Josephine van Dongen

8 Summary and general discussion 195 MRC infants experience a SAE. The potential benefit of vaccination we calculate based on a 30% vaccine effectiveness and a 7.6% incidence of severe rotavirus AGE up to 18 months of age (derived from rotavirus incidence of 14.6 per 100 person years and 43% severe disease in the unvaccinated population as described in chapter 2 ). This leads to a 2.3% population attributable risk reduction of severe rotavirus AGE by vaccination in medical risk infants. Jointly, these calculations result in a risk-benefit ratio of 1:6, meaning that per induced SAE six severe rotavirus AGE cases were prevented. In this comparison of risks and benefits we ignored all non-serious adverse events, that occur at one in 10 rotavirus vaccinated infants. Our previous analyses which assumed over 80% vaccine effectiveness and higher AGE incidence, 4 described in chapter 3 , resulted in a far more favorable risk-benefit ratio of targeted vaccination. Some fur ther discussion is needed on infants born after 32 weeks of gestation and term infants with congenital disorders. Within RIVAR the focus was on extreme vulnerable medical risk infants with prolonged care, i.e. infants should still receive care at time of first dose rotavirus vaccination. Consequently, our results cannot be extrapolated to healthy and stable premature infants without prolonged postnatal care. This includes mostly infants born after 32 weeks of gestation. For moderately premature infants it might be best to rely on the prior effectiveness studies ( table 1 ) and pre-licensure trials of Omenaca and Goveia et al. 59,60 In these trials, 303 and 2070 premature infants were studied for immunogenicity and efficacy of rotavirus vaccination respectively. Only a small propor tion had a gestational age below 32 weeks and none had comorbidities. IgA seroconversion rate after two doses of Rotarix was 85.7% (95%CI 79.0;90.9%) 59 and efficacy against rotavirus AGE of any severity was 73% (95%CI -2.2;95.5%) after three doses of RotaTeq. 60 Another group that could benefit more from rotavirus vaccination includes the subgroup within RIVAR of term infants with congenital disorders. The point estimate for vaccine effectiveness in this group was slightly higher (hazard ratio: 0.51). However, due to fewer par ticipants in the subgroups the estimates are less precise. For these infants, evidence from the post-licensure studies of Javid and Fang et al should also be considered. 61,62 These two studies showed sufficient seroconversion and an acceptable safety profile of rotavirus vaccination for infants with intestinal disorders or failure. Vaccination strategy Based on the RIVAR study, vaccination of infants with MRC is no longer cost-effective and the estimated risk-benefit ratio gives reason for concern. In order to protect these infants from rotavirus disease, an alternative vaccination strategy should be considered. Routine universal rotavirus vaccination or universal mass vaccination, as 107 countries worldwide have implemented, 16 could be such a strategy. With universal rotavirus vaccination included in the national immunization program at well-baby clinics, indirect effectiveness (herd effect)