MMR Studies that Count, Studies that Don't - F.E. Yazbak, MD, FAAP

http://autismautoimmunityproject.org/Yazbak.doc

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Just published  (26 February 2004)

Studies that Count, Studies that Don't


Parents in England have a big choice: They can believe Andrew Wakefield or
they can believe Tony Blair, Liam Donaldson and Richard Horton. They can
trust Andy or they can trust the experts from the Committee on Safety of
Medicines and the
Joint Committee on Vaccination and Immunization, several of whom have ties
with the drug company that distributes the MMR in England.

We in the United States also have a choice between on one side, clinical
research, with real children and on the other, one more epidemiological
study by the CDC.

The following quotes from presentations on February 9, 2004 to the Vaccine
Safety Committee of the Institute of Medicine deserve attention:

"In light of encephalopathy, presenting in children as autistic regression
closely following MMR vaccination . The findings confirm a highly
significant statistical association between the presence of MV RNA in CSF
and autistic regression following MMR vaccination."  Jeff Bradstreet MD,
Director, International Child Development Resource Center, Melbourne, Florida.

"The current genetic research estimates that no more than 10% of all
autistic cases are genetic in origin. Simply put, the remainder 90% of
autistic cases is sporadic with a non-genetic etiology. I tend to think
that the sporadic form is by and large an "acquired" subset involving
autoimmunity. This subset is likely triggered by a virus, possibly measles
virus or MMR vaccine... Based upon our experimental research, it is
plausible to postulate that an atypical measles infection that does not
produce a typical measles rash but manifests neurological symptoms might be
etiologically linked to autoimmunity in autism. The source of measles virus
could potentially be MMR vaccine or a mutant measles strain, but more
research is necessary to establish either of these two possibilities.
Fundamentally, I tend to think that autistic children have a problem of
their immune system, which is the "faulty immune regulation." Hence they
have abnormal immune reactions to measles virus and/or MMR vaccine"
Vijendra K. Singh, Ph.D., Research Associate Professor of Neuroimmunology,
Utah State University, an international expert in the autoimmune causes of
autism:

US Representative Dave Weldon, a physician, commenting on the on-going
clinical research said: "Mind you, half of Dr. Wakefield's theory has been
proven correct and accepted in the medical community. Hundreds of children
with regressive autism and GI dysfunction have been scoped and clinicians
are seeing the inflammatory bowel disease he first described. The NIH is
finally funding an attempt to repeat Dr. O'Leary's findings of measles RNA
in Wakefield's biopsy specimens, though I am disappointed it has taken this
long..A clinician in New York was poised to repeat Wakefield's work two
years ago, but he ultimately was refused by his IRB and then subsequently
had his clinical privileges withdrawn."

Instead of telling parents why they are suddenly losing their children, the
CDC just published another long, pedantic and rather useless MMR
"damage-control" epidemiological study: Age at First Measles-Mumps-Rubella
Vaccination in Children with Autism and School-Matched Control Subjects: A
Population-Based Study in Metropolitan Atlanta by Dr. Frank DeStefano and
others [Pediatrics Vol. 113 No. 2 February 2004, 259-266].

The authors did not discuss the causes of the present epidemic now
affecting the United States (1) and the world (2), but simply stated that
the MMR was unlikely to be the cause of regressive autism because children
diagnosed with autistic disorders in Atlanta, Georgia received their first
MMR vaccine at about the same age as unaffected children.  

The CDC had previously published two local epidemiological studies, in
which serious increases in autism were documented (3, 4). It also funded a
third study in Denmark (5) that, though much publicized, was flawed and
irrelevant to the situation in the United States. That study also seemed to
have been primarily intended to exonerate the MMR vaccine and it will be
discussed in some detail later.

The CDC has never proposed, designed, funded or carried out a single
clinical study on autism.

The only credible way to prove that the MMR vaccination does or does not
precipitate autistic symptoms in children, who are genetically predisposed
and have been previously exposed to Thimerosal-containing vaccines, is to
compare affected children who have received the MMR vaccine with children
who have not. This is obviously practically impossible because most
children in Atlanta have received the MMR vaccine. The theoretical question
is therefore: "How many children in Atlanta would have developed autism if
they had not received the MMR vaccine?"

A relatively easy study would be to compare the age of onset of autistic
symptoms in children vaccinated at 15 months and those vaccinated at 30
months in Atlanta.
I believe, from my own research, that such a study will show that:
1. Autistic behavior follows MMR vaccination and
2. That fewer cases and less severe manifestations are noticed among the
cohort vaccinated at 30 months, since vaccination at a younger age appears
most damaging.

Another easy study would be to compare Measles, MMR and Myelin Basic
Protein antibody titers of children who developed autism shortly after MMR
vaccination in Atlanta to an equal sample of normal children similarly
vaccinated.

Dr. DeStefano states [under conclusions, page 259] "Similar proportions of
case and control children were vaccinated by the recommended age or shortly
after (ie, before 18 months) and before the age by which atypical
development is usually recognized in children with autism (i.e. 24
months)."  The CDC, certain pediatricians and the MMR lobby have
consistently argued that autism is not due to the triple vaccine because
autistic symptoms are "usually first noted" around the time the MMR is
administered and that therefore the relationship between the two events is
casual and not causal; in other words just a coincidence. Historically,
this is not so.

