Background/Objectives: Takeda’s tetravalent dengue vaccine TAK-003 has been approved by the Brazilian regulatory agency ANVISA for dengue disease prevention in individuals aged 4 to 60 years. Dourados, in the state of Mato Grosso do Sul, became the world’s first city to implement a mass vaccination campaign targeting approximately 120,000 individuals. An ongoing collaborative, observational, population-based study using national surveillance and vaccination data was planned to measure the impact of the vaccine on the reduction in dengue incidence. Methods: In this manuscript, the study’s methodology, including its programmatic steps and public health relevance, is described. A collaborative assessment with multidisciplinary researchers in Brazil was conducted to identify key programmatic areas for the successful implementation of the study. These areas included feasibility and site selection assessment, methodology selection, vaccination program implementation, and public health importance. Results/Conclusions: Identification of the public health problem and understanding the disease burden, local healthcare infrastructure, and strategic partnerships were critical for a robust feasibility assessment. One of the feasibility criteria identified was the ability of the Dourados Municipal Health Secretary and the principal investigator to conduct an active vaccination campaign, utilizing extramural activities and diverse communication channels to increase vaccine acceptance and coverage. The selection of analytical methods, such as time series analysis, was dependent on the national and local structures of the databases and data availability.
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