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. 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. 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). 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. 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.

中文翻译：

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菲律宾宿务市，对曾患或未患登革热的儿童使用单剂量登革热减毒活疫苗对随后发生经病毒学证实的登革热风险的影响：一项纵向、前瞻性、基于人群的队列研究


从 2015 年开始，三剂登革热疫苗 (CYD-TDV) 在几个登革热流行国家获准用于 9 岁及以上儿童。 2016年，菲律宾卫生部实施了登革热疫苗接种计划，但由于安全问题而终止。我们评估了在基线时接受过或未接受过单剂 CYD-TDV 的既往登革热病毒 (DENV) 感染儿童中发生经病毒学确诊的登革热的相对风险，分为无感染、一次感染和两次或以上感染。在这项纵向、前瞻性、基于人群的队列研究中，我们招募了2017年5月2日至6月2日大规模登革热疫苗接种运动之前居住在菲律宾宿雾市博戈或巴兰班的健康儿童（9-14岁），通过博戈的农村卫生单位和巴兰班的三个农村卫生单位。我们收集了人口统计信息和血清以了解基线 DENV 血清状态，并对急性发热性疾病进行主动监测。确定出现急性发热性疾病的儿童，收集临床数据，并抽血通过 RT-PCR 确认登革热。主要结果是根据基线 DENV 血清状态，在接受或未接受单剂量 CYD-TDV 的儿童中发生病毒学确诊的登革热的相对风险。对于基线时未感染或既往感染过 DENV 的儿童，单剂 CYD-TDV 不能提供针对病毒学证实的登革热的保护作用。对于在前 3 年内基线时曾感染过两次或两次以上 DENV 的参与者，一剂可显着防止因病毒学确诊的登革热入院（70%，95% CI 20–88；p=0·017）和整个随访上升期 (67%, 19–87; p=0·016)。 单剂 CYD-TDV 后发生病毒学证实的登革热的风险因基线 DENV 血清状态而异。由于该研究仅评估了单剂疫苗的效果，因此研究结果无法为公共卫生官员的疫苗接种决策提供依据。然而，这些发现对接受不完整疫苗接种方案的儿童有影响，这些结果应该促使未来登革热疫苗试验中进行更详细的分析。菲律宾卫生部、花子基金会、世界卫生组织、瑞典国际开发合作署、国际疫苗研究所、北卡罗来纳大学和美国国家过敏和传染病研究所。