Introduction

I am a regular reader of Dr. Rob. And a big fan. Very cool site for both patients and medical professionals. He has a clear focus on advocacy and education (both us and patients). Recently he posted an entry about vaccines which I felt to compelled to comment on. I was going to reply to his but it got out of control long way too fast. So a post I will make.

Dr. Rob was talking about the rise in cases of Haemophilus influenzae type B infection. It can cause inflammation of a flap of tissue in the throat called the epiglottis–which normally serves the function of covering up your airway when you swallow, so you don’t choke. Bad things can happen when you have epiglottitis. Like the flap swelling up so large the child cannot breathe. In fact, when examining a child with epiglottitis we are told to have an anesthesiologist on hand ready to intubate, and if possible, defer the examination to a specialist in pediatric ear, nose, and throat disease. Nasty nasty stuff.

Where he lost me was invoking argument by anecdote and the use of the picture of an admittedly cute 7 month old.

I have a tragic tale to tell regarding vaccines myself. I’m not nearly as cute as the kid in Dr. Rob’s post though. After my second hepatitis B shot, a little more than eleven years ago, I developed a painful atrophic condition called Neuralgic Amyotrophy. And so a young swimmer’s career ended, a young musician found it a struggle to hold the bow of his violin, and his right arm withered away. I have worked hard to gain functionality, spending anywhere from 8-15 hours a week in the gym, rehabbing and gaining strength. I have developed an absurd pain tolerance. And have just barely failed to make an athletic comeback on 4 separate occasions (currently on my fifth, in an attempt to become a strongman and powerlifter). Even though I can shoulder press a barbell weighing as much as I do, I still struggle to shave, hold a phone, or write. And it was worse before I got this strong. Despite my passion for fast cars, I’m stuck driving an automatic, because my stupid hand can’t manage a stick shift. But the ravages of nerve damage and muscle imbalances have continued to take their toll. Today I suffer from cervical and thoracic radiculopathy, facet syndrome, and rib dysfunction syndrome. Next week, I’m being evaluated for wrist surgery due to the atrophy of connective tissue in the affected arm.  But to me the best way to sum it up is, at the age of 25 years old, I’ve actually forgotten what it’s like not to hurt.

That said, I am not in the anti-vaccination camp. I doubt that the mercury in vaccines causes autism. And I think that vaccines play a very crucial role in public and personal health. I am however, a trained scientist, and was taught to value epistemology, background knowledge, and study design in research. If I ever get around to blogging regularly again, you will see that those are core values of mine in the appraisal and pursuit of science and medicine. There are glaring issues and gaping holes in the evaluation of vaccines for safety, in post-marketing surveillance, and in attempts at exoneration of vaccines from charges leveled at them.

Dr. Rob stated: ‘As sad as your experience is, it was not due to negligence or ignorance.’ This is where I beg to differ. Negligence and ignorance (willful or otherwise) in vaccine safety studies is rampant. Even worse, people continue to trumpet vaccine as ’safe’ when they don’t have any reliable data from which to draw said conclusion.

Potential Vaccine Side Effects

There are known risks to vaccines, and there are theoretical risks to vaccines. A lot of people faint when they get vaccines. Others develop pain at the injection site. Neither are all that surprising, and, assuming a person is watched for 15-20 minutes after their vaccination, no harm is likely to come from fainting. However, there are two categories of side effects that can be debilitating and/or fatal. One type is the anaphylactic/allergic response, which can manifest as anything from excessive bruising and redness at the injection site to a rash to, in a full-blown anaphylactic response, swelling of tissues leading to respiratory compromise and in the worst cases, death.

The other class of worrisome reactions are autoimmune reactions. Autoimmune diseases are nasty situations in which your body’s own defenses turn against you. Both infections and vaccines can precipitate an autoimmune reaction. Reiter’s Syndrome is a famous (among medical students) example in which a gonorrheal infection leads to arthritis and eye irritation. Peripheral nerve damage is another relatively common complication of viral infection. Up to 50% of those who suffer from my condition developed it after an infection. Even relatively benign infections like uncomplicated upper respiratory infections can lead to these devastating sequelae. In some cases this is due to the fact that certain properties of these viruses are shared by properties of certain populations of our own cells. Antibodies that attacked one could thus potentially attack the other. This is believed to be behind the high rate of neurological symptoms in people with Hepatitis B infections.

Case reports have also consistently implicated vaccines in the precipitation and exacerbation of autoimmune phenomena, from lupus, to rheumatoid arthritis, to kidney disease, to multiple sclerosis. Anywhere from 15-25% of the sufferers of neuralgic amyotrophy are believed to have developed it due to vaccination.  Given that we think these kinds of things are caused by an immune reaction, it makes sense that if an immune reaction to a virus can cause autoimmune problems, than an immune reaction to a vaccine for that virus could as well.

