Lyme Disease-Autism Link Debunked

General or non-medical topics with information and discussion related to Lyme disease and other tick-borne diseases.
Henry
Posts: 1108
Joined: Thu 10 Nov 2011 18:49

Lyme Disease-Autism Link Debunked

Post by Henry » Sun 5 May 2013 17:46

Another fraud perpetrated by prominent members of ILADS -- including, Bransfield, its current President:

http://www.the-scientist.com/?articles. ... -Debunked/

Note that Bransfield is not only President of ILADS, but also on a Medical Advisor to the Lyme-Induced Autism Foundation (LIAF).

Lorima
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Re: Lyme Disease-Autism Link Debunked

Post by Lorima » Sun 5 May 2013 20:01

Henry, 

It's unfortunate you weren't able to provide us with any convincing evidence suggesting the 2T test has been validated as 100% sensitive in a non-circular fashion - because this supposed debunking in JAMA to which you're referring, depends upon belief that the 2T test is 100% sensitive in all but very early stage disease. Alaedini goes so far as to say, 'the insensitivity occurs only in the first 1 or 2 weeks after a tick-bite" (see quote below). I guess he hasn't even noticed, yet, Steere's patients who were technically seronegative because they had only IgM 8-12 weeks after the tick bite, mentioned in the middle portion of PMIDs 18532885 and 19947857. Let alone the other problems we've been discussing, in detail. 

So this JAMA paper is resting on a false foundation, which renders it meaningless. 

Autism is a subjective diagnosis. There are no reliable biomarkers. Presumably a population of children with that diagnosis will exhibit a fairly wide range of mildly or profoundly disabling signs, symptoms and behaviors. And it seems likely these will have been caused by a wide variety of insults to the developing neurological system. I see no reason to exclude the possibility, even the likelihood, that some children suffering from neurological symptoms of Lyme disease may have been given an autism diagnosis. 

Do you see any reason to exclude that scenario, from a biologically-informed, common-sense perspective? (That is, provided we remove "Trust the experts absolutely" which I consider an anti-science perspective, from the options that might be considered common sense, by the non-scientifically inclined.) 

Since I believe the 2T test was improperly designed and tested, and that if it has any validity it must be only among the mid-stage (say, less than 1-2 years) infected patients, and the late arthritis patients, used to develop it, I find this JAMA paper to be uninformative. 

At this point, I have no idea how many children with neurological Lyme disease might be carrying a diagnosis of "autism". 

But I am sure, that if I lived in an LD-endemic area and had a child with new-onset neuropsychiatric symptoms, I would immediately get IgM and IgG Western blots with all bands reported, and compare the results with my chart of band specificities. If the child lived or had traveled in a less-well-characterized region, I would get European and/or Western US-optimized blots, too. 

Because LD is treatable, and the earlier the better. 

http://www.the-scientist.com/?articles. ... -Debunked/ 
Indeed, due to a mistrust of the CDC-recommended test, some proponents of Lyme-induced autism are not convinced by this study. “I’m glad to see that someone has decided to pay attention to this, but the study was designed to fail,” said Robert Bransfield, a psychiatrist in Red Bank, New Jersey, who writes about the connection between autism and Lyme disease. Bransfield points to studies showing that the test is insensitive. But Alaedini counters that the insensitivity occurs only in the first 1 or 2 weeks after a tick-bite, before a person has generated sufficient antibodies against the pathogen. This short-term problem would not be an issue in a study assessing long-term problems associated with autism, he said.
"I have to understand the world, you see."
Richard Feynman

edbo
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Re: Lyme Disease-Autism Link Debunked

Post by edbo » Sun 5 May 2013 21:31

Lorima, I was thinking your exact same thoughts when this publication made the news.

But even though I am suffering from tick borne diseases myself and I don't respect the 2T too much, I am a bit skeptical about blaming the results on the incorrect testing. Even if the test picked up only every other infection and there was a definite link between autism and lyme, it might have shown a much more significant difference between autistic children and controls. But the results in both groups are virtually the same.

I think this is another classic example of using "lyme" as a synonym for "tick borne infections". Because I can, in fact, imagine that there might be a connection between autism and tick borne infections. Maybe not with lyme disease itself but instead with mycoplasma or chlamydia pneumoniae, which are other highly underrated tick borne pathogens. The most well-known supporter of the mycoplasma thesis is Prof. Dr. Garth Nicolson.

