The ICDRC Perspective the Epidemic of Autism Spectrum Disorders A view from the trenches
Executive Briefing – June 4, 2002 For Claude A. Allen, Deputy Secretary of Health and Human Services
Introduction:
Autism is clearly not any single entity, nor does it have simplistic genetic or epidemiological characteristics. Rather, it represents a rather broad spectrum of clinical disorders which share behavioral and delayed-development features. Autism and its related entities are characterized by: delayed neurodevelopment, lack or inappropriate use of language, stereotypical repetitive behaviors, and social withdrawal. The various clinicians and researchers associated or affiliated with ICDRC have been involved in treating and/or describing this disorder from its biological roots, as opposed to the genetic and psychiatric perspectives. We have medically evaluated and treated over 1500 children with autism related disorders. Therefore, the insights we have contribute primarily to an understanding of the immunology and toxicology of this condition.
Prevalence:
Various studies provide data that there are greater numbers of children with autism than previous suspected. Recently, the Congressional Reform Committee, held hearings where there was broad consensus that autism spectrum disorders (ASD), now represent an epidemic of neurodevelopmental problems for our youth. Various recent studies place the prevalence at 57 to 67/10,000 children (Scott 2002, Bertrand 2001), although older literature places the prevalence at 10/10,000 (1/1,000). However, this deceptively under estimates the problem for males. Boys suffer from autism at a four to 10 fold greater frequency than girls. So the actual problem for the male offspring in this country is more accurately represented as 100/10,000 (or greater). The 1997 US Census of disability reported 2.4% of children ages five and under suffer from developmental delays – clearly many of these are ASD related issues. Data from California further reveals the rate of growth in ASD is doubling every four years.
US Census Bureau Population, 2001 estimate 284,796,887 Persons under 5 years old, percent, 2000 6.8% Persons under 18 years old, percent, 2000 25.7%
If the current epidemiology of autism is correct, then it will affect approximately 1% of boys under 18, or an estimated 364,540, and a further approximately 60,000 girls would be affected. This is considerably less than the one million figure reported in the recent Time Magazine cover story, but probably far more accurate.
Economic Impact:
While no precise studies have attempted to look at the cost of correcting the biological problems associated with ASD, at least on report from England places the custodial costs of ASD in the range of $3-4 million per child per lifetime, with a societal cost that would likely be three times the individual cost.
Autism 2001 Mar;5(1):7-22 The economic impact of autism in Britain. Jarbrink K, Knapp M. Institute of Psychiatry, London, UK.
Little is known about the economic impact of autism. This study estimated the economic consequences of autism in the United Kingdom, based on published evidence and on the reanalysis of data holdings at the Centre for the Economics of Mental Health (CEMH). With an assumed prevalence of 5 per 10,000 (a gross underestimate), the annual societal cost for the UK was estimated to exceed l1 billion (likely 110 billion). The lifetime cost for a person with autism exceeded £2.4 million. The main costs were for living support and day activities. Family costs account for only 2.3 percent of the total cost, but a lack of relevant information limited our ability to estimate these costs. Minor improvements in life outcome for people with autism could substantially reduce costs over the lifetime.
The cost of education, medical care, and therapies for behavioral and physical symptoms is staggering. Many of our families report having paid $50,000 per year to care for their child. IDEA allows up to $35,000/year for education of children with autism. So much of this burden is already being carried by the Federal and State programs which provide for disabled children. Custodial care for autism can exceed $100,000/year. The public education system is literally swamped with children. Any survey of public educators will quickly reveal the suddenness and magnitude of the ASD problem. They lack the therapists and trained special educators to deal with the problem, so children with severe disorders receive nominal meaningful intervention. The further loss of potential earnings form the ASD children who will likely not be self-supporting are impossibly large to calculate meaningfully. Many parents must quit working to care for the child as well. We, as a nation, are therefore paying and will continue to pay an enormous price for this epidemic.
ICDRC estimates the minimal cost in present value, to care for those 420,000 existing children with autism is $1,260,000,000,000 (based on $3million/lifetime and 420,000 children affected). So a little over a $1 trillion in the next 50 years would be required if we stopped creating new cases today. Because autism is doubling every four years, this is likely an overly conservative estimate. The societal cost could easily be $3-4 trillion.
Biological Evidence of Causality:
The data will show there is sufficient cause for concern and abundant published findings that the causal relationship of MMR to ASD does not represent a narrow view held by radical or renegade physicians. Rather it is sound peer-reviewed science acceptable to one of the best child neurologists and numerous immunologists. The data does need to be evaluated in its entirety, rather than critiqued bit by bit as it has been. The implications of these findings have incredible potential impact on public health policy making and the future acceptance of voluntary vaccines by parents for their children. We desire to see safer vaccines and safer administration of vaccines, but we fear a lack of government response to the concerns of researchers and parents will result in lowered overall immunity to numerous preventable disorders, because parents will reject some of the vaccines in their current forms.
The data are also public knowledge and have been presented at numerous professional and public forums, as well as through publication in mainstream medical literature, eg Pediatrics, The Journal of Pediatric, The British Medical Journal – Molecular Pathology, The American Journal of Gastroenterology, and recently in a press release from the American Society of Microbiology. Historically, high titer measles vaccine caused more mortality than expected due to induction of immune deficiency (Halsey 1993). This caused a reversal of policy and high titer MV vaccines no longer exist. The nature of mass vaccination programs are in effect an ongoing open-label experiment. No study can predict the long-term and subtle effects of a vaccine adequately prior to introduction to a group as large as 2/3 of the population of the planet.
Unfortunately, and as true of many new discoveries in medicine, the initial reactions are that of skepticism or rejection. We have seen this historically with H.pylori and peptic ulcer disease, as well as during the emerging literature on AIDS and HIV. Eventually, the early observations in these disorders were proven accurate, medicine adapted and acceptance became universal. We believe the same is true for this literature which will be summarized below, despite the present political incorrectness of the findings.
While the Institute of Medicine has determined thimerosal, a mercury containing preservative used in vaccines, is biologically capable of causing many of the associated symptoms of autism, they felt there was insufficient evidence of direct causality. This is because no specific studies had been undertaken to explore the potential link. We feel that thimerosal is more destructive as an immune modifier than as a direct neurotoxin – where neurotoxicity was the primary mode of injury they explored. This makes their analysis less helpful. Further, attorneys for the plaintiffs in the thimerosal litigation have received data through discovery, which Sid Baker MD, a highly respected pediatrician and past Chairman of Pediatrics at Yale, believes demonstrate nothing less than a CDC cover-up. This data was withheld from the public and the IOM (see below for a graph of the relative risk of autism with thimerosal containing vaccines).
The IOM has also taken on the issue of multiple vaccines and their compromising of the immune system in children. Unfortunately, the approach taken by the committee is to look at mercury, measles and multiple vaccines as separate issues – while in the child affected with autism they are all happening simultaneously. Despite this they did find serious flaws in the presumption of immune safety for the vaccine policy as it stands. They believe immune disorders and autoimmunity are risks of vaccines and we believe autism is one such autoimmune disorder. Here is an excerpt of their recent report:
“With the government and professional recommendations calling for young children to receive increasing numbers of immunizations, it is important to respond to public concerns about possible increases in allergic or autoimmune diseases. Öthe review is inconclusive for asthma, the biological evidence does provide weak support for increased risk of allergy and autoimmunity and strong support for increased risk of infection.” Page 80.
The IOM has also entertained the possibility of an MMR vaccine-autism association. They did not feel the biological plausibility had been demonstrated, but they did state if evidence of the so-called “double-hit” phenomena were present, that would be compelling. The IOM had that data presented to them in closed session, but only mentioned the study in the revised version of their report, while suppressing it in their testimony before the House Reform Committee. The double-hit refers to children who regressed significantly after each of two MMR vaccines. That data has now been accepted for publishing. But a significant critique of the IOM report is what it failed to address. There were no references to a large body of immunological published studies which supported the MMR hypothesis. In fact, the IOM misrepresents the immunological literature severely.
