ETA 1.4.16: Gary Goldman and Neil Miller failed to disclose their conflicts of interest to Human and Experimental Toxicology. The corrigendum is here.
oh goodness, here I wanted to go to bed early and then I stumbled over this latest "peer reviewed" paper in a journal "indexed by the National Library of Medicine" (see the anti-vaccine faction gloating at those fantastic quality indicators) and "proving" with an correlation co-efficient of 0.992 and a p of 0.0009 (so "sciencey") that:
Nations requiring the most vaccines tend to have the worst infant mortality rates
Authors of this little gem, in the journal Human & Experimental Toxicology, with the impressive impact factor of 1.307 and a proud ranking of 58th of 77 in the area of Toxicology (yes, that would put them into the bottom quarter) are Think Twice's own Neil Z. Miller and Medical Veritas' Gary S. Goldman. I wonder why Miller and Goldman didn't publish their paper in Medical Veritas (here is the link to the journal, please don't go blind), seeing that item 7 in their mission is: "Create a movement to address the adverse vaccine reactions and vaccine-related injuries afflicting children and adults". I guess that is because parents have clued in that "peer review" and being indexed on PubMed is a quality measure (although very obviously no guarantee for quality).
In any case - Miller and Goldman took a list of countries and looked at the number of vaccines they schedule for infants and they also looked at infant mortality. And then they correlated one with the other, a fail safe way to find causal relationships: Storks deliver babies p=0.008.
There are a number of things wrong with this procedure - first of all, the way Miller and Goldman are counting vaccines is completely arbitrary and riddled with mistakes.
Arbitrary: they count number of vaccines in US bins (DTaP is one, hib is separate) and non-specific designations (some "polio" is still given as OPV in Singapore), rather than antigens. If they did that, Japan, still giving the live bacterial vaccine BCG, would immediately go to the top of the list. That wouldn't fit the agenda, of course. But if you go by "shot" rather than by antigen, why are DTaP, IPV, hepB and hib counted as 4 shots for example in Austria, when they are given as Infanrix hexa, in one syringe?
Mistakes: The German childhood vaccination schedule recommends DTaP, hib, IPV AND hepB, as well as PCV at 2, 3 and 4 months, putting them squarely into the 21 - 23 bin. The fourth round of shots is recommended at 11 to 14 months, and MenC, MMR and Varicella are recommended with a lower age limit of 11 months, too, which means that a number of German kids will fall into the highest bin, at least as long as you count the Miller/Goldman way.
Then, they neatly put those arbitrarily counted doses into bins. Binning (i.e. grouping numbers before correlating them to something) always makes me suspicious. I don't have the time to check each country's vaccination schedule - I assume there will be mistakes in many claims, but I am guessing that if we plotted the infant mortality against the actual number of recommended vaccines, the correlation would be less good than engineered in this paper, i.e. the dose count above is probably not all that "arbitrary".
Then I noticed that the authors totally ignore historical trends. For example, in the early 1980ies, Germany's infant mortality was about 5 times as high (10000 infants died per year) than it is today (2000 died in 2009 with approximately the same birth rate), however (in Miller's and Goldman's twisted logic), the vaccination schedule contained far fewer vaccines in the first year (essentially just DT and polio, since the whole cell pertussis was not given between 1974 and 1991, the aP not yet introduced, the MMR given in year 2, no hib, nor hepB, nor PCV given either), while Germany was already very much a "developed country".
ETA: a similar point is made by Prometheus on Science based Medicine for the declining infant mortality rate in the US.
If I believed that one factor could ever explain something as complex as infant mortality, I would go and look at the relationship of maternity leave:
Japan, for example, generally gives 14 weeks at an average of 40% of a woman's salary and mothers are also entitled to childcare leave for their new baby's first year. Childcare laws dictate that in the first year of her baby's life, a mother may take two 30-minute breaks per day to care for her child (anyone else think breastfeeding?). She may also take time off any time during the baby's first year with one month's notice.
In Sweden, all working parents are entitled to up to 16 months of paid parental leave, Norway is similarly generous. Read the table and weep, US American parents!
In the bottom countries, the USA gives 0 months of parental leave, the FMLA offers some (up to 12 weeks) generally unpaid leave under very specific conditions. Heck - Botswana and Chad have better rules. Australia has 18 weeks (not months, like Norway) at minimal wage, but then, Canada, third worst in infant mortality has up to a year of parental leave at almost $2000 a month and that is where my crude correlation fails (although, if I binned some countries...a cunning plan).
ETA: Dr. Gorski picks up on some other flaws of this study - read his post.
In general, several large studies/meta-analyses NOT cited by Miller and Goldman, have indicated that if vaccines have anything to do with infant death, then as a protective factor, as this German study and meta-analysis and this large study from the UK.
To prevent SIDS (specified 10 May after comment):
put your baby "back to sleep"
do not smoke
breastfeed if at all possible (easier in countries with 18 months of paid maternity leave)
avoid loose bedding and soft mattresses or sofas
do not bed share when intoxicated, or smoker, or taking medicine that may make you drowsy, but keep your baby in your room
keep the sleep environment cool and don't overdress your baby
That is it.
Monday, May 9, 2011
Sunday, May 8, 2011
Still no independent confirmation of Wakefield's claims
One of the things that anti-vaccines groups desperately want to have, is the scientific support for their claims. A lot of parents know that rigorous studies, peer reviewed, published in scientific journals and indexed on Pubmed are the standard in discussions about medical care. Therefore, the anti-vaccine brigade are trying to maintain that, really, countless scientific studies across the globe have shown that vaccines are bad for you.
