Priscilla KincaidSmith Oration:

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Priscilla Kincaid-Smith Oration

• Sponsored by

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Vaccines Value For Future Health

• Terry Nolan

Chair Robin Mortimer
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(No Transcript)
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Pneumococcal sepsis
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Deaths in Australia, 1926-97
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Diphtheria, 1917-2000
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Tetanus, 1917-2000
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Poliomyelitis, 1917-2000
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Rubella, 1917-2000
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Pertussis notifications and hospitalisations,
Australia,1993 to 2000, by month of onset or
admission
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Rubella notifications and hospitalisations,
Australia,1993 to 2000, by month of onset or
admission
Note varying scales between notifications and
hospitalisations
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Trends in vaccination coverage estimates from the
Australian Childhood Immunisation Register for 1
and 2 year olds
Source Australian Childhood Immunisation Register
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What went wrong?

• Success made immunisation unfashionable
• Lost national coordinated approach
• Commonwealth delegated population immunisation
  role to States
• Public and health professional complacency
• Pertussis vaccine safety concerns
• No program management, no useful data on coverage
• No research on new vaccines, on delivery or on
  program effectiveness

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New strategies

• NHMRC National Strategy
• Commonwealth resumed leadership
• Australian Childhood Immunisation register (ACIR)
• New Government priority
• Immunise Australias 7-point plan
• Incentives for parents providers
• Mobilisation of primary care workforce
• Better vaccines and combinations

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Australian Childhood Immunisation Register (ACIR)

• Introduced in 1990s to facilitate tracking
• Established within Health Insurance Commission
• Recall and reminder system
• Look-up system for providers
• Monitor healthcare provider performance
• Monitor population uptake
• 6 payment per notification

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Challenges of the 1990s

• New vaccines emerged
• Hepatitis B vaccine, conjugate Hib vaccine
• Conjugate pneumococcal and meningococcal vaccines
• Consumers wanted better vaccines
• Fewer adverse effects
• Acellular pertussis vaccine
• IPV versus OPV and vaccine associated polio
• Healthcare providers wanted efficiency
• Fewer jabs
• Simpler administration

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Effective immunisation is more than just a good
vaccine
The hepatitis B vaccine story
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Hepatitis B vaccination of adolescents in
Australia

• Prevalence lt 1
• Incidence 1.6 / 100,000
• Peak incidence at ages 15 34 y
• Marked increase in this age group in 2000
• Universal immunisation cost-effective
• Infant/ adolescent program saves 443 life-years
  for net cost-saving of A1.63 million
• Adolescent program saves 404 life-years for 4.57
  million

National acute cases reported 1993-1998
(McIntyre et al, 2000) Cost-effectiveness
analysis for NHMRC working party (Butler, 1996)
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Hepatitis B mass vaccination in Australia

• 1997 NHMRC recommended universal infant and
  young adolescent immunisation
• 1998 11-13 year olds
• Adolescent school-based delivery
• Victoria, S.A. and Tasmania (mix)
• Adolescent GP delivery
• NSW, QLD, WA
• 2000 birth dose and infant program (combination
  vaccines available)

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Victorian birth dose study

• Survey of all maternity hospitals in Victoria (n
  98) 1 July 2000 - 31 December 2000.
• Responses received from 93 hospitals, covering
  99 of Victorian births in that period.
• Vaccine uptake estimated at 85.
• HIC now planning ACIR pilot of direct reporting
  from hospitals.

Source Kathryn Whitfield and Rosemary Lester,
DHS Victoria unpublished
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Infant uptake in Australia

• Based on Australian Childhood Immunisation
  Register (ACIR), which under-estimates by 2.7 at
  12 months of age
• 94 coverage of all schedule vaccines at 12
  months of age
• DTPa-hepB course completed at 6 months, Hib-hepB
  course completed at 12 months
• Only 2-3 of parents object to immunisation at 12
  months of age

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Immunisation of adolescents

• Developmental process of adolescence militates
  against compliance with health preventive
  strategies
• Poor uptake in non-compulsory adolescent
  programs, with exceptions
• Adolescents have few interactions with GPs for
  health care
• Little known about modifiers of immunisation
  compliance in adolescence

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Adolescent uptake in Australia

• School-based
• Vic
• 2001, 81 of adolescents first dose, 75 second
  dose.
• SA
• 2001, 88 dose 1, 81 3 doses.
• Tas
• No data available (GPs and councils)
• GPs
• QLD
• VIVAS data not reliable, estimate lt30 dose 1
• WA
• No data available
• NSW

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NSW experience

• NSW Health CATI survey
• 1567 households with children aged 10 - 13 years,
  n1900.
• Verified against blue book.
• 17.9 ever received a Hep B vaccine
• Of these, 70 had received a complete course,
  making complete course uptake 12.6
• 70 had been vaccinated prior to 10 years of age.
• i.e. only about 9 being completely vaccinated at
  recommended time.

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Clinic-based hepatitis B vaccination programs
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Hepatitis B school-based programs
all non-compulsory
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Cost-effectiveness of school-based delivery for
adolescents

• NSW data show clear cost savings over
  GP-administered program
• Leon Herron (unpublished)

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Conclusions

• Birth dose program moderately successful in
  Victoria. Reliable data not available for other
  States.
• Infant uptake high and at level of population
  target.
• Catch-up program for adolescents failing in
  States that do not yet deliver through schools.
• Where school implementation effective, add-on
  promotion activity not necessary to achieve high
  uptake levels1.

1Skinner, R.S., Imberger, I., Lester, R., Glover,
S., Bowes, G., Nolan, T.M. Randomised controlled
trial of an educational strategy to increase
school-based adolescent hepatitis B vaccination.
Australian and New Zealand Journal of Public
Health 200024298-304.
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Are we doing enough about hep B?
No, we are not

• Birth dose program monitoring needs to be fixed
• School- based delivery for adolescents
• Overwhelming evidence
• Cheaper and more cost-effective than GP
• Conjugate men C program may facilitate
  introduction of school programs in NSW and QLD
• High school entry law
• Targeted home immunisation further enhances
  high-uptake school-based immunisation in
  adolescence

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Scheduling funding population vaccines in
Australia
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Concept of the Australian Standard Vaccination
Schedule (ASVS)

• Expressed both in practice and in the NHMRC
  National Immunisation Strategy of 1993
• Coordinated approach under Commonwealth
  leadership, central funding of vaccines, central
  policy advice (ATAGI), nationally led consortium
  of State and primary care providers (NIC)
• The Schedule was essentially restricted to
  publicly funded universally available vaccines
• Major change, accepted by Government and soon to
  be endorsed by NHMRC is concept of best practice,
  evidence-based ASVS.
• That is, public funding not a requirement for
  ASVS listing
• Implications for providers and consumers.

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ATAGI, NHMRC and the basis for recommendations

• Multidimensional, evidence-based assessment
• Evidence regarding
• Vaccine efficacy data, ideally from RCTs
• Vaccine safety
• Impact on disease burden reduction (mortality,
  morbidity, health service use)
• Health economic evaluation (CEA)
• Vaccine cost assessment
• Supply, quality, reliability
• Ethics and equity issues

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Health economic analysis (cost-effectiveness
ratio) and vaccine value assessment

• Same basis for value assessment as drugs and
  other health interventions (PBAC)
• Requires cabinet approval if gt10m
• Common metric permits benchmarking against
  competitors for the health dollar
• Incorporates direct health care costs, but not
  societal or indirect costs (lost work, parent
  time, other opportunity costs)
• Substantial disadvantage for high prevalence, low
  severity illnesses that still have large
  community impact (e.g. influenza, varicella).

