Individuals with a history of dengue infection face a significantly elevated risk of developing severe dengue upon subsequent infection, according to a recent meta-analysis of phase III randomized controlled trials. The study, which analyzed data from multiple vaccine efficacy trials, highlights the complex interplay between prior immunity and disease severity in dengue.
The research, published in the Pan American Journal of Public Health, assessed the association between serologically confirmed prior dengue infection and the risk of virologically confirmed dengue, severe dengue, dengue hospitalization, dengue-related death, and all-cause mortality. The meta-analysis included data from placebo groups in four studies derived from three phase III trials conducted between January 1994 and March 2024.
The analysis revealed that individuals with prior dengue infection had a lower likelihood of developing virologically confirmed dengue during the follow-up period (OR: 0.85, 95% CI: 0.75 to 0.98, P = 0.024). However, this protective effect against infection was counterbalanced by a significantly increased risk of severe dengue (OR: 2.91, 95% CI: 1.23 to 6.87, P = 0.015).
Researchers found no statistically significant differences in dengue hospitalization rates between individuals with and without prior infection (OR: 1.18, 95% CI: 0.92 to 1.53, P = 0.198). Similarly, there were no dengue-related deaths reported during the follow-up period, and no significant differences in all-cause mortality were observed between the two groups (OR: 1.74, 95% CI: 0.21 to 14.08, P = 0.76).
The study authors suggest that these findings necessitate a re-evaluation of prior infection as an independent risk factor in dengue. The increased risk of severe dengue in individuals with prior exposure has implications for vaccine development and deployment strategies, as well as clinical management of dengue cases. Further research is needed to elucidate the immunological mechanisms underlying this phenomenon and to inform strategies for mitigating the risk of severe outcomes in individuals with prior dengue infection.
