MMR vaccine controversy

The MMR vaccine controversy is over the safety of the MMR vaccine. Critics of the vaccine say that the incidence of autism has greatly increased and that the vaccine is a primary cause of this increase. They posit that the vaccine can overwhelm the young immune system, which they assert is often already struggling from the effects of other environmental factors such as exposure to heavy metals. Critics also say that the live measles virus in the formulation of the MMR harms susceptible individuals in a way that wild measles does not. [cite book |author= Cave S, Mitchell D |title= What Your Doctor May Not Tell You about Children's Vaccinations |publisher=Warner |date=2001 |isbn=0446677078 |chapter= The autism debate |pages=57–78]

The consensus of the medical and scientific community is that the vaccine's benefits greatly outweigh its risks, and that there is no scientific evidence to support the critics' claims of a link between MMR and autism. The Centers for Disease Control, [ [http://www.cdc.gov/od/science/iso/concerns/mmr_autism.htm Autism and Vaccines Theory] , from the U.S. Centers for Disease Control. Accessed June 13 2007.] the Institute of Medicine of the National Academy of Sciences, and the UK National Health Service have all concluded that there is no evidence of a link between the MMR vaccine and autism. A systematic review by the Cochrane Library concluded that there is no credible link between the MMR vaccine and autism, that MMR has prevented diseases that still carry a heavy burden of death and complications, and that the lack of confidence in MMR has damaged public health.

Urabe mumps strain

A late-1980s trial in Britain of a form of the MMR vaccine containing the Urabe mumps strain produced three cases of probably-associated febrile convulsions per 1,000 vaccinations, and concerns about adverse reactions to the this vaccine were raised by American and Canadian authorities and were based on reports from Japan linking Urabe MMR with high levels of meningoencephalitis. Despite these concerns, the British government went ahead with mass vaccinations in October 1988. [cite news |url=http://www.telegraph.co.uk/health/main.jhtml?xml=/health/2007/03/05/hmmr105.xml |accessdate=2007-09-06 |title= Early fears about MMR in secret papers |author= Watts M |work= The Daily Telegraph |date=2007-03-05] The National Health Service stopped using the Urabe mumps strain in the early 1990s due to cases of transient mild viral meningitis, and switched to a form using the Jeryl Lynn mumps strain instead. [cite journal |journal= Eur J Pediatr |year=1994 |volume=153 |issue=6 |pages=467–8 |title=Withdrawal of a mumps vaccine |author= Colville A, Pugh S, Miller E, Schmitt HJ, Just M, Neiss A |pmid=8088305 |doi=10.1007/BF01983415]

Wakefield "et al." report

1998 "Lancet" paper

In February 1998, a group led by Andrew Wakefield published a controversial paper in the respected British medical journal "The Lancet". The paper reported on twelve children with developmental disorders referred to the Royal Free Hospital in London. The parents or physicians of eight of these children had linked the start of behavioral symptoms to MMR vaccination. The paper described a collection of bowel symptoms, endoscopy findings and biopsy findings that were said to be evidence of a possible novel syndrome that Wakefield would later call autistic enterocolitis, and recommended further study into the possible link between the condition and the MMR vaccine. The paper suggested that the connection between autism and the gastrointestinal pathologies was real, but said it did not prove an association between the MMR vaccine and autism.cite journal |author= Wakefield A, Murch S, Anthony A "et al." |title= Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children |journal=Lancet |volume=351 |issue=9103 |pages=637–41 |year=1998 |doi=10.1016/S0140-6736(97)11096-0 |pmid=9500320 |url=http://briandeer.com/mmr/lancet-paper.htm |accessdate=2007-09-05]

At a press conference before the paper's publication, Wakefield said that he thought it prudent to use single vaccines instead of the MMR triple vaccine until this could be ruled out as an environmental trigger, given that parents of eight of the twelve children studied were said to have blamed the MMR vaccine, saying that symptoms of autism had set in within days of vaccination at approximately 14 months. He declared, "I can't support the continued use of these three vaccines given in combination until this issue has been resolved." [Cite web |url=http://briandeer.com/mmr/lancet-summary.htm |title= The MMR-autism scare - our story so far |accessdate=2007-09-05 |author= Deer B |date=2007-09-03] In a video news release issued by the hospital to broadcasters in advance of the press conference, he called for MMR to be "suspended in favour of the single vaccines." [cite web|author=Deer B |title= Royal Free facilitates attack on MMR, in Dr Andrew Wakefield "single shots" video |url=http://briandeer.com/wakefield/royal-video.htm |accessdate=2007-07-27] In a BBC interview Wakefield's mentor Roy Pounder, who was not a coauthor, admitted the study was controversial, and added: "In hindsight it may be a better solution to give the vaccinations separately, although administratively it is a wonderful idea. When the vaccinations were given individually there was no problem." [cite news |url=http://news.bbc.co.uk/1/low/uk/60510.stm |title= Child vaccine linked to autism |work=BBC News |date=1998-02-27 |accessdate=2007-09-05] These suggestions were not supported by Wakefield's coauthors nor by any scientific evidence.cite web |url=http://www.pm.gov.uk/output/page292.asp |accessdate=2007-09-06 |title= MMR - the controversy |date= 2005-08-01]

