Vaccines for preventing rotavirus diarrhoea: vaccines in use

TLDR: Evaluating rotavirus vaccines approved for use (RV1, RV5, and LLR) for preventingRotavirus diarrhoea in children with high-mortality rates found that RV1 probably prevents 40% of severe all-cause diarrhoeA episodes, and RV5probably prevents 40%, based on one large multicentre trial in Latin America and Finland.

Abstract: BACKGROUND:Rotavirus results in more diarrhoea-related deaths in children under five years than any other single agent in countries with high childhood mortality. It is also a common cause of diarrhoea-related hospital admissions in countries with low childhood mortality. Rotavirus vaccines that have been prequalified by the World Health Organization (WHO) include a monovalent vaccine (RV1; Rotarix, GlaxoSmithKline), a pentavalent vaccine (RV5; RotaTeq, Merck), and, more recently, another monovalent vaccine (Rotavac, Bharat Biotech). OBJECTIVES:To evaluate rotavirus vaccines prequalified by the WHO (RV1, RV5, and Rotavac) for their efficacy and safety in children. SEARCH METHODS:On 4 April 2018 we searched MEDLINE (via PubMed), the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (published in the Cochrane Library), Embase, LILACS, and BIOSIS. We also searched the WHO ICTRP, ClinicalTrials.gov, clinical trial reports from manufacturers' websites, and reference lists of included studies and relevant systematic reviews. SELECTION CRITERIA:We selected randomized controlled trials (RCTs) in children comparing rotavirus vaccines prequalified for use by the WHO versus placebo or no intervention. DATA COLLECTION AND ANALYSIS:Two review authors independently assessed trial eligibility and assessed risks of bias. One review author extracted data and a second author cross-checked them. We combined dichotomous data using the risk ratio (RR) and 95% confidence interval (CI). We stratified the analysis by country mortality rate and used GRADE to evaluate evidence certainty. MAIN RESULTS:Fifty-five trials met the inclusion criteria and enrolled a total of 216,480 participants. Thirty-six trials (119,114 participants) assessed RV1, 15 trials (88,934 participants) RV5, and four trials (8432 participants) Rotavac. RV1 Children vaccinated and followed up the first year of life In low-mortality countries, RV1 prevents 84% of severe rotavirus diarrhoea cases (RR 0.16, 95% CI 0.09 to 0.26; 43,779 participants, 7 trials; high-certainty evidence), and probably prevents 41% of cases of severe all-cause diarrhoea (RR 0.59, 95% CI 0.47 to 0.74; 28,051 participants, 3 trials; moderate-certainty evidence). In high-mortality countries, RV1 prevents 63% of severe rotavirus diarrhoea cases (RR 0.37, 95% CI 0.23 to 0.60; 6114 participants, 3 trials; high-certainty evidence), and 27% of severe all-cause diarrhoea cases (RR 0.73, 95% CI 0.56 to 0.95; 5639 participants, 2 trials; high-certainty evidence). Children vaccinated and followed up for two years In low-mortality countries, RV1 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.14 to 0.23; 36,002 participants, 9 trials; high-certainty evidence), and probably prevents 37% of severe all-cause diarrhoea episodes (rate ratio 0.63, 95% CI 0.56 to 0.71; 39,091 participants, 2 trials; moderate-certainty evidence). In high-mortality countries RV1 probably prevents 35% of severe rotavirus diarrhoea cases (RR 0.65, 95% CI 0.51 to 0.83; 13,768 participants, 2 trials; high-certainty evidence), and 17% of severe all-cause diarrhoea cases (RR 0.83, 95% CI 0.72 to 0.96; 2764 participants, 1 trial; moderate-certainty evidence). No increased risk of serious adverse events (SAE) was detected (RR 0.88 95% CI 0.83 to 0.93; high-certainty evidence). There were 30 cases of intussusception reported in 53,032 children after RV1 vaccination and 28 cases in 44,214 children after placebo or no intervention (RR 0.70, 95% CI 0.46 to 1.05; low-certainty evidence). RV5 Children vaccinated and followed up the first year of life In low-mortality countries, RV5 probably prevents 92% of severe rotavirus diarrhoea cases (RR 0.08, 95% CI 0.03 to 0.22; 4132 participants, 5 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 57% of severe rotavirus diarrhoea (RR 0.43, 95% CI 0.29 to 0.62; 5916 participants, 2 trials; high-certainty evidence), but there is probably little or no difference between vaccine and placebo for severe all-cause diarrhoea (RR 0.80, 95% CI 0.58 to 1.11; 1 trial, 4085 participants; moderate-certainty evidence). Children vaccinated and followed up for two years In low-mortality countries, RV5 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.08 to 0.39; 7318 participants, 4 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 41% of severe rotavirus diarrhoea cases (RR 0.59, 95% CI 0.43 to 0.82; 5885 participants, 2 trials; high-certainty evidence), and 15% of severe all-cause diarrhoea cases (RR 0.85, 95% CI 0.75 to 0.98; 5977 participants, 2 trials; high-certainty evidence). No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.86 to 1.01; moderate to high-certainty evidence). There were 16 cases of intussusception in 43,629 children after RV5 vaccination and 20 cases in 41,866 children after placebo (RR 0.77, 95% CI 0.41 to 1.45; low-certainty evidence). Rotavac Children vaccinated and followed up the first year of life Rotavac has not been assessed in any RCT in countries with low child mortality. In India, a high-mortality country, Rotavac probably prevents 57% of severe rotavirus diarrhoea cases (RR 0.43, 95% CI 0.30 to 0.60; 6799 participants, moderate-certainty evidence); the trial did not report on severe all-cause diarrhoea at one-year follow-up. Children vaccinated and followed up for two years Rotavac probably prevents 54% of severe rotavirus diarrhoea cases in India (RR 0.46, 95% CI 0.35 to 0.60; 6541 participants, 1 trial; moderate-certainty evidence), and 16% of severe all-cause diarrhoea cases (RR 0.84, 95% CI 0.71 to 0.98; 6799 participants, 1 trial; moderate-certainty evidence). No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.85 to 1.02; moderate-certainty evidence). There were eight cases of intussusception in 5764 children after Rotavac vaccination and three cases in 2818 children after placebo (RR 1.33, 95% CI 0.35 to 5.02; very low-certainty evidence). There was insufficient evidence of an effect on mortality from any rotavirus vaccine (198,381 participants, 44 trials; low- to very low-certainty evidence), as the trials were not powered to detect an effect at this endpoint. AUTHORS' CONCLUSIONS:RV1, RV5, and Rotavac prevent episodes of rotavirus diarrhoea. Whilst the relative effect estimate is smaller in high-mortality than in low-mortality countries, there is a greater number of episodes prevented in these settings as the baseline risk is much higher. We found no increased risk of serious adverse events.

