Regressive Autism, Ileal-Lymphoid Nodular Hyperplasia, Measles Virus and MMR Vaccine

[Sheri Nakken]

http://www.vaproject.org/thrower/mmr-br ... 070430.htm

Regressive Autism, Ileal-Lymphoid Nodular Hyperplasia, Measles Virus and
MMR Vaccine

Summary of Published Studies Offering Evidence for Linkages

By

David Thrower
(download pdf http://www.vaproject.org/thrower/mmr-br ... 070430.pdf )
This note summarizes:
o clinical evidence for the link between autism and a novel form of
inflammatory bowel disease
o clinical evidence for the link between inflammatory bowel disease and
measles virus
o clinical evidence for the link between measles virus and vaccination
with MMR
o some of the other wider safety concerns over MMR
(A) The Link Between Autism and a Novel Form of Inflammatory Bowel Disease

There is now ample evidence, confirmed by independent groups of
researchers, of a link between regressive autism and a novel form of
inflammatory bowel disease. Full publication references are at the end of
these notes.
o The possible association between MMR vaccine, regressive autism and
intestinal symptoms was first recounted by parents to Dr. Andrew Wakefield,
a UK gastroenterologist at the Royal Free Hospital, London, in 1995. The
first group of children presenting in this way to Wakefield and colleagues
at the Royal Free were reported in The Lancet as a clinical case series in
February 1998 (1). Although the interpretation put on this paper at the
time was the subject of intense controversy - particularly in the absence
of corroborative clinical research by other researchers at that time - the
strong evidence of a hitherto-unreported link between autism and a novel
intestinal disease, ileal-lymphoid nodular hyperplasia, has not been
disputed, and still stands as an important initial clue as to the causes of
regressive autism.

o A group of researchers led by Horvath (2) subsequently independently
reported in 1999 upon patients with autism who had gastrointestinal
symptoms, including a study of 36 children with autism that found grade I
or II reflux esophagitis in 25 (69.4%), chronic gastritis in 15 (42%) and
chronic duodenitis in 24 (67%).

o

et al confirmed that ileal-lymphoid nodular hyperplasia (ILNH) was found in
54 out of 58 (93%) children with autism or other disorders (50 with autism,
5 Aspergers, 2 disintegrative disorder, one ADHD, one schizophrenia, one
dyslexia), but only 5 out of 35 (14.3%) normal controls, pointing to a very
strong ILNH-autism link.

o Research published in 2001 by Furlano, Anthony et al (4) reported on
ileocolonoscopy performed on 21 consecutively-evaluated children with
autistic spectrum disorders and bowel symptoms, and made "blinded"
comparisons with 8 children who had a histologically normal ileum and
colon, plus 10 developmentally-normal children with ILNH, 15 with Crohn's
Disease, and 14 with ulcerative colitis. The study confirmed a distinct
lymphocytic colitis in the children with ASD, in which the epithelium
appeared particularly affected, offering further corroboration for gut
epithelial dysfunction in autism.

o Research reported in 2001 by Buie (5) reported that, as a result of
over 400 gastrointestinal endoscopies with biopsies and evaluation of
digestive enzyme function, on children with autism, he had found the
presence of chronic inflammation of the intestinal tract, although the
incidence was less frequent than in the Royal Free Hospital group of
patients reported by Wakefield et al, and that biopsy results indicated the
presence of chronic inflammation of the digestive tracts, including
esophagitis, gastritis and enterocolitis. Ileal lymphoid nodular
hyperplasia, as first found by the Royal Free study, had been found in 15
of 89 children examined for it.

o A review (6) published in September 2002 by Wakefield, Anthony,
Montgomery et al noted that as early as 1986, a researcher named Soddy had
noted that recurrent gastrointestinal upsets were a constant feature of
autistic children, and that in a systematic analysis of an unselected
population of 385 children on the autistic spectrum, clinically-significant
gastrointestinal symptoms occurred in 46%, compared with 10% of 97
developmentally-normal controls, strongly suggesting a
gastrointestinal-autism link. Mucosal lesions in the small and large
intestine were consistent with an autoimmune pathology, and suggested the
possibility of an autoimmune response leading to cerebral damage.

