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UNIVERSITY
OF SYDNEY
Measles, mumps, rubella vaccine,
inflammatory bowel disease and autism
Recent media reports have suggested a link between
the measles, mumps, rubella (MMR) vaccine, bowel inflammation and autism.
No reliable evidence supports a link. This fact sheet provides background
information for health professionals and parents.
What is Inflammatory Bowel Disease (IBD)?
IBD is a group of chronic inflammatory disorders of
the small and large bowel, the commonest being ulcerative colitis and
Crohn’s disease. The cause of IBD is not understood, but an immune
mechanism as well as a genetic predisposition are likely. IBD is
relatively rare, and usually occurs in people aged between 15 to 30 years,
but can also occur in children. Common symptoms include diarrhoea, fever,
stomach pain and weight loss.
What is autism?
Autism is a developmental disorder that is usually
identified between 18 months and three years of age. Autism is four times
more common in boys than girls and occurs in all racial and social groups.
Children and adults with autism typically have difficulties in verbal and
non-verbal communication, social interactions, and leisure or play
activities. A single cause of autism has not been identified, but current
research links it to developmental, genetic and environmental factors.
Many children have some of the features of autism
but do not fulfil all the diagnostic criteria. Because of this, terms such
as "Pervasive Developmental Disorder" (PDD) and Autism Spectrum
disorder are sometimes used.
What is MMR vaccine?
Measles, mumps, rubella (MMR) vaccine is a live
virus vaccine which protects against these three diseases through use of
modified types of measles, mumps and rubella viruses. They protect against
natural infection without causing disease themselves. The Australian
National Health & Medical Research Council (NHMRC) recommends MMR for
all children at 12 months of age and again at 4 years of age.
Does vaccination with MMR cause IBD and or autism?
In 1993, a group of researchers led by Dr Wakefield
at the Royal Free Hospital, London, suggested an association between both
the natural and vaccine types of measles virus and IBD based on a study of
25 children with Crohn’s disease (compared to 22 well children). In 1998
researchers from the same group reported the occurrence in 12 children of
an apparently new syndrome of an unusual type of IBD in association with
developmental disorders such as autism. In 2002 Uhlmann, Wakefield and
others published a study showing a higher rate of measles virus in the
bowel of autistic children with bowel symptoms, compared to a group of
children without autism.
The researchers suggested that MMR vaccine caused
IBD, which then resulted in decreased absorption of essential vitamins and
nutrients through the intestinal tract. They suggested that this resulted
in developmental disorders such as autism. In 2001, Wakefield modified his
theory, proposing that MMR could cause "regressive autism" with
"autistic enterocolitis". This included worsening of autistic
symptoms in children already diagnosed with autism. This, he said, could
occur a long time after MMR vaccine, and required other contributing
factors (such as another infection, antibiotic therapy, or diseases of the
immune system).
Medical and scientific experts who have reviewed
Wakefield’s studies have found them to have several flaws. Primarily the
studies were conducted on highly selected patients, all referred to the
Royal Free Hospital for gastrointestinal ailments. If IBD causes autism,
one would expect IBD to occur first, followed by autism. In only 1 of the
12 patients did the symptoms of bowel disease precede the diagnosis of
autism. In 4 cases, autism preceded the bowel symptoms, and in the
remainder, the date of onset of bowel symptoms was unknown. Such a case
series analysis is unable to determine causal links. Furthermore, the
association between vaccine and autism was primarily based on parental
recall. Parents are likely to have linked changes in behaviour with
memorable events such as vaccination. The onset of autism and MMR
vaccination may coincidentally appear associated in time because the
average age at which parents report concerns about child development is 18
to 19 months, and over 90% of children receive MMR vaccine before their
second birthday in the UK. Epidemiologic studies have found no evidence to
support Wakefield’s recently modified theory of "regressive
autism".
These data presented in the 2002 study by Uhlmann
and others have not been reproduced by any other laboratory as yet. The
validity of this study is difficult to assess because the study does not
report key information on the characteristics and the method of selection
of the cases and controls and on laboratory methods. In addition, controls
were not matched for gender (which is a known risk factor for autism) or
age. The authors did not set out to look at the role of MMR vaccination,
and the vaccination status of the children in the study is not known.
What do other studies show?
More thorough, large epidemiological studies,
including an English population-based study of the vaccination status of
498 children with autism, and rates of IBD and autism among 6100 French
school-aged children, have found no evidence of an association. US and UK
studies found no correlation between trends in early childhood MMR
immunisation rates and trends in autism. A large prospective study of
adverse events following MMR in Finland followed 1.8 million children for
14 years after MMR vaccination and found no cases of autism. Other studies
have found that the proportion of children with developmental regression
or bowel symptoms, and the age at which parents first became concerned
about their children, was the same in children who received MMR and those
who did not. This provides no support for Wakefield’s modified
hypothesis.
