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The following news release appeared in the popular media in 1998, and was a major television news item:
Cleveland, Ohio, Posted 4:00 P.M. November 20, 1998:"Studies Suggest the Measles-Mumps-Rubella Vaccine Is a Possible Cause of Autism"Evidence of a possible link between the MMR vaccination and autism came from the finding of children from villages, within two miles of each other in Scotland, being diagnosed with autism after MMR inoculation.1 The three children from different families in Ayrshire were given MMR vaccine at the same health center within four months of each other. Child neuro-psychologist, Ken Aitken, said that the cluster of cases in Ayrshire indicated the need for further research before the MMR vaccine can be declared safe beyond doubt.
News Channel 5 reports hundreds of thousands of children receive the MMR vaccine every year, but now studies show a tiny percentage of cases may cause autism. Since the MMR vaccine was introduced about 35 years ago,the incidents of autism in children have increased by 1,000 percent - from two or three in 10,000 - to one in 500.
"More children are being diagnosed with autism and clusters like these are deeply worrying", he said. "There is strong circumstantial evidence to point to the MMR ä as the reason, but there has to be much more coordinated research to look into this issue in detail. Research so far hasn't been adequate to address the questions that are being raised about the possible links and there have been a lot of queries about the validity of the conclusions which were drawn."
In the 1980s, one in 2500 children in Britain and America were diagnosed as autistic. Latest figures compiled by researchers revealed a dramatic leap - to one in 146.
The MMR immunisation was introduced in the UK in 1988 with the first dose aimed at children of 12-15 months, a the second dose at 3-5 years. It is designed to protect against measles, mumps and rubella (German Measles) and works by stimulating the immune system to produce antibodies against the viruses without causing harm. It was so well received by both parents and doctors that over 90 per cent of children were being immunised by 1992.
Most children received the vaccine with no obvious serious side-effects, but some became seriously ill within a few weeks. These children began behaving strangely, stopped talking and became socially withdrawn, staring into space for hours on end. Many developed a raging thirst, bizarre eating habits, multiple food allergies, hyperactivity and sleep problems. This was usually accompanied by abdominal pain, bloating and bowel disturbances. Some children became incontinent of urine or feces. Their development deteriorated. Thousands of children now fall into this category of abnormal development only after receiving the vaccine.
Professor John O'Leary, Director of Pathology at the Coombe Women's Hospital in Dublin, told the US Congress in April, 2000, that he had produced compelling evidence of an association between autism and the MMR vaccine. Professor O'Leary found the measles virus in the guts of 24 out of 25 children who had developed autism, after an apparently previously healthy infancy.
His research supported the findings of Andrew Wakefield, of the Royal Free Hospital, London, who claimed there was an etiological implication between persistent measles virus infection or measles vaccination and inflammatory bowel disease (IBD), mainly on the basis of epidemiological and immunohistochemical findings. Dr. Wakefield identified "autistic enterocolitis", an inflammation of the gut in 150 autistic children who became autistic after receiving the vaccine.
Dr. Aitken, based at Edinburgh University, said, "The substantial increase in cases in the US began about three years after MMR vaccine was introduced and the same thing happened three years after MMR was introduced in Britain. There has been a national increase throughout Britain and I find it very surprising that the change is so tightly linked in time with when triple vaccine was introduced."
On February 28, 1998, Wakefield reported in The Lancet a possible connection among inflammatory bowel disease, autism, and viral infection associated with measles, mumps, and rubella (MMR) vaccination. The damage from autism is thought to be provoked by an allergic reaction initiated by the body's reaction to the vaccine. This auto-immune response may also reduce levels of the dipeptidyl peptidase (DPP)-IV enzyme, thereby connecting vaccines to the opioid theory of autism.
Andrew Wakefield did his first colonoscopy on an autistic child, because the anguished mother begged him to find the reason why her son had such terrible gastrointestinal problems. Finding some very specific pathology, Dr. Wakefield proceeded to investigate 11 more autistic children, again finding similar pathology in all children. These children had lost acquired skills, including communication, after a period of apparent normality.
Among eight of the children, the onset of behavioral problems had been linked, either by the parents or the child's physician, with MMR vaccination Five had an early adverse reaction to immunization (rash, fever, delirium, and seizures in 3). The average interval from exposure to first behavioral symptom was 6.3 days (range: 1-14 days).
