Do Vaccines Cause Meningitis or Encephalitis?

Conclusion | Epidemiological Evidence | Proposed Biological Mechanism | Archives | References


Conclusion

Varicella vaccine in routine use in the United States* can very rarely cause viral meningitis. Measles-containing vaccines can very rarely cause measles inclusion body encephalitis (MIBE). Mumps vaccines used in other countries have caused meningitis and encephalitis. However, the mumps vaccine in routine use in the United States* is made from a different strain of vaccine virus and has not been shown to cause meningitis or encephalitis. The benefit of vaccination in preventing neurologic diseases such as meningitis and encephalitis greatly outweighs the minimal risk of vaccine complications.

Natural infections with measles, mumps, rubella and varicella viruses can cause encephalitis and meningitis. Thus, measles, mumps, rubella and varicella vaccines protect against encephalitis and meningitis caused by these agents. These vaccines are made from attenuated versions of the wild-type viruses, and generally do not cause central nervous system infections in normal hosts. However, these attenuated vaccine viruses can cause disease in persons with certain immune deficiencies, and are therefore contraindicated in these populations. For instance, varicella vaccine virus can persist and cause reactivation zoster, which has been very rarely associated with viral meningitis, although affected patients without immune deficiencies recover fully without any lasting effects. In addition, very rare cases of measles inclusion body encephalitis (MIBE) have occurred following administration of measles-containing vaccines.

Natural infections with Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib) can cause severe bacterial meningitis. Pneumococcal, Hib, and meningococcal vaccines protect against meningitis caused by these agents. The vaccines that protect against these infections do not cause meningitis; the vaccines are made from only the outer capsule and/or bacterial proteins so they cannot cause infections like the naturally occurring bacteria [1-7].

Epidemiological Evidence

The 2012 report by the Institute of Medicine (IOM) [8], now called the National Academy of Medicine (NAM), described three studies with sufficient validity and precision that reported null associations between MMR vaccine and meningitis [9-11]. The report also described several studies assessing meningitis, encephalitis or encephalopathy and MMR [9, 12, 13], DTaP [14, 15] or meningococcal [13] vaccines, but these studies did not provide convincing evidence due to a lack of validity and precision. The IOM found no relevant studies of quality in the literature assessing encephalitis or encephalopathy and varicella, influenza or hepatitis B vaccines, since the only applicable studies available either had serious methodological limitations or used passive surveillance systems and therefore lacked an unvaccinated comparison group [8].

Since the publication of the 2012 IOM report, one large post-licensure study found no association between herpes zoster vaccination and meningitis, encephalitis or encephalopathy [16]. A case-centered analysis of 110 childhood encephalitis cases from California found no association between vaccination and encephalitis [17]. Large Vaccine Safety Datalink studies found no association between meningitis/encephalitis and either 2012-2013 influenza vaccines [18], the DTaP-IPV combination vaccine (Kinrix®) [19], or MMR, MMRV (ProQuad®) and varicella vaccine (Varivax®) [20].

The IOM found no relevant epidemiologic studies of quality in the literature assessing an association between vaccination and MIBE [8].

Proposed Biological Mechanism

An estimated 1-10% of persons naturally infected with wild-type mumps virus develop meningitis. Natural infection with wild-type measles, mumps or rubella viruses occasionally leads to development of encephalitis, at estimated rates of one case per 1000-2000 patients infected with measles, 400-6000 patients infected with mumps, or 5000 patients infected with rubella, respectively [8]. Measles can also cause a persistent infection of the brain resulting in subacute sclerosing panencephalitis (SSPE), which occurs at a rate of approximately 22 cases of SSPE per 100,000 reported cases of measles [21]. Natural infection with wild-type influenza has also been associated with encephalitis, albeit very rarely [8].

In early-onset encephalitis after infection with mumps virus, neuronal damage is suspected to result from direct viral invasion. Natural viral infection can cause meningitis or encephalitis via either direct viral invasion or a viral-induced autoimmune reaction. Mechanisms proposed for the development of meningitis or encephalitis after viral vaccination include direct viral infection, autoimmune mechanisms resulting in post-infectious encephalitis (such as ADEM), varicella vaccine-strain viral reactivation, and persistent viral infection [8]. For more information, see the Do Vaccines Cause Acute Disseminated Encephalomyelitis (ADEM) and the Do Vaccines Cause Vaccine-Strain Viral Reactivation summaries.

Encephalitis and/or encephalopathy have even been reported as complications of bacterial infection such as diphtheria and pertussis. There is also some evidence that pertussis-specific antigens can traverse the blood-brain barrier and thereby directly affect the central nervous system [8].

The IOM also concluded that there was no mechanistic evidence of quality showing an association between encephalitis or encephalopathy and varicella, hepatitis b and meningococcal vaccines, nor for an association between meningitis and measles or rubella vaccines, as the publications reviewed provided no evidence beyond a temporal association [8]. The 2012 IOM report described several cases of encephalitis or encephalopathy after MMR [22-24], influenza [25] and DTaP [26] vaccines, and four cases of meningitis after mumps vaccine [22, 27, 28], but when considering knowledge about the natural infection the IOM concluded this mechanistic evidence was weak [8]. However, there is one well documented case of measles vaccine virus isolated from the cerebrospinal fluid of a patient with encephalitis in Canada [29], as well as documented cases of meningitis following reactivation of vaccine-type varicella zoster virus [30-32].

MMR and varicella vaccines are live attenuated viral vaccines which replicate in the body. Severe immunosuppression is a contraindication for MMR, MMRV,and varicella vaccine [7]. For more information, see the Measles, Mumps and Rubella and Varicella summaries.

In immunodeficient persons, persistent infection with live vaccine viruses is possible. Measles vaccine virus can lead to central nervous system infection and MIBE [8]. The 2012 IOM report described several cases of MIBE after measles vaccination in immunodeficient persons [29, 33, 34], and concluded that these cases together presented strong mechanistic evidence supporting an association [8].

References

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