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.
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.
Linhares
Alexandre C
AC
Instituto Evandro Chagas, Secretaria de Vigilância em Saúde, Ministry of Health, Belém, Pará, Brazil.
Velázquez
F Raúl
FR
Pérez-Schael
Irene
I
Sáez-Llorens
Xavier
X
Abate
Hector
H
Espinoza
Felix
F
López
Pío
P
Macías-Parra
Mercedes
M
Ortega-Barría
Eduardo
E
Rivera-Medina
Doris Maribel
DM
Rivera
Luis
L
Pavía-Ruz
Noris
N
Nuñez
Ernesto
E
Damaso
Silvia
S
Ruiz-Palacios
Guillermo M
GM
De Vos
Béatrice
B
O'Ryan
Miguel
M
Gillard
Paul
P
Bouckenooghe
Alain
A
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
C492457:RIX4414 vaccine; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated