18.06.2013

1

Vaccines:A success story with failures

Ursula WiedermannInstitute of Specific Prophylaxis and Tropical Medicine, Medical

University Viennawww.meduniwien.ac.at/tropenmedizin

Aims of vaccination

Individual protection!(protection againstinfection/disease)

Collective protectionHerd immunity;

reduction of transmission

Reduction of incidence of disease

– prevention of epidemics

Elimination(reduction of infection in certain geographic area;

protection of re-emergeringdiseases)

Eradication(premanent worldwide

elimination of pathogen)

High vaccinationcoverage

18.06.2013

2

Benefit-Risk, Benefit-Cost Ratio

• Benefit-Risk Ratio (important for individual consideration):– Evaluation of the risk of disease and the risk of vaccination with

respect to the same risk parameter (death, sequelae) within a certain time interval:

– For all existing vaccines the calculation of the benefit/risk ratio is positive

• Benefit-Cost Estimation (for implementation of vaccine programs) :– is calculated to document social-economic savings through high

vaccination coverage: the benefit-cost ratio is positive for diseases with high incidence and high morbidity;

– For diseases with high individual risk for morbidity/mortality but low incidence this calculation is not always positive

Ehret J, Vaccine 2003

Public health issues of vaccination programs

Collective protectionHerd immunity;

reduction of transmission

Reduction of incidence of disease

– prevention of epidemics

Positive benefit-costratio:

• Reduction of therapycosts

• Reduction of hospitalisation rates• Reduction of

prevalence andincidence

• Number of gained lifeyears

• Number of gainedworking days

High vaccinationcoverage

18.06.2013

3

Definition of efficacy versus effectiveness

„Efficacy“:Measures the protective effect of a vaccine withrespect to a defined endpoint and selected studypopulation = ideal study situation (non „real lifessituation“)

„Effectiveness“Measures the protective effect of a vaccine underreal life conditions – non selected population, non controlled (for age, disease, preexisting immunityetc - direct, indirect, total, overal effects)

Development of human vaccines

18.06.2013

4

Impact of vaccination on epidemiology of infections

Cost benefit is the sum of direct and indirect effects

18.06.2013

5

Indirect effects - Herd immunity

= Protective value of a vaccine is due to:– Direct protective effect of a vaccine– Number of vaccinated people

– Protection of unvaccinated– Improved protection of vaccinated– Improvemet of cost-benefit ratio

Leads to:

Herd immunity/protection

Results from:

Reduction of pathogen transmission in a populationthat is protected to a certain percentage via vaccination („herd protection“):

• Only possible with human to human transmission;• Possible with live or inactivated vaccines

18.06.2013

6

Erreger-Transmission von Mensch zu Mensch

„Transmissability“ = Übertragungskapazität eines Erregers wird durch die „B asisreproduktionszahl“ (R0) definiert:

= Anzahl an Personen in einer ungeschützten Population, die durch 1 Infizierten angesteckt werden

Hängt ab von:

– Biologischen Eigenschaften des Erregers (Pathogenität, Virulenz)

– Häufigkeit des Erregerkontakts und Art des Kontakts

– Umweltbedingungen (Temperatur, Kontaktbedingungen wie Schule, Altersheim, Haushalt, Immunstatus, etc)

„Herd immunity threshold“= Mindestdurchimpfungsrate die zur Verhinderung einer Epidemie ausreicht (unter der Annahme, dass Vakzine 100% wirksam)

Epidemic

Vaccinationrate: 75%

Prevention ofepidemic

Rn= Netto Reproductionsnumber; 1

18.06.2013

7

Infektion Basisreproduktionszahl (R0)

Durchimpfungsrate (%)*

Diphtherie 6-7 85

Influenza 1,2-2 40-50

Masern 12-18 92-94

Mumps 4-7 75-86

Pertussis 12-17 92-94

Polio 2-15 50-93

Röteln 6-7 83-85

Varizellen 8-10 88-90

*Assuming that the vaccine efficacy is 100% – if it < 100%, vaccination coverage needs to be higher

Correlates of vaccine-induced immunity

18.06.2013

8

Definition of correlates of protection

18.06.2013

9

18.06.2013

10

18.06.2013

11

18.06.2013

12

18.06.2013

13

Safety and acceptance

18.06.2013

14

Adverse events following immunization

Hypotonic, hyoresponsive episodes