May 25 2010

Vaccines – Too Few, Too Late

The anti-vaccine movement is nothing if not savvy about marketing their nonsense – at least in the last decade. One of their successful slogans has been “too many, too soon” – implying that children are receiving too many vaccines while they are still too young to deal with them. The result, anti-vaccinationists argue, is potential neurological toxicity or “overwhelming” the immune system.

The slogan also serves double duty, allowing anti-vaccinationists to argue that they are not “anti-vaccine” just “pro-safe vaccine.” This is just more marketing savvy, however – a deliberate deception, as many of the people who make this claim also state that they would never vaccinate. (Orac has pointed this out many times in great insolent detail.)

But there are some parents who have bought into this notion and have reduced and/or delayed the number of vaccines their children receive in the hopes that they can strike a better balance of risk vs benefit than the experts have struck. And there are fringe doctors, like Dr. Jay Gordon, who promotes his own evidence-free alternate vaccine schedule, playing into the “too many, too soon” meme.

We can argue along theoretical grounds that the vaccine schedule is safe, without making much of a psychological impact.  Paul Offit has pointed out that the environment presents a far greater daily challenge to young immune systems than a few vaccines do. Further the modern vaccine schedule contains fewer antigens (immune provoking substances) than at any time in the last 100 years (because of the elimination of the smallpox vaccine and improvements made to the pertussis vaccine).

We can also point out the safety data for the recommended vaccine schedule and the utter lack of any evidence to support the claim that Dr. Gordon’s or any other alternate schedule is safer. But fear and anecdote are easier spread than reassurance through dry data.

It is always nice, therefore, to have evidence directly comparing the standard schedule vs a delayed and reduced schedule – and now we have that data. A study published just yesterday online in Pediatrics compares neurological outcomes at age 7 and 10 in 1047 children based upon their vaccine schedule. They used publicly available data from a prior study – the VaccineSafety Datalink study of thimerosal exposure which tracked 42 neuropsychological outcomes.

The authors conclude:

Receipt of all recommended childhood vaccines on time in the first year of life in 1993–1997 had no negative impact on neuropsychological outcomes at 7 to 10 years of age, compared with delayed receipt or nonreceipt of >=1 dose during infancy. In fact, children who received each dose of each vaccine on time performed better on 2 of the 42 outcomes tested after adjustment for multiple familial and socioeconomic factors. Those with delayed receipt or nonreceipt of >=1 infant dose did not perform better on any measure.

There were actually 12 outcomes out of 42 that were superior for the on-time group than the delayed group, but only 2 of these held up after multivariable analysis. What this means is that if you take each outcome by itself there was statistical significance for 12, but because you are looking at 42 different variables that is 42 chances to reach statistical significance, and so we would expect a few to be positive by randomness alone. You can compensate for this with multivariable analysis, and after adjusting for multiple comparisons 2 outcomes remained significant in favor of the on-time group.

This could represent just noise in the data, or it could reflect the fact that parents who comply with the vaccine schedule may provide a more nurturing or healthy environment for their children in other ways. It could also reflect a decreased disease burden in vaccinated children.

In any case – the data strongly argues against any benefit from delaying or reducing vaccine. Meanwhile, delaying or skipping vaccines does come with an increased risk of contracting potential serious childhood diseases, like pertussis.

The usual caveats apply – this study is observational and not experimental. The vaccine schedule was chosen by the parents and not randomized or blinded. A randomized trial at this point, however, has serious ethical concerns and for that reason will likely never be done. Parents who believe in vaccines would probably not allow their children to potentially be randomized to a reduced or absent vaccine schedule, and parents fearful of vaccines may not want their children randomized to a full vaccine schedule. So don’t hold your breath for such a study.

Regardless, this is still a solid study and while not definitive is further evidence and reassurance for the safety of the vaccine schedule and the lack of any safety advantage (in fact a potential disadvantage) to alternate vaccine schedules.

Critics are likely to point out that the cohort of patients studied in this trial were born between 1993 and 1997 and the vaccine schedule has increased since then. However, in order to get long term follow up (like the 10 year follow up in this study) you have to look at the vaccine schedule from at least 10 years ago. Also, the schedule today actually has fewer antigens and almost no thimerosal. Further if there were any safety advantage to delaying or reducing the vaccine schedule this study should still have been able to detect it.

We’ll see how Dr. Gordon and other advocates of an alternate vaccine schedule respond to this new evidence. A science-based practitioner should alter what they do as new evidence comes in. But Gordon and the anti-vaccinationists have demonstrated adequately that they are not evidence-based, and prefer to rely more on their instincts.

