Regressive Autism And MMR Vaccination
By: Dr. F. Edward Yazbak
Autism, as an entity, was unknown before the early 1940s when it simply appeared in small numbers. A steep increase in its prevalence was noted in the United States starting in the late 70s and in the United Kingdom after 1988 following the extensive use of the MMR (Measles, Mumps and Rubella) vaccine in both countries. The vaccine authorities in both countries are convinced that there is no connection between MMR vaccination and autism.
A new clinical picture also started to emerge around the same period. While earlier, symptoms of autism were noticed shortly after birth, “He was born autistic”, lately many of the affected children are healthy and developmentally normal in the first 12 to 15 months of life. Sometime between 15 and 18 months of age, they suddenly stop acquiring new skills and then start regressing, losing speech and social dexterity. At the same time, neurological, immune and gastro-intestinal symptoms appear: some children develop seizures, some have recurrent infections and are prescribed repeated courses of antibiotics and some start with peculiar eating habits and severe diarrhea, obstinate constipation or a combination of both. Most affected children today are not simply “autistic”, a psychiatric behavioral description. They suffer from a multi-system medical syndrome, called Regressive Autism. They do not require psychiatric care and medication only; they need medical treatment, dietary intervention and the close attention of a multidisciplinary team of therapists. The parents must be taught how to cope with aberrant behavior but they also need advice on diet, supplements, detoxification, management of obstipation, control of recurrent infections and development of education plans.
Relatively more affected children now have IQs above 70, respond to dietary restrictions, improve with Applied Behavioral Analysis (ABA) and can be gradually mainstreamed. This recent more frequent clinical picture and the fact that in many cases some symptoms can be improved and behavior controlled, seem to support the parents’ conviction that their children were normal for months, that they had acquired skills and that, with help, some of those skills can be retrieved, at least partially. As far as many parents are concerned, the timing of the behavioral, speech and cognitive changes appeared to follow the first dose of MMR.
Some parents have also reported that their children, after improving on special diets, supplements and behavioral therapy, regressed a second time around the age of 5 years shortly after receiving their MMR booster. Such double-hit situation (challenge-rechallenge) has been accepted in courts and by a committee of the Institute of Medicine (IOM) as proof of causation.
The vaccine authorities do not know what causes autism but they are certain that the administration of the MMR vaccine is NOT responsible for Regressive Autism and are convinced that any “temporal association” between the two is simply a coincidence “because autism usually occurs at about the age of 18 months“, shortly after the administration of the MMR vaccine.
Bernard Rimland, Ph.D., Founder of the Autism Society of America and Founder/President of the Autism Research Institute (ARI) in San Diego, disagrees:
“Late onset autism, (starting in the 2nd year), was almost unheard of in the “˜50s, “˜60s, and “˜70s; today such cases outnumber early onset cases 5 to 1″.
Dr. Rimland bases his statement on information derived from the Autism Research Institute’s huge database, the largest nationwide.
In a large study in South London, 4 out of 5 children subsequently-diagnosed as having an autistic disorder appeared normal at 18 months, exhibiting good eye contact, fantasy play and pointing.
In a 1998 Italian study by De Giacomo and Fombonne “The mean age of children was 19.1 months when the parents first became concerned, and the first professional advice was sought when children were 24.1 months”
Obviously, no one believes that the increase in the prevalence of autism is only due to MMR or other vaccinations. The present dramatic rise in the number of cases, described by Dr. Rimland as an explosion and by others as an epidemic, is due to many causes. Some are genetic but in all likelihood, the majority will be proven to be environmental. Genetic illnesses simply do not present as epidemics.
Thimerosal, a mercury derivative added to vaccines since the late 30’s to assure sterility, has been also suspected by a well-informed group of parents and by experts in the field, of causing some cases of autism. The fact that the number of cases of regressive autism still continued to rise rapidly in the 90’s, after MMR vaccination rates had been consistently high for several years, seems to support this theory.
The vaccine authorities have also ruled out such a connection.
The possibility that a child, often a boy, who has a genetic predisposition to immune disorders, may be first affected by mercury [in the vaccines administered from birth to his first birthday] and then succumb after receiving 3 or more live virus vaccines and several other antigens on the same day at a vulnerable age, has never been ruled out conclusively, by reliable unbiased clinical studies.
Mercury has been reportedly removed from pediatric vaccines. Hopefully, the vaccine manufacturers will be able to assure sterility without injecting a known poison into newborns and little infants. If not, they can always shift to manufacturing single dose vaccines and increase their profits. The fact that mercury was added to injected pediatric vaccines in the 30s to assure sterility is hard to believe. That this practice was never reviewed in 75 years is incredible.
CDC data show that about 300,000 to 400,000 cases of measles were reported yearly between 1950 and 1960. Epidemics occurred every 2 to 3 years. The worse year of that decade was 1958 with 763,094 cases of measles and 552 deaths. In 1962, there were 481,530 cases of measles and 408 deaths. According to the CDC “Following licensure of vaccine in 1963, the incidence of measles decreased by more than 98%, and 2-3 year epidemic cycles no longer occurred.” In 1970, there were 47,351 cases of measles and 89 deaths nationwide. The MMR vaccine was licensed in 1971, and the incidence of measles continued to decrease. In 1978, there were 26,871 cases of measles and 11 deaths.
Nationwide, the number of cases of measles dropped by 90% between 1962 and 1970 compared to 43% between 1970 and 1978 [one year before to 7 years after the introduction of each vaccine]. Because many US physicians kept using the monovalent vaccine exclusively even after the MMR vaccine was introduced (See below); the decrease in the number of cases of measles after 1971 may not be solely due to the triple vaccine. Clearly the monovalent vaccine worked well and the MMR vaccine was never “better” in controlling measles.
Measles mortality in the United States decreased before the introduction of both the monovalent and the trivalent vaccines, because of improved health and better nutrition, hygiene and medical care. (Table I)
Table I Measles Mortality in the United States
|Population (,000)||Cases||Deaths||Death rate|
Source Centers for Disease Control and Prevention
Although the incidence of measles remained relatively constant and fluctuated with epidemics during the 50 years before measles vaccination, the number of deaths decreased dramatically for other reasons.
The monovalent mumps vaccine was introduced in 1967 and the rubella vaccine in 1969. The incidence of both diseases also declined remarkably.
The Measles and MMR vaccines
As mentioned, the MMR vaccine became available in 1971-72. In the United States, it has always contained the exact same three “monovalent” vaccines marketed individually as Attenuvax (measles), Mumpsvax (mumps) and Meruvax (rubella). When the new MeruvaxII was introduced, the triple vaccine became the MMRII. The vaccine manufacturer’s greatest concern was that the live virus vaccines would interfere with each other when combined. Much time was spent to prove that they did not. The data quoted by the manufacturer suggest that the MMR vaccine is almost as effective as its components and that the “slightly better statistics” of the single vaccines should not be too significant. The efficacy requirement for licensure was thus fulfilled.
The monovalent measles vaccine is still used in major vaccination programs in third world countries where measles mortality rate remains very high because of malnutrition.
The safety studies on the MMR vaccine on the other hand were short and inadequate. The relatively few and limited follow-ups lasted 3 to 4 weeks on average with only 2 extending to 8 weeks. Chronic or long-term adverse events were never investigated or looked for. The difficulties the children are facing today may have been due to the fact that in the late sixties, “vaccinology” as a science was much more advanced than immunology. Jenner inoculated Phipps with cowpox in 1796 and called the procedure vaccination from “vacca”, Latin for cow. Lately the more glamorous term “immunization” has been used more frequently, more to intimate that the vaccination results in immunity than to get rid of the bovine connection. In fact, vaccination is a more accurate term. Not all “immunizations” produce immunity every time.
Anyway, no one really knew in 1971 what happened to the immune system of a susceptible child in response to the simultaneous injection of three live viruses. In fact, it is safe to say that no one, to this day, knows for sure.
The fact is that older pediatricians [this one included] always noticed that children were very sick when they had two (or three) infectious diseases at the same time. They were therefore rightly concerned about administering three live virus vaccines, even if they had been “attenuated”, to a small child with a still immature immune system.
The immune assault (and the response) to natural disease and live viral vaccination are different. With the natural disease, the virus invades the respiratory tract where the lymphoid barrier softens the impact. Injected vaccines short-circuit the process, bypass the respiratory defenses, and introduce the live viruses directly and precipitously “into the system”, leading to a sudden unexpected immune stress and, in some cases the formation of auto-antibodies, antibodies against one’s self. This is the reason why several teams of researchers have been working furtively to develop an intra-nasal measles vaccine, which will mimic the clinical disease, and avoid the immune stress of the injected vaccine. One must wonder why the launching of this vaccine is taking so long! It would certainly make thousands of parents and doctors happy.
Many US pediatricians, who had been impressed with the performance of the single vaccines and who were concerned about increased reactions with the MMR, were slow to endorse it at first. In those years, the American Academy of Pediatrics recommended many “preventive” office visits and the administration of the measles vaccine at 15 months, the rubella vaccine at 21 months and the mumps vaccine at 24 months made a lot of sense. The monovalent vaccines were also well accepted by parents. Indeed, those of us practicing then noticed that parents rarely missed a visit in which a vaccination was scheduled.
