Frank DeStefano

Vaccines and Guillain-Barré Syndrome

Guillain-Barré syndrome (GBS) is the leading cause of acute flaccid paralysis in developed countries and is characterized by various degrees of weakness, sensory abnormalities and autonomic dysfunction. Although the underlying aetiology and pathophysiology of GBS are not completely understood, it is broadly believed that immune stimulation plays a role in its pathogenesis. Thus, since vaccines have an effect on the immune system it is biologically plausible that immunizations may be associated with subsequent GBS.The objective of this article is to review the current body of evidence that either supports or does not support a causal, rather than just temporal, association between various vaccines and GBS, and to provide an evidence-based review of this issue. The scope of the article includes published reports that, regardless of method of case ascertainment, appeared in peer-reviewed literature between 1950 and 2008.Our review indicates that, with rare exceptions, associations between vaccines and GBS have been only temporal. There is little evidence to support a causal association with most vaccines. The evidence for a causal association is strongest for the swine influenza vaccine that was used in 1976–77. Studies of influenza vaccines used in subsequent years, however, have found small or no increased risk of GBS.Older formulations of rabies vaccine cultured in mammalian brain tissues have been found to have an increased risk of GBS, but newer formulations of rabies vaccine, derived from chick embryo cells, do not appear to be associated with GBS at a greater than expected rate.In an earlier review, the Institute of Medicine concluded that the evidence favoured a causal association between oral polio vaccine and tetanus toxoid-containing vaccines and GBS. However, recent evidence from large epidemiological studies and mass immunization campaigns in different countries found no correlation between oral polio vaccine or tetanus toxoid-containing vaccines and GBS.Spontaneous reports to the US Vaccine Adverse Events Reporting System shortly after the introduction of quadrivalent conjugated meningococcal vaccine (MCV4) raised concerns of a possible association with GBS. Comparisons with expected rates of GBS, however, were inconclusive for an increased risk, and lack of controlled epidemiological studies makes it difficult to draw conclusions about a causal association.For other vaccines, available data are based on isolated case reports or very small clusters temporally related to immunizations, and no conclusion about causality can be drawn.There are certain circumstances in which immunizing individuals, particularly those with a prior history of GBS, may require caution. However, the benefit of vaccines in preventing disease and decreasing morbidity and mortality, particularly for influenza, needs to be weighed against the potential risk of GBS.

Vaccines and Autism: Evidence Does Not Support a Causal Association

A suggested association between certain childhood vaccines and autism has been one of the most contentious vaccine safety controversies in recent years. Despite compelling scientific evidence against a causal association, many parents and parent advocacy groups continue to suspect that vaccines, particularly measles–mumps–rubella (MMR) vaccine and thimerosal‐containing vaccines (TCVs), can cause autism.

Safety profile of pneumococcal conjugate vaccines: systematic review of pre- and post-licensure data

A 7-valent pneumococcal polysaccharide-protein conjugate vaccine (PCV7) was licensed in the United States of America in 2000, but no comprehensive postmarketing review of safety has been carried out. We conducted a systematic review of the safety of PCV7 and other pneumococcal conjugate vaccines. A total of 42 studies were included in the review. Reactogenicity data from some randomized trials suggest that PCV7 may result in more local reactions and fever than certain comparison vaccines. However, the reactions were mild and self-limited, and PCV7 did not carry an increased risk of severe injection-site reactions or high fever. Some, although not all, of the randomized trials in children found that mild local and systemic reactions associated with PCV7 may increase with the number of doses, at least over the three-dose primary series. In addition, PCV7 and other pneumococcal conjugate vaccines were found to have tolerable reactogenicity in Native American and African populations and in medically high-risk groups for which pneumococcal vaccination is recommended. Two of the largest studies of PCVs, one involving PCV7 and the other, PCV9, found a statistically significant increased risk of hospitalization for reactive airway disease, including asthma. Another large trial of PCV9, however, did not find an increased risk of asthma. In conclusion, this review of the evidence did not identify any major safety problems with PCV7 or any other pneumococcal conjugate vaccine, with the possible exception of reactive airway disease, which may bear further scrutiny as additional data become available.

Thimerosal-containing vaccines: evidence versus public apprehension.

Despite convincing evidence to the contrary, many parents continue to be concerned that vaccines that contain thimerosal may cause autism and other developmental disabilities. Thimerosal is an ethylmercury-based preservative that has been used in vaccines and other biological products since the 1930s. Concerns about the safety of thimerosal-containing vaccines arose as the result of an FDA review of biological products that contain mercury. As safety limits for ethylmercury were not available, FDA based its review of thimerosal on guidelines for methlymercury and determined that by age 6 months some infants could have received cumulative exposure to ethylmercury from vaccines exceeding the guidance level for methylmercury exposure established by the Environmental Protection Agency [1] . Even though the risks were theoretical and there was no direct evidence of harm, the US Public Health Service (USPHS) and the American Academy of Pediatrics (AAP) issued a statement in July 1999 recommending that thimerosal be removed from infant vaccines as soon as practical [2] . Although the USPHS and AAP statement underscored the lack of evidence that thimerosalcontaining vaccines were not safe, the recommendation to eliminate the use of thimerosal as a preservative in most routine infant vaccines raised understandable concerns among some parents and other members of the public. It was not long afterward that theories were proposed suggesting that thimerosal-containing vaccines caused autism and were responsible for the ‘epidemic’ of autism that is said to have begun in the 1990s.