title: Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study.
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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Instituto Evandro Chagas, Secretaria de Vigilância em Saúde, Ministry of Health, Belém, Pará, Brazil.
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Linhares
authors.forename: F Raúl
authors.initials: FR
authors.lastname: Velázquez
authors.forename: Irene
authors.initials: I
authors.lastname: Pérez-Schael
authors.forename: Xavier
authors.initials: X
authors.lastname: Sáez-Llorens
authors.forename: Hector
authors.initials: H
authors.lastname: Abate
authors.forename: Felix
authors.initials: F
authors.lastname: Espinoza
authors.forename: Pío
authors.initials: P
authors.lastname: López
authors.forename: Mercedes
authors.initials: M
authors.lastname: Macías-Parra
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ortega-Barría
authors.forename: Doris Maribel
authors.initials: DM
authors.lastname: Rivera-Medina
authors.forename: Luis
authors.initials: L
authors.lastname: Rivera
authors.forename: Noris
authors.initials: N
authors.lastname: Pavía-Ruz
authors.forename: Ernesto
authors.initials: E
authors.lastname: Nuñez
authors.forename: Silvia
authors.initials: S
authors.lastname: Damaso
authors.forename: Guillermo M
authors.initials: GM
authors.lastname: Ruiz-Palacios
authors.forename: Béatrice
authors.initials: B
authors.lastname: De Vos
authors.forename: Miguel
authors.initials: M
authors.lastname: O'Ryan
authors.forename: Paul
authors.initials: P
authors.lastname: Gillard
authors.forename: Alain
authors.initials: A
authors.lastname: Bouckenooghe
mesh_terms: D002423:Cause of Death; D002675:Child, Preschool; D004311:Double-Blind Method; D005243:Feces / Q000382:microbiology; D005260:Female; D005500:Follow-Up Studies; D005759:Gastroenteritis / Q000517:prevention & control* / Q000821:virology*; D006801:Humans; D007223:Infant; D007843:Latin America; D008297:Male; D012401:Rotavirus / Q000145:classification*; D012400:Rotavirus Infections / Q000517:prevention & control* / Q000821:virology*; D022243:Rotavirus Vaccines; D013045:Species Specificity; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000008:administration & dosage* / Q000276:immunology
chemical_list: C492457:RIX4414 vaccine; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated