Vaccines and Autism


Vaccines and autism: remember the politics

The vaccines were exceptionally good in preventing disease, but they were supposed to cause the production of immunity for very long periods.  MMR vaccination was expected to work until the death of the person in old age…but this was unsure.   The problem with this is that it cannot be known and safety is difficult to know for such a long period.   MMR and the other vaccines appeared to be working well and safely until 1998.

 

The possibility of the association of MMR and autism came forward generally because the parents had reported their offspring becoming autistic after an illness associated with the vaccine.  No good statistics were available on this.   The new report of GI inflammation suggested that the researchers should look in the gut wall for evidence of the vaccine.  This created extreme pressure on Public Health groups throughout the world and political worry in that stopping vaccination (from parental anxiety) might create greater problems.   It would be a good idea to look at a specific article about morbillivirus infections in humans.

Vaccines

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The shot in the dark for many parents, who felt that the potential risk of autism to their child was unacceptable.  This led to a fall in vaccination in large parts of the West.

 

 

MMR and autism. 

Evidence came out quickly showing that it was possible to stain morbillovirus (measles type) in the gut wall but this was an exceptionally difficult process and hence successful attempts were made to carry out PCR to look for the RNA of the virus.  This would be expected to much more specific and unlikely to show false positives.  Measles antibodies were found to be high in autism and cross reacting with brain tissue as an autoantibody.  Attempts to look for morbillovirus RNA in the blood was also successful in comparison with other conditions, however this could not be found in one study.   The measles vaccine in MMR is a changed form genetically but it is alive and would be expected to cause an infection and inflammation.  It is expected to be retained in the body as parts of its RNA and hence a single vaccine may well be effective against the rest of the vaccine recipient’s lifespan.   Measles is widely different from other morbillovirus (e.g. distemper in dogs) and so measles vaccine if it is given to the entire population would be expected to cause remove it from the world.   

 

First article associating autism in symptomatic patients with gut inflammation:

Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, Berelowitz M, Dhillon AP, Thomson MA, Harvey P, Valentine A, Davies SE, Walker-Smith JA. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 1998 Feb 28;351(9103):637-41.  They found this in all 12 of the cases of autism with chronic gut problems.  (this was the article following which it was suggested that measles might be involved)

 

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Measles antibodies

Increased in MMR vaccinated autistic children when compared with controls.

 

Singh VK, Jensen RL.Elevated levels of measles antibodies in children with autism. Pediatr Neurol. 2003 Apr;28(4):292-4. This antibody specifically detected a protein of 73-75 kD of MMR. This was antibody mmunopositive for measles hemagglutinin (HA) protein but not for measles nucleoprotein and rubella or mumps viral proteins. Furthermore, over 90% of MMR antibody-positive autistic sera were also positive for MBP autoantibodies, suggesting a strong association between MMR and CNS autoimmunity in autism. . The level of measles antibody, but not mumps or rubella antibodies, was significantly higher in autistic children as compared with normal children (P = 0.003) or siblings of autistic children (P <or= 0.0001). Furthermore, immunoblotting of measles vaccine virus revealed that the antibody was directed against a protein of approximately 74 kd molecular weight. The antibody to this antigen was found in 83% of autistic children but not in normal children or siblings of autistic children.We suggest an inappropriate antibody response to MMR, specifically the measles component, might be related to pathogenesis of autism.  (good science)

 

Singh VK, Lin SX, Yang VC. Serological association of measles virus and human herpesvirus-6 with brain autoantibodies in autism. Clin Immunol Immunopathol. 1998 Oct;89(1):105-8. (i) 90% of measles-IgG-positive autistic sera were also positive for anti-Myelin Basic Protein; (ii) 73% of measles-IgG-positive autistic sera was also positive for anti-Neuro Axonal Filiament Protein; (iii) 84% of HHV-6-IgG-positive autistic sera was also positive for anti-MBP; and (iv) 72% of HHV-6-IgG-positive autistic sera was also positive for anti-NAFP.

