A trivalent, live, attenuated influenza vaccine was approved in June 2003 by the U.S. Food and Drug Administration. Although this intranasally administered vaccine was determined to be safe, Izurieta and associates reviewed adverse events associated with postlicensure use during the 2003–2004 and 2004–2005 influenza seasons. The review was based on adverse event reporting. Adverse events were classified according to several criteria as related to hypersensitivity, the nervous system, possible transmission, respiratory exacerbations, asthma, or other conditions.
Among the 2,500,000 persons to whom the vaccine was administered (most during the 2004–2005 season), 460 adverse events were reported. Of these, 40 (9 percent) were deemed serious. Although the vaccine is approved for use in persons five to 49 years of age, the age range of those who received the vaccine was two to 70 years. Seven patients had events that could be classified as anaphylactic, including four patients with throat and periorbital swelling, but none required hospitalization. Each event occurred within three hours of administering the vaccine. Other allergic events included urticaria and rash. Although there were 22 reports of possible secondary transmission, only one specimen was analyzed in a laboratory, and that proved to be a wild strain unrelated to the vaccine. Twelve asthma episodes were reported; these occurred within a few hours to more than one month after vaccine administration, mostly in persons who had a history of asthma. Of 10 neurologic events reported, two were identified as Guillain-Barré syndrome, and one of the patients with this diagnosis was hospitalized. Other serious events included one report of acute disseminated encephalomyelitis and one of encephalitis. Both patients recovered without sequelae. There also were reports of constitutional symptoms such as dizziness and of ear, nose, and throat symptoms such as nasal ulcers and nosebleeds.
Seventy-three events (16 percent) occurred in patients for whom the vaccine was not indicated (i.e., those outside the recommended age range and those with preexisting chronic conditions). Most of these events involved influenza-like illnesses, rhinitis, or other respiratory symptoms, although one patient with a history of cardiovascular disease had an acute myocardial infarction two days after vaccination and was hospitalized.
The rate of anaphylaxis was two per 1 million vaccinees, which is consistent with rates associated with the measles, mumps, and rubella vaccination. No definitive conclusion can be drawn about secondary transmission, because only one report was investigated through laboratory tests, but it is likely that the respiratory symptoms in contacts were coincidental. The patients with Guillain-Barré syndrome could have been affected through means unrelated to the vaccine, because one had previous exposure to gastroenteric illness and the other had a respiratory illness. Nasal and ocular symptoms might be true adverse effects, given the vaccine’s route of administration. Two previous trials showed an increased risk of asthma exacerbation from the vaccine in patients with a history of asthma. However, the authors conclude that overall the vaccine is not associated with any serious risks in persons for whom it is approved.