Vaccine Preventable Diseases

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Epidemiological aspects of Vaccine Preventable
Diseases (VPD)
Biagio Pedalino
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Whats so special about VPD?
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Vaccines what are they?

• A vaccine is a biological preparation
  (microorganism, toxoid, subunit)
• Stimulates the body's immune system to create
  antibodies against this microorganism
• A vaccine aims to safely protect a healthy
  individual/population from a particular infection
• Vaccines need to be assessed before and after
  licensing

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Objectives of the presentation

• To define key aims and effects of different
  vaccination programmes
• To identify key principles in vaccination
  programme evaluation
• Disease surveillance
• Vaccine uptake (coverage)
• Vaccine effectiveness
• Vaccine safety

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Aims of vaccination programmes

• To protect those at highest risk
• (selective vaccination strategy)
• or
• To eradicate, eliminate or control disease
• (mass vaccination strategy)

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Selective vaccination strategy

• Vaccine given specifically to those at increased
• risk of disease
• High risk groups
• e.g. pneumococcal, meningococcal
• Occupational risk
• e.g. hepatitis B, influenza
• Travellers
• e.g. yellow fever, rabies, hepatitis A
• Outbreak control
• e.g. hepatitis A, measles

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Selective vaccination strategy

• Vaccine targeted at a specific group (although
  risk of disease affects another)
• Girls and young women (13-26 yrs)
• e.g. HPV, rubella
• Pregnant women
• e.g. tetanus (neo-natal tetanus)

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Mass vaccination

• Eradication
• Infection (pathogen) has been removed worldwide
  e.g. smallpox
• Elimination
• Disease has disappeared from one area but may
  remain elsewhere, e.g. polio, measles
• Control
• Disease no longer constitutes a significant
  public health problem in certain countries, e.g.
  neo-natal tetanus

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Progress Toward Polio Eradication
Decrease of gt99 from gt350 000 cases in 1988 to
lt2000 cases in 2008
35,251 cases
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How do mass vaccination programmes impact the
disease?

• Reduce size of susceptible population
• Reduce number of cases
• Reduce risk of infection in population
• Reduce contact of susceptibles to cases
• Lengthening of epidemic cycle (honeymoon
  phase)
• Increase mean age of infection

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All susceptible
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Basic reproductive number R04
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Mass vaccination
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Mass vaccination
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Effective reproductive number R lt 1
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Impact of mass vaccination programme Annual
measles notifications vaccine coveragePoland
1960-2000
Source National Institute of Public Health
National Institute of Hygiene, Warsaw, Poland
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Objectives of the lecture

• To understand key aims and effects of different
  vaccination programmes
• To understand key principles in vaccination
  programme evaluation, specifically
• Disease surveillance
• Vaccine uptake (coverage)
• Vaccine effectiveness
• Vaccine safety

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Considerations behind the epidemiology of
vaccine-preventable diseases

• Surveillance reflects programme
• vaccination history and disease dynamics (e.g.
  change age of vaccination change number of
  doses)
• Immunization is population-based
• role of herd immunity
• Vaccine efficacy needs monitoring

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Surveillance of VPD

• Pre-implementation
• estimate burden
• decide vaccination strategy
• Post implementation
• monitor impact and effectiveness
• Nearing elimination
• identify pockets of susceptibles
• certification process

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Impact of mass vaccination programme Annual
measles notifications vaccine coveragePoland
1960-2000
Source National Institute of Public Health
National Institute of Hygiene, Warsaw, Poland
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Surveillance of VPD

• Disease incidence (before and after introduction
  of vaccine)
• Vaccine uptake (coverage)
• Vaccine effectiveness
• Serological surveillance
• Adverse events
• Knowledge and attitudes

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Key data to collect for surveillance of vaccine
preventable diseases

• Person
• Age
• Place
• Residence
• Time
• Date of disease onset
• Date of specimen collection
• Vaccination status
• Vaccine failure or failure to vaccinate?

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Additional data for diseases of special interest
or being eliminated

• Person
• Age, gender, profession, etc.
• Place
• Residence, possible sites of exposure, hospital,
  etc.
• Time
• Date of rash onset, location during possible
  exposure period, location during infectious
  phase, etc.
• Vaccination status
• Number of doses
• Date of doses

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Disease incidence

• Main sources of data
• statutory notification
• laboratory reporting
• death registrations
• Other sources
• hospital episodes
• sentinel GP reporting
• paediatric surveillance

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Surveillance of vaccine coverage

• Number of vaccines distributed
• Number of vaccines administered
• sampling population assessment, e.g. cluster
• total population assessment (administrative)
• Number of doses of vaccine given/used
• Total (target-)population

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Use of administrative coverage data

• Usually total population
• Monitor trends over time
• Look for pockets of poor coverage
• Compare with disease epidemiology
• Estimate vaccine effectiveness

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Efficacy, effectiveness, herd immunity and
impact

• Efficacy
• is the direct protection to a vaccinated
  individual as estimated from clinical trial
• Effectiveness
• is an estimate of the direct protection in a
  field study post licensure
• Herd immunity
• is an indirect effect of vaccination due to
  reduced disease transmission
• Impact
• is the population level effect of a vaccination
  programme. This will depend on many factors such
  as vaccine coverage, herd immunity and
  effectiveness

