On October 12, the Philadelphia Neurological Society held one of its regular meetings at The College of Physicians of Philadelphia and invited Paul A. Offit, MD, to speak to the membership. Offit, chief of infectious diseases at The Children’s Hospital of Philadelphia (CHOP), vaccine developer, and advisor to The History of Vaccines, greeted the membership with his first slide and title of his talk: “Why are neurologists scared of vaccines?” Though Offit’s title was tongue-in-cheek, it spoke to a tension he has perceived between neurology and vaccinology.
Offit opened his talk with a medical case: he recounted the situation of a boy who was the youngest child in a family with a history of a neurological condition. In 2009, during the H1N1 pandemic, the family’s neurologist advised the parents that the boy should not receive the 2009 H1N1 vaccine but recommended that he receive the trivalent seasonal vaccine. The boy took the seasonal influenza vaccine, but, unprotected from H1N1, became ill seriously from it. He was hospitalized and needed a cascade of interventions, culminating in being placed on a heart lung machine. The boy lived, but he suffered residual neurological damage.
Was the neurologist’s warning against the H1N1 vaccine warranted? Need the boy have suffered as he did? Offit thinks not.
The 1976 experience with another swine origin flu vaccine, and its association with Guillain-Barré Syndrome (GBS), was most probably the root of the neurologist’s concern for the boy. Reported cases of GBS syndrome after receipt of the 1976 swine flu vaccine were the first evidence of a possible link between the two. But influenza vaccine had not been known to cause GBS before 1976, and GBS has not been linked to influenza vaccine since then. Was the evidence from 1976, which suggested that the vaccine triggered GBS in 1 in 100,000 vaccinated people, convincing?
Offit referred to the interpretation offered by Gina Kolata in her 1999 book FLU: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It. Kolata proposes that a series of misunderstandings and events led to overreporting of GBS after administration of the 1976 flu vaccine and that a causal relationship may not exist. For example, she cites evidence that the disease was poorly understood and poorly described, leading physicians to diagnose people with GBS after vaccination who did not in fact have the disease. Additionally, initial reports of GBS followed an apparent misunderstanding: a Minnesota doctor heard a lecture that mentioned that any cases of GSB following vaccination would likely be attributed to the vaccination, when in fact the only relationship was temporal. The Minnesota physician may have misinterpreted the lecture; thinking that a causal relationship did exist, he was inclined to look for and report GBS. His reports were then amplified by the efforts of the CDC to look specifically for GBS, in spite of warnings at the time that asking physicians if they had observed GBS after vaccination would incline them to overreport it.
Offit’s takeaway is that it’s difficult to be certain about a relationship between GBS and the 1976 swine flu vaccine, but that reporting of the disorder could have been due in large part to external circumstances.
He then went on to address other concerns neurologists might hear about vaccines, such as the fear that they overwhelm the immune system. Despite the increase in the number of vaccines given to children over the past 40 years, Offit illustrated that, with the removal of the smallpox vaccine from routine immunization and the switch from the whole-cell pertussis vaccine to the acellular vaccine, the total number of immunogenic proteins and sugars in the childhood vaccine schedule has decreased dramatically. (See the table at the CHOP Vaccine Education Center.) Moreover, Offit pointed out that one bacterium has thousands of structural and nonstructural proteins, and that infants are able to mount vigorous immune responses to these immunological challenges in the first week of life. These factors, he said, are powerful indicators that infants and young children are capable of responding appropriately to the very small numbers of antigens in vaccines.
In the question and answer session, a physician pointed out that neurological side effects from nervous-tissue based rabies vaccines are known to occur. Indeed, this problem has been evident since early uses of Pasteur’s rabies vaccine. Offit noted that newer, safer rabies vaccines, based on virus cultivated in human diploid cell lines, are used in much of the world now and avoid the use of nervous system cells altogether, thus reducing potential neurological side effects.
Another audience member asked about the CDC’s continued instruction that people with a history of GBS and who are not at risk for severe illness from influenza should not take the influenza vaccine. Clearly, this represents a mainstream view that influenza vaccination could cause or exacerbate GBS, and Offit thinks that it’s a very conservative approach to risk, based on all of the evidence to date. He described a similar conservative approach to instructions for the live attenuated influenza vaccine (LAIV, the inhaled vaccine). People who live in households with someone who is immune compromised are often advised by health care providers not to take LAIV because of a tiny risk of transmission to contacts via viral shedding. But the attenuated viruses in that vaccine are cold adapted and therefore do not replicate in the lungs, and have not been shown to cause illness in contacts. LAIVs provide more complete protection to the recipient than the trivalent inactivated influenza vaccine (TIV, the injected vaccine) and are better at blocking transmission of virus. Therefore, the LAIV should provide better protection to contacts of the vaccinated person than TIV. (CDC’s guidelines for LAIV are here and advise against receipt of LAIV for those in contact with others “with severely weakened immune systems when they are being cared for in a protective environment [for example, people with hematopoietic stem cell transplants]).”
To close, Offit observed that, in fact, there didn’t seem to be tension in the room between himself and the neurologists, and he welcomed continuing discussion among medical disciplines about the benefits and risks of vaccination.
Kolata G. FLU: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It. New York: Farrar, Straus and Giroux, 1999.
Langmuir AD. Guillain-Barré syndrome: the swine influenza virus vaccine incident in the United States of America, 1976-77: preliminary communication. Journal of the Royal Society of Medicine 27:660-669, September 1979. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1436986/pdf/jrsocmed00281-0040.pdf
Minnesota Department of Health. Live Attenuated Influenza Vaccine (LAIV): A Safe and Effective Choice. http://www.health.state.mn.us/divs/idepc/diseases/flu/hcp/vaccine/laiv.html