Among the remaining 4 children, one received monovalent measles vaccine at 15 months, after which his development slowed. A striking deterioration then occurred in his behavior at age 4.5 years, the day after he received an MMR vaccine. A second child received the MMR vaccine at 16 months, developing at 18 months a combination of recurrent, antibiotic resistant, otitis media, along with his first behavioral symptoms (lack of interest in siblings and lack of play). A third child received an MMR at 15 months, experienced recurrent "viral pneumonia" for the next 8 weeks, and developed behavioral symptoms 4 weeks after the MMR ( loss of speech development and deterioration in language skills). The fourth child developed self- injurious behavior 2 month after the MMR.
Urinary methylmalonic acid excretion was significantly raised in all children tested (8 of the 12). Ten of the twelve children showed lymphoid nodular hyperplasia of the terminal ileum on endoscopy. The eleventh child had prominent luteal lymph nodes and the ileum was not reached in the twelfth (who had an ulcer in the rectum along with chronic colitis).
Wakefield, concluded that a subset of autistic people may suffer brain inflammation resulting from infections that began in their intestines after they were inoculated with the measles-mumps-rubella (MMR) vaccine. Theoretically, this condition could occur after naturally-acquired infection as well. The pro-vaccine community would argue, if this is true, that vaccination still reduces the incidence of disease by reducing the number of infections.
Wakefield's studies received enormous press attention in the United Kingdom. The immediate result of Dr.Wakefield's paper was a vitriolic attack from every front. A flood of opposing articles appeared in the same issue of The Lancet, and systematic criticism, nearing persecution, of Dr. Wakefield began, and is still going on. Rates of vaccination against measles fell to about 85 percent last year. Epidemiologists have been predicting a measles epidemic to result. Ireland reported an outbreak of 300 measles cases as of summer, 2000, compared to only 30for all of 1999. Two of the new cases were infants who had to be hospitalized with pneumonia complications.
Distraught parents of affected children have become even more confused, because no one has been able to prove conclusively to them yet, that an MMR vaccine-Autism connection does not really exist.
We know from data reported before the availability of MMR vaccine, that a subset of autistic children suddenly regressed at age 15 months, long before the measles vaccine became available.There have been no safety follow-up studies looking beyond four weeks post vaccination, and many studies quoted, have been partially funded by vaccine manufacturers, with obvious commercial interests.
No serious researcher has looked at a large sample - three to nine months post MMR vaccination, when auto-immune diseases usually would occur. When some parents in England became vocal, the pro-vaccine authorities in the UK reacted forcefully, to protect the MMR vaccination program. The single measles, mumps and rubella vaccines effectively became unavailable, and every effort was made to prove Dr. Wakefield wrong.
Despite the above, Britain's National Health Service's Chief Medical Officer, Sir Kenneth Calman, felt confident enough to say, "I have concluded there is no link between MMR immunisation and autism." Questioned in Parliament in 1997 on the possible link between MMR and autism, then health minister Tessa Jowell reassured Parliament that: "No vaccine is issued in the United Kingdom unless it passes the highest standards for quality, and parents should have confidence that the vaccines that are provided are both safe and efficacious."
In 1999, two studies appeared that the Department of Health claimed "reinforce the conclusion that there is no link" between MMR and autism. The first, by the Committee on the Safety of Medicines, involved examining questionnaires sent to the parents who had suspected MMR as a cause for their child's autism - 1200 questionnaires were distributed and 126 examined in detail. The study concluded: "It is impossible to prove or refute the suggested associations between MMR vaccine and autism" - hardly convincing reassurance.
The second study cited by the DOH looked at one area - north London - and found an alarming increase in autism there. The incidence was running steadily at between four and eight of the children born there each year between 1978 and 1985. Then came a dramatic increase to just under 50 of the children born in 1992 - the last year studied by Professor Brent Taylor and colleagues at University College London. Curiously, however, they concluded: "Our analyses do not support a causal association between MMR vaccine and autism."
The Taylor study was funded by The Medicines Control Agency and The Public Health Laboratory Service and was published in The Lancet, June 1999. Taylor, et al. stated that the age of diagnosis was the same before and after the introduction of the MMR vaccine, and used this finding to conclude that the MMR vaccine did not have a causative role in autism. Dr. Taylor stated: "For age at first parental concern, no significant temporal clustering was seen for cases of core autism and atypical autism, with the exception of a single interval within six months of MMR vaccine associated with a peak in reported age of parental concern at 18 months." Taylor, et al. Could not explain the increase in autism noted in 1992, the last year for which they examined data.
To others, Taylor's failure to explain the massive increase in autism only added fuel to the controversy. Children who were born in the mid-1980s in Britain and the 1970s in the United Sates were the first to receive the MMR vaccine. In California the incidence of autism was running at 150-200 a year until 1980, when it dramatically rose to reach nearly 600 in 1990.