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Vaccine evaluation
Post-licensing
Pre-licensing

• observational studies
• Vaccine effectiveness
• protective effect under ordinary conditions of a
  public health programme
• prone to bias, more complex interpretation

• randomised, blinded, controlled clinical trials
• Vaccine efficacy
• protective effect idealised conditions
• Randomised Controlled Trials (RCT), simple
  interpretation

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Efficacy versus effectiveness

• Vaccine efficacy Preventable fraction among
  exposed (Vaccinated)
• Study conditions
• Independent of vaccine coverage
• Vaccine effectiveness Preventable fraction in
  the population
• Field conditions

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Factors influencing field vaccine efficacy
(effectiveness)

• Host
• age at vaccination (e.g., measles, influenza)
• immune status (e.g., measles)
• number and timing of doses (e.g., Hepatitis B)
• years since vaccination (e.g., pertussis)
• Vaccine
• production
• storage (e.g., temperature, light)
• transportation
• route of administration
• Agent
• strains included in the vaccine formulation

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Methods to assess VE

• Pre-licensure
• randomised control trial (RCT)
• Post-licensureobservational/field investigation
  
• cohort study / case-control study
• screening method
• household contact study

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Calculating the vaccine efficacy in the field
Reference method

• Proportion of cases potentially avoided among
  vaccinated
• Preventable fraction among exposed to a vaccine
• Formula
• VE (ARNV - ARV) / ARNV (Cohort study)
• VE 1-OR (Case control study)
• Require a confidence interval

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Vaccinated
Unvaccinated
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Calculating the vaccine efficacy in the field
Rapid screening method

• PCV Proportion of cases vaccinated
• PPV Proportion of the population vaccinated
• VE Vaccine efficacy

Orenstein WA et al. Field evaluation of vaccine
efficacy. Bull World Health Organ 1985
631055-68
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Impact of vaccine coverage on vaccination status
of cases assuming VE lt 100
Vaccine Coverage
0
100
All cases vaccinated All are primary
or secondary vaccine failures
Cases may be vaccinated or unvaccinated
All cases unvaccinated
No vaccine has 100 efficacy
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Potential pitfalls....

• case definition
• vaccine history
• case ascertainment
• comparability of vaccinated/unvaccinated groups

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Methodological issuescase definition

• Lower specificity case definition based only on
  clinical criteria may result in false-positive
  diagnoses
• ARV gt ARU
• VE () (ARU-ARV) X 100
• ARU
• artificial reduction in VE

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Methodological issuescase definition

• Changes in mumps vaccine effectiveness

Case definition Case definition Case definition Case definition
Diagnosis by school nurse by school nurse
ARV 18 (12/67)
ARU 28 (77/272)
VE 37
Kim Farley et al 1985 AJE
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Methodological issuescase definition

• Changes in mumps vaccine effectiveness

Case definition Case definition Case definition Case definition
Diagnosis by school nurse by school nurse Parotitis gt 2 days Parotitis gt 2 days
ARV 18 (12/67) 12 (8/67)
ARU 28 (77/272) 25 (68/272)
VE 37 52
Kim Farley et al 1985 AJE
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Methodological issuesvaccine history
ascertainment

• avoid misclassification of vaccination status
• equal effort to confirm vaccination status among
  cases and non-cases
• vaccination histories should be documented using
  GP, clinic, vaccination cards or computer records
• persons with missing vaccination records should
  be excluded

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Vaccine effectivenesspost licensure monitoring
of VE

• Maintenance of VE
• Problems in vaccine delivery
• cold chain failure, schedule violation, n of
  doses, vaccine strain substitution
• Epidemiological factors
• pathogen changes
• Methodological bias
• selection bias, confounding, chance effects
• Low protective efficacy
• bad batch, different target population,
  alternative patterns of use, vaccine strain used

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Herd immunity

• Definition
• Resistance of a group to a disease to which a
  large proportion of the members are immune
• Decreases the probability of contacts between
  infected patients and susceptible individuals
• Depends on
• Infectiousness of the agent
• Hepatitis A lower than measles
• Population density
• Target herd immunity for measles control
• 95 in general
• May be lower in lower population density areas

Adapted from Fox, et al. Am J Epidemiol. 1971
94179-89
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What is different about surveillance of vaccine
preventable diseases?

• Its not just about the disease
• Decision making is a complex issue
• Objectives change at different stages
• It includes vaccine effectiveness
• Adverse events following immunization (AEFI) -
  Vaccine safety issues
• Case definitions have to change as the
  epidemiology changes
• Surveillance methods have to change as the
  epidemiology changes
• Follow-up of cases in more detail (remember
  vaccination status)
• Vaccination programs have indirect effects
• Surveillance includes Coverage
• Surveillance includes Attitudes

N. Crowcroft Agency for Health Protection and
Promotion, Ontario, Canada
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Reference
Questions?
Acknowledgments EPIET Vaccination module HPA
Immunisation Training (Richard Pebody, Nick
Andrews, John Edmunds, Natasha Crowcroft, Mary
Ramsay) Revised byRichard Pebody 2007, Pawel
Stefanoff 2008, Marion Muehlen 2009, 2010, Biagio
Pedalino 2011, 2012

• Orenstein W. Assessing vaccine efficacy in the
  field. Epidemiological Reviews 1988