Dengue Vaccine Effectiveness: A Population Cohort Study from 2016 to 2019, in Paraná, Brazil

Background: Dengue has shown an increased global incidence and substantial socioeconomic impact in tropical and subtropical countries. The only vaccine currently approved for dengue prevention, Dengvaxia® was administered at the population level in Brazil and the Philippines. We report its effectiveness applied to a target population of 501,000 residents in 30 municipalities of southern Brazil. Methods: A three-year analysis of an ambispective cohort study was carried out from 2016 onwards. The age groups were 15 to 27 years in 28 municipalities and 9 to 44 years in two. The primary outcome was the presence of dengue confirmed by clinical-epidemiological or laboratory criteria (CEL) according to the number of doses and compliance. Secondary outcomes included laboratory-confirmed dengue, age group, serotype, dengue with warning signs or severe illness and hospitalization. Findings: 60∙4% received at least one dose of vaccine. A total of 4,457 dengue cases were confirmed by CEL. Overall effectiveness was 31∙2% (95% CI 26∙7 to 35∙4) for at least one dose. Considering laboratory criteria, it was 20∙1% (95% CI 9∙7 to 29∙4) under compliance. Greater effectiveness was observed in older age groups, DENV-4 and DENV-1 serotypes. The number of dengue cases increased significantly in 2019, and DENV-2 prevailed. There was no effectiveness for DENV-2, and DENV-3 cases were not observed. The small number of severe dengue cases and warning signs hindered the effectiveness analysis of such outcomes. Interpretation: The results were inferior to the efficacy studies, with a similar trend for DENV-1 and DENV-4, but lower for DENV-2. Effectiveness was influenced by circulating serotype and by age groups that could have been related to the proportion of baseline dengue seronegative subjects in the vaccinated population. It was impossible to conclude the protective effect related to severe dengue. A longer follow-up is needed to estimate the vaccine's effect more accurately, and further epidemiological studies will contribute assessing the vaccine's impact on population contexts. Funding: Sanofi Pasteur. Declaration of Interest: None to declare. Ethical Approval: The Research Ethics Committee at the Federal University of Parana study approved the study (N# 2,308,662).