Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in Asia: a randomised, double-blind, placebo-controlled trial.
BACKGROUND
Rotavirus vaccine has proved effective for prevention of severe rotavirus gastroenteritis in infants in developed countries, but no efficacy studies have been done in developing countries in Asia. We assessed the clinical efficacy of live oral pentavalent rotavirus vaccine for prevention of severe rotavirus gastroenteritis in infants in Bangladesh and Vietnam.


METHODS
In this multicentre, double-blind, placebo-controlled trial, undertaken in rural Matlab, Bangladesh, and urban and periurban Nha Trang, Vietnam, infants aged 4-12 weeks without symptoms of gastrointestinal disorders were randomly assigned (1:1) to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age, in conjunction with routine infant vaccines including oral poliovirus vaccine. Randomisation was done by computer-generated randomisation sequence in blocks of six. Episodes of gastroenteritis in infants who presented to study medical facilities were reported by clinical staff and from parent recollection. The primary endpoint was severe rotavirus gastroenteritis (Vesikari score >or=11) arising 14 days or more after the third dose of placebo or vaccine to end of study (March 31, 2009; around 21 months of age). Analysis was per protocol; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00362648.


RESULTS
2036 infants were randomly assigned to receive pentavalent rotavirus vaccine (n=1018) or placebo (n=1018). 991 infants assigned to pentavalent rotavirus vaccine and 978 assigned to placebo were included in the per-protocol analysis. Median follow up from 14 days after the third dose of placebo or vaccine until final disposition was 498 days (IQR 480-575). 38 cases of severe rotavirus gastroenteritis (Vesikari score >or=11) were reported during more than 1197 person-years of follow up in the vaccine group, compared with 71 cases in more than 1156 person years in the placebo group, resulting in a vaccine efficacy of 48.3% (95% CI 22.3-66.1) against severe disease (p=0.0005 for efficacy >0%) during nearly 2 years of follow-up. 25 (2.5%) of 1017 infants assigned to receive vaccine and 20 (2.0%) of 1018 assigned to receive placebo had a serious adverse event within 14 days of any dose. The most frequent serious adverse event was pneumonia (vaccine 12 [1.2%]; placebo 15 [1.5%]).


CONCLUSIONS
In infants in developing countries in Asia, pentavalent rotavirus vaccine is safe and efficacious against severe rotavirus gastroenteritis, and our results support expanded WHO recommendations to promote its global use.


BACKGROUND
PATH (GAVI Alliance grant) and Merck.
Zaman
K
K
International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
Dang
Duc Anh
DA
Victor
John C
JC
Shin
Sunheang
S
Yunus
Md
M
Dallas
Michael J
MJ
Podder
Goutam
G
Vu
Dinh Thiem
DT
Le
Thi Phuong Mai
TP
Luby
Stephen P
SP
Le
Huu Tho
HT
Coia
Michele L
ML
Lewis
Kristen
K
Rivers
Stephen B
SB
Sack
David A
DA
Schödel
Florian
F
Steele
A Duncan
AD
Neuzil
Kathleen M
KM
Ciarlet
Max
M
D000284:Administration, Oral; D000914:Antibodies, Viral / Q000097:blood; D001459:Bangladesh; D003906:Developing Countries; D004311:Double-Blind Method; D005260:Female; D005759:Gastroenteritis / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D007115:Immunization Schedule; D007070:Immunoglobulin A / Q000097:blood; D007223:Infant; D008297:Male; D012400:Rotavirus Infections / Q000276:immunology / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D012720:Severity of Illness Index; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014744:Vietnam
D000914:Antibodies, Viral; D007070:Immunoglobulin A; C492535:RotaTeq; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated