Varsha K. JainLuis RiveraKhalequ ZamanRoberto A. EsposChukiat SirivichayakulBeatriz P. QuiambaoDoris M. Rivera-MedinaPirunghul KerdpanichMehmet CeyhanEner C. DinleyiciAlejandro CraviotoMohammed YunusPornthep ChanthavanichKriengsak LimkittikulZafer KurugolEmre AlhanAdrian CaplanusiSerge DurviauxPhilippe BoutetOpokua Ofori-AnyinamVijayalakshmi ChandrasekaranGhassan DbaiboBruce L. InnisGlaxoSmithKline, USAHospital Maternidad Nuestra Señora de la AltagraciaInternational Centre for Diarrhoeal Disease Research BangladeshDe La Salle Health Sciences InstituteGokilaMahidol UniversityRoyal Thai ArmyOrganización para el Desarrollo y la Investigación Salud en Honduras (ODISH)Hacettepe UniversitesiEskisehir Osmangazi Universitesi Tip FakultesiEge University Medical SchoolCukurova UniversitesiGlaxoSmithKline Pharmaceuticals SAAmerican University of Beirut Medical Center2018-10-192018-10-192013-01-01New England Journal of Medicine. Vol.369, No.26 (2013), 2481-249115334406002847932-s2.0-84890902002https://repository.li.mahidol.ac.th/handle/20.500.14594/32698BACKGROUND: Commonly used trivalent vaccines contain one influenza B virus lineage and may be ineffective against viruses of the other B lineage. We evaluated the efficacy of a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages. METHODS: In this multinational, phase 3, observer-blinded study, we randomly assigned children 3 to 8 years of age, in a 1:1 ratio, to receive the QIV or a hepatitis A vaccine (control). The primary end point was influenza A or B confirmed by real-time polymerase chain reaction (rt-PCR). Secondary end points were rt-PCR-confirmed, moderate-to-severe influenza and rt-PCR-positive, culture-confirmed influenza. The vaccine efficacy and the effect of vaccination on daily activities and utilization of health care resources were assessed in the total vaccinated cohort (2584 children in each group) and the per-protocol cohort (2379 children in the QIV group and 2398 in the control group). RESULTS: In the total vaccinated cohort, 62 children in the QIV group (2.40%) and 148 in the control group (5.73%) had rt-PCR-confirmed influenza, representing a QIV efficacy of 59.3% (95% confidence interval [CI], 45.2 to 69.7), with efficacy against culturecon-firmed influenza of 59.1% (97.5% CI, 41.2 to 71.5). For moderate-to-severe rt-PCR-confirmed influenza, the attack rate was 0.62% (16 cases) in the QIV group and 2.36% (61 cases) in the control group, representing a QIV efficacy of 74.2% (97.5% CI, 51.5 to 86.2). In the per-protocol cohort, the QIV efficacy was 55.4% (95% CI, 39.1 to 67.3), and the efficacy against culture-confirmed influenza 55.9% (97.5% CI, 35.4 to 69.9); the efficacy among children with moderate-to-severe influenza was 73.1% (97.5% CI, 47.1 to 86.3). The QIV was associated with reduced risks of a body temperature above 39°C and lower respiratory tract illness, as compared with the control vaccine, in the per-protocol cohort (relative risk, 0.29 [95% CI, 0.16 to 0.56] and 0.20 [95% CI, 0.04 to 0.92], respectively). The QIV was immunogenic against all four strains. Serious adverse events occurred in 36 children in the QIV group (1.4%) and in 24 children in the control group (0.9%). CONCLUSIONS: The QIV was efficacious in preventing influenza in children. Copyright © 2013 Massachusetts Medical Society.Mahidol UniversityMedicineArticleSCOPUS10.1056/NEJMoa1215817