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William H Ahearn, Ph.D., BCBA  
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Specialties: Behavior Analysis, Learning Deficits, Autism

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More on autism and vaccines

Mar 06, 2008 - 4 comments

The news media are being fed a new line of misinformation from antivaccinationists and this is being fueled by one case that was recently decided in favor of the plaintiffs in vaccine court.  The government clearly does not think there is a link between autism and vaccines.  In fact, one prominent case has already been dismissed because of the overwhelming evidence against this hypothesis (more on that below).   The following is a summary of the case decided in favor of the parents and the vaccine court decision from a science blog called neurologica, written by a prominent neurologist from Yale, Steven Novella (the entire article can be found at this link: http://www.theness.com/neurologicablog/index.php?p=203 ).  He considers all possibilities and concludes as to which are likely.  Please pass on this information to anyone interested in the topic.

  To summarize the case history, the child in the case appeared normal and healthy, except for chronic otitis media, until about 20 months of age at which time he had a series of vaccines according to the routine vaccination schedule. Two days later the child had a fever to 102.3, was lethargic, irritable, and would arch his back when he cried. The child then developed a rash. It was later determined that the child had: “encephalopathy progressed to persistent loss of previously acquired language, eye contact, and relatedness.” The child regressed and developed symptoms similar to those of autism spectrum disorder. However, the child does not have autism - he has a regressive neurological disorder that includes blood and muscle abnormalities not seen in autism, and any clinical resemblance to autism is not a reflection of a common cause.

Six years after symptoms began the child also developed partial temporal lobe epilepsy that required treatment.

During this time the child also had an extensive workup, which discovered:

A CSF organic acids test, on January 8, 2002, displayed an increased lactate to pyruvate ratio of 28,1 which can be seen in disorders of mitochondrial oxidative phosphorylation.

A muscle biopsy test for oxidative phosphorylation disease revealed abnormal results for Type One and Three.

In February 2004, a mitochondrial DNA (”mtDNA”) point mutation analysis revealed a single nucleotide change in the 16S ribosomal RNA gene (T2387C)

It if often difficult or impossible to draw firm conclusions from a single case, so I will lay out what I see as all the possible alternative hypotheses to explain this information.

1) One possibility is that the child was perfectly normal prior to the vaccines, which caused an encephalitis (inflammation of the brain) which caused brain damage, including the later seizures. The metabolic disorder and mutation may be a red herring and have no bearing on the child’s clinical condition.

2) The mitochondrial disorder predisposed the child to have a reaction from the vaccines, resulting in encephalitis. The subsequent neurological regression was due to some combination of the vaccine-induced encephalitis and the underlying mitochondrial disorder.

3) The child’s mitochondrial mutation is the primary cause of their neurological regression, but that this regression was exacerbated by the vaccine-induced encephalitis (this seems to be the US government’s conclusion).

4) The child has a mitochondrial encephalopathy which is the sole cause of all of the child’s neurological signs and symptoms. The reaction to the vaccines may have played no role at all in the subsequent regression, and the child’s current neurological condition is exactly what it would have been had they never been vaccinated. It is even possible that the encephalitis was merely the first manifestation of the mitochondrial disorder and the timing after the vaccines was merely coincidental.

That lays out the spectrum of possibilities in this case. At this point in time we do not have (or at least I am not privy to) sufficient scientific information to say definitively where along this spectrum the truth lies. The US government’s decision was based partly on this uncertainty - erring on the side of compensating the child and family.

But we can discuss the plausibility of each scenario. Kirby dismisses anything resembling option 4, but his dismissal is naive and unjustified. In fact the patient’s clinical syndrome resembles what is called a mitochondrial encephalopathy - with increased lactic acid, abnormal muscle biopsy, neurological regression, appropriate age of onset, even seizures. It is probably not a coincidence that the child has a point mutation in a gene that has been previously linked to these very mitochondrial disorders. Kirby incorrectly argues:

While it’s true that some inherited forms of Mt disease can manifest as developmental delays, (and even ASD in the form of Rhett Syndrome) these forms are linked to identified genetic mutations, of which T2387C is not involved. In fact little, if anything, is known about the function of this particular gene.