Figures

Figure 2. Methodological quality summary: review authors’ judgements about each methodological quality item for each included study.

Figure 1. A simplified diagram of the location of rotavirus structural proteins (source: Graham Cohn, Wikipedia (public domain image)): Rotaviruses are segmented, double-stranded RNA viruses. The mature, triple-layered virus particle comprises a core (which contains the viral genome), a middle layer (comprised of viral protein (VP)6, and an outer layer (comprised of VP7 and VP4) as shown in the figure. VP6 defines rotavirus group, and most rotaviruses that infect humans are of group A. The two outer capsid proteins independently induce neutralizing antibodies: VP7, a glycoprotein, defines G-serotype; and the proteasesensitive VP4 protein defines P-serotype. G-serotype determined by serological methods correlates precisely with G-genotype obtained through molecular assays, whereas there is an imperfect correlation of P-serotype and P-genotype; P-genotype is thus included in square brackets.

Figure 3. Funnel plot of comparison: 1 RV1 versus placebo, outcome: 1.1 Rotavirus diarrhoea: severe (up to 1 year follow-up).

Full text

Vaccines for preventing rotavirus diarrhoea: vaccines in use
(Review)
Soares-Weiser K, MacLehose H, Bergman H, Ben-Aharon I, Nagpal S, Goldberg E, Pitan F,
Cunliffe N
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2012, Issue 11
http://www. thecochranelibrary.com
Vaccines for preventing rotavirus diarrhoea: vaccines in use (Review)
Copyright © 2012 The Cochrane Colla boration. Published by John Wiley & Sons, Lt d.