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Public sector vaccine prices
Prices in AUD, include GST price when formerly
used
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Immunisation policy development in Australia
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Ethics and Litigation

• Vaccine-associated polio (VAPP) risk about 1 case
  expected every 3 years in Australia
• Case-finding now intensified because of WHO
  effort towards pre-eradication declaration of
  polio-free status
• Now doubtful whether will be able to stop because
  of bioterrorism risk
• A single case of VAPP could do enormous damage to
  the national program and consumer confidence
• Ethics of mass program with known non-zero risk
  of major adverse event

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Vaccine injury litigation in Australia

• Feared litigation epidemic has not occurred
• Still at risk of massive awards in single cases
• No-fault compensation scheme needs further
  serious consideration despite substantial safety
  track record of vaccines

Its not very far away
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Supply issues and the critical role of industry

• Availability
• Market share and multiple suppliers
• Dependence and risk exposure
• Lead-time issues forward planning
• Little Australian industry
• Complexity of State and Fed purchasing
• ? Implications of free trade agreement with USA

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Changes to ASVS 2003

• The fourth dose of DTPa at 18 months now dropped.
  
• Low antigen formulation pertussis-containing
  vaccine (dTpa) recommended as a single dose at 15
  to 17 years.
• Oral poliomyelitis vaccine (OPV) is replaced by
  inactivated poliomyelitis vaccine (IPV) for the
  3-dose primary series (2, 4 and 6 months of age)
  and for the booster dose at 4 years of age. All
  doses of IPV are provided in the form of
  combinations with other vaccines (DTPa-hepB-IPV,
  DTPa-IPV, DTPa-IPV-Hib, DTPa-IPV-hepB-Hib).
• 7-valent pneumococcal conjugate vaccine (7vPCV)
  is recommended for all Australian children as a
  3-dose series at 2, 4 and 6 months.
• Meningococcal C conjugate vaccine (MenCCV) is
  recommended as a single dose at 12 months of age
  and at the age of 15 years who have not
  previously received the conjugate vaccine
  (superseded by Government policy).
• Varicella vaccine for all children at 18 months
  of age, with a catch-up dose for adolescents 10
  to 13 years of age without a history of either
  varicella or varicella vaccination.

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Proposed ASVS
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Evaluation of candidate ASVS vaccines
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Impact of vaccination
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Summary of epidemiology in developed world
settings

• Right-shift in age distribution with increasing
  number and proportion of pertussis cases in
  adolescents and adults
• Outbreak investigations show high attack rates in
  adolescents and adults
• Evidence of waning immunity in naturally infected
  as well as whole-cell pertussis immunised adults
• About 1 in 4 adults with prolonged cough have
  serologic evidence of recent pertussis infection
• Adults and adolescents in the home are the most
  frequent source of infection of infants who have
  highest mortality and morbidity

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Pertussis notificationsAustralia 2000, rate per
100,000
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Pertussis notifications by age, 1993-2001
Increased incidence in 15y and infants
Source National Centre for Immunisation Research
and Surveillance
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Pertussis deaths
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Italian NIH study

• 3 doses of 3-component DTaP (GSK or Chiron) or DT
  vaccines
• Pertussis toxin (PT), filamentous hemagglutinin
  (FHA) and pertactin in both DTaP vaccines
• 2, 4 and 6 months of age
• DTaP efficacy 84 in first 2 years of life
• Stage 2 follow-up at 33 months showed similar
  efficacy
• Stage 3 follow-up ages 3-6 years in over 9,500
  children, mean age 5.8 years.

Salmaso et al. Pediatrics 2001108(5).
http//www.pediatrics.org/cgi/content/full/108/5/e
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Vaccine efficacy estimates ()(NIH Italian study)
Salmaso et al. Pediatrics 2001108(5).
http//www.pediatrics.org/cgi/content/full/108/5/e
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History of pertussis boosters in Australia since
1980s
18 month booster

• DTwP booster dropped in early 1980s
• Concern re pertussis encephalopathy
• Surge in hospitalised infants with pertussis
• Rapidly re-introduced
• DTwP replaces DTaP as booster in 1998, about a
  year before DTaP replaces DTwP in primary course
  (2, 4 and 6 months of age)

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History of pertussis boosters in Australia since
1980s
Pre-school booster

• DTwP introduced as 5th dose in 1994, then DTaP
  replaced DTwP in 1999
• High levels of adverse effects and school absence
  after DTwP
• Uptake now good for DTaP at 5yrs
• High level of parent acceptance and support for
  government provision of free vaccine, even though
  more expensive

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History of pertussis vaccine boosters in
Australia since 1980s
Adolescent booster

• dT delivered now
• ATAGI recommendation for pertussis booster under
  consideration by Government

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Population modelling

• Adult boosting every 10 years should reduce
  number and severity of adult pertussis infections
  
• But, mathematical modelling suggests that adult
  boosting will only produce modest reduction in
  pertussis in infants and children through herd
  effects.

