Vaccines for preventing rotavirus diarrhoea: vaccines in use.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 34788488 · doi:10.1002/14651858.CD008521.pub6
What was done
A Cochrane systematic review assessed the efficacy and safety of four World Health Organization (WHO)-prequalified rotavirus vaccines (Rotarix, RotaTeq, Rotasiil, Rotavac) compared to placebo or no intervention in children. Comprehensive searches of major databases and clinical trial registers were conducted through November 30, 2020. Randomized controlled trials were pooled using risk ratios (RR) and 95% confidence intervals, stratified by national under-five mortality strata (low, medium, high) and duration of follow-up (first year of life and two years). Evidence certainty was evaluated using GRADE.
What was found
Sixty RCTs involving 228,233 participants met the inclusion criteria (Rotarix: 36 trials, n = 119,114; RotaTeq: 15 trials, n = 88,934; Rotasiil: 5 trials, n = 11,753; Rotavac: 4 trials, n = 8,432). - Rotarix (Year 1): Prevented severe rotavirus diarrhoea by 93% in low-mortality (4 trials, n = 14,976; high certainty), 79% in medium-mortality (4 trials, n = 31,671; high certainty), and 58% in high-mortality countries (4 trials, n = 15,882; high certainty). Prevented severe all-cause diarrhoea by 52% (moderate certainty), 36% (high certainty), and 27% (high certainty), respectively. - Rotarix (2 years): Prevented severe rotavirus diarrhoea by 90% (low mortality; high certainty), 77% (medium mortality; high certainty), and 35% (high mortality; moderate certainty). Severe all-cause diarrhoea was reduced by 51%, 26%, and 17%, respectively. - RotaTeq (Year 1): Prevented severe rotavirus diarrhoea by 97% (low mortality, 2 trials, n = 5,442; high certainty), 79% (medium mortality, 1 trial, n = 3,863; low certainty), and 57% (high mortality, 2 trials, n = 6,775; high certainty). Little to no difference in severe all-cause diarrhoea was observed in high-mortality countries (1 trial, n = 4,085). - RotaTeq (2 years): Prevented severe rotavirus diarrhoea by 96% (low mortality), 79% (medium mortality), and 44% (high mortality; high certainty), with a 15% reduction in severe all-cause diarrhoea in high-mortality countries. - Rotasiil (High-mortality settings only): Prevented severe rotavirus diarrhoea by 48% in Year 1 and 44% at two years (2 trials, n = 11,008; high certainty), but showed little to no difference in severe all-cause diarrhoea. - Rotavac (High-mortality settings only): Prevented 57% of severe rotavirus diarrhoea and 16% of severe all-cause diarrhoea in Year 1 (1 trial, n = 6,799; moderate certainty).
Why it matters
This review establishes high-certainty evidence that WHO-prequalified rotavirus vaccines provide robust protection against severe rotavirus diarrhoea globally, although efficacy is systematically lower in high-mortality regions where the baseline disease burden is greatest.
Limits
Rotasiil and Rotavac have only been evaluated in high-mortality countries, leaving efficacy unknown in low- and medium-mortality regions. RotaTeq trials did not report severe all-cause diarrhoea outcomes in low- or medium-mortality settings. Vaccine efficacy against both rotavirus-specific and all-cause severe diarrhoea was substantially lower in high-mortality countries compared to lower-mortality settings. Specific adverse events and safety data were not reported in the abstract.
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