While Taylor argued that MMR cannot contribute to autism, and Wakefield argued that it might, both studies may be correct. What Taylor may have missed is the susceptible child argument. He limits himself to the more typical, reductionistic, one variable theory of disease. In this theory, one agent causes a disease. All individuals exposed to this agent have equal probability of developing the disease.
A more accurate theory of disease posits susceptible individuals who succumb to the disease after multiple contributory insults. Wakefield worked backwards from children who definitely had autism with gastrointestinal symptoms. Taylor worked forward from all children receiving the MMR vaccine. While various authors question his sampling effort and point out potential bias in how he selected his subjects, the much more important problem lies in Taylor's type of study posing no help for the question of whether susceptible children could be more likely to develop autism after MMR vaccine.
We have only begun to speculate about who is susceptible to autism. We know the risk is higher if one or more family members have the condition. But what are the promoting agents that make autism more likely? Not all children with autistic siblings develop autism. The genetic penetration is not 100%. Non-genetic factors must play a role. Could vaccines be one of these promoting agents? Wakefield suggested yes, and Taylor's study did not really address that question.
Some other investigators have not been able to reproduce Wakefield's findings [M.A. Azfal and colleagues]. They could not detect measles viruses in the bowel, brain, or any other tissue of the patients in Wakefield's series.2
Subjectively, we cannot deny that many parents report developmental deterioration following MMR vaccination. Neurological sequelae following MMR are also widely reported. Dozens of heart-rending, anecdotal accounts link permanent neurologic disability or death to vaccine use. One of the leading sites in the anti-immunization field is the National Vaccine Information Centre (NVIC).
Other studies besides Wakefield's have suggested a link between autism and vaccination. H.H.Fudenberg reported that the first symptoms of autism among 15 of 20 children developed within a week of vaccination. S.Gupta commented on the striking association between MMR vaccination and the onset of behavioral symptoms in all the children he investigated for regressive autism.
The MMR vaccine is all live virus. Disintegrative psychosis is recognized as a sequela of measles encephalitis. Viral encephalitis can give rise to autistic disorders, particularly when it occur early in life.
A genetic association for autism is represented by a null allele of the complement C4B gene located in the class III region of the major histocompatibility complex. The C4B-gene is also crucial for protection against viruses. Affected individuals may not handle certain viruses appropriately - even the attenuated ones used in vaccines. In an addendum to the paper, Wakefield, et al. noted that their sample size had increased to 40 children by Jan 28,1998, with 39 of those showing similar findings. The C4b null allele is present on chromosome 6.3
These studies support our view that MMR vaccine may trigger a cascade of events leading to autism in genetically susceptible children, and not affect children who lack susceptibility. Unfortunately, vaccination among public health and medical practitioners has become almost sacred. Questioning the wisdom of vaccination for certain children is seen as professional heresy. Nevertheless, the possibility cannot be ignored.
Could killed (rather than live virus) MMR accomplish the same task? Should measles be administered separately from mumps? We know that the combination of chicken pox and measles dramatically increases the risk for subacute sclerosing panencephalitis. Perhaps other mixed viral infections are also clinically significant.
More important is the science we must use to explore this. Simple correlation analysis and comparison studies will not suffice. If autism is indeed linked to the MMR vaccine in genetically susceptible individuals, unless these individuals are selected from the larger pool, the statistical significance will cancel out in these studies.
Medical research also suffers from a failure to consider interactions and synergy in the disease process. Simple epidemiology will not suffice either, since we are not even sure what the potential genetic defect is in autism - or if autism is one syndrome or many.
The United States' Center for Disease Control (CDC) believes that the current scientific evidence does not support the hypothesis that MMR, or any combination of vaccines, cause the development of autism, including regressive forms of autism.4 CDC argues that the apparent link between MMR and autism is purely coincidental, based upon the fact that the MMR vaccine is usually given between the ages of 12 and 18 months, which is also the most common age at which autism is diagnosed. One could say, "go figure!", or pursue more sophisticated studies.
An extensive study of the evidence was recently conducted in the United Kingdom. The British Committee on Safety of Medicines convened a "Working Party on MMR Vaccine" to conduct a systematic review of reports of autism, gastrointestinal disease, and similar disorders after receipt of MMR or measles/rubella vaccine. The National Childhood Encephalopathy Study (NCES) was examined to see if there was any link between measles vaccine and neurological events.
The CDC noted that no researchers in England had found any indication that measles vaccine contributed to the development of long-term neurological damage, including educational and behavioral deficits (Miller et al. 1997). A more recent epidemiological study also found no association between MMR vaccine and autism (Taylor et al. 1999). This study compared rates of autism between children who received the MMR vaccine and children who did not. The results found no difference in rates of autism between the two groups. On the other hand, such large scale population studies, would not necessarily be expected to identify a small difference in autistic rates, which, as parents argue, is crucial to those affected.