The initial press coverage of the story was mixed. The "Guardian" and the "Independent" put it on their front pages, but the "Daily Mail" buried it in the middle of the paper, and the "Sun" ignored it. 122 articles mentioned the subject in 1998.cite news |title= The MMR hoax |author= Goldacre B |work= The Guardian |date=2008-08-30 |accessdate=2008-08-30 |url=http://www.guardian.co.uk/society/2008/aug/30/mmr.health.media]

Controversy following publication of report

The controversy gained momentum in 2001 and 2002; in the latter year, 1257 stories were published about it.The paper, press conference and video sparked a major health scare in the United Kingdom. As a result of the scare, full confidence in MMR fell from 59 to 41 per cent after publication of the Wakefield research. In 2001, 26 per cent of family doctors felt the government had failed to prove there was no link between MMR and autism and bowel disease.cite book | author = Halvorsen R | title = The Truth about Vaccines | publisher = Gibson Square | date = 2007 | isbn = 9781903933923] After it became clearer that Wakefield's claims were not supported by scientific evidence, confidence in the MMR vaccine increased. A 2003 survey of 366 family doctors in the UK reported that 77% of them would advise giving the MMR vaccine to a child with a close family history of autism, and that 3% of them thought that autism could sometimes be caused by the MMR vaccine. [cite web |url=http://www.immunisation.nhs.uk/files/HPSurveyreport.pdf |accessdate=2007-09-06 |format=PDF |date=2003 |title= Health professionals 2003 childhood immunisation survey report |publisher= NHS Immunisation Information] A similar survey in 2004 found that these percentages changed to 82% and at most 2%, respectively, and that confidence in MMR had been increasing over the previous two years. [cite web |url=http://www.immunisation.nhs.uk/files/hp_survey_2004.pdf |accessdate=2007-09-06 |format=PDF |date=2004 |title= Health professionals 2004 childhood immunisation survey executive summary |publisher= Immunisation Information England |author= BMRB Social Research]

A factor in the controversy is that through most of the UK National Health Service doctors, only the combined vaccine is available; those who do not wish to have it given to their children must either have the separate vaccines given privately, or not vaccinate their children at all. The former Prime Minister, Tony Blair, strongly supported the vaccine in public and hinted that his son Leo had received the MMR vaccine, stating that "the vaccine was safe enough for [his] young son, Leo". [cite web |url=http://news.bbc.co.uk/1/hi/uk_politics/1803609.stm |publisher=BBC NEWS | title=Blair signals support for MMR |format= |work= |accessdate=2008-07-10] On several occasions Blair refused on privacy grounds to say whether Leo received the vaccine; in contrast, the subsequent Prime Minister, Gordon Brown, has explicitly confirmed his son has been immunized. [Nic Fleming [http://www.telegraph.co.uk/news/main.jhtml?xml=/news/2006/02/07/nmmr07.xml&sSheet=/news/2006/02/07/ixhome.html My son has had MMR jab, says Brown (in dig at Blair)] "Telegraph" 07 February 2006] The privacy claims of the Blairs were later undermined when Cherie Blair mentioned Leo's vaccination history when promoting her autobiography. A close friend and other associates of the Blairs strongly opposed vaccination. In the period January to September 2002, 32% of the stories written about MMR mentioned Leo Blair, as opposed to only 25% which mentioned Wakefield. MMR was the biggest science story in the press that year, and less than a third of the stories mentioned the overwhelming evidence that MMR is safe.

Administration of the combined vaccine instead of separate vaccines decreases the risk of children catching the disease while waiting for full immunization coverage.cite web |url=http://www.hpa.org.uk/webw/HPAweb&HPAwebStandard/HPAweb_C/1195733844552 |title= Why is MMR preferable to single vaccines? |date=2008 |accessdate=2008-08-31 |publisher= Health Protection Agency] The combined vaccine's two injections results in less pain and distress to the child than the six injections required by separate vaccines, and the extra clinic visits required by separate vaccinations increases the likelihood of some being delayed or missed altogether; [MMR vs three separate vaccines:
*cite journal |journal= Pediatrics |date=2001 |volume=107 |issue=5 |pages=e84 |title= Measles-mumps-rubella vaccine and autistic spectrum disorder: report from the New Challenges in Childhood Immunizations Conference convened in Oak Brook, Illinois, June 12–13, 2000 |author= Halsey NA, Hyman SL, Conference Writing Panel |pmid=11331734 |url=http://pediatrics.aappublications.org/cgi/content/full/107/5/e84 |doi= 10.1542/peds.107.5.e84
*cite journal |journal= Pediatrics |date=2002 |volume=109 |issue=1 |pages=172 |title= MMR—Separate administration-has it been done? |author= Leitch R, Halsey N, Hyman SL |pmid=11773568 |url=http://pediatrics.aappublications.org/cgi/content/full/109/1/172 |doi= 10.1542/peds.109.1.172
*cite journal |journal= J Infect |date=2002 |volume=44 |issue=1 |pages=1–6 |title= MMR vaccine: review of benefits and risks |author= Miller E |doi=10.1053/jinf.2001.0930 |pmid=11972410
*cite web |url=http://www.pm.gov.uk/output/page289.asp |title= MMR - scientific research |accessdate=2007-03-29] vaccination uptake significantly increased in the UK when MMR was introduced in 1988. Health professionals have heavily criticized media coverage of the controversy for triggering a decline in vaccination rates [Cite web
url=http://news.bbc.co.uk/2/hi/health/5118166.stm
title=BBC News, Doctors issue plea over MMR jab
accessyear=2006
accessdaymonth=26 June] . There is no scientific basis for preferring separate vaccines, or for using any particular interval between separate vaccines.cite journal |journal= Br Med Bull |year=2004 |volume=69 |pages=143–53 |title= MMR: risk, choice, chance |author= Fitzpatrick M |pmid=15226203 |url=http://bmb.oxfordjournals.org/cgi/content/full/69/1/143 |doi= 10.1093/bmb/ldh002]

