Background Rotavirus results in more diarrhoea-related deaths in children less than five years of age than any other single agent in low-and middle-income countries. It is also a common cause of diarrhoea-related hospital admissions in high-income countries. The World Health Organization (WHO) recommends that all children should be vaccinated with a monovalent rotavirus vaccine (RV1; Rotarix, GlaxoSmithKline Biologicals) or a pentavalent rotavirus vaccine (RV5; RotaTeq, Merck & Co., Inc.), with a stronger recommendation for countries where deaths due to diarrhoea comprise more than 10% of all deaths. Lanzhou lamb rotavirus vaccine (LLR; Lanzhou Institute of Biomedical Products) is used in China only. Objectives To evaluate rotavirus vaccines approved for use (RV1, RV5, and LLR) for preventing rotavirus diarrhoea. Secondary objectives were to evaluate the efficacy of rotavirus vaccines on all-cause diarrhoea, hospital admission, death, and safety profiles. Search methods For this update, we searched MEDLINE (via PubMed) in October 2011, and in June 2011 we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (published in The Cochrane Library 2011, Issue 2),, EMBASE, LILACS, and BIOSIS. We also searched the ICTRP (28 June 2011) and checked reference lists of identified studies. Selection criteria We selected randomized controlled trials in children comparing rotavirus vaccines approved for use with placebo, no intervention, or another vaccine. Data collection and analysis Two authors independently assessed trial eligibility, extracted data, and assessed risk of bias. They combined dichotomous data using the risk ratio (RR) and 95% confidence intervals (CI) and used GRADE to evaluate evidence quality, which was reflected as follows: high quality ("vaccine prevents..."); moderate quality ("vaccine probably prevents..."); or low quality ("vaccine may prevent..."). Main results Forty-three trials, including nine new trials for this update, met the inclusion criteria and enrolled 190,551 participants. Thirty-one trials assessed RV1, and 12 trials evaluated RV5. We did not find any trials assessing LLR. In children aged less than one year, RV1, compared to placebo, probably prevents 70% of all cases of rotavirus diarrhoea (RR 0.30, 95% CI 0.18 to 0.50; seven trials, 12,130 participants; moderate-quality evidence), and 80% of severe rotavirus diarrhoea cases (RR 0.20, 95% CI 0.11 to 0.35; seven trials, 35,004 participants; moderate-quality evidence). Similarly, RV5 prevents 73% of all rotavirus diarrhoea cases (RR 0.27, 95% CI 0.22 to 0.33; four trials, 7614 participants; high-quality evidence), and 77% of severe rotavirus diarrhoea cases (RR 0.23, 95% CI 0.08 to 0.71; three trials, 6953 participants; high-quality evidence). Both vaccines prevent over 80% of rotavirus diarrhoea cases that require hospitalization. For all-cause diarrhoea, based on two multi-centred trials from South Africa, Malawi, and Europe, RV1 may reduce severe cases by 42% (RR 0.58, 95% CI 0.40 to 0.84; two trials, 8291 participants; low--quality evidence). Also, based on one trial from Finland, RV5 may reduce severe cases by 72% (RR 0.28, 95% CI 0.16 to 0.48; one trial, 1029 participants; low-quality evidence). During the second year of life, compared to placebo, RV1 probably prevents 70% of all cases of rotavirus diarrhoea of any severity (RR 0.30, 95% CI 0.21 to 0.43; six trials, 8041 participants; moderate-quality evidence), and 84% of severe rotavirus diarrhoea cases (RR 0.16, 95% CI 0.12 to 0.21; eight trials, 32,854 participants; moderate-quality evidence). RV5 prevents 49% of all rotavirus diarrhoea cases of any severity (RR 0.51, 95% CI 0.36 to 0.72; four trials, 9784 participants; high-quality evidence), and 56% of severe rotavirus diarrhoea cases (RR 0.44, 95% CI 0.22 to 0.88; four trials, 9783 participants; high-quality evidence). For all-cause diarrhoea, RV1 probably reduces severe cases by 51% (RR 0.49, 95% CI 0.40 to 0.60; two trials, 6269 participants; moderate-quality evidence), and RV5 showed no difference with placebo (three trials, 8533 participants). Reported serious adverse events (including intussusception) after vaccination were measured in 95,178 children for RV1 and 77,480 for RV5, with no difference between the vaccines. Authors' conclusions RV1 and RV5 vaccines are effective in preventing rotavirus diarrhoea. These data support the WHO's global vaccine recommendation. The potential for reduced vaccine efficacy in low-income countries needs to be investigated. No increased risk of intussusception was detected, but surveillance monitoring studies are probably advisable in countries introducing the vaccine nationally.
