How Relevant is the Latest Study from Denmark? ----F. E. Yazbak, M.D., F.A.A.P. (original) (raw)

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The MMR-Autism Debate: How Relevant is the Latest Study from Denmark?
F. E. Yazbak, M.D., F.A.A.P.

Which is true?

The study by Meldgaard Madsen et al (N Engl J Med 2002;347:1477-82)
was commissioned to find out whether MMR vaccinations was linked to autism.

The study was commissioned to clear the MMR vaccine.

Given that the CDC has yet to look into the medical illnesses of children with late-onset autism, it is more than likely that the CDC hierarchy was aware of the anticipated results of the study- to exonerate MMR-- before a decision was made to co-fund it.

Melgaard Madsen�s first sentence actually sets the tone: �_It has been suggested that vaccination against measles, mumps, and rubella (MMR) is a cause of autism_�. Parents whose children have been investigated (by endoscopies, colonoscopies, biopsies, spinal taps, PCR testing, viral cultures and antibody studies) believe that the positive findings in their children more than suggest that MMR has played a role in their child�s autism.

The study essentially goes on to compare the prevalence of autism in a group of children, who had received the MMR vaccine and in another group who had not. Their conclusion was that �overall there was no increase in the risk of autistic disorder and other autistic-spectrum disorders among vaccinated children as compared with unvaccinated children.� The authors can only claim that this statement pertains to Denmark.

Thus, even if the study findings were meaningful in Denmark, they are totally irrelevant to the situation in the United States, because of differences in the actual vaccines administered and overall vaccination practices. Also noteworthy is the fact that many physicians and parents in Denmark had serious doubts about the MMR vaccine�s efficacy and safety, as evidenced by decreased vaccination rates.

A limited Medline search for �Measles Denmark� easily yielded the following abstracts. They are listed in their entirety and in their chronological order of publication. After each abstract, certain statements are highlighted, and followed by comments as indicated.

Dan Med Bull 1988 Apr;35(2):185-7
Prevalence of IgG-antibodies to mumps and measles virus in non-vaccinated children.
Glikmann G, Petersen I, Mordhorst CH.
Ornithosis Department, Statens Seruminstitut, Copenhagen, Denmark.

The prevalence of mumps and measles IgG antibodies in a randomly selected population of children was determined by an enzyme-linked immunosorbent assay (ELISA) before routine measles-mumps-rubella (MMR) vaccination was introduced in Denmark. Testing of sera from about 2,520 Danish children between one and 17 years of age showed that mumps antibodies were acquired at an early age. The peak acquisition rate was between the ages of four and five; before the age of 15, 90% of children had antibodies to mumps. Immunity to measles occurred at an even earlier age; more than 50% of four-year-old and nearly all (98%) nine year-old children had IgG antibodies to measles virus. The study showed that about 10% of the young adult Danish population was still susceptible to mumps infection whereas only about 1% of individuals at age 17 had not acquired immunity to measles virus.

PMID: 3359817 [PubMed - indexed for MEDLINE]

Please note: �**... nearly all (98%) nine year-old children had IgG antibodies to measles virus�** and �� only about 1% of individuals at age 17 had not acquired immunity to measles virus.�

Comment: Measles is more dangerous than mumps and rubella during childhood. Mumps is mostly of concern in adult males and rubella in adult females during their child bearing years. The authors have demonstrated, by accurate serological testing, that 98% of 9-year old children and 99% of those aged 17, were immune to measles BEFORE the introduction of the MMR vaccine into Denmark. It is not clear from the abstract whether the described almost total immunity was from natural disease (cellular immunity), or as a result of the administration of the single (monovalent) vaccine.

***

Ugeskr Laeger 1989 Sep 18;151(38):2418-22
Knowledge of, attitudes toward and participation in the new vaccinations against measles, mumps and rubella during the first 2 years
[Article in Danish]
Ronne T, Kaaber K, Petersen I.

