Vaccines for preventing rotavirus diarrhoea: Vaccines in use

Enhance Reviews Ltd,Wantage, UK. 2Cochrane Editorial Unit, The Cochrane Collaboration, London, UK. 3Enhance Reviews, Kfar-Saba, Israel. .
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 11/2012; 2(2):CD008521. DOI: 10.1002/14651858.CD008521.pub2
Source: PubMed


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.
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.
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.
We selected randomized controlled trials in children comparing rotavirus vaccines approved for use with placebo, no intervention, or another vaccine.
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...").
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.
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.

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    • "Two efficacious and effective rotavirus vaccines (RV) to prevent severe rotavirus diarrhea were licensed in 2006 [5] [6]. Efficacy of both RV1 (Rotarix; GlaxoSmithKline Biologicals; Rixensart, Belgium) and RV5 (RotaTeq; Merck Vaccines; Whitehouse Station, NJ, USA) has varied in different settings with studies showing a higher efficacy in lowmortality countries compared to high-mortality countries [7]. The World Health Organization (WHO) recommends the introduction of either RV for all countries globally, particularly those with high child mortality from diarrhea. "
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    ABSTRACT: The aim of this study was to estimate the association between rotavirus vaccine (RV) introduction and reduction of all-cause diarrhea death rates among children in five Latin American countries that introduced RV in 2006. Diarrhea mortality data was gathered from 2002 until 2009 from the Pan American Health Organization Mortality Database for five "vaccine adopter" countries (Brazil, El Salvador, Mexico, Nicaragua, and Panama) that introduced RV in 2006 and four "control" countries (Argentina, Chile, Costa Rica, and Paraguay) that did not introduce RV by 2009. Time trend analyses were carried out, and effects and 95% confidence intervals (CI) were estimated. Each of the five vaccine adopter countries, except Panama, showed a significant trend in declining mortality rates during the post-vaccine period from 2006 to 2009, whereas no decline was seen in control countries during these years. Furthermore, trends of reduction of all-cause diarrhea mortality in both children <1 year of age and <5 years of age were greater in the post-vaccination period compared with the pre-vaccine period in all vaccine adopter countries (except for Nicaragua), whereas in control countries, a reverse pattern was seen with greater reduction in the early years from 2002 to 2005 versus 2006-2009. An estimatedtotal of 1777 of annual under-5 deaths were avoided in Brazil, El Salvador, Mexico, and Nicaragua during the post-vaccination period. All vaccine adopter countries, except Panama, showed a significant decrease in all-cause diarrhea-related deaths after RV implementation, even after adjusting for declining trends over time in diarrhea mortality. These data strongly support continuous efforts to increase vaccination coverage of RV vaccines, particularly in countries with high levels of child mortality from diarrhea. Copyright © 2015. Published by Elsevier Ltd.
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    • "In the USA, it has been shown that protection against RVGE after RV5 infection can last at minimum for 4 years and at least until the age of 2 years after RV1 vaccination (for RV1, data were not available for a longer period of time) [32].This is in line with data from clinical trials showing sustained protection after RV vaccination for both vaccines up to 3 years after vaccination [33,34]. TABLE 2. Studies of RV1 and RV5 effectiveness in different settings Vaccine type Age group/year Effectiveness Outcome Setting Reference RV1 <1 year 86% Severe RVGE 6 RCT; low-mortality countries [45] <1 year 40% Severe all cause GE 1 RCT; low-mortality countries (Latin America, Finland) [45] <1 year 63% Severe RVGE 2 RCT; high-mortality countries [45] <1 year 34% Severe all cause GE 1 RCT; high-mortality countries (Malawi, South Africa) [45] up to 2 years 85% Severe RVGE 8 RCT; low-mortality countries [45] up to 2 years 37% Severe all cause GE 2 RCT; low-mortality countries [45] up to 2 years 42% Severe RVGE 1 RCT; high-mortality countries (Malawi, South Africa) [45] up to 2 years 18% Severe all cause GE 1 RCT; high-mortality countries (Malawi, South Africa) [45] "
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    ABSTRACT: By January 2015, rotavirus vaccination has been implemented in national vaccination programs in 75 countries worldwide. Two live oral rotavirus vaccines are internationally available: human, monovalent vaccine and human-bovine pentavalent reassortant vaccine. Since January 2014, another live, oral human-bovine monovalent vaccine has been available in India. After implementation of rotavirus vaccines in childhood immunization programs, over 90% reduction of rotavirus hospitalizations has been observed in industrialized and resource deprived countries. Additionally, in Latin America, significant reduction of rotavirus-associated deaths has been observed. Still, numerous countries do not recommend rotavirus mass vaccination because of assumed lack of cost-effectiveness and potential risk of intussusception which is estimated at 1 per 50-70,000 doses of rotavirus vaccines. Cost-effectiveness of vaccination is affected in some countries by high price. Inclusion of herd protection and indirect costs in calculations for cost effectiveness results in clear benefit: costs saved by health systems due to reduced rotavirus gastroenteritis hospitalizations exceed by far costs for implementation of rotavirus vaccination. There have been objections that high rotavirus vaccination coverage could put selective pressure on certain rotavirus strains against which protection after vaccination is less distinct. However, data now strongly suggest that even if there might be a relative increase of some specific genotypes after the use of rotavirus vaccines, this is not an absolute increase in incidence from certain genotypes and does not affect the overall effectiveness of rotavirus mass vaccination which resulted in a major decrease of severe cases of rotavirus gastroenteritis in both industrialized and resource deprived countries. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Feb 2015 · Clinical Microbiology and Infection
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    • "Rotavirus (RV) is an important pathogen of severe diarrhoea in infants and young children globally [1]. A major reduction of severe RV diarrhoea has been observed in countries with high RV vaccine coverage, but several clinical trials have shown the vaccine efficacy to be lower in countries with high RV mortality [2]. In countries where universal RV vaccination has been established, noroviruses have replaced RVs as the most common cause of children hospitalization for acute gastroenteritis [3] [4]. "
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    ABSTRACT: Rotaviruses (RVs) are a major cause of severe diarrhea in young children. Nicaragua introduced routine immunization with the pentavalent rotavirus vaccine (RV5) in 2006; which greatly reduced the incidence of diarrhea. A remaining concern has been the possible emergence of new RV strains to which the vaccination has less effect. In this study, 837 children with diarrhea in hospital settings were investigated for RV between May 2011 and July 2013. RVs were subsequently typed by multiplex PCR and/or sequencing. Fecal anti-RV IgA titers for a subset of RV-infected (n = 137) and non-infected children (n = 52), were determined with an in-house ELISA assay. The RV detection rate was 8% in 2011, followed by a sharp increase to 29% in 2012 and 19% in 2013. This was associated with emergence and predominance of genotype G12 RV, from 0% in 2011 to 66% in 2012 and 82% in 2013, infecting children from 1 month to 10 years of age. Two sequenced G12 strains, showed a Wa-like genome with genotype G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, similar to the globally emerging G12 strains. Fecal anti-RV IgA analysis showed that most G12-infected and non-infected children had been in contact with either vaccine or wild RV strains, but such antibodies did not prevent symptomatic G12 infection. To conclude, in this study we have shown a marked increase of RV in the hospital setting associated with a nationwide emergence and predominance of RV G12 genotype in a population with high RV5 vaccine coverage. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Feb 2015 · Clinical Microbiology and Infection
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