Presentation to the Committee on Government Reform
Vaccines: Finding a Balance between Public Safety and Personal Choice

Marcel Kinsbourne, M.D.
August 3, 1999

The remarks that follow are based upon my training and experience as a pediatric neurologist and my familiarity with the scientific method, as well as my participation as a medical expert in proceedings that evaluate alleged vaccine injury under the terms of the National Vaccine Injury Compensation Act.

Types of Vaccine Injury
Offsetting their undoubted public health benefits, vaccinations incur the risk of a range of adverse side effects, some of which rarely cause long lasting or even permanent impairment of health. Depending upon the nature of the vaccine, major side effects fall into three categories, as follows:

Toxic: Killed bacteria may release toxins as their cell bodies break up. An example is pertussis vaccine, which contains at least one substance that can be poisonous to brain cells. When the toxin injures the brain, this occurs anywhere from a few hours to a few days after the vaccination.

Infectious: A vaccine that consists of attenuated virus particles may cause the very infection that it was intended to prevent. An example is oral polio vaccine. The infection presents after an incubation period of a number of days during which the virus multiplies. The virus may even remain latent in cells of the body for much longer periods of time, and then cause disease.

Autoimmune: The body responds to the vaccine with an immune reaction that attacks its components. Sometimes the immune reaction also attacks a constituent of the body itself, which bears some chemical resemblance to a constituent of the vaccine. Reports of cases in which nerve cells have been attacked have been published for tetanus, influenza and measles vaccines.

The "self-attack" is the result of a cascade of biochemical changes which takes at least five days to cause clinically observable disease, and may take at least up to six weeks. In view of these hazards, safety precautions are called for. This task is not straightforward, for reasons such as the following:

Factors that Complicate Safety Precautions
Any disease that can be caused by a vaccine can also be caused by other agents. To help distinguish causation from chance association, epidemiological studies are often required. These studies are typically time-consuming and resource-intensive. Many potential adverse effects of vaccines have not been systematically studied with the methods of epidemiology. The inventory of side effects of vaccines remains incomplete.

Common adverse side effects are likely to be detected during pre-marketing clinical trials. Rare side effects would most likely be overlooked, given the modest number of participants that is customary in clinical trials. Not all adverse effects occur within days or a few weeks of vaccination.

Autoimmune disorders may take a month or two to emerge. Virus particles may even remain latent for lengthy periods of months or years, before they begin to trigger diagnosable disease. An example of a combination of vaccines that can cause an autoimmune disorder is MMR (measles-mumps-rubella). Another example may be Hepatitis B vaccine.

Even when an injury occurs soon after a vaccination, this may not immediately be noticeable. This applies generally to injuries of the developing nervous system, regardless of the cause. Such neurological syndromes as cerebral palsy and developmental language disorder may come to light months or years after the brain damage was inflicted. The effects of severe injury may take years to show up, for example as learning and attention problems.

When several vaccines are given at the same time, they may have adverse effects that none of the individual vaccines have when they are given by themselves. Giving many vaccines at the same time is becoming increasingly prevalent, especially to "captive audiences" like infants. A possible example is measles and mumps vaccines as administered simultaneously in MMR. There is reason to suspect that this combination may cause inflammatory bowel disease and developmental regression into an autistic state in some children in the second year of life.

Post-Marketing Monitoring
The implications of points 1 through 5 are that, at the very least, after vaccines come on the market, they should be monitored comprehensively and for long periods of time. In many instances, particularly for vaccines that have been newly introduced, large-scale prospective epidemiological studies are required. The ongoing passive post-marketing surveillance (VAERS) has shortcomings. Pertussis vaccine illustrates this point.

Whether an adverse event that immediately follows DPT vaccination is reported depends on pediatricians' quite variable levels of awareness of, and index of suspicion for, such events. The ability of agency personnel to evaluate the adverse effects that are drawn to their attention can also be unreliable. It is well known that some lots of pertussis vaccine are associated with a disproportionately high number of notifications of adverse events. These are termed "hot lots". However, the manufacturer is protected by law from disclosing the number of doses that derive from a given lot. Therefore, one lacks the denominator of the function which would reveal whether a given lot appears "hot" because it is more toxic, or because it is the source of more doses. Be that as it may, hot lots offer the possibility of danger to children. Nonetheless, I have never heard that a hot lot has been ordered withdrawn on the basis of VAERS surveillance.