Evidence for Mycoplasma ssp., Chlamydia pneunomiae, and human herpes virus-6 coinfections in the blood of patients with autistic spectrum disorders.
Nicolson GL, Gan R, Nicolson NL, Haier J.
The Institute for Molecular Medicine, Huntington Beach, California 92647, USA. gnicolson@immed.org

http://www.ncbi.nlm.nih.gov/pubmed/17265454
We examined the blood of 48 patients from central and southern California diagnosed with autistic spectrum disorders (ASD) by using forensic polymerase chain reaction and found that a large subset (28/48 or 58.3%) of patients showed evidence of Mycoplasma spp. infections compared with two of 45 (4.7%) age-matched control subjects (odds ratio = 13.8, P < 0.001) . Because ASD patients have a high prevalence of one or more Mycoplasma spp. and sometimes show evidence of infections with Chlamydia pneumoniae, we examined ASD patients for other infections. Also, the presence of one or more systemic infections may predispose ASD patients to other infections, so we examined the prevalence of C. pneumoniae (4/48 or 8.3% positive, odds ratio = 5.6, P < 0.01) and human herpes virus-6 (HHV-6, 14/48 or 29.2%, odds ratio = 4.5, P < 0.01) coinfections in ASD patients. We found that Mycoplasma-positive and -negative ASD patients had similar percentages of C. pneumoniae and HHV-6 infections, suggesting that such infections occur independently in ASD patients. Control subjects also had low rates of C. pneumoniae (1/48 or 2.1%) and HHV-6 (4/48 or 8.3%) infections, and there were no coinfections in control subjects. The results indicate that a large subset of ASD patients shows evidence of bacterial and/or viral infections (odds ratio = 16.5, P < 0.001). The significance of these infections in ASD is discussed in terms of appropriate treatment.
Here is another completely independent publication where they tried to prove that a mycoplasma infection can have an effect on the babies' brains before their birth and cause autistic spectrum disorders:

Effect of experimental genital mycoplasmosis on gene expression in the fetal brain.
Burton A, Kizhner O, Brown MB, Peltier MR.
Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ, USA.

http://www.ncbi.nlm.nih.gov/pubmed/22244476
Neurodevelopmental disorders may have their origins during intrauterine development. We used a well-defined animal model to test whether hematogenous infection with genital mycoplasma would alter the expression of genes associated with autism spectrum disorders (ASD). In a preliminary experiment, rats were exposed at 14 days gestation (GD14) to Mycoplasma pulmonis or sterile broth and sacrificed at GD18. Infection and inflammation status of the pups was ascertained by culture and cytokine ELISA. Intra-cardiac injection of 10(6)CFU M. pulmonis resulted in amniotic infection of 100% of the pups and was accompanied by higher levels of IL-1β in amniotic fluids. In a second experiment, animals were infected in a similar manner but dams and their litters were sacrificed at GD18, GD21 or postpartum day 3 (PPD3). Expression of proinflammatory cytokines and neurodevelopmental genes in the fetal brains was evaluated. M. pulmonis infection significantly increased the expression of IL-1β, TNF-α and COX-2 in fetal and neonatal brains. Expression of GFAP and CD11b, markers for activation on astrocytes and microglial cells, respectively, was also increased for infected animals. M. pulmonis significantly increased SHANK-3 gene expression at GD21 and PPD3 and PCP-2 expression at GD21. No effect of M. pulmonis infection on Reelin, PTEN, BDNF or HGF was detected. These data suggest that M. pulmonis infection at GD14 increases the expression of proinflammatory genes in the perinatal brain. Further studies with earlier time-points of infection and ones that use behavioral outcomes are needed to better understand the potential role of genital mycoplasmosis on pychopathology.
This last publication would support Bransfield's hypothesis about autism already developing in the mother's womb which gets brushed off by Halperin as "conjecture" (as usual) even though there is scientific evidence for Bransfield's thinking. This is also mentioned in the TS article.
In addition to his doubts about the test Alaedini used, Bransfield speculated that Lyme disease might have caused autism while the participants were in the womb or in their first 2 years of life. The antibodies lingering from the causative infection may have waned by the time blood samples were collected. “If someone is a teen, even if they acquired autism from Lyme disease, you won’t see an active infection,” he said.

But Halperin said such a scenario is unlikely. “There is no scientific evidence to support those conjectures,” he said, calling them “fictional arguments that can’t be tested by science.” So, why do some children with autism appear improve after a bout of antibiotics? Like so many aspects of autism, that question remains open from a scientific perspective.
Bransfield also reports a high incidence of mycoplasma infections (higher than lyme disease!) in autism patients in his own publication.

