Saturday, October 31, 2009

Vaccines are the safest kind of medicine, aren't they?

You may wonder why I keep harping on inadequate testing and safety concerns. In addition to my experience treating patients who became ill following vaccinations, I have reviewed medical literature on vaccine safety. There are many stories of vaccines that appeared safe, but were later found to be dangerous. The Edmonston-Zaghreb "high titre" measles vaccine, designed to give immunity to infants at the age they are most susceptible to a bad outcome from measles infection, is one such story.

Children died at higher rates overall, in a number of countries, after receiving this measles vaccine compared to an earlier measles vaccine. Yet twenty years ago, this was the measles vaccine recommended by the WHO for children most at risk from measles. WHO later pulled its recommendation, but infants received this vaccine for several years before the problem was discovered.

No, this is not the killed ("KMV") measles vaccine of the 1960s I discussed earlier. That one caused a worse disease than measles once you were exposed to measles. This one increased the death rate from diseases other than measles. No one ever explained why. So the same 'mistake' could happen with other vaccines, since we don't know what caused the problem for either of these bad measles vaccines. With this in mind, I need sufficient assurance of a vaccine's safety and effectiveness before prescribing or recommending it.

Vaccine science is still in its infancy. Vaccines are all derived empirically: scientists don't really know which ingredients will give the desired result, so they just test various prototypes till one looks 'good.' Conversely, they cannot tell which vaccines will turn out to be 'bad' until the vaccines have undergone a lot of testing.

It is relatively easy to see how effective a vaccine will be in terms of antibody levels (though the antibodies we measure do not always predict true immunity to infection). You just measure the level of antibodies.

It is much harder to test safety. You don't know ahead of time what side effects will be caused by the vaccine, so you have to consider every adverse event that occurs after a vaccination as a possible side effect. However, statistics tells us that some adverse events will appear to occur at higher than expected rates following vaccination, but do so randomly, unrelated to causality. So regulators tend to ignore many adverse events that occur at high rates, assuming they are statistical "blips." You would need to observe large numbers of people for long periods of time to discover which were the real adverse reactions, and this is not done in prelicensure vaccine studies, and almost never done thoroughly in postmarketing surveillance.

Furthermore, the CDC's role in vaccine safety has been criticized by many (including the National Academy of Science) due to its conflict of interest in being responsible for promoting vaccine uptake as well as assessing vaccine safety.

A few adverse reactions are taken very seriously: those that are well known to be caused by vaccines. These include, for example, Guillain Barre Syndrome and brachial neuritis (nerve impairment near the site of the injection). Because they are rare and severe conditions, when they occur after a vaccination people notice.

Might asthma be caused or worsened by vaccines? It is a common illness and may result from autoimmunity. Even though hospitalizations for asthma occurred statistically more often in soldiers after anthrax (according to the Institute of Medicine here and here, but denied by military researchers) and smallpox vaccinations (soldiers "were 2.24 times more likely to be hospitalized for asthma and 2.77 times more likely to be hospitalized for autoimmune diseases" than controls in the year after anthrax and smallpox vaccinations were given, with statistical significance), no targeted study has been undertaken by any civilian federal agency to further investigate these results. And medical professionals, in general, do not believe vaccines can cause such frequent and severe adverse effects.

Illnesses that occur at many times the baseline rate after vaccination are likely to be identified as a vaccine adverse event. Rotashield vaccine caused over 20 times more intussusception than expected...but still remained on the market about 11 months. It probably caused other gastrointestinal side effects, but CDC's study of the data was not conclusive. UPDATE: And its replacement, RotaTeq, causes the same problem but is still on the market.

If, for example, the incidence of diabetes increased by a factor of 2 or 3 (instead of 20) after a vaccination, it would probably be missed given our current methods of surveillance.

The bottom line is that for most illnesses, the type of research that would resolve whether a vaccination contributed to or caused a specific illness, and in what percent of cases, has never been done.

Here is the WHO report on the Edmonston-Zaghreb high titre measles vaccine:

Wkly Epidemiol Rec. 1992 Nov 27;67(48):357-61.

Expanded Program on Immunization (EPI). Safety of high titre measles vaccine.