In the late 70’s things changed.
Â§ HMOs decided to cut down (out) the number of “regular check-ups”
Â§ They also decided that they would not pay the nominal fees ($1-3.00/injection) they were paying for the administration of each of the 3 vaccines when ONE vaccine containing all 3, was available.
Â§ The State Health Departments, which in an effort to improve vaccination rates had started providing vaccines, free of charge, to the pediatricians and well-baby clinics, opted for the triple vaccine to save on personnel and refrigerated space.
The pediatricians capitulated and the MMR vaccine became widely, and almost exclusively used in the United States. In 1988, as mentioned previously, the MMR vaccine was introduced in the United Kingdom in the midst of a highly publicized national vaccination campaign, and the use of the single measles, rubella and mumps vaccine in children was curtailed.
In 2001, Wakefield and Montgomery published “Measles, mumps and rubella vaccine: through a glass, darkly”, (1) in which they reported that:
Â§ Pre-licensing trials of the MMR vaccine revealed gastrointestinal events that persisted to the end of the trial period in significant numbers of children from developed countries. Despite this, the follow up period for subsequent trials was reduced from 28 days to 21 days.
Â§ The decision to combine the three vaccines in one (undoubtedly atypical) exposure was taken without specific consideration of the known associations between concurrent exposures to common childhood infections and later consequences.
The authors pointed out that: “”¦ in the context of MMR, one plus one plus one never did equal three.”
In the same issue of Adverse Drug Reactions and Toxicological (ADRT) Reviews, where the report appeared, the Editor endorsed Wakefield’s findings and Dr. Peter Fletcher, formerly the British counterpart of the FDA director, stated: “the granting of a product license was premature”.
As a courtesy, Dr. Wakefield had notified the health authorities several months in advance of the publication. When an attempt to coerce the editor not to publish the article failed, the vaccine authorities and Wakefield’s opponents came out “en masse” against the report. Professor Walter O. Spitzer, Emeritus Professor of Epidemiology at McGill University (2) commented comprehensibly on the controversy in the following issue of ADRT Reviews, which also contained my comments on the unexplained increasing incidence of autism (3)
Originally the MMR vaccine was administered alone at 15 months and only if the child was in good health. This has changed and the vaccine is now given as early as 12 months of age, often with the last dose of HIB (Haemophylus Influenzae B) vaccine, the third dose of hepatitis B vaccine and the live chicken pox vaccine, even if the child is sick and/or on antibiotics “as long as he does not have a high fever”.
There is no reasonable medical justification for such an overload of immune stresses at such a vulnerable age, now that the risk of contracting those diseases is nil or very low. Pressure from the vaccine authorities to continue this practice is illogical. Pressure from the HMOs in order to protect the bottom line is immoral
The Incidence of Autism
In all likelihood the most accurate figures on autism in the pediatric age group are derived from statistics obtained from the special education departments in the different school systems. These are usually reported to the Department of Education (DOE) in each state and forwarded to the US DOE. Each year, a comprehensive report is sent to the US Congress in compliance with IDEA, the Individuals with Disabilities Education Act. This act was signed into law in 1975 to ensure equal educational opportunities for children with disabilities. State and local education districts must provide a “free appropriate public education,” based upon an “individualized education program” (IEP) geared to each student’s needs. Earlier, autism was included in the larger group of Developmental Disabilities. As the number of cases of autism increased, a decision was made to list autism as a separate entity starting with the 1991-1992 school year. Services are provided to individuals with disabilities till their 21st birthday. The increase in autism among children and young adults, ages 6 to 21 in US schools is evident in Graph I.
Graph I Cases of autism in US Schools, Ages 6-21
Source: U.S. DOE, Office of Special Education Programs, Data Analysis System
In 1991-1992, there were 5,415 students with autism ages 6-21 in US schools. In the latest just released report for 2002-2003, there are now 118, 602 students with autism, in that same age group. (4) There was a 21.2% increase in the number of affected children since the previous report.
These figures do not include diagnosed children aged 2 to 6 years.
Diagnostic criteria and in all probability, the majority of the teams, medical and educational, making and approving the diagnosis, have not changed since 1994 and the introduction of the more stringent and restrictive criteria of DSM IV [Diagnostic and Statistical Manual, Fourth Edition, American Psychiatric Association.]
The increases in autism and all disabilities since 1994, in children 6 to 21 in US schools, are shown in Table II.
Table II Number of Children Ages 6-21 Served under IDEA
Source U.S. DOE, Office of Special Education Programs, Data Analysis System
The California Department of Developmental Services (DDS) regularly reports the number of NEW cases accessing services in the State. (5)
In 1994, there were 633 new cases of DSM IV autism in California, less than two cases a day. By 1999, the number of new cases had tripled to 1,944. Earlier this year, DDS reported that 3,577 cases had accessed services in the State in 2002 or 10 new cases a day, every day. New cases increased by 97% in the last 4 years and by 31% in the last year, the largest yearly increase ever recorded. Children with autism under age 3 and those with PDD-NOS and Asperger’s Syndrome were not included.
The Education Boards in all states have reported increases in their autism rates. The increases in New England in the last ten years are shown in Table III.
Table III Ten Year Increase in Autism in New England Schools, Ages 6-21
Source: U.S. DOE, Office of Special Education Programs, Data Analysis System
According to the New Jersey Department of Education, there were 514 6-year old students with autism in the state schools in the 2001-2002 school year compared to 14 students aged 21. This suggests an accelerating increase in autism with a larger number of affected younger children starting school each subsequent year.
Across the Atlantic, in the English Channel Island of Jersey, the situation is relatively worse. As of October 25, 2003, there were 64 children, mostly boys, with a diagnosis of autistic spectrum disorder in the Island’s schools. Five were older than 16.
The Island’s population is around 87,000. The population of New Jersey is around 8.5 million and there are now 4,180 students with autism ages 6-21 in the state.
In 1999 in Wakefield, England, the Local Education Authority reported that the number of children with autistic spectrum disorders (ASD) had increased from 5 to 111 in 7 years. In Scotland, according to the Scottish Education Office, the number of children with ASD attending school, increased by 18% between 1998 and 1999 and by 31% between 1999 and 2000.
A study of pre-school children from two areas of the West Midlands (UK) by the Department of Public Health and Epidemiology at the University of Birmingham, revealed that cases of childhood autism increased by about 18% yearly between 1991 and 1996 and that cases of autistic spectrum disorders increased even faster.
The Autism Research Unit at Sunderland University reported a ten-fold increase in autism in the UK between 1983 and 1999. Kaye also reported a 7-fold increase in childhood autism between 1988 and 1999 in a study published in the British Medical Journal. (See below).
According to a May 2002 report from the National Autistic Society, 1 child out of 82 in elementary schools in England carries a diagnosis of autism.
The impact of autism on school systems in Canada was also significant. In September 2000, 1,391 students with autism and Pervasive Developmental Disorders (PDD) were registered in the Province of Quebec schools. By September 2002, the number of registered affected children had reached 2,302, a 65.5% increase in two years, the highest ever recorded.
The Minister of Labor and Social Affairs in Saudi Arabia stated in an interview with Arab News that there were 42,500 confirmed cases of autism in the Kingdom in 2002 and that “there remained many undiagnosed cases”. The estimated population of Saudi Arabia was 22,757,092 in July 2001, giving an autism- prevalence rate of 1:500 in the total population. Keeping in mind that the group of children under 10 is in all probability the most affected and that boys usually outnumber girls 4 to 1, the prevalence of autism in boys under the age of 10 in Saudi Arabia is probably one of the highest in the world.
* * *
It was the mother of an English boy who developed regressive autism and gastro-intestinal difficulties after receiving his MMR vaccination who first decided that there might be a link between the vaccine, the regression and the gut problems. She investigated further and found out that an adult gastro-enterologist at the Royal Free Hospital in London named Andrew Wakefield had researched the possible link between viruses and gastro-intestinal diseases. After much insistence, this mother was able to convince Dr. Wakefield to evaluate her son. To everyone’s surprise, Wakefield included, unusual findings in the child’s intestines were noted. More parents with similarly affected children decided to consult Dr. Wakefield and again, the same rather distinctive pathology was identified.
In February 1998, Wakefield published his now well-known study of 12 children with regressive autism and similar gut findings in The Lancet: Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. He ended his publication by stating: “We have identified a chronic enterocolitis in children that may be related to neuropsychiatric dysfunction. In most cases, onset of symptoms was after measles, mumps, and rubella immunisation. Further investigations are needed to examine this syndrome and its possible relation to this vaccine“. (6)
Dr. Wakefield also added that between the time his paper was submitted for publication and the time that it was actually published, 40 more patients had been evaluated of whom 39 had similar intestinal findings.
Dr. Wakefield never said that the MMR vaccine caused autism but only advised that others investigate the possible suggested link between the triple vaccine and this recent form of autism. He also advocated the use of single vaccines, safely spaced so as not to burden the child’s immune system, until the question of the MMR is settled once and for all. Dr. Wakefield was never anti-vaccine and has always stressed the importance of measles vaccination of toddlers. His argument is that such vaccination is actually more needed now because the immunity that today’s infants get from their mothers is weaker and of shorter duration because the mothers’ immunity followed vaccination rather than disease. [That is actually the reason why the administration of the measles (MMR) vaccine was advanced from 15 to 12 months of age.]