From the IOM-MMR report: ìAutoimmune Etiology. Immune-mediated injury can be induced by a viral infection. One mechanism for such injury can be seen in the production of a cross-reactive autoimmune response to self antigens by activated T-cells and B-cells (ter Meulen and Liebert, 1993). Measles virus is known to cause post-infectious encephalitis when T-cells directed against myelin basic protein enter the CNS through loss of integrity of brain microvascular endothelial cells (Johnson, 1987; Liebert, 1997). However, no cases of vaccine-strain measles virus have been isolated in immunocompetent individuals with encephalitis (IOM, 1994a). Induction of autoimmunity due to cross-reactive immunity to self-antigens as an explanation for MMR-induced ASD or enterocolitis is unsupported because of the absence of characteristic markers for immune injury or inflammation.î
This last sentence was a clearly false statement. Singh, Connolly, Hollander and Jynouchi have independently found inflammatory and autoimmune markers in ASD. With regard to the viral isolates comment, that too is no longer true – we have isolated the F-genome from the CSF of 8 of 8 children with encephalopathy and ASD. Simultaneously we see antibodies to myelin basic protein – a requirement of the IOM for determining causality (Singh & Bradstreet 2002).
The epidemiology (relied so heavily upon by the IOM and detractors to our findings), is complex, weak in methodological construct, and inadequate to explain away the biological findings we will summarize here.
With respect to children with ASD, measles virus genome has now been detected in the blood in 3 of 9 tested cases (33%), gastrointestinal tract in 75 of 91 children with ASD (82%) and cerebral spinal fluid “CSF” in 8 of 8 children tested (100%) of children who regressed following the MMR vaccine. Data for controls demonstrate a very low occurrence of MV in the gut and even lower in the blood. We are still collecting spinal fluid for controls. Gene sequencing reveals the strain being detected is vaccine, not natural virus, in origin. Immunological studies reveal the persistence of antibodies to measles virus in the CSF of children with ASD where it is not present in controls. These same children have antibodies to myelin basic protein, a critical component of the nerve cells in the brain and peripheral nervous system. Other researchers have found activation of Tumor Necrosis Factor-alpha (TNF-alpha) in autism. This is a powerful indicator of chronic inflammation and is consistent with the reported findings of inflammatory bowel disease in autism. Other researchers have found antibodies to brain and brain blood vessels in autism. While not specific to MV, this virus has a well documented predilection for reproducing in the linings of blood vessels.
A variety of other immune disorders have been published with respect to children with autism. This represents dysfunctions which may either arise from the measles virus (which has known immune dysregulating properties) or more likely predispose to the persistence of the measles virus. Persistent viral infections are associated with sulfur and cysteine depletion, resulting in a wide array of physiological disruptions. Sulfur and cysteine deficiency has been published as occurring in 85% of children with ASD. This is consistent with the previously mentioned findings. Loss of cysteine would disrupt the body’s defenses to heavy metals and you would accumulation of background environmental toxins. It would also down-regulate the immune system. This was reported to the IOM by Dr. Bradstreet in July of 2001. Essentially children with ASD have a 500% greater total body burden of mercury than their neurologically normal peers. When compared to adults on a body mass adjusted basis and when toxic burden is accounted for – children with ASD have 2000% of the adult toxic burden of mercury. Some of that mercury is vaccine related, but much is related to accumulation of mercury from the previously mentioned defect in sulfur metabolism. The immunology group of Imani at Johns Hopkins recently reported that MMR vaccine was a likely cause of the induction of asthma and allergies. They too called for safer vaccines. Autism has a significantly increased association with allergies and autoimmune disorders. The consequence of allergy and asthma on the population, apart form ASD, represents a further financial and health burden for this nation. One of the Country’s leading pediatric neurologists, John Menkes, MD, Professor Emeritus and editor of the textbook Child Neurology, has reviewed the record and laboratory findings for an archtypical child with ASD. The child presented with all of these findings we have mentioned, including the persistence of MV genome. Dr Menkes provided a statement of causality for the Federal Court of Claims in a case brought by the family claiming MMR caused their child’s encephalopathy and ASD. It was his opinion that the MMR vaccine did indeed cause the ASD-encephalopathy in that child, and he refers to it as an atypical form of subacute sclerosis panencephalitis or atypical-SSPE.
Summary:
With the available data, we see sufficient cause to believe MMR, likely influenced by other vaccine constituents and diverse environmental factors, is the ultimate wounding event leading to the development of an encephalopathy with autistic characteristics. In part, we suspect the injection of live viruses, as opposed to natural route introduction, provides the virus an opportunity to find those preferred sites for replication (brain and lymphoid tissue in the gut).
