Effectiveness of live, attenuated intranasal influenza virus vaccine in healthy, working adults - A randomized controlled trial

Context Influenza virus is a major cause of illness, disruption to daily li fe, and increased use of health care in ail age groups. Objective To assess the safety and effectiveness of intranasally administer ed trivalent, live, attenuated influenza virus (LAIV) vaccine for reducing illness, absenteeism, and health care use among healthy, working adults. Design Randomized, double-blind, placebo-controlled trial conducted from Se ptember 1997 through March 1998. Setting Thirteen centers across the United States. Participants A total of 4561 healthy, working adults aged 18 to 64 years re cruited through health insurance plans, at work sites, and from the general population. Intervention Participants were randomized 2:1 to receive intranasally admin istered trivalent LAIV vaccine (n = 3041) or placebo (n = 1520) in the fall of 1997. Main Outcome Measures Episodes of febrile illness, severe febrile illness, febrile upper respiratory tract illness, work loss, and health care use dur ing the peak and total influenza outbreak periods, and adverse events. Results Recipients of LAIV vaccine were as likely to experience 1 or more f ebrile illnesses as placebo recipients during peak outbreak periods (13.2% for vaccine vs 14.6% for placebo; P=.19). However, vaccination significantl y reduced the numbers of severe febrile illnesses (18.8% reduction; 95% con fidence interval [CI], 7.4%-28.8%) and febrile upper respiratory tract illn esses (23.6% reduction; 95% CI, 12.7%-33.2%). Vaccination also led to fewer days of illness across all illness syndromes (22.9% reduction for febrile illnesses, 27.3% reduction for severe febrile illnesses), fewer days of wor k lost (17.9% reduction for severe febrile illnesses; 28.4% reduction for f ebrile upper respiratory tract illnesses), and fewer days with health care provider visits (24.8% reduction for severe febrile illnesses; 40.9% reduct ion for febrile upper respiratory tract illnesses). Use of prescription ant ibiotics and over-the-counter medications was also reduced across all illne ss syndromes. Vaccine recipients were more likely to experience runny nose or sore throat during the first 7 days after vaccination, but serious adver se events between the groups were not significantly different. The match be tween the type A(H3N2) vaccine strain and the predominant circulating virus strain (A/Sydney/05/97[H3N2]) for the 1997-1998 season was poor, suggestin g that LAIV provided substantial cross-protection against this variant infl uenza A virus strain. Conclusion Intranasal trivalent LAIV vaccine was safe and effective in heal thy, working adults in a year in which a drifted influenza A virus predomin ated.