T A B L E O F C O N T E N T S
1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2PLAIN LANGUAGE S U MMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . . . . . . . . . . . . . . . . . . .
7BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
11OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
11METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
13RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
27ADDITIONAL SUMMARY OF FINDINGS . . . . . . . . . . . . . . . . . . . . . . . . . .
34DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
36AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
37ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
37REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
55CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
169DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 RV1 versus placebo, Outcome 1 Rotavirus diarrhoea: severe (up to 1 year follow-up). . 176
Analysis 1.2. Comparison 1 RV1 versus placebo, Outcome 2 Rotavirus diarrhoea: severe (up to 2 years follow-up). . 177
Analysis 1.3. Comparison 1 RV1 versus placebo, Outcome 3 All-cause diarrhoea: severe cases (up to 1 year follow-up). 178
Analysis 1.4. Comparison 1 RV1 versus placebo, Outcome 4 All-cause diarrhoea: severe cases (up to 2 years follow-up). 179
Analysis 1.5. Comparison 1 RV1 versus placebo, Outcome 5 All-cause diarrhoea: severe episodes (up to 1 year follow-
up). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
Analysis 1.6. Comparison 1 RV1 versus placebo, Outcome 6 All-cause diarrhoea: severe episodes (up to 2 years follow-
up). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
Analysis 1.7. Comparison 1 RV1 versus placebo, Outcome 7 All-cause death. . . . . . . . . . . . . . . 181
Analysis 1.8. Comparison 1 RV1 versus placebo, Outcome 8 All serious adverse events. . . . . . . . . . . . 183
Analysis 1.9. Comparison 1 RV1 versus placebo, Outcome 9 Serious adverse events: intussusception. . . . . . . 185
Analysis 1.10. Comparison 1 RV1 versus placebo, Outcome 10 Serious adverse events: Kawasaki disease. . . . . 186
Analysis 1.11. Comparison 1 RV1 versus placebo, Outcome 11 Serious adverse events requiring hospitalization. . . 186
Analysis 1.12. Comparison 1 RV1 versus placebo, Outcome 12 Rotavirus diarrhoea: of any severity (up to 2 months follow-
up). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
Analysis 1.13. Comparison 1 RV1 versus placebo, Outcome 13 Rotavirus diarrhoea: of any severity (up to 1 year follow-
up). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188
Analysis 1.14. Comparison 1 RV1 versus placebo, Outcome 14 Rotavirus diarrhoea: of any severity (up to 2 years follow-
up). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
Analysis 1.15. Comparison 1 RV1 versus placebo, Outcome 15 All-cause diarrhoea: all cases (up to 2 months follow-
up). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
Analysis 1.16. Comparison 1 RV1 versus placebo, Outcome 16 All-cause diarrhoea: all cases (up to 1 year follow-up). 191
Analysis 1.17. Comparison 1 RV1 versus placebo, Outcome 17 All-cause diarrhoea: all cases (up to 2 years follow-up). 191
Analysis 1.18. Comparison 1 RV1 versus placebo, Outcome 18 All-cause diarrhoea: all episodes (up to 1 year follow-
up). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192
Analysis 1.19. Comparison 1 RV1 versus placebo, Outcome 19 Al l-cause diarrhoea: all episodes (up to 2 years follow-
up). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
Analysis 1.20. Comparison 1 RV1 versus placebo, Outcome 20 All-cause hospitalizations (up to 2 years follow-up). . 193
Analysis 1.21. Comparison 1 RV1 versus placebo, Outcome 21 Rotavirus diarrhoea: requiring hospitalization. . . . 194
Analysis 1.22. Comparison 1 RV1 versus placebo, Outcome 22 Rotavirus diarrhoea: requiring medical attention. . . 195
Analysis 1.23. Comparison 1 RV1 versus placebo, Outcome 23 All-cause diarrhoea: cases requiring hospitalization. . 196
Analysis 1.24. Comparison 1 RV1 versus placebo, Outcome 24 All-cause diarrhoea: episodes requiring hospitalization. 197
Analysis 1.25. Comparison 1 RV1 versus placebo, Outcome 25 Reactogenicity: fever. . . . . . . . . . . . 198
iVaccines for preventing rotavirus diarrhoea: vaccines in use (Review)
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Analysis 1.26. Comparison 1 RV1 versus placebo, Outcome 26 Reactogenicity: diarrhoea. . . . . . . . . . . 201
Analysis 1.27. Comparison 1 RV1 versus placebo, Outcome 27 Reactogenicity: vomiting. . . . . . . . . . . 204
Analysis 1.28. Comparison 1 RV1 versus pl acebo, Outcome 28 Adverse events requiring discontinuation (end of follow-
up). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
Analysis 1.29. Comparison 1 RV1 versus pl acebo, Outcome 29 Immunogenicity: rotavirus vaccine shedding (end of follow-
up). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208
Analysis 1.30. Comparison 1 RV1 versus placebo, Outcome 30 Immunogenicity: seroconversion. . . . . . . . 209
Analysis 1.31. Comparison 1 RV1 versus placebo, Outcome 31 Drop outs before the end of the trial. . . . . . . 211
Analysis 1.32. Comparison 1 RV1 versus placebo, Outcome 32 Subgroup analysis: rotavirus diarrhoea of any severity (by G
type). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212
Analysis 1.33. Comparison 1 RV1 versus placebo, Outcome 33 Subgroup analysis: severe cases of rotavirus diarrhoea (by G
type). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214
Analysis 1.34. Comparison 1 RV1 versus placebo, Outcome 34 Subgroup analysis: r otavirus diarrhoea in malnourished
children. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
Analysis 1.35. Comparison 1 RV1 versus placebo, Outcome 35 Subgroup analysis: rotavirus diarrhoea in HIV-infected
children. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216
Analysis 1.36. Comparison 1 RV1 versus placebo, Outcome 36 Subgroup analysis: serious adverse events in premature
babies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216
Analysis 1.37. Comparison 1 RV1 versus placebo, Outcome 37 Subgroup analysis: severe rotavirus diarrhoea in breast f ed
and formula fed infants. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
Analysis 1.38. Comparison 1 RV1 versus placebo, Outcome 38 Sensitivity analysis: allocation concealment. . . . 218
Analysis 2.1. Comparison 2 RV5 versus placebo, Outcome 1 Rotavirus diarrhoea: severe (up to 1 year follow-up). . 219
Analysis 2.2. Comparison 2 RV5 versus placebo, Outcome 2 Rotavirus diarrhoea: severe (up to 2 years follow-up). . 220
Analysis 2.3. Comparison 2 RV5 versus placebo, Outcome 3 All-cause diarrhoea: severe cases (up to 1 year follow-up). 221
Analysis 2.4. Comparison 2 RV5 versus placebo, Outcome 4 All-cause diarrhoea: severe cases (up to 2 years follow-up). 222
Analysis 2.5. Comparison 2 RV5 versus placebo, Outcome 5 All-cause death. . . . . . . . . . . . . . . 223
Analysis 2.6. Comparison 2 RV5 versus placebo, Outcome 6 All serious adverse events. . . . . . . . . . . . 224
Analysis 2.7. Comparison 2 RV5 versus placebo, Outcome 7 Serious adverse events: intussusception. . . . . . . 226
Analysis 2.8. Comparison 2 RV5 versus pl acebo, Outcome 8 Rotavirus diarrhoea: of any severity (up to 1 year follow-
up). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
Analysis 2.9. Comparison 2 RV5 versus placebo, Outcome 9 Rotavirus diarrhoea: of any severity (up to 2 years follow-
up). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
Analysis 2.10. Comparison 2 RV5 versus placebo, Outcome 10 All-cause diarrhoea: of any severity (up to 1 year follow-
up). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230
Analysis 2.11. Comparison 2 RV5 versus pl acebo, Outcome 11 All-cause diarrhoea: of any severity (up to 2 years follow-
up). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
Analysis 2.12. Comparison 2 RV5 versus placebo, Outcome 12 Rotavirus diarrhoea: requiring hospitalization. . . . 231
Analysis 2.13. Comparison 2 RV5 versus placebo, Outcome 13 Rotavirus diarrhoea: requiring medical attention. . . 232
Analysis 2.14. Comparison 2 RV5 versus placebo, Outcome 14 Reactogenicity: fever. . . . . . . . . . . . 233
Analysis 2.15. Comparison 2 RV5 versus placebo, Outcome 15 Reactogenicity: diarrhoea. . . . . . . . . . . 234
Analysis 2.16. Comparison 2 RV5 versus placebo, Outcome 16 Reactogenicity: vomiting. . . . . . . . . . . 235
Analysis 2.17. Comparison 2 RV5 versus pl acebo, Outcome 17 Adverse events requiring discontinuation (end of follow-
up). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236
Analysis 2.18. Comparison 2 RV5 versus placebo, Outcome 18 Immunogenicity: rotavirus vaccine shedding (after dose
3). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
Analysis 2.19. Comparison 2 RV5 versus placebo, Outcome 19 Immunogenicity: seroconversion (after dose 3). . . 238
Analysis 2.20. Comparison 2 RV5 versus placebo, Outcome 20 Drop outs before the end of the trial. . . . . . . 239
Analysis 2.21. Comparison 2 RV5 versus placebo, Outcome 21 Subgroup analysis: rotavirus diarrhoea of any severity (by G
type). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
Analysis 2.22. Comparison 2 RV5 versus placebo, Outcome 22 Subgroup analysis: severe cases of rotavirus diarrhoea (by G
type). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
Analysis 2.23. Comparison 2 RV5 versus placebo, Outcome 23 Subgroup analysis: HIV-infected children. . . . . 243
iiVaccines for preventing rotavirus diarrhoea: vaccines in use (Review)
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Analysis 2.24. Comparison 2 RV5 versus placebo, Outcome 24 Subgroup analysis: rotavirus diarrhoea of any severity in
premature babies (1 year follow-up). . . . . . . . . . . . . . . . . . . . . . . . . . . 244
Analysis 2.25. Comparison 2 RV5 versus placebo, Outcome 25 Sensitivity analysis: allocation concealment. . . . 245
245APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
273WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
273HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
274CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
275DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
275SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
275DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .
275INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
iiiVaccines for preventing rotavirus diarrhoea: vaccines in use (Review)
Copyright © 2012 The Cochrane Colla boration. Published by John Wiley & Sons, Lt d.

