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10/10/2011 Vaccinology. 1
OUTLINE
Introduction & Definition
Mass Vaccination
Vaccine Development
Vaccine Evaluation
Vaccine Safety
Reporting Immunizations
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What is Vaccine
• Dictionary (Dorland 30th edition 2008)
Attenuated or killed microorganisms or proteins derived from them, administered for
the prevention, treatment, or amelioration of infectious diseases
• Wikipedia
A vaccine is a biological preparation that improves immunity to a particular disease. A
vaccine typically contains an agent that resembles a disease-causing microorganism,
and is often made from weakened or killed forms of the microbe. The agent stimulates
the body's immune system to recognize the agent as foreign, destroy it, and "remember"
it, so that the immune system can more easily recognize and destroy any of these
microorganisms that it later encounters.
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What is Vaccinology?
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Vaccines-Historical Perspective
• 7th century- Indian Buddhists' drank snake venom to protect against snake bite.
• 1950-1970- The tissue culture revolution: poliomyelitis, measles, mumps and rubella.
• 1970-1990- Dawn of the molecular era: hepatitis B, Streptococcus pneumonia, Hemophilus influenza B.
• Today- Glycoconjugate vaccines, rotavirus vaccine, human papilloma virus vaccine and herpes zoster
vaccine.
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Aims of Immunisation Programmes
• To protect those at highest risk
(selective immunisation strategy)
or
• To eradicate, eliminate or control disease
(mass immunisation strategy)
Currently, it is estimated that vaccination saves the lives of 3 million children a year
• Eradication
Infection (pathogen) has been removed worldwide e.g. smallpox
• Elimination
Disease has disappeared from one area but remains elsewhere e.g. polio, measles
• Control
Disease no longer constitutes a significant public health problem e.g. neo-natal tetanus
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Vaccines Achievements 1
• With sanitation and nutrition, vaccines are hailed as one of the most
26.
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Vaccines Achievements 2
• “At the end of the 20th century the US Centers for Disease
Control and Prevention (CDC) cited vaccination as the
number one public health achievement of that century”
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The Ideal Vaccine
• Immunogenic
• Long lasting immunity
• Safe
• Stable in field conditions
• Combined
• Single dose
• Affordable (and accessible) to all
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Categorization of Current Vaccines
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Viral Vaccines
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Bacterial Vaccines
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Target Fungal Vaccines
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Target Parasitic Disease
• Malaria
• Trypanosomiasis
• Leishmaniasis
• Toxoplasmosis
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Selective Vaccination
• Vaccine given specifically to those at increased risk of disease:
• High risk groups
e.g. Pneumococcal vaccine
• Occupational risk
e.g. Hepatitis B, influenza
• Travellers
e.g. Yellow fever, rabies, meningitis
• Outbreak control
e.g. Hepatitis A. vaccine, measles
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Pipelines for Developing Countries
Much needed vaccines for the developing world
• Malaria
• Tuberculosis
• HIV
• Hookworm
• Dengue
• Enterotoxigenic Escherichia coli
• Shigella
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More Possibilities
• Therapeutic vaccines: Identification of specific tumor
antigens provide immune targets for which immunogenic
vaccines may conceivably be designed. Examples:
Leukemia
Breast cancer
Melanoma
Prostate cancer
Colon cancer
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Similarities between Vaccines and
other Drug
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Vaccination Policy Options
?
