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.