Effectiveness of mass dengue vaccination with CYD-TDV (Dengvaxia®) in the state of Paraná, Brazil: integrating case-cohort and case-control designs

BackgroundCYD-TDV (Dengvaxia®) was the first dengue vaccine approved, launched in Brazil in 2015 for individuals aged 9–44 years. We aimed to estimate the effectiveness of CYD-TDV in preventing symptomatic dengue cases during a campaign targeting individuals aged 15–27 years in selected municipalities in Paraná, Brazil. Additionally, we examined whether a history of dengue, as recorded by the surveillance system, modified the vaccine's effectiveness.MethodsWe conducted a case-cohort analysis comparing the frequency of vaccination, with at least one dose of CYD-TDV, in individuals with dengue confirmed by RT-PCR, identified by the surveillance system during 2019 and 2020, with the vaccination coverage in the target population. Moreover, in a case-control design using weighted controls, we assessed the documented history of dengue as a modifier of the vaccine's effectiveness. We used a logistic random-effects regression model, with data clustered in municipalities and incorporating covariates such as the incidence of dengue before the campaign, age, and sex. We calculated vaccine effectiveness (VE) as (1-relative risk) x 100%.Findings1869 dengue cases were identified, which had a vaccination frequency significantly lower than the overall vaccination coverage in the target population (50.3% vs. 57.2%, respectively; overall VE: 21.3%; 95% confidence interval CI: 13.4%–28.4%). In individuals with a documented history of dengue, vaccination had a VE of 71% (95% CI: 58%–80%) in reducing the incidence of dengue. However, vaccination was not associated with a significant reduction in the overall dengue case risk in individuals without a documented history of dengue (VE: 12%; 95% CI: −21% to 36%). In this last stratum, vaccination was associated with reduced cases due to DENV-1 and DENV-4, but an excess of DENV-2 cases.InterpretationVaccination led to a significant reduction in reported dengue cases within the target population. The case-control design suggested that this reduction was primarily driven by the benefits observed in individuals with a documented history of dengue. In endemic regions with limited serological testing facilities, a previous history of dengue diagnosis recorded by epidemiological surveillance could be used to triage candidates for CYD-TDV vaccination.FundingResearch supported by Sanofi.