Contents:
1. MMR vaccine introduced into UK vaccination schedule 1988
2. JABS group founded in 1994 as serious vaccine problems were reported
3. The UK adverse event surveillance system - 'yellow card'
4. Investigations
5. Withdrawn MMR brands
6. Drug manufacturers' product sheets
7. Responsibility for vaccine damage
8. Raising the issues with UK Government Minister and Health Chiefs
9. Vaccine Damage Payment Act 1979
10. US experience
11. Japanese experience and compensation
12. MMR and Autism
13. MMR Legal Cases
14. Single vaccines
15. Conflict of Interest
16. Cochrane Review
17. World Health Organisation (WHO) – Causality of Adverse Events
i. Consistency
ii. Strength of the association
iii. Specificity
iv. Temporal relation.
v. Biological plausibility
18. Financial Cost
19. Summary
20. Acknowledgements
21. References
1. MMR VACCINE INTRODUCED INTO UK VACCINATION SCHEDULE 1988:
Three brands of MMR vaccination were introduced into the UK childhood vaccination programme from October 1988. The vaccines were heralded as a one-off, life-long immunisation against three serious diseases - measles, mumps and rubella. The manufacturers’ were:
SmithKline Beecham - brand name Pluserix
Merieux - brand name Immravax
Merck Sharpe Dohme - brand name MMRII.
SmithKline Beecham and Merieux used Schwartz strain measles, Wistar RA27/3 strain rubella and Urabe AM9 strain mumps. Merck Sharpe Dohme used Enders’ Edmonston strain measles, Wistar RA 27/3 strain rubella and Jeryl Lynn strain mumps.
2. JABS GROUP FOUNDED IN 1994 AS SERIOUS VACCINE PROBLEMS WERE REPORTED:
When the JABS group was founded in January 1994 parents contacted us with their concerns about their children’s serious ill health following childhood vaccinations. We asked parents to complete questionnaires on the vaccines given and to describe in detail their children’s experience.
We were astounded by the responses. Parents stated the number of days after MMR vaccination when their children had started to become ill and in many cases the number of days quoted were consistent with the incubation period of the vaccine viruses given. Many of the symptoms described were listed in the vaccine manufacturers’ own product sheets.
The parents reported that their children had suffered serious consequences after the initial symptoms and had not recovered to the health point they had had before the vaccination was given. The most remarkable aspect of this is that the long term serious health problems that the children developed were also, in the main, listed in the same drug product sheets as the ‘rare’ events known to be associated with the vaccine.
3. THE UK ADVERSE EVENT SURVEILLANCE SYSTEM - 'YELLOW CARD':
We asked each family if their child’s doctor or consultant had reported the symptoms and change in the child to the UK's Committee on Safety of Medicines using the adverse events surveillance mechanism known as the ‘yellow card’ scheme. The vast majority responded that the health professional had declined to use the reporting system as he/she had dismissed the link with the vaccination as ‘just a coincidence’. Therefore, the suspected reactions had not been put forward to the central body for detailed investigation.
In theory the system should work to flag up any serious problems with drug products - the guidelines note that allsuspected reactions should be reported. In practice the system was and still is largely ineffective because health professionals make their own arbitrary decisions on whether to report the serious side effects of vaccination. The DoH does not enforce the collection of any reliable data on adverse events. Currently the reporting system only collects about 10% which does not make reliable data.
The Health Protection Agency in its former role as Public Health Laboratory's Service is on record in the Lancet (Vol. 345. March 4, 1995) stating ''....there is an urgent need to find more reliable methods of adverse event surveillance.'' The point being that unless all reactions are put forward to a central body instead of being dismissed as 'unrelated' or 'just a coincidence' the central database will never hold accurate information on adverse events. How many coincidences are needed before it becomes meaningful enough to warrant clinical and scientific investigation?
4. INVESTIGATIONS:
Families have urged the medical practitioners dealing with their children’s problems to investigate the suspected connection with the vaccinations. Some parents have also reported that the doctor/consultant was not interested in finding the reasons for the decline in the child’s health stating that their role was to treat the problem and, therefore, they did not want to be involved in the causal aspect.
During the course of the JABS group's investigations we discovered that the UK pre-introductory trials for MMR were inadequate in that they failed to follow up adverse reactions for more than just a few weeks. Serious degenerative conditions are known to take weeks and/or months to develop.
5. WITHDRAWN MMR BRANDS:
Proof that the pre-introductory trials were inadequate is in the knowledge that it took the Department of Health four years to identify problems and withdraw two of the three original MMR brands that had been introduced into the UK vaccination programme in 1988. These two brands, Pluserix and Immravax were withdrawn by September 1992 because they contained a mumps strain known as Urabe which had caused mumps meningitis in some children. Many of the badly affected children known to JABS had had these brands of MMR. It is also of concern that this problem was known by the Joint Committee on Vaccination and Immunisation (JCVI) see minutes. The licence for the MMR vaccine containing the Urabe strain in Canada was revoked from May 1990. In Japan the MMR vaccine was banned in 1993. A version of this vaccine made by Chiron has since been withdrawn from use in Italy in March 2006.