On a side note – the British doctor, Andrew Wakefield, whose discredited MMR study was largely responsible for spreading fears about vaccines and autism, was recently “struck off” the list of medical doctors in the UK. This essentially means he has lost his license to practice. Although now he is already on to his next career here in the US as a martyr for the anti-vaccine movement, and this latest dishonor will only enhance that career.

_____________

Reference: Michael J. Smith and Charles R. Woods. On-time Vaccine Receipt in the First Year Does Not Adversely Affect Neuropsychological Outcomes. Pediatrics. published online May 24, 2010; DOI: 10.1542/peds.2009-2489

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Addendum:

A letter has been published on the Pediatrics website concerning this study. The author, Lawrence Rosen, points out that the numbers in the results section do not add up. He writes:

If all of the subjects are added as listed, a total of 1037 (not 1047) is obtained. Furthermore, the percentages are incorrect as listed. The final group (311) is in fact 30% of the incorrect total, not 20% as listed.

He is correct, but I think he is using what is essentially a copy edit error to try to discredit publicly available data. The numbers in the tables do add up to 1047 – so one of the numbers copied to the results section was written wrong. The “20%” error is also just a copy mistake and does not affect the data at all. It should be corrected to “30%.”

Dr. Rosen also points out:

Of greater concern to me, personally, is the Financial Disclosure listings. It is very difficult in this day and age to review the authors’ conclusions without considering their considerable potential biases given where their funding comes from. I believe every known vaccine manufacturer is listed on the payroll.

This is the “Conflict of Interest” gambit now common in the anti-vaccine crowd.  Here is the full COI from the paper:

Drs Smith and Woods are or have been unfunded subinvestigators for cross-coverage purposes on vaccine clinical trials for which their colleagues receive funding from Wyeth, Sanofi Pasteur, GSK, MedImmune, and Novartis; and Dr Woods has received honoraria for speaking engagements from Merck, Sanofi Pasteur, Pfizer, and MedImmune and has received research funding from Wyeth and Sanofi Pasteur.

The first part is hardly a conflict – they worked with other researchers without getting paid. Dr. Smith has no other conflicts. Dr. Woods has received some speaking fees and has received research funding from two companies, Wyeth and Sanofi Pasteur.

In other words – they are academic researchers. This does not mean that they are “on the payroll” of pharmaceutical companies, and the COI disclosure says nothing about this study being funded by any company. This is the kind of study that academics can do without external funding, just as part of their academic activities.

But Dr. Rosen is using connections that are ultimately trivial and not relevant to this study as a way to cast doubt on the findings. This is surely to be the strategy of the anti-vaccine movement as a whole, as they have done in the past.

Of course, we need to be vigilant about real conflicts of interest in medical research. But what Dr. Rosen is doing is a COI witch hunt designed to dismiss inconvenient data.

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31 responses so far

31 Responses to “Vaccines – Too Few, Too Late”

  1. mcphadenmikeon 25 May 2010 at 9:31 am

    “Paul Offit has pointed out that the environment presents a far greater daily challenge to young immune systems than a few vaccines do.”

    I said something similar to a friend who was hesitant to vaccinate. His response was, “Then why don’t you feel as crappy as you do after a flu shot every day?” I didn’t have an answer for him.

  2. locutusbrgon 25 May 2010 at 10:22 am

    It is a sad commentary on our society that the news media will rapidly promote, in a inflammatory way, a study about pesticides and ADHD. You will probably not hear a squeak about a study that is not complementary to the Anti-Vax movement.

    One day after a significant outbreak of a deadly but preventable diseases like rubella or pertussis kills children(I hope not), the media outlets will quickly find someone to blame. They will not point at themselves and their own role in this nonsense.

  3. Steven Novellaon 25 May 2010 at 10:59 am

    Vaccines are designed to trigger a robust immune response, enough in some cases to cause minor symptoms. Whereas, our daily exposure to antigens is a constant background of activity – and of course we don’t notice it, because it’s our baseline.

  4. Watcheron 25 May 2010 at 11:05 am

    His response was, “Then why don’t you feel as crappy as you do after a flu shot every day?”

    I’ve never felt crappy after any vaccination. This seems to be a common strategy among people looking to find flaws with vaccination. There is no reason that anyone should “feel crappy” after a vaccine due to the fact that there is no actual infection. I might even suggest that his bias towards vaccines is influencing his mood.

  5. SpicyCupcakeon 25 May 2010 at 11:20 am

    I have seen this too many too soon argument a few times in comment sections with vaccine news articles. I did not know of any studies to do with it. Is this the best study to date?

    Another argument I have seen similar to the schedule upset; the combination vaccines are causing issues. My understanding is that it was originally used people learnt that thimerasole was not the culprit. The stuck to their conclusion that it was vaccines and spotted the correlation between the ages children begin to be diagnosed with autism and the MMR vaccine. I think it is a safe jump that if there is no negative effect associated with less spaced out and earlier vaccination schedules; there is a very low plausibility for a cocktail vaccine to be a cause of problems.