o A June 2002 presentation (7) by Krigsman to the US Congressional
Committee on Government Reform reported that a large percentage of his
autistic patients suffered from chronic unexplained gastrointestinal
symptoms. Of 43 patients, the majority had a clear history of
developmental regression, after previous normal development, suffering
gradual or precipitous decline between age 12 months and 18 months. Most
regressive children also exhibited poor growth. Patients had undergone
colonoscopy. Findings were that the lymphoid nodules of the terminal ileum
were markedly enlarged, thus confirming the early work of the Royal Free
team. Evaluation of biopsy specimens confirmed that 65% had colitis, 51%
had active colitis, 40% had chronic colitis, 7% had eosinophilic colitis,
90% had lymphoid nodular hyperplasia of the terminal ileum, and 35% had
neither active nor chronic nor eosinophilic colitis. Patterns of
inflammation were patchy and unpredictable, but findings were similar and
consistent from patient to patient within affected sub-groups.

o A November 2003 paper (8) published by Ashwood, Murch et al reported
on the examination of 52 affected autistic children, compared with 25
histologically-normal developmentally-normal controls and a further 54
histologically-inflamed but developmentally-normal controls. Analysis of
intestinal biopsies in regressive-autistic children indicated a novel
lymphocytic enterocolitis with autoimmune features, though the precise
linkage between the finding and cognitive functions still remained unclear.
The study concluded that it provided further evidence of a pan-enteric
mucosal immunopathology in children with regressive autism, that is
distinct from other previously-known inflammatory bowel diseases.

o An April 2004 paper (9) by Torrente, Anthony et al identified,
following earlier reports of lymphocytic colitis and small bowel
enteropathy in children with regressive autism, that the gastritis in
regressive autism was clearly distinct from that in Crohn's and other
conditions, pointing to a distinctive form of gastritis being linked with
regressive autism.

o A November 2004 paper (10) by Ashwood, Anthony et al found that
molecules (cytokines) produced by immune cells in the intestine, that cause
or control inflammation, showed an abnormal pattern in autistic children
compared with non-autistic children. The pattern was different to other
forms of intestinal inflammation, and the disease resembled a longstanding
viral disease of the intestine, not unlike the intestinal inflammation seen
on patients with other viral infections such as HIV-associated enteropathy
(intestinal disease) that often accompanies infection with HIV.

o A February 2005 paper (11) by Jyonouchi, Geng et al further confirmed
the original ileal-lymphoid nodular hyperplasia/regressive autism link
first reported by the Wakefield team in 1998. The study again found
evidence of marked inflammatory and immune abnormalities in children with
autism associated with gastrointestinal symptoms.

o An April 2005 published letter (12) by Balzola, Barbon et al,
Pan-Enteric IBD-Like Disease in a Patient with Regressive Autism Shown for
the First Time by the Wireless Capsule Enteroscopy - Another Piece in the
Jigsaw of this Gut/Brain Syndrome?, reported that a 28-year-old male with
regressive autism, severe constipation, bloating, abdomen distension and
symptoms of gastroesophageal reflux was examined. Gastroscopy under
general anaesthesia revealed hemorrhagic gastritis with inflammatory
pseudopolypsthat had reached the pylorum, with a pearl-necklace appearance,
and a panenteric IBD-like disease consistent with previously-published
descriptions of autistic enterocolitis was finally diagnosed. The wireless
capsule images were the first to be obtained beyond the limits of the
duodenum and terminal ileum, and demonstrated the potential for the entire
bowel to be implicated in this inflammatory disease.

o A May 2005 study (13) by Balzola, Daniela et al reported on 9
consecutive patients (range 7-30 years) with autism and chronic intestinal
symptoms (abdominal pain, bloating, constipation and/or diahorrea).
Routine blood and stool tests and gastroscopy and colonoscopy with multiple
biopsies were performed under sedation, and wireless enteroscopy capsules
were used in three of the adult patients. Gastroscopy revealed mucosal
gastritis in 4 patients, esophagitis in 1 patient and duodenitis in 1
patient, and histological findings showed chronic inflammation of the
stomach and duodenum in 6 patients, inconsistent with celiac disease. The
authors reported that preliminary findings were strongly consistent with
previous descriptions of autistic enterocolitis, and supported a
not-coincidental occurrence. They showed for the first time a
small-intestinal involvement, suggesting a pan-enteric localization of this
new inflammatory bowel disease.

