Effect of single-dose, live, attenuated dengue vaccine in children with or without previous dengue on risk of subsequent, virologically confirmed dengue in Cebu, the Philippines: a longitudinal, prospective, population-based cohort study.

Background: A three-dose dengue vaccine (CYD-TDV) was licensed for use in children aged 9 years and older starting in 2015 in several dengue-endemic countries. In 2016, the Philippine Department of Health implemented a dengue vaccination programme, which was discontinued because of safety concerns. We assessed the relative risk of developing virologically confirmed dengue among children who did or did not receive a single dose of CYD-TDV by previous dengue virus (DENV) infections at baseline classified as none, one, and two or more infections.
Methods: In this longitudinal, prospective, population-based cohort study, we enrolled healthy children (aged 9-14 years) residing in Bogo or Balamban, Cebu, Philippines, between May 2, and June 2, 2017, before a mass dengue vaccination campaign, via the Rural Health Unit in Bogo and three Rural Health Units in Balamban. We collected demographic information and sera for baseline DENV serostatus and conducted active surveillance for acute febrile illness. Children who developed acute febrile illness were identified, clinical data were collected, and blood was drawn for confirmation of dengue by RT-PCR. The primary outcome was the relative risk of developing virologically confirmed dengue among children who received or did not receive a single dose of CYD-TDV by DENV serostatus at baseline.
Findings: A single dose of CYD-TDV did not confer protection against virologically confirmed dengue in children who had none or one previous DENV infection at baseline. One dose conferred significant protection against hospital admission for virologically confirmed dengue among participants who had two or more previous DENV infections at baseline during the first 3 years (70%, 95% CI 20-88; p=0·017) and the entire follow-up period (67%, 19-87; p=0·016).
Interpretation: The risk of developing virologically confirmed dengue after a single dose of CYD-TDV varied by baseline DENV serostatus. Since the study assessed the effect of only a single dose, the findings cannot inform decisions on vaccination by public health officers. However, the findings have implications for children who receive an incomplete vaccination regimen and these results should prompt more detailed analyses in future trials on dengue vaccines.
Funding: The Philippine Department of Health, Hanako Foundation, WHO, Swedish International Development Cooperation Agency, International Vaccine Institute, University of North Carolina, and US National Institute of Allergy and Infectious Diseases.
Competing Interests: Declaration of interests MY, MVC, JVD, KAA, AMC, and AKS report receiving salaries from 2017 onwards as part of an ongoing separate study (effectiveness of the tetravalent dengue vaccine, CYD-TDV [Dengvaxia] in the Philippines) sponsored by the University of the Philippines Manila and funded by Sanofi Pasteur. JD was an unpaid external consultant in the Extended Study Group for dengue vaccine effectiveness evaluation studies in Asia in 2015 convened by Sanofi Pasteur and is an unpaid investigator of an ongoing separate study (effectiveness of the tetravalent dengue vaccine, CYD-TDV [Dengvaxia] in the Philippines) sponsored by the University of the Philippines Manila and funded by Sanofi Pasteur. AMdS is listed as an inventor on pending patent applications filed by the University of North Carolina related to flavivirus diagnostics. All other authors declare no competing interests. This Article reflects the points of view and thoughts of the authors, and the information, conclusions, and recommendations presented are not to be misconstrued as those of the Philippines Department of Health. The material is presented in the spirit of promoting open access and meaningful dialogue for policy, plan, or programme improvement, and the responsibility for its interpretation lies with the reader.
(Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)