  6. Enzoon 25 May 2010 at 2:44 pm

    mcphadenmike,

    “I didn’t have an answer for him”

    I hate it when I get stuck in something like that! The skeptic really has the burden in that he or she has to know EVERYTHING because the other is typically arguing from a perspective that “makes sense to him or her” ..And the only evidence required is that it “makes sense.”

    Half the hair-brained explanations for things in the anti-vaccination and alternative medicine camp are arguments completely made up so that they make sense to someone that doesn’t have all the facts.

    So frustrating.

  7. hippiehunteron 25 May 2010 at 8:04 pm

    I live a few kilometres away fro Meryl Dorey of the AVN.
    The AVN have spread thier antivaxx lies through this part of the world very effectively and now we are in the middle of a pertussis epidemic with measles making a return too.

    I have a 14 month old boy and my wife is expecting our second child in late November ( we will miss TAM ! …. please do a 2nd show !).

    So I am especially sensitive about this antivaxx crap.
    These people are endangering my children and I am more than a little angry about it.

    Your correct Steve , it is much harder to reassure with dry data than it is to frighten with lies, propaganda and anecdotes, I believe its near impossible, thats why i think we need a legislative approach.

    These people are spreading lies that terrify parents and cause disease and sometimes death to our children.

    Thanks for the article, I believe that stopping the antivaxxers is the most pressing issue facing skeptics at the moment.

    These people are real and present dangers to ours children.

  8. hippiehunteron 25 May 2010 at 8:35 pm

    Oops i meant clear and present danger !
    I shouldn’t type before coffee.

  9. Carlon 26 May 2010 at 7:08 am

    The data is public. Can’t Dr. Rosen, who presumably has no conflicts of interest, re-analyze it himself?

  10. SteveAon 26 May 2010 at 7:29 am

    I know people who have reported feeling ill after a vaccination. Could this be a real effect or is it likely to be psychosomatic?

    Telling people that vaccinations are designed to produce a “robust” response is probably not going to pacify them. The counter argument will be that the vaccination must be “too strong”, or “un-natural” or some such.

    Would it be reasonable to counter with a some sort of “no pain, no gain” argument??

  11. welshandgrumpyon 26 May 2010 at 7:52 am

    Paul Offit chats about the load issue in a great interview with FoundationBeyondBelif – http://bit.ly/9cDeAE

  12. ccbowerson 26 May 2010 at 11:42 am

    “A randomized trial at this point, however, has serious ethical concerns and for that reason will likely never be done.”

    Such a study would be unethical, period. In order to do such a study you would have to argue that we really don’t know which schedule is preferred, when in fact we know that delaying vaccination increases the time that an infant is suceptible to diseases. This is a clear risk that is not arguable. What benefit, even theoretical, could delaying vaccination provide? Neurophysical outcomes? This is not based upon any evidence that I know of (or even theoretical rationale). Since the delayed schedule has a clear risk, and no expectation of benefit… the study cannot (or should not) be done. This relates to the following:

    “But fear and anecdote are easier spread than reassurance through dry data.”

    Of course, we really cannot spend its time countering these fads with more evidence. What I mean is if the evidence is clear enough, but misconceptions are still around because of anectdotes and the marketing of misconception we should not try to counter these with more evidence. This is how we waste resources in science…. spend money on studies that do not add much to our body of knowledge, and take resources away from those that do.

    If misconceptions are still around they have to be countered in a way that is persuasive (but does not offend). It is again a marketing of ideas issue (using the term loosely) and need to be treated as such. Not to say that there are easy answers for these problems, but we have to make sure our approach matches the problem.

  13. ccbowerson 26 May 2010 at 11:58 am

    ‘I know people who have reported feeling ill after a vaccination. Could this be a real effect or is it likely to be psychosomatic’

    This is a real effect, and seems to be associated with a robust immune response. I’m not implying that if you feel fine that there is anything wrong, most people will not notice anything other than injection site discomfort for most vaccinations.

    I might as well through in an anectdote since they seem to more convincing… my daughter had a very brief mild fever after two of her immunization visits when she was an infant, (About 101F and somewhere in the 2-6 months range). The fever lasted less than a day, and she was fine by the next morning. As an aside there is some evidence suggesting that the prohylactic treatment of fever during an immunization may reduce the immune response to the vaccine. The effect is probably small, and there may be reasons to still do it for some children, but routine prophylaxis is not recommended.

  14. BillyJoe7on 27 May 2010 at 7:02 am

    In Australia there have been reports of mass vasovagal attacks in teenage girls after receiving their Gardasil vaccination at school. A study was done that concluded that….well, you guessed it.