o Also in 2005, a further paper (14) by Wakefield, Ashwood et al was
published, assessing ileocolonic lymphoid nodular hyperplasia in ASD and
normal control children. Some 148 consecutive children with ASD, with
gastrointestinal symptoms, were investigated by ileocolonoscopy, with 74
ASD children and 23 normal controls undergoing upper gastrointestinal
endoscopy. The presence of lymphoid nodular hyperplasia was significantly
greater in ASD children compared with controls, in the ileum (129 out of
144, compared with 8 out of 27 controls), and in the colon (88 out of 148,
compared with 7 out of 30 controls). Comparative percentages were 90% vs
30% and 59% vs 23%. This was whether or not controls had co-existent
colonic inflammation. The severity of ILNH was significantly greater in
ASD children compared with controls, with moderate-to-severe ILNH present
in 98 out of 144 ASD children compared with 4 out of 27 controls;
percentages were 68% and 15%. On histopathological examination,
hyperplasic lymphoid follicles were significantly more prevalent in the
ileum of ASD children (84 out of 138, or 61%) compared with normal controls
(2 out of 23, or 9%). The data thus further corroborated the finding that
ileal lymphoid nodular hyperplasia is a significant pathological finding in
autistic children.

o Additionally in 2005, a study (15) was published by Gonzalez, Lopez
et al, seeking evidence of immunological alterations in 68 autistic
children ages 22 months to 11 years and presenting with digestive systems,
and examining biopsies from their digestive tracts. Endoscopies and
colosopies were undertaken, with biopsies of the esophagus, stomach,
duodenum and colon, with verification of presence of inflammation,
eosiophil infiltration, lymphoid nodular hyperplasia and CD-4 and CD-8
cells. The results were that lymphoid nodular hyperplasia was discovered
in 2/68 esophagus, 6/68 stomachs, 8/68 duodenums and 36/68 (53%) of colons.
Eosiophil infiltration with more than 20 eosiphils per field were found in
3/68 eosphagus, 1/68 stomach, 8/68 duodenum and 24/68 (35%) colons.
Inflammatory reactions were found in 56/68 (82%) esophogitis, 64/68 (94%)
gastritis, and all (100%) presented with duodenitis and colitis. CD-4/CD-8
relationship existed of >3 in 42/68 (62%) and <1 in 16/68. The authors
concluded that the children presented immunological and immunohistochemical
alterations of the biopsies of their digestive tracts, and that there was a
significant finding of lymphoid nodular hyperplasia, eosiophilinfiltration,
and that prevalence of greater CD-4 than CD-8 cells in the inflammation of
the intestinal wall demonstrated in favour of a Th2 type allergic reaction.

Taken together, the above now provide very convincing evidence from a
number of wholly-independent groups of researchers of a link between the
novel inflammatory bowel disease of ileal lymphoid nodular hyperplasia and
regressive autism.

(B) The Link Between Inflammatory Bowel Disease and Measles Virus

These autism/inflammatory bowel disease findings were followed by findings
that linked the novel form of inflammatory bowel disease with persistent
measles virus in the gut of affected children:
o A paper (16) by Uhlmann, Sheils et al, noting that measles virus
nucleoprotein (N antigen) had been detected in association with follicular
dendritic cells (FDC) in patients, and seeking molecular confirmation of
this result, found that :solution phase RT PCR yielded specific measles
virus N gene amplification in affected children (10/10), and identified
distinct measles virus genome in FDC reactive follicular centres by in-cell
RNA amplification. None of the normal controls showed any evidence of
measles virus genome. The data highlighted a possible causal link between
measles virus infection and ileo-colonic lymphoid nodular hyperplasia in
affected children.

o A paper (17) presented in the year 2000 by Singh to the US House of
Representatives Committee on Government Reform reported a hyperimmune
response to the measles virus, with an association between measles virus
antibody levels and incidence of brain autoantibody.

o An April 2000 paper (18) presented by O'Leary to the Committee on
Government Reform reported the investigation whether measles virus was
present n the gut biopsies of autistic children, and if so, where and how
much. The paper reported that the biopsies of 24 out of 25 (96%) of the
autistic children examined were positive for measles virus, and that
amongst normal (non-autistic) controls, only 1 out of 15 children (6.6%)
were positive, strongly suggesting a connection between measles virus and
autism.

