Dengue Fever Epidemics and the Prospect of Vaccines: A Systematic Review and Meta-Analysis Using Clinical Trials in Children

Abstract

About half of the world's population is at risk of dengue infection. Epidemics of dengue fever have caused an increased risk of morbidity and mortality in recent years, which led to the exploration of vaccines as a preventive measure. This systematic review and meta-analysis aimed to evaluate the efficacy, immune response, and safety of dengue vaccines in children by analyzing clinical trials. The review followed standard procedures for data extraction using PRISMA guidelines and searching multiple databases, including PubMed, CINAHL, Medline, Health Source, Science Direct, and Academic Search Premiere. Eligible studies involved children (0-17 years old). Quality assessment was analyzed using the Cochrane Collaboration criteria, while data synthesis was conducted using thematic analysis and meta-analysis. Among the 38 selected studies, dengue vaccines showed varying efficacy against all four serotypes. The CYD-TDV (Dengvaxia^®) and Tekade (TAK-003) vaccines showed strong protection against severe dengue, but their long-term efficacy varied. Vaccines triggered satisfactory immune responses, notably in those previously exposed to dengue. Safety profiles were mostly favorable, noting mild adverse events post-vaccination. Meta-analysis supported vaccine efficacy and immune response, but safety concerns warrant further exploration. In conclusion, dengue vaccines showed promising efficacy and immune response, particularly against severe manifestations.

Keywords: PRISMA; case-cohort studies; children; clinical trials; dengue fever; meta-analysis; vaccine.

Figure 1

PRISMA Flowchart [26].

Figure 2

Risk of bias was presented in 5 domains, representing bias arising from randomization, bias due to deviations from intended intervention, bias due to missing data, measurement bias, and bias in selection of the reported results. The overall judgment presented as some concerns (yellow), low risk (green), and no information, as demonstrated in 32 studies [30,31,32,33,34,36,38,39,40,43,44,45,46,47,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67].

Figure 3

Overall distribution of risk of bias in 32 RCTs.

Figure 4

Forest plot showing pooled analysis of 27 studies by random effect model [30,31,34,36,38,39,40,43,44,45,46,47,50,51,53,54,55,56,58,60,61,62,63,64,65,66,67]. The vertical line indicates null or no effect. The horizontal lines indicate 95% confidence interval of relative risk. The horizontal lines that cross the null line show the study results are not statistically significant. The diamond shape ⧫ represents the overall effect of the summary of all studies. In this figure, it indicates favorable response toward intervention with the vaccines.

Figure 5

Subgroup analysis of dengue vaccines in children by vaccine efficacy (12 studies) [30,31,34,36,38,39,40,43,45,47,50,51], immunogenicity (9 studies) [44,46,53,55,56,58,61,62,63], and safety 6 studies) [54,60,64,65,66,67]. The vertical line indicates null or no effect. The horizontal lines indicate 95% confidence interval of relative risk. The horizontal lines that cross the null line show the study results are not statistically significant. The diamond shape ⧫ represents the overall effect of the summary of all studies. In this figure, it indicates favorable response toward intervention with the vaccines.

Figure 6

Subgroup analysis of dengue vaccines by type (CYD-TDV (Dengvaxia^®) [30,31,34,36,38,39,40,50,51,54,56,60,62,63,64,65,66,67]; and Tadeka (TAK-003) [43,44,45,46,47,53,55,58,61]. The vertical line indicates null or no effect. The horizontal lines indicate 95% confidence interval of relative risk. The horizontal lines that cross the null line show the study results are not statistically significant. The diamond shape ⧫ represents the overall effect of the summary of all studies. In this figure, the overall effect indicates favorable response toward intervention with the vaccines.

Figure 7

Funnel plots for assessment of publication bias.