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      The healthcare and societal burden associated with influenza in vaccinated and unvaccinated European and Israeli children

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          Abstract

          Few data exist regarding the healthcare and societal burden of culture-confirmed influenza illness in European and Israeli children. The current analysis describes this burden in vaccinated and unvaccinated children 2–17 years of age. Healthcare and societal burden outcomes were prospectively collected for culture-confirmed influenza illness in three previous randomized studies: a study of live attenuated influenza vaccine (LAIV) versus placebo in children aged <48 months attending day care ( N = 846–973), and studies of LAIV versus inactivated influenza vaccine (IIV) in children aged <72 months with recurrent respiratory infections ( N = 1,609) and in children aged 6–17 years with asthma ( N = 2,211). The incidence of each endpoint among enrolled subjects and subjects with influenza was determined by treatment group and by country. Among subjects with influenza, 57–91 % missed school or day care, 45–90 % used non-antibiotic medications, 29–55 % of parents missed work, 17–55 % used antibiotics, 11–62 % had additional provider visits, and 9–20 % had acute otitis media. Where evaluated, rates of outcomes were generally similar between countries. Among all children enrolled, LAIV recipients missed 324–902 and 150 fewer days of day care per 1,000 children than those of placebo and IIV recipients, respectively; parents of LAIV recipients missed 197–340 and 76 fewer days of work per 1,000 children than those of placebo and IIV recipients, respectively. Influenza illness in European and Israeli children 2–17 years of age resulted in a considerable absenteeism and healthcare utilization that was similar across the countries studied. These data underscore the potential benefits of annual vaccination of children against influenza.

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          The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children.

          Influenzavirus vaccine is used infrequently in healthy children, even though the rates of influenza in this group are high. We conducted a multicenter, double-blind, placebo-controlled trial of a live attenuated, cold-adapted, trivalent influenzavirus vaccine in children 15 to 71 months old. Two hundred eighty-eight children were assigned to receive one dose of vaccine or placebo given by intranasal spray, and 1314 were assigned to receive two doses approximately 60 days apart. The strains included in the vaccine were antigenically equivalent to those in the inactivated influenzavirus vaccine in use at the time. The subjects were monitored with viral cultures for influenza during the subsequent influenza season. A case of influenza was defined as an illness associated with the isolation of wild-type influenzavirus from respiratory secretions. The intranasal vaccine was accepted and well tolerated. Among children who were initially seronegative, antibody titers increased by a factor of four in 61 to 96 percent, depending on the influenza strain. Culture-positive influenza was significantly less common in the vaccine group (14 cases among 1070 subjects) than the placebo group (95 cases among 532 subjects). The vaccine efficacy was 93 percent (95 percent confidence interval, 88 to 96 percent) against culture-confirmed influenza. Both the one-dose regimen (89 percent efficacy) and the two-dose regimen (94 percent efficacy) were efficacious, and the vaccine was efficacious against both strains of influenza circulating in 1996-1997, A(H3N2) and B. The vaccinated children had significantly fewer febrile illnesses, including 30 percent fewer episodes of febrile otitis media (95 percent confidence interval, 18 to 45 percent; P<0.001). A live attenuated, cold-adapted influenzavirus vaccine was safe, immunogenic, and effective against influenza A(H3N2) and B in healthy children.
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            Burden of influenza in children in the community.

            Influenza vaccination of healthy children is encouraged because children are frequently hospitalized for influenza-attributable illnesses. However, most children with influenza are treated as outpatients, and scarce data are available on the burden of influenza in these children. We performed a prospective study of respiratory infections in preenrolled cohorts of children < or = 13 years old during 2 consecutive respiratory seasons (2231 child-seasons of follow-up). At any sign of respiratory infection, we examined the children and obtained a nasal swab for the detection of influenza. The parents filled out daily symptom diaries. Of all the enrollees, 94% remained active participants in the study. The average annual rate of influenza was highest (179 cases/1000 children) among children < 3 years old. Acute otitis media developed as a complication of influenza in 39.7% of children < 3 years old. For every 100 influenza-infected children < 3 years old, there were 195 days of parental work loss (mean duration, 3.2 days). Influenza causes a substantial burden of illness on outpatient children and their families. Vaccination of children < 3 years old might be beneficial for reducing the direct and indirect costs of influenza in children. Copyright 2004 Infectious Diseases Society of America
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              Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine.

              To determine the safety, immunogenicity, and efficacy of revaccination of children with live attenuated influenza vaccine. A 2-year multicenter, double-blind, placebo-controlled, efficacy field trial of live attenuated, cold-adapted trivalent influenza vaccine administered by nasal spray to children. This report summarizes year 2 results, a year in which the epidemic strain of influenza A/Sydney was not well matched to the vaccine strains. Each year, vaccine strains were antigenically equivalent to the contemporary inactivated influenza vaccine. In year 2, a single intranasal revaccination was administered. Active surveillance for influenza was conducted during the influenza season by means of viral cultures. Influenza cases were defined as illnesses with wild-type influenza virus isolated from respiratory secretions. In year 2, 1358 (85%) children, 26 to 85 months of age, returned for revaccination. The intranasal vaccine was easily accepted, well tolerated, and immunogenic. Revaccination resulted in 82% to 100% of the vaccinated children in a subset studied for immunogenicity being seropositive as compared with 26% to 65% of placebo recipients, depending on the influenza strain tested. No serious adverse events were associated with the vaccine. In addition to the strains in the vaccine, antibody was induced to the variant strain A/Sydney/H3N2. In year 2, influenza A/Sydney/H3N2, a variant not contained in the vaccine, caused 66 of 70 cases of influenza A; nonetheless, intranasal vaccine was 86% efficacious in preventing A/Sydney influenza. Eight cases of lower respiratory tract disease were associated with A/Sydney influenza; all cases were in the placebo group. This live attenuated, cold-adapted influenza vaccine was safe, immunogenic, and efficacious against influenza A/H3N2 (including a variant, A/Sydney, not contained in the vaccine) and influenza B. The characteristics of this vaccine make it suitable for routine use in children to prevent influenza.
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                Author and article information

                Contributors
                +1-301-3984454 , +1-301-3989454 , AmbroseC@MedImmune.com
                antonovae@medimmune.com
                Journal
                Eur J Clin Microbiol Infect Dis
                Eur. J. Clin. Microbiol. Infect. Dis
                European Journal of Clinical Microbiology & Infectious Diseases
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0934-9723
                1435-4373
                4 October 2013
                4 October 2013
                2014
                : 33
                : 569-575
                Affiliations
                MedImmune, One MedImmune Way, Gaithersburg, MD 20878 USA
                Article
                1986
                10.1007/s10096-013-1986-6
                3953551
                24091746
                c519c11f-4a7b-4446-9db4-1d366a8bc958
                © The Author(s) 2013

                Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 28 June 2013
                : 15 September 2013
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                Article
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2014

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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