Vaccines for preventing rotavirus diarrhoea: vaccines in use

Soares-Weiser K, MacLehose H, Bergman H, Ben-Aharon I, Nagpal S, Goldberg E, Pitan F, Cunliffe N

Published Online:

February 15, 2012

Rotavirus infection is one of the most common causes of diarrhoea in infants and young children, and the symptoms can range from mild illness, to hospitalization, and death. Rotavirus infections cause about half a million deaths per year in children younger than five years, mainly in low- and middle-income countries. Since 2009, the World Health Organization (WHO) has recommended rotavirus vaccine be included in all national immunization programmes.

This review evaluates a monovalent rotavirus vaccine (RV1; Rotarix, GlaxoSmithKline Biologicals) and a pentavalent rotavirus vaccine (RV5; RotaTeq, Merck & Co., Inc.). These vaccines have been evaluated in several large trials and are approved for use in many countries. No trials of the Lanzhou lamb rotavirus vaccine (LLR; Lanzhou Institute of Biomedical Products) were found; this vaccine is used in China only.

The review includes 43 trials with 190,551 participants; all trials compared a rotavirus vaccine with placebo. The vaccines tested were RV1 (31 trials with 105,959 participants) and RV5 (12 trials with 84,592 participants). The trials took place in a number of worldwide locations.

Compared to placebo, RV1 probably prevents 70% of all cases of rotavirus diarrhoea, and 80% of severe episodes during the first and second year of life. RV5 reduced any rotavirus diarrhoea or severe cases by more than 70% in the first year, and by approximately 50% in the second year. Both vaccines reduced severe diarrhoea from all causes by at least 40%. The vaccines when tested against placebo gave similar numbers of adverse events such as deaths, reactions to the vaccine, and other events that required discontinuation of the vaccination schedule.

In conclusion, data from this review show that RV1 and RV5 are effective vaccines, and support the WHO's recommendation to include rotavirus vaccination into national childhood immunization programmes, especially in countries with a high burden of diarrhoeal deaths in children younger than five years. Continued safety monitoring is advised in countries where vaccines are routinely used.

Abstract (click to read)

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 strategy:

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.

This record should be cited as:

Soares-Weiser K, MacLehose H, Bergman H, Ben-Aharon I, Nagpal S, Goldberg E, Pitan F, Cunliffe N. Vaccines for preventing rotavirus diarrhoea: vaccines in use. Cochrane Database of Systematic Reviews 2012, Issue 2. Art. No.: CD008521. DOI: 10.1002/14651858.CD008521.pub2

Assessed as up to date:

October 31, 2011

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Primary Review Group:

Infectious Diseases Group

PEARLS - Practical Evidence About Real Life Situations (click to read)

Clinical question:

How effective are vaccines for preventing rotavirus diarrhoea?

Bottom line:

Compared with placebo, Rotarix (given between 1 and 3 months of age) reduced cases of rotavirus diarrhoea by 83% in the first year and 52% in the second year. It also reduced hospitalisations by 81% after 1 year and 84% at 2 years. Compared with placebo, RotaTeq (given between 1 and 6 months of age) reduced cases of rotavirus diarrhoea by 73% after 1 year and 62% during the 2nd year. It also reduced hospitalisations by 96% after 1 year. The vaccines tested against placebo gave a similar number of adverse events such as deaths, reaction to the vaccine, and others that required discontinuation of the vaccination schedule.

Caveat:

All the included trials were placebo controlled, which means there are no data directly comparing Rotarix and RotaTeq. The trials provided only limited data for special groups of children, such as preterm infants and malnourished children.

Context:

Rotavirus infections cause over half a million deaths per year in children younger than 5 years, especially in low-income and middle-income countries. Since 2009, the World Health Organization has recommended rotavirus vaccination be included in national immunisation programmes, especially in countries with a high burden of diarrhoeal deaths in children younger than 5 years.

Cochrane Systematic Review:

Soares-Weiser K et al. Vaccines for preventing rotavirus diarrhoea: vaccines in use. Cochrane Reviews, 2010, Issue 5. Article No. CD008521. DOI: 10.1002/14651858.CD008521. This review contains 34 trials involving 175,944 participants.

Authored by:

Brian R McAvoy

Cochrane Primary Health Care Field

Health topics:

Gastroenterology > Diarrhoeal infections > Rotavirus

Infectious disease > Diarrhoeal infections > Rotavirus

Neonatal care > Neonatal infections > Rotavirus

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Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Vaccines for preventing rotavirus diarrhoea: vaccines in use

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