Efficacy of live attenuated influenza vaccine in children: A meta-analysis of nine randomized clinical trials
Introduction
Influenza virus causes significant morbidity and mortality worldwide [1], [2], [3], [4], and annual influenza epidemics confer a heavy burden on health care systems [2], [4], [5], [6]. Although children are among the most susceptible to influenza infection and are most likely to transmit the illness to others [2], [6], [7], [8], [9], [10], many children do not receive influenza vaccination [8], [11], [12]. Moreover, most vaccine-naive children younger than 9 years of age who do receive vaccination receive only one dose rather than the recommended two-dose regimen [8], [11], [13].
An intranasal cold-adapted, live attenuated influenza virus vaccine [LAIV; FluMist® (Influenza Virus Vaccine Live, Intranasal); MedImmune, Gaithersburg, MD, USA] was first approved for use in the United States in 2003. In September 2007, the US Food and Drug Administration expanded the indication for use in individuals 2–49 years of age, from the previous 5–49-year indication. Several pediatric studies have characterized the safety and efficacy of LAIV in children, and the vaccine was shown to be efficacious in each of these studies [14], [15], [16], [17], [18], [19], [20], [21], [22], [23] (Table 1, Table 2). Performing meta-analyses on clinically important subsets of the population of children evaluated in these studies provides more precise estimates of the efficacy of the LAIV vaccine than does reliance on a single study. Previous meta-analyses of LAIV efficacy [24], [25], [26], [27] included data from several investigational LAIV formulations and did not include data from several recently published studies. The meta-analyses conducted here focus solely on data for the LAIV that has been approved for use in the United States (FluMist). We summarize data comparing the efficacy of LAIV with either trivalent inactivated influenza vaccine (TIV) or placebo.
Section snippets
Studies used in the meta-analyses
Wyeth Vaccines Research (Pearl River, NY, USA) and MedImmune have conducted nine randomized, double-blind, controlled trials evaluating the efficacy of LAIV against culture-confirmed influenza in children. Most of the children studied were young. Six trials compared LAIV with placebo [14], [15], [16], [17], [18], [19], [20] (Table 1) in children aged between 6 and 71 months. Three trials compared LAIV with TIV [21], [22], [23] (Table 2); two of these studied children aged 6–71 months, while one
Study subjects
The nine studies included approximately 25,000 children aged 6–71 months and approximately 2000 children aged 6–17 years throughout Asia, Europe, the Middle East, South America, and the United States. Each trial included at least 1000 children. With the exception of two studies evaluating children with a history of recurrent respiratory tract infections or diagnosed with asthma, the children generally did not have significant underlying medical conditions. All but two of the studies [22], [23]
Discussion
Previous meta-analyses and study summaries that have compared LAIV against TIV or placebo [24], [25], [26], [27] have shown that both vaccines are safe and effective for protecting children against influenza; combined estimates of vaccine efficacy have ranged from 63% to 65% for TIV and 79% to 80% for LAIV. However, these previous meta-analyses included data from early investigational LAIV formulations and did not include several recently published studies. The meta-analyses discussed here are
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