 

Singh VK, Lin SX, Newell E, Nelson C. Abnormal measles-mumps-rubella antibodies and CNS autoimmunity in children with autism. J Biomed Sci. 2002 Jul-Aug;9(4):359-64.  (a serological study of measles-mumps-rubella (MMR) and MBP autoantibodies using serum samples of 125 autistic children and 92 control children, antibodies were assayed. Immunoblotting analysis revealed the presence of an unusual MMR antibody in 75 of 125 (60%) autistic sera but not in control sera. This antibody specifically detected a protein of 73-75 kD of MMR. This protein band, as analyzed with monoclonal antibodies, was immunopositive for measles hemagglutinin (HA) protein but not for measles nucleoprotein and rubella or mumps viral proteins.)

 

Vijendra K. Singh, Ph.D. Autism, Vaccines, and Immune Reactions. IOM presentation, Feb 9, 2004.  Audio only: http://www.iom.edu/view.asp?id=19132

 

Baird G, Pickles A, Simonoff E, Charman T, Sullivan P, Chandler S, Loucas T, Meldrum D, Afzal M, Thomas B, Jin L, Brown D. Measles vaccination and antibody response in autism spectrum disorders. Arch Dis Child. 2008 Feb 5.  (They have found no differential antibody response to the MMR in autistics and non-autistics)

 

Libbey JE, Coon HH, Kirkman NJ, Sweeten TL, Miller JN, Lainhart JE, McMahon WM, Fujinami RS. Are there altered antibody responses to measles, mumps, or rubella viruses in autism? J Neurovirol. 2007 Jun;13(3):252-9.  (The authors investigated antibody titers to measles, mumps, and rubella viruses and diphtheria toxoid in children with autism, both classic onset.  No significant differences in antibody titers to measles, mumps, and rubella viruses and diphtheria toxoid were found among the autistic groups and controls)

 

 

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PCR testing for Morbillovirus RNA

 

Uhlmann V, Martin CM, Sheils O, Pilkington L, Silva I, Killalea A, Murch SB, Walker-Smith J, Thomson M, Wakefield AJ, O'Leary JJ. Potential viral pathogenic mechanism for new variant inflammatory bowel disease. Mol Pathol. 2002 Apr;55(2):84-90.  (shows that a large proportion of ASD colonic biopsies had measles virus RNA present in the wall and this was not true for controls)

 

Walker SJ, Hepner K, Segal J, Krigsman.  A persistent ileal measles virus in a large cohort of regressive autistic children with ileocolitis and lymphonodular hyperplasia revisitation of an earlier study.  IMFAR.  They replicate Wakefield’s work from 1998/2002 showing measles RNA to be present in the gut wall of autistic kids with colitis but Professor Walker warns that it is not possible to make the jump to say that one causes the other.

 

Kawashima H, Mori T, Kashiwagi Y, Takekuma K, Hoshika A, Wakefield A. Detection and sequencing of measles virus from peripheral mononuclear cells from patients with inflammatory bowel disease and autism. Dig Dis Sci. 2000 Apr;45(4):723-9.  (clearly this and the next article disagree, which is difficult with the methods that they use, unless the inflammatory bowel condition is involved with the measles vaccine.  Probably this would suggest that the work was checked by both groups) (They used a nested reverse transcriptase PCR technique and also looked in the blood of patients with Crohn’s disease and ulcerative colitis as well as controls and autistic patients.  3 of 9 patients with ASD were positive and none of the controls.  Genetically they were shown to be MMR vaccine strains)

 

Afzal MA, Ozoemena LC, O'Hare A, Kidger KA, Bentley ML, Minor PD. Absence of detectable measles virus genome sequence in blood of autistic children who have had their MMR vaccination during the routine childhood immunization schedule of UK. J Med Virol. 2006 May;78(5):623-30.  (This was the opposive of found by a Japanese group in 1999).  **

 

D'Souza Y, Fombonne E, Ward BJ. No evidence of persisting measles virus in peripheral blood mononuclear cells from children with autism spectrum disorder. Pediatrics. 2006 Oct;118(4):1664-75. Erratum in: Pediatrics. 2006 Dec;118(6):2608.  (They used a nested reverse transcriptase PCR technique and in any possible positives they checked the finding and found that the gene that they had shown was not one of measles).  **

 

Bradstreet JJ, El-Dahr JM, Anthony A, Kartzinel JJ, Wakefield AJ.  Detection of measles virus genomic RNA in cerebrospinal fluid of children with regressive autism:  a report of three cases.  J Am Phys Surg  2004;9:38-45.  http://www.jpands.org/vol9no2/bradstreet.pdf  Three children underwent CSF assessment all had GI symptoms and had had measles RNA in the gut.  It was found in the CSF of all three, and in none of the controls.

 

Rima BK, Duprex WP. Molecular mechanisms of measles virus persistence. Virus Res. 2005 Aug;111(2):132-47. (this shows in what format the genome of measles virus is retained in cells in the body and how this would lead to long term immunity)

 

Rima BK, Duprex WP. Morbilliviruses and human disease. J Pathol. 2006 Jan;208(2):199-214. Review

 

 

 

**It is very difficult to state that PCR-positive results are wrong.  The result by Kawashima et al may well have found the results to be positive and the ones by Afzal et al and D’Souza et al say the opposite but an explanation must be found for this rather than an argument as to which group was right.  By rights at this point the second two may well be considered to be technically wrong (because it is such a difficult technique), but the it basically means that much more work is required. 

Global measles elimination

 

Diagram 1.   Demonstration of the way in which the live measles vaccine virus enters the cell and is produced by it to infect a further cell.  See Nature Reviews

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


Reviews and Discussions in the literature of MMR being associated with autism

 

Kennedy RC, Byers VS, Marchalonis JJ. Measles virus infection and vaccination: potential role in chronic illness and associated adverse events. Crit Rev Immunol. 2004;24(2):129-56. Review.  Tries to discuss an indication that autism is associated with vaccine.

 

Madsen KM, Vestergaard M. MMR vaccination and autism : what is the evidence for a causal association? Drug Saf. 2004;27(12):831-40. Review.  “The hypothesis has been subjected to critical evaluation in many different ways, using techniques from molecular biology to population-based epidemiology, and with a vast number of independent researchers involved, none of which has been able to corroborate the hypothesis” but note that it is from Drug Safety, a journal.

 

Wakefield AJ. Enterocolitis, autism and measles virus. Mol Psychiatry. 2002;7 Suppl 2:S44-6. Review.

 

Wakefield AJ, Montgomery SM. Autism, viral infection and measles-mumps-rubella vaccination. Isr Med Assoc J. 1999 Nov;1(3):183-7. Review.

O'Leary JJ et al. Measles virus and autism. Lancet. 2000 Aug 26;356(9231):772.  (explains the finding of the measles type virus RNA in the wall of the gut of the children with autism)

 

Quigley EM, Hurley D. Autism and the gastrointestinal tract. Am J Gastroenterol. 2000 Sep;95(9):2154-6.

 

Landrigan PJ, Witte JJ. Neurologic disorders following live measles-virus vaccination. JAMA. 1973 Mar 26;223(13):1459-62.

 

Glismann S. Danish Supreme Court rules that child with autism developed in temporal relation with MMR vaccination is not entitled to

compensation. Euro Surveill. 2005 Apr 28;10(4):E050428.3.  (it was taken that legally this could not be shown to be the cause)

 

Lett D. Vaccine autism link discounted, but effect of "study" is unknown. CMAJ. 2007 Oct 9;177(8):841.

 

Bradstreet JJ, Dahr J El, Anthony A, Kartzinel J, Wakefield AJ, Detection of meascles virus genomic RNA in Cerebrospinal fluid of children with regressive autism: a report of three cases.  J Am Physicians and Surgeons 2004;9:38-45.  (They looked for the measles virus genome RNA in the CSF of  3 of 3 autistic cases, only 2 of 3 had antibodies to measles in the CSF to measles.  They suggest that this indicates a possibility of a virally driven cerebral immunopathology in some cases of regressive autism.  None of the controls had the positive test for measles RNA)

 

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Consideration of the presence of Thimerosal (and hence mercury) in MMR and autism

It is clear that the use of thimerosal has been used for many years but the huge increase in vaccination that has taken place and the symptomatic children gave researchers the thought that it may be this that was associated with autism.  There is clearly good evidence of the drug being toxic (and this is not surprising) but because of its breakdown and excretion in a particular way will cause a low amount of mercury to be present in the body for a reasonably long time.  There is argument about the epidemiological association of thimerosal usage and autism but the Danish work makes this seem unlikely.  Geier’s work looking into the presence of mercury for long periods and potential toxicity cannot be ignored.