  15. passionlessDroneon 27 May 2010 at 12:50 pm

    Hello friends –

    Good stuff. Mr. Rosen is hardly without a conflict of interest as far as I am concerned. Check out a google search and you’ll get sent to a wootastic sounding clinic of some sort.

    That being said, this study still leaves me feeling uneasy. First and foremost, am I the only one that is bothered by the fact that nearly twenty years after an aggressive increase in the vaccination schedule, the best study we have of the cumulative effects of vaccines is a study with 1000 kids whose parents had time to have their children undergo this battery of tests? To me, that tells me we haven’t been doing a very good job of paying attention.

    @CCBowers –

    What benefit, even theoretical, could delaying vaccination provide? Neurophysical outcomes? This is not based upon any evidence that I know of (or even theoretical rationale).

    You might be interested in knowing that there are a great deal of animal studies that indicate that innate immune cytokine surges in early life can have lifelong changes in a variety of areas including seizure succeptibility, behavior, and neuro-immune behavior. For some examples, you might check out work done by Galic, Pittman, or Bilbo in the past three or four years. There have been several expirements that used straight inflammatory cytokines and/or cytokine antibodies to validate that the innate immune response is responsible for these changes. It is difficult to know if the timeframes involved in these studies map strictly to the prenatal timeframe in humans or not, but at the very least should raise some questions over the presumed benevolence of an innate immune response in infants.

    As noted by Mr. Novella, vaccines are designed to initiate a robust immune response, and yet, if you were to search high and low for empirical data on the innate immune response in infants receiving vaccines, you won’t find any. The assumption has always been that the important piece of information is the generation of antibodies, for which you will find a bazillion studies; but studies regarding the innate immune response simply aren’t there.

    Considering also the fact that the autism population has many observations of exaggerated innate immune responses (Enstrom, Ashwood, Jynouchi), or indirect measurements of a more robust innate immune response (Enzo, Grigorenko), this set of infants, could, conceivably, be at increased risk of any effects arising from an early life immune challenge, be it real or simulated.

    So, theoretically, you take a set of infants who are predisposed to react more vigorously to an immune challenge than most children and gradually increase the frequency and robustness of the vaccine schedule during infancy. If our succeptible subgroup is sufficiently small, one in a few hundred, our chances of detecting a relationship in the study like the one above seem miniscule.

    - pD

  16. trrllon 27 May 2010 at 6:26 pm

    “This is a real effect, and seems to be associated with a robust immune response”

    It probably is real in most cases (I’ve never experienced it myself); on the other hand, it is typically so mild that you probably would not remember it if it hadn’t happened the day after vaccination. It would just be one of many cases of “I felt a bit run-down today, maybe I didn’t get enough sleep.” Or “I thought for a day or two that maybe I was coming down with something, but I guess I shook it off.”

  17. EliminateVariableson 27 May 2010 at 9:20 pm

    I am surprised so many here keep a blind eye to how studies are simply thrown together.

    I found this study skeptical at first, simply because of the authors and there heavily influenced bottom lines with the Pharmaceutical Industry. While I have no problem with someone making a buck or two, many of these individuals makes an obscene amount on top of their generous salaries.

    Does this influence a study…?

    Is bias created…?

    The next part may be hard for some to fathom but behind this study:

    Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years
    http://content.nejm.org/cgi/content/full/357/13/1281

    under:

    supplementary appendix pdf.
    http://content.nejm.org/cgi/content/full/357/13/1281/DC1

    You will find a list 3 pages long of those excluded from the study.

    We see:

    VIRAL MENINGITIS NEC
    VIRAL MENINGITIS NOS
    VIRAL ENCEPHALITIS NEC
    VIRAL ENCEPHALITIS NOS
    HEMOPHILUS MENINGITIS
    PNEUMOCOCCAL MENINGITIS
    STREPTOCOCCAL MENINGITIS
    STAPHYLOCOCC MENINGITIS
    ANAEROBIC MENINGITIS
    MNINGTS GRAM-NEG BCT NEC
    BACTERIAL MENINGITIS NOS
    CHRONIC MENINGITIS
    MENINGITIS NOS
    RICKETTSIAL ENCEPHALITIS
    OTH ENCEPHALIT D/T INFEC
    POSTINFECT ENCEPHALITIS
    ENCEPHALITIS NOS
    INTRACRANIAL ABSCESS
    PHLEBITIS INTRCRAN SINUS
    LATE EFF CNS ABSCESS

    I still have 2 1/2 pages to go through and I have already seen 20 exclusions which cause neurological disorders.

    How do you propose a study could be done to find neurological disorders when you exclude anything that could cause neurological disorders…..?

