More Data on Vaccine Safety Amid New Outbreaks

The more recent issue of the Journal Pediatrics contains two article providing further evidence for the safety of vaccines and is published amid news reports of recent outbreaks of vaccine-preventable diseases in those who chose not to vaccinate over unwarranted fears. This highlights the need to continue our PR battle against the antivaccinationist movement that seeks to spread pseudoscientific fears about vaccine safety.

The Outbreaks

Haemophilus influenza type B (Hib) is a bacteria that can cause meningitis, pneumonia, and epiglotitis in young children – all serious illnesses. A Hib vaccine was introduced in 1992 followed by a significant decrease in the number of Hib infections. Last year in Minnesota, however, there were five cases of Hib meningitis, including a 7-month old infant who died. This is a significant spike above the rate we have seen since the Hib vaccine, and occuring in a cluster. Three of the five children who were affected did not have the Hib vaccine by their parent’s choice.

There are concerns that Minnesota may be the canary in a coalmine, since they have particularly good reporting of such illnesses and may simply have been the first state to catch the outbreak. This latest cluster provides further evidence that diseases that our now rare due to the routine vaccine schedule are poised to return in populations with low vaccination rates. It also highlights that not only the unvaccinated are put at risk. They allow the outbreak to occur, which then can claim those who were vaccinated but did not have an adequate antibody response and therefore have incomplete protection.

This is why so-called herd immunity is critical – high vaccination rates (above 90%) keep infectious diseases from spreading, protecting the unvaccinated and the vulnerable. Therefore individual decisions by parents not to vaccinate has clear cut public health implications.

Last year also saw unprecendented outbreaks of Measles. In 1950 there were 3-4 million cases of measles, including 450 deaths. By 1998 there were less than 1 case per million – about 50 cases per year, all imported from outside the country. Measles was no longer endemic. However, in the first half of 2008 alone there were 131 measles cases, including several outbreaks in populations with low vaccination rates. These are the first endemic outbreaks since measles was declared no longer endemic in 1998. The cases occured largely in children who were not vaccinated.

The data shows an unambiguous cause and effect relationship – these vaccines largely eradicate the diseases they are designed to prevent. And when compliance falls, outbreaks recur mostly in those who are not vaccinated.

This clear relationship contrasts sharply with claims that vaccines are linked to neurological disorders like autism- where the data does not support a link.

Thimerosal and Autism

A new study published Monday in the journal Pediatrics provides more evidence against any link between thimerosal (a mercury-based preservative in some vaccines) and autism or other neurological disorders. This study adds to the large and growing body of scientific evidence for the safety of vaccines, and contradicting the claims of the anti-vaccine movement that vaccines cause autism.

The study is a bit fortuitous in that it was not originally designed to probe this question. Rather, this was a safety and efficacy study of the acellular pertussis vaccine conducted in Italy between 1992 and 1993. But it created a cohort of children who were carefully screened and monitored, and randomized to different exposures to thimerosal. This allowed the researchers to go back 10 years later to survey and examine the children for neurological disorders.

Here are the methods:

Children who were enrolled in an efficacy trial of pertussis vaccines in 1992–1993 were contacted in 2003. Two groups of children were identified, according to thimerosal content in vaccines assigned randomly in the first year of life (cumulative ethylmercury intake of 62.5 or 137.5 µg), and were compared with respect to neuropsychological outcomes. Eleven standardized neuropsychological tests, for a total of 24 outcomes, were administered to children during school hours. Mean scores of neuropsychological tests in the domains of memory and learning, attention, executive functions, visuospatial functions, language, and motor skills were compared according to thimerosal exposure and gender. Standard regression coefficients obtained through multivariate linear regression analyses were used as a measure of effect.

The results – there was only one case of autism in the entire study, and that was in the group that received the lower dose of thimerosal. Of the 24 neuropsychological tests, only two were significantly worse in the higher dose thimerosal group:

Girls with higher thimerosal intake had lower mean scores in the finger-tapping test with the dominant hand and in the Boston Naming Test.

The differences were clinically small, even though they were statistically significant. However, by chance alone (with the statistics used) 4 outcomes on average should have varied significantly, therefore the fact that 2 outcomes were significant is almost certainly due to chance alone. Further, these same measures were not different for boys or the groups as a whole, only when girls are considered seperately, which further suggests it is statistical chance.

And finally, a previous study by the CDC that also looked at a large number of neurological measures also found a few statistical outliers – but they were different outcomes. For example, the previous CDC study showed that motor tics were increased in the thimerosal exposure group, while this study shows no difference in motor tics but does show a decrease in finger tapping. This is all consistent with statistical noise – not a real effect.

The study authors conclude:

No study conducted to date has been able to provide conclusive evidence of an effect of thimerosal on neuropsychological development. Final judgments regarding this association must rely on the entire body of results from studies conducted in different settings and with different levels of validity and on the coherence of results. The lack of consistency among the results of our study and other available studies suggests that an association between thimerosal exposure through vaccination in infancy and neuropsychological deficits is unlikely or clinically negligible. Additional data from populations with wider ranges of exposure to thimerosal and additional neuropsychological assessments at older ages may help to clarify the issue of potential associations between thimerosal and neurodevelopmental outcomes.