The vaccine authorities in the United Kingdom, afraid that any agreement with Wakefield’s stand may be construed as less “faith” in their triple vaccine decided to play a sinister game of Russian Roulette and refused to provide the monovalent vaccines. The result is that fewer children are being immunized against measles in a country where the risk to infants and children may be increased because of the arrival and transit of thousands of foreign travelers from every continent daily. The fact is that the single antigens should have never been excluded because as clearly stated in “Immunization against Infectious Disease” [Joint Committee on Vaccination and Immunisation 1988″] ” For children whose parents refuse MMR vaccine, single antigen measles will be available.”
Many parents are so desirous to protect their children that they are traveling to France, Belgium and Holland or paying substantial fees in clinics in England to obtain the single vaccines. The authorities’ argument that these convinced and concerned parents will not return for subsequent jabs is offensive. Anyway, it is the measles vaccine that is eminently important at the age of 12 to 15 months. Rubella immunity of females is needed during the childbearing years to prevent Congenital Rubella Syndrome and mumps immunity is important in males as they near puberty. Those two diseases are mild in children and the cellular immunity from disease is stronger and longer lasting.
The statement by Dr. David Salisbury who is in charge of the vaccination program in the UK that the MMR vaccine offers better protection against the individual diseases than the single antigen vaccines is not supported by evidence, as shown above…
Dr. Brent Taylor, head of the Department of Pediatrics and Child Health at the Royal Free and University College Medical School and possibly Dr. Wakefield’s most rabid critic, stated in the Sunday Herald of January 14, 2001 that: “Separate vaccines do not provide good protection for children.” This statement is not correct either.
The rigid stand of the vaccine authorities in the UK that it must be “the MMR or Nothing” will lead to measles outbreaks in a country where thousands of travelers arrive or transit daily. For the parents who remain concerned about the MMR vaccine, but cannot afford the fees charged by private clinics, the choice will unfortunately be “nothing”. The authorities should not try to blame Andrew Wakefield; He only advocated that the single vaccines be made available alongside the MMR.
“Nothing” was never one of his options.
Dr. Simon Murch should have noted that in his October 31, 2003 letter to the Lancet.
The reaction to Dr. Wakefield’s publication was immediate and relentless. Almost five years later, not a day passes without someone somewhere repeating that Wakefield’s study cannot possibly be relevant because it only included 12 patients and it was never duplicated. No one obviously cares to mention that Leo Kanner, only reported on 11 cases when he described a new disease he called infantile autism 60 years ago. As for duplicating Wakefield’s work, after witnessing what has happened to him, rare are the physicians willing to sacrifice their careers in order to investigate this particular aspect of the disease. Arthur Krigsman, MD an American pediatric gastro-enterologist had the courage to do just that. He examined some 200 children with regressive autism and gastro-intestinal symptoms and described the same histo-pathological findings that Wakefield had reported. Unfortunately, his hospital would not allow him to proceed further and test the biopsies for the presence of measles. David Weldon, MD, U.S. Representative to Congress from Florida’s District 15, and a member of the House Committee on Government Reform, discussed the situation at a meeting of the Committee on December 10, 2002. He also requested from Dr. Stephen Foote, of the National Institutes of Health (NIH), to research the matter and to find a way to test the specimens, adding that this could finally prove or disprove the Wakefield hypothesis. Foote said he would do that. As yet, nothing has been reported.
In September 2000, Wakefield published a follow-up study of 60 more patients with “autistic entero-colitis” in the American Journal of Gastro-enterology (7) This study is almost never mentioned by the vaccine authorities and lobby, neither is the editorial by Eamonn, Quigley and Hurley in the same issue, (8) which ended with the statement:
“Wakefield et al. are to be congratulated on opening yet another window onto the ever-broadening spectrum of gut-brain interactions. Their findings raise many challenging questions that should provoke further much-needed research in this area, research that may provide true grounds for optimism for affected patients and their families”
Dr,.Wakefield has now fully investigated many more cases and has authored or co-authored 32 peer-reviewed publications in distinguished journals on related subjects. They are rarely if ever mentioned by his critics. Neither are the 35 studies he published before 1998, and which earlier had been very well received.
Two of his recent studies (2002) have explored other aspects of regressive autism.
In an original research paper published in Molecular Psychiatry (9) he reported that specific intestinal findings suggesting an autoimmune etiology were found in 23 of 25 children with autism, but not in the controls: 11 children with celiac disease, 5 with cerebral palsy and mental retardation, and 18 normal children.
” A novel form of enteropathy” is now occurring in children with autism”.
In another review article (10), Dr. Wakefield described in depth how the inflamed intestine of children with regressive autism might lead to damage to the developing brain. He compared the process with another well-known gut-brain interaction, hepatic encephalopathy, in which confusion, coma and death occur when the failing liver is unable to remove toxins derived from food and bacteria in the intestines. In the summary, Wakefield adds: “For many years it has been suggested that morphine-like peptides Âfragments of partially digested protein derived from cow’s milk and cereals – are toxins that play a role in the development of autism. Similar “opioid” molecules appear to play an important role in the toxicity associated with severe liver damage. Thus the parallels between these two conditions, including the treatment approaches for both – relief of constipation, dietary restriction, de-contamination of the intestinal system, and nutritional supplementation Â indicate strongly that some forms of autism and intestinal disease are linked.”
Clearly, understanding the gut-brain interaction in children with regressive autism will help solve the mystery surrounding it, prevent further damage to affected children and make caring for them much easier.
Dr. Andrew Wakefield testified on June 19, 2002 at a special meeting of the House Committee On Government Reform, Representative Daniel Burton of Indiana, Chairman. He stated:
“The sum of the research by my group and our collaborators, taken together with additional work by independent physicians and scientists in the United States, has now confirmed the following facts:
Children with regressive autism and intestinal symptoms have a novel and characteristic inflammatory disease of their intestine.
This disease is not found in developmentally normal control children.
This disease is entirely consistent with a viral cause.
This disease may be the source of toxic damage to the brain.
Measles virus has been identified in the diseased intestine in the majority of children with regressive autism studied, precisely where it would be expected if it were the cause of the intestinal disease.
These children, who suffer the same pattern of regressive autism and intestinal inflammation, come from many countries, including the US and Ireland, where they have been investigated and biopsied independently.
Measles virus has been found in only a small minority of developmentally normal children.
The measles virus in the diseased intestine of autistic children is from the vaccine.
Children with regressive autism appear to have an abnormal immune response to measles virus
These findings are entirely consistent with parental reports that their normally developing child regressed into autism following exposure to MMR vaccine.”
Dr. John O’Leary, Professor of Pathology at Trinity College, Dublin and Associates, an independent group of researchers, devised and carried out extensive and meticulous research in order to identify any viral etiology for the pathology described in the Wakefield studies.
In 2002, the group reported in the Journal of Molecular Pathology (11) that:
Â· Measles virus genomic RNA was present in 82% of 91 children with autism compared to only 7% of the 70 developmentally normal controls and
Â· That over 95% of positive children had received MMR as the only documented exposure to measles.
The authors concluded that measles virus may be an important immunological trigger in the pathogenesis of lymphoid hyperplasia and entero-colitis
In a commentary in the same issue of the Journal of Molecular Pathology (12), Morris & Aldulaimi stated in part that:
“Epidemiology is a pretty blunt tool and the studies done do not rule out the possibility that there may be risk groups where a real link between MMR and autism/bowel inflammatory conditions exists” and “There is evidence that developmental disorders are associated with a functional disturbance of the brain-gut axis.”
On June 16, 2002, Dr. John O’Leary, announced that 12 children with autism from his original study group had been confirmed as having a vaccine strain measles virus, in their gut. They all had received the MMR vaccine. O’Leary’s results confirm the earlier findings by Kawashima and constitute further evidence of a relationship between MMR vaccination and regressive autism.
H. Kawashima and Associates, a group of Tokyo University researchers, 14investigated the presence of measles genomic RNA in peripheral mononuclear cells in 8 patients with Crohn’s disease, 3 with Ulcerative Colitis and 9 with Autistic Entero-colitis. For controls, they examined healthy children and patients with Subacute Sclerosing Panencephalitis (SSPE), Systemic Lupus Erythematosus (SLE), Human Immunodeficiency Virus 1 (HIV-1) a total of eight cases.
Using elaborate and critically accurate identification techniques, the Tokyo researchers reported that: “One of eight patients with Crohn’s 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.”
As a side note: Following MMR vaccination, the presence of measles virus from vaccine was confirmed in the brain of a child in Canada (14), in the throat of a child in France (15) and in the urine of a child in Australia (16).
While this was happening abroad, V. K. Singh Ph.D. now at the Biotechnology Center, Utah State University, was busy researching in depth the neuro-immuno-pathogenesis of autism by investigating measles, MMR and anti-neuronal antibody titers in children with the disease. On April 6, 2000, at a US House of Representatives Government Reform Committee meeting, Dr. Singh described his findings and stated: “This was probably the first laboratory-based evidence to link measles virus and/or MMR vaccine to autoimmunity in children with autism “¦ autism may be caused by a measles Âor MMR vaccine- induced autoimmune response”. Dr. Singh concluded “In summary, the rapidly accumulating evidence strongly implicates autoimmunity in autism, which in many may result from a vaccine injury”¦ the evidence also suggests a MMR vaccine infection “¦The onset of autism (or autistic regression) post-immunization should no longer be regarded as merely a coincidence with the timing of the vaccinations, as our federal health officials continue to do.”
