Older formulations of rabies vaccine did cause Acute Disseminated Encephalomyelitis (ADEM), but newer formulations of rabies vaccine have not been shown to cause ADEM, and rabies vaccine is not routinely recommended to the general population in the United States. Other vaccines that are currently routinely recommended to the general population in the U.S.* have not been shown to cause ADEM.
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 vaccination and ADEM, since the only applicable studies available used passive surveillance systems and therefore lacked an unvaccinated comparison group . Studies published since the 2012 IOM report have found no association between ADEM and the pandemic H1N1 influenza vaccine Pandemrix , quadrivalent HPV vaccine (Gardasil) [3-5] or hepatitis B vaccine . However, one Vaccine Safety Datalink study did find a possible association between ADEM and Tdap vaccine estimated at no more than 1.16 excess cases per million vaccines administered .
Proposed Biological Mechanism
ADEM has been reported very rarely after natural infections with wild-type measles, mumps, rubella, varicella, influenza, hepatitis A, and other viruses . However, the pathophysiology of ADEM is not fully understood. Also, ADEM has been reported very rarely after immunizations, but in most instances infections with other agents have not been ruled out and there is no available test to determine a causal association with a particular infection or vaccine. Biological mechanisms proposed to explain the immunogenic etiology of ADEM following infection or immunization include direct destruction  and molecular mimicry [8, 9], 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. In the case of ADEM, this abnormal immune response would be directed against the host’s myelin protein . Although a temporal association with ADEM has been described for vaccines such as Japanese encephalitis, yellow fever, measles, influenza, varicella, and hepatitis [11-13], the only clear pathological association ever demonstrated was with the Semple rabies vaccine .
The 2012 IOM report described two cases of ADEM after administration of the Engerix-B hepatitis B vaccine showing a reoccurrence of symptoms after vaccine rechallenge [15, 16]; however, these were insufficient to conclude a causal association . The report also described one case of ADEM after tetanus toxoid vaccination ; however, even after considering knowledge about the aforementioned natural infection, the IOM concluded that this mechanistic evidence was weak. The IOM concluded that the only mechanistic evidence for an association between ADEM and MMR, varicella or influenza vaccines was knowledge about the natural infections, and that there was no mechanistic evidence for all other vaccines, as the publications reviewed provided no evidence beyond a temporal association .
* 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).
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