A Case-Control Study to Determine the Effectiveness of a Tetravalent Dengue Vaccine in the State of Paraná, Brazil

Abstract

Background: The Brazilian state of Parana conducted a mass vaccination campaign against dengue with the tetravalent attenuated vaccine CYD-TDV. The campaign targeted thirty endemic municipalities. The objective of this study was to assess the effectiveness of CYD-TDV in preventing symptomatic virologically confirmed dengue cases according to specific age groups in five of the municipalities. Methods: A case-control study was carried out in the five most populous municipalities targeted by the vaccination, with a vaccine uptake of 25%. Symptomatic dengue cases were identified by the municipal health departments. The age groups targeted were 15–18 and 19–27 in four municipalities and 9–14 and 28–44 in one municipality. All cases were confirmed by real time reverse transcription quantitative polymerase chain reaction (RT-qPCR). For each case, two controls were selected: a neighborhood control and a workplace or school/college control, matched by age group. A conditional logistic regression model was used to determine the odds ratio for vaccination and the vaccine effectiveness. Findings: Study participants included 618 RT-qPCR-confirmed dengue cases and 1,236 matched controls (with a non-reactive dengue IgM serologic test). Vaccine effectiveness against dengue due to any serotype was 11·1% (95% CI: –19·0%; 33·6%). Effectiveness against DENV-1 was 33·3% (95% CI: -5·0%; 57·6%) and against DENV-2 was -56·7% (95% CI: -142·2%; -5·0%). No DENV-3 were detected. The vaccine was significantly effective in the prevention of DENV-4 cases (VE = 93·3%; 95% CI: 47·7%; 99·2%). Interpretation: CYD-TDV was effective in the prevention of symptomatic cases due to DENV-4, but not due to any serotype. The low dengue sero-prevalence in the target population could possibly be related to these results. Funding: This study was supported through a grant to the Sabin Vaccine Institute from Sanofi-Pasteur. Sanofi-Pasteur had no role in the study design, protocol development, data collection, analysis, or publication of results. Declaration of Interest: EJA Luna and JC Moraes have received consultancy fees and travel sponsorship from Sanofi-Pasteur. D Garrett, F. Crosewski, I Riediger, F Fantinato and K Ribeiro declare no conflict of interest. Ethical Approval: The Santa Casa de Sao Paulo Research Ethics Committee (Resolution no. 1817892, on November 11, 2016) and Pan American Health Organization Ethics Review Committee – PAHOERC (Resolution PAHO 2016-11-0056) approved the study protocol.