Special fevers, mitochondria and autism

30 Dec

Thats right, its back.

Ginny Hughes, writing for the Simons Foundation writes about new methods of detecting mitochondrial damages that may lead to autism. Of course, since last year that inextricably calls to mind Hannah Poling.

Just as a quick refresh, Hannah’s case was compensated by US Gvmt who accepted that vaccines caused a fever which triggered an underlying mitochondrial dysfunction which in turn led to ‘autism like symptoms’. This is oppose to ‘vaccines caused her autism’ which you’ll find a lot of people claiming.

The crux of the matter is fever. Mitochodrial dysfunction appears to be largely triggered by fever. Without the fever there’s no dysfunction. Without the dysfunction theres no autism.

Jay Gargus, professor of physiology and biophysics at the University of California, Irvine who’s studied mitochodria for 20 years makes a very telling point in this piece:

“It terrifies me that people will be making arguments [from this work] that further enhance the panic about vaccines,” Gargus adds. “Obviously, getting a vaccination will sometimes give you a fever, but the kid’s going to get a fever sooner or later anyway. It’s not like it’s a special fever.”

All kids get ill. They’re going to get fevers. In fact a lot of the things that vaccines try and prevent cause fevers. Flu for example. What vaccines don’t do is give a child a ‘special’ autism causing fever. Thats because there _is_ no special autism causing fever and no special autism causing vaccines either.

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39 Responses to “Special fevers, mitochondria and autism”

  1. passionlessDrone December 30, 2009 at 23:03 #

    Hi Kev –

    I’d be very interested in more research on a time dependent effect of fevers, mitochondrial dysfunction, and neurological outcomes. In other words, is getting a high fever at three years the same as getting one at one year, or at four months, for an infant with mitochondrial disorder? I can’t see how you would really measure this well. (?)

    I do appreciate how the authors note that not all fevers are the same, IIRC, Hannah Polling suffered from repeated ear infections and fevers prior to her autistic regression. It does seem well established that the immune system of our population of interest have some very odd properties, though if they are sufficient to cause a predisposition to fever, I can’t say. (?) There was a discussion about some of these complexities on this site a few months back.

    You might be interested in knowing that according to the manufacturers, some combination vaccines are accepted to cause fevers more frequently than their single vaccine equivalents:

    Administration of PEDIARIX is associated with higher rates of fever relative to separately administered vaccines. In a safety study that evaluated medically attended fever after PEDIARIX or separately administered vaccines when coadministered with 7-valent pneumococcal and Hib conjugate vaccines, infants who received PEDIARIX had a higher rate of medical encounters for fever within the first 4 days following the first vaccination.

    http://us.gsk.com/products/assets/us_pediarix.pdf

    Just as all fevers are not equivalent, neither are all vaccines, it would seem.

    I’d be interested in seeing if anyone had any references one way or the other towards the instances of fever if you get one, two, three, five, eight vaccines at once. I’ve been unable to find anything on this one way or the other, but this could be the result of my search capacities as opposed to an absence of study.

    – pD

    • Sullivan January 1, 2010 at 08:12 #

      In other words, is getting a high fever at three years the same as getting one at one year, or at four months, for an infant with mitochondrial disorder?

      As I understand it–According to the researchers positing the fever/mitochondrial dysfunction/autism connection, the answer is yes, there is a difference.

      Again, as I understand it, the difference isn’t in the fever, but in the developmental window of the child. A child (or adult) with mitochondrial disease/dysfunction is at risk for permanent harm from any fever, but the model is that the autistic regression only occurs within a specific age window.

  2. Laurent December 31, 2009 at 00:31 #

    Fever is also known to make changes in brain. Case example is the starting of speech with autistic nonverbal kids.

    My granmother gave me some examples but not only :

    http://www.reuters.com/article/idUSN2921232720071203

    http://www.associatedcontent.com/article/470961/fever_treatment_for_autism.html

  3. daedalus2u December 31, 2009 at 00:33 #

    I blogged about the physiology of mitochondria failure during immune system activation a while back.

    http://daedalus2u.blogspot.com/2008/06/mechanism-for-mitochondria-failure.html

    It probably isn’t the “fever” per se, but rather the NO that is often associated with fever. I think that is what is meant by “all fevers are not alike”. How much NO is produced is not determined by the temperature of the fever but by other things, mostly by how much iNOS is expressed.

    The important thing to remember is that mitochondria have a lifetime, and are continuously turned over and replaced. In the rat CNS, the lifetime is about a month. This replacement accelerates when a lot are damaged as during an acute illness. Feeling sick and not wanting to move is an extremely important signal when you are sick.

