Mirror Mirror on the Wall: is there a difference at all

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Mirror Mirror on the Wall is there a difference
at all ?
2
Mirror Mirror on the Wall is there a difference
at all ?

• Baby Jack
• Born February 12, 1996

• Baby Lucy
• Born February 12, 2005

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Jack vs. Lucy

• 2 doses of MMR as of 1996
• Acellular pertussis as of 1997
• Pneumococcal conjugate vaccine in 2001
• Meningococcal conjugate vaccine in 2001
• Varicella vaccine in 1998 and again 2003
• Public concerns about vaccine safety

4
Patricia Gerber, B.Sc (Pharm), Pharm D

• Whats new in Childhood Immunizations ?

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Measles, mumps, rubella (MMR)

• Measles the most contagious vaccine-preventable
  disease in humans
• Prior to 1964 no vaccine 300,000 cases per
  year
• 1970s 80s marked decline in incidence
• 1989 1995 large outbreaks, especially in
  children
• 10-15 of immunized children not fully
  protected
• 1996-97 2nd MMR dose added to routine schedule
• 1998 - now mostly eliminated, imported cases
  still occur

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Acellular pertussis vaccine

• 1943 Pertussis whole cell vaccine first
  introduced
• 50-60 efficacy in children
• 1997 Acellular pertussis vaccine introduced
• more purified contains only specific proteins
• fewer side effects febrile seizures,
  hyporesponsive - hypotonic episodes and
  persistent crying
• 85 efficacy, longer lasting immunity
• 2005 In Canada, Europe and US, highest
  incidence is in adolescents
• recent outbreak in BC preadolescents -
  adolescents were most affected
• Next few years? Need for further boosters ?

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Pneumococcal vaccine

• Streptococcus pneumoniae gram-ve bacteria,
  often inhabit the upper respiratory tract
• Pneumococcal disease in children
• 1cause of invasive bacterial infections (IPD)
  in young children pneumonia, bacteremia, and
  meningitis.
• Highest incidence in children lt 5 years of age,
  especially in lt 2 years of age.
• In Canada, 65 cases of meningitis, 700 cases
  of bacteremia, gt 11,000 cases of pneumonia every
  year
• In Canada, 15 deaths in children lt 5 years of age
  each year
• Can also cause non-invasive infections
  sinusitis, acute otitis media (AOM)
• Pneumococcal resistance to antibiotics is a
  growing concern
• 90 serotypes of Streptococcus pneumoniaeIn
  Canada, 7 account for gt 80 of invasive isolates
  in lt 5 years
• Until 2001 23-valent polysaccharide vaccines
  (Pneumovax 23R, Pneumo 23R, Pnu-ImmuneR).
• long sugar molecule chains antigen from 23
  serotypes which cause 90 of bacteremia,
  meningitis.
• Problem these preparations are T-cell
  independentnot immunogenic in children lt 2
  years of age.
• In June 2001 new pneumococcal conjugate vaccine,
  PrevnarR
• Conjugated to a carrier protein (CRM197, a
  non-toxic variant of diphtheria toxin),

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Vaccine efficacy

• RM, DB, controlled study in US of 38,000
  healthy infants immunized at 2, 4, 6, 12-14
  months of age.
• Primary endpoint efficacy against IPD.
• The study was terminated early all cases of IPD
  were in children in the control group.
• 89.1 decrease in the total IPD burden in the
  vaccinated children
• Pediatr Infect Dis J 200019(3)187-95
• Secondary endpoint of the study ability of the
  vaccine to prevent AOM
• 4 yr follow-up 7.8 decrease in doctor visits
  due to AOM (esp. in children lt 1 y/o those with
  frequent AOM)
• Decrease in need for placement of tympanostomy
  tubes
• Pediatr Infect Dis J 2003 22(1)10-6.
• PR, RM, DB study of 800 children in Finland
  immunized at 2, 4, 6 and 12 months of age

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Some concerns and unanswered questions

• Potential for increase in penicillin-resistance
  among non-vaccine serotypes ?
• Can the widespread use of this vaccine in young
  children cause a shift in serotypes
• In Canada 73- 95 of serotypes that are
  penicillin-resistant are included in the vaccine
  