 

Geier DA, Geier MR. A comparative evaluation of the effects of MMR immunization and mercury doses from thimerosal-containing childhood vaccines on the population prevalence of autism. Med Sci Monit. 2004 Mar;10(3):PI33-9.  (showing that the vaccine seemed to be associated with autism but could not be shown to be the cause).

 

Geier DA, Geier MR. An evaluation of the effects of thimerosal on neurodevelopmental disorders reported following DTP and Hib vaccines in comparison to DTPH vaccine in the United States. J Toxicol Environ Health A. 2006 Aug;69(15):1481-95.  (They say that they found a significantly increased odds ratios for autism, speech disorders, mental retardation, infantile spasms, and thinking abnormalities reported to VAERS were found following DTP vaccines in comparison to DTPH vaccines with minimal bias or systematic error.)

 

Baskin DS, Ngo H, Didenko VV. Thimerosal induces DNA breaks, caspase-3 activation, membrane damage, and cell death in cultured human neurons and fibroblasts.   Toxicol Sci. 2003 Aug;74(2):361-8. Epub 2003 May 28.  This merely shows that at specific levels thimerosal can be found to be toxic but the levels found in the  body after an MMR injection should not be high enough to cause some of the factors mentioned in the article.

 

Goth SR, Chu RA, Gregg JP, Cherednichenko G, Pessah IN. Uncoupling of ATP-mediated calcium signaling and dysregulated interleukin-6 secretion in dendritic cells by nanomolar thimerosal. Environ   Health Perspect. 2006 Jul;114(7):1083-91 (in fact nanomolar levels are reasonable for a compound that is being injected in millimolar levels into 10 litres of body.  As such, although thimerosal does have a known pharmacokinetics, this type of toxicity may be significant)

 

Havarinasab S, Hultman P. Organic mercury compounds and autoimmunity. Autoimmun Rev. 2005 Jun;4(5):270-5. Epub 2005 Jan 5 Recent studies have confirmed that organic mercurials such as methyl mercury (MeHg) and ethyl mercury (EtHg) are much more potent immunosuppressors than inorganic mercury (Hg).  They tried to demonstrate this with further compounds.  Havarinasab has done further work on immunosuppression and organic mercury.

 

Blaxill MF, Redwood L, Bernard S. Thimerosal and autism? A plausible hypothesis that should not be dismissed.  Med Hypotheses. 2004;62(5):788-94. (this simply suggests that the mechanism of toxicity of mercury could be involved).

 

James SJ, Slikker W 3rd, Melnyk S, New E, Pogribna M, Jernigan S.  Thimerosal neurotoxicity is associated with glutathione depletion: protection with glutathione precursors.   Neurotoxicology. 2005 Jan;26(1):1-8.  (Thimerosol is an antiseptic containing 49.5% ethyl mercury that has been used for years as a preservative in many infant vaccines and in flu vaccines. Environmental methyl mercury has been shown to be highly neurotoxic, especially to the developing brain. Because mercury has a high affinity for thiol (sulfhydryl (-SH)) groups, the thiol-containing antioxidant, glutathione (GSH), provides the major intracellular defense against mercury-induced neurotoxicity. Cultured neuroblastoma cells were found to have lower levels of GSH and increased sensitivity to thimerosol toxicity compared to glioblastoma cells that have higher basal levels of intracellular GSH.  This is well explained but its action is in vitro at this time)

 

Kaur P, Aschner M, Syversen T.  Glutathione modulation influences methyl mercury induced neurotoxicity in primary cell cultures of neurons and astrocytes. Neurotoxicology. 2006 Jul;27(4):492-500. Epub 2006 Mar 2 (Investigated the role of glutathione (GSH) and reactive oxygen species (ROS) in MeHg-induced neurotoxicity, using primary cell cultures of cerebellar neurons and astrocytes. The intracellular GSH content was modified by pretreatment with N-acetyl cysteine (NAC) or di-ethyl maleate (DEM) for 12 h. Treatment with 5 microM MeHg for 30 min led to significant (p<0.05) increase in ROS and reduction (p<0.001) in GSH content.)