[Intervention Review]
Vaccines for preventing rotavirus diarrhoea: vaccines in use
Karla Soares-Weiser
1
, Harriet MacLehose
2
, Hanna Bergman
1
, Irit Ben-Aharon
3
, Sukrti Nagpal
4
, Elad Goldberg
5
, Femi Pitan
6
, Nigel
Cunliffe
7
1
Enhance Reviews Ltd, Wantage, UK.
2
Cochrane Editorial Unit, The Cochrane Collaboration, London, UK.
3
Enhance Reviews, Kfar-
Saba, Israel.
4
Liverpool School of Tropical Medicine, Liverpool, UK.
5
Department of Medicine E, Beilinson Hospital, Rabin Medical
Center, Petah Tikva, Israel.
6
Chevron Corporation, Lagos, Nigeria.
7
Institute of Infection and Global Health, Faculty of Health and
Life Sciences, University of Liverpool, Liverpool, UK
Contact address: Karla Soares-Weiser, Enhance Reviews Ltd, Central Office, Cobweb Buildings, The Lane, Lyford, Wantage, OX12
0EE, UK.
karla@enhance-reviews.com. ksoaresweiser@gmail.com.
Editorial group: Cochrane Infectious Diseases Group.
Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 11, 2012.
Review content assessed as up-to-date: 10 May 2012.
Citation: Soares-Weiser K, MacLehose H, Bergman H, Ben-Ah aron I, Nagpal S, Goldberg E, Pitan F, Cunliffe N. Vaccines for
preventing rotavirus diarrhoea: vaccines in use. Cochrane Database of Systematic Reviews 2012, Issue 11. Art. No.: CD008521. DOI:
10.1002/14651858.CD008521.pub3.
Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
A B S T R A C T
Background
Rotavirus results in more diarrhoea-related deaths in children less than five years of age than any other single agent in countries
with high childhood mortality. It is also a common cause of diarrhoea-related hospital admissions in countries with low childhood
mortality. Currently licensed rotavirus vaccines include a monovale nt rotavirus vaccine (RV1; Rotarix, GlaxoSmithKline Biologicals)
and a pentavalent rotavirus vaccine (RV5; RotaTeq, Merck & Co., Inc.). 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.
Search methods
We searched MEDLINE (via PubMed) (1966 to May 2012), th e Cochrane Infectious Diseases Group Specialized Register (10 May
2012), CENTRAL (published in The Cochrane Library 2012, Issue 5), EMBASE (1974 to 10 May 2012), LILACS (1982 to 10 May
2012), and BIOSIS (1926 to 10 May 2012). We also searched the ICTRP (10 May 2012), www.ClinicalTrials.gov (28 May 2012) and
checked reference lists of identified studies.
Selection criteria
We selected randomized controlled trials (RCTs) 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. We combined dichotomous data using the
risk ratio (RR) and 95% confidence intervals (CI). We stratified the analysis by child mortality, and used GRADE to evaluate evidence
quality.
1Vaccines for preventing rotavirus diarrhoea: vaccines in use (Review)
Copyright © 2012 The Cochrane Colla boration. Published by John Wiley & Sons, Lt d.