The CDC agreed with an expert committee from the UK Medical Research Council (MRC) who reviewed Wakefield's research and concluded that no link had been demonstrated between MMR vaccine and inflammatory bowel disease in autism.
Wakefield's study was criticized for:
- Using too few cases to make any generalizations about the causes of autism; only 12 children were included in the study. The cases were selected by researchers and may not be representative of many cases of autism.
- There were inadequate groups of control children. As a result, it is difficult to determine whether the bowel changes were similar to changes in normal children, or to determine if the rate of vaccination in autistic children was higher than in the general population.
- The study did not identify the time period during which the cases were identified.
- In at least 4 of the 12 cases, behavioral problems appeared before the onset of symptoms of bowel disease; that is, the effect preceded the proposed cause. It is thus proposed unlikely, therefore, that bowel disease or the MMR vaccine triggered the autism.
The CDC argues against any scientific research or data indicating benefit to separating the MMR vaccine into its individual components. CDC argued that splitting the MMR vaccine into three separate doses could be harmful because it would expose children unnecessarily to potentially serious diseases. If the rubella vaccine were delayed, 4 million children would be susceptible to rubella for an additional six to 12 months. This would potentially allow otherwise preventable cases of congenital rubella syndrome (CRS) to occur. Infection of pregnant woman with "wild" rubella virus is one of the few known causes of autism. Thus, by preventing infection of pregnant women, rubella vaccine also prevents autism, asserts CDC.
CDC argues that, due to the general safety of vaccines, and the rarity of serious vaccine adverse events [Ed: although, see information from the US government contained in a Database of Vaccine Injury: The Vaccine Adverse Event Reporting System (VAERS)], it is extremely difficult to study whether a subgroup (e.g., family members) are actually at increased risk compared with the general population.
The one exception, they acknowledge, is an increased risk of neurologic events -primarily febrile seizures - after vaccination with DTP vaccine and measles-containing vaccines (MCV). The risk increases if any of these have previously occurred in immediate family members. Considering the rare occurrence of these events after DTP and MCV vaccination, the generally benign outcome of febrile convulsions, and the risk of pertussis and measles to unvaccinated people and the general population, the Advisory Committee on Immunization Practices concluded that a history of convulsions in siblings or parents should not be a contraindication to pertussis or measles vaccination.
Special care in the prevention of post-vaccination fever could be warranted in children with a family history of seizures, they admit. For instance, oral polio vaccine (OPV) is contraindicated when there is a family member with immune-deficiency, since OPV can spread to family contacts.
CDC argues for evidence of the benefits of childhood immunization, including record, or near record, low rates of vaccine preventable diseases in the United States. Last year, for example, there were fewer than 100 reported cases of measles - and no deaths - in the US, compared with 27,786 cases and 64 deaths in 1990.
Kawashima, et al.5 reported that measles virus could be present in the intestines of patients with Crohn's disease. Responding to Wakefield's data on "autistic enterocolitis (see above), the authors set out to determine if the virus found in Crohn's disease, ulcerative colitis, and autistic enterocolitis came from wild strains of measles or from vaccine strains.
To do this, they found measles RNA from peripheral blood mononuclear leukocytes (PBML) in eight patients with Crohn's disease, three patients with ulcerative colitis, and nine children with autistic enterocolitis. They used healthy children and patients with subacute sclerosing pan-encephalitis and human immunodeficiency virus 1 as controls (eight patients).
RNA was purified from PBML, followed by reverse transcription. The resulting cDNAs were subjected to nested PCR for detection of specific regions of the hemaglutinin (H) and fusion (F) gene regions. Positive samples were sequenced directly, in nucleotides 8393-8676 (H region) or 5325-5465 (from noncoding F to coding F region).
One of eight patients with Crohn disease, one of three patients with ulcerative colitis, and three of nine children with autism, were positive. Controls were all negative. The sequences obtained from the patients with Crohn's disease shared the characteristics with wild-strain virus. The sequences obtained from the patients with ulcerative colitis and children with autism were consistent with being vaccine strains. The results were concordant with the exposure history of the patients. Persistence of measles virus was confirmed in PBML in some patients with chronic intestinal inflammation.
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In Japan, the MMR vaccine was withdrawn in 1993, because of an unacceptably high level of side-effects.
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Program Director, Continuum Center for Health and Healing,
Beth Israel Hospital / Albert Einstein School of Medicine