This is misleading. Kirby refers to “this particular gene” which makes me think that he believes T2387C is a gene. It’s not - it describes a point mutation (at location 2387 a thymidine has replaced a cytosine). The gene is the 16S ribosomal RNA gene. Mutations in this gene have been identified to cause mitochondrial encephalopathy. So Kirby is just wrong. It is true that I could not find that this specific mutation has been identified before, but that is common in genetics - a disease is linked to point mutations in a specific gene (or perhaps specific regions of a gene) but most or all families identified have their own specific mutation.

This makes option 4 very plausible - it would be an incredible coincidence if this child just happened to have a mutation in a gene that was known to cause their exact constellation of neurological signs and symptoms and yet the mutation was not the sole or primary cause of those symptoms.

But it does not rule out option 3 - that the mitochondrial disorder was the primary cause of the child’s neurological disorder but that a reaction to the vaccines worsened the ultimate symptoms. Therefore the government’s decision was reasonable - but is absolutely not a concession about any claim made by the petitioners concerning a link between vaccines an autism.

It does, however, make any hypothesis resembling option 1 or 2 extremely unlikely. Further testing regarding the physiological effects of this child’s specific mutation would be helpful, and such testing may be under way but I could find nothing published to date. It is theoretically possible that the identified mutation does not cause a change in the gene product or mitochondrial function, and is therefore just a coincidence. But this is unlikely given the clinical features in this case are a good match to known mutations of that gene.

Kirby, however, apparently wants to wring as much fear and confusion out of these events as he possibly can. So now he speculates wildly that maybe children diagnosed with autism really have this mitochondrial disorder combined with vaccines (he has to keep vaccines in the loop). Given the rarity of such mutations, and the fact that there were specific features in this case that would likely be uncovered in the routine evaluation of a child with autism (like an elevated lactic acid), it is highly unlikely that there are many children with vaccine-triggered mitochondrial encephalopathy mimicking autism out there.

It has been found that some children with autism have mitochondrial dysfunction - one study found that 7.2% of subjects with autism had “definite mitochondrial respiratory chain disorder.” Poling et al, in response to this child’s case, did a retrospective study of children with autism and with other neurological disorders and found that “Aspartate aminotransferase was elevated in 38% of patients with autism compared with 15% of controls.” Such findings are preliminary - the only conclusions that can be drawn is that the association between autism and metabolic disorders requires further investigation. However, these studies did not look at the incidence of suspicious mitochondial mutations in autism, and these findings may not be relevant to this case.

Kirby also wildly speculates that perhaps the evil toxins in vaccines caused the mutation in the first place. He writes:

Use of the AIDS drug AZT, for example, can cause Mt disorders by deleting large segments of mitochondrial DNA. If that is the case, might other exposures to drugs or toxins (i.e., thimerosal, mercury in fish, air pollution, pesticides, live viruses) also cause sporadic Mt disease in certain subsets of children, through similar genotoxic mechanisms?

Among stiff competition, this is perhaps the most absurd and scientifically ignorant thing Kirby has every written. AZT does NOT cause a genetic disorder. AZT blocks DNA replication (it blocks the copying of DNA) - that is its mechanism as an anti-retroviral drug. In patients it can also block mitochondrial DNA replication, thereby causing mitochondrial depletion. This results in there being too few mitochondria (the energy factories of cells) in some cell populations and causes dysfunction in tissue that is especially susceptible to the effects of this dearth of mitochondria. This is a side effect of AZT and also other retrovirals because of sustained use at doses designed to inhibit DNA replication. This does result in some effects that are similar to mitochondrial genetic disorders - because both result in insufficient mitochondrial activity. But that is the only similarity. AZT does not cause a disseminated somatic mutation, which is the incredible analogy that Kirby is making.