o A February 2002 paper (19) by Uhlmann, Wakefield, O'Leary et al
investigated the presence of persistent measles virus in the intestinal
tissue of 91 autistic patients with new-variant inflammatory bowel disease
(ileal-lymphoid nodular hyperplasia, or ILNH). Patient samples were
provided by the Royal Free Hospital, London. The patients were ages 3-14,
and 77 out of 91 were male. There were 70 developmentally-normal controls
ages 0-17 years, 47 out of 70 being boys. Of these, 19 had normal ileal
biopsies, 13 had mild non-specific chronic inflammatory changes, 3 had ILNH
and had been investigated for abdominal pain, 8 had Crohn's Disease, one
had ulcerative colitis, and 26 had undergone appendicectomy for abdominal
pain including appendicitis. The results were that 75 out of 91 patients
with a histologically-confirmed diagnosis of ileal-lymphoid nodular
hyperplasia and enterocolitis were positive for measles virus in their
intestinal tissue, compared with 5 out of 70 controls. Using TaqMan RT-PCR
techniques, 70 out of 91 affected children were positive for measles virus,
compared with 4 out of 70 controls. Of the controls, measles virus was not
detected in normal children or children with isolated ileal-lymphoid
nodular hyperplasia. However, 4 out of 26 appendicectomy samples harboured
measles virus genome; the study suggested that the prevalence of measles
virus in the general population warranted further investigation. The study
concluded that the data confirmed an association between the presence of
gut pathology and of measles virus in children with developmental disorder.
The study did not exclude the presence of alternative infections to
measles virus.

o A February 2004 paper (20) presented by Singh to the US Institute of
Medicine, Washington DC, measured antibodies in autistic children to five
viruses, measles, mumps, rubella, CMV and human herpes virus 6.
Researchers found that the antibody level of the measles virus alone, and
not the other four, was significantly higher in autistic children than in
normal children. The research also found a correlation between measles
antibody and brain autoimmunity, which was marked by myelin basic protein
antibodies. The two markers correlated in over 90% of the autistic
children tested for them, suggesting a causal link between measles virus
and autoimmunity in autism. The serology to other viruses and other brain
autoantibodies did not show this correlation. This suggested a temporal
link of measles virus in the etiology of autism.

An early-report presentation by Walker, Hepner et al, at the International
Meeting for Autism Research, Montreal, June 2006, reported that PCR
analysis on terminal ileum biopsy tissue from an initial 82 patients found
70 (85%) positive for measles virus f-gene amplicon. These preliminary
results confirm earlier findings of measles virus RNA in the terminal
ileum. Full publication of this study is anticipated.

The above studies provide significant evidence for a link between measles
virus and ileal lymphoid nodular hyperplasia, with the latter's
earlier-demonstrated onward link with regressive autism.

(C) The Link Between Measles Virus and Vaccination with MMR
o A July 2002 paper (21) presented by O'Leary reported that the strain
of measles virus used in MMR had been detected in the gut tissue of 12
autistic children. Medical histories had indicated that each of the
children had developed autism after the date of receipt of MMR, and none
had exhibited outward signs of measles infection before becoming autistic.

o An April 2000 study (22) by Kawashima, Takayuki et al confirmed that,
amongst 8 patients with Crohn's Disease, 3 patients with ulcerative colitis
and 9 patients with autistic enterocolitis, and 8 children who were either
healthy or who had SSPE, SLE or HIV-1, 1 out of 8 patients with CD, 1 out
of 3 patients with UC and 3 out of 9 patients with autism were positive for
measles virus. Controls were all negative. The sequences from patients
with CD shared the characteristics of wild-strain measles virus. The
sequences from patients with UC and from patients with autism were
consistent with vaccine strain measles virus. These results were
consistent with patients' medical histories, and point to a connection
between autism and vaccine-strain measles virus.

o A May 2002 paper (23) by Singh, Nelson, Jensen and Bradstreet found
that a significant percentage of autistic children examined had antibodies
to myelin basic protein (up to 88% positive) and to MMR (up to 65%
positive). Normal children did not exhibit these antibodies. The analysis
of paired samples (serum and cerebral spinal fluid from 7 autistic children
also revealed a high degree of serological association between MMR and
myelin basic protein. Some 50% of CSF had MMR antibodies, 86% of CSF had
MBP antibodies, 75% of sera had MMR antibodies and 100% of sera had MBP
antibodies. Therefore there was a strong correlation between MMR
antibodies and myelin basic protein antibodies. By using monoclonal
antibodies, the authors characterized that the MMR antibodies were due to
the measles sub-unit, but not to the mumps or rubella sub-units, of MMR.
In the light of this, the authors suggested that in some cases of autism,
MMR might cause autoimmunity, and it might be doing so by bringing on an
atypical measles infection that manifests neurological symptoms.