The new vaccinations for measles, mumps and rubella (MMR) for children and the new vaccination for rubella for adult women were introduced in Denmark on 1.1.1987. An account is presented of 1) knowledge about and attitudes to the new vaccinations, investigated three months after commencement of the programme as assessed by means of a marketing investigation and 2) participation in vaccination during the first two years after introduction of the vaccination programme assessed by registration of services in the Danish National Health Service. The calculated participation in the MMR vaccination programme at the age of 15 months was found to be 72% and 31% at the age of 12 years. The calculated participation in the rubella vaccination programme at the age of 18 years was 13% in 1988 and even less for the remaining women. 95% of persons with children aged 0-12 years in the household who were questioned had heard about the new vaccinations for children and more than 50% had detailed knowledge about MMR vaccination. More than 10% were against MMR vaccination mainly because they considered that it was better for children to have these infections naturally. 90% of the women questioned knew why adult women were offered vaccination for rubella, although the percentage was less in the younger women. Compared with the goals established, participation in the MMR vaccination programme is insufficient. Participation in the rubella vaccination programme for adult women is entirely inadequate. The reasons for defective participation and proposed improvements are discussed. It is important that general practitioners and health nurses instruct parents about these possibilities.

PMID: 2800014 [PubMed - indexed for MEDLINE]

Please note: �Compared with the goals established, participation in the MMR vaccination programme is insufficient.�

Comment: Within two years, the vaccine authorities in Denmark were already concerned about MMR vaccine uptake.

***

Ugeskr Laeger 1990 Jan 1;152(1):10-6
What is cost benefit analysis?
[Article in Danish]
Pedersen KM, Alban A, Danneskiold-Samsoe B.
Dansk Sygehus Institut, Kobenhavn.

The practical and theoretical bases of cost-benefit analysis are reviewed systematically with particular emphasis on how an analysis can be carried out in practice. A Danish analysis about introduction of vaccination for mumps, measles and German measles is included as a common example. The great significance of elucidating the socio-economical questions to be answered before commencing an analysis is emphasized. It is therefore recommended that, among other things, as a side-effect of the actual cost-benefit analysis, a cash-analysis and a budget analysis should be carried out to identify the parties involved in the immediate expenses and incomes. This is particularly important in the cases where the same parties have a central position in the decision-making processes concerned in the project. In addition, costs and benefits are frequently distributed differently in time in different ways: Short-term expenses and long-term benefits. In connection with decision-making, this may also involve problems and should, therefore, be elucidated in detail. Similarly, the importance of including many alternatives in the analysis is emphasized and illustrated. In conclusion, it is demonstrated how well the theoretical principles have been followed, the employment and the process which led to the concrete analysis.

PMID: 2105000 [PubMed - indexed for MEDLINE]

Please note: �It is therefore recommended that, among other things, as a side-effect of the actual cost-benefit analysis, a cash-analysis and a budget analysis should be carried out to identify the parties involved in the immediate expenses and incomes. This is particularly important in the cases where the same parties have a central position in the decision-making processes concerned in the project.�

Comment: This excerpt highlights the need to examine the potential conflicts of interest involved in the recommendation and the execution of mass vaccination programs.

***

Ugeskr Laeger 1991 Mar 4;153(10):709-12
Attitudes to and knowledge of contraindications against measles, mumps and rubella vaccination. (MFR-vaccination) among general practitioners
[Article in Danish]
Johansen M, Haurum J.
Aarhus Universitet, Socialmedicinsk Institut.

A questionnaire investigation among general practitioners revealed that 29% of these were less positive about vaccination for measles, mumps and German measles (MFR vaccination) than for the remainder of the vaccination programme for children. Knowledge about contraindications for MFR vaccination was incomplete. Thus, only 26% of the general practitioners would advise vaccination if the parents stated that the child was hypersensitive to eggs. Only 70-80% of the general practitioners would advise vaccination if the child had cystic fibrosis, hydrocephalus, ventricle septum defect or had a cold but was apyrexial. Conversely, only 74% and 81% replied negatively to recommend vaccination if the child had had a previous anaphylactic reaction to eggs or was receiving treatment for leukemia. The replies given by the general practitioners were compared with present guidelines for contraindications to MFR vaccination and it is concluded that general practitioners should become more familiar with the knowledge about the MFR programme available at present and that further information from the official health authorities is required.