Unexpected results suggesting decreased survival when compared with standard titre vaccine administered at 9 months of age have been found in some field studies evaluating the performance of high titre measles vaccine. Analytical difficulties have arisen because the studies were not specifically designed to measure survival. Nonetheless, careful analysis of the results from all of the high titre vaccine trials showed decreased survival of high titre vaccine recipients, in areas with high background mortality rates, compared with recipients of standard measles vaccines at 9 months. No systematic biases could be found in the studies to explain these differences. Statistical analysis of these data suggested that the findings were unlikely to be attributable to chance alone. The panel recommended that high titre measles vaccine derived from the original Edmonston measles vaccine isolate should no longer be recommended for use in immunization programmes. Further post-licensure field studies of new measles vaccines should take into account the results of these studies. Additional detailed epidemiological studies in populations that have received high titre vaccines and their controls were encouraged.

PIP: A WHO group recommended in October 1989 that health workers in countries where measles is a significant cause of death for infants under 9 months old use the high titer Edmonston-Zagreb (EZ) measles vaccine for 6-month old infants, or as soon as possible thereafter, instead of the standard titer vaccine at 9 months. In 1990, reports from Senegal and Guinea Bissau showed that infants receiving the high titer measles vaccine before 9 months old were dying at a faster rate than those who received the standard titer vaccine at 9 months of age. These reports precipitated a WHO consultative meeting in February 1991 where participants reviewed the data in question. They considered the data to be inconclusive and recommended that countries continue to use the 1989 guidelines. Other issues later emerged causing WHO to reconvene the working group to reexamine all the safety immunogenicity, and efficacy data of the high titer measles vaccines in infants under 9 months old. Participants at the October 1991 meeting found that a link between the high titer measles vaccine and decreased survival was consistent in the 4 studies with high background infant mortality (relative risk = 1.25; p = .05), but such an association did not exist in the countries with low background infant mortality, suggesting that the vaccine had a multiplicative effect. In 3 of the 4 studies, girls were more likely to experience greater reduced survival than boys (p .02). In all 4 studies, the dose of the vaccine was a leading factor linked to reduced survival. The EZ vaccine was more immunogenic than the Schwartz vaccine at 4-6 months, particularly when maternal antibodies were present. The participants examined a mathematical model based on the submitted data and it indicated that the high titer vaccine would provide only a marginal benefit. They concluded that immunization programs should no longer use the EZ vaccine and that no more field trials of this vaccine should occur.


spooked said...

Good info. Of course, some people regard vaccines as a net negative-- they cause more damage than they prevent. I have resisted this line of thinking, in part due to my professional training, but I have not studied the vaccine skeptic claims extensively. One article I read claimed that smallpox was not really a problem in many areas until vaccination was started. This of course goes contrary to our standard history of vaccines and I have no easy way of evaluating these issues. It would be good to hear your input on this.

For instance:

Meryl Nass, M.D. said...

Smallpox (Variola major) can kill up to 1/3 of affected victims. There is no question that despite some problems with smallpox vaccine (like contamination since it was made from pus from infected calves' bellies until recently) the vaccine played a hugely important role in protecting against us against the disease, and wiping it out.

spooked said...

Thanks. I realize what you say is the conventional view. But what I didn't realize until recently is that there is a whole alternative view that vaccines are actually harmful, and spread disease, whereas the diseases themselves can be prevented by proper hygiene and good nutrition. It's hard for me to embrace this viewpoint but nonetheless they make some interesting points.

Meryl Nass, M.D. said...

Vaccines as a group are not good or bad. Every vaccine provides certain benefits and is associated with certain risks. Each vaccine needs to be evaluated individually.

What I am striving to do in this blog is to provide clear and valid information on the risks and benefits of individual vaccines, critique the vaccine science when I think it fails to reflect reality, and provide direction as to how the scientific evaluation of vaccines could be significantly improved.

Whether my views are considered conventional or alternative doesn't matter to me. The devil is always in the details. Naturally, a healthy lifestyle helps prevent disease, in general. But when a dangerous new microorganism enters the environment to which you are immunologically naive, you will want a safe and effective vaccine.

Until we know what makes some vaccines unsafe, their rapid deployment will remain associated with important safety questions.