New rotavirus vaccine is effective and appears to have no increased risk of intussception

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• Ruiz-Palacios GM, Pérez-Schael I, Velázquez FR, Abate H, Breuer T, Clemens SC, et al, for the Human Rotavirus Vaccine Study Group. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med 2006;354:11-22
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Ruiz-Palacios GM, Pérez-Schael I, Velázquez FR, Abate H, Breuer T, Clemens SC, et al, for the Human Rotavirus Vaccine Study Group. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med 2006;354:11-22 

Question How safe and efficacious is an attenuated G1P[8] human rotavirus (HRV) vaccine, particularly in terms of the risk of intussusception?

Design Randomized, double-blind trial.

Setting 11 Latin American countries and Finland.

Participants 63,225 healthy infants.

Intervention Infants were randomized to receive 2 oral doses of either the HRV vaccine or placebo at approximately 2 months and 4 months of age.

Outcomes Severe gastroenteritis episodes, identified by active surveillance. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccine recipients and 10,010 placebo recipients).

Main Results The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85% (P < .001 for the comparison with placebo, number needed to treat = 177) and reached 100% against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42% (95% confidence interval, 29% to 53%; P < .001, number needed to treat = 86). During the 31-day window after each dose, 6 vaccine recipients and 7 placebo recipients had definite intussusception (difference in risk, −0.32 per 10,000 infants; 95% 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.

Commentary This article demonstrates the convincing and powerful nature of a well-designed, thoughtfully and thoroughly evaluated clinical study. This will undoubtedly provide rich clinical evidence to persuade the primary caretakers of infants worldwide on the matter of vaccination against rotavirus-associated illnesses. This trial uses a large, multinational study group in 2 separate cohorts to analyze both safety and efficacy of an attenuated rotavirus vaccine. The power is adequate to detect differences within the safety cohort regarding risk of intussusception and other significant adverse events, using data on the incidence of intussusception among similarly-aged infants within their regions. The study also accounts for all participants enrolled in the study and has a minimal drop-out rate; in addition, their methods of active surveillance for cases of intussusception are thorough. Their analysis reveals no significant increase in risk of intussusception among vaccine recipients within 31 days of receiving either dose of a 2-dose schedule. Instituting a broad clinical directive to add this vaccine to the already busy standard immunization schedule recommended for U.S. children obviously involves many different considerations, including cost-benefit analysis, societal and physician perceptions of risks of rotavirus infection, and the availability of safe, large-scale vaccine production. Nonetheless, at this point, it appears this vaccine does not place healthy infants at higher risk of intussusception, as was the case with the previous rotavirus vaccine.