Identification of prior dengue-naïve Dengvaxia recipients with an increased risk for symptomatic dengue during fever surveillance in the Philippines.

Identification of prior dengue-naïve Dengvaxia recipients with an increased risk for symptomatic dengue during fever surveillance in the Philippines.
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DOI:
10.3389/fimmu.2023.1202055
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发表时间:
2023
影响因子:
7.3
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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登革病毒(DENV)是人类蚊媒病毒性疾病的主要原因。登革热是第一种获得许可的登革热疫苗,建议9-45岁的DENV血清阳性者接种。在菲律宾,2016-2017年间,超过83万名儿童在没有事先进行血清学检测的情况下接受了登革热。随后,发现接受登革热病毒感染的DENV血清阴性儿童在突破性DENV感染后发展为严重疾病。因此,参加大规模疫苗接种运动的数千名儿童患严重登革热的风险更高。至关重要的是,必须开发和验证一种鉴定基线DENV-天真登革热接受者的方法。这将允许对突破性DENV感染进行更频繁和更广泛的评估和及时治疗。我们评估了由夏威夷大学(UH)开发的一种候选检测方法--DENV1-4非结构蛋白1(NS1)Ig G酶联免疫吸附试验(EL ISA)的性能,该方法使用了有充分证据的血清/血浆样本,包括DENV感染后20年的样本,并测试了199名研究参与者的样本,其中包括来自菲律宾发烧监测项目的100名登革热患者。该方法的敏感度和特异度分别为96.6%和99.4%,高于文献报道的疫苗接种前筛查结果。在接种登革热疫苗的儿童中,登革热病毒感染的症状突破率(10/23)明显高于登革热免疫组(7/53)(p=0.004,Fisher‘s精确检验),证明了该方法和算法在临床实践中的可行性。UH-DENV1-4NS1-Ig G ELISA不仅可以在非急性登革热期间,也可以在登革热突破性感染期间检测登革热接受者的基线DENV血清状态,对评估登革热在许可证后的长期安全性和有效性具有一定的意义。
Dengue virus (DENV) is the leading cause of mosquito-borne viral diseases in humans. Dengvaxia, the first licensed dengue vaccine, is recommended for DENV-seropositive individuals aged 9–45 years. In the Philippines, Dengvaxia was administered to more than 830,000 children without prior serological testing in 2016–2017. Subsequently, it was revealed that DENV-seronegative children who received Dengvaxia developed severe disease following breakthrough DENV infection. As a result, thousands of children participating in the mass vaccination campaign were at higher risk of severe dengue disease. It is vital that an assay that identifies baseline DENV-naïve Dengvaxia recipients be developed and validated. This would permit more frequent and extensive assessments and timely treatment of breakthrough DENV infections. We evaluated the performance of a candidate assay, the DENV1–4 nonstructural protein 1 (NS1) IgG enzyme-linked immunosorbent assay (ELISA), developed by the University of Hawaii (UH), using well-documented serum/plasma samples including those >20 years post-DENV infection, and tested samples from 199 study participants including 100 Dengvaxia recipients from the fever surveillance programs in the Philippines. The sensitivity and specificity of the assay were 96.6% and 99.4%, respectively, which are higher than those reported for pre-vaccination screening. A significantly higher rate of symptomatic breakthrough DENV infection was found among children that were DENV-naïve (10/23) than among those that were DENV-immune (7/53) when vaccinated with Dengvaxia (p=0.004, Fisher’s exact test), demonstrating the feasibility of the assay and algorithms in clinical practice. The UH DENV1–4 NS1 IgG ELISA can determine baseline DENV serostatus among Dengvaxia recipients not only during non-acute dengue but also during breakthrough DENV infection, and has implications for assessing the long-term safety and effectiveness of Dengvaxia in the post-licensure period.
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