The anti-vaccine, pro-any-conspiracy theory website Whale.to (the citation of which automatically invokes Skopie's Law), provides a neat shopping list that staunch supporters of the long debunked “MMR causes inflammation of the gut which somehow causes autism and Andrew Wakefield is really a hero” notion can use to spam evidence based discussions, as recently seen on the Shot of Prevention blog where Marsha McClelland of the “We the People United for VaccineEducation Misinformation” Yahoo group copied and pasted in support for Andrew Wakefield.
She “writes”:
Note the buzz word “peer reviewed“ – also note the fundamental misconception that anyone would give a toss whether Wakefield believes that Wakefield was correct.
She goes on:
That – Martha and friends – is because no one (apart from Wakefield and his buddies) has ever been able to replicate Wakefield’s claims. I had previously looked at 5 studies supposedly „independently“ replicating Wakefield, but this list was 28 citations long (I guess the length is supposed to duly impress AND to keep anyone from checking). To quote Kenneth Branagh: “There is safety in numbers”. Luckily, both Chris and Liz Ditz were bothered enough to spend their valuable time to debunk the list (THANK YOU!) – I have created a synthesis of their and my previous searches and comments to create the “one stop copy and paste resource for the evidence minded”. Links add extra depth - sorry about the length, it may exceed the number of characters allowed for blog comments...
To summarize re-using Martha’s words: you may have been tricked into believing that Andrew Wakefield’s claims had been independently verified in 28 publications from 5 different countries. I’m afraid that is false. For those of you who have swallowed this type of reporting hook line and sinker, the below debunks each of the 28 studies from around the world that have been cited in his support.
1. The Journal of Pediatrics November 1999; 135(5):559-63 =
Horvath K., Papadimitriou J.C., Rabsztyn A., Drachenberg C., Tilden J.T. 1999. Gastrointestinal abnormalities in children with autism. J. Pediatrics 135: 559-563.
This study did not look for measles virus. Instead it looks at gastrointestinal (GI) malabsoption as an underlying mechanism for autism. It does not appear to have controls with autism & without GI symptoms OR controls without autism & with similar GI symptoms. Most children with autism & GI symptoms had upper GI problems such as reflux
This in no way “replicates” or “supports” Wakefield’s “findings”, which have been shown repeatedly to have been manufactured or the result of laboratory contamination.
2. The Journal of Pediatrics 2000; 138(3): 366-372 =
Furlano RI, Anthony A, Day R, Brown A, McGarvey L, Thomson MA, Davies SE, Berelowitz M, Forbes A, Wakefield AJ, Walker-Smith JA, Murch SH. Colonic CD8 and T cell filtration with epithelial damage in children with autism. J Pediatr 2001;138:366-72.
This paper claims to have "confirm[ed] a distinct lymphocytic colitis in autistic spectrum disorders", which is something that no other research groups find and has been the center of the recent GMC hearings against Wakefield. The extreme "engineering" towards a specific gut pathology has been summarized by Brian Deer.
Note the emergence of a theme: Wakefield is a co-author and no fewer than 7 of this paper's authors are also authors on the retracted paper in The Lancet; this paper cannot be said to independently ”replicate” or “support” Wakefield’s “findings”.
3. Journal of Clinical Immunology November 2003; 23(6): 504-517 =
Ashwood P, Anthony A, Pellicer AA, Torrente F, Wakefield AJ. Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology. Journal of Clinical Immunology, 2003;23:504-517.
Again, this paper seeks to further claim "a pan-enteric mucosal immunopathology in children with regressive autism that is apparently distinct from other inflammatory bowel diseases", but we know that Wakefield et al. are the only researchers who have "found" this in the past 15 or so years.
Same theme: Wakefield (and Anthony) is a co-author; cannot be said to support his own work.
4. Journal of Neuroimmunology 2005
A meaningless citation as this would be a whole volume of a journal - this happens if you just copy and paste without any regard to the content. Supports nothing except maybe the notion that the anti-vaccine folk cannot cite biomedical literature properly.
If you go back to whale.to, John was kind enough to link to to the paper, which is
Ashwood P, Wakefield AJ. Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms. J Neuroimmunol. 2006 Apr;173(1-2):126-34.
doesn't mention MMR, instead, the authors start from their own wrong premise "Gastrointestinal pathology, characterized by lymphoid nodular hyperplasia and entero-colitis, has been demonstrated in a cohort of children with autistic spectrum disorder (ASD)." and continue to find "In both peripheral blood and mucosa, [intracellular] CD3+ TNFalpha+ and CD3+ IFNgamma+ were increased in ASD children" ,
has Wakefield as senior author, therefore no independent replication of his results.
5. Brain, Behavior and Immunity 1993; 7: 97-103 =
Singh VK, Warren RP, Odell JD, Cole WP. Antibodies to myelin basic protein in children with autistic behavior. Brain, Behavior and Immunity 1993;7:97-103
Found some but not all children with autism had specific antibodies to myelin basic protein (MBP). Study did not look for measles virus, nor did study look for mumps or rubella virus or administration of the MMR.
It precedes the Lancet paper and in no way ”replicates” or “supports” Wakefield’s claims.
6. Pediatric Neurology 2003; 28(4): 1-3 Citation not found.
According to whale.to, this is
Singh VK, Jensen RL Elevated levels of measles antibodies in children with autism Pediatric Neurology 2003; 28(4): 292-294.
To the best of our knowledge, this study has not been replicated, and the findings refuted by several other studies, such as Baird G, Pickles A, Simonoff E, Charman T, Sullivan P, Chandler S, Loucas T, Meldrum D, Afzal M, Thomas B, Jin L, Brown D. Measles vaccination and antibody response in autism spectrum disorders. Arch Dis Child. 2008 Oct;93(10):832-7.
This study does not support Wakefield’s claims.
7. Neuropsychobiology 2005; 51:77-85 =
Jyonouchi H, Geng L, Ruby A, Zimmerman-Bier B. Dysregulated Innate Immune Responses in Young Children with Autism Spectrum Disorders: Their Relationship to Gastrointestinal Symptoms and Dietary Intervention. Neuropsychobiology. 2005;28:51 77-85
This study did not look for measles virus but evaluated inflammatory response to specific dietary proteins.
In no way ”replicates” or “supports” Wakefield’s “findings”
8. The Journal of Pediatrics May 2005;146(5):605-10 =
Jyonouchi H, Geng L, Ruby A, Reddy C, Zimmerman-Bier B. Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders. J Pediatr.2005;146(5):605-10.
This study did not look for measles virus. Instead, the study evaluated inflammatory response to specific dietary proteins.
In no way ”replicates” or “supports” Wakefield’s “findings”
9. Autism Insights 2009; 1: 1-11 citation not found on PubMed, but this refers to Krigsman, A. , Boris, M., Goldblatt, A., Stott, C. Clinical presentation and histologic findings at ileocolonoscopy in children with autistic spectrum disorder and chronic gastrointestinal symptoms Autism Insights 2010:2 1-11.
Arthur Krigsman was a colleague of Andrew Wakefield at Thoughtful House, Wakefield and Carol Stott (a contributor to this paper) are editors of the vanity press journal Autism Insights (previously discussed on LBRB. Not very likely that this "peer review" was very tough.
In no way ”replicates” or “supports” Wakefield’s “findings”
10. Canadian Journal of Gastroenterology February 2009; 23(2): 95-98 =
Galiatsatos P, Gologan A, Lamoureux E, Autistic enterocolitis: Fact or fiction? Can J Gastroenterol. 2009:23:95-98
Case report, featuring two adult patients with gastrointestinal problems and ASD diagnoses. The authors call for “more investigations” in their discussion.
In no way ”replicates” or “supports” Wakefield’s “findings”
11. Annals of Clinical Psychiatry 2009:21(3): 148-161 =
Singh VK. Phenotypic expression of autoimmune autistic disorder (AAD): a major subset of autism. Ann Clin Psychiatry. 2009 Jul-Sep;21(3):148-61.
This paper makes assertions that are not supported by the evidence base in the paper. It is mainly a summary of research, with no mention of what children were looked at. Chris found the actual paper (https://www.aacp.com/Pages.asp?AID=7937&issue=&page=C&UID=), and among the data used it included a Wakefield paper = not independent. Also included in the references are papers from questionable journals like Journal of American Physicians and Surgeons and Medical Veritas, which all suddenly makes sense if you see that Singh is associated with these folk that tick the "our treatment heals everything" quack box (see one Singh study on PTSD).
This looks like it would support a connection between MMR and autism, but since no-one has independently reproduced this and the author stands to make money off the claims this review has to be viewed with extreme reservations.
12. Journal of Child Neurology June 29, 2009; 000:1-6 =
whale.to provides the pre-print, hence the missing volume and page numbers:
Genuis S.J., Bouchard, T.P. Celiac Disease Presenting as Autism, J Child Neurol January 2010 25(1):114-119
This paper proposes that many children with autism have celiac disease, that this causes micro nutrient deficiencies and that the behaviour of the children improves when you put them on a gluten free diet. No MMR mentioned.
Does not support Wakefield's claims.
13. Journal of Autism and Developmental Disorders March 2009;39(3):405-13 =
Nikolov RN, Bearss KE, Lettinga J, Erickson C, Rodowski M, Aman MG, McCracken JT, McDougle CJ, Tierney E, Vitiello B, Arnold LE, Shah B, Posey DJ, Ritz L, Scahill L. Gastrointestinal symptoms in a sample of children with pervasive developmental disorders. J Autism Dev Disord. 2009 Mar;39(3):405-13.
This study did not look for measles virus, nor did study look for mumps or rubella virus. Study evaluated children previously diagnosed with pervasive developmental disorders (PDDs) for gastrointestinal (GI) symptoms. 22.7% were found to exhibit GI symptoms, but were otherwise no different from subjects without GI problems in demographic characteristics, measures of adaptive functioning, or autism symptom severity.
In no way ”replicates” or “supports” Wakefield’s “findings”
14. Medical Hypotheses August 1998;51:133-144. =
Bolte, ER Autism and Clostridium tetani Medical Hypotheses August 1998;51:133-144.
Speculative paper presenting the hypothesis that autism symptoms are caused by a subacute, chronic tetanus infection
In no way ”replicates” or “supports” Wakefield’s “findings”
15. Journal of Child Neurology July 2000; ;15(7):429-35 =
Sandler RH, Finegold SM, Bolte ER, Buchanan CP, Maxwell AP, Väisänen ML, Nelson MN, Wexler HM. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol. 2000;15:429-435
This study did not look for measles virus. Instead, this study evaluated 11 children’s response to a specific antibiotic. Gains faded following cessation of antibiotic.
In no way “replicates” or “supports” Wakefield’s “findings”
16. Lancet. 1972;2:883-884 =
Walker-Smith J, Andrews J. Alpha-1-antitrypsin, autism, and coeliac disease. Lancet. 1972 Oct 21;2(7782):883-4.
This is a "letter to the editor" published decades prior to the Wakefield Lancet paper and can hardly be said to “replicate” the latter. Walker-Smith and Andrews report on the investigation of alpha-1-antitrypsin levels in 8 children with autism vs in children with untreated and treated celiac disease and control children and finds levels in children with autism and celiac disease are similar. This has little to do with Wakefield or the MMR (it also predates the introduction of the MMR), however, Dr. Walker-Smith is a co-author of the retracted study in The Lancet.
In no way “replicates” or “supports” Wakefield’s “findings”
17. Journal of Autism and Childhood Schizophrenia January-March 1971;1:48-62 =
Goodwin MS, Cowen MA, Goodwin TC Malabsorption and cerebral dysfunction: a multivariate and comparative study of autistic children. J Autism Child Schizophr. 1971 Jan-Mar;1(1):48-62.
A paper published decades previously cannot be said to “replicate” a later paper, the paper predates the introduction of the MMR vaccine in the US, the authors are not concerned with vaccination at all, but is mainly concerned with finding distinguishing features between childhood autism and adult schizophrenia using a number of challenges and physiological measurement. One minor in their discussion is that "malabsorption" would lead to autistic behaviour, so more in the sense of paper 12.
In no way “replicates” or “supports” Wakefield’s “findings”
18. Journal of Pediatrics March 2001;138:366-372.
Same paper as #2 above. Wakefield and 6 others from the Lancet paper are co-authors; cannot be said to support their own work.
In no way ”replicates” or “supports” Wakefield’s “findings”
19. Molecular Psychiatry 2002;7:375-382. Torrente F., Machado N., Perez-Machado M., Furlano R., Thomson M., Davies S., Wakefield AJ, Walker-Smith JA, Murch SH. Enteropathy with T cell infiltration and epithelial IgG deposition in autism. Molecular Psychiatry. 2002;7:375-382.
Gosh, we know these guys – it’s Andy Wakefield and his colleagues from that paper in The Lancet, this time claiming IgG deposit in gut samples indicative of an autoimmune gut pathology and call me cynical, but I don't believe any of this, because it has only ever been seen by this group.
In no way ”replicates” or “supports” Wakefield’s “findings”
20. American Journal of Gastroenterolgy April 2004;598-605.=
Torrente F, Anthony A, Heuschkel RB, Thomson MA, Ashwood P, Murch SH. Focal-enhanced gastritis in regressive autism with features distinct from Crohn’s and Helicobacter pylori gastritis. Am J Gastroenterol. 2004;99:598-605
Murch SH, Anthony A, Thompson MA, Torrente F and Ashwood P were previous co-authors with Wakefield A. Again, there are no independent groups reporting similar findings and this does not look at MMR or any vaccine anyway.
In no way ”replicates” or “supports” Wakefield’s “findings”
21. Journal of Clinical Immunology November 2003;23:504-517 =
Ashwood P, Anthony A, Pellicer AA, Torrente F, Walker-Smith JA, Wakefield AJ. Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology. J Clin Immunol. 2003 Nov;23(6):504-17.
We totally get it by now – Wakefield and Wakefield’s colleagues confirm their own results.
In no way ”replicates” or “supports” Wakefield’s “findings”
22. Neuroimmunology April 2006;173(1-2):126-34 =
Ashwood P, Wakefield AJ. Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms. J Neuroimmunol. 2006;173(1-2):126-34.
same as number 4.
23. Prog. Neuropsychopharmacol Biol Psychiatry December 30 2006;30:1472-1477 =
Shinohe A, Hashimoto K, Nakamura K, Tsujii M, Iwata Y, Tsuchiyaa KJ, Sekine Y, Suda S, Suzuki K, Sugihara G, Matsuzaki H, Minabe Y, Sugiyama T, Masayoshi Kawai M, Iyo M,Takei N and Mori N Increased serum levels of glutamate in adult patients with autism- Progress in Neuro-Psychopharmacology and Biological Psychiatry Volume 30, Issue 8, 30 December 2006, Pages 1472-1477
Study of adults with autism on blood levels of amino acids, to assess whether altered glutamatergic neurotransmission was likely in autism. Study did not look for measles virus, nor did study look for mumps or rubella virus or anything connected with the gut.
In no way “replicates” or “supports” Wakefield’s “findings”
24. Clinical Infectious Diseases September 1 2002;35(Suppl 1):S6-S16 =
Finegold SM, Molitoris D, Song Y, Liu C, Vaisanen ML, Bolte E, McTeague M, Sandler R, Wexler H, Marlowe EM, Collins MD, Lawson PA, Summanen P, Baysallar M, Tomzynski TJ, Read E, Johnson E, Rolfe R, Nasir P, Shah H, Haake DA, Manning P, Kaul A. Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis. 2002 Sep 1;35(Suppl 1):S6-S16.
Stool samples from children with regressive autism were compared to samples from children without autism; differences in stool flora were found. The study did not look for measles virus, nor did it look for mumps or rubella virus. Study did not evaluate changes in gut structure.
In no way “replicates” or “supports” Wakefield’s “findings”
25. Applied and Environmental Microbiology, 2004
Another of those citation snafus -
Song Y, Liu C, Finegold SM. Real-time PCR quantitation of clostridia in feces of autistic children. Appl Environ Microbiol. 2004 Nov;70(11):6459-65.
This study describes how to do PCR for specific bacteria on stool samples of autistic and non autistic children.
In no way “replicates” or “supports” Wakefield’s “findings”
26. Journal of Medical Microbiology October 2005;54:987-991 =
Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005 Oct;54(Pt 10):987-91.
More in the same vein: This study compared fecal flora for children with autism with two control groups: siblings without autism and unrelated children without autism. Minor differences were found. The study did not look for measles virus, nor did study look for mumps or rubella virus. Study did not evaluate changes in gut structure.
In no way “replicates” or “supports” Wakefield’s “findings”
27. Archivos venezolanos de puericultura y pediatría 2006; Vol 69 (1): 19-25. = González LG., López K, Navarro DC, Negrón L, Flores LS, Rodríguez R, Martínez M, Sabrá A. Características endoscópicas, histológicas e inmunológicas de la mucosa digestiva en niños autistas con síntomas gastrointestinales [Endoscopic and Histological Characteristics of the Digestive Mucosa in Autistic Children with gastro-Intestinal Symptoms] Archivos Venezolanos de Puericultura y Pediatría Enero-Marzo 2006, Volúmen 69, Número 1 Arch Venez Pueri Pediatr 2006 69(1):19-25. 1.
The authors cannot replicate Wakefield’s 1998 “findings” of a distinct autistic enterocolitis, although they do report a higher incidence of gastrointestinal problems in their autistic group. 2. It appears that the Gonzalez paper was funded by Thoughtful House, under Wakefield’s leadership as previously shown
In no way “replicates” or “supports” Wakefield’s “findings”
28. Gastroenterology. 2005:128 (Suppl 2);Abstract-303 =
Balzola F, Daniela C, Repici , Barbon V, Sapino A, Barbera C, Calvo PL, Gandione M, Rigardetto R*, and Rizzetto M .
This is a meeting abstract that has never been published as a peer reviewed study since 2005. Nine adult males with autism and GI symptoms were evaluated for GI disease. Study did not look for measles virus, nor did study look for mumps or rubella virus. Study did not evaluate changes in gut structure.
In no way “replicates” or “supports” Wakefield’s “findings”
Numbers: of 28 studies 2 were duplicates, 3 were only retrievable because of the links on the whale.to page, 13 were written by Wakefield and/or Lancet co-authors and/or Thoughful House colleagues (counting two duplicates), 3 predate the Lancet paper by years or even decades and not one independently replicates Wakefield’s claims, made in the retracted Lancet paper, the associated press conference and in many statements since.
The anti-vaccine, pro-any-conspiracy theory website Whale.to (the citation of which automatically invokes Skopie's Law), provides a neat shopping list that staunch supporters of the long debunked “MMR causes inflammation of the gut which somehow causes autism and Andrew Wakefield is really a hero” notion can use to spam evidence based discussions, as recently seen on the Shot of Prevention blog where Marsha McClelland of the “We the People United for Vaccine
She “writes”:
In the years after his initial controversial finding, linking the MMR vaccine to Crohn’s disease and autism, he published another 19 papers on the vaccine-induced disorder.
All were peer reviewed. However, strangely enough, none of these 19 papers are ever discussed in the media. The only study that keeps seeing the light of day is the original study from 1998, along with the original questions about conflicts of interest, which he explains in great detail in this interview. (my comment - that refers to the Mercola interview with Andrew Wakefield).
Note the buzz word “peer reviewed“ – also note the fundamental misconception that anyone would give a toss whether Wakefield believes that Wakefield was correct.
She goes on:
This is very interesting indeed, because not only has he continued his own studies, but since then, a large number of replication studies have been performed around the world, by other researchers, that confirm his initial findings.
It’s been replicated in Canada, in the US., in Venezuela, in Italy [but] they never get mentioned. All you ever hear is that no one else has ever been able to replicate the findings.
That – Martha and friends – is because no one (apart from Wakefield and his buddies) has ever been able to replicate Wakefield’s claims. I had previously looked at 5 studies supposedly „independently“ replicating Wakefield, but this list was 28 citations long (I guess the length is supposed to duly impress AND to keep anyone from checking). To quote Kenneth Branagh: “There is safety in numbers”. Luckily, both Chris and Liz Ditz were bothered enough to spend their valuable time to debunk the list (THANK YOU!) – I have created a synthesis of their and my previous searches and comments to create the “one stop copy and paste resource for the evidence minded”. Links add extra depth - sorry about the length, it may exceed the number of characters allowed for blog comments...
To summarize re-using Martha’s words: you may have been tricked into believing that Andrew Wakefield’s claims had been independently verified in 28 publications from 5 different countries. I’m afraid that is false. For those of you who have swallowed this type of reporting hook line and sinker, the below debunks each of the 28 studies from around the world that have been cited in his support.
1. The Journal of Pediatrics November 1999; 135(5):559-63 =
Horvath K., Papadimitriou J.C., Rabsztyn A., Drachenberg C., Tilden J.T. 1999. Gastrointestinal abnormalities in children with autism. J. Pediatrics 135: 559-563.
This study did not look for measles virus. Instead it looks at gastrointestinal (GI) malabsoption as an underlying mechanism for autism. It does not appear to have controls with autism & without GI symptoms OR controls without autism & with similar GI symptoms. Most children with autism & GI symptoms had upper GI problems such as reflux
This in no way “replicates” or “supports” Wakefield’s “findings”, which have been shown repeatedly to have been manufactured or the result of laboratory contamination.
2. The Journal of Pediatrics 2000; 138(3): 366-372 =
Furlano RI, Anthony A, Day R, Brown A, McGarvey L, Thomson MA, Davies SE, Berelowitz M, Forbes A, Wakefield AJ, Walker-Smith JA, Murch SH. Colonic CD8 and T cell filtration with epithelial damage in children with autism. J Pediatr 2001;138:366-72.
This paper claims to have "confirm[ed] a distinct lymphocytic colitis in autistic spectrum disorders", which is something that no other research groups find and has been the center of the recent GMC hearings against Wakefield. The extreme "engineering" towards a specific gut pathology has been summarized by Brian Deer.
Note the emergence of a theme: Wakefield is a co-author and no fewer than 7 of this paper's authors are also authors on the retracted paper in The Lancet; this paper cannot be said to independently ”replicate” or “support” Wakefield’s “findings”.
3. Journal of Clinical Immunology November 2003; 23(6): 504-517 =
Ashwood P, Anthony A, Pellicer AA, Torrente F, Wakefield AJ. Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology. Journal of Clinical Immunology, 2003;23:504-517.
Again, this paper seeks to further claim "a pan-enteric mucosal immunopathology in children with regressive autism that is apparently distinct from other inflammatory bowel diseases", but we know that Wakefield et al. are the only researchers who have "found" this in the past 15 or so years.
