Effect of human rotavirus vaccine on severe diarrhea in African infants

N Engl J Med. 2010 Jan 28;362(4):289-98. doi: 10.1056/NEJMoa0904797.

Abstract

Background: Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children.

Methods: We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine--the pooled vaccine group--or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale.

Results: A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group.

Conclusions: Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.)

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral / blood
  • Diarrhea, Infantile / epidemiology
  • Diarrhea, Infantile / prevention & control*
  • Feces / virology
  • Female
  • Gastroenteritis / epidemiology
  • Gastroenteritis / prevention & control*
  • Gastroenteritis / virology
  • HIV Infections / diagnosis
  • Humans
  • Incidence
  • Infant
  • Malawi / epidemiology
  • Male
  • Rotavirus / classification
  • Rotavirus / immunology
  • Rotavirus / isolation & purification
  • Rotavirus Infections / epidemiology
  • Rotavirus Infections / immunology
  • Rotavirus Infections / prevention & control*
  • Rotavirus Vaccines* / administration & dosage
  • Rotavirus Vaccines* / adverse effects
  • Rotavirus Vaccines* / immunology
  • South Africa / epidemiology
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / adverse effects
  • Vaccines, Attenuated / immunology

Substances

  • Antibodies, Viral
  • RIX4414 vaccine
  • Rotavirus Vaccines
  • Vaccines, Attenuated

Associated data

  • ClinicalTrials.gov/NCT00241644