Determining dengue virus serostatus by indirect IgG ELISA compared with focus reduction neutralisation test in children in Cebu, Philippines: a prospective population-based study.
Determining dengue virus serostatus by indirect IgG ELISA compared with focus reduction neutralisation test in children in Cebu, Philippines: a prospective population-based study.
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DOI：
10.1016/s2214-109x(20)30392-2
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发表时间：
2021-01
影响因子：
34.3
通讯作者：
de Silva, Aravinda M.
中科院分区：
文献类型：
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作者：
Lena Lopez, Anna;Adams, Cameron;Ylade, Michelle;Jadi, Ramesh;Veronica Daag, Jedas;Molloy, Caitlyn T.;An Agrupis, Kristal;Kim, Deok Ryun;Silva, Maria Wilda;Yoon, In-Kyu;White, Laura;Deen, Jacqueline;de Silva, Aravinda M.
登革病毒抗体的检测对于了解未来登革病毒的风险和疫苗接种前筛查非常重要。我们的目的是评估登革热IgG间接ELISA在菲律宾儿童队列中确定登革热血清阳性率的性能，使用焦点减少中和试验（FRNT）作为参考试验。在这项基于人群的前瞻性队列研究中，我们招募了居住在菲律宾宿务Bogo或Balamban的健康儿童，他们在大规模登革热疫苗接种活动时年龄为9-14岁。从参与者中收集血清，并通过间接IgG ELISA和FRNT进行批量检测。主要终点是队列中的登革热血清阳性率，通过ELISA检测，并通过参考FRNT检测进行验证。本研究注册于ClinicalTrials.gov，NCT 03465254。我们在2017年5月2日至6月2日期间收集了2996份血清样本，并使用IgG ELISA检测了每份样本。使用1961份（65.5%）FRNT检测样本和1035份（34.5%）插补结果样本，我们发现2996名儿童中有320名（10.7%）为登革热初治儿童，2676名（89.3%）为既往登革热病毒感染血清阳性。根据1961例分类为登革热血清阴性或血清阳性的非插补FRNT结果，ELISA（指数值临界值为0.9）显示灵敏度为95.2%，特异性为93.4%，假阳性率为6.6%，假阴性率为4.8%。然而，在仅对一种登革热病毒血清型有免疫力的儿童中，ELISA的敏感性较差（77.1%）。在ELISA假阳性的11份血清中，7份（63.6%）样本对寨卡病毒或日本脑炎病毒呈血清阳性。我们研究中评估的大多数有资格参加大规模登革热疫苗接种活动的儿童（89.3%）既往登革热病毒感染血清反应呈阳性。与FRNT相比，ELISA具有较高的敏感性和特异性（>90%），但假阴性和假阳性率使该试验不适合用于接种前筛查。被登革热IgG ELISA错误鉴定为血清阳性的个体，然后接种疫苗，可能在随后暴露于野生型登革热病毒期间有发生严重疾病的风险。那些具有单型特征的人将从疫苗接种中获益最多，但该组中IgG ELISA的灵敏度远低于具有多型特征的人。菲律宾卫生部、Hanako基金会、世卫组织、瑞典国际开发合作署（通过国际疫苗研究所）和美国北卡罗来纳州查佩尔山的北卡罗来纳州大学。
Detection of dengue virus antibodies is important for understanding future dengue virus risk and for prevaccination screening. We aimed to evaluate the performance of a dengue IgG indirect ELISA in determining dengue seroprevalence in a cohort of children in the Philippines, using a focus reduction neutralisation test (FRNT) as the reference test. In this prospective population-based cohort study, we enrolled healthy children residing in Bogo or Balamban, Cebu, Philippines, who were to be aged 9–14 years at the time of a mass dengue vaccination campaign. Sera were collected from participants and batch tested by indirect IgG ELISA and FRNT. The primary endpoint was dengue seroprevalence in the cohort, detected by ELISA, and validated by that detected by reference FRNT. This study is registered with ClinicalTrials.gov, NCT03465254. We collected 2996 serum samples between May 2, and June 2, 2017, and we tested each sample with IgG ELISA. Using 1961 samples (65· 5%) that were tested with FRNT, and 1035 samples (34·5%) with imputed results, we found that 320 (10·7%) of 2996 children were dengue naive and 2676 (89·3%) were seropositive for previous dengue virus infection. Based on the 1961 non-imputed FRNT results classified as dengue seronegative or seropositive, the ELISA (with a 0·9 index value cutoff) showed 95·2% sensitivity, 93·4% specificity, 6·6% false positivity, and 4·8% false negativity. However, sensitivity of the ELISA was poor (77·1%) among children with immunity to just one dengue virus serotype. Of the 11 sera that were false positive with ELISA, seven samples (63·6%) were seropositive for Zika virus or Japanese encephalitis virus with FRNT. Most children (89·3%) assessed in our study and eligible to participate in the mass dengue vaccination campaign were seropositive for previous dengue virus infection. Compared with FRNT, ELISA had high sensitivity and specificity (>90%), but the false-negative and false-positive rates makes the test suboptimal for prevaccination screening. Individuals who are falsely identified as seropositive by dengue IgG ELISA and then vaccinated might be at risk of developing severe disease during a subsequent exposure to wild-type dengue virus. Those with a monotypic profile would benefit the most from vaccination, but the sensitivity of the IgG ELISA was much lower in this group than in those with a multitypic profile. Philippine Department of Health, Hanako Foundation, WHO, Swedish International Development Cooperation Agency through the International Vaccine Institute, and University of North Carolina, Chapel Hill, NC, USA.