6. DRUG MANUFACTURERS' PRODUCT SHEETS:
The drug manufacturers of MMR vaccines have provided the Government’s vaccine policy makers with product sheets which list the adverse reactions known to be associated with their vaccines. These lists are virtually identical from each of the drug companies. They state the minor side effects which doctors are happy to describe to parents: namely - rashes, raised temperature etc. These same sheets also state reactions only recently acknowledged in public by the Health Protection Agency e.g. febrile convulsions, blood disorders (ITP). The information sheets also state the severe adverse events: to name but a few - diarrhoea, nerve deafness, arthritis, Guillain-Barre syndrome (a paralysis syndrome), severe vision problems, seizures and encephalitis. Encephalitis (inflammation of the brain) can lead to a range of disabilities such as epilepsy, loss of speech and communication and acquired autism.
7. RESPONSIBILITY FOR VACCINE DAMAGE:
Richard Ley, of the Association of British Pharmaceutical Industries said in the Daily Express (May 18, 2000): ‘The Government implemented the vaccination programme knowing in full detail what the possible side-effects were. They knew what they were taking on, the damage is therefore their responsibility and they should compensate people accordingly.’
The MMR vaccine contains three live attenuated viruses; their major disadvantage is a danger of reversion of the virus strains to more reactive and virulent forms. In plain terms, if the wild virus can cause inflammation in the brain, joints, spine, eyes, ears and bowel then so can the vaccine-virus and to quote an extract from a letter published in the Times (February 9 2002) from Dr David Hall, President of Royal College of Paediatrics and Child Health : 'Some children develop encephalitis (brain swelling) when they catch measles, mumps or rubella viruses and may be left with a variety of handicaps, including physical and mental impairment, deafness, internal organ damage and autism.....'
8. RAISING THE ISSUES WITH UK GOVERNMENT MINISTER AND HEALTH CHIEFS:
In October 1997 Dr Andrew Wakefield and Professor Walker-Smith from the Royal Free Hospital, London, JABS and its legal representatives, took part in a meeting with the then Health Minister, Tessa Jowell, also the Chief Medical Officer, Principal Medical Officer and others. During the course of the one hour meeting a full list of children, then affected, was presented. We asked that the Government should instigate a scientific investigation of the children believed to have been damaged which could have been useful on at least two fronts:
i. To answer the question of MMR safety.
ii. If the vaccine was found to be causing harm it may have been possible to identify ''at-risk'' groups which may have led to a screening programme with the potential to have improved vaccine safety for all children
The Health Minister at the time stated she was willing to look at all scientific evidence but would not comment further. Until the Government instigates a full investigation of the children believed to have been damaged, the ''scientific evidence'' required by the Department of Health is unlikely to emerge.
9. VACCINE DAMAGE PAYMENT ACT 1979:
The Government is well aware that vaccines sometimes cause severe damage or death; there is a branch of the Department of Works and Pensions known as the Vaccine Damage Payment Unit. It was set up in 1979 following the Vaccine Damage Payment Act 1979. MMR vaccine damage payments have been awarded for various adverse effects including: epilepsy, Guillain-Barre syndrome (a paralysis condition), SSPE (a brain-wasting condition), neurological problems, profound deafness and death.
10. US EXPERIENCE:
Any debate on vaccine damage will have Department of Health officials quoting the massive number of doses given to children in the United States and other parts of the world. What is never admitted by UK officials is that in the US they have a National Vaccine Injury Compensation Programme. In the last 21 years this programme has paid out hundreds of millions of dollars in payments to vaccine damaged children of which a 14% share has been paid out for MMR or its components. The drug companies have to contribute to the programme and up to August 1997 they had to pay an excise tax on each dose using a risk-based formula. The DTP and MMR were taxed at $4.56 and $4.44 respectively, polio vaccines at $0.29 and DT (diphtheria/tetanus) vaccines at $0.06. This gives an indication of which vaccines carry the highest risk of a serious adverse reaction.
The problems associated with childhood vaccines are also being reflected in the United States as has been reported on the JABS web pages and on US sites.
11. JAPANESE EXPERIENCE AND COMPENSATION:
The MMR vaccine was introduced into the Japanese health programme in April 1989. Shortly after its introduction Japanese parents started to complain to the authorities that their children were suffering severe neurological damage. The Japanese Government failed to act. Many parents started to reject the MMR vaccination for their children and the Japanese Government continued to ignore public concern. Outbreaks of measles then occurred and, unfortunately, it was the most vulnerable group in society, babies under twelve months of age and too young to receive a measles vaccine, that were hit hardest and 69 deaths were recorded.
The Japanese Government banned the MMR vaccine in 1993 and introduced a policy of separate measles and rubella vaccines. (The single Urabe mumps vaccine would not have been accepted as it had been held responsible for the neurological damage when combined in the Japanese MMR vaccine.) The Japanese MMR court cases were heard in March 2003. Over 1,000 children were awarded MMR damages against the Japanese Government and the Research Foundation for Microbial Diseases at Osaka University in Suita, Osaka Prefecture. The decsion went to an appeal in April 2006 and was upheld.
12. MMR AND AUTISM:
The statement that the health secretary, John Reid, made on GMTV in November 03: "It is unequivocal that there is no evidence at all that MMR is linked to autism." needs to be challenged. World experts in the field of virology and pathology have replicated results found by Dr Wakefield's team when he was at the Royal Free Hospital, London and other independent Japanese scientists have also duplicated the findings. (Ref. 1 below)
Children who have developed autism, epilepsy and other neurological conditions were progressing normally before they were vaccinated, had passed all milestones and had acquired skills appropriate to their age.