o An earlier 1999 paper (24) by Bitnun has previously and independently
confirmed the presence of measles virus in the brain tissue of a
previously-healthy child following exposure to MMR, when the child had no
history of wild measles infection.

o A February 2004 paper (25) by Bradstreet, O'Leary, Sheils et al to
the US Institute of Medicine, and subsequently published later that year,
reported that three children with regressive autism had undergone
cerebrospinal fluid assessment, including for measles virus. All three had
had concomitant onset of gastrointestinal symptoms and had already had
measles virus genomic RNA detected in biopsies of ileal-lymphoid nodular
hyperplasia. None of the cases nor non-autistic controls had any history
of measles exposure other than possibly via MMR. Serum and cerebrospinal
fluid samples were also evaluated for antibodies to measles virus and
myelin basic protein. The result was that measles virus f-gene was present
in the cerebrospinal fluid of all three autistic cases but not in
non-autistic controls. Further, serum anti-myelin basic protein
autoantibodies were detected in all children with autistic encephalopathy.
Anti-MBP and measles virus antibodies were detected in the CSF of two
cases, but the third had neither. The study concluded that the findings
were consistent with a measles-virus etiology for autistic encephalopathy,
indicating the possibility of a virally-driven cerebral immunopathology in
some cases of regressive autism. The virus genome found in the autistic
children was "exclusively consistent with vaccine strain".

o A May 2006 study (26) by Wakefield, Stott and Limb investigated the
hypothesis as to whether a dose-response effect of measles-containing
vaccine on intestinal pathology existed. If it did exist, this would
constitute evidence of a causal association. In the study, children with
normal early development and autistic-like developmental regression were
divided into two groups. Children were divided into two groups: some 23
re-exposed children, i.e. those who had received more than one dose of a
measles-containing vaccine (MCV), and 23 children who had received only one
dose of MCV. The groups were matched for sex, age and time that had
elapsed from first exposure to time of endoscopy. Comparisons made
included secondary gastrointestinal (GI) and related physical symptoms, and
"observer-blinded" scores of endoscopic and histological disease. The
results were that re-exposed children scored significantly higher than
only-once-exposed for secondary physical symptoms, including incontinence,
presence of severe ileal-lymphoid nodular hyperplasia, the number of
biopsies with epithelial damage, and number of children with acute
inflammation. Markers of acute inflammation include number of children
affected, and proportion of biopsies affect. The conclusion of the study
was that the data confirmed a re-challenge effect (i.e. a double-hit
effect) of measles-containing vaccines on symptoms, and also confirmed a
biological gradient effect upon intestinal pathology. These findings thus
link exposure to measles-containing vaccines to autistic-like regression
and enterocolitis. (Note: it was stated in April 2001 by the Vaccine
Safety Committee of the US Institute of Medicine that in the context of MMR
and autism "challenge re-challenge would constitute strong evidence of an
association".)

Taken together, with the Walker, Hepner et al study, the above points to
MMR as the means by which measles virus enters and persists in the gut,
leading to ileal-lymphoid nodular hyperplasia, and in turn leading to
regressive autism. The evidence to fully explain the complete causational
mechanism by which this occurs is still emerging, and clearly requires
further urgent research.

The intestinal disease has the features of a viral disease. Measles virus
is known to infect the intestine, and produces the features described
originally by Wakefield and colleagues in 1998.

All the findings described in the 1998 Lancet report by the Wakefield team
- including the discovery of a possible new type of inflammatory bowel
disease, have therefore been subsequently independently confirmed by other
researchers in the US, in Italy and in Venezuela.

The studies suggest that in some children, brain damage leading to autism
may be secondary to, or occur in parallel with, a disease in the intestine,
and that vaccine strain measles virus has become the prime suspect in this
complex investigation.

The findings to date have important implications for our understanding and
treatment of the complex disorder of regressive autism.

