Josephine van Dongen

Chapter 8 186 Introduction Rotavirus is a dominant cause of acute gastroenteritis (AGE) in children. 1,2 Rotavirus AGE is characterized by acute onset of diarrhea, fever and/or vomiting. Morbidity and mor tality due to rotavirus disease in a developed country, like the Netherlands, primarily affects infants with prematurity, low bir th weight or presence of a severe congenital disorder. 3 Providing rotavirus vaccination to this specific population was thought to prevent at least those infants most at risk of severe disease. 4 This thesis described the Risk-group Infant Vaccination Against Rotavirus (RIVAR) project, in which rotavirus vaccination was provided to a specific medical risk population with the aim to study vaccine effectiveness, safety and program feasibility. The group of infants studied in the RIVAR project was defined as infants with 1) one or more medical risk conditions (MRC): premature bir th (before 36 weeks of gestation), a low bir thweight (below 2500 grams) and/ or, a severe congenital pathology. And 2) receiving prolonged in- or out-patient care (between six and 14 weeks of postnatal age) in a par ticipating hospital.This chapter includes a summary of most impor tant findings, a discussion of these findings and recommendations for clinical practice and future research on infant rotavirus vaccination. Summary of this thesis As a baseline measurement and to guide prioritization for prevention strategies we assessed the community burden of all-cause AGE, and pathogen specific disease in this population, using data from the unvaccinated RIVAR cohor t ( chapter 2 ). Community disease burden due to rotavirus was not systematically studied previously, and prior information on rotavirus infections in this medical risk population was obtained from studies conducted in hospital settings. We found that the incidence of all-cause AGE in medical risk infants was comparable to that among healthy infants, however severity in terms of symptoms, healthcare attendance and hospitalization was two to three times higher. Rotavirus and norovirus were most frequently detected as pathogen, and rotavirus resulted in a more severe disease course. In addition, the all-cause AGE in this population led to impor tant societal impact as reflected by 30% daycare absenteeism and parental work loss.We concluded that, compared to studies in healthy infants, the community AGE disease burden among medical risk infants was considerably increased. Next, we updated a previous cost-effectiveness analysis 4 of rotavirus vaccination to take into account the change in rotavirus epidemiology, lower hospitalization rates and updated estimates on community disease burden ( chapter 3 ).We estimated that universal rotavirus vaccination would generate the highest reduction in population disease burden due to rotavirus. However, targeted vaccination (of medical risk infants) was cost-saving in the main and sensitivity analysis,