    I go into the details on my blog, but the high NO level of sepsis is incompatible with high mitochondria activity to generate ATP at a high rate. If you try to force mitochondria to make ATP in a high NO environment, they will try to do so and it will kill them. Kill too many mitochondria and you get multiple organ failure. This is what kills people in sepsis.

    Some of the symptoms of mitochondria failure during sepsis are also produced in Reyes Syndrome, a condition brought about during infection by use of aspirin. Reyes syndrome is characterized by fatty liver (also a sign of mitochondria damage) and neuroinflammation. Aspirin does cause increased expression of iNOS and so will increase NO levels after it is administered. This would tend to exacerbate any NO induced mitochondria damage. Mitochondria can tolerate high NO levels so long as they are not called on to produce ATP at a high rate. This is why it is important to rest when one is sick. Activity uses ATP, if mitochondria are forced to operate at high potential they are much more vulnerable and will be shut down. If too many are shut down, the cell, tissue compartment and eventually organ will fail.

    Mitochondria failure is acute and only happens during the acute phase of immune system stimulation. If you have recovered, then you have not suffered irreversible mitochondria failure and should only get better. The most important way to recover is via rest and inactivity.

    I think the emphasis on mitochondria is misplaced. Yes, mitochondria disorders can cause acute decline if they are damaged due to overload. That is not a cause of most autism. That can’t cause increased minicolumns because that happens in the first trimester in utero. Mitochondria are not very active during the first trimester. The partial pressure of O2 in utero is quite low during the first trimester. Mitochondria have to be active because they make things like heme, and mitochondria have to be replicated to populate all the new cells being made. But the adverse effects observed which date from the first trimester are not caused by mitochondria.

  4. daedalus2u December 31, 2009 at 03:45 #

    I have a blog on fevers and austism too.

    http://daedalus2u.blogspot.com/2008/01/resolution-of-asd-symptoms-with-fever.html

    Artificially inducing fevers should be considered extremely experimental and should only be done in the context of a real clinical trial, with a real IRB, and real MDs and real researchers doing real science. If a quack wants to try that on your child, don’t let them.

    When fever therapy was used to treat neurosyphilis, there was about a 15% death rate.

  5. Laurent December 31, 2009 at 14:25 #

    “If a quack wants to try that on your child

    Read more: http://leftbrainrightbrain.co.uk/?p=3954#comment-72734#ixzz0bGwQaS1H

    Thanks my dear Sir,

    I dont understand exactly what you want to sell us ?
    Ammonia oxidizing bacteria treatments ?

    Not quite the good address…

  6. cs December 31, 2009 at 15:42 #

    This is what I do not understand. The theory years ago was that autistic children who regressed had a history of frequent ear infections leading to over use of antibiotics that lead to the yeast problems. How can it be pinpointed that the regression is from the vaccinations and not one of the many fevers from the ear infections? Hannah P had a history of ear infections. That was why her vaccinations were delayed to the point that she needed 9 in one visit. If the court ruled it was the fever, why was it that specific fever?

  7. Kev December 31, 2009 at 16:11 #

    The omnibus has a very low standard of proof. All that the Polings would have to do is show it _could_ have happened. Since it was obvious that a vaccination _could_ cause a fever, gvmt decided to not contest that case.

  8. Sid Offit December 31, 2009 at 21:56 #

    It’s not like it’s a special fever.”

    Since the immune response is immensely complex it’s unwarranted to assume a fever induced by vaccination causes the body to react in the exact same way as it would during natural infection

  9. Sid Offit December 31, 2009 at 21:58 #

    …and why would Hannah not have regressed during all those ear infection induced fevers

  10. Kev December 31, 2009 at 22:15 #

    Why is it unwarranted? I’ll put up the twenty years experience of Gargus against your….opinion, thats a kind word, in the matter.

    re: ear infections – good question. Maybe she did.

  11. Science Mom December 31, 2009 at 23:15 #

    “It’s not like it’s a special fever.”

    Since the immune response is immensely complex it’s unwarranted to assume a fever induced by vaccination causes the body to react in the exact same way as it would during natural infection

    Don’t mistake the cause for a fever with the fever production itself. Unless there is a problem with the hypothalamus, a fever is a fever is a fever.

    …and why would Hannah not have regressed during all those ear infection induced fevers

    And how do you know she didn’t experience cellular deficits during each of her illnesses that may have reached a critical level upon the receipt of that suite of vaccinations? It’s not as though her parents are being transparent and forthcoming with her medical history.