    This was quoted in the actual study:

    “Children were excluded if they had certain conditions recorded
    in their medical records that could bias neuropsychological testing (e.g., encephalitis, meningitis, or hydrocephalus)”

    …………..?

    So after reviewing the entire study, methodology, exclusion criteria and general structure…..Is this considered a study to base
    Neuropsychological Outcomes at 7 to 10 Years in vaccinated children….I would say it failed miserably and judging by the authors it does not surprise me.

    Does it surprise you the authors leave us with this:

    “Future VSD studies without this restriction would be able to assess a wider range of outcomes. These include putative vaccine adverse effects such as neurodevelopmental delay, autism, and autoimmune disorders.”

    I would say many have been duped but will they admit it…?

    It is unethical to continue to vaccinate when faulty studies like this are used as evidence. I am sure there are 1047….oops..1037 children unvaccinated that could be used as a control.

  18. BillyJoe7on 28 May 2010 at 12:08 am

    PD

    “If our succeptible subgroup is sufficiently small, one in a few hundred, our chances of detecting a relationship in the study like the one above seem miniscule. ”

    Yes, this is what the anti-vaccination crowd are reduced to, complaining that a small undetectable subgroup of children could maybe, possibly, perhaps be affected adversely by vaccines.

    Even if that was the case, it would not constitute a reason not to vaccinate, but perhaps a reason to identify that small subgroup if, in fact, the existence of such a group was considered to be at all plausible.

  19. Steven Novellaon 28 May 2010 at 12:29 pm

    eliminatevariables – ironic user name. The whole point of the study was to isolate vaccines as a variable. If you include children that have other neurological disorders that will contaminate the statistics – then we would have the anti-vaxers complaining (with some validity) that the real effect was diluted by the inclusion of kids with neurological disorders in the analysis.

    Your final conclusion is absurd, and does not even reflect the state of the evidence. There is overwhelming evidence for vaccine safety and effectiveness. One could argue that it is unethical not to vaccinate.

  20. passionlessDroneon 28 May 2010 at 4:05 pm

    Hi BillyJoe7 –

    Even if that was the case, it would not constitute a reason not to vaccinate, but perhaps a reason to identify that small subgroup if, in fact, the existence of such a group was considered to be at all plausible.

    It might be best if we attempt not to assign arguments that haven’t been made. I haven’t advocated stopping vaccinations. Likely, if I were to state that vaccines are not 100% safe you would point out you haven’t made this argument.

    In any case, regarding the biological plausability of the autism population as a group more succeptible to unexpected effects from vaccination, we have a growing body of evidence much less vague that the ‘immune system abnormalities’ clause that frequently gets thrown around in this type of discussion. In fact, we have a number of studies that clearly tell us that the innate immune system is highly dsyregulated in autism towards a more vibrant innate immune response. As noted by Mr. Novella above, vaccines are designed to initiate an immune response. The end result is an adaptive memory of a pathogen, but to get there, you have to trigger the innate immune response first. In all likelyhood, the reason that some people get fevers, or feel ill post vaccination is the result of the innate immune response, pro-inflammatory cytokines are known to participate in the generation of fever and are also associated with ‘sick behavior’ in animal models.

    In 2008, Grigorenko (1) found that an identified promoter allele for the MIF gene was associated with an autism diagnosis in two groups of children from Europe and the US. Furthermore, circulating levels of MIF were higher in the autism group than controls; and in fact, as MIF levels increased within the autism group, autistic severity worsened. MIF is a known upregulator of toll like receptors, the gate keepers of the immune system that initiate the innate immune response. The authors studied MIF exactly for this reason; its known effect on upregulating the immune response and a corresponding inflammatory environment during critical developmental timeframes:

    Thus, the central hypothesis underlying this research was that a genetic predisposition to a particular level of MIF production may lead to a proinflammatory profile of cell activation that, if present during a neurodevelopmentally sensitive period, might contribute to the etiopathogenesis of autism.

    In 2010, Enzo (2) reported that levels of HMGB1, another known upregulator of toll like receptors was also increased in the autism population, and again found that as levels of HMGB1 increased, so too, did autism behaviors.

    When we test the effects of stimulating the immune system in vitro, we find that the autism group creates more pro-inflammatory cytokines, primarily TNF-alpha, IL-6, and IL-1B than the control group. This has been demonstrated in Enstrom, Ashwood, and Jynouchi. (3,4,5).

    If we want to paint a scenario wherein the autism population reacts no differently to vaccination than their non diagnosed peers, we need to find a reason for all of our expiremental observations to be wrong in the same way, and for our knowledge how of MIF or HMGB1 operate to be different within the autism population specifically.