PMID: 2008714 [PubMed - indexed for MEDLINE]

Please note: �A questionnaire investigation among general practitioners revealed that 29% of these were less positive about vaccination for measles, mumps and German measles (MFR vaccination) than for the remainder of the vaccination programme for children.�

Comment: Almost one out of three doctors in Denmark did not think the MMR vaccine was as good as other vaccines FOUR YEARS into the campaign. This must have been as disturbing to parents as it was to the vaccine authorities.

***

Scand J Prim Health Care 1991 Mar;9(1):29-33
Doctors' attitudes and MMR-vaccination.
Trier H.
Department of Epidemiology, Statens Seruminstitut, Copenhagen, Denmark.

97 general practices, representing 171 practitioners, were asked about attitudes and certain procedures in relation to vaccination against measles, mumps, and rubella (MMR). Answers were correlated with their actual vaccination rate, calculated from the National Health Service Computer System. 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. All practices offered MMR-vaccination with the routine health examinations at the age of 15 months, and all except three practices recommended vaccination. The vaccination was usually done by a doctor. Differences in vaccination rates were not associated with the way of presentation of MMR, the profession of the person who carried out the vaccinations, or the average number of years of postgraduate experience of the doctors in a practice. Unreservedly positive attitudes among general practitioners are necessary, if sufficient vaccine coverage is to be achieved.

PMID: 2041925 [PubMed - indexed for MEDLINE]

Please Note: �but only 56% of the respondents expressed a whole-hearted positive attitude� The average vaccination rate �69% in practices with more guarded attitudes.�

Comment: This study, published at the same time as the previous one, does not compare how Danish physicians felt about the MMR vaccine in comparison to other vaccines. It just reveals that almost HALF of the physicians questioned were neither certain about nor comfortable with the MMR vaccine�s efficacy. This was reflected in the decreased vaccination rates in their practices.

***

Ugeskr Laeger 1991 Mar 4;153(10):705-9
Attitudes and knowledge among parents who do not want their children to be vaccinated against measles, mumps and rubella (MFR-vaccination) [Article in Danish]
Haurum J, Johansen M.
Aarhus Universitet, Socialmedicinsk Institut.

In a questionnaire investigation concerning attitudes to and knowledge about MFR vaccination among 81 parents who did not want their children to be vaccinated against measles, mumps and German measles, the parents could be divided into two main groups with reasons formulated in advance: 41% stated that "infectious diseases are beneficial for children" including here their somatic and mental development and the parent-child relationship. The remaining parents based their attitudes on defective knowledge about MFR vaccination, fear of side effects, erroneous contraindications and attitudes such as: the MFR diseases are not serious and vaccination may cause serious disease, does not protect effectively or lowers the resistance of the population and that economy is a poor argument in favour of vaccination. Parents who were critical about the total information concerning the MFR programme were also more critical about their general practitioner than the remaining parents. 80% stated that the MFR programme had been introduced because it involved social economy while 56% thought that health benefits were the reason. It is concluded that further well-directed information about the MFR programme is essential, if the necessary vaccine coverage is to be obtained.

Please Note: �fear of side effects � vaccination may cause serious disease, does not protect effectively� 80% stated that the MMR programme had been introduced because it involved social economy while 56% thought that health benefits were the reason.�

Comment: These parents� concerns must have persisted. According to Meldgaard Madsen, 18% of children born between 1991 and 1998 did not receive the MMR vaccine. Only 3% did not receive the HIB vaccine.