- They did not simply fail to progress; they actually regressed, losing skills which they had already attained. In many instances this is borne out by videos taken of the children before and after they were vaccinated.
- They showed other physical changes at the time that they became autistic (such as sleep patterns, appetite changes, temperature control etc. in addition to many of them suffering bowel problems).
- The development of autism and other conditions are closely linked in time to the administration of the vaccine. The onset of this condition generally started within about a month of vaccination whenever the vaccination took place. In other words, it would be later for children vaccinated at 18 months than those vaccinated at 12 months. On top of that, a substantial proportion of the children had an immediate reaction to the vaccination, and the change which came over them dates directly from that reaction.
13. MMR LEGAL CASES:
Unfortunately, the UK MMR victims had their legal aid stopped just six months before the cases were to be heard at the High Court in April 2004. In some cases legal aid had been provided for nearly ten years to children with wide ranging health problems including autism, epilepsy, loss of speech and communication skills, chronic arthritis and deafness.
Each family had to personally apply to try and prevent their child's legal aid certificate from being discharged. In the interest of justice, these children deserved to have the issue of MMR safety resolved in court and for this reason families needed the help of legal aid.
Many parents believe that the withdrawal of legal aid prior to the court cases being heard was another way to delay or prevent access to justice for vaccine damaged children. The families' representatives were able to present to the legal aid appeal committee (the Funding Review Committee) evidence not only that measles virus had been found in cerebro spinal fluid (CSF) taken from three out of six of the test cases, but also that it had not been found in 19 out of 20 controls. If the measles virus is in the CSF then it must almost certainly be in the brain. Bearing in mind: that these children, like all autistic children, suffer from a form of brain damage, that measles is known to be able to cause brain damage and that no other cause of autism has been suggested for the overwhelming majority of the families involved.
Added to the stress of this situation, one of the MMR drug companies had sent some parents a letter offering not to seek costs against the child or them if they signed an undertaking "not to issue any further proceedings arising out of vaccination with MMR against them in this or any other jurisdiction''.
The MMR court cases were and still are vital not only to the families involved in the pursuit of justice for their children, but for all parents who are concerned about whether the vaccines they are giving their healthy children are safe. JABS believes the Government can no longer claim that MMR is the "safest way to protect your child" as they have denied the parents an opportunity to have all the information out in the open and heard properly. Until the evidence is formally presented in court the question mark over the issue remains.
At present (October 2007) two sets of parents have had MMR legal aid certificates re-instated for their children.
14. SINGLE VACCINES:
The Government’s Chief Medical Officer needs to reconsider the availability of single dose vaccines as a matter of choice. If there is a potential for measles epidemics they must provide a real choice for those parents who have lost confidence in the combined MMR but still want to vaccinate against the separate illnesses. It should not have to be an MMR or nothing situation.
It does not require new legislation it just needs the Department of Health to place orders with the drug companies currently supplying the UK market with the MMR vaccines.
When the MMR vaccine was introduced into the childhood vaccination schedule the doctors' Green Book, 'Immunisation against Infectious Disease' clearly stated: ‘MMR vaccine will replace measles vaccine in the second year of life, or after this age if appointments have been missed. For children whose parents refuse MMR vaccine, single antigen measles vaccine will be available.’ (Page 60, 10.2 Recommendations) Reference to this choice appeared in the 1988, 1992 and 1996 editions of this book.
This choice has been removed for no good reason other than to protect the pharmaceutical industries vaccine patents. The single doses have no real profit margin, new money comes from new combination vaccines.
15. CONFLICT OF INTEREST:
The DoH and the pharmaceutical companies have become too closely linked. The protection of vaccination policy and the promotion of new vaccines has become the main objective of the DoH to the extent of almost denying the existence of vaccine damaged children.
Adverse events/serious health problems get covered up to ensure that the prevailing system remains. The DoH does not want to sow any seeds of doubt which might deter new parents from being drawn into the system. Serious vaccine side effects are dismissed point blank.
Health professionals are protected by the Government's 'guidelines' and can press forward with the DoH vaccine policy by fair means or foul, by coaxing, cajoling, intimidating and bullying, all these methods have been reported by new parents to our help line.
If a child has an adverse reaction and is damaged by a vaccine, health professionals and the DoH usually deny any responsibility leaving parents on their own with a damaged child. Until the DoH and medical profession accept responsibility for vaccine damaged children parents have every right to question, research and demand choice on vaccines.
16. COCHRANE REVIEW:
A study by the respected Cochrane Library (October 2005) has said, on the basis of 31 pieces of research into the possible side effects of MMR, that it found no association between MMR, autism, Crohn's disease and long-term disability.
The Department of Health has hailed it as another 'final nail' in the MMR controversy but there is another side to this that they have missed.
Since the MMR vaccine was introduced in 1988 many parents have complained publicly that they believe their children have been seriously damaged by MMR vaccine. Each time the Department of Health have cited many reports as being conclusive proof that the vaccine is both safe and effective. It is important to note that the authors of the Cochrane Review have scrutinised 5,000 related studies and in this context found the majority lacking. Only 31 of the 5,000 studies were thought to "possibly fulfill their inclusion criteria".