• Could serotypes not currently covered in the
  vaccine become more prevalent ?
• What would be the clinical implications ?
• In Canada, although immunologic memory has been
  shown after 18 - 20 months in infants and
  toddlers, the long-term efficacy of the vaccine
  is still unclear
• How would the use of this vaccine affect the
  indirect protection of unvaccinated children ?
• a relatively new vaccine in Canadadifferences in
  routine schedules between jurisdictions

10
Some concerns and unanswered questions

• Potential for increase in penicillin-resistance
  among non-vaccine serotypes ?
• Can the widespread use of this vaccine in young
  children cause a shift in serotypes
• In Canada 73- 95 of serotypes that are
  penicillin-resistant are included in the vaccine
  
• Could serotypes not currently covered in the
  vaccine become more prevalent ?
• What would be the clinical implications ?
• In Canada, although immunologic memory has been
  shown after 18 - 20 months in infants and
  toddlers, the long-term efficacy of the vaccine
  is still unclear
• How would the use of this vaccine affect the
  indirect protection of unvaccinated children ?
• a relatively new vaccine in Canadadifferences in
  routine schedules between jurisdictions

11
Some concerns and unanswered questions

• Potential for increase in penicillin-resistance
  among non-vaccine serotypes ?
• Can the widespread use of this vaccine in young
  children cause a shift in serotypes
• In Canada 73- 95 of serotypes that are
  penicillin-resistant are included in the vaccine
  
• Could serotypes not currently covered in the
  vaccine become more prevalent ?
• What would be the clinical implications ?
• In Canada, although immunologic memory has been
  shown after 18 - 20 months in infants and
  toddlers, the long-term efficacy of the vaccine
  is still unclear
• How would the use of this vaccine affect the
  indirect protection of unvaccinated children ?
• a relatively new vaccine in Canadadifferences in
  routine schedules between jurisdictions

12
Some concerns and unanswered questions

• Potential for increase in penicillin-resistance
  among non-vaccine serotypes ?
• Can the widespread use of this vaccine in young
  children cause a shift in serotypes
• In Canada 73- 95 of serotypes that are
  penicillin-resistant are included in the vaccine
  
• Could serotypes not currently covered in the
  vaccine become more prevalent ?
• What would be the clinical implications ?
• In Canada, although immunologic memory has been
  shown after 18 - 20 months in infants and
  toddlers, the long-term efficacy of the vaccine
  is still unclear
• How would the use of this vaccine affect the
  indirect protection of unvaccinated children ?
• a relatively new vaccine in Canadadifferences in
  routine schedules between jurisdictions

13
Some concerns and unanswered questions

• Potential for increase in penicillin-resistance
  among non-vaccine serotypes ?
• Can the widespread use of this vaccine in young
  children cause a shift in serotypes
• In Canada 73- 95 of serotypes that are
  penicillin-resistant are included in the vaccine
  
• Could serotypes not currently covered in the
  vaccine become more prevalent ?
• What would be the clinical implications ?
• In Canada, although immunologic memory has been
  shown after 18 - 20 months in infants and
  toddlers, the long-term efficacy of the vaccine
  is still unclear
• How would the use of this vaccine affect the
  indirect protection of unvaccinated children ?
• a relatively new vaccine in Canadadifferences in
  routine schedules between jurisdictions

14
Meningococcal vaccine

• Neisseria meningitidis (meningococcus)
  gram-negative bacterium
• Most common presentation of invasive
  meningococcal disease (IMD) is meningitis
• highest incidence of IMD in infants lt 12 months
  of age and adolescents
• 10 fatality rate
• Also, meningococcal septicemia (fatality rate 40
  ) /- meningitis pneumonia, AOM
• Most cases of invasive disease in Canada caused
  by serogroups B, C, Y, and W-135
• Sporadic disease or outbreaks
• B mostly in children lt 5 years old mostly
  associated with septicemia higher incidence of
  death
• C in both lt 5 years old and adolescents mostly
  associated with invasive disease
• Potential for significant sequelae (hearing loss,
  neurological damage)
• Until 2001, meningococcal vaccines in Canada were
  polysaccharide vaccines
• A and C (Mencevax ACR)
• A, C, Y, and W-135 (MenomuneR).
• no vaccine available against serogroup B !