 

Wu X, Liang H, O'Hara KA, Yalowich JC, Hasinoff BB.  Thiol-modulated mechanisms of the cytotoxicity of thimerosal and inhibition of DNA topoisomerase II alpha. Chem Res Toxicol. 2008 Feb;21(2):483-93. Epub 2008 Jan 16.  (Thimerosal-induced single and double strand breaks in K562 cells were consistent with a rapid induction of apoptosis)

 

Madsen KM, Lauritsen MB, Pedersen CB, Thorsen P, Plesner AM, Andersen PH, Mortensen PB. Thimerosal and the occurrence of autism: negative ecological evidence from Danish population-based data. Pediatrics. 2003 Sep;112(3 Pt 1):604-6. (The discontinuation of thimerosal-containing vaccines in Denmark in 1992 was followed by an increase in the incidence of autism.  They showed that the statistics would not hold the thimerosal to be the cause).

Magos L. Neurotoxic character of thimerosal and the allometric extrapolation of adult clearance half-time to infants.

J Appl Toxicol. 2003 Jul-Aug;23(4):263-9. Review  (The decomposition rate of organomercurials and the potency of the blood-brain barrier increase with the size of the organic radical. Thus methylmercury damages the brain more than thimerosal does, and when intake limits set for methylmercury are applied to thimerosal the safety margin is increased even if the clearances were the same. However, the clearance half-time of ethylmercury in adults is about one-third of the 50 days' clearance half-time of methylmercury given for 60 kg body weight. Moreover, because metabolic rates (e.g. basal metabolism, daily loss of mercury in per cent of body burden) in different weight groups are related to the fractional power of body weight (rule of allometry), mercury clears from the infant body faster than from the adult body. Blood mercury concentrations observed after vaccination showed agreement with allometrically extrapolated concentrations. This is a very useful article in that it goes through the pharmacokinetics of thimerosal and its breakdown products)  see also: Magos L.  Review on the toxicity of ethylmercury, including its presence as a preservative in biological and pharmaceutical products.  J Appl Toxicol. 2001 Jan-Feb;21(1):1-5. Review. 

 

Pichichero ME, Gentile A, Giglio N, Umido V, Clarkson T, Cernichiari E, Zareba G, Gotelli C, Gotelli M, Yan L, Treanor J. Mercury levels in newborns and infants after receipt of thimerosal-containing vaccines.   Pediatrics. 2008 Feb;121(2):e208-14 (unlike the findings of Magos, above, they found a relatively slow halflife: the blood half-life of intramuscular ethyl mercury from thimerosal in vaccines in infants is substantially shorter than that of oral methyl mercury in adults. This also is a useful article that goes through pharmacokinetics. )

 

Stajich GV, Lopez GP, Harry SW, Sexson WR Iatrogenic exposure to mercury after hepatitis B vaccination in preterm infants. J Pediatr. 2000 May;136(5):679-81. (Comparison of pre- and post-vaccination mercury levels showed a significant increase in both preterm and term infants after vaccination. Additionally, post-vaccination mercury levels were significantly higher in preterm infants as compared with term infants.)

 

Ueha-Ishibashi T, Oyama Y, Nakao H, Umebayashi C, Nishizaki Y, Tatsuishi T, Iwase K, Murao K, Seo H. Effect of thimerosal, a preservative in vaccines, on intracellular Ca2+ concentration of rat cerebellar neurons. Toxicology. 2004 Jan 15;195(1):77-84. (in vitro demonstration of relatively high concentrations of thimerosal on neurones)

Ueha-Ishibashi T, Tatsuishi T, Iwase K, Nakao H, Umebayashi C, Nishizaki Y, Nishimura Y, Oyama Y, Hirama S, Okano Y. Property of thimerosal-induced decrease in cellular content of glutathione in rat thymocytes: a flow cytometric study with 5-chloromethylfluorescein diacetate. Toxicol In Vitro. 2004 Oct;18(5):563-9. (similar to the gut endothelial work in vitro, these cells also show a decrease in glutathione presumably because of –SH and interactions with mercury).

 

Verstraeten T, Davis RL, DeStefano F, Lieu TA, Rhodes PH, Black SB, Shinefield H, Chen RT; Vaccine Safety Datalink Team. Safety of thimerosal-containing vaccines: a two-phased study of computerized health maintenance organization databases. Pediatrics. 2003 Nov;112(5):1039-48. Erratum in: Pediatrics. 2004 Jan;113(1):184. (No consistent significant associations were found between thiomersal containing vaccines and neurodevelopmental outcomes.)