The association between tick-borne infections, Lyme borreliosis and autism spectrum disorders.
Bransfield RC, Wulfman JS, Harvey WT, Usman AI.
Department of Psychiatry, Riverview Medical Center, 225 State Route 35, Red Bank, NJ, United States. bransfield@comcast.net

http://www.ncbi.nlm.nih.gov/pubmed/17980971
Chronic infectious diseases, including tick-borne infections such as Borrelia burgdorferi may have direct effects, promote other infections and create a weakened, sensitized and immunologically vulnerable state during fetal development and infancy leading to increased vulnerability for developing autism spectrum disorders. A dysfunctional synergism with other predisposing and contributing factors may contribute to autism spectrum disorders by provoking innate and adaptive immune reactions to cause and perpetuate effects in susceptible individuals that result in inflammation, molecular mimicry, kynurenine pathway changes, increased quinolinic acid and decreased serotonin, oxidative stress, mitochondrial dysfunction and excitotoxicity that impair the development of the amygdala and other neural structures and neural networks resulting in a partial Klüver-Bucy Syndrome and other deficits resulting in autism spectrum disorders and/or exacerbating autism spectrum disorders from other causes throughout life. Support for this hypothesis includes multiple cases of mothers with Lyme disease and children with autism spectrum disorders; fetal neurological abnormalities associated with tick-borne diseases; similarities between tick-borne diseases and autism spectrum disorder regarding symptoms, pathophysiology, immune reactivity, temporal lobe pathology, and brain imaging data; positive reactivity in several studies with autistic spectrum disorder patients for Borrelia burgdorferi (22%, 26% and 20-30%) and 58% for mycoplasma; similar geographic distribution and improvement in autistic symptoms from antibiotic treatment. It is imperative to research these and all possible causes of autism spectrum disorders in order to prevent every preventable case and treat every treatable case until this disease has been eliminated from humanity.
Overall, I would say that these papers so far are just puzzle pieces. They still don't really prove anything and more research is needed. But it seems there is a strong collection of indices that would support the thesis of a higher incidence of autism in families affected by tick borne diseases.

There is an interesting talk by Prof. Nicolson. He explores his hyopthesis a bit more, especially why he thinks that vaccines can trigger autism as well. Or the connection with the gulf war syndrome. Some interesting thoughts in there. The biowarfare stuff is a bit over the top but a lot of his other thesises are worth investigating IMO.
https://www.youtube.com/watch?v=eVOptdKkmz4

And finally, here are some other scientific papers (maybe for Henry ?) about the possible connection between infections and autism, e.g. viruses. Here I find it interesting that autistic disorders do not necessarily have to develop before birth but can be triggered after a person has become adolescent which would absolutely speak against a "genetic predisposition" for autism, as mentioned by a commenter of the TS article.
http://www.science-autism.org/infections.htm#specific

Henry
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Re: Lyme Disease-Autism Link Debunked

Post by Henry » Sun 5 May 2013 22:14

Oh, there's another paper entitled "Lack of serum antibodies against Borrelia burgdoferi in children with autism", by Burbelo et al. It has been posted on-line as an ahead-of-print paper in the May, 2013 issue of Clinical Vaccine Immunology. They use a different assay for antibody. Now, tell me about all of the flaws of that method. You still haven't told me about how you arrive at an objective diagnosis of Lyme disease even ILADS and IGenex used the 2 tiered test.

Lorima
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Re: Lyme Disease-Autism Link Debunked

Post by Lorima » Mon 6 May 2013 3:44

Henry,

It has become customary here, to provide a link, a full reference, and relevant quotes from papers one is introducing in order to illustrate a point in debate. Would you please do that for the Burbelo paper?

If you look at my previous posts, you will find my thoughts about how doctors and patients might benefit from Lyme serology, even though there is no absolute black-and-white, yes-or-no answer that can be derived from it. In fact, you will find my view described, in my post above. Please re-read it.

I realize most doctors want a slip of paper with an easy answer on it. However, if they are as smart as we've been told, they should be able to handle the news that this is not actually possible for LD without an unacceptably high risk of error. A flat "positive/negative" dichotomy suggests a certainty that the test's actual characteristics don't warrant. I don't think doctors are stupid, but I think they are rushed, and pressured to conform, and consequently, suggestible. Without the decision made for them by a rigid algorithm, it might take them 2 minutes to look at the Western blot reports(s), once they get some practice, and integrate it with the clinical picture, instead of the 2 seconds it takes to read "pos" or "neg" at the top of the test report. But it will be 2 minutes well spent.