The Problems with Vaccine Safety Studies

There are two components to assessing the safety of vaccines. The first is pre-marketing safety trials, and the second is post-marketing surveillance. Both are found sorely wanting. I am most familiar with these processes with respect to Gardasil and the Hepatitis B vaccination, so my examples will mainly come from there. My discussion will center around autoimmune and neurologic phenomena, which I and many health professionals believe are the most concerning potential side effects (whether in fact present or not).

As indicated earlier, I believe that proper study design involves the judicious application of background knowledge. A full immune response can take anywhere from 3-6 weeks to mount. It would make sense then, that we monitor for at least that long in order to detect any possible autoimmune side effects. Arguably it would be better to monitor patients for at least 6 months. The immune effects of vaccines can last anywhere from 1 year to a lifetime, so arguably side effects could manifest anywhere within this time period. Furthermore, it may take significant time for autoimmune damage to mount to clinically detectable levels. In the case of the Hepatitis B Vaccine, adverse events were monitored for 5(!) days. At 5 days, I pessimistically think that I would have been reported as a ‘minor’ localized ‘pain at the injection site’ despite the fact that my entire arm tingled and throbbed and I wasn’t able to swim, play tennis, or the violin. At one month, it would have been a different story. Likewise, the Gardasil safety trial monitored adverse events for only two weeks. Better, but still not very good.

A second problem comes in the choice of ‘placebo’. Now, the definition of a placebo is an inert substance with no innate biological activity. 4 of the 5 Gardasil safety trials used a compound called Amorphous Aluminum Hydroxyphosphate Sulfate or AAHS as the ‘placebo’. First problem, this compound is used in both the HPV and HBV vaccines (and many others) as an ‘adjuvant’. An adjuvant is a compound used to amplify the immune response to an antigen. Aluminum compounds do this in two ways: First, by making the antigen more available to be recognized by the immune system. Second, by increasing the activity of our immune system in a more general sense. Although Merck did not provide separate data for AAHS versus saline solution among side effects that potentially signaled the development of autoimmune phenomena (Table 5, page 7), they did do so for local reactions in Table 2 and Table 3 on pages 4-5. It is plain to see that the rates of infection are similar in the Gardasil and AAHS groups, and significantly lower in the saline group. In the real world, you either get a vaccination or you don’t. Your pediatrician doesn’t say ‘well since you’ve turned down Gardasil, I’m going to have to go ahead and inject you with this aluminum salt’. Since adverse effects are measured in terms of how much more often they occur in relation to placebo, it is plainly evident that such trials obscure the real incidence of adverse effects. They also obscure the role that the aluminum adjuvant may have in causing the side effects.

Aluminum salts have been implicated in a number of side effects and even vaccine-related syndromes such as gulf war syndrome, Macrophagic Myofascitis, seizures, joint aches, muscle pains, and a host of other ailments that also top the list of the most common and serious adverse events associated with many vaccines. Aluminum buildup has also been implicated in alzheimer’s disease, autism, infantile seizures, demyelination, and motor neuron death. And we know that vaccinating with aluminum leads to transient increases in brain levels (perhaps what is behind the scary increase in seizures in those who receive aluminum versus saline placebos). But I want to avoid belaboring the point. The take home message is that aluminum compounds found in vaccines can increase the intensity of the immune system and potentially precipitate autoimmune and neurologic phenomena in and of themselves. A starting list of citations can be found here which deals with everything from the effects of aluminum adjuvants to the reduced ability of infants to clear aluminum from their system. Another good overview can be found here. I should note before moving on that I don’t necessarily agree with everything the author has wrote but many of his concerns are valid and largely unaddressed.

So from pre-marketing safety trials, we learn that neither are people monitored long enough to determine the rate of serious side effects, nor are we given a true placebo rate with which to determine how much more likely one is to suffer from a potential side effect if given the vaccine (which is composed of two potentially harmful substances; the antigen, and the adjuvant).

Moving on to post-marketing surveillance. It is perhaps here that willful ignorance is most obvious. Post-marketing surveillance is achieved through something called the Vaccine Adverse Events Reporting System. This is a voluntary reporting system in which doctors must put forth extra effort to phone or submit online a report of an adverse event. Estimates of how often adverse events are actually reported range from 1%-10%, by the FDA and CDC’s own admission. Part of this is because VAERS is passive, rather than active. Another, more insidious reason is that some doctors will actively refuse to report an adverse event to VAERS because they don’t believe it was caused by the vaccine. VAERS works (if something with a 1-10% rate of reporting can be said to work at all) by comparing the rate of events in the vaccinated population to the rate of background events. This means, whether or not it was caused by the vaccine, it should be reported. I know for a fact that I am nowhere to be found in the VAERS database, despite seeing three different doctors and a physical therapist within a few months of the incident.