    The question as towards wether or not an exaggerated innate immune response could be a causal participant in autism means we need to look towards the studies performed using animal models of early life immune challenges I referenced earlier. There are more than a dozen studies that show that a robust innate immune response during critical developmental timeframes is capable of causing lifelong outcomes in the animals including disturbances to the HPA-Axis, increased succeptibility to seizures, and altered neuro-immune functioning; all of which have similarities or strong parallels to the autism realm. Specifically, Galic, Spenser, Ellis, and Bilbo (6,7,8,9, 10) are very compelling studies in this regard, but there are many others. All of this research is very new, within the past four years, long, long after the drastic increase in the number of shots given to our infants. I am willing to stipulate that these effects, if present in humans, may only be factors in the prenatal environment, but this possibility is not a good foundation for which to stand behind the absolute lack of the study of vaccination as opposed to thimerosal, or the effects of an individual vaccine (the MMR), given much, much later than the bulk of our schedule, in the autism realm.

    - pD

    References

    1. Macrophage Migration Inhibitory Factor and Autism Spectrum Disorders [Grigorenko, 2008]

    2. Increased serum levels of high mobility group box 1 protein in patients with autistic disorder. [Enzo, 2010]

    3. Differential monocyte responses to TLR ligands in children with autism spectrum disorders [Enstrom, 2010]

    4. Preliminary evidence of the in vitro effects of BDE-47 on innate immune responses in children with autism spectrum disorders [Ashwood, 2009]

    5. Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression [Jyomouchi, 2001]

    6. Postnatal programming of the innate immune response [Galic, 2009]

    7. Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats [Galic, 2008]

    8. Early-life immune challenge: defining a critical window for effects on adult responses to immune challenge [Spenser, 2006]

    9. Long term alterations in neuroimmune responses of female rats after neonatal exposure to lipopolysaccharide [Spenser, 2005]

    10. Neonatal programming of the rat neuroimmune response: stimulus specific changes elicited by bacterial and viral mimetics [Ellis, 2006]

    11. Early-life programming of later-life brain and behavior: a critical role for the immune system [Bilbo, 2009]

  21. Carlon 28 May 2010 at 7:29 pm

    passionlessDrone, would you mind giving actual references? Just the year and article title is not all that useful. Any of these from major journals? Available online?

  22. passionlessDroneon 29 May 2010 at 12:02 am

    Hi Carl –

    would you mind giving actual references? Just the year and article title is not all that useful. Any of these from major journals? Available online?

    Will the journal titles and PMIDs help? Many are available online in full.

    1. Macrophage Migration Inhibitory Factor and Autism Spectrum Disorders [Grigorenko, 2008, Pediatrics] PMID: 18676531 [Full version available online]

    2. Increased serum levels of high mobility group box 1 protein in patients with autistic disorder. [Enzo, 2010, Progress in Neuro-Psychopharmacology and Biological Psychiatry] PMID: 20302902

    3. Differential monocyte responses to TLR ligands in children with autism spectrum disorders [Enstrom, 2010, Brain, Behavior and Immunity] PMID: 19666104

    4. Preliminary evidence of the in vitro effects of BDE-47 on innate immune responses in children with autism spectrum disorders [Ashwood, 2009, Journal of Neuroinflammation] PMID: 19211157 [Full version available online]

    5. Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression [Jyomouchi, 2001, Jounral of Neuroinflammation] PMID: 11694332

    6. Postnatal programming of the innate immune response [Galic, 2009, Integrative and Comparative Biology] No PMID available [full version available online]

    7. Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats [Galic, 2008, Journal of Neuroscience] PMID: 18596165 [full version available online]

    8. Early-life immune challenge: defining a critical window for effects on adult responses to immune challenge [Spenser, 2006, Neuropsychopharmacology] PMID: 16395304 [full version available]

    9. Long term alterations in neuroimmune responses of female rats after neonatal exposure to lipopolysaccharide [Spenser, 2005, Brain Behavior and Immunity] PMID: 16226008

    10. Neonatal programming of the rat neuroimmune response: stimulus specific changes elicited by bacterial and viral mimetics [Ellis, 2006, Journal of Physiology]. PMID: 16423854 [full version available online]

    11. Early-life programming of later-life brain and behavior: a critical role for the immune system [Bilbo, 2009, Frontiers in Behavioral Neuroscience] PMID: 19738918 [full version availalbe online]

    I’m not qualified to comment on the prestige of these journals, except, if I am not mistaken, Pediatrics is considered a ‘major’ journal. Does this help?

    - pD

  23. BillyJoe7on 29 May 2010 at 3:13 am

    PD,

    “It might be best if we attempt not to assign arguments that haven’t been made.”

    You must have missed my introductory sentence “Yes, this is what the anti-vaccination crowd are reduced to.”

