who did not receive any zoster vaccine but received tetanus toxoid-containing vaccines in the VAERS database within the same time frame were considered unexposed. Tetanus toxoid-containing vaccines are not known to be associated with SAAEs.16 The cases and controls were then matched based onage and gender, with each case having at least one matched control.
The controls were selected from patients with a set of outcomes that had previously been shown to be neither associated with the exposed nor the unexposed groups.16 These were identified to account for potential confounders or systemic errors in the VAERS database. These control outcomes include cardiovascular disorder (VAERS code: 10007649), cerebrovascular accident (VAERS code: 10008190), medication error (VAERS code: 10027091), urinary tract infection (VAERS code: 10046571), and death (VAERS code: 10011906).
The statistical package for social sciences (IBM SPSS Verson 22) was utilized to perform the Fisher’s exact test and evaluate statistical significance. Odds ratio (OR), 95% OR confidence interval (CI), and P-values were calculated to test the null hypothesis that zoster vaccine was not associated with SAAEs. A two-sided P-value of < 0.05 was considered statistically significant.
RESULTS
A total of 18534 adverse events were reported after zoster vaccination from May 2006 to November 2014 in the VAERS database. Out of these, 102 events were SAAEs. More than half (64.7%) of these events occurred in females. The median age of patients who developed SAAEs was above 65 years old. The median time of onset to each event is about seven days. Table 1 shows a summary of the SAAEs reported for zoster vaccine. Arthritis has the highest number of reported adverse events (n = 42), followed by GBS (n = 25). More than half of the thrombocytopenia cases (n = 5) were deemed to be life threatening, while approximately a third of the GBS cases (n = 8) were considered life threatening.
Table 2 shows the ORs for various SAAEs. There was a significant increase in the odds of alopecia and arthritis in patients who received the zoster vaccine, compared to those who received the tetanus toxoid-containing vaccine. Patients who received zoster vaccine had 2.7 times the odds of having arthritis (95% CI: 1.7 to 4.3, P<0.001) and 2.2 times the odds of developing alopecia (95% CI: 1.2 to 4.3, P= 0.015). For other autoimmune adverse events, including GBS, multiple sclerosis, optic neuritis, SLE, thrombocytopenia, and vasculitis, there were no significantly increased odds among those who received the zoster vaccine, compared to those who received the tetanus toxoid-containing vaccine.
DISCUSSION
Herpes zoster is more common and severe in older adults and patients with immunosuppression.1 The condition can potentially be serious and persistently painful, which substantially reduces daily functioning and quality of life of affected patients.1 It has been demonstrated that the vaccine decreases the likelihood of developing herpes zoster and postherpetic neuralgia by 51% and 67%, respectively.17 Patients with certain autoimmune diseases are frequently mildly immunosuppressed.2 Zoster vaccine would be useful in such patients to prevent herpes zoster reactivation as well as its sequela.
Zoster vaccine contains residual components of MRC-5 cells, including DNA and protein, as well as bovine calf serum,18 which can theoretically induce autoimmunity. As a DNA vaccine, it may contain antigens that cross-react with self antigens, causing