 

Andrews N, Miller E, Grant A, Stowe J, Osborne V, Taylor B. Thimerosal exposure in infants and developmental disorders: a retrospective cohort study in the United kingdom does not support a causal association.  Pediatrics. 2004 Sep;114(3):584-91 (they could not show any association between autism and the use of thimerosal)

 

Westphal GA, Asgari S, Schulz TG, Bünger J, Müller M, Hallier E. Thimerosal induces micronuclei in the cytochalasin B block micronucleus test with human lymphocytes. Arch Toxicol. 2003 Jan;77(1):50-5. Epub 2002 Nov 6.

 

See Fombonne et al below

 

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MMR withdrawal and Autism in Japan  (also see the work from Denmark under Thimerosal)

This is the best evidence that MMR does not cause the increase in autism cases that has been seen over the past 15 years. 

 

Honda H, Shimizu Y, Rutter M.  No effect of MMR withdrawal on the incidence of autism: a total population study. J Child Psychol Psychiatry. 2005 Jun;46(6):572-9. (this is one of the most effective pieces of evidence that MMR was not involved in the increase in autism seen in the 1990s).

 

Chen W, Landau S, Sham P, Fombonne E. No evidence for links between autism, MMR and measles virus. Psychol Med. 2004 Apr;34(3):543-53. No increased risk of AD following exposures to wild measles and vaccinations with monovalent measles, and Urabe or Jeryl-Lynn variants of MMR was detected. (This seems to have been agreed to some degree since the results from Japan.  However, without this, the data from the UK, the USA etc are difficult to demonstrate as well as the various Governments would like to see).

 

Takahashi H, Suzumura S, Shirakizawa F, Wada N, Tanaka-Taya K, Arai S, Okabe N, Ichikawa H, Sato T. An epidemiological study on Japanese autism concerning routine childhood immunization history. Jpn J Infect Dis. 2003 Jun;56(3):114-7 (the Japanese had problems with their MMR vaccination early in the 1990s partly due to aseptic meningitis.  They decided to bring back the MMR much later.  What they could see from the results was that the cases of autism rose with no interaction with MMR usage)

 

Sugiyama T, Abe T. The prevalence of autism in Nagoya, Japan: a total population study. J Autism Dev Disord. 1989 Mar;19(1):87-96.

 

 

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Other vaccines

 

See large amounts or argument concerning the involvement of thimerosal

 

Fombonne E, Zakarian R, Bennett A, Meng L, McLean-Heywood D. Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations. Pediatrics. 2006 Jul;118(1):e139-50 “The prevalence of pervasive developmental disorder in Montreal was high, increasing in recent birth cohorts as found in most countries. Factors accounting for the increase include a broadening of diagnostic concepts and criteria, increased awareness and, therefore, better identification of children with pervasive developmental disorders in communities and epidemiologic surveys, and improved access to services. The findings ruled out an association between pervasive developmental disorder and either high levels of ethylmercury exposure comparable with those experienced in the United States in the 1990s or 1- or 2-dose measles-mumps-rubella vaccinations.”  They also showed that the number of cases rose dramatically but, although they guessed that awareness was the reason, this could not be demonstrated. The slight decrease in thiomersal exposure and MMR injections were not enough to demonstrate their involvement.  NB Fombonne an epidemiologist had been brought into this field much earlier (1998) saying MMR not being involved long before this could be certain and that there had been no increase in the disease at all (and hence he disagrees with many other researchers).

 

Jick H, Kaye JA. Autism and DPT vaccination in the United Kingdom. N Engl J Med. 2004 Jun 24;350(26):2722-3.

 

Rümke HC, Visser HK. Childhood vaccinations anno 2004. II. The real and presumed side effects of vaccination  Ned Tijdschr Geneeskd. 2004 Feb 21;148(8):364-71. (in Dutch)

 

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Has the Incidence of autism increased anyway?

Overall it does seem that the incidence and prevalence has increased but the reason for this is still unclear according to many of the epidemiologists.  Some seem to have changed their mind during the period of argument (e.g. Fombonne) but this is not under great argument at this point.

