Vaccine Safety

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Vaccine Safety
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Vaccine Safety

• FUD Fear, uncertainty, doubt
• The antivaccine movement is based upon FUD
• Supposed connection between vaccines and autisms
• In 1991, two new vaccines containing thimerosal,
  an organic mercury-based preservative, were added
  to the childhood immunization list
• In 1992, the incidence of ASD began to rise
• This correlation led to some assuming a causal
  relationship between vaccines and ASD
• The result of this movement has been
• Increased incidence of vaccine-preventable
  disease
• Deaths of children

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Autism Spectrum Disorders (ASD)

• A family of pervasive developmental disorders
  (PDD) that range from mild to severe in phenotype
• Typically is first noticed by parents when
  children are 2 or 3 years of age
• This is also when routine vaccinations are
  administered
• Incidence
• Prior to 1990 in the United States, the incidence
  of autisms was 1 in several hundred
• Currently, the incidence is about 1 in 60 children

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A Genetic Basis To ASD

• A clear genetic linkage is associated with some,
  and perhaps all, ASDs
• Autisms occur in 3.5 boys for every girl
• At least 16 loci have been implicated, including
  X chromosome loci
• Strongly implies a multigenic trait
• There may be environmental factors involved
• The biological bases of ASDs are largely unknown
• No animal model (complex behavioral disorder)

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Engrailed Homeobox 2
One Example EN2 (alias - AUTS1)
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Functions of EN2

• A transcription factor
• It can be transported between cells in culture by
  unconventional secretion and internalization
  mechanisms
• EN-2 had been considered to be an important
  transcriptional factor during embryonic
  development
• It controls synaptic formation and axon
  projections
• Some relationships between EN-2 and Parkinson's
  disease.
• Two polymorphisms in this gene occur in some
  Chinese children with ASD

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The Wakefield Paper

• Wakefield et al. Ileal-lymphoid-nodular
  hyperplasia, non-specific colitis and pervasive
  developmental disorder. Lancet. 1998. 351637-41.
• Paper asserted that attenuated measles virus in
  MMR vaccine was associated with autism
• Half of the 12 children in the study had
  exhibited symptoms of autism prior to vaccination
• Wakefield was a paid consultant for Legal Aid
  Board, a British legal fund representing parents
  of children suing the vaccines maker over
  alleged injuries
• Wakefield was working on a measles vaccine
  himself
• Paper was retracted in 2004 by 10 of the 13
  authors (one could not be located, and Wakefield
  and another refused the retraction)
• This paper and Wakefields subsequent public
  campaign dramatically affected vaccination rates
  in Great Britain
• As of 2008, measles is endemic in Great Britain
  again

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The FUD of Thimerosal

• All claims of thimerosals in vivo toxicity are
  based upon other forms of mercury
• Mercury salts (e.g., mercury chloride) that cross
  membranes by diffusion
• Elemental mercury
• Methylmercury that cross membranes by diffusion
• Inferences are inaccurate because the
  symptomology of these compounds are completely
  different than what is observed in autistic
  children

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Thimerosal As A Vaccine Preservative

• Bacteriostatic agent used in inactivated vaccines
• An organic mercury
• Principal metabolic product is ethylmercury
• Cannot cross plasma membranes by diffusion
  (requires active transport)
• Ethylmercury interacts with thiol groups found on
  bacterial cell walls and other proteins
  (including viruses and fungi)
• Used in vaccines and other medical injectables
  since the 1930s
• Inexpensive and highly effective
• Low toxicity
• gt90 is excreted within 30 days

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Thimerosal and the Danish Study

• Denmark has extensive medical records of its
  citizens
• Abandoned thimerosal in childhood vaccines in
  1992
• Evaluated the incidence of autisms in children
  immunized with thimerosal-free and
  thimerosal-containing vaccines
• Results
• 956 autistic children
• 3.51 malefemale ratio
• From 1970 to 1990, no increased incidence of
  autisms was observed
• After removal of thimerosal, the incidence of
  autisms began to increase

Thimerosal removed
Madsen et al. Thimerosal and the occurrence of
autism negative ecological evidence from Danish
population-based data.Pediatrics. 2003. 12604-6.
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The Institute of Medicines Report

• IOM is the National Academy of Sciences public
  health review board
• They reviewed the data and concluded that
• No evidence exists supporting a link between
  thimerosal and autisms
• However, it is plausible that thimerosal may have
  an impact on some children
• Recommended removal of thimerosal from childhood
  vaccines
• FDA approved and thimerosal was removed from
  childhood vaccine formulations in 2001
• This removal has had no impact on the incidence
  of autisms in the United States

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Incidence of ASD in the United States
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Why Has ASD Incidence Increased?

• Change in definition
• Autism in 1980s was a narrowly-defined term
• Autistic persons were largely incompetent
• In about 1990 it was broadened to include mild
  and moderate PDD
• In 1988, the Congress increased funding for
  special education
• Is it all that surprising that the incidence of
  autism (now including other forms of autism)
  has increased?

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