Yet, despite this known, severe, and asymmetric reporting, VAERS figures are frequently, if not always, used uncorrected. That means that if the reported VAERS rate and the background rate of a given adverse event are even similar, it is likely that the rate of adverse events for vaccinated individuals is actually significantly higher than background. This study is an enlightening read, in which VAERS-captured rates were identical to background. While real-world rates of intussusception following rotavirus vaccination were between 5 and 10 times higher than that in individuals who weren’t vaccinated. (Note: This is the old rotavirus vaccine and not the currently used vaccine). This must give pause, given that the VAERS rates for symptoms potentially heralding the onset of autoimmune disease, neurologic phenomena, and morbidity and mortality for many vaccines are at least at background rate or worse. More worrisome is that despite the well-known phenomenon of under-reporting of adverse events to VAERS, the uncorrected figures are frequently used without any discussion of the problems associated with them. Clearly, if post-marketing surveillance is going to be of any benefit, reporting rates need to be closer to 100% than 0%.

Although not necessarily a part of safety monitoring, there exists a third category of study that can be helpful in determining the relationship between vaccines and adverse events. And that’s the retrospective case-control study. In recent years, we have used such studies to examine the link between various vaccines and autism, multiple-sclerosis, seizures, lupus, rheumatoid arthritis, and others. I’m not linking to any studies because quite frankly everything is contradictory. Some find associations, some don’t. But even here, these studies don’t truly help out in developing a picture of the overall safety of a given vaccine. The biggest problem is that they are far too specific in the illnesses they look at. For example, lupus–one of the more common and devastating autoimmune disease–can manifest as a rash, as psychiatric problems, obstetric problems, arthritis, a propensity to develop dangerous blood clots, or kidney disease. Similarly, the Hepatitis B Vaccine–like the infection itself–has been implicated in any number of neurologic derangements from peripheral demyelination and axonopathy to multiple sclerosis-like disease (emphasis on ‘like’). The latter disease and a possible link to HBV has been the subject of several of these case-control series, with some finding associations and others not. But if you look at the actual case reports that prompted this discussion, you find that although in some ways the pathologies appeared similar to MS, in other ways they didn’t. By taking only a subset of the greater issue (neurologic sequelae) and then using perhaps too restrictive criteria for the definition of illness, they in effect do nothing to resolve the larger question.

Conclusion

In his original post, Dr. Rob said:

But there are some who would suggest that I am deluded. I am brainwashed by the vaccine manufacturers, drug reps, or narrow-minded training. Yes, I can be trusted to rescue their child from the brink of death, but can I be counted on when I recommend vaccines?

I don’t happen to think anything of the sort about Dr. Rob. I do however feel that the knee-jerk reaction to counter the anti-vaccine posturing with hysterics of our own is both counter-productive and disingeuous. We really have very little idea about just how safe or unsafe vaccines are. And anti-vaccination groups are more than cognizant of this fact. Much of what I’ve written about here is likewise trumpeted by many anti-vaccination groups. These criticisms are valid and ultimately our failure to answer them will only cause vaccine skepticism to increase. Yes, vaccines are no doubt effective in reducing the incidence of infectious disease. But do they outweigh the potential negatives? I don’t know, and you don’t. None of us do. And as long as this remains true, the case against vaccination can always be made.

Initial safety trials do not monitor adverse events long enough to reveal the incidence of the most debilitating adverse events. Many fail to use proper placebos. Post-marketing surveillance is subject to under-reporting such that actual rates may be an order of magnitude or more higher. And most retrospective case-control studies do little to advance our knowledge of the broader issues of vaccine safety.

To me, these are glaring problems. But how many in our profession look at the uncorrected VAERS data, or the pathetic nature of initial safety trials and take them as gospel? How many even think about the methodologic problems associated with our methods of assessing vaccine safety? The height of our ignorance in this matter far outweighs the depth of our knowledge. So when we find ourselves troubled by the number of parents refusing vaccinations for their children, when we see un-vaccinated children becoming sick, being hospitalized, and dying from vaccine-preventable illness, it is imperative that we correct this error. It is not enough to argue from authority: ‘I am a doctor and I say this is good.’ We have been doing this, and it hasn’t been working. There is no doubt that irrational fears play a part in the rise of anti-vaccination sentiments. But we should not dismiss rational concerns about vaccine safety. We must be able to argue from a convincing position of knowledge, something not currently possible. Furthermore as physicians we (well, not me personally until June when I graduate) owe it to our patients, our profession, and ourselves to know the truth about vaccines.

Perhaps there really is nothing to the assertion that certain vaccines can cause or exacerbate autoimmune phenomena. Perhaps aluminum adjuvants really do pose little to no risk of neurologic sequelae. Then again, perhaps the risks are real and large enough to make us sit up and take notice. Perhaps the side effect profile is poor enough that the risk of vaccination isn’t outweighed by the risk of infection. And if this is true, if the vaccination skeptics turn out to be right in some respects, shouldn’t we as physicians know that too?

I welcome dialog with doctors and other health professionals on this issue. And I hope that we as a profession learn to open-mindedly tackle the as-yet unresolved issue of vaccine safety.