 

Yes it has

a.      Bertrand J, Mars A, Boyle C, Bove F, Yeargin-Allsopp M, Decoufle P. Prevalence of autism in a United States population: the Brick Township, New Jersey, investigation. Pediatrics. 2001 Nov;108(5):1155-61.  (The study used 4 sources for active case finding: special education records, records from local clinicians providing diagnosis or treatment for developmental or behavioral disabilities, lists of children from community parent groups, and families who volunteered for participation in the study in response to media attention. The autism diagnosis was verified (or ruled out) for 71% of the children through clinical assessment.  They found the numbers to be marginally higher in the Brick Townships and to agree with the rising number figures as shown by other studies.

b.      Chakrabarti S, Fombonne E. Pervasive developmental disorders in preschool children: confirmation of high prevalence. Am J Psychiatry. 2005 Jun;162(6):1133-41. (Higher than 15 yrs ago but relatively stable currently)

c.      Baird G, Simonoff E, Pickles A, Chandler S, Loucas T, Meldrum D, Charman T. Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP). Lancet. 2006 Jul 15;368(9531):210-5. (Substantially greater than previously recognised.  They then discuss as to the reason why this might have been and include possibilities of diagnostic changes).

d.      Jick H, Beach KJ, Kaye JA. Incidence of autism over time. Epidemiology. 2006 Jan;17(1):120-1. 

e.      Jick H, Kaye JA. Epidemiology and possible causes of autism. Pharmacotherapy. 2003 Dec;23(12):1524-30. Erratum in: Pharmacotherapy. 2004;24(4):following table of contents.  (Goes over the reports and indicates the increases since the early 1980s)

f.        Lauritsen MB, Pedersen CB, Mortensen PB. The incidence and prevalence of pervasive developmental disorders: a Danish population-based study. Psychol Med. 2004 Oct;34(7):1339-46.  (although the numbers were increasing throughout the 1990s, it was not clear that this was due to an increase in the prevalence of the disease and not just a diagnostic change)

g.      Powell JE, Edwards A, Edwards M, Pandit BS, Sungum-Paliwal SR, Whitehouse W. Changes in the incidence of childhood autism and other autistic spectrum disorders in preschool children from two areas of the West Midlands, UK. Dev Med Child Neurol. 2000 Sep;42(9):624-8. (Children diagnosed before the age of 5 years and residing within the study areas at diagnosis were detected from the records of four child development centres. The incidence rate per 10,000 children per year for the combined areas was 8.3 for all children with ASDs, 3.5 for classical childhood autism (CA), and 4.8 for other ASDs. Rates were similar in both areas, despite differences in social deprivation and proportions of ethnic minorities. While rates for classical CA increased by 18% per year, a much larger increase (55% per year) was seen for 'other ASDs', suggesting that clinicians are becoming increasingly able)  They clearly attempted to avoid problems of clinicians and the tendency to diagnose more than they should.

h.      Fombonne E, Zakarian R, Bennett A, Meng L, McLean-Heywood D. Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations. Pediatrics. 2006 Jul;118(1):e139-50 (The prevalence of pervasive developmental disorder in Montreal was high, increasing in recent birth cohorts as found in most countries. Factors accounting for the increase include a broadening of diagnostic concepts and criteria, increased awareness and, therefore, better identification of children with pervasive developmental disorders in communities and epidemiologic surveys, and improved access to services.) 

 

No it probably has not

i.        Coo H, Ouellette-Kuntz H, Lloyd JE, Kasmara L, Holden JJ, Lewis ME. Trends in Autism Prevalence: Diagnostic Substitution Revisited. J Autism Dev Disord. 2007 Nov 2.  (They did a retrospective survey and showed that of the very large increase in diagnostic cases that appeared in British Columbia between 1996 and 2007, about half could be put to the change of the child’s school or education category.  They realised that this was difficult to be certain of and could not explain the rest of the increase).

j.        Croen LA, Grether JK, Hoogstrate J, Selvin S. The changing prevalence of autism in California. J Autism Dev Disord. 2002 Jun;32(3):207-15. (They feel that the increase in autism may well just be a change in the diagnosis of other mental retardation diagnosis)

 


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