John Walker-Smith, a coauthor of Wakefield's report and a supporter of the MMR vaccine, wrote in 2002 that epidemiology has shown that MMR is safe in most children, but observed that epidemiology is a blunt tool and studies can miss at-risk groups that have a real link between MMR and autism. [cite journal |journal=Lancet |year=2002 |volume=359 |issue=9307 |pages=705–6 |title= Autism, bowel inflammation, and measles |author= Walker-Smith J |doi=10.1016/S0140-6736(02)07783-8 |pmid=11879886] However, if a rare subtype of autism were reliably identified by clinical or pathological characteristics, epidemiological research could address the question whether MMR causes that autism subtype. [cite journal |journal=Lancet |year=2002 |volume=359 |issue=9323 |pages=2112–3 |title= Autism, bowel inflammation, and measles |author= Smeeth L, Hall A, Rodrigues L, Cook C, Fombonne E |doi=10.1016/S0140-6736(02)08918-3 |pmid=12086784] As yet there is no scientific evidence that MMR causes damage to the infant immune system, and there is much evidence to the contrary.

In 2001, Berelowitz, one of the co-authors of the paper, said "I am certainly not aware of any convincing evidence for the hypothesis of a link between MMR and autism". [cite web |url=http://www.mmrthefacts.nhs.uk/basics/truths.php |accessdate=2008-08-31 |year=2004 |title= MMR: myths and truths |publisher= NHS Immunisation Information] The Centers for Disease Control, [ [http://www.cdc.gov/od/science/iso/concerns/mmr_autism.htm Autism and Vaccines Theory] , from the U.S. Centers for Disease Control. Accessed June 13 2007.] the Institute of Medicine of the National Academy of Sciences, [http://www.iom.edu/CMS/3793/4705/20155.aspx Immunization Safety Review: Vaccines and Autism] . From the Institute of Medicine of the National Academy of Sciences. Report dated May 17 2004; accessed June 13 2007.] and the UK National Health Servicecite web |url=http://www.mmrthefacts.nhs.uk/ |accessdate=2007-09-19 |year=2004 |title= MMR The facts |publisher= NHS Immunisation Information] have all concluded that there is no evidence of a link between the MMR vaccine and autism.

Conflict of interest allegations

In February 2004, investigative reporter Brian Deer wrote in "The Sunday Times" of London that Wakefield had received £55,000 funding from Legal Aid Board solicitors seeking evidence to use against vaccine manufacturers, that several of the parents quoted as saying that MMR had damaged their children were also litigants, and that Wakefield did not inform colleagues or medical authorities of the conflict of interest."The Sunday Times" 2004:
*cite news |author= Deer B |title= Revealed: MMR research scandal |work= The Sunday Times |date=2004-02-22 |url=http://www.timesonline.co.uk/tol/news/uk/health/article1027603.ece |accessdate=2007-09-23
*cite web |author= Deer B |title= The Lancet scandal |url=http://briandeer.com/mmr-lancet.htm |date=2007 |accessdate=2007-09-23] Although Wakefield maintained that the legal aid funding was for a separate, unpublished study, [cite journal |journal=Lancet |year=2004 |volume=363 |issue=9411 |pages=823–4 |title= A statement by Dr Andrew Wakefield |author= Wakefield A |doi=10.1016/S0140-6736(04)15710-3 |pmid=15022650] the editors of "The Lancet" judged that the funding source should have been disclosed to them. [cite journal |journal=Lancet |year=2004 |volume=363 |issue=9411 |pages=820–1 |title= A statement by the editors of "The Lancet" |author= Horton R |doi=10.1016/S0140-6736(04)15699-7 |pmid=15022645] Richard Horton, the editor-in-chief, wrote, "It seems obvious now that had we appreciated the full context in which the work reported in the 1998 "Lancet" paper by Wakefield and colleagues was done, publication would not have taken place in the way that it did." [cite journal |journal=Lancet |year=2004 |volume=363 |issue=9411 |pages=747–9 |title= The lessons of MMR |author= Horton R |doi=10.1016/S0140-6736(04)15714-0 |pmid=15016482] Several of Dr. Wakefield's co-researchers also strongly criticized the lack of disclosure.