    Oh well. :(

  24. BillyJoe7on 29 May 2010 at 3:16 am

    …unless you are claiming that the anti-vaccination crowd has not made that argument. But you couldn’t be claiming that. Could you?

  25. ccbowerson 29 May 2010 at 10:18 am

    Passionless-

    We already know that autism has a genetic component to its cause, and it is not a surprise that autistic children may be different in several ways. The problem is that we are hung up on the vaccine thing when there appears to be nothing there. What you are pointing to is some basic research, which is interesting but does not provide much insight into the question we are discussing.

    The whole reason why vaccines are in the discussion was a fraud, but people keep wating to cling to something. There have been several large trials attempting to find an association between vaccines and autism, and all have been negative. Now there is the argument that there is a specific subpopulation within the larger, and that is an unsubstantiated claim. Of course you can always make that argument when studies are negative, but you need some real proof of this.

    There are studies that indicate that there likely is no large increase in autism at all, but due to better detection of the disease. Do you think 20 years ago the average parent even knew what autism was? The problem is that no matter what research is done some people will still claim that more is needed, but we can never do double blind placebo controlled trials on this issue. There are enough studies on the topic to conclude that there is likely nothing there, and more money into the vaccine idea is talking money away from other areas, (like genetic or other environmental factors). Lets not let irrational fears dictate where reasearch dollars should go

  26. passionlessDroneon 29 May 2010 at 10:43 am

    Hi BillyJoe7 –

    You must have missed my introductory sentence “Yes, this is what the anti-vaccination crowd are reduced to.”

    The problem to my mind is that I do not consider myself part of the “anti-vaccination” crowd, and therefore, would not like to have their arguments assigned to me.

    For example, I have absolutely no doubt that vaccines work at preventing disease and that they have saved millions and millions of lives. I also have no doubt that herd immunity is real, and the idea of widespread vaccination refusal has very real and dangerous implications for the return of diseases.

    It is entirely possible to believe this while simultaneously recognizing the frailty of our existing understanding of the effects of vaccination.

    You might be surprised to find that I consider myself a skeptic. The facts on the ground are that here in 2010, decades after we began aggressively incresing our vaccine schedule, we have exactly one study that tests for the effects of cumulative vaccination on neurological outcomes. When the overriding narrative is that ‘the question has been answered, this level of supporting data bugs the heck out of me.

    The underlying assumption of vaccination has always been that an a robust innate immune response is harmless absent the pathogenic mechanisms of the actual bacterial or viral organism. To illustrate this, try to find a study that shows the innate immune parameters in infants pre and post vaccination. I am making the assertion that thesee studies do not exist. Instead of worrying about what the “anti-vaccination crowd” may or may not say, why don’t you try posting a study like this to allay my concerns?

    - pD

  27. passionlessDroneon 29 May 2010 at 11:04 am

    Hi CCBowers –

    We already know that autism has a genetic component to its cause, and it is not a surprise that autistic children may be different in several ways. The problem is that we are hung up on the vaccine thing when there appears to be nothing there. What you are pointing to is some basic research, which is interesting but does not provide much insight into the question we are discussing.

    What I have posted here is also a small subset of the data regarding the immune dysfunction involved in autism, and less than half of our data concerning early life immune challenges in animal models. Similarly to what I have told BillyJoe7, the very idea that immune activation in early life could have lifelong consequences is a very new idea. I will not argue against a very strong genetic component to autism; I happen to think that with a condition that manifests as heterogeneously as autism, there will likely be a great number of roads to the same behavioral endpoint.

    I for one, am not particularly hung up on the vaccine thing, but it happens to represent 99% of the online conversations involving autism. I do happen to be alarmed at how weak our existing research is when compared to how strong it is portrayed.

    There have been several large trials attempting to find an association between vaccines and autism, and all have been negative. Now there is the argument that there is a specific subpopulation within the larger, and that is an unsubstantiated claim. Of course you can always make that argument when studies are negative, but you need some real proof of this.

    But those trials have not been about vaccines and autism! They have been about thimerosal, or a single vaccine, the MMR, which is given much, much later in life than the bulk of our schedule. Seriously, try going to pubmed and finding a signle study regarding autism and vaccination that does not
    involve one of those two parameters. They aren’t there. The fact that this study is ‘news’ ough to clue you as to why your assertion is incorrect. A single trial with one thousand children that included none with autism.

    If you look at references 7 and 8 I posted above, you will see that the authors found time-dependencies of effect, in other words, there was only an impact on the animal if the challenge occurred within specific developmental timeframes. For that reason, making broad assumptions that studying the MMR is a valid proxy for the entire vaccine schedule is a big, massive confound that ought to drive a rationalist up the wall. We don’t give the MMR at two months for very good reasons, why should we expect that the generation of antibodies is the only a system as complicated as the immune system?