Dr. Singh’s has also reported:
1. Elevated Myelin Basic Protein (MBP) auto-antibody titers in 28 of 32 children with autism who had elevated measles antibodies and in none (0) of the controls.
2. Elevated MMR antibody titers in 59% (16/27) children with Autism Spectral Disorders (ASD) compared to only 10% (2/ 20) of controls.
3. The presence of MBP auto-antibodies in 81% (13/16) of the children with ASD and in none (0) of the controls.
Dr. Singh concluded: “Children with ASD were positive for MMR antibodies compared to none (0/92) of the developmentally normal children tested (Controls). “Over 90% of MMR antibody-positive autistic sera were also positive for MBP auto-antibody “suggesting a causal association between MMR and brain auto-immunity in autism”.
Drs. Singh, Jensen and Bradstreet presented results of yet another study on “Serological Detection of Measles Virus in Relation to Autoimmunity in Autism” at the 102nd General Meeting of the American Society for Microbiology [Salt Lake City, Utah May 19-23, 2002].
Â§ A significant number of children with autism had antibodies to Myelin Basic Protein (MBP) (up to 88% positive) and also antibodies to MMR (up to 65% positive).
Â§ Normal children did not harbor these antibodies.
Â§ The analysis of paired samples (serum and cerebrospinal fluid) from children with autism revealed a high degree of serological association and correlation between MMR and MBP antibodies.
The authors concluded by stating: “In light of the new evidence presented here, we suggest that the MMR vaccine in some cases of autism might cause autoimmunity and it might do so by bringing on an atypical measles infection that does not produce a typical measles rash but manifests neurological symptoms upon immunization“.
Last year, Dr. Singh was awarded the 2002 O. Spurgeon English Humanitarian Award. The award honors “leading physicians and scientists who have made major humanitarian contributions to human welfare”.
Not surprisingly, funding for Dr. Singh’s research has become scarce lately.
Dr. Robin Hansen, of the MIND [Medical Investigation of Neuro-developmental Disorders] Institute at the University of California, Davies has tested “newborn blood spots” of 15 normal children and 15 children with autism for the presence of MBP antibodies. All 30 specimens were negative.
Dr. Tina Zecca et al., New Jersey Medical Center (NJMS), Children’s Hospital of NJ, (19) has reported a 3-fold increase in measles titers in 16 children with autism compared to normal controls and added: “Subjectively, parents have stated that their children’s developmental milestones deteriorated following MMR vaccination. Neurological sequelae following MMR are widely reported. MMR therefore may play a role in the pathogenesis of autism. The elevated titers of anti-measles antibodies in autistic children may signify a chronic activation of the immune system against this neurotropic virus.”
The above studies involved both actual patients and controls. All viral, endoscopic and serological investigations were carefully carried out and all results have always been available for review.
The Anti-Wakefield Movement
Expensive and extensive campaigns have been mounted in the US and the UK in defense of the MMR vaccine and against Andrew Wakefield and the parents who dare question a vaccine connection. The anti-Wakefield fronts have repeatedly quoted certain epidemiological studies in support of their argument. Not a single parent was interviewed and not a single child examined in any of those studies; most have been “supported” (funded) by the vaccine manufacturer and or authorities.
Since 1998, the UK Government has spent immensely more money defending the MMR vaccine and depicting Wakefield as a maverick, than it did on autism research.
As mentioned earlier, the message to the parents remains “We do not know what caused your child’s autism “¦but we are absolutely sure that it is not the MMR or another vaccine.”
The studies from Finland
Merck financed all studies and reports on MMR and autism by the Peltola group.
The first publication by Peltola, Patja et al. was published in Lancet in May 1998, just 3 months after Wakefield’s first paper on children with autism. It was titled: No evidence for measles, mumps, and rubella vaccine-associated inflammatory bowel disease or autism in a 14-year prospective study. (17)
The conclusion of the authors was that: “Over a decade’s effort to detect all severe adverse events associated with MMR vaccine could find no data supporting the hypothesis that it would cause pervasive developmental disorder or inflammatory bowel disease”
The second paper by Patja, Peltola et al. was published in the Pediatric Infectious Disease Journal in December 2000 (18). It was titled: Serious adverse events after measles-mumps-rubella vaccination during a fourteen-year prospective follow-up.
The authors reported some of the adverse events pointing out that there were no cases of autism and Inflammatory Bowel disease (IBD).
Those two studies (and others by the same groups) were based on a review of adverse events reported following the administration of some 3 million doses of MMR vaccine to about 1.8 million individuals during a “national immunization campaign” in Finland between 1982 and 1996. During the campaign, children were vaccinated between 14 and 18 months of age and again at 6. Also receiving the vaccine were older children and selected groups of young adults, such as military recruits and nursing students
The cases that were followed for 14 years were those that developed adverse events within 3 weeks of vaccination, less than 200 in all. There was NO follow-up on the rest of the 1.8 million vaccine-recipients in the Country.
Both autism and inflammatory bowel disease (IBD) are chronic illnesses, which develop over months or years. Certainly no one ever claimed that they start within 21 days of vaccination and Wakefield never contended that children who develop diarrhea immediately after vaccination, a known and accepted reaction, are those who will go on to develop IBD as young adults.
Peltola himself, when questioned on BBC Radio-4 on January 13, 2001, stated that the main study was not designed to look at IBD and autism.
In summary, Peltola and Associates never looked for autism and IBD following MMR vaccination. Neither did anyone else before 1998. In spite of that, the findings of these studies from Finland were highly publicized for a long while and interpreted in the Press, and over the Internet, as proving conclusively that there was no increase in autism and IBD among the millions who received the MMR vaccine during the national vaccination campaign and were followed for 14 years.
This is not true.
Autism & Inflammatory Bowel Disease have increased in Finland in recent years.
Autism: M. Kielinen et al, in a study published in 2000 (19), described a significant rise in autism in the northern provinces of Oulu and Lapland, which represent 1/8 of the total population of Finland. The Kielinen study included all children born in the two provinces, between 1979 and 1994. Every single one of those children was eligible and must have received the MMR vaccine. The authors personally reviewed all records of children with autism to determine that they fulfilled the criteria of ICD-10 and DSM-IV. The cumulative incidence of autism was 12.2/10,000, a significant increase when compared to the previously reported incidence of 4.75/10,000 by Vinni and Timonen. The increase in the younger children, all born in the second half of the MMR campaign, was even more striking. In the 5 to 7 age group, the cumulative incidence was 20.7/10,000 or more than 1 in 500. At the time, I predicted that the increase in autism was not limited to the Northern Provinces and that it would keep accelerating.
On November 11, 2002, a spokesperson for autismiliitto.fi informed me that she did not have accurate figures but that “we are estimated to have 10,000 autistic people in Finland and about 40,000 people with Asperger’s syndrome“.
Better diagnosis may have led to the identification of some of these cases, but the increase in the prevalence of autism is clearly as real in Finland as it is elsewhere, even if Peltola does not think so. The above figures show that in Finland 1 of every 100 individuals may have an autistic spectrum disorder (50,000 cases in a population of slightly over 5 million). This would translate, in the US, to 2.88 million individuals with Autistic Spectral Disorder (ASD). Taking into account the fact that the incidence is higher in children and younger adults and the well-known gender difference, one can only guess the affliction in young Finnish males. The high ratio of Asperger’s Syndrome (AS) is also relevant. Kielinen pointed out in the study mentioned above, that in the Northern Provinces, there were more children recently with IQs above 70 than had been reported in earlier studies. Other investigators have reported a similar trend worldwide.
Children affected since birth and in early infancy, are usually more profoundly brain damaged than those who develop normally until their first birthday and then sink into autism in the second year of life, some reportedly after receiving the MMR vaccine.
Inflammatory Bowel Disease: According to figures obtained from the Statistical Branch of the Social Insurance Institution of Finland, the number of patients entitled for special refunds because of Crohn’s and Ulcerative Colitis more than doubled between 1992 and 2001, from 9,737 to 20,807. In the same period, the prevalence rate per thousand of the two conditions also doubled while the population of Finland only increased by 3%. Also of concern is the fact that, not only did the number of patients with IBD reporting to Social Services increase yearly, but that the rate of increase is accelerating, with more patients having registered in the last five years than in the previous five.
Inflammatory Bowel Disease is most often diagnosed between the ages of 15 and 35. The older children, adolescents, nursing students and army recruits who received the MMR vaccine in Finland starting in 1982, reached that vulnerable age in the last ten years and figure in all likelihood, in the increasing statistics.
There are obviously many other factors causing IBD. Nevertheless when the rates of Crohn’s Disease and Ulcerative Colitis continue to increase and accelerate in Finland in the next few years as the younger vaccinees reach adulthood, it will become increasingly difficult for Peltola and his group to prove to everyone that such increases are NOT related to vaccination.
