www.thelancet.com/infection Published online November 23, 2010 DOI:10.1016/S1473-3099(10)70255-3 1 Articles Published Online November 23, 2010 DOI:10.1016/S1473- 3099(10)70255-3 See Online/Reﬂection and Reaction DOI:10.1016/S1473- 3099(10)70263-2 Department of Paediatrics, Turku University Hospital, Turku, Finland (S Heinonen MD, H Silvennoinen MD, P Lehtinen MD, Terho Heikkinen MD); Department of Virology, University of Turku, Turku, Finland (R Vainionpää PhD); and National Inﬂuenza Centre, National Institute for Health and Welfare, Helsinki, Finland (T Ziegler PhD) Correspondence to: Dr Terho Heikkinen, Department of Paediatrics, Turku University Hospital, Kiinamyllynkatu 4–8, FI-20520 Turku, Finland terho.heikkinen@utu.ﬁ Eﬀectiveness of inactivated inﬂuenza vaccine in children aged 9 months to 3 years: an observational cohort study Santtu Heinonen, Heli Silvennoinen, Pasi Lehtinen, Raija Vainionpää, Thedi Ziegler, Terho Heikkinen Summary Background Few prospectively collected data are available to support the eﬀectiveness of inactivated inﬂuenza vaccines in children younger than 2 years. We aimed to establish the eﬀectiveness of trivalent inactivated inﬂuenza vaccine against laboratory-conﬁrmed inﬂuenza A and B infections in a cohort of children younger than 3 years. Methods In a prospective cohort study during the inﬂuenza season of 2007–08 in Turku, Finland, between Jan 14 and April 9, 2008, we assessed the eﬀectiveness of trivalent inactivated inﬂuenza vaccine against laboratory-conﬁrmed inﬂuenza A and B infections in children aged 9 months to 3 years. Our study was part of a clinical trial on antiviral treatment of inﬂuenza in children (ClinicalTrials.gov, number NCT00593502). The vaccine was given as part of the Finnish vaccination programme as a 0·5 mL injection. Children enrolled into our study through mailed announcements and local advertisements were examined every time they had fever or signs of respiratory infection. No exclusion criteria were used for enrolment. Inﬂuenza was diagnosed with viral culture, antigen detection, and RT-PCR assays of nasal swab specimens. Vaccination status of children was determined by parental report. We calculated the primary eﬀectiveness of inﬂuenza vaccination by comparing the proportions of infections in fully vaccinated and unvaccinated children in the follow-up cohort. Findings We enrolled 631 children into our study with a mean age of 2·13 years (range 9–40 months). Seven (5%) of 154 fully vaccinated children and 61 (13%) of 456 unvaccinated children contracted inﬂuenza during the study (eﬀectiveness 66%, 95% CI 29–84; p=0·003). In the subgroup of children younger than 2 years, four (4%) of 96 fully vaccinated children and 21 (12%) of 172 unvaccinated children contracted inﬂuenza (66%, 9–88, p=0·03). We were unable to record any adverse events associated with the vaccination of the children in our study. Interpretation Trivalent inactivated inﬂuenza vaccine was eﬀective in preventing inﬂuenza in young children, including those younger than 2 years. Our ﬁndings suggest that inﬂuenza vaccine recommendations should be reassessed in most countries. Funding F Hoﬀmann-La Roche Ltd. Introduction During the past decade, inﬂuenza has been increasingly recognised as an infection that places a heavy burden of illness on infants and young children. 1–5 In the USA, inﬂuenza vaccination of healthy young children has been recommended since 2003, but despite evidence of disease burden, few other countries recommend inﬂuenza vaccination of children of any age unless they have certain underlying medical disorders. 6,7 In Europe, Finland is the only country that has, since 2007, included inﬂuenza vaccine in the routine vaccination programme for all children aged 6–35 months. 7 The decisions in Finland and the USA were on the basis of extensive assessment of the epidemiology and disease burden of inﬂuenza in children and the cost-eﬀectiveness of vaccinating children against inﬂuenza, but not on any clear evidence of the eﬀectiveness of vaccination in the youngest children. 4,8,9 An obstacle to more widespread immunisation of children is the paucity of data on the eﬀectiveness of inactivated inﬂuenza vaccines in young children. 10–12 The latest Cochrane review on this topic 13 concluded that “in children under two, the eﬃcacy of inactivated vaccine was similar to placebo”. Although the authors acknowledged that this ﬁnding was on the basis of a single, small study, the absence of further eﬀectiveness studies in young children has substantially diminished the enthusiasm to consider vaccination of children in many countries. This issue has also contributed to the reluctance of the European Centre for Disease Prevention and Control to recommend universal vaccination of young children. 14,15 We aimed to establish the eﬀectiveness of a trivalent inactivated inﬂuenza vaccine against laboratory-conﬁrmed inﬂuenza A and B infections in a prospectively followed up cohort of children aged from 9 months to 3 years. Methods Participants Our prospective non-randomised cohort study was done during the inﬂuenza season of 2007–08 in Turku, Finland, between Jan 14 and April 9, 2008, as part of a clinical trial on antiviral treatment of inﬂuenza in children (ClinicalTrials.gov, number NCT00593502). The inﬂuenza season of 2007–08 was the ﬁrst one after the introduction of inﬂuenza vaccination of all children aged 6–35 months to the Finnish vaccination programme. In late November and December, 2007, children born between June 1, 2004,