Dataset Information

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 3 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 5 years after the last injection.

Results

In those aged ≥9 years and baseline seropositive, CYD-TDV protected against hospitalized and severe VCD over 6 years compared to placebo (HR [95% confidence interval] multiple imputation from month 0 method, .19 [.12-.30] and .15 [.06-.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 6-year follow-up in participants who were seropositive and ≥9 years old. Protection was also observed in seropositive 6-8 year-olds. Clinical Trials Registration: NCT00842530, NCT01983553, NCT01373281, NCT01374516.

SUBMITTER: Forrat R

PROVIDER: S-EPMC8442794 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDengue hemorrhagic fever is the leading cause of hospitalization and death in children living in Asia and Latin America. There is an urgent need for an effective and safe dengue vaccine to reduce morbidity and mortality in this high-risk population given the lack of dengue specific treatment at present. This review aims to determine the efficacy, safety, and immunogenicity of CYD-TDV vaccine in children.MethodsThis is a systematic review including meta-analysis of randomized controlled clinical trial data from Embase, Medline, the Cochrane Library, Web of Science, and ClinicalTrials.gov. Studies that assessed CYD-TDV vaccine efficacy [(1 - RR)*100], safety (RR), and immunogenicity (weighted mean difference) in children were included in this study. Random effects model was employed to analyze patient-level data extracted from primary studies.ResultsThe overall efficacy of CYD-TDV vaccine was 54% (40-64), while serotype-specific efficacy was 77% (66-85) for DENV4, 75% (65-82) for DENV3, 50% (36-61) for DENV1, and 34% (14-49) for DENV2. 15% (-174-74) vaccine efficacy was obtained for the unknown serotype. Meta-analysis of included studies with longer follow-up time (25 months) revealed that CYD-TDV vaccine significantly increased the risk of injection site reactions (RR = 1.1: 1.04-1.17; p-value = 0.001). Immunogenicity (expressed as geometric mean titers) in descending order was 439.7 (331.7-547.7), 323 (247 - 398.7), 144.1 (117.9-170.2), and 105 (88.7-122.8) for DENV3, DENV2, DENV1, and DENV4, respectively.ConclusionCYD-TDV vaccine is effective and immunogenic in children overall. Reduced efficacy of CYD-TDV vaccine against DENV2 notoriously known for causing severe dengue infection and dengue outbreaks cause for serious concern. Post hoc meta-analysis of long-term follow-up data (≥25 months) from children previously vaccinated with CYD-TDV vaccine is needed to make a conclusion regarding CYD-TDV vaccine safety in children. However, CYD-TDV vaccine should be considered for use in regions where DENV2 is not endemic as currently there is no specific treatment for dengue infection.

Project description:BackgroundRandomised controlled trials have evaluated the recombinant tetravalent dengue vaccine (CYD-TDV). However, individual results may have little power to identify differences among the populations studied.ObjectiveTo evaluate efficacy, immunogenicity and safety of CYD-TDV in the prevention of dengue in children aged 2-17 years.DesignSystematic review and meta-analysis.Data sourcesMEDLINE (from 1950 to 5 December 2018), EMBASE (from 1947 to 5 December 2018) and Cochrane (from 1993 to 5 December 2018).Eligibility criteria of studiesRandomised trials comparing efficacy, immunogenicity and safety of CYD-TDV with placebo or other vaccines for preventing dengue cases in children aged 2-17 years.Outcome measuresEfficacy, immunogenicity and safety of CYD-TDV.Study appraisal and methodsCalculations were made of relative risk (RR) and mean difference (MD) for dichotomous and continuous outcomes, respectively. All estimates were calculated considering a 95% CI estimate. A p<0.05 was considered statistically significant.ResultsNine studies involving 34 248 participants were included. The overall efficacy of CYD-TDV was 60% (RR 0.40 (0.30 to 0.54)). Serotype-specific efficacy of the vaccine was 51% for dengue virus type-1 (DENV-1) (RR 0.49 (0.39 to 0.63)); 34% for DENV-2 (RR 0.66 (0.50 to 0.86)); 75% for DENV-3 (RR 0.25 (0.18 to 0.35)) and 77% for DENV-4 (RR 0.23 (0.15 to 0.34)). Overall immunogenicity (MD) of CYD-TDV was 225.13 (190.34 to 259.93). Serotype-specific immunogenicity was: DENV-1: 176.59 (123.36 to 229.83); DENV-2: 294.21 (181.98 to 406.45); DENV-3: 258.78 (146.72 to 370.84) and DENV-4: 189.35 (141.11 to 237.59). The most common adverse events were headache and pain at the injection site.LimitationsThe main limitation of this study was unclear or incomplete data.Conclusions and implications of key findingsCYD-TDV is considered safe and able to partially protect children and adolescents against four serotypes of DENV for a 1-year period. Despite this, research should prioritise improvements in vaccine efficacy, thus proving higher long-term protection against all virus serotypes.Prospero registration numberCRD42016043628.