Impact of prior dengue infection on severity and outcomes: meta-analysis of placebo-controlled trials.

Abstract

Objective: This study evaluated the association between serologically confirmed prior dengue infection and the subsequent risk of virologically confirmed dengue, severe dengue, dengue hospitalization, dengue-related death and all-cause mortality.

Methods: A systematic review and meta-analysis were conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed, CINAHL, MEDLINE, the Cochrane Library and Web of Science were searched for reports of phase III randomized controlled trials of vaccine efficacy that had data about the placebo group and information about prior infections and were published between January 1994 and March 2024. Random-effects models were used to calculate combined odds ratios (ORs), and heterogeneity was assessed.

Results: Four studies from three phase III trials were included. Participants with prior infection had a lower likelihood of developing virologically confirmed dengue during follow up (OR: 0.85, 95% confidence interval [CI]: 0.75 to 0.98, P = 0.024) and the same risk of dengue hospitalization as those without prior infection (OR: 1.18, 95% CI: 0.92 to 1.53, P = 0.198). However, they had a higher rate of severe dengue (OR: 2.91, 95% CI: 1.23 to 6.87, P = 0.015). No dengue-related deaths occurred during follow up. There were no statistically significant differences in all-cause mortality between individuals with and without prior dengue (OR: 1.74, 95% CI: 0.21 to 14.08, P = 0.76).

Conclusions: Prior dengue infection significantly reduced the risk of virologically confirmed dengue and increased the risk of severe dengue, but had no significant effect on dengue hospitalization, dengue-related death or all-cause mortality during follow up. These findings suggest the need to reconsider prior infection as an independent risk factor.