***

Ugeskr Laeger 1992 Jul 13;154(29):2014-8
Changes in measles, mumps and rubella (MMR) immunity until the year of 2002 after the introduction of MMR vaccination
[Article in Danish]
Ronne T, Trier H.
Epidemiologisk afdeling, Statens Seruminstitut, Kobenhavn.

In order to decide whether vaccination for measles, mumps and rubella should be introduced at the age of five years, calculations of the immunities in various age groups were performed until the year 2002 with and without vaccination at the age of five years. These calculations are based on the knowledge of immunity in the various age groups before the MMR vaccination programme was instituted in 1987 and knowledge of the compliance with vaccination obtained to date. Future predictions reveal that it is of decisive significance that compliance with vaccination among 12-year-olds is increased as rapidly as possible to 0.7 and to 0.8 in the subsequent year, if the level of immunity present prior to institution of the vaccination programme is to be maintained. The second vaccination given at a shorter interval after the first would prevent about 150 cases of illness in all per annum among 6-12 years-old. However, this should not be introduced at the expense of vaccination at the age of 12 years, which should be continued for at least 10-15 years yet. Possible abandoning of vaccination at the age of 12 years 10-15 years hence presupposes that adequate numbers of the children have been vaccinated twice at an early age and that it is sufficiently certain that secondary failure of vaccination does not occur to any significant extent.

PMID: 1509567 [PubMed - indexed for MEDLINE]

Please note: �Future predictions reveal that it is of decisive significance that compliance with vaccination among 12-year-olds is increased as rapidly as possible � if the level of immunity present prior to institution of the vaccination programme is to be maintained.�

Comment: The authors correctly refer to the MMR program in Denmark as a �vaccination program� (whereby vaccinations are provided, regardless of their efficacy in conferring sufficient immunity) and not an �immunization program� (whereby immunity is promised). They express concern about its results and advocate a second MMR vaccine for each child, in order to attain the exceptional levels of immunity, which were previously recorded in Denmark, via the use of monovalent vaccines and natural disease, BEFOREthe MMR program was instituted.

***

Ugeskr Laeger 1992 Jul 13;154(29):2008-13
Duration of immunity and occurrence of secondary vaccine failure following vaccination against measles, mumps and rubella
[Article in Danish]
Trier H, Ronne T.
Epidemiologisk afdeling, Statens Seruminstitut, Kobenhavn.

The present article illustrates the extent of secondary vaccine failure after vaccination for measles, mumps and rubella (MMR). Secondary vaccine failure means loss of the immunity induced by vaccination to such an extent that infection becomes possible. Serological investigations carried out with follow-up periods of up to 16 years after vaccination for measles, 21 years after vaccination for rubella and 12 years after vaccination for mumps reveal that loss of antibodies occurs with the elapse of time but that the clinical significance of this is probably very limited. Where all three types of vaccination are concerned, secondary vaccine failure has hitherto been very seldom. Infection with measles after secondary vaccine failure is generally described as running a milder course. In rare cases, rubella re-infection has resulted in infection in utero, so that a slight risk of congenital rubella cannot be entirely excluded after successful vaccination. No extensive systematic investigations of the effect of revaccination have been carried out and, similarly, the optimal interval between two or more vaccinations has not been illustrated in more detail in the literature. Subclinical infection is not uncommon after all three vaccines. Where measles is concerned, immunity may possibly be regarded as a continuum which, depending upon the antibody level, protects the individual from various degrees of clinical disease. If wild virus can be spread via individuals with subclinical infections, it is doubtful whether population immunity (herd immunity), which is necessary to eliminate the three diseases, can be attained in large populations. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 1509566 [PubMed - indexed for MEDLINE]

Please note: �Subclinical infection is not uncommon after all three vaccines. � If wild virus can be spread via individuals with subclinical infections, it is doubtful whether population immunity (herd immunity), which is necessary to eliminate the three diseases, can be attained in large populations.�

Comment: Before the vaccination program was initiated, practically all children were immune to measles. Five years into the program, and with the administration of two triple vaccine doses, it does not seem that Denmark will ever achieve future population immunity.