Kanner's autism was known as Infantile Autism because affected children
exhibited symptoms in early infancy. The more recent form of the disease,
Regressive Autism, occurs at a older age with symptoms usually starting at
18 to 24 months or later: A child, most often a boy who is developmentally,
socially and verbally on par for his age, suddenly stops acquiring new
words and skills in the second year of life and then actually regresses,
losing speech, cognitive abilities and social dexterity. Many parents have
reported and documented such regression in their children after MMR
vaccination.

Bernard Rimland, Ph.D., Founder and President of the Autism Research
Institute (ARI), a full-time professional research scientist in the field
of autism for 45 years, stated after a thorough analysis of the extensive
ARI database: "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, the increase paralleling the increase in required
vaccines." (6)

The study by DeStefano, though dazzling with figures and tables proves
little, just like the epidemiological studies by Taylor, Kaye and Dales
that were supposed to have previously "convincingly proven that there is no
relationship between MMR vaccination and autism".  Interestingly, Kreesten
Meldgaard Madsen, author of "A Population-Based Study of Measles, Mumps and
Rubella vaccination and Autism", (5) the study funded by the CDC stated
"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)." In the Madsen
bibliography, reference 10 is the first Taylor study (The Lancet);
reference 11 is the one by Kaye (BMJ) and reference 12 is the study by
Dales (JAMA). For reasons known only to him, Dr. DeStefano still mentioned
the Taylor, Kaye and Dales studies as reliable and listed them as
references 23, 22 and 19 respectively.
Dr. DeStefano and Associates describe the Madsen MMR study as "particularly
persuasive". In fact, that study, because of an integral flaw in its
design, could not have shown, that indeed there had been an increase in
autism after routine MMR vaccination was initiated in Denmark.

The following is part of the analysis by Dr. Gary Goldman and myself of
data from the Danish Psychiatric Central Register, the same data that
Madsen used. It clearly shows that there has been a serious increase in
autism in children under 14 in Denmark in the last few years. (Graph I)
 
Graph I 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 triple 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 three
years about 95% of the 15-month old children in Denmark received the MMR
vaccine.

The present rise in autism in Denmark has clearly started 4 to 5 years
after the introduction of the MMR vaccine and it 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.") Approximately 25% of
autism cases in Denmark are reported in children under the age of 5 with
the remainder 75% of affected children being reported when they are 5 to 19
years old. Given these percentages, any inferences about disease in the
under-5 group, in which the disease has not yet become manifest, are
potentially flawed.

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 temporal connection between MMR vaccination and
autism.

The 0-4 year old group of children (Graph I, 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.

The 5 - 9 age group is the earliest cohort that received the MMR vaccine
after coverage has improved and is also old enough to be diagnosed. There
are consistently more and more affected children in this age grouping.

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.

Even when one takes into account the classification change that took place
in 1993/1994 and the addition of outpatients to the database in 1995, it is
evident, when five additional years are considered, that the conclusions of
the Madsen group are invalidated and that the data appears 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 I, 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 that 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.

Approximately 65,000 babies are born every year in Denmark. Graph I shows
the early slow ramp-up period due to low vaccination rates. When MMR
vaccination coverage improved beyond a certain level, from 1993 to 2001,
there was a steady and increasing trend in autism every year. That gradual
rise leveled out after the entire cohort aged <10 was almost "completely"
vaccinated (vaccine coverage at >95%). It is entirely possible 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 II)

Graph II 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. 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 was
probably because pediatric vaccines in the US contained Thimerosal, further
supporting the argument that the study was flawed in principle because
countries with strikingly different vaccination practices cannot and must
not be compared.  

Conclusions

Autism has increased in Denmark after the introduction of the MMR vaccine
as evidenced by the fact that the rate ratio i.e. the incidence of autism
after vs. before MMR vaccination is 8.8 (95% C.I., 6.3 to 12.1) among 5 to
9 year old Danish children.
The Madsen study did not reveal this statistically significant increase.

Dr. DeStefano and his colleagues at the CDC should research the causes of
Regressive Autism rather than defend a vaccine in trouble.

Parents are more likely to forgive errors than cover-ups.


 References:

1. Yazbak FE. Autism in the United States: a Perspective. J Am Phys Surg
2003;8:103-107
                                                          Available at
http://www.jpands.org/vol8no4/yazbak.pdf.        (accessed February 10, 2004)

2. Yazbak F E. Autism seems to be increasing worldwide, if not in London.
BMJ 2003;328:226227.        Available at
http://bmj.bmjjournals.com/cgi/content/full/328/7433/226-c
(accessed February 10, 2004)

      3.  Prevalence of Autism in Brick Township, New Jersey, 1998:
Community Report.
Available at: www.cdc.gov/ncbddd/pub/BrickReport.pdf.
               
(accessed February 10,   2004)

4. Yeargin-Allsopp M, Rice C, Karapurkar T, Doernberg N, Boyle C, Murphy C. 
     Prevalence of autism in a US metropolitan area. JAMA 2003;289:49-55.

5. Madsen MK, et. al. A population-based study of measles mumps rubella
vaccination and autism. NEJM 2002;347:1478-1482

6. The Autism Epidemic is Real and Excessive Vaccinations Are the Cause
A Statement: Bernard Rimland, PH.D.July 14, 2003
Available at: http://autismautoimmunityproject.org/Rimland.htm
          
(accessed February 10, 2004)     


F.Edward Yazbak, MD, FAAP
TL Autism Research, Falmouth, Massachusetts
E-mail: TLAutStudy@aol.com