The Cochrane Review is a significant piece of work because it actually exposes all the 5,000 related studies as being inadequate in some way, as all fail to find any link with long-term disability for which compensation has been paid or acknowledged by the vaccine manufacturers in their own product sheets.
Of course the MMR vaccine is responsible for long-term disability in some children. All drug products have the potential to cause both minor and serious adverse reactions, one has only to read the manufacturers' product information sheets to be aware of this.
Vaccine damage, and in this case, MMR vaccine damage has been recognised by Governments, three examples are:
1. The US Government has a National Vaccine Injury Compensation Programme and 14% of all claims have been paid out to children damaged by MMR vaccination.
2. The Japanese authorities have paid out substantial compensation to parents of MMR vaccine damaged children after a successful court case in March 2004. (There is an on-going UK case.)
3. The UK Government has a Vaccine Damage Payment Unit which has paid out hundreds of thousands of pounds to children affected by childhood vaccines including MMR vaccine.
Many children who suffer adverse reactions are individually assessed by Government doctors panels. These panels determine the reported adverse event and association with vaccination (known to the manufacturers) and make recommendation for compensation for the individual. The criteria used is extremely high and compensation awards are not made lightly.
For the medical authorities now to conclude that this review gives the MMR vaccine a clean bill of health does a great injustice to all those children who have been awarded vaccine damage payments by ignoring their existence. It will also bolster those that sustain the failed passive vaccine reaction surveillance system which continues to ensure very few reactions are put forward or recorded in medical data. It is this poor data that was used in many of the reports reviewed by Cochrane which they identified as inadequate. Therefore a continued cycle of failure by the medical authorities to identify and reduce vaccine adverse events in children will be assured.
For the Department of Health to continue trying to convince parents, many of whom have family and friends with children believed to have been affected by MMR vaccine, exposes them to being blind to the reality.
17. WORLD HEALTH ORGANISATION (WHO) – CAUSALITY OF ADVERSE EVENTS:
“Since the inception of vaccination, it has been recognized that adverse events following immunization (AEFIs) will occur.” (Ref. 2 below)
The WHO gives criteria to be considered when an adverse event is reported:
i. Consistency.
The association of a purported adverse event with the administration of a vaccine should be consistent, i.e. the findings should be replicable in different localities, by different investigators not unduly influencing one another, and by different methods of investigation, all leading to the same conclusion(s).
As already mentioned problems following MMR vaccination have been reported and accepted in Japan and the United States. A report from Finland described the immunization of 1.8 million individuals and gave rise to 173 potentially serious reactions claimed to have been caused by MMR vaccination. In all, 77 neurologic, 73 allergic and 22 miscellaneous reactions and 1 death were reported. (Ref. 3) Furthermore most of these cases were not followed up for more than a few weeks. And this Finnish study “did not examine the relationship of MMR and autistic spectrum disorders.....and does not therefore provide useful evidence on this point." Medical Research Council December 2001.
ii. Strength of the association.
The association should be strong in the magnitude of the association (in an epidemiological sense), and in the dose-response relationship of the vaccine with the adverse effect.
JABS has been contacted by thousands of families who believe their children have suffered severe damage or have died following the MMR/MR vaccination. In the main, doctors cannot give any other medical explanation for the child’s deterioration or death. It must be remembered that many of the children have been given the now withdrawn Urabe containing MMR vaccines which were known to cause inflammation of the brain. Furthermore, many of JABS children shared the same batches of MMR vaccine and subsequently suffered the same long term effects.iii.
Specificity.
The association should be distinctive and the adverse event should be linked uniquely or specifically with the vaccine concerned, rather than its occurring frequently, spontaneously or commonly in association with other external stimuli or conditions.
The three viruses, measles, mumps and rubella, are known to be linked with the children’s conditions in their wild state. The vaccines contain the live viruses.
iv. Temporal relation.
There should be a clear temporal relationship between the vaccine and the adverse event, in that receipt of the vaccine should precede the earliest manifestation of the event or a clear exacerbation of an ongoing condition. For example, an anaphylactic reaction seconds or minutes following immunization would be strongly suggestive of causality; such a reaction several weeks after vaccination would be less plausible evidence of a causal relation.
A substantial proportion of the children had an immediate reaction to the vaccination, and the change which came over them dates directly from that reaction.
v. Biological plausibility.
The association should be coherent; that is, plausible and explicable biologically according to known facts in the natural history and biology of the disease.
The viruses are known to be linked with the health problems when caught as the wild diseases. The vaccine manufacturers’ acknowledge this by recording these problems as the ‘rare’ adverse events associated with their products. Many of the children have had a variety of medical tests and examinations to rule out other causes.
The WHO continues with:
a. The requirement for biological plausibility should not unduly influence negatively a consideration of causality. Biological plausibility is a less robust criterion than the others described. If an adverse event does not fit into known facts and the preconceived understanding of the adverse event or the vaccine under consideration, it clearly does not necessarily follow that new or hitherto unexpected events are improbable. Biological plausibility is most helpful when it is positive; it is less so when negative.
