another way, more than 40 percent of the individuals who received the flu shot received no protection from it.
- None of the studies selected under the standards of this meta-analysis showed TIV protected children aged 8 to 17 years or adults aged 65 years or older.
- Ten trials showed that the live attenuated influenza vaccine (LAIV), or nasal-spray vaccine, was protective in nine of 12 flu seasons, for a combined efficacy of 83 percent (an impressive showing) — but only in children aged 6 months to 7 years.
- One trial found that LAIV had an efficacy level of 42 percent in people aged 60 and older, with the protection highest (57 percent) in those 70 and older.
- None of the randomized controlled trials showed LAIV significantly protected individuals aged 8 to 59.
The researchers also found that, according to the results of five observational studies, the effectiveness of the 2009 monovalent pandemic (H1N1) vaccine was 69 percent — a level far too low to effectively respond to a pandemic, said Osterholm.
A call for better vaccines
The one piece of really good news in this study, Osterholm noted, is that the live nasal-spray vaccine works well in young children.
Yet, the live vaccine, which was first approved for use in the U.S. in 2003, accounts for less than 10 percent of the flu vaccines given out each year. Furthermore, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) doesn’t currently recommend the live vaccine for children under the age of 8.
Most of the findings from the U of M study are troubling, however — particularly the lack of evidence about the flu vaccine’s effectiveness among the elderly. After all, older people are among the most in need of an effective vaccine, for their weakened immune defenses put them at increased risk of dying from the illness. An estimated 90 percent of flu-related deaths and more than 60 percent of flu-related hospitalizations in the United States each year involve people aged 65 and older, according to the CDC.
Ironically, one of the key reasons we have so little information about the effectiveness of the flu vaccine on the elderly is the fact that the vaccine is recommended for them. It’s considered unethical to deny them the vaccine, which is, of course, what would happen to some of them if they were to enter a trial and be randomized into the placebo group.
“We clearly need better vaccines,” said Osterholm — ones with a level of protection similar to the 90 percent or higher protection offered by childhood vaccines.
“We’re currently working with what I would call an iPhone 1.0 device,” he added. “What we need is an iPhone 10.0 device if we really want to have an impact on the morbidity and mortality of influenza.”