The third study from Finland is more recent (2002). It is also based on the data of passive reporting from the “National Campaign” and is titled Neurologic Disorders After Measles-Mumps-Rubella Vaccination. The authors Makela, Peltola et al. compared the numbers of events of encephalitis and aseptic meningitis, within a 3-month risk interval after vaccination with the expected numbers estimated on the basis of occurrence of encephalitis and aseptic meningitis during the subsequent 3-month intervals. Examining the incidence of encephalitis and aseptic meningitis in the two weeks following vaccination would have been much better, because cases occurring during that period, would be considered ipso facto vaccine complications.
Again in this study, although no one in Finland was looking for autism before 1986, the authors went ahead and included it. Interestingly, by stating: “The aim of this study was to assess whether an association prevails between MMR vaccination and encephalitis, aseptic meningitis, and autism” in an article titled “Neurologic Disorders after Measles-Mumps-Rubella Vaccination” the authors in fact imply that autism is a neurological complication of MMR vaccination.
Of interest, though not directly related to the topic of this study is the fact that Finland has the highest incidence of childhood Type 1 (insulin-dependent) diabetes mellitus in the world. (20) According to Tuomilehto: “During 1987-1989, the overall incidence of Type 1 diabetes was about 35.2 per 100,000 per year. It was higher in boys (38.4) than in girls (32.2). There was no clear geographic variation in incidence among the 12 provinces of Finland. Of the 1,014 cases during these 3 years only six cases were diagnosed before their first birthday. The incidence was high already in the age group 1-4-years old: 33.2 in boys and 29.5 in girls.”
It has been suggested that a possible connection between MMR vaccination and juvenile diabetes exists. The sudden increase in the incidence of diabetes after age 1 during a national campaign (1982-1996), during which a vaccine is administered at 15 months of age, deserves attention.
Our vaccine authorities have denied any connection between vaccination and the present steep increase in Juvenile Diabetes in the United States. Obesity and increased intake of junk food / sweets, increased television watching and computer games plus lack of exercise are believed to be responsible for the present record high incidence of the disease.
It is important to stress that juvenile diabetes remains a serious problem in Finland. According to the Social Welfare and Health Report 2000 of the Ministry of Social Affairs and Health “Finland has the highest incidence of juvenile onset or insulin-dependent diabetes in the world and it is continuing to grow.“
The following from the same report is also of interest: “Asthma has become more common among children and adolescents and in the past 10 years, its prevalence among the under-20s has increased threefold.”
“International comparisons show that Finnish school-age girls head the intoxication statistics and that boys are near the top. The number of non-drinkers has declined among all 12-18 year-olds in the past ten years. The combined use of alcohol and medicines affecting the central nervous system is still common”.
“Thanks to vaccinations and other preventive measures, the frequency of the most common dangerous infectious diseases has plummeted in Finland. This is not to say however, that such diseases are a thing of the past. On the contrary, they are still a major single cause of short- term absences from work among people of working age and account for the bulk of children’s outpatient visits.”
The Autism and MMR IOM Committee Report
The Institute of Medicine (IOM) convened a special Committee to study Autism and MMR. The committee met in early March 2001. The Chairperson rushed to publish its findings by April 23rd, a historical record for any IOM special committee report.
In addition, the Chairperson reportedly “shared” the committee’s findings and conclusions with certain interested parties prior to publication and played an active and very vocal role in promptly and widely publicizing its results. Her statement: “It [MMR] is as safe as a vaccine can get” was immediately construed as a seal of approval and translated in the lay press to: “Vaccine is off the hook” [Actual words].
The “conclusive report by the Institute of Medicine“ is widely quoted.
The vaccine authorities (and lobby) like to state that the special committee found that the “”¦evidence favors rejection of a causal relationship at the population level, between MMR vaccine and autistic spectrum disorders “. They are careful not to mention that the Committee actually “did not exclude the possibility that MMR vaccine could contribute to ASD in a small number of children”.
The committee also recommended that more research be done.
Andrew Wakefield also said that MMR vaccination could contribute to autism and pervasive disorders in a small number of children and he also said that more research was needed; for that, he was forced to resign.
Historically, the IOM Committees’ conclusions are based on epidemiological data and therefore need large numbers of cases to justify one of the following classifications:
1. No evidence bearing on a causal relation.
2. The evidence is inadequate to accept or reject a causal relation.
3. The evidence favors rejection of a causal relation.
4. The evidence favors acceptance of a causal relation.
5. The evidence establishes a causal relation.
Clearly the possible MMR-Autism connection was placed beyond the third group somewhat closer to the fourth. This is traditionally unusual for a first examination. The criticism that was heaped on the report is almost sure to lead to a review in the not too-distant future.
One can best understand the nuances of the MMR-Autism IOM study by having a look at the special report published immediately before it, on April 19, 2001.
That special report on “Agent Orange” was commissioned in 1991 & completed nine years later, in April 2000, a whole year before it was published (23). In that report, Diabetes Mellitus & Children’s Myelogenous Leukemia were moved from a lower category to Category 4: “The evidence favors acceptance of a causal relation”.
The undeniable fact is that since the Vietnam War, hundreds of veterans and a multitude of VA physicians have been thoroughly convinced that Diabetes and this particular form of Leukemia belong not in Category 4 but actually in Category 5 “The evidence establishes a causal relation”.
The following remarks (24) on the IOM MMR report, by Walter O. Spitzer, MD, Emeritus Professor of Epidemiology at McGill University are sobering: “As an epidemiologist who has been a Member of the IOM since 1986, I have been proud of IOM reports in my field that I have examined or co-authored. I am embarrassed by the process of this latest Report and would urge President Shine of the IOM to retract the Report until the message has been clarified. What was released, the IOM Report or the
Other IOM Committee reports on vaccines have also been questionable. The trust all citizens should have in the august Institute of Medicine will certainly be eroded by the continued bias of vaccine reports. It is imperative that the committee members insist on receiving TOTAL information prior to making a final decision. They are responsible to the people of the United States, not only to the CDC because it funds the studies.
The Studies by Brent Taylor
“Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association” (21) was the first Taylor publication on the subject (1999). The Medicines Control Agency and the Public Health Laboratory Service (somewhat the equivalents of the FDA and the CDC, financed the study. Any incrimination of the MMR vaccine therefore would have been unlikely, regardless of the findings.
Taylor reported on 498 cases of autism (261 of core autism, 166 of atypical autism, and 71 of Asperger’s syndrome).
“In 293 cases the diagnosis could be confirmed: 214 [82%] core autism, 52 [31%] atypical autism, 27 [38%] Asperger’s syndrome. There was a steady increase in cases by year of birth with no sudden “step-up” or change in the trend line after the introduction of MMR vaccination. There was no difference in age at diagnosis between the cases vaccinated before or after 18 months of age and those never vaccinated. There was no temporal association between onset of autism within 1 or 2 years after vaccination with MMR”¦Developmental regression was not clustered in the months after vaccination “¦ No significant temporal clustering for age at onset of parental concern was seen for cases of core autism or atypical autism with the exception of a single interval within 6 months of MMR vaccination This appeared to be an artifact related to the difficulty of defining precisely the onset of symptoms in this disorder.”
Interpretation: Our analyses do not support a causal association between MMR vaccine and autism. If such an association occurs, it is so rare that it could not be identified in this large regional sample.”
Though this study was somewhat better than subsequent Taylor studies, it still had many weaknesses, the small number of cases evaluated being one.
Taylor himself stated: “The study has some limitations: two of these [meaning there are more] are that we could not verify the diagnosis according to ICD 10 criteria in some cases, and that the ascertainment may have been incomplete. The clinical notes were of variable quality and many did not contain systematic or regularly updated information, which would have allowed independent validation of the diagnosis, particularly in the children with atypical autism or Asperger’s syndrome.
Later he goes on to say: ” There is uncertainty about whether the prevalence of autism is increasing” and then adds: “Our study is consistent with an increase in the incidence of autism in recent birth cohorts”
He then inserts Figure 1 showing the sudden and acute rise in the number of cases of core autism starting in 1991.
Two pages later, Taylor states: 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 6 months of MMR vaccine associated with a peak in reported age of parental concern at 18 months“ and then, unashamedly adds: “Our results do not support the hypothesis that MMR vaccination is causally related to autism…”
Taylor has consistently refused to reveal, share or discuss the study’s raw data. Two requests from Dr. Bernard Rimland (ARI), two from Dr. Jane Orient, Executive Director, The Association of American Physicians and Surgeons and one from US Congressman Daniel Burton, Chairman of the House Government Reform Committee at the April 6, 2000 meeting, were turned down. Interestingly, Yvette Cooper, the UK Minister for Public Health, defended Taylor’s stand. Just as odd was the fact that the Lancet, a prestigious medical journal, published the article without insisting that raw data be available on request. Taylor’s excuse was that the clinic records were confidential.
There were several critiques of that particular Taylor study. Those by Dr. Andrew Wakefield and Dr. James Roger, an expert on medical statistics stand out.