Eradication Activities
New Vaccine
Introduction
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Role of disease burden studies in the development and
introduction of new and underutilized vaccines
Disease Epidemiology
• Geographical distribution
• Age groups
• Seasonality, risk factors
Disease-Burden Studies
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Mass Vaccination
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Impact of Mass Vaccination Programmes
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No Mass Vaccination
Each host in contact with infected host becomes infected (with a certain
probability)
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Mass Vaccination
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Impact of Mass Immunisation Programme
90
500.0
80
60
300.0 50
40
200.0
30
20
100.0
10
0.0 0
Year 1964 1969 1974 1979 1984 1989 1994 1999
Year
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Surveillance of Vaccine Preventable Disease
• Vaccine uptake
• Vaccine effectiveness
• Serological surveillance
• Adverse events
• Vaccine uptake
• Disease incidence
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Objectives of Surveillance
Vaccine Preventable Diseases
• Pre-implementation
Estimate burden
Decide vaccination strategy
• Post implementation
Monitor impact and effectiveness
• Nearing elimination
Identify pockets of susceptible
Certification process
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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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Measles Case Definitions
• Suspect case
Rash and fever
• Probable case
Rash, fever, and either: cough, coryza or conjunctivitis
• Laboratory confirmed
• Saliva/serum IgM positive
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Predictive Value of Notified Measles
Effect of Change in Incidence
Non-measles Genuine measles
1000000 100%
100000 80%
10000
Number of cases
60%
PV+
1000
40%
100
10 20%
1 0%
Pre-vaccine Low coverage High coverage Near elimination
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Surveillance of Vaccine Coverage
• Vaccine distributed
• Vaccine administered
Sampling population assessment e.g. Cluster
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Use of Administrative Coverage Data
• Usually total population
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Steps on Vaccine Development 1
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Steps on Vaccine Development 2
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Steps on Vaccine Development 3
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Vaccine Evaluation
Pre-licensing Post-licensing
Randomised, Blinded, Observational Studies
Controlled Clinical Trials
Vaccine effectiveness:
Vaccine efficacy: Protective Effect under
Ordinary Conditions of a
Protective Effect under public health programme
Idealised Conditions
prone to bias, more complex
RCT: controlled experiments, interpretation
simple interpretation
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Efficacy, Effectiveness, Impact and Herd Immunity
•Efficacy is the direct protection to a vaccinated individual as estimated from clinical trial
•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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Basic Calculation of VE
% reduction in attack rate of disease in vaccinated (ARV)
compared to unvaccinated (ARU) individuals
VE (%) = (ARU-ARV) X 100
ARU
Where ARU ARV
1 RR
ARU and ARU
IV = 2/10 = 0,2
Unvaccinated
IU = 9/10 = 0,9
0,9 – 0,2
VE = = 78%
0,9
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Methods to Assess VE
• Pre-licensure:
Randomised control trial (RCT)
• Post-licensure:
Observational/Field investigation
• Screening method
• Cohort study
• Household contact study
• Case-control study
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Observational study: Screening Method
VE = 1 - PCV x (1-PPV)
(1-PCV) x PPV
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Observational study: Screening Method
0.8
vaccinated
0.6 VE=60%
VE=80%
0.4 VE=90%
VE=95%
0.2
0
0.5 0.6 0.7 0.8 0.9 1
Proportion of population vaccinated
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Potential Pitfalls....
• Case definition;
• Vaccine history;
• Case ascertainment;
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Methodological Issues: Case Definition 1
artificial reduction in VE
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Methodological Issues: Case Definition 2
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Methodological Issues: Case Definition 2
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Methodological issues: Vaccine History Ascertainment
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Vaccine effectiveness: Post licensure monitoring of VE
Post-licensure: 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
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Summary of VE
• Multiple sources of data are valuable to
evaluate vaccine programmes
• Source of data and case definitions change
with stage of vaccination programme
• Monitoring VE is integral
• VE can be carefully estimated from routine
data
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Let’s GO An Example
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A Randomized, Controlled Experiment
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A Randomized, Controlled Double-Blind Experiment
Treatment 200,000 28
Control 200,000 71
Total 400,000 99
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Analysis: The Devil’s Advocate
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A Probability Model
• Put 400,000 balls in an urn with 99 black and the rest white.
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Calculating Probabilities
• A statistician relies on the theory of probability to
calculate probabilities.
•
99 399901 400000
x 200000 x 200000
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Conclusion: Get vaccinated!
• We must reject the hypothesis that the treatment has no
effect; otherwise we must believe we are incredibly
unlucky.
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Vaccine Safety
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Today’s Agenda
• The Good
The benefits of vaccination
• The Bad
Vaccines “rocky” past
Acceptable risk?
