Analysis of Hospitalized and Severe Dengue Cases Over the 6 years of Follow-up of the Tetravalent Dengue Vaccine (CYD-TDV) Efficacy Trials in Asia and Latin America

Abstract

Background CYD-TDV, a live, attenuated, tetravalent dengue vaccine, has been approved for the prevention of symptomatic dengue in previously dengue exposed individuals. This post-hoc analysis assessed hospitalized and severe virologically-confirmed dengue (VCD) over the complete 6-year follow-up of three CYD-TDV efficacy studies (CYD14, CYD15 and CYD23/CYD57). Methods The main outcomes were hazard ratios (HRs) for hospitalized or severe VCD by baseline dengue serostatus, focusing on those who were seropositive, and by age at immunization (<9 years/≥9 years). Baseline dengue serostatus was measured or inferred using several methods. Hospitalized VCD cases were characterized in terms of clinical signs and symptoms and wild-type viremia level. Antibody persistence was assessed up to five years after the last injection. Results In those aged ≥9 years and baseline seropositive, CYD-TDV protected against hospitalized and severe VCD over six years compared to placebo (HR [95% confidence interval] Multiple Imputation from Month 0 method, 0.19 [0.12–0.30] and 0.15 [0.06–0.39]; other methods were consistent). Vaccine protection was observed over the different study periods, being highest during the first 2 years. Evidence for a decreased risk of hospitalized and severe VCD was also observed in seropositive participants aged 6–8 years. Clinical signs and symptoms, and quantified dengue viremia from participants with hospitalized VCD were comparable between groups. Conclusions CYD-TDV demonstrated robust protection against hospitalized and severe VCD over the entire six-year follow-up in participants who were seropositive and ≥9 years old. Protection was also observed in seropositive 6–8 year olds.

Accuracy and efficacy of pre-dengue vaccination screening for previous dengue infection with a new dengue rapid diagnostic test: a retrospective analysis of phase 3 efficacy trials

“…We selected performance age cutoffs on the basis of evidence of CYD-TDV safety and efficacy in individuals aged 9 years or older and in those aged 6-8 years. 9 years is the lower age limit for vaccination in most countries where CYD-TDV is approved, and evidence published in 2021 suggested a positive benefit-risk profile in children aged 6-8 years as well; 16 these subgroup analyses were prespecified for practical reasons to inform policy makers on the safety and accuracy of the new IgG RDT for pre-vaccination screening. For sensitivity, specificity, and predictive values, the 95% CIs were estimated using the exact binomial method (Clopper-Pearson method).…”

Dengue Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021

“…Vaccine efficacy against hospitalization decreased from 91% (95% CI: 80%-96%) during the first and second years combined after vaccination to 56% (95% CI: 25%-78%) during the fifth and sixth years combined after vaccination. Vaccine efficacy against hospitalization remained significant throughout the 6-year follow-up period (54).…”

Efficacy of Dengue Vaccines in the Prevention of Severe Dengue in Children: A Systematic Review

“…After six years, they found that the CYD-TDV vaccine protected against severe and hospitalized VCD in children aged nine years and more who were seropositive. The vaccine also demonstrated good efficacy in seropositive children aged six to eight during most follow-up years [ 25 ]. These results seem to confirm the findings made by Arredondo-García et al in 2018, who demonstrated the efficacy of Dengvaxia® in the same age range.…”