Those who claim that an accurate, unambiguous positive/negative result is available (for example, those who claim the 2T test is 100% sensitive and specific, and require it for diagnosis) are fooling themselves and their followers. They might best be regarded as having been inappropriately swayed by the wishes of doctors, patients, and public health agencies, for perfect tests and sure cures. There may be some diseases that allow that, but Lyme disease isn't one of them.
"I have to understand the world, you see."
Richard Feynman

Lorima
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Re: Lyme Disease-Autism Link Debunked

Post by Lorima » Mon 6 May 2013 3:58

Edbo, thanks for writing. I don't want to participate in widening and complicating the topic right now, so I'll PM you, when I've had a chance to think about it. Or maybe we can discuss other possible infections resulting in some autism diagnoses, in another thread; it's not an area I've studied, but of course it is an interesting topic.

I don't really know if there are many Lyme/autism mix-ups. As I said, it seems like common sense to me that there would be, considering the serious under-diagnosis of neuropsych LD, due to the IDSA guidelines. I have family members who went undiagnosed for years with neurological LD, so perhaps I'm extraordinarily aware of the problem. Certainly I don't think most cases of autism, are actually LD, even in LD-hyperendemic locales.
Best regards,
Lorima
"I have to understand the world, you see."
Richard Feynman

Henry
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Re: Lyme Disease-Autism Link Debunked

Post by Henry » Mon 6 May 2013 14:27

Lorima: Although a copy of the Burbela et al paper was sent to me by the authors, copy right law prohibits duplicating the paper on this website.

Your argument for circular reasoning is flawed. The many studies used to provide information on the sensitivity and validity of 2-tiered testing were based on panels of well-characterized specimens obtained at later times from patients who were culture positive, and/or had EM rashes. It is here that convalescent serum, as well as sera acquired late during infection are especially valuable, since such sera would be expected to be seropositive. In other words, specimens were used in which there was little doubt that they came from patients who have/had Lyme disease. To evaluate the limitations of a diagnostic test based on the use of such specimens makes good sense to me. Furthermore, different panels of such specimens were used in the different studies described, all of which gave the same results. So, is everyone involved in such work stupid and using circular reasoning to make their point? I rather doubt that very much. Too many people of integrity are involved. No one should believe that they would get away with such a thing anyway.
Last edited by Henry on Mon 6 May 2013 15:53, edited 1 time in total.

Lorima
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Re: Lyme Disease-Autism Link Debunked

Post by Lorima » Mon 6 May 2013 15:53

Henry, 
In other words, you have no data for us today. 
A more humble style of conversation might be warranted, then. 
Specifically, you might want to be more careful about using words like "fraud", as you did in your opening post in this thread. 

That word implies intent to deceive, rather than honest differences in attempts to interpret complex observations, which have too many variables to yield simple, definitive conclusions. The sensible solution is to stop trying to enforce one interpretation prematurely. Medicine likes simple rules and tolerates false certainty, for the (temporary) psychological advantage of doctor and patient. I see this frankly assertive approach in many communications, from both IDSA and dissenting physicians, and from physicians in other fields. I fall into it myself, when communicating with doctors who are using that style exclusively. 

But we scientists know, or should know, better than to allow that camel's nose into our tent. 

Once people start making things up for convenience, and then insisting they are "true" and "evidence-based", we are not in the territory of science any longer. Please return to your roots, at least temporarily and in private, and consider this. 

Karl Popper called this distinction between science and other human activities a "problem of demarcation". 
http://www.stephenjaygould.org/ctrl/pop ... ation.html 
Popper didn't necessarily disrespect these other human activities; neither do I. But he and I both think it's important to recognize the difference. 
"I have to understand the world, you see."
Richard Feynman

Henry
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Joined: Thu 10 Nov 2011 18:49

Re: Lyme Disease-Autism Link Debunked

Post by Henry » Mon 6 May 2013 16:20

Lorima: I would say that to establish a Lyme-Induced Autism Foundation based on unpublished and non-reproducible "observations", and to make money treating falsely diagnosed children with extended antibiotic therapy is fraud -- pure and simple. In contrast, the results that I described have been published in peer -reviewed journals and are reproducible.I find it interesting that the same cast of ILADS-based characters seems to be associated with non-scientific and unproven misadventures such as Lyme-induced autism, Lyme-induced Morgellans (it also has a foundation of its own), and now Lyme-induced Alzheimers disease -- soon to be followed by a foundation as well? The basis for their erroneous views may be found in their many non-scientific opinion papers, rather than in peer-reviewed scientific journals.