  12. Joseph December 31, 2009 at 23:29 #

    I understand the odds of getting a fever from vaccination is 5%. Meanwhile, a young child will have about 7 viral infections a year. Which is more likely to be a problem?

  13. Joseph December 31, 2009 at 23:32 #
    …and why would Hannah not have regressed during all those ear infection induced fevers

    And how do you know she didn’t experience cellular deficits during each of her illnesses that may have reached a critical level upon the receipt of that suite of vaccinations?

    And even if she didn’t, what’s the point? That’s a statistically meaningless observation. (In other words: mere chance.)

  14. passionlessDrone January 1, 2010 at 01:00 #

    Hi Joseph –

    I understand the odds of getting a fever from vaccination is 5%. Meanwhile, a young child will have about 7 viral infections a year. Which is more likely to be a problem?

    Could you provide a reference for either of these statements? Paul Offit seems to think that the numbers are 4 – 6 per year.

    Further, vaccines represent a minute fraction of what a child’s immune system routinely navigates; the average child is infected with 4–6 viruses per year [32].

    http://www.journals.uchicago.edu/doi/pdf/10.1086/596476?cookieSet=1

    Although, I would admit that it wouldn’t necessarily surprize me to find that you know more than Paul Offit.

    In any case, however, just because something happens sometimes doesn’t mean that you can add additional insults without having an impact.

    In terms of frequency of fever, for example, the pediarix package insert I listed above includes rates of fever, far, far in excess of 5%. [see table 3, on page 15].

    – pD

  15. passionlessDrone January 1, 2010 at 01:15 #

    Hi Science Mom –

    Unless there is a problem with the hypothalamus, a fever is a fever is a fever.

    What if there is a problem (or as they say, a difference), in the triggers that tell the hypothalmus to initiate a change in temprature? We do know that children with autism are more likely to create increased levels of cytokine pyrogens than their undiagnosed peers.

    Differential monocyte responses to TLR ligands in children with autism spectrum disorders

    Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression

    I’m not sure we are nearly clever enough to understand what this means in terms of febrile response.

    And how do you know she didn’t experience cellular deficits during each of her illnesses that may have reached a critical level upon the receipt of that suite of vaccinations?

    Well, from what I’ve read, she had met all developmental milestones previous to her mass vaccination and the attending physician noted no problems. While what you describe is certainly possible, it hadn’t managed to present clincially. Suppose I were to suggest that the vaccines she was given earlier in her life were components in said cellular deficits? Or are we only allowed to flirt with this type of hypothesis if natural infections could be causing the problem?

    – pD

  16. daedalus2u January 1, 2010 at 04:42 #

    A great many antibiotics work by inhibiting protein synthesis by bacteria. Mitochondria use the same ribosome protein as bacteria, and that ribosome protein is inhibited by many of the antibiotics that inhibit the ribosome in bacteria.

    Inhibiting mitochondrial protein synthesis with an antibiotic would make someone a lot more susceptible to a fever induced mitochondrial failure. The type of mitochondria polymorphism that Hannah Poling has (mtDNA T2387C) is in the machinery that synthesizes proteins. Did that make her more susceptible to inhibition by certain antibiotics? That is a good question.

    Some antibiotics bind very tightly to the ribosome protein, and so bacteria can be inhibited by them long after the levels in the blood stream have gone down. Protein synthesis by mitochondria is thought to be an essential part of their long term regulation. That would be most important in tissue compartments where mitochondria are the longest lived, that would be in the nervous system.

    Hannah Poling’s medical records have never been released. It is said that she had many ear infections. If she was given antibiotics for those ear infections that blocked mitochondrial protein synthesis, that may have had a residual effect on her mitochondria, especially on mitochondria in her nervous system. That might explain why she had neuropathy and not liver failure. The mitochondria in the liver turn over much faster than in the nervous system.

  17. Joseph January 1, 2010 at 05:01 #

    @pD: I stand corrected about the chance of fever. It depends on the vaccine, according to CDC data. For the MMR vaccine, that would be 17% chance. For the HepB vaccine, it’s 7%. For the DTaP, it’s 20%.

    About the other stat, Dr. Offit’s figure is probably more accurate (he’s a infectious disease specialist, after all) but I’ve read 7 to 10 in various places, e.g. here.

  18. passionlessDrone January 1, 2010 at 06:37 #

    Hi Joseph –

    About the other stat, Dr. Offit’s figure is probably more accurate (he’s a infectious disease specialist, after all) but I’ve read 7 to 10 in various places, e.g. here.