Dr. Andrew Wakefield wrote: “A case-series analysis is unlikely to identify a relation between exposure and disease, in which the onset is insidious and in which, very often, there is diagnostic delay” and later: “However, it pales into insignificance compared with their failure to declare the fact of an MMR catch-up campaign that was initiated in 1988 with the introduction of this vaccine. This campaign was targeted at children, whatever their age, who presumably had not received monovalent mumps or rubella vaccine whatever their exposure status. As such it was a novel and, in terms of safety, untested policy. On the basis of Taylor and colleagues’ inclusion criteria, and taking account of the catch-up campaign, then those first birth cohorts who actually received MMR (circa 1986) were precisely those in whom a doubling of the numbers of cases of autism were seen”.
Dr. James Roger in a letter to the Editor of The Lancet (July 8, 2000) stated:
Sir–Rather than clarify the measles, MMR, and autism confusion with your editorial, you perpetuated the myth that good scientific evidence rejects a link between MMR vaccination and autism.
You quote Taylor and colleagues as publishing “epidemiological evidence contradicting this alleged association.” On March 28, 2000, I presented a talk to the Royal Statistical Society, in which I showed how the currently published data, including that from this study, are consistent with an appreciable number of autism cases being triggered by MMR vaccination. In short, Taylor and colleagues used the wrong study design to detect an association between immunisation and a disease with chronic onset, such as autism. Rather than use a conventional case-control approach, the study used a case-series design. The case-series approach is appropriate for investigating acute adverse events such as febrile convulsion but is not suitable for long-term effects of vaccination.
As stated, the above underlined statement was made at a Royal Statistical Society meeting. Dr. C.P. Farrington, the statistician who co-authored the article, participated in the debate.
Taylor and Associates published two other studies on autism, gut pathology and MMR.
These were never given the publicity that the above paper received and for the sake of brevity, they will not be discussed here.
The Kaye Study
Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: A Time Trend Analysis, by Dr. James Kaye, was published in 2001, in the BMJ. (22)
The study did not receive funding. Dr. Kaye is a member of the Boston Collaborative Drug Surveillance Program, which is supported in part by grants from AstraZeneca, Berlex Laboratories, Boehringer Ingelheim Pharmaceuticals, Boots Healthcare International, Bristol-Myers Squibb Pharmaceutical Research Institute, GlaxoWellcome, Hoffmann-La Roche, Janssen Pharmaceutica Products, R W Johnson Pharmaceutical Research Institute; McNeil Consumer Products, and Novartis Farmaceutica.
It is not clear from the article why a group of researchers from Boston chose to do a study based on data from the UK general practice research database.
Kaye claimed there was no MMR – autism connection because the incidence of autism in children in the UK continued to increase even after MMR take-up was constant at around 97%. The study did attest that autism increased sevenfold from 0.3 per 10,000 (1988) to 2.1 per 10,000 (1999) and almost fourfold, from 8 per 10,000 for boys born in 1988, to 29 per 10,000 for boys born in 1993. Again, the MMR campaign in the UK started in 1988.
The authors acknowledged that the study design was not ideal because it would have been better to examine the autism incidence in vaccinated and unvaccinated groups of children. But this, they added, was impossible because of the small number of unvaccinated children. They also acknowledged that time trend analysis is a “relatively crude method” and speculated that the detected increase in autism “could be due to increased awareness of the condition among parents and GPs, changing diagnostic criteria or environmental factors.”
The Kaye study precipitated multiple letters to the British Medical Journal. In my published letter, (23) I commented that:
Â§ A cohort of children born in the years 1988-1993 was chosen. MMR was introduced in the UK in 1988 and therefore it is unlikely that an uptake of 90-95% was achieved from year one.
Â§ By their selection, Kaye et al effectively excluded children born before 1988, who were vaccinated in/after 1988.
Â§ The restriction of the cases in the main analysis to 114 boys is of concern. A breakdown of the 290 children in the 1990-1999 birth cohorts by sex and year of birth would have been informative. A larger proportion of girls among the 176 cases excluded might have been relevant to the completeness of the autism figures.
Â§ The fact that neither DSM-IV nor IC-10 was systematically used in the U.K. creates further doubts as to the significance of the reported findings.
I concluded that 1. Kaye cannot exonerate MMR without offering a reasonable explanation for the increase in autism after 1988 and 2. That until safety studies on
MMR are comprehensive and independent of drug companies and until researchers review with parents the documented adverse reactions of bowel disease and autism, the triple jab remains suspect.
Clearly, there were serious questions about the autism portion of the MMR-Autism equation in that study.
Another critique by Branell (Sweden) points to serious flaws in the other part of the equation in the Kaye study, the MMR vaccination rates. (24) It was also published in the BMJ and was titled “How was the “MMR Prevalence” estimated? In a short but careful analysis, Branell criticized Kaye’s assertions relative to MMR vaccination rates in different years and concludes by stating: “Instead the data shows that as more kids get MMR-vaccine rises the autism rate.”
The Dales California Study
“Time Trends in Autism and in MMR Immunization Coverage in California”, by Loring Dales, MD et al. in 2001 in JAMA (The Journal of the American Medical Association.) (25)
Dr. Dales and Associates are employed by the California Department of Health
Dr. Dales stated: “ Essentially no correlation was observed between the secular trend of early childhood MMR immunization rates in California and the secular trend in numbers of children with autism enrolled in California’s regional service center system. For the 1980-1994 birth cohorts, a marked, sustained increase in autism case numbers was noted, from 44 cases per 100,000 live births in the 1980 cohort to 208 cases per 100, 000 live births in the 1994 cohort (a 373% relative increase), but changes in early childhood MMR immunization coverage over the same time period were much smaller and of shorter duration. Immunization coverage by the age of 24 months increased from 72% to 82%, a relative increase of only 14%, over the same time period”.
Dr. Dales himself acknowledged the following weaknesses in the study:
Â§ “Diagnosis is not always straightforward.
Â§ The California Department of Developmental Services’ report stresses that its patient caseload data cannot be used as a true measure of changes over time in autism incidence because other factors can affect trends in system case numbers
Â§ Observation of parallel trends over time or across geographic locations for 2 events, generally do not constitute strong evidence for a causal association between the 2 events
Â§ As the system expanded and matured over time, the proportions of California children enrolling and the distribution of ages at enrolment likely) changed over time as a result.
Â§ Also, the proportions of children enrolling in the system who were born outside California may have changed over this time period.
Â§ The data presented herein have some limitations. It would have been useful to examine individual immunization and autism records on the same children; however, these could not be linked.
Â§ Further, the childhood immunization coverage data used in this study do not provide precise quantification of the percentage of children who received the combined MMR vaccine product vs. separate injections.
Clearly, Dr. Dales states that one of the two elements examined in the statistical comparison is flawed.
After listing all these difficulties, the authors of the study state that they were “unable to demonstrate a correlation between secular trends in early childhood MMR immunization coverage and autism caseload.”
Drs. Edwardes and Baltzan, (26) both from McGill University promptly responded in JAMA to the Dales study: “Dr. Dales and colleagues reported that there was “essentially no correlation” between rates of autism and measles-mumps-rubella (MMR) vaccine, but this conclusion is based on their Figure, which seems to be an optical illusion. We took the y-axis values directly from the Figure and computed the correlation coefficients, which are 0.73 and 0.90 between the total number of autism cases and the percentage of children receiving immunization by 24 months and 17 months respectively. The illusion of no relationship is due to vertically compressed graph…Furthermore their data show that the age of immunization was becoming younger between 1981 and 1993. In Figure 1, we plot the ratio of children immunized before 17 months with those immunized between 17 and 24 months. The ratio increased 200% from 1981 to 1993. Thus, if the total number of autism cases divided by the total number of births are near the true incidence rates for California, the data also suggest that the rate of early MMR immunization is correlated with the incidence of autism.
So in summary, Dales could not and should not have concluded that no correlation existed between MMR vaccination and the incidence of autism in California. Actually, his study seems to suggest that such a correlation exists.
The MMR Study from Denmark
A Population-Based Study of Measles, Mumps and Rubella vaccination and Autism, by Dr. Kreesten Meldgaard Madsen and Associates is presently the most quoted anti-Wakefield study. It was funded by the CDC and published in the New England Journal of Medicine (NEJM) on November 7, 2002.
Immediately, in the second paragraph, Madsen states: “Studies designed to evaluate the suggested link between MMR vaccination and autism do not support an association, but the evidence is weak and based on case-series, cross-sectional, and ecologic studies, No studies have had sufficient statistical power to detect an association, and none has a population-based cohort design” (References 10-16).
Reference 10 in the Madsen bibliography is the Taylor study; Reference 11 is the Kaye study and Reference 12 is the Dales study discussed above. Madsen is therefore stating that the studies by Drs. Taylor, Dales and Kaye could not have detected an association between MMR and autism.
In the last paragraph, Madsen reported: “The prevalence rates among 8-year-old children in our cohort were 7.7 per 10,000 for autistic disorder and 22.2 per 10,000 for other autistic-spectrum disorders. These rates are similar to the prevalence rates of 5.4 per 10,000 for autistic disorder and 16.3 per 10,000 for other autistic-spectrum disorders in a cohort of 325, 347 French children (ICD-10 criteria), reported by Fombonne et al. “¦”
Choosing this particular Fombonne study was interesting. Fombonne’s earlier claim to fame was his insistence that autism had not dramatically increased and that any perceived increase was due to changing diagnostic criteria and improved methods of case finding. Professor Fombonne who started his career in France moved to England for a while and is now at McGill University, in Montreal.
