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Live attenuated influenza vaccine (LAIV4), or FluMist, was less effective at preventing flu, especially influenza A/H1N1, in recent flu seasons among kids than inactivated influenza vaccine (IIV) was, researchers found.

A pooled analysis found that vaccine effectiveness for quadrivalent live attenuated influenza vaccine among children was 20% (95% CI -6% to 39%) for children ages 2-17 against influenza A/H1N1 (pdm09) compared with 67% (95% CI 62%-72%) for the inactivated influenza vaccine, reported Jessie Chung, MPH, of the CDC, and colleagues.

Moreover, patients who received LAIV4 had significantly higher odds of contracting the H1N1 strain compared with those who received IIV (OR 2.66, 95% CI 2.06-3.44), the authors wrote in .

When combining data from the 2013-2014 to the 2015-2016 flu seasons, overall vaccine effectiveness against any flu was 26% (95% CI 15%-36%) for LAIV4 compared with 51% (95% CI 47%-54%) for IIV, and recipients of LAIV4 had higher odds of testing positive for any flu (OR 1.48, 95% CI 1.28-1.70), they noted.

FluMist has had a roller coaster of highs and lows in recent years -- going from the CDC's Advisory Committee on Immunization Practices (ACIP) giving a preferential recommendation to this type of vaccine during the 2014-2015 season, to kicking it off the roster entirely during the 2016-2017 flu season, to adding it back as an option during the 2018-2019 flu season.

Regardless, the American Academy of Pediatrics (AAP) recently encouraged clinicians to use inactivated influenza vaccine as the "primary choice" when possible, and AAP liaison members spoke out against reinstating FluMist at the February 2018 ACIP meeting.

In this study, the authors raised questions about the accuracy of prior LAIV4 vaccine efficacy estimates, citing "heterogeneous findings," as well as potential differences between U.S. and European vaccine effectiveness, where prior vaccination in the U.S. may have had an impact.

Researchers examined pooled individual patient-level data from five studies ranging from 2013-2014 to 2015-2016 in the CDC's .

Overall, data from over 17,000 children ages 2-17 was included, with an average age of around 7. One-fourth of patients tested positive for influenza, and among them 37% were infected with influenza A/H3N2, with 25% infected with influenza A/H1N1 (pdm09), and 25% infected with influenza B.

One third of patients were vaccinated and 30% of those received quadrivalent live attenuated influenza vaccine, the authors said. The authors noted that LAIV4 and IIV had similar effectiveness against influenza A/H3N2 and B viruses.

An by Pedro Piedra, MD, of Baylor College of Medicine in Houston, said that the results of these five combined observational studies "provide a compelling argument why ACIP made the interim recommendation against... use" of LAIV4 in two recent flu seasons.

Piedra also reviewed potential hypotheses from the World Health Organization, including "methodological study differences; inadequate vaccine handling at vaccine distribution centers; intrinsic virological characteristics of the novel A/H1N1pdm09... used in the initial formulations of LAIV4."

Other considerations included improved coverage across age groups since the ACIP made a universal influenza vaccine recommendation in 2010 and potential "viral interference" from the second B strain when the vaccine changed from a trivalent to a quadrivalent during the 2013-2014 season, Piedra said.

He cited an interim analysis on vaccine effectiveness from England, which found an interim end-of-season adjusted vaccine effectiveness for LAIV4 in children ages 2-17 of 90.3% (95% CI 16.4%-98.9%) against influenza A/H1N1 (pdm09) for the 2017-2018 season. Piedra characterized this result as "encouraging."

Limitations to the data cited by Chung and colleagues, they said, included that "descriptive patient information beyond age, sex, and geographic region of enrollment" was not available for all studies, which could result in unmeasured confounding. The authors also said that historical vaccination data was limited to the season prior to enrollment as opposed to an entire vaccination history for most patients.