What Kirby is suggesting is that in infants and toddlers toxins can cause the same point mutation in millions of different cells throughout the body. Toxin-induced mutations do not cause genetic diseases, unless they occur in a germ cell in which case a mother or father can pass the mutation onto their children. If it occurs in the womb then large cell populations may be affected (whatever cells derive from the cell that had the mutation). But in a child a point mutation would affect only one cell and any cells that derive from it. A toxic mutagen would cause different random point mutations in different cells. This could not cause the mitrochondrial encephalopathy in this child. It can increase the risk of cancer, because cancer can develop from a single mutation in a single cell that causes it to become neoplastic.

Conclusion

This is a unique and idiosyncratic case that raises more questions than it answers. In my opinion as a neurologist, with the information provided, the child has a mitochondrial encephalopathy. The role of the vaccines is unclear, but at worst a rare vaccine reaction exacerbated the underlying mitochondrial disorder. This case has no clear implication for the larger question concerning vaccines and autism, which is likely why both sides agreed to settle.

Yet those who insist, despite the evidence, on claiming that vaccines or mercury are linked to autism are likely to add this permanently to their litany of misinformation and fear-mongering.



Basically, the antivaccination people are pushing this as a victory and it really is not.  As mentioned above, there has already been one case that clearly tested the autism-vaccine hypothesis that was dismissed.  You can read about that here (http://neurodiversity.com/weblog/article/145/)



Blackwell Case Dismissed · Feb 20, 03:45 PM
On February 8, 2008, Judge Stuart R. Berger of the Circuit Court for Baltimore City, Maryland, granted vaccine manufacturer Wyeth’s motion for summary judgment in Blackwell v. Sigma Aldrich, Inc. et al (No. 24-C-04-004829) — a lawsuit in which the plaintiffs alleged that their child’s exposure to thimerosal-containing vaccines caused him to become autistic.

Judge Berger ruled that:

“Upon consideration of Defendant Wyeth’s Motion for Summary Judgment, and the Plaintiffs’ Response filed thereto… [t]his court finds that there is no genuine dispute as to any material fact… Defendant Wyeth is entitled to judgment as a matter of law.”

This ruling comes eight weeks after the court precluded the testimony of plaintiffs’ expert witnesses Dr. Mark Geier. Dr. Stephen Siebert, Dr. Elizabeth A. Mumper, Prof. Richard C. Deth, and Prof. Boyd E. Haley:

“In sum, the plaintiffs, the proponents of the above-identified expert witnesses, have failed in their burden of proving that the bases of the expert witnesses’ testimony are generally accepted as reliable within the relevant scientific field… [T]hey have failed to show that the methodologies underlying their expert witness’ opinions are generally accepted to be reliable in the relevant scientific community.”

“[I]t is generally accepted in the relevant scientific community that autism is genetic in origin except in rare instances of prenatal exposures to certain substances at defined periods during pregnancy… [I]t is generally accepted in the relevant scientific community that thimerosal in vaccines does not cause or contribute to neurodevelopmental disorders such as autism.”



Autism and vaccines: Jenny McCarthy

Dec 18, 2007 - 6 comments

Former MTV personality and model Jenny McCarthy has recently published a book, and has appeared on numerous television shows, promoting the notion that autism is caused by vaccines.  She claims that vaccines caused her son’s autism and also claims that her son has been cured via chelation, diets, antifungal medication, and various other unsubstantiated therapies.  McCarthy also writes in her book that she “chain smoked” throughout her pregnancy prior to deciding to live a healthier life after her son was born.  Smoking during pregnancy has been well documented as being associated with a higher prevalence of autism and other psychiatric symptoms (e.g., Rizwan et al., 2007).