This is appropriately conservative prose for a technical paper, but even so the conclusion is solid – any association between thimerosal and neurological disorders is “unlikely or clinically negligible.”

Of course, no one study by itself is definitive, especially in establishing the absence of a correlation. But this new study adds to an already large body of evidence, and therefore raises our confidence further that thimerosal in vaccines did not cause autism or other neurological disorders.

The authors are also candid about the strengths and weaknesses of the study. Anti-vaccinationists have been calling for years for a randomized study with and without vaccines – because that is the one type of data that was not available. It is unethical to randomize a patient not to receive a standard therapy.

This study, however, is close because subjects were randomized to two very different doses of thimerosal.

Another likely source of criticism is that the total cumulative dose of ethylmercury in the higher exposure group was 137.5 µg and that this might be below the threshold of toxicity, and therefore says nothing about the risks of higher exposures. This is true, but not likely to be relevant to the thimerosal question. In the US thimerosal exposure was about 75 µg in 1989 and peaked in 1997 at 187.5 µg cumulative exposure through the routine childhood schedule.

It does not seem plausible that the increase in µg of ethylmercury from 75 to 187.5 resulted in a dramatic increase in autism, but the difference between 62.5 and 137.5 in this study was sub-threshold. Also, I have to point out that since 2000 the use of thimersal in the US has decreased and now there are less than 3 µg in the childhood schedule and the rate of increase in autism diagnoses has not decreased even six years later.

Contrary to popular opinion, the typical response to evidence that contradicts one’s belief is not to ignore it but rather to rationalize it away. The antivaccine crowd has had the expected reaction to this study – dismissing it by pointing out its weaknesses without putting them into contex. Writing at Age of Autism, a dediate antivaccinationist group, J.B. Handley dismisses the study by listing the various characteristics of the study followed by his single word commentary, “vomit,” as if that is sufficient.

He focuses on the fact that the study compared those who received 62.5 vs 137.5 µg of ethylmercury from thimerosal, but did not compare to a no-thimerosal group. This was acknowledge in the study, of course, but more importantly he is entirely missing the point of this study. Toxicity is all about dose and should follow a dose-response curve – as the dose increases so should the toxicity. This study looked at the effects of more than doubling the dose of thimerosal, and found no difference. Further, the antivaccinationists have been arguing that roughly this same increase in dose is what lead to the inrease in autism in the 1990’s. They can’t have it both ways – they cannot claim that increasing the dose increased autism, but the same increase would not show up in this study, only a comparison to a no-thimerosal group would. This is profoundly sloppy thinking on Handley’s part, consistent with his previous arguments and those of the antivaccinationists in general. When one is ideologically dedicated to a particular conclusion, sloppy thinking is inevitable, even necessary.

Anti-vaccine journalist David Kirby also piled on this study, focussing on the same point as Handley, that all the children in this study received thimerosal. Rather than respond to this study, he responded to the blog of the editor-in-chief of Pediatrics, Dr. Lewis First. In an entry summarizing the articles in the recent issue Dr. First wrote:

You’ll be reassured that the results show essentially no differences between groups who did or did not get thimerosal in their vaccines—and you’ll want to know this information when talking with parents of your patients about the safety and benefits of vaccines.

This is an unfortunate mistake by Dr. First.  Kirby wrote an open letter to him pointing out the error and First responded:

I have used the word “essentially” in my blog to express my own opinion/interpretation and to note, by using that phrase “essentially”  that the data may still note associations but not ones that I personally feel are meaningful as per the data they have presented.

Ack – he missed the point. Kirby was not criticizing the interpration of the data, but the characterization of the groups as one having no exposure.  I honestly don’t know if First just keeps missing this point or is trying to save face. He should have immediately acknowledged the error and corrected his blog entry. This is all, of course, and irrelevant distraction from the implications of this study. But First’s clumsy blogging is feeding the conspiracy mongers.

This is an unfortunate pattern, in my opinion. Officials from the CDC and various medical organizations are not as savvy at dealing with the public as they need to be. We are in a new world of Web 2.0, of the immediacy and interactiveness of blogs, with dedicated anti-scientific groups who know how to use the technology to influence public opinion. Scientific organizations need to get much better at playing this game. First’s mistake and inadequate response indicates to me that he doesn’t get it. Knowing the depth of this controversy and the tactics of the anti-vaccine croud, utter care needs to be taken not to open the door for conspiracy mongering.


This latest study adds to the consensus of existing evidence for a lack of association between thimerosal in vaccines and autism or other neurological disorders. It is not by itself definitive, like all studies there are open questions, but it shows a lack of a dose-response toxicity to thimerosal in a dosing range relevant to the vaccine schedule.

However, since the anti-vaccination movement is largely ideological and disconnected from the scientific evidence I do not anticipate that this will end the controversy. The response of Handley and Kirby was predictable and shows this to be true. Meanwhile outbreaks of vaccine-preventable diseases appears to be on the rise, highlighting the need for better public education about vaccines.

Posted in: Public Health, Vaccines

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