Saturday, April 25, 2009

MMR Vaccine, Roseola and Autism

Recently, Dr. Bob Sears made this comment to one of his readers with regards to concerns with a study conducted by Singh et al. in 1998,
What I CAN tell you is that SOME (maybe about 25%) of kids with autism show improvements in some autistic symptoms when they are treated with an anti-viral medication that treats herpes and roseola viruses. I wil [sic] provide more details and research on this issue in the Autism Book next year (so don't ask me to post any more info on that right now). So, roseola virus MAY play a role in some kids' autism.
What we don't know, however, is whether or not getting roseola or another viral illness near the MMR vaccine poses any risk for autism.
Since this scared several moms on the board, we decided to take a look at that and some other papers that infer such an association. Singh et al. had a patient group (with autism) aged 4-12 years old (n=48) with no mention of how these children were selected but blood samples from the autistic group were 'supplied by their parents nationwide'. A 'control' group, if you can even call it that, consisted of serum samples they had from previous studies from non-autistic people aged 5-50 years old (n=34; <12 n="19;">12 years old, n=15).

They did not describe how they set their positive serology criteria, only what they were, nor did they define how many replicates, if any they performed. The information provided is inadequate to reference manufacturers' protocols. Since they were testing for measles IgG and hhv-6 IgG, the former would have, presumably, been acquired via vaccination, the latter by natural infection yet the authors did not ascertain any medical history regarding these parameters. It is also important to note that the brain autoantibody assays were internally validated only, not by any other investigators.

There were no differences between either of the groups in terms of antibodies detected for either measles or hhv-6. In Table 1, there were 6 results in each group left off for the hhv-6 IgG analysis with no explanation as to why. Selection biases were not controlled for since there were no selection criteria to begin with. The anti-MBP and anti-NAFP presences in the autistic group cannot be explained by the mere presence of measles and HHV-6 antibodies without having adequate medical histories on the groups.

Congenital viral illnesses, i.e. in-utero infections, such as rubella, herpes and cytomegalovirus and possibly even transfer of maternal autoantibodies, have been shown to be aetiological agents in the onset of autism in a small subset of children (Yamashita et al. 2003 and Zimmerman et al. 2006). Singh et al. are attempting to establish viral or vaccine-derived autoantibody reactions in children with autism. They say,
This was an excellent rate of seroconversion post-MMR immunisation since virtually all subjects in the study had their MMR immunisations and none had any history of wild-type measles virus infection.
Something is off with this statement since they didn't provide any medical history for any of the subjects and since they didn't detect anti-measles IgG in 18% and 15% of their control and autistic groups, respectively, either something is wrong with the sensitivity of their test and/or virtually all of the subjects were not vaccinated. This is the erroneous conclusion that the authors then make,
As reported here, we found that positive titres of both measles and HHV-6 antibodies are related to brain autoantibodies, I.e., the higher the virus antibody titre the greater the chance of brain autoantibody. Since this chance was higher for measles virus antibody and MBP autoantibody, it is quite possible that the measles infection is an earlier event in autoimmunity to myelin (MBP) whereas HHV-6 infection may exist as a co-infection or reactivation mechanism.
So the authors are inferring a measles infection when they only had antibodies from vaccination and then hhv-6 reacted synergystically with measles vaccination to cause autism. That is quite a leap since they could have found antibodies to anything and correlated those with anti-brain autoantibodies since we don't know the selection criteria and medical histories for the autistic group. Also, they are not presenting any statistical analysis of the relationship between antibody titers. Furthermore, no other clinical findings were reported in the autistic group to support what is nothing more than a hand-waving, free-association.

A related publication by T. Binstock (2001) that appeared in Medical Hypotheses, need we say more? We tried hard to find any science to analyse, but failed. The author just waxes moronically about infections, immune responses and ASD children without a shred, nothing, to support this 'hypothesis'. The author is clearly setting up a post hoc argument using sources that don't support such a conclusion. But to give an example, part of Binstock's hypothesis is predicated upon the observations of wild-type measles infection in monocytes and lymphocytes and of course, the well-known fraudulent and specious report by Wakefield et al. (1998) that measles vaccine virus persists in intestinal M-cells.
The immune impairments associated with autism would, in some individuals, increase the likelihood of significant effects from gastrointestinal pathogens.
What 'immune impairments' associated with autism? The author has leapt over any other aetiologies right to autism is an immune disorder. The author is the founder of 'The Institute for Molecular Introspections', which, unremarkably, has no information about what she does there.

Another related publication by Nicolson et al. (2007), Evidence for Mycoplasma ssp., Chlamydia pneunomiae, and Human Herpes Virus-6 Coinfections in the Blood of Patients With Autistic Spectrum Disorders . also relies upon weak associations and hand-waving. The introduction sets the hypothesis up that infectious organisms are responsible for or exacerbate autism spectrum disorders (ASDs). The authors do this by making tenuous relationships of Mycoplasma spp., Chlamydia pneumoniae and human herpes virus-6 (hhv-6) with ASD children. Their gratuitous use of letters and non-indexed 'studies', along with cherry-picked data from studies describing congenital infections emphasise this grasp to correlate these infections with ASD aetiology and aggravations thereof.

Recruitment was unclear in terms of which support groups they were derived from in addition to how control patients were recruited. They did not perform adequate statistical analyses to determine if the groups were well-matched (more comment on this below). They also mentioned 'routine laboratory test' but did not describe what those were.

