Acute Demyelinating Events Following Vaccines: A Case-Centered Analysis

This a summary of an article that was published in 2016 by Roger Baxter et al. in the journal Clinical Infectious Diseases.

A study was conducted to determine whether vaccines may have a causal effect on Transverse Myelitis (TM) and Acute Disseminated Encephalomyelitis (ADEM). Previous studies consist of mostly anecdotal case reports which do not look at population-level data and do not allow us to see if vaccinations were the cause of the TM or ADEM. However, concern remains among the TM and ADEM community that vaccines could be responsible for triggering autoimmune demyelinating events like TM or ADEM.

The researchers in this study used the Vaccine Safety Datalink (VSD) to analyze 64 million vaccine doses over the period of January 1, 2007 to December 31, 2012. The VSD is a collection of data from participating healthcare systems across the United States in collaboration with the Centers for Disease Control and Prevention’s Immunization Safety Office. This automated database includes immunization registries, and collects information on more than 9 million patients per year. The study population for this research consisted of all children and adults of any age who received one or more vaccines during the study period, and were enrolled in health plans at six VSD sites.

First-ever TM and ADEM diagnoses were identified using each VSD site’s internal electronic medical record, and the cases required at least one diagnosis by a neurologist within 3 months of initial diagnosis. The researchers did not include individuals with a history of Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorders. The cases were first reviewed by trained medical records analysts and then reviewed by a neurologist with expertise in demyelinating illnesses to ensure the cases met research criteria. The study utilized the database to match a comparison group to each case based on type of vaccination, age, sex, VSD site, and whether their vaccination occurred during the exposure intervals, which were chosen by the researchers based on prior studies and expert opinion. The two exposure periods analyzed were: (1) 5-28 days from vaccination as the most likely interval to result in a demyelinating event; and (2) 2-48 days from vaccination to the demyelinating event to ensure an increased risk was not missed. The comparison interval that the researchers chose was 43 days through nine months prior to the demyelinating event to avoid duplicate influenza vaccines over two seasons.

The researchers looked at whether or not each case received a vaccine during the exposure interval or the comparison interval before the demyelinating event occurred. They then compared this to the proportion of the entire study population that received a vaccination during the exposure interval before the demyelinating event date. Eighty-one cases of TM and fifty-six cases of ADEM were included. The researchers found that for TM, there was not a statistically significant increased risk of a demyelinating event in either the 5-28 day exposure interval or the 2-48 day exposure interval after receiving any vaccination. The researchers also found that for ADEM, only the Tdap vaccine had a statistically significant association with an increased risk of a demyelinating event. This was only found in the 5-28 day exposure interval. The Tdap vaccine is used for adolescent and adult tetanus, reduced diphtheria, and acellular pertussis. However, the authors noted that there are some concerns with the validity of this outcome. For example, there were only two cases of ADEM that occurred during this time period, which is a very small number, and if there had only been one case, this finding would not have been statistically significant. Also, the authors wrote that they did many statistical tests and did not adjust for this, so they stated that the results could be due to chance. Furthermore, the authors noted that even if we accept an increased risk for ADEM after the Tdap vaccine, the extra risk is very small and not likely to be more than 1.16 cases of ADEM per million doses of the Tdap vaccine. Dr. Benjamin Greenberg from the University of Texas Southwestern Medical Center also noted the study does not reveal the six clinical centers used to collect cases. If these centers were referral centers they may have an overrepresentation of TM and ADEM cases – thus overestimating the risk.

Overall, the authors stated that the results of this study conclude that vaccinations mostly do not have a statistically significant association with demyelinating events that occur in TM and ADEM.  They also noted that one limitation of the study was that they chose the exposure interval, so if the interval was chosen incorrectly, an increased risk might have been missed. Also, they stated they did not review combinations of vaccines but rather analyzed each vaccine’s risk separately. Finally, the researchers stated that they purposefully did not adjust for multiple observations so that they could achieve higher sensitivity in their results; nonetheless, they noted that they only identified one statistically significant result (the Tdap vaccine). Despite its limitations, the authors noted the study’s strength was its review of all TM and ADEM cases by medical records analysts and a neurologist, which likely limited misclassification of cases with these disorders, which reduces bias and makes results more likely to be accurate. According to the authors “In conclusion, TM and ADEM are rarely, if ever, associated with vaccines.”

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