No association between enterovirus 71 (EV71) vaccination and risk of febrile seizures: a population-based near real-time surveillance study

ABSTRACT

Background

Since 2016, vaccines against enterovirus 71 (EV71) infection have been approved for use in China. Reports to the national passive surveillance system raised concerns about febrile seizures (FS) after EV71 vaccination. Rapid safety assessment of this novel vaccine is a public health priority. The objective was to assess risks of FS following EV71 vaccination in China.

Methods

We used data from a Regional Health Information Platform in Ningbo. The exposed population was children aged 6–71 months who received any dose of EV71 vaccine from 1 January 2016 to 31 December 2019. We implemented a multilayered approach to actively monitor FS following EV71 vaccination that included near real-time surveillance using two complementary sequential designs and further signal evaluation performing self-controlled risk interval (SCRI) analyses.

Results

A total of 330,668 EV71 doses were administered to the study population. During 157 weeks of sequential analyses, no statistically increased risks were detected, when compared with the self-matched control interval or the background risk. Further SCRI analyses confirmed no associations between EV71 vaccination and FS (adjusted incidence rate ratio: 1.04, 95% CI: 0.75 to 1.43).

Conclusions

Our results reassured the safety of FS after EV71 vaccination using postlicensure data for the first time.

KEYWORDS:

• Vaccine safety
• active surveillance
• near real-time surveillance
• electronic health databases
• sequential analysis
• pharmacoepidemiology

Data availability statement

The data that support the findings of this study are available from the Ningbo Center for Disease Control and Prevention, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are, however, available from the authors upon reasonable request and with permission of the Ningbo Center for Disease Control and Prevention.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Ethics approval and consent to participate

The study protocol was approved by the ethical review committee of the Peking University Health Science Center (IRB. No: IRB00001052-15,045). The requirement for informed consent was waived.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Author Contributions

Concept and design: YS, ZL, LZ, and SZ. Drafting of the manuscript: YS and SZ. Critical revision of the manuscript for important intellectual content: YS, ZL, HZ, and SZ. Provision of study material or patients: NL, LZ, RM, TF, TY, and GX. Collection and assembly of data: NL, LZ, and GX. Check and approval of clinical definition: RM, TF, and TY. Data analysis: YS, ZL, and HZ. Data interpretation: YS, ZL, and SZ. Administrative, technical, or material support: LZ, GX, and SZ. Supervision: GX and SZ. Final approval of manuscript: all authors.

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (Grant no. 81973146) and the Advanced Project of Beijing Natural Science Foundation (Grant no. BMU2019GJJXK003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.