Josephine van Dongen

Chapter 1 16 Targeted versus universal rotavirus vaccination Targeting a selective population is uncommon for rotavirus vaccination, only Croatia and Spain have implemented a selective rotavirus vaccination program for infants with gestational age before 33 weeks, infants with congenital hear t- or metabolic pathologies, chronic liver or kidney disease and/or severe neurological damage. 85,86 No evaluation data about their vaccination pro- gram are made available. For the Netherlands it was estimated that a selective rotavirus vacci- nation program for infants with MRC (i.e. premature infants, low bir thweight or with congenital disorders) would prevent the majority of rotavirus related infant deaths. To select and immunize eligible medical risk infants, however, a selective vaccination program would require a novel infrastructure, separate from the existing Dutch national immunization program, involving secondary and ter tiary neonatal care centers. In addition, the cost-effective analysis results were based on a vaccine effectiveness of at least 88% against severe disease among all, including medical risk, infants, but data to support this were largely lacking. RIVAR project In 2014, the lack of experience with targeted vaccination and uncer tainties about the vaccine effectiveness in infants with MRC were reasons to initiate the Risk-group Infant Vaccination Against Rotavirus (RIVAR) project. In thir teen hospitals over 15 locations it provided an oppor- tunity for infants born premature, small for gestational age and/or with a severe congenital pa- thology to receive immunization against rotavirus as par t of routine medical care. 87 Throughout the RIVAR project we used the human rotavirus vaccination (Rotarix). Aims of this thesis The RIVAR project was designed to answer two main questions. First, what is the vaccine ef- fectiveness of rotavirus vaccination in this specific medical risk population? And second, is a se- lective rotavirus vaccination program in second and third line care feasible? As secondary aims vaccine safety and, potential non-specific effects of rotavirus vaccination are assessed. These questions are answered, after first estimating the community burden of disease due to rotavirus in this population of infants with MRC and updating the cost-effectiveness analysis. Outline of this thesis Chapter 2 contains a description of the acute gastroenteritis disease burden among infants with MRC in the Netherlands. Based on observational data of the unvaccinated infant cohor t in the RIVAR project we were able to quantify the full spectrum of community burden of rotavirus disease; incidence, severity, health care attendance and societal impact. From 2014 onwards a change in rotavirus epidemiology is seen in the Netherlands, therefore we updated the previous cost-effectiveness analysis for universal and targeted rotavirus vaccina- tion strategies. In chapter 3, we describe a health-economic evaluation of rotavirus vaccination