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Vaccine efficacy

• Immunogenicity data able to predict protection in
  infants gt 2 months old
• But limited clinical data on efficacy and no
  published studies looking at meningitis as an
  endpoint
• Surveillance data from England, 4 yrs after
  introduction of the vaccine
• Vaccine effectiveness remained high
• Children ranged in age from 5 months to 18 years
• But effectiveness decreased after 1 yr of
  immunizing children as per the routine infant
  immunization schedule Lancet 2004
  364365-7
• In England, vaccine coverage rate of 89 lead to
  reduction of 80 in the incidence of meningitis
  (serogroup C)
• Number of deaths decreased from 78 to 8
• Common Dis Public Health 2002
  5(3)220-5

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Some concerns and unanswered questions

• Long-term effectiveness remains unclear
• What effects, if any, will it have on disease
  rates and herd immunity?
• Will it induce a shift in meningococcal
  serogroups from C (vaccine covered) to
  non-vaccine serogroups
• What will be the long-term clinical implications
  of this ?
• Will booster doses be required by the children
  who were immunized once they reach adolescence (a
  time when the disease can become problematic
  again)
• Canadian Paediatric Society recommends that
  Canadian children be immunized with the
  Meningococcal vaccine as per the NACI guidelines
  (Canadian Immunization Guide)

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Some concerns and unanswered questions

• Long-term effectiveness remains unclear
• What effects, if any, will it have on disease
  rates and herd immunity?
• Will it induce a shift in meningococcal
  serogroups from C (vaccine covered) to
  non-vaccine serogroups
• What will be the long-term clinical implications
  of this ?
• Will booster doses be required by the children
  who were immunized once they reach adolescence (a
  time when the disease can become problematic
  again)
• Canadian Paediatric Society recommends that
  Canadian children be immunized with the
  Meningococcal vaccine as per the NACI guidelines
  (Canadian Immunization Guide)

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Some concerns and unanswered questions

• Long-term effectiveness remains unclear
• What effects, if any, will it have on disease
  rates and herd immunity?
• Will it induce a shift in meningococcal
  serogroups from C (vaccine covered) to
  non-vaccine serogroups
• What will be the long-term clinical implications
  of this ?
• Will booster doses be required by children who
  were immunized once they reach adolescence (when
  the disease can be problematic again)
• Canadian Paediatric Society recommends that
  Canadian children be immunized with the
  Meningococcal vaccine as per the NACI guidelines
  (Canadian Immunization Guide)

19
Some concerns and unanswered questions

• Long-term effectiveness remains unclear
• What effects, if any, will it have on disease
  rates and herd immunity?
• Will it induce a shift in meningococcal
  serogroups from C (vaccine covered) to
  non-vaccine serogroups
• What will be the long-term clinical implications
  of this ?
• Will booster doses be required by children who
  were immunized once they reach adolescence (when
  the disease can be problematic again)
• Canadian Paediatric Society recommends that
  Canadian children be immunized with the
  Meningococcal vaccine as per the NACI guidelines
  (Canadian Immunization Guide)

20
Some concerns and unanswered questions

• Long-term effectiveness remains unclear
• What effects, if any, will it have on disease
  rates and herd immunity?
• Will it induce a shift in meningococcal
  serogroups from C (vaccine covered) to
  non-vaccine serogroups
• What will be the long-term clinical implications
  of this ?
• Will booster doses be required by children who
  were immunized once they reach adolescence (when
  the disease can be problematic again)
• Canadian Paediatric Society recommends that
  Canadian children be immunized with the
  Meningococcal vaccine as per the NACI guidelines
  (Canadian Immunization Guide)

21
Some concerns and unanswered questions

• Long-term effectiveness remains unclear
• What effects, if any, will it have on disease
  rates and herd immunity?
• Will it induce a shift in meningococcal
  serogroups from C (vaccine covered) to
  non-vaccine serogroups
• What will be the long-term clinical implications
  of this ?
• Will booster doses be required by children who
  were immunized once they reach adolescence (when
  the disease can be problematic again)
• Canadian Paediatric Society recommends that
  Canadian children be immunized with the
  Meningococcal vaccine as per the NACI guidelines
  (Canadian Immunization Guide)

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Varicella vaccine

• Varicella (chickenpox) varicella zoster virus
• Mostly a disease of childhood 50 of cases by 5
  years and 90 by 12 years
• Generally mild, self-limited disease rash,
  malaise, pruritus, fever x 2-3 days
• Complications in children 2ry skin infection,
  cerebellar ataxia, meningitis, encephalitis,
  pneumonia, cellulitis, and necrotizing fasciitis
• risk of complications highest in children lt 1
  year of age and adults
• In kids, risk of cerebellar ataxia, and
  encephalitis is 1 in 4,000 and 1.7 in 100,000,
  respectively
• mortality rate in children is 1-3 per 100,000
  cases
• 85 - 90 of hospitalizations, 50 of deaths
  are in previously healthy children
• Latent varicella virus may reactivate and cause
  herpes zoster (HZ)
• Since 1998 live, attenuated varicella vaccines
  became available in Canada
• Most recently and currently available are Varivax
  IIIR and VarilrixR

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• Viewer discretion is advised...

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Typical varicella rash Courtesy Centers
for Disease Control and Prevention and Dr. CW
Leung, Department of Paediatrics Adolescent
Medicine, Princess Margaret Hospital, Hong Kong
25
Resolving varicella rash, with scabs falling
off Courtesy of Centers for Disease
Control and Prevention
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Secondary skin infection due to
varicella Courtesy of Centers for Disease
Control and Prevention
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Herpes Zoster rash Courtesy of Dr. CW
Leung, Department of Paediatrics Adolescent
Medicine, Princess Margaret Hospital, Hong Kong
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Vaccine efficacy

• Overall, 70 - 90 effective against varicella
  infection 95 effective against severe infection
• Canada Commun Dis Rep 1999 251-16
• JAMA 2002287(5)606-11
• Study of incidence of death before vs after
  introduction of vaccine average rate of decline
  in varicella mortality was greater after vaccine
  implementation
• Pediatr Infect Dis J. 2004 23(6)498-503.
• US study of the contagiousness of varicella
  amongst close contacts.
• - In children 1-14 yrs were exposed to
  unvaccinated cases, secondary attack rate was
  71.5 if unvaccinated and 15.1 if vaccinated.
• JAMA 2004292(6)704-8
• During an outbreak of varicella in a daycare in
  the US, vaccine was 86 at preventing mild
  disease and 100 effective preventing moderate -
  severe disease
• these numbers have been confirmed in two more
  recent studies

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Some concerns and unanswered questions

• Varicella antibodies are still detectable in
  100 of cases for up to 4 years after
  vaccination and in 95 of cases for up to 10
  years
• In Japan the vaccine has been available for gt 20
  yrs protection lasts
• Only one published study on the long-term
  efficacy of the vaccine in Canada
• reported a high level of protection for up to 3
  years after vaccination
• Can J Infect Dis 2002 13(6)382-6.
• Does time since vaccination predict vaccine
  failure ?
• Large US study effectiveness decreased from 97
  in the 1st year post-vaccination to 84 in the
  subsequent 7 years
• CDCs Epidemiology Prevention of
  Vaccine-Preventable Diseases. Satellite
  Broadcast, Mar2004. Varicella.
• Will there be a need for a booster dose or a
  two-dose primary schedule ?

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Some concerns and unanswered questions

• Varicella antibodies are still detectable in
  100 of cases for up to 4 years after
  vaccination and in 95 of cases for up to 10
  years
• In Japan the vaccine has been available for gt 20
  yrs protection lasts
• Only one published study on the long-term
  efficacy of the vaccine in Canada
• reported a high level of protection for up to 3
  years after vaccination
• Can J Infect Dis 2002 13(6)382-6.
• Does time since vaccination predict vaccine
  failure ?
• Large US study effectiveness decreased from 97
  in the 1st year post-vaccination to 84 in the
  subsequent 7 years
• CDCs Epidemiology Prevention of
  Vaccine-Preventable Diseases. Satellite
  Broadcast, Mar2004. Varicella.
• Will there be a need for a booster dose or a
  two-dose primary schedule ?

