ArticlesEfficacy of human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in European infants: randomised, double-blind controlled study
Introduction
Worldwide, an estimated 611 000 children die every year from rotavirus disease, mainly in low-income countries.1 In the European Union, the annual burden of rotavirus disease is estimated at more than 200 deaths, over 87 000 admissions, and almost 700 000 outpatient visits in children younger than 5 years of age.2
An oral live attenuated human rotavirus vaccine Rotarix (RIX4414) containing the G1P[8] strain, derived from the 89-12 parent candidate,3, 4, 5 has been developed by GlaxoSmithKline (GSK) Biologicals. Two doses of the vaccine tested at different concentrations in phase II clinical trials were immunogenic, well-tolerated, and protective against rotavirus gastroenteritis.6, 7, 8, 9 In a multicentre phase III trial in Latin America (n=17 867), 85% vaccine efficacy was noted in the first efficacy follow-up period (from 2 weeks post-dose two until 1 year of age) against severe rotavirus gastroenteritis and rotavirus-related admissions, reaching 100% efficacy against the most severe episodes.10 Findings of the safety trial in 63 225 infants showed no increased risk of intussusception in vaccinated infants versus placebo.10
We aimed to investigate the efficacy of RIX4414 at the titre level and composition corresponding to the licensed Rotarix vaccine when administered concomitantly with other routine childhood vaccines, following typical European routine immunisation schedules. We report vaccine efficacy recorded during follow-up of infants over two consecutive rotavirus epidemic seasons after vaccination.
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Participants
We undertook a phase IIIb, double-blind, randomised, placebo-controlled trial in six European countries. The protocol, amendments, and consent forms were reviewed and approved by the independent ethics committee for every centre and country. The study was done according to good clinical practice guidelines and the 1996 version of the Declaration of Helsinki.
We enrolled healthy infants aged 6–14 weeks who weighed more than 2000 g at birth and whose parent or legal guardian signed an informed
Results
Between Sept 8, 2004, and Feb 1, 2005, 3994 infants were enrolled into the study (figure 1), from the Czech Republic (n=299), Finland (2890), France (146), Germany (289), Italy (25), and Spain (345). All enrolled infants received the first dose of vaccine or placebo and 3959 (99%) received both doses. The two treatment arms were similar for demographic characteristics in terms of age, sex, race, height, and weight (table 1). The study population was predominantly white. One infant received dose
Discussion
Our findings confirm the high incidence of rotavirus gastroenteritis during the first 2 years of life and, hence, a need for long-term protection induced by rotavirus vaccination. The human rotavirus vaccine RIX4414 showed high and sustained efficacy against severe rotavirus gastroenteritis and admission for rotavirus gastroenteritis. Efficacy against rotavirus gastroenteritis of any severity was high in the first year after vaccination but fell in the second year, which is in line with
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