Recommendations:
Certainly, we desire replication of our data and further exploration of the findings, but given the high stakes of hundred’s of thousands of children with ASD and the rate of expansion of this disorder, we believe it is time to rapidly explore contingency plans for introducing alternative vaccine schedules and alternative delivery systems. Predicate work in this area has already been accomplished and the Sabine Center at Georgetown University has a nasal measles vaccine that has been extensively tested in Mexico. The nation cannot afford to allow the expansion of autism to continue. The government needs to explore the possibility (we would say probability) that the ICDRC view of ASD is at least largely correct. Given the personal, societal and economic magnitude of the crisis and relative state of emergency regarding ASD, we recommend the following:
The establishment & funding of an Autism Taskforce under the direction of HHS, independent of CDC, FDA and NIH. The taskforce would integrate private and public efforts and provide an independent review of these agencies with regard to their activities in ASD. The taskforce would report directly to the Director/Deputy Director HHS. The taskforce should consist of parents and professionals knowledgeable with the current findings and issues. Dissident views need to be accounted for and considered as well. However, the current group of experts the government had trusted, have missed the problem and often are attempting to cover-up the findings. It should also provide a means for the executive to coordinate efforts and expenditures between the Department of Education and the various HHS directorates responsible for the multiple aspects of ASD. The taskforce would go a long way to encourage parents, educators and clinicians that this vital issue was getting high level attention. Further, since this is a disorder of unparalleled importance to our youth, the Executive Branch of government must knowledgeably address the crisis. Define ASD as a biological entity so parents could access insurance benefits where many or most are denied benefits at the present time. Fast track authorization for the Nasal Measles Vaccine developed by Dr Bellanti at Georgetown. It would be irresponsible to not provide a safer alternative for measles. Require unbundling of the MMR – at the very least as an option for parents. Provide informed consent of the most recent literature and adequate addressing of the controversy. Requirement to provide high dose Vitamin A (supported by a vast amount of WHO policy and other publications) with measles vaccines. Funding of the research initiatives recommended by the IOM in its recent reviews of MMR, Thimerosal and Multiple Vaccinations. To this end HHS could be a great help in its funding requests in future budgets. Recall of all thimerosal containing vaccines, and the banning of thimerosal as a preservative in human injectables (strangely it is already banned in topicals). Funding research into the cost effectiveness of various treatment modalities in use for autism today, including traditional and alternative approaches. Since governments (Federal and State) are presently paying billions of dollars for ASD education and medical treatment – a cost analysis is appropriate. Legal initiatives: Since Merck is the primary supplier of MMR to the United States, we would like to explore a way to resolve potential liability issues Merck will soon be facing in civil court. To that end we feel the government should investigate a means of allowing Merck to assist in funding the various activities we have presented in exchange for legislative considerations. Alternatively or concurrently, since numerous vaccine manufacturers used thimerosal as a preservative and since the levels of mercury in thimerosal have exceeded federal guidelines, those entities could also be asked to contribute to the research and initiatives discussed – again in exchange for legislative consideration. We also recommend the Justice Department reform the management of vaccine injury claims by creating a non-adversarial program. This program must give parents fair standing. Presently, the government has nearly unlimited funds to hire attorneys and experts to fight parents of children with serious problems. The parents must pay for their experts and attorneys, or find someone willing to wait until the case is settled perhaps years or even decades in the future. The current system is so unwieldy that parents are opting to take their claims to civil court. The legislative consideration would be revisions of the existing and proposed NVICP, increasing the reserves of the NVICP trust fund through increased fees on the vaccines to manage future contingencies (as mentioned), removing the processing of claims from the Justice Department, and streamline of the payment of claims to reduce the need for parents to find answers in civil court.
Respectfully Submitted,
James Jeffrey Bradstreet, MD, FAAFP Director of Clinical Programs ICDRC
Cell: 321-403-4308
Conflict of Interest Disclosure: Neither I, nor anyone affiliated directly with ICDRC receive money from the government for research or support, no one with ICDRC receives outside compensation for any research performed, and we receive no funding from any pharmaceutical company. We have no interest in the production of any vaccine or pharmaceutical.