    There are studies that indicate that there likely is no large increase in autism at all, but due to better detection of the disease. Do you think 20 years ago the average parent even knew what autism was? The problem is that no matter what research is done some people will still claim that more is needed, but we can never do double blind placebo controlled trials on this issue. There are enough studies on the topic to conclude that there is likely nothing there, and more money into the vaccine idea is talking money away from other areas, (like genetic or other environmental factors). Lets not let irrational fears dictate where reasearch dollars should go

    I am well aware of the arguments involving diagnostic substitution, increased “awareness” and a broadening of the criteria for autism. For the record, I’ll state that I have no doubt that these things are having an impact on our rates of autism.

    But, these concepts also ought to be driving a skeptic mad; they are completely unfalsifiable and maleable to whatever the latest counts are on the ground. For example, if autism rates quintipled next year, what would keep us from just saying, “Well, greater awareness. It can’t be real!”? We’d have exactly the same rationale, and evidence, that we’ve been using as a crutch for the past decade.

    This has already happened if you pay close attention; we have several studies that show advanced parental age has a small effect on autism risk, nowhere near large enough to account for our observations, but still very likely real. It also has a biologically plausaible mechanism behind it. Now, the narrative is along the lines of “Well, advanced parental age is contributing to our observations of increase, but the rest is due to diagnostic changes.” If you dig deeper, and try to figure out how such a conclusion can be made with certainty, there’s nothing there except for expediency to a favored conclusion.

    I happen to think that the potential ramifications of a true increase in autism are too goddamned important to leave up to the soft scientists.

    I appreciate your tone. Thank you.

    - pD

  28. BillyJoe7on 29 May 2010 at 6:11 pm

    PD,

    “The problem to my mind is that I do not consider myself part of the “anti-vaccination” crowd, and therefore, would not like to have their arguments assigned to me. ”

    Again, I was clearly referring to “the anti-vaccination crowd”. If you assumed that I was including you in that group, I can only reiterate that I did not have that in mind when I wrote that response.

  29. ccbowerson 30 May 2010 at 8:19 am

    Passionlessdrone-
    I agree that the research has not specifically addressed the question you have put forth because it is SO broad. You are basically arguing the possibility of too much too soon, but with every limited basic research to back that up. Try to think of a satisfactory study design to address that broad question. I can’t because no matter how you altered the schedule someone could still say too much too soon. It is really a prblem of moving the goalpost. First it was MMR, then thimerosal, now its this. This is what I mean about being stuck on vaccines… how did we get to this point?

    My point about the genetic link is that autistic children are likely very different in many ways, and the basic research you point to is just further evidence of that.

    “these concepts also ought to be driving a skeptic mad”

    Well the world is full of grays. Most diseases are multifactorial, complex, and we should just get used to it. Very few things are like Huntington’s or even lung cancer.

  30. chrisdbarryon 25 Jun 2010 at 4:53 am

    And now the epidemics begin:

    http://blogs.discovermagazine.com/badastronomy/2010/06/23/whooping-cough-now-an-epidemic-in-california/

  31. andrew23on 27 Jun 2010 at 5:58 pm

    Hello, Sir,

    This is a story which may be of some interest to you. Thank-you.

    NaturalNews) A 16-year-old girl lost nearly all of her vision within 10 days of receiving the second course of her vaccine against the human papilloma virus (HPV), reports a case study in the Journal of Child Neurology.

    The HPV vaccine is designed to prevent infection by the strains of the virus that are responsible for the majority of cervical cancer and genital warts cases.

    The study recounts the case of a previously healthy teenage girl who developed a headache on the left side of her head and began to lose vision in her right eye eight days after receiving her second HPV vaccine shot. Over the course of the following 48 hours, the pain spread across her head and she began to lose sight in her left eye as well.

    At this point, the girl went to the emergency room, where doctors found her vital signs to be normal with no indication of infection or systemic illness. While under supervision, her vision continued to deteriorate until she was able to identify light and movement only from the left eye, and then only inconsistently. She reported no symptoms prior to the onset of headache and vision loss and had not experienced any recent disease or trauma.

    Further examination revealed demyelination in her brain and along her optic nerves. In demyelination, characteristic of multiple sclerosis and similar diseases, the protective myelin sheath around nerve cells degrades, leading to interrupted nerve signaling.

    Eighteen months after her initial visit, the teenager had recovered from her weakness but her vision had not improved.

    Although the HPV vaccine is widely promoted for teenage girls, its safety and effectiveness have primarily been tested in women over the age of 18. No evidence yet exists that vaccination reduces rates of genital warts or cervical cancer, or deaths from cervical cancer.

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