Rotavirus infection and vaccination in Norway: Epidemiological studies of infection and intussusception events before and after vaccine introduction

Abstract

Rotavirus is the most common cause of severe acute gastroenteritis (AGE) among young children globally. In 2014, Norway added the rotavirus vaccine into the national immunization program. The overall aim of this thesis is to understand the burden of rotavirus disease in Norway and the benefits and potential risk of vaccination. We used registry data and sentinel hospital surveillance to assess the rotavirus burden before vaccine introduction and the vaccine impact after four years. As the vaccine has been associated with a small risk of intussusception, and the risk seems to be age-dependent, the vaccine is given within strict age limits (first dose before 12 weeks and second dose by 16 weeks of age). Using validated registry data we estimated the baseline intussusception incidence, and calculated the number of expected vaccine-associated intussusception cases in Norway. Our work shows that rotavirus was the primary cause of severe AGE in children <5 years of age in Norway, and constituted a substantial burden before vaccine introduction. Intussusception was confirmed to be a rare disease among Norwegian children. We estimated that 1360 rotavirus hospitalizations would be averted for each vaccine-associated intussusception case under the current situation, and that vaccination beyond the age limits results in a marginal increase in intussusception cases. Finally, our data demonstrate a substantial impact of rotavirus vaccination on severe AGE among children four years after vaccine introduction; AGE hospitalizations in children <5 years of age were reduced by 45% compared with pre-vaccine years. The effectiveness against hospital admission for rotavirus AGE after two vaccine doses was estimated to be around 75%. Exclusive use of the monovalent vaccine, high coverage from the start and population-based health registries provided a valuable opportunity to generate scientific evidence on the benefits and risk of vaccine introduction, in a low-mortality setting.