(D) Wider Safety Concerns Over MMR:

It is also instructive to examine the original, and any subsequent, safety
studies of MMR.
o An authoritative independent review by the Cochrane Collaboration
(27) of the safety studies of MMR vaccine concluded that "the design and
reporting of safety outcomes in MMR vaccine studies, both pre- and
post-marketing, are largely inadequate". It further confirmed that neither
before nor after the introduction of the MMR vaccine were proper safety
trials carried out.

o A more recent review (28) from the same organization identified that
safety studies for the single measles vaccine were better than those
conducted for MMR: "We found only limited evidence of safety of MMR
compared to the single component vaccines, that had a low risk of bias".
The authors of the Cochrane reviews were highly critical of the safety
studies of MMR, which they stated "need to be improved". Cochrane
mentioned a specific concern that safety studies followed up the children
involved for no more than three weeks, except for one study that lasted
just six weeks.

o Concern over MMR's safety has been expressed (29) by a key former
scientific adviser to the UK licensing authorities. Dr. Peter Fletcher,
former Principal Medical Officer in the (then) UK Medicines Division, who
was medical assessor to the Committee on Safety of Medicines, commented:
"Evidence on safety was very thin", and "Too few children were followed for
a sufficient time... Big numbers were necessary, and computerised
databases were already in place to permit this, but it was not done...
Caution should have ruled the day... There should have been strong
encouragement to conduct a 12-month observational study on 10,000-15,000
children..." (this was not done) "The granting of a product licence was
premature."

o A year-2000 review (30 by Wakefield & Montgomery examined early
safety studies of MMR, by Buynak et al 1969, Stokes et al 1971, Minekawa et
al 1974, Schwartz et al 1975, Crawford and Gremillion 1981, and Miller et
al 1987. The Buynak study identified viral "interference", but the
follow-up period was only 12 days. The Stokes study revealed persistent
gastrointestinal problems in the US trial children, but the follow-up was
only 28 days. Stokes compared 228 MMR children with 106 unvaccinated
controls. Data, from Philadelphia and Costa Rica and San Salvador, was
merged - a major methodological error. Gastroenteritis was found to be
significantly more common in the Philadelphia vaccines (24%) compared with
the unvaccinated Philadelphia controls (5.6%). No significant difference
was found between the vaccinated and the unvaccinated in Costa Rica and San
Salvador because of high ambient levels of gastroenteritis anyway (50% in
vaccines, 44% in controls). Combining all the data masked these
instructive differences. There was also significant "unrelated" illness in
39% of Philadelphia vaccines (otitis, allergy, viral infection, abdominal
pain), compared with 12.2% in controls. The potential relevance of this
was not seen at time. The Minekawa study confirmed viral interference.
The follow-up period was only 15 days. The Schwartz study also merged its
data, so provided insufficient insight, and again follow-up was only 21
days. The study looked at two different populations, 282 children in Ohio
and 926 children in Santo Domingo, Dominican Republic. Again, the merging
of data from different countries was a serious error. No data was provided
to permit analysis of adverse events. Crawford and Gremillion's study of
USAF recruits confirmed viral interference, but the follow-up period was
only 19 days. Some 512 vaccines were compared with 835 unvaccinated
controls. The study noted increased fever and diarrhoea in those that
received measles and rubella vaccines simultaneously. But the potential
effect of trivalent vaccine was only seen as additive instead of
potentially synergistic - a key point. The Eddes study (a small UK study)
in 1991 compared reactions to MMR with monovalent measles vaccine. High
rates of gastrointestinal disorders (41.9% and 37.8%) were found, but the
authors dismissed these as normal background illness. The Dr. Elizabeth
Miller study noted that diarrhoea was common (26% of vaccinees), but the
follow-up again was only 21 days. This was a major missed opportunity to
follow up a large cohort. The Stokes, Schwartz, Miller and Eddes studies
were therefore all too small or too superficial to pick up uncommon adverse
events. The Plesner et al study of gait disturbance following MMR (Acta
Paediatrica, 2000, 89, 58-63) confirmed an association, and indicated that
more severe cerebellar ataxias following MMR may be associated with
residual cognitive deficits.

