Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis.
BACKGROUND
The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial.


METHODS
We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients).


RESULTS
The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78).


CONCLUSIONS
Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.)
Ruiz-Palacios
Guillermo M
GM
Instituto Nacional de Ciencas Medicas y Nutricion, México Distrito Federal, Mexico.
Pérez-Schael
Irene
I
Velázquez
F Raúl
FR
Abate
Hector
H
Breuer
Thomas
T
Clemens
SueAnn Costa
SC
Cheuvart
Brigitte
B
Espinoza
Felix
F
Gillard
Paul
P
Innis
Bruce L
BL
Cervantes
Yolanda
Y
Linhares
Alexandre C
AC
López
Pío
P
Macías-Parra
Mercedes
M
Ortega-Barría
Eduardo
E
Richardson
Vesta
V
Rivera-Medina
Doris Maribel
DM
Rivera
Luis
L
Salinas
Belén
B
Pavía-Ruz
Noris
N
Salmerón
Jorge
J
Rüttimann
Ricardo
R
Tinoco
Juan Carlos
JC
Rubio
Pilar
P
Nuñez
Ernesto
E
Guerrero
M Lourdes
ML
Yarzábal
Juan Pablo
JP
Damaso
Silvia
S
Tornieporth
Nadia
N
Sáez-Llorens
Xavier
X
Vergara
Rodrigo F
RF
Vesikari
Timo
T
Bouckenooghe
Alain
A
Clemens
Ralf
R
De Vos
Béatrice
B
O'Ryan
Miguel
M
D000284:Administration, Oral; D003968:Diarrhea, Infantile / Q000453:epidemiology / Q000517:prevention & control / Q000821:virology; D004311:Double-Blind Method; D005260:Female; D005759:Gastroenteritis / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D007223:Infant; D007443:Intussusception / Q000209:etiology; D008297:Male; D012306:Risk; D012401:Rotavirus; D012400:Rotavirus Infections / Q000150:complications / Q000401:mortality / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects
C492457:RIX4414 vaccine; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated