Transcript Epidemiological aspects of vaccine preventable diseases

Epidemiological aspects of
Vaccine Preventable Diseases (VPD)
Biagio Pedalino
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What’s so special about VPD?
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
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
Aims of vaccination programmes
• To protect those at highest risk
(selective vaccination strategy)
or
• To eradicate, eliminate or control disease
(mass vaccination strategy)
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
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)
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
Progress Toward Polio Eradication
35,251 cases
Decrease of >99% from
>350 000 cases in 1988
to <2000 cases in 2008
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
All susceptible
Basic reproductive number:
R0=4
Mass vaccination
Mass vaccination
Effective reproductive number: R < 1
Impact of mass vaccination programme
Annual measles notifications & vaccine coverage
Poland 1960-2000
Source: National Institute of Public Health – National Institute of Hygiene, Warsaw, Poland
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
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
Surveillance of VPD
• Pre-implementation
 estimate burden
 decide vaccination strategy
• Post implementation
 monitor impact and effectiveness
• Nearing elimination
 identify pockets of susceptibles
 certification process
Impact of mass vaccination programme
Annual measles notifications & vaccine coverage
Poland 1960-2000
Surveillance of VPD
• Disease incidence (before and after
introduction of vaccine)
• Vaccine uptake (coverage)
• Vaccine effectiveness
• Serological surveillance
• Adverse events
• Knowledge and attitudes
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?
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
Disease incidence
• Main sources of data
 statutory notification
 laboratory reporting
 death registrations
• Other sources
 hospital episodes
 sentinel GP reporting
 paediatric surveillance
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
Use of administrative coverage data
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Usually total population
Monitor trends over time
Look for pockets of poor coverage
Compare with disease epidemiology
Estimate vaccine effectiveness
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
Vaccine evaluation
Pre-licensing
randomised, blinded,
controlled clinical trials
Vaccine efficacy:
protective effect idealised
conditions
Randomised Controlled Trials
(RCT), simple interpretation
Post-licensing
observational studies
Vaccine effectiveness:
protective effect under ordinary
conditions of a public health
programme
prone to bias, more complex
interpretation
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
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
Methods to assess VE
• Pre-licensure:
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randomised control trial (RCT)
• Post-licensure:
observational/field investigation
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cohort study / case-control study
screening method
household contact study
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
Vaccinated
ARV = 2/10 = 0,2
Unvaccinated
ARU = 9/10 = 0,9
0,9 – 0,2
VE =
= 78%
0,9
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; 63:1055-68
Impact of vaccine coverage on vaccination
status of cases assuming VE < 100%
Vaccine Coverage
100 %
0
All cases
unvaccinated
Cases may be vaccinated or
unvaccinated
All cases vaccinated;
All are primary or
secondary vaccine
failures
No vaccine has 100% efficacy
Potential pitfalls....
• case definition
• vaccine history
• case ascertainment
• comparability of vaccinated/unvaccinated groups
Methodological issues:
case definition
Lower specificity: case definition based only on clinical
criteria may result in false-positive diagnoses
ARV
> ARU
VE (%) = (ARU-ARV) X 100
ARU
artificial reduction in VE
Methodological issues:
case definition
Changes in mumps vaccine effectiveness
Case definition
Diagnosis by school nurse
ARV
18%
(12/67)
ARU
28%
(77/272)
VE
37%
Kim Farley et al 1985 AJE
Methodological issues:
case definition
Changes in mumps vaccine effectiveness
Case definition
Diagnosis by school nurse
Parotitis > 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
Methodological issues:
vaccine 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
Vaccine effectiveness:
post 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
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; 94:179-89
What is different about surveillance of
vaccine preventable diseases?
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It’s 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
Questions?
Acknowledgments:
EPIET Vaccination module
HPA Immunisation Training (Richard Pebody, Nick Andrews, John Edmunds, Natasha
Crowcroft, Mary Ramsay)
Revised by:
Richard Pebody 2007, Pawel Stefanoff 2008, Marion Muehlen 2009, 2010, Biagio Pedalino
2011, 2012
Reference
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Orenstein W. Assessing vaccine efficacy in the field. Epidemiological
Reviews 1988