Laboratory studies (by Iizuka et al. and Haga
et al. in Japan) using a similar methodology to Wakefield et al.
did not find any measles virus in patients with IBD. Other groups using
more sensitive testing methods have not found any evidence of measles
virus in the gastrointestinal tract of patients with Crohn’s disease or
ulcerative colitis.
What do the experts conclude?
Reviews by Canadian and World Health Organization
experts have concluded that ‘current scientific data do not permit a
causal link to be drawn between the measles virus and IBD’. In 1998 Sir
Kenneth Calman, British Chief Medical Officer, convened a meeting of the
Medical Research Council and a group of national and international
experts, including the World Health Organization, to review the work of
Wakefield and the Royal Free Hospital IBD study group. The meeting
concluded that based on current evidence ‘there is no link between
measles, measles vaccine, and either Crohn’s Disease or autism’.
Is there any benefit in giving the component vaccines separately?
There is no evidence that giving the vaccine
components of MMR separately is of any benefit. In fact, giving them
separately may even be harmful because children and their contacts would
be exposed to serious diseases over a longer period of time if the
vaccines are given sequentially. National and international expert bodies,
including The NHMRC, the World Health Organization, the Institute of
Medicine, and the American Academy of Pediatrics, all independently
recommend that MMR should continue to be used. At present, only the
rubella vaccine is available separately in Australia.
Further reading
Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lymphoid-nodular
hyperplasia, non-specific colitis, and pervasive developmental disorder in
children. Lancet 1998;351:637-41.
http://www.thelancet.com/newlancet/reg/issues/vol351no9103/early637.html
DeStefano F. Chen RT. Autism and measles, mumps, and
rubella vaccine: No epidemiological evidence for a causal association. Journal
of Pediatrics 2000;136:125-126.
Feeney M, Ciegg A, Winwood P, Snook J. A
case-control study of measles vaccination and inflammatory bowel disease.
The East Dorset Gastroenterology Group. Lancet 1997;350:764-6.
http://www.thelancet.com/newlancet/reg/issues/vol350no9080/article764.html
Taylor B, Miller E, Farrington CP, et al. Autism and
measles, mumps, and rubella vaccine: no epidemiological evidence for a
causal association. Lancet 1999;353:2026-9.
http://www.thelancet.com/newlancet/reg/issues/vol353no9169/article2026.html
Fombonne E, Du Mazauabrun C, Cans C, Grandjean H.
Autism and associated medical disorders in a French epidemiological
survey. American Academy of Child and Adolescent Psychiatry
1997;36:1561-9.
Iizuka M, Nakagomi O, Chiba M, Ueda S, Masamune O.
Absence of measles virus in Crohn's disease [letter]. Lancet
1995;345:199.
Haga Y, Funakoshi O, Kuroe K, et al. Absence of
measles viral genomic sequence in intestinal tissues from Crohn's disease
by nested polymerase chain reaction. Gut 1996;38:211-5.
Department of Health. MMR vaccine update 2000.
http://www.doh.gov.uk/mmrvac.htm
Centers for Disease Control and Prevention: MMR
Vaccine and Autism
http://www.cdc.gov/nip/vacsafe/concerns/autism/default.htm
Inflammatory Bowel Disease (IBD) and vaccines.
http://www.cdc.gov/nip/vacsafe/concerns/IBD.htm
Patja A, Davidkin I, Kurki T, Kallio MJ, Valle M,
Peltola H. Serious adverse events after measles-mumps-rubella vaccination
during a fourteen-year prospective follow-up. Pediatric Infectious
Disease Journal 2000;19:1127-34.
Dales L, Hammer SJ, Smith NJ. Time trends in autism
and in MMR immunization coverage in California. Journal of the American
Medical Association 2001; 285:1183-5.
Kaye JA, del Mar Melero-Montes M, Jick H. Mumps,
measles, and rubella vaccine and the incidence of autism recorded by
general practitioners: a time trend analysis. British Medical Journal
2001;322:460-3. http://www.bmj.com/cgi/content/full/322/7284/460
Uhlmann V, Martin CM, Sheils O, et al. Potential
viral pathogenic mechanism for new variant inflammatory bowel disease. Molecular
Pathology 2002;55:84-90.
Taylor B, Miller E, Lingam R, et al. Measles, mumps,
and rubella vaccination and bowel problems or developmental regression in
children with autism: population study. British Medical Journal
2002; 324:393-6.
Fombonne E, Chakrabarti S. No evidence for a new
variant of measles-mumps-rubella-induced autism. Pediatrics
2001;108:58-9
Further information for parents is available from:
Commonwealth Department of Health and Aged Care. Immunisation
myths and realities: responding to arguments against immunisation. 3rd
ed. Canberra: Australian Government Publishing Service, 2001.
http://immunise.health.gov.au/myths_2.pdf
This document was written by Dr Raina MacIntyre,
A/Professor Peter McIntyre, Dr Peter Horby and Ms Janaki Amin, of the
National Centre for Immunisation Research and Surveillance of Vaccine
Preventable Diseases, and Dr Katrina Williams of the Children’s Hospital
at Westmead, Westmead, NSW, Australia.
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