Meningococcal conjugate vaccination is recommended in the United States. This study evaluates the safety of quadrivalent meningococcal conjugate vaccine in a cohort aged 11 to 21 years.
This cohort study with self-controlled case-series analysis was conducted at Kaiser Permanente Southern California. Individuals receiving MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, during September 30, 2011 to June 30, 2013, were included. Twenty-six prespecified events of interest (EOIs), including neurologic, rheumatologic, hematologic, endocrine, renal, pediatric, and pediatric infectious disease EOIs, were identified through electronic health records 1 year after vaccination. Of these, 16 were reviewed by case review committees. Specific risk and comparison windows after vaccination were predefined for each EOI. The relative incidence (RI) and 95% confidence intervals (CIs) were estimated through conditional Poisson regression models, adjusted for seasonality.
This study included 48 899 vaccinated individuals. No cases were observed in the risk window for 14 of 26 EOIs. The RI for Bell’s palsy, a case review committee-reviewed EOI, was statistically significant (adjusted RI: 2.9, 95% CI: 1.1–7.5). Stratified analyses demonstrated an increased risk for Bell’s palsy in subjects receiving concomitant vaccines (RI = 5.0, 95% CI = 1.4–17.8), and no increased risk for those without concomitant vaccine (RI = 1.1, 95% CI = 0.2–5.5).
We observed a temporal association between occurrence of Bell’s palsy and receipt of MenACWY-CRM concomitantly with other vaccines. The association needs further investigation as it could be due to chance, concomitant vaccination, or underlying medical history predisposing to Bell’s palsy.
Ideally, when a new vaccine is introduced to the public, one should consider giving it at the same time as other vaccines to increase coverage levels and minimize administration costs, if there are no immunogenicity and safety concerns. Among 26 pre-specified events that were examined in the study, only 1 event (Bell's palsy) was found to have some temporal association (5-10 weeks after vaccination) with the vaccine (Menveo) given concomitantly with other vaccines (Tdap, flu, or HPV). The association could be due to chance alone or due to some recipients having conditions which predispose to Bell's palsy. All Bell's palsy cases in our study resolved. No major safety concerns were observed. The possibility of a temporal association between concomitant vaccination (including Menveo) and Bell's palsy should be weighed against the risk of severe consequences of meningococcal or other infections if the opportunity to vaccinate is missed. At the 10-12 age group, children do not necessarily see their primary care physician annually, and middle school entry requirements are probably the main driver for getting immunized at age 11-12. Indeed, we found that MCV4 administration was greatest in the summer months during which most school physicals are performed and Tdap, required for entry into 7th grade in California, is most often administered. Spreading out these vaccines can potentially lead to missed opportunities to vaccinate. Furthermore, this doesn't address influenza vaccine, which is also received concomitantly in this age group and should be given annually.
We have for years reassured parents about not splitting vaccines as there has been no significant evidence for it. I know the authors state that we need further investigation, but the RI = 5.0, 95% CI = 1.4–17.8. Given the split recommendations on doing this vaccine at 11, the results of this study, won't we have more confidence in our approach if we split the vaccines rather than ignore this study? We started to give the TdaP at 10 years of age a few years ago. This was done as we saw the FDA approval, the rising cases of pertussis and the immunogenicity of the DtaP fading after just a few years. Why not recommend the TdaP universally at 10, start the Meningococcal vaccine at 11 and the HPV at 12? Harry Miller, MD hmiller@fourseasonspediatrics.com