This is an important statement as it makes it quite clear that just because something has not been recognized as linked with the vaccine in the past doesn’t mean it isn’t linked. This supports our concern that with the failure of the post-vaccination adverse event surveillance system to collect data on unexpected reactions and therefore a failure to investigate them could be allowing a serious problem to go undetected.
This could lead to a catch 22 system; because the problem hasn’t been linked with MMR vaccine before, further reports of the same problem are not put forward because they are not known to be linked with the MMR vaccine.
b. Consideration of whether the vaccine is serving as a trigger (trigger in this context is an agent that causes an event to happen which would have happened some time later anyway). When acting as a trigger, the vaccine may expose an underlying or pre-existing condition or illness. An example of the latter would be an auto-immune condition triggered non-specifically by the immune stimulus of the vaccine.
This is an interesting point. Many of the parents report that their child’s health problems are not known in the family’s medical history but they have been told by their medical practitioner that the vaccine acted as a trigger to reveal the underlying condition.
What is particularly worrying is that the child usually has more than one, supposedly, rare condition that started at the same time e.g. autism and bowel problems, epilepsy and loss of speech and communication and a failure to move on mentally from the point of vaccination. Some children developed health problems when vaccinated at four years of age or ten years of age or sixteen years of age after many years of good health and development progress.
c. In the case of live attenuated vaccines, if the adverse event may be attributable to the pathogenicity of the attenuated vaccine microorganism and thus not be distinguishable (except, perhaps, in severity) from the disease against which the vaccine is being administered, a causal connection is more plausible. Identification of the vaccine organism in diseased tissue and/or in the body fluids of the patient in such a situation would add weight to causality. There are exceptions to both these above points.
Measles virus has been found in the spinal fluid - and therefore the brain - in three of the six children at the centre of the huge UK high court battle over the safety of the vaccine. It has also been found in 18 children in the United States who developed autism after receiving MMR.
18. FINANCIAL COST:
Letter submitted to the Lancet (Spring 2004) by David Thrower
Sir,
AUTISM
As one of the parents who, through enforced circumstance, has become involved in the controversy surrounding the causes and consequences of autism, I wish to respond to your commentary (1).
As you imply, the 2002 UK autism research funding of $2.75m was lamentably inadequate, and should be set against the very considerable economic costs of autism. It has previously been estimated that just one severe case of autism will cost the community up to £3m over that person’s lifetime. The degree of severity and consequent precise costings could be debated at length. Costs include special needs education, home-to-school taxiing, escorts, daily respite care, overnight respite breaks, transport, health care, attendance and disability allowances, carer’s allowance, and loss of tax revenues from the parent who has to cease work to become the child’s carer. From age 16, you can add-on independent living fund payments and incapacity benefit. From age 19, schooling costs cease, but most of the other costs continue for life, and you also have to add in the lost tax revenue from the autistic person. In these circumstances, the estimate of £3m for the costs of a severe case of autism may well be an underestimate. But let us stay with £3m, for the sake of simplicity. So the 2002 autism research grant, for the UK, was actually less than the lifetime cost of just one severe case of autism.
And then you can try to estimate the numbers of UK cases. The recent unsuccessful UK High Court action alone involved 1,300 families. There have been many attempts at trying to gauge the numbers of UK autism cases. But hard State-collected data from the US Individuals With Disabilities Education Act database points to there being 120,000 children and young people ages 6-21 in full time education in the US with a primary diagnosis of autism, so a pro-rata application of those figures to the UK would give around 35,000 cases in the UK within that age-band. Obviously, not all cases are severe, but a reasonable estimate would be that an assumed 35,000 cases would cost the taxpayer somewhere between £35 billion and £100 billion over the next seven decades, or between £500m and £1.4 billion per annum. This, of course, excludes any future cases that enter the autistic population over that time, plus the present existing small numbers of autistic adults. If autistic children continue to emerge at the rate now being recorded across the US, then the UK taxpayer could be facing an immense autism bill of several billion pounds per annum, within a couple of decades.
On those terms, even your sought-after £12.5m for autism research therefore seems grossly inadequate to research a condition that is clearly already creating an economic burden, and one that seems set to increase. And these future autism costs will apply wholly irrespective of the current controversy about autism’s actual detailed causes. The children already exist now, today, for whatever reason. The economic stakes over seeking autism’s causes are therefore extremely high.
I would also strongly support the efforts of Dr. Tom Jefferson in bringing adverse event surveillance out of the nineteenth century and into the twenty-first (2). But I would ask, how genuinely keen is our Department of Health, and government departments in other countries, to actively seek out every potential case of vaccine damage, and to analyse the data proactively? There seems to have been a marked lack of enthusiasm to date. The Medicines & Healthcare Products Regulatory Agency’s existing Yellow Card system has been admitted by its predecessor, the Medicines Control Agency, to record only 10%-15% of even serious adverse events, yet the Agency seems quite content to live with that. In other areas of life, it is very difficult to imagine (say) the Vehicle Inspectorate being content with such a poor system for vehicle inspections, so why is medicine’s Yellow Card scheme’s inadequacy tolerated so readily? Perhaps the Agency lacks the determination that parents of damaged children have to investigate adverse outcomes.