Deer continued his reporting in a BBC television documentary, "MMR: What They Didn't Tell You", broadcast on November 18 2004, which alleged that Wakefield had applied for patents on a vaccine that was a rival of the MMR vaccine, and that he knew of test results from his own laboratory at the Royal Free Hospital that contradicted his claims. [2004 BBC documentary:
*cite web |author=Deer B |title= The Wakefield factor |year=2007 |url=http://briandeer.com/wakefield-deer.htm |accessdate=2007-09-23
*cite journal |journal=BMJ |year=2004 |volume=329 |issue=7477 |pages=1293 |title=Dispatches. MMR: What They Didn't Tell You |author=Berger A |url=http://www.bmj.com/cgi/content/full/329/7477/1293 |doi=10.1136/bmj.329.7477.1293]

In 2006, Deer reported in "The Sunday Times" that Wakefield had been paid more than £400,000 by British trial lawyers attempting to prove that the vaccine was dangerous, with the undisclosed payments beginning two years before the "Lancet" paper's publication. [cite news |author= Deer B |title= MMR doctor given legal aid thousands |url=http://www.timesonline.co.uk/tol/newspapers/sunday_times/britain/article1265373.ece |accessdate=2007-09-23 |work= The Sunday Times |date=2006-12-31]

Retraction of an interpretation

"The Lancet", and many medical journals, requires papers to include the authors' conclusions about their research, known as the "interpretation". The summary of the 1998 "Lancet" paper ended as follows:

Interpretation We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.

In March 2004, immediately following the news of the conflict of interest allegations, ten of Wakefield's twelve coauthors retracted this interpretation. [cite journal |author=Murch SH, Anthony A, Casson DH "et al." |title= Retraction of an interpretation |journal=Lancet |volume=363 |issue=9411 |pages=750 |year=2004 |pmid=15016483 |doi=10.1016/S0140-6736(04)15715-2]

General Medical Council investigation

The General Medical Council, which is responsible for licensing doctors and supervising medical ethics in the UK, is investigating the affair [cite web |url=http://www.timesonline.co.uk/tol/news/uk/article565188.ece |title=MMR scare doctor faces list of charges |publisher=The Sunday Times |format= |work= |accessdate=2008-07-10 |date=2005-09-11] . Wakefield's colleagues Professor John Walker-Smith and Professor Simon Murch also face charges of serious professional misconduct over their roles in the affair. The General Medical Council alleges that the trio acted unethically and dishonestly in preparing the research into the MMR vaccine. They deny the allegations. [cite news |title=MMR scare doctor 'paid children' |url=http://news.bbc.co.uk/1/hi/health/6289166.stm |publisher=BBC |date=2007-07-16 |accessdate=2008-03-09 ] The case is proceeding in front of a fitness to practice panel, of three medical and two lay members, at the GMC. [cite web |author= General Medical Council | title= Dr Andrew Wakefield, Professor John Walker-Smith, Professor Simon Murch |url=http://www.gmcpressoffice.org.uk/apps/news/events/detail.php?key=1960 |accessdate=2007-09-06] Due to scheduling issues for the large number of lawyers and doctors involved in the proceedings, after the prosecution presented its case, between August and October 2007, they were agreed by the parties to be postponed until January 2008.

Recent studies

The number of reported cases of autism increased dramatically in the 1990s and early 2000s. This increase is largely attributable to changes in diagnostic practices; it is not known how much, if any, growth came from real changes in autism's prevalence, and no causal connection to the MMR vaccine has been demonstrated.cite journal |author=Rutter M |title= Incidence of autism spectrum disorders: changes over time and their meaning |journal= Acta Paediatr |volume=94 |issue=1 |date=2005 |pages=2–15 |pmid=15858952 |doi= 10.1080/08035250410023124] The following studies were published after the 1998 Wakefield "et al." paper.

*A 1998 population study of Swedish children found no difference in the prevalence of autistic children born before and after the 1982 introduction of the MMR vaccine in Sweden. [cite journal|author=Gillberg C, Heijbel H|title=MMR and autism|journal=Autism|date=1998|volume=2|issue=4|pages=423–4|url=http://aut.sagepub.com/cgi/reprint/2/4/423|doi=10.1177/1362361398024007]

*A 2002 retrospective cohort study of all 537,303 children born in Denmark from January 1991 through December 1998 found no statistically significant difference in risk of autism among the 440,655 who were vaccinated with MMR. This study provided strong evidence against the hypothesis that MMR vaccination causes autism. [cite journal |journal= N Engl J Med |date=2002 |volume=347 |issue=19 |pages=1477–82 |title= A population-based study of measles, mumps, and rubella vaccination and autism |author= Madsen KM, Hviid A, Vestergaard M "et al." |pmid=12421889 |doi= 10.1056/NEJMoa021134]

*In February 2004, a population-based case-controlled study of 624 cases and 1,824 matched controls, conducted by the Centers for Disease Control, found no evidence to support an association between MMR and autism. [cite journal |journal=Pediatrics |date=2004 |volume=113 |issue=2 |pages=259–66 |title= Age at first measles-mumps-rubella vaccination in children with autism and school-matched control subjects: a population-based study in metropolitan Atlanta |author= DeStefano F, Bhasin TK, Thompson WW, Yeargin-Allsopp M, Boyle C |pmid=14754936 |url=http://pediatrics.aappublications.org/cgi/content/full/113/2/259 |laysummary=http://www.bmj.com/cgi/content/full/328/7437/421-a |laydate=2004-02-21 |laysource=BMJ |doi= 10.1542/peds.113.2.259]