NECC has closely followed the autism-vaccine hypotheses and research related to it.  As we have reported in the past, the findings of many large scale studies show no link between autism and either thimerosal in vaccines or the measles, mumps, and rubella (MMR) vaccine.  (Previous coverage in our Research Newsletter can be accessed at the first link below).  In fact, the September 27th issue of this year’s New England Journal of Medicine contains a study that “does not support a causal association between early exposure to mercury from thimerosal-containing and immune globins and deficits in neuropsychological functioning…” (This study can be accessed at the second link below.) Though this study did not specifically investigate autism, it is likely that children with autism would perform poorly on the neuropsychological testing used.  Furthermore, a similar study that specifically tested for autism will be completed and published in the near future.  Despite the accumulating evidence against the link between vaccines and autism, it is likely that people will continue to ignore this scientific evidence in favor of a belief that a link exists.

NECC Research Newsletter:
http://www.necc.org/research/newsletter.asp

NEJM article:
http://content.nejm.org/cgi/content/full/357/13/1281


Evidence suggests that there is no link between vaccines and autism

Dec 12, 2007 - 6 comments

The prevalence of autism has risen dramatically in the past two decades.  Prevalence is an estimate of the number of affected persons at a point in time.  Prevalence studies conducted in the United States show that the prevalence of ASDs in 2003-2004 is somewhere between 1 in 139 and 1 in 181 children between the ages of 4 and 17.  This implies that there are around 300,000 children diagnosed with an ASD.  Most scientists feel the rise in prevalence is due to a combination of changes in the diagnostic criteria for autism spectrum disorders (ASDs) and increased awareness of the disorder (e.g., Wing and Potter, 2002).  

However, some have suggested that the increased prevalence of ASDs corresponds with an increase in the number of vaccinations recommended for children.  Correlation of two events is not sufficient evidence to assert that one caused the other as the two events could be unrelated.  For example, if a child is born during a full moon one could suggest that the lunar event caused the birth.  This would be an example of a likely false correlation.  Therefore, further study of such correlations is necessary to reveal evidence to either support or disconfirm a causal hypothesis.  One specific hypothesis of vaccines being linked to autism suggests that thimerosal, a preservative previously used in childhood vaccines that was removed from vaccines manufactured in the US in 1999, can cause autism.  Thimerosal is still present in some versions of the flu vaccine.  Several versions of this theory target different mechanisms for how thimerosal damages the child and causes autism.  They all, however, state that some damage occurs to the developing child after vaccination.  Advocates of the “thimerosal causes ASDs” hypothesis have also suggested that the prevalence of ASDs will substantially decrease subsequent to thimerosal being removed from childhood vaccines.  

A recent study published in Pediatrics by Fombonne and colleagues (2006) has shown that decreased thimerosal in childhood vaccines is not correlated with decreased prevalence of ASDs.  Fombonne and colleagues have collected data on the prevalence of ASDs in children in Montreal from 1987 through 1998.  Thimerosal was removed from vaccines in Canada by 1996.  Fombonne et al. found that there was a statistically significant increase in the prevalence of ASDs for children who received thimerosal-free versions of the recommended childhood vaccines.  If one were to apply the false correlation influenced thinking here it could be suggested that thimerosal should be added back into vaccines because they are correlated with a lower prevalence of autism.  Similar findings to Fombonne et al. have been obtained in Denmark and Sweden and will likely be revealed in the US in the not too distant future.  Informal review of several educational data systems suggests that the prevalence of ASDs is continuing to increase in the US.  

Another hypothesis suggests that the measles-mumps-rubella (MMR) vaccine causes autism.  ASDs clearly have a genetic origin but one environmental trigger has been identified.  If a pregnant mother contracts rubella, there is an increased chance of the child having an ASD (Chess et al., 1971/74/77).  As the MMR vaccine decreases the chance of rubella infections, its use should decrease the likelihood of this environmental triggering of autism.  However, some have posited that the MMR vaccine triggers regression that is sometimes part of the course autism (i.e., some children with ASDs lose skills that they previously acquired in early development).  Most of the popularization of this theory has been spurred by Andrew Wakefield.  He suggested that the MMR injures a child’s gut in a specific manner producing problems similar to those caused by irritable bowel syndrome.  He also stated that measles was the cause because he and his colleagues purportedly detected components of the measles virus in the gastrointestinal tracts and blood of children with autism that were not present in typically developing children.  

