2009-10 Influenza Prevention & Control Recommendations

Adverse Events After Receipt of Live, Attenuated Influenza Vaccine (LAIV)

Children

In a subset of healthy children aged 60—71 months from one clinical trial, certain signs and symptoms were reported more often after the first dose among LAIV recipients (n = 214) than among placebo recipients (n = 95), including runny nose (48 % and 44%, respectively); headache (18% and 12%, respectively); vomiting (5% and 3%, respectively); and myalgias (6% and 4%, respectively). However, these differences were not statistically significant. In other trials, signs and symptoms reported after LAIV administration have included runny nose or nasal congestion (20%--75%), headache (2%--46%), fever (0--26%), vomiting (3%—13%), abdominal pain (2%), and myalgias (0—21%). These symptoms were associated more often with the first dose and were self-limited. A placebo-controlled trial in 9,689 children aged 1--17 years assessed pre-specified medically attended outcomes during the 42 days after vaccination. Following >1,500 statistical analyses in the 42 days after LAIV, elevated risks that were biologically plausible were observed for the following conditions: asthma, upper respiratory infection, musculoskeletal pain, otitis media with effusion, and adenitis/adenopathy. The increased risk for wheezing events after LAIV was observed among children aged 18--35 months (RR: 4.06; 90% CI = 1.3—17.9). In this study, the rate of severe adverse events was 0.2% in LAIV and placebo recipients; none of the severe adverse events was judged to be related to the vaccine by the study investigators.

In a randomized trial published in 2007, LAIV and TIV were compared among children aged 6—59 months. Children with medically diagnosed or treated wheezing within 42 days before enrollment or with a history of severe asthma were excluded from this study. Among children aged 24--59 months who received LAIV, the rate of medically significant wheezing, using a pre-specified definition, was not greater compared with those who received TIV. Wheezing was observed more frequently among younger LAIV recipients aged 6—23 months in this study; LAIV is not licensed for this age group. In a previous randomized placebo-controlled safety trial among children aged 12 months—17 years without a history of asthma by parental report, an elevated risk for asthma events (RR: 4.1; CI = 1.3—17.9) was documented among 728 children aged 18—35 months who received LAIV. Of the 16 children with asthma-related events in this study, seven had a history of asthma on the basis of subsequent medical record review. None required hospitalization, and elevated risks for asthma were not observed in other age groups.

Another study was conducted among >11,000 children aged 18 months—18 years in which 18,780 doses of vaccine were administered for 4 years. For children aged 18 months—4 years, no increase was reported in asthma visits 0—15 days after vaccination compared with the pre-vaccination period. A significant increase in asthma events was reported 15—42 days after vaccination, but only in vaccine year 1. A 4–year, open–label field trial study assessed LAIV safety of more than 2000 doses administered to children aged 18 months—18 years with a history of intermittent wheeze who were otherwise healthy. Among these children, no increased risk was reported for medically attended acute respiratory illnesses, including acute asthma exacerbation, during the 0—14 or 0—42 days after LAIV compared with the pre– and post– vaccination reference periods.

Initial data from VAERS during 2007—2008, following ACIP's recommendation for LAIV use in healthy children aged 2—4 years, did not suggest a concern for wheezing after LAIV in young children. However data also suggest uptake of LAIV was limited, and safety monitoring for wheezing events after LAIV is ongoing.

Adults

Among adults, runny nose or nasal congestion (28%—78%), headache (16%—44%), and sore throat (15%—27%) have been reported more often among vaccine recipients than placebo recipients. In one clinical trial among a subset of healthy adults aged 18—49 years, signs and symptoms reported significantly more often (p<0.05) among LAIV recipients (n = 2,548) than placebo recipients (n = 1,290) within 7 days after each dose included cough (14% and 11%, respectively), runny nose (45% and 27%, respectively), sore throat (28% and 17%, respectively), chills (9% and 6%, respectively), and tiredness/weakness (26% and 22%, respectively).

Persons at Higher Risk from Influenza-related Complications

Limited data assessing the safety of LAIV use for certain groups at higher risk for influenza-related complications are available. In one study of 54 HIV-infected persons aged 18—58 years and with CD4 counts 200 cells/mm3 or greater who received LAIV, no severe adverse events were reported during a 1-month follow-up period. Similarly, one study demonstrated no significant difference in the frequency of adverse events or viral shedding among HIV-infected children aged 1—8 years on effective antiretroviral therapy who were administered LAIV compared with HIV-uninfected children receiving LAIV. LAIV was well-tolerated among adults aged 65 years and older with chronic medical conditions. These findings suggest that persons at risk for influenza complications who have inadvertent exposure to LAIV would not have significant adverse events or prolonged viral shedding and that persons who have contact with persons at higher risk for influenza-related complications may receive LAIV.