31
Some concerns and unanswered questions

• Varicella antibodies are still detectable in
  100 of cases for up to 4 years after
  vaccination and in 95 of cases for up to 10
  years
• In Japan the vaccine has been available for gt 20
  yrs protection lasts
• Only one published study on the long-term
  efficacy of the vaccine in Canada
• reported a high level of protection for up to 3
  years after vaccination
• Can J Infect Dis 2002 13(6)382-6.
• Does time since vaccination predict vaccine
  failure ?
• Large US study effectiveness decreased from 97
  in the 1st year post-vaccination to 84 in the
  subsequent 7 years
• CDCs Epidemiology Prevention of
  Vaccine-Preventable Diseases. Satellite
  Broadcast, Mar2004. Varicella.
• Will there be a need for a booster dose or a
  two-dose primary schedule ?

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• What effects will the vaccine have on the
  epidemiology of the varicella virus?
• Will the decrease in circulating natural virus
  create a cohort of adults at risk for serious
  disease (will unimmunized / unexposed children
  enter adulthood without immunity ?)
• Need for catch-up immunization ?
• Pediatrics 2000 105(1 Pt 1)136-41.
• What effect does the vaccine have on the
  epidemiology of herpes zoster ?
• post marketing surveillance data age-specific
  risk of developing HZ seems lower in immunized
  children than in those who had the natural
  infection
• Pediatrics 2000 105(1 Pt 1)136-41.
• Does vaccine effectiveness depend on the age at
  vaccination ?
• Its been suggested that children immunized 12
  months may still have circulating maternal
  antibodies to the virus and therefore, may be at
  higher risk of vaccine failure.
• Study showed higher breakthrough rates in
  children vaccinated at 12-14 months vs those who
  received it when they were older than 15 months
• CDCs Epidemiology Prevention of
  Vaccine-Preventable Diseases. Satellite
  Broadcast, Mar 2004. Varicella
• Does timing of administration (vs the MMR
  vaccine) affect the risk of breakthrough disease
  ?

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PUBLIC CONCERNS

• Growing number of opponents of childhood
  immunization
• Easy to loose perspective
• Vaccine-preventable diseases are rare in Canada
• Yet the media bombards the public with concerns
  about vaccine safety
• In a survey of Canadian households, parents named
  the media as the 2nd most frequent source of
  information on the benefits of immunization
• Can Commun Dis Rep. 200430(5)37-50

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Common public concerns

• Vaccines can cause autism
• In 1998, a UK study of 12 children claimed the
  measles vaccine could lead to autism
• 10 children with autism. In 8, the onset of
  symptoms was linked to the MMR vaccine they
  received
• Authors theory MMR vaccine causes intestinal
  inflammation specific peptides cross intestinal
  barrieropioid-like effect on the brain, disrupt
  normal brain development
• Subsequent studies of better design did not
  detect measles virus in patients intestines and
  found no evidence that MMR causes autism
• Study of gt 500,000 children risk of autism was
  similar in vaccinated and unvaccinated
• Subsequent to the 1998 study, MMR vaccination
  rates fell in the UK and the incidence of measles
  infection increased
• Most recently, authors of the 1998 study
  retracted their conclusions no causal link
  was established between MMR vaccine and autism as
  the data were insufficient
• American Academy of Pediatrics, the Canadian
  Paediatric Society, and the World Health
  Organization no evidence of a link between the
  measles vaccine and autism

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Concern of the day

• Vaccines can cause inflammatory bowel disease
• Good review J Pediatr Pharmacol Ther
  20038187-99
• Vaccines can cause diabetes
• Good review NEJM 20043501398-404

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• Vaccines contain mercury, and mercury is not
  good for you
• Thimerosal an organic preservative that contains
  50 ethyl-mercury (and metabolized into mercury)
• Serious health effects 2ry to exposure to high
  doses of mercury have been documented in humans
• Concern is regarding neurodevelopment autism,
  ADHD
• Data suggests low dose exposure (e.g., found in
  some vaccines) does not lead to any adverse
  effects
• But, a theoretical concern does exist for young
  infants
• Higher concentrations of ethyl-mercury when
  thimerosal is metabolized by young infants but,
  dilutional effect
• Greater potential for side effects in young
  infants because of their on-going
  neurodevelopment
• In fact, less than 0.5 µg of mercury per dose,
  (still found in only one of the Hepatitis B
  vaccines and one of the Influenza vaccines) is
  considered clinically insignificant
• Position Statements by WHO, American Academy of
  Pediatrics, Canadian Paediatric Society

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A day in the life of

• you and I

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Why are we faced with problems / concerns about
childhood vaccines in our daily practice?