Another study recently published in Pediatrics attempted to determine whether measles was more likely to be found in the bodies of children with ASDs than in typically developing children.  D’Souza and colleagues (2006) collected the largest sample of subjects for this type of study and used the same technique, polymerase chain reaction assays, that had purportedly detected measles in children with ASDs.  They found that this technique produced many positive reactions in both children with ASDs and typical children.  However, these reactions were further analyzed and found to be false positives for all subjects.  The products of the reactions were cloned and genetically sequenced and none of these sequences contained the components of the measles virus.  That is, neither the children with ASDs nor the typical children showed any evidence of measles virus in their bodies.  Furthermore, there were no differences found in anti-measles antibodies across the study groups of children.  

This, taken in combination with numerous other studies showing no relation between the MMR vaccine and ASDs, provides fairly definitive evidence against the “MMR causes autism” hypothesis.  It should also be noted that Andrew Wakefield was found to have been paid over $150,000 by a group seeking to pursue litigation against vaccine manufacturers in the United Kingdom.  Once this severe conflict of interest was revealed, ten of Wakefield’s co-authors requested that their names be withdrawn from the original publication used as support for this hypothesis.  More information on Andrew Wakefield can be found at BrianDeer.com, a website maintained by the investigative journalist who revealed the conflict of interest

D’Souza et al., (2006).  No Evidence of Persisting Measles Virus in Peripheral Blood Mononuclear Cells From Children With Autism Spectrum Disorder.  Pediatrics, 118(4), 1744-1745.

Fombonne et al., (2006).  Pervasive Developmental Disorders in Montreal: Prevalence and Links with Immunizations.  Pediatrics, 118(1), 139-150. 37.

Wing, L. & Potter, D. (2002).  The epidemiology of autistic spectrum disorders: Is the prevalence rising?  Mental Retardation and Developmental Disabilities Research Reviews, 8(3), 151-161


Newsday report on fever and autism

Dec 10, 2007 - 2 comments
Tags:

Autism

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Fever

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children



The December 4, 2007 report from Newsday covers a controversial topic.  The article suggests that fever can lessen the symptoms of autism.  The study was conducted at the well respected Kennedy Krieger Institute at Johns Hopkins in Baltimore.  The authors state that episodes of fever were correlated with less problem behavior and more appropriate social interaction.  However, the study is based solely on anecdotal report (a survey) and though potentially interesting, there is no current empirical support behind the notion that fever temporarily abates the symptoms of autism.  Anecdotal report is a very poor means of establishing a causal relation between events.  We at The New England Center for Children have worked with persons with ASDs for many decades and have not encountered a child showing temporary recovery from autism.  Certainly children with ASDs who exhibit problem behavior often have lower levels during fever but they also tend to play less and sleep more.  Perhaps children with fever are more motivated to request assistance or social interaction but our clinical experience does not match up with this report.  Having been a postdoctoral fellow at the Kennedy Krieger Institute, I have a great deal of respect for the work conducted there but I'm not sure this study adds any information.  More systematic research is necessary to determine whether or not there is any substance to this hypothesis.  What we do know about febrile events and autism is that there are correlations between certain febrile events and an increased likelihood of a child being diagnosed with autism.  Encephalitis, severe malaria (with high fever), rheumatic fever, rubella (maternal), and other similar maladies are correlated with a higher incidence of autism.  That said, there has been some speculation that there is an increasing prevalence of autism due to the prevalent use of fever reducers.  Again, this notion is not supported by sound empirical evidence but systematic investigation has not been done on this topic.