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panda
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Re: Lyme Disease-Autism Link Debunked

Post by panda » Mon 6 May 2013 20:11

Henry wrote:
Oh, there's another paper entitled "Lack of serum antibodies against Borrelia burgdoferi in children with autism", by Burbelo et al. It has been posted on-line as an ahead-of-print paper in the May, 2013 issue of Clinical Vaccine Immunology.
Although a copy of the Burbela et al paper was sent to me by the authors, copy right law prohibits duplicating the paper on this website.
Which is the correct name? Couldn't find anything.
Searching for "Burbela" in Pubmed is resulting in one single article:
J Med Soc N J. 1981 May;78(5):374-6.
Pseudo-bladder neck syndrome in women: value of gray-scale ultrasonography.
Gould L, Patel R, Burbella R.
Searching for "Burbelo" in Pubmed:
http://www.ncbi.nlm.nih.gov/pubmed/?term=Burbelo

Searching for "Burbelo" AND "burgdorferi" in Pubmed:
http://www.ncbi.nlm.nih.gov/pubmed/?ter ... urgdorferi
2 results [both free full articles]:
Antibody profiling of Borrelia burgdorferi infection in horses.
Burbelo PD, Bren KE, Ching KH, Coleman A, Yang X, Kariu T, Iadarola MJ, Pal U.
Clin Vaccine Immunol. 2011 Sep;18(9):1562-7. doi: 10.1128/CVI.05123-11. Epub 2011 Jul 20.

Rapid, simple, quantitative, and highly sensitive antibody detection for lyme disease.
Burbelo PD, Issa AT, Ching KH, Cohen JI, Iadarola MJ, Marques A.
Clin Vaccine Immunol. 2010 Jun;17(6):904-9. doi: 10.1128/CVI.00476-09. Epub 2010 Apr 14.
Searching in CVI shows no such article:
http://cvi.asm.org/search?fulltext=Burb ... es&x=0&y=0

Actual Table of Contents:
http://cvi.asm.org/content/current (May 6)

Manuscripts published ahead of print:
http://cvi.asm.org/content/early/recent

The only 'source' (http://relative-risk.blogspot.de/2013/0 ... ckery.html) is RR, which is a blog, describing itself as:
Disclaimer: this is a personal blog full of referenced facts, and personal opinions, and those opinions should not be taken to represent the views, ideas or opinions of anyone else.
http://www.blogger.com/profile/14269491377948003249


Peter D. Burbelo, Ph.D.
Staff Scientist, Neurobiology and Pain Therapeutics Section
We have developed a novel antibody profiling technology, Luciferase Immunoprecipitation Systems (LIPS), which harnesses light-emitting recombinant proteins for quantitatively measuring antibody responses to any antigenic target. The simplicity of LIPS enables us to quickly clone and test antigenic targets making the technology an ideal system to uncover new disease biomarkers for infection, autoimmunity, cancer, and other conditions. My primary interest is applying LIPS in three clinical areas: understanding humoral responses to human pathogens, improving autoimmune diagnosis and prediction, and developing a generalized disease surveillance technology.
[...]
http://www.nidcr.nih.gov/Research/NIDCR ... urbelo.htm


Some interesting snippets of an interview of the NIDCR scientists Dr. Peter Burbelo and Dr. Michael Iadarola, concerning the new technique (LIPS):
Antibody Technique Shows Diagnostic Promise
April 2008

In the February 1 issue of the journal Biochemical and Biophysical Research Communications, a team of NIH researchers report early results with a tremendously sensitive and accurate new diagnostic technique to quantify antibodies in blood and saliva.
[...]
When you do an ELISA, it means you’ve taken a protein made by E. coli or another non-mammalian source and spot it on a plastic dish. You’re assuming the protein looks like it does naturally in solution. But its three-dimensional shape will be very different once it is affixed to plastic. So, the antibodies will recognize a stretch of amino acids here and maybe there. But they won’t recognize other pieces of the protein that have denatured and lost their natural conformations.
[...]
Right now, protein profiling technologies spot proteins on glass or a plastic membrane. Like the ELISAs, spotting can alter the natural three-dimensional folds of the proteins and affect the sensitivity of the antibody recognition and binding.
http://www.nidcr.nih.gov/Research/Resea ... hnique.htm
Last edited by panda on Mon 6 May 2013 21:01, edited 1 time in total.

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