• Hard to keep up with the changes and
  controversies
• Vaccine-preventable diseases still occur
• The media overwhelms the public with concerns
  about vaccine safety
• Vaccines are licensed federally through Health
  Canada
• Which vaccines are included in each Province /
  Territory s schedule varies from jurisdiction
  to jurisdiction
• Which ones are free of charge to the public
  varies across Canada
• Canadian families move from jurisdiction to
  jurisdiction
• Children get vaccinated at different settings
  within one jurisdiction (e.g., a walk-in clinic
  vs a hospital vs a GPs office)

39
Why are we faced with problems / concerns about
childhood vaccines in our daily practice?

• Hard to keep up with the changes and
  controversies
• Vaccine-preventable diseases still occur
• The media overwhelms the public with concerns
  about vaccine safety
• Vaccines are licensed federally through Health
  Canada
• Which vaccines are included in each Province /
  Territory s schedule varies from jurisdiction
  to jurisdiction
• Which ones are free of charge to the public
  varies across Canada
• Canadian families move from jurisdiction to
  jurisdiction
• Children get vaccinated at different settings
  within one jurisdiction (e.g., a walk-in clinic
  vs a hospital vs a GPs office)

40
Why are we faced with problems / concerns about
childhood vaccines in our daily practice?

• Hard to keep up with the changes and
  controversies
• Vaccine-preventable diseases still occur
• The media overwhelms the public with concerns
  about vaccine safety
• Vaccines are licensed federally through Health
  Canada
• Which vaccines are included in each Province /
  Territory s schedule varies from jurisdiction
  to jurisdiction
• Which ones are free of charge to the public
  varies across Canada
• Canadian families move from jurisdiction to
  jurisdiction
• Children get vaccinated at different settings
  within one jurisdiction (e.g., a walk-in clinic
  vs a hospital vs a GPs office)

41
Why are we faced with problems / concerns about
childhood vaccines in our daily practice?

• Hard to keep up with the changes and
  controversies
• Vaccine-preventable diseases still occur
• The media overwhelms the public with concerns
  about vaccine safety
• Vaccines are licensed federally through Health
  Canada
• Which vaccines are included in each Province /
  Territory s schedule varies from jurisdiction
  to jurisdiction
• Which ones are free of charge to the public
  varies across Canada
• Canadian families move from jurisdiction to
  jurisdiction
• Children get vaccinated at different settings
  within one jurisdiction (e.g., a walk-in clinic
  vs a hospital vs a GPs office)

42
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Our role as Pharmacists

• Encourage parents to keep detailed, up-to-date
  immunization records
• Discuss immunizations with families
• De-mystify any fears or misconceptions
• Use open-ended questions ( when was the last
  time your child was immunized?)
• Be aware of the reasons why parents choose not to
  immunize their children
• Religious or philosophic concerns
• Safety, and efficacy concerns
• Unnatural disease-prevention
• Be aware of common misconceptions
• Todays hygiene and sanitation standards have
  almost eliminated disease
• Vaccine-preventable diseases have been mostly
  eliminated no need for them
• Report any actual or suspected vaccine-related
  adverse effects
• Educate, educate, educate !

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USEFUL RESOURCES

• Canadian Immunization Guide, 6th Ed, 2002
• Canadian Immunization Guide on Google and its
  the 1st listing !
• Talking with Patients about Immunization
• Listing of all vaccine products available in
  Canada
• Comparison of Effects of Diseases and Vaccines

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Mirror Mirror on the WallCan we predict the
future at all ?
Varicella vaccine booster ? Pertussis booster
every 10 yrs ? More on vaccine safety ? New
vaccines ? Varicella MMR vaccine ? Combined
Pneumococcal Meningococcal conjugate vaccine
?
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