Infectious Disease
Comparative Effectiveness of Different Dosing Schedules of Pneumococcal Conjugate Vaccines among Children in Brazil: A Target Trial Emulation Study Using National Registries Katherine Jia* Katherine Jia Jia Jia Jia Jia Jia Jia Jia Department of Global Health, Boston University School of Public Health
Background: Pneumococcal conjugate vaccines (PCVs) prevent pneumococcal diseases in children but are among the most expensive vaccines in routine immunization programs, prompting interest in evaluating real world effectiveness of reduced dosing schedules. Brazil currently follows the WHO-recommended 3 dose schedule (a 2+1 schedule with two primary doses plus a booster). Considering recent evidence that a reduced 1+1 schedule (one primary dose plus a booster) achieved equivalent disease control in selected settings, we aimed at evaluating comparative effectiveness of different dosing schedules in a large developing country with a robust and high coverage PCV program. Target trial emulation (TTE) can leverage nationwide registry data to generate generalizable real-world evidence.
Methods: We emulated a target trial comparing 2+1 and 1+1 schedules among children born in Brazil, 2021-2024. Nationwide live birth, vaccination, hospitalization, and notifiable disease registries were individually linked by the Ministry of Health, covering all municipalities in Brazil. The study included children under four, who were followed up until end of 2024. We applied clone-censor-weight analysis to adjust for immortal time bias and baseline confounding.
Results: By age four, the cumulative incidence of hospitalization for all-cause pneumonia had children followed the 1+1 schedule was similar to that had they followed 2+1 (relative risk [RR]: 0.90; 95% CI: 0.76, 1.03). Likewise, the cumulative incidence of all-cause meningitis was similar (RR: 1.12; 95% CI: 0.82, 1.64) (Figure). Further analyses will include mortality outcome and use negative control exposures and outcomes to assess residual confounding.
Conclusions: In this nationwide TTE, a 1+1 PCV schedule appeared non-inferior to 2+1 for preventing all-cause pneumonia and meningitis hospitalization by age four. TTE offers a powerful and practical approach for generating real-world vaccine effectiveness evidence to inform policy.