Same theme: Wakefield (and Anthony) is a co-author; cannot be said to support his own work.
4. Journal of Neuroimmunology 2005
A meaningless citation as this would be a whole volume of a journal - this happens if you just copy and paste without any regard to the content. Supports nothing except maybe the notion that the anti-vaccine folk cannot cite biomedical literature properly.
If you go back to whale.to, John was kind enough to link to to the paper, which is
Ashwood P, Wakefield AJ. Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms. J Neuroimmunol. 2006 Apr;173(1-2):126-34.
doesn't mention MMR, instead, the authors start from their own wrong premise "Gastrointestinal pathology, characterized by lymphoid nodular hyperplasia and entero-colitis, has been demonstrated in a cohort of children with autistic spectrum disorder (ASD)." and continue to find "In both peripheral blood and mucosa, [intracellular] CD3+ TNFalpha+ and CD3+ IFNgamma+ were increased in ASD children" ,
has Wakefield as senior author, therefore no independent replication of his results.
5. Brain, Behavior and Immunity 1993; 7: 97-103 =
Singh VK, Warren RP, Odell JD, Cole WP. Antibodies to myelin basic protein in children with autistic behavior. Brain, Behavior and Immunity 1993;7:97-103
Found some but not all children with autism had specific antibodies to myelin basic protein (MBP). Study did not look for measles virus, nor did study look for mumps or rubella virus or administration of the MMR.
It precedes the Lancet paper and in no way ”replicates” or “supports” Wakefield’s claims.
6. Pediatric Neurology 2003; 28(4): 1-3 Citation not found.
According to whale.to, this is
Singh VK, Jensen RL Elevated levels of measles antibodies in children with autism Pediatric Neurology 2003; 28(4): 292-294.
To the best of our knowledge, this study has not been replicated, and the findings refuted by several other studies, such as Baird G, Pickles A, Simonoff E, Charman T, Sullivan P, Chandler S, Loucas T, Meldrum D, Afzal M, Thomas B, Jin L, Brown D. Measles vaccination and antibody response in autism spectrum disorders. Arch Dis Child. 2008 Oct;93(10):832-7.
This study does not support Wakefield’s claims.
7. Neuropsychobiology 2005; 51:77-85 =
Jyonouchi H, Geng L, Ruby A, Zimmerman-Bier B. Dysregulated Innate Immune Responses in Young Children with Autism Spectrum Disorders: Their Relationship to Gastrointestinal Symptoms and Dietary Intervention. Neuropsychobiology. 2005;28:51 77-85
This study did not look for measles virus but evaluated inflammatory response to specific dietary proteins.
In no way ”replicates” or “supports” Wakefield’s “findings”
8. The Journal of Pediatrics May 2005;146(5):605-10 =
Jyonouchi H, Geng L, Ruby A, Reddy C, Zimmerman-Bier B. Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders. J Pediatr.2005;146(5):605-10.
This study did not look for measles virus. Instead, the study evaluated inflammatory response to specific dietary proteins.
In no way ”replicates” or “supports” Wakefield’s “findings”
9. Autism Insights 2009; 1: 1-11 citation not found on PubMed, but this refers to Krigsman, A. , Boris, M., Goldblatt, A., Stott, C. Clinical presentation and histologic findings at ileocolonoscopy in children with autistic spectrum disorder and chronic gastrointestinal symptoms Autism Insights 2010:2 1-11.
Arthur Krigsman was a colleague of Andrew Wakefield at Thoughtful House, Wakefield and Carol Stott (a contributor to this paper) are editors of the vanity press journal Autism Insights (previously discussed on LBRB. Not very likely that this "peer review" was very tough.
In no way ”replicates” or “supports” Wakefield’s “findings”
10. Canadian Journal of Gastroenterology February 2009; 23(2): 95-98 =
Galiatsatos P, Gologan A, Lamoureux E, Autistic enterocolitis: Fact or fiction? Can J Gastroenterol. 2009:23:95-98
Case report, featuring two adult patients with gastrointestinal problems and ASD diagnoses. The authors call for “more investigations” in their discussion.
In no way ”replicates” or “supports” Wakefield’s “findings”
11. Annals of Clinical Psychiatry 2009:21(3): 148-161 =
Singh VK. Phenotypic expression of autoimmune autistic disorder (AAD): a major subset of autism. Ann Clin Psychiatry. 2009 Jul-Sep;21(3):148-61.
This paper makes assertions that are not supported by the evidence base in the paper. It is mainly a summary of research, with no mention of what children were looked at. Chris found the actual paper (https://www.aacp.com/Pages.asp?AID=7937&issue=&page=C&UID=), and among the data used it included a Wakefield paper = not independent. Also included in the references are papers from questionable journals like Journal of American Physicians and Surgeons and Medical Veritas, which all suddenly makes sense if you see that Singh is associated with these folk that tick the "our treatment heals everything" quack box (see one Singh study on PTSD).
This looks like it would support a connection between MMR and autism, but since no-one has independently reproduced this and the author stands to make money off the claims this review has to be viewed with extreme reservations.
12. Journal of Child Neurology June 29, 2009; 000:1-6 =
whale.to provides the pre-print, hence the missing volume and page numbers:
Genuis S.J., Bouchard, T.P. Celiac Disease Presenting as Autism, J Child Neurol January 2010 25(1):114-119
This paper proposes that many children with autism have celiac disease, that this causes micro nutrient deficiencies and that the behaviour of the children improves when you put them on a gluten free diet. No MMR mentioned.
Does not support Wakefield's claims.
