Ontology-Based Combinatorial Comparative Analysis of Adverse Events Associated with Killed and Live Influenza Vaccines
Ontology-Based Combinatorial Comparative Analysis of Adverse Events Associated with Killed and Live Influenza Vaccines
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DOI：
10.1371/journal.pone.0049941
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发表时间：
2012-11-28
期刊：
影响因子：
3.7
通讯作者：
He, Yongqun
中科院分区：
文献类型：
--
作者：
Sarntivijai, Sirarat;Xiang, Zuoshuang;He, Yongqun
疫苗不良事件（VAE）是指接种疫苗后发生的不良身体变化。了解不良事件（AE）特征是识别严重AE的关键步骤。市场上使用了两种不同类型的季节性流感疫苗：三价（灭活）灭活流感疫苗（TIV）和三价减毒活流感疫苗（LAIV）。根据CDC疫苗不良事件报告系统（VAERS）的数据，研究了这两组季节性流感疫苗诱导的不同不良事件特征。从VAERS中提取了4种TIV（Aturia、Fluarix、Fluvirin和Fluzone）的37，621份AE报告和唯一LAIV（FluMist）的3，707份AE报告。AE报告数据进行了分析，一种新的组合，基于本体的检测方法（CODAE）。CODAE使用比例报告比（PRR）、卡方显著性检验和基础水平过滤检测AE，并通过基于本体的分层分类对识别的AE进行分组。总共确定了48例TIA富集和68例LAIV富集AE（PRR>2，卡方评分>4，病例数>总报告的0.2%）。使用不良事件本体（OAE）、MedDRA和SNOMED-CT对这些AE术语进行分类。OAE方法提供了更好的分类结果比其他两种方法。48例TIA富集AE中有13例与神经和肌肉处理相关，如瘫痪、运动障碍和肌无力。相比之下，68例LAIV富集AE中有15例与炎症反应和呼吸系统疾病相关。有证据表明TIV中存在两起严重不良事件（格林-巴利综合征和瘫痪）。尽管这些严重不良事件的发生率较低，但发现它们在接受TIV疫苗接种的患者中比在接受LAIV疫苗接种的患者中更显著富集。因此，我们新的组合生物信息学分析发现，LAIV比TIV诱导这两种严重不良事件的机会更低。此外，我们的荟萃分析发现，所有先前报道的GBS和流感疫苗免疫之间的正相关性都是基于三价流感疫苗而不是单价流感疫苗。
Vaccine adverse events (VAEs) are adverse bodily changes occurring after vaccination. Understanding the adverse event (AE) profiles is a crucial step to identify serious AEs. Two different types of seasonal influenza vaccines have been used on the market: trivalent (killed) inactivated influenza vaccine (TIV) and trivalent live attenuated influenza vaccine (LAIV). Different adverse event profiles induced by these two groups of seasonal influenza vaccines were studied based on the data drawn from the CDC Vaccine Adverse Event Report System (VAERS). Extracted from VAERS were 37,621 AE reports for four TIVs (Afluria, Fluarix, Fluvirin, and Fluzone) and 3,707 AE reports for the only LAIV (FluMist). The AE report data were analyzed by a novel combinatorial, ontology-based detection of AE method (CODAE). CODAE detects AEs using Proportional Reporting Ratio (PRR), Chi-square significance test, and base level filtration, and groups identified AEs by ontology-based hierarchical classification. In total, 48 TIV-enriched and 68 LAIV-enriched AEs were identified (PRR>2, Chi-square score >4, and the number of cases >0.2% of total reports). These AE terms were classified using the Ontology of Adverse Events (OAE), MedDRA, and SNOMED-CT. The OAE method provided better classification results than the two other methods. Thirteen out of 48 TIV-enriched AEs were related to neurological and muscular processing such as paralysis, movement disorders, and muscular weakness. In contrast, 15 out of 68 LAIV-enriched AEs were associated with inflammatory response and respiratory system disorders. There were evidences of two severe adverse events (Guillain-Barre Syndrome and paralysis) present in TIV. Although these severe adverse events were at low incidence rate, they were found to be more significantly enriched in TIV-vaccinated patients than LAIV-vaccinated patients. Therefore, our novel combinatorial bioinformatics analysis discovered that LAIV had lower chance of inducing these two severe adverse events than TIV. In addition, our meta-analysis found that all previously reported positive correlation between GBS and influenza vaccine immunization were based on trivalent influenza vaccines instead of monovalent influenza vaccines.