The Fombonne publication quoted by Madsen was based on an epidemiological survey from INSERM (Institut National de la Sante et de la Recherche Medicale, Paris). Though reported in 1997 the study investigated children born between 1976 and 1985..
Madsen could have quoted more recent and pertinent data by Fombonne, such as that presented in November 2001 at the International Meeting for Autism Research (IMFAR). At that conference, Dr. Fombonne stated that though in 50 previously published epidemiological studies, he and others had established the prevalence rate of autism at between 2 and 10 per 10,000, his most recent research points to a prevalence at present, of 68 per 10,000 or 1 in 147. This is an increase of 600 to 3400% in 25 years.
Obviously comparing the Danish results with those of an old French study was a good way to suggest that there had been little or no increase in autism in Denmark after the introduction of the MMR vaccine.
Madsen’s study had several problems. As a clinician, I did not believe that the findings were very relevant to the situation in the United States. Professor Walter O. Spitzer M.D., M.P.H., F.R.C.P.C, Emeritus Professor of Epidemiology at McGill University and Emeritus Editor, Journal Of Clinical Epidemiology also had many questions about the statistical and epidemiological aspects of the research.
In sworn testimony at the December 10, 2002 Hearing of the Government Reform Committee, Professor Spitzer stated: “
Only 40 cases (13%) were reviewed. That is very inadequate especially if done for validity purposes only. To fail to examine all records among the 787 children in the numerators of the cohort (738 in Table 2), with a clinical multidisciplinary approach leaves the project wide open to errors and misclassification.
Review of all cases could have easily been done as it was done in an English study of autism where 7 medical professionals reviewed records of 493 affected children in one month.
Assume hypothetically that there is a vulnerability to MMR-induced disease in a subgroup of 10% of the autistic cases. Assume further that in the main autism group 80% have been vaccinated and 95% vaccinated in the subgroup. In a nested case control design within the Danish cohorts, the odds ratio (OR) for MMR in the subgroup would be 4.17; combining all autistics the OR would be 0.97 masking the strong association in a small subgroup”.
According to Dr. Spitzer, the percentage of cases of regressive autism, in an unselected series is likely to be between 10% and 15%. Dr. Spitzer calculated: “Conservatively, 10% would represent approximately 50,000 children in the U.S. alone with a yearly burden of $1.25 billion.”
He goes on to add that Madsen described a very important subgroup in the introduction but did not examine it specifically and did not or could not test the most relevant hypothesis proposed by Wakefield et al.
Dr. Spitzer then went on to raise several questions in reference to analytic issues:
a. Why did Madsen et al do an adjustment to the sub-cohort that removed 6 autistic (and a total of 13 cases of progressive developmental disorder) cases from the vaccinated sub-cohort and placed them in the unvaccinated one? This single adjustment reduces relative risk of autism due to MMR vaccination by 17%, from 1.26 to 1.09.
b. Why did Madsen et al not simply exclude all cases involving early (non-regressive) diagnoses of autism? If they had removed all cases diagnosed before two years of age from both sub-cohorts, the relative risk would have risen from 1.26 to 1.28.
He then discussed what he called a “classical problem of computerized databases”: Data gathered for other purposes, are rarely adequate to examine a problem, which was not investigated originally, because of variables that cannot be examined.
Professor Spitzer then discussed the ethical aspects of the study: “The concerns are about the process of funding, the interaction of sponsors with protocol formulation and approval, compliance with protocol, the role of investigators vis-a-vis sponsors in the actual conduct of research and the input of CDC epidemiologists in the preparation of the report with its conclusions:
a) Was there a protocol?
b) Who approved it?
c) Were there changes as the study progressed?
d) Who approved the changes?
e) Who monitored work-in-progress?
f) Who approved the final report?
g) Was there a Scientific Advisory Board?
h) What exactly was the role of the CDC and its professionals?”
Professor Spitzer also touched on the mercury in preceding vaccines:
“The immature infant immune system is biased towards an allergic response. As the immune system matures it becomes better able to deal with and clear viral infections. Impairing this immune system maturation (e.g. with heavy metals) may increase the susceptibility to an adverse event from a live viral vaccine.”
He then went on to describe the possible synergistic adverse effects of MMR and Thimerosal, upon the immune system of susceptible children triggering allergy, autoimmunity and eventually autism. “There is no mention of the role of heavy metals in a likely multi-factorial causal situation. This is not the fault of the investigators; it just can’t be done with the data sources available”.
For “Total Transparency” Dr. Spitzer advocated:
1. That the main protocol should be published in advance of the fieldwork, notably including the analysis plan with attendant definitions declared in advance.
2. A Scientific Advisory Board be created to monitor all phases especially protocol changes in progress and proposed publications.
3. A Community Advisory Board to look at conflicts of interest in finances.
The Yazbak comments (November 2002)
It is more than likely that the CDC would not have supported a study in Denmark without being assured, in advance, that the results provided evidence against an MMR-Autism association.
My disagreement with the Madsen study was based on the fact, that whatever it proved in Denmark, was not relevant to the situation in the United States.
The MMR story in Denmark
Based on a Medline search. (27)
Â§ Before the MMR was introduced in Denmark (The Campaign), 98% of Danish children aged 9 were immune to measles.
Â§ Within two years from the beginning of the campaign, the Health Authorities were concerned about acceptance already.
Â§ Almost HALF of the physicians questioned were neither certain about nor comfortable with the MMR vaccine’s efficacy.
Â§ Parents were concerned about the adverse effects and efficacy of the MMR
Â§ “All practices expressed a positive attitude towards the usefulness of MMR vaccination, but only 56% of the respondents expressed a whole-hearted positive attitude. The average vaccination rate in practices with unreservedly positive attitudes was 85%, compared with 69% in practices with more guarded attitudes.”
Note: According to the authors of the study themselves, 18% of children born between 1991 and 1998 did not receive the MMR vaccine. This is quite high. Only 3% of the children in the study had not received the HIB vaccine.
Vaccination Practices: USA & Denmark (1991-1998)
The Hepatitis B vaccine was not administered routinely to infants in Denmark during the study period. In the USA, the first dose is often administered a few hours after birth; the second at age 1 to 2 months and the third at age 6 to 12 months. Each dose of Hepatitis B vaccine, at the time, contained 12.5ug of ethyl mercury. DTP (or DTAP) and HIB contained each 25ug of ethyl mercury per dose
During the period in question, infants in the USA potentially received 12 vaccines in the first six months of life: DTP (DTaP) x3, HIB x3, Polio x3, Hepatitis B x3. [More vaccines are administered now and even more are planned.]
Infants in Denmark received 6 vaccines by age 6 months: DTP (DtaP) x2, HIB x2, Polio x2 [The third series was administered at age 12 months]
The Potential Ethyl Mercury Load (ug.)
The adult “safe” amount of mercury is 0.1Âµg/kg/day according to the Environmental Protection Agency (EPA). In the United States, a 2-month old infant (4-5 kg) who received the second dose of hepatitis B vaccine with DTP and HIB would be getting 62.5 ug of ethyl mercury or 12-15 ug/kg that day. An infant receiving 187 ug of ethyl mercury through vaccines over 6 months has had an average daily exposure in excess of the EPA adult safe amount.
The MMR vaccine was almost always administered alone, at age 15 months, in Denmark. In the U.S., the MMR was administered at age 12 months, frequently with the chicken pox vaccine and the last dose of HIB and Hepatitis B vaccines.
Again, both Professor Spitzer and I based our critiques (above) of the study from Denmark only on information and data published by the authors in the NEJM in November 7, 2002.
The Danish investigators reviewed information on a group of children born between January 1991 and December 1998, and who would be therefore 5 to 12 year old now.
” Results Of the 537,303 children in the cohort (representing 2,129,864 person-years), 440,655 (82.0%) had received the MMR vaccine. We identified 316 children with a diagnosis of autistic disorder and 422 with a diagnosis of other autistic-spectrum disorders. After adjustment for potential confounders, the relative risk of autistic disorder in the group of vaccinated children, as compared with the unvaccinated group, was 0.92 (95 percent confidence interval, 0.68 to 1.24) and the relative risk of another autistic-spectrum disorder was 0.83 (95 percent confidence interval, 0.65 to 1.07). There was no association between the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autistic disorder.
Conclusion This study provides strong evidence against the hypothesis that MMR vaccination causes autism”.
The vaccine authorities widely publicized the results of the research and reassured everyone that the “Danish Study” had proved that the MMR vaccine did not cause autism, not only in Denmark but elsewhere also. Feeling that they had won that battle and considering the subject closed, the researchers from Denmark turned their attention to Thimerosal in vaccines and published a study on the subject. They were immediately confronted by an informed group of parents who found serious problems with their data.
While preparing this presentation, I decided to review any available autism statistics from Denmark. The following important analysis is lengthy and detailed; it is intended for parents as well as professionals. To the best of my knowledge, this information has not been published to date.
Examination of the autism data from the Danish Psychiatric Central Register reveals that there has been a serious increase in autism in children under 14 in the last few years. (Graph II).