***

Ugeskr Laeger 1994 Dec 12;156(50):7497-503
The childhood vaccination program. Background, status and future
[Article in Danish]
Plesner AM, Ronne T.
Epidemiologisk afdeling, Statens Seruminstitut, Kobenhavn.

Surveillance of the Danish childhood immunization programme has taken place at Statens Seruminstitut since 1980. A description of the prevalence of the diseases, which are included in the programme, is presented. The Danish childhood immunization programme has for many years been one of the best in the world although it differs markedly from other countries. The polio immunization programme with inactivated polio vaccine given first and then later live attenuated vaccine is probably the optimal polio immunization programme. The childhood immunization programme began in 1943 with free diphtheria vaccination, and tetanus immunization was added in 1949. There was a big polio epidemic in 1952/53 and the polio vaccine was introduced in 1955. All three vaccines have markedly reduced the prevalence of these diseases. Pertussis vaccine was introduced in 1961 and measles, mumps and rubella vaccination in 1987. Vaccination against Haemophilus Influenzae type b was introduced with success in 1993. In the future several changes will probably be made in the programme because of the possibility using new combined vaccines.

PMID: 7839512 [PubMed - indexed for MEDLINE

***

Vaccination Practices: USA & Denmark

1991-1998

(Meldgaard Madsen Study Intake Period)

The Hepatitis B vaccine is not administered routinely to infants in Denmark. In the USA, the first dose is usually administered a few hours after birth, the second at age 1-2 months and the third at age 6-12 months. Each dose of Hepatitis B vaccine contained 12.5 ug of ethyl mercury. DTP and HIB contained 25 ug of ethyl mercury per dose.

During the first six months of life

Infants in the USA potentially received 12 vaccines:
DTP (DTaP) x3, HIB x3, Polio x3, Hepatitis B x3.

Infants in Denmark potentially received 6 vaccines:
DTP (DTaP) x2, HIB x2, Polio x2 (The third series was administered at age 12 months)

Potential ethyl mercury load (ug)

The adult safe amount of mercury is 0.1�g/kg/day according to the 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 have actually been exposed to 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.

MMR Vaccination

The MMR vaccine was always administered alone, at age 15 months, in Denmark. In the US, the MMR was administered at age 12 months, frequently with the chicken pox vaccine, and at times with DTP #4, HIB #3 and Hepatitis B #3 vaccine doses.

Discussion

In 1942, Kanner described 11 children who were socially isolated and had abnormal behaviors and communication skills. For the next twenty-five years, more children with �infantile autism� were identified and referred to psychologists and psychiatrists for treatment. Because symptoms appeared early, it was felt the children were born with the affliction. Dr. Bernard Rimland, Founder and President of the Autism Research Institute (ARI) was first to suspect that other than genetic causes contributed to the steady increase in the prevalence of autism in the last quarter century. In �The Autism Explosion�, Dr. Rimland described a striking rise in autism in California starting in 1978 and a similar one in the United Kingdom ten years later, closely following the introduction of the MMR vaccination (http://www.autism.com/ari/editorials/explosion.html).

Epidemiological studies by Taylor and Kaye, which were intended to refute any MMR vaccine- autism connection, also confirmed a steep rise in spectral disorders in the UK.

The United States Department of Education (US DOE) must report annually to Congress to comply with IDEA, the individuals with Disabilities Education Act. Starting in 1991, autism has been listed independently in the annual reports. That year, there were 5,400 children with autism, aged 6 to 21, known to the DOE. Not included were affected children under six and those who had not yet been fully diagnosed.

In the last annual report, almost 80,000 children, age 6 to 21, are listed as having autism.

This increase in autism is NOT due to better diagnosis or looser criteria as claimed by some. Since the more restrictive DSM IV was introduced in 1994, the diagnostic criteria have NOT changed, and to suggest that developmental pediatricians, psychiatrists and special education specialists are over-diagnosing autism is ridiculous.