Vaccine refusal
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Vaccines Work
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Pre-licensure Safety Monitoring1
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Pre-licensure Safety Monitoring2
Limitations
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Safety Monitoring -
Who looks at all that data?
Institute of Medicine (IOM)
• Part of the National Academy of Science
• Non-profit, non-governmental organization, volunteer
• Provide the CDC, NIH and congress on data interpretation on matters of
bio-medical science
• IOM Vaccine Safety Reports – The “Gold Standard” in vaccine safety
analysis
MMR and Autism (2001)
Thimerosal and Neurodevelopmental Disorders (2001)
Multiple Immunizations and Immune Dysfunction (2002)
HepB Vaccine and Demyelinating Neurological Disorders (2002)
SV40 Contamination of Polio Vaccine and Cancer (2002)
Influenza vaccines and Neurological Complications (2003)
Vaccines and Autism (2004)
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The Bad
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The Cutter Incident
• 1950s Jonas Salk pioneering work with IPV
• 5 companies stepped forward to manufacture IPV
after licensure
• Cutter (the smallest) made a bad batch
100,000 children injected with live virus
70,000 got mild polio
200 were permanently paralyzed
10 died
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Vaccine-Associated Paralytic Polio
(VAPP)
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“Swine Flu” vaccine of 1976-1977
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“Acceptable” Risk?
• Local side effects
Swelling, redness
• Systemic side effects
Fever, pain, allergic reaction
• MMR and Thrombocytopenia
• MMR(V) and febrile seizures
• Adolescent vaccines and syncope
• Guillain-Barré and MCV4
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MMR & Thrombocytopenia
• Yes
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MMR(V) & Febrile Seizures
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Syncope and Adolescent Vaccines
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Guillain-Barré Syndrome and MCV4
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and the Ugly
• Wealth of misinformation
MMR and Autism
Mercury poisoning
• Vaccine refusal
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Reporting Immunization Requirements
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Reporting immunization requirements: Documenting
administration of vaccine Content
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Reporting immunization requirements: Documenting
administration of vaccine Content-Lot Number
On adjuvant carton
On shoe box
• Vaccine management
• Informed consent
• Administration of vaccine
• Documentation
• Anaphylaxis management
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Immunization practice standards: Vaccine
management-Storage and handling of vaccine
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Immunization practice standards
Informed consent
Screening Questions (Examples)
• Is unwell today?
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Immunization practice standards
Administration of vaccine
Intramuscular injection
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Source : http://www.health.gov.nl.ca/health/publications/immunization/S4/
Immunization practice standards
Administration of vaccine
Post-vaccination
• Check
• Instruct client
To wait 15 minutes
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Immunization practice standards Documentation
• CSDS – as directed
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Immunization practice standards Anaphylaxis
management
• Administer epinephrine
• Call 115
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Immunization practice standards
Reporting AEFI -
Current surveillance process
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Immunization practice standards Reporting AEFI -
Enhanced severe AEFI surveillance
• Refer to GNB website for reporting process, case definition and form
http://www.gnb.ca/0053/h1n1/audience_professionals-e.asp
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Immunization practice standards
Reporting AEFI -
Enhanced severe AEFI surveillance
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Immunization practice standards
Occupational health issues
• Used injection material
Handling
Disposal
Sharp containers
Where to place
When to replace
How to dispose of
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Reliable web sites
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CDC Vaccines and Immunization
Contact Information
• Telephone 800.CDC.INFO
• Email nipinfo@cdc.gov
• Website
www.cdc.gov/vaccines
• Vaccine Safety
www.cdc.gov/od/science/iso
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Promote Epidemiology Training & Research
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References
• Geoffrey A. Weinberg and Peter G. Szilagyi. Vaccine Epidemiology: Efficacy, Effectiveness ,and the Translational Research Roadmap. The
10.10.2011
• Geert Leroux-Roels, Paolo Bonanni, Terapong Tantawichien,Fred Zepp. Understanding Modern Vaccines: Perspectives in Vaccinology
• Thomas D. Szucs. Health economic research on vaccinations and immunization practices—an intro uctory primer. Vaccine 23 (2005):
2095–2103
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