Wide-spread Use Of Intranasal Flu Vaccine Does Not Show Unexpected Serious Risks

Annual influenza vaccination is the primary method for protection against influenza illness, according to background information in the article. Until the 2002-2003 influenza season, the only licensed influenza vaccine in the United States was the inactivated, trivalent (reacting immunologically with three different combining sites [as of antigens or antibodies]) injectable vaccine, with recommendations emphasizing use among individuals for whom influenza is of particular concern. In June 2003, the U.S. Food and Drug Administration (FDA) licensed a trivalent live, attenuated influenza vaccine (LAIV-T [FluMist]) for intranasal use among healthy persons 5 to 49 years of age. Each dose contains live attenuated influenza virus of the 3 strains recommended by the U.S. Public Health Service for the corresponding influenza season. Although the number of vaccinees studied during prelicensure LAIV-T clinical trials was relatively large (20,228), postlicensure administration of the vaccine to much larger populations could reveal new safety issues.

Hector S. Izurieta, M.D., M.P.H., of the Food and Drug Administration, Rockville, Md., and colleagues examined the adverse events reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) during the first 2 influenza seasons (2003-2004, 2004-2005) following LAIV-T licensure to identify new or unexpected adverse events, including rare events.

Approximately 2,500,000 persons received LAIV-T during the first 2 postlicensure seasons. As of August 16, 2005, VAERS received 460 adverse event reports for vaccinations received from August 2003 through July 2005. No fatalities were reported. There were 7 reports of possible anaphylaxis (hypersensitivity reaction to the injection of a substance resulting from prior contact with a substance), 2 reports of Guillain-Barré syndrome (GBS - a temporary inflammation of the nerves, causing pain, weakness, and paralysis in the extremities), 1 report of Bell palsy (paralysis of the facial muscles), and 8 reports of asthma exacerbation among individuals with a prior asthma history. Events in individuals for whom the vaccine was not indicated accounted for 73 reports (16 percent).

"Reports to VAERS in the first 2 seasons of LAIV-T use did not identify any unexpected serious risk with this vaccine when used according to approved indications. Like many vaccines and other medical products, LAIV-T may rarely cause anaphylaxis. As with other vaccines, LAIV-T could carry the risk of anaphylaxis or other allergic events. Continued monitoring of neurological events, such as GBS, appears warranted. Determination of the risk of secondary transmission of the vaccine virus would require a focused clinical study," the authors write.

"The reports of asthma exacerbations in vaccinees with prior asthma history highlight the potential risks of not following the approved indications and support the need for continued close surveillance for asthma exacerbations following use of this vaccine. The finding of a high proportion of vaccine administration errors and the reports of use among persons for whom this vaccine was not indicated underscore the need for the clinician to follow the package insert indications regarding vaccine administration and patient eligibility," the researchers conclude.

(JAMA.2005; 294:2720-2725. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: The study was implemented by FDA and CDC scientists and the only funds used were from CDC and FDA budgets. This study had no external sponsors.

Editorial: Vaccine Safety - Achieving the Proper Balance

In an accompanying editorial, Kathleen M. Neuzil, M.D., M.P.H., of the University of Washington, Seattle, and Marie R. Griffin, M.D., M.P.H., of Vanderbilt University School of Medicine, Nashville, Tenn., discuss the issue of vaccine safety.

"In an era in which influenza vaccine delays and shortages have become the norm, LAIV represents an important option to increase vaccination rates among healthy persons for their own protection and for the protection of those with whom they have close contact. Currently, LAIV is licensed for healthy persons 5 to 49 years of age, although expanded indications may be forthcoming (based on the intent of the company to file for broader licensure). As with any licensed product, continued monitoring of the safety of LAIV will be important. However, the cumulative evidence, including the VAERS experience, should reassure clinicians and patients of the safety of both licensed influenza vaccines. Decisions regarding which influenza vaccine to choose in the healthy 5- to 49-year-old age group should be based on availability, patient preference, and cost," the authors write.

(JAMA.2005; 294:2763-2765. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: Dr. Neuzil has received research funding from MedImmune for participation in a multicenter clinical trial of an LAIV in 2004-2005.