Long-term safety follow-up of children from a randomized—controlled phase II b proof—of—concept efficacy study of the live, attenuated, tetravalent dengue vaccine (CYD—TDV) in Thailand

Objective: To investigate the long-term safety of a tetravalent dengue vaccine (CYD-TDV) in children in a phase II b follow-up study in Thailand. Methods: In the phase II b study, children aged 4-11 years were randomized (2:1) to receive three injections of CYD-TDV or serve as control at 6-month intervals, with 25 months' active follow-up (active phase). This study was an additional four-year passive surveillance for hospitalized virologically-confirmed dengue (VCD; hospital phase). Cases of hospitalized VCD, severe hospitalized VCD, vaccine-related serious adverse events, and deaths were reported for the total population, with post-hoc analyses by enrollment age (<9 and >= 9 years). Results: Of 3 997 participants receiving >= 1 injection, 80.1% were recruited to the hospital phase [2 131 (CYD-TDV); 1 072 (control)]. Eighty-five hospitalized VCD cases were reported in the CYD-TDV group and 46 in the control group during the four-year hospital phase [relative risk (RR): 0.93, 95% confidence interval (CI): 0.64-1.36]. The RR over six years of follow-up was 0.77 (95% CI: 0.57-1.05). In those aged >= 9 years, the cumulative RRs in the active phase, hospital phase, and entire six years were 0.28 (95% CI: 0.08-0.81), 0.51 (95% CI: 0.25-1.05), and 0.42 (95% CI: 0.24-0.75), respectively. In the overall population, there were ten severe hospitalized VCD cases in the CYD-TDV group and five in the control group over six years (RR: 1.00, 95% CI: 0.31-3.75). Conclusions: Over six years of follow-up, in children aged >= 9 years, CYD-TDV administration is associated with a reduced risk of hospitalized VCD.