Cochrane was forced to conclude that "the safety record of MMR is probably
best attested by its almost universal use." Or to put it another way, "the
best evidence of MMR's safety we can find is that fact that it's being
widely used" - hardly a scientific test of a product's actual safety,
particularly when the evidence of problems is through a
hitherto-unsuspected link between MMR and autism, that would not have been
monitored prior to 1998.
References

(on the link between autism and a novel form of inflammatory bowel disease)

(1) Wakefield et al, Inflammatory Bowel Disease Study Group, Royal Free
Hospital London, Ileal Lymphoid Nodular Hyperplasia, Non Specific Colitis
and Pervasive Development Disorder in Children, Lancet, 28th February 1998

(2) Horvath, Papadimitiou et al, Department of Pediatrics, University of
Maryland School of Medicine, Baltimore, Gastrointestinal Abnormalities in
Children With Autistic Disorder, Journal of Pediatrics, 1999 November, Vol
135 (5), pp559-563

(3) Wakefield, Anthony et al, Enterocolitis in Children with Developmental
Disorders, American Journal of Gastroenterology, Sept 2000, Vol 95, No. 9,
pp2285-2295

(4) Furlano, Anthony et al, Colonic CD8 and T-Cell Infiltration With
Epithelial Damage in Children with Autism, Journal of Pediatrics, 2001;
138; No. 3, 366-372

(5) Paper by Dr. Timothy Buie, Harvard Massachusetts General Hospital,
presented to the Oasis 2001 Conference for Autism, Portland, Oregon,
November 2001

(6) Wakefield, Anthony, Montgomery et al, Inflammatory Bowel disease Study
Group, Royal Free Hospital, University College Medical School, London, and
Coombe Women's Hospital and Trinity College Dublin, The Concept of
Enterocolonic Encepalopathy, Autism and Opioid Receptor Ligands, Aliment
Pharmacological Ther, 16: pp663-674

(7) Presentation by Krigsman to the US Congressional Committee on
Government Reform's June 2002 hearing, The Status of Research into Vaccine
Safety and Autism, held in Washington DC

(8) Ashwood, Murch et al, Royal Free Hospital, London, Intestinal
Lymphocyte Populations in Children with Regressive Autism: Evidence for
Extensive Mucosal Immunopathology, Journal of Clinical Immunology, Vol 23
No. 6 Nov 2003 pp504-517

(9) Torrente, Anthony et al, Centre for Pediatric Gastroenterology, Royal
Free Hospital and University College Medical School, London, Focal-Enhanced
Gastritis in Regressive Autism, With Features Distinct from Crohn's and
Helicobacter Pylori Gastritis, American Journal of Gastroenterology, Vol
99, Issue 4, p598, April 2004

(10) Ashwood, Anthony et al, Spontaneous Mucosal Lymphocyte Cytokine
Profiles in Children with Autism and Gastrointestinal Symptoms: Mucosal
Immune Activation and Reduced Counter-Regulatory Interleukin-10, Journal of
Clinical Immunology, Vol 24, No. 6, November 2004

(11) Jyonouchi, Geng et al, Department of Pediatrics, New Jersey Medical
School, Dysregulated Innate Immune Responses in Young Children with
Autistic Spectrum Disorders - Their Relationship in Gastrointestinal
Symptoms and Dietary Intervention, Neuropsychobiology, February 2005, 51
(2) pp77-85

(12) Letter by Balzola, Barbon et al, Department of Gastroenterology,
Department of Neuropsychiatry for Children, Department of Pediatric
Gastroenterology and Department of Biomedical Sciences and Human Oncology,
University of Turin, Pan-Enteric IBD-Like Disease in a Patient with
Regressive Autism Shown for the First Time by the Wireless Capsule
Enteroscopy - Another Piece in the Jigsaw of this Gut/Brain Syndrome?,
American Journal of Gastroenterology, 2005; 100 (4) p979

(13) Balzola, Daniela et al, Department of Gastroenterology, Department of
Neuropsychiatry for Children, Department of Pediatric Gastroenterology and
Department of Biomedical Science and Human Oncology, University of Turin,
Autistic Enterocolitis - Autistic Enterocolitis: Confirmation of a New
Inflammatory Bowel Disease in an Italian Cohort of Patients, paper
presented to the American Gastroenterological Association, May 2005 and
published in Gastroenterology 2005: 128 Suppl 2, A-303

(14) Wakefield, Ashwood et al, The Significance of Ileo-Colonic Lymphoid
Nodular Hyperplasia in Children with Autistic Spectrum Disorder, European
Journal of Gastroenterology and Hepatology, 2005, Vol 17 No. 8

