Game plan

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Game plan
Lecture Vaccinations ELISAs
Lab Continue Staph, Strep and Enteric
Unknowns
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Immunological applications vaccines
1796- Edward Jenner
Table 18.3
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Immunological applications vaccines
Attenuated whole-agent vaccines- weakened
microbes (measles, mumps, rubella,
chickenpox) Inactivated (killed) whole-agent
vaccines- killed microbes (polio,
rabies, pertussis) Toxoids- inactivated toxins
(tetanus, diptheria, pertussis) Subunit
vaccines- partial antigenic fragments of microbes
(hepatitis B) Conjugated vaccines-
polysaccharides combined with proteins (H.
influenza b)
Table 18.3
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Vaccine schedule
Table 18.3
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Why not vaccinate?

• Complacency about disease
• Benefits of vaccination not immediately evident
• (adverse reactions are immediate)
• Medias inaccurate and biased role
• Need to link tragic events (eg. autism) with
  cause
• Philosophical beliefs based on above
• Vaccines dont work.
• Why vaccinate when the disease is so rare?
• Vaccines cause secondary disease.

6
Complacency/ benefits smallpox success story

• Caused by variola virus (major
• and minor)
• First disease for which immunity
• was artificially induced
• Last case in 1977

Source Centers for Disease Control and
Prevention
7
Complacency/ benefits polio success story
Courtesy of Centers for Disease Control and
Prevention

• Caused by poliovirus
• Inactivated (Salk) vaccines and
• attenuated (Sabin or OPV) vaccines
• Currently endemic in Africa/ Asia
• only

Courtesy of World Health Organization
8
Adverse reactions- these can be immediate and
obvious

• 1955- IPV or Salk polio vaccine induced 260 cases
  polio,
• resulted in 10 deaths (not fully inactivated).
  Current Salk
• vaccine is inactivated.
• 1997- MMR (measles mumps rubella) vaccine and
  aseptic
• meningitis
• - 2005 studies show no risk of new MMR vaccines
• and aseptic meningitis
• 1999- Rotavirus vaccine and intussesception
  (bowel obstruction)
• 1 in 10,000 to 15,000 cases
• 2006 OPV/ Sabin vaccine causes paralysis in 1/
  6.2 million

9
Medias role inaccurate reporting
Case study 1000 students at school 995
received MMR vaccine all exposed to 1 student
with measles 12 cases of measles resulted 5
were not previously immunized 7 were immunized
(less severe cases) MEDIA REPORT MMR Vaccine
Does Not Work!!
10
Need to link tragedies with cause
MMR vaccine and autism data

• 1998 Wakefield et al. suggest MMR vaccine
  caused autism
• in 12 children
• ISSUES MMR vaccine/ autism diagnosis occurs at
  same time
• Studies of autism in vaccinated vs.
  unvaccinated
• not done
• Claim that autism is consequence of
  gastrointestinal
• inflammation caused by vaccine, but GI issues
• occurred before vaccine in 8 cases
• RESULT Paper was retracted by all but one
  author
• Paper was retracted by publishing journal

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Need to link tragedies with cause
MMR vaccine and autism data

• 2002 2nd Wakefield paper tried to use RT-PCR to
  identify
• measles virus genome in intestinal biopsy samples
  of autistic children
• (case study of 90 autistic children, 70 control)
• ISSUES No correlation between immunization
  status and
• test results
• No data showing time between MMR vaccine and
• biopsy collection
• No blind study or false positive discussion
• Did not use primers to identify wild versus
  vaccine
• virus in biopsies

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Need to link tragedies with cause
Studies by multiple independent groups to
determine causal relationship between MMR vaccine
and autism

• 1999 Taylor et al. examines receipt of MMR
  vaccine and autism (case
• study of 500 children)
• RESULTS vaccinated children with autism
  same as
• those without
• No difference in age of diagnosis
  between
• vaccinated and unvaccinated children
• Onset of symptoms did not occur within 6
• months of MMR vaccine

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Need to link tragedies with cause
Studies by multiple independent groups to
determine causal relationship between MMR vaccine
and autism

• 2001 Smith et al. examines relationship between
  increasing incidence of
• autism in CA and MMR vaccine
• RESULTS of autistic children between
  1980-1994
• increased dramatically but of
• children vaccinated did not
• -2001 Hershel et al. did similar study in
  England (1998-1993) and found
• similar results
• Taylor et al. 2nd paper- examined children with
  inflammatory intestinal
• symptoms before 1988 (when MMR vaccine was
  introduced) and after-
• no change

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Need to link tragedies with cause
Genetic basis of autism and timing of development
of disease

• Genetics Look at percentage of autism in
  twins. If one has it
• Strict definition of autism
• 60 of monozygotic twin will have it
• 0 of dizygotic twin
• Broad defintion (autistic spectrum disorder)
• 92 monozygotic twin will have it
• 10 of dizygotic twin will have it
• Timing Autism symptoms present before 1 year of
  age (studies
• done in 1991, 1992, 1993, 1994, 1998)
• Autism symptoms present before 4 months (studies
  done
• in 1998)

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Need to link tragedies with cause
WHAT NOW?