*In September 2004, a case–controlled study of 1,294 cases of pervasive developmental disorder and 4,469 controls from the UK General Practice Research Database found a relative risk of 0.86 for MMR vaccine, which suggests that MMR is not associated with an increased risk of pervasive developmental disorders such as autism, and, if anything, is protective. [cite journal |journal= Lancet |date=2004 |volume=364 |issue=9438 |pages=963–9 |title= MMR vaccination and pervasive developmental disorders: a case-control study |author= Smeeth L, Cook C, Fombonne E "et al." |doi=10.1016/S0140-6736(04)17020-7 |pmid=15364187]

*In October 2004, a meta review, financed by the European Union, was published in the October 2004 edition of Vaccine [cite journal | author=Jefferson T, Price D, Demicheli V, Bianco E | title=Unintended events following immunization with MMR: a systematic review | journal=Vaccine | year=2003 | pages=3954–60 | volume=21 | issue=25-26 | pmid=12922131 | doi=10.1016/S0264-410X(03)00271-8] that assessed the evidence given in 120 other studies and considered unintended effects of the MMR vaccine. The authors concluded that
**the vaccine is associated with some positive and negative side effects,
**it was "unlikely" that there was a connection between MMR and autism, and
**"The design and reporting of safety outcomes in MMR vaccine studies ... are largely inadequate".

*In January 2005, a study of all younger residents of Olmsted County, Minnesota reported an eightfold increase in the age-adjusted incidence of research-identified autism over a period beginning in the early eighties and ending in the late nineties, but found no evidence of a link with MMR. The study's authors said that the timing of the increase suggested that it may have been due to improved awareness of the disorder, a growth in services, and changing definitions. [cite journal |journal= Arch Pediatr Adolesc Med |year=2005 |volume=159 |issue=1 |pages=37–44 |title= The incidence of autism in Olmsted County, Minnesota, 1976–1997: results from a population-based study |author= Barbaresi WJ, Katusic SK, Colligan RC, Weaver AL, Jacobsen SJ |pmid=15630056 |url=http://archpedi.ama-assn.org/cgi/content/abstract/159/1/37 |doi= 10.1001/archpedi.159.1.37]

* From January 2005 through July 2007, Dan Olmsted, a senior editor for UPI, conducted a journalistic investigation reported in his "Age of Autism" columncite news|author=Dan Olmsted|title=The Age of Autism: the last word|publisher=UPI|date=2007-07-18|url=http://www.upi.com/Consumer_Health_Daily/Reports/2007/07/18/the_age_of_autism_the_last_word/5761/|accessdate=2007-07-23] and found no unvaccinated children with autism. Olmsted looked for autistic children among unvaccinated Amish; in a subset of homeschooled children who are not vaccinated for religious reasons; and in a pediatric practice in Chicago with several thousand never-vaccinated children. However, in a critical 2005 assessment Olmsted's reporting was characterized as "misguided" by two anonymous reporters. Both sources "believed that Olmsted has made up his mind on the question and is reporting the facts that support his conclusions". [cite news|author=Daniel Schulman|title=Drug test|work=Columbia Journalism Review|date=2005|issue=6|url=http://www.cjr.org/issues/2005/6/schulman.asp|accessdate=2007-07-23] A 2006 study contradicted Olmsted by demonstrating a genetically determined syndrome of autism and mental retardation prevalent in the Old Order Amish population.cite journal|author=Strauss KA, Puffenberger EG, Huentelman MJ "et al."|title=Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2|journal=N Engl J Med|date=2006|volume=354|pages=1370–7|pmid=16571880|doi=10.1056/NEJMoa052773]

*Japan provided a natural experiment on the subject: combined MMR vaccine was introduced in 1989, but the programme was terminated in 1993 and only single vaccines used thereafter. In March 2005 a study of over 30,000 children (278 cases) born in one district of Yokohama concluded "The incidence of all autistic spectrum disorders (ASD), and of autism, continued to rise after MMR vaccine was discontinued. The incidence of autism was higher in children born after 1992 who were not vaccinated with MMR than in children born before 1992 who were vaccinated. The incidence of autism associated with regression was the same during the use of MMR and after it was discontinued." The authors concluded: "The significance of this finding is that MMR vaccination is most unlikely to be a main cause of ASD, that it cannot explain the rise over time in the incidence of ASD, and that withdrawal of MMR in countries where it is still being used cannot be expected to lead to a reduction in the incidence of ASD." [cite journal |author= Honda H, Shimizu Y, Rutter M |title= No effect of MMR withdrawal on the incidence of autism: a total population study |journal= J Child Psychol Psychiatry |volume=46 |issue=6 |pages=572–9 |year=2005 |pmid=15877763 |doi=10.1111/j.1469-7610.2005.01425.x |laysource=Bandolier |laysummary=http://www.jr2.ox.ac.uk/bandolier/booth/Vaccines/noMMR.html |laydate=2005]