    I actually think that the real issue here is that this is difficult to track efficiently, or maybe people just haven’t really been trying to track it at all. (?) Take a look at the paper that Mr. Offit used to source this value; it was written in 1964!

    32. Dingle JH, Badger GF, Jordan WS Jr. Illness in the home: a study of 25,000 illnesses in a group of Cleveland families. Cleveland: Press of Western Reserve University, 1964.

    How on Earth he found this paper to use as a source, I don’t know. I tried for a good while to find a oopy and came up blank. I guess it just goes to show you the state of our understanding today; the preeminent infectious disease specialist and expert on autism of our time is using references forty five years old! Oh well!

    – pD

    – pD

    • Sullivan January 1, 2010 at 07:21 #

      “How on Earth he found this paper to use as a source, I don’t know.”

      How hard did you look? In about 2 minutes, I found this link which shows that it isn’t a paper, but a book. Perhaps it is on his shelf? Also, he has access to an academic library. He’s been doing infectious disease research for, what, a few decades now?

      In my search, I found a number of links to articles that cite the book.

      Since you didn’t read the book, how are you sure it isn’t a good reference?

  19. Joseph January 1, 2010 at 15:28 #

    Here’s another study from 1976. It compares children attending day-care vs. those in home care. To summarize, children in day-care get 4 to 5 febrile illnesses in an 8 to 9 month period. So something like 6.3 infections a year.

  20. Science Mom January 2, 2010 at 00:13 #

    Hello pD

    Unless there is a problem with the hypothalamus, a fever is a fever is a fever.

    What if there is a problem (or as they say, a difference), in the triggers that tell the hypothalmus to initiate a change in temprature? We do know that children with autism are more likely to create increased levels of cytokine pyrogens than their undiagnosed peers.

    Differential monocyte responses to TLR ligands in children with autism spectrum disorders

    Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression

    I’m not sure we are nearly clever enough to understand what this means in terms of febrile response.

    I can see how my response would invoke yours but is moot since exogenous and endogenous pyrogens signal the hypothalmus to change the set-point of body temperature, hence a fever is a fever. Hannah Poling does not have autism, nor are mitochondrial disorders caused by immune dysfunction, as far as I know.

    And how do you know she didn’t experience cellular deficits during each of her illnesses that may have reached a critical level upon the receipt of that suite of vaccinations?

    Well, from what I’ve read, she had met all developmental milestones previous to her mass vaccination and the attending physician noted no problems. While what you describe is certainly possible, it hadn’t managed to present clincially. Suppose I were to suggest that the vaccines she was given earlier in her life were components in said cellular deficits? Or are we only allowed to flirt with this type of hypothesis if natural infections could be causing the problem?

    You could certainly suggest that if she experienced sufficient febrile episodes from previous vaccinations, but as Joseph suggested, it doesn’t really matter since it is more likely that she experienced more natural infections preceding her regression. Again, the problem is, is that we are only privy to information that the Polings have been willing to release so all of this is purely speculative anyhow.

  21. Sid Offit January 2, 2010 at 01:07 #

    Review: Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed
    Charles A. Dinarello

    …fever is the result of either cytokine receptor or TLR triggering; in autoimmune diseases, fever is mostly cytokine mediated whereas both cytokine and TLR account for fever during infection.
    —————-

    This paper, while not addressing vaccine induced fever, does indicate that not all fevers are the same

    as does the following:

    Complement reduction impairs the febrile response of guinea pigs to endotoxin
    E. Sehic, S. Li, A. L. Ungar, and C. M. Blatteis

    …increasing evidence is accumulating from various studies that diverse mechanisms may underlie the febrile response. Thus distinct potencies and response profiles have been demonstrated among different pyrogen types, routes of administration, and test species.

  22. passionlessDrone January 2, 2010 at 01:54 #

    Hi Science Mom –

    I can see how my response would invoke yours but is moot since exogenous and endogenous pyrogens signal the hypothalmus to change the set-point of body temperature, hence a fever is a fever.

    Hm. Is a 104 degree fever the same as a 100 degree fever? What about a fever that lasts four days; is that the same as one that lasts overnight? And, as Sullivan mentioned, is a fever at two months of age the same as getting one at a year, or ten years of age?

    Your assertion rests on the notion that there is not a dose relationship between endogenous pyrogens and resultant degree and time length of the fever, something I would would like very much to see you support with references.

