Does an off-label two-dose RotaTeq vaccine schedule translate into a higher incidence of rotavirus hospital admissions compared to the approved three-dose RotaTeq schedule? A Canadian immunization research network study

BACKGROUND: Rotavirus (RV) vaccination programs were implemented between 2011 and 2012 in Canada and have considerably reduced the burden of RV disease. In September 2018, the province of Quebec implemented a reduced-dose RotaTeq vaccination schedule (two doses). Other provinces, such as British Columbia and Ontario, continued to use the approved three-dose schedule for this product. Our aim was to determine whether using a reduced-dose RotaTeq schedule was associated with an increased burden of RV disease. METHODS: This quasi-experimental study spanned from September 2006 to March 2023. The main analysis focused on children aged 6-23 months in Quebec, Ontario, and British Columbia. Data were retrieved from administrative databases using diagnosis-specific ICD-10 codes. A difference-in-differences approach using Poisson regression was used to compare admission rates for rotavirus-associated acute gastroenteritis (RV-AGE) and for any acute gastroenteritis (AGE) before and after the implementation of a reduced-dose RotaTeq vaccination schedule in Quebec. FINDINGS: A total of 3875 RV-AGE and 36,568 AGE hospital admissions were identified. Across the three provinces, the rates of admission for RV-AGE and AGE were 87% and 56% lower, respectively, after vaccine program introduction as compared to before. After the implementation of the reduced-dose RotaTeq vaccination schedule in Quebec, between September 2018 and August 2020, only 19 RV-AGE hospital admissions were identified among children between 6 and 23 months of age in the three provinces. In Quebec, the reduced schedule was not associated with a statistically significant increase in RV-AGE admissions (rate ratio = 2.32; 95%CI = 0.80-6.69), or for AGE admissions in general (rate ratio = 1.02; 95%CI = 0.91-1.14), compared to temporal trends in the other two provinces. INTERPRETATION: This study provides reassuring evidence regarding the use of a two-dose RotaTeq schedule in a high-income country with relatively high vaccination coverage and reaffirms the substantial impact of RV vaccination introduction at a population level.