* In October 2005, the Cochrane Library published a review of 31 scientific studies, which found no credible evidence of an involvement of MMR with either autism or Crohn's disease. The review also stated "Measles, mumps and rubella are three very dangerous infectious diseases which cause a heavy disease, disability and death burden in the developing world.… [T] he impact of mass immunisation on the elimination of the diseases has been demonstrated worldwide." However the authors of the report also stated that "the design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate."cite journal |doi=10.1002/14651858.CD004407.pub2 |pmid=16235361 |title= Vaccines for measles, mumps and rubella in children |author=Demicheli V, Jefferson T, Rivetti A, Price D |journal= Cochrane Database Syst Rev |year=2005 |volume=19 |issue=4 |laysummary=http://www.cochrane.org/press/MMR_final.pdf |laydate=2005-10-19 |laysource=Press release]

* In July 2006, a study of 27,749 Canadian children ruled out an association between pervasive developmental disorder and MMR vaccinations. [cite journal|journal=Pediatrics|date=2006|volume=118|issue=1|pages=e139–50|title=Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations|author=Fombonne E, Zakarian R, Bennett A, Meng L, McLean-Heywood D|doi=10.1542/peds.2005-2993|pmid=16818529|url=http://pediatrics.aappublications.org/cgi/content/full/118/1/e139]

* A review published in September 2006 found no scientific evidence that the MMR vaccine plays any part in the causes or triggering of autism, even in a subgroup of children with the condition. [cite journal |journal= Child Care Health Dev |year=2006 |volume=32 |issue=5 |pages=511–9 |title= Vaccines and the changing epidemiology of autism |author= Taylor B |doi=10.1111/j.1365-2214.2006.00655.x |pmid=16919130]

* A 2006 study found no evidence of measles virus genome sequences persisting in the blood of autistic children vaccinated with MMR. [cite journal |journal=Pediatrics |date=2006 |volume=118 |issue=4 |pages=1664–75 |title= No evidence of persisting measles virus in peripheral blood mononuclear cells from children with autism spectrum disorder |author= D'Souza Y, Fombonne E, Ward BJ |doi=10.1542/peds.2006-1262 |pmid=17015560 Erratum (2006): "Pediatrics" 118 (6): 2608. doi|10.1542/peds.2006-3102.]

* A 2006 multi-site study of 351 children with ASD found no evidence that onset of autistic symptoms or of regression was related to MMR vaccination. [cite journal |journal= J Autism Dev Disord |date=2006 |volume=36 |issue=3 |pages=299–316 |title= Is there a 'regressive phenotype' of Autism Spectrum Disorder associated with the measles-mumps-rubella vaccine? A CPEA Study |author= Richler J, Luyster R, Risi S "et al." |doi=10.1007/s10803-005-0070-1 |pmid=16729252]

* A 2007 study found that there was no change in the rates of regressive autism after MMR was withdrawn from Japan. [cite journal |journal= J Autism Dev Disord |date=2007 |volume=37 |issue=2 |pages=210–7 |title= MMR-vaccine and regression in autism spectrum disorders: negative results presented from Japan |author= Uchiyama T, Kurosawa M, Inaba Y |doi=10.1007/s10803-006-0157-3 |pmid=16865547]

* A 2007 case study used the figure in Wakefield's 1999 letter to "The Lancet" alleging a temporal association between MMR vaccination and autism [cite journal |journal=Lancet |year=1999 |volume=354 |issue=9182 |pages=949–50 |title=MMR vaccination and autism |author= Wakefield AJ |pmid=10489978 |doi=10.1016/S0140-6736(05)75696-8] to illustrate how a graph can misrepresent its data, and gave advice to authors and publishers to avoid similar misrepresentations in the future. [cite journal |journal= Drug Saf |year=2007 |volume=30 |issue=10 |pages=831–6 |title= A case study of a graphical misrepresentation: drawing the wrong conclusions about the measles, mumps and rubella virus vaccine |author= Cox AR, Kirkham H |pmid=17867721]

* A 2007 review of independent studies performed after the publication of Wakefield "et al."s original report found that these studies provide compelling evidence against the hypothesis that MMR is associated with autism. [cite journal |journal= Clin Pharmacol Ther |year=2007 |volume=82 |issue=6 |pages=756–9 |title= Vaccines and autism: evidence does not support a causal association |author= DeStefano F |doi=10.1038/sj.clpt.6100407 |pmid=17928818]

* A review of the work conducted in 2004 for UK court proceedings but not revealed until 2007 found that the polymerase chain reaction analysis essential to the Wakefield "et al." results was fatally flawed due to contamination, and that it could not have possibly detected the measles that it was supposed to have detected.