    By way of example in the opposite direction:

    Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1

    Recombinant human tumor necrosis factor (rTNF alpha) injected intravenously into rabbits produces a rapid-onset, monophasic fever indistinguishable from the fever produced by rIL-1. On a weight basis (1 microgram/kg) rTNF alpha and rIL-1 produce the same amount of fever and induce comparable levels of PGE2 in rabbit hypothalamic cells in vitro; like IL-1, TNF fever is blocked by drugs that inhibit cyclooxygenase. At higher doses (10 micrograms/kg) rTNF alpha produces biphasic fevers. The first fever reaches peak elevation 45-55 min after bolus injection and likely represents a direct action on the thermoregulatory center. During the second fever peak (3 h later), a circulating endogenous pyrogen can be shown present using passive transfer of plasma into fresh rabbits. This likely represents the in vivo induction of IL-1. In vitro, rTNF alpha induces the release of IL- 1 activity from human mononuclear cells with maximal production observed at 50-100 ng/ml of rTNF alpha.

    If you have some evidence that such a dose relationship doesn’t exist in humans, please post it.

    Or we could just look at the real world, again referencing the pediarix package insert I linked above:

    In a safety study that evaluated medically attended fever after PEDIARIX or separately administered vaccines when coadministered with 7-valent pneumococcal and Hib conjugate vaccines, infants who received PEDIARIX had a higher rate of medical encounters for fever within the first 4 days following the first vaccination.

    If stimulating agent are not salient, and indeed, “a fever is a fever”, why would we observe differential febrile responses in groups receiving different vaccines? Considering these vaccines aren’t acting on the hypothalmus directly, but rather through their triggering of the innate immune response, why should we see different febrile responses with different vaccines? How come the hypothalmus isn’t treating all of them the same?

    Hannah Poling does not have autism, nor are mitochondrial disorders caused by immune dysfunction, as far as I know.

    Hannah Poling has a diagnosis of autism, that has been acknowledged on this board, and everywhere else, many times. To my knowledge, the particular de novo mutation Ms. Poling posses has not been shown to be associated with developmental problems in any study. If I am incorrect, a reference would be nice.

    – pD

  23. Kev January 2, 2010 at 12:26 #

    Sid – unless I’m mistaken, those papers describe the mechanics of fever, not what effect they have or potentially have. In that respect, a fever is a fever is a fever.

    pD – Hannah Poling does (did?) indeed have autism. But thats not to say that the vaccine caused the autism. Even the paper co-authored by John Poling doesn’t carry enough diagnostically appropriate symptoms to say that.

  24. Joseph January 2, 2010 at 17:20 #

    Sid seems to be thinking that if the causes of fever can be of different types, then fevers are of different types as well. This is non-obvious. I could grant that fevers can be of different types in terms of severity and duration, but outside of this, do they actually work differently depending on their cause?

    BTW, based on this study I posted, should children not be put in day-care if they are too young? I’m being pretty serious with that question, but I also wanted to note that perhaps Big Day-Care wants to cover up this information.

  25. Science Mom January 2, 2010 at 17:57 #

    pD, you and Sid seem obsessed with the mechanisms of fever causation, rather than the effect on mitochondria and subsequent depression of ATP production with a mitochondrial disorder. Of course duration and severity of a febrile episode can have a profound effect on mitochondrial function or damage but the cause of the fever is irrelevant, be it via vaccination or natural infection.

    I have also not seen any reliable documentation that states that Hannah Poling was definitively diagnosed with autism, but rather statements such as, “”regressive encephalopathy with features consistent with an autistic spectrum disorder, following normal development.” and, “The clinicians concluded that CHILD was developmentally delayed and demonstrated features of autistic disorder.” From: http://www.huffingtonpost.com/david-kirby/the-vaccineautism-court-_b_88558.html

    To my knowledge, the particular de novo mutation Ms. Poling posses has not been shown to be associated with developmental problems in any study. If I am incorrect, a reference would be nice.

    First, I don’t know what makes you think that her T2387C point mutation is a de novo one and secondly, this is a point mutation on the 16S ribosomal RNA gene and other point mutations on this gene have been associated with encephalopathy: http://www.theness.com/neurologicablog/?p=203 Furthermore, the girl had a biochemical profile that was consistent for mitochondrial function deficits so it is rather difficult to argue that this mutation didn’t have anything to do with clinical manifestations of a mitochondrial disorder and subsequent encephalopathy.