In California, the Department of Developmental Services (DDS) regularly lists the number of new cases of autism in the State. In 1994, there were 633 new cases of type I autism (299.00). In 1999, that number had jumped to 1944 new cases or 7 cases a day. In just one quarter in 2002, DDS has reported that 812 new cases of type I autism were added to the system, a staggering 9 NEW cases EVERY day.

There were more new cases of type I autism in California in 2001 than in 1994, 1995 and 1996, the first 3 years after DSM IV. There were also more cases (6,596) added in the last three full years than in the first 25 years on record (6,527).

A review of the ARI huge database has revealed an important change in the timing of first symptoms according to Dr. Rimland. Before 1980, the majority of parents noticed autistic symptoms in their children shortly after birth or in the first few months of life (early-onset autism). Since 1980, two thirds of the parents are now reporting that their children appeared normal during their first year of life and only exhibited symptoms of autism and regression after the age of 18 months (late-onset autism).

Extensive research into the genetic causes of autism has not and will never explain its spectacular increase. All possible environmental factors, including vaccines, must be investigated by serious and unbiased clinical research. Redundant and irrelevant epidemiological studies are offensive and a waste of money.
It is known that some children with autism born after 1991 have distinct pathological changes in their gastro-intestinal tract and evidence of vaccine-strain measles in their gut wall (Wakefield, O�Leary and Kawashima). It is also known that vaccine-strain measles virus has been retrieved from the brain of two boys who had serious reactions to MMR vaccination. Lastly, high titers of measles, MMR and anti-brain antibodies have been detected in the blood and the cerebrospinal fluid of children with autism, who were given the MMR vaccine but were never exposed to the diseases (Singh and others).

Logically, the spectacular increase in the prevalence of autism in the USA, during the nineties, cannot be blamed on the MMR vaccination alone. Other changes in vaccination practices must be considered. They include routine Hepatitis B vaccination, and the administration of multiple vaccines on the same day or when the child is not in perfect health.

It was the arduous research of parents, that first attracted attention to a possible connection between the mercury used in certain vaccines and autism. It was also revealed that unpublished research by the CDC found statistically significant positive correlation between �the cumulative exposure at 2 months of age and unspecified developmental delay and � the cumulative exposure at 1, 3, and 6 months of age and neurodevelopmental delays in general. The study concluded that specific conditions that may warrant detailed study include �autism.

Many informed and reliable parents are convinced that their children developed autism in the first year of life, after receiving the DTP or Hepatitis B vaccines. Because of the early onset of the disease, it was often erroneously attributed to genetic causes.

Because the vaccination schedule was so different in Denmark and because all pediatric vaccines in Denmark did not contain mercury (1992), the conclusions of the latest study by Meldgaard Madsen and associates are not relevant to the situation in the United States. It is therefore of concern that the CDC commissioned the study altogether.

The mere fact that this study is all what the CDC could come up with, is significant by itself, particularly when precious little information has been made available about the vaccine-autism study that the CDC has been conducting in Atlanta, Georgia.

The unique circumstances surrounding this study from Denmark leave some unanswered questions. They will be listed after the conclusions.

Conclusions

*Danish children had better measles immunity before the MMR vaccine was used.
*Many parents and physicians in Denmark had doubts about the MMR vaccine.
*The Danish authorities were concerned about vaccination rates and immunity.
*Vaccination practices differ greatly between Denmark and the United States.
*Children in Denmark did not receive vaccines with mercury and certainly not shortly after birth.
*Epidemiological studies comparing the causes and incidence of autism in Denmark and the USA are not meaningful.
*Federal (and private) funds should be spent to discover the real causes for autism whatever they are.

Questions about the Meldgaard Madsen Study

*Why did 18% of children born in Denmark between 1991 and 1998 not receive the MMR vaccine, when in the same period, the vaccination rate for HIB was above 97% nationally?
*Did the study completely reassure parents in the USA about the MMR vaccine?
*Did the study help find a cause for autism?

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

December 3, 2002
� 2002