* A 2008 study examined the blood of children aged about 10 years that had been given the MMR vaccine, and found no difference in levels of measles virus or antibodies between children diagnosed with autism and those who had not. [cite journal |journal=Arch Dis Child |date=2008 |title= Measles vaccination and antibody response in autism spectrum disorders |author= Baird G, Pickles A, Simonoff E "et al." |pmid=18252754 |doi=10.1136/adc.2007.122937 |laysource= The Guardian |laysummary=http://www.guardian.co.uk/society/2008/feb/05/health.children |laydate=2008-02-05]

* A 2008 study found a significant increase in selective nonreceipt of MMR vaccine in the U.S. that was temporally associated with the publication of the Wakefield report, and which decreased to baseline levels by the time significant media coverage began two years later; this suggests that parents learned about the controversy from sources other than the media. [cite journal |author= Smith MJ, Ellenberg SS, Bell LM, Rubin DM |title= Media coverage of the measles-mumps-rubella vaccine and autism controversy and its relationship to MMR immunization rates in the United States |journal=Pediatrics |volume=121 |issue=4 |pages=e836–43 |year=2008 |pmid=18381512 |doi=10.1542/peds.2007-1760]

* A 2008 study found that children with autism had no more peptides in their urine than typical children, casting doubt on the proposed mechanism for the hypothesized diagnosis of autistic enterocolitis. [cite journal |journal= Arch Dis Child |date=2008 |title= Absence of urinary opioid peptides in children with autism |author= Cass H, Gringras P, March J "et al." |doi=10.1136/adc.2006.114389 |pmid=18337276 |laysummary=http://news.bbc.co.uk/1/hi/health/7300327.stm |laysource= BBC News |laydate=2008-03-17]

* A 2008 preliminary case-control study based on a parent survey presented evidence that the common pain/fever reliever paracetamol (acetaminophen) following MMR vaccination is apparently associated with development of autism in children aged 1–5 years. The effect seemed to appear only in children who show some post-vaccination regression together with other post-vaccination sequelae such as fever, and it was not seen with other painkillers such as ibuprofen. The effect has not been independently confirmed. [cite journal |journal=Autism |date=2008 |volume=12 |issue=3 |pages=293–307 |title= Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: the results of a parent survey |author= Schultz ST, Klonoff-Cohen HS, Wingard DL, Akshoomoff NA, Macera CA, Ji M |doi=10.1177/1362361307089518 |pmid=18445737]

* A 2008 letter reported that younger siblings of Canadian children with autism are significantly less likely to receive MMR and other immunizations, suggesting that their parents are delaying or avoiding these children's vaccinations. [cite journal |author= Kuwaik G, Roberts W, Brian J "et al." |title= Immunization uptake in siblings of children with autism |journal=Pediatrics |volume=122 |issue=3 |pages=684–5 |year=2008 |pmid=18762548 |doi=10.1542/peds.2008-1624]

* A 2008 study of children with gastrointestinal disturbances found no difference between those with ASD and those without, with respect to the presence of measles virus RNA in the bowel; it also found that gastrointestinal symptoms and the onset of autism were unrelated in time to the administration of MMR vaccine. [cite journal |journal= PLoS ONE |year=2008 |volume=3 |issue=9 |pages=e3140 |title= Lack of association between measles virus vaccine and autism with enteropathy: a case-control study |author= Hornig M, Briese T, Buie T "et al." |doi=10.1371/journal.pone.0003140 |pmid=18769550 |url=http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003140 |laysummary=http://www.washingtonpost.com/wp-dyn/content/article/2008/09/03/AR2008090303396.html |laysource= Washington Post |laydate=2008-09-04]

Litigation

During the 1980s and 1990s, a number of lawsuits were brought in the United States against manufacturers of vaccines, alleging the vaccines had caused a variety of physical and mental disorders in children. While these lawsuits were inconclusive,Fact|date=April 2007 they did lead to a massive jump in the costs of the MMR vaccine, as pharmaceutical companies sought to cover potential liabilities by lobbying for legislative protection.Fact|date=March 2007 By 1993, Merck KGaA had become the only company willing to sell MMR vaccines in the United States and the United Kingdom. Two other MMR vaccines were withdrawn in the UK in 1992 on safety grounds arising from the strain of mumps component.Fact|date=March 2007

In September 1995, the Legal Aid Board in the UK granted a number of families financial assistance to pursue legal claims against the state health authorities and the vaccine's manufacturers, claiming that their children were killed or seriously injured by the MMR vaccine.Fact|date=February 2007 A pressure group called JABS (Justice, Awareness, Basic Support) was established to represent families with children who, their parents said, were "vaccine-damaged." This litigation is now discontinued [http://briandeer.com/wakefield/keith-judgment.doc] . ₤15 million in public legal aid funding was spent on the litigation, of which ₤9.7 million went to solicitors and barristers, ₤4.3 million to expert witnesses, and nothing went to the children.cite news |work=spiked |date=2007-07-04 |title= 'The MMR-autism theory? There's nothing in it' |author= Fitzpatrick M |url=http://spiked-online.com/index.php?/site/article/3562/ |accessdate=2008-01-22]

