Vaccine Preventable Diseases
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Transcript Vaccine Preventable Diseases
Vaccine Preventable Diseases (VPD):
Surveillance & Evaluation
17th EPIET introductory course
Lazareto, Menorca, Spain
30 September 2011
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
Mass vaccination
Effective reproductive number: R < 1
Impact of mass vaccination programme
Annual measles notifications & vaccine coverage
Poland 1960-2000
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
Measles case definitions
• Suspect case
rash and fever
• Probable case
rash, fever, and either: cough, coryza or
conjunctivitis
• Laboratory confirmed
saliva/serum IgM positive
difference between two IgG measurements
Which one is measles?
N. Crowcroft
Agency for Health Protection and Promotion, Ontario, Canada
Predictive value of notified measles
Effect of change in incidence
Non-measles
Genuinemeasles
1000000
100%
100000
80%
60%
1000
40%
100
20%
10
1
0%
Pre-vaccine
Low coverage
High coverage Near elimination
PV+
Number of cases
10000
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
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
Note: 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
Phase IV surveillance is special
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)
Yvan Hutin
Revised by:
Richard Pebody 2007, Pawel Stefanoff 2008, Marion Muehlen 2009, 2010, Biagio Pedalino
2011
Reference
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Orenstein W. Assessing vaccine efficacy in the field. Epidemiological
Reviews 1988