Frequently asked questions

Q1. What are the contributions mentioned in the paper "Vaccines for preventing rotavirus diarrhoea: vaccines in use" ?

This review evaluates a monovalent rotavirus vaccine ( RV1 ; Rotarix, GlaxoSmithKline Biologicals ) and a pentavalent rotavirus vaccine ( RV5 ; RotaTeq, Merck & Co., Inc. ). 

Q2. What are the future works in "Vaccines for preventing rotavirus diarrhoea: vaccines in use" ?

CI: confidence interval ; RR: risk ratio GRADE Working Group grades of evidence High-quality: further research is very unlikely to change their confidence in the estimate of effect. Moderate-quality: further research is likely to have an important impact on their confidence in the estimate of effect and may change the estimate. Low-quality: further research is very likely to have an important impact on their confidence in the estimate of effect and is likely to change the estimate. Infection may be asymptomatic or result in a severe, lifethreatening illness characterized by vomiting, fever, watery diarrhoea, and dehydration ( AAP 1998 ). 

Q3. How many cases of diarrhoea were prevented by RV1 in low-?

In the first two years of life, RV1 prevented more than 80% of severe cases of rotavirus diarrhoea in low-mortality countries, and at least 40% of severe rotavirus diarrhoea in high-mortality countries. 

Q4. What is the common cause of rotavirus infection in children?

Rotavirus infections results in approximately half a million deaths per year in children aged under five years, mainly in low- and2Vaccines for preventing rotavirus diarrhoea: vaccines in use (Review) Copyright © 2012 The Cochrane Collaboration. 

Q5. What is the significance of a rotavirus vaccine?

The enormous diversity and capacity of human rotaviruses for change suggest that rotavirus vaccines must demonstrate protective efficacy against all of the major circulating strain types (de Quadros 2004) as well as new strains that will continue to emerge (Gentsch 2005). 

Q6. how much was the diarrhoea reduced after vaccination with RV1?

Severe cases of diarrhoea from all causes (such as any viral infection, bacterial infections, toxins, or allergies) were reduced after vaccination with RV1 by 35 to 40% in low-mortality countries, and 15 to 30% in high-mortality countries. 

Q7. how much was the diarrhoea reduced in low-mortality countries?

Severe cases of diarrhoea from all causes were reduced by 73% to 96% in low-mortality countries, and 15% in high-mortality countries, after vaccination with RV5. 

Q8. how many children have been vaccinated with RV1?

Serious adverse events were reported in 4565 out of 99,438 children vaccinated with RV1 and in 1884 out of 78,226 children vaccinated with RV5. 

Q9. how much did the rotavirus prevent diarrhoea in low-?

In the first two years of life, RV5 reduced severe cases of rotavirus diarrhoea by more than 80% in low-mortality countries, and by 40 to 57% in high-mortality countries. 

Q10. What is the common cause of diarrhoea in children?

P L A The authorN L A N G U A G E S U M M A R YVaccines for preventing rotavirus diarrhoea: vaccines in useRotavirus infection is a common cause of diarrhoea in infants and young children, and can cause mild illness, hospitalization, and death. 

Q11. How many cases of diarrhoea were prevented by the vaccine?

Severe episodes of allcause diarrhoea Follow-up: up to 2 years 39 per 1000 24 per 1000 (22 to 28)Rate Ratio 0.63 (0.56 to 0.71)39,091 (2 studies)⊕⊕⊕© moderate3 

Q12. how did the rotavirus vaccine affect the faecal?

Epidemiological and clinical features of rotavirus infectionRotavirus is transmitted primarily via the faecal-oral route with symptoms typically developing one to two days following infection. 

Q13. What databases were used to evaluate rotavirus vaccines in children?

The authors searched MEDLINE (via PubMed) (1966 to May 2012), the Cochrane Infectious Diseases Group Specialized Register (10 May 2012), CENTRAL (published in The Cochrane Library 2012, Issue 5), EMBASE (1974 to 10 May 2012), LILACS (1982 to 10 May 2012), and BIOSIS (1926 to 10 May 2012). 

Q14. Why is the rotavirus vaccine efficacious in high-mortality countries?

The vaccine efficacy is lower in high-mortality countries; however, due to the higher burden of disease, the absolute benefit is higher in these settings.