Graph II Incidence of Autism in Denmark by Age Group
Source The Danish Psychiatric Central Register.
The MMR vaccine was introduced in Denmark in 1987. It has been estimated that only 70% of the 15-month old children received the MMR vaccine in 1987-1988. The percentage of vaccinated toddlers then reached and remained at 80 to 88% for several years. It is estimated that in the last two to three years, about 95% of the 15-month old children in Denmark received the MMR vaccine.
The present rise in autism in Denmark appears to have started 4 to 5 years after the introduction of the MMR vaccine. It also appears to correspond with the percentage of children who received the MMR.
The mean age at the time of diagnosis in Denmark is probably around 4.7 years (“The mean age at diagnosis for autism was 4 years, 3 months, and for autistic spectrum disorders 5 years, 3 months.”)
This would be compatible with the following analysis. Looking at the mean value of autism incidence for 2002-2003, there are approximately
70 cases per 100000 among 5 to 9 age group
41 cases per 100000 among 0 to 4 age group
35 cases per 100000 among 10 to 14 age group
16 cases per 100000 among 15 to 19 age group
If all 4 age groups under the age of 20 are combined, there are 162 [70+41+35+16] individuals with autism per 100000. By computing the percentage contribution of each age group we find that:
43% of cases of autism are diagnosed in the 5 to 9 age group
25% of cases are diagnosed in to 0 to 4 age group
22% of cases are diagnosed in the 10 to 14 age group
10% of cases are diagnosed in the 15 to 19 age group
When one looks for further validation at the percentages in 1998 (the last year examined by Dr. Madsen), similar findings are noted:
39% among 5 to 9 age group
26% among 0 to 4 age group
19% among 10 to 14 age group
17% among 15 to 19 age group
In summary, using the 2002-2003 mean values (1st set of percentages above) we find that about 25% (1/4) of autism cases in Denmark are reported under the age of 5 and the remainder 75% (3/4) of affected children are reported when they are 5 to 19 years old.
The 2,129,864 person-years reported in the Madsen study divided by the number of children 537,303 indicates that the average age of the children in the study is less than 4 years (range 1 to 7 years). Those children would be 5 to 12 years old in 2003. Because the mean age at diagnosis is 4.7 years in Denmark, the Madsen study could NOT have detected many of the cases of autism that were subsequently diagnosed when these children were older, thereby missing the connection between MMR vaccination and autism.
The 0-4 year old group of children (Graph II, black) remains the lowest from 1980 to 1991, because autism was/is rarely diagnosed under the age of 4 in Denmark. The prevalence of autism in that age group starts climbing after 1991, 4 years after the introduction of the MMR vaccine, to become the second highest by 1993 but it always remains distinctly lower than in the 5 to 9 year old group.
The 5-9 age group is the earliest cohort to first receive the MMR vaccine after coverage has improved and is also old enough to be diagnosed. That group (red) is the largest all along and the spread between it and the next older age group increases with the passing years.
The 10-14 age group (dark green) represents the earlier cohort that first received the MMR vaccine, but at lower coverage rates. . Those affected children aged 10 to 14 in 2003 were aged 1 to 5 in 1994. They reflect the startup of the autism increase associated with the startup and progression of the MMR vaccination program.
The 15-19 age group (light green) were aged 1 to 5 in 1989; their number increases but at a much slower rate than in the younger age groups.
Lastly, the 20-24 age group (brown) shows only a slight increase starting in 1994 possibly because few if any of this cohort received the MMR vaccine at a vulnerable age.
Looking at data similar to that used in the Danish study, but with five additional years added, appears to invalidate the conclusions of the Madsen group and to support the hypothesis, that increases in autism in Denmark, may be correlated with increases in percentage coverage and number of children receiving MMR vaccination.
It is likely that in Graph II, the 0-4 year group of affected children represents those who were not generally diagnosed earlier, that the 5-9 age group represents the highest increase which occurred after wide-spread coverage of the MMR vaccine and that the 10-14 age group represents the earlier cohort that first received the MMR vaccine, but at a low coverage rate.
It is possible that the rate of autism will now level off at the higher rate since children receiving MMR immunization have now saturated the age groups and replaced individuals in the age groups that were previously unvaccinated.
Around 65,000 babies are born every year in Denmark. Graph II shows the early slow ramp-up period due to low vaccination rates as my literature review had suggested. (28). When MMR vaccination coverage improved beyond a certain level, from 1993 to 2001, there was a steady and increasing trend in autism yearly. That gradual rise leveled out after the entire cohort aged <10 was almost completely vaccinated (vaccine coverage at >95%). One must keep in mind that many of the children of the most affected 5 to 9 group, could have started with symptoms as early as the second year of life.
The prevalence rate of autism in Danish children under the age of 14 has increased by 729% from 17.67 per 100,000 Population in 1980 to 146.42 in 2002. (Graph III)
Graph III Children with Autism under Age 14 In Denmark per 100,000 Population.
Source The Danish Psychiatric Central Register.
The prevalence of autism in children and teens under the age of 14 in Denmark, which was 131.42/100000 in the 7 years before the MMR vaccine, increased by 542% to 843.73/100000 in the last 7 years. Indeed, the prevalence of autism in that group was 11% higher (146.42/131.42) in 2002 alone than in the combined 7 years before the introduction of the MMR vaccine.
Two doses of MMR are administered in Denmark, one at age 15 months, and one at age 12 years. (29) The data suggest that the main concern is the vaccination given at age 15 months.
The prevalence of autism in Denmark in the 0 to 14 year-olds leveled off in the last 3 years, when toddler MMR coverage reached the 95-98% level. The reason why this did not take place in the United States in the 90’s (Graph I) may have been because pediatric vaccines in the US contained Thimerosal, further supporting the argument that countries with strikingly different vaccination practices should not be compared.
I: The Madsen study, as designed, could NOT have detected an increase in Autism in Denmark after MMR vaccination.
II: Autism HAS INCREASED in Denmark after the introduction of the MMR vaccine. The rate ratio (incidence of autism after vs. before MMR vaccine) is 8.8 (95% C.I., 6.3 to 12.1) among 5 to 9 year olds.
III. Honest, accurate and unbiased clinical studies are needed. Parents must be interviewed and children must be examined and thoroughly evaluated. Looking at databases is not the answer.
Questions and Parting Thoughts
There are two questions for Dr. Madsen
- Why did an autism study involve an age group that was so young, when it was well known that the majority of cases were diagnosed at a later age?
- If the MMR vaccine is not responsible for the more than 700% increased prevalence in pediatric autism in Denmark after 1992 then what is?
There is only one question for the CDC Director:
“When will the CDC sponsor and support clinical studies of autism?
* * *
The health authorities in Denmark should take a close look at the autism situation. If autism is due to an autoimmune problem and if indeed a brain-gut relationship exists, then delaying the diagnosis to age 4 or later is unacceptable. Early strict diet management and intensive ABA have been clearly associated over the years with improved outcomes.
It is clear that there are many problems with several anti-Wakefield studies. It is unfortunate that so much faith was put in their conclusions. The Wakefield hypothesis remains valid and ongoing results and replications are encouraging.
The blind acceptance of the anti-Wakefield studies has resulted in a dangerous situation. The health authorities and the research community, by accepting their conclusions at face value, are essentially saying that a vaccine-autism connection does not exist and that scientists should stop looking. If the authorities are wrong in their assumption and if Dr. Wakefield is correct, even greater harm to our children may be occurring.
In the UK, believing these same flawed studies that deny an MMR-Autism link has just resulted in the cancellation of legal aid funds necessary for a class action suit. The research that would have been revealed in Court has thus been snuffed. Only Â£10m ($15m US) more was needed to see the parents’ legal case through to conclusion; this amount represents the approximate cost for lifetime care for only four children suffering from severe autism.
The UK Government has been spending considerably more money on a propaganda campaign to defend the MMR vaccine than it has on autism research. In January 2002 funds were promised for autism research as long as it did not involve the MMR vaccine. To date, not a single study has been launched. At his annual report on July 3, 2003, Sir Liam Donaldson, the UK Chief Medical Officer, did not even mention autism His five priorities at present were the health risks of second-hand smoke, West Nile virus, obesity, poor clinical performance by physicians and the safe administration of intrathecal chemotherapy.
This year, the CDC has spent immensely more time discussing SARS in China than it has looking at the causes of this true epidemic of autism.
Meanwhile a whole generation of beautiful children is being lost.
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United States Department of Education, Washington, DC 20202-2641
Previous reports can be accessed through the US Department of Education
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Changes in the Population of Persons with Autism and Pervasive Developmental Disorders in California’s Developmental Services System: 1987 through 1998.
Autistic Spectrum Disorders: Changes in the California Caseload. An Update: 1999 through 2002 [March 2003]. http://www.dds.ca.gov/autism/pdf/AutismReport2003.pdf.
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I am most grateful to Gary S. Goldman, Ph.D., for his help in refining the hypotheses presented.
I wish to thank Else Jensen of Vaccinationforum for her assistance and support.
Conflict: Grandfather of a beautiful boy with regressive autism, autistic entero-colitis and measles genomic RNA in the gut wall. His regressions at 18 months and 60 months have been clearly documented.