established in 1812
january 28, 2010
Effect of Human Rotavirus Vaccine on Severe Diarrhea in African Infants
Shabir A. Madhi, M.D., Nigel A. Cunliffe, M.B., Ch.B., Ph.D., Duncan Steele, Ph.D., Desirée Witte, M.D., Mari Kirsten, M.D., Cheryl Louw, M.D., Bagrey Ngwira, M.D., John C. Victor, Ph.D., M.P.H., Paul H. Gillard, M.D.,Brigitte B. Cheuvart, Ph.D., Htay H. Han, M.B., B.S., and Kathleen M. Neuzil, M.D., M.P.H.
A BS T R AC T
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.
We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166infants; 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, and14 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.
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 thevaccine, 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, thenumber 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
From the Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg (S.A.M.); the Department of Paediatric Surgery, University of Pretoria, Pretoria (M.K.); Madibeng Center for Research, Brits (C.L.); and the Medical Research Council Diarrhoeal Pathogens Research Unit, University of Limpopo, Limpopo (C.L.)— all in South Africa; the Division of Medical Microbiology, University of Liverpool, Liverpool, United Kingdom (N.A.C., D.W.); Initiative for Vaccine Research, World Health Organization, Geneva (D.S.); the College of Medicine, University of Malawi, Blantyre, Malawi (D.W., B.N.); the Rotavirus Vaccine Program, PATH, Seattle (J.C.V., K.M.N.); and GlaxoSmithKline Biologicals, Rixensart, Belgium(P.H.G., B.B.C., H.H.H.). Address reprint requests to Dr. Cunliffe at the Division of Medical Microbiology, School of Infection and Host Defence, University of Liverpool, Daulby St., Liverpool L69 3GA, United Kingdom, or at n.a.cunliffe@liv .ac.uk. Drs. Madhi and Cunliffe contributed equally to this article. N Engl J Med 2010;362:289-98.
Copyright © 2010 Massachusetts Medical Society.
Humanrotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.)
n engl j med 362;4 nejm.org january 28, 2010
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