Conclusion
Natural viral infections with influenza, hepatitis A, measles, mumps and rubella and varicella have all been associated with transverse myelitis, albeit rarely. Thus, these viral vaccines may prevent transverse myelitis by protecting against natural infection. Vaccines currently routinely recommended to the general population in the U.S.* have not been shown to cause transverse myelitis.
Epidemiological evidence
The 2012 report by the Institute of Medicine (IOM), now called the National Academy of Medicine (NAM), found no relevant studies of quality in the literature assessing an association between transverse myelitis and MMR, varicella, influenza, hepatitis A, hepatitis B, HPV, meningococcal conjugate, diphtheria, tetanus or pertussis vaccines, since the only applicable studies available either had serious methodological limitations or used passive surveillance systems and therefore lacked an unvaccinated comparison group 1.
Two Vaccine Safety Datalink (VSD) studies published since the 2012 IOM report found no cases of transverse myelitis in over 200,000 pregnant individuals within 42 days after receiving trivalent inactivated influenza vaccine 2 and in over 9,000 pregnant individuals within 42 days after receiving 2009 H1N1 pandemic influenza vaccine 3.
Another VSD study covering nearly 64 million vaccine doses, with 67 relevant cases of transverse myelitis, found no statistically significant association between transverse myelitis and prior immunization 4.
A cohort study of 3,983,824 females 10-44 years of age in Denmark and Sweden found no association between quadrivalent HPV vaccine and demyelinating diseases, including transverse myelitis 5.
Analyses of safety surveillance data from the Vaccine Safety Datalink found no significant associations between mRNA COVID-19 vaccines and 23 serious health outcomes (including transverse myelitis) 6.
Proposed biological mechanism
Natural infection with wild-type influenza, hepatitis A, measles, mumps and rubella viruses, as well as herpes zoster and reactivation of latent wild-type varicella virus, have all been associated with transverse myelitis, albeit rarely. Mechanisms that could contribute to transverse myelitis include viral reactivation 1, as well as molecular mimicry, which refers to the possibility that similar epitopes shared between self-peptides and foreign peptides (introduced via infection or immunization) inadvertently cause the activation of autoreactive T or B cells, leading to autoimmunity.
The 2012 IOM report described a few cases of transverse myelitis after MMR 7-9, varicella 10, and hepatitis B vaccines 11, but even when also considering knowledge about the aforementioned natural infections the IOM concluded this mechanistic evidence was weak. The IOM also concluded that there was no mechanistic evidence for an association between transverse myelitis and HPV, meningococcal conjugate, diphtheria, tetanus and pertussis vaccines 1.
* These conclusions do not necessarily consider vaccines recommended only for special populations in the United States such as Yellow Fever vaccine (international travelers) or Smallpox vaccine (military personnel), or vaccines no longer recommended to the public such as the Janssen (J&J) COVID-19 vaccine.
References
1. Institute of Medicine. In: Stratton K, Ford A, Rusch E, Clayton EW, eds. Adverse Effects of Vaccines: Evidence and Causality. Washington (DC): National Academies Press (US); 2012.
2. Nordin JD, Kharbanda EO, Benitez GV, Nichol K, Lipkind H, Naleway A, Lee GM, Hambidge S, Shi W, Olsen A. Maternal safety of trivalent inactivated influenza vaccine in pregnant women. Obstet Gynecol 2013; 121(3): 519-25.
3. Nordin JD, Kharbanda EO, Vazquez-Benitez G, Lipkind H, Lee GM, Naleway AL. Monovalent H1N1 influenza vaccine safety in pregnant women, risks for acute adverse events. Vaccine 2014; 32(39): 4985-92.
4. Baxter R, Lewis E, Goddard K, Fireman B, Bakshi N, DeStefano F, Gee J, Tseng HF, Naleway AL, Klein NP. Acute Demyelinating Events Following Vaccines: A Case-Centered Analysis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2016.
5. Scheller NM, Svanstrom H, Pasternak B, Arnheim-Dahlstrom L, Sundstrom K, Fink K, Hviid A. Quadrivalent HPV vaccination and risk of multiple sclerosis and other demyelinating diseases of the central nervous system. Jama 2015; 313(1): 54-61.
6. Klein NP, Lewis N, Goddard K, Fireman B, Zerbo O, Hanson KE, Donahue JG, Kharbanda EO, Naleway A, Nelson JC, Xu S, Yih WK, Glanz JM, Williams JTB, Hambidge SJ, Lewin BJ, Shimabukuro TT, DeStefano F, Weintraub ES. Surveillance for Adverse Events After COVID-19 mRNA Vaccination. Jama 2021; 326(14): 1390-9.
7. Holt S, Hudgins D, Krishnan KR, Critchley EM. Diffuse myelitis associated with rubella vaccination. Br Med J 1976; 2(6043): 1037-8.
8. Joyce KA, Rees JE. Transverse myelitis after measles, mumps, and rubella vaccine. BMJ 1995; 311(7002): 422.
9. Lim S, Park SM, Choi HS, Kim DK, Kim HB, Yang BG, Lee JK. Transverse myelitis after measles and rubella vaccination. J Paediatr Child Health 2004; 40(9-10): 583-4.
10. LaRovere KL, Raju GP, Gorman MP. Postvaricella acute transverse myelitis in a previously vaccinated child. Pediatr Neurol 2008; 38(5): 370-2. 11. Tartaglino LM, Heiman-Patterson T, Friedman DP, Flanders AE. MR imaging in a case of postvaccination myelitis. AJNR Am J Neuroradiol 1995; 16(3): 581-2.