  26. dr treg January 2, 2010 at 18:40 #

    “I could grant that fevers can be of different types in terms of severity and duration, but outside of this, do they actually work differently depending on their cause?”
    Malarial fevers seem to be related to which type of malaria is causing the infection.
    “Paroxysms (of fever) occur every 48 to 72 hours when malaria is caused by P. malariae and every 42 to 50 hours when malaria is caused by P. vivax or P. ovale. All three types have low levels of parasitosis and are self-limiting as a result of early acquired immunity.”

    http://www.wrongdiagnosis.com/m/malaria/book-diseases-7a.htm

    Perhaps the fever profile does correlate with the degree of viraemia in viral infections.
    When looking for the bacterial cause of a fever blood cultures are taken when in-patients “spike a temperature” as the “spike” may be correlated with a surge of bacteria in the blood.
    It does seem that fever may be correlated with the severity of the infection/immunogenic response.

  27. passionlessDrone January 2, 2010 at 19:32 #

    Hi Joseph –

    I could grant that fevers can be of different types in terms of severity and duration, but outside of this, do they actually work differently depending on their cause?

    Very interesting question, I think that to some, ahem, degree, the answer is yes. Take a look at the abstract I posted above:

    Recombinant human tumor necrosis factor (rTNF alpha) injected intravenously into rabbits produces a rapid-onset, monophasic fever indistinguishable from the fever produced by rIL-1. On a weight basis (1 microgram/kg) rTNF alpha and rIL-1 produce the same amount of fever and induce comparable levels of PGE2 in rabbit hypothalamic cells in vitro; like IL-1, TNF fever is blocked by drugs that inhibit cyclooxygenase. At higher doses (10 micrograms/kg) rTNF alpha produces biphasic fevers. The first fever reaches peak elevation 45-55 min after bolus injection and likely represents a direct action on the thermoregulatory center. During the second fever peak (3 h later), a circulating endogenous pyrogen can be shown present using passive transfer of plasma into fresh rabbits. This likely represents the in vivo induction of IL-1. In vitro, rTNF alpha induces the release of IL- 1 activity from human mononuclear cells with maximal production observed at 50-100 ng/ml of rTNF alpha.

    Here, we observe the initiation of a biphasic fever, but only at specific concentrations of the pyrogenic cytokine in question. I guess it could be debated as to if a secondary increase in temperature is really a “different” fever or not, but my view is that if it bothered to be defined, it has distinctive characteristics. But even if we disagreed on this, severity and duration are very important components of a fever.

    I imagine that daedulus2u could speak intelligently towards this question, his post concerning fever therapy is rather robust. Daedulus2u?

    BTW, based on this study I posted, should children not be put in day-care if they are too young? I’m being pretty serious with that question, but I also wanted to note that perhaps Big Day-Care wants to cover up this information.

    Indeed. To my mind this is a similar mass cultural change that has occurred in the past generation that could be having very difficult to understand impacts; very similar to the gradual increase in parental age. By way of example, some studies indicate that attendance at day care is provides protection from asthma, though other studies indicate that this effect is time dependent. But then again, a more recent study found no such protective effect, but did report additional infections in children attending daycare.

    – pD

  28. passionlessDrone January 2, 2010 at 21:44 #

    Hi Science Mom –

    Of course duration and severity of a febrile episode can have a profound effect on mitochondrial function or damage but the cause of the fever is irrelevant, be it via vaccination or natural infection.

    However, the creation of cytokines, which can affect the severity and duration of fever isn’t necessarily equivalent between natural infection and vaccination, especially if, as did Hannah Poling, you get many vaccines simultaneously. Why? Because the toll like receptors which initiate the innate immune response respond synergistically when several are triggered simultaneously.

    Toll-like receptor ligands synergize through distinct dendritic cell pathways to induce T cell responses: Implications for vaccines

    Although TLR ligands individually may be ignored at certain low doses, the host may have evolved to recognize some together as a combinatorial assault and mount immune responses against these combinations in a synergistic manner. This strategy would allow the immune system to rapidly respond to infection. Studies have addressed the questions on what combinations of TLR ligands can synergistically increase the magnitude of cytokine production by DCs (15–22). However, in addition to discovering new synergistic combinations, questions still remain about whether there is a logic to the TLR synergistic patterns that can be identified, what the underlying mechanism is for TLR synergy within target cells, and from a translational point of view, what can be learned for vaccine design.

    We first found that the MyD88-dependent and MyD88-independent DC functions are divergent in response to nonrandom, synergistic TLR ligands. MALP-2- and CpG-ODN-associated MyD88-dependent DC function in producing IL-12, TNF?, and IL-6 was remarkably augmented when poly(I·C) was included.

