Infectious Disease
Comparative Effectiveness of Recommended vs. Delayed Dosing Schedules for Rotavirus Vaccines: Target Trial Emulation Shae Gantt* Shae Gantt Toshiaki Komura Elizabeth Rogawski McQuade Kayoko Shioda
Background: Live oral rotavirus vaccines are less effective in low- and middle-income countries (LMICs) compared to high-income countries when following the same dosing schedule. We hypothesized that altering dose timing may improve immune protection in LMICs.
Methods: We emulated a target trial with clone-censor weighting to compare the effectiveness of the recommended two-dose rotavirus vaccine schedule with a delayed schedule in preventing rotavirus infection among children under two in Peru and Brazil. Secondary data from the Malnutrition and Enteric Disease Study (MAL-ED) multisite birth cohort (2009-2014) were analyzed. The recommended schedule administers the first dose at 38-65 days and the second dose at 66-168 days after birth, with at least four weeks between doses. The delayed schedule administers the first dose at 66-104 days and the second dose at 105-240 days after birth, also with at least four weeks between doses. Children were followed until the earliest of rotavirus infection, protocol nonadherence, or their second birthday. Cox proportional hazards models estimated inverse probability of censoring weights, adjusted for birth weight, birth height, and duration of exclusive breastfeeding.
Results: We included 145 children in Brazil and 191 in Peru in the clone-censor weight analysis. Under the recommended schedule, the weighted cumulative risk of rotavirus infection at two years was 0.07 (95% confidence interval CI: 0.02-0.12) in Brazil and 0.55 (95% CI: 0.48-0.64) in Peru. For the delayed schedule, the weighted cumulative risk was 0.06 (95% CI: 0.01-0.13) in Brazil and 0.62 (95% CI: 0.38-0.87) in Peru. The risks did not differ significantly between schedules in both countries.
Discussion: We found no difference in the effectiveness of rotavirus vaccines between the recommended and delayed dosing schedules in these settings.
