Abstract

Background: Peak incidence of rotavirus gastroenteritis is seen in infants between 6 and 24 months of age. We therefore aimed to assess the 2-year efficacy and safety of an oral live attenuated human rotavirus vaccine for prevention of severe gastroenteritis in infants. Methods: 15 183 healthy infants aged 6-13 weeks from ten Latin American countries randomly assigned in a 1 to 1 ratio to receive two oral doses of RIX4414 or placebo at about 2 and 4 months of age in a double-blind, placebo-controlled phase III study were followed up until about 2 years of age. Primary endpoint was vaccine efficacy from 2 weeks after dose two until 1 year of age. Treatment allocation was concealed from investigators and parents of participating infants. Efficacy follow-up for gastroenteritis episodes was undertaken from 2 weeks after dose two until about 2 years of age. Analysis was according to protocol. This study is registered with ClinicalTrials.gov, number NCT00140673 (eTrack444563-023). Findings: 897 infants were excluded from the according-to-protocol analysis. Fewer cases (p<0·0001) of severe rotavirus gastroenteritis were recorded for the combined 2-year period in the RIX4414 group (32 [0·4%] of 7205; 95% CI 0·3-0·6) than in the placebo group (161 [2·3%] of 7081; 1·9-2·6), resulting in a vaccine efficacy of 80·5% (71·3-87·1) to 82·1% (64·6-91·9) against wild-type G1, 77·5% (64·7-86·2) against pooled non-G1 strains, and 80·5% (67·9-88·8) against pooled non-G1 P[8] strains. Vaccine efficacy for hospital admission for rotavirus gastroenteritis was 83·0% (73·1-89·7) and for admission for diarrhoea of any cause was 39·3% (29·1-48·1). No cases of intussusception were reported during the second year of follow-up. Interpretation: Two doses of RIX4414 were effective against severe rotavirus gastroenteritis during the first 2 years of life in a Latin American setting. Inclusion of RIX4414 in routine paediatric immunisations should reduce the burden of rotavirus gastroenteritis worldwide. Funding: GlaxoSmithKline. © 2008 Elsevier Ltd. All rights reserved.