    If your body believes it is under attack by several agents simultaneously, it responds synergistically; in this observation, by creating aditional pyrogenic cytokines. If our measurement of interest is robustness of the innate immune response, which can in turn affect febrile response, triggering several TLRs at once is qualitatively different than one at a time.

    The argument has long been that getting one vaccine, two vaccine, or eight vaccines at once didn’t make a difference; but clinically we are beginning to understand that this isn’t true.

    – pD

  29. daedalus2u January 3, 2010 at 01:13 #

    The immune system is very complex. The simple symptom of fever may not correlate with the complexity of what is actually going on.

    My research relates to basal levels of NO. These cannot be measured in vivo because there are no techniques to do so. The levels that are important are in the nM/L range, less than a ppb. All immune system responses are characterized by both pro-inflammatory and anti-inflammatory responses. When these two responses are balanced, nothing much bad happens. When they are not balanced, then the patient can die.

    Nitric oxide is mostly an anti-inflammatory agent. Its production during immune system stimulation is balanced by the production of superoxide which is mostly pro-inflammatory. When these two things get out of whack, then the patient dies. In sepsis, too much NO can cause generalized vasodilatation and low blood pressure. That takes a very high NO level, around 10 nM/L (which for NO is very high). Usually NO that is so high that it causes systemic hypotension can be dealt with temporarily (in an ICU). If the high NO goes on for too long, then the patient becomes depleted in glucose and there is insufficient glucose to produce ATP via glycolysis, so the mitochondria have to turn on to generate ATP via oxidation. It is mitochondria turning on in a high NO environment that causes mitochondria failure. I think this is what causes the multiple organ failure of sepsis (my hypothesis).

    Each tissue compartment and each cell, and each mitochondrion regulates the NO/superoxide balance itself. If a few get out of whack, a few mitochondria may be damaged. A few mitochondria are expendable. It probably takes a loss of 50-90% of mitochondria to cause cell death (depending on a lot of other things), but that is really hard to measure.

    What determines the NO level during immune system stimulation is how much iNOS is expressed. That is regulated by NFkB, which is inhibited by NO. So the lower the basal NO level, the higher the NO level will be following immune system stimulation. Much of this NO is generated in immune cells, and these cells move around, and are also controlled by multiple cytokines and also by temperature.

    A high fever is not necessary for a good immune response. I suspect that a vaccine with an adjuvant like aluminum hydroxide would be safer than a vaccine that produces the same antibody titer without an adjuvant. Much of the antigen in an aluminum hydroxide adjuvanted vaccine is sequestered on the aluminum hydroxide and so it takes a longer time for the immune system to process it. That longer time translates into a lower peak level of cytokines and (probably) a reduced peak fever.

    I think that a lot of the malaise effects during fever are a consequence of the interaction between the pro and anti-inflammatory responses. Blocking those responses might (my hypothesis) adversely affect the body’s ability to regulate them and so keep them in balance.

    The immune system is far too complex to be able to predict what is going to happen in great detail, particularly at the extreme ends of the distribution. Vaccines are demonstrably safe for virtually all children; there is no way to predict who they might not be safe for at which time under what conditions. It is inconceivable to me that a vaccine could possibly be worse than the disease. An actual infection with an actual disease agent would almost certainly be far worse than the vaccine which has been demonstrated to be safer in 99.99% of cases, which is about at the limit of what clinical trials can measure.

    Virtually all cases of ASDs are not characterized by neuropathy and are not characterized by mitochondrial dysfunction. An acute vaccination can’t have long term effects on mitochondria unless the regulation of mitochondria biosynthesis is affected long term. There is nothing special about vaccines that would cause long term disruption of mitochondria regulation. An actual infection would be expected to be much worse. If Hannah Poling had gotten one of the diseases she had been vaccinated for, it might have killed her. A single dose of some antibiotics might affect long term regulation of mitochondria (months even). If Hannah Poling was given antibiotics that affected mitochondrial protein synthesis, that might explain her sensitivity to mitochondrial damage. I am speculating, but it might be the combination of an antibiotic and her mitochondrial polymorphism that gave her that increases sensitivity. If so, then the Polings are being reckless by not releasing information on her antibiotic history.

    It isn’t the fever per se that damages neurons. Temperatures have to get very high to do that, it is something associated with the immune response that is associated with the fever that does it. That something is unknown.

  30. dr treg January 3, 2010 at 12:15 #

    “It isn’t the fever per se that damages neurons. Temperatures have to get very high to do that,”
    What studies are there proving that temperature itself does not affect neuronal structure?