No P-value is reported for age analysis between controls and patients. Rural vs. Urban was only examined for patients and there was a high degree of significance ((P<0.05)>Interestingly, though not reported, common diagnoses of illness in the children of Gulf War veterans with mycoplasmal infections included ASD-like illnesses, among others, and we found the same infection, primarily M. fermentans, in both the sick adults and the children in these families. Curiously, this observation is found in their previous work only and don't report what treatments, if any, were offered and subsequent results. Their PCR techniques have only been validated by themselves and there are many other techniques that are far more sensitive and specific. The authors are trying to create a relationship between Gulf War syndrome and ASD via vaccine exposure. They, at least, have the good sense to list some limitations of their study but do not include some of the most glaring ones which is potential exposure. They then go on to make this most interesting statement,
The infections found in ASD patients in the
present and previous studies (Takahashi et al., 2001; Yamashita et al., 2003; Libbey et al., 2005; Nicolson et al., 2003c, 2005b) could have originated from vaccines or from opportunistic infections in immune-suppressed children. Bacterial contamination has been found in commercial vaccines, and in one study 6% of commercial vaccines were contaminated with mycoplasmas (Thornton, 1986). Thus the appearance of infections in children diagnosed with ASD may eventually be linked to the multiple vaccines received during childhood either as a source or from opportunistic infections in immune-suppressed recipients of multiple vaccines.
The paper was published in 2007 and those contaminated vaccines the authors reference were for veterinary, not human use, from over 21 years ago. That is an example of the appalling, inflammatory tactics, inferior investigators must make in order to support their hypotheses. How this paper ever got through peer-review is certainly beyond us. The lead author G.L. Nicolson, refers to himself as professor (I guess PhD is too hackneyed) and is the founder of The Institute for Molecular Medicine which conveniently 'researches' and 'treats' Mycoplasma infections. A closer look at the website shows that according to him, mycoplasma is the cause for almost every illness on the planet and his treatment the cure.

Most children are seropositive to hhv-6, specifically roseola infantum by the age of 2 (Stoekle, M.Y. 2000). It is normally self-limiting but can be associated with febrile seizures in 6-15% during the febrile phase of the illness. Rarely, hhv-6 manifests as encephalitis and fulminant hepatitis (Lewis, 2007). So what does this have to do with the MMR vaccine? Well, it has and will be again, postulated that the MMR vaccine can either 'reactivate' a latent hhv-6 or CMV infection or the MMR vaccine will act synergystically with hhv-6 or CMV infection to cause regressive autism. This is a preposterous notion predicated on the wild assumption that the MMR vaccine causes active measles infection and also that hhv-6 and CMV will somehow exhibit more severe pathology than has been observed. The other postulation is that some autism can be treated with anti-viral therapy. We searched Pubmed and the Cochrane database, but, not surprisingly, there is nothing to support this notion. It is hard to imagine that a therapy that helps 25% of all children should have been missed. It would be dangerous practise to recommend anti-viral therapy be initiated based upon antibody presence alone but rather based upon clinical presentation and confirmation of virus. There is quite clearly no reason to imply hhv-6 in the aetiology of ASDs.

References: Vaccine Discussion Forum. Accessed April 25, 2009.

Binstock T. Intra-monocyte pathogens delineate autism subgroups [abstract]. Med Hypotheses. 2001 Apr;56(4):523-31. Accessed April 25, 2009.

Lewis LS. Pediatrics, Roseola Infantum. Emedicine from WebMD. Accessed April 25, 2009.

Nicolson GL, Gan R, Nicolson NL, Haier J. Evidence for Mycoplasma ssp., Chlamydia
pneunomiae, and Human Herpes Virus-6 Coinfections in the Blood of Patients With Autistic Spectrum Disorders [abstract]. J Neurosci Res. 2007 Apr;85(5):1143-8. Accessed April 25, 2009.

Singh VK, Lin SX, Yang VC. Serological Association of Measles Virus and Human Herpesvirus-6 with Brain Autoantibodies in Autism [abstract]. Clin Immunol Immunopathol. 1998 Oct;89(1):105-8. Accessed April 25, 2009.

Stoeckle MY. The Spectrum of Human Herpesvirus 6 Infection: From Roseola Infantum to Adult Disease [abstract]. Annu Rev Med. 2000;51:423-30.$=citationsensor. Accessed April 25, 2009. PMID: 10774474

Thornton DH. A survey of mycoplasma detection in veterinary vaccines [abstract]. Vaccine. 1986 Dec;4(4):237-40.$=citationsensor. Accessed April 25, 2009. PMID: 3799018

Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, Berelowitz M, Dhillon AP, Thomson MA, Harvey P, Valentine A, Davies SE, Walker-Smith JA. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children [abstract]. Lancet. 1998 Feb 28;351(9103):637-41.$=citationsensor. Accessed April 25, 2009. PMID: 9500320

Yamashita Y, Fujimoto C, Nakajima E, Isagai T, Matsuishi T. Possible Association between Congenital Cytomegalovirus Infection and Autistic Disorder [abstract]. J Autism Dev Disord. 2003 Aug;33(4):455-9. Accessed April 25, 2009.

Zimmerman AW, Connors SL, Matteson KJ, Lee LC, Singer HS, Castaneda JA, Pearce DA. Maternal antibrain antibodies in autism [abstract]. Brain Behav Immun. 2007 Mar;21(3):351-7. Epub 2006 Oct 6. Accessed April 25, 2009

1 comment:

  1. The role of the lawyers in helping should not be ignored here.Their actions deserve to be called into question. Read the article... is astonishing how many millions of public money were wasted by their actions.