Finally, as you rightly point out, “the discovery of a possible link between bowel disease and autism is a serious scientific idea......and one that deserves further investigation.” The original Royal Free team paper was in February 1998. It is now Spring 2004. It is the continued abject failure to fund clinical research in this area, based upon the detailed examination of regressive-autism cases, that is the least acceptable aspect of the autism controversy, and I would welcome some candid explanation from the relevant authority, the Medical Research Council, as to what it has - or has not - been doing over the past six years.
Yours faithfully,
David Thrower
49, Ackers Road, Stockton Heath, Warrington, Cheshire WA4 2DZ 01925 264156
References
(1) Commentary, The Lessons of MMR, Lancet, 2004, 363
(2) Jefferson T, Price D, Demicheli V et al. Unintended events following immunisation with MMR: a systematic review. Vaccine 2003; 21: 3954-60 (PubMed)
19. SUMMARY:
In our opinion the current Government has failed in its duty of care. At the meeting in 1997 the Health Minister should have instigated a scientific study of the children believed to have been damaged to discover why the children's lives changed so dramatically within such a short time of MMR/MR vaccine being given. Since that meeting the reports of MMR/MR damaged children to JABS has greatly increased.
The issue of safety surrounding the MMR vaccine has not yet been resolved. The Department of Health has relied on epidemiological studies as its basis for stating the vaccine is safe. These studies are not designed to collect data on ‘rare’ events.
The Department of Health has failed to adopt the precautionary principle. Until the question of MMR safety is resolved the option of single dose vaccines should be made available for parents who have lost confidence in the combined vaccine.
A question that must be asked of the present Health Minister is: if the drug companies have informed the Department of Health's doctors of the known vaccine problems and parents have informed the doctors that these problems are occurring. Why is the Department of Health denying the problems and ignoring the parents?
It could be argued that the vaccine manufacturers have a duty to provide compensation, as they have to in the United States by contributing to the US National Vaccine Injury Programme. The pharmaceutical industry profits from the supply of vaccines to the UK and also, ironically, from the victims because they produce the anti-convulsants, pain killers and other medical products these children need. At the moment however, in the UK, they do not contribute financially in any way to the vaccine damage payment scheme.
The UK Vaccine Damage Payment Act 1979 has gone some way to address the issue. Unfortunately, because the criteria are so strict most families cannot access justice for their children through this Government scheme and therefore it is relatively ineffective. Until a compensation programme similar to the US scheme is implemented in the UK, parents will seek redress through the courts and for this reason families need the support of legal aid to pursue justice. Legal aid should be re-instated.
Critics of the JABS group must think of this: If our members had been anti-vaccine lobbyists our children would not have been taken for vaccines and subsequently damaged. We are parents who put our faith in the UK healthcare system; our children have reacted usually in the time frame known to the manufacturer and, in the main, are living with long term problems also known to the manufacturer. We want the children to be recognised and compensated and clinically investigated to help develop a screening programme to improve vaccine safety.
JABS believes in a safe vaccination programme but the emphasis is on safe and reducing risk wherever possible.
20. ACKNOWLEDGEMENTS:
We are extremely grateful to:-
David Thrower for his input
Parents who submitted the JABS questionnaire.
21. REFERENCES:
Ref. 1:
MMR and Acquired Autism (Autistic Enterocolitis) - A Briefing Note by David Thrower March 2006
http://www.jabs.org.uk/pages/Autism_Review.pdf
Relevant Extracts:
93. Paper by Uhlmann, Sheils et al, Measles Virus In Reactive Lympho-Nodular Hyperplasia and Ileo-Colitis of Children, (publication date not known), Department of Pathology, Coombe Womens' Hospital, Dublin, Trinity College Dublin and Royal Free Hospital London.
This paper noted that measles virus nucleoprotein (N antigen) had been detected in association with follicular dendritic cells (FDC) in patients, and sought molecular confirmation of this result. It found that:
* Solution phase RT PCR yielded specific MV N gene amplification in affected children (10/10)
* Distinct measles virus genome was identified in FDC reactive follicular centres by in-cell RNA amplification
* None of the normal controls showed any evidence of measles virus genome
* The data highlighted a possible causal link between measles virus infection and ileo-colonic lymphoid nodular hyperplasia in affected children
96. Paper Presented to US Congressional Oversight Committee on Autism and Immunisation, Professor John O'Leary, Dublin Womens Hospital, April 2000
This paper reported a study using biopsy material from children examined at the Royal Free in London. Dr. Wakefield at the Royal Free had posed three questions to the O'Leary team,
(1) was measles virus present in gut biopsies of affected children?
(2) where was measles virus located in the gut biopsies of the affected children?
(3) how much virus was present?
* The O'Leary team used in-situ hybridisation (with/without tyramide signal amplification), in-cell PCR, solution-phase PCR, TaqMan quantitative PCR and DNA sequencing to determine the answers to these questions.
* Using TaqMan PCR the team was able to quantify the measles virus copy number per 1,000 mucosal cells using gene dosage correction formulations. The copy number of measles virus in gut biopsies from children with autistic enterocolitis was low, at approx. 30-50 measles virus genomes per 2,000 mucosal cells (inc. Gut, epithelial, lymphoid and dendritic cells).
* Confirmation of the presence of measles virus genomes was achieved using positive and negative strand sequencing of cDNA measles amplicons.