13. Journal of Autism and Developmental Disorders March 2009;39(3):405-13 =
Nikolov RN, Bearss KE, Lettinga J, Erickson C, Rodowski M, Aman MG, McCracken JT, McDougle CJ, Tierney E, Vitiello B, Arnold LE, Shah B, Posey DJ, Ritz L, Scahill L. Gastrointestinal symptoms in a sample of children with pervasive developmental disorders. J Autism Dev Disord. 2009 Mar;39(3):405-13.
This study did not look for measles virus, nor did study look for mumps or rubella virus. Study evaluated children previously diagnosed with pervasive developmental disorders (PDDs) for gastrointestinal (GI) symptoms. 22.7% were found to exhibit GI symptoms, but were otherwise no different from subjects without GI problems in demographic characteristics, measures of adaptive functioning, or autism symptom severity.
In no way ”replicates” or “supports” Wakefield’s “findings”
14. Medical Hypotheses August 1998;51:133-144. =
Bolte, ER Autism and Clostridium tetani Medical Hypotheses August 1998;51:133-144.
Speculative paper presenting the hypothesis that autism symptoms are caused by a subacute, chronic tetanus infection
In no way ”replicates” or “supports” Wakefield’s “findings”
15. Journal of Child Neurology July 2000; ;15(7):429-35 =
Sandler RH, Finegold SM, Bolte ER, Buchanan CP, Maxwell AP, Väisänen ML, Nelson MN, Wexler HM. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol. 2000;15:429-435
This study did not look for measles virus. Instead, this study evaluated 11 children’s response to a specific antibiotic. Gains faded following cessation of antibiotic.
In no way “replicates” or “supports” Wakefield’s “findings”
16. Lancet. 1972;2:883-884 =
Walker-Smith J, Andrews J. Alpha-1-antitrypsin, autism, and coeliac disease. Lancet. 1972 Oct 21;2(7782):883-4.
This is a "letter to the editor" published decades prior to the Wakefield Lancet paper and can hardly be said to “replicate” the latter. Walker-Smith and Andrews report on the investigation of alpha-1-antitrypsin levels in 8 children with autism vs in children with untreated and treated celiac disease and control children and finds levels in children with autism and celiac disease are similar. This has little to do with Wakefield or the MMR (it also predates the introduction of the MMR), however, Dr. Walker-Smith is a co-author of the retracted study in The Lancet.
In no way “replicates” or “supports” Wakefield’s “findings”
17. Journal of Autism and Childhood Schizophrenia January-March 1971;1:48-62 =
Goodwin MS, Cowen MA, Goodwin TC Malabsorption and cerebral dysfunction: a multivariate and comparative study of autistic children. J Autism Child Schizophr. 1971 Jan-Mar;1(1):48-62.
A paper published decades previously cannot be said to “replicate” a later paper, the paper predates the introduction of the MMR vaccine in the US, the authors are not concerned with vaccination at all, but is mainly concerned with finding distinguishing features between childhood autism and adult schizophrenia using a number of challenges and physiological measurement. One minor in their discussion is that "malabsorption" would lead to autistic behaviour, so more in the sense of paper 12.
In no way “replicates” or “supports” Wakefield’s “findings”
18. Journal of Pediatrics March 2001;138:366-372.
Same paper as #2 above. Wakefield and 6 others from the Lancet paper are co-authors; cannot be said to support their own work.
In no way ”replicates” or “supports” Wakefield’s “findings”
19. Molecular Psychiatry 2002;7:375-382. Torrente F., Machado N., Perez-Machado M., Furlano R., Thomson M., Davies S., Wakefield AJ, Walker-Smith JA, Murch SH. Enteropathy with T cell infiltration and epithelial IgG deposition in autism. Molecular Psychiatry. 2002;7:375-382.
Gosh, we know these guys – it’s Andy Wakefield and his colleagues from that paper in The Lancet, this time claiming IgG deposit in gut samples indicative of an autoimmune gut pathology and call me cynical, but I don't believe any of this, because it has only ever been seen by this group.
In no way ”replicates” or “supports” Wakefield’s “findings”
20. American Journal of Gastroenterolgy April 2004;598-605.=
Torrente F, Anthony A, Heuschkel RB, Thomson MA, Ashwood P, Murch SH. Focal-enhanced gastritis in regressive autism with features distinct from Crohn’s and Helicobacter pylori gastritis. Am J Gastroenterol. 2004;99:598-605
Murch SH, Anthony A, Thompson MA, Torrente F and Ashwood P were previous co-authors with Wakefield A. Again, there are no independent groups reporting similar findings and this does not look at MMR or any vaccine anyway.
In no way ”replicates” or “supports” Wakefield’s “findings”
21. Journal of Clinical Immunology November 2003;23:504-517 =
Ashwood P, Anthony A, Pellicer AA, Torrente F, Walker-Smith JA, Wakefield AJ. Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology. J Clin Immunol. 2003 Nov;23(6):504-17.
We totally get it by now – Wakefield and Wakefield’s colleagues confirm their own results.
In no way ”replicates” or “supports” Wakefield’s “findings”
22. Neuroimmunology April 2006;173(1-2):126-34 =
Ashwood P, Wakefield AJ. Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms. J Neuroimmunol. 2006;173(1-2):126-34.
same as number 4.
23. Prog. Neuropsychopharmacol Biol Psychiatry December 30 2006;30:1472-1477 =
Shinohe A, Hashimoto K, Nakamura K, Tsujii M, Iwata Y, Tsuchiyaa KJ, Sekine Y, Suda S, Suzuki K, Sugihara G, Matsuzaki H, Minabe Y, Sugiyama T, Masayoshi Kawai M, Iyo M,Takei N and Mori N Increased serum levels of glutamate in adult patients with autism- Progress in Neuro-Psychopharmacology and Biological Psychiatry Volume 30, Issue 8, 30 December 2006, Pages 1472-1477
Study of adults with autism on blood levels of amino acids, to assess whether altered glutamatergic neurotransmission was likely in autism. Study did not look for measles virus, nor did study look for mumps or rubella virus or anything connected with the gut.
