Safety Assessment of Influenza Vaccination for Neurological Outcomes Among Older Adults in Japan: A Self-Controlled Case Series Study

Overview

Journal Pharmacoepidemiol Drug Saf

Publisher Wiley

Date 2025 Jan 8

PMID 39777941

Authors

Mitsunori Ogawa

Yoshinori Takeuchi

Yukino Iida

Masao Iwagami

Kohei Uemura

Sachiko Ono

Nobuaki Michihata

Daisuke Koide

Yutaka Matsuyama

Hideo Yasunaga

Affiliations

Soon will be listed here.

Abstract

Purpose: To assess adverse neurological risks following influenza vaccination in older adults.

Methods: Using a linked database of healthcare administrative claims data and vaccination records from an urban city in Japan (April 1, 2014, to March 31, 2020), we conducted an observational study utilizing a self-controlled case series design. We identified individuals aged ≥ 65 years who experienced adverse neurological outcomes, defined as hospitalizations related to epilepsy, paralysis, facial paralysis, neuralgia, neuritis, optic neuritis, migraine, extrapyramidal disorders, Guillain-Barre syndrome, or narcolepsy. We used conditional Poisson regression to analyze within-subject incidence rate ratios, comparing the risk of these outcomes during risk periods following influenza vaccination (0-6 days and 7-29 days after each vaccination) with nonvaccination periods. Our analysis was adjusted for age and season groups as time-varying covariates.

Results: We enrolled 3283 eligible individuals (men: 1643; mean [standard deviation] age: 76 [7.3] years). The incidence rate ratio for the outcome during the risk periods was 0.93 (95% confidence interval, 0.66-1.30) in risk period 1 (0-6 days after vaccination) and 1.14 (0.96-1.35) in risk period 2 (7-29 days after vaccination), respectively.

Conclusions: We found no evidence that the risk of adverse neurological events was increased after influenza vaccination in older adults. These results may help reassure older adults who are hesitant to receive influenza vaccination because of concerns regarding adverse neurological outcomes.

References

Kwong J, Vasa P, Campitelli M, Hawken S, Wilson K, Rosella L . Risk of Guillain-Barré syndrome after seasonal influenza vaccination and influenza health-care encounters: a self-controlled study. Lancet Infect Dis. 2013; 13(9):769-76. DOI: 10.1016/S1473-3099(13)70104-X. View

Petersen I, Douglas I, Whitaker H . Self controlled case series methods: an alternative to standard epidemiological study designs. BMJ. 2016; 354:i4515. DOI: 10.1136/bmj.i4515. View

Grohskopf L, Blanton L, Ferdinands J, Chung J, Broder K, Talbot H . Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022-23 Influenza Season. MMWR Recomm Rep. 2022; 71(1):1-28. PMC: 9429824. DOI: 10.15585/mmwr.rr7101a1. View

Chung H, Buchan S, Campigotto A, Campitelli M, Crowcroft N, Dubey V . Influenza Vaccine Effectiveness Against All-Cause Mortality Following Laboratory-Confirmed Influenza in Older Adults, 2010-2011 to 2015-2016 Seasons in Ontario, Canada. Clin Infect Dis. 2020; 73(5):e1191-e1199. PMC: 8423473. DOI: 10.1093/cid/ciaa1862. View

Chang K, Lyu R, Lin W, Huang Y, Lin H, Chang S . Gulllain-Barre Syndrome After Trivalent Influenza Vaccination in Adults. Front Neurol. 2019; 10:768. PMC: 6667925. DOI: 10.3389/fneur.2019.00768. View

Arnheim-Dahlstrom L, Hallgren J, Weibull C, Sparen P . Risk of presentation to hospital with epileptic seizures after vaccination with monovalent AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine (Pandemrix): self controlled case series study. BMJ. 2013; 345:e7594. PMC: 3532724. DOI: 10.1136/bmj.e7594. View

Yang T, Ma R, Ye L, Mei Q, Wang J, Feng Y . Risk of peripheral facial palsy following parenteral inactivated influenza vaccination in the elderly Chinese population. Front Public Health. 2023; 11:1047391. PMC: 9902766. DOI: 10.3389/fpubh.2023.1047391. View

Kajikawa N, Kataoka Y, Goto R, Maeno T, Yokoya S, Umeyama S . Factors associated with influenza vaccination in Japanese elderly outpatients. Infect Dis Health. 2019; 24(4):212-221. DOI: 10.1016/j.idh.2019.07.002. View

Rothberg M, Haessler S, Brown R . Complications of viral influenza. Am J Med. 2008; 121(4):258-64. PMC: 7172971. DOI: 10.1016/j.amjmed.2007.10.040. View

10.

Jun B, Fraunfelder F . Atypical Optic Neuritis After Inactivated Influenza Vaccination. Neuroophthalmology. 2018; 42(2):105-108. PMC: 5858858. DOI: 10.1080/01658107.2017.1335333. View

11.

Haberg S, Aaberg K, Suren P, Trogstad L, Ghaderi S, Stoltenberg C . Epilepsy in Children After Pandemic Influenza Vaccination. Pediatrics. 2018; 141(3). DOI: 10.1542/peds.2017-0752. View

12.

Bardage C, Persson I, Ortqvist A, Bergman U, Ludvigsson J, Granath F . Neurological and autoimmune disorders after vaccination against pandemic influenza A (H1N1) with a monovalent adjuvanted vaccine: population based cohort study in Stockholm, Sweden. BMJ. 2011; 343:d5956. PMC: 3192001. DOI: 10.1136/bmj.d5956. View

13.

Jeong N, Kim Y, Kim C, Park S, Lee J, Choi N . Association between Influenza Vaccination and the Risk of Bell's Palsy in the Korean Elderly. Vaccines (Basel). 2021; 9(7). PMC: 8310133. DOI: 10.3390/vaccines9070746. View

14.

Thompson W, Comanor L, Shay D . Epidemiology of seasonal influenza: use of surveillance data and statistical models to estimate the burden of disease. J Infect Dis. 2006; 194 Suppl 2:S82-91. DOI: 10.1086/507558. View

15.

Wells C . A neurological note on vaccination against influenza. Br Med J. 1971; 3(5777):755-6. PMC: 1798870. DOI: 10.1136/bmj.3.5777.755. View

16.

Hull T, Bates J . Optic neuritis after influenza vaccination. Am J Ophthalmol. 1997; 124(5):703-4. DOI: 10.1016/s0002-9394(14)70918-3. View

17.

Kawai A, Li L, Kulldorff M, Vellozzi C, Weintraub E, Baxter R . Absence of associations between influenza vaccines and increased risks of seizures, Guillain-Barré syndrome, encephalitis, or anaphylaxis in the 2012-2013 season. Pharmacoepidemiol Drug Saf. 2014; 23(5):548-53. DOI: 10.1002/pds.3575. View

18.

Rubinov A, Beiran I, Krasnitz I, Miller B . Bilateral optic neuritis after inactivated influenza vaccination. Isr Med Assoc J. 2012; 14(11):705-7. View

19.

Wong C, Chan K, Hedley A, Peiris J . Influenza-associated mortality in Hong Kong. Clin Infect Dis. 2004; 39(11):1611-7. DOI: 10.1086/425315. View

20.

Farrington C . Relative incidence estimation from case series for vaccine safety evaluation. Biometrics. 1995; 51(1):228-35. View