Twelve Dutch pilot-hospitals with Neonatal Intensive Units and associated post IC/HC hospitals will participate in an implementation project of a hospital-based RV vaccination program for high-risk infants (RIVAR-program).
The RV vaccination program consists of offering a 2-dose course of the oral monovalent RV vaccine free of charge to all high-risk infants receiving care in one of the participating hospitals at discharge or during routine clinic visits and will be accompanied by a RV active surveillance program within the participating hospitals
Background and motivation
In a recent Dutch study it was demonstrated that high-risk infants had increased risks of requiring hospitalization due to RV (1.7 to 4.4), of ICU admission (RR: 4.2 to 7.9) and of acquiring nosocomial RV infection (OR: 3.2 to 3.6) compared to healthy infants. High-risk infants also experienced prolonged hospitalization (1.5 to 3.0 excess days) and generated higher healthcare costs (€648 to €1533 per patient). Most importantly, it was estimated that on average 6-7 high-risk infants succumbed due to direct and indirect consequences of RV infection annually in the Netherlands.
No mortality was observed among healthy infants. A subsequent cost-effectiveness analysis demonstrated that RV vaccination of high-risk infants would be very cost-effective and potentially cost-saving from the healthcare payer perspective.
The results demonstrate that prevention against RV gastroenteritis is urgently needed for high-risk infants. Yet, there is no RV vaccination program in the Netherlands. Organizing a successful RV vaccination program within the Dutch infant immunization framework generates additional challenges concerning adequate reach-out to high-risk infants because of the strict age-window indicated for RV vaccine administration.
The first dose of RV vaccine should be administered between 6 and 14 weeks of age and vaccination completed no later than 24 or 32 weeks of age, depending on the vaccine. Secondary and tertiary pediatric care would provide an excellent environment for RV vaccination in order to reach optimal RV vaccine coverage rates in high-risk infants and to ascertain timely vaccination, because high-risk infants are closely followed here during their first month of life. There is however little experience in the Netherlands with organizing immunization programs for target groups through secondary and tertiary pediatric care.
Furthermore, there is a lack of data on RV vaccine performance among the special populations of high-risk infants, although these patients require protection most. Further data on vaccine effectiveness are needed to improve vaccination guidelines pertaining to high-risk infants. This project will study the feasibility and impact of implementing a RV vaccination program for high-risk infants organized through secondary and tertiary care. This study will also determine RV vaccine effectiveness among high-risk infants.
ZonMw projectnumber 80-83600-98-20129
National Trial Register number 5361
An observational study accompanying both the pre-and post-implementation periods of the RIVAR-program in participating hospitals will assess vaccine effectiveness, program impact, RV epidemiology within hospitals, vaccine coverage rates and timeliness of vaccination among RV vaccine eligible high-risk infants.
The RIVAR-program is implemented in a step-wedged design across hospitals to account for inter-season variability of RV epidemics in the analysis. To study vaccine effectiveness, high-risk infants will be recruited to participate in an observational study measuring occurrence of (RV) gastroenteritis until 18-months of age. Recruitment will cover both pre- (unvaccinated) and post-implementation (vaccinated) periods.
Measurments includes parental reporting of gastroenteritis, symptom and severity scoring and collection of stool samples.
Rotavirus is the leading cause of dehydrating gastroenteritis among infants and young children worldwide. Infants with underlying medical conditions, prematurity and low birth weight are at increased risk of hospitalizations due to rotavirus (RV) gastroenteritis, RV related complications and mortality.
These infants could therefore benefit most from RV vaccination. Yet, there is currently no vaccination program for RV in the Netherlands that could offer protection these infants. This multicenter study and implementation project combined, will assess the feasibility and impact of a Risk-Group Infant Vaccination program Against Rotavirus (RIVAR-program) implemented in pediatric hospital/secondary care in the Netherlands.
The RIVAR study will also determine RV vaccine effectiveness among high-risk infant populations, where there is currently a lack of such data.
- To evaluate the feasibility of RV vaccination of high-risk infants organized through secondary and tertiary pediatric care as measured by vaccine coverage and timeliness of vaccination.
- To evaluate the impact of RV vaccination of high-risk infants organized through secondary and tertiary pediatric care on rotavirus related hospitalizations among this patientgroup.
- To evaluate the protective effectiveness of at least 1 dose of RV vaccine against severe RV gastroenteritis up to 18 months of life.