Since different lots of DPT vaccine vary greatly in the concentration of bacteria per unit volume, and therefore in the amount of potential toxin they contain, even when they are produced by the same manufacturer, research to determine whether hot lots contain relatively high levels of bacteria and toxins would seem important. A chemical/bacteriological study that
compares hot lots with standard lots seems indicated. We anticipate that the newly licensed acellular pertussis vaccine will cause far fewer serious adverse neurological reactions, but we do not yet know this for certain. In any cases, many children still receive the whole cell pertussis vaccine, with its cargo of potentially harmful endotoxin. Studies of vaccine safety could be supported by initiatives of the National Institutes of Health, with specially earmarked funds. Requests for applications for research funding could be issued, and the applications be subjected to the customary NIH peer review process.

Informed Consent
The remote but real risk of serious disease that attends vaccinations must be scrupulously and comprehensively disclosed to the parents of the children that await vaccination. In a busy pediatric practice this is not an easy matter, and not all parents readily understand what some of the risks actually entail. It would be helpful if the CDC were to develop handouts that are both comprehensive and user-friendly, that list possible adverse side effects for each vaccine. These handouts should include information about what health and behavior changes parents should be alert for after the vaccination. I suggest that parents be given copies of such handouts for each vaccine well ahead of the projected date of vaccination, so that they have sufficient time to digest the information, and to ask any questions they might have. This might perhaps even be done before their newborn is discharged from the hospital.

Personal Choice
Immunization programs most effectively serve the public health if most members of the target population participate. Nonetheless, personal choice is a civil liberty that must be respected. The estimates of risk offered by medical authorities often diverge greatly from those assumed by some members of the community. It may never be possible to reconcile these entirely. However,
I believe that almost all parents would favor having their children vaccinated if more research on risk factors had visibly been performed. This includes not only identifying adverse events that might happen, but also detecting any predisposition that children in particular families might have that increase such risks.

A genuine and vigorous effort to identify risk factors would help dissipate the impression that some citizens have formed that vaccine safety is not a high priority. The Institute of Medicine (1997) publication, "Vaccine Safety Forum", presents some promising suggestions for risk factor research, particularly for those effects that arise from autoimmune reactions.

Compensation for Vaccine Injury
Congress has mandated a compensation program to meet the needs of children who were injured by a set of required vaccines. Congress made it clear that this program was to be both generous and expeditious, but in my experience as a medical expert in many such proceedings, I have found that this has not usually been the case. Although the Special Masters who adjudicate the Petitions for Compensation are generally both highly competent and compassionate, the proceedings in numerous cases extend over many years. This foils the intent of Congress that the proceedings be non-adversarial and leaves even those families whose claims are ultimately judged to have merit, unassisted and often in severe financial straits. The financial burden of raising a handicapped child can be severe.

It also burdens the law firms that assist Petitioners with expenses that are not met for up to a decade. This has a chilling effect on the participation of attorneys in the Vaccine Injury Compensation Program, and thereby limits the choice of citizens who wish to file petitions. Also, a series of Rule changes as of 1995 has so severely constricted the definition of Table Injury (an injury presumed by the statute to have been caused by the vaccine) in the case of pertussis vaccine (the vaccine that is complained of in the great majority of petitions), that those who nowadays file for compensation must anticipate a lengthy, complex and arduous proceedings with uncertain outcome.

Statute of Limitations
Compensation for injuries due to Hepatitis B vaccine has recently been authorized, retrospective to 1990. The Statute of Limitations for claims in regard to injuries that occurred more than three years ago takes effect Friday, August 6, 1999. Efforts to publicize this fact appear to have been less than enthusiastic. Unnotified citizens who feel that they or their children were injured by this vaccine between 1990 and 1996 will soon be without remedy. An outcome so clearly counter to the spirit of the National Vaccine Injury Compensation Act might be of interest to the Committee on Government Reform.