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

Background CYD-TDV (Dengvaxia (R)) (R) ) was the fi rst dengue vaccine approved, launched in Brazil in 2015 for individuals aged 9-44 - 44 years. We aimed to estimate the effectiveness of CYD-TDV in preventing symptomatic dengue cases during a campaign targeting individuals aged 15-27 - 27 years in selected municipalities in Paran & aacute;, Brazil. Additionally, we examined whether a history of dengue, as recorded by the surveillance system, modified fi ed the vaccine's ' s effectiveness. Methods We conducted a case-cohort analysis comparing the frequency of vaccination, with at least one dose of CYDTDV, in individuals with dengue confirmed fi rmed by RT-PCR, identified fi ed 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 fi er of the vaccine's ' 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%. Findings 1869 dengue cases were identified, fi ed, which had a vaccination frequency significantly fi cantly lower than the overall vaccination coverage in the target population (50.3% vs. 57.2%, respectively; overall VE: 21.3%; 95% confidence fi dence interval [CI]: 13.4%-28.4%). - 28.4%). In individuals with a documented history of dengue, vaccination had a VE of 71% (95% CI: 58%-80%) - 80%) in reducing the incidence of dengue. However, vaccination was not associated with a significant fi cant 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. Interpretation Vaccination led to a significant fi cant reduction in reported dengue cases within the target population. The case-control design suggested that this reduction was primarily driven by the benefits fi ts 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.