Effectiveness of a Single-Dose Mass Dengue Vaccination in Cebu, Philippines: A Case-Control Study

Background: Dengue fever is an important public health problem in the Philippines. In July 2017, the Department of Health launched a community-based dengue vaccination program of nine- to fourteen-year-old children in Cebu province using CYD-TDV (Dengvaxia, Sanofi Pasteur). The program was discontinued in December 2017 amidst public controversy, after the first dose had been administered. We assessed the effectiveness of a single dose of CYD-TDV against hospitalized virologically confirmed dengue (VCD). Methods: We conducted a case-control study in Cebu province following the dengue mass vaccination. Children who were nine to fourteen years of age during the mass vaccination and subsequently admitted to any of four participating public hospitals with suspected dengue were enrolled in the study as cases. Blood for RT-PCR and clinical and socio-demographic information were obtained. To estimate the level of vaccine protection, vaccination status was compared between children with hospitalized virologically confirmed dengue and controls of the same six-year age-group as the cases, matched on sex, neighborhood and time of occurrence of cases. Findings: We enrolled 490 cases and 980 controls. Receipt of one dose of CYD-TDV was associated with 26% (95 % CI, -2 to 47%; p=0.0675) overall protection against hospitalized virologically confirmed dengue and 51% (95 % CI, 23 to 68; p=0.0016) protection against dengue with warning signs.  Interpretation: A single dose of CYD-TDV given to nine to fourteen-year-old children through a community-based mass vaccination program conferred protection against dengue with warning signs but we were unable to conclude on protection against milder illness. Trial Registration:NCT03803618 Funding Statement: Sanofi Pasteur Declaration of Interests: The manuscript was written entirely by the authors, who vouch for the completeness and accuracy of the data and for the fidelity of the study to the protocol. M Ylade, KA Agrupis, JV Daag MV Crisostomo, MO Tabuco, and AL Lopez declare receiving salaries as part of this study. J Sarol received an honorarium for planning and preparation of the statistical plan. D Macina and J Nealon report being currently employed by Sanofi Pasteur. J Deen (unpaid Principal Investigator) and AV Sy report no conflicts of interest. Ethics Approval Statement: The protocol was approved by the University of the Philippines Manila Research Ethics Board.