Rotavirus vaccinatie voor zuigelingen met een medisch risico

BACKGROUND AND MOTIVATION

Children 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. 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.


PRIMARY OBJECTIVES
• 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.
 


RV VACCINATION PROGRAM
Dutch Hospitals with Neonatal Intensive Units and associated post IC/HC hospitals will be approached for participation in an implementation project of a hospital-based RV vaccination program for high-risk infants. 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.


STUDY DESIGN
An observational study accompanying the program will assess occurrence of gastroenteritis among high-risk infants pre- and post-implementation, RV epidemiology within hospitals, vaccine coverage rates and timeliness of vaccination among RV vaccine eligible high-risk infants. A step-wedged design is used to account for inter-season variability of RV epidemics. Occurrence of (RV) gastroenteritis among high-risk infants will be studied by recruiting high-risk infants, both pre- and post-implementation, for an individual follow-up study until 18-months of age. Follow-up includes parental reporting of gastroenteritis, symptom and severity scoring and collection of stool samples.


STUDY POPULATION
Hospitals and eligible high-risk infants receiving care at these hospitals.


PRIMARY ENDPOINTS
• RV vaccine coverage rates, timeliness of vaccination and impact of the RV vaccination program in reducing RV related hospitalizations among high-risk infants.

• Vaccine effectiveness against severe RV gastroenteritis among high-risk infants up to 18 months of age.

Children 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. In a recent Dutch study it was demonstrated that high-risk infants had increased risks of requiring hospitalization due to RV, of ICU admission and of acquiring nosocomial RV infection compared to healthy infants. High-risk infants also experienced prolonged hospitalization and generated higher healthcare costs.



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.



Furthermore, there is lack of data on RV vaccine performance among the special populations of high-risk infants. Further data on vaccine effectiveness are needed to improve vaccination guidelines pertaining to high-risk infants.



This project will 1)

study the feasibility and impact of implementing a RV vaccination program for high-risk infants organized through secondary and tertiary care, and

2) determine RV vaccine effectiveness among high-risk infants.

Program impact is measured 1 and 2 years post-implementation. Vaccine effectiveness is measured based on follow-up of each enrolled infant up to 18 months of age.

No randomized interventions. This is a step-wedged implementation project of a rotavirus vaccination program for high-risk infants in participating hospitals combined with and observational before-after cohort study measuring rotavirus gastroenteritis occurrence in a pre- and post-implementation cohort of high-risk infants.