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Hethcote population adult pertussis booster model
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What about a cocoon strategy to protect against
infant pertussis deaths?

• Idea is to vaccinate all family members of
  expectant mothers (including extended family)
• Protect the newborn by immunising all those who
  have contact before the age of 6 months (when
  infant primary course should be completed)
• Epidemiologic evidence suggests that this could
  work
• However, not yet demonstrated or evaluated
• Renewed interest in neonatal immunisation with
  acellular vaccines, but studies not yet done.

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Varicella vaccine and zoster protection Lesson 2
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Lack of boosting and Zoster

• Possible effect of reduced wild virus boosting of
  naturally infected individuals if high vaccine
  uptake is achieved in children.
• Epidemiologic evidence shows that contact with
  children who have chicken-pox protects against
  zoster in adults.
• Immunologic evidence shows that intimate exposure
  to children with varicella boosts VZV-specific
  CMI in seropositive adults.
• Recent modelling studies predict that the
  lifetime risk of zoster will be over 50 in those
  aged 10-44 years at the introduction of mass
  vaccination.

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Epidemiologic evidence and boosting
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Brisson et al. Vaccine 2002202500-7.
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Brisson et al. Vaccine 2002202500-7.
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Brisson et al. Vaccine 2002202500-7.
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Left shift in age of zoster

• May actually be (net) beneficial
• Less severe episodes at younger age
• May have higher risk of second episode but each
  may be less severe.
• Lower net burden possible.
• Will vaccination of naturally infected adults
  prevent zoster?
• US Veterans Cooperative Study results in 2004
• Enrolled 38,546 aged 60y
• High release titre VZV vaccine vs placebo

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What does this all mean?

• This is just a model.
• Empirical evaluation of the population impact of
  mass vaccination programs is crucial to determine
  whether modelling predictions will occur, and to
  base policy for further vaccination should it be
  required.
• Waiting 70 years for definitive evidence to fully
  evaluate these predictions must be traded off
  against the aggregate societal benefit of
  varicella prevention.
• Must have good zoster surveillance.
• If VZV vaccine is to be used, uptake must be
  achieved in a very high proportion of the
  non-immune population.

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New vaccines

• HPV (Human Papilloma Virus 6, 11, 16, 18
  cervical cancer, genital warts)
• HSV (Herpes Simplex Virus neonatal herpes,
  genital herpes)
• Rotavirus (gastroenteritis)
• Intranasal influenza (Cold-adapted,
  heat-attenuated live virus)
• PIV (Parainfluenza 1 and 3 croup)
• HIV (AIDS)
• MMR-V (MMR and varicella)
• MenCY and other conj MenC combos
• MenB
• Also CMV, malaria, TB, chlamydia, GAS, GBS, EBV

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HPV-16 vaccine efficacy
Koutsky et al. Efficacy analysis of an HPV-16 L1
virus-like-particle vaccine. NEJM
2002341645-51.
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Coronavirus virion (Holmes KV. SARS-associated
coronavirus. NEJM 20033481948-51)
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Conclusions

• Must be vigilant, flexible and adaptable
• Cost-effective health gain through vaccine
  prevention of disease still comes at a cost that
  governments with short funding cycles and
  sometimes short-sighted view of the future need
  to provide.
• Healthcare providers need to adapt to these
  changes
• Need to provide preventative healthcare
  frameworks that facilitate effective uptake of
  vaccines, especially adults and adolescents.
• Vaccines offer some of the best value for health
  maintenance. Lets take advantage of it.

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