BACKGROUND: We evaluated an inactivated quadrivalent influenza vaccine (IIV4) in children 6-35 months of age in a phase III, observer-blind trial. METHODS: The aim of this analysis was to estimate vaccine efficacy (VE) in preventing laboratory-confirmed influenza in each of 5 independent seasonal cohorts (2011-2014), as well as vaccine impact on healthcare utilization in 3 study regions (Europe/Mediterranean, Asia-Pacific and Central America). Healthy children were randomized 1:1 to IIV4 or control vaccines. VE was estimated against influenza confirmed by reverse transcription polymerase chain reaction on nasal swabs. Cultured isolates were characterized as antigenically matched/mismatched to vaccine strains. RESULTS: The total vaccinated cohort included 12,018 children (N = 1777, 2526, 1564, 1501 and 4650 in cohorts 1-5, respectively). For reverse transcription polymerase chain reaction confirmed influenza of any severity (all strains combined), VE in cohorts 1-5 was 57.8%, 52.9%, 73.4%, 30.3% and 41.4%, respectively, with the lower limit of the 95% confidence interval >0 for all estimates. The proportion of vaccine match for all strains combined in each cohort was 0.9%, 79.3%, 72.5%, 24.1% and 28.6%, respectively. Antibiotic use associated with influenza illness was reduced with IIV4 by 71% in Europe, 36% in Asia Pacific and 59% in Central America. CONCLUSIONS: IIV4 prevented influenza in children 6-35 months of age in each of 5 separate influenza seasons in diverse geographical regions. A possible interaction between VE, degree of vaccine match and socioeconomic status was observed. The IIV4 attenuated the severity of breakthrough influenza illness and reduced healthcare utilization, particularly antibiotic use.

Center for Excellence in Pediatric Infectious Diseases and Vaccines Chulalongkorn University Bangkok Thailand

Center of Postgraduate Medical Education Warsaw Poland

Centre for Community Medicine All India institute of Medical Sciences New Delhi India

Centro Médico Dominicano Santo Domingo Dominican Republic

Charles University Prague School of Medicine Hradec Kralove Czech Republic

Complutense University of Madrid Spain

Dr Castroviejo Primary Health Care Center Madrid Spain

EBA Centelles Barcelona Spain

Eskisehir Osmangazi University Eskisehir Turkey

FISABIO Public Health Valencia Spain

From the American University of Beirut Beirut Lebanon

GSK Bangalore India

GSK King of Prussia Pennsylvania

GSK Rockville Maryland

GSK Wavre Belgium

Hospital Clínico Universitario de Santiago Santiago Spain

Hospital Infantil Universitario La Paz Madrid Spain

icddr b Dhaka Bangladesh

Institut Pediàtric Marès Riera Blanes Spain

Instituto Hispalense de Pediatría Sevilla Spain

KEM Hospital Research Centre Pune India

Khon Kaen University Khon Kaen Thailand

Mary Chiles General Hospital Manila Philippines

Medicentrum 6 s r o Prague Czech Republic

National Autonomous University of Honduras Tegucigalpa Honduras

National Autonomous University of Santo Domingo Santo Domingo Dominican Republic

Nicolaus Copernicus University in Torun Collegium Medicum Bydgoszcz Poland and University Hospital No 2 Bydgoszcz Poland

Research Institute for Tropical Medicine Manila Philippines

Royal Manchester Children's Hospital Manchester United Kingdom

St Hedwig of Silesia Hospital Trzebnica Poland

Tecnologia en Investigacion San Pedro Sula Honduras

Uludag University Bursa Turkey

University of Southampton and University Hospital Southampton NHS Foundation Trust Southampton United Kingdom

University of the Philippines Philippine General Hospital Manila Philippines

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