• 10-12 years of research to refute hypothesis and
  calm fears
• Exemptions allowed in 15 states- places community
  at risk
• Increase in measles in population due to
  exemptors for MMR vaccine

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A new form of child abuse- refusing vaccinations

• Measles caused by Rubeola virus
• Symptoms fever, rash, conjunctivitis,
• pneumonia, encephalitis (permanent damage),
• death
• Pre-vaccine 3-4 million cases annually, 450
• deaths, 28,000 hospitalizations, 1,000 children
• with chronic disabilities (US ONLY)
• Highly contagious requires gt 90 vaccination
• coverage in population
• Currently leading cause of death from a
• vaccine-preventable disease (20 million cases
• annually and 345,000 deaths in 2005
• worldwide)

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A new form of child abuse- refusing vaccinations

• San Diego- February 2008
• 1 unvaccinated child returning from EU
• Documented 11 cases (all in unvaccinated
• children), 8 of whom had PBEs
• - 3 in children lt 12 months
• Spread prior to ID of etiological agent
• (MMWR)

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A new form of child abuse- refusing vaccinations

• Pertussis (whooping cough)- caused
• by Bordatella pertussis
• Symptoms paroxysmal cough, whoop,
• post-tussive vomiting, brain damage,
• death
• Part of trivalent DTP vaccination
• 1980s- Epidemic of pertussis in UK
• 100,000 affected, 36 died
• Due to lack of P in DTP vaccine
• 1996- Epidemic in Vermont
• 280 cases of pertussis
• ½ in children previously vaccinated
• (MMWR)

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A new form of child abuse- refusing vaccinations

• Hepatitis B (HPV) 1/3 world population has
• been infected 350 million chronically
• infected 22,000 new cases and 620,000
• deaths annually (CDC)
• Symptoms chronic and acute, long term
• liver damage, cirrhosis, cancer
• 1999- After thimerosol was recalled as
• preservative in vaccines- HBV vaccination
• at birth declined
• HBV infections account for 80 of
• carcinomas in adulthood (second only to
• tobacco)

Patricia Walker, MD, Ramsey Clinic Associates,
St. Paul, MN
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Vaccines- the bottom line

• Vaccines work!
• A total 98.8 reduction in vaccine preventable
  diseases
• in the US since vaccination schedule was
  implemented.
• Exemptors of vaccines break down herd immunity
  and increase
• risk of disease on a population level
• Vaccines will never be 100 effective or 100
  safe
• Primary goal of current vaccine research is
  based on
• safety and EIDs
• Personal vigilence is required to be informed and
  prevent
• complacency in public, health organizations, and
  research/ drug
• development

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Future vaccination hopes

• Nasal vaccines- administered nasally (influenza
  virus)
• Patch vaccines- administered through skin
  (influenza virus)
• Edible vaccines- genetically engineer plants to
  produce vaccine
• proteins (E. coli, Rotavirus, Norwalk virus,
  Hepatitis B virus)
• Naked DNA vaccines- inject DNA (plasmids) into
  muscle and have cells produce antigens (tumor
  antigens, infectious disease)
• 47 new vaccine clinical trials since August 2008
  in the USA alone (Influenza, Botulinum,
  Rotavirus, HIV, Meningococcal meningitis, Hep-B,
  Cancer, TB)

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Diagnostic applications Enzyme-Linked
Immunosorbent Assay(Direct ELISA)
Figure 18.12a
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Enzyme-Linked Immunosorbent Assay(Direct vs
Indirect ELISA)
Figure 18.14 - Overview
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New lateral flow (ELISA) technology
Immunocard Detects C. difficile toxins A and B
Immunocard STAT! Detects H. pylori in stool
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New lateral flow (ELISA) technology
Binax NOW Malaria Differentiates between P.
falciparum and others
NOW Flu Detects influenza A and B