* The results were that 24 out of 25 (96%) of the autistic children were positive for measles virus, including 2 children from the USA who were included in this analysis
* In the controls, only 1 of the 15 children (6.6%) was positive for measles virus.
* The study therefore localised, quantified and sequenced measles virus genomes in gut biopsies of children with autistic enterocolitis. The study team then posed the question, "how did it get there?".
97. Paper by Kawashima, Takayuki et al, Detection and Sequencing of Measles Virus from Peripheral Mononuclear Cells from Patients with Inflammatory Bowel Disease and Autism, Digestive Diseases & Sciences Vol. 45, No. 4, April 2000, pp723-729
Following reports that measles virus might be present in the intestines of children with Crohn's Disease, a new syndrome was reported in children with autism who exhibited developmental regression and gastrointestinal symptoms (autistic enterocolitis), in some cases after MMR vaccine, was reported (see papers by Wakefield et al). It was not known whether the virus, if confirmed as present in these patients, derived from wild strain or vaccine strain.
This study carried out the detection of measles genomic RNA in peripheral mononuclear cells (PBMC) in 8 patients with CD, 3 patients with UC and 9 patients with autistic enterocolitis. As controls, the study used 8 cases of either healthy children or children with SSPE, SLE or HIV-1. The results were:
* 1/8 patients with CD, 1/3 with UC and 3/9 with autism were positive. Controls were all negative
*The sequences from patients with CD shared the characteristics with wild-strain virus.
*Sequences from patients with UC and children with autism were consistent with vaccine strain measles.
*These results were consistent with the exposure history of the patient.
This study is obviously particularly important because it points to infection with vaccine-strain measles virus
Detection of Measles Virus Genomic RNA in Cerebrospinal Fluid of Children with Regressive Autism: a Report of Three Children J.J. Bradstreet, M.D., J. El Dahr, MD, A. Anthony M.B., PhD, J.J. Kartzinel, M.D., A.J. Wakefield, M.B.
Ref. 2:
http://www.who.int/vaccine_safety/causality/en/
World Health Organisation
Causality assessment of adverse events following immunization
Since the inception of vaccination, it has been recognized that adverse events following immunization (AEFIs) will occur. The frequency of AEFIs is directly related to the number of vaccine doses administered. AEFIs can be causally related to the inherent properties of the vaccine, linked to errors in the administration, quality, storage and transport of the vaccine (programmatic errors), but it must be recognized that when large populations are vaccinated, some serious events that occur rarely with or without vaccination will be observed coincidentally following vaccination. Thus, investigating causality of AEFIs, particularly those that are most serious, is challenging.
The clearest and most reliable way to determine whether an adverse event is causally related to vaccination is by comparing rates of the event in a vaccinated and non-vaccinated group in a randomized clinical trial. Such trials, however, can never be large enough to assess very rare events, and postmarketing surveillance systems are required to identify events potentially related to vaccination. Postmarketing surveillance capability is improving; more countries now have AEFI monitoring systems, and more importance is attached to the reporting of suspected links between vaccination and adverse events. These systems have been successful in bringing to light serious AEFIs after vaccines have been marketed. A recent example is intussusception after administration of reassortant rhesus rotavirus vaccine.
Assessments of whether a given vaccine causes a particular adverse reaction vary from the casual observation to the carefully controlled study. The majority of individuals are not trained in interpreting such studies and are unlikely to understand the enormous difference in significance between these two extremes. Nonetheless, the public frequently forms a decision about a vaccineís safety based on the information available to them ñ often a report based on unscientific observations or analyses that fail to stand the scrutiny of rigorous scientific investigation. Certain reports of AEFIs published in the medical literature over the past few years have resulted in controversy. The studies on which these reports are based, while generating provocative hypotheses, have generally not fulfilled the criteria that would be needed to be able to draw conclusions about vaccine safety with any degree of certainty. Yet these reports have had a major influence on public debate and opinion-making. When this debate spills over to the political arena, to policy-making and to determining the public acceptance of a vaccine by balancing the known benefits against possible but unverified risks, it is clear that a correct assessment of causality is vital.
Submitting a study to a scientific process rather than to partially informed opinion is crucial in determining whether a vaccine actually causes a given reaction. If undertaken carelessly or without scientific rigour, the study results will be inconclusive at best, may result in the inappropriate withdrawal of a valuable vaccine from use, or at worst may result in the exposure of a population to a dangerous vaccine. In 1999, WHO launched the Immunization Safety Priority Project to establish a comprehensive system to ensure the safety of all immunizations given in national immunization programmes. The development of mechanisms to respond promptly and effectively to vaccine safety concerns is a major area of focus of this project. As part of this effort, the Global Advisory Committee on Vaccine Safety (GACVS) was constituted by WHO in September 1999. The Committee's mandate is to enable WHO to respond promptly, efficiently and with scientific rigour to vaccine safety issues of potential global importance.
- Consistency. The association of a purported adverse event with the administration of a vaccine should be consistent, i.e. the findings should be replicable in different localities, by different investigators not unduly influencing one another, and by different methods of investigation, all leading to the same conclusion(s).
- Strength of the association. The association should be strong in the magnitude of the association (in an epidemiological sense), and in the dose-response relationship of the vaccine with the adverse effect.