In no way “replicates” or “supports” Wakefield’s “findings”
24. Clinical Infectious Diseases September 1 2002;35(Suppl 1):S6-S16 =
Finegold SM, Molitoris D, Song Y, Liu C, Vaisanen ML, Bolte E, McTeague M, Sandler R, Wexler H, Marlowe EM, Collins MD, Lawson PA, Summanen P, Baysallar M, Tomzynski TJ, Read E, Johnson E, Rolfe R, Nasir P, Shah H, Haake DA, Manning P, Kaul A. Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis. 2002 Sep 1;35(Suppl 1):S6-S16.
Stool samples from children with regressive autism were compared to samples from children without autism; differences in stool flora were found. The study did not look for measles virus, nor did it look for mumps or rubella virus. Study did not evaluate changes in gut structure.
In no way “replicates” or “supports” Wakefield’s “findings”
25. Applied and Environmental Microbiology, 2004
Another of those citation snafus -
Song Y, Liu C, Finegold SM. Real-time PCR quantitation of clostridia in feces of autistic children. Appl Environ Microbiol. 2004 Nov;70(11):6459-65.
This study describes how to do PCR for specific bacteria on stool samples of autistic and non autistic children.
In no way “replicates” or “supports” Wakefield’s “findings”
26. Journal of Medical Microbiology October 2005;54:987-991 =
Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005 Oct;54(Pt 10):987-91.
More in the same vein: This study compared fecal flora for children with autism with two control groups: siblings without autism and unrelated children without autism. Minor differences were found. The study did not look for measles virus, nor did study look for mumps or rubella virus. Study did not evaluate changes in gut structure.
In no way “replicates” or “supports” Wakefield’s “findings”
27. Archivos venezolanos de puericultura y pediatría 2006; Vol 69 (1): 19-25. = González LG., López K, Navarro DC, Negrón L, Flores LS, Rodríguez R, Martínez M, Sabrá A. Características endoscópicas, histológicas e inmunológicas de la mucosa digestiva en niños autistas con síntomas gastrointestinales [Endoscopic and Histological Characteristics of the Digestive Mucosa in Autistic Children with gastro-Intestinal Symptoms] Archivos Venezolanos de Puericultura y Pediatría Enero-Marzo 2006, Volúmen 69, Número 1 Arch Venez Pueri Pediatr 2006 69(1):19-25. 1.
The authors cannot replicate Wakefield’s 1998 “findings” of a distinct autistic enterocolitis, although they do report a higher incidence of gastrointestinal problems in their autistic group. 2. It appears that the Gonzalez paper was funded by Thoughtful House, under Wakefield’s leadership as previously shown
In no way “replicates” or “supports” Wakefield’s “findings”
28. Gastroenterology. 2005:128 (Suppl 2);Abstract-303 =
Balzola F, Daniela C, Repici , Barbon V, Sapino A, Barbera C, Calvo PL, Gandione M, Rigardetto R*, and Rizzetto M .
This is a meeting abstract that has never been published as a peer reviewed study since 2005. Nine adult males with autism and GI symptoms were evaluated for GI disease. Study did not look for measles virus, nor did study look for mumps or rubella virus. Study did not evaluate changes in gut structure.
In no way “replicates” or “supports” Wakefield’s “findings”
Numbers: of 28 studies 2 were duplicates, 3 were only retrievable because of the links on the whale.to page, 13 were written by Wakefield and/or Lancet co-authors and/or Thoughful House colleagues (counting two duplicates), 3 predate the Lancet paper by years or even decades and not one independently replicates Wakefield’s claims, made in the retracted Lancet paper, the associated press conference and in many statements since.
Tuesday, May 3, 2011
Death by measles
I just found the news that a young man died of measles in Germany this Spring. Germany has had more than 390 measles cases since the beginning of the year, mainly in the Southern most federal states (Bundesländer) of Bavaria and Baden-Württemberg.
In March 2011, a 26 year old man, undergoing treatment for a non life threatening tumour contracted measles and died. While in hospital, he infected at least one further patient as well as several unvaccinated medical staff, including doctors. Dr. Martin Terhardt of the Professional Association of Pediatricians (Berufsverband der Kinder- und Jugendärzte (BVKJ)) states the obvious:
Measles transmissions in a medical care setting seem to have become the norm rather than the exception (see California and Arizona 2008). In the light of the current strong measles activity in Europe (with world wide exports), everyone, especially care professionals, should check their immunization status and get boosters if necessary to avoid transmission (especially to vulnerable babies and immuno-suppressed).
In March 2011, a 26 year old man, undergoing treatment for a non life threatening tumour contracted measles and died. While in hospital, he infected at least one further patient as well as several unvaccinated medical staff, including doctors. Dr. Martin Terhardt of the Professional Association of Pediatricians (Berufsverband der Kinder- und Jugendärzte (BVKJ)) states the obvious:
"It is unacceptable that unvaccinated personnel exists in hospitals. When unvaccinated doctors or nurses have access to intensive care, it becomes very dangerous, both for the personnel themselves and for the patients. Patients who are being treated in intensive care are often immuno-compromised - an additional infection therefore has to be avoided at all cost. Doctors and other medical care personnel must have adequate protection through immunization. The fact that a patient with measles could cause an outbreak amongst medical personnel is absurd."
Measles transmissions in a medical care setting seem to have become the norm rather than the exception (see California and Arizona 2008). In the light of the current strong measles activity in Europe (with world wide exports), everyone, especially care professionals, should check their immunization status and get boosters if necessary to avoid transmission (especially to vulnerable babies and immuno-suppressed).
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