(15) Gonzalez, Lopez et al, Endoscopic and Histological Characteristics of
the Digestive Mucosa in Autistic Children with Gastrointestinal Symptoms:
Preliminary Report, G.E.N. Suplemento Especial de Pediatria, no. 1, 2005;
pp41-47
(on the link between inflammatory bowel disease and measles virus)

(16) Uhlmann, Sheils et al, Department of Pathology, Coombe Women's
Hospital Dublin, Trinity College Dublin and Royal Free Hospital London,
Measles Virus in Reactive Lympho-Nodular Hyperplasia and Ileo-colitis of
Children

(17) Paper presented by Dr. Vijendra Singh, University of Michigan College
of Pharmacy, to the US House of Representatives Committee on Government
Reform, Washington DC, 2000

(18) Paper presented by Professor John O'Leary, Dublin Women's Hospital,
to the US House of Representatives Committee on Government Reform,
Washington DC, April 2000

(19) Paper By Uhlmann, Wakefield, O'Leary et al, Potential Viral
Pathogenic Mechanism For New Variant Inflammatory Bowel Disease, Journal of
Clinical Pathology, Molecular Pathology, 2002, 55, 0-6, published 6th
February 2002

(20) Paper by Singh, Department of Biology Center for Integrated
Biosystems, Utah State University, Logan, Autism, Vaccines and Immune
Reactions, presented to the Institute of Medicine, Washington DC, February
2004
(on the link between measles virus and vaccination with MMR)

(21) Paper presented by O'Leary, Coombe Women's Hospital and Trinity
College Dublin to the Pathological Society of Great Britain and Ireland,
July 2002

(22) Kawashima, Takayuki et al, Detection and Sequencing of Measles Virus
from Peripheral Mononuclear Cells from Patients with Inflammatory Bowel
Disease and Autism, Digestive Diseases & Science, Vol 45, No. 4, April
2000, pp723-729

(23) Singh, Nelson, Jensen and Bradstreet, Abnormal Measles Serology and
Autoimmunity in Autistic Children, Journal of Allergy and Clinical
Immunology 109 (1) S232, January 2002, and also presented to the 102nd
General Meeting of the American Society for Microbiology, Salt Lake City,
Utah, May 2002

(24) Bitnun et al, Measles Inclusion-Body Encephalitis Caused by the
Vaccine Strain of Measles Virus, Clinical Infectious Diseases Journal,
1999, 29 855-61 (October)

(25) Bradstreet, O'Leary, Sheils et al, Detection of Measles Virus Genomic
RNA in Cerebrospinal Fluid in Children with Regressive Autism by TaqMan
RT-PCR: A Report of Three Cases, summarized at the Institute of Medicine,
February 2004 and subsequently published as Bradstreet, Dahr et al,
Detection of Measles Virus Genomic RNA in Cerebrospinal Fluid of Children
with Regressive Autism: A Report of Three Cases, Journal of American
Physicians and Surgeons, Vol 9, No. 2 Summer 2004

(26) Wakefield, Stott and Limb, Gastrointestinal Comorbidity, Autistic
Regression and Measles-Containing Vaccines; Positive Re-challenge and
Biological Gradient, Medical Veritas 3 (2006) 796-802

Again, taken with the latest study by Walker, Hepner et al, this now
provides evidence that it is highly likely that MMR vaccine is the source
of the measles virus that is in turn linked via significant evidence with
ileal lymphoid nodular hyperplasia, which in turn is strongly and
convincingly linked with regressive autism.

(on wider safety concerns over MMR vaccine)

(27) Jefferson, Price et al, Unintended Events Following Immunisation with
MMR; A Systematic Review, Vaccine, 2003; 21: pp3954-3960

(28) Demicheli, Jefferson et al, Vaccine For Measles, Mumps and Rubella in
Children (Review), The Cochrane Collaboration, published Wiley & Sons, UK,
from The Cochrane Library, 2005, Issue 4, art. No. CD004407

(29) Commentary by Dr. Peter Fletcher, Journal of Adverse Drug Reactions &
Toxicology, 2001, 20 (1), 47 63 Oxford University

(30) Wakefield & Montgomery Through A Glass Darkly (A Look Back At MMR's
Safety Trials), Journal of Adverse Drug Reactions, 2000 19(4), 265-283
----------------------------------------------------------------------
Sheri Nakken, R.N., MA, Hahnemannian Homeopath
Well Within & Earth Mysteries & Sacred Site Tours (worldwide)
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