The Omnibus Autism Proceeding is currently in progress before the Office of Special Masters of the U.S Court of Federal Claims, commonly called the vaccine court. The Petitioners' Steering Committee have advanced theories that MMR vaccines can cause autism, possibly in combination with thiomersal-containing vaccines. [cite press release |url=http://www.uscfc.uscourts.gov/sites/default/files/pressrelease.autismproceedings.pdf |format=PDF |accessdate=2008-05-13 |date=2008-05-07 |title= The autism proceedings |publisher= U.S. Court of Federal Claims] In 2007 three individual test cases were presented to test the theory about the combination. Test cases were also scheduled on whether MMR vaccines alone cause autism, but the special masters hearing the cases have said that these may not be needed. [cite web |url=http://www.uscfc.uscourts.gov/sites/default/files/autism/4%2016%2008%20Order%20Con%20Theories%202%20and%203.pdf |format=PDF |accessdate=2008-05-13 |title= Order concerning case processing |publisher= Office of Special Masters, U.S. Court of Federal Claims |date=2008-04-16]

Disease outbreaks

After the controversy began, the MMR vaccination compliance dropped sharply in the United Kingdom, from 92% in 1996 to 84% in 2002. In some parts of London, it was as low as 61% in 2003, far below the rate needed to avoid an epidemic of measles [cite journal |journal= Lancet |date=2003 |volume=362 |issue=9394 |pages=1498–9 |title= Separating inflammation from speculation in autism |author= Murch S |doi=10.1016/S0140-6736(03)14699-5 |pmid=14602448] . By 2006 coverage for MMR in the UK at 24 months was 85%, lower than the about 94% coverage for other vaccines. [cite journal |author= McIntyre P, Leask J |title= Improving uptake of MMR vaccine |journal=BMJ |volume=336 |issue=7647 |pages=729–30 |date=2008 |pmid=18309963 |doi=10.1136/bmj.39503.508484.80]

After vaccination rates dropped, the incidence of two of the three diseases increased greatly in the UK. In 1998 there were 56 confirmed cases of measles in the UK; in 2006 there were 449 in the first five months of the year, with the first death since 1992; cases occurred in inadequately vaccinated children. [cite journal |journal=BMJ |year=2006 |volume=333 |issue=7574 |pages=890–5 |title= Measles in the United Kingdom: can we eradicate it by 2010? |author= Asaria P, MacMahon E |doi=10.1136/bmj.38989.445845.7C |pmid=17068034 |url=http://www.bmj.com/cgi/content/full/333/7574/890] . Mumps cases began rising in 1999 after years of very few cases, and by 2005 the United Kingdom was in a mumps epidemic with almost 5000 notifications in the first month of 2005 alone. [cite journal |journal=BMJ |year=2005 |volume=330 |issue=7500 |pages=1132–5 |title=Mumps and the UK epidemic 2005 |author= Gupta RK, Best J, MacMahon E |pmid=15891229 |doi=10.1136/bmj.330.7500.1132 |url=http://www.bmj.com/cgi/content/full/330/7500/1132] The age group affected was too old to have received the routine MMR immunizations around the time the paper by Wakefield "et al." was published, and too young to have contracted natural mumps as a child, and thus to achieve a herd immunity effect. With the decline in mumps that followed the introduction of the MMR vaccine, these individuals had not been exposed to the disease, but still had no immunity, either natural or vaccine induced. Therefore, as immunization rates declined following the controversy and the disease re-emerged, they were susceptible to infection. [cite web |url=http://www.nzherald.co.nz/index.cfm?c_id=2&ObjectID=10125382 |title=England and Wales in grip of mumps epidemic - 13 May 2005 - NZ Herald: World / International News |format= |work= |accessdate=2008-07-10] [cite web |url=http://www.hpa.org.uk/infections/topics_az/mumps/gen_info.htm |title=HPA - Mumps |format= |work= |accessdate=2008-07-10] Measles and mumps cases continued in 2006, at incidence rates 13 and 37 times greater than respective 1998 levels. [cite web |title= Confirmed cases of measles, mumps & rubella |publisher= Health Protection Agency |date=2007-03-22 |url=http://www.hpa.org.uk/infections/topics_az/measles/data_mmr_confirmed.htm |accessdate=2007-09-05] Two children were severely and permanently injured by measles encephalitis despite undergoing kidney transplantation in London.

Disease outbreaks also caused casualties in nearby countries. 1,500 cases and three deaths were reported in the Irish outbreak of 2000, which occurred as a direct result of decreased vaccination rates following the MMR scare.cite journal |journal=Clin Med |date=2007 |volume=7 |issue=6 |pages=562–78 |title= Science and serendipity |author= Pepys MB |pmid=18193704]

In 2008, for the first time in 14 years, measles was declared endemic in the UK, meaning that the disease was sustained within the population; this was caused by the preceding decade's low MMR vaccination rates, which created a population of susceptible children who could spread the disease.cite journal |journal=Eurosurveillance |date=2008 |volume=13 |issue=27 |pages=18919 |title= Measles once again endemic in the United Kingdom |url=http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=18919] MMR vaccination rates for English children were unchanged in 2007–08 from the year before, at too low a level to prevent serious measles outbreaks. [cite news |url=http://news.bbc.co.uk/1/hi/health/7633115.stm |date=2008-09-24 |accessdate=2008-09-24 |title= MMR vaccine uptake rise 'stalls' |work=BBC News] In May 2008, a British 17-year-old with an underlying immunodeficiency died of measles. In 2008 Europe also faced a measles epidemic, including large outbreaks in Austria, Italy, and Switzerland.

ee also

*Vaccine controversy

References