  31. Visitor January 3, 2010 at 14:53 #

    Hannah Poling does not have a diagnosis of autism, nor did the court make any finding that MMR can cause autism.

    She was compensated for an encephalopathy – a vaccine act table injury – which the court, on a very low standard of evidence, intentionally set to favor claimants – accepted to have occurred within the time-frame set out in the table.

    Most conspicuously, her claim made no reliance on the work of Dr Andrew Wakefield, Big Pharma’s friend, whose involvement in litigation has devastated the interests of thousands of families in the US and UK.

  32. daedalus2u January 4, 2010 at 01:04 #

    Dr treg, studies of what temperature cause what kind of dysfunction in what types of human cells cannot be done for ethical reasons, so there are no such studies. I am certainly not suggesting that elevated temperature has no effects, just that it seems to me that encephalopathy is more complicated than just elevated temperature.

    Simply because temperature can be measured, and there is elevated temperature, does not mean that the elevated temperature caused what ever adverse effect is observed. In Reyes Syndrome, one of the symptoms besides fever is fatty liver. How does elevated temperature cause fatty liver?

  33. Maggie February 25, 2011 at 20:31 #

    Why the interest in fevers? Fevers have been around forever, Autism has not. I am not a scientist, but it is obvious to me that there is an external factor involved in the sudden dramatic increase in ASD in such a short period of time. You can’t just zero in on the details until you’ve analyzed the bigger picture. What changed so much in our society in the late 1980s to now that can explain this increase in ASDs? I can name a few: High Fructose Corn Syrup (dramatic increase in foods between late 1980s and 1995 – HFCS has mercury http://www.guardian.co.uk/science/2009/jan/27/high-fructose-corn-syrup-mercury), vaccines (increase in number of vaccines/boosters correlates to increase in autism; and you can’t ignore the many reports of regressive autism after receiving a large number of vaccines at same time), new wireless technologies (big companies started selling cellphones in 1988, since then have since continual increase in wireless networks and technologies – http://jama.ama-assn.org/content/305/8/808.abstract); and genetically modified foods were introduced in 1990s with increase since that time – who knows what impact they have on a cellular level.

    All I am saying is people like to nitpick the ‘details’ before they take a step back and evaluate the big picture. Stop looking at JUST thimerosal, or JUST MMR, or JUST fevers, etc. For instance, it is known that what we eat impacts mitochrondrial function, which has a direct impact on how our individual system is able to tolerate and eliminate toxins (which have their own oxidative impact on mitochondria).

    After extensive research on vaccines, I think vaccines play a large role in the neurological disorders we see in our children today, but I also think it is in conjunction with other environmental and nutritional factors. While fevers may be a small part of it, I seriously question the narrow focus on fevers as a cause of type of mitochondrial disorder that in turn leads to ASD while ignoring the more relevant issues right in front of you.

  34. Chris February 25, 2011 at 21:18 #

    Maggie:

    Why the interest in fevers? Fevers have been around forever, Autism has not.

    To help you understand the importance of fevers, please look up what the mitochondria do in cells. If they are disordered, then fevers can cause problems. Which is explained in the article:

    The crux of the matter is fever. Mitochodrial dysfunction appears to be largely triggered by fever. Without the fever there’s no dysfunction. Without the dysfunction theres no autism.

    If you do not understand what mitochondria do, I fear we cannot have much faith in the quality of research you have done on vaccines.

    How do you know autism has not been around for forever? And what possessed you to post on a year old thread?

  35. Julian Frost February 25, 2011 at 22:19 #

    Maggie, as Chris asks, how do you know Autism has not been around for forever? I personally believe that a very strong case can be made that Isaac Newton was autistic. Also, one commenter on a different thread put forward that Joseph, the 11th son of Isaac, was autistic.

  36. Chris February 25, 2011 at 22:55 #

    Indeed, there are thoughts that the myths and legends on “changelings” indicate a form of autism in history. It is also touched upon in Paul Collins’ book Not Even Wrong.

  37. sharon February 25, 2011 at 23:07 #

    Thanks Chris for link to Not Even Wrong. I was about to do the same before I got to your comment.
    I want to add that I believe ASD has been around for a very long time. I just can’t buy the whole ‘recent explosion’ theory. And it seems as if most of those who do, choose to because it fits nicely with their vaccine/mercury/Autism idea. To lecture others about seeing the whole picture when it is clear Maggie that you have not is condescending.

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