PDF(Pubmed)
Abstract：
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.
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.
摘要：
■登革热病毒（DENV）是人类蚊媒病毒性疾病的主要原因。Dengvaxia,第一个获得许可的登革热疫苗，推荐给9-45岁的DENV血清阳性个体。在菲律宾,在2016-2017年，Dengvaxia在没有事先进行血清学检测的情况下对830,000多名儿童进行了治疗。随后，据透露，接受Dengvaxia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，必须开发并验证鉴定基线DENV-天真的Dengvaxia接受者的测定。这将允许对突破性DENV感染进行更频繁和广泛的评估和及时的治疗。
■我们评估了候选测定的性能，DENV1-4非结构蛋白1（NS1）IgG酶联免疫吸附试验（ELISA），由夏威夷大学（UH）开发，使用有据可查的血清/血浆样本，包括DENV感染后20年以上的样本，并测试了199名研究参与者的样本，其中包括100名来自菲律宾发烧监测计划的登瓦夏接受者。
■检测的灵敏度和特异度分别为96.6%和99.4%,分别,高于疫苗接种前筛查报告的水平。在未接触DENV（10/23）的儿童中，发现有症状的突发性DENV感染率明显高于接种Dengvaxia疫苗的DENV免疫儿童（7/53）（p=0.004，Fisher精确检验），证明分析和算法在临床实践中的可行性。
■UHDENV1-4NS1IgGELISA不仅可以在非急性登革热期间，而且可以在突发性DENV感染期间确定登革热受者的基线DENV血清状态，并对评估登瓦夏在许可后期间的长期安全性和有效性具有影响。
■我们评估了候选测定的性能，DENV1-4非结构蛋白1（NS1）IgG酶联免疫吸附试验（ELISA），由夏威夷大学（UH）开发，使用有据可查的血清/血浆样本，包括DENV感染后20年以上的样本，并测试了199名研究参与者的样本，其中包括100名来自菲律宾发烧监测计划的登瓦夏接受者。
■检测的灵敏度和特异度分别为96.6%和99.4%,分别,高于疫苗接种前筛查报告的水平。在未接触DENV（10/23）的儿童中，发现有症状的突发性DENV感染率明显高于接种Dengvaxia疫苗的DENV免疫儿童（7/53）（p=0.004，Fisher精确检验），证明分析和算法在临床实践中的可行性。
■UHDENV1-4NS1IgGELISA不仅可以在非急性登革热期间，而且可以在突发性DENV感染期间确定登革热受者的基线DENV血清状态，并对评估登瓦夏在许可后期间的长期安全性和有效性具有影响。
