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部分有效的登革热疫苗的伦理问题:来自菲律宾的教训。

Ethics of a partially effective dengue vaccine: Lessons from the Philippines.

机构信息

Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD 20817, United States.

Research Associate, Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720, United States; Department of Biology, University of Florida, Gainesville, FL 32611, United States.

出版信息

Vaccine. 2020 Jul 31;38(35):5572-5576. doi: 10.1016/j.vaccine.2020.06.079. Epub 2020 Jul 10.

Abstract

Dengvaxia, a chimeric yellow fever tetravalent dengue vaccine developed by SanofiPasteur is widely licensed in dengue-endemic countries. In a large cohort study Dengvaxia was found to partially protect children who had prior dengue virus (DENV) infections but sensitized seronegative children to breakthrough DENV disease of enhanced severity. In 2019, the European Medicines Agency and the US FDA issued licenses that reconciled safety issues by restricting vaccine to individuals with prior dengue infections. Using revised Dengvaxia efficacy and safety data we sought to estimate hospitalized and severe dengue cases among the more than 800,000 9 year-old children vaccinated in the Philippines. Despite an overall vaccine efficacy of 69% during 4 years post-vaccination we project there will be more than one thousand vaccinated seronegative and seropositive children hospitalized for severe dengue. Assisting these children through a program of enhanced surveillance leading to improved care deserves widespread support. Clinical responses observed during breakthrough dengue infections in vaccinated individuals counsel prudence in design of vaccine policies. Recommendations concerning continued use of this dengue vaccine are: (1) obtain a better definition of vaccine efficacy and safety through enhanced phase 4 surveillance, (2) obtain a valid, accessible, sensitive, specific and affordable serological test that identifies past wild-type dengue virus infection and (3) clarify safety and efficacy of Dengvaxia in flavivirus immunes. In the absence of an acceptable serological screening test these unresolved ethical issues suggest Dengvaxia be given only to those signing informed consent.

摘要

登革热疫苗是由赛诺菲巴斯德公司开发的一种嵌合黄热病四价登革热疫苗,已在登革热流行国家广泛获得许可。在一项大型队列研究中,发现登革热疫苗对先前感染过登革病毒(DENV)的儿童有一定的保护作用,但使血清阴性的致敏儿童易发生突破性 DENV 疾病,且病情加重。2019 年,欧洲药品管理局和美国食品药品监督管理局发布了许可证,通过限制疫苗接种对象为有既往登革热感染的人群,解决了安全性问题。我们利用修订后的登革热疫苗有效性和安全性数据,试图估计在菲律宾接种超过 80 万名 9 岁儿童的登革热疫苗后,住院和重症登革热病例的数量。尽管在接种疫苗后 4 年内的总体疫苗有效性为 69%,但我们预计将有超过 1000 名血清阴性和血清阳性的儿童因重症登革热住院。通过加强监测以改善护理的方案,帮助这些儿童值得广泛支持。在接种疫苗的个体中观察到的突破性登革热感染的临床反应提醒人们在设计疫苗政策时要谨慎。关于继续使用这种登革热疫苗的建议如下:(1)通过加强第四阶段监测,更好地确定疫苗的有效性和安全性;(2)获得一种有效的、可及的、敏感的、特异的和负担得起的血清学检测方法,以确定过去的野生型登革热病毒感染;(3)澄清登革热疫苗在黄病毒免疫中的安全性和有效性。在没有可接受的血清学筛查检测的情况下,这些未解决的伦理问题表明,只有在获得知情同意的情况下,方可使用登革热疫苗。

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