- Specificity. The association should be distinctive ñ the adverse event should be linked uniquely or specifically with the vaccine concerned, rather than its occurring frequently, spontaneously or commonly in association with other external stimuli or conditions.
- Temporal relation. There should be a clear temporal relationship between the vaccine and the adverse event, in that receipt of the vaccine should precede the earliest manifestation of the event or a clear exacerbation of an ongoing condition. For example, an anaphylactic reaction seconds or minutes following immunization would be strongly suggestive of causality; such a reaction several weeks after vaccination would be less plausible evidence of a causal relation.
- Biological plausibility. The association should be coherent; that is, plausible and explicable biologically according to known facts in the natural history and biology of the disease.
Building on the seminal work on determining causality of the Surgeon Generalís Advisory Committee on Smoking and Health (1964),3 the generally established criteria underpinning vaccine adverse event causality assessment that the GACVS uses may be summarized as follows:
- The requirement for biological plausibility should not unduly influence negatively a consideration of causality. Biological plausibility is a less robust criterion than the others described. If an adverse event does not fit into known facts and the preconceived understanding of the adverse event or the vaccine under consideration, it clearly does not necessarily follow that new or hitherto unexpected events are improbable. Biological plausibility is most helpful when it is positive; it is less so when negative.
- Consideration of whether the vaccine is serving as a trigger (trigger in this context is an agent that causes an event to happen which would have happened some time later anyway). When acting as a trigger, the vaccine may expose an underlying or pre-existing condition or illness. An example of the latter would be an auto-immune condition triggered non-specifically by the immune stimulus of the vaccine.
- In the case of live attenuated vaccines, if the adverse event may be attributable to the pathogenicity of the attenuated vaccine microorganism and thus not be distinguishable (except, perhaps, in severity) from the disease against which the vaccine is being administered, a causal connection is more plausible. Identification of the vaccine organism in diseased tissue and/or in the body fluids of the patient in such a situation would add weight to causality. There are exceptions to both these above points.
Clearly, not all these criteria need to be present, and neither does each carry equal weight for a causal relationship between an adverse event and the vaccine to be determined. In addition to the general principles mentioned above, there are a number of provisos or considerations that need to be applied for determining causality in the special field of vaccine safety. They are:
- Well-conducted human studies that demonstrate a clear association in a study design that is determined a priori for testing the hypothesis of such association. Such studies will normally be one of the following, in descending order of probability of achieving the objective of the study: randomized controlled clinical trials, cohort studies, and casecontrol studies and controlled case-series analyses. Case reports, however numerous and complete, do not fulfil the requirements for testing hypotheses, although on occasion such reports can be compelling if there are clear biological markers of the association, as is the case for vaccine-associated paralytic poliomyelitis.
- An association that is demonstrated in more than one human study and consistent among the studies. The studies would need to have been well conducted, by different investigators, in different populations, with results that are consistent, despite different study designs. Demonstrable association in the studies between dose and the purported adverse effect (either the dose or the number of doses administered, or both) will, in many cases, strengthen the causal association between the vaccine and the adverse event. This is not always the case, especially if there is an immunological relationship.
- A strong similarity of the adverse event to the infection the vaccine is intended to prevent, and there is a non-random temporal relationship between administration and the adverse incident.
An association between vaccine administration and an adverse event is most likely to be considered strong when the evidence is based on:
It is important that there should be a strict definition of the adverse event in clinical, pathological and biochemical terms, as far as that is achievable. The frequency in the nonimmunized population of the adverse event should be substantially different from that in the immunized population in which the event is described, and there would not normally be obvious alternative reasons for its occurrence that are unrelated to immunization.
An adverse event may be caused by a vaccine adjuvant or excipient, rather than by the active component of the vaccine. In this case, it might spuriously influence the specificity of the association between vaccine and adverse event. As far as possible, safety issues should be clarified in premarketing controlled clinical studies, with attention being given in such studies to safety issues and their monitoring, although with extremely rare unexpected events, this may not be achievable because of the need for extremely large sample sizes to detect them.
When adverse events are attributable to a vaccine, it is important to determine whether there is a predisposed set of subjects (by age, population, genetic, immunological, environmental, ethnic, sociological or underlying disease conditions) for any particular reaction. Such predisposition is most likely to be identified in case-controlled studies.
A systematic effort should always be made to exclude confounding programmatic errors and variability and aberrations in vaccine manufacture. The latter quality issues are most likely to be revealed by careful attention to batch and lot testing.
Since observational studies are not randomized and since individuals who are ill are generally less likely to be immunized (but more likely to have an adverse outcome), epidemiological studies on vaccine safety need to pay special attention to contraindications as potentially confounding factors. The consequences of this bias may be false-negative studies.
Ref. 3:
Serious adverse events after measles-mumps-rubella vaccination during a 14 year prospective follow up. Pediatr Infec. Dis J. 2000;19:1127_34 Annamari Patja,MD, Irja Davidkin, MSC, Phd, Tapio Kurki,MD, Phd, Markku J T Kallio, MD, Martti Valle, MD, Phd and Heikki Peltola, MD, Phd
Briefing note compiled by JABS, 1 GAWSWORTH ROAD, GOLBORNE, WARRINGTON,CHESHIRE, WA3 3RF